Volume Of Interest Analysis Research Articles

Cholinergic innervation topography in GBA-associated de novo Parkinson's disease patients.

The most common genetic risk factors for Parkinson's disease are GBA1 mutations, encoding the lysosomal enzyme glucocerebrosidase. Patients with GBA1 mutations (GBA-PD) exhibit earlier age of onset and faster disease progression with more severe cognitive impairments, postural instability and gait problems. These GBA-PD features suggest more severe cholinergic system pathologies. PET imaging with the vesicular acetylcholine transporter ligand 18F-F-fluoroethoxybenzovesamicol (18F-FEOBV PET) provides the opportunity to investigate cholinergic changes and their relationship to clinical features in GBA-PD. The study investigated 123 newly diagnosed, treatment-naïve Parkinson's disease subjects-with confirmed presynaptic dopaminergic deficits on PET imaging. Whole-gene GBA1 sequencing of saliva samples was performed to evaluate GBA1 variants. Patients underwent extensive neuropsychological assessment of all cognitive domains, motor evaluation with the Unified Parkinson's Disease Rating Scale, brain MRI, dopaminergic PET to measure striatal-to-occipital ratios of the putamen and 18F-FEOBV PET. We investigated differences in regional cholinergic innervation between GBA-PD carriers and non-GBA1 mutation carriers (non-GBA-PD), using voxel-wise and volume of interest-based approaches. The degree of overlap between t-maps from two-sample t-test models was quantified using the Dice similarity coefficient. Seventeen (13.8%) subjects had a GBA1 mutation. No significant differences were found in clinical features and dopaminergic ratios between GBA-PD and non-GBA-PD at diagnosis. Lower 18F-FEOBV binding was found in both the GBA-PD and non-GBA-PD groups compared to controls. Dice (P < 0.05, cluster size 100) showed good overlap (0.7326) between the GBA-PD and non-GBA-PD maps. GBA-PD patients showed more widespread reduction in 18F-FEOBV binding than non-GBA-PD when compared to controls in occipital, parietal, temporal and frontal cortices (P < 0.05, FDR-corrected). In volume of interest analyses (Bonferroni corrected), the left parahippocampal gyrus was more affected in GBA-PD. De novo GBA-PD show a distinct topography of regional cholinergic terminal ligand binding. Although the Parkinson's disease groups were not distinguishable clinically, in comparison to healthy controls, GBA-PD showed more extensive cholinergic denervation compared to non-GBA-PD. A larger group is needed to validate these findings. Our results suggest that de novo GBA-PD and non-GBA-PD show differential patterns of cholinergic system changes before clinical phenotypic differences between carriers versus non-carrier groups are observable.

Lenalidomide Consolidation Added to Rituximab Maintenance Therapy in Patients Remaining PET Positive After Treatment for Relapsed Follicular Lymphoma: A Phase 2 Australasian Leukaemia & Lymphoma Group NHL26 Study.

Lenalidomide Consolidation Added to Rituximab Maintenance Therapy in Patients Remaining PET Positive After Treatment for Relapsed Follicular Lymphoma: A Phase 2 Australasian Leukaemia & Lymphoma Group NHL26 Study.

18F‐MK6240 tau in ento‐ and perihinal cortex is related to episodic memory in the earliest stages of Alzheimer’s disease

