Phase-by-phase analysis of the effect of contrast dilution on multiple arterial phase image quality in gadoxetic acid-enhanced liver MRI

Phase-by-phase analysis of the effect of contrast dilution on multiple arterial phase image quality in gadoxetic acid-enhanced liver MRI | 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 Phase-by-phase analysis of the effect of contrast dilution on multiple arterial phase image quality in gadoxetic acid-enhanced liver MRI Jordan Zheng Ting Sim, Xiaojia Ge, Hsien Min Low, Chau Hung Lee This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6296034/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 Gadoxetic acid-enhanced MRI is essential for detecting and characterizing focal liver lesions. However, transient severe motion artifacts in the arterial phase can degrade image quality. Gadoxetic acid dilution has been proposed to mitigate these artifacts, but its impact on multiple arterial phase acquisition remains unclear. Objective To evaluate the effect of gadoxetic acid dilution on image quality across multiple arterial phases in liver MRI, incorporating a phase-by-phase analysis. Methods This retrospective study included 81 patients (52 men, 29 women; mean age 70.1 years) who underwent serial gadoxetic acid-enhanced MRI with undiluted and diluted contrast (1:1 saline dilution). MRI was performed on 1.5-T and 3.0-T scanners with a standardized injection rate of 1.0 mL/s. Two radiologists independently rated anatomic conspicuity, respiratory motion artifacts, and overall image quality using a five-point Likert scale. A phase-by-phase analysis was conducted after a three-month washout period. Wilcoxon signed-rank tests were used for statistical comparisons, and inter-rater agreement was assessed with quadratic kappa coefficients. Results Inter-observer agreement was substantial (ƙ = 0.602–0.702). The diluted method showed higher but statistically non-significant improvements in anatomic conspicuity (3.73 vs. 3.59, p = 0.110), respiratory artifacts (3.54 vs. 3.41, p = 0.291), and overall image quality (3.67 vs. 3.51, p = 0.083). Phase-by-phase analysis revealed significant improvement in image quality for the first three arterial phases (p = 0.003, 0.005, 0.050), with a trend toward improvement in the last phase (p = 0.075). Conclusion Gadoxetic acid dilution improves image quality in early arterial phases of liver MRI, suggesting its potential to reduce motion artifacts. Imaging magnetic resonance gadoxetic acid disodium artifacts contrast media Figures Figure 1 Figure 2 Introduction Magnetic resonance imaging (MRI) plays an important role in the management of hepatobiliary disease. Liver-specific contrast agents are essential for the detection and characterization of focal liver lesions. The most common liver-specific contrast agent is gadoxetic acid marketed as Primovist (Bayer Schering Pharam) in Asia. Gadoxetic acid–enhanced MRI offers valuable insights into the enhancement patterns of liver lesions during the dynamic phase enhancing the detection and characterization of hepatobiliary lesions [1]. Although gadoxetic acid-enhanced MRI offers significant benefits, it is associated with transient severe respiratory motion artifacts in the arterial phase, with one study reporting an incidence of 12.9% [2]. Arterial phase is essential in diagnosing hepatocellular carcinomas (HCCs) as these are hypervascular tumours. These artifacts negatively impact image quality and can occur without subjective feelings of dyspnea [3]. Pietryga et al. suggested using single-breath-hold multiple arterial phase acquisition to achieve diagnostic-quality images despite the presence of transient motion artifacts [4]. This approach relies on the likelihood that at least one of the multiple arterial phases will be well-timed to provide images of sufficient diagnostic quality. Previous studies have investigated the impact of different injection protocols on image quality and artifacts. Poetter-Lang et al. found that dilution of gadoxetic acid resulted in significantly reduced artifacts and preserved signal intensity [5]. Combined with slower injection rates (1 mL/s), this approach preserved the contrast-to-normal signal ratio for focal liver lesions [6]. Polanec et al. explored three different injection protocols involving a mix of test bolus, fixed delay, contrast dilution, power-injection and manual injection. They concluded that a diluted, power-injected protocol provided good arterial phase timing while minimising artifacts [7]. This study aimed to investigate the impact of gadoxetic acid dilution on multiple arterial phase acquisition, including a phase-by-phase evaluation. To the best of our knowledge, our study is the first to incorporate a phase-by-phase analysis of image quality in the context of gadoxetic acid dilution combined with multi-arterial phase acquisition. Insights gained from this research could be significant, particularly as the use of multiple arterial phase acquisition becomes more prevalent and if gadoxetic acid dilution differentially affects specific arterial phases. Methods and Materials Patient Cohort This was a retrospective study approved by the Institution Review Board. All patients with MRI Liver scans performed from 1 Jan 2024 to 31 March 2024 with the dilution method were reviewed. Dilution method was performed with 10 ml of gadoxetic acid diluted 1:1 with an equivalent volume of saline. Injection rate was 1.0 mL/s using a power injector, which was the same rate as the standard undiluted technique. Patients with a corresponding MRI Liver scan performed with standard undiluted technique within a year prior were included. A final cohort of 81 patients was obtained (52 men, 29 women; mean age, 70.1; age range 41–89 years) MRI Acquisition The MRI examinations were performed with either 1.5- or 3.0-T MR units (Siemens Magnetom Sola; Siemens Magnetom Vida; Philips Ingenia). Multiple arterial phases acquisition was performed using the T1-fat-saturated GRASP-VIBE technique (Siemens) or THRIVE technique (Phillips). Phases were reconstructed at approximately 