Turzhitsky V, Rogers JD, Mutyal NN
… +2 more, Roy HK, Backman V
IEEE J Sel Top Quantum Electron
· 2010 · PMID 21037980
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Low-coherence enhanced backscattering (LEBS) is a technique that has recently shown promise for tissue characterization and the detection of early pre-cancer. Although several Monte Carlo models of LEBS have been describ...Low-coherence enhanced backscattering (LEBS) is a technique that has recently shown promise for tissue characterization and the detection of early pre-cancer. Although several Monte Carlo models of LEBS have been described, these models have not been accurate enough to predict all of the experimentally observed LEBS features. We present an appropriate Monte Carlo model to simulate LEBS peak properties from polystyrene microsphere suspensions in water. Results show that the choice of the phase function greatly impacts the accuracy of the simulation when the transport mean free path (ls*) is much greater than the spatial coherence length (L(SC)). When ls* < L(SC), a diffusion approximation based model of LEBS is sufficiently accurate. We also use the Monte Carlo model to validate that LEBS can be used to measure the radial scattering probability distribution (radial point spread function), p(r), at small length scales and demonstrate LEBS measurements of p(r) from biological tissue. In particular, we show that pre-cancerous and benign mucosal tissues have different small length scale light transport properties.
Pogue BW, Gibbs-Strauss S, Valdés PA
… +3 more, Samkoe K, Roberts DW, Paulsen KD
IEEE J Sel Top Quantum Electron
· 2010 May · PMID 20671936
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Fluorescence imaging in neurosurgery has a long historical development, with several different biomarkers and biochemical agents being used, and several technological approaches. This review focuses on the different cont...Fluorescence imaging in neurosurgery has a long historical development, with several different biomarkers and biochemical agents being used, and several technological approaches. This review focuses on the different contrast agents, summarizing endogenous fluorescence, exogenously stimulated fluorescence and exogenous contrast agents, and then on tools used for imaging. It ends with a summary of key clinical trials that lead to consensus studies. The practical utility of protoporphyrin IX (PpIX) as stimulated by administration of δ-aminolevulinic acid (ALA) has had substantial pilot clinical studies and basic science research completed. Recently multi-center clinical trials using PpIx fluorescence to guide resection have shown efficacy for improved short term survival. Exogenous agents are being developed and tested pre-clinically, and hopefully hold the potential for long term survival benefit if they provide additional capabilities for resection of micro-invasive disease or certain tumor sub-types that do not produce PpIX or help delineate low grade tumors. The range of technologies used for measurement and imaging ranges widely, with most clinical trials being carried out with either point probes or modified surgical microscopes. At this point in time, optimized probe approaches are showing efficacy in clinical trials, and fully commercialized imaging systems are emerging, which will clearly help lead to adoption into neurosurgical practice.
IEEE J Sel Top Quantum Electron
· 2010 May · PMID 20657761
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Optical microangiography (OMAG) is a recently developed volumetric imaging technique that is capable of producing 3D images of dynamic blood perfusion within microcirculatory tissue beds in vivo. The imaging contrast of...Optical microangiography (OMAG) is a recently developed volumetric imaging technique that is capable of producing 3D images of dynamic blood perfusion within microcirculatory tissue beds in vivo. The imaging contrast of OMAG image is based on the intrinsic optical scattering signals backscattered by the moving blood cells in patent blood vessels, thus it is a label free imaging technique. In this paper, I will first discuss its recent developments that use a constant modulation frequency introduced in the spectral interferograms to achieve the blood perfusion imaging. I will then introduce its latest development that utilizes the inherent blood flow to modulate the spectral interferograms to realize the blood perfusion imaging. Finally, examples of using OMAG to delineate the dynamic blood perfusion, down to capillary level resolution, within living tissues are given, including cortical blood perfusion in the brain of small animals and blood flow within human retina and choroids.
Wu Y, Xi J, Huo L
… +7 more, Padvorac J, Shin EJ, Giday SA, Lennon AM, Canto MIF, Hwang JH, Li X
IEEE J Sel Top Quantum Electron
· 2010 · PMID 39734745
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Fine optical coherence tomography (OCT) imaging needles that can be integrated with a standard biopsy needle have been developed with a new optics design to improve the optical quality and mechanical robustness, where a...Fine optical coherence tomography (OCT) imaging needles that can be integrated with a standard biopsy needle have been developed with a new optics design to improve the optical quality and mechanical robustness, where a fiber-optic lens (that is spliced to a single-mode fiber) and a microreflector are encased within a microglass tube. The design also minimizes the cylindrical lens effect induced by the glass tube and eases the needle assembly process. Real-time cross-sectional OCT imaging of various tissue samples were performed using the miniature-imaging needle along with a 1300-nm swept-source OCT system. The preliminary results demonstrate the improved mechanical and optical performance and suggest the potential of the fine OCT needle for minimally invasive interstitial imaging and image-guided biopsy.
