Assessment of Gray Matter Microstructural Alterations in Alzheimer's Disease by Free Water Imaging.

Background: Cortical neurodegenerative processes may precede the emergence of disease symptoms in patients with Alzheimer's disease (AD) by many years. No study has evaluated the free water of patients with AD using gray matter-based spatial statistics. Objective: The aim of this study was to explore cortical microstructural changes within the gray matter in AD by using free water imaging with gray matter-based spatial statistics. Methods: Seventy-one participants underwent multi-shell diffusion magnetic resonance imaging, 11C-Pittsburgh compound B positron emission tomography, and neuropsychological evaluations. The patients were divided into two groups: healthy controls (n = 40) and the AD spectrum group (n = 31). Differences between the groups were analyzed using voxel-based morphometry, diffusion tensor imaging, and free water imaging with gray matter-based spatial statistics. Results: Voxel-based morphometry analysis revealed gray matter volume loss in the hippocampus of patients with AD spectrum compared to that in controls. Furthermore, patients with AD spectrum exhibited significantly greater free water, mean diffusivity, and radial diffusivity in the limbic areas, precuneus, frontal lobe, temporal lobe, right putamen, and cerebellum than did the healthy controls. Overall, the effect sizes of free water were greater than those of mean diffusivity and radial diffusivity, and the larger effect sizes of free water were thought to be strongly correlated with AD pathology. Conclusions: This study demonstrates the utility of applying voxel-based morphometry, gray matter-based spatial statistics, free water imaging and diffusion tensor imaging to assess AD pathology and detect changes in gray matter.

Deep Learning-Driven Estimation of Centiloid Scales from Amyloid PET Images with 11C-PiB and 18F-Labeled Tracers in Alzheimer's Disease.

BACKGROUND: Standard methods for deriving Centiloid scales from amyloid PET images are time-consuming and require considerable expert knowledge. We aimed to develop a deep learning method of automating Centiloid scale calculations from amyloid PET images with 11C-Pittsburgh Compound-B (PiB) tracer and assess its applicability to 18F-labeled tracers without retraining. METHODS: We trained models on 231 11C-PiB amyloid PET images using a 50-layer 3D ResNet architecture. The models predicted the Centiloid scale, and accuracy was assessed using mean absolute error (MAE), linear regression analysis, and Bland-Altman plots. RESULTS: The MAEs for Alzheimer's disease (AD) and young controls (YC) were 8.54 and 2.61, respectively, using 11C-PiB, and 8.66 and 3.56, respectively, using 18F-NAV4694. The MAEs for AD and YC were higher with 18F-florbetaben (39.8 and 7.13, respectively) and 18F-florbetapir (40.5 and 12.4, respectively), and the error rate was moderate for 18F-flutemetamol (21.3 and 4.03, respectively). Linear regression yielded a slope of 1.00, intercept of 1.26, and R2 of 0.956, with a mean bias of -1.31 in the Centiloid scale prediction. CONCLUSIONS: We propose a deep learning means of directly predicting the Centiloid scale from amyloid PET images in a native space. Transferring the model trained on 11C-PiB directly to 18F-NAV4694 without retraining was feasible.

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.

Improving image quality using the pause function combination to PROPELLER sequence in brain MRI: a phantom study.

While some MRI systems offer a "pause" function, combining it with the PROPELLER method for image quality improvement remains underexplored. This study investigated whether repositioning the head after pausing during PROPELLER imaging enhances image quality. All brain phantom images in this study were obtained using a 3.0 T MRI and acquired using the fast spin-echo T2WI-based PROPELLER with motion correction. By combining the angle of rotational motion of the head phantom and the number of repositioning after a pause, two studies including seven trials were performed. Increasing the rotation angle decreased the image quality; however, pausing the image and repositioning the head phantom to the original angle improved the image quality. A similar result was obtained by repositioning the angle closer to its original angle. Experiments with multiple head movements showed that pausing the scan and repositioning the phantom with each movement improved image quality.

Performance Characteristics of a New-Generation Digital Bismuth Germanium Oxide PET/CT System, Omni Legend 32, According to NEMA NU 2-2018 Standards.