4- to 6-second intervals. At least four separate arterial phases were acquired per study. MRI parameters for the contrast-enhanced sequences are as follows: TR 4–6 ms TE 1–2 ms, flip angle 10, FOV 36 to 42 cm, matrix 432 x 432 and slice thickness 3–6 mm with slice spacing 3 mm. Imaging Review Two abdominal subspecialty radiologists (L.H.M. and L.C.H.; 8 and 10 years of experience in the interpretation of liver MR images, respectively) retrospectively reviewed MR images independently on a picture archiving and communication system. They were blinded to information regarding contrast agent injection protocol. The MR images were presented randomly in a blinded configuration. For the patient-level read, the expert reviewers analysed the multi-arterial phase sequence as a whole and rated anatomic conspicuity, respiratory motion artifacts and overall image quality using a five-point Likert scale. Higher scores denoted better diagnostic quality, for example, a score of 5 across the board meant very good anatomic conspicuity, little or no motion artifacts and very good overall image quality. Following a washout period of three months, the expert readers conducted a phase-by-phase analysis of the multiple arterial phases. To avoid rater fatigue (as each arterial phase had to be given a score), only the overall image quality was documented during this phase-by-phase analysis. The scores were averaged across the two readers. Statistical Analysis The statistical analyses were performed using R version 4.4.1. Inter-rater agreement was assessed by quadratic kappa coefficients. Image quality ratings were summarized using mean (Standard Deviation, SD), median (Inter Quartile Range, IQR), minimum and maximum values. Wilcoxon signed rank test was used for image quality comparison between undiluted method versus diluted method (paired samples). Values of P < 0.05 were considered statistically significant. Results There was substantial inter-observer agreement across both patient-level and phase-by-phase analysis (ƙ = 0.602–0.702). In the patient level analysis, the diluted method scored higher across all three categories (anatomic conspicuity 3.73 vs 3.59, respiratory artifacts 3.54 vs 3.41 and overall image quality 3.67 vs 3.51) although the results were not statistically significant (p = 0.110, 0.291 and 0.083 respectively). These results are presented in Table 1 . At the phase-by-phase level, overall image quality of the first three arterial phases were rated as significantly better in the diluted method (p = 0.003, 0.005 and 0.05 respectively). The scores for the last arterial phase were also higher for the diluted method but did not achieve statistical significance (p = 0.075). These results are presented in Table 2 . Representative examples of arterial phase images are presented in Figs. 1 and 2 . Table 1 Results of Patient-level Analysis Metric Diluted Method No Diluted Method P-value* Anatomic conspicuity Mean (SD) 3.73 (0.89) 3.59 (0.84) 0.110 Median (Q1-Q3) 4.00 (3.00–4.50) 4.00 (3.00–4.00) Min; Max 1.50; 5.00 1.50; 5.00 Respiratory Artifacts Mean (SD) 3.54 (0.90) 3.41 (0.96) 0.291 Median (Q1-Q3) 3.50 (3.00–4.50) 3.50 (2.50–4.00) Min; Max 1.50; 5.00 1.00; 5.00 Overall Image Quality Mean (SD) 3.67 (0.85) 3.51 (0.86) 0.083 Median (Q1-Q3) 3.50 (3.00–4.50) 3.50 (3.00–4.00) Min; Max 1.50; 5.00 1.50; 5.00 Table 2 Results of Phase-by-Phase Analysis Metric Diluted Method No Diluted Method P-value* Arterial Phase 1 Mean (SD) 3.62 (0.89) 3.31 (0.90) 0.003 Median (Q1-Q3) 4.00 (3.00–4.50) 3.50 (2.50–4.00) Min; Max 1.00; 5.00 1.50; 4.50 Arterial Phase 2 Mean (SD) 3.60 (0.90) 3.30 (0.92) 0.005 Median (Q1-Q3) 4.00 (3.00–4.50) 3.50 (2.50–4.00) Min; Max 1.00; 5.00 1.50; 4.50 Arterial Phase 3 Mean (SD) 3.47 (0.94) 3.27 (0.90) 0.050 Median (Q1-Q3) 3.50 (3.00–4.50) 3.50 (2.50–4.00) Min; Max 1.00; 5.00 1.50; 4.50 Arterial Phase 4 Mean (SD) 3.42 (0.97) 3.22 (0.90) 0.075 Median (Q1-Q3) 3.50 (3.00–4.50) 3.50 (2.50–4.00) Min; Max 1.00; 5.00 1.50; 4.50 Discussion In this retrospective study, we demonstrated that dilution of gadoxetic acid significantly enhances overall image quality during the first three arterial phases of multi-arterial phase liver MRI. These findings are consistent with prior literature, including the work of Motosugi et al., who reported that dilution improves image quality and enhances lesion detectability [8]. Other groups similarly produced images with fewer arterial phase artifacts while preserving signal intensity and lesion visibility through gadoxetic acid dilution [5, 7]. Importantly, a 2014 Canadian consensus statement from a multidisciplinary expert panel endorsed gadoxetic acid dilution as a protocol optimization strategy for hepatobiliary imaging, assigning it a level of evidence IIa (Evidence from at least one well-designed controlled trial without randomization) [9]. To our knowledge, this study is the first to incorporate a phase-by-phase analysis of image quality in the context of gadoxetic acid dilution combined with multi-arterial phase acquisition. In a similar study, Kim et al. showed that gadoxetic acid dilution coupled with slower injection rate (2mL/sec) resulted in significantly less artifacts in the arterial phase in both patient- and image-level analyses [10]. Transient severe motion artifacts are thought to be caused by impaired breath-hold capacity after gadoxetic acid injection [11]. Interestingly, this is accompanied by brief transient tachypnea but not subjective feelings of dyspnea [3, 12]. While the underlying pathophysiology remains poorly understood, Yoon et al. found that majority of the patients (73.9%) developed transient severe motion artifacts within the first 15 seconds after gadoxetic acid administration [11]. This finding is compatible with our results, where gadoxetic acid dilution appear to show greater impact on the early arterial phases. The lower amount of gadoxetic acid in the dilution method likely resulted in less severe motion artifacts given that the effect is possibly dose-dependent [13]. Meanwhile, signal intensity is maintained, which can be explained mainly