Remote ischemic conditioning improves cerebral hemodynamics in symptomatic intracranial atherosclerosis: A PET/CT-guided randomized controlled study.

Patients with symptomatic intracranial arterial stenosis (sICAS) suffer embarrassed hemodynamic status and acute ischemic stroke (AIS) recurrence. We aimed to assess the efficacy of remote ischemic conditioning (RIC) on improving this status by evaluating cerebral blood flow (CBF) and cerebral glucose metabolism (CGM) via PET/CT. Adult patients with unilateral sICAS in middle cerebral artery and/or intracranial segment of internal carotid artery-related AIS or transient ischemic attack within 6 months prior to randomization were enrolled. Individuals who received intravenous thrombolysis or endovascular treatment, or sICAS caused by cardiac embolism, small vessel occlusion, or other determined causes were excluded. Twenty-three eligible patients were randomly assigned to standard medical treatment (SMT) (n = 10) or RIC group (n = 13). The RIC protocol consisted of 5 cycles, each for 5-min bilateral upper limb ischemia and 5-min reperfusion period, twice a day, with a total duration of 3 months. Ten healthy volunteers were enrolled as healthy control group. We tested CBF and CGM at the rest stage and the methazolamide-induced stress stage. All patients received PET/CT at baseline and three-month followup. Both CBF and CGM in ipsilateral hemisphere of sICAS patients were significantly decreased at the rest stage and the stress stage (p < .05), which were improved by three-month RIC (p < .05). The lesions decreased notably in RIC group compared to SMT group (p < .05). RIC ameliorated the hemodynamic status and glucose metabolism in regions at high risk of infarction, which might improve the resistance capacity towards ischemic load in sICAS patients.

Gray matter morphological anomalies in the cerebellar vermis in first-episode schizophrenia patients with cognitive deficits.

BACKGROUND: Cognitive deficits are a core feature of early schizophrenia. However, the pathological foundations underlying cognitive deficits are still unknown. The present study examined the association between gray matter density and cognitive deficits in first-episode schizophrenia. METHOD: Structural magnetic resonance imaging of the brain was performed in 34 first-episode schizophrenia patients and 21 healthy controls. Patients were divided into two subgroups according to working memory task performance. The three groups were well matched for age, gender, and education, and the two patient groups were also further matched for diagnosis, duration of illness, and antipsychotic treatment. Voxel-based morphometric analysis was performed to estimate changes in gray matter density in first-episode schizophrenia patients with cognitive deficits. The relationships between gray matter density and clinical outcomes were explored. RESULTS: Patients with cognitive deficits were found to have reduced gray matter density in the vermis and tonsil of cerebellum compared with patients without cognitive deficits and healthy controls, decreased gray matter density in left supplementary motor area, bilateral precentral gyrus compared with patients without cognitive deficits. Classifier results showed GMD in cerebellar vermis tonsil cluster could differentiate SZ-CD from controls, left supplementary motor area cluster could differentiate SZ-CD from SZ-NCD. Gray matter density values of the cerebellar vermis cluster in patients groups were positively correlated with cognitive severity. CONCLUSIONS: Decreased gray matter density in the vermis and tonsil of cerebellum may underlie early psychosis and serve as a candidate biomarker for schizophrenia with cognitive deficits.

The mediating effect of 18F-FDG metabolism in right caudate between depressive symptoms and cognitive function in Alzheimer's disease.

Purpose: The objective of this study was to investigate the accumulation of 18F-fluorodeoxyglucose (18F-FDG) in the whole brain between Alzheimer's disease (AD) with depressive (ADD) symptoms compared with AD without depressive (ADND) symptoms using positron emission tomography/magnetic resonance imaging (PET/MRI). Additionally, this study aimed to explore the associations among the accumulation of 18F-FDG in the brain, depressive symptoms, and cognitive function in ADD patients. Methods: In this study, 25 AD patients and 22 healthy controls were enrolled. The AD patients were stratified into two groups, namely ADD and ADND, based on their scores of the Hamilton Depression Scale (HAMD). Both AD patients and healthy controls underwent an 18F-FDG PET/MRI scan. A standardized uptake value ratio (SUVR) was calculated to examine the accumulation of 18F-FDG in the brain. A simple mediation model was employed to examine the mediation effect between SUVR, depressive symptoms and cognitive function in ADD patients. Results: The ADD group exhibited significant cognitive impairment compared to the ADND group (p < 0.001) and healthy controls (p < 0.001). The ADD patients exhibited the reduced SUVR (0.228 ± 0.126) in the right caudate (the voxel level p < 0.005, cluster level p < 0.05, after false discovery rate (FDR) correction) compared to ADND patients (0.459 ± 0.064) and healthy controls (0.706 ± 0.122). The SUVR of the right caudate was correlated with the HAMD scores (r = -0.792, p < 0.001) and mini-mental state examination (MMSE) (r = 0.738, p < 0.01). The relationship between depressive symptoms and the cognitive function in ADD patients is mediated by the right caudate SUVR (total effects = -0.385, direct effects = -0.02, total indirect effects = -0.405). Conclusion: The ADD group exhibited the reduced SUVR in the right caudate compared to the ADND group and healthy controls. The relationship between depressive symptoms and the cognitive ability of AD patients was mediated by the right caudate SUVR. The results contribute to a deeper understanding of the neurobiological mechanisms related to AD with depressive symptoms.

