With the development of optical coherence tomography,the application optical coherence elastography(OCE)has gained more and more attention in biomechanics for its unique features including micron-scale resolution,real...With the development of optical coherence tomography,the application optical coherence elastography(OCE)has gained more and more attention in biomechanics for its unique features including micron-scale resolution,real-time processing,and non-invasive imaging.In this review,one group of OCE techniques,namely dynamic OCE,are introduced and discussed including external dynamic OCE mapping and imaging of ex vivo breast tumor,external dynamic OCE measurement of in vivo human skin,and internal dynamic OCE including acoustomotive OCE and magnetomotive OCE.These techniques overcame some of the major drawbacks of traditional static OCE,and broadened the OCE application fields.Driven by scientific needs to engineer new quantitative methods that utilize the high micron-scale resolution achievable with optics,results of biomechanical properties were obtained from biological tissues.The results suggest potential diagnostic and therapeutic clinical applications.Results from these studies also help our understanding of the relationship between biomechanical variations and functional tissue changes in biological systems.展开更多
Nonlinear optical imaging is a versatile tool that has been proven to be exceptionally useful in various research fields.However,due to the use of photomultiplier tubes(PMTs),the wide application of nonlinear optical ...Nonlinear optical imaging is a versatile tool that has been proven to be exceptionally useful in various research fields.However,due to the use of photomultiplier tubes(PMTs),the wide application of nonlinear optical imaging is limited by the incapability of imaging under am-bient light.In this paper,we propose and demonstrate a new optical imaging detection method based on optical parametric amplification(OPA).As a nonlinear optical process,OPA in-trinsically rejects ambient light photons by coherence gating.Periodical poled lithium niobate(PPLN)crystals are used in this study as the media for OPA.Compared to bulk nonlinear optical crystals,PPLN crystals support the generation of OPA signal with lower pump power.Therefore,this characteristic of PPLN crystals is particularly beneficial when using high-repetition-rate lasers,which facilitate high-speed optical signal detection,such as in spec-troscopy and imaging.A PPLN-based OPA system was built to amplify the emitted imaging signal from second harmonic generation(SHG)and coherent anti-Stokes Raman scattering(CARS)microscopy imaging,and the amplified optical signal was strong enough to be detected by a biased photodiode under ordinary room light conditions.With OPA detection,ambient-light-on SHG and CARS imaging becomes possible,and achieves a similar result as PMT detection under strictly dark environments.These results demonstrate that OPA can be used as a substitute for PMTs in nonlinear optical imaging to adapt it to various applications with complex.light ing conditions.展开更多
To date,numerous studies have been performed to elucidate the complex cellular dynamics in skin diseases,but few have attempted to characterize these cellular events under conditions similar to the native environment....To date,numerous studies have been performed to elucidate the complex cellular dynamics in skin diseases,but few have attempted to characterize these cellular events under conditions similar to the native environment.To address this challenge,a three-dimensional(3D)multimodal analysis platform was developed for characterizing in vivo cellular dynamics in skin,which was then utilized to process in vivo wound healing data to demonstrate its applicability.Special attention is focused on in vivo biological parameters that are difficult to study with ex vivo analysis,including 3D cell tracking and techniques to connect biological information obtained from different imaging modalities.These results here open new possibilities for evaluating 3D cellular dynamics in vivo,and can potentially provide new tools for characterizing the skin microenvironment and pathologies in the future.展开更多
Pre-operative X ray mammography and int raoperative X-ray specimen radiography are routinely used to identify breast cancer pathology.Recent advances in optical coherence tomography(OCT)have enabled its 1use for the i...Pre-operative X ray mammography and int raoperative X-ray specimen radiography are routinely used to identify breast cancer pathology.Recent advances in optical coherence tomography(OCT)have enabled its 1use for the intraoperative assessment of surgical margins during breast cancer surgery.While each modality offers distinct contrast of normal and pathological features,there is an essential need to correlate image based features between the two modalities to take adv antage of the diagnostic capabilities of each technique.We compare OCT to X-ray images of resected human breast tissue and correlate different tissue features between modalities for future