by higher relaxivity [14]. Several strategies have been proposed to mitigate the effects of transient severe motion artifacts including slower injection rates [7, 10, 15], free-breathing MRI sequence protocols [16, 17] and breath-hold training [18]. With the advent of artificial intelligence, many have also turned to deep learning and convolutional neural networks to reduce respiratory motion artifacts related to gadoxetic acid [19, 20]. Some of the MRI scans in our study were performed using free-breathing sequence protocols in an effort to obtain images of adequate diagnostic quality. A total of 13 participants (16% of the study population) underwent MRI with free-breathing sequences. These patients exhibited significant motion artifacts on their baseline pre-contrast images, suggesting they would derive less benefit from gadoxetic acid dilution. Excluding this subset of patients would lead to an increase in overall image quality scores—from 3.66 to 3.69 (out of 5) by reader 1 and from 3.51 to 3.57 by reader 2. This rough estimation suggests that gadoxetic acid dilution may be more beneficial for patients with some breath-holding capability but may have little effect on those who are already dyspneic at baseline. Our study has several limitations. First, we focused exclusively on gadoxetic acid dilution without accounting for variations in injection rate, which may have had additional effects in reducing transient severe motion artifacts. Second, the MR examinations were performed on both 1.5- and 3.0-T MR machines. The longer acquisition time for arterial phase images with the 1.5-T machine may have contributed to artifacts. Future studies could mitigate this by using a single scanner for all examination to reduce potential confounding variability. Third, this retrospective study had a relatively small cohort. However, it was sufficient to attain statistically significant results. Future work could adopt a lesion-based approach to increase sample size. In conclusion, phase-by-phase analysis of multiple arterial phases showed that dilution of gadoxetic acid caused significantly improved overall image quality in earlier arterial phases. Declarations Author Contribution J.Z.T.S. wrote the main manuscript text and prepared the figuresX.J.G. provided statistical support.L.C.H. and L.H.M. conceptualised the study, were the expert readers and edited the manuscript.All authors reviewed the manuscript. References Baleato-González S, Vilanova JC, Luna A, et al (2023) Current and Advanced Applications of Gadoxetic Acid–enhanced MRI in Hepatobiliary Disorders. Radiographics 43:. https://doi.org/10.1148/RG.220087/ASSET/IMAGES/LARGE/RG.220087.FIG22.JPEG Kim SY, Park SH, Wu EH, et al (2015) Transient respiratory motion artifact during arterial phase MRI with gadoxetate disodium: Risk factor analyses. Am J Roentgenol 204:1220–1227. https://doi.org/10.2214/AJR.14.13677/ASSET/IMAGES/LARGE/06_14_13677_01J.JPEG Motosugi U, Bannas P, Bookwalter CA, et al (2015) An Investigation of Transient Severe Motion Related to Gadoxetic Acid–enhanced MR Imaging. Radiology 279:93. https://doi.org/10.1148/RADIOL.2015150642 Pietryga JA, Burke LMB, Marin D, et al (2014) Respiratory Motion Artifact Affecting Hepatic Arterial Phase Imaging with Gadoxetate Disodium: Examination Recovery with a Multiple Arterial Phase Acquisition. https://doi.org/101148/radiol13131988 271:426–434. https://doi.org/10.1148/RADIOL.13131988 Poetter-Lang S, Dovjak GO, Messner A, et al (2023) Influence of dilution on arterial-phase artifacts and signal intensity on gadoxetic acid-enhanced liver MRI. Eur Radiol 33:523–534. https://doi.org/10.1007/S00330-022-08984-0 Poetter-Lang S, Ambros R, Messner A, et al (2024) Are dilution, slow injection and care bolus technique the causal solution to mitigating arterial-phase artifacts on gadoxetic acid–enhanced MRI? A large-cohort study. Eur Radiol 34:5215–5227. https://doi.org/10.1007/S00330-024-10590-1/TABLES/4 Polanec SH, Bickel H, Baltzer PAT, et al (2017) Respiratory motion artifacts during arterial phase imaging with gadoxetic acid: Can the injection protocol minimize this drawback? J Magn Reson Imaging 46:1107–1114. https://doi.org/10.1002/JMRI.25657 Motosugi U, Ichikawa T, Sou H, et al (2009) Dilution method of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). J Magn Reson Imaging 30:849–854. https://doi.org/10.1002/JMRI.21913 Jhaveri K, Cleary S, Audet P, et al (2015) Consensus Statements From a Multidisciplinary Expert Panel on the Utilization and Application of a Liver-Specific MRI Contrast Agent (Gadoxetic Acid). AJR 204. https://doi.org/10.2214/AJR.13.12399 Kim YK, Lin WC, Sung K, et al (2016) Reducing Artifacts during Arterial Phase of Gadoxetate Disodium–enhanced MR Imaging: Dilution Method versus Reduced Injection Rate. https://doi.org/101148/radiol2016160241 283:429–437. https://doi.org/10.1148/RADIOL.2016160241 Yoon JH, Lee JM, Yu MH, et al (2018) Evaluation of Transient Motion During Gadoxetic Acid–Enhanced Multiphasic Liver Magnetic Resonance Imaging Using Free-Breathing Golden-Angle Radial Sparse Parallel Magnetic Resonance Imaging. Invest Radiol 53:52. https://doi.org/10.1097/RLI.0000000000000409 Davenport MS, Malyarenko DI, Pang Y, et al (2017) Effect of Gadoxetate Disodium on Arterial Phase Respiratory Waveforms Using a Quantitative Fast Fourier Transformation-Based Analysis Gadoxetate Disodium and Arterial Phase Respiratory Wave-forms Gastrointestinal Imaging Original Research. https://doi.org/10.2214/AJR.16.16860 Morisaka H, Motosugi U, Ichikawa S, Onishi H (2018) Dose-dependence of transient respiratory motion artifacts on gadoxetic acid-enhanced arterial phase MR images. J Magn Reson Imaging 47:433–438. https://doi.org/10.1002/JMRI.25764 Zech CJ, Vos B, Nordell A, et al (2009) Vascular enhancement in early dynamic liver MR imaging in an animal model: comparison of two injection regimen and two different doses Gd-EOB-DTPA (gadoxetic acid) with standard Gd-DTPA. Invest Radiol 44:305–310. https://doi.org/10.1097/RLI.0B013E3181A24512 Cohen-Hallaleh V, Guo L, Hosseini-Nik H, et al (2017) Does