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Biomedical subjects

Ravi Bansal

Publications and source records attributed to Ravi Bansal.

At least 19 recordsLinked to original sources

Sex differences in cortical thickness mapped in 176 healthy individuals between 7 and 87 years of age.

Findings from previous magnetic resonance imaging studies of sex differences in gray matter have been inconsistent, with some showing proportionally increased gray matter in women and some showing no differences between the sexes. Regional sex differences in gray matter thickness have not yet been mapped over the entire cortical surface in a large sample of subjects spanning the age range from early childhood to old age. We applied algorithms for cortical pattern matching and techniques for measuring cortical thickness to the structural magnetic resonance images of 176 healthy individuals between the ages of 7 and 87 years. We also mapped localized differences in brain size. Maps of sex differences in cortical thickness revealed thicker cortices in women in right inferior parietal and posterior temporal regions even without correcting for total brain volume. In these regions, the cortical mantle is up to 0.45 mm thicker, on average, in women than in men. Analysis of a subset of 18 female and 18 male subjects matched for age and brain volume confirmed the significance of thicker gray matter in temporal and parietal cortices in females, independent of brain size differences. Further analyses were conducted in the adult subjects where gender differences were evaluated using height as a covariate, and similar sex differences were observed even when body size differences between the sexes were controlled. Together, these results suggest that greater cortical thickness in posterior temporal inferior parietal regions in females relative to males are independent of differences in brain or body size. Age-by-sex interactions were not significant in the temporoparietal region, suggesting that sex differences in these regions are present from at least late childhood and then are maintained throughout life. Male brains were larger than female brains in all locations, though male enlargement was most prominent in the frontal and occipital poles, bilaterally. Given the large sample and the large range of ages studied, these results help to address controversies in the study of central nervous system sexual dimorphisms.

Adolescent↗

A gradient feature weighted Minimax algorithm for registration of multiple portal images to 3DCT volumes in prostate radiotherapy.

PURPOSE: To develop an accurate, fast, and robust algorithm for registering portal and computed tomographic (CT) images for radiotherapy using a combination of sparse and dense field data that complement each other. METHODS AND MATERIALS: Gradient Feature Weighted Minimax (GFW Minimax) method was developed to register multiple portal images to three-dimensional CT images. Its performance was compared with that of three others: Minimax, Mutual Information, and Gilhuijs' method. Phantom and prostate cancer patient images were used. Effects of registration errors on tumor control probability (TCP) and normal tissue complication probability (NTCP) were investigated as a relative measure. RESULTS: Registration of four portals to CTs resulted in 30% lower error when compared with registration with two portals. Computation time increased by nearly 50%. GFW Minimax performed the best, followed by Gilhuijs' method, the Minimax method, and Mutual Information. CONCLUSIONS: Using four portals instead of two lowered the registration error. Reduced fields of view images with full feature sets gave similar results in shorter times as full fields of view images. In clinical situations where soft tissue targets are of importance, GFW Minimax algorithm was significantly more accurate and robust. With registration errors lower than 1 mm, margins may be scaled down to 4 mm without adversely affecting TCP and NTCP.

Algorithms↗

Cortisol levels and hippocampus volumes in healthy preadolescent children.

BACKGROUND: Research in animal models has demonstrated that elevated levels of glucocorticoids can inflict damage within the hippocampus. In adult humans, elevated cortisol levels have been associated with reduced hippocampal volumes; however, normative data in children are not available. The objective of this study was to examine possible associations of serum cortisol levels with hippocampal volumes and morphology in healthy children. METHODS: Morning serum cortisol levels and hippocampus magnetic resonance imaging were measured in 17 healthy children (8 girls, 9 boys) between 7 and 12 years of age. RESULTS: Cortisol levels were not associated with total hippocampal volumes; however, with an analysis of surface morphology, significant associations were found for regionally specific portions of the hippocampus. Positive associations were detected for the anterior segment of the hippocampus and inverse associations along the lateral aspects of the hippocampus. CONCLUSIONS: Associations of cortisol levels with regionally specific variations in hippocampal morphology were detected during early development in healthy preadolescent children.

