Ultrasound-modulated Optical Tomography Research Articles

Camera-based ultrasound-modulated optical tomography with isometric resolution

Ultrasound-modulated optical tomography (UOT) leverages the strengths of light and sound, enabling deep-tissue imaging with optical absorption contrast and acoustic resolution. Camera-based UOT, with its parallel detection capability, excels at handling weak light–sound interactions. However, the limited frame rate of the camera typically results in poor axial resolution and poses challenges for holographic measurements. In this study, we introduced intersected ultrasonic modulation to address these limitations, thereby achieving equal resolution in both lateral and axial dimensions through referenceless measurements. As a proof of concept, we constructed an imaging system and demonstrated two-dimensional imaging for absorptive targets buried inside a scattering medium. This approach opens avenues for improved imaging resolutions, showcasing the potential for future diagnostic endeavors.

Correlations between the optical phase modulation and the optical frequency and phase shifts in ultrasound-modulated optical tomography

In ultrasound-modulated optical tomography, ultrasound causes the phase of incident light to vary periodically with ultrasound. The periodic variation in phase is known as phase modulation. The phase modulation causes the modulated light intensity to vary periodically with the ultrasound, which is called ultrasonic modulation of light. As is well known, incident light is shifted in frequency and phase by ultrasound in acousto-optic effect, and the tomography is based on the effect. However, the correlations between the phase modulation and the frequency and phase shifts in the ultrasonic modulation of light have been ignored. In this paper, the correlations are investigated theoretically and experimentally in detail. Studies reveal that the modulated light is phase-modulated by the frequency and phase shifts, and the frequency shift is the fundamental cause for the ultrasonic modulation of light. Studies show that the frequency shift, rather than the phase shift, causes the modulated light intensity to vary periodically with the ultrasound. Additionally, the modulated light intensity signal is composed of cosine signals with frequencies Ω, 2Ω, 3Ω, etc, and the amplitude of the cosine signals depends on the amplitude of the phase modulation. Then, the modulated light intensity signal contains relatively more cosine signals with high frequency as the amplitude of the phase modulation increases. At last, for the ultrasound with lower power, the amplitude ratio of cosine signals with frequencies of 2Ω and Ω increases as the scattering coefficient of turbid media increases. Studies find that both the frequency-shifted light and the amplitude ratio can be used to image turbid media.

Single-exposure ultrasound-modulated optical tomography with a quaternary phase encoded mask.

Ultrasound-modulated optical tomography (UOT) is a deep-tissue imaging modality that provides optical contrast with acoustic resolution. Among existing implementations, camera-based UOT improves modulation depth through parallel detection but suffers from a low camera frame rate. The condition prohibits this technique from being applied to in vivo applications where speckles decorrelate on a time scale of 1 ms or less. To overcome this challenge, we developed single-exposure camera-based UOT by employing a quaternary phase encoded mask (QPEM). As a proof of concept, we demonstrated imaging of an absorptive target buried inside a dynamic scattering medium with a speckle correlation time as short as 0.49 ms, typical of living biological tissues. Benefiting from the QPEM-enabled single-exposure wavefront measurement (5.5 ms) and GPU-assisted wavefront reconstruction (0.97 ms), the point scanning and result update speed can reach up to 150 Hz. We envision that the QPEM-enabled single-exposure scheme paves the way for in vivo UOT imaging, which holds promise for a variety of medical and biological applications.

Coaxial interferometry for camera-based ultrasound-modulated optical tomography with paired illumination.

Ultrasound-modulated optical tomography (UOT), which combines the advantages of both light and ultrasound, is a promising imaging modality for deep-tissue high-resolution imaging. Among existing implementations, camera-based UOT gains huge advances in modulation depth through parallel detection. However, limited by the long exposure time and the slow framerate of modern cameras, the measurement of UOT signals always requires holographic methods with additional reference beams. This requirement increases system complexity and is susceptible to environmental disturbances. To overcome this challenge, we develop coaxial interferometry for camera-based UOT in this work. Such a coaxial scheme is enabled by employing paired illumination with slightly different optical frequencies. To measure the UOT signal, the conventional phase-stepping method in holography can be directly transplanted into coaxial interferometry. Specifically, we performed both numerical investigations and experimental validations for camera-based UOT under the proposed coaxial scheme. One-dimensional imaging for an absorptive target buried inside a scattering medium was demonstrated. With coaxial interferometry, this work presents an effective way to reduce system complexity and cope with environmental disturbances for camera-based UOT.

