Partial Volume Effect Correction Research Articles

StepBrain: A 3-Dimensionally Printed Multicompartmental Anthropomorphic Brain Phantom to Simulate PET Activity Distributions.

An innovative multicompartmental anatomic brain phantom (StepBrain) is described to simulate the invivo tracer uptake of gray matter, white matter, and striatum, overcoming the limitations of currently available phantoms. Methods: StepBrain was created by exploiting the potential of fused deposition modeling 3-dimensional printing to replicate the real anatomy of the brain compartments, as modeled through ad hoc processing of healthy-volunteer MR images. Results: A realistic simulation of 18F-FDG PET brain studies, using target activity to obtain the real concentration ratios, was obtained, and the results of postprocessing with partial-volume effect correction tools developed for human PET studies confirmed the accuracy of these methods in recovering the target activity concentrations. Conclusion: StepBrain compartments (gray matter, white matter, and striatum) can be simultaneously filled, achieving different concentration ratios and allowing the simulation of different (e.g., amyloid, tau, or 6-fluoro-l-dopa) tracer distributions, with a potentially valuable role for multicenter PET harmonization studies.

Cerebral glucose metabolic correlates of cognitive and behavioural impairments in amyotrophic lateral sclerosis

ObjectiveHalf of ALS patients are cognitively and/or behaviourally impaired. As cognition/behaviour and cerebral glucose metabolism can be correlated by means of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET), we aimed to utilise FDG-PET, first, to replicate group-level differences in glucose metabolism between non-demented ALS patients separated into non-impaired (ALSni), cognitively impaired (ALSci), behaviourally impaired (ALSbi), and cognitively and behaviourally impaired (ALScbi) groups; second, to investigate glucose metabolism and performance in various cognitive domains; and third, to examine the impact of partial volume effects correction (PVEC) of the FDG-PET data on the results.MethodsWe analysed neuropsychological, clinical, and imaging data from 67 ALS patients (30 ALSni, 21 ALSci, 5 ALSbi, and 11 ALScbi). Cognition was assessed with the Edinburgh Cognitive and Behavioural ALS Screen, and two social cognition tests. FDG-PET and structural MRI scans were acquired for each patient. Voxel-based statistical analyses were undertaken on grey matter volume (GMV) and non-corrected vs. PVE-corrected FDG-PET scans.ResultsALSci and ALScbi had lower cognitive scores than ALSni. In contrast to both ALSni and ALSci, ALScbi showed widespread hypometabolism in the superior- and middle-frontal gyri in addition to the right temporal pole. Correlations were observed between the GMV, the FDG-PET signal, and various cognitive scores. The FDG-PET results were largely unaffected by PVEC.InterpretationOur study identified widespread differences in hypometabolism in the ALScbi-ni but not in the ALSci-ni group comparison, raising the possibility that cerebral metabolism may be more closely related to the presence of behavioural changes than to mild cognitive deficits.

Anatomy-based correction of kidney PVE on 177Lu\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{177}\ ext{Lu}$$\\end{document} SPECT images

BackgroundIn peptide receptor radionuclide therapy (PRRT), accurate quantification of kidney activity on post-treatment SPECT images paves the way for patient-specific treatment. Due to the limited spatial resolution of SPECT images, the partial volume effect (PVE) is a significant source of quantitative bias. In this study, we aimed to evaluate the performance and robustness of anatomy-based partial volume correction (PVC) algorithms to recover the accurate activity concentration of realistic kidney geometries on 177\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{177}$$\\end{document}Lu SPECT images recorded under clinical conditions.MethodsBased on the CT scan data from patients, three sets of fillable kidneys with surface-to-volume (S:V) ratios ranging from 1.5 to 2.8 cm−1, were 3D printed and attached in a IEC phantom. Quantitative 177\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{177}$$\\end{document}Lu SPECT/CT acquisitions were performed on a GE Discovery NM CT 870 DR camera for the three modified IEC phantoms and for 6 different Target-To-Background ratios (TBRs: 2, 4, 6, 8, 10, 12). Two region-based (GTM and Labbé) and five voxel-based (GTM + MTC, Labbé + MTC, GTM + RBV, Labbé + RBV and IY) methods were evaluated with this data set. Additionally, the robustness of PVC methods to Point Spread Function (PSF) discrepancies, registration mismatches and background heterogeneity was evaluated.ResultsWithout PVC, the average kidney RCs across all TBRs ranged from 0.66 ± 0.05 (smallest kidney) to 0.80 ± 0.03 (largest kidney). For a TBR of 12, all anatomy-based method were able to recover the kidneys activity concentration with an error < 6%. All methods result in a comparable decline in RC restoration with decreasing TBR. The Labbé method was the most robust against PSF and registration mismatches but was also the most sensitive to background heterogeneity. Among the voxel-based methods, MTC images were less uniform than RBV and IY images at the outer edge of high uptake areas (kidneys and spheres).ConclusionAnatomy-based PVE correction allows for accurate SPECT quantification of the 177\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{177}$$\\end{document}Lu activity concentration with realistic kidney geometries. Combined with recent progress in deep-learning algorithms for automatic anatomic segmentation of whole-body CT, these methods could be of particular interest for a fully automated OAR dosimetry pipeline with PVE correction.

