Development for a novel phantom for evaluating image quality in small-animal single photon emission computed tomography and positron emission tomography.

Development for a novel phantom for evaluating image quality in small-animal single photon emission computed tomography and positron emission tomography. | 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 Development for a novel phantom for evaluating image quality in small-animal single photon emission computed tomography and positron emission tomography. Takayuki Shibutani, Masahisa Onoguchi, Takayuki Kannno This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4916789/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives The National Electrical Manufacturers Association (NEMA) has released guidelines delineating the performance of positron emission tomography (PET) devices designed for small animals. However, the NEMA NU 4 image quality phantom could not measure the known contrasts of the hot rod images and the recovery coefficient (RC) of cold rod images due to the structure of the phantom. Thus, we have devised novel hot rod and cold rod phantoms capable of evaluating uniformity and RCs for both hot rod and cold rod images. This study aimed to assess uniformity, image contrasts, and RCs in hot rod and cold rod images of single photon emission computed tomography (SPECT) and PET using the newly developed phantom. Methods The new physical phantom consisted of rod and pool sections. To assess image uniformity, the pool section, designed in a cylindrical shape, was utilized. Conversely, the rod section was created in hot rod and cold rod shapes and integrated into a cylindrical phantom with the same design as the pool section. Hot rod and cold rod phantoms were designed with six different 1–6 mm diameter rods. The rod and pool sections of the hot rod phantom were separately filled with 99m Tc and 18 F solutions. In the rod section, the cylindrical part was defined as the background (BG), with a radioactive concentration ratio of 4:1 for the hot rod and BG. The cylindrical part containing the cold rod was separately filled with 99m Tc and 18 F solutions. The 99m Tc and 18 F phantoms were acquired separately over 30 min. A transverse image with a cubic voxels of 0.8 mm length was reconstructed using a pixel-based ordered subset expectation maximization algorithm. Results The contrast of the hot rod for 99m Tc and 18 F showed lower values with a decreasing rod diameter. Furthermore, the 99m Tc image demonstrated a higher contrast than the 18 F image and approached the true contrast. The cold rod contrasts with 99m Tc and 18 F followed a similar trend as the hot rod contrast. The RCs for the hot rods with 4–6 mm diameters were similar, whereas hot rods with diameters ≤ 3 mm revealed lower values as the rod diameter decreased. The inverse RC was lower with a decreasing cold rod diameter. Moreover, the cold rod image with 18 F demonstrated a lower inverse RC than with the 99m Tc. The percent coefficient of variation (%CV) for the 99m Tc and 18 F images was 4% and 7%, respectively, with the 99m Tc image displaying a lower %CV compared to the 18 F image. Conclusion We have developed a new phantom that allows physical phenomenon evaluation in small animal SPECT and PET images, and can evaluate the image contrast, RC, and uniformity of both hot rod and cold rod images. partial volume effect small-animal SPECT PET cold rod phantom Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Small animal imaging in nuclear medicine plays a crucial role in drug development and disease elucidation [ 1 , 2 ]. The quantitative assessment of nuclear medicine images using single-photon emission computed tomography (SPECT) and positron emission tomography (PET) is pivotal for assessing drug efficacy and understanding pathological conditions at the molecular level. SPECT and PET scanners may demonstrate performance variations owing to factors such as scintillators, collimators, acquisition, and image reconstruction parameters, and over time, this variability can impact quantitative values, potentially resulting in image artifacts [ 3 ]. The National Electrical Manufacturers Association (NEMA) has published guidelines for evaluating the performance of PET devices for small animals [ 4 ]. The NEMA NU 4 image quality phantom (Fig. 1 ) is employed to assess the image quality of SPECT and PET images, allowing physical indicator evaluation such as uniformity, recovery coefficients (RCs) of hot rods, contrast, and accuracy correction [ 5 – 8 ]. However, the NEMA NU 4 image quality phantom failed to accurately measure the known contrasts of hot rod images due to the inability to fill the radioactive solution around the hot rod section. To interpret the quantitative values, accurate contrast measurements are essential. In addition, the NEMA NU 4 phantom could assess the RCs of hot rod images but could not evaluate the RCs of cold rod image. The evaluation of cold rod images is equally important as the evaluation of hot rod images, as highlighted in several previous studies [ 9 – 13 ]. Cold rod image evaluation must be understood to interpret the pathophysiology and quantitative metrics in nuclear cardiology and neurology. A new phantom capable of assessing uniformity and RCs of both hot rod and cold rod images was developed, addressing the limitations of the NEMA NU 4 phantom. In the same outer container, the new phantom can be used as a hot rod phantom or cold rod phantom. Furthermore, the hot rod phantom was used to assess known contrasts by being filled with two different radioactive solutions. To evaluate the image quality and the accuracy of quantitative metrics, the availability of the known contrasts is vital. This study aimed to assess uniformity, image contrasts, and RCs for hot rod and cold rod images with 99m Tc and 18 F using this novel phantom. Material and Methods Phantom design The new phantom manufactured by Hokuriku EP Co., Ltd. was comprised of rod and pool sections (Fig. 2 ). The pool section, designed in a cylindrical shape (40 mm diameter and 20 mm length), was utilized to evaluate image uniformity. The rod section was created in hot rod and cold rod shapes and integrated into a cylindrical phantom with a same design as the pool section. In the rod section, hot rod and cold rod parts were designed with six different rod sizes ranging from 1 to 6 mm in diameter (length: 20 mm). Acrylic tubes and acrylic rods without cavities, respectively, were used to construct the hot rod and cold rod parts, and hot rod and cold rod parts can be exchanged in the same pool section. To reduce the impact on image quality from radiation interference, such