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Purpose: The cortical uptake of tau positron emission tomography (PET) tracers corresponds to the Braak stage and reflects the distribution and progression of tau neurofibrillary tangles. The present study aimed to develop and validate the basic performance of a novel tau PET phantom, as well as to establish standard test procedures and analytical methods., Methods: The tau PET phantom consisted of a brain simulation section simulated medial temporal lobe region and resolution and uniformity sections. The brain simulation section and hot rods and uniformity section contained 4 and 2 kBq/mL of 18 F, respectively and images were acquired three times for 20 min with a PET/CT scanner. The resolution section was visually assessed with two sets of hot and cold rods. Recovery coefficients (RCs) as a quantitative value and coefficient of variation (CV) as image noise were determined based on the brain simulation and the uniformity section, respectively., Results: Preparation of activity in the phantom was repeatable among three measurements. The quality of images in the brain simulation and uniformity section with the rods was good. The 5- or 6-mm rods were detected separately. The mean RCs calculated based on the VOI template were between 0.75 and 0.83. The CV at the center slice of uniformity section was 5.54%., Conclusions: We developed a novel tau PET phantom to assess quantitative value, image noise, and detectability and resolution from brain simulation section, uniformity section, and rods, respectively. This phantom will contribute to the standardization and harmonization of tau PET imaging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Objective. To compare the accuracy with which different hadronic inelastic physics models across ten Geant4 Monte Carlo simulation toolkit versions can predict positron-emitting fragments produced along the beam path during carbon and oxygen ion therapy. Approach. Phantoms of polyethylene, gelatin, or poly(methyl methacrylate) were irradiated with monoenergetic carbon and oxygen ion beams. Post-irradiation, 4D PET images were acquired and parent 11 C, 10 C and 15 O radionuclides contributions in each voxel were determined from the extracted time activity curves. Next, the experimental configurations were simulated in Geant4 Monte Carlo versions 10.0 to 11.1, with three different fragmentation models-binary ion cascade (BIC), quantum molecular dynamics (QMD) and the Liege intranuclear cascade (INCL++) - 30 model-version combinations. Total positron annihilation and parent isotope production yields predicted by each simulation were compared between simulations and experiments using normalised mean squared error and Pearson cross-correlation coefficient. Finally, we compared the depth of the maximum positron annihilation yield and the distal point at which the positron yield decreases to 50% of peak between each model and the experimental results. Main results. Performance varied considerably across versions and models, with no one version/model combination providing the best prediction of all positron-emitting fragments in all evaluated target materials and irradiation conditions. BIC in Geant4 10.2 provided the best overall agreement with experimental results in the largest number of test cases. QMD consistently provided the best estimates of both the depth of peak positron yield (10.4 and 10.6) and the distal 50%-of-peak point (10.2), while BIC also performed well and INCL generally performed the worst across most Geant4 versions. Significance. The best predictions of the spatial distribution of positron annihilations and positron-emitting fragment production along the beam path during carbon and oxygen ion therapy was obtained using Geant4 10.2.p03 with BIC or QMD. These version/model combinations are recommended for future heavy ion therapy research., (Creative Commons Attribution license.)

The Alzheimer disease (AD) continuum is a neurodegenerative disorder with cognitive decline and pathologic changes. Tau PET imaging can detect tau pathology, and 18 F-flortaucipir PET imaging is expected to visualize progression through the stages of AD, for which quantitative assessment is essential. Two measurement methods, statistically defined multiblock barycentric discriminant analysis (MUBADA)/parametric estimation of reference signal intensity (PERSI) and anatomically defined tau meta-volume of interest (VOI)/cerebellar gray matter (CGM) for SUV ratio (SUVR), were compared in this study to assess their relationship to AD clinical stage using 2 open multicenter PET databases. Methods: Data were selected for 106 cases from 2 databases, AMED Preclinical AD study (AMED-PRE) ( n = 15) and Alzheimer Disease Neuroimaging Initiative 3 ( n = 91). The data of the participants were categorized into 4 groups based on the clinical criteria. Tau PET imaging was conducted using 18 F-flortaucipir, and the 2 SUVR measurement methods, MUBADA/PERSI and tau meta-VOI/CGM, were compared among different clinical categories: amyloid-negative cognitively normal, preclinical AD, amyloid-negative mild cognitive impairment (MCI), and amyloid-positive MCI. Results: Significant differences were found between cognitively normal and preclinical AD, as well as between cognitively normal and amyloid-positive MCI and between amyloid-negative MCI and -positive MCI in SUVR derived by MUBADA/PERSI, whereas SUVR by tau meta-VOI/CGM did not provide significant differences between any pair. The tau meta-VOI/CGM method consistently provided higher SUVRs and larger individual variations than MUBADA/PERSI, with a mean SUVR difference of 0.136 for the studied databases. Conclusion: MUBADA/PERSI provided the SUVR of 18 F-flortaucipir uptake with better association with the clinical severity of the AD continuum and with smaller variability. The results support the usefulness of MUBADA/PERSI as a quantitative measure of 18 F-flortaucipir uptake in multicenter studies using different PET systems and scanning methods. However, limitations of the study include the small sample size and the unbalanced distribution among clinical categories in the AMED Preclinical AD study database., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: This study aimed to identify disposable items with low amyloid positron emission tomography (PET) agent radioactivity adsorption for accurate injections using a radiopharmaceutical activity supplier., Methods: First, we investigated disposable items currently used for amyloid PET agent injection. Next, we measured the residual radioactivity rates of amyloid PET agents on three-way stopcocks, extension tubes, butterfly needles, and indwelling needles to identify disposable items with low radioactivity adsorption. Finally, we evaluated the accuracy of amyloid PET agent injection using the selected disposable items and a radiopharmaceutical activity supplier., Results: The polybutadiene extension tube exhibited a significantly lower residual activity rate than that of the polyvinyl chloride extension tube. Similarly, the indwelling needles showed significantly lower residual activity rate than that of butterfly needles. The dose indicated by a radiopharmaceutical activity supplier was 184.1 MBq, while the dose calibrator measured the radioactivity which flowed into the vial as 170.2 MBq, resulting in an administration accuracy of 8.2%., Conclusion: To ensure accurate amyloid PET agent injections, we recommend using polybutadiene extension tubes and indwelling needles due to their lower radioactivity adsorption.

