Computational Anatomy Toolbox Research Articles

SDPS-26 UNINTENDED RADIOTHERAPY DOSE ON THE NEUROGENIC NICHES IS ASSOCIATED WITH DECREASED OVERALL SURVIVAL IN PATIENTS WITH LUNG CANCER BRAIN METASTASES

Abstract INTRODUCTION Radiotherapy is the primary local intervention for cerebral metastases (BMs). Despite decades of advancements in this field, inadvertent collateral irradiation of adjacent healthy tissue in proximity to neoplastic site remains a persistent challenge. Neural stem cells (NSCs), crucial for the establishment and preservation of the nervous system, exhibit heightened sensitivity to radiation. Consequently, radiation-induced damage to NSCs may influence Overall Survival (OS) in patients with BMs. NSCs are primarily located in the subventricular zone (SVZ) and the subgranular zone (SGZ) within the hippocampus (HPC). In this study, our objective is to assess the influence of unintended radiotherapy dose on NSCs and its subsequent effect on OS. METHODS In this retrospective study, we incorporated data from 138 Non-Small Cell Lung Cancer (NSCLC) patients with BMs, from a single academic institution. NSC regions were projected on non-enhanced T1 MR images with Computational Anatomy Toolbox 12 and Statistical Parametric Mapping. The association between regional mean doses to the SVZ and HPC and OS was examined using a Cox regression model. Additionally, survival differences between lesion contact and no direct contact with SVZ and HPC were investigated with Kaplan-Meier (KM) analysis. RESULTS Multivariable Cox regression analysis of the dose on the SVZ and HPC showed a significant negative correlation, with a hazard ratio (HR) of 1.366 (p = 0.041 [95% (CI) 1.013– 1.842]) and 1.194 (p = 0.037 [95% CI 1.010 – 1.411]), respectively. KM analysis did not identify a relationship between direct lesion contact with NSC-regions and OS. CONCLUSION Any unintended dose on the neurogenic niches is correlated with poorer OS in patients with BMs from NSCLC. Interestingly, there was no association between direct contact or invasion of these regions and the OS. We recommend conducting further investigation into the impact on neurocognitive function within this specific group in a prospective study design.

Lower fractional dimension in Alzheimer's disease correlates with reduced locus coeruleus signal intensity

This study aimed to determine the pattern of fractional dimension (FD) in Alzheimer's disease (AD) patients, and investigate the relationship between FD and the locus coeruleus (LC) signal intensity.A total of 27 patients with AD and 25 healthy controls (HC) were collected to estimate the pattern of fractional dimension (FD) and cortical thickness (CT) using the Computational Anatomy Toolbox (CAT12), and statistically analyze between groups on a vertex level using statistical parametric mapping 12. In addition, they were examined by neuromelanin sensitive MRI(NM-MRI) technique to calculate the locus coeruleus signal contrast ratios (LC-CRs). Additionally, correlations between the pattern of FD and LC-CRs were further examined.Compared to HC, AD patients showed widespread lower CT and FD Furthermore, significant positive correlation was found between local fractional dimension (LFD) of the left rostral middle frontal cortex and LC-CRs. Results suggest lower cortical LFD is associated with LCCRs that may reflect a reduction due to broader neurodegenerative processes. This finding may highlight the potential utility for advanced measures of cortical complexity in assessing brain health and early identification of neurodegenerative processes.

Alterations in cortical morphometry of the contralesional hemisphere in children, adolescents, and young adults with perinatal stroke

Perinatal stroke causes most hemiparetic cerebral palsy and cognitive dysfunction may co-occur. Compensatory developmental changes in the intact contralesional hemisphere may mediate residual function and represent targets for neuromodulation. We used morphometry to explore cortical thickness, grey matter volume, gyrification, and sulcal depth of the contralesional hemisphere in children, adolescents, and young adults after perinatal stroke and explored associations with motor, attention, and executive function. Participants aged 6–20 years (N = 109, 63% male) with unilateral perinatal stroke underwent T1-weighted imaging. Participants had arterial ischemic stroke (AIS; n = 36), periventricular venous infarction (PVI; n = 37) or were controls (n = 36). Morphometry was performed using the Computational Anatomy Toolbox (CAT12). Group differences and associations with motor and executive function (in a smaller subsample) were assessed. Group comparisons revealed areas of lower cortical thickness in contralesional hemispheres in both AIS and PVI and greater gyrification in AIS compared to controls. Areas of greater grey matter volume and sulcal depth were also seen for AIS. The PVI group showed lower grey matter volume in cingulate cortex and less volume in precuneus relative to controls. No associations were found between morphometry metrics, motor, attention, and executive function. Cortical structure of the intact contralesional hemisphere is altered after perinatal stroke. Alterations in contralesional cortical morphometry shown in perinatal stroke may be associated with different mechanisms of damage or timing of early injury. Further investigations with larger samples are required to more thoroughly explore associations with motor and cognitive function.

