Resting cerebral blood flow: a potential biomarker of the effects of HIV in the brain

Abstract

Objective: HIV enters the brain soon after infection causing neuronal damage and microglial/astrocyte dysfunction leading to neuropsychological impairment. We examined the impact of HIV on resting cerebral blood flow (rCBF) within the lenticular nuclei (LN) and visual cortex (VC).

Methods: This cross-sectional study used arterial spin labeling MRI (ASL-MRI) to measure rCBF within 33 HIV+ and 26 HIV- subjects. Nonparametric Wilcoxon rank sum test assessed rCBF differences due to HIV serostatus. Classification and regression tree (CART) analysis determined optimal rCBF cutoffs for differentiating HIV serostatus. The effects of neuropsychological impairment and infection duration on rCBF were evaluated.

Results: rCBF within the LN and VC were significantly reduced for HIV+ compared to HIV- subjects. A 2-tiered CART approach using either LN rCBF < or =50.09 mL/100 mL/min or LN rCBF >50.09 mL/100 mL/min but VC rCBF < or =37.05 mL/100 mL/min yielded an 88% (29/33) sensitivity and an 88% (23/26) specificity for differentiating by HIV serostatus. HIV+ subjects, including neuropsychologically unimpaired, had reduced rCBF within the LN (p = 0.02) and VC (p = 0.001) compared to HIV- controls. A temporal progression of brain involvement occurred with LN rCBF significantly reduced for both acute/early (<1 year of seroconversion) and chronic HIV-infected subjects, whereas rCBF in the VC was diminished for only chronic HIV-infected subjects.

Conclusion: Resting cerebral blood flow (rCBF) using arterial spin labeling MRI has the potential to be a noninvasive neuroimaging biomarker for assessing HIV in the brain. rCBF reductions that occur soon after seroconversion possibly reflect neuronal or vascular injury among HIV+ individuals not yet expressing neuropsychological impairment.

Figure 1 Resting cerebral blood flow (rCBF) within the lenticular nuclei (LN) and visual cortex (VC) for HIV− and HIV+ subjects A significant reduction in resting cerebral blood flow (rCBF) was seen for HIV+ compared to HIV− subjects within both regions. *p < 0.01 compared to HIV− controls. All error bars are SEM.

Figure 2 A nonparametric classification and regression tree (CART) analysis determined thresholds for classification of subjects according to serostatus A 2-tiered approach using a resting cerebral blood flow (rCBF) ≤50.09 mL/100 mL/min in the lenticular nuclei (LN) or rCBF in the LN >50.09 mL/100 mL/min but rCBF ≤37.05 mL/100 mL/min in the visual cortex (VC) yielded a sensitivity of 88% (29/33) and specificity of 88% (23/26).

Figure 3 Effects of degree of neuropsychological impairment on rCBF within the LN and VC For both the lenticular nuclei (LN) and visual cortex (VC), a significant reduction in resting cerebral blood flow (rCBF) was seen for both neuropsychologically unimpaired and impaired HIV+ subjects compared to HIV− controls. *p < 0.01 compared to HIV− controls. All error bars are SEM.

Figure 4 Effects of HIV disease duration on rCBF within the LN and VC For the lenticular nuclei (LN), a significant reduction in resting cerebral blood flow (rCBF) was seen for both acute/early and chronic HIV-infected subjects. (A) Within the VC, only chronic HIV-infected subjects had a significant reduction compared to HIV− controls. *p < 0.01 compared to HIV− controls. All error bars are SEM.