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.

Combining plasma Aß and p-tau217 improves detection of brain amyloid in non-demented elderly.

BACKGROUND: Maximizing the efficiency to screen amyloid-positive individuals in asymptomatic and non-demented aged population using blood-based biomarkers is essential for future success of clinical trials in the early stage of Alzheimer's disease (AD). In this study, we elucidate the utility of combination of plasma amyloid-ß (Aß)-related biomarkers and tau phosphorylated at threonine 217 (p-tau217) to predict abnormal Aß-positron emission tomography (PET) in the preclinical and prodromal AD. METHODS: We designed the cross-sectional study including two ethnically distinct cohorts, the Japanese trial-ready cohort for preclinica and prodromal AD (J-TRC) and the Swedish BioFINDER study. J-TRC included 474 non-demented individuals (CDR 0: 331, CDR 0.5: 143). Participants underwent plasma Aß and p-tau217 assessments, and Aß-PET imaging. Findings in J-TRC were replicated in the BioFINDER cohort including 177 participants (cognitively unimpaired: 114, mild cognitive impairment: 63). In both cohorts, plasma Aß(1-42) (Aß42) and Aß(1-40) (Aß40) were measured using immunoprecipitation-MALDI TOF mass spectrometry (Shimadzu), and p-tau217 was measured with an immunoassay on the Meso Scale Discovery platform (Eli Lilly). RESULTS: Aß-PET was abnormal in 81 participants from J-TRC and 71 participants from BioFINDER. Plasma Aß42/Aß40 ratio and p-tau217 individually showed moderate to high accuracies when detecting abnormal Aß-PET scans, which were improved by combining plasma biomarkers and by including age, sex and APOE genotype in the models. In J-TRC, the highest AUCs were observed for the models combining p-tau217/Aß42 ratio, APOE, age, sex in the whole cohort (AUC = 0.936), combining p-tau217, Aß42/Aß40 ratio, APOE, age, sex in the CDR 0 group (AUC = 0.948), and combining p-tau217/Aß42 ratio, APOE, age, sex in the CDR 0.5 group (AUC = 0.955), respectively. Each subgroup results were replicated in BioFINDER, where the highest AUCs were seen for models combining p-tau217, Aß42/40 ratio, APOE, age, sex in cognitively unimpaired (AUC = 0.938), and p-tau217/Aß42 ratio, APOE, age, sex in mild cognitive impairment (AUC = 0.914). CONCLUSIONS: Combination of plasma Aß-related biomarkers and p-tau217 exhibits high performance when predicting Aß-PET positivity. Adding basic clinical information (i.e., age, sex, APOE Îµ genotype) improved the prediction in preclinical AD, but not in prodromal AD. Combination of Aß-related biomarkers and p-tau217 could be highly useful for pre-screening of participants in clinical trials of preclinical and prodromal AD.

Loss of methylthioadenosine phosphorylase immunoreactivity correlates with poor prognosis and elevated uptake of 11C-methionine in IDH-mutant astrocytoma.

PURPOSE: The proximate localization of MTAP, which encodes methylthioadenosine phosphorylase, and CDKN2A/B on Chromosome 9q21 has allowed the loss of MTAP expression as a surrogate for homozygous deletion of CDKN2A/B. This study aimed to determine whether MTAP status correlates with clinical outcomes and 11C-methionine uptake in astrocytomas with IDH mutations. METHODS: We conducted immunohistochemistry for MTAP in 30 patients with astrocytoma, IDH-mutant who underwent 11C-methionine positron emission tomography scans prior to surgical resection. The tumor-to-normal (T/N) ratio of 11C-methionine uptake was calculated using the mean standardized uptake value (SUV) for tumor and normal brain tissues. Cox regression analysis was used for multivariate survival analysis. RESULTS: Among IDH-mutant astrocytomas, 26.7% (8/30) exhibited the loss of cytoplasmic MTAP expression, whereas 73.3% (22/30) tumors retained MTAP expression. The median progression-free survival (PFS) was significantly shorter in patients with MTAP loss than those with MTAP retention (1.88 years vs. 6.80 years, p = 0.003). The median overall survival (OS) was also shorter in patients with MTAP loss than in MTAP-retaining counterparts (5.23 years vs. 10.69 years, p = 0.019). Multivariate analysis identified MTAP status (hazard ratio (HR), 0.081) and extent of resection (HR, 0.104) as independent prognostic factors for PFS. Astrocytomas lacking cytoplasmic MTAP expression showed a significantly higher median T/N ratio for 11C-methionine uptake than tumors retaining MTAP (2.12 vs. 1.65, p = 0.012). CONCLUSION: Our study revealed that the loss of MTAP expression correlates with poor prognosis and an elevated T/N ratio of 11C-methionine uptake in astrocytoma, IDH-mutant.

