Detection of Autism Using Structural Brain MRI with Improved Nimble Filter-Based Preprocessing and an EfficientNet Classifier

To explore the neuroimage change in Parkinson's disease (PD) patients with cognitive impairments, this study investigated the correlation between plasma biomarkers and morphological brain changes in patients with normal cognition and mild cognitive impairment. The objective was to identify the potential target deposition regions of the plasma biomarkers and to search for the relevant early neuroimaging biomarkers on the basis of different cognitive domains. Structural brain MRI and diffusion weighted images were analyzed from 49 eligible PD participants (male/female: 27/22; mean age: 73.4 ± 8.5years) from a retrospective analysis. Plasma levels of α-synuclein, amyloid beta peptide, and total tau were collected. A comprehensive neuropsychological assessment of the general and specific cognitive domains was performed. Difference between PD patients with normal cognition and impairment was examined. Regression analysis was performed to evaluate the correlation between image-derived index and plasma biomarkers or neuropsychological assessments. Significant correlation was found between plasma Aβ-42 level and fractional anisotropy of the middle occipital, angular, and middle temporal gyri of the left brain, as well as plasma T-tau level and the surface area of the isthmus or the average thickness of the posterior part of right cingulate gyrus. Visuospatial and executive function is positively correlated with axial diffusivity in bilateral cingulate gyri. In nondemented PD patients, the target regions for plasma deposition might be located in the cingulate, middle occipital, angular, and middle temporal gyri. Changes from multiple brain regions can be correlated to the performance of different cognitive domains. Cognitive impairment in Parkinson's disease is primarily linked to biomarkers associated with Alzheimer's disease rather than those related to Parkinson's disease and resembles the frontal variant of Alzheimer's disease, which may guide management strategies for cognitive impairment in Parkinson's disease. • Fractional anisotropy, surface area, and thickness in the cingulate, middle occipital, angular, and middle temporal gyri can be significantly correlated with plasma Aβ-42 and T-tau level. • Axial diffusivity in the cingulate gyri was correlated with visuospatial and executive function. • The pattern of cognitive impairment in Parkinson's disease can be similar to the frontal variant than typical Alzheimer's disease.

With the advent of disease-modifying therapies for Alzheimer's disease, there is a growing demand for more cost-effective methods that predict amyloid PET positivity. In Japan, the combination of structural brain MRI and regional cerebral blood flow (rCBF) single-photon emission computed tomography (rCBF SPECT) is routinely used in clinical practice for neuroimaging. The present study investigated the utility of this imaging approach for amyloid PET positivity in real-world clinical settings. A retrospective analysis of 101 patients who visited the Memory Clinic at Juntendo University Hospital between April 2019 and September 2023 was performed. All patients had undergone amyloid PET imaging at their own expense, in addition to a neuropsychological assessment, structural brain MRI and rCBF SPECT. Among 58 cases that underwent a voxel-based specific regional analysis system for Alzheimer's disease (VSRAD), volumetric differences between the amyloid-positive and -negative groups were assessed using Statistical Parametric Mapping (SPM) version 12. Among the 101 patients analysed, 68 were positive and 33 were negative for amyloid. Twenty-nine patients had a change in clinical diagnosis after amyloid PET imaging, which affected subsequent management. Using VSRAD, VOI severity (continuous value) was set to 0.95 based on Youden's index and AUC (95% CI) was 0.72 (0.572-0.867), with a sensitivity of 90%, specificity of 52% and accuracy of 78%. In the visual assessment, MRI and rCBF SPECT were combined, and AUC (95% CI) was 0.767 (0.629-0.905), with a sensitivity decrease to 21% and specificity increase to 95%. The SPM12 analysis revealed clusters in the right medial temporal lobe at an uncorrected threshold (p < 0.001). However, no voxels survived family-wise error (FWE) correction (p < 0.05). A VSRAD analysis of brain MRI has moderate discriminatory ability as a screening tool for predicting amyloid PET positivity. The addition of SPECT to MRI was not associated with a statistically significant improvement compared with MRI alone. SPECT may contribute to the differential diagnosis of non-Alzheimer's disease. MRI alone could be considered an option to increase the pre-test probability of amyloid PET positivity.

