BACKGROUND AND PURPOSE: Involvement of the corpus callosum (CC) is reported to be a consistent feature of amyotrophic lateral sclerosis (ALS). We examined the CC pathology using diffusion tensor tractography analysis to identify precisely which fiber bundles are involved in ALS. METHODS: Diffusion tensor imaging was performed in 14 sporadic ALS patients and 16 age-matched healthy controls. Whole brain tractography was performed using the multiple-region of interest (ROI) approach, and CC fiber bundles were extracted in two ways based on functional and structural relevance: (i) cortical ROI selection based on Brodmann areas (BAs), and (ii) the sulcal-gyral pattern of cortical gray matter using FreeSurfer software, respectively. RESULTS: The mean fractional anisotropy (FA) values of the CC fibers interconnecting the primary motor (BA4), supplementary motor (BA6), and dorsolateral prefrontal cortex (BA9/46) were significantly lower in ALS patients than in controls, whereas those of the primary sensory cortex (BA1, BA2, BA3), Broca's area (BA44/45), and the orbitofrontal cortex (BA11/47) did not differ significantly between the two groups. The FreeSurfer ROI approach revealed a very similar pattern of abnormalities. In addition, a significant correlation was found between the mean FA value of the CC fibers interconnecting the primary motor area and disease severity, as assessed using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale, and the clinical extent of upper motor neuron signs. CONCLUSIONS: Our findings suggest that there is some degree of selectivity or a gradient in the CC pathology in ALS. The CC fibers interconnecting the primary motor and dorsolateral prefrontal cortices may be preferentially involved in ALS.
Amyotrophic Lateral Sclerosis* ; Anisotropy ; Brain ; Corpus Callosum* ; Diffusion Tensor Imaging ; Diffusion* ; Humans ; Motor Neuron Disease ; Motor Neurons ; Pathology ; Prefrontal Cortex

For more anatomically precise quantitation of mouse brain PET, spatial normalization (SN) of PET onto MR template and subsequent template volumes-of-interest (VOIs)-based analysis are commonly used. Although this leads to dependency on the corresponding MR and the process of SN, routine preclinical/clinical PET images cannot always afford corresponding MR and relevant VOIs. To resolve this issue, we propose a deep learning (DL)-based individual-brain-specific VOIs (i.e., cortex, hippocampus, striatum, thalamus, and cerebellum) directly generated from PET images using the inverse-spatialnormalization (iSN)-based VOI labels and deep convolutional neural network model (deep CNN). Our technique was applied to mutated amyloid precursor protein and presenilin-1 mouse model of Alzheimer’s disease. Eighteen mice underwent T2-weighted MRI and 18 F FDG PET scans before and after the administration of human immunoglobin or antibody-based treatments. To train the CNN, PET images were used as inputs and MR iSN-based target VOIs as labels. Our devised methods achieved decent performance in terms of not only VOI agreements (i.e., Dice similarity coefficient) but also the correlation of mean counts and SUVR, and CNN-based VOIs was highly accordant with ground-truth (the corresponding MR and MR template-based VOIs). Moreover, the performance metrics were comparable to that of VOI generated by MR-based deep CNN. In conclusion, we established a novel quantitative analysis method both MR-less and SN-less fashion to generate individual brain space VOIs using MR template-based VOIs for PET image quantification.

Purpose: We compared the feasibility of quantitative analysis methods using bone SPECT/CT with those using planar bone scans to assess active sacroiliitis. Methods: We retrospectively reviewed whole-body bone scans and pelvic bone SPECT/CTs of 8 patients who had clinically confirmed sacroiliitis and enrolled 24 patients without sacroiliitis as references. The volume of interest of each sacroiliac joint, including both the ilium and sacrum, was drawn. Active arthritis zone (AAZ) was defined as the zone of voxels with higher SUV than sacral mean SUV within the VOI of SI joint. Then, the following SPECT/CT quantitative parameters, SUVmax (maximum SUV), SUV50% (mean SUV in highest 50% of SUV), and SUV-AAZ, and the ratio of those values to sacral mean SUV (SUVmax/S, SUV50%/S, SUV-AAZ/S) were calculated. For the planar bone scan, the mean count ratio of SI joint/sacrum (SI/S) was conventionally measured. Results: Most of the SPECT/CT parameters of the sacroiliitis group were significantly higher than the normal group, whereas SI/S of the planar bone scan was not significantly different between the two groups. In receiver operating characteristic curve analysis, SUV-AAZ/S showed the highest AUC of 0.992, followed by SUV50%/S and SUVmax/S. All ratio parameters of the SPECT/CT showed higher AUC values than the SUV parameters of SI joint or SI/S of the planar scan. Conclusions The quantitative analyses of bone SPECT/CT showed better performance in assessing active sacroiliitis than the planar bone scan. SPECT/CT parameters using the ratio of the SI joint to sacrum showed more favorable results than SUV parameters such as SUVmax, SUV50%, and SUV-AAZ.

