PET imaging of 11C-labeled thiamine tetrahydrofurfuryl disulfide, vitamin B1 derivative: First-in-human study.

Vitamine B1 thiamine is an essential component for glucose metabolism and energy production. The disulfide derivative, thiamine tetrahydrofurfuryl disulfide (TTFD), is more absorbent compared to readily-available water-soluble thiamine salts since it does not require the rate-limiting transport system required for thiamine absorption. However, the detailed pharmacokinetics of thiamine and TTFD under normal and pathological conditions were not clarified yet. Recently, 11C-labeled thiamine and TTFD were synthesized by our group, and their pharmacokinetics were investigated by PET imaging in normal rats. In this study, to clarify the whole body pharmacokinetics of [11C]TTFD in human healthy volunteers, we performed first-in-human PET imaging study with [11C]TTFD, along with radiation dosimetry of [11C]TTFD in humans. METHODS: Synthesis of [11C]TTFD was improved for clinical study. Dynamic whole-body PET images were acquired on three young male normal subjects after intravenous injection of [11C]TTFD. VOIs were defined for source organs on the PET images to measure time-course of [11C]TTFD uptake as percentage injected dose and the number of disintegrations for each organ. Radiation dosimetry was calculated with OLINDA/EXM. RESULTS: We succeeded in developing the improved synthetic method of [11C]TTFD for the first-in-human PET study. In the whole body imaging, uptake of [11C]TTFD by various tissues was almost plateaued at 10 min after intravenous injection, afterward gradually increased for the brain and urinary bladder (urine). %Injected dose was high in the liver, kidney, urinary bladder, heart, spine, brain, spleen, pancreas, stomach, and salivary glands, in this order. %Injected dose per gram of tissue was high also in the pituitary. By dosimetry, the effective radiation dose of [11C]TTFD calculated was 5.5 µSv/MBq (range 5.2-5.7). CONCLUSION: Novel synthetic method enabled clinical PET study with [11C]TTFD, which is a safe PET tracer with a dosimetry profile comparable to other common 11C-PET tracers. Pharmacokinetics of TTFD in the pharmacological dose and at different nutritional states could be further investigated by future quantitative PET studies. Noninvasive in vivo PET imaging for pathophysiology of thiamine-related function may provide diagnostic evidence of novel information about vitamin B1 deficiency in human tissues.

Technical Considerations on Scanning and Image Analysis for Amyloid PET in Dementia.

Brain imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET), can provide essential and objective information for the early and differential diagnosis of dementia. Amyloid PET is especially useful to evaluate the amyloid-ß pathological process as a biomarker of Alzheimer's disease. This article reviews critical points about technical considerations on the scanning and image analysis methods for amyloid PET. Each amyloid PET agent has its own proper administration instructions and recommended uptake time, scan duration, and the method of image display and interpretation. In addition, we have introduced general scanning information, including subject positioning, reconstruction parameters, and quantitative and statistical image analysis. We believe that this article could make amyloid PET a more reliable tool in clinical study and practice.

[Harmonization of Standardized Uptake Value among Different Generation PET/ CT Cameras Based on a Phantom Experiment -Utility of SUV(peak)].

Standardized uptake value (SUV) has been widely used as a semi-quantitative metric of uptake in FDGPET/ CT for diagnosis of malignant tumors and evaluation of tumor therapies. However, the SUV depends on various factors including PET/CT scanner specifications and reconstruction parameters. The purpose of this study is to harmonize the SUV among two PET/CT models of different generation: two units of Discovery ST Elite Performance(DSTEP) and Discovery 690 (D690) PET/CT scanners. The NEMA body phantom filled with 18F solution was scanned for 30 minutes in list-mode. The D690 PET images were reconstructed with OSEM, OSEM+TOF, and OSEM+PSF. Gaussian post-filters of 4-9 mm FWHM were applied to find the parameters that provides harmonized SUV. We determined the SUV-harmonized parameter for each reconstruction algorithm. Then, the 10 PET images simulating clinical scan conditions were respectively generated to evaluate the bias and variability of SUV(max) and SUV(peak). The SUV(max) strongly depended not only on spatial resolution but also on image noise. On the other hand, the SUV(peak) was a robust metric to image noise level. TOF improved the variability of SUV(max) and SUV(peak). Thus, we were able to harmonize the spatial resolution using SUV(peak) based on the phantom study. Because SUV(max) was also strongly affected by image noise, sufficient count statistics is essential for SUV(max) harmonization. We recommended that TOF reconstruction and SUV(peak) metric should be used to harmonize SUV.

