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Showing papers in "Journal of Biomedical Optics in 2014"


Journal ArticleDOI
TL;DR: An overview of the literature on medical hyperspectral imaging technology and its applications is presented, an introduction for those new to the field, an overview for those working in the field and a reference for those searching for literature on a specific application are presented.
Abstract: Hyperspectral imaging (HSI) is an emerging imaging modality for medical applications, especially in disease diagnosis and image-guided surgery. HSI acquires a three-dimensional dataset called hypercube, with two spatial dimensions and one spectral dimension. Spatially resolved spectral imaging obtained by HSI provides diagnostic information about the tissue physiology, morphology, and composition. This review paper presents an overview of the literature on medical hyperspectral imaging technology and its applications. The aim of the survey is threefold: an introduction for those new to the field, an overview for those working in the field, and a reference for those searching for literature on a specific application.

1,605 citations


Journal ArticleDOI
TL;DR: Various multimodal imaging modalities with OCT incorporated are reviewed, in that these multi-modal implementations can synergistically compensate for the fundamental limitations of OCT when it is used alone.
Abstract: In the last 25 years, optical coherence tomography (OCT) has advanced to be one of the most innovative and most successful translational optical imaging techniques, achieving substantial economic impact as well as clinical acceptance. This is largely owing to the resolution improvements by a factor of 10 to the submicron regime and to the imaging speed increase by more than half a million times to more than 5 million A-scans per second, with the latter one accomplished by the state-of-the-art swept source laser technologies that are reviewed in this article. In addition, parallelization of OCT detection, such as line-field and full-field OCT, has shortened the acquisition time even further by establishing quasi-akinetic scanning. Besides the technical improvements, several functional and contrast-enhancing OCT applications have been investigated, among which the label-free angiography shows great potential for future studies. Finally, various multimodal imaging modalities with OCT incorporated are reviewed, in that these multimodal implementations can synergistically compensate for the fundamental limitations of OCT when it is used alone.

383 citations


Journal ArticleDOI
TL;DR: Due to a reduction in scattering and minimal absorption, longer attenuation lengths and clearer optical images could be seen in the second and third Nir optical windows compared to the conventional first NIR optical window.
Abstract: Light at wavelengths in the near-infrared (NIR) region allows for deep penetration and minimal absorption through high scattering tissue media. NIR light has been conventionally used through the first NIR optical tissue window with wavelengths from 650 to 950 nm. Longer NIR wavelengths had been overlooked due to major water absorption peaks and a lack of NIR-CCD detectors. The second NIR spectral window from 1100 to 1350 nm and a new spectral window from 1600 to 1870 nm, known as the third NIR optical window, were investigated. Optical attenuation measurements from thin tissue slices of normal and malignant breast and prostate tissues, pig brain, and chicken tissue were obtained in the spectral range from 400 to 2500 nm. Optical images of chicken tissue overlying three black wires were also obtained using the second and third spectral windows. Due to a reduction in scattering and minimal absorption, longer attenuation lengths and clearer optical images could be seen in the second and third NIR optical windows compared to the conventional first NIR optical window. A possible fourth optical window centered at 2200 nm was noted.

299 citations


Journal ArticleDOI
TL;DR: It is found that the curvelet-denoising filter followed by FIRE, a process the authors call CT-FIRE, outperforms the other algorithms under investigation and was successfully applied to track collagen fiber shape changes over time in an in vivo mouse model for breast cancer.
Abstract: Second-harmonic generation (SHG) imaging can help reveal interactions between collagen fibers and cancer cells. Quantitative analysis of SHG images of collagen fibers is challenged by the heterogeneity of collagen structures and low signal-to-noise ratio often found while imaging collagen in tissue. The role of collagen in breast cancer progression can be assessed post acquisition via enhanced computation. To facilitate this, we have implemented and evaluated four algorithms for extracting fiber information, such as number, length, and curvature, from a variety of SHG images of collagen in breast tissue. The image-processing algorithms included a Gaussian filter, SPIRAL-TV filter, Tubeness filter, and curvelet-denoising filter. Fibers are then extracted using an automated tracking algorithm called fiber extraction (FIRE). We evaluated the algorithm performance by comparing length, angle and position of the automatically extracted fibers with those of manually extracted fibers in twenty-five SHG images of breast cancer. We found that the curvelet-denoising filter followed by FIRE, a process we call CT-FIRE, outperforms the other algorithms under investigation. CT-FIRE was then successfully applied to track collagen fiber shape changes over time in an in vivo mouse model for breast cancer.

