Focused Ultrasound Surgery Core
Nathan McDannold, Ph.D., Core PI
Cycle II 2010-2015
Previous work by our laboratory and by others has established the feasibility of using MRI to guide and monitor thermal ablation with focused ultrasound (FUS), a completely non-invasive alternative to surgical resection. Ultrasound (US) and MRI technologies developed in extensive research studies over more than a decade at our institution were successfully translated to industrial collaborators and now MRI-guided FUS (MRgFUS) is an approved clinical procedure with numerous sites performing treatments worldwide. While the development of treatment protocols and our participation in clinical trials with MRgFUS thermal ablation treatments will continue to be a major focus of our service and dissemination activities in the NCIGT, our major research role aims to increase the use of therapeutic US in the clinic through the development of novel US therapies and to enable their use for clinical targets that are currently not be well addressed. Thus, we have proposed research studies with topics that we expect will be the significant “next steps” for non-invasive US therapies: drug delivery, new modes of ablation, and US therapies in moving organs.
Several challenges have to be resolved before these “next step” US applications can reach their potential. Among them, in our view, are key issues that need to be addressed before these can be applied widely to the clinic: the development of treatment planning protocols so that one can predict and control drug delivery, determining optimal ablation mechanisms for different procedures, and developing robust tracking techniques to provide continuous control of the ultrasound beam and the image guidance for therapies in moving organs.
We have proposed the following specific aims to address these challenges.
Specific Aim 1: Measurement and modeling of drug delivery with US-induced blood-brain barrier (BBB) disruption. We will use dynamic contrast-enhanced MRI, pharmacokinetic models, histology, and measurements of tissue drug concentrations to: (1) investigate the net drug delivery achieved after US-induced BBB disruption and its subsequent clearance, and (2) evaluate whether the BBB disruption can safely be maintained over longer periods to increase the total delivery. Overall, we aim to create a drug delivery model for treatment planning and post-therapy evaluation that takes into account the dynamics of the US-induced changes in tissue permeability in tumor and normal brain blood vessels and the drug circulation time.
Specific Aim 2: Investigating the tissue response to different modes of US-induced tissue ablation. We will investigate different modes of FUS ablation other than high temperature thermal coagulation and how the body responds to them over time. We will compare ablated tissue volumes created with high-temperature thermal ablation to those created using: (1) a lethal thermal dose that does not produce a solid, coagulated core, (2) mechanical tissue disintegration, and (3) combining FUS with an ultrasound contrast agent (USCA) to destroy the vasculature in the targeted volume.
Specific Aim 3: Real-time tissue tracking to guide MRgFUS therapies using US sensors. We will develop a US-based tracking system for MRI-guided thermal ablation in moving organs that can dynamically control the MRI acquisition and the focal point position of a phased array FUS transducer. We will utilize the simultaneous, co-registered acquisition of MRI and US data to create a simplified system with a minimal number of transducer elements.
- Fischer K., McDannold N.J., Zhang Y., Kardos M., Szabo A., Szabo A., Reusz G.S., Jolesz F.A. Renal Ultrafiltration Changes Induced by Focused US. Radiology. 2009 Dec;253(3):577-8. PMID: 19703861. PMCID: PMC2786196.
- Colen R.R., Jolesz F.A. Future Potential of MRI-guided Focused Ultrasound Brain Surgery. Neuroimaging Clin N Am. 2010 Aug;20(3):355-66. PMID: 20708551.
Cycle I 2005-2010
The Focused Ultrasound Surgery (FUS) Core aims to explore the full potential of medical ultrasound as a therapeutic, diagnostic, and a monitoring agent. Special attention is given to the integration of ultrasound with other imaging and therapeutic modalities.
Current research focuses are:
- Ultrasound Therapy Delivery Through an Intact Skull
- Biological Effects of Ultrasound
- Targeted Drug Delivery to the Brain by MRI-guided Focused Ultrasound
- MR-Guided Focused Ultrasound Surgery
- Ultrasound Shear Mode Transcranial Ultrasound Imaging
- Intraoperative Monitoring
- Microbubble Interactions
- FUS Treatment Planning Methods
- Transducer Array Design