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

Nearly 40 MRIdian-focused presentations will be part of the ASTRO Scientific Sessions
News | Magnetic Resonance Imaging (MRI) | October 26, 2020
October 26, 2020 — ViewRay, Inc. announced that the company's MRIdian Linac MRI-guided radiation therapy system will
An example of a HeartFlow FFR-CT image showing the blood flow through what looked like a significant blockage on CT angiography alone, actually was not flow-limiting based on computational fluid dynamics. Use of the technology was supposed to reduce the number of diagnostic catheterizations in the FORECAST trial, but the costs of FFR-CT were not offset enough to show cost savings.

An example of a HeartFlow FFR-CT image showing the blood flow through what looked like a significant blockage on CT angiography alone, actually was not flow-limiting based on computational fluid dynamics. Use of the technology was supposed to reduce the number of diagnostic catheterizations in the FORECAST trial, but the costs of FFR-CT were not offset enough to show cost savings.

Feature | CT Angiography (CTA) | October 23, 2020
October 22, 2020 – In the FORECAST randomized clinical trial, the use of ...
This illustration show the complexity of the data obtained from one single patient with moderate/severe traumatic brain injury. Different imaging approaches and techniques have their own unique sensitivity in assessing different aspects of neuroanatomy and neuropathology. What can be seen on images also changes with time since injury. Data from comprehensive clinical and functional assessments using a range of other tools is also important for evaluating patient outcome. Through data harmonization and large

This illustration show the complexity of the data obtained from one single patient with moderate/severe traumatic brain injury. Different imaging approaches and techniques have their own unique sensitivity in assessing different aspects of neuroanatomy and neuropathology. What can be seen on images also changes with time since injury. Data from comprehensive clinical and functional assessments using a range of other tools is also important for evaluating patient outcome. Through data harmonization and large-scale analyses of data combined across multiple research sites, the ENIGMA Brain Injury will develop and test methods and procedures for making sense of the complexity in this data. Images courtesy of Olsen et al., Brain Imaging and Behavior, 2020

News | Magnetic Resonance Imaging (MRI) | October 23, 2020
October 23, 2020 — Trau...
The fMRI hyperscanning environment.

(A) The fMRI hyperscanning environment. The clinician (1) and patient (2) were positioned in two different 3T MRI scanners. An audio-video link enabled online communication between the two scanners (3), and video images were used to extract frame-by-frame facial expression metrics. During simultaneous acquisition of blood oxygen level–dependent (BOLD)–fMRI data, the clinician used a button box (4) to apply electroacupuncture (EA) treatment (real/sham, double-blind) to the patient (5) to alleviate evoked pressure pain to the leg (6; Hokanson cuff inflation). Pain and affect related to the treatment were rated after each trial. (B) Study overview. After an initial behavioral visit, each individual participated in a Clinical-Interaction (hyperscan preceded by a clinical intake) and No-Interaction condition (hyperscan without a preceding intake), in a counterbalanced order, with two different partners. (C) Experimental protocol. Each hyperscan was composed of 12 repeated trials (four verum EA, four sham EA, and four no treatment) in a pseudo-randomized order. After a resting period (far left), both participants were shown a visual cue to indicate whether the next pain stimulus would be treated (green frame) or not treated (red frame) by the clinician. These cues prompted clinicians prepare to either apply or not apply treatment while evoking corresponding anticipation for the patient. Following the anticipation cue, moderately painful pressure pain was applied to the patient’s left leg, while the clinician applied or did not apply treatment, respectively. After another resting period, participants rated pain (patients), vicarious pain (clinicians), and affect (both) using a visual analog scale (VAS).

News | Clinical Trials | October 22, 2020
October 22, 2020 — The potential impact of the patient-clinician relationship on a patient's response to treatment is
The FDA clearance, Quantib’s 6th to date, marks the first time a comprehensive AI prostate solution will be available to radiologists in the United States
News | Prostate Cancer | October 21, 2020
October 21, 2020 — Quantib, a market leader in...
Lesion was originally reported as indeterminate enhancing mass, and outside report recommended biopsy. Classic features of benign hemangioma are shown. Error was attributed to faulty reasoning. A, Axial MR image obtained 5 minutes after contrast agent administration shows peripheral nodular discontinuous enhancement. B, Axial MR image obtained 10 minutes after contrast agent administration shows centripetal progression of enhancement (arrow). C, Axial fast imaging employing steady-state acquisition (FIESTA)

Lesion was originally reported as indeterminate enhancing mass, and outside report recommended biopsy. Classic features of benign hemangioma are shown. Error was attributed to faulty reasoning. A, Axial MR image obtained 5 minutes after contrast agent administration shows peripheral nodular discontinuous enhancement. B, Axial MR image obtained 10 minutes after contrast agent administration shows centripetal progression of enhancement (arrow). C, Axial fast imaging employing steady-state acquisition (FIESTA) MR image shows lesion is homogeneously hyperintense compared with liver parenchyma. Image courtesy of American Roentgen Ray Society (ARRS), American Journal of Roentgenology (AJR)

News | Magnetic Resonance Imaging (MRI) | October 21, 2020
October 21, 2020 — According to an artic...
Flowchart of patient inclusion and exclusion.

Figure 1. Flowchart of patient inclusion and exclusion.

News | Coronavirus (COVID-19) | October 20, 2020
October 20, 2020 — A new multi-institutional study published in the journal ...
Ezra, a NY-based startup transforming early cancer screening using magnetic resonance imaging (MRI), announced that it has received FDA 510(k) premarket authorization for its Artificial Intelligence, designed to decrease the cost of MRI-based cancer screening, assisting radiologists in their analysis of prostate MRI scans. It is the first prostate AI to be cleared by the FDA.
News | Artificial Intelligence | October 20, 2020
October 20, 2020 — Ezra, a NY-based startup transforming early cancer screening using...
Lesion was originally reported as indeterminate enhancing mass, and outside report recommended biopsy. Classic features of benign hemangioma are shown. Error was attributed to faulty reasoning. A, Axial MR image obtained 5 minutes after contrast agent administration shows peripheral nodular discontinuous enhancement. B, Axial MR image obtained 10 minutes after contrast agent administration shows centripetal progression of enhancement (arrow). C, Axial fast imaging employing steady-state acquisition (FIESTA)

56-Year-Old Woman With Benign Hemangioma: Lesion was originally reported as indeterminate enhancing mass, and outside report recommended biopsy. Classic features of benign hemangioma are shown. Error was attributed to faulty reasoning. A, Axial MR image obtained 5 minutes after contrast agent administration shows peripheral nodular discontinuous enhancement. B, Axial MR image obtained 10 minutes after contrast agent administration shows centripetal progression of enhancement (arrow). C, Axial fast imaging employing steady-state acquisition (FIESTA) MR image shows lesion is homogeneously hyperintense compared with liver parenchyma.

News | Magnetic Resonance Imaging (MRI) | October 16, 2020
October 16, 2020 —