Integrated and efficient diffusion-relaxometry using ZEBRA

The emergence of multiparametric diffusion models combining diffusion and relaxometry measurements provide powerful new ways to explore tissue microstructure with the potential to provide new insights into tissue structure and function. However, their ability to provide rich analyses and the potential for clinical translation critically depends on the availability of efficient, integrated, multi-dimensional acquisitions. We propose a fully integrated sequence simultaneously sampling the acquisition parameter spaces required for T1 and T2* relaxometry and diffusion MRI. Slice-level interleaved diffusion encoding, multiple spin/gradient echoes and slice-shuffling are combined for higher efficiency, sampling flexibility and enhanced internal consistency. In-vivo data was successfully acquired on healthy adult brains. Obtained parametric maps as well as clustering results demonstrate the potential of the technique regarding its ability to provide eloquent data with an acceleration of roughly 20 compared to conventionally used approaches. The proposed integrated acquisition, called ZEBRA, offers significant acceleration and flexibility compared to existing diffusion-relaxometry studies and thus facilitates wider use of these techniques both for research-driven and clinical applications

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

Diffusion tensor imaging: application to the study of the developing brain

pre-printObjective: To provide an overview of diffusion tensor imaging (DTI) and its application to the study of white matter in the developing brain, in both healthy and clinical samples. Method: The development of DTI and its application to brain imaging of white matter tracts is discussed. 48 studies using DTI to examine diffusion properties of the developing brain are reviewed in the context of the structural magnetic resonance imaging (MRI) literature. Reports of how brain diffusion properties are affected in pediatric clinical samples and how they relate to cognitive and behavioral phenotypes are reviewed. Results: DTI has been successfully used to describe white matter development in pediatric samples. Changes in white matter diffusion properties are consistent across studies, with anisotropy increasing and overall diffusion decreasing with age. Diffusion measures in relevant white matter regions correlate with behavioral measures in healthy children and in clinical pediatric samples. Conclusions: DTI is an important tool for providing a more detailed picture of developing white matter than can be obtained with conventional MRI alone. Keywords: brain, development, white matter, diffusion tensor imaging, magnetic resonance imaging

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'

Development of Multiscale Spectro-microscopic Imaging System and Its Applications

A novel multi-modality spectro-microscopic system that combines far-field interferometry based optical microscopy imaging techniques (differential interference contrast microscopy and cross-polarized light microscopy), total internal reflection microscopy (total internal reflection fluorescence and scattering microscopy) and confocal spectroscopy (Raman spectroscopy and photoluminescence spectroscopy) is developed. Home-built post treatment stages (thermal annealing stage and solvent annealing stage) are integrated into the system to realize in situ measurements. Departing from conventional characterization methods in materials science mostly focused on structures on one length scale, the in situ multi-modality characterization system aims to uncover the structural information from the molecular level to the mesoscale. Applications of the system on the characterization of photoactive layers of bulk heterojunction solar cell, two-dimensional materials, gold nanoparticles, fabricated gold nanoparticle arrays and cells samples are shown in this dissertation

Novel approaches to MRI of glioma

Gliomas are extremely heterogeneous, both morphologically and biologically, which contributes to a very poor prognosis. Current imaging of glioma is insufficient for a thorough diagnosis, therapy assessment and prognosis prediction. Moreover, refined and more sophisticated imaging technique could help in furthering our knowledge of gliomas. In order to facilitate proliferation, cancer cells undergo a change in structure and an increase in metabolism that results in distortion and disruption of tissue architecture. Gliomas are characterised by an increase in cells of variable sizes, as well as changes in the tissue microstructure. Diffusion-Weighted Imaging (DWI) and the apparent diffusion coefficient (ADC), have been extensively studied as potential imaging biomarkers for cellularity and tissue architecture. However, several studies have shown partial overlap in the measured values between tumour subtypes. Moreover, ADC is influenced by several factors and does not provide detailed information on the tissue microstructure. The Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumours (VERDICT) is a novel diffusion model that infers tissue microstructure compartment from conventional DWI measurements. This model derives metrics for the intracellular, intravascular and extracellular– extravascular spaces providing a more detailed interpretation of the tissue microstructure. To date, VERDICT has been applied to xenograft models of colorectal cancer, patient studies of prostate cancer and recently its feasibility in glioma has been shown. In this PhD I have applied a shortened version of the VERDICT method to image intratumoral and intertumoral heterogeneity in glioma. The results have also been validated with histology as part of a prospective study. Gliomas also exhibit a significant increase in mitotic activity within the tumour. The increased number of mitosis alters cell density which, in turn, affects the total concentration of tissue sodium as the concentration of tissue sodium is approximately ten-fold higher in the extracellular compared to the intracellular space. In addition, there is a decrease in Na+/K+-ATPase activity in tumours due to ATP depletion, which contributes to disturb sodium homeostasis. Non-invasive detection of 23Na with MRI has the potential to quantify sodium concentration and therefore could be an imaging probe of cell morphology and membrane function within the tumour microenvironment, as well as a method of probing tissue heterogeneity. During my PhD, a novel 23Na-MRI technique has been used to evaluate sodium distribution within glioma and in the surrounding tissue. Metabolic reprogramming is one of the major driving forces for determining glioma growth and invasion. Therefore, the non-invasive characterization of metabolic intratumoral, peritumoral and intertumoral heterogeneity in vivo could help to better stratify patients and to develop novel therapeutic strategies targeting cancer-specific metabolic pathways. 13C magnetic resonance imaging (MRI) using dynamic nuclear polarization (DNP) is a novel technique that allows non-invasive assessment of the metabolism of hyperpolarized (HP) 13C-labelled molecules in vivo, such as the exchange of [1-13C]pyruvate to [1-13C]lactate in tumours (Warburg effect). Part of my PhD has focused on developing and translating HP [1-13C]pyruvate MRI to explore metabolic reprogramming in glioma and the surrounding microenvironment. The overall aim of my PhD has been to develop novel approaches to imaging glioma with MRI to probe both the architectural and metabolic changes of Glioma. The preliminary evidence suggests that these tools can more deeply phenotype tumours than conventional imaging approaches. Although the main focus of this work has been gliomas, the techniques developed and presented here may be applied to study other pathological conditions within the brain, which raises the possibility of other potential clinical applications for this work

Musculoskeletal MRI at 7 T: do we need more or is it more than enough?

Ultra-high field magnetic resonance imaging (UHF-MRI) provides important diagnostic improvements in musculoskeletal imaging. The higher signal-to-noise ratio leads to higher spatial and temporal resolution which results in improved anatomic detail and higher diagnostic confidence. Several methods, such as T2, T2*, T1rho mapping, delayed gadolinium-enhanced, diffusion, chemical exchange saturation transfer, and magnetisation transfer techniques, permit a better tissue characterisation. Furthermore, UHF-MRI enables in vivo measurements by low-γ nuclei (23Na, 31P, 13C, and 39K) and the evaluation of different tissue metabolic pathways. European Union and Food and Drug Administration approvals for clinical imaging at UHF have been the first step towards a more routinely use of this technology, but some drawbacks are still present limiting its widespread clinical application. This review aims to provide a clinically oriented overview about the application of UHF-MRI in the different anatomical districts and tissues of musculoskeletal system and its pros and cons. Further studies are needed to consolidate the added value of the use of UHF-MRI in the routine clinical practice and promising efforts in technology development are already in progress