Deep tissue photoacoustic imaging with light and sound

Abstract

Photoacoustic computed tomography (PACT) can harvest diffusive photons to image the optical absorption contrast of molecules in a scattering medium, with ultrasonically-defined spatial resolution. PACT has been extensively used in preclinical research for imaging functional and molecular information in various animal models, with recent clinical translations. In this review, we aim to highlight the recent technical breakthroughs in PACT and the emerging preclinical and clinical applications in deep tissue imaging.

Keywords: Biomedical engineering; Optical techniques.

Fig. 1. Principle of photoacoustic imaging.

a Physical process for photoacoustic signal generation and detection. Short-pulse optical illumination excites the target, resulting in optical absorption and, subsequently, nonradiative relaxation. This is followed by thermoelastic expansion, causing an ultrasound wave to propagate away from the absorber to ultrasound detectors (adapted from ref. ). b Optical absorption spectrum of common biological molecules (adapted from ref. ). The strong absorption of hemoglobin in the visible and near-infrared bands allows for angiographic imaging by PACT. HbO₂ oxygenated hemoglobin, HbR deoxygenated hemoglobin, MbO₂ oxygenated myoglobin, MbR reduced myoglobin, DNA deoxyribonucleic acid, RNA ribonucleic acid.

Fig. 2. Common PACT excitation and detection configurations.

a PACT with a focused single-element transducer. By sweeping or scanning the single-element transducer, a synthetic 1D or 2D detection aperture can be made for 2D or 3D PACT, respectively. b PACT with a linear-array transducer, which allows for parallel detection of ultrasound along one dimension, providing real-time 2D imaging. c PACT with a full ring-array transducer. By providing surrounding ultrasound detection, limited-view artifacts are reduced. d PACT with a rotating half ring-array transducer, which can achieve a 4$\pi$-steradians detection coverage, making it a full-view detection method. e, f PACT with 2D transducer arrays such as the matrix-array (e) or the hemispherical-array (f), which can provide real-time 3D imaging by detecting along a 2D surface in parallel. g, h PACT with optics-based ultrasound detectors such as the micro-ring resonator (MRR) (g) or the Fabry-Perot interferometer (h), which can provide broad detection bandwidths, wide detection angles, and improved SNR compared with traditional piezoelectric-based transducers. Note that all detection configurations here can be translated or rotated to expand the effective detection aperture and field-of-view, at the expense of imaging time.

Fig. 3. Multimodal PACT systems.

a Multimodal PAULM system based on a hemispherical transducer array. PAULM integrates photoacoustic imaging, power doppler (PD) ultrasound, and ultrasound localization microscopy (ULM) for high-resolution structural, functional, and molecular imaging (adapted from ref. ). b Acquisition modes for ring-array-based TROPUS imaging system. c Representative images of TROPUS in a mouse abdominal region, including PACT, reflection ultrasound computed tomography (RUCT), transmission ultrasound computed tomography (TUCT), speed-of-sound (SoS) mapping, and TUCT acoustic attenuation (AA) mapping. 1: spinal cord; 2: liver; 3: vena porta; 4: vena cava; 5: aorta; 6: stomach; 7: ribs; 8: skin/fat layer; 9: spleen; 10: right kidney; 11: cecum; 12: pancreas; 13: intestines; 14: muscle (adapted from ref. ).

Fig. 4. Representative preclinical applications of PACT.

a Whole-body ventral (left) and dorsal (right) depth-encoded images of a rat using a hemispherical-array-based PACT system (adapted from ref. ). b PACT image of the brain vasculature (left) and relative increase in PA signals (right) in response to stimulation of GCaMP6f-expressing mice using a hemispherical-array-based PACT system (adapted from ref. ). c Ring-array-based PACT of a transverse section of a BphP1-expressing mouse, showing total hemoglobin concentration (left), BphP1 concentration (middle), and an overlay (right). Concentrations of BphP1 were measured in the liver, stomach, intestine, spleen, and skin of the mice (adapted from ref. ).

Fig. 5. Representative clinical applications of PACT.

a Schematic of multispectral hemispherical-array-based PACT system used for breast imaging (adapted from ref. ). b 3D PACT image of a healthy patient’s breast vasculature (left, adapted from ref. ), and of a breast tumor vasculature (right, adapted from ref. ) (color encodes depth). c Schematic of the iRAI system, which uses pulsed x-ray excitation with a matrix-array transducer for real-time 3D imaging of radiation dose delivery. d Measured radiation dose delivery using iRAI (left) compared to planned dose delivery (right). The iRAI image is overlaid with the X-ray CT image. c, d are adapted from ref. .

Fig. 6. Innovative emerging solutions for deep-tissue PACT.

a Principle of AH-VIEW, wherein focused ultrasound applied concurrently with light excitation provides a waveguide for light through the tissue. b PA images of mouse brain vasculature without AH-VIEW (top) and with AH-VIEW (bottom). The signal profile shows the increased signal strength with AH-VIEW in deep tissues. a, b are adapted from ref. . c Schematic showing the ER uses a single ultrasound transducer to encode 6400 virtual transducers in a matrix-array configuration. d Example 1D signal of human vasculature transformed to 4D data via the unique echo signals from each virtual detector in the ER. c, d are adapted from ref. .