276 citations


Journal ArticleDOI
TL;DR: The Toast++ open-source software environment for solving the forward and inverse problems in diffuse optical tomography (DOT) contains model-based iterative inverse solvers for reconstructing the volume distribution of absorption and scattering parameters from boundary measurements of light transmission.
Abstract: We present the Toast++ open-source software environment for solving the forward and inverse problems in diffuse optical tomography (DOT). The software suite consists of a set of libraries to simulate near-infrared light propagation in highly scattering media with complex boundaries and heterogeneous internal parameter distribution, based on a finite-element solver. Steady-state, time- and frequency-domain data acquisition systems can be modeled. The forward solver is implemented in C++ and supports performance acceleration with parallelization for shared and distributed memory architectures, as well as graphics processing computation. Building on the numerical forward solver, Toast++ contains model-based iterative inverse solvers for reconstructing the volume distribution of absorption and scattering parameters from boundary measurements of light transmission. A range of regularization methods are provided, including the possibility of incorporating prior knowledge of internal structure. The user can link to the Toast++ libraries either directly to compile application programs for DOT, or make use of the included MATLAB and PYTHON bindings to generate script-based solutions. This approach allows rapid prototyping and provides a rich toolset in both environments for debugging, testing, and visualization.

218 citations


Journal ArticleDOI
TL;DR: This study gives new clues on the contrast mechanisms of polarization sensitive measurements for different cancers and may provide new diagnostic techniques for clinical applications.
Abstract: Polarization measurements allow one to enhance the imaging contrast of superficial tissues and obtain new polarization sensitive parameters for better descriptions of the micro- and macro- structural and optical properties of complex tissues. Since the majority of cancers originate in the epithelial layer, probing the morphological and pathological changes in the superficial tissues using an expended parameter set with improved contrast will assist in early clinical detection of cancers. We carry out Mueller matrix imaging on different cancerous tissues to look for cancer specific features. Using proper scattering models and Monte Carlo simulations, we examine the relationship between the microstructures of the samples, which are represented by the parameters of the scattering model and the characteristic features of the Mueller matrix. This study gives new clues on the contrast mechanisms of polarization sensitive measurements for different cancers and may provide new diagnostic techniques for clinical applications.

148 citations


Journal ArticleDOI
TL;DR: This work reports label-free photoacoustic (PA) nanoscopy, which is exquisitely sensitive to optical absorption, with an 88 nm resolution, which provides super-resolution imaging with optical sectioning.
Abstract: Super-resolution microscopy techniques—capable of overcoming the diffraction limit of light—have opened new opportunities to explore subcellular structures and dynamics not resolvable in conventional far-field microscopy. However, relying on staining with exogenous fluorescent markers, these techniques can sometimes introduce undesired artifacts to the image, mainly due to large tagging agent sizes and insufficient or variable labeling densities. By contrast, the use of endogenous pigments allows imaging of the intrinsic structures of biological samples with unaltered molecular constituents. Here, we report label-free photoacoustic (PA) nanoscopy, which is exquisitely sensitive to optical absorption, with an 88 nm resolution. At each scanning position, multiple PA signals are successively excited with increasing laser pulse energy. Because of optical saturation or nonlinear thermal expansion, the PA amplitude depends on the nonlinear incident optical fluence. The high-order dependence, quantified by polynomial fitting, provides super-resolution imaging with optical sectioning. PA nanoscopy is capable of super-resolution imaging of either fluorescent or nonfluorescent molecules.

128 citations


Journal ArticleDOI
TL;DR: It is demonstrated that it is possible to clearly distinguish and quantitatively analyze several cells grouped in a “3-D cluster” as well as subcellular organelles like the nucleoli and local internal refractive index changes.
Abstract: A successful application of self-interference digital holographic microscopy in combination with a sample-rotation-based tomography module for three-dimensional (3-D) label-free quantitative live cell imaging with subcellular resolution is demonstrated. By means of implementation of a hollow optical fiber as the sample cuvette, the observation of living cells in different 3-D matrices is enabled. The fiber delivers a stable and accurate rotation of a cell or cell cluster, providing quantitative phase data for tomographic reconstruction of the 3-D refractive index distribution with an isotropic spatial resolution. We demonstrate that it is possible to clearly distinguish and quantitatively analyze several cells grouped in a “3-D cluster” as well as subcellular organelles like the nucleoli and local internal refractive index changes.

