Dr. Dheeraj Gandhi has been involved in all aspects of clinical focused ultrasound work at the University of Maryland, with a specific focus on facilitating direct image-based targeting of brain structures using advanced MR techniques. He is Professor of Radiology, Neurology, and Neurosurgery Director of Interventional Neuroradiology. He is also the Clinical Director of the Center for Metabolic Imaging and Therapeutics (CMIT), the state-of-the-art facility where MR-guided focused ultrasound therapies take place. Dr. Gandhi has worked side-by-side with Dr. Howard Eisenberg, Dr. Elias Melhem, and Dr. Paul Fishman to develop the program into the Focused Ultrasound Center of Excellence that it has become. He has been involved in more than 65 focused ultrasound procedures and is now Principal Investigator for a new clinical trial that uses focused ultrasound to treat neuropathic pain. Furthermore, he is working with his imaging colleagues to develop a precision medicine-based approach to focused ultrasound treatment planning. We recently interviewed Dr. Gandhi to learn more about his new study, his career, and his work.
Focused Ultrasound Work
When and how did you get interested in focused ultrasound?
I have known about focused ultrasound technology and its potential for a long while, but my interest grew exponentially when I learned that our new Chair of the Department of Diagnostic Radiology & Nuclear Medicine, Dr. Elias Melhem, had secured funding to establish a focused ultrasound center here at the University of Maryland. My clinical and research involvement in focused ultrasound started with our first patient treated in the pivotal clinical trial for essential tremor. That day, I became convinced that this technology would be at the forefront for treating a wide range of neurological, neurosurgical, and psychiatric disorders. Since then, I’ve been involved in nearly every clinical study that has been done here.
What are your areas of interest in focused ultrasound?
With my background in interventional neuroradiology, I am focused on minimally invasive treatments of brain disorders. My interest in focused ultrasound for the brain is wide ranging, and I have been involved in performing thalamotomy for essential tremors and neuropathic pain as well as pallidotomy for Parkinson’s disease. In the near future, I will be collaborating with Dr. Graeme Woodworth as we embark on the blood-brain barrier (BBB) disruption study.
What mechanisms and clinical indications do you study?
Most of my effort so far has been related to precise targeting of brain structures for ablative procedures. I am focused specifically on advanced imaging for direct targeting of brain structures rather than relying on indirect targeting methods that have been in widespread clinical use (e.g., stereotactic or atlas-based coordinates). Along with my colleagues in MR physics, Dr. Rao Gullapalli and Dr. Jiachen Zhuo, we have begun to develop innovative targeting methods, such as synthetic MRI, FGATIR sequences overlaid with diffusion tractography to directly target the nuclei in the thalamus and GPi. We import these composite images into the Insightec brain system in order to more precisely target the structure and create the lesions.
The advantage of these new methods is that they create a treatment that is specific to each individual patient depending on their brain structure, brain volume, and the shape of their skull. It is a type of precision medicine, not a one-size-fits-all approach like traditional methods. For example, the ventral intermediate nucleus (VIM), which is the brain target for essential tremor, cannot be directly imaged with standard MRI, but we can define it and target it directly with our advanced imaging technologies. This allows us to reduce the treatment time, make the treatment more accurate, and improve its durability.
What is the goal of your work?
My goal is to expand focused ultrasound’s applications in brain disorders and fine-tune the treatment to make it more precise, efficacious, and able to reach more targets in the brain. This technique is going to be a powerful, precise, and incisionless way to treat not only essential tremor, Parkinson’s disease and neuropathic pain, but also brain tumors and many neuropsychiatric disorders. With some additional work, the technique has a potential to be adapted as a tool for low-intensity neuromodulation. I also want to spread awareness of the technology because most patients and even clinicians are not familiar with this technology and its applications.
Who are your team members?
For the neuropathic pain study, we have an excellent multi-disciplinary team from Radiology, Neurosurgery, Neurology, and the Center to Advance Chronic Pain Research. Dr. Gullapalli is our medical physicist, Dr. Eisenberg is the neurosurgeon, Dr. Melhem and Dr. Miller are the radiologists, Dr. Robert Lavin and Dr. James Russell are the consulting neurologists, and Joel Greenspan, PhD, is our chronic pain expert. Our excellent research coordinator is Charlene Aldrich, RN, MSN. She is the Senior Clinical Research Specialist and backbone of our research program. Dr. Zhuo and Dr. Gullapalli are helping us with advanced imaging algorithms.
Who are your internal and external collaborators?
