News | Focused Ultrasound Therapy | August 21, 2018

First FDA-Approved Study of Focused Ultrasound to Open Blood-Brain Barrier

Study will test MRI-guided focused ultrasound procedure to possibly enhance delivery of cancer-fighting drugs to brain tumors

First FDA-Approved Study of Focused Ultrasound to Open Blood-Brain Barrier

August 21, 2018 — In the first such clinical trial in the United States, physician-scientists with the University of Maryland School of Medicine (UMSOM) are investigating the use of magnetic resonance imaging (MRI)-guided focused ultrasound to open the blood-brain barrier. The trial will be conducted with patients undergoing brain cancer surgery at the University of Maryland Medical Center (UMMC).

The blood-brain barrier is a specialized network of vascular and brain cells that acts as the brain’s security system, helping to safeguard the brain and regulate the flow of substances into and out of it. While this network protects the brain, it also limits doctors’ ability to deliver effective doses of disease-fighting drugs to the brain, particularly in the case of brain tumors, which are notoriously treatment-resistant. This safety and feasibility study is a first step in attempting to overcome a major hurdle in treating these often-deadly cancers.

“The ability to temporarily disrupt the blood-brain barrier without causing tissue damage has the potential to dramatically alter the landscape of drug delivery to the brain for many diseases,” said the principal investigator, Graeme F. Woodworth, M.D., professor of neurosurgery at UMSOM and director of the Brain Tumor Treatment and Research Center at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC) at UMMC.

“If successful, this approach would allow us to use chemotherapy and other therapies in the brain in ways that are currently not possible,” said Woodworth, noting that 98 percent of currently approved drugs don’t enter the brain because of the blood-brain barrier. “If we can selectively open the blood-brain barrier, then in the future we could give a much lower dose of powerful drugs, which would likely reduce toxic side effects and make treatments safer and more effective for patients.”

The process involves injecting microscopic inert gas-filled bubbles into a patient’s bloodstream and then oscillating the microbubbles (causing them to move back and forth) with highly targeted sound waves, stretching the blood vessel walls to create temporary openings.

The U.S. Food and Drug Administration (FDA) approved the clinical trial in October 2017 after a lengthy review process. Although there are similar research studies in Canada and other countries, this was the first time the FDA approved a clinical study using this technology and approach.

Within a few months, University of Maryland researchers expect to open another FDA-approved clinical trial in which newly diagnosed glioblastoma patients will undergo blood-brain barrier opening prior to treatment with standard chemotherapy, temozolomide. This new ultrasound-augmented approach would target the areas where tumor recurrence would be most likely to occur.

Nearly 80,000 people are diagnosed with a primary brain tumor each year; 26,000 of these tumors are malignant. Glioblastoma is the most common type of brain cancer and the most deadly. Patients live an average of 15 months after diagnosis; the average five-year survival is only 5.5 percent.

“Glioblastoma is the most aggressive and lethal type of brain tumor, but treatment has been severely limited by our inability to get chemotherapy and other therapeutics through the blood-brain barrier,” said Kevin J. Cullen, M.D., the Marlene and Stewart Greenebaum Distinguished Professor in Oncology at UMSOM and director of the UMGCCC. “Dr. Woodworth’s study is an important first step in finding an effective way to administer drug therapies that would improve patients’ quality of life and increase their survival.”

In the initial study, researchers plan to enroll up to 15 patients with suspected glioblastoma, an aggressive brain cancer, who will undergo surgery at UMMC to remove their tumor.

The morning of the scheduled surgery, patients will undergo a standard MRI scan as part of the preoperative planning process. Guided by this MRI, doctors will target a precise region within the tumor with ultrasound, while the injected microbubbles are circulating within the bloodstream. The microbubbles will oscillate within the ultrasound field, causing temporary openings in the walls of the brain blood vessels, and allowing the MRI contrast agent, gadolinium, to pass into the brain tissue. The MRI scan will then be completed, documenting the extent to which the blood-brain barrier was disrupted.