use in real-tine intraoperative OCT imaging.X ray imaging(specimen radiography)is currently used during surgical breast cancer procedures to verify tumor margins,but cannot image tissue in situ.OCT has the potential to solve this problem by providing intrao-perative imaging of the resected specimen as well as the in situ tumor cavity.OCT and micro-CT(X-ray)images are automatically segmented using different computational approaches,and quantitatively compared to determine the ability of these algorithms to automat ically differentiate regions of adipose tissue from tumor.Furthermore,two-dimensional(2D)and three-dimensional(3D)results are compared.These correlations,combined with real-time intraoperative OCT,have the potential to identify possible regions of tumor within breast tissue which correlate to tumor regions identified previously on X-ray imaging(mammography or specimen radiography).展开更多
In this study, we report the fabrication of engineered iron oxide magnetic nanoparticles (MNPs)functionalized with anti-human epidermal growth factor receptor type 2 (HER2) antibody totarget the tumor antigen HER2. Th...In this study, we report the fabrication of engineered iron oxide magnetic nanoparticles (MNPs)functionalized with anti-human epidermal growth factor receptor type 2 (HER2) antibody totarget the tumor antigen HER2. The Fc-directed conjugation of antibodies to the MNPs aidstheir efficient immunospecific targeting through free Fab portions. The directional specificity ofconjugation was verified on a macrophage cell line. Immunofluorescence studies on macrophagestreated with functionalized MNPs and free anti-HER2 antibody revealed that the antibodymolecules bind to the MNPs predominantly through their Fc portion. Different cell lines with different HER2 expression levels were used to test the specificity of our functionalized nanoprobe formolecular targeting applications. The results of cell line targeting demonstrate that these engineered MNPs are able to differentiate between cell lines with different levels of HER2 expression.展开更多
The emission wavelength of a laser is physically predetermined by the gain medium used. Consequently, arbitrary wavelength generation is a fundamental challenge in the science of light. Present solutions include optic...The emission wavelength of a laser is physically predetermined by the gain medium used. Consequently, arbitrary wavelength generation is a fundamental challenge in the science of light. Present solutions include optical parametric generation, requiring complex optical setups and spectrally sliced supercontinuum, taking advantage of a simpler fiber technology: a fixed-wavelength pump laser pulse is converted into a spectrally very broadband output, from which the required resulting wavelength is then optically filtered. Unfortunately, this process is associated with an inherently poor noise figure, which often precludes many realistic applications of such supercontinuum sources. Here, we show that by adding only one passive optical element—a tapered photonic crystal fiber—to a fixed-wavelength femtosecond laser, one can in a very simple manner resonantly convert the laser emission wavelength into an ultra-wide and continuous range of desired wavelengths, with very low inherent noise, and without mechanical realignment of the laser. This is achieved by exploiting the double interplay of nonlinearity and chirp in the laser source and chirp and phase matching in the tapered fiber. As a first demonstration of this simple and inexpensive technology, we present a femtosecond fiber laser continuously tunable across the entire red–green–blue spectral range.展开更多
Characterizing the performance of fluorescence microscopy and nonlinear imaging systems is an essential step required for imaging system optimization and quality control during longitudinal experiments. Emerging multi...Characterizing the performance of fluorescence microscopy and nonlinear imaging systems is an essential step required for imaging system optimization and quality control during longitudinal experiments. Emerging multimodal nonlinear imaging techniques require a new generation of microscopy calibration targets that are not susceptible to bleaching and can provide a contrast across the multiple modalities. Here, we present a nanodiamond-based calibration target for microscopy, designed for facilitating reproducible measurements at the object plane. The target is designed to support day-to-day instrumentation development efforts in microscopy laboratories. The images of a phantom contain information about the imaging performance of a microscopy system across multiple spectral windows and modalities. Since fluorescent nanodiamonds are not prone to bleaching, the proposed imaging target can serve as a standard, shelf-stable sample to provide rapid reference measurements for ensuring consistent performance of microscopy systems in microscopy laboratories and imaging facilities.展开更多
基金supported in part by grants from the National Institutes of Health(NIBIB,R21 EB005321,R01 EB005221,R01 EB009073NCI RC1 CA147096,S.A.B.).