Caution: shortcomings of traditional segmentation methods from magnetic resonance imaging brain scans intended for 3-dimensional surface modelling in children with pathology

This technical innovation assesses the adaptability of some common automated segmentation tools on abnormal pediatric magnetic resonance (MR) brain scans. We categorized 35 MR scans by pathologic features: (1) “normal”; (2) “atrophy”; (3) “cavity”; (4) “other.” The following three tools, (1) Computational Anatomy Toolbox version 12 (CAT12); (2) Statistical Parametic Mapping version 12 (SPM12); and (3) MRTool, were tested on each scan—with default and adjusted settings. Success was determined by radiologist consensus on the surface accuracy. Automated segmentation failed in scans demonstrating severe surface brain pathology. Segmentation of the “cavity” group was ineffective, with success rates of 23.1% (CAT12), 69.2% (SPM12) and 46.2% (MRTool), even with refined settings and manual edits. Further investigation is required to improve this workflow and automated segmentation methodology for complex surface pathology.

Volumetric hippocampal changes in glioblastoma: a biomarker for neuroplasticity?

PurposeThe pleiotropic effect of gliomas on the development of cognitive disorders and structural brain changes has garnered increasing interest in recent years. While it is widely accepted that multimodal therapies for brain cancer can foster cognitive impairment, the direct effect of gliomas on critical cognitive areas before anti-tumor therapies is still controversial. In this study, we focused on the effect of IDH1 wild-type glioblastoma on the human hippocampus volume.MethodsWe carried out a case-control study using voxel-based morphometry assessment, analyzed with the Computational Anatomy Toolbox software. Glioblastoma diagnosis was performed according to the latest 2021 WHO classification. Due to stringent inclusion criteria, 15 patients affected by IDH1 wild type glioblastoma were included and compared to 19 age-matched controls.ResultsWe observed a statistically significant increase in the absolute mean hippocampal volume (p = 0.017), as well as in the ipsilateral (compared to the lesion, p = 0.027) and the contralateral hippocampal volumes (p = 0.014) in the group of patients. When the data were normalized per total intracranial volume, we confirmed a statistically significant increase only in the contralateral hippocampal volume (p = 0.042).ConclusionsTo the best of our knowledge, this is the first study to explore hippocampal volumetric changes in a cohort of adult patients affected by IDH1 wild-type glioblastoma, according to the latest WHO classification. We demonstrated an adaptive volumetric response of the hippocampus, which was more pronounced on the side contralateral to the lesion, suggesting substantial integrity and resilience of the medial temporal structures before the initiation of multimodal treatments.

Left insular cortical thinning differentiates the inattentive and combined subtype of adult attention-deficit/hyperactivity disorder

BackgroundNeuroimaging studies in attention-deficit/hyperactivity disorder (ADHD) demonstrated decreased global gray matter volume. In terms of surface parameters, most investigations focused on cortical thickness with a multi-center MEGA-analysis indicating cortical thinning in children, but not in adults with ADHD.In this single-scanner study, for the first time in adult ADHD, we additionally examined metrics beyond cortical thickness and surface area, namely sulcal depth and fractal dimension as measures of cortical alteration and complexity. Unlike most previous studies, ADHD subtypes were considered. MethodsAs part of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), surface parameters were analyzed in 131 adults with ADHD (66 combined, 60 inattentive and 5 hyperactive/impulsive subtype) and 95 healthy controls with the Computational Anatomy Toolbox (CAT12) using Statistical Parametric Mapping Software (SPM). ResultsNeither at the vertex- nor at the region of interest-level, the ADHD and control group differed significantly with regard to cortical thickness, gyrification index, sulcal depth or fractal dimension. Contrasting the combined and the inattentive subtype, patients of the combined subtype showed a significant thinning of the left anterior insular cortex. Thinner left pars opercularis cortical thickness was associated with symptoms of hyperactivity/restlessness. ConclusionsResembling previous findings of a correlation of the left anterior insular gray matter volume with oppositional symptoms in adolescents with ADHD, we detected left anterior insular cortical thinning in the ADHD combined subtype. Left insular cortical thickness could represent a potential marker to distinguish the predominantly inattentive and the combined ADHD subtype in adulthood.

