Combination antiretroviral therapy has decreased dramatically the complications of HIV infection in perinatally HIV-infected youth, but many perinatally HIV-infected individuals continue to have cognitive impairment and may experience indolent ongoing brain injury. Modern neuroimaging techniques, such as proton magnetic resonance spectroscopy/spectroscopic imaging (1H MRS/MRSI) and volumetric MRI can assess some of the processes underlying HIV brain injury. But brain connectivity changes have not been studied in perinatally HIV- infected youth. Also the relationships of cognitive impairment to brain network changes and cerebral metabolic disturbances in perinatally HIV-infected youth have not been well delineated. Here we use resting state functional MRI (rs-fMRI), to evaluate functional connectivity of the brain and to further define the pathology of perinatal infection as these patients age and survive their infections for many years. Alterations in functional connectivity between brain regions affected by HIV infection may provide further information about mechanisms behind neurocognitive decline. The proposed study will also analyze the metabolic changes in multiple locations using a semi-localized by adiabatic selective refocusing (sLASER)-based three dimensional (3D) MRSI sequence. The adiabatic refocussing pulses in this sequence overcome in homogeneities of the B1 transmit field and their relatively high bandwidth provide an acceptable chemical shift displacement error enabling acquisition of high-quality spectra in almost the entire 3D volume. Hence the specific aims of this study are: (1) to determine resting connectivity across five networks: default-mode network (DMN), control network (CON), salience network (SAL), dorsal attention network (DAN) and sensorimotor network (SMN) and assess connectivity differences between 30 perinatally HIV-infected youths, ages 18-30 years of age, receiving antiretroviral therapy and 30 individually age, race and gender-matched healthy controls; (2) to evaluate the HIV-induced alterations in cerebral metabolite ratios using the recently implemented sLASER-based 3D MRSI sequence; (3) to identify the relationships between altered cognitive function assessed with neurocognitive tests, resting brain connectivity, cerebral metabolite concentrations, and clinical variables (CD4, viral load, previous AIDS diagnosis, duration/CNS penetrance of ART) in antiretroviral treated perinatally HIV-infected youths. We hypothesize that resting brain connectivity will be altered in HIV-infected youth compared to healthy controls and these changes will correlate with poorer cognitive performance. The sLASER-based 3D MRSI data combined with rs-fMRI data will provide biochemical information and functional information to assess brain abnormalities in perinatally HIV-infected youths before symptoms of cognitive deficits appear. The proposed work will impact the field with a better understanding of the functional, metabolic, and neurocognitive changes in aging, perinatally HIV-infected youth which should lead to improved treatment and improved brain health over many years of infection.
This application evaluates two novel noninvasive MRI imaging techniques to better assess and preserve brain health in young adults who have been infected with HIV for their entire lives. Early detection of subtle changes associated with HIV infection and cognitive decline will permit a change of medications to prevent further damage and preserve quality of life. These techniques can also be used to follow adults with sexually transmitted HIV to maintain brain health and function.
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