Light is one of the most important and versatile phenomena in nature with salient properties . Like a courier, it can transfer information from one point to another, like an alchemist, it can alter matter by initiating and moderating key processes in chemistry, biology and condensed matter. And of course, without it one could not see. Light possess color , fastest speed , coherence , polarization and wave fronts . The Short pulses of light allow expose the riot of activity hidden in molecular world . A major discovery occur in 1969, made by Robert Alfano and Stanley L. Shapiro members of GTE Labs (now Verizon) together when they made a startling observation of a new kind of laser light that spanned a large part of the visible spectrum over 10,000 cm-1 under excitation of 532 nm green ps pulses. This light now is called Supercontinuum (SC), It was published in three seminal paper in same volume of Phys Rev Letters :PRL 24, 584, 592, and 1217, (1970). Today researchers produce SC light that spans an entire octave or more using optical fibers from uv to NIR . The visible spectrum is approximately an octave, and thus the SC realizes the dream of white laser light source. The basic technique that Shapiro and I used to produce the SC involved sending very high intensity picosecond pulses of green laser light through crystals and glasses. The mechanism to explain the observed white light was self phase modulation. The SC is now 50 years old.

As the supercontinuum source reaches its fiftieth anniversary, in this short presentation I will highlight some of the steps in its development, from Alfano’s and Shapiro’s discovery and application of this phenomena using high energy, table-top, pulsed solid state lasers to the compact, all-fibre integrated configurations which have had a marked commercial impact. The principal scientific processes as well as some of the vital technological advances will be outlined which have led to extensive spectral versatility and allows the temporal format of the excitation pumps to range from the continuous wave to the femtosecond regimes.

Label-free intravital optical imaging and optical biopsies of fresh, unstained, resected tissue specimens offer a wealth of new biomarkers for assessing the tumor microenvironment and diagnosing disease. By developing widely coherent supercontinuum from photonic crystal fibers, new excitation wavelengths can be generated to tailor the light stimulus in new ways. As a result, Simultaneous Label-free Auto-fluorescence Multi-harmonic (SLAM) microscopy can visualize the rich intrinsic molecular, metabolic, and structural information in cells and tissues. Results suggest broad potential of this stain-free, slide-free, imaging technology and methodology for real-time point-of-procedure applications, including the histopathological assessment of living biopsy specimens.

We are developing a novel near-infrared spectroscopy (NIRS) technique for mTBI screening by using broadband light to detect the relative level of Cytochrome-C-Oxidase (CCO), which is a marker for brain cellular metabolism. Since mTBI is a functional injury disrupting brain metabolism, changes in CCO concentration can be identified by NIRS, making it a candidate for mTBI diagnosis. We have developed novel Super-Continuum Lasers (SCL) that can provide more than three to four orders of magnitude improvement in signal-to-noise ratio (SNR) compared to tungsten-halogen lamps currently employed for CCO measurements.

Ultrafast supercontinua are marvellous when generated in χ3 bulk, where they retain the coherence properties of their seed pulses. Such true “white laser light” is alluring to biology, chemistry and physics. However, effects such as self-focussing and filamentation fundamentally constrain its pulse energy to less than few micro-joules. Having stronger supercontinua can enhance our limit of detection in spectroscopy and accelerate micromachining. Thus, we present a novel method for supercontinuum generation in theory and experiment, liberating the fundamental energy constraints. Our preliminary world-first results indicate a doubled conversion efficiency and 104 stronger, few femtosecond pulses, compared to conventional methods.

The MIR (mid-infrared) spectral region is 3-50 m wavelength. Many molecular absorptions lie within 3-15 m wavelength, coinciding with the low-loss window of chalcogenide glass fiber-optics, giving a ‘window of opportunity’ for a new generation of molecular sensors. New bright, fiber MIR-supercontinuum (-SC) laser sources have been demonstrated in chalcogenide glass for wideband MIR molecular sensing. Recently we announced gain beyond 4 m wavelength in a Pr3+ doped chalcogenide glass fiber, with potential for long wavelength fiber lasing for pumping fiber MIR-SC. Our goal is for new portable, MIR spectroscopic systems for in vivo sensing in healthcare, including for cancer-diagnosis.

