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

项目摘要/摘要 慢性下腰痛(CLBP)是全球残疾的主要原因，被认为与椎间疼痛有关 部分患者有腰椎间盘退变。软骨终板(CEP)通过影响关节盘的功能，对椎间盘的健康起关键作用 无血管间盘和椎体毛细血管之间的营养物质运输。通过它对圆盘养分供应的影响， CEP还可能影响旨在再生椎间盘的基于细胞的生物疗法的疗效，因为 这些疗法增加了椎间盘内的营养需求。这一提议的前提是非侵入性 对CEP成分的评估可提供对椎间盘退变病因的洞察并指导患者选择 用于基于细胞的生物疗法，进而帮助解决与cLBP相关的全球健康负担。 CEP成分的一种新的成像生物标志物--平均CEP T2*弛豫时间 短回声时间(UTE)MRI-最近被证明与CEP成分影响的各个方面相关 慢性腰痛患者的营养物质向椎间盘的运输和椎间盘退变的程度。这种非侵入性 生物标记物对于阐明CEP在椎间盘退变/再生中的作用具有重要意义。然而， CEP产生的MR信号取决于其在MRI孔中的相对原位取向。差异在于 成像过程中由取向引起的T2*可能超过与生化或微结构相关的T2* 恶化，从而混淆了准确的分析。不了解取向对CEP T2的影响* 价值，研究人员-最终临床医生-不能准确地评估患者的CEP组成。 这里提出的研究解决了这些局限性，并促进了开发和临床翻译 基于MRI的CEP组成的生物标记物独立于个体间和个体内的解剖变异 CEP方向。Aim 1a将以不同角度使用UTE MRI对身体运动节段进行成像，以开发 基于原位定向调整CEP T2*值的校准曲线目标1b将测试的临床效用 这一校准曲线在cLBP患者和无症状对照的临床队列中进行了UTE MRI成像。 目标2将量化CEP的微观结构和生化成分对CEP间和CEP内的贡献 CEP T2*值的变化，增强了对影响CEP T2*的因素的机械性理解，从而 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核磁共振、生化和核磁共振等先进技术方面的专业知识。 肌肉骨骼组织的微观结构特征、数学和统计建模以及概念 在临床医学上，重点是cLBP。该奖学金由两位赞助商支持--亚伦·菲尔兹博士 (骨科主赞助商)和罗兰·克鲁格博士(联合赞助商，骨科 放射学)-在拟议的研究领域拥有深厚的领域专业知识。这项工作将在 加州大学旧金山分校，美国首屈一指的生物医学和生命科学研究中心 整个世界。

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.