Quantitative whole body imaging at high field

In this thesis methods of accurately and reproducibly measuring intestinal content and transverse relaxation to study the fate of food in the gastrointestinal tract are reported. In addition to this a technique for measuring relaxation parameters in the brain at ultra-high field is also investigated. Several methods can be used when quantifying the fate of food through the gastrointestinal tract; there are many factors that can be measured using MRI and these are discussed along with other non-MRI techniques. In this work a method for quantifying small bowel water content (SBWC) is optimised and validated for use at 3.0 T and a technique for measuring T2 in the abdomen is developed and optimised called T2-prepared balanced turbo field echo (T2-prep bTFE). These two methods are then used, in conjunction with other established MRI techniques, to study the fate of food in the gastrointestinal tract from the stomach all the way through to the colon. A hybrid gradient echo-spin echo (GESSE) sequence is also investigated and optimised for measuring T2 and T2* simultaneously in the brain at 7.0 T. This sequence is also proved to have applications in the liver at lower field strengths. The GESSE sequence is used to measure the first T2 values in deep grey structures in the brain at 7.0 T. In this work cross-field (1.5, 3.0 and 7.0 T) variations in T2 are studied. Also differences in T2 and T2* are measured in the brain to determine variations between white matter tracts and to ascertain any effects of Parkinson’s disease on deep grey matter structures

Equivalent-source acoustic holography for projecting measured ultrasound fields through complex media

Holographic projections of experimental ultrasound measurements generally use the angular spectrum method or Rayleigh integral, where the measured data is imposed as a Dirichlet boundary condition. In contrast, full-wave models, which can account for more complex wave behaviour, often use interior mass or velocity sources to introduce acoustic energy into the simulation. Here, a method to generate an equivalent interior source that reproduces the measurement data is proposed based on gradient-based optimisation. The equivalent-source can then be used with full-wave models (for example, the open-source k-Wave toolbox) to compute holographic projections through complex media including nonlinearity and heterogeneous material properties. Numerical and experimental results using both time-domain and continuous-wave sources are used to demonstrate the accuracy of the approach

Evaluation of 2D Imaging Schemes for Pulsed Arterial Spin Labeling of the Human Kidney Cortex

Purpose A number of imaging readout schemes have been proposed for renal arterial spin labelling (ASL) to quantify kidney cortex perfusion, including gradient echo based methods of balanced fast field echo (bFFE) and gradient-echo echo-planar imaging (GE-EPI), or spin echo based schemes of spin-echo echo planar imaging (SE-EPI) and turbo spin-echo (TSE). Here, we compare these 2D imaging schemes to evaluate the optimal imaging scheme for pulsed ASL (PASL) assessment of human kidney cortex perfusion at 3 T.MethodsTen healthy volunteers with normal renal function were scanned using each 2D multislice imaging scheme, in combination with a respiratory triggered FAIR (flow-sensitive alternating inversion recovery) ASL scheme on a 3T Philips Achieva scanner. All volunteers returned for a second identical scan session within two weeks of the first scan session. Comparisons were made between the imaging schemes in terms of perfusion weighted image (PWI) signal-to-noise ratio (SNR) and perfusion quantification, temporal SNR (tSNR), spatial coverage, and repeatability.Results:For each imaging scheme, renal cortex perfusion was calculated (bFFE: 276 ± 29 ml/100g/min, GE-EPI: 222 ± 18 ml/100g/min, SE-EPI: 201 ± 36 ml/100g/min, TSE: 200 ± 20 ml/100g/min). Perfusion was found to be higher for GE based readouts compared to SE based readouts, with significantly higher measured perfusion for the bFFE readout compared to all other schemes (P < 0.05), attributed to the greater vascular signal present. Despite the PWI-SNR being significantly lower for SE-EPI compared to all other schemes (P < 0.05), the SE-EPI readout gave the highest tSNR and was found to be the most reproducible scheme for the assessment of kidney cortex, with a CoV of 17.2%, whilst minimizing variability of the perfusion weighted signal across slices for whole kidney perfusion assessment.ConclusionFor the assessment of kidney cortex perfusion using 2D readout schemes, SE-EPI provides optimal tSNR, minimal variability across slices and repeatable data acquired in a short scan time with low specific absorption rate

