We present a review of methods for the forward and inverse problems in optical tomography. We limit ourselves to the highly scattering case found in applications in medical imaging, and to the problem of absorption and scattering reconstruction. We discuss the derivation of the diffusion approximation and other simplifications of the full transport problem. We develop sensitivity relations in both the continuous and discrete case with special concentration on the use of the finite element method. A classification of algorithms is presented, and some suggestions for open problems to be addressed in future research are made.

https://iopscience.iop.org/article/10.1088/0266-5611/15/2/022/pdf

Optical tomography in medical imaging

References http://genesdev.cshlp.org/content/17/5/545.full.html#related-urls Article cited in: http://genesdev.cshlp.org/content/17/5/545.full.html#ref-list-1 This article cites 228 articles, 79 of which can be accessed free at: service Email alerting click here top right corner of the article or Receive free email alerts when new articles cite this article sign up in the box at the Collections Topic (33 articles) Molecular Physiology and Metabolism  (98 articles) Cancer and Disease Models  Articles on similar topics can be found in the following collections

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Molecular imaging in living subjects: seeing fundamental biological processes in a new light

Optical sensing of specific molecular targets and pathways deep inside living mice has become possible as a result of a number of advances. These include design of biocompatible near-infrared fluorochromes, development of targeted and activatable 'smart' imaging probes, engineered photoproteins and advances in photon migration theory and reconstruction. Together, these advances will provide new tools making it possible to understand more fully the functioning of protein networks, diagnose disease earlier and speed along drug discovery.

Shedding light onto live molecular targets

Successful development of ultra-sensitive molecular imaging nanoprobes for the detection of targeted biological objects is a challenging task Although magnetic nanoprobes have the potential to perform such a role, the results from probes that are currently available have been far from optimal Here we used artificial engineering approaches to develop innovative magnetic nanoprobes, through a process that involved the systematic evaluation of the magnetic spin, size and type of spinel metal ferrites These magnetism-engineered iron oxide (MEIO) nanoprobes, when conjugated with antibodies, showed enhanced magnetic resonance imaging (MRI) sensitivity for the detection of cancer markers compared with probes currently available Also, we successfully visualized small tumors implanted in a mouse Such high-performance, nanotechnology-based molecular probes could enhance the ability to visualize other biological events critical to diagnostics and therapeutics

Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging.

An endoscopic bipolar forceps includes an elongated shaft having opposing jaw members at a distal end thereof. The jaw members are movable relative to one another from a first position wherein the jaw members are disposed in spaced relation relative to one another to a second position wherein the jaw members cooperate to grasp tissue therebetween. The forceps also includes a source of electrical energy connected to each jaw member such that the jaw members are capable of conducting energy through tissue held therebetween to effect a seal. A generally tube-like cutter is included which is slidably engaged about the elongated shaft and which is selectively movable about the elongated shaft to engage and cut tissue on at least one side of the jaw members while the tissue is engaged between jaw members.

Vessel sealer and divider

The study of pathogenic processes is often limited to ex vivo assays and cell-culture correlates. A greater understanding of infectious diseases would be facilitated by in vivo analyses. Therefore, we have developed a method for detecting bacterial pathogens in a living host and used this method to evaluate disease processes for strains of Salmonella typhimurlum that differ in their virulence for mice. Three strains of Salmonella were marked with bioluminescence through transformation with a plasmid conferring constitutive expression of bacterial luciferase. Detection of photons transmitted through tissues of animals infected with bioluminescent Salmonella allowed localization of the bacteria to specific tissues. In this manner progressive infections were distinguished from those that were persistent or abortive. We observed patterns of bioluminescence that suggested the caecum may play a pivotal role in Salmonella pathogenesis. In vivo efficacy of an antibiotic was monitored using this optical method. This study demonstrates that real time non-invasive analyses of pathogenic events and pharmacological monitoring can be performed in vivo.