Structural Correlates of Lifetime Voice-Hearing in Patients with Borderline Personality Disorder: A Pilot Study

Introduction: Auditory verbal hallucinations (AVH) are transdiagnostic phenomena that can occur in several mental disorders, including borderline personality disorder (BPD). Despite the transdiagnostic relevance of these symptoms, very little is known about neural signatures of AVH in BPD. Methods: We used structural magnetic resonance imaging to investigate multiple markers of brain morphology in BPD patients presenting with a lifetime history of AVH (AVH, n = 6) versus BPD patients without AVH (nAVH, n = 10) and healthy controls (HC, n = 12). The Computational Anatomy Toolbox (CAT12) was used for surface-based morphometric analyses that considered cortical thickness (CTh), gyrification (CG), and complexity of cortical folding (CCF). Factorial models were used to explore differences between AVH patients and HC, as well as between the patient groups. Results: Compared to HC, AVH patients showed distinct abnormalities in key regions of the language network, i.e., aberrant CTh and CG in right superior temporal gyrus and abnormal CCF in left inferior frontal gyrus. Further abnormalities were found in right prefrontal cortex (CTh) and left orbitofrontal cortex (CCF). Compared to nAVH patients, individuals with AVH showed abnormal CTh in right prefrontal cortex, along with CCF differences in right transverse temporal, superior parietal, and parahippocampal gyri. CG differences between the patient groups were found in left orbitofrontal cortex. Conclusion: The data suggest a transdiagnostic neural signature of voice-hearing that converges on key regions involved in speech generation and perception, memory and executive control. It is possible that cortical features of distinct evolutionary and genetic origin, i.e., CTh and CG/CCF, differently contribute to AVH vulnerability in BPD.

Differentiation of claustrum resting-state functional connectivity in healthy aging, Alzheimer's disease, and Parkinson's disease.

The claustrum is a sheet-like of telencephalic gray matter structure whose function is poorly understood. The claustrum is considered a multimodal computing network due to its reciprocal connections with almost all cortical areas as well as subcortical structures. Although the claustrum has been involved in several neurodegenerative diseases, specific changes in connections of the claustrum remain unclear in Alzheimer's disease (AD), and Parkinson's disease (PD). Resting-state fMRI and T1-weighted structural 3D images from healthy elderly (n=15), AD (n=16), and PD (n=12) subjects were analyzed. Seed-based FC analysis was performed using CONN FC toolbox and T1-weighted images were analyzed with the Computational Anatomy Toolbox for voxel-based morphometry analysis. While we observed a decreased FC between the left claustrum and sensorimotor cortex, auditory association cortex, and cortical regions associated with social cognition in PD compared with the healthy control group (HC), no significant difference was found in alterations in the FC of both claustrum comparing the HC and AD groups. In the AD group, high FC of claustrum with regions of sensorimotor cortex and cortical regions related to cognitive control, including cingulate gyrus, supramarginal gyrus, and insular cortex were demonstrated. In addition, the structural results show significantly decreased volume in bilateral claustrum in AD and PD compared with HC. There were no significant differences in the claustrum volumes between PD and AD groups so the FC may offer more precise findings in distinguishing changes for claustrum in AD and PD.

Problems using structural MRIs from the oldest‐old, and some solutions: Lessons learned from The 90+ Study and ADNI

