Bhaswati Roy

Comparative evaluation of 3-dimensional pseudocontinuous arterial spin labeling with dynamic contrast-enhanced perfusion magnetic resonance imaging in grading of human glioma.

Introduction The study was performed to compare dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) with 3-dimensional (3D) pseudocontinuous arterial spin labeling (PCASL) MRI in gliomas with an aim to see whether arterial spin labeling (ASL)–derived cerebral blood flow (CBF) values can be used as an alternative to DCE-MRI for its grading. Materials and Methods Sixty-four patients with glioma (37 male; mean age, 43 years; 38 high grade and 26 low grade) underwent 3D-PCASL and DCE-MRI. The DCE indices (relative cerebral blood volume, rCBV; relative CBF, rCBF; permeability, ktrans and kep; and leakage, ve) and ASL (absolute and rCBF) values were quantified from the tumors. Student independent t test was used to compare ASL and DCE-MRI indices. Pearson correlation was used to see correlation between DCE- and ASL-derived CBF values in tumor and normal parenchyma. Results On Student t test, neither ASL-derived absolute CBF (P = 0.78) nor rCBF (P = 0.12) values were found to be significantly different in 2 groups, whereas DCE indices except ve were significantly higher in high-grade gliomas. Arterial spin labeling–derived rCBF values weakly correlated with DCE-derived rCBF values, whereas these did not show correlation in normal grey (P = 0.12, r = 0.2) and white (P = 0.26, r = 0.14) matter regions. Conclusions Three-dimensional pseudocontinuous arterial spin labeling does not appear to be a reliable technique in the current form and may not be a suitable replacement for DCE in grading of glioma.

Prevalence of MR imaging abnormalities in vitamin B12 deficiency patients presenting with clinical features of subacute combined degeneration of the spinal cord

BACKGROUND AND AIMS Subacute combined degeneration (SACD) of the spinal cord, characterized by degeneration of lateral and posterior columns, is often found in vitamin B12 deficiency. Our aim was to look for sensitivity of imaging in depicting the spinal cord abnormality in vitamin B12 deficient patients and to find any correlation of vitamin B12 levels with clinical scores/severity at time of presentation. MATERIAL AND METHODS A total 54 patients with biochemically proven vitamin B12 deficiency were included in the study. In all these patients MR study of cervico-dorsal spine was done. All the patients after initiation of appropriate treatment were followed up for a minimum of two months. RESULTS MRI showed cord signal abnormality in only 8 patients out of 54 patients with low sensitivity of 14.8%. After appropriate therapy, complete resolution of cord signal abnormalities was observed in all these 8 patients, on follow-up MR imaging. Significant negative correlation (r=-0.503, p<0.000) was seen between the clinical severity scores and initial vitamin B12 levels. CONCLUSION Conventional MRI may not be a useful tool for the diagnosis of SACD as it has very low sensitivity. Inverse correlation of Vitamin B12 levels with clinical scoring suggests that initial serum vitamin B12 levels may help in predicting the clinical severity.

Reduced regional cerebral blood flow in patients with heart failure

Heart failure (HF) patients show significant lateralized neural injury, accompanied by autonomic, mood and cognitive deficits. Both gray and white matter damage occurs and probably develops from altered cerebral blood flow (CBF), a consequence of impaired cardiac output. However, the distribution of regional CBF changes in HF patients is unknown, but is an issue in determining mechanisms of neural injury. Our aim was to compare regional CBF changes in HF with CBF in control subjects using non‐invasive pseudo‐continuous arterial spin labelling (ASL) procedures.

Associations between brain white matter integrity and disease severity in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway blockage, with continued diaphragmatic efforts to breathe during sleep. Brain structural changes in OSA appear in various regions, including white matter sites that mediate autonomic, mood, cognitive, and respiratory control. However, the relationships between brain white matter changes and disease severity in OSA are unclear. This study examines associations between an index of tissue integrity, magnetization transfer (MT) ratio values (which show MT between free and proton pools associated with tissue membranes and macromolecules), and disease severity (apnea‐hypopnea index [AHI]) in OSA subjects. We collected whole‐brain MT imaging data from 19 newly diagnosed, treatment‐naïve OSA subjects (50.4 ± 8.6 years of age, 13 males, AHI 39.7 ± 24.3 events/hr], using a 3.0‐Tesla MRI scanner. With these data, whole‐brain MT ratio maps were calculated, normalized to common space, smoothed, and correlated with AHI scores by using partial correlation analyses (covariates, age and gender; P < 0.005). Multiple brain sites in OSA subjects, including superior and inferior frontal regions, ventral medial prefrontal cortex and nearby white matter, midfrontal white matter, insula, cingulate and cingulum bundle, internal and external capsules, caudate nuclei and putamen, basal forebrain, hypothalamus, corpus callosum, and temporal regions, showed principally lateralized negative correlations (P < 0.005). These regions showed significant correlations even with correction for multiple comparisons (cluster‐level, family‐wise error, P < 0.05), except for a few superior frontal areas. Predominantly negative correlations emerged between local MT values and OSA disease severity, indicating potential usefulness of MT imaging for examining the OSA condition. These findings indicate that OSA severity plays a significant role in white matter injury.

