Double diffusion encoding and applications for biomedical imaging

Diffusion Magnetic Resonance Imaging (dMRI) is one of the most important contemporary non-invasive modalities for probing tissue structure at the microscopic scale. The majority of dMRI techniques employ standard single diffusion encoding (SDE) measurements, covering different sequence parameter ranges depending on the complexity of the method. Although many signal representations and biophysical models have been proposed for SDE data, they are intrinsically limited by a lack of specificity. Advanced dMRI methods have been proposed to provide additional microstructural information beyond what can be inferred from SDE. These enhanced contrasts can play important roles in characterizing biological tissues, for instance upon diseases (e.g. neurodegenerative, cancer, stroke), aging, learning, and development. In this review we focus on double diffusion encoding (DDE), which stands out among other advanced acquisitions for its versatility, ability to probe more specific diffusion correlations, and feasibility for preclinical and clinical applications. Various DDE methodologies have been employed to probe compartment sizes (Section 3), decouple the effects of microscopic diffusion anisotropy from orientation dispersion (Section 4), probe displacement correlations, study exchange, or suppress fast diffusing compartments (Section 6). DDE measurements can also be used to improve the robustness of biophysical models (Section 5) and study intra-cellular diffusion via magnetic resonance spectroscopy of metabolites (Section 7). This review discusses all these topics as well as important practical aspects related to the implementation and contrast in preclinical and clinical settings (Section 9) and aims to provide the readers a guide for deciding on the right DDE acquisition for their specific application

A novel mechanism of contrast in MRI: pseudo super-diffusion of water molecules unveils microstructural details in biological tissues

The goal of this work is to investigate the properties of the contrast provided by Anomalous Diffusion (AD) γ-imaging technique and to test its potential in detecting tissue microstructure. The collateral purpose is to implement this technique by optimizing data acquisition and data processing, with the long term perspective of adoption in massive in vitro, in vivo and clinical studies. The AD γ-imaging technique is a particular kind of Diffusion Weighted- Magnetic Resonance Imaging (DW-MRI). It represents a refinement of conventionally used DW-MRI methods, sharing with them the advantage of being non invasive, since it uses water as an endogenous contrast agent. Besides, it is more suitable to the study of complex tissues, because it is based on a theoretical model that overcomes the simplistic Gaussian assumption. While the Gaussian assumption predicates the linearity between the average molecular displacement of water and the diffusing time, as in case of diffusion in isotropic, homogeneous and infinite environments, a number of experiments performed in vitro and in vivo on both animals and humans showed an anomalous behavior of water molecules, with a non linear relation between the distance travelled and the elapsed time. In particular, the γ-parameter quantifies water pseudo super-diffusion, a peculiarity due to the fact that water diffusion occurs in multi-compartments and it is probed by means of MRI. In fact, a restricted diffusion is rather predicted for water diffusing in biological tissues. Recently, the trick that allows to make the traditional DW-MRI acquisition sequence suitable for pseudo super-diffusion quantification has been unveiled, and in short it consists in performing DW experiments varying the diffusion gradient strengths, at a constant diffusive time. The γ-parameter is extracted by fitting DW-data to a stretched-exponential function. Finally, probing water diffusion in different directions allows to reconstruct a γ-tensor, with scalar invariants that quantify the entity of AD and its anisotropy in a given volume element. In vitro results on inert materials revealed that γ correlates with internal gradients arising from magnetic susceptibility differences (Δ) between neighboring compartments, and that it reflects the multi-compartmentalization of the space explored by diffusing molecules. Furthermore, values of γ compatible with a description of super-diffusive motion were found. This anomaly can be explained considering that the presence of Δ induce an additional attenuation to the signal, simulating a pseudo super-diffusion. Finally, In vivo results on human brain showed that γ is more effective in discriminating among different brain regions compared to conventional DWMRI parameters. These studies suggest that the contrast provided by AD γ-imaging is influenced by an interplay of two factors, Δ -effects on one hand, multicompartmentalization on the other hand, through which γ could reflect tissue microstructure. With the aim to shed some light on this issue I performed AD γ-imaging in excised mouse spinal cord (MSC) at 9.4 T and healthy human brain at 3.0 T. The adoption of MSC was motivated by its current use in studies of demyelination due to an induced pathology that mimics Multiple Sclerosis alterations, and by its simplified geometry. I acquired DW-data with parameters optimized for the particular system chosen: the MSC was scanned along 3 orthogonal directions, thus an apparent γ was derived; for the in vivo studies I used more directions and I extracted a γ-tensor. I found that γ and its anisotropy reflected the microstructure of spinal cord tracts (such as the axon diameters and the axonal density). I investigated both in MSC and human brain the relation between γ and the rate of relaxation (R2*), a parameter well-known to reflect Δ, and found significant linear correlations. Because of this γ was able to differentiate white matter regions on the basis of their spatial orientation, and gray matter regions on the basis of their intrinsic iron content in human brain imaged at 3.0 T. These results suggest that AD γ-imaging could be an alternative or complementary technique to DW-MRI in the field of neuroscience. Indeed it could be useful for the assessment of the bulk susceptibility inhomogeneity, which reflects iron deposition, the hallmark of several neurodegenerative diseases. The part of this thesis work concerning the in vivo experiment in human brain gave rise to a paper published on NeuroImage, a relevant scientific journal in the field of MRI applied to brain investigation