To describe the structural brain changes, neurocognitive and mental health associations in adolescents perinatally infected with HIV-1 infection. Cross-sectional. Two hundred and four adolescents with perinatally acquired HIV and 44 uninfected frequency-matched controls aged 9-11 years were enrolled within the Cape Town Adolescent Antiretroviral Cohort. Diffusion tensor imaging and structural brain MRI was done to determine fractional anisotropy, mean diffusivity, grey and white matter volumes, cortical thickness and cortical surfractional anisotropy area. Correlation coefficients were calculated between total grey and white matter volume, cortical surface area, cortical thickness, whole brain fractional anisotropy and whole brain mean diffusivity and clinical and laboratory parameters including general intellectual functioning, Becks Youth Inventory, Child Motivation Scale and Child Behaviour Checklist. HIV-infected adolescents performed worse than controls on the Wechsler Abbreviated Scale of Intelligence (WASI; P < 0.01). HIV-infected adolescents had significant fractional anisotropy decreases, mean diffusivity increases and decreases in cerebral grey matter volumes, cortical surface area and decreased gyrification. Whole-brain mean fractional anisotropy was significantly reduced in the HIV-infected group (P = 0.031). There were significant correlation coefficients between greater total grey (P = 0.008) and white matter volume (P = 0.004) with the WASI and the Becks self-concept subscale (P = 0.038). Lower whole brain fractional anisotropy was associated with higher scores on the Becks anger (P = 0.018) and disruptive behaviour subscales (P = 0.031). Higher whole brain mean diffusivity was associated with apathy (P = 0.046). The pattern of increased risk of white matter microstructure alterations, smaller grey matter volumes, reduced cortical surface area and decreased gyrification, suggests abnormal neurodevelopment in perinatally infected younger adolescents.

Perivascular Spaces (PVS), also known as Virchow-Robin spaces, seen on structural brain MRI, are important fluid drainage conduits and are associated with small vessel disease (SVD). Computational quantification of visible PVS may enable efficient analyses in large datasets and increase sensitivity to detect associations with brain disorders. We assessed the associations of computationally-derived PVS parameters with vascular factors and white matter hyperintensities (WMH), a marker of SVD. Community dwelling individuals (n=700) from the Lothian Birth Cohort 1936 who had multimodal brain MRI at age 72.6 years (SD=0.7). We assessed PVS computationally in the centrum semiovale and deep corona radiata on T2-weighted images. The computationally calculated measures were the total PVS volume and count per subject, and the mean individual PVS length, width and size, per subject. We assessed WMH by volume and visual Fazekas scores. We compared PVS visual rating to PVS computational metrics, and tested associations between each PVS measure and vascular risk factors (hypertension, diabetes, cholesterol), vascular history (cardiovascular disease and stroke), and WMH burden, using generalized linear models, which we compared using coefficients, confidence intervals and model fit. In 533 subjects, the computational PVS measures correlated positively with visual PVS ratings (PVS count r=0.59; PVS volume r=0.61; PVS mean length r=0.55; PVS mean width r=0.52; PVS mean size r=0.47). PVS size and width were associated with hypertension (OR 1.22, 95% CI [1.03 to 1.46] and 1.20, 95% CI [1.01 to 1.43], respectively), and stroke (OR 1.34, 95% CI [1.08 to 1.65] and 1.36, 95% CI [1.08 to 1.71], respectively). We found no association between other PVS measures and diabetes, hypercholesterolemia or cardiovascular disease history. Computational PVS volume, length, width and size were more strongly associated with WMH (PVS mean size versus WMH Fazekas score β=0.66, 95% CI [0.59 to 0.74] and versus WMH volume β=0.43, 95% CI [0.38 to 0.48]) than computational PVS count (WMH Fazekas score β=0.21, 95% CI [0.11 to 0.3]; WMH volume β=0.14, 95% CI [0.09 to 0.19]) or visual score. Individual PVS size showed the strongest association with WMH. Computational measures reflecting individual PVS size, length and width were more strongly associated with WMH, stroke and hypertension than computational count or visual PVS score. Multidimensional computational PVS metrics may increase sensitivity to detect associations of PVS with risk exposures, brain lesions and neurological disease, provide greater anatomic detail and accelerate understanding of disorders of brain fluid and waste clearance.