128 citations


Journal ArticleDOI
TL;DR: A user-guided segmentation method is proposed to perform the segmentation of retinal layers and features in OCT images by interactively navigating three-dimensional OCT images and demonstrating the reliability and efficiency of this method.
Abstract: Despite the existence of automatic segmentation techniques, trained graders still rely on manual segmentation to provide retinal layers and features from clinical optical coherence tomography (OCT) images for accurate measurements. To bridge the gap between this time-consuming need of manual segmentation and currently available automatic segmentation techniques, this paper proposes a user-guided segmentation method to perform the segmentation of retinal layers and features in OCT images. With this method, by interactively navigating three-dimensional (3-D) OCT images, the user first manually defines user-defined (or sketched) lines at regions where the retinal layers appear very irregular for which the automatic segmentation method often fails to provide satisfactory results. The algorithm is then guided by these sketched lines to trace the entire 3-D retinal layer and anatomical features by the use of novel layer and edge detectors that are based on robust likelihood estimation. The layer and edge boundaries are finally obtained to achieve segmentation. Segmentation of retinal layers in mouse and human OCT images demonstrates the reliability and efficiency of the proposed user-guided segmentation method.

127 citations


Journal ArticleDOI
TL;DR: The "Basic Instrumental Performance" protocol for direct measurement of relevant characteristics is presented and the relevance of the responsivity measure is demonstrated by simulations of diffuse reflectance as a function of source-detector separation and optical properties.
Abstract: Performance assessment of instruments devised for clinical applications is of key importance for validation and quality assurance. Two new protocols were developed and applied to facilitate the design and optimization of instruments for time-domain optical brain imaging within the European project nEUROPt. Here, we present the "Basic Instrumental Performance" protocol for direct measurement of relevant characteristics. Two tests are discussed in detail. First, the responsivity of the detection system is a measure of the overall efficiency to detect light emerging from tissue. For the related test, dedicated solid slab phantoms were devel- oped and quantitatively spectrally characterized to provide sources of known radiance with nearly Lambertian angular characteristics. The responsivity of four time-domain optical brain imagers was found to be of the order of 0.1 m 2 sr. The relevance of the responsivity measure is demonstrated by simulations of diffuse reflectance as a function of source-detector separation and optical properties. Second, the temporal instrument response func- tion (IRF) is a critically important factor in determining the performance of time-domain systems. Measurements of the IRF for various instruments were combined with simulations to illustrate the impact of the width and shape of the IRF on contrast for a deep absorption change mimicking brain activation. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original

114 citations


Journal ArticleDOI
TL;DR: This work investigated the imaging improvements gained by utilizing a larger number of detectors and inquired whether more detectors will result in measurable image quality improvements, pointing to significant improvements in image quality for the 256 detector array, over 64 or 128 detectors.
Abstract: Optoacoustic (photoacoustic) imaging has already showcased the capacity to offer high-resolution small animal visualization in vivo in a variety of cancer, cardiovascular, or neuroimaging applications. In particular, multispectral optoacoustic tomography (MSOT) has shown imaging along the spectral and the time dimensions, enabling sensing of multiple molecules over time and, more recently, in real time. Furthermore, cross-sectional imaging of at least 20 mm diameter has been showcased in vivo in animals and humans using 64-element curved transducers placed along a single curved line. Herein, we investigated the imaging improvements gained by utilizing a larger number of detectors and inquired whether more detectors will result in measurable image quality improvements. For this reason, we implemented MSOT using 64-, 128-, and 256-element transducers and imaged the same phantoms and animals under similar conditions. Further, corroborated by numerical simulation analysis, our findings quantify the improvements in resolution and overall image quality for the increasing number of detectors used pointing to significant improvements in image quality for the 256 detector array, over 64 or 128 detectors.