文摘With the development of optical coherence tomography,the application optical coherence elastography(OCE)has gained more and more attention in biomechanics for its unique features including micron-scale resolution,real-time processing,and non-invasive imaging.In this review,one group of OCE techniques,namely dynamic OCE,are introduced and discussed including external dynamic OCE mapping and imaging of ex vivo breast tumor,external dynamic OCE measurement of in vivo human skin,and internal dynamic OCE including acoustomotive OCE and magnetomotive OCE.These techniques overcame some of the major drawbacks of traditional static OCE,and broadened the OCE application fields.Driven by scientific needs to engineer new quantitative methods that utilize the high micron-scale resolution achievable with optics,results of biomechanical properties were obtained from biological tissues.The results suggest potential diagnostic and therapeutic clinical applications.Results from these studies also help our understanding of the relationship between biomechanical variations and functional tissue changes in biological systems.
基金supported in part by grants from the National Institutes of Health (R01CA213149,R01CA241618).
文摘Nonlinear optical imaging is a versatile tool that has been proven to be exceptionally useful in various research fields.However,due to the use of photomultiplier tubes(PMTs),the wide application of nonlinear optical imaging is limited by the incapability of imaging under am-bient light.In this paper,we propose and demonstrate a new optical imaging detection method based on optical parametric amplification(OPA).As a nonlinear optical process,OPA in-trinsically rejects ambient light photons by coherence gating.Periodical poled lithium niobate(PPLN)crystals are used in this study as the media for OPA.Compared to bulk nonlinear optical crystals,PPLN crystals support the generation of OPA signal with lower pump power.Therefore,this characteristic of PPLN crystals is particularly beneficial when using high-repetition-rate lasers,which facilitate high-speed optical signal detection,such as in spec-troscopy and imaging.A PPLN-based OPA system was built to amplify the emitted imaging signal from second harmonic generation(SHG)and coherent anti-Stokes Raman scattering(CARS)microscopy imaging,and the amplified optical signal was strong enough to be detected by a biased photodiode under ordinary room light conditions.With OPA detection,ambient-light-on SHG and CARS imaging becomes possible,and achieves a similar result as PMT detection under strictly dark environments.These results demonstrate that OPA can be used as a substitute for PMTs in nonlinear optical imaging to adapt it to various applications with complex.light ing conditions.
基金funded in part by grants from the National Institutes of Health(1R01CA213149,5R01EB023232)the National Science Foundation(CBET 18-41539).
文摘To date,numerous studies have been performed to elucidate the complex cellular dynamics in skin diseases,but few have attempted to characterize these cellular events under conditions similar to the native environment.To address this challenge,a three-dimensional(3D)multimodal analysis platform was developed for characterizing in vivo cellular dynamics in skin,which was then utilized to process in vivo wound healing data to demonstrate its applicability.Special attention is focused on in vivo biological parameters that are difficult to study with ex vivo analysis,including 3D cell tracking and techniques to connect biological information obtained from different imaging modalities.These results here open new possibilities for evaluating 3D cellular dynamics in vivo,and can potentially provide new tools for characterizing the skin microenvironment and pathologies in the future.
基金supported in part by a grant from the U.S.National Institutes of Health,R01 EB012479(S.A.B.).