Specific structuro-metabolic pattern of thalamic subnuclei in fatal familial insomnia: A PET/MRI imaging study.

BACKGROUND: Dysfunction of the thalamus has been proposed as a core mechanism of fatal familial insomnia. However, detailed metabolic and structural alterations in thalamic subnuclei are not well documented. We aimed to address the multimodal structuro-metabolic pattern at the level of the thalamic nuclei in fatal familial insomnia patients, and investigated the clinical presentation of primary thalamic alterations. MATERIALS AND METHODS: Five fatal familial insomnia patients and 10 healthy controls were enrolled in this study. All participants underwent neuropsychological assessments, polysomnography, electroencephalogram, and cerebrospinal fluid tests. MRI and fluorodeoxyglucose PET were acquired on a hybrid PET/MRI system. Structural and metabolic changes were compared using voxel-based morphometry analyses and standardized uptake value ratio analyses, focusing on thalamic subnuclei region of interest analyses. Correlation analysis was conducted between gray matter volume and metabolic decrease ratios, and clinical features. RESULTS: The whole-brain analysis showed that gray matter volume decline was confined to the bilateral thalamus and right middle temporal pole in fatal familial insomnia patients, whereas hypometabolism was observed in the bilateral thalamus, basal ganglia, and widespread cortices, mainly in the forebrain. In the regions of interest analysis, gray matter volume and metabolism decreases were prominent in bilateral medial dorsal nuclei, anterior nuclei, and the pulvinar, which is consistent with neuropathological and clinical findings. A positive correlation was found between gray matter volume and metabolic decrease ratios. CONCLUSIONS: Our study revealed specific structuro-metabolic pattern of fatal familial insomnia that demonstrated the essential roles of medial dorsal nuclei, anterior nuclei, and pulvinar, which may be a potential biomarker in diagnosis. Also, primary thalamic subnuclei alterations may be correlated with insomnia, neuropsychiatric, and autonomic symptoms sparing primary cortical involvement.

Involvement of striatal motoric subregions in familial frontotemporal dementia with parkinsonism harboring the C9orf72 repeat expansions.

The chromosome 9 open reading frame 72 (C9ORF72) has been proposed as the causative gene of frontotemporal dementia with parkinsonism (FTDP), but its pathophysiological mechanism of parkinsonism is poorly understood. To explore the roles of striatal motor subdivisions in the pathogenesis of parkinsonism resulting from C9ORF72 repeat expansions in the FTDP, two patients with FTDP from one pedigree and seventeen healthy controls were enrolled. The participants received clinical interviews, physical examinations, genetic testing, [18F]-fluorodeoxyglucose PET/MRI, and [18F]-dihydrotetrabenazine PET/CT. Voxel-wise and region of interest analysis were conducted with respect to gray matter volume, metabolism, and dopamine transport function between patients and controls, focusing on the motor part of the striatum according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. Patient 1 presented with parkinsonism as the initial symptom, while patient 2 exhibited behavior disturbance as the first symptom, followed by parkinsonism within one year. Both patients had the hexanucleotide expansion detected in C9ORF72(>52 repeats). Gray matter volume atrophy, hypometabolism and dopamine dysfunction were observed in the motor areas of the striatum. Of the two patients, marked glucose hypometabolism within the striatal motor subregion was observed in patient 1, with corresponding gray matter atrophy. In addition, presynaptic dopaminergic integrity of patient 2 was deteriorated in the motor subregions which was consistent with gray matter atrophy. These findings imply that parkinsonism in FTDP may be associated with the degeneration and dopaminergic dysfunction of the striatal motor subregion, which might be attributed to C9orf72 repeat expansions.

Brain structural and functional anomalies associated with simultanagnosia in patients with posterior cortical atrophy.