Measurement of Cerebral Glucose Metabolism in the Visual Cortex Predicts the Prognosis of Hemianopia.

BACKGROUND AND OBJECTIVE: Homonymous hemianopia caused by cerebrovascular disease may improve over time. This study investigated whether functional neuroimaging can predict the prognosis of hemianopia due to cerebral infarction. METHODS: We studied 19 patients (10 men and 9 women) with homonymous hemianopia and compared them with 34 healthy subjects (20 men and 14 women). Cerebral glucose metabolism was measured by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), 1 to 6 months after the onset. Bilateral regions of interest (ROIs) were selected from the posterior and, anterior striate cortices, extrastriate cortex, and thalamus. Furthermore, semi-quantitative data on cerebral glucose metabolism were obtained for ROIs and compared with the data obtained for homologous regions in the contralateral hemisphere by calculating the ipsilateral/contralateral (I/C) ratio. RESULTS: The I/C ratio for the cerebral glucose metabolism in the posterior striate cortex was high (>0.750) in 8 patients, and the central visual field of these patients improved or showed macular sparing. The I/C ratio for cerebral glucose metabolism in the anterior striate cortex was high (>0.830) in 7 patients, and the peripheral visual field of these patients improved. However, no improvement was observed in 9 patients with a low I/C ratio for cerebral glucose metabolism in both the posterior and anterior striate cortices. CONCLUSION: Measurement of cerebral glucose metabolism in the striate cortex is useful for estimating visual field prognosis. Furthermore, FDG-PET is useful in predicting the prognosis of hemianopia.

Phantom and clinical evaluation of the Bayesian penalised likelihood reconstruction algorithm Q.Clear without PSF correction in amyloid PET images.

PURPOSE: Bayesian penalised likelihood (BPL) reconstruction, which incorporates point-spread-function (PSF) correction, provides higher signal-to-noise ratios and more accurate quantitation than conventional ordered subset expectation maximization (OSEM) reconstruction. However, applying PSF correction to brain PET imaging is controversial due to Gibbs artefacts that manifest as unpredicted cortical uptake enhancement. The present study aimed to validate whether BPL without PSF would be useful for amyloid PET imaging. METHODS: Images were acquired from Hoffman 3D brain and cylindrical phantoms for phantom study and 71 patients administered with [18F]flutemetamol in clinical study using a Discovery MI. All images were reconstructed using OSEM, BPL with PSF correction, and BPL without PSF correction. Count profile, %contrast, recovery coefficients (RCs), and image noise were calculated from the images acquired from the phantoms. Amyloid ß deposition in patients was visually assessed by two physicians and quantified based on the standardised uptake value ratio (SUVR). RESULTS: The overestimated radioactivity in profile curves was eliminated using BPL without PSF correction. The %contrast and image noise decreased with increasing ß values in phantom images. Image quality and RCs were better using BPL with, than without PSF correction or OSEM. An optimal ß value of 600 was determined for BPL without PSF correction. Visual evaluation almost agreed perfectly (κ = 0.91-0.97), without depending on reconstruction methods. Composite SUVRs did not significantly differ between reconstruction methods. CONCLUSION: Gibbs artefacts disappeared from phantom images using the BPL without PSF correction. Visual and quantitative evaluation of [18F]flutemetamol imaging was independent of the reconstruction method. The BPL without PSF correction could be the standard reconstruction method for amyloid PET imaging, despite being qualitatively inferior to BPL with PSF correction for [18F]flutemetamol amyloid PET imaging.

Decreased diffusivity along the perivascular space and cerebral hemodynamic disturbance in adult moyamoya disease.