Aging↗

A statistical framework for the classification of tensor morphologies in diffusion tensor images.

Tractography algorithms for diffusion tensor (DT) images consecutively connect directions of maximal diffusion across neighboring DTs in order to reconstruct the 3-dimensional trajectories of white matter tracts in vivo in the human brain. The performance of these algorithms, however, is strongly influenced by the amount of noise in the images and by the presence of degenerate tensors-- i.e., tensors in which the direction of maximal diffusion is poorly defined. We propose a simple procedure for the classification of tensor morphologies that uses test statistics based on invariant measures of DTs, such as fractional anisotropy, while accounting for the effects of noise on tensor estimates. Examining DT images from seven human subjects, we demonstrate that this procedure validly classifies DTs at each voxel into standard types (nondegenerate DTs, as well as degenerate oblate, prolate or isotropic DTs), and we provide preliminary estimates for the prevalence and spatial distribution of degenerate tensors in these brains. We also show that the P values for test statistics are more sensitive tools for classifying tensor morphologies than are invariant measures of anisotropy alone.

Algorithms↗

Age, rapid-cycling, and pharmacotherapy effects on ventral prefrontal cortex in bipolar disorder: a cross-sectional study.

BACKGROUND: Neuroimaging data suggest that deficits in ventral prefrontal cortex (VPFC) function in bipolar disorder (BD) progress during adolescence and young adulthood. However, the developmental trajectory of VPFC morphological abnormalities in BD is unknown. This study investigated potential age-dependent volume abnormalities in VPFC in BD. METHODS: Thirty-seven individuals diagnosed with BD I (14 adolescents, 10 young adults and 13 older adults) and 56 healthy comparison subjects (HC) participated in imaging. Gray and white matter volumes of VPFC were measured using high-resolution structural magnetic resonance imaging (MRI). We used a mixed model, repeated measures analysis to examine VPFC volumes across age groups while co-varying for total brain volume. Potential effects of illness features including rapid-cycling and medication were explored. RESULTS: VPFC volumes declined with age (p < .001). The diagnosis-by-age group interaction was significant (p = .01). Relative to HC subjects, VPFC gray and white matter volumes were significantly smaller in BD patients only in young adulthood (p = .04). In participants with BD, VPFC volumes were significantly smaller in participants with rapid-cycling than participants without rapid-cycling (p = .02). Conversely, current use of medication was associated with larger VPFC gray matter volumes (p = .005), independent of age. CONCLUSIONS: These preliminary findings suggest the presence of a more rapid initial decline in VPFC volumes with age in adolescents and young adults with BD than HC. These findings also suggest that the rapid-cycling subtype of BD is associated with larger VPFC volume deficits than the non-rapid-cycling subtype, and that pharmacotherapy may have trophic or protective effects on VPFC volumes in BD patients.

Adult↗

Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder.

