Advanced Diffusion MRI in the Human Brain: Microstructure Imaging and Structural Connectivity

Diffusion MRI (dMRI) is one of the most powerful MRI techniques for exploring the brain's microstructure in vivo. By measuring how water molecules move within tissue, it provides unique insight into the cellular and fiber architecture of the brain-information that conventional MRI cannot reveal. In clinical settings, diffusion imaging is now a valuable tool for early stroke diagnosis, tumour characterization, and surgical planning. In research, it enables the study of brain development, ageing, and disease progression, linking imaging findings to cellular and molecular processes. Over the past three decades, diffusion MRI has evolved from simple diffusion-weighted imaging and apparent diffusion coefficient (ADC) maps to advanced models that capture the complexity of tissue organization. Techniques such as diffusion tensor imaging (DTI), diffusional kurtosis imaging (DKI), and multi-compartment biophysical models now allow estimation of parameters related to axonal density, myelination, and water exchange between cellular compartments. Combined with tractography, these methods enable noninvasive reconstruction of white-matter pathways and network-level connectivity, transforming dMRI into a central tool for both neuroscience and clinical use. This chapter introduces the principles and applications of diffusion MRI in a progressive manner. We begin with the fundamental physics of diffusion contrast and its clinical relevance, then move to advanced microstructural models that provide richer biological specificity. Subsequent sections describe tractography methods used to map brain connectivity and analyze structural networks. Together, these sections aim to provide readers, especially those with limited imaging background, with an accessible understanding of how diffusion MRI reveals the brain's hidden microstructure and connects it to biological function.