AbstractBackgroundThe oldest‐old (≥85 years) have the highest rates of dementia. However, because of pronounced brain atrophy, standard neuroimaging programs face unique challenges in this cohort. Here, using data from both The 90+ Study and Alzheimer’s Disease Neuroimaging Initiative (ADNI), we report the prevalence of errors when processing brain MRIs from oldest‐old participants using standard approaches and present some strategies for ameliorating these issues.MethodFirst, we analyzed image quality issues and segmentation errors (FreeSurfer) for the last available scans by age‐groups (oldest‐old, ≥85 years, vs younger‐old, <85 years) in ADNI. Second, we evaluated the utility of an age‐specific template (the 90+ T1w Template) for realigning MRIs from the oldest‐old compared to a standard template (Montreal Neurological Institute T1w template, MNI) using linear and nonlinear registration (FSL) and evaluating alignment quality using visual and deformation (Jacobian) measures for oldest‐old participants in both The 90+ Study and ADNI. Lastly, we evaluated whether stringent preprocessing (bias field removal, denoising, brain extraction, intensity normalization using Computational Anatomy Toolbox (CAT12)) helped reduce FreeSurfer segmentation errors in frontal, parietal, and temporal regions in MRIs from the oldest‐old. Comparisons were performed using Chi‐square tests.ResultIn ADNI data (Table‐1), MRIs from oldest‐old participants (∼10% of cohort) were around twice as likely to have image quality issues (20% vs 13%, P<0.001) and brain segmentation errors (45% vs 29%, P<0.001) compared to younger‐old participants. Figure‐1 shows a histogram of image quality issues and segmentation errors, which become more common with greater age. Compared to the MNI template, MRIs from participants aged 90 and older from both The 90+ Study (N=163, Table‐2) and ADNI (N=75) had fewer registration errors (∼5% vs ∼23%, P<0.001 for all) and less severe deformation when using the 90+ T1w Template (Figure‐2). Our proposed preprocessing pipeline (see Figure‐3 for example) roughly halved segmentation errors in the oldest‐old (P<0.001 for all regions, Figure‐4).ConclusionOur results show that adapting pipelines specifically for processing brain MRIs of oldest‐old participants minimizes errors, enabling more effective use of neuroimaging to study neural correlates of neurodegeneration and dementia in this important portion of our aging population.

Problems using structural MRIs from the oldest‐old, and some solutions: Lessons learned from The 90+ Study and ADNI

AbstractBackgroundThe oldest‐old (≥85 years) have the highest rates of dementia. However, because of pronounced brain atrophy, standard neuroimaging programs face unique challenges in this cohort. Here, using data from both The 90+ Study and Alzheimer’s Disease Neuroimaging Initiative (ADNI), we report the prevalence of errors when processing brain MRIs from oldest‐old participants using standard approaches and present some strategies for ameliorating these issues.MethodFirst, we analyzed image quality issues and segmentation errors (FreeSurfer) for the last available scans by age‐groups (oldest‐old, ≥85 years, vs younger‐old, 55 to 85 years) in ADNI. Second, we evaluated the utility of an age‐specific template (the 90+ T1w Template) for realigning MRIs from the oldest‐old compared to a standard template (Montreal Neurological Institute T1w template, MNI) using linear and nonlinear registration (FSL) and evaluating alignment quality using visual and deformation (Jacobian) measures for oldest‐old participants (≥90 years) in both The 90+ Study and ADNI. Lastly, we evaluated whether stringent preprocessing (bias field removal, denoising, brain extraction, intensity normalization using Computational Anatomy Toolbox (CAT12)) helped reduce FreeSurfer segmentation errors in frontal, parietal, and temporal regions in MRIs from the oldest‐old. Comparisons were performed using Chi‐square tests.ResultIn ADNI data (Table‐1), MRIs from oldest‐old participants (∼10% of cohort) were around twice as likely to have image quality issues (20% vs 13%, P<0.001) and brain segmentation errors (45% vs 29%, P<0.001) compared to younger‐old participants. Figure‐1 shows a histogram of image quality issues and segmentation errors, which become more common with greater age. Compared to the MNI template, MRIs from participants aged 90 and older from both The 90+ Study (N=163, Table‐2) and ADNI (N=75) had fewer registration errors (∼5% vs ∼23%, P<0.001 for all) and less severe deformation when using the 90+ T1w Template (Figure‐2). Our proposed preprocessing pipeline (see Figure‐3 for example) roughly halved segmentation errors in the oldest‐old (P<0.001 for all regions, Figure‐4).ConclusionOur results show that adapting pipelines specifically for processing brain MRIs of oldest‐old participants minimizes errors, enabling more effective use of neuroimaging to study neural correlates of neurodegeneration and dementia in this important portion of our aging population.

Heritability of Subcortical Grey Matter Structures.

