Partial Volume Correction Research Articles

Corrections of myocardial tissue sodium concentration measurements in human cardiac 23Na MRI at 7 Tesla

To quantify the tissue sodium concentration (TSC) in cardiac 23 Na MRI. To evaluate the influence of different correction methods on the measured myocardial TSC. 23 Na MRI of four healthy subjects was conducted at a whole-body 7T MRI system using an oval-shaped 23 Na birdcage coil. Data acquisition was performed with a density-adapted 3D radial pulse sequence using a golden angle projection scheme. 1 H MRI data were acquired at a 3T MRI system to generate a myocardial mask. Retrospective cardiac and respiratory gating were used to reconstruct 23 Na MRI data in the diastolic phase and exhaled state. B0 and B1 inhomogeneity and partial volume (PV) effects were corrected. Relaxation times and TSC of ex vivo blood samples and calf muscle were determined. These values were used in the PV correction to estimate myocardial TSC, which was compared with the measured TSC of calf muscle. Without any correction the measured myocardial TSC was (54 ± 5) mM. The applied correction methods reduced these values by (48 ± 5)% to (29 ± 3) mM, where PV correction had the largest effect (reduction of (34 ± 1)%). Respiratory and cardiac motion gating decreased the concentrations by (11 ± 1)%. With the applied setup, the corrections of B0 and B1 inhomogeneity (reduction of (3 ± 2)%) had negligible influences on TSC values. The resulting myocardial TSC was approximately 1.4-fold higher than the measured TSC of calf muscle tissue of the same healthy subjects ((20 ± 3) mM). For quantitative human cardiac 23 Na MRI several corrections are needed and ranked for our setup: PV correction, respiratory and cardiac gating, correction for B1 inhomogeneity effects.

Comparison of Pittsburgh compound B and florbetapir in cross-sectional and longitudinal studies

IntroductionQuantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B–based and florbetapir-based amyloid imaging in the same participants from two independent cohorts using a crossover design. MethodsPittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter-individual variability of the two tracers were compared using multivariate linear models both cross-sectionally and longitudinally. ResultsGlobal amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers. DiscussionAlthough the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers.

Patient body motion correction for dynamic cardiac PET-CT by attenuation-emission alignment according to projection consistency conditions.

Patient body motion is known to cause large deviations in the determination of myocardial blood flow (MBF) with errors exceeding 300%. Accurate correction for patient whole-body motion is still a largely unsolved problem in cardiac positron emission tomography (PET) imaging. This study evaluated the efficacy of using Natterer's formulation of the Helgason-Ludwig consistency conditions on the two-dimensional Radon transform to align computed tomography to PET projection data in multiple time frames of a dynamic sequence for the purpose of frame-by-frame correction of rigid whole-body motion. The correction algorithm was evaluated with digital NCAT phantoms using realistic noise added by the analytical simulator. Count rates used in the simulation were derived from clinical patient data. In addition, a proof of concept test using measured data with a cardiac torso phantom was conducted. Motion correction resulted in significant improvement in the accuracy of MBF estimates, especially for high count-rate acquisitions. Maximum errors for 2cm of motion dropped from 325% to 25% and from 250% to 25% using global and regional partial-volume correction, respectively. Median MBF errors dropped from 33% to 4.5% and 27% to 3.8%, respectively. Importantly, the correction algorithm performed equally well to compensate for body motion in both early and late time frames. Cardiac PET-CT data used for attenuation correction (CTAC) alignment using projection consistency conditions was effective for reducing errors in MBF measurements due to simulated patient motion, and can be integrated into the image reconstruction workflow.

