Ultrashort Echo Time Magnetic Resonance Imaging of the Lumbar Intervertebral Disc.

腰椎间盘超短回波时间磁共振成像。

• 批准号: 10446888
• 负责人: Yajun Ma
• 金额: $ 55.21万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10446888
• 关键词: 3-Dimensional; Address; Affect; Age; Animals; Biochemical; Biochemistry; Biological Markers; Body mass index; Chronic; Chronic low back pain; Clinical; Collagen; Complex; Dehydration; Development; Diagnosis; Diffuse; Diffusion; Elderly; Evaluation; Fatty acid glycerol esters; Fiber; Frequencies; Goals; Health; Health Care Costs; Histologic; Histology; Hydration status; Image; Imaging Techniques; Inferior; Injections; Intervertebral disc structure; Location; Low Back Pain; Magic; Magnetic Resonance Imaging; Maps; Measures; Modeling; Nutrient; Oryctolagus cuniculus; Pain; Patients; Population; Proteoglycan; Puncture procedure; Quality of life; Recovery; Reference Standards; Relaxation; Research; SF-36; Saline; Sampling; Series; Signal Transduction; Specimen; Techniques; Testing; Time; Tissues; Translating; Vertebral column; base; calcification; cartilaginous; contrast imaging; disability; disc regeneration; glucose transport; growth differentiation factor 6; healthy volunteer; intervertebral disk degeneration; non-invasive imaging; nucleus pulposus; oxygen transport; research clinical testing; sex; translational study; wasting

Abstract Intervertebral disc (IVD) degeneration and related low back pain (LBP) affect up to 85% of the U.S. population over their lifetime, resulting in annual healthcare costs that exceed $100 billion. The IVD is largely avascular and consists of a central proteoglycan (PG)-rich nucleus pulposus (NP), and a surrounding collagen- rich annulus fibrosus (AF), as well as superiorly and inferiorly located endplates. The IVD relies on diffusion of nutrients and waste through the cartilaginous endplate (CEP) to maintain its health. IVD degeneration is characterized by loss of PGs, dehydration of the NP, collagen loss within the AF, and degradation of the CEP. Dehydration and calcification of the CEP reduce its diffusivity, leading to a reduction in oxygen and glucose transport to the remainder of the disc. Changes in the CEP may occur at the same time or even precede disc degeneration. Evaluation of this complex situation requires a comprehensive, non-invasive imaging technique that can assess PG in the NP, collagen in the AF, and diffusivity of the CEP. Magnetic resonance imaging (MRI) is routinely used in the diagnosis of IVD degeneration. However, conventional MRI techniques do not provide reliable assessment of disc biochemical content nor of CEP function. This study aims to further develop a 3D ultrashort echo time (UTE) adiabatic T1r (UTE-AdiabT1r) sequence for robust mapping of PGs, a UTE magnetization transfer (UTE-MT) sequence for mapping of macromolecular fraction (MMF), an adiabatic inversion recovery UTE with fat saturation (IR-FS-UTE) sequence for T2* mapping of the CEP to evaluate calcification and dehydration, and a UTE dual echo steady state (UTE-DESS) sequence to study its apparent diffusion coefficient (ADC). In Aim 1 we will develop 3D UTE sequences to evaluate IVD in lumbar spines from young (<40y, n=10), mid-age (40-70y, n=10), and elderly (>70y, n=10) donors, and correlate UTE (AdiabT1r, MMF, T2*, ADC) and clinical MRI measures with reference including CT, µCT, histology, biochemistry, and diffusion test of three groups of spine samples. In Aim 2 we will evaluate 3D UTE sequences to assess IVD degeneration and regeneration using a mature rabbit annular puncture chronic disc degeneration model. We will study IVD degeneration in four groups of rabbits (n=16 per group) at 4, 8, 16, and 28 weeks post-AF puncture, as well as IVD regeneration using six groups of rabbits (n=16 per group) at 4, 12 and 24 weeks post- injection of saline and growth differentiation factor-6 (GDF-6). We will correlate UTE and clinical MRI findings with reference including µCT, histology, biochemistry, and diffusion test of ten groups of rabbit lumbar spines. In Aim 3 we will translate UTE sequences to study IVD degeneration in patients with chronic LBP (n=40) and normal IVDs in healthy volunteers (n=40), compare UTE and clinical MRI metrics of the NP, AF, and CEP of the lumbar spine in the two groups, and correlate them with clinical evaluations. Our central hypothesis is that UTE sequences can detect changes in PG and collagen in the disc as well as changes in diffusivity of the CEP, allowing more comprehensive and accurate evaluation of disc degeneration than is now possible.

抽象的 椎间盘（IVD）变性和相关的腰痛（LBP）影响多达85％的美国 人口一生，导致年度医疗保健成本超过1000亿美元。 IVD主要是 血管群，由中央蛋白聚糖（PG） - 富含核核（NP）和周围的胶原蛋白 丰富的环纤维（AF）以及位置上下的终结物。 IVD依赖于 通过软骨端板（CEP）浪费营养和浪费，以保持其健康状况。 IVD变性是 以PG的流失，NP的脱水，AF内的胶原蛋白损失以及CEP降解为特征。 CEP的脱水和计算降低了其扩散率，导致氧气和葡萄糖的降低 运输到光盘的其余部分。 CEP的变化可能同时发生，甚至在光盘之前发生 退化。对这种复杂情况的评估需要一种全面的，无创的成像技术 可以评估NP中的PG，AF中的胶原蛋白以及CEP的难度。磁共振成像 （MRI）通常用于诊断IVD变性。但是，传统的MRI技术没有 提供可靠的评估圆盘生化含量或CEP功能的评估。这项研究旨在进一步 开发3D Ultrastort Echo时间（UTE）绝热T1R（UTE-ADIABT1R）序列，用于稳健的PG映射，A UTE磁化转移（UTE-MT）序列，用于映射大分子分数（MMF），一种绝热 以脂肪满意度（ir-fs-ut）序列进行T2*映射的反转恢复UTE以评估 钙化和脱水，以及研究其外观的UTE双回波稳态（UTE-DESS）序列 扩散系数（ADC）。在AIM 1中，我们将开发3D UTE序列，以评估腰椎中的IVD Young（<40y，n = 10），中年（40-70y，n = 10）和较早的（> 70y，n = 10）供体，并相关（AdiaBt1r，， MMF，T2*，ADC）和临床MRI指标，包括CT，µCT，组织学，生物化学和 三组脊柱样品的扩散测试。在AIM 2中，我们将评估3D UTE序列以评估IVD 使用成熟的兔环形穿刺慢性椎间盘变性模型的退化和再生。我们 将在4、8、16和28周的四组兔子（每组n = 16）中研究IVD变性。 穿刺以及IVD再生，使用六组兔子（每组n = 16），在4、12和24周之后 注射盐水和生长分化因子-6（GDF-6）。我们将关联UTE和临床MRI发现 参考文献包括µCT，组织学，生物化学和十组兔腰椎的扩散测试。 在AIM 3中，我们将翻译UTE序列以研究慢性LBP患者（n = 40）和 健康志愿者（n = 40）中的正常IVD，比较NP，AF和CEP的UTE和临床MRI指标 两组的腰椎，并将其与临床评估相关。我们的中心假设是 UTE序列可以检测椎间盘中PG和胶原蛋白的变化，并检测 CEP，可以比现在更全面，准确地评估光盘退化。