文摘Pre-operative X ray mammography and int raoperative X-ray specimen radiography are routinely used to identify breast cancer pathology.Recent advances in optical coherence tomography(OCT)have enabled its 1use for the intraoperative assessment of surgical margins during breast cancer surgery.While each modality offers distinct contrast of normal and pathological features,there is an essential need to correlate image based features between the two modalities to take adv antage of the diagnostic capabilities of each technique.We compare OCT to X-ray images of resected human breast tissue and correlate different tissue features between modalities for future use in real-tine intraoperative OCT imaging.X ray imaging(specimen radiography)is currently used during surgical breast cancer procedures to verify tumor margins,but cannot image tissue in situ.OCT has the potential to solve this problem by providing intrao-perative imaging of the resected specimen as well as the in situ tumor cavity.OCT and micro-CT(X-ray)images are automatically segmented using different computational approaches,and quantitatively compared to determine the ability of these algorithms to automat ically differentiate regions of adipose tissue from tumor.Furthermore,two-dimensional(2D)and three-dimensional(3D)results are compared.These correlations,combined with real-time intraoperative OCT,have the potential to identify possible regions of tumor within breast tissue which correlate to tumor regions identified previously on X-ray imaging(mammography or specimen radiography).
基金the National Institutes of Health(Roadmap Initiative,NIBIB,R21 EB005321,S.A.B.,and NIBIB,R01 EB005221,S.A.B.).
文摘In this study, we report the fabrication of engineered iron oxide magnetic nanoparticles (MNPs)functionalized with anti-human epidermal growth factor receptor type 2 (HER2) antibody totarget the tumor antigen HER2. The Fc-directed conjugation of antibodies to the MNPs aidstheir efficient immunospecific targeting through free Fab portions. The directional specificity ofconjugation was verified on a macrophage cell line. Immunofluorescence studies on macrophagestreated with functionalized MNPs and free anti-HER2 antibody revealed that the antibodymolecules bind to the MNPs predominantly through their Fc portion. Different cell lines with different HER2 expression levels were used to test the specificity of our functionalized nanoprobe formolecular targeting applications. The results of cell line targeting demonstrate that these engineered MNPs are able to differentiate between cell lines with different levels of HER2 expression.
基金Teknologi og Produktion,Det Frie Forskningsrad(FTP,DFF)(ALFIE)Research Executive Agency(REA)(EU Career Integration Grant 334324LIGHTER)+2 种基金H2020 European Research Council(ERC)(ERC-617521 NLL)National Cancer Institute(NCI)(1 R01 CA166309)Max-Planck-Gesellschaft(MPG)
文摘The emission wavelength of a laser is physically predetermined by the gain medium used. Consequently, arbitrary wavelength generation is a fundamental challenge in the science of light. Present solutions include optical parametric generation, requiring complex optical setups and spectrally sliced supercontinuum, taking advantage of a simpler fiber technology: a fixed-wavelength pump laser pulse is converted into a spectrally very broadband output, from which the required resulting wavelength is then optically filtered. Unfortunately, this process is associated with an inherently poor noise figure, which often precludes many realistic applications of such supercontinuum sources. Here, we show that by adding only one passive optical element—a tapered photonic crystal fiber—to a fixed-wavelength femtosecond laser, one can in a very simple manner resonantly convert the laser emission wavelength into an ultra-wide and continuous range of desired wavelengths, with very low inherent noise, and without mechanical realignment of the laser. This is achieved by exploiting the double interplay of nonlinearity and chirp in the laser source and chirp and phase matching in the tapered fiber. As a first demonstration of this simple and inexpensive technology, we present a femtosecond fiber laser continuously tunable across the entire red–green–blue spectral range.
基金National Institutes of Health(R01CA241618,R01EB023232)Air Force Office of Scientific Research(FA9550-17-1-0387)。
文摘Characterizing the performance of fluorescence microscopy and nonlinear imaging systems is an essential step required for imaging system optimization and quality control during longitudinal experiments. Emerging multimodal nonlinear imaging techniques require a new generation of microscopy calibration targets that are not susceptible to bleaching and can provide a contrast across the multiple modalities. Here, we present a nanodiamond-based calibration target for microscopy, designed for facilitating reproducible measurements at the object plane. The target is designed to support day-to-day instrumentation development efforts in microscopy laboratories. The images of a phantom contain information about the imaging performance of a microscopy system across multiple spectral windows and modalities. Since fluorescent nanodiamonds are not prone to bleaching, the proposed imaging target can serve as a standard, shelf-stable sample to provide rapid reference measurements for ensuring consistent performance of microscopy systems in microscopy laboratories and imaging facilities.