as contamination of photons or scattering from another section, a 27 mm acrylic cap is attached between the pool and rod sections. Since the full width at half maximum (FWHM) values of an index of the spatial resolution of commercial small-animal SPECT or PET scanners were approximately 1–2 mm for both 18 F and 99m Tc, the acrylic cap thickness is designed to be at least 10 times the FWHM value [ 15 – 18 ]. This design also prevents mutual interference between the images of the rod and pool sections owing to the partial volume effects (PVE). If radiation interference affects the image and quantitative assessments, the rod and pool sections can be effectively separated. Phantom preparation The hot rod phantoms with 99m Tc and 18 F were separately created. Hot rods were assembled into the cylindrical holder that was utilized as the background (BG). The radioactive concentrations of the hot rod and the BG part in the rod section were set at 8 and 2 MBq/mL with 99m Tc, or 48 and 12 MBq/mL with 18 F, respectively. The radioactive concentration ratio of the hot rod to BG was set at 4:1. Moreover, the pool section of the hot rod phantom was set at 8 MBq/mL with 99m Tc or 48 MBq/mL with 18 F, respectively. The cold rod phantom was inserted into the rod section, and the rod section was filled with a 99m Tc solution of 8 MBq/mL or a 18 F solution of 48 MBq/mL, respectively. Additionally, the pool section was filled with a nonradioactive water as BG. Hot rod and cold rod phantoms were separately prepared. Acquisition and image reconstruction parameters The SPECT-PET/computed tomography (CT) scanner was utilized as a VECTor + /CT (MILabs B.V., Netherlands) of a triple-detectors gamma camera with high-energy ultrahigh-resolution rat and mouse-type clustered multi-pinhole collimator. The 99m Tc and 18 F phantoms were acquired separately over 30 min. The photon energy window for 99m Tc was set at 141 keV ± 10%, with a 7% scatter window on each side. A transverse image with a cubic voxels of 0.8 mm length was reconstructed using a pixel-based ordered subset expectation maximization algorithm. [ 19 ]. The numbers of subset and iteration were set to 32 and 8 for 99m Tc, and 32 and 17 for 18 F, respectively. A Gaussian filter, with a FWHM of 1.6 mm, was applied as a postfilter for both 99m Tc and 18 F. Attenuation and scatter corrections were conducted using the triple energy window technique and CT-based attenuation correction [ 20 ]. Image assessment Image analysis was performed using PMOD software (version 4.002, PMOD Technologies LLC, Fallanden, Switzerland). Circular regions of interest (ROIs) were drawn on hot rods and cold rods with diameters ranging from 1 to 6 mm. Furthermore, a circular ROI with a 12-mm diameter was also drawn in the BG region inside the 1–6 mm rod parts (Fig. 3 ). The hot rod and cold rod image contrasts were calculated by the following equations (1) and (2): Contrast hot = \(\:\frac{B}{A}\) (1) Contrast cold = \(\:\frac{A-B}{A}\) × 100 (2) where A and B represent the average values of each rod and the average value of the BG part. RCs for hot rod images were calculated as relative values using 6 mm as the reference, according to the maximum value in the ROI for each hot rod. Inverse RCs of cold rod images were calculated using the following Eq. (3) [ 21 ]: Inverse RC= \(\:1-\frac{{B}_{i}}{A}\) (i= 1–6) where A represents the minimum counts in the ROI of the BG region inside the 1–6 mm cold rod parts, and B i reflects the minimum counts in the ROI of the 1–6 mm cold rod parts. For uniformity evaluation, the pool section of the hot rod phantom was employed. A circular ROI covering 80% of the area was drawn on the transverse image of the pool section (Fig. 3 ). The percent coefficient of variation (%CV) was calculated from the average value and standard deviation in the ROI. The contrast, RC, and %CV were compared between 99m Tc and 18 F. Results The contrast of hot rod and cold rod images was shown in Fig. 4 . The contrasts for the 1–6 mm hot rods were 1.1, 2.1, 2.8, 3.3, 3.6, and 3.8 for 99m Tc, and 1.0, 1.6, 2.4, 2.9, 3.2, and 3.3 for 18 F, respectively. The contrast of the hot rod for 99m Tc and 18 F demonstrated lower values with a decreasing rod diameter. Moreover, the 99m Tc image showed a higher contrast than the 18 F image and approached the true contrast. The contrasts for 1–6 mm cold rod parts were 10%, 32%, 59%, 70%, 80%, and 86% for 99m Tc, and 0%, 7%, 28%, 49%, 63%, and 71% for 18 F, respectively. The contrast in cold rod images with 99m Tc and 18 F revealed a similar tendency as the hot rod contrast. The RCs of 1–6 mm hot rods were 0.27, 0.51, 0.81, 0.98, 0.97, and 1.00 for 99m Tc and 0.28, 0.46, 0.76, 0.97, 1.05, and 1.00 for 18 F, respectively (Fig. 5 a). The RCs for the hot rods with 4–6 mm diameters were similar, whereas hot rods with diameters ≤ 3 mm demonstrated lower values as the rod diameter declined. Furthermore, the RC of the 5 mm hot rod in 18 F was higher than that of the 6 mm hot rod. The inverse RCs of 1–6 mm cold rod parts were 0.06, 0.33, 0.68, 0.84, 0.93, and 0.96 for 99m Tc, and 0.00, 0.26, 0.53, 0.76, 0.83, and 0.94 for 18 F, respectively (Fig. 5 b). The inverse RC revealed lower values with a declining cold rod diameter. Moreover, the inverse RC for the cold rod image with 18 F was lower than that with 99m Tc. The %CV of the pool section for 99m Tc and 18 F images was 4% and 7%, with the 99m Tc image displaying a lower %CV compared to the 18 F image. Transverse images of the hot rod, cold rod, and pool sections were shown in Fig. 6 . The hot rod and cold rod images with 99m Tc revealed a higher contrast compared with those with 18 F. The pool image with 99m Tc appeared more homogeneous than that with 18 F. Discussion We evaluated the physical indices of SPECT and PET images utilizing the new phantom. Our phantom allows for the assessment of known contrast in hot rod images, as well as the contrast and RC of cold rod images, in addition to the physical indices assessable with the NEMA NU 4 phantom. The influence of PVE on the cold rod image is necessary to interpret the quantitative evaluation of the ischemic region [ 22 , 23 ]. Furthermore, the overestimation or underestimation of the quantitative value in the tumor region may lead to PVE and Gibbs artifacts in nuclear oncology [ 24 , 25 ]. While the NEMA NU 4 phantom is useful for verifying the accuracy of absolute quantitation using Bq/mL with a well counter or dose calibrator as a reference [ 26 , 27 ], the accuracy of the absolute quantitative index is dependent on the dosimeter error, such as the dose calibrator and well-counter, as well as the variation of the cross-calibration