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We present a detailed characterization of noise sources in multiple reference optical coherence tomography (MR-OCT) compared to time-domain OCT (TD-OCT). The noise characteristics were modeled based on the TD-OCT noise model and modified for MR-OCT and confirmed with measurements. The MR-OCT sensitivity characteristics are significantly affected by the reflection from the partial mirror, which also introduces a natural attenuation in the reference arm, partially matching the reflectivity intensity profile of human tissue. At optimal balance between sample and reference arm and using balanced detection, the peak sensitivity was measured to be 95 dB, which is close to simple Fourier-domain systems. The results provide a better understanding of the application range for MR-OCT and higher order effects observed, suggesting a nontrivial noise model for MR-OCT. All authors have a financial interest in Compact Imaging, Inc. peer-reviewed

Dual-channel spectral domain optical coherence tomography (SD-OCT) is one of the effective methods for improving imaging depth and imaging speed. In this paper, we design a dual-channel SD-OCT system based on a single spectrometer that can operate in two modes: (1) Increasing imaging speed and (2) expanding imaging depth. An optical path offset is preintroduced between the two channels to separate the two-channel data. However, this offset increases the requirement for the spectral resolution of the spectrometer in mode (1), so compressive sensing (CS) technology is used herein to overcome this problem. Consequently, in mode (1), when the spectral resolution of the spectrometer is the same as that used in the single-channel system, we use a dual-channel SD-OCT system combined with CS technology to double the imaging speed. In mode (2), when the spectral resolution of the spectrometer is only half of that used in a single-channel system, the imaging depth can be nearly doubled. We demonstrate the feasibility and effectiveness of the method proposed in this work by imaging a mirror, a fish fin, a fish eye, and an onion.

Photoacoustic imaging (PAI) provides high-resolution and high-optical-contrast imaging beyond optical diffusion limit. Further improvement in imaging depth has been achieved by using near-infrared window-I (NIR-I, 700 to 900 nm) for illumination, due to lower scattering and absorption by tissues in this wavelength range. Recently, near-infrared window-II (NIR-II, 900 to 1700 nm) has been explored for PAI. We studied the imaging depths in biological tissues for different illumination wavelengths in visible, NIR-I, and NIR-II regions using Monte Carlo (MC) simulations and validated with experimental results. MC simulations were done to compute fluence in tissue, absorbance in blood vessel, and in a spherical absorber (mimicking sentinel lymph node) embedded at different depths in breast tissue. Photoacoustic tomography and acoustic resolution photoacoustic microscopy experiments were conducted to validate the MC results. We demonstrate that maximum imaging depth is achieved by wavelengths in NIR-I window (∼800 nm) when the energy density deposited is same for all wavelengths. However, illumination using wavelengths around 1064 nm (NIR-II window) gives the maximum imaging depth when the energy density deposited is proportional to maximum permissible exposure (MPE) at corresponding wavelength. These results show that it is the higher MPE of NIR-II window that helps in increasing the PAI depth for chromophores embedded in breast tissue. NMRC (Natl Medical Research Council, S’pore) Published version

We designed and fabricated a telecentric f-theta imaging lens (TFL) to improve the imaging performance of spectral domain optical coherence tomography (SD-OCT). By tailoring the field curvature aberration of the TFL, the flattened focal surface was well matched to the detector plane. Simulation results showed that the spot in the focal plane fitted well within a single pixel and the modulation transfer function at high spatial frequencies showed higher values compared with those of an achromatic doublet imaging lens, which are commonly used in SD-OCT spectrometers. The spectrometer using the TFL had an axial resolution of 7.8 μm, which was similar to the theoretical value of 6.2 μm. The spectrometer was constructed so that the achromatic doublet lens was replaced by the TFL. As a result, the SD-OCT imaging depth was improved by 13% (1.85 mm) on a 10 dB basis in the roll-off curve and showed better sensitivity at the same depth. The SD-OCT images of a multi-layered tape and a human palm proved that the TFL was able to achieve deeper imaging depth and better contrast. This feature was seen very clearly in the depth profile of the image. SD-OCT imaging performance can be improved simply by changing the spectrometer’s imaging lens. By optimizing the imaging lens, deeper SD-OCT imaging can be achieved with improved sensitivity.

The effect of optical cleaning method combined with laser speckle imaging (LSI) was discussed to improve the detection depth of LSI due to high scattering characteristics of skin, which limit its clinical application. A double-layer skin tissue model embedded with a single blood vessel was established, and the Monte Carlo method was used to simulate photon propagation under the action of light-permeating agent. 808[Formula: see text]nm semiconductor and 632.8[Formula: see text]nm He–Ne lasers were selected to study the effect of optical clearing agents (OCAs) on photon deposition in tissues. Results show that the photon energy deposition density in the epidermis increases with the amount of tissue fluid replaced by OCA. Compared with glucose solution, polyethylene glycol 400 (PEG 400) and glycerol can considerably increase the average penetration depth of photons in the skin tissue, thereby raising the sampling depth of the LSI. After the action of glycerol, PEG 400, and glucose, the average photon penetration depth is increased by 51.78%, 51.06%, and 21.51% for 808nm, 68.93%, 67.94%, and 26.67% for 632.8 nm lasers, respectively. In vivo experiment by dorsal skin chamber proves that glycerol can cause a substantial decrease in blood flow rate, whereas PEG 400 can significantly improve the capability of light penetration without affecting blood velocity, which exhibits considerable potential in the monitoring of blood flow in skin tissues.

