Non-invasive measurement of hepatic venous oxygen saturation (ShvO₂) with quantitative susceptibility mapping in normal mouse liver and livers bearing colorectal metastases

PURPOSE: The purpose of this prospective study was to investigate the potential of QSM to noninvasively measure hepatic venous oxygen saturation (ShvO2). Materials & Methods: All animal studies were performed in accordance with the UK Home Office Animals Science Procedures Act (1986) and UK National Cancer Research Institute (NCRI) guidelines. QSM data was acquired from a cohort of mice (n=10) under both normoxic (medical air, 21% O2/balance N), and hyperoxic conditions (100% O2). Susceptibility measurements were taken from large branches of the portal and hepatic vein under each condition and were used to calculate venous oxygen saturation in each vessel. Blood was extracted from the IVC of three mice under norm- and hyperoxic conditions, and oxygen saturation was measured using a blood gas analyser to act as a gold standard. QSM data was also acquired from a cohort of mice bearing colorectal liver metastases (CRLM). SvO2 was calculated from susceptibility measurements made in the portal and hepatic veins, and compared to the healthy animals. RESULTS: SvO2 calculated from QSM measurements showed a significant increase of 14.93% in the portal vein (p < 0.05), and an increase of 21.39% in the hepatic vein (p < 0.01). Calculated results showed excellent agreement with those from the blood gas analyser (26.14% increase). ShvO2 was significantly lower in the disease cohort (30.18 ± 11.6%), than the healthy animals (52.67 ± 17.8%) (p < 0.05), but differences in the portal vein were not significant. CONCLUSION: QSM is a feasible tool for non-invasively measuring hepatic venous oxygen saturation and can detect differences in oxygen consumption in livers bearing colorectal metastases

Quantitative Susceptibility Mapping: Contrast Mechanisms and Clinical Applications.

Quantitative susceptibility mapping (QSM) is a recently developed MRI technique for quantifying the spatial distribution of magnetic susceptibility within biological tissues. It first uses the frequency shift in the MRI signal to map the magnetic field profile within the tissue. The resulting field map is then used to determine the spatial distribution of the underlying magnetic susceptibility by solving an inverse problem. The solution is achieved by deconvolving the field map with a dipole field, under the assumption that the magnetic field is a result of the superposition of the dipole fields generated by all voxels and that each voxel has its unique magnetic susceptibility. QSM provides improved contrast to noise ratio for certain tissues and structures compared to its magnitude counterpart. More importantly, magnetic susceptibility is a direct reflection of the molecular composition and cellular architecture of the tissue. Consequently, by quantifying magnetic susceptibility, QSM is becoming a quantitative imaging approach for characterizing normal and pathological tissue properties. This article reviews the mechanism generating susceptibility contrast within tissues and some associated applications

Introduction to quantitative susceptibility mapping and susceptibility weighted imaging.

Quantitative Susceptibility Mapping (QSM) and Susceptibility Weighted Imaging (SWI) are magnetic resonance imaging techniques that measure and display differences in the magnetisation that is induced in tissues, i.e. their magnetic susceptibility, when placed in the strong external magnetic field of an MRI system. SWI produces images in which the contrast is heavily weighted by the intrinsic tissue magnetic susceptibility. It has been applied in a wide range of clinical applications. QSM is a further advancement of this technique that requires sophisticated post-processing in order to provide quantitative maps of tissue susceptibility. This review explains the steps involved in both SWI and QSM as well as describing some of their uses in both clinical and research applications.Mr Ruetten is funded by a Medical Research Council/Sackler Stipend. The project was supported by the Addenbrooke’s Charitable Trust and the National Institute for Health Research [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust]

The implementation and application of quantitative susceptibility mapping in the pre-clinical liver

Quantitative Susceptibility Mapping (QSM) is a relatively new Magnetic Resonance Imaging (MRI) technique that gives information about the relative quantities of magnetically active constituents of a biological system. Using phase data, not normally utilised in standard MRI, measurements are made of local variations in the main magnetic field, B0. This data is then processed to calculate a map of local magnetic susceptibility within an organ of interest. This map yields relatively quantitative information, and compositional inferences can be made regarding the organ. Thus far, the body of literature on QSM has focussed almost exclusively on the brain, and has been performed on clinical data. This will be a preclinical project, and will focus primarily on the liver. The first two chapters of this thesis will establish the context of the research, as well as the background theory of QSM, including a detailed discussion of the set of algorithms selected to calculate the susceptibility maps for this body of work. The implementation of QSM in the preclinical liver has not been performed previously, and the novelty of the technique and the experimental work performed necessitated optimising both data acquisition and processing protocols. This was done on an empirical basis, and comprises the experimental work detailed in chapter 3. Chapters 4 – 6 describe the application of QSM to a number of hepatic conditions. It was established in chapter 4 that QSM is sensitive to changes in the oxygen saturation of blood in large branches of the major hepatic blood vessels in healthy mice. Chapter 5 discusses the application of QSM to a preclinical model of colorectal liver metastases, and also examines the ability of QSM to assess the efficacy of a Vascular Disrupting Agent (VDA), a novel chemotherapeutic drug. Finally, chapter 6 details the application of QSM to a model of liver cirrhosis