injection flow rate have an impact on arterial phase image degradation in liver MRI? A comparison of gadoxetic acid versus gadobutrol. Clin Radiol 72:994.e1-994.e8. https://doi.org/10.1016/J.CRAD.2017.06.005 Park SH, Yoon JH, Park JY, et al (2023) Performance of free-breathing dynamic T1-weighted sequences in patients at risk of developing motion artifacts undergoing gadoxetic acid-enhanced liver MRI. Eur Radiol 33:4378–4388. https://doi.org/10.1007/S00330-022-09336-8 Young Park J, Min Lee S, Sub Lee J, et al (2022) Free-breathing dynamic T1WI using compressed sensing-golden angle radial sparse parallel imaging for liver MRI in patients with limited breath-holding capability. Eur J Radiol 152:110342. https://doi.org/10.1016/J.EJRAD.2022.110342 Jiang Y, Pu D, Dang S, Yu N (2024) Effect of Breath Training on Image Quality of Chest Magnetic Resonance Free-breathing Sequence. Curr Med Imaging 20:. https://doi.org/10.2174/0115734056286441240123052927 Kromrey ML, Tamada D, Johno H, et al (2020) Reduction of respiratory motion artifacts in gadoxetate-enhanced MR with a deep learning–based filter using convolutional neural network. Eur Radiol 30:5923. https://doi.org/10.1007/S00330-020-07006-1 Duffy BA, Zhao L, Sepehrband F, et al (2021) Retrospective motion artifact correction of structural MRI images using deep learning improves the quality of cortical surface reconstructions. Neuroimage 230:117756. https://doi.org/10.1016/J.NEUROIMAGE.2021.117756 Additional Declarations No competing interests reported. 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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-6296034","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":436173701,"identity":"3eec60b2-0406-4c1a-b660-ca16760cdd44","order_by":0,"name":"Jordan Zheng Ting Sim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEElEQVRIie2PsUoDMRzGvxC4W1Jcc4jmFVI6FYX4KD0Ep+vuIBIQ0qXdTxR9hbocjtFCXfoAV3BocRZanARFU09LB2MdBfPb/gk/vu8DAoE/CNEA/zosDrFyrlPYhzKSfK0CrCgg5hcK7fSm5fM1lEI8vR1fvByLM01m8wxK7HmKde8azd4IlIHJQbuQXN5bmpwWSK+sR8kPIl4ziJyCSuGtiNYKtOrarySvBowhngza55KLvFLUT8qmS+Fuvium3fyyUsilZz7pDunOloFk1m3Jho2kX6YnbgtP+x6l3jFk/GigYh0/PGVH2xsi37+ZzYtdJTzFPgu/AWKyTF68cUj7vSI86YsvT0ogEAj8O94BFB1P++A79JUAAAAASUVORK5CYII=","orcid":"","institution":"Tan Tock Seng Hospital","correspondingAuthor":true,"prefix":"","firstName":"Jordan","middleName":"Zheng Ting","lastName":"Sim","suffix":""},{"id":436173702,"identity":"1cdbbd3e-c207-4de5-bc3d-f2bef85ac90c","order_by":1,"name":"Xiaojia Ge","email":"","orcid":"","institution":"Tan Tock Seng Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiaojia","middleName":"","lastName":"Ge","suffix":""},{"id":436173703,"identity":"47698a5d-c779-49e3-a9ea-d8c11a216dff","order_by":2,"name":"Hsien Min Low","email":"","orcid":"","institution":"Tan Tock Seng Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hsien","middleName":"Min","lastName":"Low","suffix":""},{"id":436173704,"identity":"01a62d38-0995-4a31-affb-9c6902d51412","order_by":3,"name":"Chau Hung Lee","email":"","orcid":"","institution":"Tan Tock Seng Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chau","middleName":"Hung","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2025-03-24 13:53:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6296034/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6296034/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79831298,"identity":"4a4d53fb-278e-4b22-8d26-8629f69fbd71","added_by":"auto","created_at":"2025-04-03 10:32:16","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":301608,"visible":true,"origin":"","legend":"\u003cp\u003ePost-contrast MR images in the arterial phase. (A) represents the examination done with no contrast dilution. (B) in the middle was done less than 6 months later with contrast dilution. Note the remarkable improvement in motion artifacts and image quality. The yellow arrow in all three images denote an observation that was difficult to detect in (A) but clearly seen in (B) and shows growth in the examination done 6 months following that in (C).\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6296034/v1/57319b5d543f61bc03f2614a.jpeg"},{"id":79830615,"identity":"93fd7382-f250-48d6-a5eb-f58a1cc987c4","added_by":"auto","created_at":"2025-04-03 10:24:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":525223,"visible":true,"origin":"","legend":"\u003cp\u003ePost-contrast MR images at the level of the celiac axis following administration of gadoxetic acid in the arterial phase. (A) on the left was done without dilution method while (B) on the right was done with dilution method. In this case, dilution of contrast did not seem to make a notable difference to motion artifact or image quality.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6296034/v1/7911481a9e8a2717e3b92035.png"},{"id":82529437,"identity":"f89ffc85-22a4-44dc-8e99-c668f000666f","added_by":"auto","created_at":"2025-05-12 14:24:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1412762,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6296034/v1/c3ff63a5-3811-46b3-a8ef-74d22881e1ec.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Phase-by-phase analysis of the effect of contrast dilution on multiple arterial phase image quality in gadoxetic acid-enhanced liver MRI","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMagnetic resonance imaging (MRI) plays an important role in the management of hepatobiliary disease. Liver-specific contrast agents are essential for the detection and characterization of focal liver lesions. The most common liver-specific contrast agent is gadoxetic acid marketed as Primovist (Bayer Schering Pharam) in Asia. Gadoxetic acid\u0026ndash;enhanced MRI offers valuable insights into the enhancement patterns of liver lesions during the dynamic phase enhancing the detection and characterization of hepatobiliary lesions [1].