Optical imaging of live animals has grown into an important tool in biomedical research as advances in photonic technology and reporter strategies have led to widespread exploration of biological processes in vivo. Although much attention has been paid to microscopy, macroscopic imaging has allowed small-animal imaging with larger fields of view (from several millimeters to several centimeters depending on implementation). Photographic methods have been the mainstay for fluorescence and bioluminescence macroscopy in whole animals, but emphasis is shifting to photonic methods that use tomographic principles to noninvasively image optical contrast at depths of several millimeters to centimeters with high sensitivity and sub-millimeter to millimeter resolution. Recent theoretical and instrumentation advances allow the use of large data sets and multiple projections and offer practical systems for quantitative, three-dimensional whole-body images. For photonic imaging to fully realize its potential, however, further progress will be needed in refining optical inversion methods and data acquisition techniques.

Looking and listening to light: the evolution of whole-body photonic imaging.

We review the current state-of-the-art of diffuse optical imaging, which is an emerging technique for functional imaging of biological tissue. It involves generating images using measurements of visible or near-infrared light scattered across large (greater than several centimetres) thicknesses of tissue. We discuss recent advances in experimental methods and instrumentation, and examine new theoretical techniques applied to modelling and image reconstruction. We review recent work on in vivo applications including imaging the breast and brain, and examine future challenges.

https://iopscience.iop.org/article/10.1088/0031-9155/50/4/R01/pdf

Recent advances in diffuse optical imaging.

This review describes the diffusion model for light transport in tissues and the medical applications of diffuse light. Diffuse optics is particularly useful for measurement of tissue hemodynamics, wherein quantitative assessment of oxy- and deoxy-hemoglobin concentrations and blood flow are desired. The theoretical basis for near-infrared or diffuse optical spectroscopy is developed, and the basic elements of diffuse optical tomography are outlined. We also discuss diffuse correlation spectroscopy, a technique whereby temporal correlation functions of diffusing light are transported through tissue and are used to measure blood flow. Essential instrumentation is described, and representative brain and breast functional imaging and monitoring results illustrate the workings of these new tissue diagnostics.

/pdf/diffuse-optics-for-tissue-monitoring-and-tomography-curjv2s4p6.pdf

Diffuse optics for tissue monitoring and tomography

Diffuse optical tomography, also known as near infrared tomography, has been under investigation, for non-invasive functional imaging of tissue, specifically for the detection and characterization of breast cancer or other soft tissue lesions. Much work has been carried out for accurate modeling and image reconstruction from clinical data. NIRFAST, a modeling and image reconstruction package has been developed, which is capable of single wavelength and multi-wavelength optical or functional imaging from measured data. The theory behind the modeling techniques as well as the image reconstruction algorithms is presented here, and 2D and 3D examples are presented to demonstrate its capabilities. The results show that 3D modeling can be combined with measured data from multiple wavelengths to reconstruct chromophore concentrations within the tissue. Additionally it is possible to recover scattering spectra, resulting from the dominant Mie-type scatter present in tissue. Overall, this paper gives a comprehensive over view of the modeling techniques used in diffuse optical tomographic imaging, in the context of NIRFAST software package.

/pdf/near-infrared-optical-tomography-using-nirfast-algorithm-for-2c1yi2s9a5.pdf

Near infrared optical tomography using nirfast: algorithm for numerical model and image reconstruction