Quantification performance of silicon photomultiplier-based PET for small 18F-, 68Ga- and 124I-avid lesions in the context of radionuclide therapy planning

PurposeThe aim of this study was to investigate conditions for reliable quantification of sub-centimeter lesions with low18F,68Ga, and124I uptake using a silicon photomultiplier-based PET/CT system. MethodsA small tumor phantom was investigated under challenging but clinically realistic conditions resembling prostate and thyroid cancer lymph node metastases (6 spheres with 3.7–9.7 mm in diameter, 9 different activity concentrations ranging from about 0.25–25 kBq/mL, and a signal-to-background ratio of 20). Radionuclides with different positron branching ratios and prompt gamma coincidence contributions were investigated. Maximum-, contour-, and oversize-based partial volume effect (PVE) correction approaches were applied. Detection and quantification performance were estimated, considering a ±30 % deviation between imaged-derived and true activity concentrations as acceptable. A standard and a prolonged acquisition time and two image reconstruction algorithms (time-of-flight with/without point spread function modelling) were analyzed. Clinical data were evaluated to assess agreement of PVE-correction approaches indicating lesion quantification validity. ResultsThe smallest 3.7-mm sphere was not visible. If the lesions were clearly observed, quantification was, except for a few cases, acceptable using contour- or oversized-based PVE-corrections. Quantification accuracy did not substantially differ between 18F, 68Ga, and 124I. No systematic differences between the analyzed reconstruction algorithms or shorter and larger acquisition times were observed. In the clinical evaluation of 20 lesions, an excellent statistical agreement between oversize- and contour-based PVE-corrections was observed. ConclusionsAt the lower end of size (<10 mm) and activity concentration ranges of lymph-node metastases, quantification with reasonable accuracy is possible for 18F, 68Ga, and 124I, possibly allowing pre-therapeutic lesion dosimetry and individualized radionuclide therapy planning.

Partial Volume Effect (PVE) Correction in Single Photon Emission Computed Tomography (SPECT) Imaging

Partial Volume Effect (PVE) Correction in Single Photon Emission Computed Tomography (SPECT) Imaging

A PET-CT study on neuroinflammation in Huntington's disease patients participating in a randomized trial with laquinimod.

Microglia activation, an indicator of central nervous system inflammation, is believed to contribute to the pathology of Huntington's disease. Laquinimod is capable of regulating microglia. By targeting the translocator protein, 11C-PBR28 PET-CT imaging can be used to assess the state of regional gliosis in vivo and explore the effects of laquinimod treatment. This study relates to the LEGATO-HD, multi-centre, double-blinded, Phase 2 clinical trial with laquinimod (US National Registration: NCT02215616). Fifteen patients of the UK LEGATO-HD cohort (mean age: 45.2 ± 7.4 years; disease duration: 5.6 ± 3.0 years) were treated with laquinimod (0.5 mg, N = 4; 1.0 mg, N = 6) or placebo (N = 5) daily. All participants had one 11C-PBR28 PET-CT and one brain MRI scan before laquinimod (or placebo) and at the end of treatment (12 months apart). PET imaging data were quantified to produce 11C-PBR28 distribution volume ratios. These ratios were calculated for the caudate and putamen using the reference Logan plot with the corpus callosum as the reference region. Partial volume effect corrections (Müller-Gartner algorithm) were applied. Differences were sought in Unified Huntington's Disease Rating Scale scores and regional distribution volume ratios between baseline and follow-up and between the two treatment groups (laquinimod versus placebo). No significant change in 11C-PBR28 distribution volume ratios was found post treatment in the caudate and putamen for both those treated with laquinimod (N = 10) and those treated with placebo (N = 5). Over time, the patients treated with laquinimod did not show a significant clinical improvement. Data from the 11C-PBR28 PET-CT study indicate that laquinimod may not have affected regional translocator protein expression and clinical performance over the studied period.

