Prostate cancer assessment using MR elastography of fresh prostatectomy specimens at 9.4 T

Purpose: Despite its success in the assessment of prostate cancer (PCa), in vivo multiparametric MRI has limitations such as interobserver variability and low specificity. Several MRI methods, among them MR elastography, are currently being discussed as candidates for supplementing conventional multiparametric MRI. This study aims to investigate the detection of PCa in fresh ex vivo human prostatectomy specimens using MR elastography. Methods: Fourteen fresh prostate specimens from men with clinically significant PCa without formalin fixation or prior radiation therapy were examined by MR elastography at 500 Hz immediately after radical prostatectomy in a 9.4T preclinical scanner. Specimens were divided into 12 segments for both calculation of storage modulus (G ' in kilopascals) and pathology (Gleason score) as reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve were calculated to assess PCa detection. Results: The mean G ' and SD were as follows: all segments, 8.74 ± 5.26 kPa; healthy segments, 5.44 ± 4.40 kPa; and cancerous segments, 10.84 ± 4.65 kPa. The difference between healthy and cancerous segments was significant with P ≤ .001. Diagnostic performance assessed with the Youden index was as follows: sensitivity, 69%; specificity, 79%; area under the curve, 0.81; and cutoff, 10.67 kPa. Conclusion: Our results suggest that prostate MR elastography has the potential to improve diagnostic performance of multiparametric MRI, especially regarding its 2 major limitations: interobserver variability and low specificity. Particularly the high value for specificity in PCa detection is a stimulating result and encourages further investigation of this method

Development of Magnetic Resonance Elastography for Assessing Small Regions of Interest in Murine Models

Magnetic Resonance Elastography (MRE) is a noninvasive diagnostic imaging technique capable of determining the mechanical properties of biological tissue and has diagnostic potential for a variety of diseases. Application of MRE for murine studies presents some fundamental challenges such as the fact that higher resolution leads to a loss in the image signal-to-noise ratio (SNR) as a result of reduced voxel size. This challenge is further exacerbated by the dispersive nature of mechanical wave propagation, which results in frequency-dependent regions of wave interferences. Therefore, the mechanical assessment of small regions of interest in mice is a challenging exercise. In this dissertation, a multifrequency based viscoelastic parameter recovery approach known as multifrequency dual elastovisco (MDEV) inversion and intravoxel phase dispersion (IVPD) based MRE or IVPD-MRE have been implemented in the murine MRE pipeline in order to investigate their capability to increase the spatial resolution of elastograms and to improve the stability of the inverse problem in small regions of interest. Studies using phantoms and mouse brain validate the capability of multi-frequency inversion to provide reliable elastograms in small regions of interest, while this is not the case for IVPD-MRE in its current stage of development. The dissertation also presents the application of SampLe Interval Modulation MRE (SLIM-MRE) for assessing viscoelastic changes occurring inside the mouse brain due to the progression of Alzheimer’s disease and inside the mouse liver due to hepatic fibrosis. Combining SLIM-MRE with multifrequency inversion has highlighted early changes inside the cortex and the hippocampus of mice from the Alzheimer’s disease model. SLIM-MRE has also reported higher liver stiffness values in mice which have been medicated to produce fibrotic tissue. Utilizing SLIM-MRE in conjunction with multifrequency-based assessments improves the efficacy of disease diagnosis in the presented preclinical mouse studies

Correlating Tumor Microstructure With Hypoxia Using Magnetic Resonance Imaging

Knowledge of oxygen concentration in tumors is important as hypoxic or oxygen deficient regions in tumors have been known to offer greater resistance to radiation treatment. Electron paramagnetic resonance oxygen imaging (EPROI) is an established technique for measuring absolute partial oxygen pressure (pO2) in tissues. Tumors also possess highly disorganized microstructure that can be measured using magnetic resonance imaging (MRI). Both these imaging modalities when used in conjunction, show the promise to create the opportunity for targeted radiation delivery to tumors. This work describes the initial pilot experiments that were done to correlate viscosity and fractional anisotropy with pO2 in FSa and MCa4 tumors in murine model. Using diffusion weighted MRI, the relationship between tissue viscosity and fractional anisotropy maps from MRI have been correlated to pO2 maps obtained using EPROI. EPROI is a functional imaging procedure, whereas MRI provides the best soft tissue contrast. Thus, further research in correlating structural information through MRI to oxygen information through EPROI will open the doors to create an effective targeted radiation delivery system, where areas inside a tumor can be differentiated based on their oxygen concentration and tissue microstructure, and subjected to different radiation treatment plans. This may lead to better post-treatment healing and minimize dysfunction by sparing healthy tissue structure with optimized radiation doses. The long-term goal of this study is to help create efficient intensity modulated radiation therapy (IMRT) treatment plan for solid tumors

Simultaneous 3D MR elastography of the in vivo mouse brain

The feasibility of sample interval modulation (SLIM) magnetic resonance elastography (MRE) for the in vivo mouse brain is assessed, and an alternative SLIM-MRE encoding method is introduced. In SLIM-MRE, the phase accumulation for each motion direction is encoded simultaneously by varying either the start time of the motion encoding gradient (MEG), SLIM-phase constant (SLIM-PC), or the initial phase of the MEG, SLIM-phase varying (SLIM-PV). SLIM-PC provides gradient moment nulling, but the mutual gradient shift necessitates increased echo time (TE). SLIM-PV requires no increased TE, but exhibits non-uniform flow compensation. Comparison was to conventional MRE using six C57BL/6 mice. For SLIM-PC, the Spearman's rank correlation to conventional MRE for the shear storage and loss modulus images were 80% and 76%, respectively, and likewise for SLIM-PV, 73% and 69%, respectively. The results of the Wilcoxon rank sum test showed that there were no statistically significant differences between the spatially averaged shear moduli derived from conventional-MRE, SLIM-PC, and SLIM-PV acquisitions. Both SLIM approaches were comparable to conventional MRE scans with Spearman's rank correlation of 69%-80% and with 3 times reduction in scan time. The SLIM-PC method had the best correlation, and SLIM-PV may be a useful tool in experimental conditions, where both measurement time and T2 relaxation is critical