Light scattering spectroscopy (LSS) is a spectroscopic technique typically used to evaluate morphological changes in epithelial cells in order to study mucosal tissue and detect early cancer and precancer. [1] [2] [3]
Light scattering spectroscopy relies upon elastic scattering of photons reflected from the epithelium. Most of the signal is generated by light scattering from small intracellular structures, but larger intracellular structures, such as nuclei, also scatter light, with their relative contribution increasing in the backscatter direction. As changes in the morphology of epithelial cells are hallmarks of pre-cancer and early cancer, LSS can be used for early cancer diagnosis.
In addition to photons backscattering from epithelial cells, a major portion of photons penetrates the epithelium, reaching optically turbid connective tissue where they are scattered multiple times and partially absorbed by hemoglobin. As a result, it is not possible to measure single backscattering events directly in human tissue, [4] with polarization gating [5] and spatial gating [6] well-suited for endoscopy applications. [7] [8] [9] [10] [6] [11]
Lev T. Perelman, principal scientist at MIT, and Vadim Backman, graduate student in Harvard- MIT Health Sciences and Technology program introduced LSS in 1998. [1]
Light scattering spectroscopy has been applied for detection of precancer in many organs including esophagus, [1] [2] [3] [9] [10] [12] colon, [2] [13] [14] urinary bladder, [2] oral cavity, [2] cervix, [15] [16] pancreatic cyst, [11] [17] stomach, [18] skin, [19] and bile duct. [11]
Spectroscopy is the field of study that measures and interprets electromagnetic spectra. In narrower contexts, spectroscopy is the precise study of color as generalized from visible light to all bands of the electromagnetic spectrum.
Raman spectroscopy is a spectroscopic technique typically used to determine vibrational modes of molecules, although rotational and other low-frequency modes of systems may also be observed. Raman spectroscopy is commonly used in chemistry to provide a structural fingerprint by which molecules can be identified.
Resonance Raman spectroscopy is a variant of Raman spectroscopy in which the incident photon energy is close in energy to an electronic transition of a compound or material under examination. This similarity in energy (resonance) leads to greatly increased intensity of the Raman scattering of certain vibrational modes, compared to ordinary Raman spectroscopy.
Autofluorescence is the natural emission of light by biological structures such as mitochondria and lysosomes when they have absorbed light, and is used to distinguish the light originating from artificially added fluorescent markers (fluorophores).
A single-molecule experiment is an experiment that investigates the properties of individual molecules. Single-molecule studies may be contrasted with measurements on an ensemble or bulk collection of molecules, where the individual behavior of molecules cannot be distinguished, and only average characteristics can be measured. Since many measurement techniques in biology, chemistry, and physics are not sensitive enough to observe single molecules, single-molecule fluorescence techniques caused a lot of excitement, since these supplied many new details on the measured processes that were not accessible in the past. Indeed, since the 1990s, many techniques for probing individual molecules have been developed.
Surface-enhanced Raman spectroscopy or surface-enhanced Raman scattering (SERS) is a surface-sensitive technique that enhances Raman scattering by molecules adsorbed on rough metal surfaces or by nanostructures such as plasmonic-magnetic silica nanotubes. The enhancement factor can be as much as 1010 to 1011, which means the technique may detect single molecules.
Near-field scanning optical microscopy (NSOM) or scanning near-field optical microscopy (SNOM) is a microscopy technique for nanostructure investigation that breaks the far field resolution limit by exploiting the properties of evanescent waves. In SNOM, the excitation laser light is focused through an aperture with a diameter smaller than the excitation wavelength, resulting in an evanescent field on the far side of the aperture. When the sample is scanned at a small distance below the aperture, the optical resolution of transmitted or reflected light is limited only by the diameter of the aperture. In particular, lateral resolution of 6 nm and vertical resolution of 2–5 nm have been demonstrated.
Dynamic light scattering (DLS) is a technique in physics that can be used to determine the size distribution profile of small particles in suspension or polymers in solution. In the scope of DLS, temporal fluctuations are usually analyzed using the intensity or photon autocorrelation function. In the time domain analysis, the autocorrelation function (ACF) usually decays starting from zero delay time, and faster dynamics due to smaller particles lead to faster decorrelation of scattered intensity trace. It has been shown that the intensity ACF is the Fourier transform of the power spectrum, and therefore the DLS measurements can be equally well performed in the spectral domain. DLS can also be used to probe the behavior of complex fluids such as concentrated polymer solutions.
Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion of the uterine lining that predisposes to endometrioid endometrial adenocarcinoma. It is composed of a collection of abnormal endometrial cells, arising from the glands that line the uterus, which have a tendency over time to progress to the most common form of uterine cancer—endometrial adenocarcinoma, endometrioid type.
Angle-resolved low-coherence interferometry (a/LCI) is an emerging biomedical imaging technology which uses the properties of scattered light to measure the average size of cell structures, including cell nuclei. The technology shows promise as a clinical tool for in situ detection of dysplastic, or precancerous tissue.
Diffusing-wave spectroscopy (DWS) is an optical technique derived from dynamic light scattering (DLS) that studies the dynamics of scattered light in the limit of strong multiple scattering. It has been widely used in the past to study colloidal suspensions, emulsions, foams, gels, biological media and other forms of soft matter. If carefully calibrated, DWS allows the quantitative measurement of microscopic motion in a soft material, from which the rheological properties of the complex medium can be extracted via the microrheology approach.
Plasmonic nanoparticles are particles whose electron density can couple with electromagnetic radiation of wavelengths that are far larger than the particle due to the nature of the dielectric-metal interface between the medium and the particles: unlike in a pure metal where there is a maximum limit on what size wavelength can be effectively coupled based on the material size.
Atmospheric lidar is a class of instruments that uses laser light to study atmospheric properties from the ground up to the top of the atmosphere. Such instruments have been used to study, among other, atmospheric gases, aerosols, clouds, and temperature.
Tip-enhanced Raman spectroscopy (TERS) is a variant of surface-enhanced Raman spectroscopy (SERS) that combines scanning probe microscopy with Raman spectroscopy. High spatial resolution chemical imaging is possible via TERS, with routine demonstrations of nanometer spatial resolution under ambient laboratory conditions, or better at ultralow temperatures and high pressure.
Nano-FTIR is a scanning probe technique that utilizes as a combination of two techniques: Fourier transform infrared spectroscopy (FTIR) and scattering-type scanning near-field optical microscopy (s-SNOM). As s-SNOM, nano-FTIR is based on atomic-force microscopy (AFM), where a sharp tip is illuminated by an external light source and the tip-scattered light is detected as a function of tip position. A typical nano-FTIR setup thus consists of an atomic force microscope, a broadband infrared light source used for tip illumination, and a Michelson interferometer acting as Fourier-transform spectrometer. In nano-FTIR, the sample stage is placed in one of the interferometer arms, which allows for recording both amplitude and phase of the detected light. Scanning the tip allows for performing hyperspectral imaging with nanoscale spatial resolution determined by the tip apex size. The use of broadband infrared sources enables the acquisition of continuous spectra, which is a distinctive feature of nano-FTIR compared to s-SNOM. Nano-FTIR is capable of performing infrared (IR) spectroscopy of materials in ultrasmall quantities and with nanoscale spatial resolution. The detection of a single molecular complex and the sensitivity to a single monolayer has been shown. Recording infrared spectra as a function of position can be used for nanoscale mapping of the sample chemical composition, performing a local ultrafast IR spectroscopy and analyzing the nanoscale intermolecular coupling, among others. A spatial resolution of 10 nm to 20 nm is routinely achieved.
Choi Wonshik is an optical physicist researching deep-tissue imaging and imaging through scattering media. He is a full professor in the Department of Physics of Korea University where he serves as the associate director at the IBS Center for Molecular Spectroscopy and Dynamics. Inside the Center, he leads the Super-depth Imaging Lab. He has been cited more than 4,000 times and has an h-index of 32. He is a fellow of The Optical Society and the Korean Academy of Science and Technology.
Irene Georgakoudi is a Greek biophysicist and Professor of Biomedical Engineering at Tufts University, where her work focuses on developing non-invasive medical imaging techniques based on optical spectroscopy for applications in medical diagnostics and therapeutics.
Gabriel Popescu was an American optical engineer, who was the William L. Everitt Distinguished Professor in Electrical and Computer Engineering at University of Illinois Urbana-Champaign. He was best known for his work on biomedical optics and quantitative phase-contrast microscopy.
Lev T. Perelman is an American biological physicist and bioengineer at Harvard. He holds the Mary Tolan and Edward Grzelakowski Endowed Chair, is a professor of medicine at Harvard Medical School, and is the Director of the Center for Advanced Biomedical Imaging and Photonics at Beth Israel Deaconess Medical Center. He is known for his work on biomedical light scattering spectroscopy and application of optics and spectroscopy to life sciences and developmental and cell biology.
Katrin Kneipp is a German physicist.