factor (CCF) and errors caused by the reconstructed image [ 28 – 30 ]. Consequently, CCF uncertainty may arise from factors such as acquisition, image reconstruction, and other variables. Delineating between these factors will enhance quantitative accuracy. Relative evaluation in phantom experiments is excellent for detecting acquisition and image reconstruction errors in SPECT and PET systems. The contrast can be briefly set to a theoretical value by preparing solutions of two different radioactivity concentrations. The contrast ratio was set to 4, and the hot rod with a 6 mm diameter at 99m Tc obtained a contrast close to 4 in this study. The contrast of 18 F was lower than that of 99m Tc owing to spatial resolution limitations. The spatial resolution of 99m Tc and 18 F for VECTor + /CT has been reported to be better for 99m Tc [ 17 ]. High spatial resolution systems display a high contrast owing to the small PVE. Hence, the relationship of the hot rod contrast between 99m Tc and 18 F reflected the previous study findings, and a similar trend was noted for cold rod contrasts. The RC of the hot rod phantom remained relatively constant between 4–6 mm. Generally, PVE occurs for diameters < 2–3-fold the FWHM. The FWHM measured by the line source in VECTor + /CT is approximately 1.0 mm for both 99m Tc and 18 F, aligning with the physical index [ 18 ]. Conversely, the RC was overestimated for the 5 mm diameter hot rod with 18 F. The VECTor + /CT system applies a spatial resolution correction to 18 F only. Although spatial resolution correction can improve the high-resolution image quality, it also produces Gibbs artifacts [ 25 , 31 ]. The overestimation of the 5 mm diameter hot rod with 18 F may be influenced by Gibbs artifacts. The inverse RC of the cold rod phantom showed low values with a decreasing rod diameter, demonstrating a different behavior compared to the hot rod phantom. This disparity may be attributed to the presence of scattered radiation included in the cold rods. The 18 F photons are strongly influenced by septal penetration from the collimator, as well as Compton scattering, due to their higher radiation energy compared with 99m Tc photons [ 32 ]. The uniformity of the pool section with 99m Tc and 18 F also reflects these differences. Scattered radiation, septal penetration, and image noise are more pronounced in cold rod parts than in hot rod parts. Consequently, the inverse RC of 18 F is predicted to be lower than that of 99m Tc. In small animal studies, the radioactivity concentrations of 18 F were higher than those typically encountered. PET images on the VECTor + /CT scanner were acquired using a SPECT system rather than a coincidence system. Moreover, the detector uses a NaI(Tl) scintillator with a 9.5 mm crystal thickness, resulting in counting losses for high-energy photons such as 18 F. A previous study reported that only 10% of all 18 F photons are detected as signals [ 17 ]. Hence, high-energy nuclides such as 18 F require higher radioactivity concentrations. The new phantom could evaluate PVE using RC due to its structure, which included large rods corresponding to the small animal SPECT and PET systems. Hot rods with RC values of 4–6 mm demonstrated similar values. This indicates that PVE is not considerably affected in rods larger than 4 mm under the acquisition and imaging conditions at our institution. In addition, the new phantom will facilitate the interpretation of quantitative evaluations of small animal SPECT and PET images, allowing the assessment of physical phenomena in both hot rods and cold rods. Conclusion We have developed a new phantom that allows physical phenomenon evaluation in small animal SPECT and PET images. This new phantom can assess the image contrast, RC, and uniformity of both hot rod and cold rod images. Additionally, it can evaluate the performance of small-animal SPECT and PET systems. Declarations Acknowledgments We would like to thank Akira E of Hokuriku E.P., Japan for his excellent technical support of phantom production. Funding This study was supported by JSPS KAKENHI Grant Number 18K15628. Disclosure The authors report no potential conflicts of interest relevant to this study. References Liu T, Wu Y, Shi L, Li L, Hu B, Wang Y, et al. 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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-4916789","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":342873717,"identity":"d5b2f359-3f9a-4e6a-9c77-e3b3d1543de0","order_by":0,"name":"Takayuki Shibutani","email":"","orcid":"","institution":"Kanazawa University","correspondingAuthor":false,"prefix":"","firstName":"Takayuki","middleName":"","lastName":"Shibutani","suffix":""},{"id":342873718,"identity":"b6409eb7-1303-42e6-9417-cf8254ca9d51","order_by":1,"name":"Masahisa Onoguchi","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0001-7508-5975","institution":"Department of Quantum Medical Technology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University","correspondingAuthor":true,"prefix":"","firstName":"Masahisa","middleName":"","lastName":"Onoguchi","suffix":""},{"id":342873719,"identity":"6b2de97e-5973-4d6e-918e-7fa87eea130c","order_by":2,"name":"Takayuki Kannno","email":"","orcid":"","institution":"Nagoya University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Takayuki","middleName":"","lastName":"Kannno","suffix":""}],"badges":[],"createdAt":"2024-08-15 03:21:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4916789/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4916789/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66649577,"identity":"7f949312-e431-4c57-90cf-8bfba727f2e2","added_by":"auto","created_at":"2024-10-15 07:29:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":533898,"visible":true,"origin":"","legend":"\u003cp\u003eAppearance of the NEMA NU 4 image quality phantom\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4916789/v1/71b143ca2f11aeaa693b5887.png"},{"id":66649579,"identity":"035f2307-1197-416b-9cce-0d307126feec","added_by":"auto","created_at":"2024-10-15 07:29:00","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":715748,"visible":true,"origin":"","legend":"\u003cp\u003eAppearance of a new physical phantom\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4916789/v1/948c822c2051c67edce4145f.png"},{"id":66649582,"identity":"92cb9154-2240-4a4e-a351-8d284400a3fe","added_by":"auto","created_at":"2024-10-15 07:29:01","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":674888,"visible":true,"origin":"","legend":"\u003cp\u003eRegion of interest (ROI) setting of hot rod, pool and cold rod images\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4916789/v1/3c6f52dbcc52ba39cdd9f31b.png"},{"id":66649581,"identity":"787ccbd6-0662-4fa5-95dd-43a75a63323d","added_by":"auto","created_at":"2024-10-15 07:29:00","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":118078,"visible":true,"origin":"","legend":"\u003cp\u003eThe contrast of hot rod (a) and cold rod (b) images. The dotted line indicates the true value (hot rod: 4.0, cold rod: 100%).