In vivo ultrasound modulated optical tomography with a persistent spectral hole burning filter.

We present in vivo ultrasound modulated optical tomography (UOT) results on mice, using the persistent spectral hole burning (PSHB) effect in a Tm3+:YAG crystal. Indocyanine green (ICG) solution was injected as an optical absorber and was clearly identified on the PSHB-UOT images, both in the muscle (following an intramuscular injection) and in the liver (following an intravenous injection). This demonstration also validates an experimental setup with an improved level of performance combined with an increased technological maturity compared to previous demonstrations.

Contrast-enhanced ultrasound-modulated laser feedback imaging with microbubbles

A contrast-enhanced ultrasound-modulated laser feedback imaging system is proposed. Compared with traditional ultrasound modulated optical tomography (UOT), the system exhibits high sensitivity and contrast-to-noise (CNR). The usage of the laser feedback technique decreases the photon consumption in imaging. On the other hand, clinical SonoVue microbubbles are used to enhance the attenuation of light in the ultrasound labeled area inside tissues. In experiments, vessels in phantom are imaged and can be distinguished clearly at a penetration depth of 5.5 cm in reflective mode. Using microbubbles, the contrast-to-noise is increased from 0.78 to 3.73 with the lateral imaging resolution of 0.75 mm. Phantoms of different penetration depths with microbubbles in different concentrations were imaged. The experiment results show that with higher microbubbles concentration and thinner depth comes higher CNR. Although a lot remains to be improved, the proposed method is promising for further development toward practical clinical application.

A New Nonlinear Sparse Optimization Framework in Ultrasound-Modulated Optical Tomography

A New Nonlinear Sparse Optimization Framework in Ultrasound-Modulated Optical Tomography

Single-shot ultrasound-modulated optical tomography with enhanced speckle contrast.

Ultrasound-modulated optical tomography (UOT) images optical contrast deep inside biological tissue. Among existing approaches, camera-based parallel detection is beneficial in modulation depth but is limited to the relatively slow framerate of cameras. This condition prevents such a scheme from achieving maturity to image live animals with sub-millisecond speckle correlation time. In this work, we developed on-axis single-shot UOT by investigating the statistics of speckles, breaking the restriction imposed by the slow camera framerate. As a proof of concept, we experimentally imaged a one-dimensional absorptive object buried inside a moving scattering medium with speckle correlation time down to 0.48 ms. We envision that this single-shot UOT is promising to cope with live animals with fast speckle decorrelation.

Dependences of ultrasonic modulation of coherent light on optical frequency shift and phase modulation

In ultrasound-modulated optical tomography, the incident light is frequency-shifted and phase-modulated simultaneously by ultrasound. Both the optical frequency shift and phase modulation can cause ultrasonic modulation of coherent light. However, the two types of ultrasonic modulation have not been obtained separately so far. In this paper, the two types of ultrasonic modulation are obtained separately by Raman–Nath diffraction, and analyzed theoretically and experimentally. The dependences of ultrasonic modulation on the optical frequency shift and phase modulation are therefore revealed. The intensity of ultrasound-modulated light based on the optical frequency shift varies periodically with the ultrasonic frequency. Additionally, the intensity of ultrasound-modulated light based on the optical phase modulation varies periodically at twice the ultrasonic frequency. At last, the maximum modulation depths based on the optical frequency shift and phase modulation are 0.5 and 1.67, respectively.

Efficient inversion strategies for estimating optical properties with Monte Carlo radiative transport models.