Photonic detection of bacterial pathogens in living hosts

Control of gene expression often involves an interwoven set of regulatory processes. As information regarding regulatory pathways may be lost in ex vivo analyses, we used bioluminescence to monitor gene expression in living mammals. Viral promoters fused to firefly luciferase as transgenes in mice allowed external monitoring of gene expression both superficially and in deep tissues. In vivo bioluminescence was detectable using either intensified or cooled charge-coupled device cameras, and could be detected following both topical and systemic delivery of substrate. In vivo control of the promoter from the human immunodeficiency virus was demonstrated. As a model for DNA-based therapies and vaccines, in vivo transfection of a luciferase expression vector (SV-40 promoter and enhancer controlling expression) was detected. We conclude that gene regulation, DNA delivery and expression can now be noninvasively monitored in living mammals using a luciferase reporter. Thus, real-time, noninvasive study of gene expression in living animal models for human development and disease is possible.

Visualizing gene expression in living mammals using a bioluminescent reporter.

Imaging the interior of living bodies with light may assist in the diagnosis and treatment of a number of clinical problems, which include the early detection of tumors and hypoxic cerebral injury. An existing picosecond time-of-flight and absorbance (TOFA) optical system has been used to image a model biologic system and a rat. Model measurements confirmed TOFA principles in systems with a high degree of photon scattering; rat images, which were constructed from the variable time delays experienced by a fixed fraction of early-arriving transmitted photons, revealed identifiable internal structure. A combination of light-based quantitative measurement and TOFA localization may have applications in continuous, noninvasive monitoring for structural imaging and spatial chemometric analysis in humans.

https://science.sciencemag.org/content/sci/259/5100/1463.full.pdf

Optical time-of-flight and absorbance imaging of biologic media

A tool for nondestructive interrogation of the tissue including a light source emitter and detector which may be mounted directly on the surgical tool in a tissue contacting surface for interrogation or mounted remotely and guided to the surgical field with fiber optic cables. The light source may be broadband and wavelength differentiation can be accomplished at the detector via filters or gratings, or using time, frequency, or space resolved methods. Alternatively, n discrete monochromatic light sources may be provided which are subsequently multiplexed into a single detector by time or by frequency multiplexing. The optical sensing elements can be built into a surgical tool end effector tip such as a tissue grasping tool which has cooperating jaws (bivalve or multi-element). In the preferred embodiment the light source (or the fiber optic guide) is mounted on one jaw and the detector (or fiber optic guide) is mounted in the opposing jaw so that the light emitter and detector are facing one another either directly (i.e., on the same optical axis when the tool is closed) or acutely (i.e., with intersecting optical axes so that the light emitted is detected). In this case, the sensor is working in a transmission modality. Arrangements with the optical components mounted on the same member of a single member or a multi member structure, operating in a reflective modality, are disclosed.

Tissue interrogating device and methods

Analysis of photon transit time for low-power light passing into the head, and through both skull and brain, of human subjects allowed for tomographic imaging of cerebral hemoglobin oxygenation based on photon diffusion theory. In healthy adults, imaging of changes in hemoglobin saturation during hand movement revealed focal, contralateral increases in motor cortex oxygenation with spatial agreement to activation maps determined by functional magnetic resonance imaging; in ill neonates, imaging of hemoglobin saturation revealed focal regions of low oxygenation after acute stroke, with spatial overlap to injury location determined by computed tomography scan. Because such slow optical changes occur over seconds and co-localize with magnetic resonance imaging vascular signals whereas fast activation-related optical changes occur over milliseconds and co-localize with EEG electrical signals, optical methods offer a single modality for exploring the spatiotemporal relationship between electrical and vascular responses in the brain in vivo, as well as for mapping cortical activation and oxygenation at the bedside in real-time for clinical monitoring.

https://journals.sagepub.com/doi/pdf/10.1097/00004647-200003000-00005

David A. Benaron

Papers

Photonic detection of bacterial pathogens in living hosts

Visualizing gene expression in living mammals using a bioluminescent reporter.

Optical time-of-flight and absorbance imaging of biologic media

Tissue interrogating device and methods

Noninvasive Functional Imaging of Human Brain Using Light