Journal ArticleDOI
TL;DR: The study results suggest that tLLLT may improve TBI both by reducing cell death in the lesion and by stimulating neurogenesis.
Abstract: The use of transcranial low-level laser (light) therapy (tLLLT) to treat stroke and traumatic brain injury (TBI) is attracting increasing attention. We previously showed that LLLT using an 810-nm laser 4 h after controlled cortical impact (CCI)-TBI in mice could significantly improve the neurological severity score, decrease lesion volume, and reduce Fluoro-Jade staining for degenerating neurons. We obtained some evidence for neurogenesis in the region of the lesion. We now tested the hypothesis that tLLLT can improve performance on the Morris water maze (MWM, learning, and memory) and increase neurogenesis in the hippocampus and subventricular zone (SVZ) after CCI-TBI in mice. One and (to a greater extent) three daily laser treatments commencing 4-h post-TBI improved neurological performance as measured by wire grip and motion test especially at 3 and 4 weeks post-TBI. Improvements in visible and hidden platform latency and probe tests in MWM were seen at 4 weeks. Caspase-3 expression was lower in the lesion region at 4 days post-TBI. Double-stained BrdU-NeuN (neuroprogenitor cells) was increased in the dentate gyrus and SVZ. Increases in double-cortin (DCX) and TUJ-1 were also seen. Our study results suggest that tLLLT may improve TBI both by reducing cell death in the lesion and by stimulating neurogenesis.

Journal ArticleDOI
TL;DR: The Grüneisen parameter, a constitutive parameter in photoacoustics, is usually measured from isobaric thermal expansion, which may not be valid for a biological medium due to its heterogeneity, is measured by applying photoacoustic spectroscopy.
Abstract: The Gruneisen parameter, a constitutive parameter in photoacoustics, is usually measured from isobaric thermal expansion, which may not be valid for a biological medium due to its heterogeneity Here, we directly measured the Gruneisen parameter by applying photoacoustic spectroscopy Laser pulses at wavelengths between 460 and 1800 nm were delivered to tissue samples, and photoacoustic signals were detected by flat water-immersion ultrasonic transducers Least-squares fitting photoacoustic spectra to molar optical absorption spectra showed that the Gruneisen parameter was 081±005 (mean±SD) for porcine subcutaneous fat tissue and 069±002 for porcine lipid at room temperature (22°C) The Gruneisen parameter of a red blood cell suspension was linearly related to hemoglobin concentration, and the parameter of bovine serum was 9% greater than that of water at room temperature

Journal ArticleDOI
TL;DR: A single-camera imaging system that can simultaneously acquire brightfield, darkfield, and phase contrast images in real time through computational illumination via a programmable light-emitting diode (LED) array at the source plane is demonstrated.
Abstract: We demonstrate a single-camera imaging system that can simultaneously acquire brightfield, darkfield, and phase contrast images in real time. Our method uses computational illumination via a programmable light-emitting diode (LED) array at the source plane, providing flexible patterning of illumination angles. Brightfield, darkfield, and differential phase contrast images are obtained by changing the LED patterns, without any moving parts. Previous work with LED array illumination was only valid for static samples because the hardware speed was not fast enough to meet real-time acquisition and processing requirements. Here, we time multiplex patterns for each of the three contrast modes in order to image dynamic biological processes in all three contrast modes simultaneously. We demonstrate multicontrast operation at the maximum frame rate of our camera (50 Hz with 2160 × 2560 pixels).

Journal ArticleDOI
TL;DR: A canine study to investigate the in vivo feasibility of photoacoustic imaging for intraoperative updates to brachytherapy treatment plans finds signal-to-noise ratios (SNRs) were similar while the contrast-to thenoise ratio (CNR) was higher in SLSC compared to DAS images.
Abstract: We conducted a canine study to investigate the in vivo feasibility of photoacoustic imaging for intraoperative updates to brachytherapy treatment plans. A fiber coupled to a 1064-nm Nd:YAG laser was inserted into high-dose-rate brachytherapy needles, which diffused light spherically. These needles were inserted through the perineum into the prostate for interstitial light delivery and the resulting acoustic waves were detected with a transrectal ultrasound probe. Postoperative computed tomography images and ex vivo photoacoustic images confirmed seed locations. Limitations with insufficient light delivery were mitigated with short-lag spatial coherence (SLSC) beamforming, providing a 10-20 dB contrast improvement over delay-and-sum (DAS) beamforming for pulse energies ranging from 6.8 to 10.5 mJ with a fiber-seed distance as large as 9.5 mm. For the same distance and the same range of energy densities, signal-to-noise ratios (SNRs) were similar while the contrast-to-noise ratio (CNR) was higher in SLSC compared to DAS images. Challenges included visualization of signals associated with the interstitial fiber tip and acoustic reverberations between seeds separated by ≤ 2 mm. Results provide insights into the potential for clinical translation to humans.

