Ul­tra­sound could rev­o­lu­tion­ize treat­ment

The Hamilton Spectator - - HEALTH - SH­ERYL UBELACKER

TORONTO — Karen Heller­man sits pa­tiently in her hos­pi­tal gown as Dr. Nir Lips­man gen­tly shaves her head. The neu­ro­sur­geon then in­jects freez­ing into her newly shorn scalp be­fore fit­ting her head with a cir­cu­lar frame, snug­ging the hel­met­like de­vice with screws so it can’t shift dur­ing the up­com­ing pro­ce­dure.

The for­mer ele­men­tary school teacher and prin­ci­pal from Chatham, Ont., has early-on­set Alzheimer’s and she has vol­un­teered to take part in a bold new ex­per­i­men­tal pro­ce­dure at Sun­ny­brook Health Sciences Cen­tre in Toronto — one which doc­tors there hope may some day rev­o­lu­tion­ize the treat­ment of de­men­tia and other de­bil­i­tat­ing neu­ro­log­i­cal dis­or­ders.

Heller­man is then taken into the MRI suite, where for the next few hours she lies se­dated in the huge, noisy scan­ner as her brain is imaged and low-in­ten­sity ul­tra­sound waves are passed through her skull, tar­get­ing the right frontal lobe of her brain.

The goal is to poke mi­cro­scopic holes in the blood-brain bar­rier, a fine mem­brane that keeps “bad things out of the brain,” in­clud­ing disease-caus­ing mi­crobes, Lips­man ex­plains. “But it also keeps po­ten­tially good things out of the brain as well, in­clud­ing med­i­cal treat­ments for very common brain­based dis­or­ders, of which Alzheimer’s is a good ex­am­ple,” he says.

“So what we have, there­fore, po­ten­tially, are med­i­cal treat­ments that may work ... but just can­not get into the brain in suf­fi­cient con­cen­tra­tions to have a good ef­fect.”

Be­ing able to breach the bar­rier should al­low drugs to pass more eas­ily into the brain, where they could de­liver a much stronger ther­a­peu­tic punch, he says.

The Sun­ny­brook team has been test­ing MRI-guided fo­cused ul­tra­sound in a small num­ber of pa­tients with brain tu­mours and more re­cently in those with Alzheimer’s. But Lips­man stresses these stud­ies are strictly aimed at es­tab­lish­ing that the pro­ce­dure is safe for pa­tients — no treat­ment is given after the blood-brain bar­rier is opened, and it closes on its own in about six to eight hours.

Heller­man is the third Alzheimer’s patient to un­dergo the pro­ce­dure and she had no hes­i­ta­tion about be­ing a hu­man guinea pig even though she knows it may not be fully de­vel­oped soon enough to help her con­di­tion. It could be years be­fore patient tri­als prove the tech­nique is a safe and ef­fec­tive means of en­hanc­ing drug treat­ment to di­min­ish the amy­loid plaque and pro­tein tan­gles that pro­gres­sively de­stroy brain cells.

“I’m not do­ing it for me. I’m do­ing it for other peo­ple,” says the 63year-old mother of two grown chil­dren.

Doc­tors at Sun­ny­brook have used MRI-guided fo­cused ul­tra­sound to treat a con­di­tion called es­sen­tial tremor, in which a per­son’s ex­trem­i­ties, par­tic­u­larly the arms and hands, de­velop un­con­trol­lable shak­ing that can pre­vent them from per­form­ing the sim­plest of tasks, from eat­ing and drink­ing to writ­ing their name. In that case, high-in­ten­sity ul­tra­sound waves de­stroy a tiny area of the brain where the tremor orig­i­nates.

With this pro­ce­dure, the ul­tra­sound waves have an en­tirely dif­fer­ent role — they act by ex­cit­ing mi­crobub­bles that are in­jected into the blood­stream, caus­ing them to vi­brate and tease open minute gaps be­tween the cells that make up the blood-brain bar­rier.

“The way we do that is we ex­pose the brain to pulses of low-fre­quency ul­tra­sound,” says Lips­man. “So with fo­cused ul­tra­sound, com­bined with these mi­crobub­bles, what we can do is open a tem­po­rary win­dow in that blood-brain bar­rier, per­mit­ting po­ten­tially ther­a­peu­tic com­pounds ac­cess to the brain.”

Dr. Kullervo Hyny­nen, di­rec­tor of phys­i­cal sciences at the Sun­ny­brook Re­search In­sti­tute, de­vel­oped the idea of pair­ing MRI with fo­cused ul­tra­sound while at the Univer­sity of Ari­zona in the early 1990s. He has worked with in­dus­try part­ner InSightec of Is­rael for more than two decades to de­velop the tech­nol­ogy.

“The long-term goal is to de­velop a tech­nique where we can put any kind of mol­e­cules or cells in spe­cific lo­ca­tions in the brain,” Hyny­nen says after watch­ing images of Heller­man’s brain on com­puter screens out­side the MRI suite, where a team of tech­ni­cians had re­motely trig­gered bursts of ul­tra­sound waves through her skull.

Those mol­e­cules could in­clude not only med­i­ca­tions to slow down — or pos­si­bly even halt — the rav­ages of Alzheimer’s, but also chemo­ther­apy agents for brain tu­mours and stem cells to re­pair the dam­age from a stroke, for in­stance.

“I think this tech­nique will rev­o­lu­tion­ize how we are go­ing to treat brain disease and maybe even en­hance brain per­for­mance,” he says. “This is a very first step for us. But if all goes well — it’s a long road — even­tu­ally this will be able to help mil­lions of pa­tients if it’s suc­cess­ful and safe.”


Doc­tors at­tach head­gear to early on­set Alzheimer’s patient Karen Heller­man in prepa­ra­tion for MRI-guided fo­cused ul­tra­sound through her skull at Sun­ny­brook Hos­pi­tal in Toronto.

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