Whole-brain Volume Research Articles

DOP18 Brain structural correlates of fatigue in active and quiescent Crohn’s Disease

Abstract Background Fatigue is a common and debilitating symptom in IBD, affecting the majority of patients with active disease. While impaired energy metabolism may contribute to the development of fatigue during active phases of the disease, the high prevalence of fatigue in remitted IBD is less comprehensible. The underlying mechanisms of fatigue are poorly understood, but a disturbance along the microbiota-gut-brain-axis seems likely. This study examined brain structural correlates of fatigue in patients with Crohn’s Disease (CD) in an active (aCD) or quiescent (qCD) state and healthy controls (HC). Methods Patients with CD (n=45; aCD=22, qCD=23) and HC (n=35) underwent structural MRI at 3T and completed a questionnaire (WEIMuS) to assess somatic (sFat) and cognitive fatigue (cFat). Whole-brain grey matter volume (GMV) was analysed using CAT12 in SPM12. We calculated group differences between HC and CD as well as CD subgroups and extracted raw values of anatomical regions with significant differences between the groups (at p<.005; k=173) for subsequent correlation analyses with sFat and cFat (Spearman’s ρ). Results Patients had significantly higher mean fatigue scores than HC (both sFat and cFat, p<0.001). Patients with aCD had higher mean fatigue scores than qCD, but differences between groups were not significant (p>0.2). Differences in GMV between CD (aCD+qCD) and HC were detected in frontal, temporal, parietal, and occipital cortex, as well as in the putamen and cerebellum (all p<.005). Across the patient group, GMV in the majority of the above mentioned regions was negatively correlated with sFat and cFat (Fig. 1). Subgroup analysis revealed a negative correlation between sFat and GMV in inferior frontal gyrus in aCD, while several other regions were negatively associated with both sFat and cFat in qCD (all p<.05). No positive correlations between GMV and fatigue were observed. Conclusion This study suggests a brain structural involvement in fatigue symptoms in CD. While fatigue is more common in active CD, the symptom correlation with GMV in this study was more widespread in patients with quiescent disease. The results indicate possible differences in the development and/or processing of fatigue in different disease states and may reflect disturbed brain-gut-interactions in quiescent CD with fatigue. These findings can help to increase our understanding of fatigue in CD and indicate that different therapeutic approaches targeting fatigue in CD may need to be considered depending on the state of disease activity.

Overexpression of VIPR2 in mice results in microencephaly with paradoxical increased white matter volume

Large scale studies in populations of European and Han Chinese ancestry found a series of rare gain-of-function microduplications in VIPR2, encoding VPAC2, a receptor that binds vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide with high affinity, that were associated with an up to 13-fold increased risk for schizophrenia. To address how VPAC2 receptor overactivity might affect brain development, we used a well-characterized Nestin-Cre mouse strain and a knock-in approach to overexpress human VPAC2 in the central nervous system. Mice that overexpressed VPAC2 were found to exhibit a significant reduction in brain weight. Magnetic resonance imaging analysis confirmed a decrease in brain size, a specific reduction in the hippocampus grey matter volume and a paradoxical increase in whole-brain white matter volume. Sex-specific changes in behavior such as impaired prepulse inhibition and contextual fear memory were observed in VPAC2 overexpressing mice. The data indicate that the VPAC2 receptor may play a critical role in brain morphogenesis and suggest that overactive VPAC2 signaling during development plays a mechanistic role in some forms of schizophrenia.

Optical coherence tomography reflects clinically relevant gray matter damage in patients with multiple sclerosis

BackgroundRetinal degeneration leading to optical coherence tomography (OCT) changes is frequent in patients with multiple sclerosis (PwMS).ObjectiveTo investigate associations among OCT changes, MRI measurements of global and regional brain volume loss, and physical and cognitive impairment in PwMS.Methods95 PwMS and 52 healthy controls underwent OCT and MRI examinations. Mean peripapillary retinal nerve fiber layer (pRNFL) thickness and ganglion cell/inner plexiform layer (GCIPL) volume were measured. In PwMS disability was quantified with the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT). Associations between OCT, MRI, and clinical measures were investigated with multivariable regression models.ResultsIn PwMS, pRNFL and GCIPL were associated with the volume of whole brain (p < 0.04), total gray matter (p < 0.002), thalamus (p ≤ 0.04), and cerebral cortex (p ≤ 0.003) –both globally and regionally–, but not white matter. pRNFL and GCIPL were also inversely associated with T2-lesion volume (T2LV), especially in the optic radiations (p < 0.0001). The brain volumes associated with EDSS and SDMT significantly overlapped with those correlating with pRNFL and GCIPL.ConclusionsIn PwMS, pRNFL and GCIPL reflect the integrity of clinically-relevant gray matter structures, underling the value of OCT measures as markers of neurodegeneration and disability in multiple sclerosis.

