DOCK-PET: database of CNS kinetic parameters in the healthy human brain for existing PET tracers.

PURPOSE: Information about developed positron emission tomography (PET) tracers and obtained clinical PET images is publicly available in a database. However, findings regarding the kinetic parameters of PET tracers are yet to be summarized. Therefore, in this study, we created an open-access database of central nervous system (CNS) kinetic parameters in the healthy human brain for existing PET tracers (DOCK-PET). METHODS: Our database includes information on the kinetic parameters and compounds of existing CNS-PET tracers. The kinetic parameter dataset comprises the analysis methods, VT, BPND, K parameters, relevant literature, and study details. The list of PET tracers and kinetic parameter information was compiled through keyword-based searches of PubMed and the Molecular Imaging and Contrast Agent Database (MICAD). The kinetic parameters obtained, including VT, BPND, and K parameters, were reorganized based on the defined brain anatomical regions. All data were rigorously double-checked before being summarized in Microsoft Excel and JavaScript Object Notation (JSON) formats. RESULTS: Of the 247 PET tracers identified through searches using the PubMed and MICAD websites, the kinetic parameters of 120 PET tracers were available. Among the 120 PET tracers, compound structures with chemical and physical properties were obtained from the PubChem website or the ChemDraw software. Furthermore, the affinity information of the 104 PET tracers was gathered from PubChem or extensive literature surveys of the 120 PET tracers. CONCLUSIONS: We developed a comprehensive open-access database, DOCK-PET, that includes both kinetic parameters of healthy humans and compound information for existing CNS-PET tracers.

Preclinical Characterization of the Tau PET Tracer [18F]SNFT-1: Comparison of Tau PET Tracers.

Tau PET tracers are expected to be sufficiently sensitive to track the progression of age-related tau pathology in the medial temporal cortex. The tau PET tracer N-(4-[18F]fluoro-5-methylpyridin-2-yl)-7-aminoimidazo[1,2-a]pyridine ([18F]SNFT-1) has been successfully developed by optimizing imidazo[1,2-a]pyridine derivatives. We characterized the binding properties of [18F]SNFT-1 using a head-to-head comparison with other reported 18F-labeled tau tracers. Methods: The binding affinity of SNFT-1 to tau, amyloid, and monoamine oxidase A and B was compared with that of the second-generation tau tracers MK-6240, PM-PBB3, PI-2620, RO6958948, JNJ-64326067, and flortaucipir. In vitro binding properties of 18F-labeled tau tracers were evaluated through the autoradiography of frozen human brain tissues from patients with diverse neurodegenerative disease spectra. Pharmacokinetics, metabolism, and radiation dosimetry were assessed in normal mice after intravenous administration of [18F]SNFT-1. Results: In vitro binding assays demonstrated that [18F]SNFT-1 possesses high selectivity and high affinity for tau aggregates in Alzheimer disease (AD) brains. Autoradiographic analysis of tau deposits in medial temporal brain sections from patients with AD showed a higher signal-to-background ratio for [18F]SNFT-1 than for the other tau PET tracers and no significant binding with non-AD tau, α-synuclein, transactiviation response DNA-binding protein-43, and transmembrane protein 106B aggregates in human brain sections. Furthermore, [18F]SNFT-1 did not bind significantly to various receptors, ion channels, or transporters. [18F]SNFT-1 showed a high initial brain uptake and rapid washout from the brains of normal mice without radiolabeled metabolites. Conclusion: These preclinical data suggest that [18F]SNFT-1 is a promising and selective tau radiotracer candidate that allows the quantitative monitoring of age-related accumulation of tau aggregates in the human brain.

Brain partial volume correction with point spreading function reconstruction in high-resolution digital PET: comparison with an MR-based method in FDG imaging.

