Detection of prostate cancer has frequently been plagued with inadequate sensitivity and specificity. Hypoxia is the hallmark of malignancy because aggressive cancers outgrow their blood supply. Optical imaging is emerging as a physiologic tool capable of quantifying hypoxia, but only at centimeter spatial resolution, which is unacceptable for prostate cancer imaging.

A schematic of the experimental configuration for Acousto-Optic Detection with gain-modulated image intensifier.
Using optical imaging in conjunction with ultrasound technology, an instrument was created called OPUS wherein the acousto-optic (AO) effect will be used to only modulate light (at the ultrasound frequency), which propagates through a small ultrasound focal point zone. Optical images generated from only ultrasound-modulated light will thus have the improved spatial resolution of the ultrasound focal zone. The main difficulty is the detection and discrimination of ultrasound-modulated light from the overwhelming presence of non-modulated light not passing through the ultrasound focal zone.

A novel detection idea has been developed based on quadrature measurements with a gain-modulated, image-intensified charge-coupled device (CCD) camera. Furthermore, the novel idea of using microbubble-based contrast agents can significantly increase the light modulation. Also, the use of fluorescent microbubbles provides additional enhancement.

The first year of this research project involved the detection of ultrasound-modulated incoherent photons, based on the principle of modulating the optical attenuation, followed by the novel quadrature detection of ultrasound-modulated photons and fluorescence photons with a gain-modulated image intensified CCD. This research demonstrated the potential to perform acousto-optic imaging with incoherent and fluorescence photons, providing novel opportunities for in vivo acousto-optic molecular imaging based on endogenous contrast and fluorescent probes.

In the second year, it was demonstrated that microbubbles dramatically enhance AO photon modulation at both the fundamental and higher-order harmonic frequencies. This signal enhancement should greatly improve detection of ultrasound-modulated photons, especially for challenging, highly scattering in vivo environments. Furthermore, the specific harmonic signature of microbubbles helps to identify and discriminate them from ultrasound-modulation of native tissue optical properties, thus leading to high specificity with targeted microbubbles. Ultrasound-modulated fluorescence from fluorophores in the vicinity (or attached) of microbubbles should also be encoded with their harmonic signature, thus differentiating them from fluorophores not in the vicinity of microbubbles.

Ultimately, acousto-optic imaging could be used to diagnose prostate cancer in vivo based on optical contrast of endogenous hypoxia and/or cancer-targeted fluorescent microbubbles at ultrasound spatial resolution.

This work was done by David Hall of the University of California for the Army Research Laboratory. For more information, download the Technical Support Package (free white paper) at ARL-0087

Medical Design Briefs Magazine

This article first appeared in the March, 2010 issue of Medical Design Briefs Magazine.

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