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.

A review on continuous wave functional near-infrared spectroscopy and imaging instrumentation and methodology.

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

A recent development in biomedical imaging is the non-invasive mapping of molecular events in intact tissues using fluorescence. Underpinning to this development is the discovery of bio-compatible, specific fluorescent probes and proteins and the development of highly sensitive imaging technologies for in vivo fluorescent detection. Of particular interest are fluorochromes that emit in the near infrared (NIR), a spectral window, whereas hemoglobin and water absorb minimally so as to allow photons to penetrate for several centimetres in tissue. In this review article we concentrate on optical imaging technologies used for non-invasive imaging of the distribution of such probes. We illuminate the advantages and limitations of simple photographic methods and turn our attention to fluorescence-mediated molecular tomography (FMT), a technique that can three-dimensionally image gene expression by resolving fluorescence activation in deep tissues. We describe theoretical specifics, and we provide insight into its in vivo capacity and the sensitivity achieved. Finally, we discuss its clinical feasibility.

/pdf/fluorescence-imaging-with-near-infrared-light-new-1cbygnpd0x.pdf

Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging.

http://li.mit.edu/Stuff/CNSE/Paper/Klose06Larsen.pdf

Light transport in biological tissue based on the simplified spherical harmonics equations

Currently available tomographic image reconstruction schemes for optical tomography (OT) are mostly based on the limiting assumptions of small perturbations and a priori knowledge of the optical properties of a reference medium. Furthermore, these algorithms usually require the inversion of large, full, ill-conditioned Jacobian matrixes. In this work a gradient-based iterative image reconstruction (GIIR) method is presented that promises to overcome current limitations. The code consists of three major parts: (1) A finite-difference, time-resolved, diffusion forward model is used to predict detector readings based on the spatial distribution of optical properties; (2) An objective function that describes the difference between predicted and measured data; (3) An updating method that uses the gradient of the objective function in a line minimization scheme to provide subsequent guesses of the spatial distribution of the optical properties for the forward model. The reconstruction of these properties is completed, once a minimum of this objective function is found. After a presentation of the mathematical background, two- and three-dimensional reconstruction of simple heterogeneous media as well as the clinically relevant example of ventricular bleeding in the brain are discussed. Numerical studies suggest that intraventricular hemorrhages can be detected using the GIIR technique, even in the presence of a heterogeneous background.

/pdf/gradient-based-iterative-image-reconstruction-scheme-for-24myvmti49.pdf

Gradient-based iterative image reconstruction scheme for time-resolved optical tomography

Optical tomography is a novel imaging modality that is employed to reconstruct cross-sectional images of the optical properties of highly scattering media given measurements performed on the surface of the medium. Recent advances in this field have mainly been driven by biomedical applications in which near-infrared light is used for transillumination and reflectance measurements of highly scattering biological tissues. Many of the reconstruction algorithms currently utilized for optical tomography make use of model-based iterative image reconstruction (MOBIIR) schemes. The imaging problem is formulated as an optimization problem, in which an objective function is minimized. In the simplest case the objective function is a normalized-squared error between measured and predicted data. The predicted data are obtained by using a forward model that describes light propagation in the scattering medium given a certain distribution of optical properties. In part I of this two-part study, we presented a forward model that is based on the time-independent equation of radiative transfer. Using experimental data we showed that this transport-theory-based forward model can accurately predict light propagation in highly scattering media that contain void-like inclusions. In part II we focus on the details of our image reconstruction scheme (inverse model). A crucial component of this scheme involves the efficient and accurate determination of the gradient of the objective function with respect to all optical properties. This calculation is performed using an adjoint differentiation algorithm that allows for fast calculation of this gradient. Having calculated this gradient, we minimize the objective function with a gradient-based optimization method, which results in the reconstruction of the spatial distribution of scattering and absorption coefficients inside the medium. In addition to presenting the mathematical and numerical background of our code, we present reconstruction results based on experimentally obtained data from highly scattering media that contain void-like regions. These types of media play an important role in optical tomographic imaging of the human brain and joints.

/pdf/optical-tomography-using-the-time-independent-equation-of-1m8azdr5md.pdf

Optical tomography using the time-independent equation of radiative transfer-Part 1: Forward model

http://orion.bme.columbia.edu/optical-tomography/resources/articles/2005_optical_tomography_adklose.pdf

The inverse source problem based on the radiative transfer equation in optical molecular imaging

We report on the development of an iterative image reconstruction scheme for optical tomography that is based on the equation of radiative transfer. Unlike the commonly applied diffusion approximation, the equation of radiative transfer accurately describes the photon propagation in turbid media without any limiting assumptions regarding the optical properties. The reconstruction scheme consists of three major parts: (1) a forward model that predicts the detector readings based on solutions of the time-independent radiative transfer equation, (2) an objective function that provides a measure of the differences between the detected and the predicted data, and (3) an updating scheme that uses the gradient of the objective function to perform a line minimization to get new guesses of the optical properties. The gradient is obtained by employing an adjoint differentiation scheme, which makes use of the structure of the finite-difference discrete-ordinate formulation of the transport forward model. Based on the new guess of the optical properties a new forward calculation is performed to get new detector predictions. The reconstruction process is completed when the minimum of the objective function is found within a defined error. To illustrate the performance of the code we present initial reconstruction results based on simulated data.

Alexander D. Klose

Papers

Light transport in biological tissue based on the simplified spherical harmonics equations

Gradient-based iterative image reconstruction scheme for time-resolved optical tomography

Optical tomography using the time-independent equation of radiative transfer-Part 1: Forward model

The inverse source problem based on the radiative transfer equation in optical molecular imaging

Iterative reconstruction scheme for optical tomography based on the equation of radiative transfer.