Moyamoya disease (MMD) causes cerebral arterial stenosis and hemodynamic disturbance, the latter of which may disrupt glymphatic system activity, the waste clearance system. We evaluated 46 adult patients with MMD and 33 age- and sex-matched controls using diffusivity along the perivascular space (ALPS) measured with diffusion tensor imaging (ALPS index), which may partly reflect glymphatic system activity, and multishell diffusion MRI to generate freewater maps. Twenty-three patients were also evaluated via 15O-gas positron emission tomography (PET), and all patients underwent cognitive tests. Compared to controls, patients (38.4 (13.2) years old, 35 females) had lower ALPS indices in the left and right hemispheres (1.94 (0.27) vs. 1.65 (0.25) and 1.94 (0.22) vs. 1.65 (0.19), P < 0.001). While the right ALPS index showed no correlation, the left ALPS index was correlated with parenchymal freewater (ρ = -0.47, P < 0.001); perfusion measured with PET (cerebral blood flow, ρ = 0.70, P < 0.001; mean transit time, ρ = -0.60, P = 0.003; and oxygen extraction fraction, ρ = -0.52, P = 0.003); and cognitive tests (trail making test part B for executive function; ρ = -0.37, P = 0.01). Adult patients with MMD may exhibit decreased glymphatic system activity, which is correlated with the degree of hemodynamic disturbance, increased interstitial freewater, and cognitive dysfunction, but further investigation is needed.

Comparison of consistency in centiloid scale among different analytical methods in amyloid PET: the CapAIBL, VIZCalc, and Amyquant methods.

OBJECTIVE: The Centiloid (CL) scale is a standardized measure for quantifying amyloid deposition in amyloid positron emission tomography (PET) imaging. We aimed to assess the agreement among 3 CL calculation methods: CapAIBL, VIZCalc, and Amyquant. METHODS: This study included 192 participants (mean age: 71.5 years, range: 50-87 years), comprising 55 with Alzheimer's disease, 65 with mild cognitive impairment, 13 with non-Alzheimer's dementia, and 59 cognitively normal participants. All the participants were assessed using the three CL calculation methods. Spearman's rank correlation, linear regression, Friedman tests, Wilcoxon signed-rank tests, and Bland-Altman analysis were employed to assess data correlations, linear associations, method differences, and systematic bias, respectively. RESULTS: Strong correlations (rho = 0.99, p < .001) were observed among the CL values calculated using the three methods. Scatter plots and regression lines visually confirmed these strong correlations and met the validation criteria. Despite the robust correlations, a significant difference in CL value between CapAIBL and Amyquant was observed (36.1 ± 39.7 vs. 34.9 ± 39.4; p < .001). In contrast, no significant differences were found between CapAIBL and VIZCalc or between VIZCalc and Amyquant. The Bland-Altman analysis showed no observable systematic bias between the methods. CONCLUSIONS: The study demonstrated strong agreement among the three methods for calculating CL values. Despite minor variations in the absolute values of the Centiloid scores obtained using these methods, the overall agreement suggests that they are interchangeable.

Preclinical validation of a novel brain-penetrant PET ligand for visualization of histone deacetylase 6: a potential imaging target for neurodegenerative diseases.

PURPOSE: Histone deacetylase 6 (HDAC6) has emerged as a therapeutic target for neurodegenerative diseases such as Alzheimer's disease. Noninvasive imaging of HDAC6 in the brain by positron emission tomography (PET) would accelerate research into its roles in these diseases. We recently discovered an 18F-labeled derivative of the selective HDAC6 inhibitor SW-100 ([18F]FSW-100) as a potential candidate for brain HDAC6 radioligand. As a mandatory step prior to clinical translation, we performed preclinical validation of [18F]FSW-100. METHODS: Process validation of [18F]FSW-100 radiosynthesis for clinical use and assessment of preclinical toxicity and radiation dosimetry estimated from mouse distribution data were performed. In vitro selectivity of FSW-100 for 28 common receptors in the brain and HDAC isoforms was characterized. [18F]FSW-100 PET imaging was performed in non-human primates in a conscious state to estimate the feasibility of HDAC6 imaging in humans. RESULTS: Three consecutive validation runs of the automated radiosynthesis gave [18F]FSW-100 injections with radiochemical yields of 12%, and the injections conformed to specified quality control criteria for batch release. No acute toxicity was observed for non-radiolabeled FSW-100 or radioactivity decayed [18F]FSW-100 injection, and the former was negative in the Ames test. The whole-body effective dose estimated from biodistribution in mice was within the range of that of previously reported 18F-radioligands in humans. In vitro selectivity against common receptors and other HDAC isoforms was confirmed. [18F]FSW-100 demonstrated good penetration in monkey brain, and in vivo blocking studies suggested that the uptake was specific. CONCLUSION: These results support the clinical utility of [18F]FSW-100 for in vivo imaging of HDAC6 in the brain.