SPECT/CT-based dosimetry of salivary glands and iodine-avid lesions following 131I therapy

The purpose was to provideuptake and radiation dose estimates to salivary glands (SG) and pathologic lesions following radioiodine therapy (RIT)of differentiated thyroid cancer patients (DTC). A group of DTCpatients (n = 25) undergoing 131I therapy joined this study with varying amounts of therapeuticactivity. SequentialSPECT/CT scanswere acquiredat 4 ± 2, 24 ± 2, and 168 ± 3h following administration of 3497-9250MBq131I. An earlier experiment withAcrylic glass body phantom (PET Phantom NEMA 2012 / IEC 2008) was conducted for system calibration includingscatter, partial volume effect and count loss correction.Dose calculation was made via IDAC-Dose 2.1 code. The absorbed dose to parotid glands was 0.04-0.97Gy/GBq (median: 0.26Gy/GBq). The median absorbed dose to submandibular glands was 0.14Gy/GBq (0.05 to 0.56Gy/GBq). The absorbed dose to thyroid residues was from 0.55 to 399.5Gy/GBq (median: 21.8Gy/GBq), and that to distal lesions ranged from 0.78 to 28.0Gy/GBq (median: 3.12Gy/GBq). 41% of the thyroid residues received dose > 80Gy, 18% between 70-80Gy, 18% between 40-70Gy, and 23% has dose < 40Gy. In contrast, 18% of the metastases exhibited a dose > 80Gy, 9% between 40-60Gy, and the dose to the vast majority of lesions (64%) was < 40Gy. It was inferred that dose estimation after RIT with SPECT/CT is feasible to apply, together with good agreement with published 124I PET/CT dose estimates. A broad and sub-effective dose range was estimated for thyroid residues and distal lesions. Moreover, the current methodology might be useful for establishing a dose-effect relationship and radiation-induced salivary glands damage after RIT.

Quantification and dosimetry of small volumes including associated uncertainty estimation

BackgroundAccurate quantification of radioactivity in a source of interest relies on accurate registration between SPECT and anatomical images, and appropriate correction of partial volume effects (PVEs). For small volumes, exact registration between the two imaging modalities and recovery factors used to correct for PVE are unreliable. There is currently no guidance relating to quantification or the associated uncertainty estimation for small volumes.Material and methodsA method for quantification of small sources of interest is proposed, which uses multiple oversized volumes of interest. The method was applied to three Na[131I]I activity distributions where a Na[131I]I capsule was situated within a cylindrical phantom containing either zero background, uniform background or non-uniform background and to a scenario with small lesions placed in an anthropomorphic phantom. The Na[131I]I capsule and lesions were quantified using the proposed method and compared with measurements made using two alternative quantification methods. The proposed method was also applied to assess the absorbed dose delivered to a bone metastasis following [131I]mIBG therapy for neuroblastoma including the associated uncertainty estimation.ResultsThe method is accurate across a range of activities and in varied radioactivity distributions. Median percentage errors using the proposed method in no background, uniform backgrounds and non-uniform backgrounds were − 0.4%, − 0.3% and 1.7% with median associated uncertainties of 1.4%, 1.4% and 1.6%, respectively. The technique is more accurate and robust when compared to currently available alternative methods.ConclusionsThe proposed method provides a reliable and accurate method for quantification of sources of interest, which are less than three times the spatial resolution of the imaging system. The method may be of use in absorbed dose calculation in cases of bone metastasis, lung metastasis or thyroid remnants.

Decreased 5-HT1A binding in mild Alzheimer's disease-A positron emission tomography study.

