Cardiac atrial metabolism quantitative assessment with analog and digital TOF-PET/CT

Cardiac atrial metabolism quantitative assessment with analog and digital TOF-PET/CT | 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 Cardiac atrial metabolism quantitative assessment with analog and digital TOF-PET/CT Michel Hesse, Sébastien Marchandise, Bernhard Gerber, Véronique Roelants This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1719799/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: Evaluation of left atrial (LA) remodeling is becoming increasingly relevant in understanding several pathological cardiac conditions. While 18 F-FDG-PET/CT is currently the gold standard for metabolic evaluation of the left ventricle, it could be extended to LA metabolism evaluation using the latest PET technologies. We sought to perform a phantom study in order to determine the most appropriate advanced reconstruction algorithm in this context. Methods: The liver, heart cavity and walls of an anthropomorphic phantom were filled with typical patient 18 F-FDG activity concentrations. Acquisitions were performed on an analog and on a digital TOF-PET/CT, and reconstructed with and without resolution recovery (RR). For the RR the Richardson-Lucy method was used, either as a post processing of the reconstructed images through a third-party plug-in software, or through the algorithm implemented by the PET/CT manufacturer. Activity recoveries in the atria and ventricles and signal-to-noise ratios were evaluated to rate the reconstructions and identify the best reconstruction and RR parameters. The same methodology was applied on a patient cardiac study to validate the phantom results. Results: Analog PET/CT with third-party RR cannot improve the activity recovery without markedly degrading the image quality. For the digital PET/CT, the manufacturer RR reconstruction improved LA activity recovery from about 58% to about 70% when using 4 iterations and 15 subsets combined with a 5 RR iterations, while preserving images of diagnostic quality. Similar results were obtained on the SUV values for the patient study. Conclusions: The digital TOF-PET/CT combined with the manufacturer reconstruction with 4 iterations and 15 subsets together with 5 RR iterations can be used to quantitatively analyze the LA uptake in patient 18 F-FDG heart studies while still preserving image reading quality. This may lead to more precise cardiovascular disease status evaluation, especially when atria are concerned. Atria Quantitation TOF-PET/CT Cardiac Figures Figure 1 Figure 2 Figure 3 Figure 4 Background The prognostic value of the left atrium (LA) remodeling as biomarker of outcome in several cardiovascular diseases, such as atrial fibrillation or heart failure with preserved ejection fraction, is becoming increasingly recognised [ 1 ]. Echocardiography, cardiac magnetic resonance or cardiac computed tomography have emerged as interesting non-invasive imaging techniques able to evaluate left atrial remodeling in response to electrical, mechanical or metabolic stressors [ 2 , 3 ]. On the other hand, LA remodeling can also be characterized from his metabolic changes observed by 18 F-FDG imaging with PET/CT [ 4 – 6 ]. In fact, this modality is currently the gold standard for metabolic evaluation of the left ventricle and recently, it has been suggested that, despite the thinness of the LA wall, LA metabolism evaluation is also feasible using the latest PET camera technologies [ 7 , 8 ]. The last decade has seen the development of PET/CT systems along two axes that leaded to improvement of the spatial resolution. The first one is the strong improvement of the timing resolution from about 650 ps in the first time of flight (TOF)-PET/CT commercialized by Philips [ 9 ] to about 300 ps and even less in the last TOF-PET generations [ 10 – 12 ] (partially thanks to the use of digital SiPM detectors). The second one is the improvement of dedicated reconstruction algorithms using TOF and point spread function (PSF) information [ 10 – 13 ]. Consequently, the purpose of this cardiac phantom study was twofold: first, to compare images quality and uptake quantification obtained on an analog (first generation) and on a digital (last generation) LYSO TOF-PET/CT and, secondly, to determine the most appropriate advanced TOF + PSF reconstruction algorithm to quantify the LA uptake. The methodology was also evaluated clinically on one patient imaged with 18 F-FDG on both PET systems. Methods Phantoms An anthropomorphic Heart/thorax phantom (Radiology Support Devices, Inc, Long Beach, CA, USA) was used, whose liver, heart cavity and walls were filled with typical 18 F-FDG activity concentrations observed in patient studies, i.e., 5, 3.8 and 15 kBq/ml, respectively. The heart part of the phantom has only 2 fillable regions: the cavities (about 284 ml) and the walls (about 183 ml excluding the defects volumes). It also includes 2 unremovable defects of about 14 and 42 ml within the walls. The defect located in the interventricular septum (42 ml) was filled with the same 18 F-FDG concentration as the heart walls, while the defect in the lateral wall of the left ventricle (14 ml) was only filled with water. One bed position acquisitions of 10 minutes were performed, first using the analog camera (Philips Gemini TF64 TOF-PET/CT - Philips Healthcare, Cleveland OH) and then, immediately after, using the digital one (Philips Vereos TOF-PET/CT - Philips Healthcare, Cleveland OH). Reconstruction List file data were reconstructed with a 2mm voxel size using standard manufacturer OSEM algorithms with different numbers of iterations and subsets without and with RR. Images were first reconstructed using OSEM algorithms with the recommended manufacturer parameters, i.e. 3 iterations and 33 subsets for the analog camera and 2 iterations and 15 subsets for the digital camera, respectively. As only the digital PET/CT includes a manufacturer PSF RR correction based on the Richardson-Lucy method, a post-reconstruction PSF RR based on the same technique, implemented as a plug-in of the open source ImageJ software [ 14 , 15 ], was also tested on the reconstructed images of both TOF-PET/CT. The ImageJ RR plug-in has only one input parameter, i.e. the PSF FWHM that we measured for both PET systems using a 18 F point source set at the FOV center. In contrary, the manufacturer RR method includes a spatially variant PSF library and has 2 input parameters: a RR iteration number and a regularization factor [ 13 ]. For the digital PET, in addition to the standard manufacturer reconstruction without RR, we performed 3 reconstructions with the PSF RR method by setting the RR iteration parameter equal to 1, 5 and 10. The regularization parameter was not changed and was equal to 6 in all cases. Activity recovery assessment