\u003c/p\u003e \u003cp\u003eAlthough gadoxetic acid-enhanced MRI offers significant benefits, it is associated with transient severe respiratory motion artifacts in the arterial phase, with one study reporting an incidence of 12.9% [2]. Arterial phase is essential in diagnosing hepatocellular carcinomas (HCCs) as these are hypervascular tumours. These artifacts negatively impact image quality and can occur without subjective feelings of dyspnea [3]. Pietryga et al. suggested using single-breath-hold multiple arterial phase acquisition to achieve diagnostic-quality images despite the presence of transient motion artifacts [4]. This approach relies on the likelihood that at least one of the multiple arterial phases will be well-timed to provide images of sufficient diagnostic quality.\u003c/p\u003e \u003cp\u003ePrevious studies have investigated the impact of different injection protocols on image quality and artifacts. Poetter-Lang et al. found that dilution of gadoxetic acid resulted in significantly reduced artifacts and preserved signal intensity [5]. Combined with slower injection rates (1 mL/s), this approach preserved the contrast-to-normal signal ratio for focal liver lesions [6]. Polanec et al. explored three different injection protocols involving a mix of test bolus, fixed delay, contrast dilution, power-injection and manual injection. They concluded that a diluted, power-injected protocol provided good arterial phase timing while minimising artifacts [7].\u003c/p\u003e \u003cp\u003eThis study aimed to investigate the impact of gadoxetic acid dilution on multiple arterial phase acquisition, including a phase-by-phase evaluation. To the best of our knowledge, our study is the first to incorporate a phase-by-phase analysis of image quality in the context of gadoxetic acid dilution combined with multi-arterial phase acquisition. Insights gained from this research could be significant, particularly as the use of multiple arterial phase acquisition becomes more prevalent and if gadoxetic acid dilution differentially affects specific arterial phases.\u003c/p\u003e"},{"header":"Methods and Materials","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient Cohort\u003c/h2\u003e \u003cp\u003e This was a retrospective study approved by the Institution Review Board. All patients with MRI Liver scans performed from 1 Jan 2024 to 31 March 2024 with the dilution method were reviewed. Dilution method was performed with 10 ml of gadoxetic acid diluted 1:1 with an equivalent volume of saline. Injection rate was 1.0 mL/s using a power injector, which was the same rate as the standard undiluted technique. Patients with a corresponding MRI Liver scan performed with standard undiluted technique within a year prior were included. A final cohort of 81 patients was obtained (52 men, 29 women; mean age, 70.1; age range 41\u0026ndash;89 years)\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMRI Acquisition\u003c/h3\u003e\n\u003cp\u003eThe MRI examinations were performed with either 1.5- or 3.0-T MR units (Siemens Magnetom Sola; Siemens Magnetom Vida; Philips Ingenia). Multiple arterial phases acquisition was performed using the T1-fat-saturated GRASP-VIBE technique (Siemens) or THRIVE technique (Phillips). Phases were reconstructed at approximately 4- to 6-second intervals. At least four separate arterial phases were acquired per study. MRI parameters for the contrast-enhanced sequences are as follows: TR 4\u0026ndash;6 ms TE 1\u0026ndash;2 ms, flip angle 10, FOV 36 to 42 cm, matrix 432 x 432 and slice thickness 3\u0026ndash;6 mm with slice spacing 3 mm.\u003c/p\u003e\n\u003ch3\u003eImaging Review\u003c/h3\u003e\n\u003cp\u003eTwo abdominal subspecialty radiologists (L.H.M. and L.C.H.; 8 and 10 years of experience in the interpretation of liver MR images, respectively) retrospectively reviewed MR images independently on a picture archiving and communication system. They were blinded to information regarding contrast agent injection protocol. The MR images were presented randomly in a blinded configuration. For the patient-level read, the expert reviewers analysed the multi-arterial phase sequence as a whole and rated anatomic conspicuity, respiratory motion artifacts and overall image quality using a five-point Likert scale. Higher scores denoted better diagnostic quality, for example, a score of 5 across the board meant very good anatomic conspicuity, little or no motion artifacts and very good overall image quality. Following a washout period of three months, the expert readers conducted a phase-by-phase analysis of the multiple arterial phases. To avoid rater fatigue (as each arterial phase had to be given a score), only the overall image quality was documented during this phase-by-phase analysis. The scores were averaged across the two readers.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eThe statistical analyses were performed using R version 4.4.1. Inter-rater agreement was assessed by quadratic kappa coefficients. Image quality ratings were summarized using mean (Standard Deviation, SD), median (Inter Quartile Range, IQR), minimum and maximum values. Wilcoxon signed rank test was used for image quality comparison between undiluted method versus diluted method (paired samples). Values of P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThere was substantial inter-observer agreement across both patient-level and phase-by-phase analysis (ƙ = 0.602\u0026ndash;0.702). In the patient level analysis, the diluted method scored higher across all three categories (anatomic conspicuity 3.73 vs 3.59, respiratory artifacts 3.54 vs 3.41 and overall image quality 3.67 vs 3.51) although the results were not statistically significant (p\u0026thinsp;=\u0026thinsp;0.110, 0.291 and 0.083 respectively). These results are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eAt the phase-by-phase level, overall image quality of the first three arterial phases were rated as significantly better in the diluted method (p\u0026thinsp;=\u0026thinsp;0.003, 0.005 and 0.05 respectively). The scores for the last arterial phase were also higher for the diluted method but did not achieve statistical significance (p\u0026thinsp;=\u0026thinsp;0.075). These results are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Representative examples of arterial phase images are presented in Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of Patient-level Analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetric\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiluted Method\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo Diluted Method\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnatomic conspicuity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.73 (0.