Decreased 5‐HT1A receptor binding has been associated with Alzheimer's disease (AD) and interpreted as a consequence of neuron loss. The purpose of the present study was to compare [11C]WAY100635 binding to the 5‐HT1A receptor in the hippocampus, entorhinal cortex, amygdala and pericalcarine cortex in mild AD patients and elderly controls. AD patients (n = 7) and elderly control subjects (n = 8) were examined with positron emission tomography (PET) and [11C]WAY100635. PET data acquisition was performed with an ECAT EXACT HR system. Wavelet‐aided parametric images of nondisplaceable binding potential (BP ND) were generated using Logan's graphical analysis with cerebellum as the reference region. Correction for partial volume effects was performed with the Müller–Gärtner method. Regions of interest (ROIs) were applied to the individual parametric images, and the regional BP ND was calculated as the average parametric voxel value within each ROI. In addition to comparisons between subject groups, correlations between BP ND values and scores on the Mini‐Mental State Examination, Disability Assessment for Dementia (DAD), and Neuropsychiatric Inventory were expressed by Pearson correlation coefficients. Mean regional BP ND was lower in AD patients than in control subjects, and the difference was statistically significant for the hippocampus, entorhinal cortex, and amygdala. A statistically significant correlation was obtained between hippocampal BP ND values and DAD scores. The results of the present study corroborate and extend previous findings of decreased 5‐HT1A binding in AD and strengthen the support for 5‐HT1A receptor PET as a tool for the assessment of neurodegenerative changes in mild AD.

Prognostic significance of conventional and volumetric PET parameters with and without partial volume correction in the assessment of head and neck squamous cell carcinoma.

The optimal quantification of PET in assessment of head and neck squamous cell carcinoma (HNSCC) is still under development. The effect of partial volume correction (PVC) on the evaluation of survival in the HNSCC patients has not been investigated yet. Pretreatment 18F-FDG-PET/CT scans of a selected group of 57 patients with advanced stage HNSCC were collected. Conventional (SUVmean and SUVmax) and volumetric [total lesion glycolysis (TLG) and metabolic tumor volume (MTV)] PET metrics were calculated. The ROVER software (ABX GmbH, Radeberg, Germany) automatically applied PVC to the PET metrics. Cox proportional hazards regression model calculated hazard ratio (HR) for assessment of predictive parameters of progression-free survival (PFS). In multivariate Cox regression analysis, including age, gender, race, human papillomavirus status, and stage, the only significant predictors of PFS were the volumetric PET parameters (TLG: HR, 1.003; 95% CI, 1.001-1.005; P = 0.02), pvcTLG (HR, 1.002; 95% CI, 1.001-1.004; P = 0.01) and MTV (HR, 1.050; 95% CI, 1.024-1.077; P < 0.01). The partial volume-corrected values were significantly higher than the noncorrected values (Wilcoxon sign test; P < 0.05). However, there was not a statistically significant difference between the nonpartial volume corrected and partial volume-corrected PET metrics for assessment of PFS. Volumetric PET metrics were predictors of PFS in Cox regression analysis. Applying PVC could not significantly improve the accuracy of PET metrics for assessment of PFS.

Phantom Validation of a Conservation of Activity-Based Partial Volume Correction Method for Arterial Input Function in Dynamic PET Imaging

Dynamic PET (dPET) imaging can be utilized to perform kinetic modelling of various physiologic processes, which are exploited by the constantly expanding range of targeted radiopharmaceuticals. To date, dPET remains primarily in the research realm due to a number of technical challenges, not least of which is addressing partial volume effects (PVE) in the input function. We propose a series of equations for the correction of PVE in the input function and present the results of a validation study, based on a purpose built phantom. 18F-dPET experiments were performed using the phantom on a set of flow tubes representing large arteries, such as the aorta (1” 2.54 cm ID), down to smaller vessels, such as the iliac arteries and veins (1/4” 0.635 cm ID). When applied to the dPET experimental images, the PVE correction equations were able to successfully correct the image-derived input functions by as much as 59 ± 35% in the presence of background, which resulted in image-derived area under the curve (AUC) values within 8 ± 9% of ground truth AUC. The peak heights were similarly well corrected to within 9 ± 10% of the scaled DCE-CT curves. The same equations were then successfully applied to correct patient input functions in the aorta and internal iliac artery/vein. These straightforward algorithms can be applied to dPET images from any PET-CT scanner to restore the input function back to a more clinically representative value, without the need for high-end Time of Flight systems or Point Spread Function correction algorithms.

