Preclinical Evaluation of an MR Conditional Forceps for MRI-Guided Endomyocardial Biopsy: A Multimodal Imaging Approach Using a Hybrid Vessel Phantom and Porcine In Vivo Models

Preclinical Evaluation of an MR Conditional Forceps for MRI-Guided Endomyocardial Biopsy: A Multimodal Imaging Approach Using a Hybrid Vessel Phantom and Porcine In Vivo Models | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Preclinical Evaluation of an MR Conditional Forceps for MRI-Guided Endomyocardial Biopsy: A Multimodal Imaging Approach Using a Hybrid Vessel Phantom and Porcine In Vivo Models Denis Gholami Bajestani, C. Martin Reich, Jan Birkigt, Christina Mulik, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7269885/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background MRI-guided cardiovascular procedures provide high-resolution, radiation-free imaging, but clinical translation is limited due to the lack of MR Conditional medical devices. This study presents a structured preclinical approach for validating MRI-guided devices and interventions, focusing on visibility and handling of a passively marked MR Conditional endomyocardial biopsy (EMB) forceps. Methods The EMB forceps was evaluated in a three-stage preclinical protocol. First, device visibility was assessed in a water-filled test box using fluoroscopy (Philips Allura Xper) and three MRI systems (Siemens MAGNETOM Skyra 3T, GE Signa HDxt 3.0T, and GE Signa HDxt 1.5T). Tissue samples from MR Conditional (n = 5) and standard Cordis biopsy forceps (n = 5) underwent histological analysis. Second, devices were assessed during fluoroscopy-guided EMB using a hybrid vessel phantom, with handling compared by experienced interventionists (n = 4). Next, MRI-guided testing of MR Conditional forceps was performed in the phantom (Siemens Biograph mMR 3.0T). Finally, in vivo testing was conducted in a porcine model (n = 4) using the same MRI system, following ethics committee approval. Results Visibility was confirmed in all three MRI systems (artifact coverage > 45% for EMB forceps head; >40% passive MR markers) and fluoroscopy. Handling was rated medium or higher by all operators. No significant difference in histological tissue quality and tissue sampling times (p > 0.05) was observed between MR Conditional and standard forceps. In vivo, five tissue samples of equivalent quality were successfully harvested (out of six attempts), with smaller artifact sizes compared to in vitro measurements. Conclusions The MR Conditional EMB forceps showed reliable visibility, handling, and accurate tissue sampling in both in vitro and in vivo testing. The developed in vitro testing protocol effectively evaluated key device characteristics, providing valuable insights in the early stages of in vivo trials. Biomedical Engineering Minimally invasive procedure interventional MRI endomyocardial biopsy MRI phantom MR Conditional device biopsy forceps Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 1. Introduction Endomyocardial biopsy (EMB) is a commonly used catheter-based diagnostic technique for investigating myocardial pathologies ( 1 , 2 ). Catheter-based interventions are usually performed using fluoroscopy, which allows real-time imaging of medical devices and the target anatomy ( 3 ). However, fluoroscopy is associated with ionizing radiation, nephrotoxic contrast agents, and lack of soft tissue contrast ( 4 – 6 ). Magnetic resonance imaging (MRI)-guided interventions have been shown to overcome these drawbacks and benefit from arbitrary slice orientation ( 7 , 8 ). Several feasibility studies have demonstrated successful targeted extraction of focal pathological myocardial tissue with MRI-guided EMB ( 9 – 11 ). However, broader clinical translation is still hindered by the lack of MR Safe or MR Conditional and technically suitable medical devices providing appropriate handling ( 9 , 11 , 12 ). Approval of Class III medical devices often requires human cadaveric and animal studies ( 13 ). Based on the 3R principle (Replace, Reduce & Refine) in animal research, it is necessary to carry out extensive tests outside animal models in advance ( 14 ). Anatomically correct models that mimic human vessel systems are needed and could bridge the gap between in vitro and in vivo application for conclusive testing and training before preclinical animal studies. In this study, an MR Conditional biopsy forceps previously developed by EPflex Feinwerktechnik GmbH was evaluated for its functionality, MR- and fluoroscopic visibility, and handling characteristics during EMB interventions using an MR Safe hybrid biological heart and polymer-based vessel phantom, as well as a porcine in vivo model involving multiple pigs ( 15 , 16 ). In addition, an MRI-adapted interventional workflow was developed for image acquisition during MRI-guided EMBs and validated against the gold standard, a fluoroscopic workflow. 2. Material and methods 2.1 MR Conditional EMB forceps MRI-guided catheter-based EMBs were performed using a 6 Fr MR Conditional biopsy forceps (Fig. 1 ) supplied by EPflex Feinwerktechnik GmbH (Dettingen an der Erms, Germany). The MR visualization of the forceps was based on susceptibility artifacts of the forceps' jaws and punctual passive MRI-visible markers along the device shaft. 2.3 Histological examination of biopsies The quality of the obtained tissue samples was assessed by histological examination. For this purpose, tissue samples (n = 10) were obtained from the left ventricle of a fresh porcine heart, five each using the MR Conditional biopsy forceps and an approved 5.5 Fr standard biopsy forceps (Cordis, Hialeah, Florida, US), respectively. All samples were stored in formalin buffer (4%, v/v) for at least 24 hours. An experienced physician from the Institute of Pathology of the University of Leipzig Medical Center processed the obtained tissue samples. After paraffin embedment and sectioning (3–4 µm), tissue samples were stained with hematoxylin-eosin (HE) solution and evaluated with light microscope images. 2.4 In vitro artifact assessment of EMB forceps using fluoroscopy and MRI The applicability of the MR Conditional EMB forceps for image-guided interventions was assessed based on their imaging properties. Due to expected variations in MR imaging and susceptibility artifacts across different MRI systems and field strengths ( 17 ), the MR Conditional forceps' MR visibility properties were assessed. Three MRI systems were used: Siemens Biograph 3.0T (Siemens Healthcare, Erlangen, Germany), GE Signa HDxt 3.0T, and GE Signa HDxt 1.5T (GE Healthcare, Milwaukee, WI, USA). Standard real-time sequences for cardiac MRI (True FISP) were used for the assessment. Visualization in fluoroscopy has been performed at the local hospital using an Allura Xper angiographic system (Philips Healthcare, BeSIst, Netherlands) to ensure applicability in the gold standard. Fluoroscopy images were captured in ambient air with the EMB forceps positioned on the patient table. For MR imaging, the EMB forceps was placed inside a polymer test box (29 x 22 x 19 cm) filled with physiological saline solution (0.9% NaCl). The MR images were evaluated with Matlab (MathWorks, Natick, Massachusetts, USA) using an ASTM F2119-07 (Standard Test Method for Evaluation of MR Image Artifacts from Passive Implants) based approach. Acquired artifact pixels were identified as described in ASTM F2119-07. A bounding box (smallest possible rectangle) was then defined around the identified artifacts of each MR marker. The proportional artifact coverage was determined by calculating the ratio between the total area occupied by valid artifact pixels and the area of the defined bounding box. The calculated proportional artifact coverages were used together with the dimensions of the bounding box to evaluate and quantify the artifact's appearance. MRI artifact dimensions from both phantom and in vivo experiments were manually assessed. Measurements were performed on DICOM images using the distance tool in MicroDicom (MicroDicom, Bulgaria), focusing on artifact size around the EMB forceps head. Differences between experimental settings were statistically evaluated using an independent t-test. 2.5 Imaging workflow for MRI-guided EMB An imaging workflow for MRI-guided EMB interventions was developed based on clinical standard operating procedures, expert interviews, and clinical observations of fluoroscopy-guided EMB interventions. Based on the standard workflow of the respective interventional steps performed in the Cath lab, the corresponding imaging tasks during fluoroscopy-guided EMB procedures were outlined. Based on the defined interventional steps during an EMB, MRI-guided imaging tasks were derived and transferred into a corresponding MRI-adapted workflow, which was reviewed, tested, and optimized in close collaboration with interventionalists and MR radiographers. All MRI-guided interventions presented in this study were performed using a developed interventional MRI (iMRI) setup, which allows communication and control of the MRI system in the room as well as display of the acquired MR images, as described elsewhere ( 18 ). 2.6 Assessment of EMB forceps inside hybrid vessel phantom MRI- and fluoroscopy-guided EMBs were performed using a hybrid biological heart and polymer-based phantom (Fig. 2 ), developed in collaboration with Phacon GmbH (Leipzig, Germany). The model consisted of a silicone aortic vascular structure based on human anatomical CT-scan data (68 y/o, female) attached to a Thiel-embalmed porcine heart (Duroc and Pietrain pig breed, approx. six months) ( 15 ). The vascular structure was housed in an acrylic glass case (56 x 25 x 20 cm) embedded in a tissue-mimicking gel of water-binding superabsorbent multipurpose polymer (HVDE 235, Schauch Granulate, Lauffen am Neckar, Germany). Blood flow through the phantom vessels was simulated using a physiological saline solution mixed with 30% glycerol (WHC GmbH, Hilgertshausen-Tandern, Germany) and a pulsatile flow pump (MultiFlow centrifugal pump, GAMPT mbH, Merseburg, Germany). The model was designed to allow the usage of a wide range of varying heart sizes to account for the individual differences in hearts purchased from a local butcher shop. The left atrium of the porcine heart was sealed with surgical suture material (3 − 0, Vicryl, Ethicon, Inc., Bridgewater, US) to facilitate pressurization by the pump. Femoral access for interventional devices such as guidewires and catheters was realized by puncturing silicone tubes (Deutsch & Neumann GmbH, Hennigsdorf, Germany) at the proximal femoral section of the polymer-based vascular phantom (outside the housing) with lumen diameters of 6 to 10 mm (wall thickness 1.5 to 2 mm). A questionnaire-based evaluation of the phantom is provided in the Supporting Information (S1 and S2). 2.6.1 Handling study: fluoroscopy-guided assessment of MR Conditional and standard EMB forceps in hybrid vessel phantom Handling properties of the MR Conditional biopsy forceps was evaluated in a comparative study against an approved 5.5 Fr standard biopsy forceps (Cordis, Hialeah, Florida, USA) under fluoroscopy (Allura Xper, Philips Healthcare, Best, Netherlands) using the hybrid vessel phantom. The study was performed at the Department of Cardiology of the local hospital. An approved 0.035" (0.89 cm) hydrophilic-coated MR Conditional guidewire with a length of 150 cm (REF 39012526, EPflex Feinwerktechnik GmbH) was used for probing and guidance during the intervention, along with the following medical instruments: an 8.5 Fr, 15 cm, Fastcath Introducer Sheath (Abbott Laboratories, Chicago, Illinois, USA); a 6 Fr Introducer Fortress (Biotronik, Berlin, Germany), and a 0.038" PTFE-coated J-curve guidewire Emerald (Cordis, Hialeah, Florida, USA). EMBs were conducted according to the developed clinical workflow using conventional and MR Conditional devices, respectively, under standard conditions. In short, after the facilitation of blood vessel access (Seldinger technique ( 19 )), the guidewire was placed into the left ventricle, followed by the placement of the femoral sheath inside the left ventricle with subsequent myocardial tissue extraction using EMB forceps (until five adequate tissue samples were obtained). After the interventions, experienced interventional clinicians (n = 4) were asked to rate the utilized medical devices according to different features using a dedicated questionnaire, as shown in supporting information (S3). 2.6.2 MRI-guided assessment of MR Conditional EMB forceps Five MRI experiments were conducted using the developed hybrid in vitro vessel phantom (see Fig. 2 ). The procedures took place at the local hospital using a Biograph_mMR 3.0T scanner (Siemens Healthineers, Erlangen, Germany). During scanning, the MR Conditional EMB forceps was manipulated within the phantom to assess artifact characteristics and device visibility. Imaging focused on the artifact size at the forceps head and the visibility of passive markers along the guiding shaft. Finally, myocardial tissue samples were obtained using the MR Conditional EMB forceps (see Fig. 1 ). EMBs were conducted according to the developed clinical workflow using following MR Conditional devices. An approved 0.035" (0.89 cm), 150 cm hydrophilic-coated MR Conditional guidewire (REF 39012526, EPflex Feinwerktechnik GmbH) was used for probing and device guidance during MRI-guided interventions, along with the following instruments: a 9 Fr, 85 cm non-braided Check-Flo Performer Introducer (Cook Medical, Bloomington, IN, USA); an 18 G MR-compatible cannula and a short guidewire (REF 46012082), both provided by EPflex Feinwerktechnik GmbH. After the facilitation of blood vessel access (Seldinger technique ( 19 )), the guidewire was placed into the left ventricle, followed by the placement of the femoral sheath inside the left ventricle with subsequent myocardial tissue extraction using the MR Conditional EMB forceps. MR imaging during in vitro and in vivo experiments was performed with prepared MRI sequences (Table 1) based on the workflow derived from the catheterization lab. Table 1. Utilized MRI parameters with applied ranges for EMB interventions, Siemens Biograph_mMR 3.0T (customized TrueFISP). MRI parameter Range of values TR 380 ms to 430 ms TE 2 ms to 2.5 ms ST 5 ms to 10 ms FA 40° BW 560 Hz/pxl Pixel 1.3 mm 2 to 2 mm 2 FoV 300 x 300 mm 2 Abbreviations: TR: Repetition Time; TE: Echo Time; ST: Slice Thickness; FA: Flip Angle; BW: Bandwidth; Pixel: Pixel Size; FoV: Field of View 2.7 In vivo evaluation of MR Conditional EMB forceps Four female pigs (Sus scrofa domesticus) aged 12-16 weeks and weighing 34-58 kg were subjected to the MRI-guided EMB intervention. For transportation from the rearing station, they were sedated using the following intramuscularly administered anesthesia: 0.5‑1 mg/kg Midazolam, 15‑20 mg/kg Ketamine, and 0.5 mg/25kg. Anesthesia was maintained stable during transport using 0.5 mg/kg/h Midazolam. Before intubation, the animals received optional 0.3 mg/kg