Due to the low dose CT scan, as routinely used for patients, jointly to the close HU values of plexiglass and water, automatic drawing of the VOIs based on a threshold was not possible. So volumes of interest (VOI) were manually drawn around the right (RA) and left atria (LA) and ventricles (RLV) on the CT image. Measured 18 F-FDG activity concentrations in the atria and ventricles walls were compared to exact values to assess the activity recovery. These CT VOIs were applied on the PET images to assess the walls activity, whatever the analyzed PET reconstruction (no adaptation of the VOIs to the PET activity was performed) to avoid introduction of a bias in the quantitative comparison between reconstructions with and without RR. Signal to noise ratio assessment To evaluate and compare the PET images reading quality, signal to noise ratio (SNR) values were measured from a VOI obtained by using a 9 kBq/ml threshold, i.e. the mean activity concentration of the heart cavity and walls, on the PET original image, i.e. without RR, resulting in a volume including both the atria and ventricles walls. The SNR was evaluated from the VOI by dividing the mean counts value by the standard deviation (SD). Patient To validate the phantom results, one patient of the ongoing prospective study TRIATLON (EudraCT number 2019-001813-17) was acquired on both TOF-PET/CT and these data were analyzed similarly to the phantom data. The TRIATLON study was approved by the Institutional Ethics Committee of Brussels Cliniques Universitaires Saint-Luc, and all patients provided written informed consent. One bed position acquisition of 10 minutes was performed on the Vereos 90 minutes after intravenous injection of about 8 mCi of 18 F-FDG, then repeated directly after on the Gemini. Acquisitions were non gated and reconstructed with a 2mm voxel size using 3 iterations and 33 subsets for the Gemini and 4 iterations and 15 subsets for the Vereos acquisition, respectively. As for a patient the actual uptakes are unknown, the activity recovery and SNR assessments were replaced by the measures of the SUV mean and SD values of the considered VOI. Results Phantoms The PET images of the anthropomorphic phantom acquired on the analog and on the digital PET/CT are depicted on Fig. 1 . The reconstructions without RR already clearly show the better image quality (less noise and better delineation of the walls) provided by the digital TOF-PET/CT (Fig. 1 D) versus the analog one (Fig. 1 A) due to its improved physical characteristics [ 10 , 11 ]. As expected from deconvolution techniques [ 16 ], such as the ImageJ plug-in Richardson-Lucy method [ 14 , 15 ] (Fig. 1 B and 1 E), the spatial resolution improvement (characterized by the appearance of a thinner wall) is accompanied by an image noise increase, especially in the case of the analog PET/CT (Fig. 1 B). For the digital PET/CT (Fig. 1 F), the manufacturer reconstruction RR algorithm which includes the spatially variant PSF, appears to provide, in 5 iterations, a spatial resolution as good as the ImageJ RR method together with a less noisy image appearance. As seen on Fig. 2 , VOIs were manually drawn around the right and left atria and around the ventricles walls of the cardiac phantom. The defect located in the lateral wall of the left ventricle and the remaining air bubbles in the phantom walls were excluded from the VOIs. As we are looking for the best imaging technique for atrial uptake evaluation, we optimized the reconstruction parameters only for the images obtained with the Vereos digital TOF-PET/CT. The convergence of the LA activity recovery as a function of the reconstruction iteration number is displayed on Fig. 3A. Similar curves are obtained for the RA and RLV activity recoveries with slightly different absolute values (data not shown). For all reconstructions, the convergence of the activity recovery is reached at about 60 OSEM iterations. The maximum LA activity recovery increases from about 58% without RR to about 74% with a 10 iterations RR. Figure 3B shows that the SNR in the digital PET final image is impacted by both the reconstruction and the RR iteration numbers. We choose as best reconstruction parameters, 4 iterations x 15 subsets for the OSEM algorithm and of 5 iterations for the manufacturer RR algorithm (we will later discuss this choice). Table 1 Activity recoveries for the right and left atria and ventricles walls together with the SNR for the standard manufacturer reconstructions on the Gemini and Vereos TOF-PET/CT, without RR, with ImageJ RR and, for the Vereos, with the manufacturer PSF RR. Activity recoveries (%) SNR TOF-PET/CT Reconstruction Left atrium Right atrium Ventricles Gemini without RR 60 63 74 6.8 3 it x 33 subs with third party RR 73 71 81 3.9 Vereos without RR 58 57 72 8.9 4 it x 15 subs with ImageJ RR 68 66 78 5.1 with 5 it PSF RR 70 71 80 5.6 Table 1 illustrates the quantitative impact of the RR correction on the activity recoveries in the right and left atria and ventricles walls and on the image quality for both TOF-PET/CT. Standard reconstruction parameters were used for the Gemini while optimum values were selected for the Vereos. As seen on Fig. 1 , using a RR method leads to an improved spatial resolution, and as a consequence to an improved activity recovery, whatever the TOF-PET/CT considered. However, the SNR, quantifying the image quality, is already worse in the analog PET image without RR and drops strongly after applying the ImageJ RR. Using the selected optimum set of manufacturer RR reconstruction parameters for the digital TOF-PET/CT provides improved activity recoveries of about 70% for the atria and 80% for the ventricles, i.e. about the same as the ImageJ RR method, but with a drop of only 37% of the SNR versus 43% with the ImageJ RR. Patient Figure 4 compares the PET images of one patient FDG cardiac studies on the Gemini and Vereos TOF-PET/CT and reconstructed using OSEM algorithms with the standard 3 iterations and 33 subsets for the Gemini and the optimized 4 iterations and 15 subsets for the Vereos, respectively. Like for the phantom images, the Vereos reconstruction without RR is clearly superior to the Gemini one, as can be seen from the hardly visible left atrium wall and interatrial septum on the Gemini image (Fig. 4 A). On the Vereos images, the atria walls become better defined after RR, with the manufacturer spatially variant PSF method providing the best results in terms of image quality (Fig. 4 F). Table 2 provides a quantitative analysis of the patient cardiac PET reconstructions. The RR increases the mean SUV but also the SD, as expected from the phantom results (Table 1 ). Like for the heart phantom, the manufacturer spatially variant PSF RR reconstruction available on the Vereos TOF-PET/CT provides the best compromise between the atria