Clinicians at the Center for Neuromodulation continue to pioneer the advanced use of high-intensity focused ultrasound (HIFU) as a minimally invasive alternative to deep brain stimulation for patients with essential tremor. With MRI-enabled precision emerging from a collaboration with the neuroradiology team and an eye toward future clinical applications, center specialists are poised to extend HIFU’s transformative outcomes to even more patients impacted by tremor.

A New Approach to Reach Tremor’s Root Cause

Patients with essential tremor have traditionally been presented with a variety of invasive treatment options, including surgical ablation and deep brain stimulation—both of which target tremor by disrupting abnormal signaling in the thalamus.

HIFU similarly targets the thalamus, but instead uses a noninvasive focused ultrasound beam that creates a lesion, eliminating the abnormal signaling at the root of tremor and thus normalizing the region’s circuitry. Candidates for the procedure typically have tremor symptoms that interfere with their quality of life—persisting despite conservative treatment. Requiring only a few hours to complete, HIFU is a safer, noninvasive treatment option with a much lower risk of complications and minimal recovery time.

The safe use of HIFU requires close partnership between neurosurgeons, neurologists, and neuroradiologists in order to visualize brain response during the procedure. “The ability to regulate temperature as you precisely target the tremor-inducing misfiring neurons in the thalamus is vital to avoid brain injury,” notes Alon Mogilner, MD, PhD, associate professor in the Departments of Neurosurgery and Anesthesiology, Perioperative Care, and Pain Medicine and co-director of the Center for Neuromodulation. “The combination of ultrasound with MRI thermography enables real-time visualization and temperature feedback—and makes HIFU both a safe and viable option for patients.”

As the use of HIFU has expanded, the partnership with neuroradiologists has fostered new imaging modalities that achieve even more finely tuned targeting. An advanced protocol developed by Timothy M. Shepherd, MD, PhD, assistant professor in the Department of Radiology, that incorporates detailed preoperative MRI has honed the beam’s range to 0.5 mm for even more precise targeting. “Preoperative imagery is then combined with the MRIs we obtain the day of the surgery, allowing us to accurately optimize our targeting,” Dr. Shepherd says.

Breaking New Ground with HIFU

The multidisciplinary approach extends to new applications for HIFU, as Dr. Mogilner and Dr. Shepherd investigate new uses in the context of tremor associated with other conditions, while shedding light on factors that optimize the treatment’s efficacy for all patients.

In one study, Dr. Shepherd and team are investigating factors that contribute to individual variability in procedure times and patient outcomes. The researchers are applying novel imaging sequences to pre- and post-HIFU MRIs to compare patient outcomes both six weeks and six months after the procedure, with the goal of identifying imaging markers associated with clinical progress or side effects. “We want to better understand the factors that impact patients’ individual recoveries, so we can uncover ways to further refine the procedure,” says Michael H. Pourfar, MD, assistant professor in the Departments of Neurosurgery and Neurology, and the center’s other co-director.

Expanding beyond tremor, clinicians in the Center for Neuromodulation received IRB approval in 2019 to join a multicenter study investigating the use of HIFU to address stiffness and slowness associated with Parkinson’s disease. Researchers hope to use the results of this study to establish efficacy of HIFU in treating a different part of the brain. HIFU protocols for other targets in the brain and blood–brain barrier could unlock potential applications for the procedure in Alzheimer’s disease and even conditions such as glioblastomas, which are difficult to reach with standard medications. “We want to bring the precision and safety of HIFU to more patients living with diminished function that conservative measures are unable to target,” he notes.

Symptoms Abated, a Patient Returns to Everyday Function

In a recent case, a 77-year-old retired physician traveled from North Carolina for consultation and treatment for his tremor, which had progressed over the course of 5 years with diminished response to standard medications, including beta blockers and primidone. “He was experiencing increasing difficulty with regular functions such as writing, using a computer, or even holding a cup, and it was negatively impacting his everyday life by the time he reached us,” says Dr. Mogilner.

Though the patient had considered deep brain stimulation surgery, typically the next line of treatment when conservative therapeutics fail, he was reluctant to pursue the invasive treatment due to his age. “Now that there’s a safer option available, the risk–benefit analysis made sense for him, so we proceeded with an evaluation to ensure his tremor warranted HIFU,” says Dr. Pourfar.

During the procedure, Dr. Mogilner and the team assessed his progress, asking him to perform simple movements and report any weakness or tingling, as the ability to note observable outcomes is a key advantage of the procedure. With real-time MRI confirming that the target area would not evoke untoward side effects, Dr. Mogilner slowly increased the waves’ intensity to create a permanent lesion.

For this patient, progressive improvement during the three-hour procedure led to a dramatic and immediate resolution of his pre-HIFU symptoms. “Once we performed the final lesions, he sat up and his tremor was gone,” Dr. Mogilner says. “It’s remarkable to see a patient who has been suffering for years walk out the same day with his tremor gone.”

For more patients like this, and those with other brain-based conditions, the development of refined and expanded applications, supported by the center’s expertise and patient volume, has made HIFU a promising treatment option when few others are available or viable. “As we gain insights into the mechanisms that lead to HIFU’s excellent outcomes, and explore other areas of the brain where it can be used, this treatment will find new ways to restore more patients’ quality of life,” concludes Dr. Pourfar.