.Significance: Indirect imaging problems in biomedical optics generally require repeated evaluation of forward models of radiative transport, for which Monte Carlo is accurate yet computationally costly. We develop an approach to reduce this bottleneck, which has significant implications for quantitative tomographic imaging in a variety of medical and industrial applications.Aim: Our aim is to enable computationally efficient image reconstruction in (hybrid) diffuse optical modalities using stochastic forward models.Approach: Using Monte Carlo, we compute a fully stochastic gradient of an objective function for a given imaging problem. Leveraging techniques from the machine learning community, we then adaptively control the accuracy of this gradient throughout the iterative inversion scheme to substantially reduce computational resources at each step.Results: For example problems of quantitative photoacoustic tomography and ultrasound-modulated optical tomography, we demonstrate that solutions are attainable using a total computational expense that is comparable to (or less than) that which is required for a single high-accuracy forward run of the same Monte Carlo model.Conclusions: This approach demonstrates significant computational savings when approaching the full nonlinear inverse problem of optical property estimation using stochastic methods.

Imaging through highly scattering human skulls with ultrasound-modulated optical tomography.

Advances in human brain imaging technologies are critical to understanding how the brain works and the diagnosis of brain disorders. Existing technologies have different drawbacks, and the human skull poses a great challenge for pure optical and ultrasound imaging technologies. Here we demonstrate the feasibility of using ultrasound-modulated optical tomography, a hybrid technology that combines both light and sound, to image through human skulls. Single-shot off-axis holography was used to measure the field of the ultrasonically tagged light. This Letter paves the way for imaging the brain noninvasively through the skull, with optical contrast and a higher spatial resolution than that of diffuse optical tomography.

Investigating ultrasound-light interaction in scattering media.

.Significance: Ultrasound-assisted optical imaging techniques, such as ultrasound-modulated optical tomography, allow for imaging deep inside scattering media. In these modalities, a fraction of the photons passing through the ultrasound beam is modulated. The efficiency by which the photons are converted is typically referred to as the ultrasound modulation’s “tagging efficiency.” Interestingly, this efficiency has been defined in varied and discrepant fashion throughout the scientific literature.Aim: The aim of this study is the ultrasound tagging efficiency in a manner consistent with its definition and experimentally verify the contributive (or noncontributive) relationship between the mechanisms involved in the ultrasound optical modulation process.Approach: We adopt a general description of the tagging efficiency as the fraction of photons traversing an ultrasound beam that is frequency shifted (inclusion of all frequency-shifted components). We then systematically studied the impact of ultrasound pressure and frequency on the tagging efficiency through a balanced detection measurement system that measured the power of each order of the ultrasound tagged light, as well as the power of the unmodulated light component.Results: Through our experiments, we showed that the tagging efficiency can reach 70% in a scattering phantom with a scattering anisotropy of 0.9 and a scattering coefficient of for a 1-MHz ultrasound with a relatively low (and biomedically acceptable) peak pressure of 0.47 MPa. Furthermore, we experimentally confirmed that the two ultrasound-induced light modulation mechanisms, particle displacement and refractive index change, act in opposition to each other.Conclusion: Tagging efficiency was quantified via simulation and experiments. These findings reveal avenues of investigation that may help improve ultrasound-assisted optical imaging techniques.

Inverse transport problem in fluorescence ultrasound modulated optical tomography with angularly averaged measurements

We consider an inverse transport problem in fluorescence ultrasound modulated optical tomography (fUMOT) with angularly averaged illuminations and measurements. We study the uniqueness and stability of the reconstruction of the absorption coefficient and the quantum efficiency of the fluorescent probes. Reconstruction algorithms are proposed and numerical validations are performed. This paper is an extension of Li et al (2019 SIAM J. Appl. Math. 79 356–76), where a diffusion model for this problem was considered.

Ultrasound-modulated laser feedback tomography in the reflective mode.

A novel method of ultrasound-modulated optical tomography (UOT) detection based on the laser feedback technology is proposed in this Letter. The system has advantages such as a simple structure, high sensitivity, and reflective configuration. Effective penetration depths of up to 9cm and 5cm in phantom and biological tissues, respectively, have been demonstrated experimentally. The detection capability is comparable with the state of the art in the transmission mode but with a much lower photon consumption. Although a lot remains to be improved, the proposed method is promising for further development toward practical applications.