Journal ArticleDOI
TL;DR: FPM demonstrates high image quality, efficiency, and consistency in detection of tumor cells when comparing corresponding microfilter samples to standard microscopy with high correlation, and it is believed that FPM will have important implications for improved, high throughput, filtration-based CTC analysis, and, more generally, image analysis of uneven surfaces.
Abstract: Circulating tumor cells (CTCs) are recognized as a candidate biomarker with strong prognostic and predictive potential in metastatic disease. Filtration-based enrichment technologies have been used for CTC characterization, and our group has previously developed a membrane microfilter device that demonstrates efficacy in model systems and clinical blood samples. However, uneven filtration surfaces make the use of stan- dard microscopic techniques a difficult task, limiting the performance of automated imaging using commercially available technologies. Here, we report the use of Fourier ptychographic microscopy (FPM) to tackle this chal- lenge. Employing this method, we were able to obtain high-resolution color images, including amplitude and phase, of the microfilter samples over large areas. FPM's ability to perform digital refocusing on complex images is particularly useful in this setting as, in contrast to other imaging platforms, we can focus samples on multiple focal planes within the same frame despite surface unevenness. In model systems, FPM demonstrates high image quality, efficiency, and consistency in detection of tumor cells when comparing corresponding microfilter samples to standard microscopy with high correlation (R 2 ¼ 0.99932). Based on these results, we believe that FPM will have important implications for improved, high throughput, filtration-based CTC analysis, and, more generally, image analysis of uneven surfaces. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported

Journal ArticleDOI
TL;DR: This review paper provides the necessary background to understand how optical fibers function, to describe the various categories of available fibers, and to illustrate how specific fibers are used for selected biomedical photonics applications.
Abstract: Optical fiber technology has significantly bolstered the growth of photonics applications in basic life sciences research and in biomedical diagnosis, therapy, monitoring, and surgery. The unique operational characteristics of diverse fibers have been exploited to realize advanced biomedical functions in areas such as illumination, imaging, minimally invasive surgery, tissue ablation, biological sensing, and tissue diagnosis. This review paper provides the necessary background to understand how optical fibers function, to describe the various categories of available fibers, and to illustrate how specific fibers are used for selected biomedical photonics applications. Research articles and vendor data sheets were consulted to describe the operational characteristics of conventional and specialty multimode and single-mode solid-core fibers, double-clad fibers, hard-clad silica fibers, conventional hollow-core fibers, photonic crystal fibers, polymer optical fibers, side-emitting and side-firing fibers, middle-infrared fibers, and optical fiber bundles. Representative applications from the recent literature illustrate how various fibers can be utilized in a wide range of biomedical disciplines. In addition to helping researchers refine current experimental setups, the material in this review paper will help conceptualize and develop emerging optical fiber-based diagnostic and analysis tools.

Journal ArticleDOI
TL;DR: The results indicate that paraffin-embedded brain gliomas have a higher refractive index, absorption coefficient, and dielectric constant than normal brain tissue.
Abstract: The refractive indices, absorption coefficients, and complex dielectric constants of paraffin-embedded brain glioma and normal brain tissues have been measured by a terahertz time-domain spectroscopy (THz-TDS) system in the 0.2- to 2.0-THz range. The spectral differences between gliomas and normal brain tissues were obtained. Compared with normal brain tissue, our results indicate that paraffin-embedded brain gliomas have a higher refractive index, absorption coefficient, and dielectric constant. Based on these results, the best THz frequencies for different methods of paraffin-embedded brain glioma imaging, such as intensity imaging, coherent imaging with continuum THz sources, and THz pulsed imaging with short-pulsed THz sources, are analyzed.