We established a photoacoustic imaging (PAI) system that can provide variable gain at different depths. The PAI system consists of a pulsed laser with an optical parametric oscillator working at a 728[Formula: see text]nm wavelength and an imaging-acquisition-and-processing unit with an ultrasound transducer. A voltage-controlled attenuator was used to realize variable gain at different depths when acquiring PAI signals. The proof-of-concept imaging results for variable gain at different depths were achieved using specific phantoms. Both resolution and optical contrast obtained through the results of variable gain for a targeted depth range are better than those of constant gain for all depths. To further testify the function, we imaged the sagittal section of the body of in vivo nude mice. In addition, we imaged an absorption sample embedded in a chicken breast tissue, reaching a maximum imaging depth of [Formula: see text]4.6[Formula: see text]cm. The results obtained using the proposed method showed better resolution and contrast than when using 50[Formula: see text]dB gain for all depths. The depth range resolution was [Formula: see text]1[Formula: see text]mm, and the maximum imaging depth of our system reached [Formula: see text]4.6[Formula: see text]cm. Furthermore, blood vessels can be revealed and targeted depth range can be selected in nude mice imaging.

Epi-style optoacoustic (OA) imaging provides flexibility by integrating the irradiation optics and ultrasound receiver, yet clutter generated by optical absorption near the probe obscures deep OA sources. Localised vibration tagging (LOVIT) retrieves OA signal from images that are acquired with and without a preceding ultrasonic pushing beam: Radiation force leads to a phase shift of signals coming from the focal area resulting in their visibility in a difference image, whereas clutter from outside the pushing beam is eliminated. Disadvantages of a single-focus approach are residual clutter from inside the pushing beam above the focus, and time-intensive scanning of the focus to retrieve a large field-of-view. To speed up acquisition, we propose to create multiple foci in parallel, forming comb-shaped ARF patterns. By subtracting OA images obtained with interleaved combs, this technique moreover results in greatly improved clutter reduction in phantoms mimicking optical, acoustic and elastic properties of breast tissue. Keywords: Photoacoustic, Imaging depth, Handheld, Ultrasound, Radiation force, Shear wave, Image contrast

Reflection artifacts caused by acoustic inhomogeneities are a main challenge to deep-tissue photoacoustic imaging. Photoacoustic transients generated by the skin surface and superficial vasculature will propagate into the tissue and reflect back from echogenic structures to generate reflection artifacts. These artifacts can cause problems in image interpretation and limit imaging depth. In its basic version, PAFUSion mimics the inward travelling wave-field from blood vessel-like PA sources by applying focused ultrasound pulses, and thus provides a way to identify reflection artifacts. In this work, we demonstrate reflection artifact correction in addition to identification, towards obtaining an artifact-free photoacoustic image. In view of clinical applications, we implemented an improved version of PAFUSion in which photoacoustic data is backpropagated to imitate the inward travelling wave-field and thus the reflection artifacts of a more arbitrary distribution of PA sources that also includes the skin melanin layer. The backpropagation is performed in a synthetic way based on the pulse-echo acquisitions after transmission on each single element of the transducer array. We present a phantom experiment and initial in vivo measurements on human volunteers where we demonstrate significant reflection artifact reduction using our technique. The results provide a direct confirmation that reflection artifacts are prominent in clinical epi-photoacoustic imaging, and that PAFUSion can reduce these artifacts significantly to improve the deep-tissue photoacoustic imaging.

Flexible imaging of the human body, a requirement for broad clinical application, is obtained by direct integration of optoacoustic (OA) imaging with echo ultrasound (US) in a multimodal epi-illumination system. Up to date, successful deep epi-OA imaging is difficult to achieve owing to clutter. Clutter signals arise from optical absorption in the region of tissue irradiation and strongly reduce contrast and imaging depth. Recently, we developed a displacement-compensated averaging (DCA) technique for clutter reduction based on the clutter decorrelation that occurs when palpating the tissue. To gain first clinical experience on the practical value of DCA, we implemented this technique in a combined clinical OA and US imaging system. Our experience with freehand scanning of human volunteers reveals that real-time feedback on the clutter-reduction outcome is a key factor for achieving superior contrast and imaging depth.

This paper investigates a novel method which allows clutter elimination in deep optoacoustic imaging. Clutter significantly limits imaging depth in clinical optoacoustic imaging, when irradiation optics and ultrasound detector are integrated in a handheld probe for flexible imaging of the human body. Strong optoacoustic transients generated at the irradiation site obscure weak signals from deep inside the tissue, either directly by propagating towards the probe, or via acoustic scattering. In this study we demonstrate that signals of interest can be distinguished from clutter by tagging them at the place of origin with localised tissue vibration induced by the acoustic radiation force in a focused ultrasonic beam. We show phantom results where this technique allowed almost full clutter elimination and thus strongly improved contrast for deep imaging. Localised vibration tagging by means of acoustic radiation force is especially promising for integration into ultrasound systems that already have implemented radiation force elastography.