Partial-volume correction in dynamic PET-CT: effect on tumor kinetic parameter estimation and validation of simplified metrics

BackgroundPartial-volume effects generally result in an underestimation of tumor tracer uptake on PET-CT for small lesions, necessitating partial-volume correction (PVC) for accurate quantification. However, investigation of PVC in dynamic oncological PET studies to date is scarce. The aim of this study was to investigate PVC’s impact on tumor kinetic parameter estimation from dynamic PET-CT acquisitions and subsequent validation of simplified semi-quantitative metrics. Ten patients with EGFR-mutated non-small cell lung cancer underwent dynamic 18F-fluorothymidine PET-CT before, 7 days after, and 28 days after commencing treatment with a tyrosine kinase inhibitor. Parametric PVC was applied using iterative deconvolution without and with highly constrained backprojection (HYPR) denoising, respectively. Using an image-derived input function with venous parent plasma calibration, we estimated full kinetic parameters VT, K1, and k3/k4 (BPND) using a reversible two-tissue compartment model, and simplified metrics (SUV and tumor-to-blood ratio) at 50–60 min post-injection.ResultsPVC had a non-linear effect on measured activity concentrations per timeframe. PVC significantly changed each kinetic parameter, with a median increase in VT of 11.8% (up to 25.1%) and 10.8% (up to 21.7%) without and with HYPR, respectively. Relative changes in kinetic parameter estimates vs. simplified metrics after applying PVC were poorly correlated (correlations 0.36–0.62; p < 0.01). PVC increased correlations between simplified metrics and VT from 0.82 and 0.81 (p < 0.01) to 0.90 and 0.88 (p < 0.01) for SUV and TBR, respectively, albeit non-significantly. PVC also increased correlations between treatment-induced changes in simplified metrics vs. VT at 7 (SUV) and 28 (SUV and TBR) days after treatment start non-significantly. Delineation on partial-volume corrected PET images resulted in a median decrease in metabolic tumor volume of 14.3% (IQR − 22.1 to − 7.5%), and increased the effect of PVC on kinetic parameter estimates.ConclusionPVC has a significant impact on tumor kinetic parameter estimation from dynamic PET-CT data, which differs from its effect on simplified metrics. However, it affected validation of these simplified metrics both as single measurements and as biomarkers of treatment response only to a small extent. Future dynamic PET studies should preferably incorporate PVC.Trial registrationDutch Trial Register, NTR3557.

Partial volume correction for arterial spin labeling using the inherent perfusion information of multiple measurements

BackgroundArterial spin labeling (ASL) provides a noninvasive way to measure cerebral blood flow (CBF). The CBF estimation from ASL is heavily contaminated by noise and the partial volume (PV) effect. The multiple measurements of perfusion signals in the ASL sequence are generally acquired and were averaged to suppress the noise. To correct the PV effect, several methods were proposed, but they were all performed directly on the averaged image, thereby ignoring the inherent perfusion information of mixed tissues that are embedded in multiple measurements. The aim of the present study is to correct the PV effect of ASL sequence using the inherent perfusion information in the multiple measurements.MethodsIn this study, we first proposed a statistical perfusion model of mixed tissues based on the distribution of multiple measurements. Based on the tissue mixture that was obtained from the high-resolution structural image, a structure-based expectation maximization (sEM) scheme was developed to estimate the perfusion contributions of different tissues in a mixed voxel from its multiple measurements. Finally, the performance of the proposed method was evaluated using both computer simulations and in vivo data.ResultsCompared to the widely used linear regression (LR) method, the proposed sEM-based method performs better on edge preservation, noise suppression, and lesion detection, and demonstrates a potential to estimate the CBF within a shorter scanning time. For in vivo data, the corrected CBF values of gray matter (GM) were independent of the GM probability, thereby indicating the effectiveness of the sEM-based method for the PV correction of the ASL sequence.ConclusionsThis study validates the proposed sEM scheme for the statistical perfusion model of mixed tissues and demonstrates the effectiveness of using inherent perfusion information in the multiple measurements for PV correction of the ASL sequence.