OBJECTIVE: In quantitative positron emission tomography (PET) of the brain, partial volume effect due mainly to the finite spatial resolution of the PET scanner (> 3 mm full width at half maximum [FWHM]) is a primary source of error in the measurement of tracer uptake, especially in small structures such as the cerebral cortex (typically < 3 mm thickness). The aim of this study was to evaluate the partial volume correction (PVC) performance of point spread function-incorporated reconstruction (PSF reconstruction) in combination with the latest digital PET scanner. This evaluation was performed through direct comparisons with magnetic resonance imaging (MR)-based PVC (used as a reference method) in a human brain study. METHODS: Ten healthy subjects underwent brain 18F-FDG PET (30-min acquisition) on a digital PET/CT system (Siemens Biograph Vision, 3.5-mm FWHM scanner resolution at the center of the field of view) and anatomical T1-weighted MR imaging for MR-based PVC. PSF reconstruction was applied with a wide range of iterations (4 to 256; 5 subsets). FDG uptake in the cerebral cortex was evaluated using the standardized uptake value ratio (SUVR) and compared between PSF reconstruction and MR-based PVC. RESULTS: Cortical structures were visualized by PSF reconstruction with several tens of iterations and were anatomically well matched with the MR-derived cortical segments. Higher numbers of iterations resulted in higher cortical SUVRs, which approached those of MR-based PVC (1.76), although even with the maximum number of iterations they were still smaller by 16% (1.47), corresponding to approximately 1.5-mm FWHM of the effective spatial resolution. CONCLUSION: With the latest digital PET scanner, PSF reconstruction can be used as a PVC technique in brain PET, albeit with suboptimal resolution recovery. A relative advantage of PSF reconstruction is that it can be applied not only to cerebral cortical regions, but also to various small structures such as small brain nuclei that are hardly visualized on anatomical T1-weighted imaging, and thus hardly recovered by MR-based PVC.

Noninvasive estimation of human radiation dosimetry of 18F-FDG by whole-body small animal PET imaging in rats.

PURPOSE: Small animal PET provides the biodistribution of administrated radiotracer in vivo and have a potential to contribute on dosimetry study. The aim of this study is to investigate the effect of region-of-interest (ROI)-delineation in whole-body rat PET image toward non-invasive estimation of human dosimetry of 18F-FDG. METHOD: After administration of 18F-FDG (averaged 11.7 MBq), 3.5-h PET and 20-min CT scans were sequentially performed for three rats by Clairvivo PET/CT system. Seven source organs, and the remainder of the body, were studied to extrapolate %ID(t) and estimate time-integrated activity coefficients [kBq-h/MBq] in human. The mean absorbed dose in each target organ and the effective dose were estimated by MIRD method. Effects of ROI-definitions on both extrapolated %ID(t) in human and estimated doses were also investigated by using (i) small ROIs of high uptake region and (ii) whole organ ROIs. RESULTS: Averaged effective doses of 18F-FDG in human by using high-uptake and whole-organ ROIs were 27.8 ± 6.54 and 19.3 ± 2.72 µSv/MBq, respectively. CONCLUSION: The use of small animal PET scanner, which allows repeatedly PET scans, have a potential to contribute on the reduction of the number of experimental animals. However, the ways of ROI drawing influences on the estimated effective dose and safe-side ROI definition may be preferred.

18F-SMBT-1: A Selective and Reversible PET Tracer for Monoamine Oxidase-B Imaging.

Reactive astrocytes play a key role in the pathogenesis of various neurodegenerative diseases. Monoamine oxidase-B (MAO-B) is one of the promising targets for the imaging of astrogliosis in the human brain. A novel selective and reversible MAO-B tracer, (S)-(2-methylpyrid-5-yl)-6-[(3-18F-fluoro-2-hydroxy)propoxy]quinoline (18F-SMBT-1), was successfully developed via lead optimization from the first-generation tau PET tracer 18F-THK-5351. Methods: SMBT-1 was radiolabeled with 18F using the corresponding precursor. The binding affinity of radiolabeled compounds to MAO-B was assessed using saturation and competitive binding assays. The binding selectivity of 18F-SMBT-1 to MAO-B was evaluated by autoradiography of frozen human brain tissues. The pharmacokinetics and metabolism were assessed in normal mice after intravenous administration of 18F-SMBT-1. A 14-d toxicity study after the intravenous administration of 18F-SMBT-1 was performed using rats and mice. Results: In vitro binding assays demonstrated a high binding affinity of 18F-SMBT-1 to MAO-B (dissociation constant, 3.7 nM). In contrast, it showed low binding affinity to MAO-A and protein aggregates such as amyloid-ß and tau fibrils. Autoradiographic analysis showed higher amounts of 18F-SMBT-1 binding in the Alzheimer disease brain sections than in the control brain sections. 18F-SMBT-1 binding was completely displaced with the reversible MAO-B inhibitor lazabemide, demonstrating the high selectivity of 18F-SMBT-1 for MAO-B. Furthermore, 18F-SMBT-1 showed a high uptake by brain, rapid washout, and no radiolabeled metabolites in the brain of normal mice. 18F-SMBT-1 showed no significant binding to various receptors, ion channels, or transporters, and no toxic effects related to its administration were observed in mice and rats. Conclusion:18F-SMBT-1 is a promising and selective MAO-B PET tracer candidate, which would be useful for quantitative monitoring of astrogliosis in the human brain.