Attenuation correction (AC) is essential for quantitative positron emission tomography (PET) images. Attenuation coefficient maps (μ-maps) are usually generated from computed tomography (CT) images when PET-CT combined systems are used. If CT has been performed prior to PET imaging, pre-acquired CT can be used for brain PET AC, because the human head is almost rigid. This pre-acquired CT-based AC approach is suitable for stand-alone brain-dedicated PET, such as VRAIN (ATOX Co. Ltd., Tokyo, Japan). However, the headrest of PET is different from the headrest in pre-acquired CT images, which may degrade the PET image quality. In this study, we prepared three different types of μ-maps: (1) based on the pre-acquired CT, where namely the headrest is different from the PET system (μ-map-diffHr); (2) manually removing the headrest from the pre-acquired CT (μ-map-noHr); and (3) artificially replacing the headrest region with the headrest of the PET system (μ-map-sameHr). Phantom images by VRAIN using each μ-map were investigated for uniformity, noise, and quantitative accuracy. Consequently, only the uniformity of the images using μ-map-diffHr was out of the acceptance criteria. We then proposed an automated method for removing the headrest from pre-acquired CT images. In comparisons of standardized uptake values in nine major brain regions from the 18 F-fluoro-2-deoxy-D-glucose-PET of 10 healthy volunteers, no significant differences were found between the μ-map-noHr and the μ-map-sameHr. In conclusion, pre-acquired CT-based AC with automated headrest removal is useful for brain-dedicated PET such as VRAIN., (© 2023. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)