We report on our efforts towards fiber-based mid-infrared supercontinuum generation starting from ultrafast fiber lasers at 2,000 nm. Properly designed ultrafast lasers lead to supercontinuum performance similar to that of the synchrotron source in the C-H stretching region (from 3,000 nm to 4,000 nm). By routing our supercontinuum source to the FTIR microscope we demonstrate that the laser source competes or even surpasses the synchrotron source. Our latest developments extending the spectral coverage of the source up to 9,000 nm show that all-fiber supercontinuum sources are about to become available for any application across the fingerprint region.

Supercontinuum (SC) lasers are of high interest for applications like multispectral photoacoustic imaging (MSPAI), where the wide optical bandwidth of the SC laser system facilitates functional investigations on top of the structural information of various endogenous agents inside the human body. The current work addresses a promising attempt at devising high pulse energy SC laser source using telecom-range diode laser systems and few meters of standard single-mode fibers for various MSPAI applications in near-infrared (NIR) and extended-NIR wavelength regions.

As the world's leading manufacturer of supercontinuum sources over the last 15 years, NKT Photonics will present the applications that have driven the supercontinuum technology forward: From the earliest introduction in commercial microscopes to the most recent industrial applications in highly demanding industries like semiconductor metrology. Over the years, the supercontinuum technology has made the development of several state-of-the-art applications possible, e.g. confocal microscopy, FLIM, STED, OCT, etc.. The supercontinuum technology started in research lab applications but is now mature and reliable and can be used in a wide variety of industrial process monitoring applications.

In this presentation, we will introduce some of the promising applications where mid-infrared supercontinuum lasers covering from 2-10 μm can have an advantage over competing technologies, such as multi-species gas spectroscopy, fiber evanescent wave spectroscopy, waveguide characterization, and photo-acoustic imaging. One novel application using mid-IR SC is non-destructive testing using optical coherence tomography. By combining broadband supercontinuum and upconversion detection, it is possible to penetrate deeper into materials while maintaining high resolution and real-time imaging capabilities. To demonstrate this, we show results with sub-surface inspection of marine and automotive paints and coatings for evaluation of thickness, uniformity, and defects.

We present the performance of a hand-held near-infrared (NIR) imager. This point-of-care device is the next version of our portable system that was used to predict outcome of surgeries on patients with Cushing syndrome by measuring the blood content in the cheek of patients and quantifying facial plethora. The device uses a custom CMOS imaging camera with on-chip NIR filters. Illumination is provided by an incandescent lamp. Simultaneous acquisition of eight images in the wavelength range 700 nm to 980 nm avoids the effect of camera or subject motion. Therefore, this lightweight device can be easily incorporated in clinical settings.

Monitoring acute subdural hematoma (SDH) in real-time has been a clinical challenge. This study examined the feasibility of near infrared diffuse optical tomography in characterizing the three-dimensional expansion of SDH. The system was examined using a phantom with an intact human skull and disk-shaped optical absorbers. We used finite element methods for image reconstruction. The preliminary results show that our proposed method can distinguish between surface bruise and SDH, as well as localize the depths of the optical absorber at an accuracy of 75%. The accuracy of recovering the volumes of the optical absorbers is under investigation.

The inability to efficiently separate autofluorescence signals from bright background illumination is a key issue that hinders widespread deployment of optical techniques such as time-correlated single photon counting (TCSPC) in clinical settings. We introduce a novel approach to TCSPC measurements that synchronizes the fluorescence acquisition with an externally modulated light source at 50 Hz, thus guaranteeing background-free fluorescence detection and “continuous” eye-perceived specimen illumination. A color camera synchronized with fluorescence detection provides spatial resolution to the single-point measurements, to generate autofluorescence lifetime maps in real-time. We believe this method provides a new research pathway for clinical translation of optical techniques.

