From the imagery of babies blasting apart kidney stones, ultrasound has proven to be a versatile tool for doctors. Now, several research teams aim to release the technology on some of the most dreaded diseases of the brain.
The blood-brain barrier, a busy layer of cells lining the blood vessels of the brain, it protects against infections, toxins and other threats, but makes the frustrating organ difficult to treat. A strategy that combines ultrasound with microscopic blood bubbles may briefly open the gate, in theory give medication or access of the immune system in the brain. In the clinic and the laboratory, this promise is being evaluated.
This month, in one of the first clinical trials, Todd Mainprize, a neurosurgeon at the University of Toronto in Canada, hopes to use ultrasound to provide a dose of chemotherapy for a malignant brain tumor . And some elements of the most dramatic evidence of the potential of the technique, a research team reports this week Science Translational Medicine they used to rid mice of abnormal clumps in the brain similar to those of Alzheimer's disease, restoring lost memory and cognitive function. If these results can be translated from mice to humans, "it will revolutionize the way we treat brain diseases," says biophysicist Kullervo Hynynen Sunnybrook Research Institute in Toronto, originally from ultrasonic method.
Some scientists stress that rodents results can be difficult to translate to humans and caution that there are safety concerns about zapping the brain with even low-intensity ultrasound used in the new study, which is similar to that used in diagnostic tests. the opening of the dam just enough to get a beneficial effect without burning tissue, triggering an excessive immune reaction, or cause bleeding is the blood-brain "heart," said Brian Bacskai, a neurologist at Massachusetts General Hospital in Boston who studies Alzheimer's disease and used to work with Hynynen.
safely and temporarily opening the blood-brain barrier a goal long sought in medicine. There are about a decade Hynynen began exploring a strategy combining ultrasound and microbubbles. The premise is that ultrasound causes such bubbles expand and contract, pushing the cells forming the blood-brain barrier and making it slightly leaky.
EMMANUEL THÉVENOT / LAB OF ISABELLE AUBERT; COURTESY OF THE RESEARCH INSTITUTE SUNNYBROOK 
This could help cancer doctors Mainprize such as delivering chemotherapy drugs into the brain. Hynynen also speculated that the brief flight would rev the brain's inflammatory response against β-amyloid toxic protein clumps neurons outside in Alzheimer's disease and may be responsible for killing them. The removal of this debris is normally the role of microglia, a type of brain cells. But previous studies have shown that when beta amyloid forms clumps in the brain, it "seems to overwhelm microglia," said Bacskai. Exposing the anti bodies cells leaking when the blood brain barrier is breached could encourage them to "wake up and do their job," he said. Some antibodies in the blood can also bind directly to the β-amyloid protein and the flag tufts for destruction.
Hynynen and others have recently tested the ultrasound strategy in a mouse model of Alzheimer's disease. in December 2014, for example, he and his colleagues reported in Radiology that the method reduces amyloid plaques in a mouse strain modified to develop deposits, leading to improvements in cognition and spatial learning. Microglia consumed more amyloid β after treatment , suggesting that the cells play a role in the effect, said neuroscientist Isabelle Aubert, working with Hynynen at Sunnybrook.
this week, neuroscientist Jürgen Götz of the Queensland Brain Institute in St. Lucia, Australia, and his doctoral student Gerhard Leinenga report that they built on Hynynen Aubert and protocol, using a model of Alzheimer's disease different mouse. After injection of these animals with a solution of microscopic bubbles, they scanned an ultrasonic beam in a zigzag pattern over the entire skull of each animal, rather than focusing on discrete areas that others fact. After six to eight weekly treatments, the team tested the rodents on three different memory tasks. Alzheimer mice in the control group who received injections of microbubbles but no stimulation showed no improvement. The mice whose blood-brain barrier has been made permeable, however, saw "the full restoration of memory in the three tasks," says Götz.
The team also found two to five times reductions in different types of β-amyloid beta plaques in the brain tissue of the treated group's attempt to stir the appetite of microglia seemed to work;. Götz Leinenga and found much of β-amyloid proteins in cells wheelie bin eating animals treated. Yet catchy microglia may not be the only mechanism responsible for rodents boost memory, Aubert note. She and Hynynen recently reported in Brain Stimulation as ultrasound also stimulates the birth and growth of new neurons in mice.
Götz and Leinenga next plan to test the whole brain ultrasound scanning method in larger animals with deposits of amyloid-beta, such as sheep . The approach, which could in theory be used for other brain diseases involving abnormal clumps of proteins, "is exciting," says Gerald Grant, a neurosurgeon at Stanford University School of Medicine in Palo Alto, California. " we thought to open the blood-brain barrier as a way to make things happen in the brain, but is careful to do things. "
is far from settled as the elimination of deposits of beta-amyloid outside the neuron is the key to treatment or stopping Alzheimer's disease, however. Bacskai and is skeptical that the results of the mice speak volumes about the potential of the technique in humans. The range between a mouse that can learn and who can not learn "is quite small," so big gains in behavioral tests in mice may not mean humans, he said. He added that the ultrasound equipment not standardized, it is difficult to answer basic safety questions: "How long the blood-brain barrier is open What is the pore size What's the harm"
Hynynen, who works??? with a medical imaging company to commercialize the technology, notes that the application of ultrasound to the brains of animals, including rabbits and monkeys produced no negative side effects. And Mainprize clinical trial can provide more safety data. He hopes to open the blood-to increase the benefit of chemotherapy for a brain cancer patient just before he works to remove the tumor. With Hynynen technology, he and his colleagues will apply ultrasound and microbubbles in tissue in and around the tumor, and several areas of the brain are affected. Then they will examine excised tissue to bleeding and see if the treatment has boosted drug concentration. A similar trial is currently enrolling participants in France.
If these Phase I trials establish security, "it opens the door for Phase II trials looking to see if there is no advantage" to the opening of the blood-barrier brain, including conditions beyond cancer, said Mainprize. Despite his doubts, Bacskai can not fully resist the dream of driving it off area. "Imagine if your grandmother went to the clinic once a year and it cleared amyloid β and that was all it took, no surgery, no medicine. it would be amazing. "
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