Objective: Tau positron emission tomography (PET) imaging is a recently developed non-invasive tool that can detect the density and extension of tau neurofibrillary tangles. Tau PET tracers have been validated to harmonize and accelerate their development and implementation in clinical practice. Whereas standard protocols including injected dose, uptake time, and duration have been determined for tau PET tracers, reconstruction parameters have not been standardized. The present study conducted phantom experiments based on tau pathology to standardize quantitative tau PET imaging parameters and optimize reconstruction conditions of PET scanners at four Japanese sites according to the results of phantom experiments., Methods: The activity of 4.0 and 2.0 kBq/mL for Hoffman 3D brain and cylindrical phantoms, respectively, was estimated from published studies of brain activity using [ 18 F]flortaucipir, [ 18 F]THK5351, and [ 18 F]MK6240. We developed an original tau-specific volume of interest template for the brain based on pathophysiological tau distribution in the brain defined as Braak stages. We acquired brain and cylindrical phantom images using four PET scanners. Iteration numbers were determined as contrast and recover coefficients (RCs) in gray (GM) and white (WM) matter, and the magnitude of the Gaussian filter was determined from image noise., Results: Contrast and RC converged at ≥ 4 iterations, the error rates of RC for GM and WM were < 15% and 1%, respectively, and noise was < 10% in Gaussian filters of 2-4 mm in images acquired using the four scanners. Optimizing the reconstruction conditions for phantom tau PET images acquired by each scanner improved contrast and image noise., Conclusions: The phantom activity was comprehensive for first- and second-generation tau PET tracers. The mid-range activity that we determined could be applied to later tau PET tracers. We propose an analytical tau-specific VOI template based on tau pathophysiological changes in patients with AD to standardize tau PET imaging. Phantom images reconstructed under the optimized conditions for tau PET imaging achieved excellent image quality and quantitative accuracy., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Objective: A new tau PET tracer [ 18 F]MK-6240 has been developed; however, its dosimetry and pharmacokinetics have been published only for a European population. This study investigated the safety, radiation dosimetry, pharmacokinetics and biodistribution of [ 18 F]MK-6240 in Japanese elderly subjects. Also, the pattern and extent of brain retention of [ 18 F]MK-6240 in Japanese healthy elderly subjects and patients with Alzheimer's disease (AD) were investigated. These Japanese results were compared with previous reports on non-Japanese., Methods: Three healthy elderly subjects and three AD patients were enrolled. Dynamic whole-body PET scans were acquired for up to 232 min after starting injection of [ 18 F]MK-6240 (370.4 ± 27.0 MBq) for the former, while a dynamic brain scan was performed from 0 to 75 min post injection for the latter. For both groups, brain PET scans were conducted from 90 to 110 min post injection. Sequential venous blood sampling was performed to measure the radioactivity concentration in the whole blood and plasma as well as the percentages of parent [ 18 F]MK-6240 and radioactive metabolites in plasma. Organ doses and effective doses were estimated using the OLINDA Ver.2 software. Standardized uptake value ratios (SUVRs) and distribution volume ratios (DVRs) by Logan reference tissue model (LRTM) were measured in eight brain regions using the cerebellar cortex as the reference. Blood tests, urine analysis, vital signs and electrocardiography were performed for safety assessments., Results: No adverse events were observed. The highest radiation doses were received by the gallbladder (257.7 ± 74.9 μGy/MBq) and the urinary bladder (127.3 ± 11.7 μGy/MBq). The effective dose was 26.8 ± 1.4 μSv/MBq. The parent form ([ 18 F]MK-6240) was metabolized quickly and was less than 15% by 35 min post injection. While no obvious accumulation was found in the brain of healthy subjects, focal accumulation of [ 18 F]MK-6240 was observed in the cerebral cortex of AD patients. Regional SUVRs of the focal lesions in AD patients increased gradually over time, and the difference of SUVRs between healthy subjects and AD patients became large and stable at 90 min after injection. High correlations of SUVR and DVR were observed (p < 0.01)., Conclusion: The findings supported safety and efficacy of [ 18 F]MK-6240 as a tau PET tracer for Japanese populations. Even though the number of subjects was limited, the radiation dosimetry profiles, pharmacokinetics, and biodistribution of [ 18 F]MK-6240 were consistent with those for non-Japanese populations., Trial Registration: Japan Pharmaceutical Information Center ID, JapicCTI-194972., (© 2022. The Author(s).)

PET can reveal in vivo biological processes at the molecular level. PET-derived quantitative values have been used as a surrogate marker for clinical decision-making in numerous clinical studies and trials. However, quantitative values in PET are variable depending on technical, biological, and physical factors. The variability may have a significant impact on a study outcome. Appropriate scanner calibration and quality control, standardization of imaging protocols, and any necessary harmonization strategies are essential to make use of PET as a biomarker with low bias and variability. This review summarizes benefits, limitations, and remaining challenges for harmonization of quantitative PET, including whole-body PET in oncology, brain PET in neurology, PET/MR, and non- 18 F PET imaging. This review is expected to facilitate harmonization of quantitative PET and to promote the contribution of PET-derived biomarkers to research and development in medicine., (© 2023. The Author(s).)

Objective. For PET imaging systems, a smaller detector ring enables less intrinsic spatial resolution loss due to the photon non-collinearity effect as well as better balance between production cost and sensitivity, and a hemispherical detector arrangement is more appropriate for brain imaging than a conventional cylindrical arrangement. Therefore, we have developed a brain-dedicated PET system with a hemispherical detector arrangement, which has been commercialized in Japan under the product name of VRAIN TM . In this study, we evaluated imaging performance of VRAIN. Approach. The VRAIN used 54 detectors to form the main hemispherical unit and an additional half-ring behind the neck. Each detector was composed of a 12 × 12 array of lutetium fine silicate crystals (4.1 × 4.1 × 10 mm 3 ) and a 12 × 12 array of silicon photomultipliers (4 × 4 mm 2 active area) with the one-to-one coupling. We evaluated the physical performance of VRAIN according to the NEMA NU 2-2018 standards. Some measurements were modified so as to fit the hemispherical geometry. In addition, we performed 18 F-FDG imaging in a healthy volunteer. Main results. In the phantom study, the VRAIN showed high resolution for separating 2.2 mm rods, 229 ps TOF resolution and 19% scatter fraction. With the TOF gain for a 20 cm diameter object (an assumed head diameter), the peak noise-equivalent count rate was 144 kcps at 9.8 kBq ml -1 and the sensitivity was 25 kcps MBq -1 . Overall, the VRAIN provided excellent image quality in phantom and human studies. In the human FDG images, small brain nuclei and gray matter structures were clearly visualized with high contrast and low noise. Significance. We demonstrated the excellent imaging performance of VRAIN, which supported the advantages of the hemispherical detector arrangement., (Creative Commons Attribution license.)

