Photoacoustic imaging (also called optoacoustic or thermoacoustic imaging) has the potential to image animal or human organs, such as the breast and the brain, with simultaneous high contrast and high spatial resolution. This article provides an overview of the rapidly expanding field of photoacoustic imaging for biomedical applications. Imaging techniques, including depth profiling in layered media, scanning tomography with focused ultrasonic transducers, image forming with an acoustic lens, and computed tomography with unfocused transducers, are introduced. Special emphasis is placed on computed tomography, including reconstruction algorithms, spatial resolution, and related recent experiments. Promising biomedical applications are discussed throughout the text, including (1) tomographic imaging of the skin and other superficial organs by laser-induced photoacoustic microscopy, which offers the critical advantages, over current high-resolution optical imaging modalities, of deeper imaging depth and higher absorptioncontrasts, (2) breast cancerdetection by near-infrared light or radio-frequency–wave-induced photoacoustic imaging, which has important potential for early detection, and (3) small animal imaging by laser-induced photoacoustic imaging, which measures unique optical absorptioncontrasts related to important biochemical information and provides better resolution in deep tissues than optical imaging.

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Photoacoustic imaging in biomedicine

Optical microscopy has been a fundamental tool of biological discovery for more than three centuries, but its in vivo tissue imaging ability has been restricted by light scattering to superficial investigations, even when confocal or multiphoton methods are used. Recent advances in optical and optoacoustic (photoacoustic) imaging now allow imaging at depths and resolutions unprecedented for optical methods. These abilities are increasingly important to understand the dynamic interactions of cellular processes at different systems levels, a major challenge of postgenome biology. This Review discusses promising photonic methods that have the ability to visualize cellular and subcellular components in tissues across different penetration scales. The methods are classified into microscopic, mesoscopic and macroscopic approaches, according to the tissue depth at which they operate. Key characteristics associated with different imaging implementations are described and the potential of these technologies in biological applications is discussed.

Going deeper than microscopy: the optical imaging frontier in biology

Within the last several years, the field of terahertz science and technology has changed dramatically. Many new advances in the technology for generation, manipulation, and detection of terahertz radiation have revolutionized the field. Much of this interest has been inspired by the promise of valuable new applications for terahertz imaging and sensing. Among a long list of proposed uses, one finds compelling needs such as security screening and quality control, as well as whimsical notions such as counting the almonds in a bar of chocolate. This list has grown in parallel with the development of new technologies and new paradigms for imaging and sensing. Many of these proposed applications exploit the unique capabilities of terahertz radiation to penetrate common packaging materials and provide spectroscopic information about the materials within. Several of the techniques used for terahertz imaging have been borrowed from other, more well established fields such as x-ray computed tomography and synthetic aperture radar. Others have been developed exclusively for the terahertz field, and have no analogies in other portions of the spectrum. This review provides a comprehensive description of the various techniques which have been employed for terahertz image formation, as well as discussing numerous examples which illustrate the many exciting potential uses for these emerging technologies.

https://iopscience.iop.org/article/10.1088/0034-4885/70/8/R02/pdf

Imaging with terahertz radiation

Raman spectroscopy is a potentially important clinical tool for real-time diagnosis of disease and in situ evaluation of living tissue. The purpose of this article is to review the biological and physical basis of Raman spectroscopy of tissue, to assess the current status of the field and to explore future directions. The principles of Raman spectroscopy and the molecular level information it provides are explained. An overview of the evolution of Raman spectroscopic techniques in biology and medicine, from early investigations using visible laser excitation to present-day technology based on near-infrared laser excitation and charge-coupled device array detection, is presented. State-of-the-art Raman spectrometer systems for research laboratory and clinical settings are described. Modern methods of multivariate spectral analysis for extracting diagnostic, chemical and morphological information are reviewed. Several in-depth applications are presented to illustrate the methods of collecting, processing and analysing data, as well as the range of medical applications under study. Finally, the issues to be addressed in implementing Raman spectroscopy in various clinical applications, as well as some long-term directions for future study, are discussed.

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Prospects for in vivo Raman spectroscopy.

The present invention relates generally to systems and methods for measuring an analyte in a host. More particularly, the present invention relates to systems and methods for transcutaneous measurement of glucose in a host.

