Emerging Techniques in Breast MRI

As indicated throughout this chapter, there is a constant effort to move to more sensitive, specific, and quantitative methods for characterizing breast tissue via magnetic resonance imaging (MRI). In the present chapter, we focus on six emerging techniques that seek to quantitatively interrogate the physiological and biochemical properties of the breast. At the physiological scale, we present an overview of ultrafast dynamic contrast-enhanced MRI and magnetic resonance elastography which provide remarkable insights into the vascular and mechanical properties of tissue, respectively. Moving to the biochemical scale, magnetization transfer, chemical exchange saturation transfer, and spectroscopy (both “conventional” and hyperpolarized) methods all provide unique, noninvasive, insights into tumor metabolism. Given the breadth and depth of information that can be obtained in a single MRI session, methods of data synthesis and interpretation must also be developed. Thus, we conclude the chapter with an introduction to two very different, though complementary, methods of data analysis: (1) radiomics and habitat imaging, and (2) mechanism-based mathematical modeling

Caractérisation ultrasonore de l'angiogenèse, de l'élasticité et de la microstructure tumorale sous l'effet de thérapies conventionnelles et innovantes

Tumor development is complex process made possible thanks to the microenvironment surrounding tumor cell. Modifications induced by tumor cells on their environment enable their own development by remodeling tissues sustaining them and by creating a new vascular network (angiogenesis). The use of several antiangiogenic therapies, inhibiting the sprout of a new vascular network, has been authorized in clinic. These therapies induce strong modifications in tumors at the functional level and following tumor size changes are is not sufficient to fully characterize tumor modifications. The main goal of this thesis was to use different ultrasound-based imaging modalities in order to assess their sensitivity to modifications induced in murine tumor model (colorectal and lung carcinomas) during different type of therapy (chemical: cytotoxic, antiangiogenic / physical: cold plasma, sonosensitization). Modifications of the spatial distribution of microvessels and their functionality were characterized using contrast-enhanced ultrasound (CEUS), alteration of tumor microstructure was assessed using spectral analysis of radiofrequency signal, known as quantitative ultrasound (QUS) and finally variations of mechanical properties in tumor tissues were measured in shear wave elastography (SWE). In order to better understand the origin of the modifications observed in vivo, standard parameters such as level of fibrosis and necrosis were characterize ex vivo in tumor tissue using immunochemistry as gold standard.Les modifications induites par les cellules tumorales sur leur environnement ont pour but de permettre leur développement en remodelant le tissu la soutenant et en créant un nouveau réseau vasculaire (angiogenèse). Plusieurs thérapies anti-angiogéniques inhibant le développement du réseau vasculaire tumoral ont obtenu l’autorisation de mise sur le marché et sont actuellement utilisées en clinique. Ces thérapies induisent de fortes modifications fonctionnelles au sein de la tumeur mais le simple suivi de l’évolution du volume tumoral n’est pas suffisant pour rendre compte de ces modifications. L’objectif principal de la thèse a consisté à utiliser différentes modalités d’imagerie ultrasonore afin d’évaluer leur sensibilité aux modifications générées dans des tumeurs murine (carcinome colorectal et pulmonaire) au cours de plusieurs types de thérapie (chimique : cytotoxique, anti-angiogénique / physique : plasma froid, sono-sensibilisation). Les modifications de la distribution spatiale des micro-vaisseaux et leur fonctionnalité ont été caractérisées à l’aide de l’imagerie de contraste ultrasonore (CEUS), l’altération de la microstructure de la tumeur a été évaluée grâce à l’analyse spectrale des signaux radiofréquences, connu comme « quantitative ultrasound » (QUS) et enfin les variations des propriétés mécaniques des tissus tumoraux ont été mesurées en élastographie à l’aide de la technique « Shear Wave Elastography » (SWE). Afin de comprendre l’origine des modifications observées in vivo, des paramètres standard comme les niveaux de fibrose ou de nécrose ont été caractérisés ex vivo dans le tissu tumoral, grâce à l’immunohistochimie, une technique de référence

Updates on Quantitative MRI of Diffuse Liver Disease. A Narrative Review

Diffuse liver diseases are highly prevalent conditions around the world, including pathological liver changes that occur when hepatocytes are damaged and liver function declines, often leading to a chronic condition. In the last years, Magnetic Resonance Imaging (MRI) is reaching an important role in the study of diffuse liver diseases moving from qualitative to quantitative assessment of liver parenchyma. In fact, this can allow noninvasive accurate and standardized assessment of diffuse liver diseases and can represent a concrete alternative to biopsy which represents the current reference standard. MRI approach already tested for other pathologies include diffusion-weighted imaging (DWI) and radiomics, able to quantify different aspects of diffuse liver disease. New emerging MRI quantitative methods include MR elastography (MRE) for the quantification of the hepatic stiffness in cirrhotic patients, dedicated gradient multiecho sequences for the assessment of hepatic fat storage, and iron overload. Thus, the aim of this review is to give an overview of the technical principles and clinical application of new quantitative MRI techniques for the evaluation of diffuse liver disease