uptake improvement and the noise level increase, i.e. highest mean SUV associated with SD values similar to the ImageJ RR. Left atrium Right atrium Left ventricle TOF-PET/CT Reconstruction Mean SUV SD SUV Mean SUV SD SUV Mean SUV SD SUV Gemini without RR 2.16 0.87 1.95 0.54 11.84 2.92 3 it x 33 subs with third party RR 2.26 1.45 2.33 1.01 13.49 4.52 Vereos without RR 2.13 0.64 2.10 0.59 11.27 2.49 4 it x 15 subs with ImageJ RR 2.24 1.03 2.37 0.93 12.59 3.68 with 5 it PSF RR 2.44 0.99 2.50 0.90 13.84 3.71 Table 2 : SUV mean and standard deviation (SD) values for the right and left atria and left ventricle walls of a patient cardiac study for the manufacturer reconstructions on the Gemini and Vereos TOF-PET/CT, without RR, with ImageJ RR and, for the Vereos, with the manufacturer PSF RR. Discussion To the best of our knowledge, it is the first time that a phantom study is performed to identify the best reconstruction algorithm to compare the LA uptake in patient cardiac FDG studies between an analog and a digital TOF-PET/CT. As the older analog TOF-PET/CT system does not include any RR option in the reconstruction algorithm, a third party post-reconstruction RR based on the Richardson-Lucy method was considered. While a third party post-reconstruction RR method clearly improves the spatial resolution and cardiac walls activity recoveries by using a constant PSF (see figure 1 and table 1), it is not optimized to the PET image specificities like the manufacturer algorithm that includes a RR that takes into account the variations of the PSF according to the location in the field of view [13]. This results in noisier images, especially in the case of the analog TOF-PET/CT whose original reconstruction is already more impacted by noise (figure 1). Noisier images will result in less reliable activity measurements as very sensitive to the VOIs drawing. It should then be recommended to use the best TOF-PET/CT available to perform this kind of quantitative studies. Figure 3B shows, for the Vereos TOF-PET/CT, that when no RR or only a light RR (only 1 iteration) is performed, the SNR behaves like an increasing function of the LA activity recovery, while for higher RR iteration numbers, it becomes a decreasing function. This induces that a compromise has to be made between the LA activity recovery and the image reading quality. A post filtering of the image is still possible to make a noisier image more readable. However, one should be careful when pushing the RR algorithms too far (disregarding the SNR) as one might end up with artefactual images that are no more representative of the activity distribution, typically by producing edge artefacts [18,19]. Based on the evaluation of the image quality by our nuclear medicine physicians, we selected as best reconstruction parameters of the OSEM algorithm the values of 4 iterations and 15 subsets as these values correspond to the beginning of the convergence plateau of the activity recovery (see figure 3A), and higher values lead to noisier images. For the manufacturer RR parameters we decided to limit the number of iterations to 5 as the SNR drops quite fast for higher values (see figure 3B). In the present study we did not play with the regularization parameter of the manufacturer RR algorithm that was fixed to the recommended value of 6. Optimizing this parameter, whose function is to drive the image smoothness, might still improve the image quality by reducing the noise level but we do not expect it to alter much the optimized set of parameters found in the present quantitative study. Together these parameters provide a LA activity recovery of about 70%. The FDG cardiac studies performed on both TOF-PET/CT with the same patient nicely confirmed the results obtained with the phantom. Compared to the phantom the patient heart was about 10 percent larger, but ventricular and atrial wall thicknesses were very similar, with values measured on RMI between 0.9 and 1.5 cm for the LV and between 1 and 3 mm for the LA. The limited spatial resolution of the Gemini PET makes it unfit to study the atria metabolism as the atria walls and interatrial septum are hardly seen on the reconstructed images (see figure 4). On the other hand, these structures are already visible on the Vereos reconstruction without RR, and become sharper when using a RR algorithm. The manufacturer reconstruction including the PSF RR still provide a better image quality compared to post-reconstruction RR (see figure 4 and table 2). Unlike the cardiac phantom filled in the present study with a homogeneous activity distribution in the walls, patients may suffer from pathologies inducing heterogeneities in RA or LA uptake. However, resolution recovery methods tend to reconcentrate the detected activity in the regions where it originates. If heterogeneities larger than the spatial resolution of the PET system are located in the RA or LA walls, they will still be visible after RR. One limitation of the present study is that patient motions, like breathing and cardiac motions, were not taken into account. The heart motion impact on the present results is difficult to evaluate. Using cardiac gating acquisition would help the quantification with the RR method applied on each gated bin separately, and afterwards summing together the activities of the bins in order to recover the non-gated statistics. Without gating the RA and LA walls on the PET image are enlarged by the heart motion. The RR cannot correct for that motion but it will still bring back the activity in that enlarged wall, improving the quantification as anyway in that case the VOIs will have to be enlarged too to take the motion blurring into account. As the reconstruction algorithms with RR, seen as black-boxes by the end user, might strongly differ between manufacturers, the optimized parameters found in this study are only adapted to the Philips Vereos TOF-PET/CT. The observed trends for the activity recovery and for the SNR convergences would probably be similar for other systems but this needs to be checked per TOF-PET/CT system in order to extract the best set of reconstruction parameters. Conclusions The Philips Vereos TOF-PET/CT images reconstructed with the manufacturer 4 iterations/15 subsets OSEM algorithm including a PSF RR with 5 iterations/6 regularization can be used to quantitatively analyze the left atrium uptake in patient 18 F-FDG heart studies while still preserving image reading quality. This may lead to more precise evaluation of the metabolic cardiac status of cardiovascular disease, especially when atria are concerned. Abbreviations LA: Left atrium RA: Right atrium RLV: Right and left ventricles TOF-PET/CT: Time of flight positron emission tomography/computed tomography PSF: Point spread function OSEM: Ordered subset expectation maximization SUV: Standardized uptake value SD: Standard deviation FDG: Fluoro-deoxy-glucose VOI: Volume of interest Declarations Ethics approval and consent to participate All patients provided written informed consent. The TRIATLON study was approved by the Institutional Ethics Committee of Brussels Cliniques Universitaires Saint-Luc. All methods were carried out in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards Consent for publication Not applicable Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding Sébastien Marchandise received funding from a Daiichi Sankyo grant. Authors' contributions MH has performed the phantom scans and analysed the corresponding data. SM, BG and VR have managed the patient scans of the TRIATHLON study, and analyzed the patient data. MH and VR have written the article. All authors read and approved the final manuscript. Acknowledgements Not applicable. 