Comparison of Image Quality of Breast-Specific Positron Emission Tomography: Insights from Phantom and Clinical Studies in a Japanese Multicenter Trial ​

Comparison of Image Quality of Breast-Specific Positron Emission Tomography: Insights from Phantom and Clinical Studies in a Japanese Multicenter Trial ​ | 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 Comparison of Image Quality of Breast-Specific Positron Emission Tomography: Insights from Phantom and Clinical Studies in a Japanese Multicenter Trial ​ Yoko Satoh, Satoe Aoyama, Koji Itagaki, Yuka Naoi, Kanae K. Miyake, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7966789/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Feb, 2026 Read the published version in Annals of Nuclear Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Objective Breast-specific positron emission tomography (breast PET), including positron emission mammography (PEM) and dedicated breast PET (dbPET), provides high-resolution functional imaging for detecting small breast cancers. However, direct cross-system comparisons and acquisition protocol optimizations remain underexplored. This study aimed to directly compare the imaging performance of the opposed-type PEM, first-generation photomultiplier tube (PMT)-based dbPET (dbPET1), and second-generation silicon photomultiplier (SiPM)-based dbPET (dbPET2) using clinical imaging protocols, and determine the requisite acquisition conditions for achieving comparable depiction of breast lesions across systems. Methods A cylindrical phantom with four spheres (diameter: 3–10 mm) was prepared with sphere-to-background ratios (SBRs) of 2:1, 4:1, and 8:1, based on clinical images. The phantom was scanned for 10 min in list mode with the spheres at the center and periphery of each detector and reconstructed at 1–10 min. Visual and quantitative evaluations were performed using the coefficient of variation of the background (CV BG ), detection index (DI), and contrast recovery coefficient (CRC). Representative clinical images of three lesion types, viz. mass-like uptake near the nipple, mass-like uptake close to the chest wall, and non-mass uptake, were also assessed using visual evaluation and the tumor-to-background ratio (TBR). Results Phantom images with SBRs of 2:1 and 4:1 did not sufficiently visualize the small spheres; therefore, an 8:1 ratio was chosen for the analysis. dbPET was capable of visualizing smaller spheres compared with PEM. At the periphery, image quality was reduced for all systems, while all systems were able to identify spheres ≥ 7.5 mm in diameter at a contrast ratio of 1:8 under clinical imaging protocols. The DI decreased with shorter acquisition time, while the CRC remained relatively stable. The CV BG increased, especially in dbPET2. Clinical evaluation confirmed that clarified the minimum acquisition times required to ensure adequate diagnostic image quality for different breast PET systems (≥ 5 min for dbPET, ≥ 7 min for PEM). dbPET provided superior detectability, whereas PEM had advantages near the chest wall. TBR analysis supported the consistency between the results of evaluation of the phantom and patients. Conclusions This study demonstrated that all breast-specific PET systems can achieve image quality capable of identifying sub-centimeter lesions within clinically feasible scan times (5 min for dbPET, 7 min for PEM). These findings provide the foundation for harmonizing protocols across systems and optimizing their clinical application in breast cancer diagnosis. breast PET positron emission mammography (PEM) dedicated breast PET (dbPET) image quality acquisition time Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Introduction Breast-specific positron emission tomography (breast PET) was developed to overcome the limitations of conventional whole-body PET in small breast cancer (BC) detection, such as insufficient spatial resolution for delineating small intramammary lesions [1,2]. By placing detectors in close proximity to the breast, breast PET has achieved higher spatial resolution and sensitivity than whole-body PET, enabling a more reliable visualization of primary breast lesions. The two main modalities are positron emission mammography (PEM), which employs two flat-panel detectors arranged in opposition with the breast lightly held between them while the patient is seated, and ring-shaped dedicated breast PET (dbPET), in which the patient lies prone, with the breast hanging through an opening in the bed into the cylindrical detector [3,4,5]. In Japan, breast PET received public insurance coverage in July 2013, along with whole-body PET-CT scans. In the same year, the Japanese Society of Nuclear Medicine (JSNM) published the first edition of the Breast-Specific PET Clinical Practice Guidelines to support the appropriate use of breast PET. Thereafter, the increase in the number of breast PET scanners in Japan and their widespread clinical application, and the concurrent accumulation of scientific evidence, led to the publication of a revised edition of these guidelines in 2019 [6]. These guidelines provide recommendations for the appropriate clinical use of two different types of breast PET systems: PEM and dbPET. However, they did not address the technical aspects of either device, particularly the comparison of image quality between the two systems or their standardization. Currently, PEM and dbPET systems manufactured domestically are in clinical use in Japan. In recent years, new-generation dbPET systems have been released, necessitating harmonization of images across systems. To the best of our knowledge, this is the first study to directly compare the PEM and dbPET devices and their images. The objective of this study was to identify a method to achieve comparable visualization of similarly small BC lesions using both PEM and dbPET through a common phantom study and clinical evaluations. Methods Breast PET scanners Three dedicated breast PET systems were evaluated in this study: opposed-type PEM, photomultiplier tube-based dbPET (dbPET1), and silicon photomultiplier-based dbPET (dbPET2) (Fig. 1 ). PEM (PEMGRAPH, Mirai Imaging Inc., Japan) The PEM system is composed of an opposed-type device equipped with two flat-panel detectors arranged in a face-to-face configuration, enabling high-resolution imaging of the soft-compressed breast (Fig. 1 a). Previous studies have described its basic design and clinical performance, demonstrating its utility for detecting small BCs [7,8]. PEM has a larger defection of the lines of response (LOR) compared with dbPET scanners, in which cylindrical detector arrays are placed around the breast. Therefore, usually only one direction of maximum intensity projection (MIP) is adopted per acquisition (not tomographic images). In this study, the images were reconstructed using the 3D-Maximum Likelihood Expectation Maximization algorithm with eight iterations and an anti-aliasing filter with dead time, random and decay correction, and no attenuation correction. Based on a phantom scan with known 18 F- fluorodeoxyglucose (FDG) radioactivity, the pixel values of clinical PEM images were converted into standardized uptake values (SUVs). dbPET1 (Elmammo Avant Class™, Shimadzu Corporation, Japan) and dbPET2 (BresTome™, Shimadzu Corporation, Japan) The dbPET system is equipped with a cylindrical detector module arrangement, enabling high-resolution imaging of the breast while it is hanging due to gravity [5,9]. Because dbPET scanners have fewer missing LORs than PEM scanners, both mediolateral and craniocaudal MIPs as well as cross-sectional images are usually used for diagnosis per acquisition. In dbPET, pixel values are converted to the SUV through attenuation correction using a µ-map, which is obtained by detecting the skin surface from the emission scan data and assuming the breast is a homogeneous absorber. dbPET1 is an earlier-generation ring-type dbPET system that employs conventional photomultiplier tubes, and dbPET2 is a next-generation ring-type dbPET system incorporating digital silicon photomultipliers, offering better sensitivity and spatial resolution compared with dbPET1(Fig. 1 B and C ) [5,10]. The primary specifications of these three systems are summarized in Table 1 . Further technical details can be found in previous studies [11]. Table 1 Main specifications of the three breast-specific PET systems evaluated in this study System Type PEM dbPET1 dbPET2 Scanner Name PEMGRAPH Elmammo™ BresTome™ Vendor Mirai Imaging Co., Ltd. Shimadzu Shimadzu Detector shape Opposed plate-type Ring- type Ring- type Detector aperture 100–250 mm * (gap, plate) φ195 mm (circ.) φ300 mm (circ.) FOV (mm) 202.4×140.8 (rect.)×100–250 mm * φ182 (circ.)