Faculty Bibliography

BACKGROUND:It has been well documented that, along with tonsillar herniation, Chiari Malformation Type I (CMI) is associated with smaller posterior cranial fossa (PCF) and altered cerebrospinal fluid (CSF) flow and tissue motion in the craniocervical junction. OBJECTIVE:This study assesses the relationship between PCF volumetry and CSF and tissue dynamics toward a combined imaging-based morphological-physiological characterization of CMI. Multivariate analysis is used to identify the subset of parameters that best discriminates CMI from a healthy cohort. METHODS:Eleven length and volumetric measures of PCF, including crowdedness and 4th ventricle volume, 4 measures of CSF and cord motion in the craniocervical junction, and 5 global intracranial measures, including intracranial compliance and pressure, were measured by magnetic resonance imaging (MRI) in 36 symptomatic CMI subjects (28 female, 37 ± 11 years) and 37 control subjects (24 female, 36 ± 12 years). The CMI group was further divided based on symptomatology into "typical" and "atypical" subgroups. RESULTS:Ten of the 20 morphologic and physiologic measures were significantly different between the CMI and the control cohorts. These parameters also had less variability and stronger significance in the typical CMI compared with the atypical. The measures with the most significance were clival and supraocciput lengths, PCF crowdedness, normalized PCF volume, 4th ventricle volume, maximal cord displacement (P < .001), and MR measure of intracranial pressure (P = .007). Multivariate testing identified cord displacement, PCF crowdedness, and normalized PCF as the strongest discriminator subset between CMI and controls. MR measure of intracranial pressure was higher in the typical CMI cohort compared with the atypical. CONCLUSION/CONCLUSIONS:The identified 10 complementing morphological and physiological measures provide a more complete and symptomatology-relevant characterization of CMI than tonsillar herniation alone.

We propose a fused lasso logistic regression to analyze callosal thickness profiles. The fused lasso regression imposes penalties on both the l1-norm of the model coefficients and their successive differences, and finds only a small number of non-zero coefficients which are locally constant. An iterative method of solving logistic regression with fused lasso regularization is proposed to make this a practical procedure. In this study we analyzed callosal thickness profiles sampled at 100 equal intervals between the rostrum and the splenium. The method was applied to corpora callosa of elderly normal controls (NCs) and patients with very mild or mild Alzheimer's disease (AD) from the Open Access Series of Imaging Studies (OASIS) database. We found specific locations in the genu and splenium of AD patients that are proportionally thinner than those of NCs. Callosal thickness in these regions combined with the Mini Mental State Examination scores differentiated AD from NC with 84% accuracy.

Background: Alzheimer's disease (AD) has been shown to be associated with shrinkage of the corpus callosum mid-sagittal cross-sectional area (CCA). Objective: To study temporal rates of corpus callosum atrophy not previously reported for early AD. Methods: We used longitudinal MRI scans to study the rates of change of CCA and circularity (CIR), a measure of its shape, in normal controls (NC, n = 75), patients with very mild AD (AD-VM, n = 51), and mild AD (AD-M, n = 21). Results: There were significant reduction rates in CCA and CIR in all three groups. While CCA reduction rates were not statistically different between groups, the CIR declined faster in AD-VM (p < 0.03) and AD-M (p < 0.0001) relative to NC, and in AD-M relative to AD-VM (p < 0.0004). Conclusion: CIR declines at an accelerated rate with AD severity. Its rate of change is more closely associated with AD progression than CCA or any of its sub-regions. CIR may be a useful group biomarker for objective assessment of treatments that aim to slow AD progression.

Correctly identifying voxels or regions of interest (ROI) that actively respond to a given stimulus is often an important objective/step in many functional magnetic resonance imaging (fMRI) studies. In this article, we study a nonparametric method to detect active voxels, which makes minimal assumption about the distribution of blood oxygen level-dependent (BOLD) signals. Our proposal has several interesting features. It uses time lagged correlation to take into account the delay in response to the stimulus, due to hemodynamic variations. We introduce an input permutation method (IPM), a type of block permutation method, to approximate the null distribution of the test statistic. Also, we propose to pool the permutation-derived statistics of preselected voxels for a better approximation to the null distribution. Finally, we control multiple testing error rate using the local false discovery rate (FDR) by Efron [Correlation and large-scale simultaneous hypothesis testing. J Am Stat Assoc 102 (2007) 93-103] and Park et al. [Estimation of empirical null using a mixture of normals and its use in local false discovery rate. Comput Stat Data Anal 55 (2011) 2421-2432] to select the active voxels.