Kang JU, Han JH, Liu X
… +3 more, Zhang K, Song CG, Gehlbach P
IEEE J Sel Top Quantum Electron
· 2010 Jul · PMID 22899880
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A single-arm interferometer based optical coherence tomography (OCT) system known as common-path OCT (CPOCT) is rapidly progressing towards practical application. Due in part to the simplicity and robustness of its desig...A single-arm interferometer based optical coherence tomography (OCT) system known as common-path OCT (CPOCT) is rapidly progressing towards practical application. Due in part to the simplicity and robustness of its design, Fourier Domain CPOCT (FD-CP-OCT) offers advantages in many endoscopic sensing and imaging applications. FD-CP-OCT uses simple, interchangeable fiber optic probes that are easily integrated into small and delicate surgical tools. The system is capable of providing not only high resolution imaging but also optical sensing. Here, we report progress towards practical application of FD-CP-OCT in the setting of delicate microsurgical procedures such as intraocular retinal surgery. To meet the challenges presented by the microsurgical requirements of these procedures, we have developed and initiated the validation of applicable fiber optic probes. By integrating these probes into our developing imaging system, we have obtained high resolution OCT images and have also completed a demonstration of their potential sensing capabilities. Specifically, we utilize multiple SLEDs to demonstrate sub 3-micron axial resolution in water; we propose a technique to quantitatively evaluate the spatial distribution of oxygen saturation levels in tissue; and we present evidence supportive of the technology's surface sensing and tool guidance potential by demonstrating topological and motion compensation capabilities.
IEEE J Sel Top Quantum Electron
· 2010 Jul · PMID 22190845
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We demonstrate a miniature, near-infrared microscope (λ = 785 nm) that uses a novel dual axes confocal architecture. Scalability is achieved with post-objective scanning, and a MEMS mirror provides real time (>4 Hz) in v...We demonstrate a miniature, near-infrared microscope (λ = 785 nm) that uses a novel dual axes confocal architecture. Scalability is achieved with post-objective scanning, and a MEMS mirror provides real time (>4 Hz) in vivo imaging. This instrument can achieve sub-cellular resolution with deep tissue penetration and large field of view. An endoscope-compatible version can image digestive tract epithelium to guide tissue biopsy and monitor therapy.
Choudhury N, Chen F, Shi X
… +2 more, Nuttall AL, Wang RK
IEEE J Sel Top Quantum Electron
· 2009 Oct · PMID 20495618
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Changes in blood flow to the inner ear are thought to influence a number of cochlear diseases, including noise-induced hearing loss, sudden hearing loss, and Meniere's disease. Advances have been made in the areas of vit...Changes in blood flow to the inner ear are thought to influence a number of cochlear diseases, including noise-induced hearing loss, sudden hearing loss, and Meniere's disease. Advances have been made in the areas of vital microscopic studies of micro-circulation, and the laser Doppler flowmetry. But none of these techniques can provide in vivo three-dimensional (3-D) mapping of microvascular perfusion within the cochlea. To overcome this limitation we have developed and used a method of optical microangiography (OMAG) that can generate 3-D angiograms within millimeter of tissue depths by analyzing the endogenous optical scattering signal obtained from an illuminated sample. We used OMAG to visualize the cochlear microcirculation of adult living gerbil through the intact cochlea, which would be difficult, if not impossible, by use of any other current techniques.
Brown JQ, Bydlon TM, Richards LM
… +8 more, Yu B, Kennedy SA, Geradts J, Wilke LG, Junker M, Gallagher J, Barry W, Ramanujam N
IEEE J Sel Top Quantum Electron
· 2010 Mar · PMID 21544237
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Breast conserving surgery, in which the breast tumor and surrounding normal tissue are removed, is the primary mode of treatment for invasive and in situ carcinomas of the breast, conditions that affect nearly 200,000 wo...Breast conserving surgery, in which the breast tumor and surrounding normal tissue are removed, is the primary mode of treatment for invasive and in situ carcinomas of the breast, conditions that affect nearly 200,000 women annually. Of these nearly 200,000 patients who undergo this surgical procedure, between 20-70% of them may undergo additional surgeries to remove tumor that was left behind in the first surgery, due to the lack of intra-operative tools which can detect whether the boundaries of the excised specimens are free from residual cancer. Optical techniques have many attractive attributes which may make them useful tools for intra-operative assessment of breast tumor resection margins. In this manuscript, we discuss clinical design criteria for intra-operative breast tumor margin assessment, and review optical techniques appied to this problem. In addition, we report on the development and clinical testing of quantitative diffuse reflectance imaging (Q-DRI) as a potential solution to this clinical need. Q-DRI is a spectral imaging tool which has been applied to 56 resection margins in 48 patients at Duke University Medical Center. Clear sources of contrast between cancerous and cancer-free resection margins were identified with the device, and resulted in an overall accuracy of 75% in detecting positive margins.