Background and Objectives: Subcortical grey matter structures play essential roles in cognitive, affective, social, and motoric functions in humans. Their volume changes with age, and decreased volumes have been linked with many neuropsychiatric disorders. The aim of our study was to examine the heritability of six subcortical brain volumes (the amygdala, caudate nucleus, pallidum, putamen, thalamus, and nucleus accumbens) and four general brain volumes (the total intra-cranial volume and the grey matter, white matter, and cerebrospinal fluid (CSF) volume) in twins. Materials and Methods: A total of 118 healthy adult twins from the Hungarian Twin Registry (86 monozygotic and 32 dizygotic; median age 50 ± 27 years) underwent brain magnetic resonance imaging. Two automated volumetry pipelines, Computational Anatomy Toolbox 12 (CAT12) and volBrain, were used to calculate the subcortical and general brain volumes from three-dimensional T1-weighted images. Age- and sex-adjusted monozygotic and dizygotic intra-pair correlations were calculated, and the univariate ACE model was applied. Pearson's correlation test was used to compare the results obtained by the two pipelines. Results: The age- and sex-adjusted heritability estimates, using CAT12 for the amygdala, caudate nucleus, pallidum, putamen, and nucleus accumbens, were between 0.75 and 0.95. The thalamus volume was more strongly influenced by common environmental factors (C = 0.45-0.73). The heritability estimates, using volBrain, were between 0.69 and 0.92 for the nucleus accumbens, pallidum, putamen, right amygdala, and caudate nucleus. The left amygdala and thalamus were more strongly influenced by common environmental factors (C = 0.72-0.85). A strong correlation between CAT12 and volBrain (r = 0.74-0.94) was obtained for all volumes. Conclusions: The majority of examined subcortical volumes appeared to be strongly heritable. The thalamus was more strongly influenced by common environmental factors when investigated with both segmentation methods. Our results underline the importance of identifying the relevant genes responsible for variations in the subcortical structure volume and associated diseases.

Effects of Mindfulness-Based Interventions on Gray Matter Volume in Patients with Opioid Dependence

Introduction: Recently, several mindfulness-based programs showed promising clinical effects in the treatment of psychiatric disorders including substance use disorders. However, very little is known about the effects of mindfulness-based interventions (MBIs) on brain structure in such patients. Methods: This study aimed to detect changes in gray matter volume (GMV) in opioid-dependent patients receiving MBI during their first month of treatment. Thirty patients were assigned to either 3 weeks of MBI (n = 16) or treatment as usual (TAU, n = 14) and were investigated using structural magnetic resonance imaging before and after treatment. Longitudinal pipeline of the Computational Anatomy Toolbox for SPM (CAT12) was used to detect significant treatment-related changes over time. The identified GMV changes following treatment were related to clinically relevant measures such as impulsivity, distress tolerance, and mindfulness. Results: After treatment, increased mindfulness scores were found in individuals receiving MBI compared to TAU. In the MBI group, there were also significant differences with respect to distress tolerance and impulsivity. Effects on mindfulness, distress tolerance, and impulsivity were also found in the TAU group. Longitudinal within-group analysis revealed increased left anterior insula GMV in individuals receiving MBI. Anterior insula volume increase was associated with decreased impulsivity levels. In the TAU group, significant GMV changes were found in the right lingual gyrus and right entorhinal cortex. Discussion/Conclusion: MBI can yield significant clinical effects during early abstinence from opioid dependence. MBI is particularly associated with increased insula GMV, supporting an important role of this region in the context of MBI-induced neural changes.

Quantitative evaluation of cortical thickness in 3T in Behçet’s patients without neurological involvement and parenchymal neuro-Behçet’s disease

PurposeTo evaluate the spatial distribution of cortical damage in Behcet’s Disease (BD) with or without neurological involvement using a cortical thickness measurement approach using three-dimensional T1-weighted imaging. Material and methodsFifty-eight BD patients without neurological involvement, twenty-two Parenchymal Neuro-Behçets disease (PNBD) patients, and fifty healthy controls were included in the prospective study. Anatomical 3D T1 images were obtained from all participants using 3T MRI. Using a computational anatomy toolbox (CAT12), we calculated and compared group differences in cortical thickness. ResultsPatients with BD without neurological involvement showed cortical thickness reduction in bilateral frontal, bilateral parietal, and right precuneus compared with the healthy controls (HCs) (p < 0.05 FWE corrected [FWEc]). PNBD patients showed frontoparietal cortical thickness reduction when compared with BD patients without neurological involvement (p < 0.05 FWEc). The PNBD patients showed widespread cortical thickness reduction compared with the HC patients (p < 0.05 FWEc). Disease duration was correlated with cortical thickness in the right pericalcarine (p = 0.012 false discovery rate [FDR], r = −0.40), left pericalcarine (p = 0.013 FDR, r = −0.44), and left transverse temporal (p = 0.007 FDR, r = −0.41) regions. ConclusionThere is a decrease in cortical thickness in BD patients without neurological involvement. Cortical thickness reduction is more prominent in parenchymal neurobehçet's patients. Cortical thickness shows a negative correlation with disease duration in some regions.