AbstractBackgroundIn a previous study, we showed the sensitivity of the Buschke Selective Reminding test Total Retention (BSRT TR) for detecting and predicting 4‐year cognitive change in cognitively intact older adults. Here, we examined how BSRT TR related to tau load.MethodThe study sample consisted of 29 cognitively intact participants of the Flemish Prevent AD cohort KU Leuven (CDR global=0, MMSE=28‐30, mean age=68.5 year) and eight memory‐clinic recruited patients with prodromal AD (CDR global=0.5, MMSE=21‐30, mean age=71 year). All participants underwent neuropsychological testing, MRI and 18F‐MK6240 PET. Structural T1‐weighted MRI images were processed using CAT12. Tau load was quantified as 18F‐MK6240 DVR with the inferior cerebellum used as reference region. The primary analysis was based on voxel‐wise regression analysis between 18F‐MK6240 DVR scans and BSRT TR mean scores, with age as covariate. The second primary endpoint was the correlation between BSRT TR mean scores and tau DVR in an entorhinal and perirhinal volume of interest (VOI) based on the Brainnetome atlas. The secondary analysis was a VOI analysis based on an early metaVOI also containing hippocampus, parahippocampus, fusiform gyrus and inferior temporal cortex. Results were compared to those obtained for other episodic memory scores (BSRT delayed recall (DR), Auditory Verbal Learning Test (AVLT) total learning (TL) and AVLT DR), and an MRI volumetric analysis.ResultVoxel‐wise regression analysis showed a negative correlation between BSRT TR mean and DVR in ento‐ and perirhinal cortex bilaterally (x=22, y=‐4, z=‐32, extent=612 voxels, cluster level pcorr&lt;0.001) (x=‐30, y=‐22, z=‐20, extent=2910 voxels, cluster level pcorr&lt;0.001) (Figure A). This was confirmed by the analysis of the entorhinal/perirhinal VOI (rho=‐0.44, p=0.0063; Figure B). Significant correlations with ento‐ and perirhinal DVR were also present for BSRT DR (rho=‐0.39, p=0.017) and AVLT TL (rho=‐0.41, p=0.012), but not for AVLT DR (rho=‐0.29, p=0.084). No significant correlation was found with tau in the early metaVOI for any of the verbal episodic memory measures. Voxel‐wise regression analysis between gray matter volume and BSRT TR mean scores did not show significant results.ConclusionThe earliest measurable tau aggregate levels in ento‐ and perirhinal cortex correlate with classical episodic memory parameters.

68Ga-DOTA PET for Diagnosis of Spinal Cerebrospinal Fluid Leaks.

Spontaneous intracranial hypotension due to spinal cerebrospinal fluid (CSF) leakage causes substantial disease burden. In many patients, the course is protracted and refractory to conservative treatment, requiring targeted therapy. We propose PET of the CSF space with 68Ga-DOTA as a state-of-the-art approach to radionuclide cisternography (RC) and validate its diagnostic value. Methods: This study is a retrospective analysis of patients with suspected intracranial hypotension due to spinal CSF leaks and who underwent whole-body PET/CT at 1, 3, and 5 h after intrathecal lumbar injection of 68Ga-DOTA. Two independent raters unaware of the clinical data analyzed all scans for direct and indirect RC signs of CSF leakage. Volume-of-interest analysis was performed to assess the biologic half-life of the tracer in the CSF space and the ratio of decay-corrected activity in the CSF space at 5 and 3 h (simplified marker of tracer clearance). Comprehensive stepwise neuroradiologic work-up served as a reference; additional validation was provided by surgical findings and follow-up. Results: Of 40 consecutive patients, 39 patients with a working diagnosis of intracranial hypotension due to a spinal CSF leak (spontaneous, n = 31; postintervention, n = 8) could be analyzed. A spinal CSF leak was verified by the neuroradiologic reference method in 18 of 39 patients. As the only direct and indirect diagnostic signs, extrathecal tracer accumulation at the cervicothoracic junction (67% sensitivity and 90% specificity) and lack of activity over the cerebral convexities (5 h; 94% sensitivity and 67% specificity) revealed a high diagnostic value for spinal CSF leaks. Their combination provided little improvement (71% sensitivity and 95% specificity). Additional quantitative analyses yielded no benefit (94% sensitivity and 53% specificity for biological half-life; 94% sensitivity and 58% specificity for the ratio of total radioactivity within the CSF space at 5 and 3 h). The location of direct signs (extrathecal tracer accumulation) did not correlate with verified sites of spinal CSF leakage. Conclusion: We propose CSF PET with 68Ga-DOTA as a novel, fast, and convenient approach to RC for verification but not localization of spinal CSF leaks with high sensitivity and specificity. CSF PET may fulfill an important gatekeeper function for stratifying patients toward escalation (ruling in) or deescalation (ruling out) of diagnostic and therapeutic measures. Further prospective studies are needed to validate the present results and determine the potential of the methods to reduce the burden to patients.

