Effects of in situ orientation on quantitative MR-based measures of cartilage endplate health

项目概要/摘要 慢性下背痛（cLBP）是全球残疾的主要原因，被认为与椎间关节炎有关。 部分患者椎间盘退变。软骨终板（CEP）通过影响椎间盘的健康， 营养物质在无血管椎间盘和脊椎毛细血管之间的运输。通过其对盘营养供应的影响， CEP还可能影响旨在再生椎间盘的基于细胞的生物疗法的功效， 这些疗法增加了椎间盘内的营养需求。这项提议的前提是， CEP成分的评估可以提供椎间盘退变病因的深入了解，并指导患者的选择 用于基于细胞的生物疗法，从而有助于解决与cLBP相关的全球健康负担。 CEP组成的一种新的成像生物标志物-使用超声波测量的平均CEP T2* 弛豫时间， 短回波时间（UTE）MRI-最近已被证明与CEP成分影响方面相关 cLBP患者椎间盘营养转运和椎间盘退变程度。这种非侵入性 生物标志物对于阐明CEP在椎间盘退变/再生中的作用具有重要意义。然而，在这方面， 由CEP产生的MR信号取决于其在MRI孔中的相对原位取向。差异 在成像过程中由方向引起的T2* 可能超过与生化或显微结构相关的T2 *。 恶化，从而混淆准确的分析。如果不了解方位对CEP T2* 的影响， 价值观，研究人员--最终是临床医生--无法准确评估患者的CEP组成。 本文提出的研究解决了这些局限性，并促进了开发和临床翻译 CEP组成的基于MRI的生物标志物，独立于个体间和个体内解剖变异， CEP方向。目标1a将使用UTE MRI以不同角度对尸体运动节段进行成像，以开发 基于原位取向调整CEP T2* 值的校准曲线。目标1b将测试 该校准曲线在用UTE MRI成像的cLBP患者和无症状对照的临床群组中。 目的2将量化CEP微结构和生化成分对CEP间和CEP内的贡献 CEP T2* 值的变化，增强对影响CEP T2* 的因素的机理理解， 基于UTE的CEP生物标志物的诊断解释。 拟议的培训计划涉及发展MRI、生物化学和 肌肉骨骼组织的微观结构特征，数学和统计建模，以及概念 在临床医学中，重点是cLBP。该奖学金是由两个博士亚伦菲尔兹 （主要申办者，骨科）和罗兰克鲁格博士（共同申办者， 放射学）-谁在拟议的研究领域有深厚的专业知识。这项工作将在 加州大学旧金山分校弗朗西斯科是美国首屈一指的生物医学和生命科学研究中心之一， 世界

Project Summary/Abstract Chronic low back pain (cLBP) is a leading cause of disability globally and is thought to relate to intervertebral disc degeneration in some patients. The cartilage endplate (CEP) plays a key role in disc health by influencing nutrient transport between the avascular disc and the vertebral capillaries. By its influence on disc nutrient supply, the CEP may also influence the efficacy of cell-based biologic therapies designed to regenerate the disc, as these therapies increase intradiscal nutrient demands. The premise of this proposal is that non-invasive assessment of CEP composition could provide insight into disc degeneration etiology and guide patient selection for cell-based biologic therapies, in turn helping to address the global health burden associated with cLBP. A novel imaging biomarker of CEP composition—the mean CEP T2* relaxation time measured using ultra- short echo time (UTE) MRI—has recently been shown to correlate with aspects of CEP composition influencing nutrient transport to the disc and the extent of disc degeneration in patients with cLBP. This non-invasive biomarker has major implications for elucidating the role of the CEP in disc degeneration/regeneration. However, the MR signal generated by the CEP depends on its in situ orientation relative in the MRI bore. Differences in T2* caused by orientation during imaging could exceed those associated with biochemical or microstructural deterioration, thus confounding accurate analysis. Without understanding the effects of orientation on CEP T2* values, researchers—and eventually clinicians—cannot accurately assess CEP composition in patients. The studies proposed here address these limitations and facilitate the development and clinical translation of MRI-based biomarkers of CEP composition independent of inter- and intra-individual anatomic variations in CEP orientation. Aim 1a will image cadaveric motion segments with UTE MRI at varying angles to develop a calibration curve for adjusting CEP T2* values based on in situ orientation. Aim 1b will test the clinical utility of this calibration curve in clinical cohorts of patients with cLBP and asymptomatic controls imaged with UTE MRI. Aim 2 will quantify the contributions of CEP microstructure and biochemical composition to inter- and intra-CEP variations in CEP T2* values, enhancing mechanistic understanding of the factors influencing CEP T2* and thus the diagnostic interpretation of UTE-based CEP biomarkers. The proposed training plan involves developing expertise in advanced techniques in MRI, biochemical and microstructural characterization of musculoskeletal tissues, mathematical and statistical modeling, and concepts in clinical medicine with a focus on cLBP. The fellowship is supported by two sponsors—Dr. Aaron Fields (primary sponsor, Department of Orthopaedic Surgery) and Dr. Roland Krug (co-sponsor, Department of Radiology)—who have deep domain expertise in the proposed research areas. The work will be conducted at the University of California, San Francisco, one of the premier biomedical and life sciences research centers in the world.