Nguchu Benedictor Alexander, Zhao Jing, Fan Jiajun, Han Yifei, Lu Yu, Jin Han, Wang Yanming, Li Hongjun, Shaw Peter
Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, Zhejiang, China.
School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Front Neurol. 2025 May 19;16:1516168. doi: 10.3389/fneur.2025.1516168. eCollection 2025.
While the adjustment of intracranial volume (ICV) is reported to have a significant influence in the outcomes of the analyses of brain structural measures, our study offers a paradigm shift, positing that adjusting for lateral ventricle (LV) inter-individual variability may reveal more atrophic patterns that might be overlooked in analyses without this adjustment,-and such LV-adjusted atrophic patterns may reduce discrepancies observed in earlier studies and better elucidate complex conditions associated with HIV, such as HAND.
To test this hypothesis, we employed a number of adjustment strategies on MRI T1-image-derived data extracted using deep learning models and compared their ability to identify the presence and extent of HIV-specific atrophic patterns based on statistical measures and strength.
Our results show that both ICV adjustments may be effective to identify atrophic patterns associated with either aging or HIV in areas of the thalamus, basal ganglia, ventral DC and lateral ventricle, some of which may be overlooked without these adjustments. We also report that LV adjustmenst detect most atrophic patterns associated with HIV and HAND across multiple subcortical regions with more strong statistical strengths, especially the areas of the basal ganglia (putamen, pallidum, caudate nucleus), hippocampus, thalamus, ventral DC, basal forebrain, third ventricle, fourth ventricle, and inferior lateral ventricle. The analyses of LV-adjusted metrics also show that atrophic patterns observed in the hippocampus, thalamus and pallidum were strongly correlated with HAND(especially dysfunction in executive function) and clinical markers (i.e., CD4/CD8 ratio).
We conclude that models that control for individual variability in intracranial and ventricular volumes have the potential to minimize discrepancies and variations in structural reports of HIV, improving the diagnostic power of identified patterns and fostering greater consistency across research studies. More importantly, adjusting for LV may not only detect atrophic patterns that could be overlooked in analyses performed without any adjustments, but the outcomes obtained from the adjustments may better explain HIV-associated conditions such as HAND and underlying immunological issues often observed in subjects with HIV treated with combination antiretroviral therapy, considering that the adjustments account for certain aspects of regional interaction.
虽然据报道颅内体积（ICV）的调整对脑结构测量分析的结果有重大影响，但我们的研究提供了一种范式转变，认为调整侧脑室（LV）个体间变异性可能会揭示更多在未进行这种调整的分析中可能被忽视的萎缩模式，并且这种经LV调整的萎缩模式可能会减少早期研究中观察到的差异，并更好地阐明与HIV相关的复杂情况，如HAND。
为了验证这一假设，我们对使用深度学习模型提取的MRI T1图像数据采用了多种调整策略，并根据统计指标和强度比较了它们识别HIV特异性萎缩模式的存在和程度的能力。
我们的结果表明，两种ICV调整在识别丘脑、基底神经节、腹侧背侧丘脑和侧脑室区域与衰老或HIV相关的萎缩模式方面可能是有效的，其中一些在没有这些调整的情况下可能会被忽视。我们还报告说，LV调整在多个皮质下区域检测到与HIV和HAND相关的大多数萎缩模式，具有更强的统计强度，特别是基底神经节（壳核、苍白球、尾状核）、海马体、丘脑、腹侧背侧丘脑、基底前脑、第三脑室、第四脑室和外侧脑室下部区域。对经LV调整的指标的分析还表明，在海马体、丘脑和苍白球中观察到的萎缩模式与HAND（特别是执行功能障碍）和临床标志物（即CD4/CD8比率）密切相关。
我们得出结论，控制颅内和脑室体积个体变异性的模型有可能最大限度地减少HIV结构报告中的差异和变化，提高所识别模式的诊断能力，并促进各研究之间更大的一致性。更重要的是，调整LV不仅可以检测在未进行任何调整的分析中可能被忽视的萎缩模式，而且从调整中获得的结果可能更好地解释与HIV相关的情况，如HAND以及在接受联合抗逆转录病毒治疗HIV的受试者中经常观察到的潜在免疫问题，因为这些调整考虑了区域相互作用的某些方面。
