Ultrasound-mediated optical tomography: a review of current methods

Abstract

Ultrasound-mediated optical tomography (UOT) is a hybrid technique that is able to combine the high penetration depth and high spatial resolution of ultrasound imaging to overcome the limits imposed by optical scattering for deep tissue optical sensing and imaging. It has been proposed as a method to detect blood concentrations, oxygenation and metabolism at depth in tissue for the detection of vascularized tumours or the presence of absorbing or scattering contrast agents. In this paper, the basic principles of the method are outlined and methods for simulating the UOT signal are described. The main detection methods are then summarized with a discussion of the advantages and disadvantages of each. The recent focus on increasing the weak UOT signal through the use of the acoustic radiation force is explained, together with a summary of our results showing sensitivity to the mechanical shear stiffness and optical absorption properties of tissue-mimicking phantoms.

Keywords: acoustic radiation force; acousto-optics; ultrasound-mediated optical tomography.

Figure 1.

Schematic showing the propagation of representative highly scattered photons through a biological tissue in the presence of a focused ultrasound beam. The resulting speckle pattern at the output face is illustrated together with the modulation in intensity of a single speckle grain. Note that the scattering is low in this illustration, resulting in a well-defined optical beam, and that no absorbers are included.

Figure 2.

(a) Results from a simulation of a UOT system showing the phase shifts φ_j for 9103 detected photons for a focal pressure of P_focal = 2 MPa and k_a of 2.1 × 10⁴. The histogram bins have a width of 2°. (b) The speckle pattern modulation depth contributed by the index of refraction alone, M_n; the modulation depth contributed by displacement alone, M_d; and the modulation depth contributed by both, M_sum; k_a is the acoustic wavevector. The Monte Carlo simulation is based on Wang [41]. (a) Mean value, 6.7°; standard deviation, 10.8°; (b) blue circles, M_sum; red squares, M_n; green triangles, M_d.

Figure 3.

Summary of the main methods used to detect UOT signals. (a) Photodetector measurement, (b) confocal Fabry–Perot interferometer detection, (c) speckle image contrast analysis, (d) lock-in image detection, (e) heterodyne holographic detection, (f) detection using a photorefractive crystal, and (g) spectral hole-burning detection. PD, photodetector; AOM, acousto-optic modulator; PR, photorefractive crystal; ν_O, optical frequency; ν_US, ultrasound frequency; ν_X, frequency shift (typically approx. 70–80 MHz), ν_CCD, charge coupled device (CCD) camera frequency.

Figure 4.

Experimental set-up. FG, frequency generator; US, ultrasound transducer. The trigger timing controlled by a Stanford DG535 is also illustrated showing: T1, triggering the CCD camera when the ultrasound is off; T2, triggering the function generators to produce the ultrasound signal; T3, triggering the CCD camera when the ultrasound is on. The UOT signal is found from the difference in contrast between the two CCD exposures.

Figure 5.

(a) Contrast difference versus CCD trigger delay time for a 250 Hz AM ultrasound burst with 0.2 ms and 2 ms CCD exposure time in a homogeneous area (blue line) and an absorbing area (red line). (b) Comparison between a one-dimensional profile of an optical absorber obtained with a 0.2 ms CCD exposure time measured 2 ms after launching a 250 Hz AM acoustic burst (red line) and one-dimensional profiles with a 2 ms CCD exposure time measured at varying delay times after launching a 250 Hz AM acoustic burst (adapted from [100]).

Figure 6.

(a) Illustration of the phantom and a photograph of the cross section taken after the experiments. The diameter of the Indian ink optical inclusion (on the left) was approximately 3.5 mm. The diameter of the stiffer inclusion (on the right inside the red, dashed circle) was approximately 8 mm. (b) B-mode ultrasound image of the phantom in the Y–Z plane showing no contrast from the optical or mechanical inclusions. (c) One-dimensional profiles of the inhomogeneous phantom measured with various CCD exposure times and CCD delay times. Again the optical inclusion was on the left and the stiffer inclusion was on the right. (adapted from [100]). Blue line, exposure 2 ms; red line, exposure 0.2 ms.

Figure 7.

(a) A two-dimensional profile of an inhomogeneous phantom measured with a 0.2 ms CCD exposure time and a 2 ms CCD trigger delay time. (b) A two-dimensional profile of an inhomogeneous phantom measured with a 2 ms CCD exposure time and a 1 ms CCD trigger delay time. (c) One-dimensional profiles taking along the midline (Z = 9 mm) from (a) and (b). (d) One-dimensional profiles taking along the midline (Y = 0 mm) from (a) and (b). Circles with continuous line, CCD exposure time: 0.2 ms; squares with continuous line, CCD exposure time: 2 ms.