Volumetric brain changes in MOGAD: A cross-sectional and longitudinal comparative analysis

Relatively little is known about how global and regional brain volumes changes in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) compare with Multiple Sclerosis (MS), Neuromyelitis optica spectrum disorder (NMOSD), and healthy controls (HC). To compare global and regional brain volumes in MOGAD, MS, NMOSD, and HC cross-sectionally as well as longitudinally in a subset of patients. We retrospectively reviewed all adult MOGAD and NMOSD patients with brain MRI performed in stable remission and compared them with MS patients and HC. Volumetric parameters were assessed using the FDA-approved icobrain software. adjusted for age and sex. Twenty-four MOGAD, 47 NMOSD, 40 MS patients, and 37 HC were included in the cross-sectional analyses. Relative to HC, the age-adjusted whole brain (WB) volume was significantly lower in patients with MOGAD (p=0.0002), NMOSD (p=0.042), and MS (p=0.01). Longitudinal analysis of a subset of 8 MOGAD, 22 NMOSD, and 34 MS patients showed a reduction in the WB and cortical gray matter (CGM) volumes over time in all three disease groups, without statistically significant differences between groups. The MOGAD group had a greater loss of thalamic volume compared to MS (p=0.028) and NMOSD (p=0.023) and a greater loss of hippocampal volumes compared to MS (p=0.007). Age-adjusted WB volume loss was evident in all neuroinflammatory conditions relative to HC in cross-sectional comparisons. In longitudinal analyses, MOGAD patients had a higher thalamic atrophy rate relative to MS and NMOSD, and a higher hippocampal atrophy rate relative to MS. Larger studies are needed to validate these findings and to investigate their clinical implications.

An MRI-based morphometric and structural covariance network study of Brazilian adolescents stratified by depression risk.

To explore differences in regional cortical morphometric structure between adolescents at risk for depression or with current depression. We analyzed cross-sectional structural neuroimaging data from a sample of 150 Brazilian adolescents classified as low-risk (n=50) or high-risk for depression (n=50) or with current depression (n=50) through a vertex-based approach with measurements of cortical volume, surface area and thickness. Differences between groups in subcortical volumes and in the organization of networks of structural covariance were also explored. No significant differences in brain structure between groups were observed in whole-brain vertex-wise cortical volume, surface area or thickness. Also, no significant differences in subcortical volume were observed between risk groups. In relation to the structural covariance network, there was an indication of an increase in the hippocampus betweenness centrality index in the high-risk group network compared to the low-risk and current depression group networks. However, this result was only statistically significant when applying false discovery rate correction for nodes within the affective network. In an adolescent sample recruited using an empirically based composite risk score, no major differences in brain structure were detected according to the risk and presence of depression.

Artificial neural network applied to fragile X-associated tremor/ataxia syndrome stage diagnosis based on peripheral mitochondrial bioenergetics and brain imaging outcomes.

No proven prognosis is available for the neurodegenerative disorder fragile X-associated tremor/ataxia syndrome (FXTAS). Artificial neural network analyses (ANN) were used to predict FXTAS progression using data from 127 adults (noncarriers and FMR1 premutation carriers with and without FXTAS) with five outcomes from brain MRI imaging and 22 peripheral bioenergetic outcomes from two cell types. Diagnosis accuracy by ANN predictions ranged from 41.7 to 86.3% (depending on the algorithm used), and those misclassified usually presented a higher FXTAS stage. ANN prediction of FXTAS stages was based on a combination of two imaging findings (white matter hyperintensity and whole-brain volumes adjusted for intracranial volume) and four bioenergetic outcomes. Those at Stage 3 vs. 0-2 showed lower mitochondrial mass, higher oxidative stress, and an altered electron transfer consistent with mitochondrial unfolded protein response activation. Those at Stages 4-5 vs. 3 had higher oxidative stress and glycerol-3-phosphate-linked ATP production, suggesting that targeting mGPDH activity may prevent a worse prognosis. This was confirmed by the bioenergetic improvement of inhibiting mGPDH with metformin in affected fibroblasts. ANN supports the prospect of an unbiased molecular definition in diagnosing FXTAS stages while identifying potential targets for personalized medicine.

Prenatal heroin exposure alters brain morphology and connectivity in adolescent mice.