Midazolam and 10 mg/kg Propofol. After intubation, anesthesia was deepened with 1‑4 μg/kg/h Isoflurane via inhalation. Additionally, 7.5 μg/kg/h Fentanyl Citrate was given to ensure adequate analgesia during planned MRI-guided interventions. The regularly performed monitoring protocol included corneal and interdigital reflex, respiratory rate, heart rate, pulse waveform, CO 2 and O 2 saturation, minimum alveolar concentration, and invasive blood pressure. ECG monitoring was performed to detect early changes in the cardiovascular system. The in vivo experiments were performed at the local hospital in a Biograph_mMR 3.0T (Siemens Healthineers, Erlangen, Germany), using the developed clinical workflow and MR Conditional EMB forceps (EPflex Feinwerktechnik GmbH). The left femoral artery was accessed by the Seldinger technique, outside the MRI suite (19) under ultrasound (US)-guidance using a portable Clarius L7 HD3 ultrasound scanner (Clarius Mobile Health, Corp., Vancouver, BC, Canada) or, in case of failure, by open laparotomy. Therefore, an 18 G MR-cannula (EPflex Feinwerktechnik GmbH), J3-SFU-040-035/NiTi-0.52/non-magnetic-sterile short guidewire (REF 46012082, Epflex Feinwerktechnik GmbH), and 12 Fr, non-braided Check-Flo Performer introducer (Cook Medical, Bloomington, Indiana, USA) were used. After transfer to the MR scanner room, the experimental animals were positioned supine on the patient table and covered with three body coils (Body 6, Siemens Healthineers, Erlangen, Germany). Subsequent to initial plane planning, a 0.035", 260 cm long hydrophilic-coated MR Conditional guidewire (Epflex Feinwerktechnik GmbH) was inserted into the left ventricle using a 5 Fr pigtail catheter (Merit Medical Systems, South Jordan, UT, USA), additionally passively marked with iron oxide (Fe 3 O 4 , Goodfellow Cambridge, UK). In the next phase, a 9 Fr, 85 cm long, non-braided Check-Flo Performer introducer (Cook Medical, Bloomington, Indiana, USA), also passively marked with iron oxide (Fe 3 O 4 , Goodfellow, Cambridge, UK), was inserted into the left ventricle with subsequent myocardial tissue extraction using the MR Conditional EMB forceps (Epflex Feinwerktechnik GmbH). The described animal protocols were reviewed and approved by the local animal ethics committee and the governmental animal care and use committee (Landesdirektion Sachsen, Germany) (16). 2.8 Tissue sampling times Time measurements were recorded during fluoroscopy- and MRI-guided studies and later compared with those from fluoroscopy-guided endomyocardial biopsy (EMB) procedures performed on patients in the catheterization laboratory. Time capture started with the insertion of the EMB forceps into the sheath already seated in the left ventricle and ended with the withdrawal of the dedicated tissue sample outside the model. 2.9 Statistical analysis Questionnaire results were summarized using the median and interquartile range (IQR), calculated in Microsoft Excel (Microsoft Corp., Redmond, WA, USA). MRI artifact measurements of MR Conditional EMB forceps heads from in vitro phantom and in vivo studies were analyzed using an independent t-test in MATLAB (MathWorks, Natick, MA, USA). Tissue extraction times were evaluated using the mean and standard deviation (SD). Pairwise group comparisons were performed with the Kruskal-Wallis test in MATLAB. A p-value of < 0.05 was considered statistically significant. 3. Results 3.1 Histological assessment of biopsy samples The in vitro obtained tissue samples (n=10) exhibit an identical appearance with well-preserved cell contours and distinguishable cell nuclei without any artificial damage caused by the extraction method. There was no recognizable difference in the performed HE-stain between the specimens obtained by the MR Conditional forceps (Figure 3, A) and the utilized standard biopsy forceps (Figure 3, B). 3.2 In vitro artifact quantification in MRI and fluoroscopy The fluoroscopy imaging (figure 4, B) showed distinct and clearly defined artifacts of the forceps head but no artifacts at the guiding shaft. The MR images showed artifacts of the bioptome head and passive markings applied along the device's guiding shaft. These susceptibility-based MRI artifacts allowed continuous visual observation of the device during manipulation. MR images acquired at 3.0T field strength (figure 4, C & D) demonstrated artifacts with blooming effects and radial lines surrounding the applied MRI-visible markers at the EMB forceps head and guiding shaft. MR imaging performed at 1.5T field strength (figure 4, E) showed less blooming and no distinct radial lines but punctual increased intensity around the markers. The artifact size evaluation of the captured MR images (Figure 4, C.2, D.2, & E.2) using three different MRI systems can be derived from Table 2. The data shows proportional artifact coverages of at least 45% for the acquisitions of the forceps head. All investigated distal MRI visible markers (marker one to marker three) showed proportional artifact coverages of at least 40%. Table 2. Artifact size evaluation of MR Conditional EMB forceps using MATLAB script based on ASTM F2119-07. The table shows proportional artifact coverages (ratio of total area occupied by valid artifact pixels to area of defined bounding box) and dimensions of the corresponding bounding box (width and height). MRI System Medical Device Section 3.0T Siemens Biograph mMR 3.0T GE SIGNA HDx 1.5T GE SIGNA HDx EMB forceps head 54.07 % W: 13 mm 47.85 % W: 12.2 mm 61.32 % W: 8.3 mm H: 21.6 mm H: 15.1 mm H: 16.1 mm First marker 41.67 % W: 5.8 mm 48.33 % W: 5.4 mm 47.92 % W: 5.9 mm H: 8.7 mm H: 9.8 mm H: 9.8 mm Second marker 44.29 % W: 10.1 mm 56.48 % W: 8.8 mm 60.83 % W: 7.3 mm H: 14.2 mm H: 7.3 mm H: 7.8 mm Third marker 48.57 % W: 10.1 mm 62.04 % W: 8.8 mm 41.67 % W: 6.8 mm H: 14.4 mm H: 13.7 mm H: 7.8 mm Statistical analysis using independent t-test of manual measurements of MRI artifacts from MR Conditional EMB forceps heads in in vitro phantom and in vivo studies revealed significant differences (see Table S4 in SI, 2,07 × 10⁻⁵). For height, in vivo (M = 11.8 mm, SD = 0.8, n = 5) was significantly smaller than in vitro (M = 16.3 mm, SD = 1.6, n = 14), p < 0.001. A similar trend was observed for width, where in vivo (M = 6.9 mm, SD = 1.3, n = 5) was smaller than in vitro (M = 10.9 mm, SD = 1.7, n = 14), p < 0.001. 3.3 Imaging workflow for MRI-guided EMB The three flowcharts (Figure 5) show key interventional steps (lane A) of the EMB protocol. It begins with femoral artery access under ultrasound (US) guidance, performed outside the MR scanner room in MRI-guided cases using a portable US device. After the procedure, the patient is transferred outside the scanner room for closure with a standard sealing device. 3.4 Fluoroscopy and MRI assessment of EMB forceps in hybrid vessel phantom The developed in vitro phantom allowed probing of the left ventricle using conventional and MR Safe guidewires with subsequent insertion of long sheaths (Figure 6). The attached Thiel-embalmed porcine heart enabled tissue extraction using conventional and MR Conditional EMB forceps. Due to the material selection, the assembly of the vessel phantom can be categorized as MR Safe according to ASTM F2503 – 13. In addition, the phantom showed adequate radiolucent behavior during qualitative assessment based on ASTM F640 (standard test methods for determining radiopacity for medical use; test metrics: Philips Allura Xper, 15 fps, 4 mA, 69.79 kV). The fluoroscopy imaging of the conventional and the MR Conditional forceps inside the hybrid vessel phantom (figure 6, A & B) showed distinct and clearly defined artifacts of both forceps heads but comparably no significant artifacts on the guiding shaft of the MR Conditional forceps. MR imaging of the MR Conditional forceps inside the vessel phantom (figure 6, C) showed artifacts with blooming effects and radial lines surrounding the pearl-string-shaped applied passive MR markers at the EMB forceps-guiding shaft. The EMB forceps head showed a distinctively more extensive artifact. In comparison to the fluoroscopic images (figure 6, A & B), the MR image (figure 6, C) shows adequate visualization of the in vitro reproduced anatomical structures of the vessel phantom, like the vessel wall and lumen of the aorta and the heart including the left ventricle. The position of the forceps could be traced during real-time MRI, which allowed immediate visual feedback of the performed manipulation. 3.4.1 Handling study: Phantom-based handling assessment under fluoroscopy Handling of the MR Conditional EMB forceps was evaluated using a dedicated survey (Table 3). Due to the usage of conventional medical devices, which are classified as MR Unsafe, interventions were performed using fluoroscopy. Table 3: Questionnaire results for medical device handling study performed using the hybrid biological heart and polymer-based vessel phantom using fluoroscopy. After having conducted EMBs (extraction of five tissue samples), physicians were asked to rate the utilized conventional and MR Conditional EMB forceps according to different features. Participants were practicing cardiac interventionists with a minimum of six years of interventional experience (n = 4). Conventional EMB Forceps MR Conditional EMB Forceps Median Interquartile range (IQR) Median Interquartile range (IQR) Experienced force required for opening/closing bioptome 0.5 1 0.5 1.25 Gliding property during probing 1 2 0 0.5 Experienced force required for extraction of tissue samples 0 0.25 0 0.5 Graduated scale: -2 low; 0 intermediate; 2 high Controllability (torque) 0 1 0 1 Bendability during passage of aortic arch 0.5 1.25 0.5 1 Detectability of forceps (fluoroscopy) shaft 2 0.25 0.5 1.5 Detectability of forceps (fluoroscopy) tip 1 0.25 0.5 1.5 Detectability of bioptome (fluoroscopy) opening status 1.5 1.25 0.5 1.5 Intuitive operability of EMB forceps 1 0.5 -0.5 1.25 Graduated scale: -2 poor; 0 intermediate; 2 excellent All attributes except intuitive forceps operability were rated in an intermediate region or above. Further, the experienced force required for opening and closing the bioptome, force needed for extracting tissue samples, controllability (torque), and bendability were rated in approximately the same region (intermediate) for both conventional and MR Conditional forceps. Other attributes showed a higher rating for the conventional EMB forceps. Intuitive operability was rated higher for the conventional (1±0.5) than for the MR Conditional EMB forceps (-0.5±1.25). 3.4.2 Phantom-based assessment of MRI artifacts and feasibility In five MRI experiments using the developed in vitro phantom, the MR Conditional EMB forceps showed distinct artifact sizing of the forceps head and passive markers along the guiding shaft. The pearl-string-shaped application of susceptibility-based artifacts facilitated continuous visual observation of the device during manipulation (figure 6, C). The setup enabled the simulation of MRI-guided left ventricular tissue sampling and extraction of 14 tissue samples. he experiments were distributed across several sessions conducted over an extended period. 3.5 In vivo MRI During the in vivo tests, the sufficiently good handling performance already shown both in the dry state and during the in vitro model tests was confirmed. The visibility of the MR Conditional forceps showed distinct and clearly defined artifacts of the forceps head (Figure 7) and pearl-string-shaped passive artifacts along the guiding shaft, which made tracking possible during the entire duration of the in vivo test. During the opening and closing of the forceps head, the MR images showed no precise, distinguishable artifact size or shape changes. During the EMB intervention, five tissue samples were successfully harvested from six attempts using the MR Conditional EMB forceps. Both the developed iMRI setup and the clinical workflow were successfully tested during the in vivo trials. 3.6 Comparison of tissue sampling times The times required for tissue sampling during EMBs were compared (Table 4) to evaluate the performance. For this purpose, the durations of EMB interventions in the Cath lab on patients (conventional forceps), on the in vitro phantom, and during in vivo experiments (16) were derived. The recorded times during EMBs showed shorter times for tissue extractions in the in vitro phantom tests compared to the actual patients in the catheterization laboratory or the porcine model. A Kruskal-Wallis-test showed no significant difference (p > 0.05) between the five groups. Table 4: Measured tissue extraction times during EMB, from forceps insertion into sheath to sample extraction. Utilized medical device Model Imaging modality Time measurement of EMB tissue extraction Mean [min] ± SD [min] Conventional forceps Cath lab patients fluoroscopy 1 1.2 ± 0.5 (n=30) Conventional forceps Hybrid biological heart and polymer-based vessel phantom fluoroscopy 1 0.8 ± 0.4 (n=20) MR Conditional forceps Hybrid biological heart and polymer-based vessel phantom fluoroscopy 1 1.1 ± 0.4 (n=20) MR Conditional forceps Hybrid biological heart and polymer-based vessel phantom MRI-guidance 2,3 1.0 ± 0.6 (n=14) MR Conditional forceps Porcine in vivo model MRI-guidance 3 1.3 ± 0.8 (n=5) 1: Philips Allura Xper 2: Siemens MAGNETOM Skyra 3T 3: Siemens Biograph mMR 3T 4. Discussion 4.1 Performance and visibility of MR Conditional biopsy forceps This study shows adequate MR visibility properties of the MR Conditional forceps in one 1.5T and two 3.0T MRI systems, which outlines a broad range of applications. Multimodally visible (fluoroscopy & MRI) EMB forceps could be beneficial for establishing EMBs in co-localized interventional suites due to their higher practicability (11,12). Moreover, the use of wireless ultrasound, i.e., Clarius, is beneficial for vascular access and allows the use of conventional devices without needing a catheterization laboratory. During all MR imaging, the MR Conditional forceps exhibited appropriately sized susceptibility-based artifacts for the bioptome jaws and passive markers. Our in vitro study using a saline-filled test box measured an artifact size of 16.1 x 8.3 mm, which was larger than the artifact observed in vivo. Significant differences were found between in vivo and in vitro measurements. In vivo, the artifact size for both height (M = 11.8 mm) and width (M = 6.9 mm) was significantly smaller compared to in vitro measurements (height: M = 16.3 mm, width: M = 10.9 mm). These findings suggest that in vivo conditions, including physiological motion, respiratory movements, and the complex tissue structure, contribute to a reduction in artifact size. This difference may be due to the limitations of ex vivo models, supporting the need for in vivo assessments to more accurately evaluate the clinical impact of EMB forceps artifacts in MRI. The histological assessment showed comparable integrity of deducted tissue samples, with acceptable quality in histologic overview in terms of other performed HE-stainings (9,20). Svetlove et al. demonstrated the feasibility of two MR Compatible bioptomes and used synchrotron radiation microtomography (SRμCT) to assess tissue volumes and microstructural integrity (21). Their focus lay on evaluating diagnostic quality and cutting performance of different bioptome designs ex vivo and in vivo. In contrast, our study focuses on procedural feasibility of a specific MR Conditional forceps under real-time MRI, combining in vitro phantom-based testing followed by in vivo application. Beyond tissue quality, we present a structured framework for preclinical validation, including artifact quantification and handling assessment, aligned with the 3R principle. Svetlove et al. provide valuable insights into biopsy quality and tissue characterization, while our study complements this by addressing the procedural feasibility and integration of MR-guided EMB into a clinical workflow. 