Assessment of functional and structural damage in brain parenchyma in patients with vitamin B12 deficiency: A longitudinal perfusion and diffusion tensor imaging study

INTRODUCTION Vitamin B12 deficiency may cause neural tissue damage. Even in advanced stages, conventional imaging of brain usually appears normal in vitamin B12 deficient patients. The aim of this study was to assess the structural and functional changes in brain of patients with vitamin B12 deficiency before and after six weeks of vitamin B12 supplementation using diffusion tensor imaging and pseudo-continuous arterial spin labelling (PCASL). METHODS MR imaging including DTI and PCASL and neuropsychological tests (NPT) were performed in 16 patients with vitamin B12 deficiency and 16 controls before and after 6weeks of therapy. Cerebral blood flow (CBF) derived from PCASL and DTI indices was calculated in brain of patients with vitamin B12 deficiency and controls. RESULTS Patient with vitamin B12 deficiency showed altered neuropsychological scores and altered CBF as well as fractional anisotropy (FA) values in various brain regions as compared with controls. Both CBF values and neuropsychological scores showed complete reversibility at 6weeks post therapy. Though FA values showed significant recovery, it failed to show complete recovery. CONCLUSION Our results suggest that micro-structural recovery lags behind functional recovery in patients with vitamin B12 deficiency following therapy and CBF change may be used as an early predictor of complete recovery in patients with B12 deficiency.

Lateralized Resting-State Functional Brain Network Organization Changes in Heart Failure.

Heart failure (HF) patients show brain injury in autonomic, affective, and cognitive sites, which can change resting-state functional connectivity (FC), potentially altering overall functional brain network organization. However, the status of such connectivity or functional organization is unknown in HF. Determination of that status was the aim here, and we examined region-to-region FC and brain network topological properties across the whole-brain in 27 HF patients compared to 53 controls with resting-state functional MRI procedures. Decreased FC in HF appeared between the caudate and cerebellar regions, olfactory and cerebellar sites, vermis and medial frontal regions, and precentral gyri and cerebellar areas. However, increased FC emerged between the middle frontal gyrus and sensorimotor areas, superior parietal gyrus and orbito/medial frontal regions, inferior temporal gyrus and lingual gyrus/cerebellar lobe/pallidum, fusiform gyrus and superior orbitofrontal gyrus and cerebellar sites, and within vermis and cerebellar areas; these connections were largely in the right hemisphere (p<0.005; 10,000 permutations). The topology of functional integration and specialized characteristics in HF are significantly changed in regions showing altered FC, an outcome which would interfere with brain network organization (p<0.05; 10,000 permutations). Brain dysfunction in HF extends to resting conditions, and autonomic, cognitive, and affective deficits may stem from altered FC and brain network organization that may contribute to higher morbidity and mortality in the condition. Our findings likely result from the prominent axonal and nuclear structural changes reported earlier in HF; protecting neural tissue may improve FC integrity, and thus, increase quality of life and reduce morbidity and mortality.

Regional brain tissue changes and associations with disease severity in children with sleep-disordered breathing

Study Objectives Children with sleep-disordered breathing (SDB) exhibit behavioral, cognitive, and autonomic deficits, suggestive of neural injury. We assessed whether the tissue alterations resulted from acute or chronic processes, and if alterations correlated with disease severity. Methods Brain tissue integrity was examined with mean diffusivity (MD) (3.0-Tesla scanner) in 20 non-snoring controls (mean age±sem, 12.2±0.6y; 10 male) and 18 children with SDB (12.3±0.7y; 11 male). Sleep, cognitive, and behavioral measures were compared between groups following overnight polysomnography using Students t-tests. Whole-brain MD maps were realigned and averaged, normalized, smoothed, and compared between groups using ANCOVA (covariates; age, gender, and socioeconomic status). Partial correlations were calculated between whole-brain smoothed MD maps and obstructive apnea hypopnea indices (OAHI). Results Age, gender, and sleep variables did not differ between groups. The SDB group showed higher OAHI, body mass indices, and systolic blood pressure. Significantly reduced MD values (acute changes) appeared in the hippocampus, insula, thalamus, temporal and occipital cortices, and cerebellum, but were increased (chronic damage) in the frontal and prefrontal cortices in the SDB group over controls. Both positive and negative correlations appeared with extent of tissue changes and disease severity. Externalizing and Total Problem Behaviors were significantly higher in SDB children. Verbal, performance and total IQ scores trended lower, and behavioral scores trended higher. Conclusions Pediatric SDB is accompanied by predominantly acute brain changes in areas that regulate autonomic, cognitive, and mood functions, and chronic changes in frontal cortices essential for behavioral control. Interventions need to be keyed to address acute vs chronic injury.

