KG Jebsen Centre for MS-Research, Department of Clinical Medicine, University of Bergen, Bergen, Norway ; The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Neuroinformatics and Image Analysis Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway ; Department of Radiology, Haukeland University Hospital, Bergen, Norway.
PLoS One. 2013 Dec 30;8(12):e84162. doi: 10.1371/journal.pone.0084162. eCollection 2013.
In multiple sclerosis (MS), the correlation between lesion load on conventional magnetic resonance imaging (MRI) and clinical disability is weak. This clinico-radiological paradox might partly be due to the low sensitivity of conventional MRI to detect gray matter demyelination. Magnetization transfer ratio (MTR) has previously been shown to detect white matter demyelination in mice. In this study, we investigated whether MTR can detect gray matter demyelination in cuprizone exposed mice. A total of 54 female C57BL/6 mice were split into one control group () and eight cuprizone exposed groups ([Formula: see text]). The mice were exposed to [Formula: see text] (w/w) cuprizone for up to six weeks. MTR images were obtained at a 7 Tesla Bruker MR-scanner before cuprizone exposure, weekly for six weeks during cuprizone exposure, and once two weeks after termination of cuprizone exposure. Immunohistochemistry staining for myelin (anti-Proteolopid Protein) and oligodendrocytes (anti-Neurite Outgrowth Inhibitor Protein A) was obtained after each weekly scanning. Rates of MTR change and correlations between MTR values and histological findings were calculated in five brain regions. In the corpus callosum and the deep gray matter a significant rate of MTR value decrease was found, [Formula: see text] per week ([Formula: see text]) and [Formula: see text] per week ([Formula: see text]) respectively. The MTR values correlated to myelin loss as evaluated by immunohistochemistry (Corpus callosum: [Formula: see text]. Deep gray matter: [Formula: see text]), but did not correlate to oligodendrocyte density. Significant results were not found in the cerebellum, the olfactory bulb or the cerebral cortex. This study shows that MTR can be used to detect demyelination in the deep gray matter, which is of particular interest for imaging of patients with MS, as deep gray matter demyelination is common in MS, and is not easily detected on conventional clinical MRI.
在多发性硬化症 (MS) 中，病变负荷与临床残疾之间的相关性较弱。这种临床-放射学矛盾可能部分归因于常规 MRI 检测灰质脱髓鞘的敏感性较低。磁化传递率 (MTR) 先前已被证明可在小鼠中检测到白质脱髓鞘。在这项研究中，我们研究了 MTR 是否可以检测到铜染暴露小鼠的灰质脱髓鞘。总共 54 只雌性 C57BL/6 小鼠分为一组对照 ( ) 和八组铜染暴露组 ([Formula: see text])。小鼠暴露于 [Formula: see text] (w/w) 铜染长达六周。在铜染暴露之前，在 7 特斯拉 Bruker MR 扫描仪上获得 MTR 图像，在铜染暴露期间每周进行一次，在铜染暴露终止后每周进行一次。每周扫描后获得髓鞘（抗蛋白脂质蛋白）和少突胶质细胞（抗神经突生长抑制蛋白 A）的免疫组织化学染色。在五个脑区计算 MTR 变化率和 MTR 值与组织学发现之间的相关性。在胼胝体和深部灰质中，发现 MTR 值显著下降，每周分别为 [Formula: see text]（[Formula: see text]）和 [Formula: see text]（[Formula: see text]）。MTR 值与免疫组织化学评估的髓鞘丢失相关（胼胝体：[Formula: see text]。深部灰质：[Formula: see text]），但与少突胶质细胞密度无关。在小脑、嗅球或大脑皮层未发现显著结果。这项研究表明，MTR 可用于检测深部灰质的脱髓鞘，这对于 MS 患者的成像特别感兴趣，因为深部灰质脱髓鞘在 MS 中很常见，并且在常规临床 MRI 上不易检测到。