4.2 Multimodal hybrid biological heart and polymer-based in vitro phantom The built-up phantom showed usability for simulating catheter-based interventions using fluoroscopy- and MRI guidance. The phantom allowed the visibility and handling studies to be performed without the involvement of living animals. Such in vitro studies are demanded by the 3R principle (Replace, Reduce, and Refine) for humane animal research before preclinical animal studies (14). Furthermore, the developed in vitro model bridges the gap between commercially available fully synthetic phantoms for EMB simulation (e.g., Heartroid Myocardial Biopsy Model, JMC Corporation, Kanagawa, Japan) and simplified ex vivo models used in in vitro MRI research (22,23). While most in vitro phantoms focus primarily on the heart's anatomy, expanding anatomical coverage improves the simulation's realism. 4.3 Imaging workflow of MRI-guided EMB The imaging workflow can serve as a foundation for new MR-based clinical research and enhance the integration of MRI-guided EMBs into clinical practice. Additionally, it can be expanded into more detailed frameworks, as demonstrated by Fernández Gutiérrez et al. (24). While the workflow developed by Rube et al. laid the groundwork for a preclinical study, it lacks a dedicated lane for MR imaging, unlike our workflow. This omission complicates the replication of the MR imaging steps (25). 4.4 Medical device performance during MRI-guided EMB Unterberg-Buchwald et al. state that the achievement of appropriate handling parameters like traction and other mechanical features remains a central issue associated with catheter-based medical devices suitable for iMRI (9). This is mainly caused due to the restricted material applicability in the MR environment due to the high magnetic field strengths. The handling study using the vessel phantom showed, in most cases, comparable results (intermediate or higher ratings) of assessed handling properties for the tested conventional and MR Conditional EMB forceps. Detectability under fluoroscopy of the MR Conditional forceps was rated with high variability and should be further increased by incorporating radiopaque markers. Experienced interventional clinicians rated the 'intuitive operability' of the MR Conditional forceps under intermediate. This issue was mainly caused by the prototype stage 3D-printed spring of the return mechanism (see Figure 1) in the handpiece. It could be remedied using an improved polymer or nonmagnetic spring (e.g., Beryllium or Nitinol). Increasing the number of participants would enhance the robustness of the data presented in the handling study, making the findings more statistically significant. However, this presents challenges, mainly due to the limited availability of professional interventional personnel. However, due to the high qualification of the participants, the data obtained also includes an increased force of expression. The pairwise comparison of tissue extraction times using the Kruskal-Wallis test revealed no significant differences (p = 0.05), suggesting that the conventional and MR Conditional EMB forceps) could be handled similarly. 4.5 In vivo testing The mechanical properties of the guidewires and sheaths posed a limitation during MRI-guided EMB. Although the in vivo EMB procedure was successful in most cases (five out of six attempts), establishing prior access to the left ventricle with the medical devices posed a significant challenge. A stronger, nonmetallic braided sheath would help gain safer ventricle access. Due to the low stiffness of the guidewire, it had to be introduced into the left ventricle using a pigtail catheter. Once the methodology for accessing the ventricle was established, the procedures could be performed without issues. Especially during in vivo studies, the visualization of the forceps head was highly dependent on the slice positioning during MRI. The pearl-string-shaped passive artifacts along the device shaft were beneficial for providing continuous orientation and facilitating navigation across the different slices during MRI-guided intervention. However, observing the exact opening status of the bioptome under MR imaging posed difficulties, especially in motion inside the living organism. Other researchers have also reported challenges regarding the distinguishability of the opening status of forceps heads during MRI acquisition (9,20,21). For safe use, the forceps' opening status must be clearly visible; otherwise, it poses a hazard. This issue could be addressed by adding passive markers or modifying the forceps head design. Several published in vivo studies outline the benefits and feasibility of lesion-targeted MRI-guided EMBs (9,10,20). Our experiments were part of a broader study focused on establishing various MRI-guided interventions. This approach assessed general feasibility, facilitated multiple MRI-guided procedures, and provided valuable insights into the iMRI setup and imaging workflows. 5. Conclusion This study demonstrated the practical usability of the MR Conditional and passively marked EMB forceps for fluoroscopy- and MRI-guided interventions. The developed hybrid biological heart and polymer vessel phantom proved to be an effective training tool for novice interventionalists under MRI guidance. Additionally, the adapted MRI imaging workflow facilitated in vitro studies of MRI-guided EMBs, laying the groundwork for successful in vivo experiments. These in vivo results confirmed the earlier findings, highlighting the efficacy and practicality of the MR Conditional EMB forceps for clinical application. Further investigation will explore the applicability of MR Conditional EMB forceps in low-field MRIs (under 1.5T), as suggested by Campbell-Washburn et al. (26). Declarations Ethics approval and consent to participate The animal protocols were reviewed and approved in 2022 by the local ethics committee and the Landesdirektion Sachsen governmental animal care and use committee (Germany) under approval number TVV 54/21. All study participants provided written consent for the collection and processing of their data. Consent for publication All participants provided explicit consent for the publication of their anonymized data and survey results in this manuscript. Availability of data and materials The data and materials supporting the findings of this study are available in the Supporting Information (SI) or can be obtained upon reasonable request from the corresponding author. Competing interests This research was funded by the Federal Ministry of Education and Research (BMBF). The MR Conditional forceps and other medical devices used in this study were provided by Epflex Feinwerktechnik GmbH (Dettingen an der Erms, Germany), a company involved in the project. The authors declare no other competing interests. Funding This research was funded by KMU-innovativ (MR-Biopsy, grant no. 13GW0242B) of the Federal Ministry of Education and Research Germany BMBF. Authors' contributions DGB wrote the initial manuscript draft with support from CMR. Together, they conceptualized, designed, and facilitated the study, and were involved in data acquisition, analysis, and interpretation, with assistance from JB and CM. DGB, as corresponding author, was also responsible for the in vivo study design and implementation, the questionnaires, statistical analysis, and the creation and conceptualization of graphics. HB, TD, TJ, BS, and OS contributed significantly during the review phase and aided the practical implementation of the study, particularly regarding MRI testing, through their roles in supervision and interpretation. RH led the histological component of the study, drafting and reviewing relevant manuscript sections. JK, HS, and DGB collaboratively prepared and submitted the animal experimentation application, and JK and HS contributed extensively to the in vivo work. DGB and AM performed the in vivo studies. KL supervised the in vitro validation of the EMB forceps, managed its execution, and played a substantial role in reviewing the manuscript. AM, as Principal Investigator for MRI-Guided Interventions, defined the overall project scope, secured funding, and contributed throughout the research process and manuscript preparation. All authors critically reviewed and approved the final manuscript and accepted accountability for the work presented. Acknowledgements We thank Lisa Wahl from the Clinic for Hoofed Animals, Swine, and Reproductive Biology at Leipzig University for her contribution to the veterinary management of the in vivo experiments. We thank Prof. Ulrich Laufs from the Department of Cardiology at Leipzig University Hospital for support during device and model evaluation. PD Hanno Steinke from the Anatomy Institute at Leipzig University Hospital for his support and provision of Thiel-embalming fluids. We thank Dr. Senta Schauer, Michael Schmid, Dr. Johannes Uihlein, and Bernhard Uihlein of EPflex Feinwerktechnik GmbH, for the supply of the medical devices and their continuous support within the research project MR-Biopsy. Furthermore, we will thank Felix Weber, Anja Neuman, Leon Melzer, Johanna Fleck, Moritz Lenhardt, and Annekatrin Pfahl for their contributing work within affiliated research projects at Innovation Center Computer Assisted Surgery (ICCAS), Institute at the Faculty of Medicine, Leipzig University. Declaration of Generative AI and AI-assisted technologies in the writing process During the preparation of this work, the authors used the Grammarly Word plugin (version 1.0.0, Grammarly Inc., San Francisco, CA) and the GPT-4 language model (OpenAI, San Francisco, CA) for grammar and language editing. After using these tools, the authors reviewed and edited the content as needed and take full responsibility for the final version of the publication. No content was generated by AI; the tools were used solely to enhance clarity and ensure adherence to language and reporting standards. References Thiene G, Bruneval P, Veinot J, Leone O. Diagnostic use of the endomyocardial biopsy: a consensus statement. Virchows Arch. 2013 Jul;463(1):1–5. Bussani R, Silvestri F, Perkan A, Gentile P, Sinagra G. Endomyocardial Biopsy. In: Sinagra G, Merlo M, Pinamonti B, editors. Dilated Cardiomyopathy [Internet]. Cham: Springer International Publishing; 2019 [cited 2023 Aug 3]. p. 135–47. Available from: http://link.springer.com/10.1007/978-3-030-13864-6_9 Ammirati E, Buono A, Moroni F, Gigli L, Power JR, Ciabatti M, et al. State-of-the-Art of Endomyocardial Biopsy on Acute Myocarditis and Chronic Inflammatory Cardiomyopathy. Curr Cardiol Rep. 2022 May;24(5):597–609. James MT, Samuel SM, Manning MA, Tonelli M, Ghali WA, Faris P, et al. Contrast-Induced Acute Kidney Injury and Risk of Adverse Clinical Outcomes After Coronary Angiography: A Systematic Review and Meta-Analysis. Circ: Cardiovascular Interventions. 2013 Feb;6(1):37–43. Liu Q, Wu Q. Radiation Protection in Cardiovascular Interventions: What Can We Do? Med Princ Pract. 2015 Mar 21;24(3):299–299. Seals KF, Lee EW, Cagnon CH, Al-Hakim RA, Kee ST. Radiation-Induced Cataractogenesis: A Critical Literature Review for the Interventional Radiologist. Cardiovasc Intervent Radiol. 2016 Feb;39(2):151–60. Holland SK, Altaye M, Robertson S, Byars AW, Plante E, Szaflarski JP. Data on the safety of repeated MRI in healthy children. NeuroImage: Clinical. 2014;4:526–30. Lurz P, Luecke C, Eitel I, Föhrenbach F, Frank C, Grothoff M, et al. Comprehensive Cardiac Magnetic Resonance Imaging in Patients With Suspected Myocarditis. Journal of the American College of Cardiology. 2016 Apr;67(15):1800–11. Unterberg-Buchwald C, Ritter CO, Reupke V, Wilke RN, Stadelmann C, Steinmetz M, et al. Targeted endomyocardial biopsy guided by real-time cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2017 Dec;19(1):45. Rogers T, Ratnayaka K, Karmarkar P, Campbell-Washburn AE, Schenke WH, Mazal JR, et al. Real-Time Magnetic Resonance Imaging Guidance Improves the Diagnostic Yield of Endomyocardial Biopsy. JACC: Basic to Translational Science. 2016 Aug;1(5):376–83. Rogers T, Campbell-Washburn AE, Ramasawmy R, Yildirim DK, Bruce CG, Grant LP, et al. Interventional cardiovascular magnetic resonance: state-of-the-art. J Cardiovasc Magn Reson. 2023 Aug 14;25(1):48. Amin EK, Campbell-Washburn A, Ratnayaka K. MRI-Guided Cardiac Catheterization in Congenital Heart Disease: How to Get Started. Curr Cardiol Rep. 2022 Apr 1;24(4):419–29. Hampshire VA, Gilbert SH. Refinement, Reduction, and Replacement (3R) Strategies in Preclinical Testing of Medical Devices. Toxicol Pathol. 2019 Apr;47(3):329–38. Adamovich A, Park S, Siskin GP, Englander MJ, Mandato KD, Herr A, et al. The ABCs of the FDA: A Primer on the Role of the United States Food and Drug Administration in Medical Device Approvals and IR Research. Journal of Vascular and Interventional Radiology. 2015 Sep;26(9):1324–30. Gholami Bajestani D, Reich CM, Mulik C, Mokosch M, Melzer A. Hybrid polymer vessel phantoms for feasibility studies and clinical training of MRI-guided interventions. Current Directions in Biomedical Engineering. 2022 Sep 2;8(2):656–9. Landesdirektion S. Approval of animal experiment protocol [TVV 54/21]. 2022. Soher BJ, Dale BM, Merkle EM. A Review of MR Physics: 3T versus 1.5T. Magnetic Resonance Imaging Clinics of North America. 2007;15(3):277–90. Reich CM, Sattler B, Jochimsen TH, Unger M, Melzer L, Landgraf L, et al. Practical setting and potential applications of interventions guided by PET/MRI. Q J Nucl Med Mol Imaging [Internet]. 2021 Mar [cited 2023 Aug 16];65(1). Available from: https://www.minervamedica.it/index2.php?show=R39Y2021N01A0043 Venous Access. In: Diagnostic Imaging: Interventional Procedures [Internet]. Elsevier; 2018 [cited 2023 Sep 7]. p. 88–101. Available from: https://linkinghub.elsevier.com/retrieve/pii/B9780323524810500197 Behm P, Gastl M, Jahn A, Rohde A, Haberkorn S, Krueger S, et al. CMR-guidance of passively tracked endomyocardial biopsy in an in vivo porcine model. Int J Cardiovasc Imaging. 