3D microscopy could open new doors for CV disease diagnosis

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Researchers at Purdue University have developed a new type of imaging technology which could be used to take 3D images of plaque lining arteries, according to study findings scheduled to be published June 17 in Physical Review Letters. The  authors said the technology could be used to diagnose cardiovascular disease and other “lipid-related disorders,” by measuring ultrasound signals from chemical bonds in molecules exposed to a pulsing laser.

Ji-Xin Cheng, PhD, associate professor of biomedical engineering and chemistry at Purdue University in West Lafayette, Ind., and colleagues used a vibrational photoacoustic (VPA) microscopy technology to measure fat in pig tissues and fruit fly larvae, according to the study.

“You can see fat inside fly larvae, representing the potential to study how obesity affects physiology in humans,” Cheng said.

The new method creates a wider field of view and deeper penetration than previous microscopy methods, according to the report authors. The VPA microscopy permits 3D vibrational imaging of tissue, a method developed by the experimenters based on the excitation of molecular overtone vibration and acoustic detection of the resultant pressure waves in the tissue. The new method is an improvement over another technique, called the coherent anti-Stokes Raman spectroscopy, according to the authors.

“For biomedical applications, we have performed 3D VPA imaging of lipid-rich atherosclerotic plaques optically excited from the lumen side,” authors wrote. “Accurate monitoring of the lipid content in an arterial wall would provide a phenomenal improvement of vascular intervention in diagnosis and treatment of atherosclerosis.”

By providing a 3D image of plaque in the arteries, the method would make it possible to better diagnose patients with cardiovascular problems, according to Cheng. Prior to the new technology, obtaining such a picture would not be possible.

“You would have to cut a cross-section of an artery to really see the 3D structure of the plaque,” Cheng said. “Obviously, that can’t be used for living patients.”

The new technology's potential isn’t limited to diagnosing cardiovascular disease, however, Cheng noted. The technique might also be used to detect fat molecules in muscles to diagnose diabetes and other lipid-related disorders. By detecting chemical bonds, the imaging tool could be used for diagnosing multiple diseases and disorders.

“Being able to key on specific chemical bonds is expected to open a completely new direction for the field,” Cheng said.

The technique uses nanosecond laser pulses to generate wavelengths not absorbed by the blood. The laser causes tissue to heat and expand locally, generating pressure waves at the ultrasound frequency that can be measured by a transducer. By measuring the time delay between the laser and the ultrasound waves, it provides precise distance, making it possible to image layers three dimensionally, according to Cheng.

"We are working to miniaturize the system so that we can build an endoscope to put into blood vessels using a catheter," Cheng said. "This would enable us to see the exact nature of plaque formation in the walls of arteries to better quantify and diagnose cardiovascular disease.

 “With a penetration depth of millimeters and chemical information to identify the composition in biological samples with the need for labeling, our method opens up exciting opportunities for non-invasive, high resolution, intravital imaging of lipid-related disorders,” the authors continued. “Though the imaging speed is limited by the low repetition rate laser used in our work, the speed can be significantly improved using a laser at kilo-hertz repetition for excitation. With such improvements, we envision a new avenue toward intravital diagnosis of, but not limited to, lipid-related disorders.”