Background: COPD, cardiovascular disease and structural brain disease commonly coexist, but the relative contributions of COPD and cardiovascular disease to structural brain disease is unclear. Aim: The aim of this study was to determine the association between two different COPD phenotypes and structural brain disease. Methods: COPD patients were recruited from two populations. Group 1 were recruited from people attending for elective coronary angiography who had no exacerbations in the preceding year. Group 2 were recruited from people attending the respiratory outpatient department who had had at least 1 exacerbation in the preceding year. Participants underwent measurement of Framingham score (10-year risk of cardiovascular event), spirometry, arterial stiffness, skin capillary density, cardiac biomarkers, systemic inflammatory markers and structural brain MRI. Results: Group 1 had mild/moderate COPD with significantly higher cardiovascular risk whereas group 2 had moderate/severe COPD with lower cardiovascular risk (FEV1 % predicted 78±19 v 54±24 p Conclusion: Cardiovascular risk, rather than respiratory health, appears more strongly associated with white matter brain disease in these two groups of patients with COPD.

Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE), but its aetiology is unknown. MRI scans often reveal no structural brain abnormalities that could explain the cognitive impairment. This does not exclude more subtle morphological abnormalities that can only be detected by automated morphometric techniques. With these techniques, we investigate the relationship between cortical brain morphology and cognitive functioning in a cohort of children with FLE and healthy controls. Thirty-four children aged 8-13 years with FLE of unknown cause and 41 healthy age-matched controls underwent neuropsychological assessment and structural brain MRI. Patients were grouped as cognitively impaired or unimpaired. Intracranial volume, white matter volume, lobular cortical volume, cortical thickness and volumes of cortex structures were compared between patients and controls, and potential correlations with cognitive status were determined. The group of cognitively impaired children with FLE had significantly smaller left temporal cortex volumes, specifically middle temporal grey matter volume and entorhinal cortex thickness. In addition, cognitively impaired children with FLE had smaller volumes of structures in the left and right frontal cortex, right temporal cortex and the left subcortical area. Cognitively impaired children with FLE have smaller volumes of various cortex structures within the frontal lobes and in extra-frontal regions, most notably temporal cortex volumes. These findings might well explain the broad scale of cognitive domains affected in children with FLE complicated by cognitive impairment and highlight that FLE impacts on areas beyond the frontal lobe.

Objective: Traditional episodic memory tests employ a delayed recall length ranging from 10 to 30 min. The neurobiological process of memory consolidation extends well beyond these time intervals, however, raising the possibility that these tests might not be fully sensitive to the subtle neurocognitive changes found in early disease or age-related decline. We aimed to determine the sensitivity of a 1-week delayed recall paradigm to medial temporal lobe (MTL) structure among neurologically normal older adults. Methods: One hundred and forty functionally intact, older adults (mean age = 75.8) completed a story recall test in which participants learned to 90% criterion. Recall was tested after 30-min and 1-week. Participants also completed a standardized list learning task with a 20-min delay (n = 129) and a structural brain MRI. The MTL, including the parahippocampal gyrus, hippocampus, and entorhinal, was our primary region of interest. Results: Controlling for age, education, gender and total intracranial volume, the standard 20- and 30-min recalls showed no significant relationship with MTL. In contrast, 1-week recall was uniquely associated with MTL structure (partial r = .24, p = .006), specifically entorhinal (partial r = .27; p = .001) and hippocampal (partial r = .21, p = .02) volumes. Conclusion: Memory paradigms that utilize 1-week delays are more sensitive than standard paradigms to MTL volumes in neurologically normal older adults. Longer delay periods may improve detection of memory consolidation abilities associated with age-related, and potentially pathological, neurobehavioral change.

Comprehension of concrete and abstract words in semantic variant primary progressive aphasia and Alzheimer’s disease: A behavioral and neuroimaging study

Effect of intrathecal recombinant human arylsulfatase A enzyme replacement therapy on structural brain MRI in children with metachromatic leukodystrophy