×103 φ264 (circ.) ×162 Material of crystal LuAG LGSO LGSO Crystal size (mm 3 ) 1.5×1.5×11 1.44×1.44×18 2.1×2.1×15 Photo device PMT PMT SiPM Number of DOI layers 1 4 1 TOF Technology Not available Not available Available Matrix size (mm) 254 (X)×176 (Y) 236 (X)×132(Y)×236 (Z) 240 (X)×148 (Y)×240 (Z) Pixel size (mm 2 ) 0.8 0.78 1.1 Spatial resolution at 5 mm offset from the center of the FOV (mm) ⁑ up to 2.0 up to 1.5 from to 1.0 to 2.5 Sensitivity at 0cm in the center of the FOV (cps/kBq) ⁑ 0.005 from 0.05 to 0.09 from 0.06 to 0.11 * Adjustable in 25 mm increments , ⁑ NEMA NU 4-2008 22 Na source Abbreviations: PET, positron emission tomography; PEM, positron emission mammography; dbPET, dedicated breast PET; FOV, field of view; rect., rectangular; circ., circular; LuAG, lutetium aluminum garnet; LGSO, lutetium gadolinium oxyorthosilicate; PMT, photomultiplier tube; SiPM, silicon photomultiplier; DOI, depth-of-interaction; TOF, time of flight; NEMA-NU, National Electrical Manufacturers Association – NU standard; cps/Bq, counts per second per becquerel Phantom preparation A cylindrical phantom containing four hot spheres was used for the comparison of the breast PET scanners. In order to detect BC lesions with a diameter of 5 mm, which corresponds to T1a in the Union for International Cancer Control (UICC) TNM classification, spheres of four different sizes (3, 5, 7.5, and 10 mm) were adopted. For PET image evaluation based on phantom studies, the sphere-to-background radioactivity concentration ratio (SBR) is commonly set at 8:1. However, most previous studies were designed for whole-body PET scanners, lacking verification of the suitability of this SBR for breast PET. Therefore, in this study, the SBR was determined by measuring the radioactivity counts of the breast lesion, background mammary glands, and subcutaneous fat on the clinical breast PET images of patients with BC or suspected BC. Phantom setup For the PEM system, a cylindrical phantom was positioned between the two flat-panel detectors, and a custom-made acrylate–styrene acrylonitrile stand was used to prevent rolling (Fig. 2 ). For dbPET1 and dbPET2, the phantom was placed directly within the ring-shaped detector bore. When the position of the hot spheres needed to be changed, the phantom was elevated with spacers to adjust the vertical alignment. Data acquisition Based on previous studies [1,5], the phantom was placed with four hot spheres arranged in the center of the field of view (FOV) ( center ) and 2 cm inside the edge of the FOV ( periphery ) of each scanner. A custom-made acrylate–styrene–acrylonitrile stand was prepared to hold the cylindrical phantom on the PEM detector. The phantom prepared in each SBR was imaged for 10 min in list-mode at two positions ( center and periphery ) [12,13]. Image reconstruction All the breast PET images were reconstructed using the clinical conditions for each scanner, which were determined based on the results of previous studies and clinical experience [7,10,11]. However, the acquisition time can vary in routine clinical practice depending on the patient’s condition. To determine the minimum acquisition time required for diagnosis, the phantom images were reconstructed using full data (10 min) and short-time acquisitions (1, 3, 5, and 7 min) by dividing the list-mode data. The reconstruction conditions specific to each scanner are summarized in Table 2 . Table 2 Main reconstruction parameters of the three breast-specific PET systems evaluated in this study System Type PEM dbPET1 dbPET2 Iterative reconstruction 3D-MLEM 3D-DRAMA 3D-DRAMA Scatter correction Not available Convolution Subtraction True estimate subtraction Attenuation correction Not available Uniform attenuation map with object boundaries obtained from emission data Uniform attenuation map with object boundaries obtained from emission data Iterations / Subsets 8/1 1/128 1/100 Post filter MRP Median, Gaussian Median, Gaussian, NLM SUV conversion Available Available Available Abbreviations: PET, positron emission tomography; 3D, three-dimensional; ML-EM, maximum likelihood-expectation maximization; DRAMA, dynamic row-action maximum likelihood algorithm; MRP, Modified Ramp; NLM, non local means Analysis of phantom image quality All transverse phantom images that lined the largest cross-section of the hot spheres were displayed in inverse grayscale, with SUVs ranging from 0 to 4. In dbPET, all four hot spheres were displayed as a single transverse image, whereas in PEM, two spheres were displayed per image, resulting in two images covering all four spheres. First, two experienced nuclear medicine physicians and PET technologists each, who were blinded to the SBR settings, visually evaluated the visibility of the hot spheres in the reconstructed breast PET images using 10 min of acquisition data. Thereafter, the full-length and short-time acquired images were compared visually and quantitatively. For quantitative evaluation, circular regions of interest (ROIs) with the same diameter as the sphere were placed on the spheres in the phantom images. Additionally, eight ROIs with a diameter of 10 mm were placed in the background, and the coefficient of variation of the background (CV BG ), detection index (DI), and contrast recovery coefficient (CRC) were calculated using the following formulae: CV BG = \(\:\frac{{SD}_{BG,10mm}}{{C}_{BG,10mm}}\) , where SD BG,10mm is the standard deviation of the background ROI for a 10-mm diameter circle, and C BG,10mm is the average of the background ROI values for a 10-mm diameter circle DI = \(\:\frac{{C}_{H,5mm;max}-{C}_{BG,10mm;mean}}{{SD}_{BG}}\) , where C H,5mm;max is the maximum SUV (SUV max ) of the ROI for a 5-mm diameter sphere and C BG,10mm;mean is the average of the background ROIs for a 10-mm diameter circle CRC = \(\:\frac{\left({C}_{H;max}/{C}_{BG:mean}\right)-1}{\left({a}_{H}/{a}_{BG}\right)-1}\) , where a H and a BG represent the activity concentrations in the hot sphere and background, respectively. Human imaging This study was approved by the Medical Research Ethics Review Committee of the Fujita Health University (HM25-186). All procedures were performed in accordance with the ethical standards outlined in the 1964 Declaration of Helsinki and its subsequent revisions. Based on the retrospective observational study design, informed consent was waived for all patients. Patients fasted for at least 6 h before the 18 F-FDG (3.7 MBq/kg) injection. Following a whole-body PET/CT scan, the breasts were scanned separately on each side, with breast PET commencing approximately 90 min after the administration of 18 F-FDG. Breast PET images were also reconstructed using clinical conditions. Full and short-acquisition-time clinical PET images of representative cases scanned using each scanner were reviewed and discussed, along with the results of the phantom studies. Representative BC images were presented using three breast PET scans and other modalities to compare the characteristics of the three breast PET systems. These cases were selected to demonstrate the typical imaging features of three different types of lesions based on previous studies[14,15]: i) mass-like uptake near the nipple, ii) mass-like uptake slightly near the chest wall, and iii) non-mass uptake (NMU). In accordance with the phantom study, short-time acquisition images were reconstructed from the list-mode data of the clinical NMU lesions. For quantitative evaluation, SUV max and tumor-to-background ratio (TBR) were calculated using the following equations: TBR = \(\:\frac{{SUV}_{\:T,max}}{{SUV}_{BG,\:mean}}\) , where SUV T,max is the SUV max of the tumor (BC lesion) and SUV BG,mean is the mean value of the largest circular ROI placed on the background to avoid breast tumors, skin, and noise at the edge of the FOV, respectively. Results Phantom study Based on clinical PET image measurements of 68 patients with BC, the background radioactivity concentration of 2.56 kBq/mL and SBRs of 2:1, 4:1, and 8:1 were determined. The phantom images with SBRs of 2:1 and 4:1 did not sufficiently visualize the hot spheres (Fig. 3 ). Accordingly, phantom images with an SBR of 8:1 were used for quantitative evaluation. The phantom images acquired at 1, 3, 5, 7, and 10 min using breast PET were reconstructed from 10 min of list-mode data from a phantom with an SBR of 8:1 (Fig. 4 ). We found that dbPET had the ability to better visualize smaller spheres than PEM and that silicon photomultiplier (SiPM)-based dbPET could visualize spheres more clearly compared with photomultiplier tube (PMT)-based dbPET. In addition, the ability to visualize the spheres was lower at the periphery than at the center for all the scanners. Visual assessment of the short-time acquisition images showed that 7.5-mm and 10-mm diameter spheres were visualized in all images acquired in 1 min. Even with a 10-min acquisition time, the PEM system could not visualize spheres measuring 5 mm or smaller, and the PMT-based dbPET system also had difficulty visualizing 3-mm spheres at the periphery. In contrast, a 3-mm sphere could be identified at the periphery at 5-min acquisition using SiPM-based dbPET. Quantitative evaluation revealed that the shorter the acquisition time, the higher the CV BG , which was markedly elevated with SiPM-based dbPET at the periphery (Fig. 5 ). The DI and CRC were calculated for the 5-mm spheres that could be visually identified. The 5-mm sphere was not identified in any image at an SBR of 2:1. The shorter the acquisition time, the smaller the DI; however, the CRC value showed little change with respect to the acquisition time. The DI and CRC decreased in the following order: SiPM-based dbPET, PMT-based dbPET, and PEM. In the PEM image, no 5-mm spheres were identified in the periphery. The results of the phantom study suggested that, even with breast PET, it was difficult to visualize BC with a low uptake approximately twice that of the background and a size of 10 mm or less. Furthermore, considering the identification of BC with a contrast against the background lesser than 8:1, the minimum acquisition time was 5 min, and 7 min was considered optimal if possible. Clinical case review The first set of images presents BC lesions with mass-like uptake located near the nipple (Fig. 6 ) . All three breast PET systems clearly visualized the lesions. However, the lesion margins appeared slightly sharper on images obtained with dbPET than on those obtained with PEM, which offered a slightly lower spatial resolution. This trend was consistent with the results of the preceding phantom study. The next set of cases presents BC images showing mass-like uptake closer to the chest wall (Fig. 7 ). All breast PET images visualized BC with higher contrast and greater clarity compared with other modalities. Notably, among the three cases, PEM easily visualized the BC lesion located closest to the chest wall because PEM can scan the entire thorax with two plate-like detectors, resulting in no blind areas, unlike dbPET. The third set of cases comprised non-mass uptake BC (Fig. 8 ). Breast PET visualized BC in a manner similar to contrast-enhanced magnetic resonance imaging (MRI). Furthermore, the high tumor-background contrast on breast PET images made it easier to evaluate the extent of the BC lesions. Additionally, to determine the minimum acquisition time for each breast PET scan, short-time acquisition images of NMU BCs were reconstructed based on the phantom study (Fig. 9 ). Visually, shorter acquisition times resulted in increased noise at the edge of the FOV near the chest wall in all breast PET images, which was particularly marked in the PEM and dbPET2 images. In quantitative evaluation, both SUV max