Background: To confirm the performance of the first hemispherical positron emission tomography (PET) for the brain (Vrain) that we developed to visualise the small nuclei in the deep brain area, we compared 18 F-fluorodeoxyglucose (FDG) brain images with whole-body PET images., Methods: Ten healthy male volunteers (aged 22-45 years) underwent a representative clinical whole-body PET, followed by Vrain each for 10 min. These two scans were initiated 30 min and 45 min after FDG injection (4.1 ± 0.5 MBq/kg), respectively. First, we visually identified the small nuclei and then compared their standardised uptake values (SUVs) with the participants' age. Next, the SUVs of each brain region, which were determined by applying a volume-of-interest template for anatomically normalised PET images, were compared between the brain images with the Vrain and those with the whole-body PET images., Results: Small nuclei, such as the inferior colliculus, red nucleus, and substantia nigra, were more clearly visualised in Vrain than in whole-body PET. The anterior nucleus and dorsomedial nucleus in the thalamus and raphe nucleus in the brainstem were identified in Vrain but not in whole-body PET. The SUVs of the inferior colliculus and dentate gyrus in the cerebellum positively correlated with age (Spearman's correlation coefficient r = 0.811, p = 0.004; r = 0.738, p = 0.015, respectively). The SUVs of Vrain were slightly higher in the mesial temporal and medial parietal lobes than those in whole-body PET., Conclusions: This was the first time that the raphe nuclei, anterior nuclei, and dorsomedial nuclei were successfully visualised using the first hemispherical brain PET. TRIAL REGISTRATION  : Japan Registry of Clinical Trials, jRCTs032210086, Registered 13 May 2021, https://jrct.niph.go.jp/latest-detail/jRCTs032210086 ., (© 2022. The Author(s).)

Objective: Head motions during brain PET scan cause degradation of brain images, but head fixation or external-maker attachment become burdensome on patients. Therefore, we have developed a motion correction method that uses a 3D face-shape model generated by a range-sensing camera (Kinect) and by CT images. We have successfully corrected the PET images of a moving mannequin-head phantom containing radioactivity. Here, we conducted a volunteer study to verify the effectiveness of our method for clinical data., Methods: Eight healthy men volunteers aged 22-45 years underwent a 10-min head-fixed PET scan as a standard of truth in this study, which was started 45 min after 18 F-fluorodeoxyglucose (285 ± 23 MBq) injection, and followed by a 15-min head-moving PET scan with the developed Kinect based motion-tracking system. First, selecting a motion-less period of the head-moving PET scan provided a reference PET image. Second, CT images separately obtained on the same day were registered to the reference PET image, and create a 3D face-shape model, then, to which Kinect-based 3D face-shape model matched. This matching parameter was used for spatial calibration between the Kinect and the PET system. This calibration parameter and the motion-tracking of the 3D face shape by Kinect comprised our motion correction method. The head-moving PET with motion correction was compared with the head-fixed PET images visually and by standard uptake value ratios (SUVRs) in the seven volume-of-interest regions. To confirm the spatial calibration accuracy, a test-retest experiment was performed by repeating the head-moving PET with motion correction twice where the volunteer's pose and the sensor's position were different., Results: No difference was identified visually and statistically in SUVRs between the head-moving PET images with motion correction and the head-fixed PET images. One of the small nuclei, the inferior colliculus, was identified in the head-fixed PET images and in the head-moving PET images with motion correction, but not in those without motion correction. In the test-retest experiment, the SUVRs were well correlated (determinant coefficient, r 2  = 0.995)., Conclusion: Our motion correction method provided good accuracy for the volunteer data which suggested it is useable in clinical settings., (© 2022. The Author(s).)

Objective. In carbon ion therapy, the visualization of the range of incident particles in a patient body is important for treatment verification. In-beam positron emission tomography (PET) imaging is one of the methods to verify the treatment in ion therapy due to the high quality of PET images. We have shown the feasibility of in-beam PET imaging of radioactive 15 O and 11 C ion beams for range verification using our OpenPET system. Recently, we developed a whole gamma imager (WGI) that can simultaneously work as PET, single gamma ray and triple gamma ray imaging. The WGI has high potential to detect the location of 10 C, which emits positrons with a simultaneous gamma ray of 718 keV, within the patient's body during ion therapy. Approach. In this work, we focus on investigating the performance of WGI for 10 C imaging and its feasibility for range verification in carbon ion therapy. First, the performance of the WGI was studied to image a 10 C point source using the Geant4 toolkit. Then, the feasibility of WGI was investigated for an irradiated polymethyl methacrylate (PMMA) phantom with a 10 C ion beam at the carbon therapy facility of the Heavy Ion Medical Accelerator in Chiba. Main results. The average spatial resolution and sensitivity for the simulated 10 C point source at the centre of the field of view were 5.5 mm FWHM and 0.010%, respectively. The depth dose of the 10 C ion beam was measured, and the triple gamma image of 10 C nuclides for an irradiated PMMA phantom was obtained by applying a simple back projection to the detected triple gammas. Significance. The shift between Bragg peak position and position of the peak of the triple gamma image in an irradiated PMMA phantom was 2.8 ± 0.8 mm, which demonstrates the capability of triple gamma imaging using WGI for range verification of 10 C ion beams., (© 2022 Institute of Physics and Engineering in Medicine.)