Impact of Partial Volume Correction on [18F]GE-180 PET Quantification in Subcortical Brain Regions of Patients with Corticobasal Syndrome.

Corticobasal syndrome (CBS) is a rare neurodegenerative condition characterized by four-repeat tau aggregation in the cortical and subcortical brain regions and accompanied by severe atrophy. The aim of this study was to evaluate partial volume effect correction (PVEC) in patients with CBS compared to a control cohort imaged with the 18-kDa translocator protein (TSPO) positron emission tomography (PET) tracer [18F]GE-180. Eighteen patients with CBS and 12 age- and sex-matched healthy controls underwent [18F]GE-180 PET. The cortical and subcortical regions were delineated by deep nuclei parcellation (DNP) of a 3D-T1 MRI. Region-specific subcortical volumes and standardized uptake values and ratios (SUV and SUVr) were extracted before and after region-based voxel-wise PVEC. Regional volumes were compared between patients with CBS and controls. The % group differences and effect sizes (CBS vs. controls) of uncorrected and PVE-corrected SUVr data were compared. Single-region positivity in patients with CBS was assessed by a >2 SD threshold vs. controls and compared between uncorrected and PVE-corrected data. Smaller regional volumes were detected in patients with CBS compared to controls in the right ventral striatum (p = 0.041), the left putamen (p = 0.005), the right putamen (p = 0.038) and the left pallidum (p = 0.015). After applying PVEC, the % group differences were distinctly higher, but the effect sizes of TSPO uptake were only slightly stronger due to the higher variance after PVEC. The single-region positivity of TSPO PET increased in patients with CBS after PVEC (100 vs. 83 regions). PVEC in the cortical and subcortical regions is valuable for TSPO imaging of patients with CBS, leading to the improved detection of elevated [18F]GE-180 uptake, although the effect sizes in the comparison against the controls did not improve strongly.

Development of a new quantification method using partial volume effect correction for individual energy peaks in 111In-pentetreotide SPECT/CT

Objective(s):Somatostatin receptor scintigraphy (SRS) using 111In-pentetreotide has no established quantification method. The purpose of this study was to develop a new quantitative method to correct the partial volume effect (PVE) for individual energy peaks in 111In-pentetreotide single-photon emission computed tomography (SPECT).Methods:Phantom experiments were performed to construct a new quantitative method. In the phantom experiments, a NEMA IEC body phantom was used. Acquisition was performed using two energy peaks (171 keV and 245 keV) on the SPECT/CT system. The volume of interest was set at each hot sphere and lung insert in the SPECT images of each energy peak, and the recovery coefficient (RC) was calculated to understand the PVE. A new quantitative index, the indium uptake index (IUI), was calculated using the RC to correct the PVE. The quantitative accuracy of the IUI in the hot sphere was confirmed. Case studies were performed to clarify the quantitative accuracy. In a case study, the relationship between the IUI and the Krenning score, which is used as a visual assessment, was evaluated for each lesion.Results:The obtained RCs showed that the energy peak at 171 keV was faster in recovering the effect of PVE than that at 245 keV. The IUI in the 17-mm-diameter hot sphere was overestimated by 4.8% and 8.3% at 171 keV and 245 keV, respectively, compared to the actual IUIs. The relationship between IUI and Krenning score was rs=0.773 (p<0.005) at sum, rs=0.739 (p<0.005) at 171 keV, and rs=0.773 (p<0.005) at 245 keV.Conclusion: We have developed a new quantification method for 111In-pentetreotide SPECT/CT using RC-based PVE correction for an individual energy peak of 171 keV. The quantitative accuracy of this method was high even for accumulations of less than 20 mm, and it showed a good relationship with the Krenning score; therefore, the clinical usefulness of IUI was demonstrated.

脳&lt;sup&gt;18&lt;/sup&gt;F-FDG PETにおけるCT画像を用いた部分容積効果補正の検討

We performed partial volume effect correction of PET images using 18F-FDG-PET and CT images taken consecutively, compared it with correction using MRI images, and investigated the usefulness of correction using CT images. A total of 9 clinically normal subjects were included in the study, and the CT and MRI images of each subject were segmented and normalized. PET images were coregistered to each morphological image and then normalized. The normalized morphological images of each subject were used to mask the brain atlas and to correct for the partial volume effect. For each brain region, comparison of counts, two-group test between CT- and MRI-corrected groups, and correlation analysis were performed. As a result of correction, some error was observed between the two groups. Correlation analysis showed strong positive correlations in many areas, but weak correlations were found in some areas. In the region where significant differences were found, the two groups showed strong positive correlation, and in the region where weak correlation was found, the error tended to be small. It is suggested that the correction by CT can be performed with the same accuracy, although some errors are generated compared with MRI.