\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4916789/v1/be21d08816d41f3053832a91.png"},{"id":66649578,"identity":"9071b713-09b2-4fe7-9116-68f313bde7ca","added_by":"auto","created_at":"2024-10-15 07:29:00","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":124641,"visible":true,"origin":"","legend":"\u003cp\u003eRecovery coefficients (RCs) with hot rod parts and inverse RCs with cold rod parts\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-4916789/v1/51b17779c77d3f2533d501da.png"},{"id":66650628,"identity":"10364960-bbe0-4d0c-9ca6-3baf80b8685a","added_by":"auto","created_at":"2024-10-15 07:37:00","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1241314,"visible":true,"origin":"","legend":"\u003cp\u003eTransverse images with hot rod, cold rod and pool parts. The upper and lower rows indicate \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF images.\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-4916789/v1/5fe8154a0893f97910511915.png"},{"id":79730279,"identity":"9d64d193-2240-4013-8f30-1188bfb55aa9","added_by":"auto","created_at":"2025-04-02 05:29:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5996972,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4916789/v1/853edb0a-92d9-490e-a342-ac3afbd893db.pdf"}],"financialInterests":"","formattedTitle":"Development for a novel phantom for evaluating image quality in small-animal single photon emission computed tomography and positron emission tomography.","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSmall animal imaging in nuclear medicine plays a crucial role in drug development and disease elucidation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The quantitative assessment of nuclear medicine images using single-photon emission computed tomography (SPECT) and positron emission tomography (PET) is pivotal for assessing drug efficacy and understanding pathological conditions at the molecular level. SPECT and PET scanners may demonstrate performance variations owing to factors such as scintillators, collimators, acquisition, and image reconstruction parameters, and over time, this variability can impact quantitative values, potentially resulting in image artifacts [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The National Electrical Manufacturers Association (NEMA) has published guidelines for evaluating the performance of PET devices for small animals [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The NEMA NU 4 image quality phantom (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) is employed to assess the image quality of SPECT and PET images, allowing physical indicator evaluation such as uniformity, recovery coefficients (RCs) of hot rods, contrast, and accuracy correction [\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, the NEMA NU 4 image quality phantom failed to accurately measure the known contrasts of hot rod images due to the inability to fill the radioactive solution around the hot rod section. To interpret the quantitative values, accurate contrast measurements are essential. In addition, the NEMA NU 4 phantom could assess the RCs of hot rod images but could not evaluate the RCs of cold rod image. The evaluation of cold rod images is equally important as the evaluation of hot rod images, as highlighted in several previous studies [\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Cold rod image evaluation must be understood to interpret the pathophysiology and quantitative metrics in nuclear cardiology and neurology.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA new phantom capable of assessing uniformity and RCs of both hot rod and cold rod images was developed, addressing the limitations of the NEMA NU 4 phantom. In the same outer container, the new phantom can be used as a hot rod phantom or cold rod phantom. Furthermore, the hot rod phantom was used to assess known contrasts by being filled with two different radioactive solutions. To evaluate the image quality and the accuracy of quantitative metrics, the availability of the known contrasts is vital. This study aimed to assess uniformity, image contrasts, and RCs for hot rod and cold rod images with \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF using this novel phantom.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePhantom design\u003c/h2\u003e \u003cp\u003eThe new phantom manufactured by Hokuriku EP Co., Ltd. was comprised of rod and pool sections (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The pool section, designed in a cylindrical shape (40 mm diameter and 20 mm length), was utilized to evaluate image uniformity. The rod section was created in hot rod and cold rod shapes and integrated into a cylindrical phantom with a same design as the pool section. In the rod section, hot rod and cold rod parts were designed with six different rod sizes ranging from 1 to 6 mm in diameter (length: 20 mm). Acrylic tubes and acrylic rods without cavities, respectively, were used to construct the hot rod and cold rod parts, and hot rod and cold rod parts can be exchanged in the same pool section. To reduce the impact on image quality from radiation interference, such as contamination of photons or scattering from another section, a 27 mm acrylic cap is attached between the pool and rod sections. Since the full width at half maximum (FWHM) values of an index of the spatial resolution of commercial small-animal SPECT or PET scanners were approximately 1\u0026ndash;2 mm for both \u003csup\u003e18\u003c/sup\u003eF and \u003csup\u003e99m\u003c/sup\u003eTc, the acrylic cap thickness is designed to be at least 10 times the FWHM value [\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This design also prevents mutual interference between the images of the rod and pool sections owing to the partial volume effects (PVE). If radiation interference affects the image and quantitative assessments, the rod and pool sections can be effectively separated.