Impact of [11C]methionine PET with Bayesian penalized likelihood reconstruction on glioma grades based on new WHO 2021 classification.

OBJECTIVE: The uptake of [11C]methionine in positron emission tomography (PET) imaging overlapped in earlier images of tumors. Bayesian penalized likelihood (BPL) reconstruction increases the quantitative values of tumors compared with conventional ordered subset-expectation maximization (OSEM). The present study aimed to grade glioma malignancy based on the new WHO 2021 classification using [11C]methionine PET images reconstructed using BPL. METHODS: We categorized 32 gliomas in 28 patients as grades 2/3 (n = 15) and 4 (n = 17) based on the WHO 2021 classification. All [11C]methionine images were reconstructed using OSEM + time-of-flight (TOF) and BPL + TOF (ß = 200). Maximum standardized uptake value (SUVmax) and tumor-to-normal tissue ratio (T/Nmax) were measured at each lesion. RESULTS: The mean SUVmax was 4.65 and 4.93 in grade 2/3 and 6.38 and 7.11 in grade 4, and the mean T/Nmax was 7.08 and 7.22 in grade 2/3 and 9.30 and 10.19 in grade 4 for OSEM and BPL, respectively. The BPL significantly increased these values in grade 4 gliomas. The area under the receiver operator characteristic (ROC) curve (AUC) for SUVmax was the highest (0.792) using BPL. CONCLUSIONS: The BPL increased mean SUVmax and mean T/Nmax in lesions with higher contrast such as grade 4 glioma. The discrimination power between grades 2/3 and 4 in SUVmax was also increased using [11C]methionine PET images reconstructed with BPL.

Pitfalls of Amyloid-Beta PET: Comparisons With 18 F-MK-6240 and 18 F-THK5351 PET.

ABSTRACT: We present 3 patients as pitfalls of amyloid-beta (Aß) PET, who underwent 11 C-PiB (Aß), 18 F-MK-6240 (Alzheimer disease [AD]-tau), and 18 F-THK5351 (astrogliosis) PET examinations. Despite negligible or tiny Aß pathology, patients 1 and 2 were diagnosed with AD as the cause of symptoms. Despite widespread Aß pathology, patient 3 was not diagnosed with AD as the cause of symptoms. However, if we had only conducted Aß PET, patients 1 and 2 might not have been diagnosed with AD, whereas patient 3 might have been diagnosed with AD. Hence, both Aß and AD-tau assessments are necessary to relate clinical symptoms to AD pathology.

Ventral Variant Posterior Cortical Atrophy with Occipito-temporal Accumulation of Tau Proteins/Astrocyte Gliosis.

A 73-year-old woman with posterior cortical atrophy (PCA) presented with progressive apperceptive visual agnosia, alexia, agraphia, ventral simultanagnosia, prosopagnosia, and allocentric (stimulus-centered) left-sided hemispatial neglect. All of these symptoms were attributed to damage to the bilateral occipito-temporal cortices, consistent with ventral variant PCA. While the Pittsburgh compound B uptake was extensively distributed throughout the occipito-parietal (dorsal) and occipito-temporal (ventral) areas, the THK5351 (ligand binding to tau aggregates/astrocyte gliosis) accumulation was limited to the ventral area. These findings suggest that local accumulation of tau proteins and/or astrocyte gliosis over the occipito-temporal cortices can result in ventral variant PCA.

What digital health technology types are used in mental health prevention and intervention? Review of systematic reviews for systematization of technologies.

Digital health technology has been widely applied to mental health interventions worldwide. Using digital phenotyping to identify an individual's mental health status has become particularly important. However, many technologies other than digital phenotyping are expected to become more prevalent in the future. The systematization of these technologies is necessary to accurately identify trends in mental health interventions. However, no consensus on the technical classification of digital health technologies for mental health interventions has emerged. Thus, we conducted a review of systematic review articles on the application of digital health technologies in mental health while attempting to systematize the technology using the Delphi method. To identify technologies used in digital phenotyping and other digital technologies, we included 4 systematic review articles that met the inclusion criteria, and an additional 8 review articles, using a snowballing approach, were incorporated into the comprehensive review. Based on the review results, experts from various disciplines participated in the Delphi process and agreed on the following 11 technical categories for mental health interventions: heart rate estimation, exercise or physical activity, sleep estimation, contactless heart rate/pulse wave estimation, voice and emotion analysis, self-care/cognitive behavioral therapy/mindfulness, dietary management, psychological safety, communication robots, avatar/metaverse devices, and brain wave devices. The categories we defined intentionally included technologies that are expected to become widely used in the future. Therefore, we believe these 11 categories are socially implementable and useful for mental health interventions.