Marker-less head motion correction methods have been well-studied; however, no reports discussing potential issues in positional calibration between a PET system and an external sensor remain limited. In this study, we develop a method for positional calibration between the PET system and an external range sensor to achieve practical head motion correction. The basic concept of the developed method involves using the subject's face model as a marker not only for head motion detection but also for the system positional calibration. The face model of the subject, which can be obtained easily using the range sensor, can also be calculated from a computed tomography (CT) image of the same subject. The CT image, which is acquired separately for attenuation correction in PET, has the same coordinates as the PET image because of the appropriate matching algorithm between CT and PET images. The proposed method was implemented in the helmet-type PET and the motion correction accuracy was assessed quantitatively using a mannequin head. The phantom experiments demonstrated the performance of the developed motion correction method; high-resolution images with no trace of the applied motion were obtained as if no motion was provided. Statistical analysis supported the visual assessment results in terms of the spatial resolution, contrast recovery; uniformity, and the results implied that motion with correction slightly improved image quality compared with the motionless case. The tolerance of the developed method against potential tracking errors had a minimum 10% difference in the amplitude of the rotation angle., (© 2022. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)

Not only visual interpretation for lesion detection, staging, and characterization, but also quantitative treatment response assessment are key roles for 18 F-FDG PET in oncology. In multicenter oncology PET studies, image quality standardization and SUV harmonization are essential to obtain reliable study outcomes. Standards for image quality and SUV harmonization range should be regularly updated according to progress in scanner performance. Accordingly, the first aim of this study was to propose new image quality reference levels to ensure small lesion detectability. The second aim was to propose a new SUV harmonization range and an image noise criterion to minimize the inter-scanner and intra-scanner SUV variabilities. We collected a total of 37 patterns of images from 23 recent PET/CT scanner models using the NEMA NU2 image quality phantom. PET images with various acquisition durations of 30-300 s and 1800 s were analyzed visually and quantitatively to derive visual detectability scores of the 10-mm-diameter hot sphere, noise-equivalent count (NEC phantom ), 10-mm sphere contrast (Q H,10 mm ), background variability (N 10 mm ), contrast-to-noise ratio (Q H,10 mm /N 10 mm ), image noise level (CV BG ), and SUVmax and SUVpeak for hot spheres (10-37 mm diameters). We calculated a reference level for each image quality metric, so that the 10-mm sphere can be visually detected. The SUV harmonization range and the image noise criterion were proposed with consideration of overshoot due to point-spread function (PSF) reconstruction. We proposed image quality reference levels as follows: Q H,10 mm /N 10 mm  ≥ 2.5 and CV BG  ≤ 14.1%. The 10th-90th percentiles in the SUV distributions were defined as the new SUV harmonization range. CV BG  ≤ 10% was proposed as the image noise criterion, because the intra-scanner SUV variability significantly depended on CV BG . We proposed new image quality reference levels to ensure small lesion detectability. A new SUV harmonization range (in which PSF reconstruction is applicable) and the image noise criterion were also proposed for minimizing the SUV variabilities. Our proposed new standards will facilitate image quality standardization and SUV harmonization of multicenter oncology PET studies. The reliability of multicenter oncology PET studies will be improved by satisfying the new standards., (© 2021. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Objective. Small animal positron emission tomography (PET) requires a submillimeter resolution for better quantification of radiopharmaceuticals. On the other hand, depth-of-interaction (DOI) information is essential to preserve the spatial resolution while maintaining the sensitivity. Recently, we developed a staggered 3-layer DOI detector with 1 mm crystal pitch and 15 mm total crystal thickness, but we did not demonstrate the imaging performance of the DOI detector with full ring geometry. In this study we present initial imaging results obtained for a mouse brain PET prototype developed with the staggered 3-layer DOI detector. Approach. The prototype had 53 mm inner diameter and 11 mm axial field-of-view. The PET scanner consisted of 16 DOI detectors each of which had a staggered 3-layer LYSO crystal array (4/4/7 mm) coupled to a 4 × 4 silicon photomultiplier array. The physical performance was evaluated in terms of the NEMA NU 4 2008 protocol. Main Results. The measured spatial resolutions at the center and 15 mm radial offset were 0.67 mm and 1.56 mm for filtered-back-projection, respectively. The peak absolute sensitivity of 0.74% was obtained with an energy window of 400-600 keV. The resolution phantom imaging results show the clear identification of a submillimetric rod pattern with the ordered-subset expectation maximization algorithm. The inter-crystal scatter rejection using a narrow energy window could enhance the resolvability of a 0.75 mm rod significantly. Significance. In an animal imaging experiment, the detailed mouse brain structures such as cortex and thalamus were clearly identified with high contrast. In conclusion, we successfully developed the mouse brain PET insert prototype with a staggered 3-layer DOI detector., (© 2021 Institute of Physics and Engineering in Medicine.)