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePhantom preparation\u003c/h2\u003e \u003cp\u003eThe hot rod phantoms with \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF were separately created. Hot rods were assembled into the cylindrical holder that was utilized as the background (BG). The radioactive concentrations of the hot rod and the BG part in the rod section were set at 8 and 2 MBq/mL with \u003csup\u003e99m\u003c/sup\u003eTc, or 48 and 12 MBq/mL with \u003csup\u003e18\u003c/sup\u003eF, respectively. The radioactive concentration ratio of the hot rod to BG was set at 4:1. Moreover, the pool section of the hot rod phantom was set at 8 MBq/mL with \u003csup\u003e99m\u003c/sup\u003eTc or 48 MBq/mL with \u003csup\u003e18\u003c/sup\u003eF, respectively.\u003c/p\u003e \u003cp\u003eThe cold rod phantom was inserted into the rod section, and the rod section was filled with a \u003csup\u003e99m\u003c/sup\u003eTc solution of 8 MBq/mL or a \u003csup\u003e18\u003c/sup\u003eF solution of 48 MBq/mL, respectively. Additionally, the pool section was filled with a nonradioactive water as BG. Hot rod and cold rod phantoms were separately prepared.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eAcquisition and image reconstruction parameters\u003c/h2\u003e \u003cp\u003eThe SPECT-PET/computed tomography (CT) scanner was utilized as a VECTor\u003csup\u003e+\u003c/sup\u003e/CT (MILabs B.V., Netherlands) of a triple-detectors gamma camera with high-energy ultrahigh-resolution rat and mouse-type clustered multi-pinhole collimator. The \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF phantoms were acquired separately over 30 min. The photon energy window for \u003csup\u003e99m\u003c/sup\u003eTc was set at 141 keV\u0026thinsp;\u0026plusmn;\u0026thinsp;10%, with a 7% scatter window on each side. A transverse image with a cubic voxels of 0.8 mm length was reconstructed using a pixel-based ordered subset expectation maximization algorithm. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The numbers of subset and iteration were set to 32 and 8 for \u003csup\u003e99m\u003c/sup\u003eTc, and 32 and 17 for \u003csup\u003e18\u003c/sup\u003eF, respectively. A Gaussian filter, with a FWHM of 1.6 mm, was applied as a postfilter for both \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF. Attenuation and scatter corrections were conducted using the triple energy window technique and CT-based attenuation correction [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eImage assessment\u003c/h2\u003e \u003cp\u003eImage analysis was performed using PMOD software (version 4.002, PMOD Technologies LLC, Fallanden, Switzerland). Circular regions of interest (ROIs) were drawn on hot rods and cold rods with diameters ranging from 1 to 6 mm. Furthermore, a circular ROI with a 12-mm diameter was also drawn in the BG region inside the 1\u0026ndash;6 mm rod parts (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The hot rod and cold rod image contrasts were calculated by the following equations (1) and (2):\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eContrast\u003csub\u003ehot\u003c/sub\u003e= \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\frac{B}{A}\\)\u003c/span\u003e\u003c/span\u003e (1)\u003c/p\u003e \u003cp\u003eContrast\u003csub\u003ecold\u003c/sub\u003e= \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\frac{A-B}{A}\\)\u003c/span\u003e\u003c/span\u003e \u0026times; 100 (2)\u003c/p\u003e \u003cp\u003ewhere A and B represent the average values of each rod and the average value of the BG part. RCs for hot rod images were calculated as relative values using 6 mm as the reference, according to the maximum value in the ROI for each hot rod. Inverse RCs of cold rod images were calculated using the following Eq.\u0026nbsp;(3) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]:\u003c/p\u003e \u003cp\u003eInverse RC= \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:1-\\frac{{B}_{i}}{A}\\)\u003c/span\u003e\u003c/span\u003e (i= 1\u0026ndash;6)\u003c/p\u003e \u003cp\u003ewhere A represents the minimum counts in the ROI of the BG region inside the 1\u0026ndash;6 mm cold rod parts, and B\u003csub\u003ei\u003c/sub\u003e reflects the minimum counts in the ROI of the 1\u0026ndash;6 mm cold rod parts. For uniformity evaluation, the pool section of the hot rod phantom was employed. A circular ROI covering 80% of the area was drawn on the transverse image of the pool section (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The percent coefficient of variation (%CV) was calculated from the average value and standard deviation in the ROI. The contrast, RC, and %CV were compared between \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe contrast of hot rod and cold rod images was shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. The contrasts for the 1\u0026ndash;6 mm hot rods were 1.1, 2.1, 2.8, 3.3, 3.6, and 3.8 for \u003csup\u003e99m\u003c/sup\u003eTc, and 1.0, 1.6, 2.4, 2.9, 3.2, and 3.3 for \u003csup\u003e18\u003c/sup\u003eF, respectively. The contrast of the hot rod for \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF demonstrated lower values with a decreasing rod diameter. Moreover, the \u003csup\u003e99m\u003c/sup\u003eTc image showed a higher contrast than the \u003csup\u003e18\u003c/sup\u003eF image and approached the true contrast. The contrasts for 1\u0026ndash;6 mm cold rod parts were 10%, 32%, 59%, 70%, 80%, and 86% for \u003csup\u003e99m\u003c/sup\u003eTc, and 0%, 7%, 28%, 49%, 63%, and 71% for \u003csup\u003e18\u003c/sup\u003eF, respectively. The contrast in cold rod images with \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF revealed a similar tendency as the hot rod contrast.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe RCs of 1\u0026ndash;6 mm hot rods were 0.27, 0.51, 0.81, 0.98, 0.97, and 1.00 for \u003csup\u003e99m\u003c/sup\u003eTc and 0.28, 0.46, 0.76, 0.97, 1.05, and 1.00 for \u003csup\u003e18\u003c/sup\u003eF, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ea). The RCs for the hot rods with 4\u0026ndash;6 mm diameters were similar, whereas hot rods with diameters\u0026thinsp;\u0026le;\u0026thinsp;3 mm demonstrated lower values as the rod diameter declined. Furthermore, the RC of the 5 mm hot rod in \u003csup\u003e18\u003c/sup\u003eF was higher than that of the 6 mm hot rod. The inverse RCs of 1\u0026ndash;6 mm cold rod parts were 0.06, 0.33, 0.68, 0.84, 0.93, and 0.96 for \u003csup\u003e99m\u003c/sup\u003eTc, and 0.00, 0.26, 0.53, 0.76, 0.83, and 0.94 for \u003csup\u003e18\u003c/sup\u003eF, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eb). The inverse RC revealed lower values with a declining cold rod diameter. Moreover, the inverse RC for the cold rod image with \u003csup\u003e18\u003c/sup\u003eF was lower than that with \u003csup\u003e99m\u003c/sup\u003eTc.