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Diffusion MRI and MRS outside the brain: from methodology to practice

It has been more than 2 years since Klaas Nicolay and I discussed the idea and potential value of a Special Issue on diffusion magnetic resonance imaging (MRI) outside the brain. Although there have been several recent review articles that have been oriented towards the clinical utility of diffusion-weighted imaging (DWI), we agreed that a Special Issue would be highly valuable if it focused more strongly on basic theoretical and technical advances and bridged those to clinical applications. As a result, we are now very proud to present a Special Issue introduced with an outstanding article by Valerij Kiselev establishing the theoretical basis, followed by a collection of high-quality reviews on topics specific to certain organs or diseases (muscle, abdomen, heart, vertebral bone marrow, spinal cord, early cancer), or to the applied method or nucleus investigated [hyperpolarized gas, diffusion magnetic resonance spectroscopy (MRS)]. All contributions have a strong methodological part in order to provide a solid background for the reader. Finally, this Special Issue also profits from one original research contribution, which may point towards the future direction of diffusion MRI outside the brain. As a result of the dependence of the diffusion coefficient on the cellular microstructure in biological tissue, in combination with the dependence on the diffusion time, diffusion magnetic resonance (MR) has found numerous applications in non-invasive studies of pathology, for tissue characterization and for the determination of tissue connectivity. The vast majority of diffusion MR measurements has been performed in the brain, with tremendous success. Yoram Cohen points out in his contribution to this Special Issue that, ‘diffusion is one of the major contrast mechanisms used to non-invasively image and study brain architecture and pathologies’. Many of the problems associated with diffusion MR in the brain also apply to other organs and tissues, although, however, additional specific challenges exist. Several papers in this Special Issue emphasize the difficulties of performing diffusion MRI outside the brain. Among the challenges are susceptibility differences, reducing the magnetic field homogeneity, shorter T2 relaxation than in the brain and, in particular, physiological motion. However, all contributions demonstrate ways to overcome these difficulties and all contributions show that diffusion outside the brain has numerous current or potential future applications in various organs and tissue types. The versatility of the method is impressively demonstrated. Valerij Kiselev’s opening contribution on the fundamentals of diffusion MRI provides a very thorough and comprehensive background exposure at a deep theoretical level. He describes initial steps for using diffusion MRI in order to gain insight into tissue microstructure. He emphasizes the complicated relation between diffusion metrics and tissue structure, and addresses the many difficulties and pitfalls in the assessment of structural parameters. This fundamental paper is followed by two review contributions dealing with non-water diffusion MR methods, which also have strong theoretical components. The first article by Dmitriy A. Yablonskiy et al. reports on hyperpolarized gas MRI. They concentrate their outstanding and thorough review on the quantitative information that can be obtained on lung microstructure using He and Xe diffusion MRI. They describe the threedimensional information and parameters that can be obtained on lung microstructure from a short MRI scan. Traditionally, the same physiological parameters have required invasive stereology. They also describe the benefits of combining diffusion MRI with computed tomography (CT) to obtain additional parameters. The second of these two review papers summarizes all the important aspects of diffusion MRS. Peng Cao and Ed X. Wu review diffusion MRS studies in adipose tissue, bone marrow, muscle, intervertebral disk and tumor tissue and also – as an exception in this Special Issue – diffusion MRS studies in the brain. The authors point out possibilities for obtaining compartmentspecific information by characterizing the restricted diffusion behaviours of, for example, metabolites in extracellular and intracellular, neuronal and glial components or lipids in lipid droplets. The review also elaborates on technical considerations of diffusion MRS and emphasizes the information on tissue microstructure that can be gained. These reviews focusing on two different diffusion MR methods are followed by reviews focusing on different organs or tissue types. The paper by Choukri Mekkaouia et al. describes the technical challenges of diffusion tensor imaging (DTI) in the heart, including non-rigid deformation and displacements, short T2 or increased B0 and B1 inhomogeneities, and discusses in detail pulse sequences and approaches to overcome them. The first part is devoted to a detailed discussion of sequence designs. This is followed in the second part by a description of the fiber architecture of the myocardium and microstructural changes in ischemic heart diseases. They demonstrate in the text and with impressive figures the potential of DTI in the heart. DTI of the spinal cord is reviewed by Yoram Cohen et al. They review methods to study the spinal cord microstructure, with a special emphasis on q-space diffusion MRI to extract the size of the compartments. They emphasize the high anisotropy of the white matter in the spinal cord, which makes diffusion MRI sensitive to changes in the microstructure of the spinal cord. Applications of diffusion MRI in spinal cord, especially in demyelinating diseases, are also presented. The determination of muscle architecture by DTI that is pertinent to muscle biomechanics is described in detail by Bruce M. Damon et al. The precise estimation of structural muscle parameters from DTI data, including muscle fiber length, pennation angle and curvature, are explained and examples are presented. The results from diffusion MRI are related to more traditional methods, such as ultrasound imaging. The importance of muscle structure for its function is discussed. Diffusion MRI in vertebral bone faces strong susceptibility differences between trabecular bone and bone marrow, in addition to susceptibility variations caused by the proximity of Editorial