Internal collaborators are mentioned above. I am also working with Dr. Henry York, Dr. Melita Thyagraja, and Dr. Peter Gorman at the University of Maryland Rehabilitation and Orthopedic Institute.
We are exploring possible collaborations with the Department of Defense and Johns Hopkins University.
What are your greatest achievements? Any major disappointments?
I believe that our greatest achievements are yet to come. However, there have been many high points. One of them is University of Maryland’s high enrollment in the Parkinson’s disease trials – both the pilot study and now the multi-center pivotal study. It has been my distinct honor to serve as the clinical director for the CMIT Center where all of these treatments have been performed. Another important milestone was treating our very first case of neuropathic pain, after jumping through all the regulatory hurdles. No major disappointments that I can think of so far.
What do you see as impediments to your success?
The greatest challenge will be to continue to secure funding and regulatory approvals for ongoing research and to continue to expand the indications. For example, we have three approved indications for the neuropathic pain study, but there are additional types of neuropathic pain that could benefit significantly from this procedure. Approximately 8% of the US population has neuropathic pain of one kind or another, and this type of pain does not respond well to pharmacotherapy. We need to produce good quality evidence for focused ultrasound procedures so that we can carve a path forward and add more indications in the future.
Could your work have an impact on the national opioid addiction crisis?
We do think that we could contribute with this new type of pain therapy that could prevent people from developing opioid addiction. Focused ultrasound procedures might have the ability go a long way toward providing a long-lasting, side effect-free, non-drug cure for chronic pain conditions. Chronic pain has staggering costs associated with its treatment and loss of productivity. We are definitely interested in proposing research that could provide solutions in this area and have already been working with collaborators to develop research models for this purpose.
What is on your research wish list?
We would like to develop tools for safe neuromodulation using focused ultrasound technology, and we are in the early discussion phase of developing studies in this area. This will allow us to investigate a number of brain targets using stimulation or inhibition with non-ablative low intensity focused ultrasound. Within the next few years, we are hoping to translate the preclinical work to human studies.
How does the Focused Ultrasound Foundation play a role in your work?
Not only is the Foundation completely funding my neuropathic pain study, but it has also been a great partner for us in many other ways. We are collaborating on some simulation projects and have plans to continue that work into new areas and new indications, such as temporal lobe epilepsy. We are proud to be a Focused Ultrasound Foundation designated Center of Excellence, and that recognition helps us raise awareness about the technology, be visible to other clinicians, and collaborate with other institutions.
How many patients have you treated?
We have now treated more than 65 patients with essential tremor and Parkinson’s dyskinesia at the University of Maryland.
Do you have a clinical research story or any highlights to share?
We have had many patients who have become strong advocates for focused ultrasound after having remarkable treatment experiences. The patients that come to mind are Kimberly Spletter and Timothy Dobbins, who have both been featured in patient stories by the University of Maryland. Additionally, the patient who was the first to enroll in the neuropathic pain study is thrilled with being able to walk long distances, lay down flat again and drive her car without pain for the first time in many years. We want to help more patients like her, and we hope to share her story soon.
What future projects do you have in mind?
We are excited on many fronts. Successfully completing the pilot study for neuropathic pain will hopefully allow us to obtain the data needed to expand indications and create a larger study.
In the near future, we hope to begin enrollment in the clinical trial for BBB disruption. Our team is ready to go and has been looking for the right candidates.
We are also making steady progress in developing MR-guided focused ultrasound-based human neuromodulation as a possible treatment modality for neuropsychiatric disorders.
Focused Ultrasound Featured at CIBR Event on Capitol Hill April 2018
University of Maryland Center of Excellence Dedicated to Brain Research September 2016
Key Focused Ultrasound Publications
Elias WJ, Lipsman N, Ondo WG, Ghanouni P, Kim YG, Lee W, Schwartz M, Hynynen K, Lozano AM, Shah BB, Huss D, Dallapiazza RF, Gwinn R, Witt J, Ro S, Eisenberg HM, Fishman PS, Gandhi D, Halpern CH, Chuang R, Butts Pauly K, Tierney TS, Hayes MT, Cosgrove GR, Yamaguchi T, Abe K, Taira T, Chang JW. A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. N Engl J Med. 2016;375(8):730-9.
Khanna N, Gandhi D, Steven A, Frenkel V, Melhem ER. Intracranial Applications of MR Imaging-Guided Focused Ultrasound. AJNR Am J Neuroradiol. 2017; 38(3):426-431.