Athinoula A. Martinos Center for Biomedical Imaging and Harvard Medical School, Boston, MA, USA; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
Instituto de Neurociencias de Alicante (CSIC-UMH), San Juan de Alicante, Spain; Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, Cardiff, UK.
Neuroscience. 2019 Apr 1;403:27-34. doi: 10.1016/j.neuroscience.2019.01.022. Epub 2019 Jan 29.
In multiple sclerosis (MS), it would be of clinical value to be able to track the progression of axonal pathology, especially before the manifestation of clinical disability. However, non-invasive evaluation of short-term longitudinal progression of white matter integrity is challenging. This study aims at assessing longitudinal changes in the restricted (i.e. intracellular) diffusion signal fraction (FR) in early-stage MS by using ultra-high gradient strength multi-shell diffusion magnetic resonance imaging. In 11 early MS subjects (disease duration ≤5 years), FR was obtained at two timepoints (one year apart) through the Composite Hindered and Restricted Model of Diffusion, along with conventional Diffusion Tensor Imaging metrics. At follow-up, no statistically significant change was detected in clinical variables, while all imaging metrics showed statistically significant longitudinal changes (p < 0.01, corrected for multiple comparisons) in widespread regions in normal-appearing white matter (NAWM). The most extensive longitudinal changes were observed in FR, including areas known to include a large fraction of crossing fibers. Furthermore, FR was also the only metric showing significant longitudinal changes in lesions that were present at both time points (p = 0.007), with no significant differences found for conventional diffusion metrics. Finally, FR was the only diffusion metric (as compared to Diffusion Tensor Imaging) that revealed pre-lesional changes already present at baseline. Taken together, our data provide evidence for progressive microstructural damage in the NAWM of early MS cases detectable already at 1-year follow-up. Our study highlights the value of multi-shell diffusion imaging for sensitive tracking of disease evolution in MS before any clinical changes are observed. This article is part of a Special Issue entitled: SI: MRI and Neuroinflammation.
在多发性硬化症 (MS) 中，能够追踪轴突病理学的进展将具有临床价值，尤其是在出现临床残疾之前。然而，非侵入性评估白质完整性的短期纵向进展具有挑战性。本研究旨在通过使用超高梯度强度多壳扩散磁共振成像来评估早期 MS 中受限（即细胞内）扩散信号分数 (FR) 的纵向变化。在 11 名早期 MS 受试者（病程≤5 年）中，通过复合受限和扩散模型，在两个时间点（相隔一年）获得 FR，同时还获得了常规扩散张量成像指标。在随访时，临床变量没有检测到统计学上的显著变化，而所有成像指标在正常表现白质 (NAWM) 的广泛区域均显示出统计学上显著的纵向变化（p<0.01，经多重比较校正）。在 FR 中观察到最广泛的纵向变化，包括已知包含大量交叉纤维的区域。此外，FR 也是唯一在两个时间点均存在病变的指标显示出统计学上显著的纵向变化（p=0.007），常规扩散指标没有发现显著差异。最后，与扩散张量成像相比，FR 是唯一显示基线时已经存在的病变前变化的扩散指标。总之，我们的数据提供了证据，表明在早期 MS 病例的 NAWM 中存在进行性微观结构损伤，这种损伤在 1 年随访时即可检测到。我们的研究强调了多壳扩散成像在观察到任何临床变化之前对 MS 疾病演变进行敏感跟踪的价值。本文是一个特刊的一部分，主题是：SI：MRI 和神经炎症。