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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-1719799","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":112379298,"identity":"ee4bc4f9-03e2-4bcb-a45e-4698220c2397","order_by":0,"name":"Michel Hesse","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/UlEQVRIiWNgGAWjYDACZgY2BoYChgQw5wMDgwyYkcAAFcGpxQCigHEGAwMPYS0MSFqYeWBaGPBo0W1nfvbggwFDHj//8YePbdvsePglcgw/PNwBFMGhxewwm7nhDAOGYskZOcbGuW3JPCCGROIZoEgDLi08bNI8BgyJG24AGbltB3gMbqQlSCS2AUUO4NHyB6hl//njz39bQrQk/wBp2Y9PCwPIFoYEM2ZGsJbkYxBbcPvFTLLHQCJxxo0cY8mec0C/9Dw+ZpHYJlEsgcuW84efSfyosEns7z/+8MOPMjs5fvbE5ps/22zy+HF4HwokiBAZBaNgFIyCUUA8AADVE1UoCk8rVQAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-9434-751X","institution":"Cliniques Universitaires Saint-Luc","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Michel","middleName":"","lastName":"Hesse","suffix":""},{"id":112379299,"identity":"3700fe8c-abc5-4d70-b131-294a75668fd9","order_by":1,"name":"Sébastien Marchandise","email":"","orcid":"","institution":"Cliniques Universitaires Saint-Luc","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sébastien","middleName":"","lastName":"Marchandise","suffix":""},{"id":112379300,"identity":"cd1966fe-6e95-4ee6-8ed4-fea146e20a21","order_by":2,"name":"Bernhard Gerber","email":"","orcid":"","institution":"Cliniques Universitaires Saint-Luc","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Bernhard","middleName":"","lastName":"Gerber","suffix":""},{"id":112379301,"identity":"e456ebac-24bc-4d02-8b27-a2b9828a3b26","order_by":3,"name":"Véronique Roelants","email":"","orcid":"","institution":"Cliniques Universitaires Saint-Luc","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Véronique","middleName":"","lastName":"Roelants","suffix":""}],"badges":[],"createdAt":"2022-06-02 14:21:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1719799/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1719799/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":22748912,"identity":"9b24f200-5f5e-42c3-b2ec-9cfc125555d5","added_by":"auto","created_at":"2022-06-16 22:13:35","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":60059,"visible":true,"origin":"","legend":"\u003cp\u003ePET reconstructions of the heart insert of the anthropomorphic phantom. A,B: Gemini acquisition; D,E,F: Vereos acquisition. A,D: standard manufacturer reconstructions; B,E: reconstructions with ImageJ (IJ) RR; F: standard manufacturer reconstruction including Philips (Ph) RR with 5 iterations/6 regularization; C: manually drawn VOIs around the left atrium (blue), the right atrium (green) and the ventricles (red) shown on the standard Vereos image\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1719799/v1/cf9e222e7ada00db0c71f1be.jpg"},{"id":22749034,"identity":"d3ce09e5-37d0-46fe-b4af-a3b337d3a67f","added_by":"auto","created_at":"2022-06-16 22:18:36","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":57559,"visible":true,"origin":"","legend":"\u003cp\u003ePET reconstructions of a patient FDG cardiac study. A,B: Gemini acquisition; D,E,F: Vereos acquisition. A,D: manufacturer reconstructions; B,E: reconstructions with ImageJ (IJ) RR; F: optimized manufacturer reconstruction including Philips (Ph) RR with 5 iterations/6 regularization; C: manually drawn VOIs around the right (in green) and left (in blue) atria shown on the standard Vereos image\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1719799/v1/4e10f544864d37d92d6287bf.jpg"},{"id":22748913,"identity":"8b601e15-d91d-41ba-9b39-3e2c8c8a3482","added_by":"auto","created_at":"2022-06-16 22:13:36","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":51704,"visible":true,"origin":"","legend":"\u003cp\u003eA: Activity recovery values for the left atrium wall as a function of the iteration number of the reconstruction OSEM algorithm for the digital acquisition. B: SNR value with respect to the LA wall activity recovery. Red squares correspond to the reconstruction without RR (0 RR). Blue triangles, green diamonds and purple circle dots correspond to the reconstruction with the manufacturer RR using 1, 5 and 10 RR iterations, respectively\u003c/p\u003e\u003cp\u003eFigure 3B shows that the SNR in the digital PET final image is impacted by both the reconstruction and the RR iteration numbers.\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1719799/v1/d6a2c0b8dc685a4108162d9e.jpg"},{"id":22748915,"identity":"8564a6be-fafd-422d-b4a2-0df71c760e1f","added_by":"auto","created_at":"2022-06-16 22:13:36","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":82722,"visible":true,"origin":"","legend":"\u003cp\u003ePET reconstructions of a patient FDG cardiac study. A,B: Gemini acquisition; D,E,F: Vereos acquisition. A,D: manufacturer reconstructions; B,E: reconstructions with ImageJ (IJ) RR; F: optimized manufacturer reconstruction including Philips (Ph) RR with 5 iterations/6 regularization; C: manually drawn VOIs around the right (in green) and left (in blue) atria shown on the standard Vereos image\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1719799/v1/3a437990ddbb692facfd5391.jpg"},{"id":24099515,"identity":"f02c76cc-46bc-46a7-b2eb-13bd733102b3","added_by":"auto","created_at":"2022-07-20 15:39:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":424601,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1719799/v1/b2d3a05a-07e7-4b78-9e9c-c957efbc07af.pdf"}],"financialInterests":"","formattedTitle":"Cardiac atrial metabolism quantitative assessment with analog and digital TOF-PET/CT","fulltext":[{"header":"Background","content":"\u003cp\u003eThe prognostic value of the left atrium (LA) remodeling as biomarker of outcome in several cardiovascular diseases, such as atrial fibrillation or heart failure with preserved ejection fraction, is becoming increasingly recognised [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Echocardiography, cardiac magnetic resonance or cardiac computed tomography have emerged as