Purpose: Neuroinflammation is considered an important pathway associated with several diseases that result in cognitive decline. 18F-THK5351 positron emission tomography (PET) signals might indicate the presence of neuroinflammation, as well as Alzheimer’s disease-type tau aggregates. β-amyloid (Aβ)-negative (Aβ–) amnestic mild cognitive impairment (aMCI) may be associated with non-Alzheimer’s disease pathophysiology. Accordingly, we investigated associations between 18F-THK5351 PET positivity and cognitive decline among Aβ– aMCI patients. Materials and Methods: The present study included 25 amyloid PET negative aMCI patients who underwent a minimum of two follow-up neuropsychological evaluations, including clinical dementia rating-sum of boxes (CDR-SOB). The patients were classified into two groups: 18F-THK5351-positive and -negative groups. The present study used a linear mixed effects model to estimate the effects of 18F-THK5351 PET positivity on cognitive prognosis among Aβ– aMCI patients. Results: Among the 25 Aβ– aMCI patients, 10 (40.0%) were 18F-THK5351 positive. The patients in the 18F-THK5351-positive group were older than those in the 18F-THK5351-negative group (77.4±2.2 years vs. 70.0±5.5 years; p<0.001). There was no difference between the two groups with regard to the proportion of apolipoprotein E ε4 carriers. Interestingly, however, the CDR-SOB scores of the 18F-THK5351-positive group deteriorated at a faster rate than those of the 18F-THK5351-negative group (B=0.003, p=0.033). Conclusion The results of the present study suggest that increased 18F-THK5351 uptake might be a useful predictor of poor prognosis among Aβ– aMCI patients, which might be associated with increased neuroinflammation (ClinicalTrials.gov NCT02656498).

PURPOSE: Dopamine transporter imaging is suggested to be a useful imaging biomarker for Parkinson's disease (PD) progression and monitoring drug effects.We investigated the longitudinal decline characteristics of striatal [¹⁸F]FP-CIT uptake in PD.METHODS: We retrospectively reviewed 35 PD patients and 9 non-PD patients. All patients underwent [¹⁸F]FP-CIT PET at the initial diagnosis and follow-up. PET images were spatially normalized and analyzed with eight striatal and one occipital VOI templates. We measured the specific to non-specific binding ratio (SNBR) of the striatal subregions and calculated the absolute annual reduction (AAR) and relative annual reduction (%RAR) of the SNBRs.RESULTS: Total striatal SNBRs in PD patients were significantly lower than those in non-PD patients, with the most significant difference in the posterior putamen. Both AAR (0.26 ± 0.14 vs. 0.09 ± 0.19, p < 0.05) and %RAR (6.9 ± 3.5 vs. 1.2 ± 2.7, p < 0.001) of total striatal SNBRs were significantly greater in PD than non-PD patients. There were no significant differences in the AAR and %RAR of total striatal SNBRs between elderly and young onset PD. The AARs of the posterior putamen were higher in early PD than in advanced PD. Conversely, the %RARs were not significantly different between early and more advanced PD. The disease duration was significantly negatively correlated with the AAR but not with the %RAR of the posterior putamen.CONCLUSIONS: The longitudinal decline of striatal [¹⁸F]FP-CIT uptake in PD was nonlinear and significantly faster than that in non-PD, with a different rate of decline among the striatal subregions.
Aged ; Diagnosis ; Dopamine Plasma Membrane Transport Proteins ; Follow-Up Studies ; Humans ; Parkinson Disease ; Putamen ; Retrospective Studies