and TBR increased with shorter acquisition times for PEM and dbPET2 showing BC lesions near the chest wall, while they decreased for dbPET1 showing BC lesion near the nipple. The evaluation of clinical images reconstructed from the short-time acquisition data indicated that 1) the longer the acquisition time, the better the image quality, and 2) a minimum acquisition time of 5 min or longer for PEM and 3 min or longer for dbPET are needed. Discussion To the best of our knowledge, this is the first study to directly compare three breast PET systems. All images in this study were reconstructed under the clinical conditions routinely used for each scanner, with the acquisition time being the only parameter modified. This approach was adopted because extensive optimization studies, particularly for dbPET, have already been reported and further fine-tuning of the reconstruction settings is neither practical nor clinically meaningful [16]. The acquisition duration is the most critical factor in clinical practice, since it directly affects both patient comfort—longer scans increase discomfort—and image quality—shorter scans compromise diagnostic reliability. In this study, we directly compared the imaging performances of the opposed-type PEM and two generations of ring-type dbPET devices using both phantom and clinical data. The phantom study demonstrated that dbPET systems, particularly SiPM-based dbPET2, achieved superior detectability of small spheres compared with PEM, while the image quality was consistently lower at the periphery of the detectors. These findings were further supported by the clinical image review, which revealed similar trends across different lesion types. In addition, minimum acquisition times required to maintain diagnostic quality were determined to be ≥5 min for PEM and ≥3 min for dbPET. These results correspond to the difference in the defection rate of the LOR based on the difference in detector shape between the opposed-type and ring-shaped detectors. In fact, at the periphery of the FOV, where LOR deficiency was significant, deterioration in the PEM image quality was remarkable in the phantom study. However, in the review of the clinical images, no disadvantage of PEM was observed in the visualization of BC close to the chest wall. PEM allows adjustment of the distance between the two plate-like detectors, enabling deeper inclusion of the chest wall within the FOV. Thus, PEM demonstrated superiority in visualizing lesions close to the chest wall owing to the shape of the detector. In contrast, dbPET has a fixed gantry diameter, which means that lesions close to the chest wall may fall outside the FOV, a limitation that persists even with the newer SiPM-based system [16]. Consequently, PEM remains the only breast PET modality without blind areas, which highlights its value in clinical practice. In 2019, the JSNM published a revised version of clinical practice guidelines for breast PET [5]. Compared with the first edition issued in 2013, the more recent guidelines include more clinical evidence, enhancing their coverage of clinical applications and safety considerations. However, because of significant differences in the geometric structures of the PEM and dbPET scanners, recommendations for standardizing image quality were not included. Recently, with the release of new-generation dbPET, the need for intersystem harmonization has become even more critical. The present study aimed to fill this gap by providing a comparative evaluation of PEM and two generations of dbPET under standardized phantom and clinical conditions. Importantly, the purpose of this investigation was not to determine which device is superior but rather to clarify how each system can be appropriately utilized to maximize patient benefit. Breast PET can provide valuable diagnostic information, irrespective of the scanner type, provided that the acquisition conditions are optimized. Our results emphasize that patients should not be disadvantaged simply because one type of breast PET system was used instead of another. Based on our findings, patients with BC scanned with different breast PET systems will benefit equally. Contrast-enhanced breast MRI is considered the gold standard for evaluating the extent of the primary breast lesion. This study did not systematically compare breast PET with contrast-enhanced breast MRI. However, previous studies comparing these two modalities have demonstrated that their detection rates are equivalent or that breast PET exhibits higher specificity, if the lesion lies in the FOV [8,19,20]. On contrast-enhanced MRI, background parenchymal enhancement is marked in young women and often masks breast lesions; however, even in such patients, physiological FDG uptake in the background mammary gland has little impact on the detection of breast lesions. The use of MRI is restricted to patients who cannot receive contrast agents due to allergies, renal impairment, those with claustrophobia, or those with metallic implants (in their bodies). In such cases, breast PET may serve as a valuable alternative or complementary tool. At our institution, PEM is prioritized for patients who are unable to undergo contrast-enhanced breast MRI. This study had a limitation. The number of clinical cases was relatively small. Thus, future studies with larger patient cohorts and a broader range of scanners are warranted to validate and generalize the present findings. Because this study focused on domestically developed systems, further studies investigating other breast PET platforms are important for broader generalization. Moreover, as body habitus and breast size vary across populations, international studies that include diverse ethnic groups are essential to fully establish the clinical utility of breast PET. Declarations Financial support: This research was supported by research grants from the Japanese Society of Nuclear Medicine in fiscal years 2024 and 2025. Funding and Acknowledgments This work was supported by research grants (for the fiscal years 2023 and 2024) conferred by the Japanese Society of Nuclear Medicine. The authors sincerely thank the society for their support. Conflict of Interest SI is an employee of Mirai Imaging Inc., and YI is an employee of Shimadzu. 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Multiparametric imaging of breast cancer: An update of current applications. Diagn Interv Imaging. 2022;103:574–83. Fowler AM, Miyake KK, Nakamoto Y. Clinical Applications of Dedicated Breast Positron Emission Tomography. PET Clin 2024;19:105–17. Cite Share Download PDF Status: Published Journal Publication published 07 Feb, 2026 Read the published version in Annals of Nuclear Medicine → Version 1 posted Reviewers agreed at journal 31 Oct, 2025 Reviewers invited by journal 30 Oct, 2025 Editor assigned by journal 28 Oct, 2025 First submitted to journal 28 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-7966789","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":537773750,"identity":"9b207b07-6d45-4b01-94b9-c582a1296171","order_by":0,"name":"Yoko Satoh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7UlEQVRIiWNgGAWjYHAD5gMMjA1QtgRxWtgSSNbCY4DQgg+Yszc//HRzh408/7Qz3yR+7rCRY2A/fIDBcgduLZY9x4ylc8+kGc64nbtNsvdMmjEDT1oCg+QZ3FoMbuQwSOe2HU5gAGqR4G07nNggAXShZBseLfffMP/ObfufIH8755nkX6K03OBhA9pyIMHgdg6bNFG2WPakmVnnnkk23Hg7zdhati3NmA3olwP4/GLOfvjx7dwddvJyt5Mf3nzbZiPHz3744GNJPCFmACKg0cECjkA2ID4s2UCcFuYPMFHGj3i0jIJRMApGwYgDAJqiUJG/E4liAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-0188-0906","institution":"Fujita Medical Innovation Center Tokyo","correspondingAuthor":true,"prefix":"","firstName":"Yoko","middleName":"","lastName":"Satoh","suffix":""},{"id":537773751,"identity":"a54fc11d-999b-4bc2-bbf8-03d811b8c05c","order_by":1,"name":"Satoe Aoyama","email":"","orcid":"","institution":"Clinical Imaging Center for Healthcare, Nippon Medical School, Tokyo, Japan","correspondingAuthor":false,"prefix":"","firstName":"Satoe","middleName":"","lastName":"Aoyama","suffix":""},{"id":537773752,"identity":"a359e472-9630-4960-91fe-455ba59b8c42","order_by":2,"name":"Koji Itagaki","email":"","orcid":"","institution":"Division of Clinical Radiology Service, Kyoto University Hospital, Kyoto, Japan","correspondingAuthor":false,"prefix":"","firstName":"Koji","middleName":"","lastName":"Itagaki","suffix":""},{"id":537773753,"identity":"7d653af4-45cd-4314-afcb-fa2590142f5b","order_by":3,"name":"Yuka Naoi","email":"","orcid":"","institution":"Clinical Imaging Center for Healthcare, Nippon Medical School, Tokyo, Japan","correspondingAuthor":false,"prefix":"","firstName":"Yuka","middleName":"","lastName":"Naoi","suffix":""},{"id":537773754,"identity":"979b010f-1f6c-4e99-95e1-c027690fc247","order_by":4,"name":"Kanae K. 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emission tomography; PEM, positron emission mammography; dbPET1, photomultiplier tube–based dedicated breast PET; dbPET2, silicon photomultiplier–based dedicated breast PET\u003c/p\u003e","description":"","filename":"Fig1BreastPETscanners.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7966789/v1/1b57eda0c23a5fbcfd96a8db.jpg"},{"id":95665044,"identity":"21ba1b54-c1c2-488b-8359-28b432f60753","added_by":"auto","created_at":"2025-11-11 16:43:48","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":258882,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePlacement of the cylindrical phantom on the breast-specific PET scanners\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe cylindrical phantom was placed on the PEM detector using a dedicated stand (a), and in the center of the dbPET detector with height adjusted by spacers (b).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviation:\u003c/strong\u003e PET, positron emission tomography; PEM, positron emission mammography; dbPET, dedicated breast PET\u003c/p\u003e","description":"","filename":"Fig2BreastPETPhantomphotos.