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe %CV of the pool section for \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF images was 4% and 7%, with the \u003csup\u003e99m\u003c/sup\u003eTc image displaying a lower %CV compared to the \u003csup\u003e18\u003c/sup\u003eF image. Transverse images of the hot rod, cold rod, and pool sections were shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e. The hot rod and cold rod images with \u003csup\u003e99m\u003c/sup\u003eTc revealed a higher contrast compared with those with \u003csup\u003e18\u003c/sup\u003eF. The pool image with \u003csup\u003e99m\u003c/sup\u003eTc appeared more homogeneous than that with \u003csup\u003e18\u003c/sup\u003eF.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe evaluated the physical indices of SPECT and PET images utilizing the new phantom. Our phantom allows for the assessment of known contrast in hot rod images, as well as the contrast and RC of cold rod images, in addition to the physical indices assessable with the NEMA NU 4 phantom. The influence of PVE on the cold rod image is necessary to interpret the quantitative evaluation of the ischemic region [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Furthermore, the overestimation or underestimation of the quantitative value in the tumor region may lead to PVE and Gibbs artifacts in nuclear oncology [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile the NEMA NU 4 phantom is useful for verifying the accuracy of absolute quantitation using Bq/mL with a well counter or dose calibrator as a reference [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], the accuracy of the absolute quantitative index is dependent on the dosimeter error, such as the dose calibrator and well-counter, as well as the variation of the cross-calibration factor (CCF) and errors caused by the reconstructed image [\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Consequently, CCF uncertainty may arise from factors such as acquisition, image reconstruction, and other variables. Delineating between these factors will enhance quantitative accuracy. Relative evaluation in phantom experiments is excellent for detecting acquisition and image reconstruction errors in SPECT and PET systems. The contrast can be briefly set to a theoretical value by preparing solutions of two different radioactivity concentrations. The contrast ratio was set to 4, and the hot rod with a 6 mm diameter at \u003csup\u003e99m\u003c/sup\u003eTc obtained a contrast close to 4 in this study. The contrast of \u003csup\u003e18\u003c/sup\u003eF was lower than that of \u003csup\u003e99m\u003c/sup\u003eTc owing to spatial resolution limitations. The spatial resolution of \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF for VECTor\u003csup\u003e+\u003c/sup\u003e/CT has been reported to be better for \u003csup\u003e99m\u003c/sup\u003eTc [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. High spatial resolution systems display a high contrast owing to the small PVE. Hence, the relationship of the hot rod contrast between \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF reflected the previous study findings, and a similar trend was noted for cold rod contrasts.\u003c/p\u003e \u003cp\u003eThe RC of the hot rod phantom remained relatively constant between 4\u0026ndash;6 mm. Generally, PVE occurs for diameters\u0026thinsp;\u0026lt;\u0026thinsp;2\u0026ndash;3-fold the FWHM. The FWHM measured by the line source in VECTor\u003csup\u003e+\u003c/sup\u003e/CT is approximately 1.0 mm for both \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF, aligning with the physical index [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Conversely, the RC was overestimated for the 5 mm diameter hot rod with \u003csup\u003e18\u003c/sup\u003eF. The VECTor\u003csup\u003e+\u003c/sup\u003e/CT system applies a spatial resolution correction to \u003csup\u003e18\u003c/sup\u003eF only. Although spatial resolution correction can improve the high-resolution image quality, it also produces Gibbs artifacts [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The overestimation of the 5 mm diameter hot rod with \u003csup\u003e18\u003c/sup\u003eF may be influenced by Gibbs artifacts.\u003c/p\u003e \u003cp\u003eThe inverse RC of the cold rod phantom showed low values with a decreasing rod diameter, demonstrating a different behavior compared to the hot rod phantom. This disparity may be attributed to the presence of scattered radiation included in the cold rods. The \u003csup\u003e18\u003c/sup\u003eF photons are strongly influenced by septal penetration from the collimator, as well as Compton scattering, due to their higher radiation energy compared with \u003csup\u003e99m\u003c/sup\u003eTc photons [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. The uniformity of the pool section with \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF also reflects these differences. Scattered radiation, septal penetration, and image noise are more pronounced in cold rod parts than in hot rod parts. Consequently, the inverse RC of \u003csup\u003e18\u003c/sup\u003eF is predicted to be lower than that of \u003csup\u003e99m\u003c/sup\u003eTc.\u003c/p\u003e \u003cp\u003eIn small animal studies, the radioactivity concentrations of \u003csup\u003e18\u003c/sup\u003eF were higher than those typically encountered. PET images on the VECTor\u003csup\u003e+\u003c/sup\u003e/CT scanner were acquired using a SPECT system rather than a coincidence system. Moreover, the detector uses a NaI(Tl) scintillator with a 9.5 mm crystal thickness, resulting in counting losses for high-energy photons such as \u003csup\u003e18\u003c/sup\u003eF. A previous study reported that only 10% of all \u003csup\u003e18\u003c/sup\u003eF photons are detected as signals [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Hence, high-energy nuclides such as \u003csup\u003e18\u003c/sup\u003eF require higher radioactivity concentrations.\u003c/p\u003e \u003cp\u003eThe new phantom could evaluate PVE using RC due to its structure, which included large rods corresponding to the small animal SPECT and PET systems. Hot rods with RC values of 4\u0026ndash;6 mm demonstrated similar values. This indicates that PVE is not considerably affected in rods larger than 4 mm under the acquisition and imaging conditions at our institution. In addition, the new phantom will facilitate the interpretation of quantitative evaluations of small animal SPECT and PET images, allowing the assessment of physical phenomena in both hot rods and cold rods.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe have developed a new phantom that allows physical phenomenon evaluation in small animal SPECT and PET images. This new phantom can assess the image contrast, RC, and uniformity of both hot rod and cold rod images. Additionally, it can evaluate the performance of small-animal SPECT and PET systems.