A study on the transferability of the sigma enlarging bridge function for an accurate evaluation of solvation free energy: The case of homonuclear Lennard-Jones diatomic solute solvated in a Lennard-Jones monatomic solvent

We study the applicability of sigma enlarging bridge (SEB) function to a homonuclear Lennard-Jones (LJ) diatomic solute molecule solvated in an LJ monatomic solvent, where the SEB was originally proposed for a monatomic solute molecule to improve the accuracy of the solvation free energy (SFE) [T. Miyata, Bull. Chem. Soc. Jpn. 90, 1095 (2017)]. Our interest is focused on the transferability of the SEB parameter, which is a parameter included in the SEB function. We employ the two-dimensional Ornstein-Zernike (OZ) theory. Hypernetted chain (HNC), Kovalenko-Hirata (KH) and Percus-Yevick (PY) closures are considered. The HNC closure with the SEB correction (SEB-HNC) and the counterpart for the KH closure (SEB-KH) are also examined in terms of the SFE. It is found that by comparing with the molecular dynamics simulation, the SFE is overestimated under both HNC and KH closures, whereas it tends to be underestimated under PY closures. These results are similar to those obtained for systems of LJ monatomic solute molecules. Both the SEB-HNC and the SEB-KH closures provide quite an accurate SFE, when the SEB parameter values that were originally evaluated for a monatomic solute molecule are applied to the homonuclear LJ diatomic solute. This indicates that the SEB parameter is transferable. The transferability of the SEB parameter is also confirmed in terms of the angular-dependent one-dimensional distribution function, which is obtained from the two-dimensional distribution function. The validity of the partial molar volume correction is also discussed by examining the dependence of the SFE errors on the solute volume.

Partial volume and motion correction in cardiac PET: First results from an in vs ex vivo comparison using animal datasets

BackgroundIn a previous study on ex vivo, static cardiac datasets, we investigated the benefits of performing partial volume correction (PVC) in cardiac 18F-Fluorodeoxyglucose(FDG) PET datasets. In the present study, we extend the analysis to in vivo cardiac datasets, with the aim of defining which reconstruction technique maximizes quantitative accuracy and, ultimately, makes PET a better diagnostic tool for cardiac pathologies. MethodsIn vivo sheep datasets were acquired and reconstructed with/without motion correction and using several reconstruction algorithms (with/without resolution modeling, with/without non-anatomical priors). Corresponding ex vivo scans of the excised sheep hearts were performed on a small-animal PET scanner (Siemens Focus 220, microPET) to provide high-resolution reference data unaffected by respiratory and cardiac motion. A comparison between the in vivo cardiac reconstructions and the corresponding ex vivo ground truth was performed. ResultsThe use of an edge-preserving prior (Total Variation (TV) prior in this work) in combination with motion correction reduces the bias in absolute quantification when compared to the standard clinical reconstructions (− 0.83 vs − 3.74 SUV units), when the end-systolic gate is considered. At end-diastole, motion correction improves absolute quantification but the PVC with priors does not improve the similarity to the ground truth more than a regular iterative reconstruction with motion correction and without priors. Relative quantification was not influenced much by the chosen reconstruction algorithm. ConclusionsThe relative ranking of the algorithms suggests superiority of the PVC reconstructions with dual gating in terms of overall absolute quantification and noise properties. A well-tuned edge-preserving prior, such as TV, enhances the noise properties of the resulting images of the heart. The end-systolic gate yields the most accurate quantification of cardiac datasets.

The effect of ApoE ε4 on longitudinal brain region-specific glucose metabolism in patients with mild cognitive impairment: a FDG-PET study.