2018 Dec 1;34(12):1917–26. Svetlove A, Ritter CO, Dullin C, Schmid M, Schauer S, Uihlein J, et al. Evaluation of MR‑safe bioptomes for MR‑guided endomyocardial biopsy in minipigs: a potential radiation‑free clinical approach. European Radiology Experimental. 2023;7(76). Lossnitzer D. Feasibility of real-time magnetic resonance imaging-guided endomyocardial biopsies: An in-vitro study. WJC. 2015;7(7):415. Seitz SA, Haberkorn SM, Maslanka H, Katus HA, Steen H. In-vitro evaluation of a novel MR-compatible cardiac bioptome catheter for MR-guided myocardial biopsies. Journal of Cardiovascular Magnetic Resonance. 2012 Feb 1;14(1):O32. Mustafee N, Katsaliaki K, Gunasekaran A, Williams MD, Fernández‐Gutiérrez F, Barnett I, et al. Framework for detailed workflow analysis and modelling for simulation of multi‐modal image‐guided interventions. Journal of Enterprise Information Management [Internet]. 2013 Feb 8 [cited 2019 Aug 27]; Available from: https://www.emerald.com/insight/content/doi/10.1108/17410391311289550/full/html Rube MA, Fernandez-Gutierrez F, Cox BF, Holbrook AB, Houston JG, White RD, et al. Preclinical feasibility of a technology framework for MRI-guided iliac angioplasty. Int J CARS. 2015 May 1;10(5):637–50. Campbell-Washburn AE, Ramasawmy R, Restivo R, et al. Opportunities in Interventional and Diagnostic Imaging by Using High-Performance Low-Field-Strength MRI. Radiology. 293(2):384–93. Additional Declarations The authors declare potential competing interests as follows: This research was funded by the Federal Ministry of Education and Research (BMBF). The MR Conditional forceps and other medical devices used in this study were provided by Epflex Feinwerktechnik GmbH (Dettingen an der Erms, Germany), a company involved in the project. The authors declare no other competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7269885","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":494213322,"identity":"82b6c9e0-ac67-4a6d-846f-1e38affa8c44","order_by":0,"name":"Denis Gholami Bajestani","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0001-9033-9726","institution":"Innovation Center for Computer-Assisted Surgery, University of Leipzig, Faculty of Medicine, Leipzig, Germany","correspondingAuthor":true,"prefix":"","firstName":"Denis","middleName":"Gholami","lastName":"Bajestani","suffix":""},{"id":494213411,"identity":"98787454-71c7-46f6-9c1e-941bdca2aeee","order_by":1,"name":"C. Martin Reich","email":"","orcid":"","institution":"Innovation Center for Computer-Assisted Surgery, University of Leipzig, Faculty of Medicine, Leipzig, Germany","correspondingAuthor":false,"prefix":"","firstName":"C.","middleName":"Martin","lastName":"Reich","suffix":""},{"id":494216627,"identity":"268bfc57-8d03-41a7-9035-6b2901e6a115","order_by":2,"name":"Jan Birkigt","email":"","orcid":"","institution":"Innovation Center for Computer-Assisted Surgery, University of Leipzig, Faculty of Medicine, Leipzig, Germany","correspondingAuthor":false,"prefix":"","firstName":"Jan","middleName":"","lastName":"Birkigt","suffix":""},{"id":494216628,"identity":"0bbe8f9e-bfb3-416e-80fd-578cc496368d","order_by":3,"name":"Christina Mulik","email":"","orcid":"","institution":"Innovation Center for Computer-Assisted Surgery, University of Leipzig, Faculty of Medicine, Leipzig, Germany","correspondingAuthor":false,"prefix":"","firstName":"Christina","middleName":"","lastName":"Mulik","suffix":""},{"id":494216632,"identity":"5ccd9b5b-c39f-482b-b2e9-533a81dd40ec","order_by":4,"name":"Grit Gesine Ruth Hiller","email":"","orcid":"","institution":"Department of Pathology, University of Leipzig Medical Center, Leipzig, Germany","correspondingAuthor":false,"prefix":"","firstName":"Grit","middleName":"Gesine Ruth","lastName":"Hiller","suffix":""},{"id":494216634,"identity":"fafe21f7-7e12-4a64-8ba5-702331d936ef","order_by":5,"name":"Harald Busse","email":"","orcid":"","institution":"Department of Diagnostic and Interventional Radiology, University of Leipzig Medical Center, Leipzig, Germany","correspondingAuthor":false,"prefix":"","firstName":"Harald","middleName":"","lastName":"Busse","suffix":""},{"id":494216636,"identity":"40363c51-0fd0-4dc0-9f55-5cc5bbc273ed","order_by":6,"name":"Timm Denecke","email":"","orcid":"","institution":"Department of Diagnostic and Interventional Radiology, University of Leipzig Medical Center, Leipzig, Germany","correspondingAuthor":false,"prefix":"","firstName":"Timm","middleName":"","lastName":"Denecke","suffix":""},{"id":494216637,"identity":"e90c99f2-2a81-4fd9-9936-023b3f09ec69","order_by":7,"name":"Johannes Kauffold","email":"","orcid":"","institution":"Clinic for Hoofed Animals, Swine, and Reproductive Biology, University of Leipzig, Germany","correspondingAuthor":false,"prefix":"","firstName":"Johannes","middleName":"","lastName":"Kauffold","suffix":""},{"id":494216638,"identity":"bd4f05ea-3c12-4165-882f-9526c69f1ee4","order_by":8,"name":"Haukur Lindberg Sigmarsson","email":"","orcid":"","institution":"Clinic for Hoofed Animals, Swine, and Reproductive Biology, University of Leipzig, Germany","correspondingAuthor":false,"prefix":"","firstName":"Haukur","middleName":"Lindberg","lastName":"Sigmarsson","suffix":""},{"id":494216639,"identity":"016091d1-2bd5-4978-aa36-c4bb7d9dbd0f","order_by":9,"name":"Thies Jochimsen","email":"","orcid":"","institution":"Department of Nuclear Medicine, University of Leipzig Medical Center, Leipzig, Germany","correspondingAuthor":false,"prefix":"","firstName":"Thies","middleName":"","lastName":"Jochimsen","suffix":""},{"id":494216640,"identity":"71a0aabc-b8c2-4eba-b836-c57ec52b18ea","order_by":10,"name":"Bernhard Sattler","email":"","orcid":"","institution":"Department of Nuclear Medicine, University of Leipzig Medical Center, Leipzig, Germany","correspondingAuthor":false,"prefix":"","firstName":"Bernhard","middleName":"","lastName":"Sattler","suffix":""},{"id":494216641,"identity":"4fdabfa9-d0eb-4090-9de0-0dada1bda743","order_by":11,"name":"Osama Sabri","email":"","orcid":"","institution":"Department of Nuclear Medicine, University of Leipzig Medical Center, Leipzig, Germany","correspondingAuthor":false,"prefix":"","firstName":"Osama","middleName":"","lastName":"Sabri","suffix":""},{"id":494216642,"identity":"188b790e-57a8-4583-8612-eed46daeeca9","order_by":12,"name":"Karsten Lenk","email":"","orcid":"","institution":"Department of Cardiology, University of Leipzig Medical Center, Leipzig, Germany","correspondingAuthor":false,"prefix":"","firstName":"Karsten","middleName":"","lastName":"Lenk","suffix":""},{"id":494216643,"identity":"4c450539-6a0c-49de-a5ad-37b721fd0b63","order_by":13,"name":"Andreas Melzer","email":"","orcid":"","institution":"Innovation Center for Computer-Assisted Surgery, University of Leipzig, Faculty of Medicine, Leipzig, Germany","correspondingAuthor":false,"prefix":"","firstName":"Andreas","middleName":"","lastName":"Melzer","suffix":""}],"badges":[],"createdAt":"2025-08-01 09:45:07","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":true,"conflictsOfInterestStatement":true,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":true},"doi":"10.21203/rs.3.rs-7269885/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7269885/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88236732,"identity":"38b99be0-8fa0-4179-9bdd-a05109553e6d","added_by":"auto","created_at":"2025-08-04 10:26:03","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":143714,"visible":true,"origin":"","legend":"\u003cp\u003eHandle and forceps head (closed) of the MR Conditional biopsy forceps used for minimally invasive EMB. Opened forceps head with biopsied EMB tissue sample 3x magnification (right).\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7269885/v1/bc1a44f705b7ddd75cc4f063.jpg"},{"id":88235454,"identity":"97935526-044c-4b15-8fb3-57190c5e80d9","added_by":"auto","created_at":"2025-08-04 10:10:04","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":88917,"visible":true,"origin":"","legend":"\u003cp\u003eTop view of the hybrid biological heart and polymer-based phantom used for simulation of MRI- and fluoroscopy-guided EMBs. The vessel phantom was connected to the porcine heart at the aortic root (A) and the apex (B), with the heart shown in (C).\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7269885/v1/c57d8583d9193533752c0f31.jpg"},{"id":88235426,"identity":"2665cdb3-4792-4e09-89bd-cf75ac16a164","added_by":"auto","created_at":"2025-08-04 10:10:03","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":97523,"visible":true,"origin":"","legend":"\u003cp\u003eHE-stained endomyocardial biopsies obtained from the left ventricle of a porcine heart (ex vivo) with MR Conditional forceps (A) and standard forceps (B). Visualization at a magnification of 13x.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7269885/v1/f7138d228b095914fd637119.jpg"},{"id":88235429,"identity":"7650b904-bf3c-40fa-81e0-afa2dccb7edb","added_by":"auto","created_at":"2025-08-04 10:10:03","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":77105,"visible":true,"origin":"","legend":"\u003cp\u003eComparative imaging of MR Conditional EMB forceps of the same size using photography (A), fluoroscopy (B), and MR images of different systems and imaging parameters (C-E). The labeled sections C.1, D.1, and E.1 represent acquired MR images, while C.2, D.2, and E.2 show the corresponding evaluations based on the developed Matlab algorithm. Bounding boxes are illustrated by red rectangles and valid artifact pixels by red pixels. Imaging parameters used were: B: fluoroscopy Philips Allura Xper: 15 fps, 4 mA, 69.79 kV; C: 3.0T Siemens Biograph mMR customized TrueFISP: TR=396.08 ms, TE=2.04 ms, ST=8 mm, FA=40°, BW 560 Hz/px, matrix=0\\208\\207\\0, pixel=2.08 mm\u003csup\u003e2\u003c/sup\u003e, FoV=300x300 mm\u003csup\u003e2\u003c/sup\u003e; D: 3.0T GE SIGNA HDx FIESTA: TR=7.393 ms, TE=2.144 ms, ST=3.2 mm, FA=70°, BW 325.5 Hz/px, matrix=0\\224\\320\\0, pixel=0.4883\\0.4883 mm\u003csup\u003e2\u003c/sup\u003e, FoV=512x512 mm\u003csup\u003e2\u003c/sup\u003e; E: 1.5T GE SIGNA HDx FLAIR: TR=8002 ms, TE=122.148 ms, ST=3 mm, FA=90°, BW 122.07 Hz/px, matrix=0\\352\\224\\0, pixel=0.4688/0.4688 mm\u003csup\u003e2\u003c/sup\u003e, FoV=512x512 mm\u003csup\u003e2\u003c/sup\u003e.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7269885/v1/131e8728f2f94057e8b714e4.jpg"},{"id":88235444,"identity":"79986b82-83c8-440e-ba2e-b6e736802664","added_by":"auto","created_at":"2025-08-04 10:10:03","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":107410,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of the endomyocardial biopsy (EMB) protocol (A) and standard imaging protocol for -guided EMB (B) and the developed imaging protocol for MRI-guided interventions (C).\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7269885/v1/26bed7c812e6867f909649a9.jpg"},{"id":88235779,"identity":"2b8d2dbb-59b9-4dda-87f1-c937cddd6136","added_by":"auto","created_at":"2025-08-04 10:18:03","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":68673,"visible":true,"origin":"","legend":"\u003cp\u003eMinimally invasive EMB intervention inside the heart and aorta ascendens of the hybrid phantom under fluoroscopy (A, B) and MRI (C) using standard biopsy forceps (A) and MR Conditional biopsy forceps (B, C). Marked artifacts of forceps head during cardiac biopsy (white arrow), femoral sheath tip (blue arrow), and passively marked shaft (yellow arrow). Imaging parameters were: fluoroscopy: Philips Allura Xper, 15 fps, 4 mA, 69.79 kV; MRI parameters: Siemens Biograph_mMR 3.0 T customized TrueFISP: TR=396.08 ms, TE=2.04 ms, ST=8 mm, FA=40°, BW 560 Hz/px, matrix=0\\208\\207\\0, pixel=2.08 mm\u003csup\u003e2\u003c/sup\u003e, FoV=300x300 mm\u003csup\u003e2\u003c/sup\u003e.\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7269885/v1/4b6b5a5e680e0c0e31c1ad32.jpg"},{"id":88235432,"identity":"03d09fad-2ad3-4bbd-8f3d-e8afdc4781c3","added_by":"auto","created_at":"2025-08-04 10:10:03","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":57652,"visible":true,"origin":"","legend":"\u003cp\u003eMinimally invasive EMB intervention using MR Conditional biopsy forceps inside the porcine model. EMB forceps head with closed (A, white arrow) and open (B, white arrow) jaws. Visible pearl-string-shaped applied passive markings at the device shaft (yellow arrows) and passively marked femoral sheath tip (blue arrows). MR Conditional biopsy forceps during extraction of tissue sample (C, white arrow). MRI parameters were: 1.5T Siemens Biograph_mMR trufi: TR=233.26 ms, TE=1.31 ms, ST=3.2 mm, FA=52°, BW 325.5 Hz/px, matrix=0\\224\\320\\0, pixel=0.4883 mm\u003csup\u003e2\u003c/sup\u003e, FoV=255*340 mm\u003csup\u003e2\u003c/sup\u003e.\u003c/p\u003e","description":"","filename":"7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7269885/v1/fa94ccf5d3ff220a0e168b3e.jpg"},{"id":88237001,"identity":"b038fd23-97d6-4b8b-9b4b-8fc657ad55e6","added_by":"auto","created_at":"2025-08-04 10:34:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2000441,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7269885/v1/5a8d0bb0-98c8-474a-8c6e-2d4ec141c520.pdf"}],"financialInterests":"The authors declare potential competing interests as follows: This research was funded by the Federal Ministry of Education and Research (BMBF). The MR Conditional forceps and other medical devices used in this study were provided by Epflex Feinwerktechnik GmbH (Dettingen an der Erms, Germany), a company involved in the project. The authors declare no other competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003ePreclinical Evaluation of an MR Conditional Forceps for MRI-Guided Endomyocardial Biopsy: A Multimodal Imaging Approach Using a Hybrid Vessel Phantom and Porcine In Vivo Models\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eEndomyocardial biopsy (EMB) is a commonly used catheter-based diagnostic technique for investigating myocardial pathologies (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Catheter-based interventions are usually performed using fluoroscopy, which allows real-time imaging of medical devices and the target anatomy (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). However, fluoroscopy is associated with ionizing radiation, nephrotoxic contrast agents, and lack of soft tissue contrast (\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Magnetic resonance imaging (MRI)-guided interventions have been shown to overcome these drawbacks and benefit from arbitrary slice orientation (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Several feasibility studies have demonstrated successful targeted extraction of focal pathological myocardial tissue with MRI-guided EMB (\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). However, broader clinical translation is still hindered by the lack of MR Safe or MR Conditional and technically suitable medical devices providing appropriate handling (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Approval of Class III medical devices often requires human cadaveric and animal studies (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Based on the 3R principle (Replace, Reduce \u0026amp; Refine) in animal research, it is necessary to carry out extensive tests outside animal models in advance (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Anatomically correct models that mimic human vessel systems are needed and could bridge the gap between in vitro and in vivo application for conclusive testing and training before preclinical animal studies. In this study, an MR Conditional biopsy forceps previously developed by EPflex Feinwerktechnik GmbH was evaluated for its functionality, MR- and fluoroscopic visibility, and handling characteristics during EMB interventions using an MR Safe hybrid biological heart and polymer-based vessel phantom, as well as a porcine in vivo model involving multiple pigs (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). In addition, an MRI-adapted interventional workflow was developed for image acquisition during MRI-guided EMBs and validated against the gold standard, a fluoroscopic workflow.