Salan Teddy, Willen Elizabeth J, Cuadra Anai, Sheriff Sulaiman, Maudsley Andrew A, Govind Varan
Department of Radiology, University of Miami Miller School of Medicine, Miami, FL, United States.
Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, United States.
Front Neurosci. 2023 Mar 2;17:1134867. doi: 10.3389/fnins.2023.1134867. eCollection 2023.
Perinatally acquired HIV (PHIV) has been associated with brain structural and functional deficiencies, and with poorer cognitive performance despite the advent of antiretroviral therapy (ART). However, investigation of brain metabolite levels in PHIV measured by proton magnetic resonance spectroscopy (MRS) methods, is still limited with often inconclusive or contradictory findings. In general, these MRS-based methods have used a single voxel approach that can only evaluate metabolite concentrations in a few select brain anatomical regions. Additionally, most of the published data have been on children perinatally infected with HIV with only a few studies examining adult populations, though not exclusively. Therefore, this prospective and cross-sectional study aims to evaluate metabolite differences at the whole-brain level, using a unique whole-brain proton magnetic resonance spectroscopy imaging (MRSI) method, in a group of PHIV infected young adults ( = 28) compared to age and gender matched control sample ( = 28), and to find associations with HIV clinical factors and neurocognitive scores. MRSI data were acquired on a 3T scanner with a TE of 70 ms. Brain metabolites levels of total N-acetylaspartate (tNAA), total choline (tCho) and total creatine (tCre), as well as ratios of tNAA/tCre, tCho/tCre, and tNAA/tCho, were obtained from the whole brain level and evaluated at the level of gray matter (GM) and white matter (WM) tissue types and anatomical regions of interest (ROI). Our results indicate extensive metabolic abnormalities throughout the brains of PHIV infected subjects with significantly elevated levels of tCre and tCho, notably in GM regions. Decreases in tNAA and ratios of tNAA/tCre and tNAA/tCho were also found mostly in WM regions. These metabolic alterations indicate increased glial activation, inflammation, neuronal dysfunction, and energy metabolism in PHIV infected individuals, which correlated with a reduction in CD4 cell count, and lower cognitive scores. Our findings suggest that significant brain metabolite alterations and associated neurological complications persist in the brains of those with PHIV on long-term ART, and advocates the need for continued monitoring of their brain health.
围产期获得性艾滋病毒(PHIV)与脑结构和功能缺陷有关,并且尽管有抗逆转录病毒疗法(ART),认知表现仍较差。然而,通过质子磁共振波谱(MRS)方法测量的PHIV患者脑代谢物水平的研究仍然有限,结果往往不确定或相互矛盾。一般来说,这些基于MRS的方法采用单一体素方法,只能评估少数选定脑解剖区域的代谢物浓度。此外,大多数已发表的数据是关于围产期感染艾滋病毒的儿童,只有少数研究调查了成人人群,尽管并非仅限于成人。因此,这项前瞻性横断面研究旨在使用独特的全脑质子磁共振波谱成像(MRSI)方法,评估一组感染PHIV的年轻成人(n = 28)与年龄和性别匹配的对照样本(n = 28)在全脑水平上的代谢物差异,并找出与艾滋病毒临床因素和神经认知评分的关联。MRSI数据在3T扫描仪上采集,回波时间(TE)为70毫秒。从全脑水平获得总N-乙酰天门冬氨酸(tNAA)、总胆碱(tCho)和总肌酸(tCre)的脑代谢物水平,以及tNAA/tCre、tCho/tCre和tNAA/tCho的比率,并在灰质(GM)和白质(WM)组织类型以及感兴趣的解剖区域(ROI)水平上进行评估。我们的结果表明,感染PHIV的受试者大脑中存在广泛的代谢异常,tCre和tCho水平显著升高,尤其是在GM区域。tNAA以及tNAA/tCre和tNAA/tCho的比率降低也主要出现在WM区域。这些代谢改变表明,感染PHIV的个体中胶质细胞激活、炎症、神经元功能障碍和能量代谢增加,这与CD4细胞计数减少和较低的认知评分相关。我们的研究结果表明,长期接受ART治疗的PHIV患者大脑中存在显著的脑代谢物改变和相关的神经并发症,并主张需要持续监测他们的脑健康。