While the ApoE ε4 allele is a known risk factor for mild cognitive impairment (MCI) and Alzheimer's disease, brain region specific effects remain elusive. In this study, we investigate whether the ApoE ε4 allele exhibits brain region specific effects in longitudinal glucose uptake among patients with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed FDG PET images, MRIs, and demographic information were downloaded from the ADNI database. An iterative reblurred Van Cittertiteration method was used for partial volume correction (PVC) on all PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. Longitudinal changes in ROI FDG standardized uptake value ratio (SUVR) relative to cerebellum in 24 ApoE ε4 carriers and 24 age-matched ApoE ε4 non-carriers were measured for up to 84-months (median 72 months, SD = 11.2 months) and compared using a generalized linear mixed effects model controlling for gender, education, baseline age, and follow-up period. Additionally, voxelwise analysis was performed by implementing a paired t-test comparing matched baseline and 72 month FDG SUVR images in ApoE carriers and non-carriers separately. Results with PVC were compared with ones from non-PVC based analysis. After applying PVC, the superior fontal, parietal, lateral temporal, medial temporal, caudate, thalamus, and post-cingulate, and amygdala regions had greater longitudinal decreases in FDG uptake in ApoE ε4 carriers with MCI compared to non-carriers with MCI. Similar forebrain and limbic clusters were found through voxelwise analysis. Compared to the PVC based analysis, fewer significant ApoE-associated regions and clusters were found in the non-PVC based PET analysis. Our findings suggest that the ApoE ε4 genotype is associated with a longitudinal decline in glucose uptake in 8 forebrain and limbic brain regions in the context of MCI. In conclusion, this 84-months longitudinal FDG PET study demonstrates a novel ApoE ε4-associated brain-region specific glucose metabolism pattern in patients with MCI. Partial volume correction improved FDG PET quantification.

Unchanged type 1 metabotropic glutamate receptor availability in patients with Alzheimer's disease: A study using 11C-ITMM positron emission tomography.

Imaging of type 1 metabotropic glutamate receptor (mGluR1) has recently become possible using positron emission tomography (PET). To date, little evidence exists on the role of mGluR1 in the pathophysiology of Alzheimer's disease (AD). We aimed to examine mGluR1 availability in patients with AD. Ten patients with AD (78.9 ± 5.9 years) and 12 age-matched volunteers (74.6 ± 2.6 years) underwent PET using an mGluR1 radiotracer. All patients were anti-dementia drug-naive. Volumes-of-interest were placed on the anterior and posterior lobes and vermis in the cerebellum and frontal, parietal, and temporal cortices. The binding potential (BPND) was calculated to estimate mGluR1 availability, and partial volume correction was applied to the BPND values. Mini Mental State Examination (MMSE) scores were also obtained (22.0 ± 4.8). No significant difference was observed in BPND between the AD and control groups in the anterior lobe (p = .30), posterior lobe (p = .95), vermis (p = .96), frontal cortex (p = .61), parietal cortex (p = .59), or temporal cortex (p = .27). No significant correlation was observed between BPND and MMSE scores in the anterior lobe (p = .59), posterior lobe (p = .35), vermis (p = .92), frontal cortex (p = .78), parietal cortex (p = .83), or temporal cortex (p = .82). In conclusions, this study suggests that mGluR1 availability is unchanged in the relatively early stage of AD. However, because regional mGluR1 availability may change with the progression of AD, further longitudinal follow-up is necessary.

Sex modulates the ApoE ε4 effect on brain tau deposition measured by 18F-AV-1451 PET in individuals with mild cognitive impairment.

