Investigating Tissue Heterogeneity using MRI in Prostate Cancer

Multi-parametric MRI, a promising new technique for grading prostate cancer using MRI, classifies a high number of regions as indeterminate. This is a symptom of the wider problem that clinical usage of MRI in prostate cancer only includes basic techniques and does not directly categorise tissue microstructure. This work provides insight into the microstructure of the prostate using a combination of new tissue models and acquisition schemes. Each is tested with the aim of producing a method that is better at detecting and grading prostate cancer. The first section utilises microstructural diffusion models to better quantify tissue heterogeneity in the prostate. The two models investigated provided more information about the heterogeneous nature of the prostate that ADC and showed significant difference between lesions and normal tissue. The next section looks into combining multi-echo T2 (ME-T2) sequences with quantitative tissue modelling called Luminal Water Imaging (LWI). This work produced an optimal LWI fitting technique and acquisition. Then the ability of LWI to detect the PI-RADS v2.0 score of regions of interest was examined, showing that it was able to differentiate between scores better than ADC. This work also showed that LWI can differentiate between tumour and normal tissue with an AUC of 0.81 (p<0.05) when compared to ADC with an AUC of 0.75 (p<0.05) in this dataset. The next section further improves the acquisitions using larger datasets. It showed that correcting for imperfect pulse refocusing could improve on the performance of LWI in detecting PCa. This work also showed that fewer echoes could be used in the acquisition. Neural networks were then used to detect and grade prostate cancer using the data points from both multiple b-value diffusion and ME-T2 decay curves. The neural network’s ability to distinguish between different PIRADS scores was shown to have an AUC of 0.87 (p<0.05) using 32-echo data

Robust Magnetic Resonance Imaging of Short T2 Tissues

Tissues with short transverse relaxation times are defined as ‘short T2 tissues’, and short T2 tissues often appear dark on images generated by conventional magnetic resonance imaging techniques. Common short T2 tissues include tendons, meniscus, and cortical bone. Ultrashort Echo Time (UTE) pulse sequences can provide morphologic contrasts and quantitative maps for short T2 tissues by reducing time-of-echo to the system minimum (e.g., less than 100 us). Therefore, UTE sequences have become a powerful imaging tool for visualizing and quantifying short T2 tissues in many applications. In this work, we developed a new Flexible Ultra Short time Echo (FUSE) pulse sequence employing a total of thirteen acquisition features with adjustable parameters, including optimized radiofrequency pulses, trajectories, choice of two or three dimensions, and multiple long-T2 suppression techniques. Together with the FUSE sequence, an improved analytical density correction and an auto-deblurring algorithm were incorporated as part of a novel reconstruction pipeline for reducing imaging artifacts. Firstly, we evaluated the FUSE sequence using a phantom containing short T2 components. The results demonstrated that differing UTE acquisition methods, improving the density correction functions and improving the deblurring algorithm could reduce the various artifacts, improve the overall signal, and enhance short T2 contrast. Secondly, we applied the FUSE sequence in bovine stifle joints (similar to the human knee) for morphologic imaging and quantitative assessment. The results showed that it was feasible to use the FUSE sequence to create morphologic images that isolate signals from the various knee joint tissues and carry out comprehensive quantitative assessments, using the meniscus as a model, including the mappings of longitudinal relaxation (T1) times, quantitative magnetization transfer parameters, and effective transverse relaxation (T2*) times. Lastly, we utilized the FUSE sequence to image the human skull for evaluating its feasibility in synthetic computed tomography (CT) generation and radiation treatment planning. The results demonstrated that the radiation treatment plans created using the FUSE-based synthetic CT and traditional CT data were able to present comparable dose calculations with the dose difference of mean less than a percent. In summary, this thesis clearly demonstrated the need for the FUSE sequence and its potential for robustly imaging short T2 tissues in various applications

Multi-component MRI transverse-relaxation parameter estimation to detect and monitor neuromuscular disease

We aimed to optimise the estimation of skeletal muscle-water spin-spin relaxation time (T2m), and fat fraction estimated from multi-echo MRI, as potential biomarkers, by accounting for instrumental factors such as B1 errors, non-Gaussian noise and non-ideal echo train evolution. A multi-component slice-profile-compensated extended phase graph (sEPG) model for multi-echo Carr-Purcell-Meiboom-Gill (CPMG) spin-echo sequence signals was implemented, modelling the fat signal as two empirically calibrated sEPG components with fixed parameters, and the remaining unknown parameters (B1 field factor, T2m, fat fraction (ffa), global amplitude and Rician noise SD) determined by maximum likelihood estimation. After validation using a calibrated test object the algorithm was used to analyse clinical muscle study data from patient groups with amyotrophic lateral sclerosis (ALS), Kennedy’s disease (KD) and Duchenne muscular dystrophy (DMD) and matched healthy controls. Parameter maps were generated using quality control steps to reject pixels failing fit quality or physical meaningfulness criteria. Muscle fat-fraction was also determined independently by 3-point Dixon MRI (ffd). In ALS and KD median T2m were significantly elevated compared with healthy controls in varied patterns and time courses, whereas it was decreased in DMD; other T2m distribution histogram metrics such as the skewness and full width at quarter maximum also differed significantly between patients and healthy volunteers. Quantitative comparison of ffa and ffd in the same muscles revealed a monotonic relationship deviating from linearity due to differing deviations from the assumed ideal signal behaviour in each method. Finally, the effects upon estimation accuracy and precision of practically realisable pulse sequence parameter choices were explored in simulations and with real data. Recommendations are presented for optimal choices. Clinically practical conventional CPMG sequences, combined with an appropriate signal model and parameter estimation method can provide robust T2m and ffa measures which change in disease and may sensitively reflect different aspects of neuromuscular pathology

Time-efficient combined morphologic and quantitative joint MRI based on clinical image contrasts -- An exploratory in-situ study of standardized cartilage defects

OBJECTIVES: Quantitative MRI techniques such as T2 and T1$\rho$ mapping are beneficial in evaluating cartilage and meniscus. We aimed to evaluate the MIXTURE (Multi-Interleaved X-prepared Turbo-Spin Echo with IntUitive RElaxometry) sequences that provide morphologic images with clinical turbo spin-echo (TSE) contrasts and additional parameter maps versus reference TSE sequences in an in-situ model of human cartilage defects. MATERIALS AND METHODS: Prospectively, standardized cartilage defects of 8mm, 5mm, and 3mm diameter were created in the lateral femora of 10 human cadaveric knee specimens (81$\pm$10 years, nine male/one female). Using a clinical 3T MRI scanner and knee coil, MIXTURE sequences combining (i) proton-density weighted fat-saturated (PD-w FS) images and T2 maps and (ii) T1-weighted images and T1$\rho$ maps were acquired before and after defect creation, alongside the corresponding 2D TSE and 3D TSE reference sequences. Defect delineability, bone texture, and cartilage relaxation times were quantified. Inter-sequence comparisons were made using appropriate parametric and non-parametric tests. RESULTS: Overall, defect delineability and texture features were not significantly different between the MIXTURE and reference sequences. After defect creation, relaxation times increased significantly in the central femur (for T2) and all regions combined (for T1$\rho$). CONCLUSION: MIXTURE sequences permit time-efficient simultaneous morphologic and quantitative joint assessment based on clinical image contrasts. While providing T2 or T1$\rho$ maps in clinically feasible scan time, morphologic image features, i.e., cartilage defect delineability and bone texture, were comparable between MIXTURE and corresponding reference sequences.Comment: 12 pages (main body), 3 tables, 6 figure