Toward imaging the brain’s tiniest arteries

At a few hundred microns in diameter, the arteries that lie just upstream of the brain’s capillaries are hard to resolve using computed tomography or magnetic resonance imaging. In principle, ultrasound in combination with tiny injected bubbles as contrast agents could yield the required resolution (see the article by Carr Everbach in Physics Today, March 2007, page 44 ). Unfortunately, the best imaging frequencies are significantly attenuated and dispersed by the skull. Meaghan O’Reilly and Kullervo Hynynen of Sunnybrook Research Institute in Toronto have recently tested a way to overcome that limitation. To generate ultrasound, they use an array of elements that emit periodic sonar-like bursts. In the test, the emitters were placed on the surface of a section of human skull submerged in water. Inside the phantom skull lay a phantom artery: a length of spiral tubing 255 µm in diameter through which water containing micron-sized bubbles circulated to mimic blood suffused with contrast agents. When pulsed with ultrasound, the bubbles resonated harmonically. An array of sensors placed on the skull and tuned to twice the emission frequency detected the reemitted pulses. Blurring ordinarily induced by the skull was mitigated in two ways. First, the emitters’ frequency, at 306 kHz, was low enough to avoid the worst effects. Second, by treating each sensor as an interferometer and by analyzing the outputs from all the sensors together, the researchers could measure and compensate for the blurring of the reemitted pulses. As the figure shows, individual bubbles were clearly resolved. Potentially, the technique could help diagnose brain cancer, Alzheimer’s, and other diseases in which small-vessel pathology plays a role. (M. A. O’Reilly, K. Hynynen, Med. Phys. 40, 110701, 2013, doi:10.1118/1.4823762 .)