The United States is experiencing a dramatic increase in maternal opioid misuse and, consequently, the number of individuals exposed to opioids in utero. Prenatal opioid exposure has both acute and long-lasting effects on health and wellbeing. Effects on the brain, often identified at school age, manifest as cognitive impairment, attention deficit, and reduced scholastic achievement. The neurobiological basis for these effects is poorly understood. Here, we examine how in utero exposure to heroin affects brain development into early adolescence in a mouse model. Pregnant C57BL/6J mice received escalating doses of heroin twice daily on gestational days 4-18. The brains of offspring were assessed on postnatal day 28 using 9.4 T diffusion MRI of postmortem specimens at 36 μm resolution. Whole-brain volumes and the volumes of 166 bilateral regions were compared between heroin-exposed and control offspring. We identified a reduction in whole-brain volume in heroin-exposed offspring and heroin-associated volume changes in 29 regions after standardizing for whole-brain volume. Regions with bilaterally reduced standardized volumes in heroin-exposed offspring relative to controls include the ectorhinal and insular cortices. Regions with bilaterally increased standardized volumes in heroin-exposed offspring relative to controls include the periaqueductal gray, septal region, striatum, and hypothalamus. Leveraging microscopic resolution diffusion tensor imaging and precise regional parcellation, we generated whole-brain structural MRI diffusion connectomes. Using a dimension reduction approach with multivariate analysis of variance to assess group differences in the connectome, we found that in utero heroin exposure altered structure-based connectivity of the left septal region and the region that acts as a hub for limbic regulatory actions. Consistent with clinical evidence, our findings suggest that prenatal opioid exposure may have effects on brain morphology, connectivity, and, consequently, function that persist into adolescence. This work expands our understanding of the risks associated with opioid misuse during pregnancy and identifies biomarkers that may facilitate diagnosis and treatment.

Cerebral blood flow dependency on systemic arterial circulation in progressive multiple sclerosis

Background: Cerebrovascular reactivity (CVR) is a regulatory mechanism responsible for redistributing cerebral blood flow based on vasoactive stimuli and fluctuations in metabolic demand. Under normal conditions and proper functioning of the neurovascular unit, a direct association between cerebral arterial blood flow and systemic arterial blood flow (SABF) is not expected. Previous studies have suggested impairment of CVR in multiple sclerosis (MS).1 Moreover, lower cerebral perfusion in MS has been linked with greater neuronal pathology and worse disability outcomes.2,3&#x0D; Objectives: To determine the relationship between SABF and cerebral perfusion measures in MS patients.&#x0D; Мaterials and methods: Cerebral perfusion and SABF were assessed in 118 patients (75 clinically isolated syndrome (CIS)/relapsing-remitting MS and 43 progressive MS) through magnetic resonance imaging (MRI) examination with dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) and Doppler ultrasound, respectively. Measures of mean transit time (MTT) and time-to-peak (TTP), measured in seconds, of the normal-appearing whole brain (NAWB) and gray matter (GM) were calculated. Blood flow through the bilateral common carotid and vertebral arteries (in mL/min) represents the SABF. Whole brain volume (WBV) and body mass index (BMI) were used as additional covariates.&#x0D; Results: Higher systolic blood pressure was associated with lower SABF (-0.256, p=0.006). In the total MS sample, higher SABF was associated with shorter MTT and TTP of the NAWB (r=-0.256, p=0.007 and r=-0.307, p=0.001) and GM (r=-0.239, p=0.012 and r=-0.3, p=0.001). The SABF and TTP associations were driven by the progressive multiple sclerosis (PMS) patients (r=-0.451, p=0.004 and r=-0.451, p=0.011). Only in PMS, SABF remained a significant predictor of NAWB (standardized β=-0.394, p=0.022) and GM TTP (standardized β=-0.351, p=0.037). MTT and TTP were significantly lower in patients within lower SABF quartiles when compared to the higher quartiles (age, sex, BMI and WBV-adjusted ANCOVA p&lt;0.025). (Figure 1) The differences in PWI-based measured remained significant after additional correction for the prevalence of hypertension. Although statistically non-significant, PMS patients within the lower SABF quartiles had a numerically greater disability (expanded disability status scale scores of 5.9 vs 5.0 for Q1 and Q4), (multiple sclerosis severity score of 5.8 vs 3.8), slower walking as measured by timed 25-foot walk test (23.9 s vs 15.8 s) and worse hand dexterity as measured by 9-hole peg test (50.8 s vs. 29.3 s).&#x0D; Conclusions: The direct relationship between systemic and cerebral blood flow seen in PMS patients may suggest a failure in cerebrovascular reactivity mechanisms and insufficient perfusion control. Cerebral blood flow in PMS may be increasingly dependent on the SABF.

