Multi-channel Enhancement and Validation of Subcortical Morphometry in HIV

HIV 皮质下形态测量的多通道增强和验证

• 批准号: 7938681
• 负责人: CHRISTINE FENNEMA-NOTESTINE
• 金额: $ 19.12万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7938681
• 关键词: Affect; Amygdaloid structure; Anisotropy; Anti-Retroviral Agents; Automation; Basal Ganglia; Biological Markers; Brain; Caring; Classification; Clinical; Cognitive; Data; Diffusion; Diffusion Magnetic Resonance Imaging; Effectiveness; Exhibits; Functional disorder; Future; Gold; HIV; Highly Active Antiretroviral Therapy; Hippocampus (Brain); Image Analysis; Image Enhancement; Impaired cognition; Impairment; Individual; Investigation; Label; Learning; Life; Light; Magnetic Resonance Imaging; Manuals; Measures; Medical; Methodology; Methods; Modality; Monitor; Neuraxis; Neurocognitive; Neurologic; Neuropathogenesis; Nucleus Accumbens; Performance; Performance at work; Procedures; Process; Recommendation; Relative (related person); Reliance; Research; Resources; Risk; Severity of illness; Shapes; Site; Structure; Systematic Bias; Testing; Thalamic structure; Therapeutic Intervention; Tissues; Validation; Viral Load result; Virus Diseases; Work; base; caudate nucleus; cohort; expectation; gray matter; improved; insight; interest; lateral ventricle body; morphometry; multidisciplinary; neurobehavioral; neuroimaging; programs; public health relevance; putamen; response; tool; white matter

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.

描述（由申请人提供）：尽管在高度活跃的抗逆转录病毒疗法的时代，人类免疫缺陷病毒（HIV）的影响仍然很普遍。鉴于这个观点，我们继续寻找敏感的，非侵入性的生物标志物来指导治疗，监测治疗性干预并确定有CNS下降风险的人。先前的工作支持神经影像学对于鉴定HIV中的生物标志物的价值，尤其是在白质和尾状核中。在多站点中枢神经系统HIV抗逆转录病毒疗法研究（Charter）计划中，最近的临床神经影像学工作已采用多种模式，包括结构性和扩散张量MR成像来评估大脑对HIV感染的反应。 Charter已使用多通道MRI（T1，T2，PD）来生产通过手动描述全球区域的组织分割，从而成功鉴定了HIV的神经影像学相关性，例如白质的异常（ABWM）。然而，对单个结构的手动描述（例如，尾状）在大规模研究中都非常刺激。最近的方法学进步为自动化区域描述提供了希望，但是，这些方法尚未在艾滋病毒中得到验证。这些方法仅对T1序列的依赖可能导致ABWM作为灰质的错误分类，从而导致结构体积估计值的灵敏度和错误降低。由于ABWM与疾病严重程度的相关性，这种分类错误可能导致系统偏见。利用宪章中的数据，我们建议批判性地评估艾滋病毒中两种相对自动化的亚皮质标记方法的性能，并检查可能会增强这些方法性能的统计预处理程序。特别是，我们将研究与形态“金标准”相对于形态计量学的ABWM影响方法的程度。现有的宪章形态计量法将定义利益的黄金标准区域（例如，尾状），从而提高了手动描述的可靠性。我们还将通过使用交替的条件期望（ACE）来研究来自PD，T2和扩散量张量成像（DTI）体积的信息的统计增强输入T1体积的价值，这些信息将使用补充体积来增强T1量的组织对比度。进一步的验证工作将研究产生的结构量与神经行为和医学生物标志物之间的关系。结构性神经影像学方法的系统评估和增强将使我们能够更好地表征HIV的潜在神经病发生，从而有可能验证这些工具用于HIV，以向最终用户提供指导，并为开发人员提供洞察力。重要的是，这项工作将为宪章提供区域形态数据，作为探索其他更具体的假设检验的资源计划，例如，尾状体积作为与HIV相关的认知能力下降，下降或治疗干预效果的生物标志物的价值。 公共卫生相关性：尽管在高度活跃的抗网状病毒疗法时代，人类免疫缺陷病毒（HIV）的影响仍然很普遍，并且神经认知障碍和神经认知功能障碍对个人日常生活，工作绩效以及医疗服务的影响很大。正在进行的多站点中枢神经系统HIV抗逆转录病毒治疗效应研究（Charter）计划为表征这种影响提供了独特的多学科环境，在其中我们提出了对结构性神经影像学方法的系统评估和增强，以前未在HIV中验证。这项工作将为宪章提供区域形态数据，作为探索HIV的其他更具体的神经影像相关性的资源计划，以指导治疗，监测治疗性干预并确定有CNS下降风险的人。