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7966789/v1/d814a8afebcdf659181146f5.jpg"},{"id":95665048,"identity":"051a9d28-2e91-41a1-a8ca-873f4cbd3b76","added_by":"auto","created_at":"2025-11-11 16:43:48","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":496578,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePhantom images obtained with the three breast-specific PET systems (PEM, PMT-based dbPET, and SiPM-based dbPET, from top to bottom)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe hot spheres were located at the center of the detector and acquired for 10 min at an SBR 2:3, 4:1, and 8:1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e PET, positron emission tomography; SBR, sphere-to-background ratio; PEM, positron emission mammography; dbPET, dedicated breast PET; PMT, photomultiplier tube; SiPM, silicon photomultiplier\u003c/p\u003e","description":"","filename":"Fig3phantomimages4SBR.png","url":"https://assets-eu.researchsquare.com/files/rs-7966789/v1/e989db90c642e34b8c6117c0.png"},{"id":95797447,"identity":"8d6b334c-0c9e-4048-a3e2-e48e8061220c","added_by":"auto","created_at":"2025-11-13 08:05:15","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":169638,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBreast-specific PET images acquired at 1, 3, 5, 7, and 10 min in a phantom with an SBR of 8:1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe hot spheres were placed at the center (a) and periphery (b) of the detectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e PET, positron emission tomography; SBR, sphere-to-background ratio\u003c/p\u003e","description":"","filename":"Fig4BreastPETphantomimagesCenterPeriphery.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7966789/v1/772922cf6e392f30e02949b9.jpg"},{"id":95798043,"identity":"bdea3aea-c335-43a0-8221-ae6295a9027e","added_by":"auto","created_at":"2025-11-13 08:14:51","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":503262,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eQuantitative evaluation of phantom images scanned with three breast-specific PET scanners\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe hot spheres were located at the center of the detector (\u003cem\u003ecenter\u003c/em\u003e) and 2 cm from the edge of the detector (\u003cem\u003eperiphery\u003c/em\u003e), and the images were reconstructed from 1, 3, 5, 7, and 10-min acquisition data at three different sphere-to-background radioactivity concentration ratios (1:2, 4:1, and 8:1). The DI (B) and CRC (C) were calculated for the 5-mm spheres that could be visually identified.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e PET, positron emission tomography; DI, detection index; CRC, contrast recovery coefficient\u003c/p\u003e","description":"","filename":"Fig5BreastPETphantomgraphs.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7966789/v1/ac6a86a81b1f7211e914e95e.jpg"},{"id":95665050,"identity":"0bae43c1-7518-4dd7-b935-803626056ed1","added_by":"auto","created_at":"2025-11-11 16:43:48","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":482133,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of breast-specific PET images for mass-like uptake near the nipple obtained using three systems\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e. PEM and US images of a 71-year-old woman with IDC of the left breast, luminal A, cT1cN0M0, stage I. Due to claustrophobia, PEM was performed instead of MRI. Two lesions were identified on the PEM image (arrow: IDC, arrowhead: DCIS with invasive components). \u003cstrong\u003eb\u003c/strong\u003e. dbPET1, MMG (MLO), US, and MRI (DWI) images of a 61-year-old woman with IDC of the left breast, luminal B, cT1pN0M0, stage I. The BC lesion was slightly unclear on MMG and breast US. In contrast, it was clearly visualized by dbPET. MRI was performed without contrast because of an allergy to contrast media. \u003cstrong\u003ec\u003c/strong\u003e. A 50-year-old woman with IDC of the right breast, triple negative, pT1cN0M0, stage IA. dbPET and contrast-enhanced MRI visualized breast cancer lesions identically. However, compared with the contrast effect of the background mammary gland on the MRI image, physiological uptake on dbPET image was minimal, resulting in high contrast with the BC lesion. dbPET2, MMG (MLO), US, CE-MRI (early phase, sagittal), and US images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e PET, positron emission tomography; PEM, positron emission mammography; US, ultrasonography; IDC, invasive ductal carcinoma; DCIS, ductal carcinoma in situ; dbPET, dedicated breast PET; MMG, mammography; MLO, mediolateral oblique view; DWI, diffusion weighted imaging; CE, contrast-enhanced, BC: breast cancer\u003c/p\u003e","description":"","filename":"Fig6BreastPETClinicalMassnearnippler1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7966789/v1/f0ce8638125a3754c629b8fe.jpg"},{"id":95797521,"identity":"ff889b68-579f-4283-a082-d6e6be32a518","added_by":"auto","created_at":"2025-11-13 08:06:10","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":460817,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of breast-specific PET images for mass-like uptake slightly closer to the chest wall obtained using three systems\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e. PEM, MMG (MLO), and US images. Due to an allergy to contrast media, PEM was performed instead of contrast-enhanced MRI. Compared with MMG and US, PEM visualized the BC lesion (arrow) more clearly (\u003cstrong\u003eFig. 6a\u003c/strong\u003e). \u003cstrong\u003eb and c\u003c/strong\u003e. dbPET1, dbPET2, MMG (MLO), US, and CE-MRI (early-axial and delay-sagittal) images. On dbPET images, the BC lesions (arrows) were clearly visible, although increasing noise near the edge of the FOV close to the chest wall was observed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e PET, positron emission tomography; PEM, positron emission mammography; MMG, mammography; MLO, mediolateral oblique view; US, ultrasound; BC, breast cancer; FOV, field of view; dbPET, dedicated breast PET; CE,contrast-enhanced\u003c/p\u003e","description":"","filename":"Fig7BreastPETClinicalMassnearchestwallr1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7966789/v1/9aa38fedf05da6b1a9918ab6.jpg"},{"id":95665046,"identity":"b02a0108-a4f2-4613-a50b-7d39793004f1","added_by":"auto","created_at":"2025-11-11 16:43:48","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":385155,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of breast-specific PET and other breast modalities\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e. PEM and US images of a 42-year-old woman with IDC with DCIS (Luminal A) in the left breast. Due to claustrophobia, PEM was performed instead of MRI. The PEM image clearly showed the distribution of DCIS, the main component (arrows). \u003cstrong\u003eb\u003c/strong\u003e. dbPET1, CE-MRI (delay-sagittal), MMG (MLO), and MRI (contrast enhanced) images of a 71-year-old woman with DCIS (ER negative) of the left breast. MMG showed no abnormal findings, and even contrast-enhanced MRI failed to identify any abnormalities. \u003cstrong\u003ec\u003c/strong\u003e. A 50-year-old woman with IDC of the right breast, triple negative, pT1cN0M0, stage IA. dbPET and contrast-enhanced MRI visualized BC lesions identically. However, compared with the contrast effect of the background mammary gland on the MRI image, physiological uptake on the dbPET image was minimal, resulting in high contrast with the BC lesion. dbPET2, MMG (MLO), US, CE-MRI (early phase, sagittal), and US images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e PET, positron emission tomography; PEM, positron emission mammography; US, ultrasonography; IDC, invasive ductal carcinoma; DCIS, ductal carcinoma in situ; dbPET, dedicated breast PET; CE, contrast-enhanced; MMG, mammography; MLO, mediolateral oblique view; ER, estrogen receptor; BC, breast cancer\u003c/p\u003e","description":"","filename":"Fig8BreastPETClinicalNonMassr1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7966789/v1/342b2ae18448cb9b8d9e9bf9.jpg"},{"id":95665053,"identity":"0e92d802-e24f-44a9-b1e4-0d3e79d6fcb9","added_by":"auto","created_at":"2025-11-11 16:43:48","extension":"jpg","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":237749,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of breast-specific PET short-time acquisition images of breast cancer with non-mass uptake obtained using three systems\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eML-MIP of breast-specific PET acquired up to 7 minutes with PEM, dbPET1, and dbPET2. Short-time acquisition images were also reconstructed from 1-, 3-, and 5-min data extracted from 7 min of list-mode data. The values in the figure indicate the tumor SUV\u003csub\u003emax\u003c/sub\u003e (tumor-to-background ratio).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e PET, positron emission tomography; ML-MIP, medio-lateral maximum intensity projection; PEM, positron emission mammography; dbPET, dedicated breast PET\u003c/p\u003e","description":"","filename":"Fig9BreastPETClinicalnonmasssplit.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7966789/v1/302e96c5a927251192341d5d.jpg"},{"id":102234258,"identity":"28452b97-43be-4a0c-8c91-ac916abd46cb","added_by":"auto","created_at":"2026-02-09 16:08:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4155405,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7966789/v1/ad2faf7b-61e6-4de4-9ff2-715162c4e8bc.pdf"}],"financialInterests":"","formattedTitle":"Comparison of Image Quality of Breast-Specific Positron Emission Tomography: Insights from Phantom and Clinical Studies in a Japanese Multicenter Trial ​","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast-specific positron emission tomography (breast PET) was developed to overcome the limitations of conventional whole-body PET in small breast cancer (BC) detection, such as insufficient spatial resolution for delineating small intramammary lesions [1,2]. By placing detectors in close proximity to the breast, breast PET has achieved higher spatial resolution and sensitivity than whole-body PET, enabling a more reliable visualization of primary breast lesions. The two main modalities are positron emission mammography (PEM), which employs two flat-panel detectors arranged in opposition with the breast lightly held between them while the patient is seated, and ring-shaped dedicated breast PET (dbPET), in which the patient lies prone, with the breast hanging through an opening in the bed into the cylindrical detector [3,4,5].