The strongest genetic risk factor for Alzheimer's disease (AD) is the Apolipoprotein E type 4 allele (ApoE ε4). The interaction between sex and ApoE ε4 carrier status on AD risk remains an area of intense investigation. We hypothesized that sex modulates the relationship between ApoE ε4 carrier status and brain tau deposition (a quantitative endophenotype in AD) in individuals with mild cognitive impairment (MCI).Methods: Preprocessed 18F-AV-1451 tau and 18F-AV-45 amyloid PET images, T1-weighted structural magnetic resonance imaging (MRI) scans, demographic information, and cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau) measurements from 108 MCI subjects in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. After downloading pre-processed images from ADNI, an iterative reblurred Van Cittertiteration partial volume correction (PVC) method was applied to all PET images. MRIs were used for PET spatial normalization. Regions of interest (ROIs) were defined in standard space, and standardized uptake value ratio (SUVR) images relative to cerebellum were computed. ApoE ε4 by sex interaction analyses on 18F-AV-1451 and CSF tau (t-tau, p-tau) were assessed using generalized linear models. The association between 18F-AV-1451 SUVR and CSF tau (t-tau, p-tau) was assessed.Results: After applying PVC and controlling for age, education level and global cortical 18F-AV-45 SUVR, we found that the entorhinal cortex, amygdala, parahippocampal gyrus, posterior cingulate, and occipital ROIs exhibited a significant ApoE ε4 by sex interaction effect (false discovery rate P < 0.1) among MCI individuals. We also found a significant ApoE ε4 by sex interaction effect on CSF t-tau and p-tau. 18F-AV-1451 SUVR in the 5 ROIs with ApoE ε4 by sex interaction was significantly correlated with CSF p-tau and t-tau.Conclusions: Our findings suggest that women are more susceptible to ApoE ε4-associated accumulation of neurofibrillary tangles in MCI compared to males. Both CSF tau (p-tau, t-tau) and brain tau PET are robust quantitative biomarkers for studying ApoE ε4 by sex effects on brain tau deposition in MCI participants.

An Automated Pipeline for the Analysis of PET Data on the Cortical Surface.

We present a fully automatic pipeline for the analysis of PET data on the cortical surface. Our pipeline combines tools from FreeSurfer and PETPVC, and consists of (i) co-registration of PET and T1-w MRI (T1) images, (ii) intensity normalization, (iii) partial volume correction, (iv) robust projection of the PET signal onto the subject's cortical surface, (v) spatial normalization to a template, and (vi) atlas statistics. We evaluated the performance of the proposed workflow by performing group comparisons and showed that the approach was able to identify the areas of hypometabolism characteristic of different dementia syndromes: Alzheimer's disease (AD) and both the semantic and logopenic variants of primary progressive aphasia. We also showed that these results were comparable to those obtained with a standard volume-based approach. We then performed individual classifications and showed that vertices can be used as features to differentiate cognitively normal and AD subjects. This pipeline is integrated into Clinica, an open-source software platform for neuroscience studies available at www.clinica.run.

Quantification of intramyocardial blood volume with 99mTc-RBC SPECT-CT imaging: A preclinical study

BackgroundCurrently, there is no established non-invasive imaging approach to directly evaluate myocardial microcirculatory function in order to diagnose microvascular disease independent of co-existing epicardial disease. In this work, we developed a methodological framework for quantification of intramyocardial blood volume (IMBV) as a novel index of microcirculatory function with SPECT/CT imaging of 99mTc-labeled red blood cells (RBCs). MethodsDual-gated myocardial SPECT/CT equilibrium imaging of 99mTc-RBCs was performed on twelve canines under resting conditions. Five correction schemes were studied: cardiac gating with no other corrections (CG), CG with attenuation correction (CG + AC), CG + AC with scatter correction (CG + AC + SC), dual cardiorespiratory gating with AC + SC (DG + AC + SC), and DG + AC + SC with partial volume correction (DG + AC + SC + PVC). Quantification of IMBV using each approach was evaluated in comparison to those obtained from all corrections. The in vivo SPECT estimates of IMBV values were validated against those obtained from ex vivo microCT imaging of the casted hearts. ResultsThe estimated IMBV with all corrections was 0.15 ± 0.03 for the end-diastolic phase and 0.11 ± 0.03 for the end-systolic phase. The cycle-dependent change in IMBV (ΔIMBV) with all corrections was 23.9 ± 8.6%. Schemes that applied no correction or partial correction resulted in significant over-estimation of IMBV and significant under-underestimation of ΔIMBV. Estimates of IMBV and ΔIMBV using all corrections were consistent with values reported in the literature using invasive techniques. In vivo SPECT estimates of IMBV strongly correlated (R2 ≥ 0.70) with ex vivo measures for the various correction schemes, while the fully corrected scheme yielded the smallest bias. ConclusionsNon-invasive quantification of IMBV is feasible using 99mTc-RBCs SPECT/CT imaging, however, requires full compensation of physical degradation factors.

