Microstructure for In-Vivo Human Applications
Susie Huang1

1Massachusetts General Hospital, United States


This lecture will provide a brief overview of technical considerations involved in in vivo diffusion MR microstructural imaging studies with a focus on human neuroimaging. We will cover biophysical models and signal representations of the diffusion MRI signal as they relate to probing tissue microstructure in the human brain. We will study metrics derived using different diffusion models and acquisition schemes in the setting of normal development and pathological changes in white matter disease. In addition, the specific advantages of high-gradient systems for characterizing tissue microstructure for in vivo human imaging will be explored.

Target audience

Scientists and clinicians interested in diffusion MR microstructural imaging.


- To familiarize the user with technical considerations involved in in vivo diffusion MR microstructural imaging

- To understand the applications of in vivo diffusion microstructural imaging in gaining insight into normal brain development and white matter pathology

- To explore the benefits of using high diffusion-encoding gradient strengths for imaging of tissue microstructure


Diffusion MRI is a key research tool in imaging studies of the human brain due to its unique ability to investigate tissue architectural features on the cellular level, at length scales (~μm) much smaller than the imaging voxel (~mm). In the past decade, advancements in MR technology have resulted in higher strength magnets and gradient systems, introduction of more sophisticated imaging sequences, and refinement of modeling and theoretical approaches that have furthered interest in diffusion MRI as a probe of tissue microstructure in vivo. This lecture will provide an overview of technical considerations for diffusion MR microstructural imaging in humans and introduce emerging applications of microstructure imaging techniques to study human neuroanatomy, development, and pathology.

Technical considerations for in vivo diffusion MR microstructural imaging in humans

Diffusion MRI approaches for inferring information regarding tissue microstructure fall into two general categories: those based on biophysical models, in which tissue components are modeled as geometric compartments, such as CHARMED (1, 2), AxCaliber (3) and related models (4), and NODDI (5); and model-independent approaches to representing the diffusion signal, such as diffusion kurtosis imaging (6). A wealth of modeling and theoretic approaches for diffusion microstructural imaging have emerged in the last decade and remain an active area of research and debate (7, 8).

Experimental constraints that must be considered in applying tissue microstructure models for in vivo diffusion MR imaging include the range of acquisition parameters accessible on human MR scanners, such as diffusion-encoding gradient strength(s), diffusion time, and diffusion pulse duration, as well as signal-to-noise ratio considerations with regard to echo time, spatial resolution and overall imaging time. Techniques for mitigating motion, susceptibility, and eddy current artifacts will be briefly discussed.

Applications of diffusion MR microstructural imaging techniques in humans

Recent advances in human MR systems (e.g., high performance gradients and high sensitivity RF coils) and imaging pulse sequences have enabled a rich array of diffusion measurements that allow unparalleled in vivo assessment of neural tissue microstructure, such as the relative size and packing density of cells and axons. The sensitivity of compartment size mapping techniques to small pore sizes is limited by the maximum gradient strength of clinical MR scanners (9, 10). The recent availability of higher maximum gradient strengths on human MRI scanners (11-14) has enabled the translation of these methods from animal (15) and ex vivo studies (3, 4, 16-18) to the in vivo human brain (4, 10, 19-21). Such technological advancements offer the possibility of in vivo diffusion microscopy with unprecedented resolution of fine white matter structure (14) and micron-sized axons (10, 21) in the living human brain for the study of multiple sclerosis (22) and other neurological disorders affecting white matter.

Related techniques such as NODDI measure orientational dispersion and neurite density (5), which has been shown to provide better distinction of microstructural disruption in white matter compared to conventional DTI metrics. NODDI utilizes a two-shell optimized acquisition at modest b-values and is supported by a user-friendly toolbox that is well-suited for large-scale studies (23) and clinical imaging. To date, NODDI has been applied to study white matter microstructure in newborns (24) and the developing human brain (25). NODDI has also been used to detect changes in neurite density across the lifespan (26) and probe gray matter pathology in a number of neurological conditions such as epilepsy (27) and neurodegenerative disorders (28).

The advent of dedicated high-gradient human MR scanners has enabled advanced applications of diffusion MRI to examine brain tissue microstructure and its disruption under pathological conditions. A valuable contribution of these systems, beyond signal-to-noise ratio improvements for diffusion MRI, is elucidating the dependence of microstructural metrics on the accessible diffusion MRI parameters in vivo, which is critical for gaining a better understanding of the complex relationship between the diffusion-weighted MR signal and underlying tissue microstructure. In addition, there remains a great need for systematic validation studies that relate microstructural metrics estimated in vivo to histopathology. These multi-faceted efforts will ultimately help to facilitate the translation of microstructural imaging methods to the clinical arena.


Work presented here was supported in part by NIH grant K23NS096056 and the Conrad N. Hilton Foundation.


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Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)