Quantitative assessment of renal structural and functional changes in chronic kidney disease using multi-parametric magnetic resonance imaging

BACKGROUND:Multi-parametric magnetic resonance imaging (MRI) provides the potential for a more comprehensive non-invasive assessment of organ structure and function than individual MRI measures, but has not previously been comprehensively evaluated in chronic kidney disease (CKD).METHODS:We performed multi-parametric renal MRI in persons with CKD (n = 22, 61 ± 24 years) who had a renal biopsy and measured glomerular filtration rate (mGFR), and matched healthy volunteers (HV) (n = 22, 61 ± 25 years). Longitudinal relaxation time (T1), diffusion-weighted imaging, renal blood flow (phase contrast MRI), cortical perfusion (arterial spin labelling) and blood-oxygen-level-dependent relaxation rate (R2*) were evaluated.RESULTS:MRI evidenced excellent reproducibility in CKD (coefficient of variation

MRI assessment of altered dynamic changes in liver haemodynamics following a meal challenge in compensated cirrhosis

Background: To use magnetic resonance imaging (MRI) to dynamically assess postprandial changes in hepatic and collateral blood flow, liver perfusion and oxygenation in healthy participants and patients with liver disease with compensated cirrhosis (CC).Methods: We evaluated blood flow in the portal vein, hepatic artery, and azygos vein (using phase-contrast MRI), liver perfusion (using arterial spin labelling) and blood oxygenation (using transverse relaxation time [T2*] mapping). Measures were collected at baseline and at 6-7 min intervals from 20 to 65 min following a test meal (440 ml; 660 kcal) in 10 healthy participants and 10 CC patients.Results: In healthy participants, we observed a significant postprandial increase in portal vein flow from baseline (+137 ± 26% [mean ± standard deviation], p < 0.001) coupled with a reduction in hepatic artery flow from baseline (-30 ±18%, p = 0.008), reflecting the hepatic artery buffer response. In CC patients, a lower but still significant increase in portal vein (67 ±50 %, p = 0.014) was observed, without a clear hepatic artery buffer response. Healthy participants showed a significant increase in postprandial liver perfusion (138 ± 75%, p < 0.001), not observed in CC patients. There was no change in liver T2* for either group. Conclusions: Postprandial changes in liver perfusion, oxygenation, and hepatic and collateral circulation can be measured non-invasively using MRI. Differences between healthy participants and CC patients were shown, which may help stratify liver cirrhosis in patients

A randomized, controlled, double-blind crossover study on the effects of isoeffective and isovolumetric intravenous crystalloid and gelatin on blood volume, and renal and cardiac hemodynamics

Background & aimsBlood volume expanding properties of colloids are superior to crystalloids. In addition to oncotic/osmotic properties, the electrolyte composition of infusions may have important effects on visceral perfusion, with infusions containing supraphysiological chloride causing hyperchloremic acidosis and decreased renal blood flow. In this non-inferiority study, a validated healthy human subject model was used to compare effects of colloid (4% succinylated gelatin) and crystalloid fluid regimens on blood volume, renal function, and cardiac output.MethodsHealthy male participants were given infusions over 60 min > 7 days apart in a randomized, crossover manner. Reference arm (A): 1.5 L of Sterofundin ISO, isoeffective arm (B): 0.5 L of 4% Gelaspan®, isovolumetric arm (C): 0.5 L of 4% Gelaspan® and 1 L of Sterofundin ISO (all B. Braun, Melsungen, Germany). Participants were studied over 240 min. Changes in blood volume were calculated from changes in weight and hematocrit. Renal volume, renal artery blood flow (RABF), renal cortex perfusion and diffusion, and cardiac index were measured with magnetic resonance imaging.ResultsTen of 12 males [mean (SE) age 23.9 (0.8) years] recruited, completed the study. Increase in body weight and extracellular fluid volume were significantly less after infusion B than infusions A and C, but changes in blood volume did not significantly differ between infusions. All infusions increased renal volume, with no significant differences between infusions. There was no significant difference in RABF across the infusion time course or between infusion types. Renal cortex perfusion decreased during the infusion (mean 18% decrease from baseline), with no significant difference between infusions. There was a trend for increased renal cortex diffusion (4.2% increase from baseline) for the crystalloid infusion. All infusions led to significant increases in cardiac index.ConclusionsA smaller volume of colloid (4% succinylated gelatin) was as effective as a larger volume of crystalloid at expanding blood volume, increasing cardiac output and changing renal function. Significantly less interstitial space expansion occurred with the colloid