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Akira E of Hokuriku E.P., Japan for his excellent technical support of phantom production.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by JSPS KAKENHI Grant Number 18K15628.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors report no potential conflicts of interest relevant to this study.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLiu T, Wu Y, Shi L, Li L, Hu B, Wang Y, et al. Preclinical evaluation of [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-labeled anti-EpCAM nanobody for EpCAM receptor expression imaging by immuno-SPECT/CT. Eur J Nucl Med Mol Imaging. 2022;49(6):1810\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJang BS. MicroSPECT and MicroPET Imaging of Small Animals for Drug Development. Toxicol Res. 2013;29(1):1\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCase JA, Bateman TM. Taking the perfect nuclear image: quality control, acquisition, and processing techniques for cardiac SPECT, PET, and hybrid imaging. J Nucl Cardiol. 2013;20(5):891\u0026ndash;907.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNational Electrical Manufacturers Association. NEMA, Standards Publication. NU 4\u0026ndash;2008 performance measurements of small animal positron emission tomographs. Rosslyn: National Electrical Manufacturers Association; 2008.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarteveld AA, Meeuwis AP, Disselhorst JA, Slump CH, Oyen WJ, Boerman OC, et al. Using the NEMA NU 4 PET image quality phantom in multipinhole small-animal SPECT. J Nucl Med. 2011;52(10):1646\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTeuho J, Han C, Riehakainen L, Honkaniemi A, Tirri M, Liljenb\u0026auml;ck H, et al. NEMA NU 4-2008 and in vivo imaging performance of RAYCAN trans-PET/CT X5 small animal imaging system. Phys Med Biol. 2019;64(11):115014.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGaitanis A, Kastis GA, Vlastou E, Bouziotis P, Verginis P, Anagnostopoulos CD. Investigation of Image Reconstruction Parameters of the Mediso nanoScan PC Small-Animal PET/CT Scanner for Two Different Positron Emitters Under NEMA NU 4-2008 Standards. Mol Imaging Biol. 2017;19(4):550\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLajtos I, Czernin J, Dahlbom M, Daver F, Emri M, Farshchi-Heydari S, et al. Cold wall effect eliminating method to determine the contrast recovery coefficient for small animal PET scanners using the NEMA NU-4 image quality phantom. Phys Med Biol. 2014;59(11):2727\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi S, Zhang J, Krol A, Schmidtlein CR, Feiglin D, Xu Y. Preconditioned alternating projection algorithm for solving the penalized-likelihood SPECT reconstruction problem. Phys Med. 2017;38:23\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNoori-Asl M, Sadremomtaz A, Bitarafan-Rajabi A. Evaluation of three scatter correction methods based on estimation of photopeak scatter spectrum in SPECT imaging: a simulation study. Phys Med. 2014;30(8):947\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMok GS, Tsui BM, Beekman FJ. The effects of object activity distribution on multiplexing multi-pinhole SPECT. Phys Med Biol. 2011;56(8):2635\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiwa K, Yoshii T, Wagatsuma K, Nezu S, Kamitaka Y, Yamao T, et al. Impact of γ factor in the penalty function of Bayesian penalized likelihood reconstruction (Q.Clear) to achieve high-resolution PET images. EJNMMI Phys. 2023;10(1):4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen S, Gu Y, Yu H, Chen X, Cao T, Hu L, Shi H. NEMA NU2-2012 performance measurements of the United Imaging uPMR790: an integrated PET/MR system. Eur J Nucl Med Mol Imaging. 2021;48(6):1726\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAttarwala AA, Hardiansyah D, Roman\u0026oacute; C, Jim\u0026eacute;nez-Franco LD, Roscher M, W\u0026auml;ngler B, et al. Performance assessment of the ALBIRA II pre-clinical SPECT S102 system for \u003csup\u003e99m\u003c/sup\u003eTc imaging. Ann Nucl Med. 2021;35(1):111\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAttarwala AA, Karanja YW, Hardiansyah D, Roman\u0026oacute; C, Roscher M, W\u0026auml;ngler B, et al. Investigation of the imaging characteristics of the ALBIRA II small animal PET system for \u003csup\u003e18\u003c/sup\u003eF, \u003csup\u003e68\u003c/sup\u003eGa and \u003csup\u003e64\u003c/sup\u003eCu. Z Med Phys. 2017;27(2):132\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMagota K, Kubo N, Kuge Y, Nishijima K, Zhao S, Tamaki N. Performance characterization of the Inveon preclinical small-animal PET/SPECT/CT system for multimodality imaging. Eur J Nucl Med Mol Imaging 38(4): 742\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiwa K, Inubushi M, Takeuchi Y, Katafuchi T, Koizumi M, Saga T, et al. Performance characteristics of a novel clustered multi-pinhole technology for simultaneous high-resolution SPECT/PET. Ann Nucl Med. 2015;29(5):460\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShibutani T, Onoguchi M, Kanno T, Ogihara S, Wakabayashi H, Inaki A, et al. Characteristics among three multi-pinhole collimators using a new small animal SPECT-PET/CT system. J Nucl Med. 2017;58(suppl 1):1124.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBranderhorst W, Vastenhouw B, Beekman FJ. Pixel-based subsets for rapid multi-pinhole SPECT reconstruction. Phys Med Biol. 2010;55(7):2023\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOgawa K, Harata Y, Ichihara T, Kubo A, Hashimoto S. A practical method for position-dependent Compton-scattered correction in single photon emission CT. IEEE Trans Med Imaging. 1991;10(3):408\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIchikawa H, Shibutani T, Shimada H, Okuda K, Kato T, Nosaka H, et al. Feasibility of using counts-per-volume approach with a new SPECT phantom to optimize the relationship between administered dose and acquisition time. Radiol Phys Technol. 2023;16(2):244\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWakabayashi H, Taki J, Inaki A, Hiromasa T, Okuda K, Shibutani T, et al. Quantification of Myocardial Perfusion Defect Size in Rats: Comparison between Quantitative Perfusion SPECT and Autoradiography. Mol Imaging Biol. 2018;20(4):544\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHess A, Nekolla SG, Meier M, Bengel FM, Thackeray JT. Accuracy of cardiac functional parameters measured from gated radionuclide myocardial perfusion imaging in mice. J Nucl Cardiol. 