Regional quantification of cerebral venous oxygenation from MRI susceptibility during hypercapnia

There is an unmet medical need for noninvasive imaging of regional brain oxygenation to manage stroke, tumor, and neurodegenerative diseases. Oxygenation imaging from magnetic susceptibility in MRI is a promising new technique to measure local venous oxygen extraction fraction (OEF) along the cerebral venous vasculature. However, this approach has not been tested in vivo at different levels of oxygenation. The primary goal of this study was to test whether susceptibility imaging of oxygenation can detect OEF changes induced by hypercapnia, via CO[subscript 2] inhalation, within selected a priori brain regions. Ten healthy subjects were scanned at 3 T with a 32-channel head coil. The end-tidal CO[subscript 2] (ETCO[subscript 2]) was monitored continuously and inspired gases were adjusted to achieve steady-state conditions of eucapnia (41 ± 3 mm Hg) and hypercapnia (50 ± 4 mm Hg). Gradient echo phase images and pseudo-continuous arterial spin labeling (pcASL) images were acquired to measure regional OEF and CBF respectively during eucapnia and hypercapnia. By assuming constant cerebral oxygen consumption throughout both gas states, regional CBF values were computed to predict the local change in OEF in each brain region. Hypercapnia induced a relative decrease in OEF of − 42.3% in the straight sinus, − 39.9% in the internal cerebral veins, and approximately − 50% in pial vessels draining each of the occipital, parietal, and frontal cortical areas. Across volunteers, regional changes in OEF correlated with changes in ETCO[subscript 2]. The reductions in regional OEF (via phase images) were significantly correlated (P < 0.05) with predicted reductions in OEF derived from CBF data (via pcASL images). These findings suggest that susceptibility imaging is a promising technique for OEF measurements, and may serve as a clinical biomarker for brain conditions with aberrant regional oxygenation

Magnetic Resonance Imaging of Susceptibility Effects in Carotid Atherosclerosis

This thesis explores the use of susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM), to characterize carotid artery plaques with and without the use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle contrast agents. The overall hypothesis is that QSM can serve to differentiate carotid artery plaque features of different susceptibility and provide a positive contrast mechanism for imaging the uptake of USPIOs. Chapter 1 describes the pathophysiology of carotid atherosclerosis. Vulnerable plaques, i.e. those at risk of rupture, can be characterized by the presence of a lipid rich necrotic core (LRNC), intraplaque haemorrhage (IPH), and inflammation. In addition, plaques may develop calcifications that may be protective of rupture. The chapter describes the established multi-contrast imaging protocols used for characterizing plaques. Furthermore, the use of USPIO-contrast agents to image inflammation is described. Chapter 2 describes the physical principles of MR image generation including the sensitivity to magnetic susceptibility. The principles of T2*w imaging, and susceptibility weighted imaging (SWI) are explained. Chapter 3 reviews the principles and post-processing steps involved in commonly used algorithms for QSM in terms of the underlying physical and mathematical principles which are then demonstrated in the form of numerical simulations. Chapter 4 presents the application of SWI to a group of patients who underwent USPIO enhanced MRI on a 1.5T MRI system. Images were acquired prior to infusion and 48 hours post infusion. SWI and gradient echo phase images were used to depict the field inhomogeneities generated by diamagnetic and paramagnetic materials within the plaques, calcification and USPIO-uptake. These results were then compared to a conventional carotid multi-contrast protocol, which includes R2*-mapping and T2*w imaging, and, where available, CT and histology. In chapter 5 QSM is performed in the carotid artery wall of a cohort of normal volunteers on a 1.5T MRI system. Unlike the brain, the neck contains fat which can cause severe errors in the field estimate, which propagate into the susceptibility map. Therefore, QSM was combined with water-fat separation for application in the neck to correct for these artifacts. This correctly estimated a high fat-fraction in fatty tissue in the neck and allowed for a detailed depiction of the anatomy of healthy volunteers. The susceptibility value measured in fatty tissue agreed with literature values. Chapter 6 applies QSM with water-fat separation to a subset of the patient group on a 1.5T MRI system. On pre-contrast scans QSM successfully identified calcification as diamagnetic tissue and the water-fat separation identified a lipid core. On the post-contrast susceptibility maps, USPIO-uptake was identified as hyperintense signal. This allows QSM to provide quantitative contrast in carotid imaging that can identify multiple features simultaneously and to simplify the imaging of USPIO-contrast. The results were confirmed using the multi-contrast carotid MRI protocol and, where available, histology and CT. Chapter 7 discusses the limitations of the current studies and the potential future improvements of the current methodology in terms of MR acquisition, post-processing algorithms and MR protocols. Future studies could serve to further evaluate the potential of QSM in carotid imaging and use it as a novel tool to quantify USPIO uptake in atherosclerotic carotid arteries