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.59 (0.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.110\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.00 (3.00\u0026ndash;4.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.00 (3.00\u0026ndash;4.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMin; Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.50; 5.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.50; 5.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory Artifacts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.54 (0.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.41 (0.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.291\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.50 (3.00\u0026ndash;4.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.50 (2.50\u0026ndash;4.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMin; Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.50; 5.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.00; 5.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverall Image Quality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.67 (0.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.51 (0.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.083\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.50 (3.00\u0026ndash;4.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.50 (3.00\u0026ndash;4.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMin; Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.50; 5.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.50; 5.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of Phase-by-Phase Analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetric\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiluted Method\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo Diluted Method\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArterial Phase 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.62 (0.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.31 (0.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.00 (3.00\u0026ndash;4.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.50 (2.50\u0026ndash;4.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMin; Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.00; 5.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.50; 4.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArterial Phase 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.60 (0.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.30 (0.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.00 (3.00\u0026ndash;4.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.50 (2.50\u0026ndash;4.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMin; Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.00; 5.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.50; 4.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArterial Phase 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.47 (0.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.27 (0.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.050\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.50 (3.00\u0026ndash;4.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.50 (2.50\u0026ndash;4.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMin; Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.00; 5.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.50; 4.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArterial Phase 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.42 (0.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.22 (0.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.075\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.50 (3.00\u0026ndash;4.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.50 (2.50\u0026ndash;4.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMin; Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.00; 5.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.50; 4.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective study, we demonstrated that dilution of gadoxetic acid significantly enhances overall image quality during the first three arterial phases of multi-arterial phase liver MRI. These findings are consistent with prior literature, including the work of Motosugi et al., who reported that dilution improves image quality and enhances lesion detectability [8]. Other groups similarly produced images with fewer arterial phase artifacts while preserving signal intensity and lesion visibility through gadoxetic acid dilution [5, 7]. Importantly, a 2014 Canadian consensus statement from a multidisciplinary expert panel endorsed gadoxetic acid dilution as a protocol optimization strategy for hepatobiliary imaging, assigning it a level of evidence IIa (Evidence from at least one well-designed controlled trial without randomization) [9]. To our knowledge, this study is the first to incorporate a phase-by-phase analysis of image quality in the context of gadoxetic acid dilution combined with multi-arterial phase acquisition. In a similar study, Kim et al. showed that gadoxetic acid dilution coupled with slower injection rate (2mL/sec) resulted in significantly less artifacts in the arterial phase in both patient- and image-level analyses [10].