Lower cerebral arterial blood flow is associated with greater serum neurofilament light chain levels in multiple sclerosis patients

Background: Hypoperfusion, vascular pathology, and cardiovascular risk factors are associated with disease severity in multiple sclerosis (MS).1,2 In particular, the total cerebral arterial blood flow (CABF), measured as a sum of all arterial flow in the neck, was associated with the cognitive performance of MS patients.3&#x0D; Objective: To assess relationships between CABF and serum neurofilament light chain (sNfL), as neuronal damage biomarker with good prognostic value and treatment responsiveness.4 If the cerebrovascular changes are an independent pathophysiological factor in MS, a relationship should remain significant after controlling for common MS-based disease measures (i.e., T2 lesion volume and brain volume).&#x0D; Materials and methods: Total CABF was measured in 137 patients (86 clinically isolated syndrome (CIS)/relapsing-remitting (RR) and 51 progressive MS (PMS)) and 48 healthy controls (HCs) using Doppler ultrasound. sNfL was quantitated using a single molecule assay (Simoa). Three point zero T magnetic resonance imaging (MRI) examination allowed quantification of T2 lesion and whole-brain volume (WBV). Multiple linear regression models determined the sNfL associated with CABF after correction for demographic and MRI-derived variables.&#x0D; Results: After adjustment for age, sex and body mass index (BMI), total CABF remained statistically significant and model comparisons showed that CABF explained additional 2.6% of the sNfL variance (β=-0.167, p=0.044). (Table 1) CABF also remained significant in a step-wise regression model (β=0.18, p=0.034) upon the inclusion of T2 lesion burden and WBV effects. The explained sNfL variance improved from 17.4%, 22.7% with the presence of at least 2 CVD variable and 25.8% with both CVD and CABF predictors. Lastly, the disease-modifying therapy was not kept in the final model as an independent predictor of sNfL. Patients in the lowest CABF quartile (CABF≤761 mL/min) had significantly higher sNfL (34.6 pg/mL versus 23.9 pg/mL, adjusted-p=0.042) when compared to the highest quartile (CABF≥1130 mL/min).&#x0D; Conclusions: Lower CABF is associated with increased sNfL in MS patients, highlighting direct and independent relationship between cerebral hypoperfusion and axonal pathology. This relationship remained significant in the CIS/RRMS after adjusting for age, sex, and BMI effects.

Predicting Cognitive Decline in Older Adults Using Baseline Metrics of AD Pathologies, Cerebrovascular Disease, and Neurodegeneration.

Dementia is a growing socioeconomic challenge that requires early intervention. Identifying biomarkers that reliably predict clinical progression early in the disease process would better aid selection of individuals for future trial participation. Here, we compared the ability of baseline, single time-point biomarkers (CSF amyloid 1-42, CSF ptau-181, white matter hyperintensities (WMH), cerebral microbleeds, whole-brain volume, and hippocampal volume) to predict decline in cognitively normal individuals who later converted to mild cognitive impairment (MCI) (CNtoMCI) and those with MCI who later converted to an Alzheimer disease (AD) diagnosis (MCItoAD). Standardized baseline biomarker data from AD Neuroimaging Initiative 2 (ADNI2)/GO and longitudinal diagnostic data (including ADNI3) were used. Cox regression models assessed biomarkers in relation to time to change in clinical diagnosis using all follow-up time points available. Models were fit for biomarkers univariately and together in a multivariable model. Hazard ratios (HRs) were compared to evaluate biomarkers. Analyses were performed separately in CNtoMCI and MCItoAD groups. For CNtoMCI (n = 189), there was strong evidence that higher WMH volume (individual model: HR 1.79, p = 0.002; fully adjusted model: HR 1.98, p = 0.003) and lower hippocampal volume (individual: HR 0.54, p = 0.001; fully adjusted: HR 0.40, p < 0.001) were associated with conversion to MCI individually and independently. For MCItoAD (n = 345), lower hippocampal (individual model: HR 0.45, p < 0.001; fully adjusted model: HR 0.55, p < 0.001) and whole-brain volume (individual: HR 0.31, p < 0.001; fully adjusted: HR 0.48, p = 0.02), increased CSF ptau (individual: HR 1.88, p < 0.001; fully adjusted: HR 1.61, p < 0.001), and lower CSF amyloid (individual: HR 0.37, p < 0.001; fully adjusted: HR 0.62, p = 0.008) were most strongly associated with conversion to AD individually and independently. Lower hippocampal volume was a consistent predictor of clinical conversion to MCI and AD. CSF and brain volume biomarkers were predictive of conversion to AD from MCI, whereas WMH were predictive of conversion to MCI from cognitively normal. The predictive ability of WMH in the CNtoMCI group may be interpreted as some being on a different pathologic pathway, such as vascular cognitive impairment.