An all-fiberized tunable repetition rate (50kHz-10MHz) SC source for photoacoustic microscopy (PAM) and optical coherence tomography (OCT) is developed. OCT is a scattering based imaging technique, requiring low spectral noise. Noise level requirement in OCT is usually mitigated using high repetition rate (MHz) laser sources. On the other hand, PAM is a hybrid imaging modality based on optical absorption that requires high pulse energies, thus, sources operating at lower repetition rates (kHz) are preferred. Nevertheless, it is always important to quantify and understand the RIN dynamics of the SC sources for good quality PAM and OCT images.

In the current era of personalized cancer therapy, various drugs need to be rapidly tested to determine their efficacy in killing cancer cells. In this way, the most effective drug can be administered to improve therapy effectiveness. However, since the biopsy specimens are heterogeneous, efficient testing requires the use only of the viable tumor part of the specimen. Therefore, rapid and automated evaluation of specimen heterogeneity is needed. In this paper presents an automated algorithm for tissue heterogeneity estimation based on OCT images. This algorithm use image texture features to differentiate between healthy and cancer tissue.

We present a study of a potential technique to diagnose brain disease using quantum-entangled twin photons. Our method consists of preparing polarization-entangled photon pairs and sending one member of each pair through brain tissue that is either healthy or suffering brain disease, such as Alzheimers, glioblastoma or other. The tissue imparts a decohering effect on the state of the light that we examine via quantum state tomography. Our preliminary experimental data shows a difference in the entanglement measures between healthy tissue and tissue bearing Alzheimers disease. We also explore an imaging technique of brain tissue based on quantum entanglement.

In the current report, we present further developments of a unified open-access Monte Carlo (MC) based computational tool for simulation of twisted light propagation in turbid tissue-like scattering medium. We introduce an online browser-based application and a media model which considers both spatial and volumetric variations such surface roughness and subsurface scattering optical properties. The online application has been integrated with the parallel simulation framework developed in-house and is being extensively used in the ongoing studies of twisted light propagation in turbid media (e.g. phantoms and cancerous lesions). Rigorous validation against data obtained during experimental studies is presented.

Majorana-like photons are introduced from a special function class of vector vortex beams known as cylindrically vector beams. They are Laguerre-Gaussian, Bessel and Airy beams. These Majorana-like photons and their anti-photons are the same being neutral, massless, and following the state function of a Majorana self-transposed ( 𝜓 = 𝜓∗). A Majorana photon has the characteristic of both chiralities in its spin angular momentum (SAM) and orbital angular momentum (OAM). They have an inhomogeneous polarization structure and a non-separable state. These Majorana-like photons have various types of applications such as in transmission in bio-media, classical and quantum communication, microscopy among others.

We utilize the Stokes-vector and Mueller-matrix polarimetry techniques for the pathology screening of fixed mouse brain tissue at different stages of Alzheimer’s disease. We demonstrate that the presence of amyloid plaques associated with the progression of Alzheimer’s disease influences the properties of scattered polarized light. Using Poincaré sphere as a graphical tool for the visualization of the alterations of Stokes vector and statistical analysis of depolarization maps acquired with Mueller-matrix polarimetry, we demonstrate the sensitivity of both Stokes vector and high-order statistical moments of depolarization to the structural alterations in a brain tissue, associated with the progression of the disease.

This study evaluated breast cancer cells and metastasis potential using visible (532 nm) resonance Raman spectroscopy (VRRS). Three cell lines were investigated, MCF-10 (fibrocystic disease (benign)), MCF-7 (estrogen- and progesterone-receptive invasive ductal carcinoma (IDC)), and MDA-MB-231 (triple negative IDC). Peak analysis and multivariate unmixing methods including principal component analysis, partial least squares and nonnegative matrix factorization along with support vector machines were used to classify the samples. The cell lines were accurately classified with leave-one-out cross-validation. Optimal features were selected using a wrapper feature selection algorithm which helped to identify key biomarkers related to metastasis potential of the cell lines.

