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Focusing on New Treatments with Ultrasound

Todd Mainprize
Todd Mainprize

Todd Mainprize is focusing on clinical research in neuro-oncology. He works with Kullervo Hynynen, a physicist who has developed a technique of putting ultrasound through the bone - brain barrier, using the skull as a lens to focus the modality on intracranial lesions.

There are two trials currently recruiting patients. One is for ablation, using ultrasound to abolish tumors or treat motor disorders causing tremor. This will be the second centre in the world to undertake these studies. The second trial will work on opening the blood-brain barrier accurately in short and limited areas for drug delivery: drugs for psychiatric or for chemo-therapeutic treatment. Both of these studies are now funded and waiting entry of their first patients. The blood- brain barrier puncture seals in 12 hours. There are extensive animal trials to prove the principle, most of them carried out at Sunnybrook and at Brigham and Women’s Hospital, where Kullervo practiced before he came to Toronto. Because of publicity of the potential benefits of this modality, there are many calls from patients requesting entry into treatment. The Foundation that funds these studies- The Focused Ultrasound Foundation - was started by novelist John Grisham.

The treatment is delivered from a helmet with 1024 arrays to focus the treatment. There are two such helmets purchased through grants: one for high and one for low intensity ultrasound. If the treatment proves effective, it will have applications, for example, metastases in bone and liver. There are currently high intensity ultrasound ablation programs, such as those described in Dr. Choti’s Palmer Lecture in the summer issue (http://www.surgicalspotlight.ca/Article.aspx?ver=Spring-Summer_2012&f=PalmerHepatic). The blood brain barrier penetration protocol can be used for primary tumors in the brain, such as glioblastoma, as well as for brain metastases. It will allow penetration of drugs, such as Taxol, which is effective against glioblastoma in vitro, but is unable to penetrate the blood-brain barrier in the absence of a disrupting force, such as ultrasound. Glioblastomas migrate along the white matter of the brain, 93% of them recur within 2 centimeters of the primary lesion, despite apparently complete excision. The blood-brain barrier penetration protocol may allow access of drugs for non-oncologic condition, such as Parkinson’s disease, Alzheimer’s disease and psychiatric conditions. Todd is working on the proof of principle phase, penetrating the blood –brain barrier prior to surgical therapy, adding the drug and then sampling the tumor and surrounding tissue at the time of surgery.

“Talking to patients about these preliminary trials has been easy, as patients understand the uncertainty and novelty of the treatment when it is explained to them honestly.” The instruments used in this research cost several millions of dollars. The accounting for the cost of neurosurgical treatment was described in an earlier article about Michael Tymianski and his colleagues at Toronto Western. The technique is being applied in a preliminary form at Sunnybrook.

“The limitation of this treatment is the intense heat generated by the energy form. The skull absorbs much energy despite a 17 degree water cap. Energy sufficient to cause ablation can only be focused centrally, not near to the scalp or skull. It is thus not useful for meningiomas or for metastases which generally occur along the graywhite barrier. Those somewhat rare tumors of appropriate size that occur in basal ganglia are appropriate for the protocol.

“In general, ultrasound is benign when it is used diffusely, but coordinated at 1 point, it can raise the tissue temperature to 55 degrees, causing coagulation. Penetration of the blood brain barrier requires far less energy. For example, around 1% of the energy used in the ablation studies produces bubbles in the capillaries. They expand under ultrasound activation, disrupt the intracellular junctions, and allow drugs to cross the barrier. Oscillation of the bubbles does not take a great deal of energy and the bubble does the surgery”.

Todd and Kullervo are currently working with lipo-somes, which can be ruptured by ultrasound to facilitate the spread of drugs such as Doxyrubicin in a focal area. One of the problems with the protocol is that the lesions must be of a prescribed size -2.5 centimeters or less. This is not usually possible with recurrent glioblastomas.

Todd joined the Neurosurgery residency in 1996, spent several years in Jim Rutka’s laboratory and joined the faculty at Sunnybrook in the Neurosurgery division in 2008. There are six surgeons in the Division. He is married to Susan, a pharmacist and informatics specialist. They live in Leaside with their children, Graham 7, Thomas 4 and Victoria 2.


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