\u003c/p\u003e \u003cp\u003eTransient severe motion artifacts are thought to be caused by impaired breath-hold capacity after gadoxetic acid injection [11]. Interestingly, this is accompanied by brief transient tachypnea but not subjective feelings of dyspnea [3, 12]. While the underlying pathophysiology remains poorly understood, Yoon et al. found that majority of the patients (73.9%) developed transient severe motion artifacts within the first 15 seconds after gadoxetic acid administration [11]. This finding is compatible with our results, where gadoxetic acid dilution appear to show greater impact on the early arterial phases. The lower amount of gadoxetic acid in the dilution method likely resulted in less severe motion artifacts given that the effect is possibly dose-dependent [13]. Meanwhile, signal intensity is maintained, which can be explained mainly by higher relaxivity [14].\u003c/p\u003e \u003cp\u003eSeveral strategies have been proposed to mitigate the effects of transient severe motion artifacts including slower injection rates [7, 10, 15], free-breathing MRI sequence protocols [16, 17] and breath-hold training [18]. With the advent of artificial intelligence, many have also turned to deep learning and convolutional neural networks to reduce respiratory motion artifacts related to gadoxetic acid [19, 20].\u003c/p\u003e \u003cp\u003eSome of the MRI scans in our study were performed using free-breathing sequence protocols in an effort to obtain images of adequate diagnostic quality. A total of 13 participants (16% of the study population) underwent MRI with free-breathing sequences. These patients exhibited significant motion artifacts on their baseline pre-contrast images, suggesting they would derive less benefit from gadoxetic acid dilution. Excluding this subset of patients would lead to an increase in overall image quality scores\u0026mdash;from 3.66 to 3.69 (out of 5) by reader 1 and from 3.51 to 3.57 by reader 2. This rough estimation suggests that gadoxetic acid dilution may be more beneficial for patients with some breath-holding capability but may have little effect on those who are already dyspneic at baseline.\u003c/p\u003e \u003cp\u003eOur study has several limitations. First, we focused exclusively on gadoxetic acid dilution without accounting for variations in injection rate, which may have had additional effects in reducing transient severe motion artifacts. Second, the MR examinations were performed on both 1.5- and 3.0-T MR machines. The longer acquisition time for arterial phase images with the 1.5-T machine may have contributed to artifacts. Future studies could mitigate this by using a single scanner for all examination to reduce potential confounding variability. Third, this retrospective study had a relatively small cohort. However, it was sufficient to attain statistically significant results. Future work could adopt a lesion-based approach to increase sample size.\u003c/p\u003e \u003cp\u003eIn conclusion, phase-by-phase analysis of multiple arterial phases showed that dilution of gadoxetic acid caused significantly improved overall image quality in earlier arterial phases.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJ.Z.T.S. wrote the main manuscript text and prepared the figuresX.J.G. provided statistical support.L.C.H. and L.H.M. conceptualised the study, were the expert readers and edited the manuscript.All authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBaleato-Gonz\u0026aacute;lez S, Vilanova JC, Luna A, et al (2023) Current and Advanced Applications of Gadoxetic Acid\u0026ndash;enhanced MRI in Hepatobiliary Disorders. Radiographics 43:. https://doi.org/10.1148/RG.220087/ASSET/IMAGES/LARGE/RG.220087.FIG22.JPEG\u003c/li\u003e\n\u003cli\u003eKim SY, Park SH, Wu EH, et al (2015) Transient respiratory motion artifact during arterial phase MRI with gadoxetate disodium: Risk factor analyses. Am J Roentgenol 204:1220\u0026ndash;1227. https://doi.org/10.2214/AJR.14.13677/ASSET/IMAGES/LARGE/06_14_13677_01J.JPEG\u003c/li\u003e\n\u003cli\u003eMotosugi U, Bannas P, Bookwalter CA, et al (2015) An Investigation of Transient Severe Motion Related to Gadoxetic Acid\u0026ndash;enhanced MR Imaging. Radiology 279:93. https://doi.org/10.1148/RADIOL.2015150642\u003c/li\u003e\n\u003cli\u003ePietryga JA, Burke LMB, Marin D, et al (2014) Respiratory Motion Artifact Affecting Hepatic Arterial Phase Imaging with Gadoxetate Disodium: Examination Recovery with a Multiple Arterial Phase Acquisition. https://doi.org/101148/radiol13131988 271:426\u0026ndash;434. https://doi.org/10.1148/RADIOL.13131988\u003c/li\u003e\n\u003cli\u003ePoetter-Lang S, Dovjak GO, Messner A, et al (2023) Influence of dilution on arterial-phase artifacts and signal intensity on gadoxetic acid-enhanced liver MRI. Eur Radiol 33:523\u0026ndash;534. https://doi.org/10.1007/S00330-022-08984-0\u003c/li\u003e\n\u003cli\u003ePoetter-Lang S, Ambros R, Messner A, et al (2024) Are dilution, slow injection and care bolus technique the causal solution to mitigating arterial-phase artifacts on gadoxetic acid\u0026ndash;enhanced MRI? A large-cohort study. Eur Radiol 34:5215\u0026ndash;5227. https://doi.org/10.1007/S00330-024-10590-1/TABLES/4\u003c/li\u003e\n\u003cli\u003ePolanec SH, Bickel H, Baltzer PAT, et al (2017) Respiratory motion artifacts during arterial phase imaging with gadoxetic acid: Can the injection protocol minimize this drawback? J Magn Reson Imaging 46:1107\u0026ndash;1114. https://doi.org/10.1002/JMRI.25657\u003c/li\u003e\n\u003cli\u003eMotosugi U, Ichikawa T, Sou H, et al (2009) Dilution method of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). J Magn Reson Imaging 30:849\u0026ndash;854. https://doi.org/10.1002/JMRI.21913\u003c/li\u003e\n\u003cli\u003eJhaveri K, Cleary S, Audet P, et al (2015) Consensus Statements From a Multidisciplinary Expert Panel on the Utilization and Application of a Liver-Specific MRI Contrast Agent (Gadoxetic Acid). AJR 204. https://doi.org/10.2214/AJR.13.12399\u003c/li\u003e\n\u003cli\u003eKim YK, Lin WC, Sung K, et al (2016) Reducing Artifacts during Arterial Phase of Gadoxetate Disodium\u0026ndash;enhanced MR Imaging: Dilution Method versus Reduced Injection Rate. https://doi.org/101148/radiol2016160241 283:429\u0026ndash;437. https://doi.org/10.1148/RADIOL.2016160241\u003c/li\u003e\n\u003cli\u003eYoon JH, Lee JM, Yu MH, et al (2018) Evaluation of Transient