Journal ArticleDOI
TL;DR: The nEUROPt protocol addresses the characteristic of optical brain imaging to detect, localize, and quantify absorption changes in the brain and could be a useful step toward performance tests for future standards in diffuse optical imaging.
Abstract: The nEUROPt protocol is one of two new protocols developed within the European project nEUROPt to characterize the performances of time-domain systems for optical imaging of the brain. It was applied in joint measurement campaigns to compare the various instruments and to assess the impact of technical improvements. This protocol addresses the characteristic of optical brain imaging to detect, localize, and quantify absorption changes in the brain. It was implemented with two types of inhomogeneous liquid phantoms based on Intralipid and India ink with well-defined optical properties. First, small black inclusions were used to mimic localized changes of the absorption coefficient. The position of the inclusions was varied in depth and lateral direction to investigate contrast and spatial resolution. Second, two-layered liquid phantoms with variable absorption coefficients were employed to study the quantification of layer-wide changes and, in particular, to determine depth selectivity, i.e., the ratio of sensitivities for deep and superficial absorption changes. We introduce the tests of the nEUROPt protocol and present examples of results obtained with different instruments and methods of data analysis. This protocol could be a useful step toward performance tests for future standards in diffuse optical imaging.

Journal ArticleDOI
TL;DR: The proposed methodology is able to detect the lumen borders in the OCT frames, identify the plaque region, and detect four tissue types: calcium (CA), lipid tissue (LT), fibrous tissue (FT), and mixed tissue (MT).
Abstract: Optical coherence tomography (OCT) is a light-based intracoronary imaging modality that provides high-resolution cross-sectional images of the luminal and plaque morphology. Currently, the segmentation of OCT images and identification of the composition of plaque are mainly performed manually by expert observers. However, this process is laborious and time consuming and its accuracy relies on the expertise of the observer. To address these limitations, we present a methodology that is able to process the OCT data in a fully automated fashion. The proposed methodology is able to detect the lumen borders in the OCT frames, identify the plaque region, and detect four tissue types: calcium (CA), lipid tissue (LT), fibrous tissue (FT), and mixed tissue (MT). The efficiency of the developed methodology was evaluated using annotations from 27 OCT pullbacks acquired from 22 patients. High Pearson's correlation coefficients were obtained between the output of the developed methodology and the manual annotations (from 0.96 to 0.99), while no significant bias with good limits of agreement was shown in the Bland-Altman analysis. The overlapping areas ratio between experts' annotations and methodology in detecting CA, LT, FT, and MT was 0.81, 0.71, 0.87, and 0.81, respectively.

Journal ArticleDOI
TL;DR: Using an MB2 solution that strongly attenuated all photoac acoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800-fold increase), providing a new method for spatiotemporal control ofphotoacoustic signal generation.
Abstract: Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800-fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.

Journal ArticleDOI
TL;DR: The preliminary study of simultaneous measurement of BR and HR in a clinical trial conducted on 11 healthy subjects during magnetic resonance imaging (MRI) showed very good agreement with measurements obtained from conventional MR-compatible devices.
Abstract: We propose and demonstrate the feasibility of using a highly sensitive microbend multimode fiber optic sensor for simultaneous measurement of breathing rate (BR) and heart rate (HR). The sensing system consists of a transceiver, microbend multimode fiber, and a computer. The transceiver is comprised of an optical transmitter, an optical receiver, and circuits for data communication with the computer via Bluetooth. Comparative experiments conducted between the sensor and predicate commercial physiologic devices showed an accuracy of ±2 bpm for both BR and HR measurement. Our preliminary study of simultaneous measurement of BR and HR in a clinical trial conducted on 11 healthy subjects during magnetic resonance imaging (MRI) also showed very good agreement with measurements obtained from conventional MR-compatible devices.

Journal ArticleDOI
TL;DR: Evaluated the performances of a variety of mental task combinations to determine the mental task pairs that are best suited for customized NIRS-based BCIs and found that mental task combination consisting of two of these three mental tasks showed the highest mean classification accuracies.
Abstract: A number of recent studies have demonstrated that near-infrared spectroscopy (NIRS) is a promising neuroimaging modality for brain-computer interfaces (BCIs). So far, most NIRS-based BCI studies have focused on enhancing the accuracy of the classification of different mental tasks. In the present study, we evaluated the performances of a variety of mental task combinations in order to determine the mental task pairs that are best suited for customized NIRS-based BCIs. To this end, we recorded event-related hemodynamic responses while seven participants performed eight different mental tasks. Classification accuracies were then estimated for all possible pairs of the eight mental tasks ( 8 C 2 ¼ 28). Based on this analysis, mental task combinations with rel- atively high classification accuracies frequently included the following three mental tasks: "mental multiplication," "mental rotation," and "right-hand motor imagery." Specifically, mental task combinations consisting of two of these three mental tasks showed the highest mean classification accuracies. It is expected that our results will be a useful reference to reduce the time needed for preliminary tests when discovering individual-specific mental task combinations. © 2014 Society of Photo-Optical Instrumentation Engineers (SPIE) (DOI: 10.1117/1.JBO.19.7.077005)

