TC015154

U.Va. Researchers

SONG HU
Assistant Professor
Biomedical Engineering

The Department of Biomedical Engineering is internationally recognized for the strength of its research in ultrasound imaging. With the addition of Assistant Professor Song Hu two years ago, the department is extending its leadership to include photoacoustic microscopy (PAM). By making structural, functional, molecular and metabolic information available for ultrasound detection, this ingenious hybrid technology has the potential to become an essential tool for such tasks as cancer detection, stroke assessment and other diagnoses.

Ultrasound machines generate sound pulses, which are reflected depending on the characteristics of the tissue they encounter. This system is particularly useful for delineating boundaries between tissues.

PAM uses a short-pulsed or intensity-modulated laser pulse to cause the target tissue to emit its own ultrasound wave. The energy-absorbing substance converts some of the light energy to heat, producing a thermoelastic expansion and subsequent contraction that in turn generates an ultrasound wave. In effect, PAM combines the superior resolution and rich contrast of optical microscopy with the depth penetration of ultrasound. Call it medical imaging 2.0.

Because different wavelengths excite different absorbers, Hu can tune his lasers to highlight the presence of specific cells and molecules. This means that PAM can provide information about how well the body is functioning.

Photoacoustic microscopy (PAM) of blood oxygenation in the mouse brain through the intact skull. Arteries/arterioles and veins/venules are pseudocolored in red and green respectively. This functional information, in combination with the hemoglobin concentration and cerebral blood flow that PAM can measure simultaneously, enables quantification of cerebral oxygen metabolism at the microscopic level. This technical innovation opens a new way to study the metabolic basis of a broad spectrum of neurological disorders, including ischemic stroke and Alzheimer’s disease.
Photoacoustic microscopy (PAM) of blood oxygenation in the mouse brain through the intact skull. Arteries/arterioles and veins/venules are pseudocolored in red and green respectively. This functional information, in combination with the hemoglobin concentration and cerebral blood flow that PAM can measure simultaneously, enables quantification of cerebral oxygen metabolism at the microscopic level. This technical innovation opens a new way to study the metabolic basis of a broad spectrum of neurological disorders, including ischemic stroke and Alzheimer’s disease.

For instance, Hu is using a dual-wavelength PAM system to assess oxygen metabolism. He has tuned the PAM system for blood hemoglobin, the primary oxygen carrier in the circulation system. The resulting images reveal microvascular diameter, the hemoglobin’s oxygen saturation and blood’s flow speed. “Taking this dynamically recorded information together, you will have a set of time-lapse snapshots of the local metabolic rate, which often is an indicator of disease,” Hu says. “Tumor tissues have a high metabolic rate, while brain tissue affected by ischemic stroke has a low rate.”

Hu has received an American Heart Association Scientist Development Grant to apply this technique to test the effectiveness of a new stroke therapy on brain oxygen metabolism.

Hu is also pushing the field forward in other ways. He is experimenting with using multispectral PAM to image a number of different absorbers simultaneously. Some of his students have imaged DNA/RNA, lipids and hemoglobin at the same time. Irregular cell nuclei, aberrant lipid and oxygen metabolism and extensive blood vessel growth are all hallmarks of cancer. Other students are focusing on the hardware side of PAM, working on ways to miniaturize the PAM instrument with optical detection of ultrasound. “If we can do everything optically, we can scale down our system so that it can be transported through the human body using a catheter,” Hu says.

In a recent Science review article, Hu pointed out PAM’s translational potential, noting that upscaling photoacoustic imaging “from small animals to humans is expected to revolutionize the screening, diagnosis and treatment of metabolic diseases, particularly cancers and cerebral disorders.”

Others agree. Of all the papers to appear in the Journal of Biomedical Optics since 2009, his were the fourth and sixth most cited. He also wrote the fifth most-cited article in Optics Letters since 2007.

REPRESENTATIVE PUBLICATIONS
B.N. Zope, D.D. Hibbitts, M. Neurock and R.J. Davis, “Reactivity of the Gold-Water Interface during Selective Oxidation Catalysis,” Science 330 (2010), 74-78. Pouy MJ, Milczek EM, Figg TM, Otten BM, Prince BM, Gunnoe TB, Cundari TR, Groves JT, “Flavin-catalyzed insertion of oxygen into rhenium-methyl bonds,” J. Am Chem Soc. 2012 Aug 8;134(31):12920-3 (2012).

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