Enhancement of Partial Volume Correction in MR-Guided PET Image Reconstruction by Using MRI Voxel Sizes.

Positron emission tomography (PET) suffers from poor spatial resolution which results in quantitative bias when evaluating the radiotracer uptake in small anatomical regions, such as the striatum in the brain which is of importance in this paper of neurodegenerative diseases. These partial volume effects need to be compensated for by employing partial volume correction (PVC) methods in order to achieve quantitatively accurate images. Two important PVC methods applied during the reconstruction are resolution modeling, which suffers from Gibbs artifacts, and penalized likelihood using anatomical priors. The introduction of clinical simultaneous PET-MR scanners has attracted new attention for the latter methods and brought new opportunities to use MRI information to assist PET image reconstruction in order to improve image quality. In this context, MR images are usually down-sampled to the PET resolution before being used in MR-guided PET reconstruction. However, the reconstruction of PET images using the MRI voxel size could achieve a better utilization of the high resolution anatomical information and improve the PVC obtained with these methods. In this paper, we evaluate the importance of the use of MRI voxel sizes when reconstructing PET images with MR-guided maximum a posteriori (MAP) methods, specifically the modified Bowsher method. We also propose a method to avoid the artifacts that arise when PET reconstructions are performed in a higher resolution matrix than the standard for a given scanner. The MR-guided MAP reconstructions were implemented with a modified Lange prior that included anatomical information with the Bowsher method. The methods were evaluated with and without resolution modeling for simulated and real brain data. We show that the use of the MRI voxel sizes when reconstructing PET images with MR-guided MAP enhances PVC by improving the contrast and reducing the bias in six different regions of the brain using regional metrics for a single simulated data set and ensemble metrics for ten noise realizations. Similar results were obtained for real data, where a good enhancement of the contrast was achieved. The combination of MR-guided MAP reconstruction with point-spread function modeling and MRI voxel sizes proved to be an attractive method to achieve considerable enhancement of PVC, while reducing and controlling the noise level and Gibbs artifacts.

APPIAN: Automated Pipeline for PET Image Analysis.

APPIAN is an automated pipeline for user-friendly and reproducible analysis of positron emission tomography (PET) images with the aim of automating all processing steps up to the statistical analysis of measures derived from the final output images. The three primary processing steps are coregistration of PET images to T1-weighted magnetic resonance (MR) images, partial-volume correction (PVC), and quantification with tracer kinetic modeling. While there are alternate open-source PET pipelines, none offers all of the features necessary for making automated PET analysis as reliably, flexibly and easily extendible as possible. To this end, a novel method for automated quality control (QC) has been designed to facilitate reliable, reproducible research by helping users verify that each processing stage has been performed as expected. Additionally, a web browser-based GUI has been implemented to allow both the 3D visualization of the output images, as well as plots describing the quantitative results of the analyses performed by the pipeline. APPIAN also uses flexible region of interest (ROI) definition—with both volumetric and, optionally, surface-based ROI—to allow users to analyze data from a wide variety of experimental paradigms, e.g., longitudinal lesion studies, large cross-sectional population studies, multi-factorial experimental designs, etc. Finally, APPIAN is designed to be modular so that users can easily test new algorithms for PVC or quantification or add entirely new analyses to the basic pipeline. We validate the accuracy of APPIAN against the Monte-Carlo simulated SORTEO database and show that, after PVC, APPIAN recovers radiotracer concentrations within 93–100% accuracy.

Image-based assessment of uncertainty in quantification of carotid lumen.