Journal ArticleDOI
TL;DR: The preliminary study demonstrated that HSI has the potential to be applied in vivo for noninvasive detection of tumors and a spectral-spatial classification method to distinguish cancer from normal tissue on hyperspectral images.
Abstract: Early detection of malignant lesions could improve both survival and quality of life of cancer patients. Hyperspectral imaging (HSI) has emerged as a powerful tool for noninvasive cancer detection and diagnosis, with the advantage of avoiding tissue biopsy and providing diagnostic signatures without the need of a contrast agent in real time. We developed a spectral-spatial classification method to distinguish cancer from normal tissue on hyperspectral images. We acquire hyperspectral reflectance images from 450 to 900 nm with a 2-nm increment from tumor-bearing mice. In our animal experiments, the HSI and classification method achieved a sensitivity of 93.7% and a specificity of 91.3%. The preliminary study demonstrated that HSI has the potential to be applied in vivo for noninvasive detection of tumors.

Journal ArticleDOI
TL;DR: The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device.
Abstract: The goal of this study was to determine the diagnostic capability of a multimodal spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using custom-built optical fiber-based clinical systems. Biopsies of lesions were classified using standard histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL), basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma (SCC). Spectral data were analyzed using principal component analysis. Using multiple diagnostically relevant principal components, we built leave-one-out logistic regression classifiers. Classification results were compared with histopathology of the lesion. Sensitivity/specificity for classifying MM versus PL (12 versus 17 lesions) was 100%/100%, for SCC and BCC versus AK (57 versus 14 lesions) was 95%/71%, and for AK and SCC and BCC versus normal skin (71 versus 71 lesions) was 90%/85%. The best classification for nonmelanoma skin cancers required multiple modalities; however, the best melanoma classification occurred with Raman spectroscopy alone. The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device.

Journal ArticleDOI
TL;DR: It is shown that the use of telecentric DHM provides larger field of view for a given magnification and permits more accurate QPI measurements with less number of computational operations.
Abstract: The advantages of using a telecentric imaging system in digital holographic microscopy (DHM) to study biological specimens are highlighted. To this end, the performances of nontelecentric DHM and telecentric DHM are evaluated from the quantitative phase imaging (QPI) point of view. The evaluated stability of the microscope allows single-shot QPI in DHM by using telecentric imaging systems. Quantitative phase maps of a section of the head of the drosophila melanogaster fly and of red blood cells are obtained via single-shot DHM with no numerical postprocessing. With these maps we show that the use of telecentric DHM provides larger field of view for a given magnification and permits more accurate QPI measurements with less number of computational operations.

Journal ArticleDOI
TL;DR: An approach for finding medically suitable retinal images for retinal diagnosis using a three-class grading system that consists of good, bad, and outlier classes is presented and can be integrated into any automatic retinal analysis system with sufficient performance scores.
Abstract: Retinal image quality assessment (IQA) is a crucial process for automated retinal image analysis systems to obtain an accurate and successful diagnosis of retinal diseases. Consequently, the first step in a good retinal image analysis system is measuring the quality of the input image. We present an approach for finding medically suitable retinal images for retinal diagnosis. We used a three-class grading system that consists of good, bad, and outlier classes. We created a retinal image quality dataset with a total of 216 consecutive images called the Diabetic Retinopathy Image Database. We identified the suitable images within the good images for automatic retinal image analysis systems using a novel method. Subsequently, we evaluated our retinal image suitability approach using the Digital Retinal Images for Vessel Extraction and Standard Diabetic Retinopathy Database Calibration level 1 public datasets. The results were measured through the F1 metric, which is a harmonic mean of precision and recall metrics. The highest F1 scores of the IQA tests were 99.60%, 96.50%, and 85.00% for good, bad, and outlier classes, respectively. Additionally, the accuracy of our suitable image detection approach was 98.08%. Our approach can be integrated into any automatic retinal analysis system with sufficient performance scores.

