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NEUROLOGY 2009;73:702-708
© 2009 American Academy of Neurology

Resting cerebral blood flow

A potential biomarker of the effects of HIV in the brain

B. M. Ances, MD, PhD, D. Sisti, BA, F. Vaida, PhD, C. L. Liang, BA, O. Leontiev, MD, J. E. Perthen, PhD, R. B. Buxton, PhD, D. Benson, BA, D. M. Smith, MD, S. J. Little, MD, D. D. Richman, MD, D. J. Moore, PhD, R. J. Ellis, MD, PhD On behalf of the HNRC group*

From the Department of Neurology (B.M.A.), Washington University in St. Louis, MO; Departments of Medicine (D.S., O.L., D.M.S., S.J.L., D.D.R.), Family and Preventive Medicine (F.V., D.B.), Radiology (C.L.L., J.E.P., R.B.B.), Psychiatry (D.D.R., D.J.M.), and Neurosciences (R.J.E.), University of California San Diego; and Veterans Administration San Diego Healthcare System (D.M.S., D.D.R.), San Diego, CA.

Address correspondence and reprint requests to Dr. Beau M. Ances, 660 South Euclid Avenue, Box 8111, St. Louis, MO 63110 bances{at}wustl.edu

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 ≤50.09 mL/100 mL/min or LN rCBF >50.09 mL/100 mL/min but VC rCBF ≤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.

Abbreviations: AEH = acute/early HIV infection; ANOVA = analysis of variance; ASL-MRI = arterial spin labeling MRI; CART = classification and regression tree; CBF = cerebral blood flow; CH = chronic HIV infection; FOV = field of view; GDS = global deficit score; HAART = highly active antiretroviral therapy; HAND = HIV-associated neurocognitive disorders; LN = lenticular nuclei; rCBF = resting cerebral blood flow; TE = echo time; TI = inversion time; TR = repetition time; VC = visual cortex.

Supplemental data at www.neurology.org

*Members of the San Diego HIV Neurobehavioral Research Center (HNRC) group are listed in the appendix.

The HNRC is supported by Center award MH 62512 from the National Institute of Mental Health.

Disclosure: Author disclosures are provided at the end of the article.

Received December 31, 2008. Accepted in final form June 8, 2009.






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