Opening the blood-brain barrier to deliver a chemotherapy in Diffuse Intrinsic Pontine Gliomas (DIPG)
A team of researchers at Sunnybrook Health Sciences Centre and The Hospital for Sick Children (SickKids) are the first in the world to deliver chemotherapy to pediatric patients diagnosed with Diffuse Intrinsic Pontine Glioma (DIPG) using MRI-guided focused ultrasound by temporarily opening the blood-brain barrier (BBB).
DIPG tumours are the most common form of brain tumour in children under the age of 15 and make up nearly 10 to 15 per cent of all childhood brain tumours. It affects the region of the brainstem known as the pons which regulates the body’s involuntary activities such as breathing, heart rate and important functions such as swallowing. DIPG is considered a terminal cancer.
The BBB protects the brain from toxins but at the same time limits potentially beneficial medications from accessing diseased regions the brain.
This ground-breaking clinical trial is exploring the safety of delivering chemotherapy directly to the brain tumour in patients diagnosed with DIPG via the BBB using low-intensity focused ultrasound.
Interested in finding out about a referral?
Please email harquailcentre@sunnybrook.ca
Please use the email subject line: FUS DIPG
Read more about the focused ultrasound DIPG clinical trial in the news release.
Learn more about focused ultrasound at Sunnybrook.
Frequently asked questions
What is Focused Ultrasound?
Focused ultrasound is a non-invasive, image-guided surgical technology that harnesses the power of ultrasound energy. Using a specially designed helmet, ultrasound is delivered across the skull to deep brain targets without requiring scalpels or incisions. At Sunnybrook, focused ultrasound is delivered in an MRI so real time image guidance can be used.
How will this help me/my family member?
Clinical and research teams from Sunnybrook and SickKids are collaborating on this ground-breaking Phase I clinical trial which is investigating the safety and feasibility of temporarily opening the blood-brain barrier using MRI-guided low-intensity focused ultrasound in combination with the delivery of chemotherapy in pediatric patients with DIPG.
Current treatment for DIPG is radiation, which typically does not last long-term. Focused ultrasound technology is a promising and novel approach to breaching the blood-brain barrier to potentially deliver chemotherapy more effectively to DIPG. There is currently no cure for DIPG.
How is the blood-brain barrier opened?
The patient is fitted with a specialized headframe, which directs ultrasound waves to precise targets in the brain. The patient is then placed in an MRI for the focused ultrasound treatment.
An ultrasound contrast agent, or microscopic bubbles, are injected intravenously and circulate in the bloodstream. These microbubbles are smaller than red blood cells; when low-intensity focused ultrasound energy is applied the circulating microbubbles vibrate, temporarily expanding the junctions between the cells of the BBB.
The small and temporary opening in the BBB created by focused ultrasound, allows the direct delivery of the chemotherapy to the tumour.
What is the chemotherapy being used in this clinical trial?
Doxorubicin is the chemotherapy agent that will be used as investigation in the study.
What will happen in the focused ultrasound clinical trial for DIPG?
Study participants will receive general anesthesia ahead of focused ultrasound treatment at Sunnybrook, which will involve three cycles of chemotherapy about four weeks apart.
A specialized helmet is used to deliver ultrasound energy to brain targets without requiring scalpels or incision. At Sunnybrook, focused ultrasound is delivered with MRI to enhance image guidance in real time.
Patients will be treated and observed at Sunnybrook.
SickKids physicians and nurses will assist with the treatment procedure at Sunnybrook, and the children will receive post-treatment care at SickKids.
Follow-up visits will occur after one day, and weekly after each procedure up to four. After the final treatment, patients will be followed at one, three, six, and nine months. Each visit will include physical and neurological examination, bloodwork, and MR imaging.
Where will I / my loved one be treated?
Patients will receive focused ultrasound treatment at Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON.
Post-treatment care will take place at SickKids, 555 University Avenue, Toronto, ON.
What is Sunnybrook’s expertise in focused ultrasound?
Sunnybrook is a global leader in focused ultrasound research in challenging brain disorders. Sunnybrook is a Focused Ultrasound Centre of Excellence. It is the only Canadian site as designated by the Focused Ultrasound Foundation in 2016 and recognizes the pioneering work of Sunnybrook’s research and clinical teams.
In 2015, Sunnybrook researchers were the first in the world to study low-intensity focused ultrasound in the opening of the blood-brain barrier and delivery of chemotherapy brain cancer. In 2018, researchers began a Phase II clinical trial in 2018 investigating the use of focused ultrasound in glioblastoma.
Highlights of ground-breaking focused ultrasound research at Sunnybrook:
- First in North America: Sunnybrook’s clinical trials in high-intensity focused ultrasound for severe depression and obsessive-compulsive disorder.
- First in the World: Sunnybrook researchers are the first in the world to study low-intensity focused ultrasound in the opening of the blood-brain barrier or delivery of therapies directly to the brain in brain cancer, Parkinson’s disease, Alzheimer’s disease, and Amyotrophic Lateral Sclerosis (ALS).
Who is eligible for the DIPG focused ultrasound clinical trial?
Participants who are identified at SickKids will be referred to Sunnybrook for neurosurgical consult.
Patients, or their substitute decision maker (SDM), depending on patient’s age, who appear eligible via screening (case history, laboratory charts, latest MRI scan of brain tumours(s), physical and neurological status) at SickKids will be asked to participate in this study.
Eligibility to enrol in this trial includes:
- Patients with a diagnosis of Diffuse Intrinsic Pontine Gliomas aged 5-18 years old.
- Ability and willingness to give consent (or legal guardian) and attend all visits with life expectancy of 6 months.
- Various assessments including measurement of head circumference will occur to determine eligibility for participation.
- Patient must be 4 to 12 weeks from completion of radiation therapy.
- At least 14 days passed since last brain surgery (if occurred) and patient is stable and fully recovered.
- Stable or improving neurologic status and if on steroids, stable/decreasing.
Who do I contact for more information about this focused ultrasound clinical trial?
Contact us using one of the three options:
- Fill out our online form
- Email: Please use subject line: FUS DIPG - harquailcentre@sunnybrook.ca
- Phone: 416-480-6100 ext. 63773 (please leave your contact information)
For more information about this trial or focused ultrasound at Sunnybrook Health Sciences Centre: sunnybrook.ca/fus
