New method allows for fast, functional imaging.

Oncology researchers rely on high-resolution imaging to see tumors and other activity deep within body tissues. Using a new high-speed, high-resolution imaging method, Lihong Wang, PhD, and his team at Washington University in St Louis (WUSTL), were able to see blood flow, blood oxygenation, oxygen metabolism, and other functions inside a living mouse brain at faster rates than ever before.

Fig. 1 – These images show fast functional photoacoustic microscopy of the mouse brain: (d) shows a representative x-y projected brain vasculature image through the skull; (e) shows a representative enhanced x-z projected brain vasculature image; and (f) shows photoacoustic microscopy of oxygen saturation of hemoglobin using the single-wavelength pulse-width-based method with two lasers. (Credit: Lihong Wang, PhD, WUSTL)
Using photoacoustic microscopy (PAM), a single-wave - length, pulse-width-based technique developed in Wang’s lab, the team of biomedical engineers were able to take images of blood oxygenation 50 times faster than their previous results using fast-scanning PAM; 100 times faster than their acoustic-resolution system; and more than 500 times faster than phosphorescence-lifetime-based two-photon micros copy (TPM).

Other existing methods, including functional MRI (fMRI), TPM, and wide-field optical microscopy, can provide information about the mouse brain structure, oxygenation, and flow dynamics; however, they have speed and resolution limits, Wang says. So, to get around those limitations, the team implemented fast-functional PAM, which allowed them to get high-resolution, high-speed images of a living mouse brain through an intact skull.

This method, they say, achieved a lateral spatial resolution five times finer than the lab’s previous fast-scanning system, 25 times finer than its previous acoustic-resolution system, and more than 35 times finer than ultrasound-array-based photoacoustic-computed tomography. (See Figure 1)

Most importantly, PAM allowed 3D blood oxygenation imaging with capillary-level resolution at a one-dimensional imaging rate of 100 kHz, or 10 microseconds. All red blood cells imaged were intact, and there was no damage to brain tissue. Wang says that the team was able to map the mouse brain oxygenation vessel by vessel using this method.

“Without injecting any exogenous contrast agent, PAM allows us to quantify vessel by vessel all of the vital parameters about hemoglobin and to even compute the metabolic rate of oxygen. Given the importance of oxygen metabolism in basic biology and diseases such as diabetes and cancer, PAM is expected to find broad applications,” Wang says.

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