Association of entorhinal cortical tau deposition and hippocampal synaptic density in older individuals with normal cognition and early Alzheimer's disease

Sites of early neuropathologic change provide important clues regarding the initial clinical features of Alzheimer's disease (AD). We have shown significant reductions in hippocampal synaptic density in participants with AD, consistent with the early degeneration of entorhinal cortical (ERC) cells that project to hippocampus via the perforant path. In this study, [11C]UCB-J binding to synaptic vesicle glycoprotein 2A (SV2A) and [18F]flortaucipir binding to tau were measured via PET in 10 participants with AD (5 mild cognitive impairment, 5 mild dementia) and 10 cognitively normal participants. In the overall sample, ERC tau was inversely associated with hippocampal synaptic density (r = -0.59, p = 0.009). After correction for partial volume effects, the association of ERC tau with hippocampal synaptic density was stronger in the overall sample (r = -0.61, p = 0.007) and in the AD group where the effect size was large, but not statistically significant (r = -0.58, p = 0.06). This inverse association of ERC tau and hippocampal synaptic density may reflect synaptic failure due to tau pathology in ERC neurons projecting to the hippocampus.

Correction for the Partial Volume Effects (PVE) in Nuclear Medicine Imaging: A Post-Reconstruction Analytic Method

Quantitative analyses in nuclear medicine are increasingly used, both for diagnostic and therapeutic purposes. The Partial Volume Effect (PVE) is the most important factor of loss of quantification in Nuclear Medicine, especially for evaluation in Region of Interest (ROI) smaller than the Full Width at Half Maximum (FWHM) of the PSF. The aim of this work is to present a new approach for the correction of PVE, using a post-reconstruction process starting from a mathematical expression, which only requires the knowledge of the FWHM of the final PSF of the imaging system used. After the presentation of the theoretical derivation, the experimental evaluation of this method is performed using a PET/CT hybrid system and acquiring the IEC NEMA phantom with six spherical “hot” ROIs (with diameters of 10, 13, 17, 22, 28, and 37 mm) and a homogeneous “colder” background. In order to evaluate the recovery of quantitative data, the effect of statistical noise (different acquisition times), tomographic reconstruction algorithm with and without time-of-flight (TOF) and different signal-to-background activity concentration ratio (3:1 and 10:1) was studied. The application of the corrective method allows recovering the loss of quantification due to PVE for all sizes of spheres acquired, with a final accuracy less than 17%, for lesion dimensions larger than two FWHM and for acquisition times equal to or greater than two minutes.

Hybrid 2-[18F] FDG PET/MRI in premanifest Huntington's disease gene-expansion carriers: The significance of partial volume correction.

BackgroundHuntington’s disease (HD) is an inherited, progressive neurodegenerative disease that has no cure. Striatal atrophy and hypometabolism has been described in HD as far as 15 years before clinical onset and therefore structural and functional imaging biomarkers are the most applied biomarker modalities which call for these to be exact; however, most studies are not considering the partial volume effect and thereby tend to overestimate metabolic reductions, which may bias imaging outcome measures of interventions.ObjectiveEvaluation of partial volume effects in a cohort of premanifest HD gene-expansion carriers (HDGECs).Methods21 HDGECs and 17 controls had a hybrid 2-[18F]FDG PET/MRI scan performed. Volume measurements and striatal metabolism, both corrected and uncorrected for partial volume effect were correlated to an estimate of disease burden, the CAG age product scaled (CAPS).ResultsWe found significantly reduced striatal metabolism in HDGECs, but not in striatal volume. There was a negative correlation between the CAPS and striatal metabolism, both corrected and uncorrected for the partial volume effect. The partial volume effect was largest in the smallest structures and increased the difference in metabolism between the HDGEC with high and low CAPS scores. Statistical parametric mapping confirmed the results.ConclusionsA hybrid 2-[18F]FDG PET/MRI scan provides simultaneous information on structure and metabolism. Using this approach for the first time on HDGECs, we highlight the importance of partial volume effect correction in order not to underestimate the standardized uptake value and thereby the risk of overestimating the metabolic effect on the striatal structures, which potentially could bias studies determining imaging outcome measures of interventions in HDGECs and probably also symptomatic HD.

