Bae Jonghyun, Joynes Cassandra M, Gong Zhaoyuan, Duggan Michael R, Walker Keenan A, Bouhrara Mustapha
National Institute on Aging, Baltimore, 21224 MD, USA.
medRxiv. 2025 Sep 8:2025.08.27.25334582. doi: 10.1101/2025.08.27.25334582.
The myelin sheath is critical for efficient neural signaling and central nervous system function, yet noninvasive methods to quantify myelin content remain limited and require robust biological validation. Myelin Water Fraction (MWF) derived from the Bayesian Monte Carlo analysis of multicomponent Driven Equilibrium Single Pulse Observation of T and T (BMC-mcDESPOT) imaging method offers a promising biomarker of myelin content, but its biological specificity requires further validation. To elucidate the molecular underpinnings of MWF derived using BMC-mcDESPOT, we integrated this advanced MRI method with high-throughput plasma proteomics and spatial transcriptomics across major white and deep gray matter regions in adults. Plasma protein analyses using the SomaScan 7k platform revealed significant associations between MWF and proteins highly expressed by oligodendrocytes, a key cell type for myelin synthesis and maintenance. Furthermore, spatial mapping of Myelin Basic Protein () gene expression obtained from the Allen Human Brain Atlas demonstrated a strong positive correlation with regional MWF values, consistent with known myelin distribution patterns. These convergent findings validate MWF as a biologically relevant, myelin-specific imaging marker and highlight the potential of integrating omics data to validate and enhance neuroimaging biomarkers. Our work evinces and advances the utility of MWF for studying white matter integrity in health and disease, offering new avenues for clinical and translational neuroscience.
髓鞘对于高效的神经信号传导和中枢神经系统功能至关重要，然而，用于量化髓鞘含量的非侵入性方法仍然有限，并且需要强有力的生物学验证。从多组分驱动平衡单脉冲T和T观测的贝叶斯蒙特卡罗分析（BMC-mcDESPOT）成像方法得出的髓鞘水分数（MWF）提供了一种有前景的髓鞘含量生物标志物，但其生物学特异性需要进一步验证。为了阐明使用BMC-mcDESPOT得出的MWF的分子基础，我们将这种先进的磁共振成像方法与高通量血浆蛋白质组学和空间转录组学整合，覆盖了成年人主要的白质和深部灰质区域。使用SomaScan 7k平台进行的血浆蛋白分析揭示了MWF与少突胶质细胞高度表达的蛋白质之间存在显著关联，少突胶质细胞是髓鞘合成和维持的关键细胞类型。此外，从艾伦人类大脑图谱获得的髓鞘碱性蛋白（）基因表达的空间图谱显示与区域MWF值呈强正相关，这与已知的髓鞘分布模式一致。这些趋同的发现验证了MWF作为一种与生物学相关的、髓鞘特异性的成像标志物，并突出了整合组学数据以验证和增强神经影像学生物标志物的潜力。我们的工作证明并推进了MWF在研究健康和疾病中的白质完整性方面的效用，为临床和转化神经科学提供了新的途径。
