Imaging myelin content changes: A bridge between tissue and clinics

The development of remyelinating therapies is becoming an increasingly important strategy in the treatment of diseases such as multiple sclerosis. In this context, reliable measurement of myelin content is essential for the objective assessment of therapeutic efficacy. Over the past two decades, quantitative MRI has emerged as a method of choice for this purpose, supported by several postmortem validation studies that combine MRI with histology, the latter serving as the reference standard. In this review, we summarize the most relevant quantitative MRI contrasts sensitive to myelin changes and describe the mechanisms by which each contrast provides an estimate of myelin content. In addition, we outline the key steps involved in histological myelin quantification, highlighting the different methodological approaches as well as their limitations and potential pitfalls.