Research

The overarching goal of the Vlaisavljevich laboratory is to investigate the physical mechanisms with which ultrasound interacts with tissue in order to develop non-invasive therapies for a wide range of clinical applications. This work is separated into four primary research areas including Non-invasive Tissue Ablation (Histotripsy), Nanoparticle-mediated Histotripsy, Acoustically Active Biomaterials, and Low-Intensity Focused Ultrasound for Drug Delivery and Neuromodulation. In addition, the Vlaisavljevich lab has a separate research track that aims to develop Ultrasonic Technologies for Environmental Conservation and Global Health. Summaries of these research areas can be found in the sections below.

A primary focus of our research laboratory is the development of Focused Ultrasound (FUS) as an image-guided and non-invasive ablation method for the treatment of cancer. More specifically, our lab is developing histotripsy for the treatment of multiple cancer types including liver, kidney, pancreatic, and brain cancer. Histotripsy is a non-thermal and completely non-invasive ultrasonic ablation method that destroys targeted tumors through the precise control of acoustic cavitation. The histotripsy “bubble cloud” can be visualized with ultrasound imaging, allowing for precise targeting and real-time monitoring. Histotripsy is capable of generating precise lesions with sharp boundaries between treated and untreated tissue, with no recognizable cellular structures remaining inside the lesion. The goal of our lab is to answer the key preclinical questions necessary to demonstrate the long-term oncological and immunological response of different cancer types to histotripsy in order to advance this technology into a broader patient population and curative endpoints. In addition, our lab is also developing novel therapy methods that combine histotripsy with thermal FUS ablation for the treatment of stiff tissues (cholangiocarcinoma, uterine fibroids).

Histotripsy has been shown to be efficacious for the treatment of primary tumors, such as liver tumors, however, treatment is limited to tumors that can be imaged before and during treatment. Nanoparticle-mediated Histotripsy (NMH) is being developed for the treatment of late-stage cancers, focusing on metastatic breast cancer and diffuse brain cancers. NMH utilizes perfluorocarbon-filled nanoparticles as cavitation agents, which significantly decrease the cavitation threshold and allow for selective cavitation in regions containing nanoparticles. Current work in our laboratory is developing NMH for the selective ablation of multi-focal tumors and micro-metastases of metastatic breast and brain cancer. We are also investigating nanoparticle-guided strategies and the dual-use functionality of cavitation agents for targeted drug and gene delivery in addition to immune system modulation using NMH.

Our group is developing ultrasonic technologies for conservation and global health applications. Current conservation projects in our laboratory include the development of ultrasonic methods for enhancing DNA extraction, improving infectious disease screening, and preventing the illegal trafficking of protected plants and animals. As part of these efforts, our lab is specifically focused on the development of new technologies to improve enforcement capabilities of illicit timber and wildlife trafficking and supply chain traceability by developing tools for species-specific identification. Our group is also developing next-generation focused ultrasound systems for use in low- and middle-income countries through our TEAM Malawi program.

Biofilm formation by pathogenic bacteria are a challenge in healthcare as biofilms make bacteria more resistant to antibiotics and increase the persistence of bacteria on indwelling medical devices. In this project, we are exploring innovative approaches for biofilm ablation utilizing histotripsy. Currently, we are interested in catheter associated urinary tract infections (CAUTIs) which are among the most common hospital acquired infections and a significant cause of morbidity, mortality, and increased health care costs. Our aim is to develop histotripsy as a noninvasive ablation method to treat and prevent CAUTIs.

We also have several ongoing projects developing low-intensity focused ultrasound (LIFU) as a means to modulate, rather than destroy, target tissues. Currently, we are investigating whether LIFU be used as a therapy for depression and ischemic stroke, as well as studying how LIFU can open the blood-brain barrier and improve drug delivery to the brain for the treatment of diffuse midline glioma (DMG) and diffuse intrinsic pontine glioma (DIPG). We are also interested in the effects of LIFU on the healing profiles of injured tendons and have future interests in the treatment of other disorders using LIFU.