Abstract 15485: Tectonic Infarct Analysis: A User-Friendly Standalone Software for Whole-Brain Infarct Volume Estimation From 2,3,5-Triphenyltetrazolium Chloride-Stained Tissues

Introduction: Infarct volume measured from 2,3,5-Triphenyltetrazolium Chloride (TTC)-stained brain slices is critical for in vivo stroke models. However, current image tools are not automated and severely limited in their capability. Here, we developed an interactive, trainable software application that computes whole-brain infarct volume metrics from batches of serial TTC-stained brain sections. Methods: Male Wistar Rats ( n =21) received middle cerebral artery occlusion and were euthanized after 24 h. Brains were serially sectioned (2 mm, coronal), stained with TTC, and optically scanned (anterior and posterior sides). Manual annotations of infarcted regions and calculation of infarct volume were used as ground truth. We performed computational image analysis to segment brain tissue and develop a custom semantic segmentation model for infarct detection ( n =3 training cases) (Figure, top). Stroke parameters, including brain volume, infarct volume, infarct/non-infarct volume ratio (V), and % infarct were computed by measuring each feature per section, averaging over anterior and posterior faces, and summing across all slices. Results were compared against manual ground truth ( n =18 testing cases) using accuracy, f1-score, and Spearman correlation. The pipeline was then packaged as a standalone, opensource software named Tectonic Infarct Analysis (Figure, bottom). Results: The software performed well for brain (accuracy=0.95, f1-score=0.90) and infarct (accuracy=0.96, f1-score=0.89) segmentation. Strong, significant correlation was observed between manual and computational calculation of infarct parameters: V brain ( ρ =0.91, p &lt;0.001), V infarct (0.97, p &lt;0.001), V non-infarct (0.96, p &lt;0.001), and % infarct (0.81, p =0.001). The software reduced analysis time by 25 min per case vs. manual effort. Conclusions: Tectonic Infarct Analysis software offers a robust and adaptable approach for rapid TTC-based stroke assessment.

Grey matter volume and its association with cognitive impairment and peripheral cytokines in excited individuals with schizophrenia.

Although excited behavior in patients with schizophrenia has been linked to brain structural abnormalities, whether cortical abnormalities in this subgroup are related to cognitive impairment or peripheral immune responses is unknown. We included 28 patients with excitability (EC), 28 patients without excitability (NEC), and 48 healthy controls (HCs) to evaluate the associations. Compared with the HC group, the EC and NEC groups showed significant cognitive impairment and increased serum cytokine levels. Analysis of variance in whole-brain grey matter volume (GMV) showed that the volumes of several brain areas, including the superior frontal gyrus (SFG), superior temporal gyrus, and cingulate gyrus, were decreased in patients with schizophrenia. Notably, the left SFG volume was significantly lower in the EC group than in the NEC group. Spearman correlation analysis showed that elevated cytokines were negatively correlated with the GMV of the bilateral SFG, bilateral inferior parietal gyrus, left anterior cingulate gyrus, right fusiform gyrus and parahippocampal gyrus, which were mainly positive correlated with cognitive tests. Moreover, interleukin 4 may contribute to poor scores on Brief Assessment of Cognition and Neuropsychological Assessment Battery by reducing the left SFG volume (17%, Pmediation = 0.044; and 24%, Pmediation = 0.040,respectively). In conclusion, our results confirm GMV changes in excited patients with schizophrenia, and characterize the GMV as an important interface between inflammatory cytokines and cognitive impairment. Therefore, targeted anti-inflammatory adjuvant antipsychotic therapy may improve cognitive function and volumetric brain abnormalities in these patients.

Polygenic coronary artery disease association with brain atrophy in the cognitively impaired.

While a number of low-frequency genetic variants of large effect size have been shown to underlie both cardiovascular disease and dementia, recent studies have highlighted the importance of common genetic variants of small effect size, which, in aggregate, are embodied by a polygenic risk score. We investigate the effect of polygenic risk for coronary artery disease on brain atrophy in Alzheimer's disease using whole-brain volume and put our findings in context with the polygenic risk for Alzheimer's disease and presumed small vessel disease as quantified by white-matter hyperintensities. We use 730 subjects from the Alzheimer's disease neuroimaging initiative database to investigate polygenic risk score effects (beyond APOE) on whole-brain volumes, total and regional white-matter hyperintensities and amyloid beta across diagnostic groups. In a subset of these subjects (N = 602), we utilized longitudinal changes in whole-brain volume over 24 months using the boundary shift integral approach. Linear regression and linear mixed-effects models were used to investigate the effect of white-matter hyperintensities at baseline as well as Alzheimer's disease-polygenic risk score and coronary artery disease-polygenic risk score on whole-brain atrophy and whole-brain atrophy acceleration, respectively. All genetic associations were examined under the oligogenic (P = 1e-5) and the more variant-inclusive polygenic (P = 0.5) scenarios. Results suggest no evidence for a link between the polygenic risk score and markers of Alzheimer's disease pathology at baseline (when stratified by diagnostic group). However, both Alzheimer's disease-polygenic risk score and coronary artery disease-polygenic risk score were associated with longitudinal decline in whole-brain volume (Alzheimer's disease-polygenic risk score t = 3.3, P FDR = 0.007 over 24 months in healthy controls) and surprisingly, under certain conditions, whole-brain volume atrophy is statistically more correlated with cardiac polygenic risk score than Alzheimer's disease-polygenic risk score (coronary artery disease-polygenic risk score t = 2.1, P FDR = 0.04 over 24 months in the mild cognitive impairment group). Further, in our regional analysis of white-matter hyperintensities, Alzheimer's disease-polygenic risk score beyond APOE is predictive of white-matter volume in the occipital lobe in Alzheimer's disease subjects in the polygenic regime. Finally, the rate of change of brain volume (or atrophy acceleration) may be sensitive to Alzheimer's disease-polygenic risk beyond APOE in healthy individuals (t = 2, P = 0.04). For subjects with mild cognitive impairment, beyond APOE, a more inclusive polygenic risk score including more variants, shows coronary artery disease-polygenic risk score to be more predictive of whole-brain volume atrophy, than an oligogenic approach including fewer larger effect size variants.