Fluorescence sampling of cellular function is widely used in all aspects of biology, allowing the visualization of cellular and sub-cellular biological processes with spatial resolutions in the range from nanometers up to centimeters. Imaging of fluorescence in vivo has become the most commonly used radiological tool in all pre-clinical work. In the last decade, full-body pre-clinical imaging systems have emerged with a wide range of utilities and niche application areas. The range of fluorescent probes that can be excited in the visible to near-infrared part of the electromagnetic spectrum continues to expand, with the most value for in vivo use being beyond the 630 nm wavelength, because the absorption of light sharply decreases. Whole-body in vivo fluorescence imaging has not yet reached a state of maturity that allows its routine use in the scope of large-scale pre-clinical studies. This is in part due to an incomplete understanding of what the actual fundamental capabilities and limitations of this imaging modality are. However, progress is continuously being made in research laboratories pushing the limits of the approach to consistently improve its performance in terms of spatial resolution, sensitivity and quantification. This paper reviews this imaging technology with a particular emphasis on its potential uses and limitations, the required instrumentation, and the possible imaging geometries and applications. A detailed account of the main commercially available systems is provided as well as some perspective relating to the future of the technology development. Although the vast majority of applications of in vivo small animal imaging are based on epi-illumination planar imaging, the future success of the method relies heavily on the design of novel imaging systems based on state-of-the-art optical technology used in conjunction with high spatial resolution structural modalities such as MRI, CT or ultrasound.

/pdf/pre-clinical-whole-body-fluorescence-imaging-review-of-5bmhg5ipa7.pdf

Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications

Near-Infrared Optical Imaging of the Breast with Model-Based Reconstruction

We present for the first time a full three-dimensional (3-D) reconstruction of absorption images of breast from continuous-wave (cw) measurements performed on a premenopausal woman. Our 3-D optical images clearly reveal a large primary tumor as well as a small secondary tumor in a separate location of the breast. The multiple tumors identified by our 3-D optical imaging have been confirmed by the subsequent biopsy examination of the breast. Quantitative information of the optical images obtained is provided in terms of the location, size, and absorption coefficient of the tumors.

Three-dimensional optical tomographic imaging of breast in a human subject

We present what is believed to be the first absorption and scattering images of in vitro and in vivo bones and joints from continuous-wave tomographic measurements. Human finger and chicken bones embedded in cylindrical scattering media were imaged at multiple transverse planes with Clemson multi-channel diffuse optical imager. Both absorption and scattering images were obtained using our nonlinear, finite element based reconstruction algorithm. This study shows that diffuse optical tomography (DOT) has the potential to be used for detection and monitoring of bone and joint diseases such as osteoporosis and arthritis.

Imaging of in vitro and in vivo bones and joints with continuous-wave diffuse optical tomography.

We present for the first time full three-dimensional (3D) volumetric reconstruction of absorption images of in vitro and in vivo bones and joints from near-infrared tomographic measurements. Im- aging experiments were conducted on human finger and chicken bones embedded in cylindrical scattering media using a Clemson multichannel diffuse optical imager. The volumetric optical images were recovered with our 3D finite element based reconstruction algo- rithm. Our results show that 3D imaging methods can provide details of the joint structure/composition that would be impossible from two- dimensional imaging methods. © 2002 Society of Photo-Optical Instrumentation

Three-dimensional diffuse optical tomography of bones and joints.

We present a carefully designed phantom experimental study aimed to provide solid evidence that both absorption and scattering images of heterogeneous scattering media can be reconstructed independently from dc data. We also study the important absorption-scattering cross-talk issue. In this regard, we develop a simple normalizing scheme that is incorporated into our nonlinear finite-element-based reconstruction algorithm. Our results from the controlled phantom experiments show that the cross talk of an absorption object appearing in scattering images can be eliminated and that the cross talk of a scattering object appearing in absorption images can be reduced considerably. In addition, these carefully designed phantom experiments clearly suggest that both absorption and scattering images can be simultaneously recovered and quantitatively separated in highly scattering media by use of dc measurements. Finally, we discuss our results in light of recent theoretical findings on nonuniqueness for dc image reconstruction.

https://www.uta.edu/rfmems/N_041101/Reference/70.pdf

Yong Xu

Papers

Near-Infrared Optical Imaging of the Breast with Model-Based Reconstruction

Three-dimensional optical tomographic imaging of breast in a human subject

Imaging of in vitro and in vivo bones and joints with continuous-wave diffuse optical tomography.

Three-dimensional diffuse optical tomography of bones and joints.

Absorption and scattering images of heterogeneous scattering media can be simultaneously reconstructed by use of dc data