Various detectors have been utilized to realize a TR-NIRS system, such as PMT, SiPM, and SPAD. This paper proposed a prototype NIRS device implemented using a 128 x 128 lock-in pixel CMOS image sensor (CIS) based on lateral electric field charge modulator (LEFM) to achieve high time resolution. Preliminary experiments on a liquid phantom with varying absorption coefficient have been conducted and the ability to detect the changes of absorption coefficient has been demonstrated. The results suggest that a NIRS device using CIS is feasible, which opens the potential of a miniature wearable NIRS device.

We present a novel optical configuration for direct time-resolved measurements of luminescence from singlet oxygen both in solutions and from suspension of cells. The system is based on the superconducting single photon counting detector coupled to the confocal scanner that is modified for near-infrared measurements. The recording of a phosphorescence signal from singlet oxygen at 1270 nm have been done by time-correlated single photon counting. The performance of the system is verified by measurement of phosphorescence from singlet oxygen generated by the photosensitizers that are commonly used in photodynamic therapy: methylene blue and chlorine e6.

Optical spectroscopy – being a fast and label-free method for analysing tissue composition – has the potential for improving detection and diagnosis of diseased brain tissues such as malformations and tumours. In this study, we used a quadrifurcated optical fibre-probe system combining multiple spectroscopic techniques (fluorescence, Raman, reflectance) for examining ex vivo human brain freshly excised biopsies taken from both tumour and dysplastic tissues. The presented method and data analysis demonstrated high sensitivity and specificity in discriminating different tissue types in good agreement with the corresponding histopathological examination, paving the way for its clinical application.

In glaucoma, degeneration occurs in the retinal ganglion cells, whose cell bodies reside in the retinal nerve fiber layer (RNFL), leading to a decrease in the RNFL thickness. In clinical practice, optical coherence tomography (OCT) is used to measure the RNFL thickness for glaucoma diagnosis. Recent studies have shown that the degenerative process induces changes in optical properties of the RNFL, such as reflectivity. Because such properties can also be determined with OCT, we quantify this reduced scattering effect by determining spectroscopic attenuation coefficient (AC) in the RNFL with our proprietary autoConfoal algorithm, from two OCT B-scans of glaucomatous eyes.

Diffuse Reflectance Spectroscopy (DRS) measurements can discriminate pure fat tissue from pure invasive carcinoma. Here we investigate 1) the difference between DRS measurements of invasive carcinoma and ductal carcinoma in situ (DCIS), and 2) the classification accuracy of DRS measurements of a mixture of tissue types. DRS measurements (850–1600nm) were acquired from 107 slices (n = 1493 locations) of breast specimens. There were no significant differences between the DRS spectra of invasive carcinoma or DCIS. All locations with >75% malignant tissue were correctly classified, including DCIS locations. With a decreasing percentage of malignant tissue, the classification accuracy decreased.

Various machine learning algorithms will be presented to analyze spectral data collected by visible resonance Raman (VRR) spectroscopy to identify the cancer grades of human brain glioma tumors. The features were either based on selected fingerprint Raman peaks of key biomolecules, or retrieved by principal component analysis and partial least squares and artificial neural network (ANN). The grading was performed using multi-class classification using support vector machines, discriminant analysis and ANN. The most relevant features were searched using nested cross validation. The study showed VRR combined with machine learning provides a rapid robust molecular diagnostic tool for identifying cancer grades.

We measure and simulate the diffuse scattering return from ~30ug/cm2 of RDX, caffeine, and acetaminophen deposited on substrates consisting of smooth aluminum, silicon, and glass at a distance of 3.6 m. We demonstrate that diffuse scattering produces chemical features in the molecular fingerprint regime (7-11 um) that are governed by refractive index and modified by particle size distribution. We also find that the short-wave spectra (2.5 - 6 um) are dependent on orientation of the illumination and collection optics and will vary with respect to angle of incidence and collection.