Background: and Purpose Alzheimer’s disease (AD) does not always mean amyloid positivity. [ 18 F]THK-5351 has been shown to be able to detect reactive astrogliosis as well as tau accompanied by neurodegenerative changes. We evaluated the [ 18 F]THK-5351 retention patterns in positron-emission tomography (PET) and the clinical characteristics of patients clinically diagnosed with AD dementia who had negative amyloid PET findings. Methods: We performed 3.0-T magnetic resonance imaging, [ 18 F]THK-5351 PET, and amyloid PET in 164 patients with AD dementia. Amyloid PET was visually scored as positive or negative. [ 18 F]THK-5351 PET were visually classified as having an intratemporal or extratemporal spread pattern. Results: The 164 patients included 23 (14.0%) who were amyloid-negative (age 74.9±8.3 years, mean±standard deviation; 9 males, 14 females). Amyloid-negative patients were older, had a higher prevalence of diabetes mellitus, and had better visuospatial and memory functions. The frequency of the apolipoprotein E ε4 allele was higher and the hippocampal volume was smaller in amyloid-positive patients. [ 18 F]THK-5351 uptake patterns of the amyloid-negative patients were classified into intratemporal spread (n=10) and extratemporal spread (n=13).Neuropsychological test results did not differ significantly between these two groups. The standardized uptake value ratio of [ 18 F]THK-5351 was higher in the extratemporal spread group (2.01±0.26 vs. 1.61±0.15, p=0.001). After 1 year, Mini Mental State Examination (MMSE) scores decreased significantly in the extratemporal spread group (-3.5±3.2, p=0.006) but not in the intratemporal spread group (-0.5±2.8, p=0.916). The diagnosis remained as AD (n=5, 50%) or changed to other diagnoses (n=5, 50%) in the intratemporal group, whereas it remained as AD (n=8, 61.5%) or changed to frontotemporal dementia (n=4, 30.8%) and other diagnoses (n=1, 7.7%) in the extratemporal spread group. Conclusions Approximately 70% of the patients with amyloid-negative AD showed abnormal [ 18 F]THK-5351 retention. MMSE scores deteriorated rapidly in the patients with an extratemporal spread pattern.

Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) may be a promising modality for treating medial temporal lobe epilepsy. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a noninvasive method for monitoring in vivo glucose metabolism. We evaluated the efficacy of hUCB-MSCs transplantation in chronic epileptic rats using FDG-PET. Rats with recurrent seizures were randomly assigned into three groups: the stem cell treatment (SCT) group received hUCB-MSCs transplantation into the right hippocampus, the sham control (ShC) group received same procedure with saline, and the positive control (PC) group consisted of treatment-negative epileptic rats. Normal rats received hUCB-MSCs transplantation acted as the negative control (NC). FDG-PET was performed at pre-treatment baseline and 1- and 8-week posttreatment. Hippocampal volume was evaluated and histological examination was done. In the SCT group, bilateral hippocampi at 8-week after transplantation showed significantly higher glucose metabolism (0.990 +/- 0.032) than the ShC (0.873 +/- 0.087; P < 0.001) and PC groups (0.858 +/- 0.093; P < 0.001). Histological examination resulted that the transplanted hUCB-MSCs survived in the ipsilateral hippocampus and migrated to the contralateral hippocampus but did not differentiate. In spite of successful engraftment, seizure frequency among the groups was not significantly different. Transplanted hUCB-MSCs can engraft and migrate, thereby partially restoring bilateral hippocampal glucose metabolism. The results suggest encouraging effect of hUCB-MSCs on restoring epileptic networks.
Animals ; Chronic Disease ; Cord Blood Stem Cell Transplantation/*methods ; Epilepsy, Temporal Lobe/*metabolism/pathology/*therapy ; Fluorodeoxyglucose F18/*pharmacokinetics ; Hippocampus/*metabolism/*pathology/surgery ; Male ; Mesenchymal Stem Cell Transplantation/methods ; Radiopharmaceuticals/pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sensitivity and Specificity ; Tissue Distribution ; Treatment Outcome

Background: Drug-induced parkinsonism (DIP) is common, but diagnosis is challenging.Although dopamine transporter imaging is useful, the cost and inconvenience are problematic, and an easily accessible screening technique is needed. We aimed to determine whether optical coherence tomography (OCT) findings could differentiate DIP from Parkinson’s disease (PD). Methods: We investigated 97 de novo PD patients and 27 DIP patients using OCT and [ 18 F] N-(3-fluoropropyl)-2b-carbon ethoxy-3b-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography. We compared peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular retinal thickness (mRT) between PD and DIP patients as well as interocular differences in the pRNFLT and the mRT. Asymmetric index (%) for retinal thickness (AIRT) was calculated to measure the interocular differences between pRNFLT and mRT. The correlation between AIRT and total striatal specificon-specific binding ratio asymmetry index (SNBRAI) was investigated in PD and DIP patients. Results: No significant differences in pRNFLT and mRT values were observed between PD and DIP patients (all Pvalues > 0.090). The mean SNBRAI was significantly higher in PD than in DIP (P = 0.008) patients; however, AIRT did not differ between PD and DIP patients in pRNFLT and mRT (all P values > 0.100). SNBRAI did not correlate with AIRT of pRNFL or mRT in PD and DIP patients (all P values > 0.060). Conclusion Our study showed no benefit of retinal thickness and interocular asymmetry measurements using OCT for distinguishing PD from DIP in the early stages. Additional investigations are needed for confirmation.