interesting non-invasive imaging techniques able to evaluate left atrial remodeling in response to electrical, mechanical or metabolic stressors [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. On the other hand, LA remodeling can also be characterized from his metabolic changes observed by \u003csup\u003e18\u003c/sup\u003eF-FDG imaging with PET/CT [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In fact, this modality is currently the gold standard for metabolic evaluation of the left ventricle and recently, it has been suggested that, despite the thinness of the LA wall, LA metabolism evaluation is also feasible using the latest PET camera technologies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe last decade has seen the development of PET/CT systems along two axes that leaded to improvement of the spatial resolution. The first one is the strong improvement of the timing resolution from about 650 ps in the first time of flight (TOF)-PET/CT commercialized by Philips [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] to about 300 ps and even less in the last TOF-PET generations [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] (partially thanks to the use of digital SiPM detectors). The second one is the improvement of dedicated reconstruction algorithms using TOF and point spread function (PSF) information [\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConsequently, the purpose of this cardiac phantom study was twofold: first, to compare images quality and uptake quantification obtained on an analog (first generation) and on a digital (last generation) LYSO TOF-PET/CT and, secondly, to determine the most appropriate advanced TOF\u0026thinsp;+\u0026thinsp;PSF reconstruction algorithm to quantify the LA uptake. The methodology was also evaluated clinically on one patient imaged with \u003csup\u003e18\u003c/sup\u003eF-FDG on both PET systems.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePhantoms\u003c/h2\u003e \u003cp\u003eAn anthropomorphic Heart/thorax phantom (Radiology Support Devices, Inc, Long Beach, CA, USA) was used, whose liver, heart cavity and walls were filled with typical \u003csup\u003e18\u003c/sup\u003eF-FDG activity concentrations observed in patient studies, i.e., 5, 3.8 and 15 kBq/ml, respectively. The heart part of the phantom has only 2 fillable regions: the cavities (about 284 ml) and the walls (about 183 ml excluding the defects volumes). It also includes 2 unremovable defects of about 14 and 42 ml within the walls. The defect located in the interventricular septum (42 ml) was filled with the same \u003csup\u003e18\u003c/sup\u003eF-FDG concentration as the heart walls, while the defect in the lateral wall of the left ventricle (14 ml) was only filled with water.\u003c/p\u003e \u003cp\u003eOne bed position acquisitions of 10 minutes were performed, first using the analog camera (Philips Gemini TF64 TOF-PET/CT - Philips Healthcare, Cleveland OH) and then, immediately after, using the digital one (Philips Vereos TOF-PET/CT - Philips Healthcare, Cleveland OH).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eReconstruction\u003c/h2\u003e \u003cp\u003eList file data were reconstructed with a 2mm voxel size using standard manufacturer OSEM algorithms with different numbers of iterations and subsets without and with RR. Images were first reconstructed using OSEM algorithms with the recommended manufacturer parameters, i.e. 3 iterations and 33 subsets for the analog camera and 2 iterations and 15 subsets for the digital camera, respectively. As only the digital PET/CT includes a manufacturer PSF RR correction based on the Richardson-Lucy method, a post-reconstruction PSF RR based on the same technique, implemented as a plug-in of the open source ImageJ software [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], was also tested on the reconstructed images of both TOF-PET/CT.\u003c/p\u003e \u003cp\u003eThe ImageJ RR plug-in has only one input parameter, i.e. the PSF FWHM that we measured for both PET systems using a \u003csup\u003e18\u003c/sup\u003eF point source set at the FOV center. In contrary, the manufacturer RR method includes a spatially variant PSF library and has 2 input parameters: a RR iteration number and a regularization factor [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. For the digital PET, in addition to the standard manufacturer reconstruction without RR, we performed 3 reconstructions with the PSF RR method by setting the RR iteration parameter equal to 1, 5 and 10. The regularization parameter was not changed and was equal to 6 in all cases.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eActivity recovery assessment\u003c/h2\u003e \u003cp\u003eDue to the low dose CT scan, as routinely used for patients, jointly to the close HU values of plexiglass and water, automatic drawing of the VOIs based on a threshold was not possible. So volumes of interest (VOI) were manually drawn around the right (RA) and left atria (LA) and ventricles (RLV) on the CT image. Measured \u003csup\u003e18\u003c/sup\u003eF-FDG activity concentrations in the atria and ventricles walls were compared to exact values to assess the activity recovery.\u003c/p\u003e \u003cp\u003eThese CT VOIs were applied on the PET images to assess the walls activity, whatever the analyzed PET reconstruction (no adaptation of the VOIs to the PET activity was performed) to avoid introduction of a bias in the quantitative comparison between reconstructions with and without RR.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eSignal to noise ratio assessment\u003c/h2\u003e \u003cp\u003eTo evaluate and compare the PET images reading quality, signal to noise ratio (SNR) values were measured from a VOI obtained by using a 9 kBq/ml threshold, i.e. the mean activity concentration of the heart cavity and walls, on the PET original image, i.e. without RR, resulting in a volume including both the atria and ventricles walls. The SNR was evaluated from the VOI by dividing the mean counts value by the standard deviation (SD).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePatient\u003c/h2\u003e \u003cp\u003eTo validate the phantom results, one patient of the ongoing prospective study TRIATLON (EudraCT number 2019-001813-17) was acquired on both TOF-PET/CT and these data were analyzed similarly to the phantom data. The TRIATLON study was approved by the Institutional Ethics Committee of Brussels Cliniques Universitaires Saint-Luc, and all patients provided written informed consent.\u003c/p\u003e \u003cp\u003eOne bed position acquisition of 10 minutes was performed on the Vereos 90 minutes after intravenous injection of about 8 mCi of \u003csup\u003e18\u003c/sup\u003eF-FDG, then repeated directly after on the Gemini. Acquisitions were non gated and reconstructed with a 2mm voxel size using 3 iterations and 33 subsets for the Gemini and 4 iterations and 15 subsets for the Vereos acquisition, respectively.