\u003c/p\u003e"},{"header":"2. Material and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 MR Conditional EMB forceps\u003c/h2\u003e\u003cp\u003eMRI-guided catheter-based EMBs were performed using a 6 Fr MR Conditional biopsy forceps (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) supplied by EPflex Feinwerktechnik GmbH (Dettingen an der Erms, Germany). The MR visualization of the forceps was based on susceptibility artifacts of the forceps' jaws and punctual passive MRI-visible markers along the device shaft.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Histological examination of biopsies\u003c/h2\u003e\u003cp\u003eThe quality of the obtained tissue samples was assessed by histological examination. For this purpose, tissue samples (n\u0026thinsp;=\u0026thinsp;10) were obtained from the left ventricle of a fresh porcine heart, five each using the MR Conditional biopsy forceps and an approved 5.5 Fr standard biopsy forceps (Cordis, Hialeah, Florida, US), respectively. All samples were stored in formalin buffer (4%, v/v) for at least 24 hours. An experienced physician from the Institute of Pathology of the University of Leipzig Medical Center processed the obtained tissue samples. After paraffin embedment and sectioning (3\u0026ndash;4 \u0026micro;m), tissue samples were stained with hematoxylin-eosin (HE) solution and evaluated with light microscope images.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.4 In vitro artifact assessment of EMB forceps using fluoroscopy and MRI\u003c/h2\u003e\u003cp\u003eThe applicability of the MR Conditional EMB forceps for image-guided interventions was assessed based on their imaging properties. Due to expected variations in MR imaging and susceptibility artifacts across different MRI systems and field strengths (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), the MR Conditional forceps' MR visibility properties were assessed. Three MRI systems were used: Siemens Biograph 3.0T (Siemens Healthcare, Erlangen, Germany), GE Signa HDxt 3.0T, and GE Signa HDxt 1.5T (GE Healthcare, Milwaukee, WI, USA). Standard real-time sequences for cardiac MRI (True FISP) were used for the assessment.\u003c/p\u003e\u003cp\u003eVisualization in fluoroscopy has been performed at the local hospital using an Allura Xper angiographic system (Philips Healthcare, BeSIst, Netherlands) to ensure applicability in the gold standard. Fluoroscopy images were captured in ambient air with the EMB forceps positioned on the patient table. For MR imaging, the EMB forceps was placed inside a polymer test box (29 x 22 x 19 cm) filled with physiological saline solution (0.9% NaCl). The MR images were evaluated with Matlab (MathWorks, Natick, Massachusetts, USA) using an ASTM F2119-07 (Standard Test Method for Evaluation of MR Image Artifacts from Passive Implants) based approach. Acquired artifact pixels were identified as described in ASTM F2119-07. A bounding box (smallest possible rectangle) was then defined around the identified artifacts of each MR marker. The proportional artifact coverage was determined by calculating the ratio between the total area occupied by valid artifact pixels and the area of the defined bounding box. The calculated proportional artifact coverages were used together with the dimensions of the bounding box to evaluate and quantify the artifact's appearance.\u003c/p\u003e\u003cp\u003eMRI artifact dimensions from both phantom and in vivo experiments were manually assessed. Measurements were performed on DICOM images using the distance tool in MicroDicom (MicroDicom, Bulgaria), focusing on artifact size around the EMB forceps head. Differences between experimental settings were statistically evaluated using an independent t-test.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.5 Imaging workflow for MRI-guided EMB\u003c/h2\u003e\u003cp\u003eAn imaging workflow for MRI-guided EMB interventions was developed based on clinical standard operating procedures, expert interviews, and clinical observations of fluoroscopy-guided EMB interventions. Based on the standard workflow of the respective interventional steps performed in the Cath lab, the corresponding imaging tasks during fluoroscopy-guided EMB procedures were outlined. Based on the defined interventional steps during an EMB, MRI-guided imaging tasks were derived and transferred into a corresponding MRI-adapted workflow, which was reviewed, tested, and optimized in close collaboration with interventionalists and MR radiographers. All MRI-guided interventions presented in this study were performed using a developed interventional MRI (iMRI) setup, which allows communication and control of the MRI system in the room as well as display of the acquired MR images, as described elsewhere (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.6 Assessment of EMB forceps inside hybrid vessel phantom\u003c/h2\u003e\u003cp\u003eMRI- and fluoroscopy-guided EMBs were performed using a hybrid biological heart and polymer-based phantom (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), developed in collaboration with Phacon GmbH (Leipzig, Germany). The model consisted of a silicone aortic vascular structure based on human anatomical CT-scan data (68 y/o, female) attached to a Thiel-embalmed porcine heart (Duroc and Pietrain pig breed, approx. six months) (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The vascular structure was housed in an acrylic glass case (56 x 25 x 20 cm) embedded in a tissue-mimicking gel of water-binding superabsorbent multipurpose polymer (HVDE 235, Schauch Granulate, Lauffen am Neckar, Germany). Blood flow through the phantom vessels was simulated using a physiological saline solution mixed with 30% glycerol (WHC GmbH, Hilgertshausen-Tandern, Germany) and a pulsatile flow pump (MultiFlow centrifugal pump, GAMPT mbH, Merseburg, Germany). The model was designed to allow the usage of a wide range of varying heart sizes to account for the individual differences in hearts purchased from a local butcher shop. The left atrium of the porcine heart was sealed with surgical suture material (3\u0026thinsp;\u0026minus;\u0026thinsp;0, Vicryl, Ethicon, Inc., Bridgewater, US) to facilitate pressurization by the pump. Femoral access for interventional devices such as guidewires and catheters was realized by puncturing silicone tubes (Deutsch \u0026amp; Neumann GmbH, Hennigsdorf, Germany) at the proximal femoral section of the polymer-based vascular phantom (outside the housing) with lumen diameters of 6 to 10 mm (wall thickness 1.5 to 2 mm). A questionnaire-based evaluation of the phantom is provided in the Supporting Information (S1 and S2).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section3\"\u003e\u003ch2\u003e2.6.1 Handling study: fluoroscopy-guided assessment of MR Conditional and standard EMB forceps in hybrid vessel phantom\u003c/h2\u003e\u003cp\u003eHandling properties of the MR Conditional biopsy forceps was evaluated in a comparative study against an approved 5.5 Fr standard biopsy forceps (Cordis, Hialeah, Florida, USA) under fluoroscopy (Allura Xper, Philips Healthcare, Best, Netherlands) using the hybrid vessel phantom. The study was performed at the Department of Cardiology of the local hospital.\u003c/p\u003e\u003cp\u003eAn approved 0.035\" (0.89 cm) hydrophilic-coated MR Conditional guidewire with a length of 150 cm (REF 39012526, EPflex Feinwerktechnik GmbH) was used for probing and guidance during the intervention, along with the following medical instruments: an 8.5 Fr, 15 cm, Fastcath Introducer Sheath (Abbott Laboratories, Chicago, Illinois, USA); a 6 Fr Introducer Fortress (Biotronik, Berlin, Germany), and a 0.038\" PTFE-coated J-curve guidewire Emerald (Cordis, Hialeah, Florida, USA).\u003c/p\u003e\u003cp\u003eEMBs were conducted according to the developed clinical workflow using conventional and MR Conditional devices, respectively, under standard conditions. In short, after the facilitation of blood vessel access (Seldinger technique (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)), the guidewire was placed into the left ventricle, followed by the placement of the femoral sheath inside the left ventricle with subsequent myocardial tissue extraction using EMB forceps (until five adequate tissue samples were obtained). After the interventions, experienced interventional clinicians (n\u0026thinsp;=\u0026thinsp;4) were asked to rate the utilized medical devices according to different features using a dedicated questionnaire, as shown in supporting information (S3).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section3\"\u003e\u003ch2\u003e2.6.2 MRI-guided assessment of MR Conditional EMB forceps\u003c/h2\u003e\u003cp\u003eFive MRI experiments were conducted using the developed hybrid in vitro vessel phantom (see Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The procedures took place at the local hospital using a Biograph_mMR 3.0T scanner (Siemens Healthineers, Erlangen, Germany). During scanning, the MR Conditional EMB forceps was manipulated within the phantom to assess artifact characteristics and device visibility. Imaging focused on the artifact size at the forceps head and the visibility of passive markers along the guiding shaft. Finally, myocardial tissue samples were obtained using the MR Conditional EMB forceps (see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). EMBs were conducted according to the developed clinical workflow using following MR Conditional devices.\u003c/p\u003e\u003cp\u003eAn approved 0.035\" (0.89 cm), 150 cm hydrophilic-coated MR Conditional guidewire (REF 39012526, EPflex Feinwerktechnik GmbH) was used for probing and device guidance during MRI-guided interventions, along with the following instruments: a 9 Fr, 85 cm non-braided Check-Flo Performer Introducer (Cook Medical, Bloomington, IN, USA); an 18 G MR-compatible cannula and a short guidewire (REF 46012082), both provided by EPflex Feinwerktechnik GmbH.\u003c/p\u003e\u003cp\u003eAfter the facilitation of blood vessel access (Seldinger technique (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)), the guidewire was placed into the left ventricle, followed by the placement of the femoral sheath inside the left ventricle with subsequent myocardial tissue extraction using the MR Conditional EMB forceps.\u003c/p\u003e\u003cp\u003eMR imaging during in vitro and in vivo experiments was performed with prepared MRI sequences (Table\u0026nbsp;1) based on the workflow derived from the catheterization lab.\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;1. Utilized MRI parameters with applied ranges for EMB interventions, Siemens Biograph_mMR 3.0T (customized TrueFISP).\u003c/p\u003e\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMRI parameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRange of values\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eTR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003e380 ms to 430 ms\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp;2 ms to 2.5 ms\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003e5 ms to 10 ms\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003e40\u0026deg;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eBW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003e560 Hz/pxl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003ePixel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003e1.3 mm\u003csup\u003e2\u003c/sup\u003e to 2 mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eFoV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003e300 x 300 mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: TR: Repetition Time; TE: Echo Time; ST: Slice Thickness; FA: Flip Angle; BW: Bandwidth; Pixel: Pixel Size; FoV: Field of View\u003c/p\u003e\n\u003ch2\u003e2.7 In vivo evaluation of MR Conditional EMB forceps\u003c/h2\u003e\n\u003cp\u003eFour female pigs (Sus scrofa domesticus) aged 12-16 weeks and weighing 34-58 kg were subjected to the MRI-guided EMB intervention. For transportation from the rearing station, they were sedated using the following intramuscularly administered anesthesia: 0.5‑1\u0026nbsp;mg/kg\u0026nbsp;Midazolam, 15‑20 mg/kg\u0026nbsp;Ketamine, and 0.5\u0026nbsp;mg/25kg. Anesthesia was maintained stable during transport using 0.5\u0026nbsp;mg/kg/h Midazolam. Before intubation, the animals received optional 0.3\u0026nbsp;mg/kg Midazolam and 10 mg/kg Propofol. After intubation, anesthesia was deepened with 1‑4\u0026nbsp;\u0026mu;g/kg/h\u0026nbsp;Isoflurane via inhalation. Additionally, 7.5\u0026nbsp;\u0026mu;g/kg/h Fentanyl Citrate was given to ensure adequate analgesia during planned MRI-guided interventions. The regularly performed monitoring protocol included corneal and interdigital reflex, respiratory rate, heart rate, pulse waveform, CO\u003csub\u003e2\u003c/sub\u003e and O\u003csub\u003e2\u003c/sub\u003e saturation, minimum alveolar concentration, and invasive blood pressure. ECG monitoring was performed to detect early changes in the cardiovascular system.\u003c/p\u003e\n\u003cp\u003eThe in vivo experiments were performed at the local hospital in a Biograph_mMR 3.0T (Siemens Healthineers, Erlangen, Germany), using the developed clinical workflow and MR Conditional EMB forceps (EPflex Feinwerktechnik GmbH).\u003c/p\u003e\n\u003cp\u003eThe left femoral artery was accessed by the Seldinger technique, outside the MRI suite (19) under ultrasound (US)-guidance using a portable Clarius L7 HD3 ultrasound scanner (Clarius Mobile Health, Corp., Vancouver, BC, Canada) or, in case of failure, by open laparotomy. Therefore, an 18\u0026nbsp;G MR-cannula (EPflex Feinwerktechnik GmbH), J3-SFU-040-035/NiTi-0.52/non-magnetic-sterile short guidewire (REF 46012082, Epflex Feinwerktechnik GmbH), and 12 Fr, non-braided Check-Flo Performer introducer (Cook Medical, Bloomington, Indiana, USA) were used.