CONTEXT: Limbic structures are implicated in the genesis of attention-deficit/hyperactivity disorder (ADHD) by the presence of mood and cognitive disturbances in affected individuals and by elevated rates of mood disorders in family members of probands with ADHD. OBJECTIVE: To study the morphology of the hippocampus and amygdala in children with ADHD. DESIGN: A cross-sectional case-control study of the hippocampus and amygdala using anatomical magnetic resonance imaging. SETTINGS: University research institute. PATIENTS: One hundred fourteen individuals aged 6 to 18 years, 51 with combined-type ADHD and 63 healthy controls. MAIN OUTCOME MEASURES: Volumes and measures of surface morphology for the hippocampus and amygdala. RESULTS: The hippocampus was larger bilaterally in the ADHD group than in the control group (t = 3.35; P < .002). Detailed surface analyses of the hippocampus further localized these differences to an enlarged head of the hippocampus in the ADHD group. Although conventional measures did not detect significant differences in amygdalar volumes, surface analyses indicated the presence of reduced size bilaterally over the area of the basolateral complex. Correlations with prefrontal measures suggested abnormal connectivity between the amygdala and prefrontal cortex in the ADHD group. Enlarged subregions of the hippocampus tended to accompany fewer symptoms. CONCLUSIONS: The enlarged hippocampus in children and adolescents with ADHD may represent a compensatory response to the presence of disturbances in the perception of time, temporal processing (eg, delay aversion), and stimulus seeking associated with ADHD. Disrupted connections between the amygdala and orbitofrontal cortex may contribute to behavioral disinhibition. Our findings suggest involvement of the limbic system in the pathophysiology of ADHD.

Adolescent↗

Correction of eddy-current distortions in diffusion tensor images using the known directions and strengths of diffusion gradients.

PURPOSE: To correct eddy-current artifacts in diffusion tensor (DT) images without the need to obtain auxiliary scans for the sole purpose of correction. MATERIALS AND METHODS: DT images are susceptible to distortions caused by eddy currents induced by large diffusion gradients. We propose a new postacquisition correction algorithm that does not require any auxiliary reference scans. It also avoids the problematic procedure of cross-correlating images with significantly different contrasts. A linear model is used to describe the dependence of distortion parameters (translation, scaling, and shear) on the diffusion gradients. The model is solved numerically to provide an individual correction for every diffusion-weighted (DW) image. RESULTS: The assumptions of the linear model were successfully verified in a series of experiments on a silicon oil phantom. The correction obtained for this phantom was compared with correction obtained by a previously published method. The algorithm was then shown to markedly reduce eddy-current distortions in DT images from human subjects. CONCLUSION: The proposed algorithm can accurately correct eddy-current artifacts in DT images. Its principal advantages are that only images with comparable signals and contrasts are cross-correlated, and no additional scans are required.

Algorithms↗

Reduced white matter connectivity in the corpus callosum of children with Tourette syndrome.

BACKGROUND: Brain imaging studies have revealed anatomical anomalies in the brains of individuals with Tourette syndrome (TS). Prefrontal regions have been found to be larger and the corpus callosum (CC) area smaller in children and young adults with TS compared with healthy control subjects, and these anatomical features have been understood to reflect neural plasticity that helps to attenuate the severity of tics. METHOD: CC white matter connectivity, as measured by the Fractional Anisotropy (FA) index from diffusion tensor images, was assessed in 20 clinically well-defined boys with Tourette syndrome and 20 age- and gender-matched controls. RESULTS: The hypothesis that children with TS would show reduced measures of connectivity in CC fibers was confirmed for all subregions of the CC. There was no significant interaction of TS and region. Reductions in FA in CC regions may reflect either fewer interhemispheric fibers or reduced axonal myelination. FA values did not correlate significantly with the severity of tic symptoms. Group differences in measures of connectivity did not seem to be attributable to the presence of comorbid ADHD or OCD, to medication exposure, or group differences in IQ. CONCLUSION: Our findings of a reduced interhemispheral white matter connectivity add to the understanding of neural connectivity and plasticity in the brains of children who have TS.

Adolescent↗

ROC-based assessments of 3D cortical surface-matching algorithms.