Simultanagnosia is a common symptom of posterior cortical atrophy, and its association with brain structural and functional changes remains unclear. In our study, 18 posterior cortical atrophy patients with simultanagnosia, 29 patients with Alzheimer's disease and 20 cognitively normal controls were recruited and subjected to full neuropsychological evaluation, including simultanagnosia tests, and structural and resting-state functional MRI. The gray matter volume was assessed by voxel-based morphometry, while the intrinsic functional connectivity was evaluated using the reduced gray matter volume regions of interest as the seed. In contrast to the patients with Alzheimer's disease, those with posterior cortical atrophy showed the following: (1) markedly lower simultanagnosia test scores, (2) an altered regional gray matter volume of the left middle occipital gyrus and ventral occipital areas, and (3) lowered intrinsic functional connectivity with the left middle occipital gyrus, left lingual gyrus and right middle occipital gyrus separately. Additionally, the gray matter volume of the left middle occipital gyrus and left inferior occipital gyrus were each correlated with simultanagnosia in posterior cortical atrophy patients. The intrinsic functional connectivity of the left middle occipital gyrus with the right superior occipital gyrus and that of the right middle occipital gyrus with the left superior parietal gyrus were also correlated with simultanagnosia in posterior cortical atrophy patients. In summary, this study indicated that simultanagnosia is associated with gray matter reductions and decreased functional connectivity in the left middle occipital gyrus and the left inferior occipital gyrus in patients with posterior cortical atrophy.

Evaluating the association between brain atrophy, hypometabolism, and cognitive decline in Alzheimer's disease: a PET/MRI study.

Glucose metabolism reduction and brain volume losses are widely reported in Alzheimer's disease (AD). Considering that neuroimaging changes in the hippocampus and default mode network (DMN) are promising important candidate biomarkers and have been included in the research criteria for the diagnosis of AD, it is hypothesized that atrophy and metabolic changes of the abovementioned regions could be evaluated concurrently to fully explore the neural mechanisms underlying cognitive impairment in AD. Twenty-three AD patients and Twenty-four age-, sex- and education level-matched normal controls underwent a clinical interview, a detailed neuropsychological assessment and a simultaneous 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET)/high-resolution T1-weighted magnetic resonance imaging (MRI) scan on a hybrid GE SIGNA PET/MR scanner. Brain volume and glucose metabolism were examined in patients and controls to reveal group differences. Multiple linear regression models were employed to explore the relationship between multiple imaging features and cognitive performance in AD. The AD group had significantly reduced volume in the hippocampus and DMN regions (P < 0.001) relative to that of normal controls determined by using ROI analysis. Compared to normal controls, significantly decreased metabolism in the DMN (P < 0.001) was also found in AD patients, which still survived after controlling for gray matter atrophy (P < 0.001). These findings from ROI analysis were further confirmed by whole-brain confirmatory analysis (P < 0.001, FWE-corrected). Finally, multiple linear regression results showed that impairment of multiple cognitive tasks was significantly correlated with the combination of DMN hypometabolism and atrophy in the hippocampus and DMN regions. This study demonstrated that combining functional and structural features can better explain the cognitive decline of AD patients than unimodal FDG or brain volume changes alone. These findings may have important implications for understanding the neural mechanisms of cognitive decline in AD.

White Matter Integrity Involvement in the Preclinical Stage of Familial Creutzfeldt-Jakob Disease: A Diffusion Tensor Imaging Study.

OBJECTIVE: The objective of the study was to explore patterns of white matter (WM) alteration in preclinical stage familial Creutzfeldt-Jakob disease (fCJD) using diffusion tensor imaging (DTI). METHODS: Seven asymptomatic carriers of the PRNP G114V mutation and six non-carriers were recruited from the same fCJD kindred and follow-up obtained from all asymptomatic carriers and two non-carriers 2 years later. Overlapping WM patterns were also explored in asymptomatic carriers and symptomatic CJD patients. All participants underwent clinical and neuropsychological assessments and DTI at baseline and follow-up. DTI data were subjected to whole-brain voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) in WM using tract-based spatial statistics. Three comparisons were conducted: baseline carriers against non-carriers (baseline analysis), changes after 2 years in carriers (follow-up analysis), and differences between patients with symptomatic CJD and healthy controls (CJD patient analysis). RESULTS: Neither carriers nor non-carriers developed any neurological symptoms during 2 years of follow-up. Baseline analysis showed no differences between the carrier and non-carrier groups in MD and FA. Follow-up analysis showed significantly increased MD in multiple WM tracts, among which increased MD in the bilateral superior longitudinal fasciculus, bilateral anterior thalamic radiation, bilateral cingulate gyrus, and left uncinate fasciculus overlapped the patterns observed in patients with symptomatic CJD. CONCLUSION: Changes in integrity within multiple WM tracts can be detected during the preclinical stage of fCJD.

