MRI Guidance of Transcranial Histotripsy Treatments

Abstract

Brain cancers account for over 250000 deaths per year worldwide, with over 300000 new cases reported every year. There are three main treatment options for patients with brain tumors: surgery, radiation therapy, and chemotherapy. Surgery and radiation therapy are the most commonly used practices, but they expose patients to infections, trauma, and damage to the surrounding cerebral parenchyma or expose patients to ionizing radiation. Chemotherapy has seen limited success in treating brain tumors due to the presence of the blood-brain barrier (BBB) that prohibits chemotherapeutic drugs from entering the brain. Histotripsy is a focused ultrasound-based therapy that uses cavitation to precisely and non-invasively treat tissues. Performing histotripsy treatments requires imaging guidance to localize the treatment region and monitor treatment outcomes. This dissertation presents methods to perform transcranial histotripsy treatments using treatment guidance from MR imaging. The first chapter discusses the prevalence of brain tumors and the treatment options available for treating tumors. The second chapter introduces the technical background of histotripsy and MRI and discusses the relevant topics that combine focused ultrasound and MRI. The third and fourth chapters discuss methods to perform histotripsy pre-treatment targeting in ex-vivo brain tissues. The method involves acquiring MR-thermometry and/or MR-Acoustic Radiation Force (MR-ARFI) images before the histotripsy treatments and then comparing the estimated focus from the two methods to the focus estimated from a histotripsy lesion generated at the same target location. Both the pre-treatment targeting methods perform similarly well in estimating histotripsy lesions with mean absolute errors along the transverse/longitudinal axis of 2.06 mm/2.95 mm and 2.13 mm/2.51 mm for MR- ARFI and MR-thermometry, respectively. The fifth chapter discusses a method to perform real-time monitoring of histotripsy treatments in ex-vivo brain. MR images are sensitized to histotripsy cavitation cloud-induced motion by encoding motion using a set of bipolar gradients. Image magnitude and phase changes are shown to provide complementary information about the lesion. The image magnitude decreases due to the increased random motion within the lesion. The image phase encodes the motion induced by the bubble cloud and indicates a net motion away from the histotripsy transducer. The sensitivity to the lesion is controlled by both the amplitude and the spacing of the encoding gradients. This method was validated by monitoring histotripsy sonications through the skull with 0.5 s temporal resolution using a spiral acquisition. The sixth chapter describes different MR-visible parameters that change with histotripsy dose in the brain. MR parameter maps of T1, T2, and Apparent Diffusion Coefficient (ADC) for varying histotripsy treatment doses are acquired. It is observed that the T1 and T2 do not correlate with the histotripsy dose. The ADC within the lesion increases as more histotripsy dose is delivered. As histotripsy breaks down the cellular structure, it significantly increases the diffusion of water within the lesion, which is quantified using the lesion’s ADC (p < 0.001). For the tissues treated in this study, the ADC increased by 6.5 × 10−4 mm2/s with 50 reps of histotripsy dose across three tissues. The final chapter summarizes the findings and contributions of this dissertation and discusses future work to advance MR methods for treating brain tumors using histotripsy.