Light in and sound out: emerging translational strategies for photoacoustic imaging

Abstract

Photoacoustic imaging (PAI) has the potential for real-time molecular imaging at high resolution and deep inside the tissue, using nonionizing radiation and not necessarily depending on exogenous imaging agents, making this technique very promising for a range of clinical applications. The fact that PAI systems can be made portable and compatible with existing imaging technologies favors clinical translation even more. The breadth of clinical applications in which photoacoustics could play a valuable role include: noninvasive imaging of the breast, sentinel lymph nodes, skin, thyroid, eye, prostate (transrectal), and ovaries (transvaginal); minimally invasive endoscopic imaging of gastrointestinal tract, bladder, and circulating tumor cells (in vivo flow cytometry); and intraoperative imaging for assessment of tumor margins and (lymph node) metastases. In this review, we describe the basics of PAI and its recent advances in biomedical research, followed by a discussion of strategies for clinical translation of the technique.

©2014 AACR.

Figures

Figure 1

Principles of photoacoustic imaging (PAI) presented for a potential clinical application: diagnostic breast imaging by integrated real-time photoacoustic/ultrasound imaging. The laser sends nano-second pulses of near-infrared light through the transducer into the tissue. This light is then absorbed inside the tissue (at different levels for each tissue type/component) causing a localized transient thermoelastic expansion. This expansion leads to the emission of pressure waves (ultrasound), which can be detected by the array in the transducer. Finally, a photoacoustic image is calculated and displayed in real-time. At the same time, the ultrasound system can be used in its b-mode to provide structural information about the tissue, in addition to the functional/molecular information obtained by PAI, and both images can be displayed on the view

Figure 2

Absorption spectra of the main light absorbing tissue components: melanin, oxy- and deoxyhemoglobin, lipid, and water. The total light absorbance in these components is lowest in the wavelength range from 600 to 1000 nm. The best tissue penetration depth can thus be reached in this “optical window”. Data obtained from http://omlc.ogi.edu/spectra.

Figure 3

Overview of potential clinical applications of photoacoustic imaging. For each organ system the main possible applications are listed. Some of these applications are male-specific (left, blue line) and some are female-specific (right, pink line). More detailed information on these clinical applications, the research progress, and challenges can be found in the text under the organ specific sections.

Figure 4

Illustration of several different types of photoacoustic imaging agents, from small to large (left to right). See Table 1 for more detailed information on these imaging agents. The displayed imaging agents are non-targeted, however, they can all be functionalized by conjugation with specific targeting moieties.

Figure 5

Triple-modality detection of brain tumors in living mice with MPR nanoparticles. After orthotopic inoculation, tumor bearing mice were injected intravenously with MPR nanoparticles. Photoacoustic, Raman and MRI images of the brain were acquired before and 2 h, 3 h and 4 h post-injection, respectively. a. 2D coronal MRI, Photoacoustic and Raman images. The post-injection images of all three modalities demonstrated clear tumor visualization. The Photoacoustic and Raman images were co-registered with the MRI image, demonstrating good co-localization between the three modalities. b. 3D rendering of MRI image with the tumor segmented in red (top), overlay of MRI and 3D Photoacoustic images (middle) and overlay of MRI, segmented tumor and Photoacoustic image (bottom) showing good co-localization of the Photoacoustic signal with the tumor. c. Quantification of signal in the tumor shows significant increase in MRI, Photoacoustic and Raman signals before versus after the injection (“***” indicates p

Figure 6

Photoacoustic imaging study of a suspicious lesion in the right breast of a 57 year old woman that was confirmed to be invasive ductal carcinoma by histopathology. Panel (a) shows the craniocaudal x-ray mammogram of this lesion; panel (b) displays the ultrasound image of the lesion; and panel (c) shows the craniocaudal photoacoustic maximum intensity projection of the same lesion; the higher intensity regions were attributed to tumor vascularization. Reprinted with permission from Manohar et al. Initial results of in vivo non-invasive cancer imaging in the human breast using near-infrared photoacoustics. Opt Express. 2007;15(19):12277-85. Copyright 2007 The Optical Society.

Figure 7

Photoacoustic images of sentinel lymph node (SLN) in a rat in vivo after indocyanine green (ICG) injection. (a) Image at 668 nm 0.2 hour after ICG injection; (b) image at 618 nm 2.2 hours after injection; (c) image at 668 nm 2.8 hours after injection; (d) graph shows comparison of spectroscopic photoacoustic (PA) signals within the SLN region over a period of time; (e) graph shows comparison of spectroscopic photoacoustic signals within blood vessels (BV) over a period of time. LV = lymphatic vessel. Numbers in colored bar at top of d and e = wavelength in nanometers. Reprinted with permission from RSNA (38).