The data from the MRI will be used in a system called intraoperative stereotactic neuro-navigation – an advanced 3-D guidance system that accurately localizes the tumor within the brain. After the surgery, researchers will also rigorously examine the tissue that was removed to study the potential therapeutic and other effects from the focused ultrasound procedure.

In this initial trial, the increased amount of contrast enhancement within the tumor provided by the focused ultrasound procedure may help the 3-D navigation during the surgery, according to Woodworth. “The standard of care is not changing in regard to the surgical procedure. We are functionally increasing the amount of navigation data available to the surgeon,” he said.

Woodworth notes that the disruption in the blood-brain barrier is not permanent, lasting about four to six hours.

The clinical trial is sponsored by InSightec, which has developed the MRI-guided focused ultrasound technology that will be used in the study. Neurosurgeons at UMMC are also using this technology to treat patients with neurological conditions, such as essential tremor and Parkinson’s disease, the latter as part of a clinical research study.

“MRI-guided focused ultrasound holds great promise in treating a variety of medical conditions, from cancer to Parkinson’s disease,” said UMSOM Dean E. Albert Reece, M.D., Ph.D., MBA, executive vice president for medical affairs at UM Baltimore and the John Z. and Akiko K. Bowers Distinguished Professor. “Our physician-scientists are leading major research studies and are at the forefront of efforts to determine how this new technology can be used to provide better treatments for patients.”

For more information: www.medschool.umaryland.edu

Related Content

Artificial Intelligence Used in Clinical Practice to Measure Breast Density
News | Artificial Intelligence | January 15, 2019
An artificial intelligence (AI) algorithm measures breast density at the level of an experienced mammographer,...
Machine Learning Uncovers New Insights Into Human Brain Through fMRI
News | Neuro Imaging | January 11, 2019
An interdisciplinary research team led by scientists from the National University of Singapore (NUS) has successfully...
Mobile App Data Collection Shows Promise for Population Health Surveys
News | Population Health | January 10, 2019
Mobile app data collection can bring access to more potential clinical study participants, reduce clinical study...
Hypertension With Progressive Cerebral Small Vessel Disease Increases Cognitive Impairment Risk
News | Magnetic Resonance Imaging (MRI) | January 08, 2019
Patients with high blood pressure and progression of periventricular white matter hyperintensities showed signs of...
Artificial Intelligence Pinpoints Nine Different Abnormalities in Head Scans

A brain scan (left) showing an intraparenchymal hemorrhage in left frontal region and a scan (right) of a subarachnoid hemorrhage in the left parietal region. Both conditions were accurately detected by the Qure.ai tool. Image courtesy of Nature Medicine.

News | Artificial Intelligence | January 07, 2019
The rise in the use of computed tomography (CT) scans in U.S. emergency rooms has been a well-documented trend1 in...
Electronic Brachytherapy Effective in Long-Term Study of 1,000 Early-Stage Breast Cancers
News | Brachytherapy Systems, Women's Healthcare | January 07, 2019
Breast cancer recurrence rates of patients treated with intraoperative radiation therapy (IORT) using the Xoft Axxent...
Brachytherapy Alone Superior Treatment for Intermediate-Risk Prostate Cancer
News | Brachytherapy Systems | January 04, 2019
Patient-reported outcomes (PROs) indicated a significantly different clinician and patient-reported late toxicity...
Breast Cancer Patients Have Less Heart Damage With Heart Drug and Trastuzumab
News | Cardio-oncology | January 03, 2019
Breast cancer patients who take a heart drug at the same time as trastuzumab have less heart damage, according to a...
First Arterial and Venous Atlas of the Human Brain Released
News | Neuro Imaging | January 02, 2019
January 2, 2019 — Imagine an atlas containing an image bank of the blood vessels of the...
MRI Effective for Monitoring Liver Fat in Obese Patients
News | Magnetic Resonance Imaging (MRI) | December 28, 2018
Magnetic resonance imaging (MRI) provides a safe, noninvasive way to monitor liver fat levels in people who undergo...