We demonstrate an all-fiber super-continuum (SC) laser based short-wave infrared (1160nm to 2350nm) spectroscopy system that can predict protein (gluten) levels in wheat flour, at a stand-off distance. In total of 32 wheat flour samples with calibrated protein concentrations are measured with a two-arm spectroscopy system. We demonstrate that reflectance spectrum between 1160nm and 2350nm can be used to predict protein levels in wheat flour. The predicted protein concentration with the partial least square regression shows a good linear correlation (R square >0.95) to the protein level measured by the Dumas method with standard error variance down to 0.5 percent.

Label-free multiphoton imaging has been a powerful tool to study the microstructure and specific chemical distributions in biological tissue, especially in tumors and their microenvironments. Thus, this technique has great potential to assist in cancer-related clinical studies. A portable label-free multiphoton imaging system was constructed with four imaging modalities: two- and three- photon fluorescence, and second and third harmonic generation. Mosaicked multimodal images can be acquired with dual-channel detection and galvo-mirror scanning. This system was demonstrated during animal surgeries for real-time, label-free assessment of tumor tissue samples acquired via core-needle biopsy and fine-needle aspiration.

The purpose was to evaluate the metabolic activity of brain cortex after an acute hypoxia caused by the impairment of breathing or blood circulation. 12 Wistar rats aged 1 month were randomized in 2 groups: impaired breathing and blood circulation failure groups. Fluorescence under 450 nm excitation and diffuse reflectance intensity at 500-900 nm range were estimated by real time biopsy. We suppose that oxygen deficiency causes an activation of the gamma aminobutyric acid shunt mechanism. In cases of blood circulation failure, intensity changes faster than in cases of breathing impairment. Obtained data gives novel approach for resuscitation procedures standards.

ICG is known for its NIR optical properties. In addition to NIR absorption, ICG also shows an absorption band with a peak position at ~400 nm. The absorption peak at ~400 nm could be referred to the transition of the electrons from the ground state (S0) to second (S2) excited state. This transition is followed by emission with a maximum at ~557 nm. ICG is an optically unstable molecule, its NIR absorption and emission deteriorate upon optical exposure. However, unlike its NIR emission, the fluorescence emission at ~557 nm increases upon continuous optical exposure of ICG.

Short wavelength infrared windows (II: 1100-1350 nm, III: 1600-1870 and IV: 2100-2350 nm) have received increased attention. We investigated total attenuation lengths (lt) from human normal and cancerous prostate and breast tissue samples using window III. lt from normal were twice as long than cancerous prostate and breast tissues. This shows how SWIR can be used to distinguish cancer from normal and suggest that SWIR may be beneficial to patients with multiple lesions where multiple biopsies is not possible such as neurofibromatosis (hundreds of skin lesions) or multiple lipomas (numerous polyps) in the small/large bowel (not malignant but may become).

We used an optical fibre-probe system combining multiple spectroscopic techniques for in vivo examination of normal and glioblastoma (GBM) tissues in mouse brain. Specifically, we collected fluorescence, Raman, and diffuse reflectance spectra through two optical windows implanted on the mice head. The Raman and reflectance dataset were analysed using Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) for obtaining an automated classification of the examined tissues, resulting in 77% and 97% accuracy, respectively. The presented results demonstrate the potential of our method for improving the diagnosis of suspicious brain areas during surgery through a fast spectroscopic inspection.

A new method has been developed to improve DOT temporal resolution by deep-learning based pre-OT guidance, which could provide prior activation information to reduce non-sensitive data measurement. Simulations and phantom experiments have been performed to evaluate the performances of the proposed method, and demonstrate the improvement in the temporal resolution.

