Micro-Structural Alterations in the Brain of Well-Treated HIV+ Patients with Mild Neurocognitive Disorders: A Multi-Contrast MRI Study at High Field (S37.001)

Abstract

Objective: To investigate MRI markers of subtle HIV effects on the brain. Background Mild neurocognitive disorders (MND) affect a subset of HIV+ patients under effective highly active antiretroviral therapies (HAART). The physiopathology of MND is however not clear, as well as the reasons why some well-treated patients suffer from MND while other not. Here, we used a multi-contrast MRI based approach at high field to test the hypothesis that well-treated aviremic MND+ patients present different brain micro-structural characteristics compared to MND- HIV patients and healthy controls (HC). Design/Methods: We enrolled 17 MND+ and 19 MND- patients with undetectable viremia and 14 age-matched HC. MRI acquisitions at 3T included: MP2RAGE for T1 relaxation times as well as Magnetization Transfer (MT), T2* and Susceptibility Weighted Imaging (SWI) to probe micro-structural integrity and iron deposition. Regions of interest were automatically extracted for white and gray matter (WM, GM), thalamus, basal ganglia and hippocampus. Statistical analysis used multivariate permutation-based Hotelling tests and correction for family-wise error rate. A linear discriminant analysis between MND+ and MND- patients was performed using multi-parametric MRI data (T1, MT ratio, SWI) and cross-validated with a leave-one-out test. Results: Multivariate analysis showed significant differences between MND+ and MND- patients in WM and GM (p=0.02 respectively), and between MND+ and HC in the caudate (p=0.02). Univariate analysis revealed that MND+ patients had lower MT ratio than MND- and HC, reaching significance in WM and caudate (p=0.01). The linear discriminant analysis distinguished MND+ and MND- patients with a classification quality of 0.73% after cross-validation. Conclusions: Our findings show the presence of micro-structural brain alterations in MND+ patients as compared to MND- and HC, suggesting loss of structural integrity. In addition, they suggest that multi-contrast MRI at high field may be a powerful approach to understand the physiopathology of MND and to discriminate between patients9 sub-groups. Supported by: Centre d9Imagerie BioMedicale of the University of Lausanne, the Swiss Federal Institute of Technology Lausanne, the University of Geneve, the Centre Hospitalier Universitaire Vaudois, the Hopitaux Universitaires de Geneve, the Leenaards, the Jeantet and the Stoicescu foundations and the Swiss National Science Foundation Grant PZ00P3_131914/1. Disclosure: Dr. Granziera has nothing to disclose. Dr. Daducci has nothing to disclose. Dr. Simioni has received personal compensation for activities with Gilead and Boehringer Ingelheim as a speaker. Dr. Cavassini has nothing to disclose. Dr. Roche has received personal compensation for activities with Siemens AG as an employee. Dr. Meskaldji has nothing to disclose. Dr. Michel has nothing to disclose. Dr. Calmy has nothing to disclose. Dr. Hirschel has nothing to disclose. Dr. Krueger has received personal compensation for activities with Siemens AG as an employee. Dr. Krueger has received research support from Siemens AG. Dr. Du Pasquier has received personal compensation for activities with Merck Serono, Biogen Idec, Abbott, and ViiV.