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

摘要 腰椎间盘(IVD)退变和相关的下腰痛(LBP)影响着高达85%的美国人。 人口的寿命，导致每年的医疗费用超过1000亿美元。IVD在很大程度上是 无血管，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)，以及位于上方和下方的终板。IVD依赖于 营养物质和废物通过软骨终板(CEP)来维持其健康。IVD变性是 以PG丢失、NP脱水、AF内胶原丢失和CEP降解为特征。 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。 运送到光盘的剩余部分。CEP的变化可能同时发生，甚至可能先于DISC发生 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 这可以评估NP中的PG、AF中的胶原以及CEP的扩散性。磁共振成像 磁共振成像(MRI)是诊断IVD变性的常规方法。然而，传统的核磁共振技术不能 为椎间盘生化含量或CEP功能提供可靠的评估。这项研究旨在进一步 开发一种3D超短回声时间(UTE)绝热T1r(UTE-AdiabT1r)序列，用于PG的稳健标测，a UTE磁化转移(UTE-MT)序列用于绘制绝热材料大分子分数(MMF) 反转恢复脂肪饱和(IR-FS-UTE)序列用于CEP的T2*标测评价 钙化和脱水，以及UTE双回波稳态(UTE-DESS)序列研究其表观 扩散系数(ADC)。在目标1中，我们将开发3D UTE序列来评估腰椎的IVD 年轻人(40岁，n=10)、中年(40-70岁，n=10)和老年(70岁，n=10)捐赠者，以及相关的UTE(AdiabT1r， MMF、T2*、ADC)和参考的临床MRI测量，包括CT、µCT、组织学、生化和 三组脊柱标本的扩散试验。在目标2中，我们将评估3D UTE序列以评估IVD 采用成熟兔环状穿刺法建立慢性腰椎间盘退变模型。我们 将研究房颤后4周、8周、16周和28周的四组兔(每组16只)的IVD变性 分别于术后4、12和24周用6组兔(每组16只)行穿刺术和IVD再生术。 注射生理盐水和生长分化因子-6(GDF-6)。我们将把UTE和临床的MRI表现联系起来。 参考文献包括10组兔腰椎的微CT、组织学、生化和扩散试验。 在目标3中，我们将翻译UTE序列来研究慢性LBP患者的IVD变性(n=40)和 健康志愿者(n=40)的正常IVD，比较UTE和临床MRI测量的NP、AF和CEP 对两组患者腰椎进行测量，并与临床评价进行对比分析。我们的中心假设是 UTE序列可以检测到椎间盘中PG和胶原的变化，以及 CEP，可以比现在更全面和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.