Figure 7

Photoacoustic images of sentinel lymph node (SLN) in a rat in vivo after indocyanine green (ICG) injection. (a) Image at 668 nm 0.2 hour after ICG injection; (b) image at 618 nm 2.2 hours after injection; (c) image at 668 nm 2.8 hours after injection; (d) graph shows comparison of spectroscopic photoacoustic (PA) signals within the SLN region over a period of time; (e) graph shows comparison of spectroscopic photoacoustic signals within blood vessels (BV) over a period of time. LV = lymphatic vessel. Numbers in colored bar at top of d and e = wavelength in nanometers. Reprinted with permission from RSNA (38).

Figure 7

Photoacoustic images of sentinel lymph node (SLN) in a rat in vivo after indocyanine green (ICG) injection. (a) Image at 668 nm 0.2 hour after ICG injection; (b) image at 618 nm 2.2 hours after injection; (c) image at 668 nm 2.8 hours after injection; (d) graph shows comparison of spectroscopic photoacoustic (PA) signals within the SLN region over a period of time; (e) graph shows comparison of spectroscopic photoacoustic signals within blood vessels (BV) over a period of time. LV = lymphatic vessel. Numbers in colored bar at top of d and e = wavelength in nanometers. Reprinted with permission from RSNA (38).

Figure 7

Photoacoustic images of sentinel lymph node (SLN) in a rat in vivo after indocyanine green (ICG) injection. (a) Image at 668 nm 0.2 hour after ICG injection; (b) image at 618 nm 2.2 hours after injection; (c) image at 668 nm 2.8 hours after injection; (d) graph shows comparison of spectroscopic photoacoustic (PA) signals within the SLN region over a period of time; (e) graph shows comparison of spectroscopic photoacoustic signals within blood vessels (BV) over a period of time. LV = lymphatic vessel. Numbers in colored bar at top of d and e = wavelength in nanometers. Reprinted with permission from RSNA (38).

Figure 7

Photoacoustic images of sentinel lymph node (SLN) in a rat in vivo after indocyanine green (ICG) injection. (a) Image at 668 nm 0.2 hour after ICG injection; (b) image at 618 nm 2.2 hours after injection; (c) image at 668 nm 2.8 hours after injection; (d) graph shows comparison of spectroscopic photoacoustic (PA) signals within the SLN region over a period of time; (e) graph shows comparison of spectroscopic photoacoustic signals within blood vessels (BV) over a period of time. LV = lymphatic vessel. Numbers in colored bar at top of d and e = wavelength in nanometers. Reprinted with permission from RSNA (38).

Figure 8

Photoacoustic imaging study of ex vivo dog prostate. Photograph of the sliced prostate (a) shows an induced lesion, (b) shows the ultrasound image of this lesion in vivo, (c) and (d) show the in vivo photoacoustic images before and after the lesion induction. Prostate capsule (PC), urethra (U), needle insertion path (NIP), and lesion (L) can be distinguished. Reprinted with permission from Yaseen MA et al. Optoacoustic imaging of the prostate: development toward image-guided biopsy. J Biomed Opt. 2010;15(2):021310. Copyright 2010 J Biomed Opt.

Figure 9

In vivo noninvasive photoacoustic (PA) time-course coronal maximum amplitude projection (MAP) images of B16 melanomas using targeted [Nle4, D-Phe7]-α-melanocyte-stimulating hormone gold nanocages([Nle4, D-Phe7]-α-MSH-AuNCs) and non-targeted polyethylene glycol gold nanocages (PEG-AuNCs). (a,e) Photographs of nude mice transplanted with B16 melanomas before injection of (a) [Nle4,d-Phe7]-α-MSH- and (e) PEG-AuNCs. Time-course photoacoustic images of the B16 melanomas after intravenous injection with 100 μL of 10 nM (b−d) [Nle4,d-Phe7]-α-MSH- and (f−h) PEG-AuNCs via tail vein. The background vasculature images were obtained at 570 nm (ultrasonic frequency = 50 MHz), and the melanoma images were obtained at 778 nm (ultrasonic frequency = 10 MHz). Color schemes: red for blood vessels and yellow for the increase in PA amplitude. Reprinted with permission from Kim C et al. In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages. ACS Nano. 2010;4(8):4559-64.). Copyright 2010 American Chemical Society.

Figure 10

(a) Photographic, (b) horizontal photoacoustic, (c) vertical ultrasound, and (d) vertical photoacoustic images of an eye of a living rabbit. The area of the eye imaged in (b) is outlined by the red boundary (dotted box) in (a), and the depth is noted by the dashed red line in (c). Reprinted with permission from de la Zerda A, et al. Photoacoustic ocular imaging. Opt Lett. 2010;35(3):270-2. Copyright 2010 Optical Society.