Diagnostic performance of the cingulate island sign ratio for differentiating dementia with Lewy bodies from Alzheimer's disease changes depending on the mini-mental state examination score.

BACKGROUND: The cingulate island sign (CIS) ratio is a diagnostic adjunct for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). A recent study showed that the CIS ratio in DLB changed depending on the Mini-Mental State Examination (MMSE) score. We aimed to evaluate whether the diagnostic performance (sensitivity and specificity) of the CIS ratio for differentiating DLB from AD changes depending on the MMSE score. METHODS: Twenty-two patients with DLB and 26 amyloid-positive patients with AD, who underwent 18F-FDG PET and completed an MMSE examination, were classified into three groups according to MMSE scores: Group A (MMSE >24), Group B (20 ≤ MMSE ≤24), and Group C (MMSE <20). In each group, we compared the CIS ratio between patients with DLB and AD and conducted receiver operating characteristic (ROC) curve analysis to calculate the sensitivity and specificity. RESULTS: Within Group B, the CIS ratio in DLB was significantly higher than that in AD (p = 0.0005), but not within Groups A (p = 0.5117) and C (p = 0.8671). ROC curve analyses showed that the sensitivities and specificities of the CIS ratio for differentiating DLB from AD were 66.7% and 77.8% in Group A, 91.7% and 100.0% in Group B, and 75.0% and 66.7% in Group C, respectively. CONCLUSIONS: The present study suggests that the diagnostic performance of the CIS ratio for differentiating DLB from AD changes depending on the MMSE score, with higher sensitivity and specificity at MMSE scores of 20-24.

Detailed Assessment of 18F-THK5351 Distribution Pattern in the Midbrain: Comparison With Progressive Supranuclear Palsy and Corticobasal Syndrome.

BACKGROUND: 18F-THK5351 PET is used to image ongoing astrogliosis by estimating monoamine oxidase B levels. 18F-THK5351 preferentially accumulates around the substantia nigra (SN) and periaqueductal gray (PG) in the midbrain under healthy conditions and exhibits a "trimodal pattern." In progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), the midbrain 18F-THK5351 uptake can be increased by astrogliosis, collapsing the "trimodal pattern." We aimed to elucidate cases in which the "trimodal pattern" collapses in PSP and CBS. PATIENTS AND METHODS: Participants in the PSP (n = 11), CBS (n = 17), Alzheimer disease (n = 11), and healthy control (n = 8) groups underwent 18F-THK5351 PET. Volumes of interest (VOIs) were placed on the SN, PG, and their midpoints. The midbrain uptake ratio (MUR) was calculated to assess the trimodal pattern as follows: MUR = (VOI value on the midpoint)/(VOI value on the SN and PG). Approximately, the trimodal pattern can be identified at MUR <1 but not at MUR >1. RESULTS: Compared with the healthy control group, MUR significantly increased in the PSP (P < 0.01) and CBS (P < 0.01) groups, but was unchanged in the Alzheimer disease group (P = 0.10). In the PSP group, all patients, including 2 with mild symptoms and a short disease duration, showed MUR >1. In the CBS group, MUR varied widely. CONCLUSIONS: In PSP, the trimodal pattern can collapse even in the early phase when symptoms are mild. In CBS, the trimodal pattern may or may not collapse depending on the underlying pathology.

Clinical Application of 18F-THK5351 PET to Identify Inflammatory Lesions Through Imaging Astrogliosis in a Case of Cytomegalovirus Ventriculoencephalitis.

ABSTRACT: 18F-THK5351 PET is used to estimate the degree of astrogliosis. Because inflammatory lesions usually accompany astrogliosis, 18F-THK5351 PET is potentially worthy of clinical application in inflammatory disorders. Here, we report a case of cytomegalovirus ventriculoencephalitis in an immunocompromised 75-year-old woman who underwent 18F-THK5351 PET and conventional neuroimaging modalities, including 11C-methionine, 18F-FDG, and MRI. 18F-THK5351 PET was clearly superior to the other modalities in identifying inflammatory lesions and can therefore be a useful marker for identifying inflammatory lesions through imaging astrogliosis. This feature of 18F-THK5351 may contribute to the early diagnosis of cytomegalovirus ventriculoencephalitis.

