Sorbonne Université, Paris Brain Institute, CNRS, Inserm, Paris, France/Padova Neuroscience Center, University of Padua, Padua, Italy; AP-HP, Hôpital Saint-Antoine, Paris, France.
Sorbonne Université, Paris Brain Institute, CNRS, Inserm, Paris, France/CEA, CNRS, Inserm, BioMaps, Service Hospitalier Frédéric Joliot, Université Paris-Saclay, Orsay, France.
Mult Scler. 2022 Oct;28(12):1881-1890. doi: 10.1177/13524585221096975. Epub 2022 Jun 16.
To investigate the clinical relevance of individual profiles of cortical and white matter lesion myelin content changes combining magnetisation transfer imaging (MTI) and 11C-PiB-positron emission tomography (PET) in patients with multiple sclerosis (MS).
MTI and [C]PiB-PET acquired in 19 patients with MS followed up over 2-4 months and in seven healthy controls (HCs), were employed to generate individual maps of cortical and white matter (WM) lesion myelin content changes, respectively. These maps were used to calculate individual indices of demyelination and remyelination, and to investigate their association with clinical scores.
Cortical remyelination ranged between 1% and 5% of the total cortical volume (17%-45% of the cortical volume demyelinated at baseline). WM lesion remyelination ranged between 8% and 22% of the lesional volume. An extensive cortical remyelination was associated with a shorter disease duration (rho = -0.63, = 0.01) and, in combination with WM lesion remyelination, explained 68%-70% of the variance of clinical scores ( < 0.01).
Our multimodal and multicompartment approach allows us to explore single-patient cortical and WM lesion demyelination and remyelination, and to generate clinically relevant indices of myelin repair. These indices may be used as outcome measures in clinical trials, thus increasing the chance to identify successful promyelinating treatments in patients with MS.
探讨多发性硬化症(MS)患者皮质和白质病变髓鞘含量变化的个体特征与磁化传递成像(MTI)和 11C-PiB 正电子发射断层扫描(PET)的临床相关性。
对 19 例随访 2-4 个月的 MS 患者和 7 例健康对照者(HCs)进行 MTI 和 [C]PiB-PET 采集,分别生成皮质和白质(WM)病变髓鞘含量变化的个体图谱。这些图谱用于计算脱髓鞘和髓鞘再生的个体指数,并探讨它们与临床评分的关系。
皮质髓鞘再生范围占总皮质体积的 1%至 5%(基线时皮质脱髓鞘体积的 17%至 45%)。WM 病变的髓鞘再生范围占病变体积的 8%至 22%。广泛的皮质髓鞘再生与疾病持续时间较短有关(rho=-0.63,=0.01),与 WM 病变的髓鞘再生相结合,可解释临床评分的 68%-70%的变异性(<0.01)。
我们的多模态和多腔室方法使我们能够探索单个患者的皮质和 WM 病变脱髓鞘和髓鞘再生,并生成与髓鞘修复相关的临床相关指数。这些指数可作为临床试验中的结果指标,从而增加在 MS 患者中识别成功的促髓鞘治疗的机会。