Clinicoanatomical substrates of selfish behaviour in amyotrophic lateral sclerosis – An observational cohort study

ObjectiveALS primarily affects motor functions, but cognitive functions, including social understanding, may also be impaired. Von Economo neurons (VENs) are part of the neuronal substrate of social understanding and these cells are histopathologically altered in ALS. We investigated whether activity in areas including VENs is associated with an impairment of cognitive tasks that mirror social functioning. MethodsIn this observational prospective study, ALS patients (N = 26) were tested for cognitive behavioural function, encompassing different aspects of empathetic understanding (interpersonal reactivity index, IRI), social behaviour (ultimatum game), recognition of faux-pas situations, and general cognitive functioning (Edinburgh Cognitive and Behavioural ALS Screen, ECAS). For in vivo pathological staging according to Braak, DTI-MRI was performed to determine those ALS patients with expected pathological involvement of VENs (B ALS stages 3 + 4) compared to those without (B ALS stages 1 + 2). Expected hypometabolism of cerebral areas was determined with 18F-FDG PET in N = 20 ALS patients and compared to N = 20 matched healthy controls. Volume of interest analysis was performed in the anterior cingulate cortex (ACC) and the anterior insular cortex (AIC), which contain high numbers of VENs. ResultsCompared to those without expected pathological involvement of VENs (B/B ALS stages 1 + 2), ALS patients with anticipated pathological involvement of VENs (B/B ALS stages 3 + 4) presented with significantly reduced fantasy to understand the mindset of others (IRI) and, social behaviour was more selfish (ultimatum game) despite the fact that cognitive understanding of socially inappropriate behaviour of others (faux-pas) was unimpaired. 18F-FDG-PET showed hypometabolism in ACC and AIC in ALS patients with anticipated pathological involvement of VENs compared to those without and this was significantly correlated to cognitive-behavioral functions in certain tasks. ConclusionHere, we present evidence of altered social behaviour in ALS patients associated with regional 18FDG-PET hypometabolism in areas with a high density of VENs, thereby suggesting a possible causal association.

Impact of the inversion time on regional brain perfusion estimation with clinical arterial spin labeling protocols

ObjectiveEvaluating the impact of the Inversion Time (TI) on regional perfusion estimation in a pediatric cohort using Arterial Spin Labeling (ASL).Materials and methodsPulsed ASL (PASL) was acquired at 3 T both at TI 1500 ms and 2020 ms from twelve MRI-negative patients (age range 9–17 years). A volume of interest (VOIs) and a voxel-wise approach were employed to evaluate subject-specific TI-dependent Cerebral Blood Flow (CBF) differences, and grey matter CBF Z-score differences. A visual evaluation was also performed.ResultsCBF was higher for TI 1500 ms in the proximal territories of the arteries (PTAs) (e.g. insular cortex and basal ganglia — P < 0.01 and P < 0.05 from the VOI analysis, respectively), and for TI 2020 ms in the distal territories of the arteries (DTAs), including the watershed areas (e.g. posterior parietal and occipital cortex — P < 0.001 and P < 0.01 from the VOI analysis, respectively). Similar differences were also evident when analyzing patient-specific CBF Z-scores and at a visual inspection.ConclusionsTI influences ASL perfusion estimates with a region-dependent effect. The presence of intraluminal arterial signal in PTAs and the longer arterial transit time in the DTAs (including watershed areas) may account for the TI-dependent differences. Watershed areas exhibiting a lower perfusion signal at short TIs (~ 1500 ms) should not be misinterpreted as focal hypoperfused areas.

Quantitative MRI T2 Mapping is Able to Assess Tissue Quality After Reparative and Regenerative Treatments of Osteochondral Lesions of the Talus.

BackgroundQuantitative MRI has potential for tissue characterization after reparative and regenerative surgical treatment of osteochondral lesions of the talus (OCLTs). However available data is inconclusive and quantitative sequences can be difficult to implement in real‐time clinical application.PurposeTo assess the potential of T2 mapping in discriminating articular tissue characteristics after reparative and regenerative surgery of OCLTs in real‐world clinical settings.Study TypeObservational and prospective cohort study.Population15 OCLT patients who had received either reparative treatment with arthroscopic microfracture surgery (MFS) for a grade I lesion or regenerative treatment with bone marrow derived cell transplantation (BMDCT) for a grade II lesion.Field Strength/Sequence1.5 T, proton density weighted TSE, T2‐weighted true fast imaging with steady‐state‐free precession and multi‐echo T2 mapping sequences.AssessmentPatients were evaluated at a minimum postoperative follow‐up of 24 months. T2 maps of the ankle were generated and the distribution of T2 values was analyzed in manually identified volumes of interest (VOIs) for both treated lesions (TX) and healthy cartilage (CTRL). The amount of fibrocartilage, hyaline‐like and remodeling tissue in TX VOIs was obtained, based on T2 thresholds from CTRL VOIs.Statistical TestsFisher's exact test for categorical data, nonparametric Mann–Whitney U test for continuous data. The statistical significance level was P < 0.05.ResultsFrom CTRL VOI analysis, T2 < 25 msec, 25 msec ≤ T2 ≤ 45 msec, and T2 > 45 msec were considered as representative for fibrocartilage, hyaline‐like and remodeling tissue, respectively. Tissue composition of the two treatment groups was different, with significantly more fibrocartilage (+28%) and less hyaline‐like tissue (−15%) in MFS than in BMDCT treated lesions. No difference in healthy tissue composition was found between the two groups (P = 0.75).Data ConclusionsT2 mapping of surgically treated OCLTs can provide quantitative information about the type and amount of newly formed tissue at the lesion site, thereby facilitating surgical follow‐up in a real‐word clinical setting.Level of Evidence2Technical EfficacyStage 3