Background: In pancreatic cancer surgery, accurate identification and resection of intrapancreatic residual tumors are quite difficult. We have developed a novel open-typed PET system (called 'OpenPET'), which enables high-resolution PET-guided surgery in real time, and demonstrated that OpenPET-guided surgery with intraperitoneally administered 64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab is useful to detect and resect primary pancreatic cancer. Here, we investigated applicability of OpenPET-guided surgery for unexpected residual intrapancreatic tumors and examined its survival benefit over conventional surgery., Methods: A mouse model with large (>1 cm) resectable pancreatic cancer of xPA-1-DC cells expressing red fluorescent protein was used. OpenPET-guided surgery was conducted 24 h after intraperitoneal administration of 64Cu-labeled cetuximab (7.4 MBq/mouse). For comparison, similar surgical procedures were conducted, and conventional tumor resection was attempted using only the naked eye (control). Survival rate after OpenPET-guided surgery was compared to that after control operations., Results: Intraoperative OpenPET guidance enabled detection and resection of small residual tumors. Ten residual tumor specimens (3-10 mm in diameter) were intraoperatively isolated with OpenPET guidance (n = 7 mice). All isolated specimens showed tumor RFP signals. No resection of tumor tissue was performed in control group because the tumor could not be clearly detected with the naked eye alone. Mice after OpenPET-guided surgery showed significantly longer survival rates than those in control group., Conclusions: OpenPET-guided surgery with 64Cu-labeled-cetuximab enabled intraoperative identification and resection of intrapancreatic small residual tumors. This technology could be useful to prevent tumor residuals during surgery and improve pancreatic cancer survival., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Amyloid PET noninvasively visualizes amyloid-β accumulation in the brain. Visual binary reading is the standard method for interpreting amyloid PET, whereas objective quantitative evaluation is required in research and clinical trials. Anatomic standardization is important for quantitative analysis, and various standard templates are used for this purpose. To address the large differences in radioactivity distribution between amyloid-positive and amyloid-negative participants, an adaptive-template method has been proposed for the anatomic standardization of amyloid PET. In this study, we investigated the difference between the adaptive-template method and the single-template methods (use of a positive or a negative template) in amyloid PET quantitative evaluation, focusing on the accuracy in diagnosing Alzheimer's disease (AD). Methods: In total, 166 participants (58 healthy controls [HCs], 62 patients with mild cognitive impairment [MCI], and 46 patients with AD) who underwent 11 C-Pittsburgh compound B ( 11 C-PiB) PET through the Japanese Alzheimer's Disease Neuroimaging Initiative study were examined. For the anatomic standardization of  11 C-PiB PET images, we applied 3 methods: a positive-template-based method, a negative-template-based method, and an adaptive-template-based method. The positive template was created by averaging the PET images for 4 patients with AD and 7 patients with MCI. Conversely, the negative template was created by averaging the PET images for 8 HCs. In the adaptive-template-based method, either of the templates was used on the basis of the similarity (normalized cross-correlation [NCC]) between the individual standardized image and the corresponding template. An empiric PiB-prone region of interest was used to evaluate specific regions where amyloid-β accumulates. The reference region was the cerebellar cortex, and the evaluated regions were the posterior cingulate gyrus and precuneus and the frontal, lateral temporal, lateral parietal, and occipital lobes. The mean cortical SUV ratio (mcSUVR) was calculated for quantitative evaluation. Results: The NCCs of single-template-based methods (the positive template or negative template) showed a significant difference among the HC, MCI, and AD groups ( P < 0.05), whereas the NCC of the adaptive-template-based method did not ( P > 0.05). The mcSUVR exhibited significant differences among the HC, MCI, and AD groups with all methods ( P < 0.05). The mcSUVR area under the curve by receiver operating characteristic analysis between the positive group (MCI and AD) and the HC group did not significantly differ among templates. With regard to diagnostic accuracy based on mcSUVR, the sensitivity of the negative-template-based and adaptive-template-based methods was superior to that of the positive-template-based method ( P < 0.05); however, there was no significant difference in specificity between them. Conclusion: In quantitative evaluation of AD by amyloid PET, the adaptive-template-based anatomic standardization method had greater diagnostic accuracy than the single-template-based methods., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: To examine the impact of acquisition time on Lutetium-177 ( 177 Lu) single-photon emission computed tomography (SPECT) images using Monte Carlo simulation., Methods: A gamma camera simulation based on the Monte Carlo method was performed to produce SPECT images. The phantom was modeled on a NEMA IEC BODY phantom including six spheres as tumors. After the administration of 7.4 GBq of 177 Lu, radioactivity concentrations of the tumor/liver at 6, 24, and 72 h after administration were set to 1.85/0.201, 2.12/0.156, and 1.95/0.117 MBq/mL, respectively. In addition, the radioactivity concentrations of the tumor at 72 h after administration varied by 1/2, 1/4, and 1/8 when comparison was made. Acquisition times examined were 1.2, 1.5, 2, 3, 6, and 12 min. To assess the impact of collimators, SPECT data acquired at 72 h after the administration using six collimators of low-energy high-resolution (LEHR), extended low-energy general-purpose (ELEGP), medium-energy, and general-purpose (MEGP-1, MEGP-2, and MEGP-3) and high-energy general-purpose (HEGP) were examined. After prefiltering using a Butterworth filter, projection images were reconstructed using ordered subset expectation maximization. The detected photons were classified into direct rays, scattered rays, penetrating rays, and characteristic X-rays from lead. The image quality was evaluated through visual assessment, and physical assessment of contrast recovery coefficient (CRC) and contrast-to-noise ratio (CNR). In this study, the CNR threshold for detectability was assumed to be 5.0., Results: To compare collimators, the highest sensitivity was observed with ELEGP, followed by LEHR and MEGP-1. The highest ratio of direct ray was also observed in ELEGP followed by MEGP-1. In comparison of the radioactivity concentration ratios of tumor/liver, CRC and CNR were significantly decreased with smaller radioactivity concentration ratios. This effect was greater with larger spheres. According to the visual assessment, the acquisition time of 6, 6, and 3 min or longer was required using ELEGP collimator at 6, 24, and 72 h after administration, respectively. Physical assessment based on CNR and CRC also suggested that 6, 6, and 3 min or longer acquisition time was necessary at 6, 24, and 72 h after administration., Conclusion: 177 Lu-SPECT images generated via the Monte Carlo simulation suggested that the recommended acquisition time was 6 min or longer at 6 and 24 h and 3 min or longer at 72 h after administration.