Metabolic Changes Detected by 18F-FDG PET in the Preclinical Stage of Familial Creutzfeldt-Jakob Disease.

BACKGROUND: Pathologic processes in Creutzfeldt-Jakob disease (CJD) are not fully understood. Familial CJD (fCJD) gives opportunities to discover pathologic changes in the preclinical stage. OBJECTIVE: To investigate cerebral glucose metabolism in the preclinical stage via 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in fCJD. METHODS: Seven asymptomatic carriers of G114V mutation and six family members without PRNP mutation from the same fCJD kindred were included, and were followed for 2 years. Ten symptomatic CJD patients were also recruited. All subjects underwent standardized clinical examinations and 18F-FDG PET scans. Results were compared in three groups: baseline carriers against non-carriers (baseline analysis), changes after 2 years in carriers (follow-up analysis), and differences between symptomatic CJD patients and healthy controls (CJD patients analysis). RESULTS: No carriers developed any neurological symptoms during 2-year follow-up. Baseline analysis: carriers demonstrates decreased metabolism (p < 0.001) in left and right postcentral, left fusiform, left superior temporal, left lingual, left superior parietal, and left Heschl gyrus. Follow-up analysis shows metabolic decline (p < 0.001) in right inferior temporal, left supra-marginal and left postcentral lobe, and increased metabolism (p < 0.001) in left fusiform, left angular, left thalamus, left Heschl's, right Rolandic operculum, and left superior parietal gyrus. CJD patients demonstrates decreased metabolism in right inferior triangularis frontal gyrus, right middle occipital gyrus, right putamen, right thalamus, and right middle temporal gyrus. CONCLUSION: Hypo-metabolism of parietal and temporal lobe can be detected by 18F-FDG PET in the preclinical stage of CJD. Subcortical area might compensate in the preclinical stage and decompensate in the symptomatic stage.

Diagnostic Approach of Early-Onset Dementia with Negative Family History: Implications from Two Cases of Early-Onset Alzheimer's Disease with De Novo PSEN1 Mutation.

For early-onset Alzheimer's disease (EOAD) cases with unclear family history, most cases are sporadic. Some cases are positive in genetic findings, that is, either incomplete penetrance or de novo mutation. We aimed to focus on EOAD cases with de novo mutations. Case reports and literature review were performed. The implication for diagnostic approach of early-onset dementia with negative family history was developed. We reported two Chinese EOAD cases with de novo mutations. The genotype PSEN1 G206S appeared to correlate with the phenotype of EOAD with pure cognitive problems. The second case had a PSEN1 M233V mutation with an earlier age of onset of 25 with cognitive decline, parkinsonism, and epilepsy. Although EOAD due to de novo mutations is not common, it should be considered in patients with a phenotype of progressive cognitive decline and amyloid positivity on PET or CSF analysis.

Intra-tumoural heterogeneity characterization through texture and colour analysis for differentiation of non-small cell lung carcinoma subtypes.

Radiomics has shown potential in disease diagnosis, but its feasibility for non-small cell lung carcinoma (NSCLC) subtype classification is unclear. This study aims to explore the diagnosis value of texture and colour features from positron emission tomography computed tomography (PET-CT) images in differentiation of NSCLC subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). Two patient cohorts were retrospectively collected into a dataset of 341 18F-labeled 2-deoxy-2fluoro-d-glucose ([18F] FDG) PET-CT images of NSCLC tumours (125 ADC, 174 SqCC, and 42 cases with unknown subtype). Quantification of texture and colour features was performed using freehand regions of interest. The relation between extracted features and commonly used parameters such as age, gender, tumour size, and standard uptake value (SUVmax) was explored. To classify NSCLC subtypes, support vector machine algorithm was applied on these features and the classification performance was evaluated by receiver operating characteristic curve analysis. There was a significant difference between ADC and SqCC subtypes in texture and colour features (P < 0.05); this showed that imaging features were significantly correlated to both SUVmax and tumour diameter (P < 0.05). When evaluating classification performance, features combining texture and colour showed an AUC of 0.89 (95% CI, 0.78-1.00), colour features showed an AUC of 0.85 (95% CI, 0.71-0.99), and texture features showed an AUC of 0.68 (95% CI, 0.48-0.88). DeLong's test showed that AUC was higher for features combining texture and colour than that for texture features only (P = 0.010), but not significantly different from that for colour features only (P = 0.328). HSV colour features showed a similar performance to RGB colour features (P = 0.473). The colour features are promising in the refinement of NSCLC subtype differentiation, and features combining texture and colour of PET-CT images could result in better classification performance.