2020;27(4):1317\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarquis H, Willowson KP, Bailey DL. Partial volume effect in SPECT \u0026amp; PET imaging and impact on radionuclide dosimetry estimates. Asia Ocean J Nucl Med Biol. 2023;11(1):44\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRogasch JM, Hofheinz F, Lougovski A, Furth C, Ruf J, Gro\u0026szlig;er OS, et al. The influence of different signal-to-background ratios on spatial resolution and F18-FDG-PET quantification using point spread function and time-of-flight reconstruction. EJNMMI Phys. 2014;1(1):12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIida H, Nakagawara J, Hayashida K, Fukushima K, Watabe H, Koshino K, et al. Multicenter evaluation of a standardized protocol for rest and acetazolamide cerebral blood flow assessment using a quantitative SPECT reconstruction program and split-dose \u003csup\u003e123\u003c/sup\u003eI-iodoamphetamine. J Nucl Med. 2010;51(10):1624\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSeo Y, Teo BK, Hadi M, Schreck C, Bacharach SL, Hasegawa BH. Quantitative accuracy of PET/CT for image-based kinetic analysis. Med Phys. 2008;35(7):3086\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSanderson T, Solomon J, Nottage C, Dickson J. Underestimation of \u003csup\u003e68\u003c/sup\u003eGa PET/CT SUV caused by activity overestimation using default calibrator settings. Phys Med. 2019;59:158\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIchikawa H, Onoguchi M, Shibutani T, Kato T, Ito T, Shimada H. Optimization of cross-calibration factor for quantitative bone SPECT without attenuation and scatter correction in the lumbar spine: head-to-head comparison with attenuation and scatter correction. Nucl Med Commun. 2021;42(12):1404\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiyaji N, Miwa K, Motegi K, Umeda T, Wagatsuma K, Fukai S, et al. Validation of Cross-calibration Schemes for Quantitative Bone SPECT/CT Using Different Sources under Various Geometric Conditions. Jpn J Radiological Technol. 2017;73(6):443\u0026ndash;50. (in Japannese).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHewitt E, Hewitt RE. The Gibbs-Wilbraham phenomenon: An episode in fourier analysis. Arch Hist Exact Sci. 1979;21:129\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaymon CM, Turkington TG. Characterization of septal penetration in 511 keV SPECT. Nucl Med Commu. 2006;27(11):901\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"partial volume effect, small-animal, SPECT, PET, cold rod phantom","lastPublishedDoi":"10.21203/rs.3.rs-4916789/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4916789/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eThe National Electrical Manufacturers Association (NEMA) has released guidelines delineating the performance of positron emission tomography (PET) devices designed for small animals. However, the NEMA NU 4 image quality phantom could not measure the known contrasts of the hot rod images and the recovery coefficient (RC) of cold rod images due to the structure of the phantom. Thus, we have devised novel hot rod and cold rod phantoms capable of evaluating uniformity and RCs for both hot rod and cold rod images. This study aimed to assess uniformity, image contrasts, and RCs in hot rod and cold rod images of single photon emission computed tomography (SPECT) and PET using the newly developed phantom.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe new physical phantom consisted of rod and pool sections. To assess image uniformity, the pool section, designed in a cylindrical shape, was utilized. Conversely, the rod section was created in hot rod and cold rod shapes and integrated into a cylindrical phantom with the same design as the pool section. Hot rod and cold rod phantoms were designed with six different 1\u0026ndash;6 mm diameter rods. The rod and pool sections of the hot rod phantom were separately filled with \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF solutions. In the rod section, the cylindrical part was defined as the background (BG), with a radioactive concentration ratio of 4:1 for the hot rod and BG. The cylindrical part containing the cold rod was separately filled with \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF solutions. The \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF phantoms were acquired separately over 30 min. A transverse image with a cubic voxels of 0.8 mm length was reconstructed using a pixel-based ordered subset expectation maximization algorithm.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe contrast of the hot rod for \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF showed lower values with a decreasing rod diameter. Furthermore, the \u003csup\u003e99m\u003c/sup\u003eTc image demonstrated a higher contrast than the \u003csup\u003e18\u003c/sup\u003eF image and approached the true contrast. The cold rod contrasts with \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF followed a similar trend as the hot rod contrast. The RCs for the hot rods with 4\u0026ndash;6 mm diameters were similar, whereas hot rods with diameters\u0026thinsp;\u0026le;\u0026thinsp;3 mm revealed lower values as the rod diameter decreased. The inverse RC was lower with a decreasing cold rod diameter. Moreover, the cold rod image with \u003csup\u003e18\u003c/sup\u003eF demonstrated a lower inverse RC than with the \u003csup\u003e99m\u003c/sup\u003eTc. The percent coefficient of variation (%CV) for the \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e18\u003c/sup\u003eF images was 4% and 7%, respectively, with the \u003csup\u003e99m\u003c/sup\u003eTc image displaying a lower %CV compared to the \u003csup\u003e18\u003c/sup\u003eF image.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eWe have developed a new phantom that allows physical phenomenon evaluation in small animal SPECT and PET images, and can evaluate the image contrast, RC, and uniformity of both hot rod and cold rod images.\u003c/p\u003e","manuscriptTitle":"Development for a novel phantom for evaluating image quality in small-animal single photon emission computed tomography and positron emission tomography.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-15 07:28:55","doi":"10.21203/rs.3.rs-4916789/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8f5d502b-2a5b-433a-ad01-9302670ecb06","owner":[],"postedDate":"October 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-04-02T05:04:59+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-15 07:28:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4916789","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4916789","identity":"rs-4916789","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}