Multi-channel Enhancement and Validation of Subcortical Morphometry in HIV

描述（由申请人提供）：尽管在高效抗逆转录病毒治疗时代取得了重大进展，但人类免疫缺陷病毒（HIV）对中枢神经系统（CNS）的影响仍然普遍存在。在这种情况下，我们继续寻找敏感的，非侵入性的生物标志物，以指导治疗，监测治疗干预，并确定个人的风险，中枢神经系统下降。以前的工作支持神经影像学在识别HIV生物标志物方面的价值，特别是在白色物质和尾状核中。最近的临床神经影像学的努力，在多站点中枢神经系统艾滋病毒抗逆转录病毒治疗效果研究（CHARTER）计划已采用多种方式，包括结构和扩散张量磁共振成像，以评估大脑的反应，艾滋病毒感染。CHARTER采用多通道MRI（T1、T2、PD）通过手动描绘全局区域来产生组织分割，从而成功识别HIV的神经成像相关性，例如白色物质（AbWM）异常。手动描绘单个结构（例如，然而，在大规模研究中是禁止的。最近的方法进步为自动化区域划分提供了希望，然而，这些方法尚未在艾滋病毒中得到验证。这些方法仅依赖于T1序列可能导致AbWM误分类为灰质，导致结构体积估计的灵敏度降低和错误。由于AbWM与疾病严重程度的相关性，此类分类错误可能导致系统偏倚。利用CHARTER的数据，我们建议严格评估两个相对自动化的皮质下标记方法在HIV中的性能，并检查统计预处理程序，可以提高这些方法的性能。特别是，我们将检查HIV相关的AbWM影响方法性能的程度相对于形态学的“金标准”。“感兴趣的黄金标准区域（例如，尾状核）将根据现有的CHARTER形态测量学进行定义，从而增加手动描绘的可靠性。我们还将研究统计学增强输入T1体积的价值，通过使用交替条件期望（ACE），使用来自PD，T2和扩散张量成像（DTI）体积的信息，这将使用补充体积来增强T1体积中的组织对比度。进一步的验证工作将检查所得结构体积与神经行为和医学生物标志物之间的关系。结构神经成像方法的系统评估和增强将使我们能够更好地表征HIV的潜在神经发病机制，潜在地验证这些工具用于HIV，为最终用户提供指导，并为开发人员提供未来工作的见解。重要的是，这项工作将为CHARTER提供区域形态测量数据，作为探索其他更具体假设检验的资源倡议，例如尾状核体积作为HIV相关认知下降的生物标志物的价值，下降风险或治疗干预的有效性。 公共卫生相关性：尽管在高活性抗逆转录病毒治疗时代取得了重大进展，但人类免疫缺陷病毒（HIV）对中枢神经系统（CNS）的影响仍然普遍存在，神经功能缺损和神经认知功能障碍对个人日常生活，工作表现和护理需求的影响可能是显着的。正在进行的多站点CNS HIV抗逆转录病毒治疗效果研究（CHARTER）计划为此类效果的表征提供了一个独特的多学科环境，在该环境中，我们提出了一种系统的评估和增强结构神经成像方法，这些方法以前未在HIV中得到验证。这项工作将为CHARTER提供区域形态测量数据，作为探索HIV的额外，更具体的神经影像学相关性的资源倡议，以指导治疗，监测治疗干预，并识别CNS下降风险的个体。

DESCRIPTION (provided by applicant): Despite significant advances in the era of highly active anti-retroviral therapy, central nervous system (CNS) effects of human immunodeficiency virus (HIV) have remained prevalent. In this light, we continue to search for sensitive, non-invasive biomarkers to guide treatment, monitor therapeutic intervention, and identify individuals at risk for CNS decline. Previous work has supported the value of neuroimaging for identifying biomarkers in HIV, particularly in the white matter and caudate nucleus. Recent clinical neuroimaging efforts within the multi-site CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) program have employed multiple modalities including structural and diffusion tensor MR imaging to assess the brain's response to HIV infection. CHARTER has employed multi-channel MRI (T1, T2, PD) to produce tissue segmentations with manual delineation of global regions, resulting in successful identification of neuroimaging correlates of HIV, such as abnormalities in the white matter (AbWM). Manual delineation of individual structures (e.g., caudate), however, is prohibitive on large-scale studies. Recent methodological advancements offer promise for automating regional delineation, however, these methods have not yet been validated in HIV. The reliance of these methods solely on T1 sequences can result in the misclassification of AbWM as gray matter, leading to decreased sensitivity and errors in structural volume estimates. Such classification errors may result in systematic bias, due to the correlation of AbWM with disease severity. Utilizing data from CHARTER, we propose to critically assess the performance of two relatively automated subcortical labeling methods in HIV and to examine a statistical pre-processing procedure that may enhance performance of these methods. In particular, we will examine the degree to which HIV-related AbWM affects method performance relative to a morphometric "gold standard." The gold standard regions of interest (e.g., caudate) will be defined upon existing CHARTER morphometry, thus increasing the reliability of the manual delineations. We also will investigate the value of statistically enhancing the input T1 volumes, with information from PD, T2, and diffusion tensor imaging (DTI) volumes, through the use of alternating conditional expectations (ACE), which will use the supplemental volumes to enhance tissue contrast in the T1 volumes. Further validation efforts will examine the relationship between resultant structural volumes and neurobehavioral and medical biomarkers. The systematic assessment and enhancement of structural neuroimaging methodology will allow us to better characterize the underlying neuropathogenesis of HIV, to potentially validate these tools for use in HIV, to provide guidance to end-users, and to offer insight to developers for future work. Importantly, this work will provide regional morphometric data to the CHARTER as a Resource initiative for the exploration of additional, more specific hypothesis testing, such as the value of caudate volume as a biomarker of HIV-related cognitive decline, risk for decline, or effectiveness of therapeutic intervention. PUBLIC HEALTH RELEVANCE: Despite significant advances in the era of highly active anti-retroviral therapy, central nervous system (CNS) effects of human immunodeficiency virus (HIV) have remained prevalent, and the impact of neurological impairment and neurocognitive dysfunction on individuals daily lives, work performance, and care needs can be significant. The on-going multi-site CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) program provides a unique multidisciplinary setting for the characterization of such effects, within which we propose a systematic assessment and enhancement of structural neuroimaging methods, not previously validated in HIV. This work will provide regional morphometric data to the CHARTER as a Resource initiative for the exploration of additional, more specific neuroimaging correlates of HIV to guide treatment, monitor therapeutic intervention, and identify individuals at risk for CNS decline.