Preclinical MRI of the Kidney

This Open Access volume provides readers with an open access protocol collection and wide-ranging recommendations for preclinical renal MRI used in translational research. The chapters in this book are interdisciplinary in nature and bridge the gaps between physics, physiology, and medicine. They are designed to enhance training in renal MRI sciences and improve the reproducibility of renal imaging research. Chapters provide guidance for exploring, using and developing small animal renal MRI in your laboratory as a unique tool for advanced in vivo phenotyping, diagnostic imaging, and research into potential new therapies. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Preclinical MRI of the Kidney: Methods and Protocols is a valuable resource and will be of importance to anyone interested in the preclinical aspect of renal and cardiorenal diseases in the fields of physiology, nephrology, radiology, and cardiology. This publication is based upon work from COST Action PARENCHIMA, supported by European Cooperation in Science and Technology (COST). COST (www.cost.eu) is a funding agency for research and innovation networks. COST Actions help connect research initiatives across Europe and enable scientists to grow their ideas by sharing them with their peers. This boosts their research, career and innovation. PARENCHIMA (renalmri.org) is a community-driven Action in the COST program of the European Union, which unites more than 200 experts in renal MRI from 30 countries with the aim to improve the reproducibility and standardization of renal MRI biomarkers

Technical advancements and protocol optimization of diffusion-weighted imaging (DWI) in liver

An area of rapid advancement in abdominal MRI is diffusion-weighted imaging (DWI). By measuring diffusion properties of water molecules, DWI is capable of non-invasively probing tissue properties and physiology at cellular and macromolecular level. The integration of DWI as part of abdominal MRI exam allows better lesion characterization and therefore more accurate initial diagnosis and treatment monitoring. One of the most technical challenging, but also most useful abdominal DWI applications is in liver and therefore requires special attention and careful optimization. In this article, the latest technical developments of DWI and its liver applications are reviewed with the explanations of the technical principles, recommendations of the imaging parameters, and examples of clinical applications. More advanced DWI techniques, including Intra-Voxel Incoherent Motion (IVIM) diffusion imaging, anomalous diffusion imaging, and Diffusion Kurtosis Imaging (DKI) are discussed

Virtual Biopsy in Soft Tissue Sarcoma. How Close Are We?

A shift in radiology to a data-driven specialty has been unlocked by synergistic developments in imaging biomarkers (IB) and computational science. This is advancing the capability to deliver "virtual biopsies" within oncology. The ability to non-invasively probe tumour biology both spatially and temporally would fulfil the potential of imaging to inform management of complex tumours; improving diagnostic accuracy, providing new insights into inter- and intra-tumoral heterogeneity and individualised treatment planning and monitoring. Soft tissue sarcomas (STS) are rare tumours of mesenchymal origin with over 150 histological subtypes and notorious heterogeneity. The combination of inter- and intra-tumoural heterogeneity and the rarity of the disease remain major barriers to effective treatments. We provide an overview of the process of successful IB development, the key imaging and computational advancements in STS including quantitative magnetic resonance imaging, radiomics and artificial intelligence, and the studies to date that have explored the potential biological surrogates to imaging metrics. We discuss the promising future directions of IBs in STS and illustrate how the routine clinical implementation of a virtual biopsy has the potential to revolutionise the management of this group of complex cancers and improve clinical outcomes

Preclinical MRI of the kidney : methods and protocols

This Open Access volume provides readers with an open access protocol collection and wide-ranging recommendations for preclinical renal MRI used in translational research. The chapters in this book are interdisciplinary in nature and bridge the gaps between physics, physiology, and medicine. They are designed to enhance training in renal MRI sciences and improve the reproducibility of renal imaging research. Chapters provide guidance for exploring, using and developing small animal renal MRI in your laboratory as a unique tool for advanced in vivo phenotyping, diagnostic imaging, and research into potential new therapies. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Preclinical MRI of the Kidney: Methods and Protocols is a valuable resource and will be of importance to anyone interested in the preclinical aspect of renal and cardiorenal diseases in the fields of physiology, nephrology, radiology, and cardiology. This publication is based upon work from COST Action PARENCHIMA, supported by European Cooperation in Science and Technology (COST). COST (www.cost.eu) is a funding agency for research and innovation networks. COST Actions help connect research initiatives across Europe and enable scientists to grow their ideas by sharing them with their peers. This boosts their research, career and innovation. PARENCHIMA (renalmri.org) is a community-driven Action in the COST program of the European Union, which unites more than 200 experts in renal MRI from 30 countries with the aim to improve the reproducibility and standardization of renal MRI biomarkers