Near-infrared (NIR) diffuse correlation spectroscopy (DCS) provides a novel tool for clinical blood flow monitoring. Although DCS has the advantages of non-invasiveness, high sensitivity and large penetration depth, increasing its acquisition speed to achieve real-time imaging is still an on-going task. In this work, we propose a multi-channel DCS system for dynamic topography of blood flow index in deep tissues, where a dynamic nature up to one frame per second is implemented by combining the concurrency of FPGA-based 10 channel hardware correlators of multi-tau-design and NIR-sensitive avalanche photodiode detectors.

In near infrared window III (NIR III), from 1500 nm to 1800 nm, the absorption of collagen is higher than that of water, potentially allowing for deep tissue imaging of collagenous structures. But a key component to our understanding of images is the color mixing and contrast of the visible spectrum, which is determined by the way red, green, and blue signals are combined within our visual system. In most cases of NIR imaging, false color is used to highlight contrasting levels of intensity, which comes with the penalty that image features of similar intensity will have the same false color, even when they are obtained from different regions of the NIR spectrum. By assigning blue to wavelengths from 1500 nm to 1650 nm, green from 1650 nm to 1750 nm, and red from 1750 nm to 1850 nm, the characteristic absorption peak of collagen around 1700 nm gives the reflected image of collagen a unique rich purple color, which sets it apart from other tissue structures.

We have developed a deep-ultraviolet excitation fluorescence microscopy for detection of sentinel lymph node metastasis, with the aid of a deep neural network. DNA and RNA were stained with DAPI and terbium ion (Kumamoto et al. 2019). Fluorescence images of metastasis-positive/-negative lymph nodes of gastric cancer patients were used for patch-based training with a deep neural network based on Inception-v3 architecture. The performance on small patches of the fluorescence images was comparable with that of H&E images. We will discuss advantages of the fluorescence-based approach, which is promising for assisting pathologists in assessment of lymph node metastasis.

Uterine cervical cancer(UCC) is a common but preventable disease in women of reproductive age. In Africa, the incidence and mortality rate of UCC is very high due to economic and postitional limitations. In this study, we developed a low cost smartphone-based colposcopy and conducted clinical trials for a total of 353 patients in Kingdom of Eswatini. Smartphone cases and vaginal insertion parts were made using 3D printing. And light source and adapter were connected to it. The cervix images were acquired before and after applying acetic acid. Pap smear were also performed to support the imaging results.

The leading hypothesis regarding ALZ causation is that it is related to abnormal aggregation of β-amyloid and tau in the brain. It is known that, under stress conditions, indoleamine 2,3-dioxygenase shifts tryptophan metabolism away from the serotonin pathway towards the kynurenine pathway. Using label-free spectroscopy of tryptophan, N-formyl-L-kynurenine, kynurenine and kynurenic acid in ALZ and age-matched controls, we showed that a reversal of normal tryptophan/kynurenine ratio occurs in heavily affected ALZ areas (hippocampus, BA9), but not in BA17. Since ALZ develops where excess kynurenines are produced, it is possible ALZ is caused by abnormal tryptophan metabolism rather than protein aggregation.

It has been shown previously that photons entangled in polarization survive the transmission through brain media [1]. This was realized via quantum state tomography of the light transmitted through tissue slices of mouse brain. Thus, transmission quantum tomography has the potential for use in diagnosing brain disease, particularly Alzheimer’s disease. In this work, we investigate the passage of polarization-entangled photons at a wavelength of 810 nm through thick human-brain tissue samples (0.5 – 0.6 mm) that are either healthy or with Alzheimer’s disease. The sample was mounted in a confocal optical arrangement that used 10x microscope objectives. We used quantum measures, such as tangle and linear entropy to quantify the entanglement. We focused the light on the gray-matter portion of the tissues. Preliminary results show promising outcomes in differentiating diseased from healthy samples.

We investigated the utility of methylene blue (MB) fluorescence polarization (FP) imaging for detecting breast cancer at the cellular level. Fine-needle aspiration biopsies were obtained from discarded benign and malignant breast tissues. MB fluorescence emission images displayed subcellular features, enabling morphological assessment of the samples. MB FP images provided quantitative contrast to distinguish benign and cancerous cells. MB FP of cancer cells was significantly higher than that of the benign. Quantitative fluorescence polarization imaging of MB shows promise for detecting breast cancer in single cells.