Higher HbA1c levels associate with lower hippocampal serotonin transporter availability in non-diabetic adults with obesity

The current study aimed to investigate whether the in vivo availability of central serotonin reuptake transporters (5-HTT) is associated with plasma levels of glycosylated hemoglobin (HbA1c) in non-diabetic humans with obesity. 5-HTT availability was measured by using positron emission tomography (PET) imaging with the 5-HTT selective radiotracer [11C]DASB in 23 non-diabetic individuals with obesity and 14 healthy, non-obesity controls. Parametric images of binding potential BPND were generated from the PET data and analyzed together with HbA1c levels by using volume of interest analysis for brain areas relevant to appetite control. Voxel-based morphometry (VBM) of individual magnetic resonance imaging data was further performed to correlate grey matter density (GMD) maps with HbA1c. We found significant negative correlations between HbA1c levels and BPND in right and left hippocampus in obesity (r = − 0.717, p < 0.001, and r = − 0.557, p = 0.006, respectively). VBM analyses revealed that higher HbA1c levels were associated with GMD in the right para-hippocampal area. Our results indicate that chronically high blood glucose levels may evoke changes in hippocampal 5-HTT levels that are in part tied to local microstructure.

Adaptive analysis of cortical plasticity with fMRI in full face and arm transplants

The aim of this study is to examine cortical plasticity and to analyze cortical reorganization following hand and facial transplantation, using functional magnetic resonance imaging. Patients who had undergone full-face transplantation, hand transplantation and scapular arm replantation, as well as healthy controls, participated in the study. The perioral area and volar surfaces of the index finger and thumb were stimulated and images were acquired using 3T functional MRI. The areas of the somatosensory cortex representing the hand and face are different in size and shape due to experience-dependent plasticity. Therefore, a new and more adaptive volume of interest analysis was created whereby the radiuses of the VOI masks were defined by the peak intensity of subsequent clusters. For each control subject, the distribution of activated voxels was observed for various cluster defining thresholds in order to determine the mean number of activated voxels for each stimulation inside the defined region. The determined numbers of voxels per subject were extracted from the defined regions using a binary search algorithm. Subsequently, the distances between the weighted centers of the extracted regions were calculated and compared. In transplant patients, the weighted centers of the hand and face clusters were separated at same-sized volumes. Two of the rehabilitated full-face transplant patients converge to the range of the controls. As a result, the weighted distribution of somatotopy indicated previous and present cortical reorganization. Additionally, referred sensation was assessed in two full-face transplant and one replant patient with activation clusters partially in BA40 in the Inferior Parietal Lobule.

Associations of [18F]-APN-1607 Tau PET Binding in the Brain of Alzheimer's Disease Patients With Cognition and Glucose Metabolism.

Molecular imaging of tauopathies is complicated by the differing specificities and off-target binding properties of available radioligands for positron emission tomography (PET). [18F]-APN-1607 ([18F]-PM-PBB3) is a newly developed PET tracer with promising properties for tau imaging. We aimed to characterize the cerebral binding of [18F]-APN-1607 in Alzheimer’s disease (AD) patients compared to normal control (NC) subjects. Therefore, we obtained static late frame PET recordings with [18F]-APN-1607 and [18F]-FDG in patients with a clinical diagnosis of AD group, along with an age-matched NC group ([18F]-APN-1607 only). Using statistical parametric mapping (SPM) and volume of interest (VOI) analyses of the reference region normalized standardized uptake value ratio maps, we then tested for group differences and relationships between both PET biomarkers, as well as their associations with clinical general cognition. In the AD group, [18F]-APN-1607 binding was elevated in widespread cortical regions (P < 0.001 for VOI analysis, familywise error-corrected P < 0.01 for SPM analysis). The regional uptake in AD patients correlated negatively with Mini-Mental State Examination score (frontal lobe: R = -0.632, P = 0.004; temporal lobe: R = -0.593, P = 0.008; parietal lobe: R = -0.552, P = 0.014; insula: R = -0.650, P = 0.003; cingulum: R = -0.665, P = 0.002) except occipital lobe (R = -0.417, P = 0.076). The hypometabolism to [18F]-FDG PET in AD patients also showed negative correlations with regional [18F]-APN-1607 binding in some signature areas of AD (temporal lobe: R = -0.530, P = 0.020; parietal lobe: R = -0.637, P = 0.003; occipital lobe: R = -0.567, P = 0.011). In conclusion, our results suggested that [18F]-APN-1607 PET sensitively detected tau deposition in AD and that individual tauopathy correlated with impaired cerebral glucose metabolism and cognitive function.