\u003c/p\u003e\n\u003cp\u003eAfter transfer to the MR scanner room, the experimental animals were positioned supine on the patient table and covered with three body coils (Body 6, Siemens Healthineers, Erlangen, Germany). Subsequent to initial plane planning, a 0.035\u0026quot;, 260 cm long hydrophilic-coated MR Conditional guidewire (Epflex Feinwerktechnik GmbH) was inserted into the left ventricle using a 5 Fr pigtail catheter (Merit Medical Systems, South Jordan, UT, USA), additionally passively marked with iron oxide (Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e, Goodfellow Cambridge, UK). In the next phase, a 9\u0026nbsp;Fr, 85\u0026nbsp;cm long, non-braided Check-Flo Performer introducer (Cook Medical, Bloomington, Indiana, USA), also passively marked with iron oxide (Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e, Goodfellow, Cambridge, UK), was inserted into the left ventricle with subsequent myocardial tissue extraction using the MR Conditional EMB forceps (Epflex Feinwerktechnik GmbH).\u003c/p\u003e\n\u003cp\u003eThe described animal protocols were reviewed and approved by the local animal ethics committee and the governmental animal care and use committee (Landesdirektion Sachsen, Germany) (16).\u003c/p\u003e\n\u003ch2\u003e2.8 Tissue sampling times\u003c/h2\u003e\n\u003cp\u003eTime measurements were recorded during fluoroscopy- and MRI-guided studies and later compared with those from fluoroscopy-guided endomyocardial biopsy (EMB) procedures performed on patients in the catheterization laboratory. Time capture started with the insertion of the EMB forceps into the sheath already seated in the left ventricle and ended with the withdrawal of the dedicated tissue sample outside the model.\u003c/p\u003e\n\u003ch2\u003e2.9 Statistical analysis\u003c/h2\u003e\n\u003cp\u003eQuestionnaire results were summarized using the median and interquartile range (IQR), calculated in Microsoft Excel (Microsoft Corp., Redmond, WA, USA). MRI artifact measurements of MR Conditional EMB forceps heads from in vitro phantom and in vivo studies were analyzed using an independent t-test in MATLAB (MathWorks, Natick, MA, USA). Tissue extraction times were evaluated using the mean and standard deviation (SD). Pairwise group comparisons were performed with the Kruskal-Wallis test in MATLAB. A p-value of \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003ch2\u003e3.1 Histological assessment of biopsy samples\u003c/h2\u003e\n\u003cp\u003eThe in vitro obtained tissue samples (n=10) exhibit an identical appearance with well-preserved cell contours and distinguishable cell nuclei without any artificial damage caused by the extraction method. There was no recognizable difference in the performed HE-stain between the specimens obtained by the MR Conditional forceps (Figure 3, A) and the utilized standard biopsy forceps (Figure 3, B).\u003c/p\u003e\n\u003ch2\u003e3.2 In vitro artifact quantification in MRI and fluoroscopy\u003c/h2\u003e\n\u003cp\u003eThe fluoroscopy imaging (figure 4, B) showed distinct and clearly defined artifacts of the forceps head but no artifacts at the guiding shaft. The MR images showed artifacts of the bioptome head and passive markings applied along the device\u0026apos;s guiding shaft. These susceptibility-based MRI artifacts allowed continuous visual observation of the device during manipulation. MR images acquired at 3.0T field strength (figure 4, C \u0026amp; D) demonstrated artifacts with blooming effects and radial lines surrounding the applied MRI-visible markers at the EMB forceps head and guiding shaft. MR imaging performed at 1.5T field strength (figure 4, E) showed less blooming and no distinct radial lines but punctual increased intensity around the markers.\u003c/p\u003e\n\u003cp\u003eThe artifact size evaluation of the captured MR images (Figure 4, C.2, D.2, \u0026amp; E.2) using three different MRI systems can be derived from Table 2. The data shows proportional artifact coverages of at least 45% for the acquisitions of the forceps head. All investigated distal MRI visible markers (marker one to marker three) showed proportional artifact coverages of at least 40%.\u003c/p\u003e\n\u003cp\u003eTable 2. Artifact size evaluation of MR Conditional EMB forceps using MATLAB script based on ASTM F2119-07. The table shows proportional artifact coverages (ratio of total area occupied by valid artifact pixels to area of defined bounding box) and dimensions of the corresponding bounding box (width and height).\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMRI System\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedical Device Section\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 29px;\"\u003e\n \u003cp\u003e3.0T Siemens\u003cbr\u003e\u0026nbsp;Biograph mMR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 27px;\"\u003e\n \u003cp\u003e3.0T GE SIGNA HDx\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 30px;\"\u003e\n \u003cp\u003e1.5T GE SIGNA HDx\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 12px;\"\u003e\n \u003cp\u003eEMB forceps head\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 12px;\"\u003e\n \u003cp\u003e54.07 %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eW: 13 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 11px;\"\u003e\n \u003cp\u003e47.85 %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eW: 12.2 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 13px;\"\u003e\n \u003cp\u003e61.32 %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eW: 8.3 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eH: 21.6 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eH: 15.1 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eH: 16.1 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 12px;\"\u003e\n \u003cp\u003eFirst marker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 12px;\"\u003e\n \u003cp\u003e41.67 %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eW: 5.8 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 11px;\"\u003e\n \u003cp\u003e48.33 %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eW: 5.4 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 13px;\"\u003e\n \u003cp\u003e47.92 %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eW: 5.9 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eH: 8.7 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eH: 9.8 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eH: 9.8 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 12px;\"\u003e\n \u003cp\u003eSecond marker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 12px;\"\u003e\n \u003cp\u003e44.29 %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eW: 10.1 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 11px;\"\u003e\n \u003cp\u003e56.48 %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eW: 8.8 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 13px;\"\u003e\n \u003cp\u003e60.83 %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eW: 7.3 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eH: 14.2 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eH: 7.3 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eH: 7.8 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 12px;\"\u003e\n \u003cp\u003eThird marker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 12px;\"\u003e\n \u003cp\u003e48.57 %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eW: 10.1 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 11px;\"\u003e\n \u003cp\u003e62.04 %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eW: 8.8 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 13px;\"\u003e\n \u003cp\u003e41.67 %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eW: 6.8 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eH: 14.4 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eH: 13.7 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eH: 7.8 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eStatistical analysis using independent t-test of manual measurements of MRI artifacts from MR Conditional EMB forceps heads in in vitro phantom and in vivo studies revealed significant differences (see Table S4 in SI, 2,07 \u0026times; 10⁻⁵). For height, in vivo (M = 11.8 mm, SD = 0.8, n = 5) was significantly smaller than in vitro (M = 16.3 mm, SD = 1.6, n = 14), p \u0026lt; 0.001. A similar trend was observed for width, where in vivo (M = 6.9 mm, SD = 1.3, n = 5) was smaller than in vitro (M = 10.9 mm, SD = 1.7, n = 14), p \u0026lt; 0.001.\u003c/p\u003e\n\u003ch2\u003e3.3 Imaging workflow for MRI-guided EMB\u003c/h2\u003e\n\u003cp\u003eThe three flowcharts (Figure 5) show key interventional steps (lane A) of the EMB protocol. It begins with femoral artery access under ultrasound (US) guidance, performed outside the MR scanner room in MRI-guided cases using a portable US device. After the procedure, the patient is transferred outside the scanner room for closure with a standard sealing device.\u003c/p\u003e\n\u003ch2\u003e3.4 Fluoroscopy and MRI assessment of EMB forceps in hybrid vessel phantom\u003c/h2\u003e\n\u003cp\u003eThe developed in vitro phantom allowed probing of the left ventricle using conventional and MR Safe guidewires with subsequent insertion of long sheaths (Figure 6). The attached Thiel-embalmed porcine heart enabled tissue extraction using conventional and MR Conditional EMB forceps. Due to the material selection, the assembly of the vessel phantom can be categorized as MR Safe according to ASTM F2503 \u0026ndash; 13. In addition, the phantom showed adequate radiolucent behavior during qualitative assessment based on ASTM F640 (standard test methods for determining radiopacity for medical use; test metrics: Philips Allura Xper, 15 fps, 4 mA, 69.79 kV).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe fluoroscopy imaging of the conventional and the MR Conditional forceps inside the hybrid vessel phantom (figure 6, A \u0026amp; B) showed distinct and clearly defined artifacts of both forceps heads but comparably no significant artifacts on the guiding shaft of the MR Conditional forceps. MR imaging of the MR Conditional forceps inside the vessel phantom (figure 6, C) showed artifacts with blooming effects and radial lines surrounding the pearl-string-shaped applied passive MR markers at the EMB forceps-guiding shaft. The EMB forceps head showed a distinctively more extensive artifact.\u003c/p\u003e\n\u003cp\u003eIn comparison to the fluoroscopic images (figure 6, A \u0026amp; B), the MR image (figure 6, C) shows adequate visualization of the in vitro reproduced anatomical structures of the vessel phantom, like the vessel wall and lumen of the aorta and the heart including the left ventricle. The position of the forceps could be traced during real-time MRI, which allowed immediate visual feedback of the performed manipulation.\u003c/p\u003e\n\u003ch2\u003e3.4.1 Handling study: Phantom-based handling assessment under fluoroscopy\u003c/h2\u003e\n\u003cp\u003eHandling of the MR Conditional EMB forceps was evaluated using a dedicated survey (Table 3). Due to the usage of conventional medical devices, which are classified as MR Unsafe, interventions were performed using fluoroscopy.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3: Questionnaire results for medical device handling study performed using the hybrid biological heart and polymer-based vessel phantom using fluoroscopy. After having conducted EMBs (extraction of five tissue samples), physicians were asked to rate the utilized conventional and MR Conditional EMB forceps according to different features. Participants were practicing cardiac interventionists with a minimum of six years of interventional experience (n = 4).\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.4756%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 22.7412%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eConventional EMB Forceps\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16.6098%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMR Conditional EMB Forceps\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.4756%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.9366%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8046%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInterquartile range (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.7913%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8046%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInterquartile range (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.4756%;\"\u003e\n \u003cp\u003eExperienced force required for opening/closing bioptome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.9366%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8046%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.7913%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.6038%;\"\u003e\n \u003cp\u003e1.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.4756%;\"\u003e\n \u003cp\u003eGliding property during probing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.9366%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8046%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.7913%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.6038%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.4756%;\"\u003e\n \u003cp\u003eExperienced force required for\u0026nbsp;extraction\u0026nbsp;of tissue samples\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.9366%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8046%;\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.7913%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.6038%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 61.6119%;\"\u003e\n \u003cp\u003eGraduated scale: -2 low; 0 intermediate; 2 high\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.4756%;\"\u003e\n \u003cp\u003eControllability (torque)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.9366%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8046%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.7913%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.6038%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.4756%;\"\u003e\n \u003cp\u003eBendability during passage of aortic arch\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.9366%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8046%;\"\u003e\n \u003cp\u003e1.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.7913%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.6038%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.4756%;\"\u003e\n \u003cp\u003eDetectability of forceps (fluoroscopy) shaft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.9366%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8046%;\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.7913%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.6038%;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.4756%;\"\u003e\n \u003cp\u003eDetectability of forceps (fluoroscopy) tip\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.9366%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8046%;\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.7913%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.6038%;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.4756%;\"\u003e\n \u003cp\u003eDetectability of bioptome (fluoroscopy) opening status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.9366%;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8046%;\"\u003e\n \u003cp\u003e1.