The Omni Legend 32 PET/CT system features silicon photomultiplier (SiPM)-based detectors with bismuth germanium oxide crystals and a 32-cm axial field of view (FOV). The present study aimed to determine the performance characteristics of the Omni Legend 32 PET/CT system according to National Electrical Manufacturers Association (NEMA) NU 2-2018 standards. Methods: The PET component of this system comprises 22 detector modules; each module contains 24 detector blocks with 72 bismuth germanium oxide crystals with a volume of 4.1 × 4.1 × 30 mm coupled to 18 SiPM devices with a 6 × 6 mm area, resulting in an axial FOV of 32 cm. The spatial resolution, sensitivity, count rate performance, and image quality delivered by PET were evaluated using the NEMA NU 2-2018 standard. PET images of 2 patients were evaluated to get a visual first impression of the Omni Legend 32 PET/CT system together with Precision DL. Results: The average spatial resolution at 1, 10, and 20 cm from the central axis was 4.3, 5.3, and 6.2 mm, respectively, for filtered backprojection and 3.7, 4.3, and 5.1 mm, respectively, for ordered-subset expectation maximization. The NEMA sensitivity was 47.30 and 47.05 cps/kBq at the axial center of the FOV and at a 10-cm radial offset, respectively. The scatter fraction, count rate accuracy, and peak noise-equivalent count rates were 35.4%, 1.7%, and 501.7 kcps, respectively, at 15.7 kBq/mL. Contrast recovery for the NEMA body phantom from the smallest to the largest sphere ranged from 61.3% to 93.0%, with a background variability of 5.4%-11.7% and a lung error of 5.1% for Q.Clear (ß-value, 50). Good patient image quality was obtained with the Omni Legend 32. Conclusion: The Omni Legend 32 has class-leading sensitivity and count rates within the category of whole-body PET systems while maintaining spatial resolution broadly comparable to that of other current SiPM-based PET/CT systems. This combination of properties results in a very good image quality.

Impact of irregular waveforms on data-driven respiratory gated PET/CT images processed using MotionFree algorithm.

OBJECTIVES: MotionFree® (AMF) is a data-driven respiratory gating (DDG) algorithm for image processing that has recently been introduced into clinical practice. The present study aimed to verify the accuracy of respiratory waveform and the effects of normal and irregular respiratory motions using AMF with the DDG algorithm. METHODS: We used a NEMA IEC body phantom comprising six spheres (37-, 28-, 22-, 17-, 13-, and 10 mm diameter) containing 18F. The sphere-to-background ratio was 4:1 (21.2 and 5.3 kBq/mL). We acquired PET/CT images from a stationary or moving phantom placed on a custom-designed motion platform. Respiratory motions were reproduced based on normal (sinusoidal or expiratory-paused waveforms) and irregular (changed amplitude or shifted baseline waveforms) movements. The "width" parameters in AMF were set at 10-60% and extracted data during the expiratory phases of each waveform. We verified the accuracy of the derived waveforms by comparing those input from the motion platform and output determined using AMF. Quantitative accuracy was evaluated as recovery coefficients (RCs), improvement rate, and %change that were calculated based on sphere diameter or width. We evaluated statistical differences in activity concentrations of each sphere between normal and irregular waveforms. RESULTS: Respiratory waveforms derived from AMF were almost identical to the input waveforms on the motion platform. Although the RCs in each sphere for expiratory-paused and ideal stationary waveforms were almost identical, RCs except the expiratory-paused waveform were lower than those for the stationary waveform. The improvement rate decreased more for the irregular, than the normal waveforms with AMF in smaller spheres. The %change was improved by decreasing the width of waveforms with a shifted baseline. Activity concentrations significantly differed between normal waveforms and those with a shifted baseline in spheres < 28 mm. CONCLUSIONS: The PET images using AMF with the DDG algorithm provided the precise waveform of respiratory motions and the improvement of quantitative accuracy in the four types of respiratory waveforms. The improvement rate was the most obvious in expiratory-paused waveforms, and the most subtle in those with a shifted baseline. Optimizing the width parameter in irregular waveform will benefit patients who breathe like the waveform with the shifted baseline.

Tau positron emission tomography in patients with cognitive impairment and suspected Alzheimer's disease.