Reduced Gray Matter Volumes among Long Term Survivors of Head and Neck Cancer Treated with Radiation Therapy

<h3>Purpose/Objective(s)</h3> To investigate brain morphometry among long term survivors of head and neck cancer (HNC) treated with radiotherapy (RT). Specifically, we sought to calculate the brain age gap estimation among HNC survivors and to perform voxel-based morphometry (VBM) to calculate local gray matter volumes between HNC survivors and controls without history of cancer. <h3>Materials/Methods</h3> We recruited 39 HNC survivors (age range: 32.6y – 71.9y, 25.6% female) who were treated with RT >2y prior and who were currently without evidence of recurrent tumor. Participants underwent a multimodal magnetic resonance imaging (MRI) protocol. Scans were performed on a technology company's Prisma 3-Tesla using a 20-channel head coil. The scan protocol included T1-weighted imaging acquired at 1mm slice thickness. Brain age was estimated utilizing total brain gray matter, white matter, and cerebrospinal fluid with brainageR v2.1 and compared to chronologic age using the paired-samples T-test. VBM analysis was performed using Computational Anatomy Toolbox v12 with a regions of interest (ROI) approach utilizing the neuromorphometrics brain atlas. Gray matter volumes for ROIs were used to compare the study cohort to a normative sample of 35 adults age >45 years from the MGH-USC Human Connectome Project. Differences in gray matter volume were compared using the independent samples T-test controlled for total intracranial volume and sex and conservatively adjusted for multiple comparisons using the Holm-Bonferroni method. <h3>Results</h3> Estimated brain age was calculated for all participants; 1 participant was excluded from VBM analysis due to inadequate imaging quality. The mean estimated gray matter brain age of 60.2y was not significantly different to the mean chronologic age of the sample at 61.2y (p=0.353). Results from the VBM analysis demonstrated significantly reduced gray matter volume in the HNC survivors group compared to control group in the bilateral orbital gyrus, cingulate cortex, basal forebrain, thalamus, and cerebellum. In total, 35 left hemisphere regions of interest (ROIs) and 34 right hemisphere ROIs demonstrated reduced gray matter volume in the HNC survivor group at the p<0.001 significance level. No ROIs had increased gray matter among HNC survivors. <h3>Conclusion</h3> To our knowledge, this study is the first to assess brain morphometry among HNC survivors. We did not observe a brain age gap, but VBM gray matter volumes were significantly reduced in multiple brain regions, mostly subcortical and in the most inferior part of the cortex. Future research is needed to characterize how brain morphometry is related to patient outcomes as well as modifiable treatment factors such as brain radiation exposure.

Alterations of gray and white matter volumes and cortical thickness in treated HIV-positive patients

Brain structural changes in HIV identified by voxel-based morphometry (VBM) alone could arise from a variety of causes that are difficult to distinguish without further information, such as cortical thickness (CT), gyrification index (GI) or sulcal depth (SD). Hence, our goal was to assess these additional metrics in HIV using high-resolution 3D T1-weighted images and investigate if surface-based morphometric (SBM) analysis would reveal significant changes in the gray matter (GM) and white matter (WM) volumes combined with alterations in cortical thickness (CT), gyrification index (GI), sulcal depth (SD). T1-w magnetization-prepared-rapid-acquisition gradient-echo (MP-RAGE) scans were acquired in 27 HIV-infected individuals on antiretroviral therapy (ART) and 15 HIV-uninfected healthy controls using a 3T MRI scanner equipped with a 16-channel head “receive” and a quadrature body “transmit” coil. Voxel-based and surface-based morphometric analyses were performed using the MATLAB based SPM Computational Anatomy Toolbox (CAT12.7(1700)). HIV-infected patients showed significantly altered GM and WM volumes, CT, GI, and SD, in multiple brain regions. This study showed the association of altered GM and WM volumes in local brain regions with the changes in region-wise CT, GI and SD measures of HIV-infected patients, especially in the parahippocampal and middle frontal regions as compared to uninfected healthy controls. The outcome of this study suggests that the findings of VBM may not necessarily indicate the volumetric shrinkage or increase alone, but might also be due to altered CT, GI, or SD. Correlation analysis showed a significantly accelerated gray matter loss with age in HIV-infected individuals compared to uninfected healthy controls.

