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

摘要 椎间盘（IVD）退变和相关的腰痛（LBP）影响了美国85%的人。 人口在其一生中，导致每年的医疗保健费用超过1000亿美元。IVD主要是 无血管的，由中央富含蛋白多糖（PG）的髓核（NP）和周围的胶原蛋白组成， 丰富的纤维环（AF），以及位于上方和上方的终板。IVD依赖于 营养物质和废物通过软骨终板（CEP），以维持其健康。IVD变性是 其特征在于PG损失、NP脱水、AF内胶原损失和CEP降解。 CEP的脱水和钙化降低了其扩散性，导致氧气和葡萄糖的减少 传送到光盘的其余部分。CEP的变化可能发生在椎间盘突出的同时，甚至在椎间盘突出之前。 退化对这种复杂情况的评估需要一种全面的、非侵入性的成像技术 可以评估NP中的PG、AF中的胶原蛋白和CEP的扩散率。磁共振成像 (MRI)常规用于诊断IVD变性。然而，常规MRI技术不 提供椎间盘生化含量或CEP功能的可靠评估。本研究旨在进一步 开发3D超短回波时间（UTE）绝热T1 r（UTE-AdiabT 1 r）序列，用于PG的稳健映射， UTE磁化转移（UTE-MT）序列映射的大分子分数（MMF），绝热 用于CEP的T2* 映射的具有脂肪饱和度的反转恢复UTE（IR-FS-UTE）序列，以评估 钙化和脱水，以及UTE双回波稳态（UTE-DESS）序列，以研究其明显的 扩散系数（ADC）。在目标1中，我们将开发3D UTE序列，以评估腰椎IVD， 年轻（<40岁，n=10）、中年（40- 70岁，n=10）和老年（> 70岁，n=10）供体，以及相关的UTE（AdiabT 1 r， MMF、T2*、ADC）和临床MRI测量，包括CT、µCT、组织学、生物化学和 三组脊柱样本的扩散试验。在目标2中，我们将评价3D UTE序列以评估IVD 使用成熟的兔环形穿刺慢性椎间盘退变模型进行退变和再生。我们 将在AF后4、8、16和28周研究4组家兔（每组n=16）的IVD变性 穿刺后4、12和24周，使用6组家兔（每组n=16）进行IVD再生。 注射生理盐水和生长分化因子-6（GDF-6）。我们将把UTE和临床MRI结果联系起来， 参照10组家兔腰椎的µCT、组织学、生物化学和扩散试验。 在目标3中，我们将翻译UTE序列以研究慢性LBP患者的IVD变性（n=40）， 健康志愿者（n=40）中的正常IVD，比较 两组的腰椎，并将其与临床评价相关联。我们的核心假设是 UTE序列可以检测椎间盘中PG和胶原的变化以及椎间盘扩散率的变化， CEP可以比现在更全面、更准确地评估椎间盘退变。

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.