Microstructural white matter changes following gait training with Hybrid Assistive Limb initiated within 1 week of stroke onset

The early initiation of robot-assisted gait training in patients with acute stroke could promote neuroplasticity. The aim of this study was to clarify the microstructural changes of white matter associated with gait training using Hybrid Assistive Limb (HAL) by diffusion tensor imaging (DTI). Patients with first-ever stroke and requiring a walking aid started gait training within 1 week of stroke onset. The patients were quasi-randomly assigned either to the conventional physical therapy (CPT) group or gait training using HAL (HAL) group. Motor function and DTI were examined at baseline and after 3–5 months. Voxel-based statistical analyses of fractional anisotropy (FA) images were performed using diffusion metric voxel-wise analyses. Volume of interest (VOI)-based analyses were used to assess changes in FA (ΔFA). Twenty-seven patients (17 in the CPT group and 10 in the HAL group) completed the study. There were improvements in motor function and independency in the CPT and HAL groups (p < .001). Compared to baseline, there were decreases in FA in the ipsi-lesional cerebral peduncle in the CPT group (p < .001) and increases in the contra-lesional rostrum of the corpus callosum in the HAL group (p < .001) at the second assessment, consistent with the mean ΔFA in each group from VOI analysis (CPT/HAL: cerebral peduncle, −0.066/−0.027, p = .027; corpus callosum, 0.002/0.042, p < .001). Gait training using HAL initiated within 1 week after stroke onset facilitated the recovery of inter-hemispheric communication and prevented the progression of Wallerian degeneration of the affected pyramidal tract.

Mild traumatic brain injury induced by primary blast overpressure produces dynamic regional changes in [18F]FDG uptake

Changes in 18F-fluorodeoxyglucose ([18F]FDG) measured by positron emission tomography (PET) can be used for the noninvasive detection of metabolic dysfunction following mild traumatic brain injury (mTBI). This study examined the time course of metabolic changes induced by primary blast injury by measuring regional [18F]FDG uptake. Adult, male rats were exposed to blast overpressure (15 psi) or sham injury, and [18F]FDG uptake was measured before injury and again at 1–3 h and 7 days post-injury, using both volume-of-interest (VOI) and voxel-based analysis. VOI analysis revealed significantly increased [18F]FDG uptake in corpus callosum and amygdala at both 1–3 h and 7 days following blast, while a transient decrease in uptake was observed in the midbrain at 1–3 h only. Voxel-based analysis revealed similar significant differences in uptake between sham and blast-injured rats at both time points. At 1–3 h post-injury, clusters of increased uptake were found in the amygdala, somatosensory cortex, and corpus callosum, while regions of decreased uptake were observed in midbrain structures (inferior colliculus, ventrolateral tegmental area) and dorsal auditory cortex. At day 7, a region of increased uptake in blast-injured rats was found in a cluster centered on the cortex-amygdala transition zone, while no regions of decreased uptake were observed. These results suggest that a relatively mild primary blast injury results in altered brain metabolism in multiple brain regions and that post-injury time of assessment is an important factor in observing regional changes in [18F]FDG uptake.