Decoding Brain Fog in Head and Neck Cancer Survivors Using Artificial Intelligence

<h3>Purpose/Objective(s)</h3> Brain fogging, which is characterized by memory decline, word-finding difficulty, and decreased multi-tasking ability, is common in head and neck cancer survivors. The precise causes of brain fog are poorly understood, as MRIs are essentially normal in these patients. The purpose of this study was to use artificial intelligence (AI) to detect micro-architectural and biological changes in the brain that are invisible to human eyes. <h3>Materials/Methods</h3> DVH of temporal lobes and whole brain were obtained in 566 and 60 patients, respectively, who underwent IMRT or proton radiation with concurrent chemotherapy for nasopharyngeal carcinoma. EORTC QLQ-C30 was obtained from 92 patients who enrolled in two prospective clinical studies. Automated cortical region segmentation using an open-source software for processing and analyzing brain MRI images was performed in 33 patients with a minimum follow-up of 4 years. Architectural and biological MRI changes in gray matter, white matter, and subcortical brain regions were determined in 34 brain regions. Graph theory-based brain connectome was evaluated to assess the connectivity between different regions of the brain. Radiomics which employs high-throughput quantitative analysis of image features were performed on the T1- and diffusion-weighted sequences. <h3>Results</h3> Patients experienced a continuous decline of cognitive function after radiation, with a 6.6% in decrease in their first year. The brain received a large low-dose bath with a median V10-20(whole brain) (volume of whole brain that received 10-20 Gy) 170cc, V20-30(whole brain) 50.8cc, V10-20(temporal lobe)11.4cc, and V20-30(temporal lobe) 6.18cc. There were global changes in gray matter thickness, with most pronounced changes occurred in parietal lobe (-4.79%, p=0.007) and occipital lobe (-5.68%, p=0.03). Similarly, there were diffuse changes in white matter and subcortical volume. After radiation, the frontal lobe increased by 17.5% (p=0.04), lateral ventricle 41% (p=0.03), and choroid plexus 34.3% (p=0.03). After radiation, the brain exhibited diffuse disrupted connectivity as characterized by increased clustering coefficient (p=0.002) and decreased modularity (p=0.003). Corpus collusum, choroid plexus, cerebellum, hippocampus, brainstem, medialorbito- and superior-frontal, temporal pole, and inferior temporal were analyzed using radiomics. First order interquartile-range, entropy, uniformity, and GLCM features were found to be statistically significant (p< 0.01). After adjusted for age, gender, and time interval between MRI, IMRT patients developed significant more changes in white matter of the temporal lobe (p=0.03) and corpus callosum (p=0.03) when compared to proton patients. <h3>Conclusion</h3> By employing artificial intelligence and computational methods, we are able to detect global disruption in architecture, connectivity, and function in the brain of head and neck cancer survivors. IMRT affects the brain differently than proton.

Changes in gray matter volume following electroconvulsive therapy in adolescent depression with suicidal ideation: A longitudinal structural magnetic resonance imaging study.