Iterative framework for image registration and partial volume correction in brain positron emission tomography.

Imprecise registration between positron emission tomography (PET) and anatomical magnetic resonance (MR) images is a critical source of error in MR imaging-guided partial volume correction (MR-PVC). Here, we propose a novel framework for image registration and partial volume correction, which we term PVC-optimized registration (PoR), to address imprecise registration. The PoR framework iterates PVC and registration between uncorrected PET and smoothed PV-corrected images to obtain precise registration. We applied PoR to the [11C]PiB PET data of 92 participants obtained from the Alzheimer's Disease Neuroimaging Initiative database and compared the registration results, PV-corrected standardized uptake value (SUV) and its ratio to the cerebellum (SUVR), and intra-region coefficient of variation (CoV) between PoR and conventional registration. Significant differences in registration of as much as 2.74 mm and 3.02° were observed between the two methods (effect size < - 0.8 or > 0.8), which resulted in considerable SUVR differences throughout the brain, reaching a maximal difference of 62.3% in the sensory motor cortex. Intra-region CoV was significantly reduced using the PoR throughout the brain. These results suggest that PoR reduces error as a result of imprecise registration in PVC and is a useful method for accurately quantifying the amyloid burden in PET.

Error propagation analysis of seven partial volume correction algorithms for [18F]THK-5351 brain PET imaging.

BACKGROUND: Novel partial volume correction (PVC) algorithms have been validated by assuming ideal conditions of image processing; however, in real clinical PET studies, the input datasets include error sources which cause error propagation to the corrected outcome. METHODS: We aimed to evaluate error propagations of seven PVCs algorithms for brain PET imaging with [18F]THK-5351 and to discuss the reliability of those algorithms for clinical applications. In order to mimic brain PET imaging of [18F]THK-5351, pseudo-observed SUVR images for one healthy adult and one adult with Alzheimer's disease were simulated from individual PET and MR images. The partial volume effect of pseudo-observed PET images were corrected by using Müller-Gärtner (MG), the geometric transfer matrix (GTM), Labbé (LABBE), regional voxel-based (RBV), iterative Yang (IY), structural functional synergy for resolution recovery (SFS-RR), and modified SFS-RR algorithms with incorporation of error sources in the datasets for PVC processing. Assumed error sources were mismatched FWHM, inaccurate image-registration, and incorrectly segmented anatomical volume. The degree of error propagations in ROI values was evaluated by percent differences (%diff) of PV-corrected SUVR against true SUVR. RESULTS: Uncorrected SUVRs were underestimated against true SUVRs (- 15.7 and - 53.7% in hippocampus for HC and AD conditions), and application of each PVC algorithm reduced the %diff. Larger FWHM mismatch led to larger %diff of PVC-SUVRs against true SUVRs for all algorithms. Inaccurate image registration showed systematic propagation for most algorithms except for SFS-RR and modified SFS-RR. Incorrect segmentation of the anatomical volume only resulted in error propagations in limited local regions. CONCLUSIONS: We demonstrated error propagation by numerical simulation of THK-PET imaging. Error propagations of 7 PVC algorithms for brain PET imaging with [18F]THK-5351 were significant. Robust algorithms for clinical applications must be carefully selected according to the study design of clinical PET data.

From the respective expert viewpoints of the ANM specialty editors.

Although it may not be well known, the Annals of Nuclear Medicine (ANM) Editorial Committee includes one specialty editor of nuclear medicine physics, one of nuclear medicine technology, one of molecular imaging, and two of radiopharmacology. In addition, a statistics editor and a language editor are also on the committee. Manuscripts submitted to ANM can be peer-reviewed by such specialty editors similar to those submitted to highly ranked journals, which is a great pride and joy to us. To offer our readers a condensed global view on the high-quality research work in the field of nuclear medicine, we have published a mini-review article every year under the joint authorship of the ANM associate editors since 2016. This is our fourth serial review article written by the ANM specialty editors from their respective expert viewpoints.