Myocardial perfusion imaging (MPI) with PET plays a vital role in the management of coronary artery disease. High sensitivity systems can contribute to maximizing the potential value of PET MPI; therefore, we have proposed two novel detector arrangements, an elliptical geometry and a D-shape geometry, that are more sensitive and more compact than a conventional large-bore cylindrical geometry. Here we investigate two items: the benefits of the proposed geometries for cardiac imaging; and the effects of scatter components on cardiac PET image quality. Using the Geant4 toolkit, we modeled four time-of-flight (TOF) PET systems: an 80 cm diameter cylinder, a 40 cm diameter cylinder, a compact ellipse, and a compact D-shape. Spatial resolution and sensitivity were measured using point sources. Noise equivalent count rate and image quality were examined using an anthropomorphic digital chest phantom. The proposed geometries showed higher sensitivity and better count rate characteristics with a fewer number of detectors than the conventional large-bore cylindrical geometry. In addition, we found that the increased intensity of the scatter components was a big factor affecting the contrast in defect regions for such a compact geometry. It is important to address the issue of the increased intensity of the scatter components to develop a high-performance compact cardiac TOF PET system., (© 2021 Institute of Physics and Engineering in Medicine.)

Positron emission tomography (PET) plays an increasingly important role in research and clinical applications, catalysed by remarkable technical advances and a growing appreciation of the need for reliable, sensitive biomarkers of human function in health and disease. Over the last 30 years, a large amount of the physics and engineering effort in PET has been motivated by the dominant clinical application during that period, oncology. This has led to important developments such as PET/CT, whole-body PET, 3D PET, accelerated statistical image reconstruction, and time-of-flight PET. Despite impressive improvements in image quality as a result of these advances, the emphasis on static, semi-quantitative 'hot spot' imaging for oncologic applications has meant that the capability of PET to quantify biologically relevant parameters based on tracer kinetics has not been fully exploited. More recent advances, such as PET/MR and total-body PET, have opened up the ability to address a vast range of new research questions, from which a future expansion of applications and radiotracers appears highly likely. Many of these new applications and tracers will, at least initially, require quantitative analyses that more fully exploit the exquisite sensitivity of PET and the tracer principle on which it is based. It is also expected that they will require more sophisticated quantitative analysis methods than those that are currently available. At the same time, artificial intelligence is revolutionizing data analysis and impacting the relationship between the statistical quality of the acquired data and the information we can extract from the data. In this roadmap, leaders of the key sub-disciplines of the field identify the challenges and opportunities to be addressed over the next ten years that will enable PET to realise its full quantitative potential, initially in research laboratories and, ultimately, in clinical practice.

