Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, MD, 21205, Baltimore, USA.
Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Neuroinflammation. 2022 Jun 3;19(1):130. doi: 10.1186/s12974-022-02493-z.
Multiple sclerosis (MS) is a neurodegenerative disease, wherein aberrant immune cells target myelin-ensheathed nerves. Conventional magnetic resonance imaging (MRI) can be performed to monitor damage to the central nervous system that results from previous inflammation; however, these imaging biomarkers are not necessarily indicative of active, progressive stages of the disease. The immune cells responsible for MS are first activated and sensitized to myelin in lymph nodes (LNs). Here, we present a new strategy for monitoring active disease activity in MS, chemical exchange saturation transfer (CEST) MRI of LNs.
We studied the potential utility of conventional (T2-weighted) and CEST MRI to monitor changes in these LNs during disease progression in an experimental autoimmune encephalomyelitis (EAE) model. We found CEST signal changes corresponded temporally with disease activity. CEST signals at the 3.2 ppm frequency during the active stage of EAE correlated significantly with the cellular (flow cytometry) and metabolic (mass spectrometry imaging) composition of the LNs, as well as immune cell infiltration into brain and spinal cord tissue. Correlating primary metabolites as identified by matrix-assisted laser desorption/ionization (MALDI) imaging included alanine, lactate, leucine, malate, and phenylalanine.
Taken together, we demonstrate the utility of CEST MRI signal changes in superficial cervical LNs as a complementary imaging biomarker for monitoring disease activity in MS. CEST MRI biomarkers corresponded to disease activity, correlated with immune activation (surface markers, antigen-stimulated proliferation), and correlated with LN metabolite levels.
多发性硬化症（MS）是一种神经退行性疾病，其中异常的免疫细胞靶向髓鞘包裹的神经。常规磁共振成像（MRI）可用于监测先前炎症引起的中枢神经系统损伤；然而，这些成像生物标志物并不一定表明疾病处于活跃、进展阶段。导致 MS 的免疫细胞最初在淋巴结（LN）中被激活并对髓鞘产生敏感性。在这里，我们提出了一种新的策略，用于监测 MS 中的活跃疾病活动，即淋巴结的化学交换饱和转移（CEST）MRI。
我们研究了常规（T2 加权）和 CEST MRI 在实验性自身免疫性脑脊髓炎（EAE）模型中监测疾病进展过程中这些 LN 变化的潜在用途。我们发现 CEST 信号变化与疾病活动具有时间相关性。EAE 活跃期 3.2ppm 处的 CEST 信号与 LN 的细胞（流式细胞术）和代谢（质谱成像）组成以及免疫细胞浸润脑和脊髓组织显著相关。通过基质辅助激光解吸/电离（MALDI）成像鉴定的相关主要代谢物包括丙氨酸、乳酸、亮氨酸、苹果酸和苯丙氨酸。
综上所述，我们证明了浅表颈淋巴结 CEST MRI 信号变化作为监测 MS 疾病活动的补充成像生物标志物的实用性。CEST MRI 生物标志物与疾病活动相关，与免疫激活（表面标志物、抗原刺激增殖）相关，与 LN 代谢物水平相关。
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