The pathophysiology of rigidity in Parkinson's disease (PD) is poorly understood. Multi-sequence functional and structural brain MRI may further clarify the origin of this clinical characteristic. To examine both joint and unique relationships of MRI-based functional and structural imaging modalities to rigidity and other clinical features of PD. Retrospective cross-sectional study. 31 PD subjects (aged 68.0 ± 5.9 years, 21 males) with average disease duration 9.3 ± 5.4 years. Multi-echo GRASE, diffusion-weighted echo planar imaging (EPI), and blood oxygen level dependent contrast EPI T2*-weighted sequences on a 3T scanner. Myelin water fraction (MWF) and fractional anisotropy (FA) of 20 white-matter regions of interest (ROIs), and functional connectivity derived from resting-state fMRI among 56 ROIs were assessed. The Unified Parkinson's Disease Rating Scale-Part III, Montreal Cognitive Assessment, Beck Depression Index, and Apathy Rating Scales were used to assess motor and non-motor symptoms. Multiset canonical correlation analysis (MCCA) and canonical correlation analysis (CCA) were utilized to examine the joint and unique relationships of multiple imaging measures with clinical symptoms of PD. A permutation test was used to determine statistical significance (P < 0.05). MCCA revealed a single significant component jointly linking MWF, FA, and functional connectivity to age, bradykinesia, and leg agility, non-motor symptoms of cognition, depression, and apathy, but not rigidity (P=0.77), tremor (P=0.50 and 0.67 on the left and right side), or sex (P=0.54). After controlling for this joint component, CCA found a unique significant association between MWF and rigidity, but no other associations were detected, including with FA (P=0.87). MWF, FA, and functional connectivity can serve as multi-sequence imaging markers to characterize many PD symptoms. However, rigidity in PD is additionally associated with widespread myelin changes. 4 TECHNICAL EFFICACY: Stage 3.

BackgroundAnxiety is prevalent among cognitively unimpaired older adults and is associated with accelerated amyloid‐β‐related cognitive decline and incident cognitive impairment. Investigating these mechanisms is challenging due to low pathologic burden, high individual variability, and subsyndromal level of symptoms. Recently, brain networks involved in AD were successfully localized by mapping the brain connectivity of atrophy patterns associated with memory impairment and delusions. In this study, we investigated anxiety symptoms in older adults with elevated amyloid‐β using the novel method of atrophy network mapping.MethodWe utilized baseline data from ∼1800 cognitively unimpaired older adults, aged 65‐85, from the Anti‐Amyloid in Asymptomatic Alzheimer’s Disease (A4) trial, including clinical assessment of anxiety measured by the 6‐item State‐Trait Anxiety Inventory as well as structural brain MRI and amyloid‐β (18F‐florbetapir) PET acquisitions. We generated a vertex‐wise general linear model of cortical thickness to create individualized atrophy maps for each participant with elevated amyloid‐β deposition, using data from older adults with low amyloid‐β deposition as a control group. Then, we used a normative human connectome (n = 1000) to estimate the functional connectivity of each participant’s unique atrophy pattern. From the network connectivity maps, we identified atrophy‐based brain networks associated with higher anxiety. To validate this brain network, we performed a spatial correlation with a pre‐established anxiosomatic network derived from focal brain stimulation sites that selectively modify anxiety and assessed significance using permutation testing. We hypothesized that atrophy patterns associated with greater anxiety would correspond to this anxiosomatic network.ResultAnxiety symptoms localized to a distinct brain network based on individuals' atrophy patterns. The identified brain network was correlated to the anxiosomatic network (r = 0.65), and the correlation was stronger when controlled for depressive symptoms (r = 0.67). The network was more similar to the anxiosomatic network than expected by chance (p&lt;0.05).ConclusionWe identified a brain network associated with anxiety symptoms in cognitively unimpaired older adults with elevated amyloid‐β. These findings help elucidate a neuropathophysiology of anxiety in preclinical AD and, possibly, its role in disease progression. The brain network identified in this project could yield new neurostimulation targets for anxiety in older adults across the AD continuum.

Additive effect of NRG1 and DISC1 genes on lateral ventricle enlargement in first episode schizophrenia