IEEE J Sel Top Quantum Electron
· 2009 Oct · PMID 25378895
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Magnetomotive optical coherence tomography (MM-OCT) is an important tool for the visualization and quantitative assessment of magnetic nanoparticles in tissues. In this study, we demonstrate the use of MM-OCT for quantit...Magnetomotive optical coherence tomography (MM-OCT) is an important tool for the visualization and quantitative assessment of magnetic nanoparticles in tissues. In this study, we demonstrate the use of MM-OCT for quantitative measurement of magnetic iron oxide nanoparticle transport and concentration in muscle, lung, and liver tissues. The effect of temperature on the dynamics of these nanoparticles is also analyzed. We observe that the rate of transport of nanoparticles in tissues is directly related to the elasticity of tissues, and describe how the origin of the MM-OCT signal is associated with nanoparticle binding. These results improve our understanding of how iron oxide nanoparticles behave dynamically in biological tissues, which has direct implications for medical and biological applications of targeted nanoparticles for contrast enhancement and therapy.
IEEE J Sel Top Quantum Electron
· 2008 Jan · PMID 24839386
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This paper provides an overview of the development and applications of plasmonics-active nanoprobes in biomedical diagnostics. Specific examples of detection techniques using surface-enhanced Raman scattering are present...This paper provides an overview of the development and applications of plasmonics-active nanoprobes in biomedical diagnostics. Specific examples of detection techniques using surface-enhanced Raman scattering are presented to illustrate the usefulness and potential of the plasmonics nanoprobes for gene detection and nanobiosensing. The detection of specific target deoxyribonucleic acids sequences using a novel "molecular sentinel" nanoprobe method is presented and discussed in detail.
IEEE J Sel Top Quantum Electron
· 2008 · PMID 23055656
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Soliton self-frequency shift (SSFS), a consequence of Raman self-pumping that continuously red-shifts a soliton pulse, has been widely studied recently for applications to fiber-based sources and signal processing. In th...Soliton self-frequency shift (SSFS), a consequence of Raman self-pumping that continuously red-shifts a soliton pulse, has been widely studied recently for applications to fiber-based sources and signal processing. In this paper, the fundamentals of SSFS are reviewed. Various fiber platforms for SSFS (single-mode fiber, microstructured fiber, and higher order mode fiber) are presented and experimental SSFS demonstrations in these fibers are discussed. Observation of Cerenkov radiation in fibers exhibiting SSFS is also presented. A number of interesting applications of SSFS, such as wavelength-agile lasers, analog-to-digital conversion, and slow light, are briefly discussed.
Maxwell A, Huang SW, Ling T
… +3 more, Kim JS, Ashkenazi S, Guo LJ
IEEE J Sel Top Quantum Electron
· 2008 Jan · PMID 20700482
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Polymer microring resonators fabricated by nanoimprinting are presented as a means of ultrasound detection. Acoustic waves impinging on a ring-shaped optical resonator cause strain in the ring dimensions, modulating opti...Polymer microring resonators fabricated by nanoimprinting are presented as a means of ultrasound detection. Acoustic waves impinging on a ring-shaped optical resonator cause strain in the ring dimensions, modulating optical output. Basic acoustic and optical characteristics of the microring sensor are presented. Measurements at several frequencies show a high sensitivity and low noise-equivalent pressure. The angular response is determined by sensing the optoacoustic excitation of a 49 μm polyester microsphere and shows wide-angle sensitivity. A 1-D array consisting of 4 microrings is demonstrated using wavelength multiplexing for addressing each element. The high sensitivity, bandwidth, and angular response make it a potentially useful sensor platform for many applications including high-frequency ultrasonic and photoacoustic imaging.
IEEE J Sel Top Quantum Electron
· 2008 Jan · PMID 19829746
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Multimodal nonlinear optical (NLO) imaging is poised to become a powerful tool in bioimaging given its ability to capitalize on the unique advantages possessed by different NLO imaging modalities. The integration of diff...Multimodal nonlinear optical (NLO) imaging is poised to become a powerful tool in bioimaging given its ability to capitalize on the unique advantages possessed by different NLO imaging modalities. The integration of different imaging modalities such as two-photon-excited fluorescence, sum frequency generation, and coherent anti-Stokes Raman scattering on the same platform can facilitate simultaneous imaging of different biological structures. Parameters to be considered in constructing a multimodal NLO microscope are discussed with emphasis on achieving a compromise in these parameters for efficient signal generation with each imaging modality. As an example of biomedical applications, multimodal NLO imaging is utilized to investigate the central nervous system in healthy and diseased states.