[Accuracy of Injection Dose of Amyloid PET Agent Using Radiopharmaceutical Activity Suppliers].

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.

Improved Correlation of 18F-Flortaucipir PET SUVRs and Clinical Stages in the Alzheimer Disease Continuum with the MUBADA/PERSI-Based Analysis.

The Alzheimer disease (AD) continuum is a neurodegenerative disorder with cognitive decline and pathologic changes. Tau PET imaging can detect tau pathology, and 18F-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 18F-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 18F-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 18F-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.

Development of a novel phantom for tau PET imaging.

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 18F, 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.

A quantitative assessment of Geant4 for predicting the yield and distribution of positron-emitting fragments in ion beam therapy.

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 parent11C,10C and15O 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.

A review of harmonization strategies for quantitative PET.

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-18F 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.

Pre-acquired CT-based attenuation correction with automated headrest removal for a brain-dedicated PET system.

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 18F-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.

Dosimetry and efficacy of a tau PET tracer [18F]MK-6240 in Japanese healthy elderly and patients with Alzheimer's disease.

OBJECTIVE: A new tau PET tracer [18F]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 [18F]MK-6240 in Japanese elderly subjects. Also, the pattern and extent of brain retention of [18F]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 [18F]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 [18F]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 ([18F]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 [18F]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 [18F]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 [18F]MK-6240 were consistent with those for non-Japanese populations. TRIAL REGISTRATION: Japan Pharmaceutical Information Center ID, JapicCTI-194972.

Toward standardization of tau PET imaging corresponding to various tau PET tracers: a multicenter phantom study.

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 [18F]flortaucipir, [18F]THK5351, and [18F]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.

Marker-less and calibration-less motion correction method for brain PET.

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.

Brain PET motion correction using 3D face-shape model: the first clinical study.

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 18F-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, r2 = 0.995). CONCLUSION: Our motion correction method provided good accuracy for the volunteer data which suggested it is useable in clinical settings.

Small nuclei identification with a hemispherical brain PET.

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 18F-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 .

Feasibility of triple gamma ray imaging of10C for range verification in ion therapy.

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 radioactive15O and11C 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 of10C, 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 for10C imaging and its feasibility for range verification in carbon ion therapy. First, the performance of the WGI was studied to image a10C point source using the Geant4 toolkit. Then, the feasibility of WGI was investigated for an irradiated polymethyl methacrylate (PMMA) phantom with a10C 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 simulated10C point source at the centre of the field of view were 5.5 mm FWHM and 0.010%, respectively. The depth dose of the10C ion beam was measured, and the triple gamma image of10C 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 of10C ion beams.

New standards for phantom image quality and SUV harmonization range for multicenter oncology PET studies.

Not only visual interpretation for lesion detection, staging, and characterization, but also quantitative treatment response assessment are key roles for 18F-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 (NECphantom), 10-mm sphere contrast (QH,10 mm), background variability (N10 mm), contrast-to-noise ratio (QH,10 mm/N10 mm), image noise level (CVBG), 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: QH,10 mm/N10 mm ≥ 2.5 and CVBG ≤ 14.1%. The 10th-90th percentiles in the SUV distributions were defined as the new SUV harmonization range. CVBG ≤ 10% was proposed as the image noise criterion, because the intra-scanner SUV variability significantly depended on CVBG. 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.

Performance evaluation of VRAIN: a brain-dedicated PET with a hemispherical detector arrangement.

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 VRAINTM. 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 mm3) and a 12 × 12 array of silicon photomultipliers (4 × 4 mm2active 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 performed18F-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-1and 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.

Improved Accuracy of Amyloid PET Quantification with Adaptive Template-Based Anatomic Standardization.

Amyloid PET noninvasively visualizes amyloid-ß 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 11C-Pittsburgh compound B (11C-PiB) PET through the Japanese Alzheimer's Disease Neuroimaging Initiative study were examined. For the anatomic standardization of 11C-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-ß 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.