Algorithms for the semi-automated analysis of brain surfaces have recently received considerable attention, and yet, they rarely receive a rigorous assessment of their performance. We present a method for the quantitative assessment of performance across differing surface analysis algorithms and across various modifications of a single algorithm. The sensitivity and specificity of an algorithm for detecting known deformations added synthetically to the brains being studied are assessed using curves for Receiver Operating Characteristics (ROC). We also present a method for the isolation of sources of variance in MRI data sets that can contribute to degradation in performance of surface-matching algorithms. Isolation of these sources of variance allows determination of whether degradation in performance of surface-matching algorithms derives primarily from errors in registration of brains to a common coordinate space, from errors in placement of the known deformation, or from interindividual or between-group variability in morphology of the cortical surface. We apply these methods to the study of surface-matching algorithms that are based on fluid flow (FF) deformation, geodesic (GD) interpolation, or nearest neighbor (NN) proximity. We show that the performances of surface-matching algorithms depend on the presence of interindividual and between-group variability in the surfaces surrounding the cortical deformation. We also show that, in general, the FF algorithm performs as well as or better than the GD and NN algorithms. The large variance in identifying point correspondences across brain surfaces using the GD and the NN algorithms suggests strongly that these point correspondences are less valid than those determined by the FF algorithm. The GD and NN algorithms, moreover, are both vulnerable to detecting false-positive activations at points of high curvature, particularly along large fissures, cisterns, and cortical sulci.

Algorithms↗

A prospective randomized study to compare ultrasound-guided with nonultrasound-guided double lumen internal jugular catheter insertion as a temporary hemodialysis access.

UNLABELLED: Internal jugular venous catheters (IJVC) for hemodialysis are a commonly employed temporary vascular access for hemodialysis. Most hospitals still follow the use of blind technique, which uses anatomical landmarks. Even in the most experienced hands this procedure has a variable success rate. Ultrasound guidance can decrease the incidence of periprocedural complications and improve the success rate. In this randomized study we compared the procedure success rate and periprocedural complications in patients undergoing ultrasound guided vs. nonultrasound guided IJVC insertion for a temporary hemodialysis access. METHODS: All patients subjected to insertion of an IJVC between March 2004 and June 2004 were enrolled into the study, randomized to either the blind (group A) or ultrasound guided (group B) procedure, which uses a portable ordinary ultrasound machine without a needle guide. The aseptic Saldinger technique was used for catheterization in both the groups. Baseline characteristics of patient and periprocedural events were recorded. RESULTS: A total of 60 patients were randomized, 30 patients each in two groups. First attempt venous cannulation success rate was 56.7% in group A compared to 86.7% in group B. Chance of occurrence of adverse outcome was significantly more in the blind procedure (P=0.020). A post-procedure chest radiograph done in all patient showed no complications. CONCLUSION: Ultrasound guided procedure for internal jugular vein catheter insertion using an ordinary ultrasound machine was significantly safer and more successful as compared to the blind technique.

Adult↗

Altered interhemispheric connectivity in individuals with Tourette's disorder.

OBJECTIVE: The corpus callosum is the major commissure connecting the cerebral hemispheres. Prior evidence suggests involvement of the corpus callosum in the pathophysiology of Tourette's disorder. The authors assessed corpus callosum size and anatomical connectivity across the cerebral hemispheres in persons with Tourette's disorder. METHOD: The size of the corpus callosum was determined on the true midsagittal slices of reformatted, high-resolution magnetic resonance imaging scans and compared across groups in a cross-sectional case-control study of 158 subjects with Tourette's disorder and 121 healthy comparison subjects, ages 5-65 years. RESULTS: In the context of increasing midsagittal corpus callosum area from childhood to age 30 years, children with Tourette's disorder had smaller overall corpus callosum size, whereas adults with Tourette's disorder on average had larger corpus callosum size, yielding a prominent interaction of diagnosis with age. Corpus callosum size correlated positively with tic severity. Corpus callosum size also correlated inversely with dorsolateral prefrontal and orbitofrontal cortical volumes in both the subjects with Tourette's disorder and the comparison subjects, but the magnitudes of the correlations were significantly greater in the group with Tourette's disorder. The effects of medication and comorbid illnesses had no appreciable influence on the findings. CONCLUSIONS: Given prior evidence for the role of prefrontal hypertrophy in the regulation of tic symptoms, the current findings suggest that neural plasticity may contribute to smaller corpus callosum size in persons with Tourette's disorder, which thereby limits neuronal trafficking across the cerebral hemispheres and reduces input to cortical inhibitory interneurons within the prefrontal cortices. Reduced inhibitory input may in turn enhance prefrontal excitation, thus helping to control tics and possibly contributing to the cortical hyperexcitatibility reported previously in patients with Tourette's disorder.