Journal ArticleDOI
TL;DR: Several results obtained with SERS show that the penetration depth of Ag NPs can exceed the stratum corneum (SC) thickness, which can be explained by both penetration of trace amounts ofAg NPs through the SC barrier and by the measurements inside the hair follicle, which cannot be excluded in the experiment.
Abstract: In order to investigate the penetration depth of silver nanoparticles (Ag NPs) inside the skin, porcine ears treated with Ag NPs are measured by two-photon tomography with a fluorescence lifetime imaging microscopy (TPT-FLIM) technique, confocal Raman microscopy (CRM), and surface-enhanced Raman scattering (SERS) microscopy. Ag NPs are coated with poly-N-vinylpyrrolidone and dispersed in pure water solutions. After the application of Ag NPs, porcine ears are stored in the incubator for 24 h at a temperature of 37°C. The TPT-FLIM measurement results show a dramatic decrease of the Ag NPs’ signal intensity from the skin surface to a depth of 4 μm. Below 4 μm, the Ag NPs’ signal continues to decline, having completely disappeared at 12 to 14 μm depth. CRM shows that the penetration depth of Ag NPs is 11.1±2.1 μm. The penetration depth measured with a highly sensitive SERS microscopy reaches 15.6±8.3 μm. Several results obtained with SERS show that the penetration depth of Ag NPs can exceed the stratum corneum (SC) thickness, which can be explained by both penetration of trace amounts of Ag NPs through the SC barrier and by the measurements inside the hair follicle, which cannot be excluded in the experiment.

Journal ArticleDOI
Ming Li1, Fusheng Zhao1, Jianbo Zeng1, Ji Qi1, Jing Lu1, Wei-Chuan Shih1 
TL;DR: A microfluidic surface-enhanced Raman scattering (SERS) sensor for rapid and label-free biomolecular detection that mitigates a common limiting factor in microfluidity SERS sensors that utilize integrated nanostructures.
Abstract: We present a microfluidic surface-enhanced Raman scattering (SERS) sensor for rapid and label-free biomolecular detection. Our sensor design mitigates a common limiting factor in microfluidic SERS sensors that utilize integrated nanostructures: low-efficiency transport of biomolecules to nanostructured surface which adversely impacts sensitivity. Our strategy is to increase the total usable nanostructured surface area, which provides more adsorption sites for biomolecules. Specifically, a nanoporous gold disk (NPGD) array, a highly effective SERS substrate, has been monolithically integrated inside a microfluidic chip. Individual NPGD is known to feature an order of magnitude larger surface area than its projected disk area. The increased surface area arises from nanoscale pores and ligaments three-dimensionally distributed in the NPGD, which manifest themselves as high-density SERS hot-spots. High-density NPGD arrays further guarantee large coverage of these hot-spots on the microchannel floor. The sensor performance has been demonstrated using Rhodamine 6G to quantify spatial uniformity and determine the shortest detection time. Next, the sensor is applied to detect two biomolecules, dopamine and urea, with unprecedented detection limit and speed compared to other existing microfluidic SERS sensors. The sensor holds great promise in point-of-care applications for various biomolecular detections. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.

Journal ArticleDOI
TL;DR: Three-dimensional Monte Carlo simulations of photon propagation combined with high resolution vascular anatomy find that 95% of the detected signal comes from the top 700 μm of tissue, and observe that single-intravascular scattering is an accurate description of photon sampling dynamics.
Abstract: Laser speckle contrast imaging (LSCI) is a powerful and simple method for full field imaging of blood flow. However, the depth dependence and the degree of multiple scattering have not been thoroughly investigated. We employ three-dimensional Monte Carlo simulations of photon propagation combined with high resolution vascular anatomy to investigate these two issues. We found that 95% of the detected signal comes from the top 700 μm of tissue. Additionally, we observed that single-intravascular scattering is an accurate description of photon sampling dynamics, but that regions of interest (ROIs) in areas free of obvious surface vessels had fewer intravascular scattering events than ROI over resolved surface vessels. Furthermore, we observed that the local vascular anatomy can strongly affect the depth dependence of LSCI. We performed simulations over a wide range of intravascular and extravascular scattering properties to confirm the applicability of these results to LSCI imaging over a wide range of visible and near-infrared wavelengths.