Transcutaneous analyte sensor

Apparatus and method for non-invasively measuring at least one optical parameter of a sample, particularly a sample of tissue that comprises a plurality of layers. The at least one parameter can be used to determine the presence or concentration of an analyte of interest in the sample of tissue. The apparatus and method of the present invention (1) measure light that is substantially reflected, scattered, absorbed, or emitted from a shallower layer of the sample of tissue, (2) measure light that is substantially reflected, scattered, absorbed, or emitted from a deeper layer of the sample of tissue, (3) determine at least one optical parameter for each of these layers, and (4) account for the effect of the shallower layer on the at least one optical parameter of the deeper layer. Specifying the sampling depth allows determinations of the optical properties of a specific layer of the sample of the tissue, e.g., dermis, and decreases interference from other layers, e.g., stratum corneum and epidermis, in these determinations.

Non-invasive sensor capable of determining optical parameters in a sample having multiple layers

Materials for solid photoacoustic breast phantoms, based on poly(vinyl alcohol) hydrogels, are presented. Phantoms intended for use in photoacoustics must possess both optical and acoustic properties of tissue. To realize the optical properties of tissue, one approach was to optimize the number of freezing and thawing cycles of aqueous poly(vinyl alcohol) solutions, a procedure which increases the turbidity of the gel while rigidifying it. The second approach concentrated on forming a clear matrix of the rigid poly(vinyl alcohol) gel without any scattering, so that appropriate amounts of optical scatterers could be added at the time of formation, to tune the optical properties as per requirement. The relevant optical and acoustic properties of such samples were measured to be close to the average properties of human breast tissue. Tumour simulating gel samples of suitable absorption coefficient were created by adding appropriate quantities of dye at the time of formation; the samples were then cut into spheres. A breast phantom embedded with such 'tumours' was developed for studying the applicability of photoacoustics in mammography.

https://iopscience.iop.org/article/10.1088/0031-9155/48/3/306/pdf

Poly(vinyl alcohol) gels for use as tissue phantoms in photoacoustic mammography

Devices and methods for non-invasively measuring at least one parameter of a sample, such as the presence or concentration of an analyte, in a body part wherein the temperature is controlled. The present invention measures light that is reflected, scattered, absorbed, or emitted by the sample from an average sampling depth, dav, that is confined within a temperature controlled region in the tissue. This average sampling depth is preferably less than 2 mm, and more preferably less than 1 mm. Confining the sampling depth into the tissue is achieved by appropriate selection of the separation between the source and the detector and the illumination wavelengths. In another aspect, the invention involves a method and apparatus for non-invasively measuring at least one parameter of a body part with temperature stepping. In another aspect, the invention involves a method and apparatus for non-invasively measuring at least one parameter of a body part with temperature modulation. In another aspect, the invention provides an improved method of measuring at least one parameter of a tissue sample comprising the steps of: (a) lowering the temperature of said tissue sample to a temperature that is lower than the normal physiological temperature of the body; and (b) determining at least one optical property of said tissue sample.

Non-invasive sensor having controllable temperature feature

https://ris.utwente.nl/ws/files/7075953/Siebinga91age.pdf

Age-related changes in local water and protein content of human eye lenses measured by Raman microspectroscopy.

We utilized a complimentary metal oxide semiconductor video camera for fast f low imaging with the laser Doppler technique. A single sensor is used for both observation of the area of interest and measurements of the interference signal caused by dynamic light scattering from moving particles inside scattering objects. In particular, we demonstrate the possibility of imaging the distribution of the moving red blood cell concentration. This is a first step toward laser Doppler imaging without scanning parts, leading to a much faster imaging procedure than with existing mechanical laser Doppler perfusion imagers.

Frits F. M. de Mul

Papers

Non-invasive sensor capable of determining optical parameters in a sample having multiple layers

Poly(vinyl alcohol) gels for use as tissue phantoms in photoacoustic mammography

Non-invasive sensor having controllable temperature feature

Age-related changes in local water and protein content of human eye lenses measured by Raman microspectroscopy.

Laser Doppler perfusion imaging with a complimentary metal oxide semiconductor image sensor