Measurements of the vessel lumen diameter are often used to determine the degree of atherosclerotic disease in carotid arteries. However, quantification results vary with imaging technique and acquisition settings. We aim at providing a tool that quantifies the lumen diameter on different image datasets and gives an estimate of quantification uncertainties, so that they can be taken into consideration when evaluating and comparing measurements. For the segmentation of the vessel lumen, we present an algorithm using ray-casting techniques and partial volume correction. We furthermore propose a scheme for the analysis and exploration of the lumen diameter. Finally, we present a clinically relevant application scenario, in which we explore agreement between lumen diameter estimations in corresponding computed tomography angiography, contrast-enhanced magnetic resonance angiography, time-of-flight, and subtraction images of carotid vessels with severe carotid atherosclerotic plaques.

PET imaging reveals lower kappa opioid receptor availability in alcoholics but no effect of age

Opioid receptors are implicated in alcoholism, other addictions, withdrawal, and depression, and are considered potential pharmacological targets for treatment. Our goal in the present study was to compare the availability of kappa opioid receptors (KOR) between an alcohol-dependent cohort (AD) and a healthy control cohort (HC). Sixty-four participants—36 AD and 28 HC—underwent PET scans with [11C]LY2795050, a selective kappa antagonist tracer. Partial-volume correction was applied to all PET data to correct for atrophy. Volume of distribution (VT) of the tracer was estimated regionally as a measure of KOR availability. VT values of AD versus HC were compared for 15 defined ROIs. Multivariate analysis showed a main effect of group on VT across these 15 ROIs. Post hoc tests showed that AD had significantly lower VT and thus a lower KOR availability than HC in amygdala and pallidum (corrected for multiple comparisons). Exploratory analysis of change in VT with age was conducted; VT was not found to vary significantly with age in any region. Our findings of lower VT in AD versus HC in multiple regions are in contrast to findings in the mu and delta opioid receptor systems of higher VT in AD versus HC. Although age-related decline in receptors has previously been observed in the mu opioid receptor system, we found that KOR availability does not change with age.

Reproducible evaluation of classification methods in Alzheimer's disease: Framework and application to MRI and PET data

A large number of papers have introduced novel machine learning and feature extraction methods for automatic classification of Alzheimer's disease (AD). However, while the vast majority of these works use the public dataset ADNI for evaluation, they are difficult to reproduce because different key components of the validation are often not readily available. These components include selected participants and input data, image preprocessing and cross-validation procedures. The performance of the different approaches is also difficult to compare objectively. In particular, it is often difficult to assess which part of the method (e.g. preprocessing, feature extraction or classification algorithms) provides a real improvement, if any. In the present paper, we propose a framework for reproducible and objective classification experiments in AD using three publicly available datasets (ADNI, AIBL and OASIS). The framework comprises: i) automatic conversion of the three datasets into a standard format (BIDS); ii) a modular set of preprocessing pipelines, feature extraction and classification methods, together with an evaluation framework, that provide a baseline for benchmarking the different components. We demonstrate the use of the framework for a large-scale evaluation on 1960 participants using T1 MRI and FDG PET data. In this evaluation, we assess the influence of different modalities, preprocessing, feature types (regional or voxel-based features), classifiers, training set sizes and datasets. Performances were in line with the state-of-the-art. FDG PET outperformed T1 MRI for all classification tasks. No difference in performance was found for the use of different atlases, image smoothing, partial volume correction of FDG PET images, or feature type. Linear SVM and L2-logistic regression resulted in similar performance and both outperformed random forests. The classification performance increased along with the number of subjects used for training. Classifiers trained on ADNI generalized well to AIBL and OASIS. All the code of the framework and the experiments is publicly available: general-purpose tools have been integrated into the Clinica software (www.clinica.run) and the paper-specific code is available at: https://gitlab.icm-institute.org/aramislab/AD-ML.