Renal statistical map for positron emission tomography with [O-15] water.

Image statistics are frequently used for functional and molecular imaging research in which images from a patient group with a specific diagnosis are compared with images from a healthy control group who have been matched for demographic variables. The success of image statistics for brain imaging has encouraged us to develop a method for obtaining volumetrically normalized kidney to perform image statistics so that we can locally visualize the statistical significant difference comparing voxel by voxel between certain groups in terms kidney blood flow kinetic parameters. For the development of this evolutionary process, we first volumetrically normalized all subjects, which include healthy control (HC) and chronic renal failure (CRF) patients, 15O water PET image with respect to one HC subject's MRI image using affine transformation. Then 15O kinetic parametric images of normalized kidneys were obtained through the basis function method. Finally, the statistical map of these parametric images was produced using the threshold-free cluster enhancement based permutation method. Kinetic parameters of kidney namely, uptake rate constant (K1), clearance rate constant (k2) and blood volume (Va), were found to be notably lower in CRF than those of in HC and k2 parameter was found to be more stable compared to K1 and Va. The statistical map of these parametric images allowed us to visualize local significant differences statistically (P<0.05) between HC and CRF groups. Though PET and MRI techniques have enormous potentiality for functional and molecular imaging of kidney, these are, at best, in experimental level. It is speculated that statistical mapping of kidney could play a significant role in the successful implementation of functional and molecular kidney imaging. However, more research involving a larger sample size and improved normalization technique will be needed for the robustness of the process.

A systematic performance evaluation of head motion correction techniques for 3 commercial PET scanners using a reproducible experimental acquisition protocol.

PURPOSES: Subject's motion during brain PET scan degrades spatial resolution and quantification of PET images. To suppress these effects, rigid-body motion correction systems have been installed in commercial PET scanners. In this study, we systematically compare the accuracy of motion correction among 3 commercial PET scanners using a reproducible experimental acquisition protocol. METHODS: A cylindrical phantom with two 22Na point sources was placed on a customized base to enable two types of motion, 5° yaw and 15° pitch rotations. Repetitive PET scans (5 min × 5 times) were performed at rest and under 2 motion conditions using 3 clinical PET scanners: the Eminence STARGATE G/L PET/CT (STARGATE) (Shimadzu Corp.), the SET-3000 B/X PET (SET-3000) (Shimadzu Corp.), and the Biograph mMR PET/MR (mMR) (Siemens Healthcare) systems. For STARGATE and SET-3000, the Polaris Vicra (Northern Digital Inc.) optical tracking system was used for frame-by-frame motion correction. For Biograph mMR, sequential MR images were simultaneously acquired with PET and used for LOR-based motion correction. All PET images were reconstructed by FBP algorithm with 1 × 1 mm pixel size. To evaluate the accuracy of motion correction, FWHMs and spherical ROI values were analyzed. RESULTS: The percent differences (%diff) in averaged FWHMs of point sources at 4 cm off-center between motion-corrected and static images were 0.77 ± 0.16 (STARGATE), 2.4 ± 0.34 (SET-3000), and 11 ± 1.0% (mMR) for a 5° yaw and 2.3 ± 0.37 (STARGATE) and 1.1 ± 0.60 (SET-3000) for a 15° pitch respectively. The averaged %diff between ROI values of motion-corrected images and static images were less than 2.0% for all conditions. CONCLUSIONS: In this study, we proposed a reproducible experimental framework to allow the systematic validation and comparison of multiple motion tracking and correction methodologies among different PET/CT and PET/MR commercial systems. Our proposed validation platform may be useful for future studies evaluating state-of-the-art motion correction strategies in clinical PET imaging.

Biomathematical screening of amyloid radiotracers with clinical usefulness index.

INTRODUCTION: To facilitate radiotracers' development, a screening methodology using a biomathematical model and clinical usefulness index (CUI) was proposed to evaluate radiotracers' diagnostic capabilities. METHODS: A total of 31 amyloid positron emission tomography radiotracers were evaluated. A previously developed biomathematical model was used to simulate 1000 standardized uptake value ratios with population and noise simulations, which were used to determine the integrated receiver operating characteristics curve (Az), effect size (Es), and standardized uptake value ratio (Sr) of conditions-pairs of healthy control-mild cognitive impaired and mild cognitive impaired-Alzheimer's disease. CUI was obtained from the product of averaged [Formula: see text], [Formula: see text], and [Formula: see text]. RESULTS: The relationships of [Formula: see text], [Formula: see text], and [Formula: see text] with CUI were different, suggesting that they assessed different radiotracer properties. The combination of Az, Es, and Sr complemented each other and resulted in CUI of 0.10 to 5.72, with clinically applied amyloid positron emission tomography radiotracers having CUI greater than 3.0. DISCUSSION: The CUI rankings of clinically applied radiotracers were close to their reported clinical results, attesting to the applicability of the screening methodology.