\u003c/p\u003e\u003cp\u003eIn Japan, breast PET received public insurance coverage in July 2013, along with whole-body PET-CT scans. In the same year, the Japanese Society of Nuclear Medicine (JSNM) published the first edition of the Breast-Specific PET Clinical Practice Guidelines to support the appropriate use of breast PET. Thereafter, the increase in the number of breast PET scanners in Japan and their widespread clinical application, and the concurrent accumulation of scientific evidence, led to the publication of a revised edition of these guidelines in 2019 [6]. These guidelines provide recommendations for the appropriate clinical use of two different types of breast PET systems: PEM and dbPET. However, they did not address the technical aspects of either device, particularly the comparison of image quality between the two systems or their standardization.\u003c/p\u003e\u003cp\u003eCurrently, PEM and dbPET systems manufactured domestically are in clinical use in Japan. In recent years, new-generation dbPET systems have been released, necessitating harmonization of images across systems.\u003c/p\u003e\u003cp\u003eTo the best of our knowledge, this is the first study to directly compare the PEM and dbPET devices and their images. The objective of this study was to identify a method to achieve comparable visualization of similarly small BC lesions using both PEM and dbPET through a common phantom study and clinical evaluations.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eBreast PET scanners\u003c/h2\u003e\n \u003cp\u003eThree dedicated breast PET systems were evaluated in this study: opposed-type PEM, photomultiplier tube-based dbPET (dbPET1), and silicon photomultiplier-based dbPET (dbPET2) (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003ePEM (PEMGRAPH, Mirai Imaging Inc., Japan)\u003c/h3\u003e\n\u003cp\u003eThe PEM system is composed of an opposed-type device equipped with two flat-panel detectors arranged in a face-to-face configuration, enabling high-resolution imaging of the soft-compressed breast (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ea). Previous studies have described its basic design and clinical performance, demonstrating its utility for detecting small BCs [7,8]. PEM has a larger defection of the lines of response (LOR) compared with dbPET scanners, in which cylindrical detector arrays are placed around the breast. Therefore, usually only one direction of maximum intensity projection (MIP) is adopted per acquisition (not tomographic images). In this study, the images were reconstructed using the 3D-Maximum Likelihood Expectation Maximization algorithm with eight iterations and an anti-aliasing filter with dead time, random and decay correction, and no attenuation correction. Based on a phantom scan with known \u003csup\u003e18\u003c/sup\u003eF- fluorodeoxyglucose (FDG) radioactivity, the pixel values of clinical PEM images were converted into standardized uptake values (SUVs).\u003c/p\u003e\n\u003ch3\u003edbPET1 (Elmammo Avant Class\u0026trade;, Shimadzu Corporation, Japan) and dbPET2 (BresTome\u0026trade;, Shimadzu Corporation, Japan)\u003c/h3\u003e\n\u003cp\u003eThe dbPET system is equipped with a cylindrical detector module arrangement, enabling high-resolution imaging of the breast while it is hanging due to gravity [5,9]. Because dbPET scanners have fewer missing LORs than PEM scanners, both mediolateral and craniocaudal MIPs as well as cross-sectional images are usually used for diagnosis per acquisition. In dbPET, pixel values are converted to the SUV through attenuation correction using a \u0026micro;-map, which is obtained by detecting the skin surface from the emission scan data and assuming the breast is a homogeneous absorber.\u003c/p\u003e\n\u003cp\u003edbPET1 is an earlier-generation ring-type dbPET system that employs conventional photomultiplier tubes, and dbPET2 is a next-generation ring-type dbPET system incorporating digital silicon photomultipliers, offering better sensitivity and spatial resolution compared with dbPET1(Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eB \u003cstrong\u003eand C\u003c/strong\u003e) [5,10].\u003c/p\u003e\n\u003cp\u003eThe primary specifications of these three systems are summarized in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Further technical details can be found in previous studies [11].\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMain specifications of the three breast-specific PET systems evaluated in this study\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSystem Type\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePEM\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003edbPET1\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003edbPET2\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eScanner Name\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePEMGRAPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eElmammo\u0026trade;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBresTome\u0026trade;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVendor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMirai Imaging Co., Ltd.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShimadzu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShimadzu\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDetector shape\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOpposed plate-type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRing- type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRing- type\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDetector aperture\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u0026ndash;250 mm\u003csup\u003e*\u003c/sup\u003e (gap, plate)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026phi;195 mm (circ.)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026phi;300 mm (circ.)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFOV (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e202.4\u0026times;140.8 (rect.)\u0026times;100\u0026ndash;250 mm\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026phi;182 (circ.)\u0026times;103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026phi;264 (circ.) \u0026times;162\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaterial of crystal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLuAG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLGSO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLGSO\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCrystal size (mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5\u0026times;1.5\u0026times;11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.44\u0026times;1.44\u0026times;18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.1\u0026times;2.1\u0026times;15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePhoto device\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePMT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePMT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSiPM\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of DOI layers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTOF Technology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNot available\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNot available\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAvailable\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMatrix size (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e254 (X)\u0026times;176 (Y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e236 (X)\u0026times;132(Y)\u0026times;236 (Z)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e240 (X)\u0026times;148 (Y)\u0026times;240 (Z)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePixel size (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpatial resolution at 5 mm offset from the center of the FOV (mm)\u003csup\u003e⁑\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eup to 2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eup to 1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efrom to 1.0 to 2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSensitivity at 0cm in the center of the FOV (cps/kBq)\u003csup\u003e⁑\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efrom 0.05 to 0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efrom 0.06 to 0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\u003csup\u003e*\u003c/sup\u003eAdjustable in 25 mm increments\u003csup\u003e, ⁑\u003c/sup\u003eNEMA NU 4-2008 \u003csup\u003e22\u003c/sup\u003eNa source\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e PET, positron emission tomography; PEM, positron emission mammography; dbPET, dedicated breast PET; FOV, field of view; rect., rectangular; circ., circular; LuAG, lutetium aluminum garnet; LGSO, lutetium gadolinium oxyorthosilicate; PMT, photomultiplier tube; SiPM, silicon photomultiplier; DOI, depth-of-interaction; TOF, time of flight; NEMA-NU, National Electrical Manufacturers Association \u0026ndash; NU standard; cps/Bq, counts per second per becquerel\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003ePhantom preparation\u003c/h3\u003e\n\u003cp\u003eA cylindrical phantom containing four hot spheres was used for the comparison of the breast PET scanners. In order to detect BC lesions with a diameter of 5 mm, which corresponds to T1a in the Union for International Cancer Control (UICC) TNM classification, spheres of four different sizes (3, 5, 7.5, and 10 mm) were adopted. For PET image evaluation based on phantom studies, the sphere-to-background radioactivity concentration ratio (SBR) is commonly set at 8:1. However, most previous studies were designed for whole-body PET scanners, lacking verification of the suitability of this SBR for breast PET. Therefore, in this study, the SBR was determined by measuring the radioactivity counts of the breast lesion, background mammary glands, and subcutaneous fat on the clinical breast PET images of patients with BC or suspected BC.