Phantom and clinical assessment of small pulmonary nodules using Q.Clear reconstruction on a silicon-photomultiplier-based time-of-flight PET/CT system

To evaluate the quantification accuracy of different positron emission tomography-computed tomography (PET/CT) reconstruction algorithms, we measured the recovery coefficient (RC) and contrast recovery (CR) in phantom studies. The results played a guiding role in the partial-volume-effect correction (PVC) for following clinical evaluations. The PET images were reconstructed with four different methods: ordered subsets expectation maximization (OSEM), OSEM with time-of-flight (TOF), OSEM with TOF and point spread function (PSF), and Bayesian penalized likelihood (BPL, known as Q.Clear in the PET/CT of GE Healthcare). In clinical studies, SUVmax and SUVmean (the maximum and mean of the standardized uptake values, SUVs) of 75 small pulmonary nodules (sub-centimeter group: < 10 mm and medium-size group: 10–25 mm) were measured from 26 patients. Results show that Q.Clear produced higher RC and CR values, which can improve quantification accuracy compared with other methods (P < 0.05), except for the RC of 37 mm sphere (P > 0.05). The SUVs of sub-centimeter fludeoxyglucose (FDG)-avid pulmonary nodules with Q.Clear illustrated highly significant differences from those reconstructed with other algorithms (P < 0.001). After performing the PVC, highly significant differences (P < 0.001) still existed in the SUVmean measured by Q.Clear comparing with those measured by the other algorithms. Our results suggest that the Q.Clear reconstruction algorithm improved the quantification accuracy towards the true uptake, which potentially promotes the diagnostic confidence and treatment response evaluations with PET/CT imaging, especially for the sub-centimeter pulmonary nodules. For small lesions, PVC is essential.

Synaptic density is associated with cognitive performance in early Alzheimer's disease: a PET imaging study with [11C]UCB-J

