Author: Yu Liu

Publisher:

Published: 2016

Total Pages:

ISBN-13: 9781369615791

Manual palpation is often used to assess mechanical changes in tissue that result from pathology, such as increased stiffness in malignant tissues. Although manual palpation is a common, inexpensive, and informative diagnostic tool, lesions that are small or located deep within the body are inaccessible via palpation. Additionally, palpation is non-quantitative, varies between physicians, and cannot be used to localize lesions. Magnetic resonance-guided focused ultrasound (MRgFUS) offers a non-invasive technique to evaluate the properties of biological tissues. Additionally, magnetic resonance imaging (MRI) can provide a three-dimensional, high resolution view of surrounding anatomy during interventions such as ultrasound (US)-mediated thermal therapies. This makes MRI-based strategies desirable for multiple clinical applications. In order to improve spatial resolution and depth-of-field (2mm) compared to the current clinical systems, the MRgFUS system in the Ferrara laboratory combines ultra-high field (7T) MR and 3MHz focused US. This combination is more effective in monitoring and delivering thermal therapies, enhancing drug delivery, and aiding in non-invasive tissue characterization. In this dissertation, a system for controlled tissue heating is developed using proportional-integral-derivative (PID) feedback control combined with 7T MR thermometry to provide temperature feedback. MR thermometry was validated by an optical temperature probe. We have measured and simulated MR estimates of transient US-induced heating in a phantom and performed controlled heating studies in an in vivo Met-1 mouse tumor. MR thermometry estimates agreed with fiber optic temperature measurements within 1°C and simulations of heating in a phantom were in agreement with the MR temperature measurements. Secondly, we developed an MR pulse sequence that can simultaneously quantify acoustic radiation, force displacements and image the resulting transient shear wave. Magnetic resonance-acoustic radiation force imaging (MR-ARFI) provides a reliable and efficient method for beam localization by detecting micron-scale displacements induced by ultrasound mechanical force in the absence of heat generation. The shear wave velocity was validated in vitro using tissue-mimicking gelatin and tofu phantoms while the sequence was validated in vivo by estimating the displacement before and after high intensity focused ultrasound (HIFU) ablation. The new MR-ARFI protocol that can rapidly acquire shear elasticity is especially useful in interventional radiology applications where minimizing scan time is highly desirable. Lastly, we developed a new transient magnetic resonance elastography (t-MRE) protocol to improve visualization of transient shear wave propagation. The new protocol was used to quantify tissue elasticity in vitro using tissue-mimicking phantoms. The MRE data were cross-validated with measurements acquired under US guidance. We then validated both MR-based and US-based methods using mechanical testing (MT) as a gold-standard. Overall, three contributions are described in this work. First, the development of the MRgFUS system provides the capability to apply thermal therapy both in vitro and in vivo. Secondly, our MRgFUS system was used for MR-ARFI in both in vitro and in vivo studies. In addition, we were able to obtain focal displacement and shear wave velocity estimates with the same MR-ARFI sequence. Third, a novel t-MRE protocol using the combination of MR shear imaging sequence and multi pulse transmission was developed and tested in vitro, which improves the visualization of shear wave propagation and allows for the quantification of tissue mechanical properties. Taken together, the contributions facilitate real-time MRgFUS for interventional guidance.