ObjectiveWe aimed to investigate changes in whole-brain gray matter volumes (GMVs) before and after electroconvulsive therapy (ECT) in adolescents with major depressive disorder (MDD) and suicidal ideation (SI).MethodsThirty adolescents with MDD and SI were observed, and structural magnetic resonance imaging (sMRI) was performed at baseline and after ECT for each patient. But Twenty-five healthy controls (HCs) were scanned only at baseline. The voxel-based morphometry (VBM) techniques were used to examine GMVs.ResultsCompared with HCs, MDDs at baseline showed decreased GMVs in the left middle temporal gyrus, right superior temporal gyrus, right middle temporal gyrus, left precuneus, right precuneus, and left superior frontal gyrus. After ECT, MDDs showed increased GMVs in the right superior frontal gyrus and right superior temporal gyrus. Pearson’s correlation found that Beck Scale for Suicide Ideation (BSSI) scores at baseline were negatively correlated with GMVs in the left superior frontal gyrus and HAMD and BSSI scores after ECT were negatively correlated with GMVs in the right superior temporal gyrus.ConclusionFrontal–temporal–precuneus structure changes may be a potential cause of depressive and suicidal symptoms in adolescents. ECT may improve depressive and suicidal symptoms in adolescents by regulating brain structures to compensate original defects.

Individual differences in visual evoked potential latency are associated with variance in brain tissue volume in people with multiple sclerosis: An analysis of brain function-structure correlates

Visual evoked potentials (VEP) index visual pathway functioning, and are often used for clinical assessment and as outcome measures in people with multiple sclerosis (PwMS). VEPs may also reflect broader neural disturbances that extend beyond the visual system, but this possibility requires further investigation. In the present study, we examined the hypothesis that delayed latency of the P100 component of the VEP would be associated with broader structural changes in the brain in PwMS. We obtained VEP latency for a standard pattern-reversal checkerboard stimulus paradigm, in addition to Magnetic Resonance Imaging (MRI) measures of whole brain volume (WBV), gray matter volume (GMV), white matter volume (WMV), and T2-weighted fluid attenuated inversion recovery (FLAIR) white matter lesion volume (FLV). Correlation analyses indicated that prolonged VEP latency was significantly associated with lower WBV, GMV, and WMV, and greater FLV. VEP latency remained significantly associated with WBV, GMV, and WMV even after controlling for the variance associated with inter-ocular latency, age, time between VEP and MRI assessments, and other MRI variables. VEP latency delays were most pronounced in PwMS that exhibited low volume in both white and gray matter simultaneously. Furthermore, PwMS that had delayed VEP latency based on a clinically relevant cutoff (VEP latency ≥ 113 ms) in both eyes had lower WBV, GMV, and WMV and greater FLV in comparison to PwMS that had normal VEP latency in one or both eyes. The findings suggest that PwMS that have delayed latency in both eyes may be particularly at risk for exhibiting greater brain atrophy and lesion volume. These analyses also indicate that VEP latency may index combined gray matter and white matter disturbances, and therefore broader network connectivity and efficiency. VEP latency may therefore provide a surrogate marker of broader structural disturbances in the brain in MS.

Brain Differences in Adolescents Living With Perinatally Acquired HIV Compared With Adoption Status Matched Controls: A Cross-sectional Study.

Background and ObjectivesDespite effective combination antiretroviral therapy (cART), adolescents with perinatally acquired HIV (PHIV) exhibit cognitive impairment, of which structural changes could be the underlying pathophysiologic mechanism. Prior MRI studies found lower brain volumes, higher white matter (WM) hyperintensity (WMH) volume, lower WM integrity, and differences in cerebral blood flow (CBF). However, these findings may be confounded by adoption status, as a large portion of adolescents with PHIV have been adopted. Adoption has been associated with malnutrition and neglect, which, in turn, may have affected brain development. We investigated the long-term effects of PHIV on the brain, while minimizing the confounding effect of adoption status.MethodsWe determined whole-brain gray matter (GM) and WM volume with 3D T1-weighted scans; total WMH volume with fluid-attenuated inversion recovery; CBF in the following regions of interest (ROIs): WM, GM, and subcortical GM with arterial spin labeling; and whole-brain WM microstructural markers: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) with diffusion tensor imaging in cART-treated adolescents with PHIV visiting our outpatient clinic in Amsterdam and controls matched for age, sex, ethnic origin, socioeconomic status, and adoption status. We assessed differences in neuroimaging parameters between adolescents with PHIV and controls using linear regression models adjusted for age and sex and applied multiple comparison correction.ResultsThirty-five adolescents with PHIV and 38 controls were included with a median age of 14.9 (interquartile range [IQR]: 10.7–18.5) and 15.6 (IQR: 11.1–17.6) years, respectively, with a similar rate of adoption. We found a lower overall FA (beta = −0.012; p < 0.014, −2.4%), a higher MD (beta = 0.014, p = 0.014, 1.3%), and a higher RD (beta = 0.02, p = 0.014, 3.3%) in adolescents with PHIV vs adoption-matched controls, but no differences in AD. We found comparable GM, WM, and WMH volume and CBF in ROIs between adolescents with PHIV and controls. We did not find an association between cognitive profiles and WM microstructural markers in adolescents with PHIV.DiscussionIrrespective of adoption status, adolescents with PHIV exhibited subtle lower WM integrity. Our findings may point toward early-acquired WM microstructural alterations associated with HIV.

