Magnetic Resonance Imaging and Spectroscopy Section, National Institute of Aging, National Institutes on Health, Baltimore, MD, USA.
NMR Biomed. 2011 Dec;24(10):1286-94. doi: 10.1002/nbm.1690. Epub 2011 Apr 5.
The noninvasive early detection of specific matrix alterations in degenerative cartilage disease would be of substantial use in basic science studies and clinically, but remains an elusive goal. Recently developed MRI methods exhibit some specificity, but require contrast agents or nonstandard pulse sequences and hardware. We present a multiexponential approach which does not require contrast agents or specialized hardware, and uses a standard multiple-echo spin-echo sequence. Experiments were performed on tissue models of degenerative cartilage using enzymes with distinct actions. MR results were validated using histologic, biochemical and infrared spectroscopic analyses. The sulfated glycosaminoglycan per dry weight (dw) in bovine nasal cartilage was 0.72 ± 0.06 mg/mg dw and was reduced through chondroitinase AC and collagenase digestion to 0.56 ± 0.12 and 0.58 ± 0.13 mg/mg dw, respectively. Multiexponential analysis of data obtained at 9.4 T permitted the identification of tissue compartments assigned to the proteoglycan component of the matrix and to bulk water. Enzymatic treatment resulted in a significant reduction in the ratio of proteoglycan-bound to free water from 0.13 ± 0.02 in control cartilage to 0.03 ± 0.02 and 0.05 ± 0.06 under chondroitinase AC and collagenase treatment, respectively. As expected, monoexponential T(2) increased with both degradation protocols, but without further specificity to the nature of the degradation. An important eventual extension of this approach may be to map articular cartilage degeneration in the clinical setting. As an initial step towards this, localized multiexponential T(2) analysis was performed on control and trypsin treated excised bovine patella. The results obtained on this articular cartilage sample were readily interpretable in terms of proteoglycan-associated and relatively free water compartments. In potential clinical applications, signal-to-noise ratio constraints will define the threshold for the detection of macromolecular compartment changes at a given spatial scale. The multiexponential approach has potential application to the early detection of cartilage degradation with the use of appropriate pulse parameters under high signal-to-noise ratio conditions.
在基础科学研究和临床实践中，对退行性软骨病特定基质改变的无创早期检测具有重要意义，但这仍然是一个难以实现的目标。最近开发的 MRI 方法具有一定的特异性，但需要造影剂或非标准脉冲序列和硬件。我们提出了一种多指数方法，不需要造影剂或特殊硬件，并且使用标准的多回波自旋回波序列。该方法在使用具有不同作用的酶的退行性软骨组织模型上进行了实验。使用组织学、生化和红外光谱分析对 MR 结果进行了验证。牛鼻软骨的每干重（dw）硫酸化糖胺聚糖为 0.72±0.06mg/mg dw，经软骨素酶 AC 和胶原酶消化后分别减少至 0.56±0.12 和 0.58±0.13mg/mg dw。在 9.4T 下获得的数据的多指数分析允许鉴定分配给基质的蛋白聚糖成分和体相水的组织隔室。酶处理导致蛋白聚糖结合水与游离水的比值从对照软骨中的 0.13±0.02 显著降低至软骨素酶 AC 和胶原酶处理下的 0.03±0.02 和 0.05±0.06。正如预期的那样，单指数 T2 随着两种降解方案而增加，但对降解的性质没有进一步的特异性。这种方法的一个重要最终扩展可能是在临床环境中对关节软骨退化进行成像。作为实现这一目标的第一步，对对照和胰蛋白酶处理的牛髌骨进行了局部多指数 T2 分析。在这个关节软骨样本上获得的结果可以根据蛋白聚糖相关和相对自由水隔室进行解释。在潜在的临床应用中，信噪比约束将定义在给定空间尺度下检测大分子隔室变化的阈值。在高信噪比条件下使用适当的脉冲参数，多指数方法具有对软骨降解进行早期检测的应用潜力。