Microstructural imaging of the human brain with a 'super-scanner': 10 key advantages of ultra-strong gradients for diffusion MRI

The key component of a microstructural diffusion MRI 'super-scanner' is a dedicated high-strength gradient system that enables stronger diffusion weightings per unit time compared to conventional gradient designs. This can, in turn, drastically shorten the time needed for diffusion encoding, increase the signal-to-noise ratio, and facilitate measurements at shorter diffusion times. This review, written from the perspective of the UK National Facility for In Vivo MR Imaging of Human Tissue Microstructure, an initiative to establish a shared 300 mT/m-gradient facility amongst the microstructural imaging community, describes ten advantages of ultra-strong gradients for microstructural imaging. Specifically, we will discuss how the increase of the accessible measurement space compared to a lower-gradient systems (in terms of Δ, b-value, and TE) can accelerate developments in the areas of 1) axon diameter distribution mapping; 2) microstructural parameter estimation; 3) mapping micro-vs macroscopic anisotropy features with gradient waveforms beyond a single pair of pulsed-gradients; 4) multi-contrast experiments, e.g. diffusion-relaxometry; 5) tractography and high-resolution imaging in vivo and 6) post mortem; 7) diffusion-weighted spectroscopy of metabolites other than water; 8) tumour characterisation; 9) functional diffusion MRI; and 10) quality enhancement of images acquired on lower-gradient systems. We finally discuss practical barriers in the use of ultra-strong gradients, and provide an outlook on the next generation of 'super-scanners'

Echocardiography

The book "Echocardiography - New Techniques" brings worldwide contributions from highly acclaimed clinical and imaging science investigators, and representatives from academic medical centers. Each chapter is designed and written to be accessible to those with a basic knowledge of echocardiography. Additionally, the chapters are meant to be stimulating and educational to the experts and investigators in the field of echocardiography. This book is aimed primarily at cardiology fellows on their basic echocardiography rotation, fellows in general internal medicine, radiology and emergency medicine, and experts in the arena of echocardiography. Over the last few decades, the rate of technological advancements has developed dramatically, resulting in new techniques and improved echocardiographic imaging. The authors of this book focused on presenting the most advanced techniques useful in today's research and in daily clinical practice. These advanced techniques are utilized in the detection of different cardiac pathologies in patients, in contributing to their clinical decision, as well as follow-up and outcome predictions. In addition to the advanced techniques covered, this book expounds upon several special pathologies with respect to the functions of echocardiography

Spin dynamics in semiconductors

This article reviews the current status of spin dynamics in semiconductors which has achieved a lot of progress in the past years due to the fast growing field of semiconductor spintronics. The primary focus is the theoretical and experimental developments of spin relaxation and dephasing in both spin precession in time domain and spin diffusion and transport in spacial domain. A fully microscopic many-body investigation on spin dynamics based on the kinetic spin Bloch equation approach is reviewed comprehensively.Comment: a review article with 193 pages and 1103 references. To be published in Physics Reports

Proximitized Materials

Advances in scaling down heterostructures and having an improved interface quality together with atomically-thin two-dimensional materials suggest a novel approach to systematically design materials. A given material can be transformed through proximity effects whereby it acquires properties of its neighbors, for example, becoming superconducting, magnetic, topologically nontrivial, or with an enhanced spin-orbit coupling. Such proximity effects not only complement the conventional methods of designing materials by doping or functionalization, but can also overcome their various limitations. In proximitized materials it is possible to realize properties that are not present in any constituent region of the considered heterostructure. While the focus is on magnetic and spin-orbit proximity effects with their applications in spintronics, the outlined principles provide also a broader framework for employing other proximity effects to tailor materials and realize novel phenomena.Comment: Invited Review to appear in Materials Today, 28 pages, 22 figure

Spin dynamics in van der Waals magnetic systems

The discovery of atomic monolayer magnetic materials has stimulated intense research activities in the two-dimensional (2D) van der Waals (vdW) materials community. The field is growing rapidly and there has been a large class of 2D vdW magnetic compounds with unique properties, which provides an ideal platform to study magnetism in the atomically thin limit. In parallel, based on tunneling magnetoresistance and magneto-optical effect in 2D vdW magnets and their heterostructures, emerging concepts of spintronic and optoelectronic applications such as spin tunnel field-effect transistors and spin-filtering devices are explored. While the magnetic ground state has been extensively investigated, reliable characterization and control of spin dynamics play a crucial role in designing ultrafast spintronic devices. Ferromagnetic resonance (FMR) allows direct measurements of magnetic excitations, which provides insight into the key parameters of magnetic properties such as exchange interaction, magnetic anisotropy, gyromagnetic ratio, spin–orbit coupling, damping rate, and domain structure. In this review article, we present an overview of the essential progress in probing spin dynamics of 2D vdW magnets using FMR techniques. Given the dynamic nature of this field, we focus mainly on broadband FMR, optical FMR, and spin-torque FMR, and their applications in studying prototypical 2D vdW magnets. We conclude with the recent advances in laboratory- and synchrotron-based FMR techniques and their opportunities to broaden the horizon of research pathways into atomically thin magnets