BACKGROUND:The use of intraoperative carbon dioxide (CO(2)) colonoscopy during a laparoscopic colon operation is becoming more common. Simultaneous intracolonic and intraabdominal CO(2) insufflation may result in significant physiologic changes, but in-depth physiologic effects have not been studied to date. This study aimed to evaluate the physiologic changes and the overall safety of simultaneous CO(2) laparoscopy and colonoscopy. METHODS:A prospective pilot study was performed with 26 subjects (17 men and 9 women) undergoing laparoscopic surgical treatment for colorectal conditions adjunctively managed with CO(2) intraoperative colonoscopy. Surgery proceeded with CO(2) insufflation to a maximum pressure of 12 mmHg by laparoscopy and with a maximum CO(2) flow of 5 l/min via colonoscopy. Serial intra- and postoperative arterial blood gases, end-tidal CO(2), and minute ventilation were recorded during predetermined periods: during initial laparoscopy, during simultaneous colonoscopy and laparoscopy, during laparoscopy after colonoscopy, and after desufflation. RESULTS:No significant morbidity resulted from simultaneous CO(2) insufflation. Three patients had a CO(2) partial pressure (PaCO(2)) greater than 50, and one patient with a body mass index (BMI) higher than 42 kg/m(2) had a PaCO(2) greater than 50 for more than 30 min and was compensated by increasing minute ventilation. The mean pH was 7.36 in the recovery room. Postoperatively, no patient had a pH lower than 7.3, prolonged intubation, or reintubation. CONCLUSION/CONCLUSIONS:Simultaneous CO(2) colonoscopy and laparoscopy lead only to transient alterations in respiratory parameters that can be compensated. Based on these findings, simultaneous insufflation of CO(2) into the peritoneal cavity and the large bowel lumen during complex endoscopic procedures may be considered safe for most patients.

BACKGROUND: Previous studies of major depressive disorder (MDD) have focused on abnormalities in the prefrontal cortex and medial temporal regions. There has been little investigation in MDD of midbrain and subcortical regions central to reward/aversion function, such as the ventral tegmental area/substantia nigra (VTA/SN), and medial forebrain bundle (MFB). METHODOLOGY/PRINCIPAL FINDINGS: We investigated the microstructural integrity of this circuitry using diffusion tensor imaging (DTI) in 22 MDD subjects and compared them with 22 matched healthy control subjects. Fractional anisotropy (FA) values were increased in the right VT and reduced in dorsolateral prefrontal white matter in MDD subjects. Follow-up analysis suggested two distinct subgroups of MDD patients, which exhibited non-overlapping abnormalities in reward/aversion circuitry. The MDD subgroup with abnormal FA values in VT exhibited significantly greater trait anxiety than the subgroup with normal FA values in VT, but the subgroups did not differ in levels of anhedonia, sadness, or overall depression severity. CONCLUSIONS/SIGNIFICANCE: These findings suggest that MDD may be associated with abnormal microstructure in brain reward/aversion regions, and that there may be at least two subtypes of microstructural abnormalities which each impact core symptoms of depression.

Recent years have witnessed an upsurge in the usage of resting-state functional magnetic resonance imaging (fMRI) to examine functional connectivity (fcMRI), both in normal and pathological populations. Despite this increasing popularity, concerns about the psychologically unconstrained nature of the 'resting-state' remain. Across studies, the patterns of functional connectivity detected are remarkably consistent. However, the test-retest reliability for measures of resting state fcMRI measures has not been determined. Here, we quantify the test-retest reliability, using resting scans from 26 participants at 3 different time points. Specifically, we assessed intersession (>5 months apart), intrasession (<1 h apart), and multiscan (across all 3 scans) reliability and consistency for both region-of-interest and voxel-wise analyses. For both approaches, we observed modest to high reliability across connections, dependent upon 3 predictive factors: 1) correlation significance (significantly nonzero > nonsignificant), 2) correlation valence (positive > negative), and 3) network membership (default mode > task positive network). Short- and long-term measures of the consistency of global connectivity patterns were highly robust. Finally, hierarchical clustering solutions were highly reproducible, both across participants and sessions. Our findings provide a solid foundation for continued examination of resting state fcMRI in typical and atypical populations