Terbium ions, Tb3+, fluoresced in a cell at deep-ultraviolet excitation. Intensity of the fluorescence was dropped by RNA decomposition. It was also found that fluorescence intensity of Tb3+ conjugated with DNA increased with strand dissociation. These results indicated specificity of Tb3+ to single-stranded nucleic acid, mostly RNA in cell and tissue. We employed Tb3+ and Hoechst, DNA-specific dyes, for deep-ultraviolet excitation fluorescence imaging. With this imaging, nucleolus, nucleoplasm, and cytoplasm were discriminated. Thanks to the small penetration depth of deep-ultraviolet light into tissue, this imaging modality was useful for slide-free histology and rapid cancer detection in a human lymph node.

Metabolic dynamics is essential to unraveling the mechanistic basis of many biological processes, and cannot be imaged in vivo by using traditional methods. Here we developed a new method that combines D2O probing and SRS (DO-SRS) to visualize metabolic dynamics in live animals. The enzymatic incorporation of D2O-derived deuterium (D) into biomolecules will generate carbon-deuterium (C-D) bonds in macromolecules. We developed spectral unmixing methods to obtain C-D signals with macromolecular selectivity, and applied DO-SRS to reveal metabolic dynamics in C. elegans, zebrafish, and mice, to study developmental biology, aging, and tissue homeostasis, and to visualize tumor boundaries and metabolic heterogeneity.

We report the development and the pre-clinical testing of a manual scanning OCT-based probe for core needle biopsy guidance. While stereotactic radiography, ultrasound, computed tomography, and magnetic resonance imaging are used to guide needle placement within a tumor, the optical probe provides the radiologist with the capability to examine tissue cellularity at the tip of the biopsy needle. The capability to investigate tissue cellularity prior to taking the biopsy could help reduce the number of non-diagnostic biopsies and increase the amount of viable tumor tissue within the biopsy core. This last aspect is very important in the new era of personalized cancer therapy, because greater tissue quantity is needed for various biomarker assays. This technology has been evaluated by us on a rabbit model of soft tissue cancer. Our results indicate the capability of this OCT-based probe for determining the in situ cellularity of the tissue at the tip of the biopsy needle.

The kidney is the most transplanted organ and two-thirds of which are obtained from deceased donors. Frozen-section microscopy techniques are often used to quickly evaluate donor kidney biopsies; however, these are often inadequate guides for predicting post-transplant allograft function. Among morphological indicators that correlate with organ quality, collagen deposition plays a primary role, and can serve as indicators of transplant success. However, special collagen stains are too time-consuming to be practical in the urgent transplant setting. We demonstrate a new kind of microscope approach, DUET (Dual mode Emission Transmission microscopy), that can highlight collagen, directly from frozen-section slides, within minutes.

Cancer diagnosis is critical in patient care yet it currently depends on time-consuming histopathology processes. We report a new method of computational staining in place of the traditional hematoxylin and eosin (H&E) staining. This method is derived from chemometric fluorescence microscopic imaging of unstained specimens. The computationally stained images visually differentiate specific cell properties, such as cellular metabolism of NADH, FAD, as well as protein production of tryptophan and elastin. Different color encoding strategies will be discussed including emulating the traditional H&E staining and optimizing for the contrast. The preliminary study on lung tissues suggests the proposed approach is a promising rapid histopathology alternative.

Glucose metabolism not only provides the energy for physiological functioning of organs, but also sustains cellular homeostasis and growth in animals and humans.we developed a new technique, Spectral TRacing of DEuterium isotope (STRIDE) microscopy, which is able to track the Raman spectra of C-D bonds in protein and lipids, and using linear algebra we would separate these signals to spectrally unmix the components. We first validated our STRIDE technique by Stimulated Raman Scattering ( SRS) imaging of cells cultured in [D7]-glucose (a glucose isotopologue) and mice administrated with [D7]-glucose in drinking water in vivo. Both experiments demonstrated distinct Raman peaks of C-D bonds, which distinguished various types of glucose-derived macromolecules (lipids, protein, DNA, RNA, and carbohydrates). Further, we applied STRIDE imaging and successfully detected metabolic dynamics in various organs in animals.