Cortical thickness in brain imaging studies using FreeSurfer and CAT12: A matter of reproducibility

A reproducibility crisis has been reported across many research fields, including neuroimaging, reaching up to 70% of studies. Neuroimaging data, such as magnetic resonance imaging (MRI), requires pre-processing to allow for inter-subject comparison, increase signal contrast and noise reduction. As manual MRI pre-processing is time consuming and requires expertise, multiple automatic pre-processing frameworks have been proposed. However, neuroimaging studies often report divergent results, even for similar populations, thus it is important to determine whether this occurs as a result of different processing tools. Two of the most used tools are FreeSurfer and the Computational Anatomy Toolbox (CAT12). In this study we assessed the reproducibility between these two automatic pre-processing frameworks for structural MRI and test-retest reliability within framework on estimation of cortical thickness. Our results show that the reproducibility between the frameworks is lower at the region-of-interest (ROI) level than at individual level. Furthermore, we found that the reproducibility was lower in paediatric samples than in adults. Finally, an acquisition site effect was also identified. Given the widespread use of these frameworks in basic and clinical neuroscience, the results of multicentric cross-sectional studies must be interpreted with caution, particularly with paediatric samples. The observed reproducibility issue might be one of the sources of discrepancies reported in neuroimaging studies. On a positive note, framework test-retest reliability within subject is high, suggesting that inconsistency of results may be less concerning in longitudinal studies. The code is available at: https://cibit-uc.github.io/fs-cat12-cortical-thickness-reproducibility.

Unraveling the Protective Effects of Cognitive Reserve on Cognition and Brain: A Cross-Sectional Study.

This study aimed to investigate the hypothesis that brain maintenance expressed in white matter hyperintensities and brain reserves, defined as gray and white matter volumes, mediate the association between cognitive reserve (CR) and cognitive performance. A cross-sectional population-based observational study was conducted, and the final study sample consisted of 763 participants (282 men and 481 women) with a mean age of 61.11 years (±9.0). Data from different categories were collected from study participants, such as demographic, lifestyle, medical, and psycho-social characteristics. All participants underwent a detailed psychometric evaluation (MoCA and DSST) followed by a brain MRI. Volumetric measurements of the total gray matter (GMvol), total white matter (WMvol), and white matter hyperintensities (WMHvol) were performed using the Computational Anatomy Toolbox 12 (CAT12) and Statistical Parametric Maps 12 (SPM12) based on 3D T1-weighted sequence. Significant direct and indirect effects of cognitive reserve on cognitive functioning were measured with both scales—the MoCA and DSST. In each mediation model, the volumes of WMH and GM were significant mediators for the association between cognitive reserve and cognitive performance. This study confirms the importance of strengthening the cognitive reserve in the course of life through potentially modifiable effects on both cognition and the brain.

Treatment with morning blue light increases left amygdala volume and sleep duration among individuals with posttraumatic stress disorder.