Post-reconstruction-based partial volume correction methods: A comprehensive review

Abstract The vital role of positron emission tomography (PET) image is to provide an accurate quantitative information. Nevertheless, the partial volume effect (PVE) can easily alter the quantification. This effect is a consequence of the limited spatial resolution in PET which is due to the non-collinear and/or inherently random photon. For several years, great effort has been devoted to study the partial volume correction (PVC) and improve the quality of the image. At first stage, only PET modality was used and then, further study of the issue involved anatomic information from high resolution modalities in the correction process. Clearly, this regularization using segmentation, correlation and the registration step between the two modalities enhanced the performance of these techniques. These methods can be, mostly, divided into two main approaches: reconstruction-based methods and a post-reconstruction-based methods. In this paper the focus of attention was to present the most used post-reconstruction PVC methods developed in the literature. We will introduce the principal of each method, its extension and their applications in different domains.

Reproducible quantification of cardiac sympathetic innervation using graphical modeling of carbon-11-meta-hydroxyephedrine kinetics with dynamic PET-CT imaging

BackgroundGraphical methods of radiotracer kinetic modeling in PET are ideal for parametric imaging and data quality assurance but can suffer from noise bias. This study compared the Logan and Multilinear Analysis-1 (MA1) graphical models to the standard one-tissue-compartment (1TC) model, including correction for partial-volume effects, in dynamic PET-CT studies of myocardial sympathetic innervation in the left ventricle (LV) using [11C]HED.MethodsTest and retest [11C]HED PET imaging (47 ± 22 days apart) was performed in 18 subjects with heart failure symptoms. Myocardial tissue volume of distribution (VT) was estimated using Logan and MA1 graphical methods and compared to the 1TC standard model values using intraclass correlation (ICC) and Bland-Altman analysis of the non-parametric reproducibility coefficient (NPC).ResultsA modeling start-time of t* = 5 min gave the best fit for both Logan and MA1 (R2 = 0.95) methods. Logan slightly underestimated VT relative to 1TC (p = 0.002), whereas MA1 did not (p = 0.96). Both the MA1 and Logan models exhibited good-to-excellent agreement with the 1TC (MA1-1TC ICC = 0.96; Logan-1TC ICC = 0.93) with no significant differences in NPC between the two comparisons (p = 0.92). All methods exhibited good-to-excellent test-retest repeatability with no significant differences in NPC (p = 0.57).ConclusionsLogan and MA1 models exhibited similar agreement and variability compared to the 1TC for modeling of [11C]HED kinetics. Using t* = 5 min and partial-volume correction produced accurate estimates of VT as an index of myocardial sympathetic innervation.

Dissociation of Tau Deposits and Brain Atrophy in Early Alzheimer’s Disease: A Combined Positron Emission Tomography/Magnetic Resonance Imaging Study

The recent advent of tau-specific positron emission tomography (PET) has enabled in vivo assessment of tau pathology in Alzheimer’s disease (AD). However, because PET scanners have limited spatial resolution, the measured signals of small brain structures or atrophied areas are underestimated by partial volume effects (PVEs). The aim of this study was to determine whether partial volume correction (PVC) improves the precision of measures of tau deposits in early AD. We investigated tau deposits in 18 patients with amyloid-positive early AD and in 36 amyloid-negative healthy controls using 18F-THK5351 PET. For PVC, we applied the SPM toolbox PETPVE12. The PET images were then spatially normalized and subjected to voxel-based group analysis using SPM12 for comparison between the early AD patients and healthy controls. We also compared these two groups in terms of brain atrophy using voxel-based morphometry of MRI. We found widespread neocortical tracer retention predominantly in the posterior cingulate and precuneus areas, but also in the inferior temporal lobes, inferior parietal lobes, frontal lobes, and occipital lobes in the AD patients compared with the controls. The pattern of tracer retention was similar between before and after PVC, suggesting that PVC had little effect on the precision of tau load measures. Gray matter atrophy was detected in the medial/lateral temporal lobes and basal frontal lobes in the AD patients. Interestingly, only a few associations were found between atrophy and tau deposits, even after PVC. In conclusion, PVC did not significantly affect 18F-THK5351 PET measures of tau deposits. This discrepancy between tau deposits and atrophy suggests that tau load precedes atrophy.