All-optical photoacoustic and laser-ultrasonic imaging in heterogeneous tissue

Abstract

Elastic waves are used across a broad spectrum in medicine to non-invasively probe and image tissues up to centimeters deep. Ultrasonic (US) imaging is the most well-known modality used to image acoustic density and velocity contrasts. US is useful for imaging overall structure in tissue, however, acoustic contrasts are relatively low in biological tissue. In contrast, optical properties are highly specific, but imaging with light is typically limited to depths of about 1mm. Therefore, we aim to create images of both acoustic and optical properties centimeters deep in tissue non-invasively. Laser-induced acoustic waves are generated by the absorption of nanosecond pulses of laser light by biological tissue. The transient thermoelastic expansion that results propagates as a pressure wave. The wavelength of the source laser can be tuned such that absorption occurs either primarily at the tissue surface, generating a laser-ultrasound (LUS) wave, or deep inside to create photoacoustic (PA) waves due to absorption by embedded tissue chromophores. LUS waves can be thought of as mini-explosions at the tissue surface, much like the man-made explosions used by seismologists to image the subsurface of the earth. Likewise, PA waves are analogous to mini-earthquakes, originating from below the surface and propagating to the boundary where they are detected. We obtain optical absorption properties by inverting for the location of PA sources, and structural images by reconstructing the location of LUS scattering/reflection. The reconstruction methods utilized for PA and LUS are accordingly inspired by seismology. Reverse-time migration is adapted for reflection-mode LUS imaging to improve the imaging aperture and reduce artifacts. The velocity model is optimized in the LUS reconstruction, and subsequently applied to reconstruct PA images with time-reversal. Laser-generated PA and LUS waves are broadband, allowing for high-resolution images to be reconstructed. Detection using contacting piezoelectric transducers allows real-time imaging with high sensitivity, however, the frequency bandwidth is relatively narrow. Optical detectors provide an alternative to piezoelectric transducers when a small sensor footprint, large frequency bandwidth, or non-contacting detection is required. We introduce a fully non-contact gas-coupled laser acoustic detector (GCLAD) for medical imaging that utilizes optical beam deflection. We describe the underlying principles of GCLAD and derive a formula for quantifying the surface displacement from a remote, line-integrated GCLAD measurement. We quantify the surface displacement with GCLAD in a LUS experiment, which shows 94% agreement to line-integrated data from a commercial laser-Doppler vibrometer point detector. We further demonstrate the feasibility of PA imaging of an artery-sized absorber using GCLAD 5:8 cm from a phantom surface. Additionally, we advance all-optical imaging techniques using a laser-Doppler vibrometer point-detector. While previous reflection-mode all-optical systems use a confocal source and detection beam, we introduce nonconfocal acquisition to obtain angle-dependent data. We demonstrate that nonconfocal acquisition with a single source improves the signal-to-noise of low-amplitude PA and LUS signals using a normal-moveout processing technique. Incorporating multiple sources in this geometry allows us to apply reverse-time migration to reconstruct LUS images. We demonstrate this methodology with both a numerical model and tissue phantom experiment to image a steep-curvature vessel with a limited aperture 2 cm beneath the surface. Nonconfocal imaging demonstrates improved focusing by 30% and 15% compared to images acquired with a single LUS source in the numerical and experimental LUS images. PA images are straightforward to acquire with the all-optical system by tuning the source wavelength or the surface properties, which we reconstruct with time reversal. Therefore, we demonstrate broadband high-resolution PA and LUS imaging with this all-optical system. Subsequently, we demonstrate PA and LUS imaging of atherosclerotic plaque ex vivo. We apply our nonconfocal PA and LUS acquisition and reconstruction techniques to a fixed human carotid artery embedded in an agar tissue phantom. The LUS image provides structural information about acoustic contrasts, in which we distinguish between the layers of the artery wall and detect calcification. PA imaging is sensitive to optical absorbers, such as lipids and hemoglobin. In this ex vivo example, we image a synthetic absorber analogous to hemoglobin in the artery. We compare our nonconfocal LUS approach to confocal LUS imaging, and see a significant improvement in contrast and resolution, and reduce the appearance of artifacts. Further, we observe that LUS aids in the interpretation of PA images, specifically to identify reflection artifacts. We validate our results with both x-ray computed tomography and histology. Finally, we introduce a method for removing reflection artifacts in PA imaging altogether. We adapt a method known as Marchenko imaging developed for two-way imaging problems in seismology to the PA source inversion problem. Iterative convolutions of PA data with nonconfocal LUS predicts reflection artifacts, which we subtract from the PA image. We eliminate dominant artifacts in numerical data using a single iteration of the Marchenko scheme. Overall, we present novel methods for all-optical PA and LUS imaging including instrumentation, acquisition, image processing, and reconstruction. We present a new non-contact optical detector for medical imaging. We demonstrate unconventional experimental methods, combined with powerful imaging methods inspired by seismology to improve the resolution and contrast of LUS images and reduce artifacts in PA and LUS imaging. Furthermore, we demonstrate the potential for all-optical PA and LUS imaging to address the clinical need for non-invasive, multi-component imaging of vulnerable atherosclerotic plaque.