137Cs transmission imaging and segmented attenuation corrections in a small animal PET scanner.

Attenuation correction (AC) is required for accurate quantitative evaluation of small animal PET data. Our objective was to compare three AC methods in the small animal Clairvivo-PET scanner. The three AC methods involve applying attenuation coefficient maps generated by simulating a cylindrical map (SAC), segmenting the emission data (ESAC), and segmenting the transmission data (TSAC), imaged using a 137Cs single-photon source. Investigation was carried out using a 65 mm uniform cylinder and an NEMA NU4 2008 mouse phantom, filled with water or tungsten liquid, to mimic bone. Evaluation was carried out using the difference of the segmented map volume from the known cylindrical phantom volume, the recovery of the radioactivity concentration, and the line profiles. The optimal transmission scan time for achieving accurate AC using TSAC was determined using 5, 10, 15, 20, and 25 min transmission scan time. The effects of scatter correction and reconstruction algorithms on ESAC were investigated. SAC showed the best performance but was unable to correct for different tissues and the scanner bed, and faced difficulty with correct positioning of the attenuation coefficient map. ESAC was affected by scatter correction and reconstruction algorithm, and may result in poor boundary delineation, and hence was unreliable. TSAC showed reasonable performance but required further optimization of the default segmentation setting. A minimum transmission scan time of 20 min is recommended for Clairvivo-PET using 137Cs source to ensure that sufficient transmission counts are obtained to generate accurate attenuation coefficient map.

A comparison of five partial volume correction methods for Tau and Amyloid PET imaging with [18F]THK5351 and [11C]PIB.

PURPOSE: To suppress partial volume effect (PVE) in brain PET, there have been many algorithms proposed. However, each methodology has different property due to its assumption and algorithms. Our aim of this study was to investigate the difference among partial volume correction (PVC) method for tau and amyloid PET study. METHODS: We investigated two of the most commonly used PVC methods, Müller-Gärtner (MG) and geometric transfer matrix (GTM) and also other three methods for clinical tau and amyloid PET imaging. One healthy control (HC) and one Alzheimer's disease (AD) PET studies of both [18F]THK5351 and [11C]PIB were performed using a Eminence STARGATE scanner (Shimadzu Inc., Kyoto, Japan). All PET images were corrected for PVE by MG, GTM, Labbé (LABBE), Regional voxel-based (RBV), and Iterative Yang (IY) methods, with segmented or parcellated anatomical information processed by FreeSurfer, derived from individual MR images. PVC results of 5 algorithms were compared with the uncorrected data. RESULTS: In regions of high uptake of [18F]THK5351 and [11C]PIB, different PVCs demonstrated different SUVRs. The degree of difference between PVE uncorrected and corrected depends on not only PVC algorithm but also type of tracer and subject condition. CONCLUSION: Presented PVC methods are straight-forward to implement but the corrected images require careful interpretation as different methods result in different levels of recovery.

Prediction of the Clinical SUV Ratio in Amyloid PET Imaging Using a Biomathematic Modeling Approach Toward the Efficient Development of a Radioligand.