Structural brain MRI has proven invaluable in understanding movement disorder pathophysiology. However, most work has focused on grey/white matter volumetric (macrostructural) and white matter microstructural effects, limiting understanding of frequently implicated grey matter microstructural differences. Using ultra-strong spherical tensor encoding diffusion-weighted MRI, a persistent MRI signal was seen in healthy cerebellar grey matter even at high diffusion-weightings (b ​≥ 10,000 s/mm2). Quantifying the proportion of this signal (denoted fs), previously ascertained to originate from inside small spherical spaces, provides a potential proxy for cell body density. In this work, this approach was applied for the first time to a clinical cohort, including patients with diagnosed movement disorders in which the cerebellum has been implicated in symptom pathophysiology. Five control participants (control group 1, median age 24.5 years (20–39 years), imaged at two timepoints, demonstrated consistency in measurement of all three measures - MD (Mean Diffusivity) fs, and Ds (dot diffusivity)- with intraclass correlation coefficients (ICC) of 0.98, 0.86 and 0.76, respectively. Comparison with an older control group (control group 2 (n = 5), median age 51 years (43–58 years)) found no significant differences, neither with morphometric nor microstructural (MD (p = 0.36), fs (p = 0.17) and Ds (p = 0.22)) measures. The movement disorder cohort (Parkinson’s Disease, n = 5, dystonia, n = 5. Spinocerebellar Ataxia 6, n = 5) when compared to the age-matched control cohort (Control Group 2) identified significantly lower MD (p < 0.0001 and p < 0.0001) and higher fs values (p < 0.0001 and p < 0.0001) in SCA6 and dystonia cohorts respectively. Lobar division of the cerebellum found these same differences in the superior and inferior posterior lobes, while no differences were seen in either the anterior lobes or with Ds measurements. In contrast to more conventional measures from diffusion tensor imaging, this framework provides enhanced specificity to differences in restricted spherical spaces in grey matter (including small cells) by eliminating signals from cerebrospinal fluid and axons. In the context of human and animal histopathology studies, these findings potentially implicate the cerebellar Purkinje and granule cells as contributors to the observed signal differences, with both cell types having been implicated in several neurological disorders through both postmortem and animal model studies. This novel microstructural imaging approach shows promise for improving movement disorder diagnosis, prognosis, and treatment.

Advanced MRI is recommended for the clinical evaluation of patients with coma. However, the implementation of these guidelines has been hindered by an inadequate identification of relevant markers among the vast amount of reported MRI-derived metrics. We developed and validated an innovative and explainable machine learning (ML) analytical pipeline to fill this critical knowledge gap. Prospective cross-sectional study. Three Intensive Critical Care Units affiliated to the University in Toulouse (France). Patients with coma (Glasgow Coma Scale score at the hospital admission ≤ 9) from either traumatic or anoxic origin. Patient's neurologic outcome was assessed at 3 months by using the Coma Recovery Scale-Revised. Whole-brain advanced structural MRI data and functional connectivity analysis of resting-state networks known to contribute to conscious processing. A specifically designed ensemble of explainable ML methods was applied and cross-validated. None. Overall, 64 patients with coma due to either traumatic (n = 26) or anoxic (n = 38) brain injuries were studied and compared with 55 controls. The median delay between ICU admission and MRI scan was 9 days (interquartile range, 6-16 d). At 3 months, 50% patients (32/64) had an unfavorable outcome. All the models showed valuable generalization capacities: coma diagnosis (mean accuracy, 0.934%), primary brain injury discrimination (mean accuracy, 0.762 %), and neurologic outcome prediction (mean accuracy, 0.824 %). A new ensemble of brain MRI-derived metrics was specifically related to coma state, its etiology, and the patient's potential for recovery at 3 months. The structural and functional integrity of mesocircuit and frontoparietal networks appeared to carry the most relevant information.

Elevated vascular disease risk associates with poorer cognitive function, but the mechanism for this link is poorly understood. A leading theory, the structural-functional model argues that vascular risk may drive adverse cardiac remodelling, which, in turn, leads to chronic cerebral hypoperfusion and subsequent brain structural damage. This model predicts that variation in heart and brain structure should associate with both greater vascular risk and lower cognitive function. This study tests that prediction in a large sample of the UK Biobank (N = 11,962). We assemble and summarise vascular risk factors, cardiac magnetic resonance radiomics, brain structural and diffusion MRI indices, and cognitive assessment. We also extract “heart-brain axes” capturing the covariation in heart and brain structure. Many heart and brain measures partially explain the vascular risk—cognitive function association, like left ventricular end-diastolic volume and grey matter volume. Notably, a heart-brain axis, capturing correlation between lower myocardial intensity, lower grey matter volume, and poorer thalamic white matter integrity, completely mediates the association, supporting the structural-functional model. Our findings also complicate this theory by finding that brain structural variation cannot completely explain the heart structure—cognitive function association. Our results broadly offer evidence for the structural functional hypothesis, identify imaging biomarkers for this association by considering covariation in heart and brain structure, and generate novel hypotheses about how cardiovascular risk may link to cognitive function.