Motion During Gadoxetic Acid\u0026ndash;Enhanced Multiphasic Liver Magnetic Resonance Imaging Using Free-Breathing Golden-Angle Radial Sparse Parallel Magnetic Resonance Imaging. Invest Radiol 53:52. https://doi.org/10.1097/RLI.0000000000000409\u003c/li\u003e\n\u003cli\u003eDavenport MS, Malyarenko DI, Pang Y, et al (2017) Effect of Gadoxetate Disodium on Arterial Phase Respiratory Waveforms Using a Quantitative Fast Fourier Transformation-Based Analysis Gadoxetate Disodium and Arterial Phase Respiratory Wave-forms Gastrointestinal Imaging Original Research. https://doi.org/10.2214/AJR.16.16860\u003c/li\u003e\n\u003cli\u003eMorisaka H, Motosugi U, Ichikawa S, Onishi H (2018) Dose-dependence of transient respiratory motion artifacts on gadoxetic acid-enhanced arterial phase MR images. J Magn Reson Imaging 47:433\u0026ndash;438. https://doi.org/10.1002/JMRI.25764\u003c/li\u003e\n\u003cli\u003eZech CJ, Vos B, Nordell A, et al (2009) Vascular enhancement in early dynamic liver MR imaging in an animal model: comparison of two injection regimen and two different doses Gd-EOB-DTPA (gadoxetic acid) with standard Gd-DTPA. Invest Radiol 44:305\u0026ndash;310. https://doi.org/10.1097/RLI.0B013E3181A24512\u003c/li\u003e\n\u003cli\u003eCohen-Hallaleh V, Guo L, Hosseini-Nik H, et al (2017) Does injection flow rate have an impact on arterial phase image degradation in liver MRI? A comparison of gadoxetic acid versus gadobutrol. Clin Radiol 72:994.e1-994.e8. https://doi.org/10.1016/J.CRAD.2017.06.005\u003c/li\u003e\n\u003cli\u003ePark SH, Yoon JH, Park JY, et al (2023) Performance of free-breathing dynamic T1-weighted sequences in patients at risk of developing motion artifacts undergoing gadoxetic acid-enhanced liver MRI. Eur Radiol 33:4378\u0026ndash;4388. https://doi.org/10.1007/S00330-022-09336-8\u003c/li\u003e\n\u003cli\u003eYoung Park J, Min Lee S, Sub Lee J, et al (2022) Free-breathing dynamic T1WI using compressed sensing-golden angle radial sparse parallel imaging for liver MRI in patients with limited breath-holding capability. Eur J Radiol 152:110342. https://doi.org/10.1016/J.EJRAD.2022.110342\u003c/li\u003e\n\u003cli\u003eJiang Y, Pu D, Dang S, Yu N (2024) Effect of Breath Training on Image Quality of Chest Magnetic Resonance Free-breathing Sequence. Curr Med Imaging 20:. https://doi.org/10.2174/0115734056286441240123052927\u003c/li\u003e\n\u003cli\u003eKromrey ML, Tamada D, Johno H, et al (2020) Reduction of respiratory motion artifacts in gadoxetate-enhanced MR with a deep learning\u0026ndash;based filter using convolutional neural network. Eur Radiol 30:5923. https://doi.org/10.1007/S00330-020-07006-1\u003c/li\u003e\n\u003cli\u003eDuffy BA, Zhao L, Sepehrband F, et al (2021) Retrospective motion artifact correction of structural MRI images using deep learning improves the quality of cortical surface reconstructions. Neuroimage 230:117756. https://doi.org/10.1016/J.NEUROIMAGE.2021.117756\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"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":"Imaging, magnetic resonance, gadoxetic acid disodium, artifacts, contrast media","lastPublishedDoi":"10.21203/rs.3.rs-6296034/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6296034/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eGadoxetic acid-enhanced MRI is essential for detecting and characterizing focal liver lesions. However, transient severe motion artifacts in the arterial phase can degrade image quality. Gadoxetic acid dilution has been proposed to mitigate these artifacts, but its impact on multiple arterial phase acquisition remains unclear.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo evaluate the effect of gadoxetic acid dilution on image quality across multiple arterial phases in liver MRI, incorporating a phase-by-phase analysis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective study included 81 patients (52 men, 29 women; mean age 70.1 years) who underwent serial gadoxetic acid-enhanced MRI with undiluted and diluted contrast (1:1 saline dilution). MRI was performed on 1.5-T and 3.0-T scanners with a standardized injection rate of 1.0 mL/s. Two radiologists independently rated anatomic conspicuity, respiratory motion artifacts, and overall image quality using a five-point Likert scale. A phase-by-phase analysis was conducted after a three-month washout period. Wilcoxon signed-rank tests were used for statistical comparisons, and inter-rater agreement was assessed with quadratic kappa coefficients.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eInter-observer agreement was substantial (ƙ = 0.602\u0026ndash;0.702). The diluted method showed higher but statistically non-significant improvements in anatomic conspicuity (3.73 vs. 3.59, p\u0026thinsp;=\u0026thinsp;0.110), respiratory artifacts (3.54 vs. 3.41, p\u0026thinsp;=\u0026thinsp;0.291), and overall image quality (3.67 vs. 3.51, p\u0026thinsp;=\u0026thinsp;0.083). Phase-by-phase analysis revealed significant improvement in image quality for the first three arterial phases (p\u0026thinsp;=\u0026thinsp;0.003, 0.005, 0.050), with a trend toward improvement in the last phase (p\u0026thinsp;=\u0026thinsp;0.075).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eGadoxetic acid dilution improves image quality in early arterial phases of liver MRI, suggesting its potential to reduce motion artifacts.\u003c/p\u003e","manuscriptTitle":"Phase-by-phase analysis of the effect of contrast dilution on multiple arterial phase image quality in gadoxetic acid-enhanced liver MRI","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-03 10:24:11","doi":"10.21203/rs.3.rs-6296034/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":"c6de537b-9803-417b-a6b2-44f2f2b96b69","owner":[],"postedDate":"April 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-12T14:23:33+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-03 10:24:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6296034","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6296034","identity":"rs-6296034","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}