<h3>Introduction</h3> For 30 years synapse loss has been referred to as the major pathological correlate of cognitive impairment in Alzheimer's disease (AD; Terry, et al. 1991; DeKosky and Scheff. 1990). However, this statement is based on remarkably few patients studied by autopsy or biopsy in limited brain regions, largely at the moderate to severe stages of disease. With the recent advent of synaptic positron emission tomography (PET) imaging, we have begun to evaluate synaptic alterations <i>in vivo</i>. Synaptic vesicle glycoprotein 2A (SV2A) is expressed in virtually all synapses and is located in synaptic vesicles at presynaptic terminals (Bajjalieh, et al. 1993). [¹¹C]UCB-J was recently developed as a PET tracer for SV2A and advanced for human studies (Finnema, et al. 2016). In our recent study of [¹¹C]UCB-J PET, we observed widespread reductions of SV2A binding in medial temporal and neocortical brain regions in early AD compared to CN participants (Mecca, et al. 2020). However, initial attempts using PET imaging to associate synaptic density with cognitive performance have been hindered by the use of limited cognitive measures. In this study we examined the relationship between synaptic density and cognitive performance in early AD using [¹¹C]UCB-J PET and an extensive neuropsychological test battery. <h3>Methods</h3> Using [¹¹C]UCB-J binding to SV2A, synaptic density was measured in 45 amyloid positive participants with AD (17 amnestic mild cognitive impairment and 28 mild dementia) and 20 amyloid negative cognitively normal (CN) participants aged 50-85 years. Synaptic density was calculated as the distribution volume ratio (<i>DVR</i>) in a composite region of interest (ROI) of AD-affected regions (prefrontal, lateral temporal, medial temporal, lateral parietal, anterior cingulate, posterior cingulate, precuneus, and lateral occipital) using cerebellum as reference region. A neuropsychological test battery was administered to assess performance in five cognitive domains: Verbal Memory (Logical Memory II, Rey Auditory Verbal Learning Test [RAVLT] total words recalled across trials 1-5, RAVLT delayed recall), Language (Boston Naming Test, Category Fluency), Executive Function (Stroop Color Word, Trails B, Letter Fluency), Processing Speed (Stroop Word, Trails A, WAIS-3 Digit Symbol Substitution), and Visuospatial Ability (Rey-Osterrieth Complex Figure, WAIS-3 Block Design, WAIS-3 Picture Completion). Neuropsychological test raw scores were converted to z-scores using the means and SDs from the pooled AD and CN sample), and cognitive domain scores were generated for each AD participant by averaging z-scores within the domain. Global cognitive scores were then generated for each participant by averaging the five domain scores. <h3>Results</h3> In a multiple linear regression model controlling for age, sex, and education, synaptic density ([¹¹C]UCB-J <i>DVR</i>) was a significant predictor of global cognitive performance in participants with AD (β=3.21, η²=0.29, <i>P</i>=0.0001; Figure 1A). Synaptic density was also a significant predictor of performance in all five cognitive domains: Verbal Memory (β=1.35, η²=0.11, <i>P</i>=0.022; Figure 1B), Language (β=3.82, η²=0.25, <i>P</i>=0.001; Figure 1C), Executive Function (β=3.28, η²=0.20, <i>P</i>=0.001; Figure 1D), Processing Speed (β=4.03, η²=0.23, <i>P</i>=0.001; Figure 1E), and Visuospatial Ability (β=3.58, η²=0.22, <i>P</i>=0.001; Figure 1F). The relatively weak association with verbal memory may have resulted from floor effects on the measures that comprised this domain. The observed associations between synaptic density and global cognition remained significant after correction for partial volume effects (β=2.16, η²=0.23, <i>P</i>=0.001), and synaptic density was a stronger predictor of cognitive performance than gray matter volume (β=0.01, η²=0.17, <i>P</i>=0.005). <h3>Conclusions</h3> These results confirm neuropathologic studies, demonstrating a significant association between synaptic density and cognitive performance, and suggest that this correlation extends to the mild and prodromal stages of AD. They further support the use of synaptic imaging as a potential surrogate biomarker outcome for therapeutic trials that is well-correlated with clinical measures. Longitudinal studies are needed to relate change in synaptic density as measured by [¹¹C]UCB-J PET with change in cognitive performance. <h3>Funding</h3> R01-AG052560 [REC, CHvD], R01-AG062276 [CHvD], RF1-AG057553 [REC, CHvD], Dana Foundation [MKC]), P50-AG047270 [CHvD, MKC], P30-AG066508 [CHvD], K23-AG057784 [APM], R25-MH071584 (RSO), T32-MH019961 [RSO], and Thomas P. Detre Fellowship [RSO].

Does the beta regularization parameter of bayesian penalized likelihood reconstruction always affect the quantification accuracy and image quality of positron emission tomography computed tomography?

PurposeThis study aims to provide a detailed investigation on the noise penalization factor in Bayesian penalized likelihood (BPL)‐based algorithm, with the utilization of partial volume effect correction (PVC), so as to offer the suitable beta value and optimum standardized uptake value (SUV) parameters in clinical practice for small pulmonary nodules.MethodsA National Electrical Manufacturers Association (NEMA) image‐quality phantom was scanned and images were reconstructed using BPL with beta values ranged from 100 to 1000. The recovery coefficient (RC), contrast recovery (CR), and background variability (BV) were measured to assess the quantification accuracy and image quality. In the clinical assessment, lesions were categorized into sub‐centimeter (<10 mm, n = 7) group and medium size (10–30 mm, n = 16) group. Signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR) were measured to evaluate the image quality and lesion detectability. With PVC was performed, the impact of beta values on SUVs (SUVmax, SUVmean, SUVpeak) of small pulmonary nodules was evaluated. Subjective image analysis was performed by two experienced readers.ResultsWith the increasing of beta values, RC, CR, and BV decreased gradually in the phantom work. In the clinical study, SNR and CNR of both groups increased with the beta values (P < 0.001), although the sub‐centimeter group showed increases after the beta value reached over 700. In addition, highly significant negative correlations were observed between SUVs and beta values for both lesion‐size groups before the PVC (P < 0.001 for all). After the PVC, SUVpeak measured from the sub‐centimeter group was no significantly different among different beta values (P = 0.830).ConclusionOur study suggests using SUVpeak as the quantification parameter with PVC performed to mitigate the effects of beta regularization. Beta values between 300 and 400 were preferred for pulmonary nodules smaller than 30 mm.