Bergstein DA, Ozkumur E, Wu AC
… +9 more, Yalçin A, Colson JR, Needham JW, Irani RJ, Gershoni JM, Goldberg BB, Delisi C, Ruane MF, Unlü MS
IEEE J Sel Top Quantum Electron
· 2008 · PMID 19823593
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The resonant cavity imaging biosensor (RCIB) is an optical technique for detecting molecular binding interactions label free at many locations in parallel that employs an optical resonant cavity for high sensitivity. Nea...The resonant cavity imaging biosensor (RCIB) is an optical technique for detecting molecular binding interactions label free at many locations in parallel that employs an optical resonant cavity for high sensitivity. Near-infrared light centered at 1512.5 nm couples resonantly through a Fabry-Perot cavity constructed from dielectric reflectors (Si/SiO(2)), one of which serves as the binding surface. As the wavelength is swept using a tunable laser, a near-infrared digital camera monitors cavity transmittance at each pixel. A wavelength shift in the local resonant response of the optical cavity indicates binding. Positioning the sensing surface with respect to the standing wave pattern of the electric field within the cavity controls the sensitivity with which the presence of bound molecules is detected. Transmitted intensity at thousands of pixel locations is recorded simultaneously in a 10 s, 5 nm scan. An initial proof-of-principle setup has been constructed. A test sample was fabricated with 25, 100-mum wide square features, each with a different density of 1-mum square depressions etched 12 nm into the SiO(2) surface. The average depth of each etched region was found with 0.05 nm rms precision. In a second test, avidin, bound selectively to biotin conjugated bovine serum albumin, was detected.
IEEE J Sel Top Quantum Electron
· 2007 · PMID 39830863
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Microendoscope is a critical technology to enable high-resolution imaging of internal luminal organs with optical coherence tomography. This paper reports the development of an achromatic compound microlens and a rapid s...Microendoscope is a critical technology to enable high-resolution imaging of internal luminal organs with optical coherence tomography. This paper reports the development of an achromatic compound microlens and a rapid scanning microendoscope based on the microlens that offers an ultrahigh transverse resolution of 4 m (and an axial resolution of 2.2 m when using a low-coherence light source with a broad spectrum bandwidth of 150 nm). The rapid scanning endoscope is capable of ultrahigh-resolution (UHR) optical coherence tomography (OCT) imaging in real time at an imaging speed of about 1220 lateral scans/s, with the image quality comparable to a slow bench-top UHR-OCT system (~100 scans/s). The superior performance of a scanning endoscope made of a compound microlens over an endoscope made of a conventional GRIN (gradient index) lens in imaging biological tissues has also been demonstrated.
Zaman RT, Diagaradjane P, Wang JC
… +8 more, Schwartz J, Rajaram N, Gill-Sharp KL, Cho SH, Rylander HG, Payne JD, Krishnan S, Tunnell JW
IEEE J Sel Top Quantum Electron
· 2007 · PMID 33859459
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This study demonstrates the use of diffuse optical spectroscopy (DOS) for the noninvasive measurement of gold nanoshell concentrations in tumors of live mice. We measured the diffuse optical spectra (500-800 nm) using an...This study demonstrates the use of diffuse optical spectroscopy (DOS) for the noninvasive measurement of gold nanoshell concentrations in tumors of live mice. We measured the diffuse optical spectra (500-800 nm) using an optical fiber probe placed in contact with the tissue surface. We performed studies on tissue phantoms illustrating an accurate measurement of gold-silica nanoshell concentration within 12.6% of the known concentration. studies were performed on a mouse xenograft tumor model. DOS spectra were measured at preinjection, immediately postinjection, 1 and 24 h postinjection times, and the nanoshell concentrations were verified using neutron activation analysis.
de Boer JF, Srinivas SM, Park BH
… +4 more, Pham TH, Chen Z, Milner TE, Nelson JS
IEEE J Sel Top Quantum Electron
· 1999 · PMID 25774083
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Polarization sensitive optical coherence tomography (PS-OCT) was used to obtain spatially resolved images of polarization changes in skeletal muscle, bone, skin and brain. Through coherent detection of two orthogonal po...Polarization sensitive optical coherence tomography (PS-OCT) was used to obtain spatially resolved images of polarization changes in skeletal muscle, bone, skin and brain. Through coherent detection of two orthogonal polarization states of the signal formed by interference of light reflected from the biological sample and a mirror in the reference arm of a Michelson interferometer, the depth resolved change in polarization was measured. Inasmuch as any fibrous structure will influence the polarization of light, PS-OCT is a potentially powerful technique investigating tissue structural properties. In addition, the effects of single polarization state detection on OCT image formation is demonstrated.