Alzheimer's disease (AD) is diagnosed by the presence of both amyloid ß and tau proteins. Recent advances in molecular PET imaging have made it possible to assess the accumulation of these proteins in the living brain. PET ligands have been developed that bind to 3R/4R tau in AD, but not to 3R tau or 4R tau alone. Of the first-generation PET ligands, 18F-flortaucipir has recently been approved by the Food and Drug Administration. Several second-generation PET probes with less off-target binding have been developed and are being applied clinically. Visual interpretation of tau PET should be based on neuropathological neurofibrillary tangle staging instead of a simple positive or negative classification. Four visual read classifications have been proposed: "no uptake," "medial temporal lobe (MTL) only," "MTL AND," and "outside MTL." As an adjunct to visual interpretation, quantitative analysis has been proposed using MRI-based native space FreeSurfer parcellations. The standardized uptake value ratio of the target area is measured using the cerebellar gray matter as a reference region. In the near future, the Centiloid scale of tau PET is expected to be used as a harmonized value for standardizing each analytical method or PET ligand used, similar to amyloid PET.

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.

Age and Sex-Related Effects on Single-Subject Gray Matter Networks in Healthy Participants.

Recent developments in image analysis have enabled an individual's brain network to be evaluated and brain age to be predicted from gray matter images. Our study aimed to investigate the effects of age and sex on single-subject gray matter networks using a large sample of healthy participants. We recruited 812 healthy individuals (59.3 ± 14.0 years, 407 females, and 405 males) who underwent three-dimensional T1-weighted magnetic resonance imaging. Similarity-based gray matter networks were constructed, and the following network properties were calculated: normalized clustering, normalized path length, and small-world coefficients. The predicted brain age was computed using a support-vector regression model. We evaluated the network alterations related to age and sex. Additionally, we examined the correlations between the network properties and predicted brain age and compared them with the correlations between the network properties and chronological age. The brain network retained efficient small-world properties regardless of age; however, reduced small-world properties were observed with advancing age. Although women exhibited higher network properties than men and similar age-related network declines as men in the subjects aged < 70 years, faster age-related network declines were observed in women, leading to no differences in sex among the participants aged ≥ 70 years. Brain age correlated well with network properties compared to chronological age in participants aged ≥ 70 years. Although the brain network retained small-world properties, it moved towards randomized networks with aging. Faster age-related network disruptions in women were observed than in men among the elderly. Our findings provide new insights into network alterations underlying aging.

Impact of γ factor in the penalty function of Bayesian penalized likelihood reconstruction (Q.Clear) to achieve high-resolution PET images.

BACKGROUND: The Bayesian penalized likelihood PET reconstruction (BPL) algorithm, Q.Clear (GE Healthcare), has recently been clinically applied to clinical image reconstruction. The BPL includes a relative difference penalty (RDP) as a penalty function. The ß value that controls the behavior of RDP determines the global strength of noise suppression, whereas the γ factor in RDP controls the degree of edge preservation. The present study aimed to assess the effects of various γ factors in RDP on the ability to detect sub-centimeter lesions. METHODS: All PET data were acquired for 10 min using a Discovery MI PET/CT system (GE Healthcare). We used a NEMA IEC body phantom containing spheres with inner diameters of 10, 13, 17, 22, 28 and 37 mm and 4.0, 5.0, 6.2, 7.9, 10 and 13 mm. The target-to-background ratio of the phantom was 4:1, and the background activity concentration was 5.3 kBq/mL. We also evaluated cold spheres containing only non-radioactive water with the same background activity concentration. All images were reconstructed using BPL + time of flight (TOF). The ranges of ß values and γ factors in BPL were 50-600 and 2-20, respectively. We reconstructed PET images using the Duetto toolbox for MATLAB software. We calculated the % hot contrast recovery coefficient (CRChot) of each hot sphere, the cold CRC (CRCcold) of each cold sphere, the background variability (BV) and residual lung error (LE). We measured the full width at half maximum (FWHM) of the micro hollow hot spheres ≤ 13 mm to assess spatial resolution on the reconstructed PET images. RESULTS: The CRChot and CRCcold for different ß values and γ factors depended on the size of the small spheres. The CRChot, CRCcold and BV increased along with the γ factor. A 6.2-mm hot sphere was obvious in BPL as lower ß values and higher γ factors, whereas γ factors ≥ 10 resulted in images with increased background noise. The FWHM became smaller when the γ factor increased. CONCLUSION: High and low γ factors, respectively, preserved the edges of reconstructed PET images and promoted image smoothing. The BPL with a γ factor above the default value in Q.Clear (γ factor = 2) generated high-resolution PET images, although image noise slightly diverged. Optimizing the ß value and the γ factor in BPL enabled the detection of lesions ≤ 6.2 mm.

