Hybrid imaging modalities are becoming more popular since they utilize the benefit of both optical and ultrasound (US) imaging modalities. They use the contrast based on optical properties and negligible scattering of US waves to extend the depth of imaging. Ultrasound modulated optical tomography (UOT) and acoustic radiation force (ARF) with speckle pattern analysis, both use the idea of utilizing a focused US wave to spatially encode in information in the diffused light. We have previously shown that compared to UOT, ARF regime can result in a stronger signal and the mean irradiance change (MIC) signal can reflect the mechanical and thermal properties of the tissue non-invasively. In addition to the mechanical and thermal properties of the medium, the MIC signal is able to reveal information about the morphology of the medium. A tumor is formed by a group of cancer cells that are result of rounds of successive mutation. Cancer cell grow without control in abnormal shapes. In this study, we have modeled cells with their nuclei, assuming that the scattering events occur at the location of the nuclei of the cells. We have shown that, although the MIC signal is not sensitive to the size of the particle, it can detect the presence of the tumor base on the higher concentration of cells in a tumor.
In optical imaging, the depth and resolution are limited due to scattering. Unlike light, scattering of ultrasound (US) waves in tissue is negligible. Hybrid imaging methods such as US-modulated optical tomography (UOT) use the advantages of both modalities. UOT tags light by inducing phase change caused by modulating the local index of refraction of the medium. The challenge in UOT is detecting the small signal. The displacement induced by the acoustic radiation force (ARF) is another US effect that can be utilized to tag the light. It induces greater phase change, resulting in a stronger signal. Moreover, the absorbed acoustic energy generates heat, resulting in change in the index of refraction and a strong phase change. The speckle pattern is governed by the phase of the interfering scattered waves; hence, speckle pattern analysis can obtain information about displacement and temperature changes. We have presented a model to simulate the insonation processes. Simulation results based on fixed-particle Monte Carlo and experimental results show that the signal acquired by utilizing ARF is stronger compared to UOT. The introduced mean irradiance change (MIC) signal reveals both thermal and mechanical effects of the focused US beam in different timescales. Simulation results suggest that variation in the MIC signal can be used to generate a displacement image of the medium.
Optical imaging modalities are proved to be able to provide images with resolution required to image subcellular particles, however, imaging depth of optical imaging modalities are limited due to strong absorption and scattering. In contrast, ultrasound imaging modalities can provide images deeper in the tissue due to negligible scattering in tissue, but they suffer from poor resolution and contrast. Hybrid imaging modalities such as ultrasound modulated optical tomography (UOT) utilize advantages of both optical and ultrasound imaging modalities. UOT utilizes pressure waves to modulate light with ultrasound frequency that results in a week signal that requires expensive detection equipment. In Contrast, we propose to use acoustic radiation force (ARF) to tag the light that travels through the ultrasound focal spot and generate a stronger signal. Monitoring the changes in the speckle pattern reflects both mechanical and thermal properties of the medium. In this paper we have utilized our model with fixed-particle Monte Carlo to simulate the mean irradiance change (MIC) signal variations due to particle displacement and temperature rise. Results suggest that neglecting the temperature rise for short ultrasound exposure times, the change in the MIC signal reflects the local stiffness of the medium at the ultrasound focal spot and can be utilized to generate the stiffness image of the medium.
Optical imaging in a turbid medium is limited because of multiple scattering a photon undergoes while traveling through the medium. Therefore, optical imaging is unable to provide high resolution information deep in the medium. In the case of soft tissue, acoustic waves unlike light, can travel through the medium with negligible scattering. However, acoustic waves cannot provide medically relevant contrast as good as light. Hybrid solutions have been applied to use the benefits of both imaging methods. A focused acoustic wave generates a force inside an acoustically absorbing medium known as acoustic radiation force (ARF). ARF induces particle displacement within the medium. The amount of displacement is a function of mechanical properties of the medium and the applied force. To monitor the displacement induced by the ARF, speckle pattern analysis can be used. The speckle pattern is the result of interfering optical waves with different phases. As light travels through the medium, it undergoes several scattering events. Hence, it generates different scattering paths which depends on the location of the particles. Light waves that travel along these paths have different phases (different optical path lengths). ARF induces displacement to scatterers within the acoustic focal volume, and changes the optical path length. In addition, temperature rise due to conversion of absorbed acoustic energy to heat, changes the index of refraction and therefore, changes the optical path length of the scattering paths. The result is a change in the speckle pattern. Results suggest that the average change in the speckle pattern measures the displacement of particles and temperature rise within the acoustic wave focal area, hence can provide mechanical and thermal properties of the medium.
We have introduced a novel illumination system for line scanning confocal microscopy. Confocal microscopy is a popular imaging tool in many applications specifically in medical imaging. Line scanning confocal microscopes have been proven to provide images with resolution comparable to point scanning microscopes. In the point scanning microscopes, the light is focused onto a diffraction limited spot. A pinhole is placed conjugate to the diffraction limited spot, in front of the detector to reject the light coming from out-of-focus planes. Therefore, confocal microscopy can provide optical sectioning. The size of the pinhole determines the amount of light that reaches the detector. A large pinhole results in a blurry image since more of the out-of-focus light contribute to the image. On the other hand, a smaller pinhole rejects more of the light, leading to a lower signal-to-noise ratio. Ideally it is desired to deliver a larger amount of optical power to the diffraction limited spot to increase the signal-to-noise ratio and have a smaller pinhole to reject more of the out-of-focus light. This is the property of the illumination system. In order to get a good signal-to noise ratio in the image, the light source has to provide sufficient radiance. We have introduced a new illumination system utilizing a high brightness LED in the line scanning confocal microscope. High brightness LEDs provide more optical power compared to ordinary LEDs from a smaller area; they have higher radiance. Preliminary results from our line scanning confocal microscope show that the high brightness LED is able to provide enough radiance to obtain an image with resolution comparable with the same microscope utilizing the laser diode. However, in high frame-rate application higher radiance or lower-noise detection system is required.
Confocal microscopy can be used as a practical tool in non-invasive applications in medical diagnostics and
evaluation. In particular, it is being used for the early detection of skin cancer to identify pathological cellular
components and, potentially, replace conventional biopsies. The detection of melanin and its spatial location and
distribution plays a crucial role in the detection and evaluation of skin cancer. Our previous work has shown that the
visible emission from melanin is strong and can be easily observed with a near-infrared CW laser using low power. This
is due to a unique step-wise, (SW) three-photon excitation of melanin. This paper shows that the same SW, 3-photon
fluorescence can also be achieved with an inexpensive, continuous-wave laser using a dual-prism scanning system. This
demonstrates that the technology could be integrated into a portable confocal microscope for clinical applications. The
results presented here are in agreement with images obtained with the larger and more expensive femtosecond laser
system used earlier.