\u003c/p\u003e\n\u003ch3\u003ePhantom setup\u003c/h3\u003e\n\u003cp\u003eFor the PEM system, a cylindrical phantom was positioned between the two flat-panel detectors, and a custom-made acrylate\u0026ndash;styrene acrylonitrile stand was used to prevent rolling (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). For dbPET1 and dbPET2, the phantom was placed directly within the ring-shaped detector bore. When the position of the hot spheres needed to be changed, the phantom was elevated with spacers to adjust the vertical alignment.\u003c/p\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eData acquisition\u003c/h2\u003e\n \u003cp\u003eBased on previous studies [1,5], the phantom was placed with four hot spheres arranged in the center of the field of view (FOV) (\u003cem\u003ecenter\u003c/em\u003e) and 2 cm inside the edge of the FOV (\u003cem\u003eperiphery\u003c/em\u003e) of each scanner. A custom-made acrylate\u0026ndash;styrene\u0026ndash;acrylonitrile stand was prepared to hold the cylindrical phantom on the PEM detector. The phantom prepared in each SBR was imaged for 10 min in list-mode at two positions (\u003cem\u003ecenter\u003c/em\u003e and \u003cem\u003eperiphery\u003c/em\u003e) [12,13].\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eImage reconstruction\u003c/h3\u003e\n\u003cp\u003eAll the breast PET images were reconstructed using the clinical conditions for each scanner, which were determined based on the results of previous studies and clinical experience [7,10,11]. However, the acquisition time can vary in routine clinical practice depending on the patient\u0026rsquo;s condition. To determine the minimum acquisition time required for diagnosis, the phantom images were reconstructed using full data (10 min) and short-time acquisitions (1, 3, 5, and 7 min) by dividing the list-mode data. The reconstruction conditions specific to each scanner are summarized in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMain reconstruction parameters of the three breast-specific PET systems evaluated in this study\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSystem Type\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePEM\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003edbPET1\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003edbPET2\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIterative reconstruction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3D-MLEM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3D-DRAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3D-DRAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eScatter correction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNot available\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConvolution Subtraction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTrue estimate subtraction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAttenuation correction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNot available\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUniform attenuation map with object boundaries obtained from emission data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUniform attenuation map with object boundaries obtained from emission data\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIterations / Subsets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8/1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePost filter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian, Gaussian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian, Gaussian, NLM\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSUV conversion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAvailable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAvailable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAvailable\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e PET, positron emission tomography; 3D, three-dimensional; ML-EM, maximum \u0026nbsp;likelihood-expectation maximization; DRAMA, dynamic row-action maximum likelihood algorithm; MRP, Modified Ramp; NLM, non local means\u003c/p\u003e\n\u003ch3\u003eAnalysis of phantom image quality\u003c/h3\u003e\n\u003cp\u003eAll transverse phantom images that lined the largest cross-section of the hot spheres were displayed in inverse grayscale, with SUVs ranging from 0 to 4. In dbPET, all four hot spheres were displayed as a single transverse image, whereas in PEM, two spheres were displayed per image, resulting in two images covering all four spheres. First, two experienced nuclear medicine physicians and PET technologists each, who were blinded to the SBR settings, visually evaluated the visibility of the hot spheres in the reconstructed breast PET images using 10 min of acquisition data. Thereafter, the full-length and short-time acquired images were compared visually and quantitatively.\u003c/p\u003e\n\u003cp\u003eFor quantitative evaluation, circular regions of interest (ROIs) with the same diameter as the sphere were placed on the spheres in the phantom images. Additionally, eight ROIs with a diameter of 10 mm were placed in the background, and the coefficient of variation of the background (CV\u003csub\u003eBG\u003c/sub\u003e), detection index (DI), and contrast recovery coefficient (CRC) were calculated using the following formulae:\u003c/p\u003e\n\u003cp\u003eCV\u003csub\u003eBG\u003c/sub\u003e = \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\frac{{SD}_{BG,10mm}}{{C}_{BG,10mm}}\\)\u003c/span\u003e\u003c/span\u003e,\u003c/p\u003e\n\u003cp\u003ewhere SD\u003csub\u003eBG,10mm\u003c/sub\u003e is the standard deviation of the background ROI for a 10-mm diameter circle, and C\u003csub\u003eBG,10mm\u003c/sub\u003e is the average of the background ROI values for a 10-mm diameter circle\u003c/p\u003e\n\u003cp\u003eDI = \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\frac{{C}_{H,5mm;max}-{C}_{BG,10mm;mean}}{{SD}_{BG}}\\)\u003c/span\u003e\u003c/span\u003e,\u003c/p\u003e\n\u003cp\u003ewhere C\u003csub\u003eH,5mm;max\u003c/sub\u003e is the maximum SUV (SUV\u003csub\u003emax\u003c/sub\u003e) of the ROI for a 5-mm diameter sphere and C\u003csub\u003eBG,10mm;mean\u003c/sub\u003e is the average of the background ROIs for a 10-mm diameter circle\u003c/p\u003e\n\u003cp\u003eCRC = \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\frac{\\left({C}_{H;max}/{C}_{BG:mean}\\right)-1}{\\left({a}_{H}/{a}_{BG}\\right)-1}\\)\u003c/span\u003e\u003c/span\u003e,\u003c/p\u003e\n\u003cp\u003ewhere a\u003csub\u003eH\u003c/sub\u003e and a\u003csub\u003eBG\u003c/sub\u003e represent the activity concentrations in the hot sphere and background, respectively.\u003c/p\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eHuman imaging\u003c/h2\u003e\n \u003cp\u003eThis study was approved by the Medical Research Ethics Review Committee of the Fujita Health University (HM25-186). All procedures were performed in accordance with the ethical standards outlined in the 1964 Declaration of Helsinki and its subsequent revisions. Based on the retrospective observational study design, informed consent was waived for all patients.\u003c/p\u003e\n \u003cp\u003ePatients fasted for at least 6 h before the \u003csup\u003e18\u003c/sup\u003eF-FDG (3.7 MBq/kg) injection. Following a whole-body PET/CT scan, the breasts were scanned separately on each side, with breast PET commencing approximately 90 min after the administration of \u003csup\u003e18\u003c/sup\u003eF-FDG. Breast PET images were also reconstructed using clinical conditions. Full and short-acquisition-time clinical PET images of representative cases scanned using each scanner were reviewed and discussed, along with the results of the phantom studies.\u003c/p\u003e\n \u003cp\u003eRepresentative BC images were presented using three breast PET scans and other modalities to compare the characteristics of the three breast PET systems. These cases were selected to demonstrate the typical imaging features of three different types of lesions based on previous studies[14,15]: i) mass-like uptake near the nipple, ii) mass-like uptake slightly near the chest wall, and iii) non-mass uptake (NMU).\u003c/p\u003e\n \u003cp\u003eIn accordance with the phantom study, short-time acquisition images were reconstructed from the list-mode data of the clinical NMU lesions. For quantitative evaluation, SUV\u003csub\u003emax\u003c/sub\u003e and tumor-to-background ratio (TBR) were calculated using the following equations:\u003c/p\u003e\n \u003cp\u003eTBR = \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\frac{{SUV}_{\\:T,max}}{{SUV}_{BG,\\:mean}}\\)\u003c/span\u003e\u003c/span\u003e,\u003c/p\u003e\n \u003cp\u003ewhere SUV\u003csub\u003eT,max\u003c/sub\u003e is the SUV\u003csub\u003emax\u003c/sub\u003e of the tumor (BC lesion) and SUV\u003csub\u003eBG,mean\u003c/sub\u003e is the mean value of the largest circular ROI placed on the background to avoid breast tumors, skin, and noise at the edge of the FOV, respectively.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003ePhantom study\u003c/h2\u003e\u003cp\u003eBased on clinical PET image measurements of 68 patients with BC, the background radioactivity concentration of 2.56 kBq/mL and SBRs of 2:1, 4:1, and 8:1 were determined. The phantom images with SBRs of 2:1 and 4:1 did not sufficiently visualize the hot spheres (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Accordingly, phantom images with an SBR of 8:1 were used for quantitative evaluation.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe phantom images acquired at 1, 3, 5, 7, and 10 min using breast PET were reconstructed from 10 min of list-mode data from a phantom with an SBR of 8:1 (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). We found that dbPET had the ability to better visualize smaller spheres than PEM and that silicon photomultiplier (SiPM)-based dbPET could visualize spheres more clearly compared with photomultiplier tube (PMT)-based dbPET. In addition, the ability to visualize the spheres was lower at the periphery than at the center for all the scanners.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eVisual assessment of the short-time acquisition images showed that 7.5-mm and 10-mm diameter spheres were visualized in all images acquired in 1 min. Even with a 10-min acquisition time, the PEM system could not visualize spheres measuring 5 mm or smaller, and the PMT-based dbPET system also had difficulty visualizing 3-mm spheres at the periphery. In contrast, a 3-mm sphere could be identified at the periphery at 5-min acquisition using SiPM-based dbPET.