Free water derived by multi-shell diffusion MRI reflects tau/neuroinflammatory pathology in Alzheimer's disease.

Introduction: Free-water (FW) imaging, a new analysis method for diffusion magnetic resonance imaging (MRI), can indicate neuroinflammation and degeneration. We evaluated FW in Alzheimer's disease (AD) using tau/inflammatory and amyloid positron emission tomography (PET). Methods: Seventy-one participants underwent multi-shell diffusion MRI, 18F-THK5351 PET, 11C-Pittsburgh compound B PET, and neuropsychological assessments. They were categorized into two groups: healthy controls (HCs) (n = 40) and AD-spectrum group (AD-S) (n = 31) using the Centiloid scale with amyloid PET and cognitive function. We analyzed group comparisons in FW and PET, correlations between FW and PET, and correlation analysis with neuropsychological scores. Results: In AD-S group, there was a significant positive correlation between FW and 18F-THK5351 in the temporal lobes. In addition, there were negative correlations between FW and cognitive function in the temporal lobe and cingulate gyrus, and negative correlations between 18F-THK5351 and cognitive function in the same regions. Discussion: FW imaging could be a biomarker for tau in AD alongside clinical correlations.

Evaluation of quantitative accuracy among different scatter corrections for quantitative bone SPECT/CT imaging.

Although scatter correction improves SPECT image contrast and thus image quality, the effects of quantitation accuracy under various conditions remain unclear. The present study aimed to empirically define the conditions for the optimal scatter correction of quantitative bone SPECT/CT images. Scatter correction was performed by applying dual and triple energy windows (DEW and TEW) with different sub-energy window widths, and effective scatter source estimation (ESSE) to CT-based scatter correction. Scattered radiation was corrected on images acquired using a triple line source (TLSP) phantom and an uniform cylinder phantom. The TLSP consisted of a line source containing 74.0 MBq of 99mTc in the middle, and a background component containing air, water or a K2HPO4 solution with a density equivalent to that of bone. The sum of all pixels in air, water and the K2HPO4 solution was measured on SPECT images. Scatter fraction (SF) and normalized mean square error (NMSE) based on counts from the air background as a reference were then calculated to assess quantitative errors due to scatter correction. The uniform cylinder phantom contained the same K2HPO4 solution and 222.0 MBq of 99mTc. The coefficient of variation (CV) was calculated from the count profile of this phantom to assess the uniformity of SPECT images across scatter correction under various conditions. Both SF and NMSE in SPECT images of phantoms containing water in the background were lower at a TEW sub-window of 3% (TEW3%), than in other scatter corrections, whereas those in K2HPO4 were lower at a DEW sub-window of 20% (DEW20%). Larger DEW and smaller TEW sub-energy windows allowed more effective correction. The CV of the uniform cylinder phantom, DEW20%, was inferior to all other tested scatter corrections. The quantitative accuracy of bone SPECT images substantially differed according to the method of scatter correction. The optimal scatter correction for quantitative bone SPECT was DEW20% (k = 1), but at the cost of slightly decreased image uniformity.

Determination of optimal regularization factor in Bayesian penalized likelihood reconstruction of brain PET images using [18 F]FDG and [11 C]PiB.