Diffusion Kurtosis Imaging in the Assessment of Cervical Carcinoma

To evaluate the additional value of diffusion kurtosis imaging (DKI) in the characterization of cervical carcinoma. Seventy-five patients (56.9 ± 13.4 years) with histologic-confirmed cervical carcinoma were included. Diffusion-weighted imaging (DWI) was acquired on a 3T MRI with five b values (0, 500, 800, 1000, and 1500 s/mm2). Data were analyzed based on DKI model (5 b values) and conventional DWI (0 and 1000 s/mm2). Largest single-slice region of interest (ROI) and volume of interest (VOI) were drawn around the tumor. Mean diffusivity (MD), mean kurtosis (MK), and apparent diffusion coefficient (ADC) of cervical carcinoma and normal myometrium were measured and compared. MD, MK, and ADC of cervical carcinoma were compared among histologic subtypes, tumor grades, and FIGO stages. ROI- and VOI-derived DKI parameters and ADC were all in excellent consistency (intraclass correlation coefficient, ICC > 0.90, respectively). Cervical carcinoma had significantly lower MD, ADC, and higher MK than normal myometrium (p < 0.001). MD and ADC showed significant differences between histologic subtypes and FIGO stages, lower in squamous cell carcinoma than adenocarcinoma and higher in FIGO I-II than FIGO III-IV (p < 0.050), but not with tumor grade. No difference was observed in MK for different clinicopathologic features tested. ROI and VOI analyses were in excellent consistency. MD and ADC were able to distinguish histologic subtypes and separating FIGO stages, MK could not. DKI showed no clear added value over conventional DWI in the characterization of cervical carcinoma.

18F]-florbetaben PET/CT Imaging in the Alzheimer's Disease Mouse Model APPswe/PS1dE9.

Positron-emission-tomography (PET) using 18F labeled florbetaben allows noninvasive in vivo-assessment of amyloid-beta (Aβ), a pathological hallmark of Alzheimer's disease (AD). In preclinical research, [18F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [18F]-florbetaben in the APPswe/ PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aβ plaques. Both, APPswe/PS1dE9 and wild type mice at an age of 12 months were investigated by smallanimal PET/CT after intravenous injection of [18F]-florbetaben. High-resolution magnetic resonance imaging data were used for quantification of the PET data by volume of interest analysis. The standardized uptake values (SUVs) of [18F]-florbetaben in vivo as well as post mortem cerebral Aβ plaque load in cortex, hippocampus and cerebellum were analyzed. Visual inspection and SUVs revealed an increased cerebral uptake of [18F]-florbetaben in APPswe/ PS1dE9 mice compared with wild type mice especially in the cortex, the hippocampus and the cerebellum. However, SUV ratios (SUVRs) relative to cerebellum revealed only significant differences in the hippocampus between the APPswe/PS1dE9 and wild type mice but not in cortex; this differential effect may reflect the lower plaque area in the cortex than in the hippocampus as found in the histological analysis. The findings suggest that histopathological characteristics of Aβ plaque size and spatial distribution can be depicted in vivo using [18F]-florbetaben in the APPswe/PS1dE9 mouse model.

Montreal Cognitive Assessment score correlates with regional cerebral blood flow in post-stroke patients

ObjectiveValid and reliable measures are needed to assess post-stroke cognitive impairment. The Montreal Cognitive Assessment (MoCA) has been considered a superior screening test to the Mini-Mental State Examination (MMSE) for patients with post-stroke cognitive impairment, particularly in executive function, which may be related to reduction in regional cerebral blood flow (rCBF). In this study, we determined whether MoCA and MMSE scores correlate with rCBF assessed with SPECT in the subacute phase after ischemic stroke. Patients and methodsWe retrospectively enrolled 28 patients who were admitted to the Red Cross Otsu Hospital with acute cerebral infarction, which was confirmed by magnetic resonance imaging (MRI), if they underwent cognitive assessment (MoCA/MMSE) and 123I-IMP SPECT imaging within 3 weeks post-stroke during a study period of 5 months. Correlation analyses between rCBF and MoCA or MMSE scores were performed by statistical parametric mapping (SPM) and volume-of-interest (VOI) analyses. ResultsTotal MoCA score correlated with the rCBF in the prefrontal cortex, cingulate cortex, caudate nucleus and thalamus by SPM analysis (uncorrected p < 0.001; cluster-level corrected p < 0.05). Among the subtest scores of MoCA, visuoexecutive function, attention, language and delayed recall scores were positively correlated with rCBF in the prefrontal cortex by VOI analysis (p < 0.05). However, total MMSE score did not correlate significantly with any of the rCBF measures. ConclusionsPost-stroke cognitive performance assessed with MoCA positively correlated with rCBF in brain regions mainly comprising the prefrontal-subcortical circuits. The findings of this hypothesis-generating study support the notion that MoCA is useful for assessing post-stroke cognitive status.

