Brain Metabolites in Patients with Asymptomatic Versus Symptomatic HIV-associated neurocognitive disorder: A 7 Tesla MR Spectroscopy Study Mohamed MA, Barker PB, Skolasky R Roosa H, Sacktor N Johns Hopkins University School of Medicine, Baltimore, MD

Author and co authors have no conflict of interest or financial interest or other relationships

Purpose HIV has been extensively studied using magnetic resonance spectroscopy (MRS) at field strengths of 1.5, 3.0 and 4.0 Tesla (T) (1, 2). The current study was undertaken to investigate the utility of 7.0T MRS in 5 brain regions for evaluating differences in brain metabolites' concentrations in HIV+ patients with asymptomatic neurocognitive impairment (ANI) versus symptomatic HIV associated neurocognitive disorder (HAND) [mild neurocognitive disorder (MND) and HIV associated dementia (HAD)].

Materials and Methods Participants: 10 HIV+ individuals with ANI (mean ± SD age of 62.3 ± 7.53) 12 with symptomatic HAND (mean ± SD age of 59.8± 5.4) 6 HIV- controls (mean ± SD age of 68.3 ± 7.8) MRS: A 7.0T Philips 'Achieva' scanner was used 32-channel head coil Single voxel STEAM spectra (TR/TE=3000/14 msec) were acquired from 5 brain regions with and without water suppression.

Materials and Methods The 5 Brain regions were:  Frontal white matter (FWM)  Basal ganglia (BG)  Precuneus (PC)  Posterior cingulate cortex (PCC)  Hippocampus (Hippo) The voxel sizes ranged from 8 to 15 cc (Figure 1).

Materials and Methods Spectra were analyzed using the LCModel Spectra were quantified relative to the cerebral water signal (‘institutional units’, i.u.) Metabolite concentrations and ratios relative to creatine (Cr) were calculated. The data was not normally distributed Comparisons of the groups' medians and interquartile (IQR) ranges were evaluated for significant differences using non-parametric median test.

Results In regards to serostatus: Significant increase in BG total choline (tCho = GPC+PCh) in HIV+ versus seronegative controls [median (IQR) = 1.71 ( ) and 1.6 ( ) mM respectively], P= No significant differences in other brain regions metabolites in regards to serostatus.

BG total choline (tCho = GPC+PCh) in HIV+ versus seronegative controls

Results In regards to cognitive impairment, FWM and PC NAA/Cr were significantly lower in symptomatic HAND versus ANI patients, P= and respectively: Symptomatic HAND patients : Median (IQR) FWM NAA/Cr =1.19 ( ) Median (IQR) PC NAA/Cr = 1.11 ( ) ANI patients: Median (IQR) FWM NAA/Cr = 1.29 ( ) Median (IQR) PC NAA/Cr = 1.24 ( )

NAA/Cr in Symptomatic HAND versus ANI patients

Results Glu/Cr was significantly lower in symptomatic HAND versus ANI patients in the FWM and PCC, P= and respectively: Symptomatic HAND patients : Median (IQR) FWM Glu/Cr = 1.08 ( ) Median (IQR) PCC Glu/Cr = 1.07 ( ) ANI patients: Median (IQR) FWM Glu/Cr = 1.15 ( ) Median (IQR) PCC Glu/Cr = 1.24 ( ) The Hippo and BG showed no significant differences in metabolites between ANI and symptomatic HAND patients.

Glu/Cr in Symptomatic HAND versus ANI patients

Discussion and Conclusions The current study confirms some of the previous 3T findings namely reduced FWM NAA/Cr and Glu/Cr ratios (3, 4). 7T MRS measurements of brain metabolites revealed significant changes particularly in Glu/Cr which is more reliably measured at 7T than at 1.5 and 3T (5). It also added new findings in other brain regions namely reduced PC NAA/Cr and decreased PCC Glu/Cr ratios reflecting neuronal impairment in association with symptomatic HAND patients.

Conclusion The study also showed increased BG tCho in HIV+ versus HIV- reflecting glial cell proliferation with change in serostatus. 7T MRS metabolites measurement of Glu/Cr, NAA/Cr ratios can be reliable biomarkers for assessment of symptomatic HAND in patients with HIV.

References 1.Chang L, Ernst T, St Hillaire C, et al. Antiretroviral treatment alters relationship between MCP-1 and neurometabolites in HIV patients. Antivir Ther 2004: 9 (3): Young A, Yiannoutsos C, Hedge M, et al. Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection. Neurology 2014: 83 (18): Sailasuta N, Shriner K, Ross B. Evidence of reduced glutamate in the frontal lobe of HIV-seropositive patients. NMR Biomed 2009: 22: Mohamed M, Barker PB, Skolasky RL et al. Brain metabolism and cognitive impairment in HIV infection: a 3-T magnetic resonance spectroscopy study. Magn Reson Imaging MRI 2010: 28(9): Mekle R, Mlynarik V, et al. MR spectroscopy of the human brain with enhanced signal intensity at ultrashort echo times on a clinical platform at 3T and 7T. MRM 2009;61(6):