\u003c/p\u003e\u003cp\u003eQuantitative evaluation revealed that the shorter the acquisition time, the higher the CV\u003csub\u003eBG\u003c/sub\u003e, which was markedly elevated with SiPM-based dbPET at the periphery (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The DI and CRC were calculated for the 5-mm spheres that could be visually identified. The 5-mm sphere was not identified in any image at an SBR of 2:1. The shorter the acquisition time, the smaller the DI; however, the CRC value showed little change with respect to the acquisition time. The DI and CRC decreased in the following order: SiPM-based dbPET, PMT-based dbPET, and PEM. In the PEM image, no 5-mm spheres were identified in the periphery.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe results of the phantom study suggested that, even with breast PET, it was difficult to visualize BC with a low uptake approximately twice that of the background and a size of 10 mm or less. Furthermore, considering the identification of BC with a contrast against the background lesser than 8:1, the minimum acquisition time was 5 min, and 7 min was considered optimal if possible.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eClinical case review\u003c/h2\u003e\u003cp\u003eThe first set of images presents BC lesions with mass-like uptake located near the nipple (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. All three breast PET systems clearly visualized the lesions. However, the lesion margins appeared slightly sharper on images obtained with dbPET than on those obtained with PEM, which offered a slightly lower spatial resolution. This trend was consistent with the results of the preceding phantom study.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe next set of cases presents BC images showing mass-like uptake closer to the chest wall (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e). All breast PET images visualized BC with higher contrast and greater clarity compared with other modalities. Notably, among the three cases, PEM easily visualized the BC lesion located closest to the chest wall because PEM can scan the entire thorax with two plate-like detectors, resulting in no blind areas, unlike dbPET.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe third set of cases comprised non-mass uptake BC (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e). Breast PET visualized BC in a manner similar to contrast-enhanced magnetic resonance imaging (MRI). Furthermore, the high tumor-background contrast on breast PET images made it easier to evaluate the extent of the BC lesions.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAdditionally, to determine the minimum acquisition time for each breast PET scan, short-time acquisition images of NMU BCs were reconstructed based on the phantom study (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e9\u003c/span\u003e). Visually, shorter acquisition times resulted in increased noise at the edge of the FOV near the chest wall in all breast PET images, which was particularly marked in the PEM and dbPET2 images. In quantitative evaluation, both SUV\u003csub\u003emax\u003c/sub\u003e and TBR increased with shorter acquisition times for PEM and dbPET2 showing BC lesions near the chest wall, while they decreased for dbPET1 showing BC lesion near the nipple. The evaluation of clinical images reconstructed from the short-time acquisition data indicated that 1) the longer the acquisition time, the better the image quality, and 2) a minimum acquisition time of 5 min or longer for PEM and 3 min or longer for dbPET are needed.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo the best of our knowledge, this is the first study to directly compare three breast PET systems. All images in this study were reconstructed under the clinical conditions routinely used for each scanner, with the acquisition time being the only parameter modified. This approach was adopted because extensive optimization studies, particularly for dbPET, have already been reported and further fine-tuning of the reconstruction settings is neither practical nor clinically meaningful [16]. The acquisition duration is the most critical factor in clinical practice, since it directly affects both patient comfort—longer scans increase discomfort—and image quality—shorter scans compromise diagnostic reliability.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn this study, we directly compared the imaging performances of the opposed-type PEM and two generations of ring-type dbPET devices using both phantom and clinical data. The phantom study demonstrated that dbPET systems, particularly SiPM-based dbPET2, achieved superior detectability of small spheres compared with PEM, while the image quality was consistently lower at the periphery of the detectors. These findings were further supported by the clinical image review, which revealed similar trends across different lesion types. In addition, minimum acquisition times required to maintain diagnostic quality were determined to be ≥5 min for PEM and ≥3 min for dbPET. These results correspond to the difference in the defection rate of the LOR based on the difference in detector shape between the opposed-type and ring-shaped detectors. In fact, at the periphery of the FOV, where LOR deficiency was significant, deterioration in the PEM image quality was remarkable in the phantom study.\u003c/p\u003e\n\u003cp\u003eHowever, in the review of the clinical images, no disadvantage of PEM was observed in the visualization of BC close to the chest wall. PEM allows adjustment of the distance between the two plate-like detectors, enabling deeper inclusion of the chest wall within the FOV. Thus, PEM demonstrated superiority in visualizing lesions close to the chest wall owing to the shape of the detector. In contrast, dbPET has a fixed gantry diameter, which means that lesions close to the chest wall may fall outside the FOV, a limitation that persists even with the newer SiPM-based system [16]. Consequently, PEM remains the only breast PET modality without blind areas, which highlights its value in clinical practice.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn 2019, the JSNM published a revised version of clinical practice guidelines for breast PET [5]. Compared with the first edition issued in 2013, the more recent guidelines include more clinical evidence, enhancing their coverage of clinical applications and safety considerations. However, because of\u0026nbsp;significant differences in the geometric structures of the PEM and dbPET scanners, recommendations for standardizing image quality were not included. Recently, with the release of new-generation dbPET, the need for intersystem harmonization has become even more critical. The present study aimed to fill this gap by providing a comparative evaluation of PEM and two generations of dbPET under standardized phantom\u0026nbsp;and clinical conditions. Importantly, the purpose of this investigation was not to determine which device is superior\u0026nbsp;but rather to clarify how each system can be appropriately utilized to maximize patient benefit. Breast PET can provide valuable diagnostic information, irrespective of the scanner type, provided that the acquisition conditions are optimized. Our results emphasize that patients should not be disadvantaged simply because one type of breast PET system\u0026nbsp;was used instead of another. Based on our findings, patients with BC scanned with different breast PET systems will\u0026nbsp;benefit equally.\u003c/p\u003e\n\u003cp\u003eContrast-enhanced breast MRI is considered the gold standard for evaluating the extent of the primary breast lesion. This study did not systematically compare breast PET with contrast-enhanced breast MRI. However, previous studies comparing these two modalities have demonstrated that their detection rates are equivalent or that breast PET exhibits higher specificity, if the lesion lies in the FOV [8,19,20]. On contrast-enhanced MRI, background parenchymal enhancement is marked in young women and often masks breast lesions; however, even in such patients, physiological FDG uptake in the background mammary gland has little impact on the detection of breast lesions. The use of MRI is restricted to patients who cannot receive contrast agents due to allergies, renal impairment, those with claustrophobia, or those with metallic implants (in their bodies). In such cases, breast PET may serve as a valuable alternative or complementary tool. At our institution, PEM is prioritized for patients who are unable to undergo contrast-enhanced breast MRI.\u003c/p\u003e\n\u003cp\u003eThis study had a limitation. \u0026nbsp;The number of clinical cases was relatively small. Thus, future studies with larger patient cohorts and a broader range of scanners are warranted to validate and generalize the present findings. Because this study focused on domestically developed systems, further studies investigating other breast PET platforms are important for broader generalization. Moreover, as body habitus and breast size vary across populations, international studies that include diverse ethnic groups are essential to fully establish the clinical utility of breast PET.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFinancial support:\u0026nbsp;\u003c/strong\u003eThis research was supported by research grants from the Japanese Society of Nuclear Medicine in fiscal years 2024 and 2025.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding and Acknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by research grants (for the fiscal years 2023 and 2024) conferred by the Japanese Society of Nuclear Medicine. The authors sincerely thank the society for their support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSI is an employee of Mirai Imaging Inc., and YI is an employee of Shimadzu. The authors declare no conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eKalinyak JE, Berg WA, Schilling K, Madsen KS, Narayanan D, Tartar M. Breast cancer detection using high-resolution breast PET compared to whole-body PET or PET/CT. Eur J Nucl Med Mol Imaging 2014; 41:260\u0026ndash;75.