Evaluation of drug effects on cerebral blood flow and glucose uptake in un-anesthetized and un-stimulated rats: application of free-moving apparatus enabling to keep rats free during PET/SPECT tracer injection and uptake.

ObjectivesThe purpose of this study is the development of novel fluorine-18-fluorodeoxyglucose (18F-FDG)-PET and 99mTc-hexamethylpropylene amine oxime (HMPAO) SPECT methods with free-moving apparatus on conscious rats to investigate brain activity without the effects of anesthesia and tactual stimulation. We also assessed the sensitivity of the experimental system by an intervention study using fluoxetine as a reference drug.Materials and methodsA catheter was inserted into the femoral vein and connected to a free-moving cannula system. After fluoxetine administration, the rats were given an injection of 18F-FDG or 99mTc-HMPAO via the intravenous cannula and released into a free-moving cage. After the tracer was trapped in the brain, the rats were anesthetized and scanned with PET or SPECT scanners. Then a volume of interest analysis and statistical parametric mapping were performed.ResultsWe could inject the tracer without touching the rats, while keeping them conscious until the tracers were distributed and trapped in the brain using the developed system. The effects of fluoxetine on glucose uptake and cerebral blood flow were perceptively detected by volume of interest and statistical parametric mapping analysis.ConclusionWe successfully developed free-moving 18F-FDG-PET and 99mTc-HMPAO-SPECT imaging systems and detected detailed glucose uptake and cerebral blood flow changes in the conscious rat brain with fluoxetine administration. This system is expected to be useful to assess brain activity without the effects of anesthesia and tactual stimulation to evaluate drug effect or animal brain function.

Beyond fractional anisotropy in amyotrophic lateral sclerosis: the value of mean, axial, and radial diffusivity and its correlation with electrophysiological conductivity changes

This paper aims to analyze the contribution of mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in the detection of microstructural abnormalities in amyotrophic lateral sclerosis (ALS) and to evaluate the degree of agreement between structural and functional changes through concomitant diffusion tensor imaging (DTI), transcranial magnetic stimulation (TMS), and clinical assessment. Fourteen patients with ALS and 11 healthy, age- and gender-matched controls were included. All participants underwent magnetic resonance imaging including DTI. TMS was additionally performed in ALS patients. Differences in the distribution of DTI-derived measures were assessed using tract-based spatial statistical (TBSS) and volume of interest (VOI) analyses. Correlations between clinical, imaging, and neurophysiological findings were also assessed through TBSS. ALS patients showed a significant increase in AD and MD involving the corticospinal tract (CST) and the pre-frontal white matter in the right posterior limb of the internal capsule (p < 0.05) when compared to the control group using TBSS, confirmed by VOI analyses. VOI analyses also showed increased AD in the corpus callosum (p < 0.05) in ALS patients. Fractional anisotropy (FA) in the right CST correlated significantly with upper motor neuron (UMN) score (r = - 0.79, p < 0.05), and right abductor digiti minimi central motor conduction time was highly correlated with RD in the left posterior internal capsule (r = - 0.81, p < 0.05). No other significant correlation was found. MD, AD, and RD, besides FA, are able to further detect and characterize neurodegeneration in ALS. Furthermore, TMS and DTI appear to have a role as complementary diagnostic biomarkers of UMN dysfunction.

Dual-phase 18F-florbetapir positron emission tomography in patients with primary progressive aphasia, Alzheimer's disease, and healthy controls: A preliminary study.

To determine whether dual-phase 18F-florbetapir positron emission tomography imaging with perfusion-like and amyloid deposition information can distinguish among primary progressive aphasia (PPA), Alzheimer's disease (AD), and healthy controls (HCs). Patients diagnosed with PPA, including four semantic dementia (SD) and two progressive nonfluent aphasia (PNFA), as well as one logopenic variant (LV) of PPA, were studied. All PPA patients, and age-/sex-matched patients with probable AD (n=8) and HCs (n=8) were subjected to dual-phase 18F-florbetapir imaging. Atlas-based quantitative volumes of interest (VOIs) analysis for six cortical areas and whole cerebellum was performed. The standardized uptake value ratios were calculated by normalizing the dual-phase-integrated activities of the six VOIs to whole cerebellum counts. Early phase 18F-florbetapir image showed significantly lower global perfusion index in six PPA patients as compared with HCs. According to VOI analysis, the hypoperfusion lesions were identified in the frontal, anterior cingulate, parietal, precuneus, and temporal regions. Similar findings were confirmed by voxel-base image comparison. 18F-florbetapir late-phase image showed significantly increased amyloid burden in the global cortex index and all six brain regions of eight AD and LV patients when compared with the other six PPA patients and eight HCs. There was no apparent uptake of amyloid tracer in both six PPA patients and eight HCs. Dual-phase 18F-florbetapir images of six PPA (SD and PNFA) patients showed hypoperfusion in the frontotemporal cortex, and little global amyloid uptake, which may be a distinct image pattern for differentiation among HC, AD, and PPA patients.