The application of advanced imaging techniques for the assessment of paediatric chest disease

Introduction – Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) both result in chronic suppurative lung disease with significant resulting morbidity and early mortality. Many clinical and academic groups advocate biennial or even annual CT surveillance from as early as 2 years of age, but new therapies and increasing life expectancy lead to concerns over the use of repeated CT imaging. There are many recent studies showing promise of MRI for structural lung imaging MRI based measures of lung function. Both CF and PCD result in multisystem disease and whilst much of the morbidity results from lung disease, monitoring of extrathoracic disease is likely also relevant. Aims and objectives – 1) To set up a clinically feasible, multisystem (lung, sinonasal and upper abdominal visceral) quantitative MRI examination for the investigation and follow up of CSLD 2) To evaluate novel imaging biomarkers of CF and PCD disease severity Hypotheses – 1) Combined structural and quantitative MRI assessment of the thorax can provide comparable information to CT such that follow up imaging via CT could be replaced with MRI. 2) Quantitative MR measures of ventilation correlate with established clinical measures of ventilation (LCI and FEV1) and provide additional spatial information. 3) A multisystem MRI assessment can provide new extra-thoracic imaging biomarkers of CF and PCD disease severity whilst being better tolerated by patients than current multimodality imaging follow up. Methods – People with CF or PCD referred for clinically indicated lung CT were prospectively recruited to undergo MR imaging of the lungs, liver and paranasal sinuses. Structural lung imaging was optimised for speed of acquisition using T2 BLADE imaging, in axial and coronal plane, during breath holds rather than more conventional respiratory triggering. Images were scored by two observers using the Eichinger scoring system and compared to CT structural scores using the CFCT scoring system. Lung T1 mapping was performed via free breathing IR-HASTE and T1 and T2 mapping performed via breath hold ufbSSFP imaging. Functional lung imaging was performed via pre and post hyperoxygenation ufbSSFP T1 mapping, free breathing dynamic oxygen enhanced IR-HASTE imaging (OE-MRI) and non-contrast ufbSSFP-based matrix pencil decomposition imaging of ventilation and pulmonary perfusion. Lung T1 maps included the superior portion of the liver enabling simultaneous liver T1 mapping. A multiparametric paranasal sinus protocol was devised containing structural (T1 and T2 TSE), susceptibility and diffusion weighted sequences for the calculation of sinus volume, mucus volume and mucosal volume, presence or absence of artefact associated with infective micro-organisms and calculation of mucus and mucosal diffusion. Participant tolerability of MR imaging assessed via a bespoke questionnaire, completed before and after both CT and MR imaging. Multiple breath wash-out testing was performed on the day of the MRI and spirometry, antibiotic usage, abdominal ultrasound and sheer wave elastography collected retrospectively from the electronic patient record. Results – 22 participants were recruited, all of whom completed the hour-long MRI protocol. The median age was 14 years (range 6 – 35). 2-plane structural lung imaging was acquired in a total of 2 minutes 4 seconds with only a single participant reporting difficulties with the required breath holds. Interclass Correlation Coefficients of interobserver variability in MRI scores were comparable to CT (0.877-0.965 compared to 0.877-0.989 respectively) suggesting good image quality with strong correlation between MR and CT component scores (bronchiectasis/bronchial wall thickening r=0.828,p<0.001; mucus plugging r=0.812, p<0.001; parenchymal score r=0.564 – 0.729, p<0.001 – 0.006). Median lung T1 did not correlate with clinical markers of disease severity, but median lung T2 demonstrated strong correlation with CT bronchial wall thickening (r=-0.655, p=0.001) and LCI2.5 (r=-0.540, p=0.046), most likely representing a surrogate of pulmonary perfusion (most pulmonary T2 signal likely originates from the pulmonary blood pool). Significant ufbSSFP enhancement was demonstrated post hyperoxygenation, but the degree of enhancement did not correlate significantly with clinical measures of disease severity. There was, however, very strong correlations between matrix pencil decomposition ventilation fraction and LCI2.5 (r=0.831, p=0.001) and CFCT scores (r= up to 0.731, p=<0.001). Significant correlation was also demonstrated between measures of ventilation heterogeneity (oxygen wash-out time skew and kurtosis) and both LCI2.5 (r=0.591, p=0.013) and CFCT component scores (r= up to 0.718, p<0.001). Liver T1 values did not correlate with evidence of liver disease on liver function tests or ultrasound imaging, but interpretation was severely limited by the very small number of recruits with CF liver disease. Sinus imaging was the last part of the protocol with failed analysis in only one patient from too much motion (a 6 year old). Association was demonstrated between exacerbation frequency and opacification of maxillary sinuses by mucusa (p=0.074), between CT hyperinflation score and increasing levels of mucus susceptibility artefact (0=0.028), between exacerbation frequency, CT bronchial wall thickening and mucus plugging and increased sinus mucus diffusion (r=0.581, p=0.048, r=0.744, p=0.006 and r=0.633, p=0.019 respectively) and between CT hyperinflation, bronchiectasis and bronchial wall thickening scores and increased sinus mucosal diffusion (r=-0.847, p=0.016; r=-0.542, p=0.017 and r=-0.427, p=0.069 respectively). A third of recruits stated that they would opt for MR imaging over CT imaging in the future and whilst 41% reported difficulties staying still for the MRI, respiratory image post processing was successful in all participants, with no parts of the MRI studies repeated. Conclusion – Multisystem lung, liver and sinus MRI is feasible, well tolerated by people with CF or PCD, down to the age of 6 years, and provides gross structural imaging of sufficient quality to replace CT for lung imaging surveillance. Furthermore, the addition of functional lung imaging provides quantitative outputs which correlate well with clinically established lung function tests with the benefit of spatially localised lung function and additional quantitative measures of relevant extrapulmonary disease, within a single ionising radiation free examination. The data from this study have supported funding for future work addressing short, medium and long-term repeatability and longitudinal trends both in times of disease stability and over the course of an infective exacerbation.Open Acces