\u003c/li\u003e\n \u003cli\u003eSatoh Y, Motosugi U, Imai M, Onishi H. Comparison of dedicated breast positron emission tomography and whole-body positron emission tomography/computed tomography images: a common phantom study. Ann Nucl Med 2020;34(2):119\u0026ndash;27.\u003c/li\u003e\n \u003cli\u003eWeinberg IN, Beylin D, Zavarzin V, Yarnall S, Stepanov PY, Anashkin E, et al. Positron emission mammography: high-resolution biochemical breast imaging. Technol Cancer Res Treat 2005;4:55\u0026ndash;60.\u003c/li\u003e\n \u003cli\u003eYamamoto Y, Tasaki Y, Kuwada Y, Ozawa Y, Inoue T. A preliminary report of breast cancer screening by positron emission mammography. Ann Nucl Med 2016; 30:130\u0026ndash;7.\u003c/li\u003e\n \u003cli\u003eMiyake KK, Matsumoto K, Inoue M, Nakamoto Y, Kanao S, Oishi T, et al. Performance Evaluation of a New Dedicated Breast PET Scanner Using NEMA NU4-2008 Standards. J Nucl Med 2014; 55:1198\u0026ndash;203.\u003c/li\u003e\n \u003cli\u003eSatoh Y, Kawamoto M, Kubota K, Murakami K, Hosono M, Senda S, et al. Clinical practice guidelines for high-resolution breast PET, 2019 edition. Ann Nucl Med 2021; 35:406\u0026ndash;14.\u003c/li\u003e\n \u003cli\u003eYanai A, Itoh M, Hirakawa H, Yanai K, Tashiro M, Harada R, et al. Newly-Developed Positron Emission Mammography (PEM) Device for the Detection of Small Breast Cancer. Tohoku J Exp Med 2018;245:13\u0026ndash;9.\u003c/li\u003e\n \u003cli\u003eYano F, Itoh M, Hirakawa H, Yamamoto S, Yoshikawa A, Hatazawa J. Diagnostic Accuracy of Positron Emission Mammography with \u003csup\u003e18\u003c/sup\u003eF-fluorodeoxyglucose in Breast Cancer Tumor of Less than 20 mm in Size. Asia Ocean J Nucl Med Biol 2019; 7:13\u0026ndash;21.\u003c/li\u003e\n \u003cli\u003eMoliner L, Gonzalez AJ, Soriano A, Sanchez F, Correcher C, Orero A, et al. Design and evaluation of the MAMMI dedicated breast PET. Med Phys 2012;39:5393\u0026ndash;404.\u003c/li\u003e\n \u003cli\u003eMorimoto-Ishikawa D, Hanaoka K, Watanabe S, Yamada T, Yamakawa Y, Minagawa S, et al. Evaluation of the performance of a high-resolution time-of-flight PET system dedicated to the head and breast according to NEMA NU 2-2012 standard. EJNMMI Phys 2022;9:88.\u003c/li\u003e\n \u003cli\u003eSatoh Y, Hanaoka K, Ikegawa C, Imai M, Watanabe S, Morimoto-Ishikawa D, et al. Organ-Specific Positron Emission Tomography Scanners for Breast Imaging: Comparison between the Performances of Prior and Novel Models. Diagnostics (Basel) 2023;13:1079.\u003c/li\u003e\n \u003cli\u003eSatoh Y, Motosugi U, Imai M, Omiya Y, Onishi H. Evaluation of image quality at the detector\u0026apos;s edge of dedicated breast positron emission tomography. EJNMMI Phys 2021;8:5.\u003c/li\u003e\n \u003cli\u003eSatoh Y, Imai M, Ikegawa C, Hirata K, Abo N, Kusuzaki M, et al. Effect of radioactivity outside the field of view on image quality of dedicated breast positron emission tomography: preliminary phantom and clinical studies. Ann Nucl Med 2022;36:1010\u0026ndash;8.\u003c/li\u003e\n \u003cli\u003eNarayanan D, Madsen KS, Kalinyak JE, Berg WA. Interpretation of positron emission mammography: feature analysis and rates of malignancy. AJR Am J Roentgenol 2011;196:956\u0026ndash;70.\u003c/li\u003e\n \u003cli\u003eMiyakeKK, KataokaM, IshimoriT, MatsumotoY, ToriiM, TakadaM, et al. A Proposed Dedicated Breast PET Lexicon: Standardization of Description and Reporting of Radiotracer Uptake in the Breast. Diagnostics (Basel) 2021;11:1267.\u003c/li\u003e\n \u003cli\u003eSatoh Y, Motosugi U, Onishi H, Asakawa Y, Ikegawa C, Onishi H. Optimal relaxation parameters of dynamic row-action maximum likelihood algorithm and post-smoothing filter for image reconstruction of dedicated breast PET. Ann Nucl Med 2021;35:292\u0026ndash;302.\u003c/li\u003e\n \u003cli\u003eSatoh Y, Ishida J, Inui Y, Takenaka A, Bando S, Ishida S, et al. Can the newer model of breast-specific PET reduce the \u0026ldquo;blind area\u0026rdquo;? Diagnostics (Basel) 2024;14:2068.\u003c/li\u003e\n \u003cli\u003eBerg WA, Madsen KS, Schilling K, Tartar M, Pisano ED, Larsen LH, et al. Comparative effectiveness of positron emission mammography and MRI in the contralateral breast of women with newly diagnosed breast cancer. AJR Am J Roentgenol 2012;198:219\u0026ndash;32.\u003c/li\u003e\n \u003cli\u003eKataoka M, Iima M, Miyake KK, Matsumoto Y. Multiparametric imaging of breast cancer: An update of current applications. Diagn Interv Imaging. 2022;103:574\u0026ndash;83.\u003c/li\u003e\n \u003cli\u003eFowler AM, Miyake KK, Nakamoto Y. Clinical Applications of Dedicated Breast Positron Emission Tomography. PET Clin 2024;19:105\u0026ndash;17.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"annals-of-nuclear-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anme","sideBox":"Learn more about [Annals of Nuclear Medicine](http://link.springer.com/journal/12149)","snPcode":"12149","submissionUrl":"https://www.editorialmanager.com/anme/default2.aspx","title":"Annals of Nuclear Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"breast PET, positron emission mammography (PEM), dedicated breast PET (dbPET), image quality, acquisition time","lastPublishedDoi":"10.21203/rs.3.rs-7966789/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7966789/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eBreast-specific positron emission tomography (breast PET), including positron emission mammography (PEM) and dedicated breast PET (dbPET), provides high-resolution functional imaging for detecting small breast cancers. However, direct cross-system comparisons and acquisition protocol optimizations remain underexplored. This study aimed to directly compare the imaging performance of the opposed-type PEM, first-generation photomultiplier tube (PMT)-based dbPET (dbPET1), and second-generation silicon photomultiplier (SiPM)-based dbPET (dbPET2) using clinical imaging protocols, and determine the requisite acquisition conditions for achieving comparable depiction of breast lesions across systems.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA cylindrical phantom with four spheres (diameter: 3\u0026ndash;10 mm) was prepared with sphere-to-background ratios (SBRs) of 2:1, 4:1, and 8:1, based on clinical images. The phantom was scanned for 10 min in list mode with the spheres at the center and periphery of each detector and reconstructed at 1\u0026ndash;10 min. Visual and quantitative evaluations were performed using the coefficient of variation of the background (CV\u003csub\u003eBG\u003c/sub\u003e), detection index (DI), and contrast recovery coefficient (CRC). Representative clinical images of three lesion types, viz. mass-like uptake near the nipple, mass-like uptake close to the chest wall, and non-mass uptake, were also assessed using visual evaluation and the tumor-to-background ratio (TBR).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003ePhantom images with SBRs of 2:1 and 4:1 did not sufficiently visualize the small spheres; therefore, an 8:1 ratio was chosen for the analysis. dbPET was capable of visualizing smaller spheres compared with PEM. At the periphery, image quality was reduced for all systems, while all systems were able to identify spheres\u0026thinsp;\u0026ge;\u0026thinsp;7.5 mm in diameter at a contrast ratio of 1:8 under clinical imaging protocols. The DI decreased with shorter acquisition time, while the CRC remained relatively stable. The CV\u003csub\u003eBG\u003c/sub\u003e increased, especially in dbPET2. Clinical evaluation confirmed that clarified the minimum acquisition times required to ensure adequate diagnostic image quality for different breast PET systems (\u0026ge;\u0026thinsp;5 min for dbPET, \u0026ge;\u0026thinsp;7 min for PEM). dbPET provided superior detectability, whereas PEM had advantages near the chest wall. TBR analysis supported the consistency between the results of evaluation of the phantom and patients.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThis study demonstrated that all breast-specific PET systems can achieve image quality capable of identifying sub-centimeter lesions within clinically feasible scan times (5 min for dbPET, 7 min for PEM). These findings provide the foundation for harmonizing protocols across systems and optimizing their clinical application in breast cancer diagnosis.\u003c/p\u003e","manuscriptTitle":"Comparison of Image Quality of Breast-Specific Positron Emission Tomography: Insights from Phantom and Clinical Studies in a Japanese Multicenter Trial ​","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-11 16:43:43","doi":"10.21203/rs.3.rs-7966789/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-10-31T05:58:04+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-31T02:18:56+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-29T02:48:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Nuclear Medicine","date":"2025-10-28T04:04:38+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-nuclear-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anme","sideBox":"Learn more about [Annals of Nuclear Medicine](http://link.springer.com/journal/12149)","snPcode":"12149","submissionUrl":"https://www.editorialmanager.com/anme/default2.aspx","title":"Annals of Nuclear Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8df02273-7361-4784-80c1-fdeb2db64b6d","owner":[],"postedDate":"November 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-09T16:04:21+00:00","versionOfRecord":{"articleIdentity":"rs-7966789","link":"https://doi.org/10.1007/s12149-026-02165-5","journal":{"identity":"annals-of-nuclear-medicine","isVorOnly":false,"title":"Annals of Nuclear Medicine"},"publishedOn":"2026-02-07 15:59:37","publishedOnDateReadable":"February 7th, 2026"},"versionCreatedAt":"2025-11-11 16:43:43","video":"","vorDoi":"10.1007/s12149-026-02165-5","vorDoiUrl":"https://doi.org/10.1007/s12149-026-02165-5","workflowStages":[]},"version":"v1","identity":"rs-7966789","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7966789","identity":"rs-7966789","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}