Objective Physical Activity Accumulation and Brain Volume in Older Adults: An MRI and Whole-Brain Volume Study.

A decrease in brain volume (ie, brain atrophy) is a marker of cognitive health in older adults. Insufficient weekly accumulation of moderate and vigorous physical activity (MVPA) has been associated with lower brain volume. As this association has been established for a small number of brain areas and structures and atrophy rates seem to be nonuniform between them, more comprehensive analyses are warranted. We compared the volume of 71 brain areas and structures in 45 older adults who met and did not meet objectively measured MVPA recommendations. In addition, we used multiple regression models to determine whether cardiorespiratory fitness (VO2PEAK), MVPA, and health-related risk factors could affect the atrophy of brain areas and structures. An accelerometer (GT9-X ActiGraph) was worn for 7days. Participants were then classified into 2 groups: <150 minutes MVPA (<150'MVPA; n=20) and ≥150 minutes MVPA (≥150'MVPA; n=25) per week. Older adults who accumulated ≥150'MVPA per week had significantly higher absolute and relative (%of intracranial volume) volumes of 39 and 9 brain areas and structures, respectively, than those who accumulated <150'MVPA per week. Higher VO2PEAK seems to be a key predictor of the atrophy of brain areas and structures. In conclusion, meeting weekly physical activity recommendations seems to have a widespread effect on preserving the volume of more than 30 brain areas and structures in older adults. VO2PEAK seems to be the most frequent and important predictor of brain volume preservation.

Mitochondrial measures in neuronally enriched extracellular vesicles predict brain and retinal atrophy in multiple sclerosis

Background: Mitochondrial dysfunction plays an important role in multiple sclerosis (MS) disease progression. Plasma extracellular vesicles are a potential source of novel biomarkers in MS, and some of these are derived from mitochondria and contain functional mitochondrial components. Objective: To evaluate the relationship between levels of mitochondrial complex IV and V activity in neuronally enriched extracellular vesicles (NEVs) and brain and retinal atrophy as assessed using serial magnetic resonance imaging (MRI) and optical coherence tomography (OCT). Methods: Our cohort consisted of 48 people with MS. NEVs were immunocaptured from plasma and mitochondrial complex IV and V activity levels were measured. Subjects underwent OCT every 6 months and brain MRI annually. The associations between baseline mitochondrial complex IV and V activities and brain substructure and retinal thickness changes were estimated utilizing linear mixed-effects models. Results: We found that higher mitochondrial complex IV activity and lower mitochondrial complex V activity levels were significantly associated with faster whole-brain volume atrophy. Similar results were found with other brain substructures and retinal layer atrophy. Conclusion: Our results suggest that mitochondrial measures in circulating NEVs could serve as potential biomarkers of disease progression and provide the rationale for larger follow-up longitudinal studies.

Whole-Brain Volume CT Angiography can Effectively Detect Early Ischemic Cerebrovascular Diseases.

To investigate the role of whole-brain volume computed tomography (CT) perfusion in assessing early ischemic cerebrovascular diseases. Seventy-two patients with early ischemic cerebrovascular diseases who had undergone routine CT scan and 320-row volume CT whole-brain perfusion imaging within 8 h after admission were retrospectively enrolled in this one-center case-sectional study. The perfusion parameters of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and dynamic CT angiogram (4D-CTA) were obtained and analyzed. Among 72 patients, 29 cases with 37 cerebral ischemic lesions were found in plain CT scan, whereas 51 cases with 76 lesions were found in whole-brain CT perfusion, with 30.6% more patients being detected. The CBF value was significantly lower in the abnormal than normal corresponding perfusion area in the healthy hemisphere (P<0.05), while the MTT and TTP values were significantly higher in the abnormal than the normal corresponding area (P<0.05). 4D-CTA image suggested that 59 cases had different degrees of stenosis or occlusion, including 11 mild, 18 moderate, 21 severe, and 9 occlusive cases. Four-D-CTA imaging could detect significantly (P<0.05) more patients with abnormal perfusion in severe cerebral vascular stenosis or occlusion than those with no, mild or moderate stenosis (93.33% vs. 16.67%) (P<0.05). The stenosis of intracranial and carotid arteries was positively correlated with MTT and TTP values (P<0.05). Whole-brain volume CT angiography can comprehensively display early cerebral ischemic lesions, cerebral blood perfusion status, and cerebral vascular stenosis, providing valuable information for early detection of ischemic cerebral diseases and appropriate treatment planning.