Adolescent↗

Effect of membrane composition on cytokine production and clinical symptoms during hemodialysis: a crossover study.

BACKGROUND: Intradialytic symptoms including hypotension have been reported during dialysis and it has been suggested that these are related to the release of cytokines like IL-1beta and TNFalpha by blood mononuclear cells when they get activated either due to contact with the dialyzer membrane or by compliment activation. OBJECTIVE: To study the relationship between hemodialysis symptoms, cytokine production, and dialyzer membrane composition. METHOD: In a randomized prospective crossover study, 20 ESRD patients on maintenance hemodialysis were studied over cuprophan (CU) and polysulfone (PS) low flux dialyzer membranes for three weeks each undergoing a biweekly dialysis schedule of 4 h sessions. Serial IL-1beta and TNFalpha levels were measured over 0, 15, 240 min during the first use of the dialyzer for all patients on both membranes. Intradialytic symptoms were monitored in a total of 240 dialysis sessions. RESULTS: IL-1beta levels increased from 16.6 +/- 2.2 to 64.8 +/- 25.1 pg/mL on CU and 21.5 +/- 3.7 to 103.5 +/- 30.7 pg/mL on PS membrane over the 4-h dialysis session. Similarly TNFalpha increased from 42.8 +/- 4.5 to 354.9 +/- 80.4 pg/mL on CU and 117.1+/- 53.7 to 387.0 +/- 78.0 pg/mL on PS membrane. IL-1beta levels increased significantly with PS membrane while TNFalpha rise was significant with both the membranes. Nausea was the most common symptom occurring in 138 dialysis sessions (57.5%). Vomiting, chest pain, fever, chills, and breathlessness occurred significantly more during dialysis with CU membrane as compared with PS membrane (P < 0.01). Nausea, cramps, back pain, itching, restlessness, post dialysis fatigue, and hypotension did not differ between the two membranes. The mean rise in the cytokine levels during the first 15 min of sessions where the symptoms occurred, when compared with the mean rise in sessions where the symptoms did not occur, did not reveal any significant difference. Cytokine release did not correlate with the occurrence of intradialytic symptoms. CONCLUSION: Both CU and PS membranes increase circulating cytokine levels. More intradialytic clinical symptoms are seen in dialysis with CU as compared with PS membrane but the rise in cytokines IL-1beta and TNFalpha does not appear to be responsible for them.

Adolescent↗

Entropy-based dual-portal-to-3-DCT registration incorporating pixel correlation.

For patient setup verification in external beam radiotherapy (EBRT) of prostate cancer, we developed an information theoretic registration framework, called the minimax entropy registration framework, to simultaneously and iteratively segment portal images and register them to three-dimensional (3-D) computed tomography (CT) image data. The registration framework has two steps, the max step and the min step, and evaluates appropriate entropies to estimate segmentations of the portal images and to find the transformation parameters. In the initial version of the algorithm (Bansal et al. 1999), we assumed image pixels to be independently distributed, an assumption not true in general. Thus, to better segment the portal images and to improve the accuracy of the estimated registration parameters, in this initial formulation of the problem, the correlation among pixel intensities is modeled using a one-dimensional Markov random process. Line processes are incorporated into the model to improve the estimation of segmentation of the portal images. In the max step, the principle of maximum entropy is invoked to estimate the probability distribution on the segmentations. The estimated distribution is then incorporated into the min step to estimate the registration parameters. Performance of the proposed framework is evaluated and compared to that of a mutual information-based registration algorithm using both simulated and real patient data. In the proposed registration framework, registration of the 3-D CT image and the portal images is guided by an estimated segmentation of the pelvic bone. However, as the prostate can move with respect to the pelvic structure, further localization of the prostate using ultrasound image data is required, an issue to be further explored in future.

