Kara Firat, Neyal Nur, Kamykowski Michael G, Schwarz Christopher G, Kendall-Thomas June, Morrison Holly A, Senjem Matthew L, Przybelski Scott A, Fought Angela J, Port John D, Deelchand Dinesh K, Lowe Val J, Öz Gülin, Kantarci Kejal, Kantarci Orhun H, Zeydan Burcu
Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA.
Department of Information Technology, Mayo Clinic, Rochester, MN 55905, USA.
Int J Mol Sci. 2025 Sep 5;26(17):8656. doi: 10.3390/ijms26178656.
The study assesses the relationship between thalamic proton-MR spectroscopy (H-MRS) metabolites and thalamic C-ER176 translocator-protein positron emission tomography (TSPO-PET) standardized uptake value ratios (SUVR) to advance our understanding of thalamic involvement in multiple sclerosis (MS)-associated neurodegeneration and disability. In this prospective cross-sectional study, patients with MS (pwMS) and controls underwent 3T-MRI, H-MRS, and C-ER176-PET targeting the thalamus. MRI-derived thalamic volume was normalized by intracranial volume. H-MRS metabolites-N-acetylaspartate (NAA), glutamate (Glu), glutamine (Gln), total choline (tCho), and myo-inositol (mIns)-were normalized to total creatine (tCr). Clinical disability was evaluated using MS-specific tests of Expanded Disability Status Scale-EDSS and MS-functional composite-MSFC (including Paced Auditory Serial Addition Test-PASAT). Compared to controls ( = 30), pwMS ( = 21) exhibited smaller thalamic volume, higher thalamic H-MRS mIns/tCr (putative gliosis marker), and higher thalamic C-ER176-PET SUVR (glial density marker). In pwMS, higher thalamic mIns/tCr (r = -0.67) and tCho/tCr (r = -0.52) correlated with smaller thalamic volume. In pwMS, higher thalamic mIns/tCr correlated with higher thalamic C-ER176-PET SUVR (r = 0.48) and decreased cognitive function (PASAT, rho = -0.48). In controls, decreased thalamic NAA/tCr correlated with increased thalamic C-ER176-PET SUVR (r = -0.41). Thalamus, a core central nervous system relay, is affected early in MS disease course. Glial-mediated innate immune activation in the thalamus, evaluated by increased H-MRS mIns/tCr and C-ER176-PET SUVR, is associated with loss of thalamic volume and increased disability in pwMS. The multimodal imaging approach with H-MRS mIns/tCr and C-ER176-PET SUVR emerges as potential glial biomarkers, to better understand disease mechanisms and evaluate therapeutic interventions targeting glial activity in MS.
本研究评估丘脑质子磁共振波谱（H-MRS）代谢物与丘脑碳-11依替膦酸转运蛋白正电子发射断层扫描（TSPO-PET）标准化摄取值比率（SUVR）之间的关系，以加深我们对丘脑在多发性硬化症（MS）相关神经退行性变和残疾中的作用的理解。在这项前瞻性横断面研究中，MS患者（pwMS）和对照组接受了针对丘脑的3T磁共振成像（MRI）、H-MRS和碳-11依替膦酸PET检查。MRI得出的丘脑体积通过颅内体积进行标准化。H-MRS代谢物——N-乙酰天门冬氨酸（NAA）、谷氨酸（Glu）、谷氨酰胺（Gln）、总胆碱（tCho）和肌醇（mIns）——以总肌酸（tCr）进行标准化。使用扩展残疾状态量表（EDSS）和MS功能综合评分（MSFC，包括听觉连续加法测验-PASAT）等MS特异性测试评估临床残疾情况。与对照组（n = 30）相比，pwMS患者（n = 21）的丘脑体积较小，丘脑H-MRS的mIns/tCr（假定的胶质细胞增生标志物）较高，丘脑碳-11依替膦酸PET的SUVR（胶质细胞密度标志物）较高。在pwMS患者中，较高的丘脑mIns/tCr（r = -0.67）和tCho/tCr（r = -0.52）与较小的丘脑体积相关。在pwMS患者中，较高的丘脑mIns/tCr与较高的丘脑碳-11依替膦酸PET SUVR（r = 0.48）和认知功能下降（PASAT，rho = -0.48）相关。在对照组中，丘脑NAA/tCr降低与丘脑碳-11依替膦酸PET SUVR升高相关（r = -0.41）。丘脑是中枢神经系统的核心中继站，在MS病程早期就受到影响。通过H-MRS的mIns/tCr和碳-11依替膦酸PET SUVR升高评估的丘脑中胶质细胞介导的先天性免疫激活与pwMS患者的丘脑体积减小和残疾增加相关。H-MRS的mIns/tCr和碳-11依替膦酸PET SUVR的多模态成像方法有望成为潜在的胶质细胞生物标志物，以更好地理解疾病机制并评估针对MS中胶质细胞活性的治疗干预措施。