The crosshair light-sharing (CLS) PET detector is our original depth-of-interaction (DOI) detector, which is based on a single-ended readout scheme with quadrisected crystals comparable in size to a photo-sensor. In this work, we developed 32 CLS PET detectors, each of which consisted of a multi-pixel photon counter (MPPC) array and gadolinium fine aluminum garnet (GFAG) crystals, and we developed a benchtop prototype of a small animal size PET. Each GFAG crystal was 1.45 × 1.45 × 15 mm 3 . The MPPC had a surface area of 3.0 × 3.0 mm 2 . The benchtop prototype had two detector rings of 16 detector blocks. The ring diameter and axial field-of-view were 14.2 cm and 4.9 cm, respectively. The data acquisition system used was the PETsys silicon photomultiplier readout system. The continuous DOI information was binned into three DOI layers by applying a look-up-table to a 2D position histogram. Also, energy and timing information was corrected using DOI information. After the calibration procedure, the energy resolution and the coincidence time resolution were 14.6% and 531 ps, respectively. Imaging test results of a small rod phantom obtained by an iterative reconstruction method showed clear separation of 1.6 mm rods with the help of DOI information.

Purpose: A standardized method for quantification is required for analyzing PET data, but such standards have not been established for tau PET imaging. The Centiloid scale has recently been proposed as a standard method for quantifying amyloid deposition on PET imaging. Therefore, the present study aimed to apply the Centiloid scale to 18 F-THK5351 PET imaging in Alzheimer's disease (AD)., Methods: We acquired 18 F-THK5351 PET, 11 C-PiB PET, and MR images from 47 cognitively normal (CN) individuals and 28 patients with AD with mild to moderate dementia. PET images were spatially normalized to Montreal Neurological Institute space. The PET signals were then normalized using the signal in the reference volume of interest (VOI). Target VOI for specific 18 F-THK5351 retention in AD was extracted by voxel-wise comparison of PET images between the 47 CN individuals and 16 AD patients with moderate dementia. Scale anchor points were defined by the CN individuals as 0-anchor points and by that of the average of the typical AD patients as 100-anchor points., Results: Specific retention of 18 F-THK5351 was predominant in the angular gyrus, inferior temporal cortex, and parieto-occipital regions in patients with AD. Standardized uptake value ratio (SUVR) of 1.227 and 1.797 were defined as 0- and 100-anchor points, respectively. 18 F-THK5351 PET data could be expressed using the Centiloid scale, with the SUVR of the 18 F-THK5351 PET images converted to Centiloid using our VOI, the standard Centiloid reference VOI, and the following equation: Centiloid = 169.0 × SUVR-204.6., Conclusion: Centiloid methods can be applied to tau PET imaging using 18 F-THK5351., (Copyright © 2021 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

To establish a feasible and practical methodology for harmonization of FDG-PET, we have investigated quantitative physical performance of recent clinical PET scanners (23 scanners) using the NEMA image quality phantom. Compared with the previous phantom data (13 scanners) acquired in the early 2000s, the current phantom data showed better contrasts of small spheres even with a smaller number of coincidence counts. This result suggests that clinical PET image quality and small lesion detectability might have been significantly improved in the past 10 years. Based on the data acquired in this working group, we are planning to update the standard phantom test methodology and harmonizing criteria for FDG-PET.

The purpose of this work is to develop a validated Geant4 simulation model of a whole-body prototype PET scanner constructed from the four-layer depth-of-interaction detectors developed at the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Japan. The simulation model emulates the behaviour of the unique depth of interaction sensing capability of the scanner without needing to directly simulate optical photon transport in the scintillator and photodetector modules. The model was validated by evaluating and comparing performance metrics from the NEMA NU 2-2012 protocol on both the simulated and physical scanner, including spatial resolution, sensitivity, scatter fraction, noise equivalent count rates and image quality. The results show that the average sensitivities of the scanner in the field-of-view were 5.9 cps kBq -1 and 6.0 cps kBq -1 for experiment and simulation, respectively. The average spatial resolutions measured for point sources placed at several radial offsets were 5.2± 0.7 mm and 5.0± 0.8 mm FWHM for experiment and simulation, respectively. The peak NECR was 22.9 kcps at 7.4 kBq ml -1 for the experiment, while the NECR obtained via simulation was 23.3 kcps at the same activity. The scatter fractions were 44% and 41.3% for the experiment and simulation, respectively. Contrast recovery estimates performed in different regions of a simulated image quality phantom matched the experimental results with an average error of -8.7% and +3.4% for hot and cold lesions, respectively. The results demonstrate that the developed Geant4 model reliably reproduces the key NEMA NU 2-2012 performance metrics evaluated on the prototype PET scanner. A simplified version of the model is included as an advanced example in Geant4 version 10.5.