[Nuclear Medicine-based Early Diagnosis of Alzheimer's Disease].

The advent of pathology-specific diagnostic methods such as amyloid positron emission tomography (PET) and tau PET has enabled early and pre-symptomatic diagnosis of Alzheimer's disease. Imaging biomarkers in nuclear medicine play a key role in elucidating the pathogenesis of Alzheimer's disease and accelerating the development of disease-modifying drugs. In this study, we describe the current status and future prospects of nuclear medicine diagnostics aimed at early detection of Alzheimer's disease to delay and prevent disease progression.

T2-FLAIR mismatch sign correlates with 11C-methionine uptake in lower-grade diffuse gliomas.

PURPOSE: The T2-FLAIR mismatch sign is recognized as an imaging finding highly suggestive of IDH-mutant astrocytomas. This study was designed to determine whether the T2-FLAIR mismatch sign correlates with uptake of 11C-methionine in lower-grade gliomas. METHODS: We included 78 histopathologically verified lower-grade gliomas (grade 2: 31 cases, grade 3: 47 cases) in this study. 78 patients underwent 11C-methionine positron emission tomography (MET-PET) scans and magnetic resonance (MR) imaging scans prior to histological diagnosis. The tumor-to-normal ratio (T/N) of 11C-methionine uptake was calculated by dividing the maximum standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain. MR imaging scans were evaluated for the presence of the T2-FLAIR mismatch sign by three independent reviewers. We compared molecular status, the T2-FLAIR mismatch sign and 11C-methionine uptake among patients with different lower-grade glioma molecular types. RESULTS: The 78 lower-grade gliomas were assigned to one of three molecular groups: Group A (IDH-mutant and 1p/19q non-codeleted, n = 22), Group O (IDH-mutant and 1p/19q codeleted, n = 20), and Group W (IDH wildtype, n = 36). T2-FLAIR mismatch was found in 16 cases (20.5%) that were comprised of 8 (36.4%), 0 (0%), 8 (22.2%) cases in the molecular group A, O and W, respectively. The median T/N ratio of MET-PET in tumors with T2-FLAIR mismatch was 1.50, which was significantly lower than that of tumors without T2-FLAIR mismatch (1.83, p < 0.001, Mann-Whitney U test). In the Groups A and W (excluding Group O), the median T/N ratio on MET-PET in groups A and W (but not group O) with T2-FLAIR mismatch was 1.50, which was significantly lower than that of tumors without T2-FLAIR mismatch (1.81, p = 0.002, Mann-Whitney U test). CONCLUSION: The T2-FLAIR mismatch sign correlated with lower 11C-methionine uptake in lower grade gliomas.

High sensitivity of asymmetric 18F-THK5351 PET abnormality in patients with corticobasal syndrome.

Corticobasal syndrome (CBS) is characterized by symptoms related to the asymmetric involvement of the cerebral cortex and basal ganglia. However, early detection of asymmetric imaging abnormalities can be challenging. Previous studies reported asymmetric 18F-THK5351 PET abnormalities in CBS patients, but the sensitivity for detecting such abnormalities in larger patient samples, including early-stage cases, remains unclear. Patients clinically diagnosed with CBS were recruited. All patients displayed asymmetric symptoms in the cerebral cortex and basal ganglia. Asymmetric THK5351 PET abnormalities were determined through visual assessment. Brain MRI, perfusion SPECT, and dopamine transporter (DAT) SPECT results were retrospectively reviewed. The 15 patients had a median age of 72 years (59-86 years) and a disease duration of 2 years (0.5-7 years). Four patients met the probable and 11 met the possible CBS criteria according to Armstrong criteria at the time of PET examination. All patients, including early-stage cases, exhibited asymmetric tracer uptake contralateral to their symptom-dominant side in the cerebral cortex/subcortical white matter and striatum (100%). The sensitivity for detecting asymmetric imaging abnormalities contralateral to the symptom-dominant side was 86.7% for brain MRI, 81.8% for perfusion SPECT, and 90% for DAT SPECT. White matter volume reduction was observed in the subcortical region of the precentral gyrus with increased THK5351 uptake, occurring significantly more frequently than gray matter volume reduction. THK5351 PET may be a sensitive imaging technique for detecting asymmetric CBS pathologies, including those in early stages.

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.