Spectroscopic optical coherence tomography (OCT) delivers spectroscopic information paired with structural information, a combination that promises to improve diagnostic accuracy of tissue abnormalities. Here we present an all-fiber based OCT system with a 550 nm bandwidth covering the spectral region from 1050 nm to 1600 nm, where both adipose fat and collagen have distinct absorption profiles, the identification of which will help distinguish healthy tissue from pathological tissue. The system is based on a conventional supercontinuum source and a dispersive Fourier transform.

Laser-based diagnostics and therapeutics show promise for many neurological disorders. However, the poor transparency of cranial bone limits the spatial resolution and interaction depth that can be achieved with these technologies. We have recently demonstrated a new method to address this challenge in biomedical research through the use of a novel transparent cranial implant made from nanocrystalline yttria-stabilized zirconia (nc-YSZ). In addition, we have also explored the use of Optical Clearing Agents (OCAs) to achieve a local, reversibly and temporarily reduction of the scalp scattering prior light irradiation. Our results show that the transparent nc-YSZ implants coupled with the OCAs perform well in providing enhanced optical access to the brain tissue, without need for repeated craniotomies or scalp removal.

The cause of mesenteric ischemia differs from the age of patients and underlying health conditions. Current intraoperative assessment of tissue viability is subjective and based on the experience of the surgeon. In this study, we examined different ischemic conditions of superior mesenteric vein (SMV) ligation, superior mesenteric artery (SMA) ligation, mesenteric segmental occlusion and reperfusion in preclinical studies using a real-time laser speckle contrast imaging (LSCI). Our results show that LSCI perfusion map clearly displays a tissue perfusion level of bowels. Quantitative analysis also reveals the difference of tissue perfusion between necrotic lesions and transitional zones for each group.

Although the basic mechanism of ECMO and related treatment have been increasingly mature, there is still a high proportion of complications. Currently, clinicians can only adjust the pattern of ECMO through basic physiological signs, but this method is not good at detecting hemodynamic changes in peripheral tissues, and there is no reliable and immediate evaluation mechanism. In this study, the ability of subknee blood circulation was evaluated by fNIRS. Monitoring and adjusting blood perfusion volume of peripheral tissues can reduce the incidence of complications and achieve the feasibility and effectiveness of the ability assessment of blood circulation function.

Fluorescence emission spectroscopic characterization of saliva and in vivo tissue of normal, oral squamous cell carcinoma, Leukoplakia, and oral submucous fibrosis conditions were studied. The samples were excited at 350 nm and their corresponding fluorescence emission were due to fluorophores NADH, FAD and Porphyrin. To resolve the overlapping peaks, the emission spectra were subjected to spectral deconvolution method. Variations in relative distribution, peak shifts and broadening of peaks were observed with respect to fluorophores NADH, FAD, and porphyrin for saliva and tissues of oral cancer patients indicating molecular changes due to the altered metabolic pathway in cells. The correlation study establishes the diagnostic potential of saliva from cancer patients.

Heart attacks and strokes represent 25.1% of worldwide deaths. 63% of stroke patients have at least one episode of hypoxia being able to cause coma, seizures, and even brain death. Previously, we introduced a transparent nanocrystalline yttria-stabilized-zirconia (nc-YSZ) cranial implant to provide optical access to the brain. This implant may enhance diagnosis and treatments of neurological disorders by optical techniques. Here, we use the Monte Carlo method to assess the optical access provided by the implant to detect normal and decreased oxygen saturation. The penetration depth and diffusely reflected energy, as well as a proof of concept, showed the feasibility of monitoring oxygen saturation through this implant.