Combined PET Imaging of the Inflammatory Tumor Microenvironment Identifies Margins of Unique Radiotracer Uptake.

The tumor microenvironment is highly heterogeneous. For gliomas, the tumor-associated inflammatory response is pivotal to support growth and invasion. Factors of glioma growth, inflammation, and invasion, such as the translocator protein (TSPO) and matrix metalloproteinases (MMP), may serve as specific imaging biomarkers of the glioma microenvironment. In this study, noninvasive imaging by PET with [18F]DPA-714 (TSPO) and [18F]BR-351 (MMP) was used for the assessment of localization and quantification of the expression of TSPO and MMP. Imaging was performed in addition to established clinical imaging biomarker of active tumor volume ([18F]FET) in conjunction with MRI. We hypothesized that each imaging biomarker revealed distinct areas of the heterogeneous glioma tissue in a mouse model of human glioma. Tracers were found to be increased 1.4- to 1.7-fold, with [18F]FET showing the biggest volume as depicted by a thresholding-based, volumes of interest analysis. Tumor areas, which could not be detected by a single tracer and/or MRI parameter alone, were measured. Specific compartments of [18F]DPA-714 (14%) and [18F]BR-351 (11%) volumes along the tumor rim could be identified. [18F]DPA-714 (TSPO) and [18F]BR-351 (MMP) matched with histology. Glioma-associated microglia/macrophages (GAM) were identified as TSPO and MMP sources. Multitracer and multimodal molecular imaging approaches may allow us to gain important insights into glioma-associated inflammation (GAM, MMP). Moreover, this noninvasive technique enables characterization of the glioma microenvironment with respect to the disease-driving cellular compartments at the various disease stages. Cancer Res; 77(8); 1831-41. ©2017 AACR.

The impact of reconstruction and scanner characterisation on the diagnostic capability of a normal database for [123I]FP-CIT SPECT imaging

BackgroundThe use of a normal database for [123I]FP-CIT SPECT imaging has been found to be helpful for cases which are difficult to interpret by visual assessment alone, and to improve reproducibility in scan interpretation. The aim of this study was to assess whether the use of different tomographic reconstructions affects the performance of a normal [123I]FP-CIT SPECT database and also whether systems benefit from a system characterisation before a database is used.Seventy-seven [123I]FP-CIT SPECT studies from two sites and with 3-year clinical follow-up were assessed quantitatively for scan normality using the ENC-DAT normal database obtained in well-documented healthy subjects. Patient and normal data were reconstructed with iterative reconstruction with correction for attenuation, scatter and septal penetration (ACSC), the same reconstruction without corrections (IRNC), and filtered back-projection (FBP) with data quantified using small volume-of-interest (VOI) (BRASS) and large VOI (Southampton) analysis methods. Test performance was assessed with and without system characterisation, using receiver operating characteristics (ROC) analysis for age-independent data and using sensitivity/specificity analysis with age-matched normal values. The clinical diagnosis at follow-up was used as the standard of truth.ResultsThere were no significant differences in the age-independent quantitative assessment of scan normality across reconstructions, system characterisation and quantitative methods (ROC AUC 0.866–0.924). With BRASS quantification, there were no significant differences between the values of sensitivity (67.4–83.7%) or specificity (79.4–91.2%) across all reconstruction and calibration strategies. However, the Southampton method showed significant differences in sensitivity between ACSC (90.7%) vs IRNC (76.7%) and FBP (67.4%) reconstructions with calibration. Sensitivity using ACSC reconstruction with this method was also significantly better with calibration than without calibration (65.1%). Specificity using the Southampton method was unchanged across reconstruction and calibration choices (82.4–88.2%).ConclusionsThe ability of a normal [123I]FP-CIT SPECT database to assess clinical scan normality is equivalent across all reconstruction, system characterisation, and quantification strategies using BRASS quantification. However, when using the Southampton quantification method, performance is sensitive to the reconstruction and calibration strategy used.