BackgroundPosttraumatic stress disorder (PTSD) is associated with numerous cognitive, affective, and psychophysiological outcomes, including problems with sleep and circadian rhythms. We tested the effectiveness of a daily morning blue-light exposure treatment (BLT) versus a matched amber light treatment (ALT) to regulate sleep in individuals diagnosed with PTSD. Moreover, PTSD is also associated with reliable findings on structural neuroimaging scans, including reduced amygdala volumes and other differences in cortical gray matter volume (GMV) that may be indicative of underlying neurobehavioral dysfunctions. We examined the effect of BLT versus ALT on GMV and its association with sleep outcomes.MethodsSeventy-six individuals (25 male; 51 female) meeting DSM-V criteria for PTSD (Age = 31.45 years, SD = 8.83) completed sleep assessments and structural neuroimaging scans, followed by random assignment one of two light groups, including BLT (469 nm; n = 39) or placebo ALT (578 nm; n = 37) light therapy daily for 30-min over 6-weeks. Participants wore a wrist actigraph for the duration of the study. After treatment, participants returned to complete sleep assessments and a structural neuroimaging scan. Neuroimaging data were analyzed using the Computational Anatomy Toolbox (CAT12) and Voxel-Based Morphometry (VBM) modules within the Statistical Parametric Mapping (SPM12) software.ResultsThe BLT condition produced significant increases in total time in bed and total sleep time from actigraphy compared to the ALT condition, while ALT improved wake after sleep onset and sleep efficiency compared to BLT. Additionally, BLT led to an increase in left amygdala volume compared to ALT but did not affect hypothesized medial prefrontal regions. Finally, within group correlations showed that improvements in sleep quality and nightmare severity were correlated with increases in left amygdala volume over the course of treatment for the BLT group but not the ALT group.ConclusionIn individuals with PTSD, daily exposure to morning blue light treatment was associated with improvements in objective sleep duration and increased volume of the left amygdala compared to amber placebo light treatment, and changes in amygdala volume correlated with subjective improvement in sleep. These findings suggest that daily morning BLT may provide an important non-pharmacologic adjunctive approach for facilitating sleep and neurobehavioral recovery from PTSD.

Reduced cortical complexity in patients with thyroid-associated ophthalmopathy.

Psychical and functional disturbances of thyroid-associated ophthalmopathy (TAO) patients are drawing increasingly attention, despite the characterized ophthalmic symptoms. We aimed to investigate the alterations of structural complexity using fractal dimension (FD) analysis in patients with TAO. Thirty-nine TAO patients and 25 healthy controls underwent high-resolution 3.0T structural brain magnetic resonance imaging (MRI). FD values of brain regions were calculated by Computational Anatomy Toolbox (CAT12) and compared between groups. The associations between clinical variables and FD values were further estimated. We found that TAO patients exhibited significantly decreased FD values in right caudal anterior cingulate cortex, right lingual gyrus, right pars orbitalis and right cuneus cortex (FDR corrected p < 0.05). FD values of right cuneus cortex were positively correlated with visual acuity, and FD values of right caudal anterior cingulate cortex were also positively correlated with cognitive performance. Meanwhile, FD values of right lingual gyrus were found to be negatively correlated with emotional function. Our study indicated disturbed cortical complexity in brain regions corresponding to known functional deficits of vision, emotion and cognition in TAO. FD might be a potential marker for reflecting the underlying neurobiological basis of TAO.

Reorganization of the Brain Structural Covariance Network in Ischemic Moyamoya Disease Revealed by Graph Theoretical Analysis.

ObjectiveIschemic moyamoya (MMD) disease could alter the cerebral structure, but little is known about the topological organization of the structural covariance network (SCN). This study employed structural magnetic resonance imaging and graph theory to evaluate SCN reorganization in ischemic MMD patients.MethodForty-nine stroke-free ischemic MMD patients and 49 well-matched healthy controls (HCs) were examined by T1-MPRAGE imaging. Structural images were pre-processed using the Computational Anatomy Toolbox 12 (CAT 12) based on the diffeomorphic anatomical registration through exponentiated lie (DARTEL) algorithm and both the global and regional SCN parameters were calculated and compared using the Graph Analysis Toolbox (GAT).ResultsMost of the important metrics of global network organization, including characteristic path length (Lp), clustering coefficient (Cp), assortativity, local efficiency, and transitivity, were significantly reduced in MMD patients compared with HCs. In addition, the regional betweenness centrality (BC) values of the bilateral medial orbitofrontal cortices were significantly lower in MMD patients than in HCs after false discovery rate (FDR) correction for multiple comparisons. The BC was also reduced in the left medial superior frontal gyrus and hippocampus, and increased in the bilateral middle cingulate gyri of patients, but these differences were not significant after FDR correlation. No differences in network resilience were detected by targeted attack analysis or random failure analysis.ConclusionsBoth global and regional properties of the SCN are altered in MMD, even in the absence of major stroke or hemorrhagic damage. Patients exhibit a less optimal and more randomized SCN than HCs, and the nodal BC of the bilateral medial orbitofrontal cortices is severely reduced. These changes may account for the cognitive impairments in MMD patients.