DYNamic assessment of multi‐organ level dysfunction in patients recovering from COVID‐19: DYNAMO COVID‐19

We evaluated the impacts of COVID‐19 on multi‐organ and metabolic function in patients following severe hospitalised infection compared to controls. Patients (n = 21) without previous diabetes, cardiovascular or cerebrovascular disease were recruited 5–7 months post‐discharge alongside controls (n = 10) with similar age, sex and body mass. Perceived fatigue was estimated (Fatigue Severity Scale) and the following were conducted: oral glucose tolerance (OGTT) alongside whole‐body fuel oxidation, validated magnetic resonance imaging and spectroscopy during resting and supine controlled exercise, dual‐energy X‐ray absorptiometry, short physical performance battery (SPPB), intra‐muscular electromyography, quadriceps strength and fatigability, and daily step‐count. There was a greater insulin response (incremental area under the curve, median (inter‐quartile range)) during the OGTT in patients [18,289 (12,497–27,448) mIU/min/L] versus controls [8655 (7948–11,040) mIU/min/L], P &lt; 0.001. Blood glucose response and fasting and post‐prandial fuel oxidation rates were not different. This greater insulin resistance was not explained by differences in systemic inflammation or whole‐body/regional adiposity, but step‐count (P = 0.07) and SPPB scores (P = 0.004) were lower in patients. Liver volume was 28% greater in patients than controls, and fat fraction adjusted liver T1, a measure of inflammation, was raised in patients. Patients displayed greater perceived fatigue scores, though leg muscle volume, strength, force‐loss, motor unit properties and post‐exercise muscle phosphocreatine resynthesis were comparable. Further, cardiac and cerebral architecture and function (at rest and on exercise) were not different. In this cross‐sectional study, individuals without known previous morbidity who survived severe COVID‐19 exhibited greater insulin resistance, pointing to a need for physical function intervention in recovery

Multi organ assessment of compensated cirrhosis patients using quantitative magnetic resonance imaging

Background and Aims: Advancing liver disease results in deleterious changes in a number of critical organs. The ability to measure structure, blood flow and tissue perfusion within multiple organs in a single scan has implications for determining the balance of benefit versus harm for therapies. Our aim was to establish the feasibility of Magnetic Resonance Imaging to assess changes in compensated cirrhosis (CC), and relate this to disease severity and future liver related outcomes (LROs). Methods: 60 CC patients, 40 healthy volunteers and 7 decompensated cirrhotics were recruited. In a single scan session, MRI measures comprised phase-contrast MRI vessel blood flow, arterial spin labelling tissue perfusion, T1 longitudinal relaxation time and volume assessment of liver, spleen and kidneys, heart rate and cardiac index. We explore MRI parameters with disease severity and differences in baseline MRI parameters in those 11 (18%) of CC patients who had future LROs. Results: In the liver compositional changes were reflected by increased T1 in progressive disease (p<0.001) and an increase in liver volume in CC (p=0.006), with associated progressive reduction in liver (p < 0.001) and splenic (p<0.001) perfusion. A significant reduction in renal cortex T1 and increase in cardiac index and superior mesenteric arterial (SMA) blood flow was seen with increasing disease severity. Baseline liver T1 (p=0.01) and perfusion (p< 0.01), and renal cortex T1 (p<0.01) were significantly different in CC patients who subsequently developed negative LROs. Conclusions: MRI allows the contemporaneous assessment of organs in liver cirrhosis in a single scan without the requirement of contrast agent. MRI parameters of liver T1, renal T1, hepatic and splenic perfusion, and SMA blood flow were related to risk of LROs