ArticleResearch square2025
CEST MRI Affirms HIV-1-Associated Neurometabolic Impairments in a Humanized Mouse Model.
Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: Human immunodeficiency virus 1 (HIV-1)-associated neurocognitive disorders (HAND) persist in people living with HIV-1 (PLWH) despite antiretroviral therapy (ART), driven by unresolved neuroinflammation and metabolic dysfunction. This study evaluates chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) detection of HIV-1-induced neurometabolic impairments and ART-mediated improvements in a humanized mouse model. Methods: HIV-1-infected CD34-NSG mice (n = 14) underwent CEST MRI to quantify metabolic profiles in the cortex, hippocampus, hypothalamus, piriform cortex, and thalamus at three timepoints: pre-infection (Week 0), 6 weeks-post-infection (WPI), and after 6 weeks of ART- or vehicle-treatment (12 WPI). CEST contrasts were analyzed at 2 ppm (creatine), 3 ppm (glutamate), and - 3.5 ppm (nuclear Overhauser effect, NOE). Neuroinflammation and infection were confirmed using immunohistology and qPCR. Results: At 6 WPI, HIV-1-infection reduced creatine in the cortex (p = 0.0006) and hippocampus (p = 0.01), and elevated NOE in the cortex (p = 0.001). At 12 WPI, vehicle-treated HIV-infected mice exhibited significantly decreased glutamate in the cortex (p = 0.004), hippocampus (p < 0.0001), and piriform cortex (p = 0.002); ART-treatment restored these levels in the cortex and hippocampus. Further, vehicle-treated mice exhibited decreased creatine in the cortex (p = 0.0002), hippocampus (p = 0.0003), piriform cortex (p = 0.0009), and thalamus (p = 0.006); ART-treatment restored these levels in the hippocampus, piriform cortex, and thalamus. Finally, vehicle-treated mice exhibited increased NOE in the cortex (p = 0.002) and thalamus (p = 0.003), but this was not restored by ART. CEST findings were supported by reductions in HIV-1 p24 + cells and neuroinflammatory markers in ART-treated brains. Discussion: CEST MRI detects region-specific HIV-1-induced neurometabolic alterations and ART-mediated restorations. This work establishes CEST MRI as a translational potential, non-invasive technique for monitoring HAND pathology and therapeutic efficacy.
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