Structured ultrasound-modulated optical tomography.

Ultrasound-modulated optical tomography (UOT) is an imaging technique that couples light and ultrasound in order to perform in-depth imaging of highly scattering media. In previous work, we introduced plane wave UOT, an imaging method analogous to x-ray tomography based on the filtered backprojection for image reconstruction. Angle-limited measurements, however, led to drastic loss of lateral spatial resolution. Here, we present a new structured ultrasonic plane wave UOT method that allows partial recovery of the resolution. For image reconstruction, we present a generalization of the Fourier slice theorem along with a generalized filtered backprojection formalism. The method is successfully tested on simulated and experimental data.

A Hybrid Inverse Problem in the Fluorescence Ultrasound Modulated Optical Tomography in the Diffusive Regime

We investigate a hybrid inverse problem in fluorescence ultrasound modulated optical tomography in the diffusive regime. We prove that the boundary measurement of the photon currents allows unique ...

Ultrasound-modulated optical tomography in scattering media: flux filtering based on persistent spectral hole burning in the optical diagnosis window.

Ultrasound-modulated optical tomography (UOT) is a powerful imaging technique to discriminate healthy from unhealthy biological tissues based on their optical signature. Among the numerous detection techniques developed for acousto-optic imaging, only those based on spectral filtering are intrinsically immune to speckle decorrelation. This Letter reports on UOT imaging based on spectral hole burning in Tm:YAG crystal under a moderate magnetic field (200G) with a well-defined orientation. The deep and long-lasting holes translate into a more efficient UOT imaging with a higher contrast and faster imaging frame rate. We demonstrate the potential of this method by imaging calibrated phantom scattering gels.

Imaging blood flow inside highly scattering media using ultrasound modulated optical tomography.

We report the use of ultrasound modulated optical tomography (UOT) with heterodyne parallel detection to locally sense and image blood flow deep inside a highly scattering medium. We demonstrate that the UOT signal is sensitive to the speed of the blood flow in the ultrasound focus and present an analytical model that relates UOT signals to the optical properties (i. e. scattering coefficient, anisotropy, absorption, and flow speed) of the blood and the background medium. We found an excellent agreement between the experimental data and the analytical model. By varying the integration time of the camera in our setup, we were able to spatially resolve blood flow in a scattering medium with a lateral resolution of 1.5 mm.

Selection of the tagged photons by off axis heterodyne holography in ultrasound-modulated optical tomography

Ultrasound-modulated optical tomography (UOT) is a technique that images optical contrast deep inside scattering media. Heterodyne holography is a promising tool that is able to detect UOT-tagged photons with high efficiency. In this work, we describe theoretically the detection of the tagged photon in heterodyne holography-based UOT, show how to filter the untagged photon, and discuss the effect of shot noise. The discussion also considers speckle decorrelation. We show that optimal detection sensitivity can be reached, if the frame exposure time of the camera used to perform the holographic detection is on the order of the decorrelation time.

Lock-in camera based heterodyne holography for ultrasound-modulated optical tomography inside dynamic scattering media.

Ultrasound-modulated optical tomography (UOT) images optical contrast deep inside scattering media. Heterodyne holography based UOT is a promising technique that uses a camera for parallel speckle detection. In previous works, the speed of data acquisition was limited by the low frame rates of conventional cameras. In addition, when the signal-to-background ratio was low, these cameras wasted most of their bits representing an informationless background, resulting in extremely low efficiencies in the use of bits. Here, using a lock-in camera, we increase the bit efficiency and reduce the data transfer load by digitizing only the signal after rejecting the background. Moreover, compared with the conventional four-frame based amplitude measurement method, our single-frame method is more immune to speckle decorrelation. Using lock-in camera based UOT with an integration time of 286 μs, we imaged an absorptive object buried inside a dynamic scattering medium exhibiting a speckle correlation time ([Formula: see text]) as short as 26 μs. Since our method can tolerate speckle decorrelation faster than that found in living biological tissue ([Formula: see text] ∼ 100-1000 μs), it is promising for in vivo deep tissue non-invasive imaging.