Deep-tissue focal fluorescence imaging with digitally time-reversed ultrasound-encoded light.

Fluorescence imaging is one of the most important research tools in biomedical sciences. However, scattering of light severely impedes imaging of thick biological samples beyond the ballistic regime. Here we directly show focusing and high-resolution fluorescence imaging deep inside biological tissues by digitally time-reversing ultrasound-tagged light with high optical gain (~5×10(5)). We confirm the presence of a time-reversed optical focus along with a diffuse background-a corollary of partial phase conjugation-and develop an approach for dynamic background cancellation. To illustrate the potential of our method, we image complex fluorescent objects and tumour microtissues at an unprecedented depth of 2.5 mm in biological tissues at a lateral resolution of 36 μm×52 μm and an axial resolution of 657 μm. Our results set the stage for a range of deep-tissue imaging applications in biomedical research and medical diagnostics

A model for ultrasound modulated light in a turbid medium

The ability to focus light in most tissue degrades quickly with depth due to high optical scattering. Researchers have investigated using both ultrasound (US) and light synergistically to overcome this difficulty. Ultrasound has been utilized to modulated light within tissue to create a diffusive wave at that is modulated at the US frequency. Recently, there has been interest in the modulated sidebands which reside at optical frequency plus or minus the US frequency. This paper will discuss a model for US-light interactions in a scattering medium. We will use this model to relate the radiance in the probe beam to the radiance in the diffusive wave. We will then employ the P-1 approximation to the radiative transport equation to find the fluence and flux of the modulated wave. We will use these parameters to write a diffusion equation for the modulated wave that can be described in terms of the incoming optical power, and the US intensity and geometry

Analysis and modeling of an ultrasound-modulated guide star to increase the depth of focusing in a turbid medium

The effects of strong scattering in tissue limit the depth to which light may be focused. However, it has been shown that scattering may be reduced utilizing adaptive optics with a focused ultrasound (US) beam guidestar. The optical signal traveling through the US beam waist is frequency shifted and may be isolated with demodulation. This paper utilizes a multiphysics simulation to model the optical and US interactions in both synthetic tissue and random scattering media. The results illustrate that optical energy may be focused within a turbid medium utilizing a US guidestar. The results also suggest that optical energy travels preferentially along optical channels within a turbid medium

Diffusion model for ultrasound-modulated light

Researchers use ultrasound (US) to modulate diffusive light in a highly scattering medium like tissue. This paper analyzes the US–optical interaction in the scattering medium and derives an expression for the US-modulated optical radiance. The diffusion approximation to the radiative transport equation is employed to develop a Green’s function for US-modulated light. The predicted modulated fluence and flux are verified using finite-difference time-domain simulations. The Green’s function is then utilized to illustrate the modulated reflectance as the US–optical interaction increases in depth. The intent of this paper is to focus on high US frequencies necessary for high-resolution imaging because they are of interest for applications such as phase conjugation

Dual-wedge scanning confocal reflectance microscope

A confocal reflectance microscope has been developed that incorporates a dual-wedge scanner to reduce the size of the device relative to current raster scanning instruments. The scanner is implemented with two prisms that are rotated about the optical axis. Spiral and rosette scans are performed by rotating the prisms in the same or opposite directions, respectively. Experimental measurements show an on-axis lateral resolution of 1.6 m and optical sectioning of 4.7 m, which compares with a diffraction-limited resolution of 0.8 and 1.9 m, respectively. © 2007 Optical Society of America OCIS codes: 110.0180, 120.3890, 120.4570, 170.1790, 180.1790 Current point-scanning microscopes generally use a raster scan, which is uniform throughout the field-ofview. However, this standard scan requires an optoelectromechanical configuration that is bulky and difficult to reduce to a handheld device. In this Letter, we discuss the implementation of a dual-wedge scanner as an alternative method to scan the focused spot within a confocal reflectance microscope. This scanner uses two prisms within a compact package to provide a circular two-dimensional scan that is capable of high speeds with a nonuniform pixel density, but requires a detailed mapping algorithm to determine the exact location of the spot. The use of two prisms to scan a laser beam was first described by Rosell in 1960 as a prism scanner The concept of the scanner is shown i

A model for ultrasound modulated light in a turbid medium

The ability to focus light in most tissue degrades quickly with depth due to high optical scattering. Researchers have investigated using both ultrasound (US) and light synergistically to overcome this difficulty. Ultrasound has been utilized to modulated light within tissue to create a diffusive wave at that is modulated at the US frequency. Recently, there has been interest in the modulated sidebands which reside at optical frequency plus or minus the US frequency. This paper will discuss a model for US-light interactions in a scattering medium. We will use this model to relate the radiance in the probe beam to the radiance in the diffusive wave. We will then employ the P-1 approximation to the radiative transport equation to find the fluence and flux of the modulated wave. We will use these parameters to write a diffusion equation for the modulated wave that can be described in terms of the incoming optical power, and the US intensity and geometry

Deep-tissue focal fluorescence imaging with digitally time-reversed ultrasound-encoded light

Fluorescence imaging is one of the most important research tools in biomedical sciences. However, scattering of light severely impedes imaging of thick biological samples beyond the ballistic regime. Here we directly show focusing and high-resolution fluorescence imaging deep inside biological tissues by digitally time-reversing ultrasound-tagged light with high optical gain (~5×10^5). We confirm the presence of a time-reversed optical focus along with a diffuse background—a corollary of partial phase conjugation—and develop an approach for dynamic background cancellation. To illustrate the potential of our method, we image complex fluorescent objects and tumour microtissues at an unprecedented depth of 2.5 mm in biological tissues at a lateral resolution of 36 μm×52 μm and an axial resolution of 657 μm. Our results set the stage for a range of deep-tissue imaging applications in biomedical research and medical diagnostics

Some approaches to infrared spectroscopy for detection of buried objects

Detection of buried objects presents a formidable challenge which requires many different approaches. Infrared imaging has proven its versatility in a number of applications. Recent advances in technology have opened the door for spectroscopic imaging systems which can produce images of reflectivity or emissivity as a function of two spatial dimensions and wavelength. These imagers have been largely unexploited for detection of buried and surface-laid landmines. Several promising opportunities exist for this application in different parts of the infrared spectrum. Variations in soil moisture content, vegetation condition, and soil composition may well be related to the presence of shallow-buried objects. In addition, polarimetric signatures appear useful in detecting man-made objects on the surface and may even help in detecting buried objects. This paper will explore both the feasibility of using infrared spectral imagery in the 1-to-2.5 and 8-to-12 micrometer infrared bands to detect surface-laid and buried objects