\u003c/p\u003e \u003cp\u003eAs for a patient the actual uptakes are unknown, the activity recovery and SNR assessments were replaced by the measures of the SUV mean and SD values of the considered VOI.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePhantoms\u003c/h2\u003e \u003cp\u003eThe PET images of the anthropomorphic phantom acquired on the analog and on the digital PET/CT are depicted on Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The reconstructions without RR already clearly show the better image quality (less noise and better delineation of the walls) provided by the digital TOF-PET/CT (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD) versus the analog one (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA) due to its improved physical characteristics [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. As expected from deconvolution techniques [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], such as the ImageJ plug-in Richardson-Lucy method [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE), the spatial resolution improvement (characterized by the appearance of a thinner wall) is accompanied by an image noise increase, especially in the case of the analog PET/CT (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). For the digital PET/CT (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eF), the manufacturer reconstruction RR algorithm which includes the spatially variant PSF, appears to provide, in 5 iterations, a spatial resolution as good as the ImageJ RR method together with a less noisy image appearance.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAs seen on Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, VOIs were manually drawn around the right and left atria and around the ventricles walls of the cardiac phantom. The defect located in the lateral wall of the left ventricle and the remaining air bubbles in the phantom walls were excluded from the VOIs.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAs we are looking for the best imaging technique for atrial uptake evaluation, we optimized the reconstruction parameters only for the images obtained with the Vereos digital TOF-PET/CT. The convergence of the LA activity recovery as a function of the reconstruction iteration number is displayed on Fig.\u0026nbsp;3A. Similar curves are obtained for the RA and RLV activity recoveries with slightly different absolute values (data not shown). For all reconstructions, the convergence of the activity recovery is reached at about 60 OSEM iterations. The maximum LA activity recovery increases from about 58% without RR to about 74% with a 10 iterations RR.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure 3B shows that the SNR in the digital PET final image is impacted by both the reconstruction and the RR iteration numbers.\u003c/p\u003e \u003cp\u003eWe choose as best reconstruction parameters, 4 iterations x 15 subsets for the OSEM algorithm and of 5 iterations for the manufacturer RR algorithm (we will later discuss this choice).\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\u003eActivity recoveries for the right and left atria and ventricles walls together with the SNR for the standard manufacturer reconstructions on the Gemini and Vereos TOF-PET/CT, without RR, with ImageJ RR and, for the Vereos, with the manufacturer PSF RR.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eActivity recoveries (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSNR\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTOF-PET/CT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReconstruction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLeft atrium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRight atrium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVentricles\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGemini\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ewithout RR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e6.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 it x 33 subs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ewith third party RR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVereos\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ewithout RR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e8.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4 it x 15 subs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ewith ImageJ RR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ewith 5 it PSF RR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e illustrates the quantitative impact of the RR correction on the activity recoveries in the right and left atria and ventricles walls and on the image quality for both TOF-PET/CT. Standard reconstruction parameters were used for the Gemini while optimum values were selected for the Vereos. As seen on Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, using a RR method leads to an improved spatial resolution, and as a consequence to an improved activity recovery, whatever the TOF-PET/CT considered. However, the SNR, quantifying the image quality, is already worse in the analog PET image without RR and drops strongly after applying the ImageJ RR. Using the selected optimum set of manufacturer RR reconstruction parameters for the digital TOF-PET/CT provides improved activity recoveries of about 70% for the atria and 80% for the ventricles, i.e. about the same as the ImageJ RR method, but with a drop of only 37% of the SNR versus 43% with the ImageJ RR.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003ePatient\u003c/h2\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e compares the PET images of one patient FDG cardiac studies on the Gemini and Vereos TOF-PET/CT and reconstructed using OSEM algorithms with the standard 3 iterations and 33 subsets for the Gemini and the optimized 4 iterations and 15 subsets for the Vereos, respectively. Like for the phantom images, the Vereos reconstruction without RR is clearly superior to the Gemini one, as can be seen from the hardly visible left atrium wall and interatrial septum on the Gemini image (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). On the Vereos images, the atria walls become better defined after RR, with the manufacturer spatially variant PSF method providing the best results in terms of image quality (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003eF).