Our study aimed to develop a method to mathematically predict the kinetic parameters K1 (influx rate constant), k2 (efflux rate constant), and BPND (nondisplaceable binding potential) of amyloid PET tracers and obtain SUV ratios (SUVRs) from predicted time-activity curves of target and reference regions. Methods: We investigated 10 clinically applied amyloid PET radioligands: 11C-Pittsburgh compound B, 11C-BF-227, 11C-AZD2184, 11C-SB-13, 18F-FACT, 18F-florbetapir, 18F-florbetaben, 18F-flutemetamol, 18F-FDDNP, and 18F-AZD4694. For each tracer, time-activity curves of both target and reference regions were generated using a simplified 1-tissue-compartment model, with an arterial plasma input function and the predicted kinetic parameters. K1, k2, and BPND were derived from the lipophilicity (logP), apparent volume, free fraction in plasma, free fraction in tissue, dissociation constant, and density of amyloid ß using biomathematic modeling. Density was fixed at 3 nM to represent healthy control conditions and 50 nM to represent severe Alzheimer disease (AD). Predicted SUVRs for the healthy and AD groups were then obtained by dividing the integrated time-activity curve of the target region by that of the reference region. To validate the presented method, the predicted K1, k2, BPND, and SUVR for the healthy and AD groups were compared with the respective clinically observed values. Results: The correlation between predicted and clinical kinetic parameters had an R2 value of 0.73 for K1 in the healthy group, 0.71 for K1 in the AD group, 0.81 for k2 in the healthy group, 0.85 for k2 in the AD group, and 0.63 for BPND in the AD group. The regression relationship between the predicted SUVR (y) and the clinical SUVR (x) for the healthy and the AD groups was y = 2.73x - 2.11 (R2 = 0.72). Conclusion: The proposed method showed a good correlation between predicted and clinical SUVR for the 10 clinically applied amyloid tracers.

18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease.

UNLABELLED: Imaging of neurofibrillary pathology in the brain helps in diagnosing dementia, tracking disease progression, and evaluating the therapeutic efficacy of antidementia drugs. The radiotracers used in this imaging must be highly sensitive and specific for tau protein fibrils in the human brain. We developed a novel tau PET tracer, (18)F-THK5351, through compound optimization of arylquinoline derivatives. METHODS: The in vitro binding properties, pharmacokinetics, and safety of (18)F-THK5351 were investigated, and a clinical study on Alzheimer disease (AD) patients was performed. RESULTS: (18)F-THK5351 demonstrated higher binding affinity for hippocampal homogenates from AD brains and faster dissociation from white-matter tissue than did (18)F-THK5117. The THK5351 binding amount correlated with the amount of tau deposits in human brain samples. Autoradiography of brain sections revealed that THK5351 bound to neurofibrillary tangles selectively and with a higher signal-to-background ratio than did THK5117. THK5351 exhibited favorable pharmacokinetics and no defluorination in mice. In first-in-human PET studies in AD patients, (18)F-THK5351 demonstrated faster kinetics, higher contrast, and lower retention in subcortical white matter than(18)F-THK5117. CONCLUSION: (18)F-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients.

Quantitative kinetic analysis of PET amyloid imaging agents [(11)C]BF227 and [(18)F]FACT in human brain.

INTRODUCTION: The purpose of this study was to compare two amyloid imaging agents, [(11)C]BF227 and [(18)F]FACT (derivative from [(11)C]BF227) through quantitative pharmacokinetics analysis in human brain. METHODS: Positron emission tomography studies were performed on six elderly healthy control (HC) subjects and seven probable Alzheimer's disease (AD) patients with [(11)C]BF227 and 10 HC subjects and 10 probable AD patients with [(18)F]FACT. Data from nine regions of interest were analyzed by several approaches, namely non-linear least-squared fitting methods with arterial input functions (one-tissue compartment model(1TCM), two-tissue compartment model (2TCM)), Logan plot, and linearized methods with reference region (Reference Logan plot (RefLogan), MRTM0, MRTM2). We also evaluated SUV and SUVR for both tracers. The parameters estimated by several approaches were compared between two tracers for detectability of differences between HC and AD patients. RESULTS: For [(11)C]BF227, there were no significant difference of VT (2TCM, 1TCM) and SUV in all regions (Student t-test; p<0.05) and significant differences in the DVRs (Logan, RefLogan, and MRTM2) and SUVRs in six neocortical regions (p<0.05) between the HC and AD groups. For [(18)F]FACT, significant differences in DVRs (RefLogan, MRTM0, and MRTM2) were observed in more than four neocortical regions between the HC and AD groups (p<0.05), and the significant differences were found in SUVRs for two neocortical regions (inferior frontal coretex and lateral temporal coretex). Our results showed that both tracers can clearly distinguish between HC and AD groups although the pharmacokinetics and distribution patterns in brain for two tracers were substantially different. CONCLUSION: This study revealed that although the PET amyloid imaging agents [(11)C]BF227 and [(18)F]FACT have similar chemical and biological properties, they have different pharmacokinetics, and caution must be paid for usage of the tracers.

[(18)F]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer's disease.