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.7913%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.6038%;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.4756%;\"\u003e\n \u003cp\u003eIntuitive operability of EMB forceps\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.9366%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8046%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.7913%;\"\u003e\n \u003cp\u003e-0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.6038%;\"\u003e\n \u003cp\u003e1.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 61.6119%;\"\u003e\n \u003cp\u003eGraduated scale: -2 poor; 0 intermediate; 2 excellent\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAll attributes except intuitive forceps operability were rated in an intermediate region or above. Further, the experienced force required for opening and closing the bioptome, force needed for extracting tissue samples, controllability (torque), and bendability were rated in approximately the same region (intermediate) for both conventional and MR Conditional forceps. Other attributes showed a higher rating for the conventional EMB forceps. Intuitive operability was rated higher for the conventional (1\u0026plusmn;0.5) than for the MR Conditional EMB forceps (-0.5\u0026plusmn;1.25).\u003c/p\u003e\n\u003ch2\u003e3.4.2 Phantom-based assessment of MRI artifacts and feasibility\u003c/h2\u003e\n\u003cp\u003eIn five MRI experiments using the developed in vitro phantom, the MR Conditional EMB forceps showed distinct artifact sizing of the forceps head and passive markers along the guiding shaft. The pearl-string-shaped application of susceptibility-based artifacts facilitated continuous visual observation of the device during manipulation (figure 6, C). The setup enabled the simulation of MRI-guided left ventricular tissue sampling and extraction of 14 tissue samples. he experiments were distributed across several sessions conducted over an extended period.\u003c/p\u003e\n\u003ch2\u003e3.5 In vivo MRI\u003c/h2\u003e\n\u003cp\u003eDuring the in vivo tests, the sufficiently good handling performance already shown both in the dry state and during the in vitro model tests was confirmed. The visibility of the MR Conditional forceps showed distinct and clearly defined artifacts of the forceps head (Figure 7) and pearl-string-shaped passive artifacts along the guiding shaft, which made tracking possible during the entire duration of the in vivo test. During the opening and closing of the forceps head, the MR images showed no precise, distinguishable artifact size or shape changes. During the EMB intervention, five tissue samples were successfully harvested from six attempts using the MR Conditional EMB forceps. Both the developed iMRI setup and the clinical workflow were successfully tested during the in vivo trials.\u003c/p\u003e\n\u003ch2\u003e3.6 Comparison of tissue sampling times\u003c/h2\u003e\n\u003cp\u003eThe times required for tissue sampling during EMBs were compared (Table 4) to evaluate the performance. For this purpose, the durations of EMB interventions in the Cath lab on patients (conventional forceps), on the in vitro phantom, and during in vivo experiments (16) were derived. The recorded times during EMBs showed shorter times for tissue extractions in the in vitro phantom tests compared to the actual patients in the catheterization laboratory or the porcine model. A Kruskal-Wallis-test showed no significant difference (p \u0026gt; 0.05) between the five groups.\u003c/p\u003e\n\u003cp\u003eTable 4: Measured tissue extraction times during EMB, from forceps insertion into sheath to sample extraction.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUtilized medical device\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eImaging modality\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime measurement of EMB tissue extraction\u003cbr\u003e\u0026nbsp;Mean [min] \u0026plusmn; SD [min]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eConventional forceps\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003eCath lab patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;fluoroscopy \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e1.2 \u0026plusmn; 0.5 (n=30)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eConventional forceps\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003eHybrid biological heart and polymer-based vessel phantom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;fluoroscopy \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e0.8 \u0026plusmn; 0.4 (n=20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eMR Conditional forceps\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003eHybrid biological heart and polymer-based vessel phantom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;fluoroscopy \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e1.1 \u0026plusmn; 0.4 (n=20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eMR Conditional forceps\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003eHybrid biological heart and polymer-based vessel phantom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eMRI-guidance \u003csup\u003e2,3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e1.0 \u0026plusmn; 0.6 (n=14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eMR Conditional forceps\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003ePorcine in vivo model\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eMRI-guidance \u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e1.3 \u0026plusmn; 0.8 (n=5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 100px;\"\u003e\n \u003cp\u003e1: Philips Allura Xper\u003c/p\u003e\n \u003cp\u003e2: Siemens MAGNETOM Skyra 3T\u003c/p\u003e\n \u003cp\u003e3: Siemens Biograph mMR 3T\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"4. Discussion","content":"\u003ch2\u003e4.1 Performance and visibility of MR Conditional biopsy forceps\u003c/h2\u003e\n\u003cp\u003eThis study shows adequate MR visibility properties of the MR Conditional forceps in one 1.5T and two 3.0T MRI systems, which outlines a broad range of applications. Multimodally visible (fluoroscopy \u0026amp; MRI) EMB forceps could be beneficial for establishing EMBs in co-localized interventional suites due to their higher practicability\u0026nbsp;(11,12). Moreover, the use of wireless ultrasound, i.e., Clarius, is beneficial for vascular access and allows the use of conventional devices without needing a catheterization laboratory.\u003c/p\u003e\n\u003cp\u003eDuring all MR imaging, the MR Conditional forceps exhibited appropriately sized susceptibility-based artifacts for the bioptome jaws and passive markers. Our in vitro study using a saline-filled test box measured an artifact size of 16.1 x 8.3 mm, which was larger than the artifact observed in vivo. Significant differences were found between in vivo and in vitro measurements. In vivo, the artifact size for both height (M = 11.8 mm) and width (M = 6.9 mm) was significantly smaller compared to in vitro measurements (height: M = 16.3 mm, width: M = 10.9 mm). These findings suggest that in vivo conditions, including physiological motion, respiratory movements, and the complex tissue structure, contribute to a reduction in artifact size. This difference may be due to the limitations of ex vivo models, supporting the need for in vivo assessments to more accurately evaluate the clinical impact of EMB forceps artifacts in MRI.\u003c/p\u003e\n\u003cp\u003eThe histological assessment showed comparable integrity of deducted tissue samples, with acceptable quality in histologic overview in terms of other performed HE-stainings (9,20). Svetlove et al. demonstrated the feasibility of two MR Compatible bioptomes and used synchrotron radiation microtomography (SR\u0026mu;CT) to assess tissue volumes and microstructural integrity (21). Their focus lay on evaluating diagnostic quality and cutting performance of different bioptome designs ex vivo and in vivo. In contrast, our study focuses on procedural feasibility of a specific MR Conditional forceps under real-time MRI, combining in vitro phantom-based testing followed by in vivo application. Beyond tissue quality, we present a structured framework for preclinical validation, including artifact quantification and handling assessment, aligned with the 3R principle.\u003c/p\u003e\n\u003cp\u003eSvetlove et al. provide valuable insights into biopsy quality and tissue characterization, while our study complements this by addressing the procedural feasibility and integration of MR-guided EMB into a clinical workflow.\u003c/p\u003e\n\u003ch2\u003e4.2 Multimodal hybrid biological heart and polymer-based in vitro phantom\u003c/h2\u003e\n\u003cp\u003eThe built-up phantom showed usability for simulating catheter-based interventions using fluoroscopy- and MRI guidance. The phantom allowed the visibility and handling studies to be performed without the involvement of living animals. Such in vitro studies are demanded by the 3R principle\u0026nbsp;(Replace, Reduce, and Refine) for humane animal research before preclinical animal studies (14).\u003c/p\u003e\n\u003cp\u003eFurthermore, the developed in vitro model bridges the gap between commercially available fully synthetic phantoms for EMB simulation (e.g., Heartroid Myocardial Biopsy Model, JMC Corporation, Kanagawa, Japan) and simplified ex vivo models used in in vitro MRI research (22,23). While most in vitro phantoms focus primarily on the heart\u0026apos;s anatomy, expanding anatomical coverage improves the simulation\u0026apos;s realism.\u003c/p\u003e\n\u003ch2\u003e4.3 Imaging workflow of MRI-guided EMB\u003c/h2\u003e\n\u003cp\u003eThe imaging workflow can serve as a foundation for new MR-based clinical research and enhance the integration of MRI-guided EMBs into clinical practice. Additionally, it can be expanded into more detailed frameworks, as demonstrated by Fern\u0026aacute;ndez Guti\u0026eacute;rrez et al. (24). While the workflow developed by Rube et al. laid the groundwork for a preclinical study, it lacks a dedicated lane for MR imaging, unlike our workflow. This omission complicates the replication of the MR imaging steps (25).\u003c/p\u003e\n\u003ch2\u003e4.4 Medical device performance during MRI-guided EMB\u003c/h2\u003e\n\u003cp\u003eUnterberg-Buchwald et al. state that the achievement of appropriate handling parameters like traction and other mechanical features remains a central issue associated with catheter-based medical devices suitable for iMRI (9). This is mainly caused due to the restricted material applicability in the MR environment due to the high magnetic field strengths.\u0026nbsp;The handling study using the vessel phantom showed, in most cases, comparable results (intermediate or higher ratings) of assessed handling properties for the tested conventional and MR Conditional\u0026nbsp;EMB forceps. Detectability under fluoroscopy of the MR Conditional forceps was rated with high variability and should be further increased by incorporating radiopaque markers. Experienced interventional clinicians rated the \u0026apos;intuitive operability\u0026apos; of the MR Conditional forceps under intermediate. This issue was mainly caused by the prototype stage 3D-printed spring of the return mechanism (see Figure 1) in the handpiece. It could be remedied using an improved polymer or nonmagnetic spring (e.g., Beryllium or Nitinol).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIncreasing the number of participants would enhance the robustness of the data presented in the handling study, making the findings more statistically significant. However, this presents challenges, mainly due to the limited availability of professional interventional personnel. However, due to the high qualification of the participants, the data obtained also includes an increased force of expression.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe pairwise comparison of tissue extraction times using the Kruskal-Wallis test revealed no significant differences (p = 0.05), suggesting that the conventional and MR Conditional EMB forceps) could be handled similarly.\u003c/p\u003e\n\u003ch2\u003e4.5 In vivo testing\u003c/h2\u003e\n\u003cp\u003eThe mechanical properties of the guidewires and sheaths posed a limitation during MRI-guided EMB. Although the in vivo EMB procedure was successful in most cases (five out of six attempts), establishing prior access to the left ventricle with the medical devices posed a significant challenge. A stronger, nonmetallic braided sheath would help gain safer ventricle access. Due to the low stiffness of the guidewire, it had to be introduced into the left ventricle using a pigtail catheter. Once the methodology for accessing the ventricle was established, the procedures could be performed without issues.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEspecially during in vivo studies, the visualization of the forceps head was highly dependent on the slice positioning during MRI. The pearl-string-shaped passive artifacts along the device shaft were beneficial for providing continuous orientation and facilitating navigation across the different slices during MRI-guided intervention. However, observing the exact opening status of the bioptome under MR imaging posed difficulties, especially in motion inside the living organism. Other researchers have also reported challenges regarding the distinguishability of the opening status of forceps heads during MRI acquisition\u0026nbsp;(9,20,21).\u0026nbsp;For safe use, the forceps\u0026apos; opening status must be clearly visible; otherwise, it poses a hazard. This issue could be addressed by adding passive markers or modifying the forceps head design.\u003c/p\u003e\n\u003cp\u003eSeveral published in vivo studies outline the benefits and feasibility of lesion-targeted MRI-guided EMBs (9,10,20). Our experiments were part of a broader study focused on establishing various MRI-guided interventions. This approach assessed general feasibility, facilitated multiple MRI-guided procedures, and provided valuable insights into the iMRI setup and imaging workflows.\u0026nbsp;\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThis study demonstrated the practical usability of the MR Conditional and passively marked EMB forceps for fluoroscopy- and MRI-guided interventions. The developed hybrid biological heart and polymer vessel phantom proved to be an effective training tool for novice interventionalists under MRI guidance. Additionally, the adapted MRI imaging workflow facilitated in vitro studies of MRI-guided EMBs, laying the groundwork for successful in vivo experiments. These in vivo results confirmed the earlier findings, highlighting the efficacy and practicality of the MR Conditional EMB forceps for clinical application. Further investigation will explore the applicability of MR Conditional EMB forceps in low-field MRIs (under 1.5T), as suggested by Campbell-Washburn et al. (26).