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Abstract #4451

Mutli-modal MRI confirms HIV-1-linked neurometabolomic impairments in humanized mice

Gabriel Gauthier1, Aditya Bade2, Balasrinivasa Sajja1, Mariano Uberti1, Santhi Gorantla2, Micah Summerlin2, and Yutong Liu1
1Department of Radiology, University of Nebraska Medical Center, Omaha, NE, United States, 2Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, United States

Synopsis

Keywords: CEST / APT / NOE, CEST & MT, HIV

Motivation: While anti-retroviral therapy (ART) is essential for combating the type-one human immunodeficiency virus (HIV-1), patients with undetectable viral load still experience HIV-associated neurocognitive disorders.

Goal(s): We aimed to use the chemical exchange saturation transfer (CEST) effects of brain metabolites with MRI to elucidate HIV-associated neurocognitive outcomes on ART patients.

Approach: Humanized mice were infected with HIV-1, then given daily treatment of ART or vehicle. CEST-MRI and MRS were used to evaluate brain metabolites at four key timepoints.

Results: Untreated mice showed declining 2ppm and 3ppm CEST signal in key brain regions, alongside increasing NOE signal. This was partially validated with MRS.

Impact: The metabolic insights that CEST-MRI offers to HIV immunological care may aid in the development of increasingly effective ART drugs, such as long-acting injectables. Increased efficacy of ART will allow for increased quality of life for people living with HIV.

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