PURPOSE: Visualization of the spatial distribution of neurofibrillary tangles would help in the diagnosis, prevention and treatment of dementia. The purpose of the study was to evaluate the clinical utility of [(18)F]THK-5117 as a highly selective tau imaging radiotracer. METHODS: We initially evaluated in vitro binding of [(3)H]THK-5117 in post-mortem brain tissues from patients with Alzheimer's disease (AD). In clinical PET studies, [(18)F]THK-5117 retention in eight patients with AD was compared with that in six healthy elderly controls. Ten subjects underwent an additional [(11)C]PiB PET scan within 2 weeks. RESULTS: In post-mortem brain samples, THK-5117 bound selectively to neurofibrillary deposits, which differed from the binding target of PiB. In clinical PET studies, [(18)F]THK-5117 binding in the temporal lobe clearly distinguished patients with AD from healthy elderly subjects. Compared with [(11)C]PiB, [(18)F]THK-5117 retention was higher in the medial temporal cortex. CONCLUSION: These findings suggest that [(18)F]THK-5117 provides regional information on neurofibrillary pathology in living subjects.

Aliased noise in X-ray CT images and band-limiting processing as a preventive measure.

X-ray CT projection data often include components with frequencies that are markedly higher than the pixel Nyquist frequency f PN, which is determined by the pixel size. Noise components higher than f PN are folded back into a region lower than f PN through the backprojection process, thereby creating aliased noise. With clinical CT scanners, we evaluated the aliased noise using an aliasing prevention measure, band-limiting processing (BLP), which suppresses frequency components higher than f PN in the projection data. Indices we used to evaluate improvement by BLP were the noise power spectrum (NPS), modulation transfer function (MTF), signal-to-noise-ratio (SNR) spectrum, matched filter SNR (MF SNR), and two-alternative forced-choice (2-AFC) test. With BLP, the NPS was decreased not only beyond f PN, but also within f PN. The same level of MTF was maintained as that without BLP within f PN. No remarkable reduction in spatial resolution was observed. The SNR spectrum and the MF SNR of the BLP image nearly agreed with those of an ideal state without aliased noise. A notable improvement in the visuoperceptual image quality by BLP was recognized with a reconstruction field of view (FOV) of more than 45 cm. We then applied BLP to clinical data and confirmed that significant aliased noise of a large FOV image was removed without notable side effects. The results showed that at least some CTs suffering from aliased noise can be improved by proper band-limiting.

Quantification of opioid receptor availability following spontaneous epileptic seizures: correction of [11C]diprenorphine PET data for the partial-volume effect.

Previous positron emission tomography (PET) studies in refractory temporal lobe epilepsy (TLE) using the non-selective opioid receptor antagonist [(11)C]diprenorphine (DPN) did not detect any changes in mesial temporal structures, despite known involvement of the hippocampus in seizure generation. Normal binding in smaller hippocampi is suggestive of increased receptor concentration in the remaining grey matter. Correction for partial-volume effect (PVE) has not been used in previous DPN PET studies. Here, we present PVE-corrected DPN-PET data quantifying post-ictal and interictal opioid receptor availability in humans with mTLE. Eight paired datasets of post-ictal and interictal DPN PET scans and eleven test/retest control datasets were available from a previously published study on opioid receptor changes in TLE following seizures (Hammers et al., 2007a). Five of the eight participants with TLE had documented hippocampal sclerosis. Data were re-analyzed using regions of interest and a novel PVE correction method (structural functional synergistic-resolution recovery (SFS-RR); (Shidahara et al., 2012)). Data were denoised, followed by application of SFS-RR, with anatomical information derived via precise anatomical segmentation of the participants' MRI (MAPER; (Heckemann et al., 2010)). [(11)C]diprenorphine volume-of-distribution (VT) was quantified in six regions of interest. Post-ictal increases were observed in the ipsilateral fusiform gyri and lateral temporal pole. A novel finding was a post-ictal increase in [(11)C]DPN VT relative to the interictal state in the ipsilateral parahippocampal gyrus, not observed in uncorrected datasets. As for voxel-based (SPM) analyses, correction for global VT values was essential in order to demonstrate focal post-ictal increases in [(11)C]DPN VT. This study provides further direct human in vivo evidence for changes in opioid receptor availability in TLE following seizures, including changes that were not evident without PVE correction. Denoising, resolution recovery and precise anatomical segmentation can extract valuable information from PET studies that would be missed with conventional post-processing procedures.