\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe animal protocols were reviewed and approved in 2022 by the local ethics committee and the Landesdirektion Sachsen governmental animal care and use committee (Germany) under approval number TVV 54/21. All study participants provided written consent for the collection and processing of their data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants provided explicit consent for the publication of their anonymized data and survey results in this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data and materials supporting the findings of this study are available in the Supporting Information (SI) or can be obtained upon reasonable request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was funded by the Federal Ministry of Education and Research (BMBF). The MR Conditional forceps and other medical devices used in this study were provided by Epflex Feinwerktechnik GmbH (Dettingen an der Erms, Germany), a company involved in the project. The authors declare no other competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was funded by KMU-innovativ (MR-Biopsy, grant no. 13GW0242B) of the Federal Ministry of Education and Research Germany BMBF.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDGB wrote the initial manuscript draft with support from CMR. Together, they conceptualized, designed, and facilitated the study, and were involved in data acquisition, analysis, and interpretation, with assistance from JB and CM. DGB, as corresponding author, was also responsible for the in vivo study design and implementation, the questionnaires, statistical analysis, and the creation and conceptualization of graphics. HB, TD, TJ, BS, and OS contributed significantly during the review phase and aided the practical implementation of the study, particularly regarding MRI testing, through their roles in supervision and interpretation. RH led the histological component of the study, drafting and reviewing relevant manuscript sections. JK, HS, and DGB collaboratively prepared and submitted the animal experimentation application, and JK and HS contributed extensively to the in vivo work. DGB and AM performed the in vivo studies. KL supervised the in vitro validation of the EMB forceps, managed its execution, and played a substantial role in reviewing the manuscript. AM, as Principal Investigator for MRI-Guided Interventions, defined the overall project scope, secured funding, and contributed throughout the research process and manuscript preparation. All authors critically reviewed and approved the final manuscript and accepted accountability for the work presented.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Lisa Wahl from the Clinic for Hoofed Animals, Swine, and Reproductive Biology at Leipzig University for her contribution to the veterinary management of the in vivo experiments.\u003c/p\u003e\n\u003cp\u003eWe thank Prof. Ulrich Laufs from the Department of Cardiology at Leipzig University Hospital for support during device and model evaluation. PD Hanno Steinke from the Anatomy Institute at Leipzig University Hospital for his support and provision of Thiel-embalming fluids.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe thank Dr. Senta Schauer, Michael Schmid, Dr. Johannes Uihlein, and Bernhard Uihlein of EPflex Feinwerktechnik GmbH, for the supply of the medical devices and their continuous support within the research project MR-Biopsy.\u003c/p\u003e\n\u003cp\u003eFurthermore, we will thank Felix Weber, Anja Neuman, Leon Melzer, Johanna Fleck, Moritz Lenhardt, and Annekatrin Pfahl for their contributing work within affiliated research projects at Innovation Center Computer Assisted Surgery (ICCAS), Institute at the Faculty of Medicine, Leipzig University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of Generative AI and AI-assisted technologies in the writing process\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the preparation of this work, the authors used the Grammarly Word plugin (version 1.0.0, Grammarly Inc., San Francisco, CA) and the GPT-4 language model (OpenAI, San Francisco, CA) for grammar and language editing. After using these tools, the authors reviewed and edited the content as needed and take full responsibility for the final version of the publication. No content was generated by AI; the tools were used solely to enhance clarity and ensure adherence to language and reporting standards.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eThiene G, Bruneval P, Veinot J, Leone O. Diagnostic use of the endomyocardial biopsy: a consensus statement. Virchows Arch. 2013 Jul;463(1):1\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eBussani R, Silvestri F, Perkan A, Gentile P, Sinagra G. Endomyocardial Biopsy. In: Sinagra G, Merlo M, Pinamonti B, editors. Dilated Cardiomyopathy [Internet]. Cham: Springer International Publishing; 2019 [cited 2023 Aug 3]. p. 135\u0026ndash;47. Available from: http://link.springer.com/10.1007/978-3-030-13864-6_9\u003c/li\u003e\n\u003cli\u003eAmmirati E, Buono A, Moroni F, Gigli L, Power JR, Ciabatti M, et al. State-of-the-Art of Endomyocardial Biopsy on Acute Myocarditis and Chronic Inflammatory Cardiomyopathy. Curr Cardiol Rep. 2022 May;24(5):597\u0026ndash;609. \u003c/li\u003e\n\u003cli\u003eJames MT, Samuel SM, Manning MA, Tonelli M, Ghali WA, Faris P, et al. Contrast-Induced Acute Kidney Injury and Risk of Adverse Clinical Outcomes After Coronary Angiography: A Systematic Review and Meta-Analysis. Circ: Cardiovascular Interventions. 2013 Feb;6(1):37\u0026ndash;43. \u003c/li\u003e\n\u003cli\u003eLiu Q, Wu Q. Radiation Protection in Cardiovascular Interventions: What Can We Do? Med Princ Pract. 2015 Mar 21;24(3):299\u0026ndash;299. \u003c/li\u003e\n\u003cli\u003eSeals KF, Lee EW, Cagnon CH, Al-Hakim RA, Kee ST. Radiation-Induced Cataractogenesis: A Critical Literature Review for the Interventional Radiologist. Cardiovasc Intervent Radiol. 2016 Feb;39(2):151\u0026ndash;60. \u003c/li\u003e\n\u003cli\u003eHolland SK, Altaye M, Robertson S, Byars AW, Plante E, Szaflarski JP. Data on the safety of repeated MRI in healthy children. NeuroImage: Clinical. 2014;4:526\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eLurz P, Luecke C, Eitel I, F\u0026ouml;hrenbach F, Frank C, Grothoff M, et al. Comprehensive Cardiac Magnetic Resonance Imaging in Patients With Suspected Myocarditis. Journal of the American College of Cardiology. 2016 Apr;67(15):1800\u0026ndash;11. \u003c/li\u003e\n\u003cli\u003eUnterberg-Buchwald C, Ritter CO, Reupke V, Wilke RN, Stadelmann C, Steinmetz M, et al. Targeted endomyocardial biopsy guided by real-time cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2017 Dec;19(1):45. \u003c/li\u003e\n\u003cli\u003eRogers T, Ratnayaka K, Karmarkar P, Campbell-Washburn AE, Schenke WH, Mazal JR, et al. Real-Time Magnetic Resonance Imaging Guidance Improves the Diagnostic Yield of Endomyocardial Biopsy. JACC: Basic to Translational Science. 2016 Aug;1(5):376\u0026ndash;83. \u003c/li\u003e\n\u003cli\u003eRogers T, Campbell-Washburn AE, Ramasawmy R, Yildirim DK, Bruce CG, Grant LP, et al. Interventional cardiovascular magnetic resonance: state-of-the-art. J Cardiovasc Magn Reson. 2023 Aug 14;25(1):48. \u003c/li\u003e\n\u003cli\u003eAmin EK, Campbell-Washburn A, Ratnayaka K. MRI-Guided Cardiac Catheterization in Congenital Heart Disease: How to Get Started. Curr Cardiol Rep. 2022 Apr 1;24(4):419\u0026ndash;29. \u003c/li\u003e\n\u003cli\u003eHampshire VA, Gilbert SH. Refinement, Reduction, and Replacement (3R) Strategies in Preclinical Testing of Medical Devices. Toxicol Pathol. 2019 Apr;47(3):329\u0026ndash;38. \u003c/li\u003e\n\u003cli\u003eAdamovich A, Park S, Siskin GP, Englander MJ, Mandato KD, Herr A, et al. The ABCs of the FDA: A Primer on the Role of the United States Food and Drug Administration in Medical Device Approvals and IR Research. Journal of Vascular and Interventional Radiology. 2015 Sep;26(9):1324\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eGholami Bajestani D, Reich CM, Mulik C, Mokosch M, Melzer A. Hybrid polymer vessel phantoms for feasibility studies and clinical training of MRI-guided interventions. Current Directions in Biomedical Engineering. 2022 Sep 2;8(2):656\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eLandesdirektion S. Approval of animal experiment protocol [TVV 54/21]. 2022. \u003c/li\u003e\n\u003cli\u003eSoher BJ, Dale BM, Merkle EM. A Review of MR Physics: 3T versus 1.5T. Magnetic Resonance Imaging Clinics of North America. 2007;15(3):277\u0026ndash;90. \u003c/li\u003e\n\u003cli\u003eReich CM, Sattler B, Jochimsen TH, Unger M, Melzer L, Landgraf L, et al. Practical setting and potential applications of interventions guided by PET/MRI. Q J Nucl Med Mol Imaging [Internet]. 2021 Mar [cited 2023 Aug 16];65(1). Available from: https://www.minervamedica.it/index2.php?show=R39Y2021N01A0043\u003c/li\u003e\n\u003cli\u003eVenous Access. In: Diagnostic Imaging: Interventional Procedures [Internet]. Elsevier; 2018 [cited 2023 Sep 7]. p. 88\u0026ndash;101. Available from: https://linkinghub.elsevier.com/retrieve/pii/B9780323524810500197\u003c/li\u003e\n\u003cli\u003eBehm P, Gastl M, Jahn A, Rohde A, Haberkorn S, Krueger S, et al. CMR-guidance of passively tracked endomyocardial biopsy in an in vivo porcine model. Int J Cardiovasc Imaging. 2018 Dec 1;34(12):1917\u0026ndash;26. \u003c/li\u003e\n\u003cli\u003eSvetlove A, Ritter CO, Dullin C, Schmid M, Schauer S, Uihlein J, et al. Evaluation of MR‑safe bioptomes for MR‑guided endomyocardial biopsy in minipigs: a potential radiation‑free clinical approach. European Radiology Experimental. 2023;7(76). \u003c/li\u003e\n\u003cli\u003eLossnitzer D. Feasibility of real-time magnetic resonance imaging-guided endomyocardial biopsies: An \u003cem\u003ein-vitro\u003c/em\u003e study. WJC. 2015;7(7):415. \u003c/li\u003e\n\u003cli\u003eSeitz SA, Haberkorn SM, Maslanka H, Katus HA, Steen H. In-vitro evaluation of a novel MR-compatible cardiac bioptome catheter for MR-guided myocardial biopsies. Journal of Cardiovascular Magnetic Resonance. 2012 Feb 1;14(1):O32. \u003c/li\u003e\n\u003cli\u003eMustafee N, Katsaliaki K, Gunasekaran A, Williams MD, Fern\u0026aacute;ndez‐Guti\u0026eacute;rrez F, Barnett I, et al. Framework for detailed workflow analysis and modelling for simulation of multi‐modal image‐guided interventions. Journal of Enterprise Information Management [Internet]. 2013 Feb 8 [cited 2019 Aug 27]; Available from: https://www.emerald.com/insight/content/doi/10.1108/17410391311289550/full/html\u003c/li\u003e\n\u003cli\u003eRube MA, Fernandez-Gutierrez F, Cox BF, Holbrook AB, Houston JG, White RD, et al. Preclinical feasibility of a technology framework for MRI-guided iliac angioplasty. Int J CARS. 2015 May 1;10(5):637\u0026ndash;50. \u003c/li\u003e\n\u003cli\u003eCampbell-Washburn AE, Ramasawmy R, Restivo R, et al. Opportunities in Interventional and Diagnostic Imaging by Using High-Performance Low-Field-Strength MRI. Radiology. 293(2):384\u0026ndash;93. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[{"identity":"091d1c50-72dd-4221-89d6-5cd3bc739fc0","identifier":"10.13039/501100002347","name":"Bundesministerium für Bildung und Forschung","awardNumber":"13GW0242B","order_by":0}],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Leipzig University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Minimally invasive procedure, interventional MRI, endomyocardial biopsy, MRI phantom, MR Conditional device, biopsy forceps","lastPublishedDoi":"10.21203/rs.3.rs-7269885/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7269885/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eMRI-guided cardiovascular procedures provide high-resolution, radiation-free imaging, but clinical translation is limited due to the lack of MR Conditional medical devices. This study presents a structured preclinical approach for validating MRI-guided devices and interventions, focusing on visibility and handling of a passively marked MR Conditional endomyocardial biopsy (EMB) forceps.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThe EMB forceps was evaluated in a three-stage preclinical protocol. First, device visibility was assessed in a water-filled test box using fluoroscopy (Philips Allura Xper) and three MRI systems (Siemens MAGNETOM Skyra 3T, GE Signa HDxt 3.0T, and GE Signa HDxt 1.5T). Tissue samples from MR Conditional (n\u0026thinsp;=\u0026thinsp;5) and standard Cordis biopsy forceps (n\u0026thinsp;=\u0026thinsp;5) underwent histological analysis. Second, devices were assessed during fluoroscopy-guided EMB using a hybrid vessel phantom, with handling compared by experienced interventionists (n\u0026thinsp;=\u0026thinsp;4). Next, MRI-guided testing of MR Conditional forceps was performed in the phantom (Siemens Biograph mMR 3.0T). Finally, in vivo testing was conducted in a porcine model (n\u0026thinsp;=\u0026thinsp;4) using the same MRI system, following ethics committee approval.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eVisibility was confirmed in all three MRI systems (artifact coverage\u0026thinsp;\u0026gt;\u0026thinsp;45% for EMB forceps head; \u0026gt;40% passive MR markers) and fluoroscopy. Handling was rated medium or higher by all operators. No significant difference in histological tissue quality and tissue sampling times (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) was observed between MR Conditional and standard forceps. In vivo, five tissue samples of equivalent quality were successfully harvested (out of six attempts), with smaller artifact sizes compared to in vitro measurements.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe MR Conditional EMB forceps showed reliable visibility, handling, and accurate tissue sampling in both in vitro and in vivo testing. The developed in vitro testing protocol effectively evaluated key device characteristics, providing valuable insights in the early stages of in vivo trials.\u003c/p\u003e","manuscriptTitle":"Preclinical Evaluation of an MR Conditional Forceps for MRI-Guided Endomyocardial Biopsy: A Multimodal Imaging Approach Using a Hybrid Vessel Phantom and Porcine In Vivo Models","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-04 10:09:58","doi":"10.21203/rs.3.rs-7269885/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"084b86d3-49c7-491f-b098-8c9d55f44be5","owner":[],"postedDate":"August 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":52488321,"name":"Biomedical Engineering"}],"tags":[],"updatedAt":"2025-08-04T10:09:58+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-04 10:09:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7269885","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7269885","identity":"rs-7269885","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}