PURPOSE: The Bayesian penalized likelihood (BPL) reconstruction algorithm, Q.Clear, can achieve a higher signal-to-noise ratio on images and more accurate quantitation than ordered subset-expectation maximization (OSEM). The reconstruction parameter (ß) in BPL requires optimization according to the radiopharmaceutical tracer. The present study aimed to define the optimal ß value in BPL required to diagnose Alzheimer disease from brain positron emission tomography (PET) images acquired using 18 F-fluoro-2-deoxy-D-glucose ([18 F]FDG) and 11 C-labeled Pittsburg compound B ([11 C]PiB). METHODS: Images generated from Hoffman 3D brain and cylindrical phantoms were acquired using a Discovery PET/computed tomography (CT) 710 and reconstructed using OSEM + time-of-flight (TOF) under clinical conditions and BPL + TOF (ß = 20-1000). Contrast was calculated from images generated by the Hoffman 3D brain phantom, and noise and uniformity were calculated from those generated by the cylindrical phantom. Five cognitively healthy controls and five patients with Alzheimer disease were assessed using [18 F]FDG and [11 C]PiB PET to validate the findings from the phantom study. The ß values were restricted by the findings of the phantom study, then one certified nuclear medicine physician and two certified nuclear medicine technologists visually determined optimal ß values by scoring the quality parameters of image contrast, image noise, cerebellar stability, and overall image quality of PET images from 1 (poor) to 5 (excellent). RESULTS: The contrast in BPL satisfied the Japanese Society of Nuclear Medicine (JSNM) criterion of ≥55% and exceeded that of OSEM at ranges of ß = 20-450 and 20-600 for [18 F]FDG and [11 C]PiB, respectively. The image noise in BPL satisfied the JSNM criterion of ≤15% and was below that in OSEM when ß = 150-1000 and 400-1000 for [18 F]FDG and [11 C]PiB, respectively. The phantom study restricted the ranges of ß values to 100-300 and 300-500 for [18 F]FDG and [11 C]PiB, respectively. The BPL scores for gray-white matter contrast and image noise, exceeded those of OSEM in [18 F]FDG and [11 C]PiB images regardless of ß values. Visual evaluation confirmed that the optimal ß values were 200 and 450 for [18 F]FDG and [11 C]PiB, respectively. CONCLUSIONS: The BPL achieved better image contrast and less image noise than OSEM, while maintaining quantitative standardized uptake value ratios (SUVR) due to full convergence, more rigorous noise control, and edge preservation. The optimal ß values for [18 F]FDG and [11 C]PiB brain PET were apparently 200 and 450, respectively. The present study provides useful information about how to determine optimal ß values in BPL for brain PET imaging.

Software development for quantitative analysis of brain amyloid PET.

INTRODUCTION: Centiloid (CL) scaling has become a standard quantitative measure in amyloid PET because it allows the direct comparison of results across sites, even when different analytical methods or PET tracers are used. METHODS: In the present study, we developed new standalone software to easily handle a pipeline for accurate calculation of the CL scale for the five currently available amyloid PET tracers-11 C-PiB, 18 F-florbetapir, 18 F-flutemetamol, 18 F-florbetaben, and 18 F-NAV4694. This pipeline requires reorientation and coregistration of PET and MRI, anatomic standardization of coregistered PET to a standardized space using a warping parameter for coregistered MRI, application of standard volumes of interest (VOIs) to the warped PET, calculation of the standardized uptake value ratio (SUVR) for the target VOIs, and finally conversion of the SUVR to the CL scale. The PET data for these tracers were collected from the publicly available Global Alzheimer's Association Interactive Network (GAAIN) repository. We also developed software to map Z-scores for the statistical comparison of a patient's PET data with a negative control database obtained from young healthy controls in the GAAIN repository. RESULTS: When whole cerebellum or whole cerebellum plus brainstem was chosen as the reference area, an excellent correlation was found between the CL scale calculated by this software and the CL scale published by GAAIN. There were no significant differences in the detection performance of significant amyloid accumulation using Z-score mapping between each 18 F-labeled tracer and 11 C-PiB. The cutoff CL values providing the most accurate detection of regional amyloid positivity in Z-score mapping were 11.8, 14.4, 14.7, 15.6, and 17.7 in the posterior cingulate gyrus and precuneus, frontal cortex, temporal cortex, parietal cortex, and striatum, respectively. CONCLUSION: This software is able to not only provide reliable calculation of the global CL scale but also detect significant local amyloid accumulation in an individual patient.

