The Application of Transcranial Histotripsy to Murine Glioblastoma

Sarah Duclos

Glioblastoma is one of the most aggressive forms of brain cancer, with a median survival rate of only 12-18 months after diagnosis. Current standard-of-care treatment includes surgical resection followed by chemotherapy, but this is often ineffective due to the invasive nature of glioblastoma. We are taking an engineering approach to this problem by applying transcranial histotripsy treatment to a murine glioblastoma model. The brain is a challenging environment for non-invasive ultrasound treatment because there is limited room for error; too much treatment will cause unwanted swelling, too little treatment will have no effect on tumor growth, and off-target treatment could result in damage of critical brain structures. To  overcome these challenges, we are currently designing a brain-specific histotripsy array that will increase treatment precision and allow for real-time treatment monitoring with feedback control. Our central hypothesis is that transcranial histotripsy treatment will increase overall survival compared to non-treated controls in both glioblastoma and metastatic brain tumors, as well as lead to improved cancer drug delivery. Our preliminary results show that histotripsy is effective at homogenizing in-vivo murine brain tissue through an intact skull (Fig. 1). Completion of this project will be a critical step towards clinical translation of histotripsy treatment for glioblastoma.


Fig. 1: We are designing a brain-specific histotripsy transducer (left) to homogenize brain tumors in mice, like what is shown in the H&E histology image on the right (HT = histotripsy treated, RBCs = red blood cells).