Tremor

Advanced MRI Techniques for Transcranial HIFU Targeting

A new review published in the journal Brain indicated that newer, advanced magnetic resonance imaging (MRI) technology could serve as a “promising alternative” to subjective landmark-based methods for transcranial high intensity focused ultrasound (HIFU) targeting.

According to the authors of the review, “These advancements should lead to improved clinical efficacy, a reduction of adverse effects, and a new era of non-invasive neural modulation based on the principles of circuit biology.”

Consultant360 discussed the implications of this review further with lead author Bhavya R. Shah, MD. Dr Shah is an assistant professor of Radiology in the Neuroradiology Section; assistant professor of Neurosurgery; assistant professor in the Advanced Imaging Research Center in the Department of Radiology; and co-director of the Focused Ultrasound Lab at the University of Texas Southwestern (UTSW).

Consultant360: What prompted you to perform this review of advanced MRI techniques for transcranial high intensity focused ultrasound targeting?

Dr Bhavya Shah: I am currently leading the efforts at UTSW to develop our clinical Neuroscience MRI guided HIFU program. The US Food and Drug Administration (FDA)-approved indications are essential tremor and tremor in the setting of Parkinson disease. Currently, the target for both of these treatments is the ventral intermediate nucleus (VIM) of the thalamus. A major limitation of targeting the VIM is that you cannot see it on standard high-resolution MRI sequences. To target the VIM, landmark or atlas-based methods have been used. The issue with this is that every brain is slightly different, or if there is another intracranial pathology, the VIM may not be where one expects it to be. In collaboration with researchers at Mayo Clinic, led by Timothy Kaufmann, MD, MS, our team has been working to optimize a few alternate methods to directly visualize the VIM. Our group and others have shown that, by using advanced imaging techniques to target the VIM, we can reduce adverse offsite effects.

Additionally, there are ongoing clinical trials to determine if it is safe to do the procedure bilaterally. Historically, bilateral surgical thalamotomies have left some patients with speech and motor deficits. I believe using advanced MRI sequences to target the VIM may reduce those adverse effects and improve patient outcomes. In short, we now have transcranial focused ultrasound, a very powerful, non-invasive, image-guided procedure, and by combining it with advanced MRI sequences, we can expand the horizon of its utility. For example, various groups are looking at treating other symptoms in Parkinson disease, and our group is looking at treating neurodegenerative diseases like Alzheimer disease.

C360: Could you give an overview of the new, advanced MRI techniques you discussed in your review and what they add to the landscape of imaging and treatment modalities for essential tremor and Parkinson disease?

Dr Shah: The methods described are quantitative susceptibility mapping, which creates contrast in the image by detecting distortions in the magnetic field caused by substances, such as iron or blood; and fast gray matter acquisition TI inversion recovery, which works by inverting the white matter signal so that its dark and its gray matter signal so that it is white, in order to provide greater contrast for the deep brain nuclei. I think the current winner is diffusion tractography because it enables us to create a map of white matter connections between nuclei. So, instead of treating a nucleus, we can start to think of ways to disconnect a white matter tract.

C360: What is the next step in terms of future research in this area?

Dr Shah: The use of tractography to target the VIM for HIFU or deep brain stimulation has become popular with some groups. I think validating this technology in treating patients will be really important. With the launch of the bilateral procedures, I think precise targeting will help overcome many historical comorbidities and complications. For us, we will be conducting a clinical trial with the Mayo Clinic in Rochester, Minnesota, to see how these techniques improve patient outcomes. I also think this is an opportunity to create better ways to treat neurologic and psychiatric diseases.

I am the co-director of the Focused Ultrasound Lab at UTSW, and there are lots of neurologic FUS applications on the horizon in neuro-oncology, neurodegenerative diseases, and genetic neurologic diseases. I think using advanced MRI sequences to better delineate and target tissue will benefit patients.

C360: What key takeaways do you hope to leave with health care practitioners on this topic?

Dr Shah: Transcranial focused ultrasound is a noninvasive procedure that is currently FDA-approved for the treatment of essential tremor and tremor in the setting of Parkinson disease. There are no incisions, no anesthesia, and no implantable devices. Clinical trials have shown that the procedure is well-tolerated and efficacious. By using advanced MRI methods for targeting, we can create a precision medicine model for our patients, reduce adverse effects, and improve patient outcomes. I think it is the beginning of the future of noninvasive therapies for other neurologic and psychiatric diseases.

*If you have a question for Dr Shah, you may reach him at bhavya.shah@UTSouthwestern.edu.

—Christina Vogt

Reference:
Shah BR, Lehman VT, Kaufmann TJ, et al. Advanced MRI techniques for transcranial high intensity focused ultrasound targeting. Brain. Published online June 15, 2020. doi:10.1093/brain/awaa107