vascuCAP: Non-invasive Computer-Aided Phenotyping of Vasculopathy

 描述（由申请人提供）：血管病包括一组血管疾病，其中包括动脉粥样硬化，这是一种具有巨大社会影响的主要疾病。动脉粥样硬化与许多心血管疾病有关，包括心肌梗死、外周血管疾病和中风。已经提出了改进诊断的方法，其中不确定或误导性的信息可能导致治疗不足和过度。此外，需要更好的生物标志物用于开发更有效的血管病药物。动脉狭窄作为一种生物标志物是一个不良事件的预测因子，但它仍然是常用的。这给护理提供者带来了高错误分类率的负担。检测所谓的“脆弱”斑块已显示出前景，但它并非没有争议，可能不太可能实现广泛采用，因为它仍然依赖于检测一个或少数“替代”特征，这些特征基于有限的尸检研究。Elucid Bioimaging的vascuCAP（CAP代表计算机辅助表型分析）处理磁共振成像（MRI）和/或计算机断层扫描（CT），这两者都是血管诊断的常规方法。CAP辅助临床医生使用多因素定量成像生物标志物面板，其具有特异性、生物学客观性和连续值测量，例如脂质核心分布和病变表型和严重程度的其他决定因素。认识到不同成像模式相对于任何给定患者需求的利弊，vascuCAP被开发为多模式分析能力，其最大化来自可用于该患者的任何模式的信息内容，无论是CT（其是快速的并且通常导致结构的最准确的测量，但是其利用电离辐射）或MR（其目前最能够测量成分，避免电离辐射，但需要更多时间来获取）。我们的主要目标是通过将血管成像的vascuCAP分析与其他客观患者数据（即临床化学和其他血液生物标志物）相结合，帮助有症状和无症状患者做出治疗决策，从而改善患者管理。它还可以用于提高开发新疗法的速度和效率。我们最近完成了动物模型和人类动脉粥样硬化的可行性研究，作为拟议研究的科学依据。这项II期研究将确定动脉粥样硬化斑块的MRI和CT特征，并将其与参考真实标准进行比较，包括动脉内膜切除术标本的组织病理学分析。我们已经在动物模型和人体研究中建立了可能的临床效用。这项II期SBIR研究将确定在大量颈动脉和外周动脉中获得的vascuCAP分析结果与离体组织学获得的结果相似的程度，以及冠状动脉中的相关参考测量值是否与先前的可行性研究一致。

 DESCRIPTION (provided by applicant): Vasculopathy encompasses a group of vascular diseases, which includes atherosclerosis, a major disease with enormous societal impact. Atherosclerosis is implicated in many cardiovascular diseases including myocardial infarction, peripheral vascular disease, and stroke. Approaches have been proposed for improving diagnostics, where inconclusive or misleading information can lead to under- and over-treatment. Additionally, better biomarkers are needed for use in developing more effective drugs for vasculopathies. Arterial stenosis as a biomarker is a poor predictor of events, yet it remains in common use. This burdens care providers with high misclassification rates. Detection of the so-called "vulnerable" plaque has demonstrated promise, but it is not without controversy and may be unlikely to achieve widespread adoption because it still relies on detecting one or a handful of "surrogate" features, that are based on limited autopsy studies. Elucid Bioimaging's vascuCAP (CAP stands for Computer Aided Phenotyping) processes magnetic resonance imaging (MRI) and/or computed tomography (CT), both of which are routinely used in vascular diagnostics. CAP aids the clinician with a multi-factorial quantitative imaging biomarker panel of specific, biologically-objective, and continuous-valued measurements such as distribution of lipid core and other determinants of lesion phenotype and severity. Recognizing the pros and cons of different imaging modalities with respect to any given patient's needs, vascuCAP is developed as a multi-modality analysis capability that maximizes the information content from whatever modality is available for that patient, whether CT (which is fast and generally leads to the most accurate measurements of structure but which utilizes ionizing radiation) or MR (which is currently most capable of measuring composition, avoids ionizing radiation, but takes more time to acquire). Our primary goal is to improve patient management by aiding therapeutic decision-making for both symptomatic and asymptomatic patients by combining the vascuCAP analysis of vascular imaging with the other objective patient data, i.e. clinical chemistry and other blood biomarkers. It may also be used to improve speed and efficiency in developing new therapeutics. We have recently completed feasibility studies in both animal models as well as human atherosclerosis that serve as the scientific rationale for the proposed study. This Phase II study will determine the MRI and CT characteristics of atherosclerotic plaques and compare them to reference truth standards including histopathological analyses of arterial endarterectomy specimens. We have established probable clinical utility in animal models as well as in human studies. This Phase II SBIR study will determine the degree to which vascuCAP analysis results, obtained in larger numbers of carotid and peripheral arteries, are similar to those obtained on ex-vivo histology and whether relevant reference measurements in the coronary arteries are in accordance with prior feasibility studies.