Brain structural changes associated with aberrant functional responses to the Valsalva maneuver in heart failure

Heart failure (HF) patients show inability to regulate autonomic functions in response to autonomic challenges. The autonomic deficits may stem from brain tissue injury in central autonomic regulatory areas, resulting from ischemic and hypoxic processes accompanying the condition. However, the direct evaluation of correlations between brain structural injury and functional timing and magnitude of neural signal patterns within affected areas, which may lead to impaired autonomic outflow, is unclear. In this study, we evaluate neural responses to the Valsalva maneuver with blood oxygen level‐dependent functional magnetic resonance imaging in 29 HF patients and 35 control subjects and brain structural changes using diffusion tensor imaging‐based mean diffusivity in a subsample of 19 HF and 24 control subjects. HF showed decreased neural activation in multiple autonomic and motor control areas, including cerebellum cortices, vermis, left insular, left putamen, and bilateral postcentral gyrus. Structural brain changes emerged in similar autonomic, as well as cognitive and mood regulation areas. Functional MRI responses in cerebellum and insula in HF subjects are delayed or decreased in magnitude to the challenge. The impaired functional responses of insular and cerebellar sites are correlated with the severity of tissue changes. These results indicate that the functions of insular and cerebellar regions, sites that are involved in autonomic regulation, are compromised, and that autonomic deficits in these areas have brain structural basis for impaired functions. Our study enhanced our understanding of brain structural and functional alterations underlying impaired autonomic regulations in HF subjects.

Non-Gaussian Diffusion Imaging Shows Brain Myelin and Axonal Changes in Obstructive Sleep Apnea.

Objective Obstructive sleep apnea (OSA) is accompanied by brain changes in areas that regulate autonomic, cognitive, and mood functions, which were initially examined by Gaussian-based diffusion tensor imaging measures, but can be better assessed with non-Gaussian measures. We aimed to evaluate axonal and myelin changes in OSA using axial (AK) and radial kurtosis (RK) measures. Materials and Methods We acquired diffusion kurtosis imaging data from 22 OSA and 26 controls; AK and RK maps were calculated, normalized, smoothed, and compared between groups using analysis of covariance. Results Increased AK, indicating axonal changes, emerged in the insula, hippocampus, amygdala, dorsolateral pons, and cerebellar peduncles and showed more axonal injury over previously identified damage. Higher RK, showing myelin changes, appeared in the hippocampus, amygdala, temporal and frontal lobes, insula, midline pons, and cerebellar peduncles and showed more widespread myelin damage over previously identified injury. Conclusions Axial kurtosis and RK measures showed widespread changes over Gaussian-based techniques, suggesting a more sensitive nature of kurtoses to injury.

Cerebral Blood Flow and DTI metrics changes in children with cerebral palsy following therapy

It is known that patients with chronic hypoxia have regional changes in their cerebral blood flow (CBF). The purpose of this study was to observe the CBF and diffusion tensor imaging (DTI) metrics changes in children with cerebral palsy (CP) at baseline and after 6 months of treatment. Thirty-eight children with cerebral diplegia (mean age = 6.4 yr) and twenty-one age/sex matched controls (mean age = 7.5 yr) were evaluated by the Gross Motor Function Classification System (GMFCS) scoring of motor disability and modified Ashworth scoring of spasticity. All subjects underwent pseudo-continuous arterial spin labeling (PCASL) and DTI, in addition to conventional magnetic resonance imaging (MRI). Significant increase in CBF values was observed in several grey and white matter regions (including areas of abnormal T2 hyperintensity in the periventricular white matter) in CP children as compared to controls based upon voxel-wise analysis. Low fractional anisotropy (FA) and high apparent diffusion coefficient (ADC) values were observed in these areas of high CBF, using a region of interest (ROI) based analysis. On follow-up study, CBF values were found to be significantly higher in two grey matter areas and lower in three white matter regions in comparison to baseline; however no significant changes in DTI indices were observed in these regions. CBF values are high in CP children as compared to controls and show alteration following therapy even when the DTI metrics remain unchanged. Arterial spin labeling (ASL) may be added to the advanced imaging protocol for studying brain plasticity in such children in future.