Teddy Salan, PhD
University of Miami
Co-Authors: Fernando M Moradel Cano1, Dario N Ayala1, Ranya Marrakchi El Fellah1, Eva Widerstrom-Noga1, Suresh Pallikkuth1, Denise C Vidot1, Allan E Rodriguez1, Robert L Cook2, Varan Govind1
1University of Miami, 2University of Florida
Background: HIV infection is associated with chronic neuroinflammation and microstructural injury in people with HIV (PWH). On the other hand, the effect of chronic cannabis use on brain tissue microstructure is less established, with some studies showing that cannabis does not negatively affect white matter (WM) microstructure. However, these findings were dependent on age, frequency/duration and mode of administration.
Objective: The goal of this study is to evaluate the effect of HIV infection and cannabis use on brain microstructure using multi-shell diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) with free-water elimination (FWE).
Methods: MRI data were collected on a 3T scanner from 44 subjects, following a 2×2 design: 14 PWH using cannabis (PWH+C; 37±7.8 y.o.), 7 PWH not using cannabis (PWH; 38.5±5.1 y.o.), 13 people without HIV (PWoH) using cannabis (PWoH+C; 37.2±7.2 y.o.), and 10 PWoH not using cannabis (PWoH; 31.3±8.5 y.o.) as healthy controls. The protocol included multi-shell diffusion-weighted MRI (DWI; b = 1000/2000 s/mm2; 30 gradient directions). DWI data were processed to obtain DTI metrics: fractional anisotropy (FA), mean-, axial-, and radial-diffusivities (MD, AD, RD); DKI metrics: kurtosis FA (kFA), mean-, axial-, and radial-kurtosis (MK, AK, RK); and FWE-DTI metrics: FWE-FA, FWE-MD, FWE-AD, FWE-RD, and free water fraction (FW). These metrics were evaluated at 33 WM regions-of-interest (ROI) from the JHU-MNI-type2 atlas. At each ROI, we performed non-parametric two-way ANOVA to find the effect of HIV and cannabis on DTI/DKI/FWE metrics (significance at p<0.05, uncorrected in this preliminary analysis).
Results: Results showed extensive WM injury (lower FA and higher MD, AD, and RD) in PWH, PWoH+C, and PWH+C groups relative to controls, with few significant differences between PWH and PWoH+C groups, and the most widespread injury observed among PWH+C subjects. The most affected ROIs were the inferior (p<0.001) and superior longitudinal fasciculus (p<0.001), and post-thalamic radiation (p<0.001). Identical results were found with FWE-DTI including FW, while differences in DKI metrics were less significant.
Conclusions: Our results show that cannabis consumption can intensify white matter injury in PWH, as shown by the lower FA and higher diffusivities in PWH+C subjects compared to all groups, while PWH and PWoH+C subjects had comparable measurements. Higher FW also suggests higher inflammation in PWH+C, which may be a driving factor for the associated WM injury. Our future analyses will investigate the effect of relevant co-variates such as BMI, sex, frequency/duration and mode of cannabis administration, and cannabinoid metabolites in blood.