Amyloid PET quantification using low-dose CT-guided anatomic standardization.

BACKGROUND: Centiloid (CL) scaling has become a standardized quantitative measure in amyloid PET because it facilitates the direct comparison of results across institutions, even when different analytical methods or tracers are used. Standard volumes of interest must be used to calculate the CL scale after the anatomic standardization of amyloid PET images using coregistered MRI; if the MRI is unavailable, the CL scale cannot be accurately calculated. This study sought to determine the substitutability of low-dose CT, which is used to correct PET attenuation in PET/CT equipment, by evaluating the measurement accuracy when low-dose CT is used as an alternative to MRI in the calculation of the CL scale. Amyloid PET images obtained using 18F-flutemetamol from 24 patients with possible or probable Alzheimer's disease were processed to calculate the CL scale using 3D T1-weighted MRI and low-dose CT of PET/CT. CLMRI and CLCT were, respectively, defined as the use of MRI and CT for anatomic standardization and compared. Regional differences in the CT-based and MRI-based standardized anatomic images were also investigated. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs031180321 (registered 18 March 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031180321 ). RESULTS: A Bland-Altman plot showed that CLCT was slightly but significantly underestimated (mean ± standard deviation, - 1.7 ± 2.4; p < 0.002) compared with CLMRI. The 95% limits of agreement ranged from - 2.8 to - 0.7. Pearson correlation analysis showed a highly significant correlation of r = 0.998 between CLCT and CLMRI (p < 0.001). The linear regression equation was CLMRI = 1.027 × CLCT + 0.762. In a Bland-Altman plot, Spearman correlation analysis did not identify a significant association between the difference in CLMRI versus CLCT and CL load (ρ = - 0.389, p = 0.060). This slight underestimation of CLCT may derive from slightly higher uptake when the cerebellum is used as a reference area in CT-based anatomically standardized PET images versus MRI-based images. CONCLUSIONS: Low-dose CT of PET/CT can substitute for MRI in the anatomic standardization used to calculate the CL scale from amyloid PET, although a slight underestimation occurs.

Single-subject gray matter networks in temporal lobe epilepsy patients with hippocampal sclerosis.

OBJECTIVE: Previous studies have demonstrated structural brain network abnormalities in patients with temporal lobe epilepsy (TLE) using cortical thickness or gray matter (GM) volume. However, no studies have applied single-subject GM network analysis. Here, we first applied an analysis of similarity-based single-subject GM networks to individual patients with TLE. MATERIALS AND METHODS: We recruited 51 patients with TLE and unilateral hippocampal sclerosis (22 left, 29 right TLE) and 51 age- and gender- matched healthy controls. Single-subject structural networks were extracted from three-dimensional T1-weighted magnetic resonance images for each subject. In this method, nodes were defined as small cortical regions and edges representing connecting regions that have high statistical similarity. The constructed graphs were analyzed using the graph theoretical approach. The following global and local network properties were calculated: betweenness centrality, clustering coefficient, and characteristic path length. In addition, small world properties (normalized path length λ, normalized clustering coefficient γ, and small-world network value σ) were obtained and compared with those for the controls. RESULTS: Although the small-world configurations were retained, impaired global clustering coefficient was observed in left and right TLE. At a regional level, patients with left TLE showed a widespread decrease of the clustering coefficient beyond the ipsilateral temporal lobe and a decreased characteristic path length in the ipsilateral temporal pole. On the other hand, patients with right TLE showed a localized decrease of the clustering coefficient in the ipsilateral temporal lobe. CONCLUSIONS: Our findings suggest that global and local network properties disrupted and moved toward randomized networks in TLE patients in comparison to controls. This network alteration was more extensive in left TLE than in right TLE patients. Single-subject GM networks may contribute to a better understanding of the pathophysiology of TLE.

Centiloid scale analysis for 18F-THK5351 PET imaging in Alzheimer's disease.

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 18F-THK5351 PET imaging in Alzheimer's disease (AD). METHODS: We acquired 18F-THK5351 PET, 11C-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 18F-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 18F-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. 18F-THK5351 PET data could be expressed using the Centiloid scale, with the SUVR of the 18F-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 18F-THK5351.