Early characterisation of neurodegeneration with high-resolution magnetic resonance elastography

This thesis contributes to recent interest within medical imaging regarding the development and clinical application of magnetic resonance elastography (MRE) to the human brain. MRE is a non-invasive phase-contrast MRI technique for measurement of brain mechanical properties in vivo, shown to reflect the composition and organisation of the complex tissue microstructure. MRE is a promising imaging biomarker for the early characterisation of neurodegeneration due to its exquisite sensitivity to variation among healthy and pathological tissue. Neurodegenerative diseases are debilitating conditions of the human nervous system for which there is currently no cure. Novel biomarkers are required to improve early detection, differential diagnosis and monitoring of disease progression, and could also ultimately improve our understanding of the pathophysiological mechanisms underlying degenerative processes. This thesis begins with a theoretical background of brain MRE and a description of the experimental considerations. A systematic review of the literature is then performed to summarise brain MRE quantitative measurements in healthy participants and to determine the success of MRE to characterise neurological disorders. This review further identified the most promising acquisition and analysis methods within the field. As such, subsequent visits to three brain MRE research centres, within the USA and Germany, enabled the acquisition of exemplar phantom and brain data to assist in discussions to refine an experimental protocol for installation at the Edinburgh Imaging Facility, QMRI (EIF-QMRI). Through collaborations with world-leading brain MRE centres, two high-resolution - yet fundamentally different - MRE pipelines were installed at the EIF-QMRI. Several optimisations were implemented to improve MRE image quality, while the clinical utility of MRE was enhanced by the novel development of a Graphical User Interface (GUI) for the optimised and automatic MRE-toanatomical coregistration and generation of MRE derived output measures. The first experimental study was performed in 6 young and 6 older healthy adults to compare the results from the two MRE pipelines to investigate test-retest agreement of the whole brain and a brain structure of interest: the hippocampal formation. The MRE protocol shown to possess superior reproducibility was subsequently applied in a second experimental study of 12 young and 12 older cognitively healthy adults. Results include finding that the MRE imaging procedure is very well tolerated across the recruited population. Novel findings include significantly softer brains in older adults both across the global cerebrum and in the majority of subcortical grey matter structures including the pallidum, putamen, caudate, and thalamus. Changes in tissue stiffness likely reflect an alteration to the strength in the composition of the tissue network. All MRE effects persist after correcting for brain structure volume suggesting changes in volume alone were not reflective of the detected MRE age differences. Interestingly, no age-related differences to tissue stiffness were found for the amygdala or hippocampus. As for brain viscosity, no group differences were detected for either the brain globally or subcortical structures, suggesting a preservation of the organisation of the tissue network in older age. The third experiment performed in this thesis finds a direct structure-function relationship in older adults between hippocampal viscosity and episodic memory as measured with verbal-paired recall. The source of this association was located to the left hippocampus, thus complementing previous literature suggesting unilateral hippocampal specialisation. Additionally, a more significant relationship was found between left hippocampal viscosity and memory after a new procedure was developed to remove voxels containing cerebrospinal fluid from the MRE analysis. Collectively, these results support the transition of brain MRE into a clinically useful neuroimaging modality that could, in particular, be used in the early characterisation of memory specific disorders such as amnestic Mild Cognitive Impairment and Alzheimer’s disease