Algorithms↗

Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%.

It is estimated that familial aggregation and genetic susceptibility play a role in as many as 10% of pancreatic ductal adenocarcinomas. To investigate the role of germ-line mutations in the etiology of pancreatic cancer, we have analyzed samples from patients with pancreatic cancer enrolled in the NFPTR for mutations in four tumor suppressor candidate genes: (a) MAP2K4; (b) MADH4; (c) ACVR1B; and (d) BRCA2 by direct sequencing of constitutional DNA. These genes are mutated in clinically sporadic pancreatic cancer, but germ-line mutations are either not reported or anecdotal in familial pancreatic cancer. Pancreatic cancer patient samples were selected from kindreds in which three or more family members were affected with pancreatic cancer, at least two of which were first-degree relatives. No mutations were identified in mitogen-activated protein kinase kinase 4 (0 of 22), MADH4 (0 of 22), or ACVR1B (0 of 29), making it unlikely that germ-line mutations in these genes account for a significant number of inherited pancreatic cancers. BRCA2 gene sequencing identified five mutations (5 of 29, 17.2%) that are believed to be deleterious and one point mutation (M192T) unreported previously. Three patients harbored the common 6174delT frameshift mutation, one had the splice site mutation IVS 16-2A > G, and one had the splice site mutation IVS 15-1G > A. Two of the five BRCA2 mutation carriers reported a family history of breast cancer, and none reported a family history of ovarian cancer. These findings confirm the increased risk of pancreatic cancer in individuals with BRCA2 mutations and identify germ-line BRCA2 mutations as the most common inherited genetic alteration yet identified in familial pancreatic cancer.

Activin Receptors, Type I↗

High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter.

Human Tp53 is normally a short-lived protein. Tp53 protein is stabilized and levels are increased in response to a variety of cellular stresses, including those induced by genotoxic anticancer drugs and environmental exposures. To engineer an efficient assay based on this property, we constructed and integrated a Tp53-specific reporter system into human cancer cells, termed p53R cells. We tested a range of conventional chemotherapeutic agents as well as over 16 000 diverse small compounds. Ionizing radiation and two-thirds of conventional chemotherapeutic agents, but only 0.2% of diverse compounds activated Tp53 activity by two-fold or greater, consistent with the presumptive genotoxic activation of Tp53 function. Cytotoxicity was independent of TP53 genetic status when paired, syngeneic wild-type TP53 and TP53-null cells in culture were treated with compounds that activated Tp53. From the unbiased survey of random compounds, Tp53 activation was strongly induced by an analog of AMSA, an investigational anti-cancer agent. Tp53 was also strongly induced by an N-oxide of quinoline and by dabequine, an experimental antimalarial evaluated in humans; dabequine was reported to be negative in other screens of mutagenicity and clastogenicity but carcinogenic in animal studies. Further exploration of antimalarial compounds identified the common medicinals chloroquine, quinacrine, and amodiaquine as Tp53-inducers. Flavonoids are known to have DNA topoisomerase activity, a Tp53-inducing activity that is confirmed in the assay. A reported clinical association of Tp53 immunopositive colorectal cancers with use of the antihypertensive agents was extended by the demonstration of hydralazine and nifedipine as Tp53-inducers. p53R cells represent an efficient Tp53 functional assay to identify chemicals and other agents with interesting biologic properties, including genotoxicity. This assay may have utility in the identification of novel chemotherapeutic agents, as an adjunct in the pharmaceutical optimization of lead compounds, in the exploration of environmental exposures, and in chemical probing of the Tp53 pathway.

Amsacrine↗