\u003c/p\u003e \u003cp\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\u003eprovides a quantitative analysis of the patient cardiac PET reconstructions. The RR increases the mean SUV but also the SD, as expected from the phantom results (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Like for the heart phantom, the manufacturer spatially variant PSF RR reconstruction available on the Vereos TOF-PET/CT provides the best compromise between the atria uptake improvement and the noise level increase, i.e. highest mean SUV associated with SD values similar to the ImageJ RR.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eLeft atrium\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eRight atrium\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eLeft ventricle\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTOF-PET/CT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReconstruction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean SUV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSD SUV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean SUV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSD SUV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMean SUV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSD SUV\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGemini\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ewithout RR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.92\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 it x 33 subs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ewith third party RR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e13.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVereos\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ewithout RR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4 it x 15 subs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ewith ImageJ RR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ewith 5 it PSF RR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e13.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e: SUV mean and standard deviation (SD) values for the right and left atria and left ventricle walls of a patient cardiac study for the manufacturer reconstructions on the Gemini and Vereos TOF-PET/CT, without RR, with ImageJ RR and, for the Vereos, with the manufacturer PSF RR.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo the best of our knowledge, it is the first time that a phantom study is performed to identify the best reconstruction algorithm to compare the LA uptake in patient cardiac FDG studies between an analog and a digital TOF-PET/CT. As the older analog TOF-PET/CT system does not include any RR option in the reconstruction algorithm, a third party post-reconstruction RR based on the Richardson-Lucy method was considered.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWhile a third party post-reconstruction RR method clearly improves the spatial resolution and cardiac walls activity recoveries by using a constant PSF (see figure 1 and table 1), it is not optimized to the PET image specificities like the manufacturer algorithm that includes a RR that takes into account the variations of the PSF according to the location in the field of view [13]. This results in noisier images, especially in the case of the analog TOF-PET/CT whose original reconstruction is already more impacted by noise (figure 1). Noisier images will result in less reliable activity measurements as very sensitive to the VOIs drawing. It should then be recommended to use the best TOF-PET/CT available to perform this kind of quantitative studies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFigure 3B shows, for the Vereos TOF-PET/CT, that when no RR or only a light RR (only 1 iteration) is performed, the SNR behaves like an increasing function of the LA activity recovery, while for higher RR iteration numbers, it becomes a decreasing function. This induces that a compromise has to be made between the LA activity recovery and the image reading quality. A post filtering of the image is still possible to make a noisier image more readable. However, one should be careful when pushing the RR algorithms too far (disregarding the SNR) as one might end up with artefactual images that are no more representative of the activity distribution, typically by producing edge artefacts [18,19].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBased on the evaluation of the image quality by our nuclear medicine physicians, we selected as best reconstruction parameters of the OSEM algorithm the values of 4 iterations and 15 subsets as these values correspond to the beginning of the convergence plateau of the activity recovery (see figure 3A), and higher values lead to noisier images. For the manufacturer RR parameters we decided to limit the number of iterations to 5 as the SNR drops quite fast for higher values (see figure 3B). In the present study we did not play with the regularization parameter of the manufacturer RR algorithm that was fixed to the recommended value of 6. Optimizing this parameter, whose function is to drive the image smoothness, might still improve the image quality by reducing the noise level but we do not expect it to alter much the optimized set of parameters found in the present quantitative study. Together these parameters provide a LA activity recovery of about 70%.\u003c/p\u003e\n\u003cp\u003eThe FDG cardiac studies performed on both TOF-PET/CT with the same patient nicely confirmed the results obtained with the phantom. Compared to the phantom the patient heart was about 10 percent larger, but ventricular and atrial wall thicknesses were very similar, with values measured on RMI between 0.9 and 1.5 cm for the LV and between 1 and 3 mm for the LA. The limited spatial resolution of the Gemini PET makes it unfit to study the atria metabolism as the atria walls and interatrial septum are hardly seen on the reconstructed images (see figure 4). On the other hand, these structures are already visible on the Vereos reconstruction without RR, and become sharper when using a RR algorithm. The manufacturer reconstruction including the PSF RR still provide a better image quality compared to post-reconstruction RR (see figure 4 and table 2). \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUnlike the cardiac phantom filled in the present study with a homogeneous activity distribution in the walls, patients may suffer from pathologies inducing heterogeneities in RA or LA uptake. However, resolution recovery methods tend to reconcentrate the detected activity in the regions where it originates. If heterogeneities larger than the spatial resolution of the PET system are located in the RA or LA walls, they will still be visible after RR.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOne limitation of the present study is that patient motions, like breathing and cardiac motions, were not taken into account. The heart motion impact on the present results is difficult to evaluate. Using cardiac gating acquisition would help the quantification with the RR method applied on each gated bin separately, and afterwards summing together the activities of the bins in order to recover the non-gated statistics. Without gating the RA and LA walls on the PET image are enlarged by the heart motion. The RR cannot correct for that motion but it will still bring back the activity in that enlarged wall, improving the quantification as anyway in that case the VOIs will have to be enlarged too to take the motion blurring into account. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs the reconstruction algorithms with RR, seen as black-boxes by the end user, might strongly differ between manufacturers, the optimized parameters found in this study are only adapted to the Philips Vereos TOF-PET/CT. The observed trends for the activity recovery and for the SNR convergences would probably be similar for other systems but this needs to be checked per TOF-PET/CT system in order to extract the best set of reconstruction parameters.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe Philips Vereos TOF-PET/CT images reconstructed with the manufacturer 4 iterations/15 subsets OSEM algorithm including a PSF RR with 5 iterations/6 regularization can be used to quantitatively analyze the left atrium uptake in patient \u003csup\u003e18\u003c/sup\u003eF-FDG heart studies while still preserving image reading quality. This may lead to more precise evaluation of the metabolic cardiac status of cardiovascular disease, especially when atria are concerned.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eLA: Left atrium\u003c/p\u003e\n\u003cp\u003eRA: Right atrium\u003c/p\u003e\n\u003cp\u003eRLV: Right and left ventricles\u003c/p\u003e\n\u003cp\u003eTOF-PET/CT: Time of flight positron emission tomography/computed tomography\u003c/p\u003e\n\u003cp\u003ePSF: Point spread function\u003c/p\u003e\n\u003cp\u003eOSEM: Ordered subset expectation maximization\u003c/p\u003e\n\u003cp\u003eSUV: Standardized uptake value\u003c/p\u003e\n\u003cp\u003eSD: Standard deviation\u003c/p\u003e\n\u003cp\u003eFDG: Fluoro-deoxy-glucose\u003c/p\u003e\n\u003cp\u003eVOI: Volume of interest\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients provided written informed consent. The TRIATLON study was approved by the Institutional Ethics Committee of Brussels Cliniques Universitaires Saint-Luc.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll methods were carried out in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS\u0026eacute;bastien Marchandise received funding from a Daiichi Sankyo grant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMH has performed the phantom scans and analysed the corresponding data. SM, BG and VR have managed the patient scans of the TRIATHLON study, and analyzed the patient data. MH and VR have written the article. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eThomas L, Abhayaratna W. Left atrial reverse remodeling. Mechanisms, evaluation, and clinical significance. J Am Coll Cardiol Img. 2017;10:65\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlfuhied A, Kanagala P, McCann G, et al. Multi-modility assessment and role of left atrial function as an imaging biomarker in cardiovascular disease. Int J Cardiovasc Imaging. 2021;37:3355\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlsen FJ, Bertelsen L, de Knegt MC, et al. 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Asia Ocean J Nucl Med Biol. 2017 Spring;5(2):134\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMunk OL, Tolbod LP, Hansen SB, et al. Point-spread function reconstructed PET images of sub-centimeter lesions are not quantitative, EJNMMI Phys 2017;4.\u003c/span\u003e\u003c/li\u003e\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":"Atria, Quantitation, TOF-PET/CT, Cardiac","lastPublishedDoi":"10.21203/rs.3.rs-1719799/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1719799/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003eEvaluation of left atrial (LA) remodeling is becoming increasingly relevant in understanding several pathological cardiac conditions. While \u003csup\u003e18\u003c/sup\u003eF-FDG-PET/CT is currently the gold standard for metabolic evaluation of the left ventricle, it could be extended to LA metabolism evaluation using the latest PET technologies. We sought to perform a phantom study in order to determine the most appropriate advanced reconstruction algorithm in this context.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003eThe liver, heart cavity and walls of an anthropomorphic phantom were filled with typical patient \u003csup\u003e18\u003c/sup\u003eF-FDG activity concentrations. Acquisitions were performed on an analog and on a digital TOF-PET/CT, and reconstructed with and without resolution recovery (RR). For the RR the Richardson-Lucy method was used, either as a post processing of the reconstructed images through a third-party plug-in software, or through the algorithm implemented by the PET/CT manufacturer. Activity recoveries in the atria and ventricles and signal-to-noise ratios were evaluated to rate the reconstructions and identify the best reconstruction and RR parameters. The same methodology was applied on a patient cardiac study to validate the phantom results.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eAnalog PET/CT with third-party RR cannot improve the activity recovery without markedly degrading the image quality. For the digital PET/CT, the manufacturer RR reconstruction improved LA activity recovery from about 58% to about 70% when using 4 iterations and 15 subsets combined with a 5 RR iterations, while preserving images of diagnostic quality. Similar results were obtained on the SUV values for the patient study.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003eThe digital TOF-PET/CT combined with the manufacturer reconstruction with 4 iterations and 15 subsets together with 5 RR iterations can be used to quantitatively analyze the LA uptake in patient \u003csup\u003e18\u003c/sup\u003eF-FDG heart studies while still preserving image reading quality. This may lead to more precise cardiovascular disease status evaluation, especially when atria are concerned.\u003c/p\u003e","manuscriptTitle":"Cardiac atrial metabolism quantitative assessment with analog and digital TOF-PET/CT","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-06-16 22:13:34","doi":"10.21203/rs.3.rs-1719799/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":"1fd0d6c2-3744-42e8-a521-9275affa3629","owner":[],"postedDate":"June 16th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-07-20T15:39:27+00:00","versionOfRecord":[],"versionCreatedAt":"2022-06-16 22:13:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1719799","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1719799","identity":"rs-1719799","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}