This PDF file contains the front matter associated with SPIE Proceedings Volume 11234 including the Title Page, Copyright information, Table of Contents, Introduction, and Conference Committee listing.

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.

Optical coherence tomography (OCT) is a non-invasive cross-sectional imaging technique with micrometer resolution. OCT is useful, non-invasive imaging technique of the internal structure, and it has been applied in many fields, especially medicine and industry. The theoretical axial resolution is determined by the center wavelength and bandwidth of the light source, and the wider the bandwidth is, the higher the axial resolution is. Supercontinuum is the high-power, ultrawideband light source. We have been investigating ultrahigh-resolution (UHR)-OCT using supercontinuum. The characteristics of OCT imaging depend on the optical wavelength used. In this talk, we report our recent work of the wavelength dependence of UHR-OCT using a supercontinuum for biomedical imaging. In order to investigate the wavelength dependence of UHR-OCT, the wideband, high-power, low-noise supercontinua were generated at wavelengths of 0.8, 1.1, 1.3, and 1.7 um based on ultrashort pulses and nonlinear fibers. The wavelength dependence of OCT imaging was examined quantitatively using biological phantoms. Ultrahigh-resolution imaging of a rat lung was demonstrated with wavelengths of 0.8 – 1.0 um UHR-OCT. The variation of alveolar volume was estimated using 3D image analysis. We also developed UHR-spectral domain-OCT and optical coherence microscopy (OCM) at 1.7 um. The high-resolution and high-penetration imaging of turbid tissue, especially mouse brain, was demonstrated. The wavelength dependence of OCM was also discussed in terms of mouse brain imaging.

For monitoring of concussion, brain function, organ condition and other medical applications, what is needed is a non-invasive method of monitoring tissue metabolism. MRI-based functional imaging technology detects changes in blood oxygenation, a correlate of neural activity, and thus may offer a prediction of prognosis in cases of concussion and other cerebral traumas. Yet, potential relationships between perturbations to cerebral metabolism and patient outcomes cannot be effectively exploited clinically because we lack a practical, low-cost, non-invasive means to monitor cerebral oxygenation and metabolism in the emergency department, operating room, or medical facilities. We have developed a device to optically assay the redox state of Cytochrome-C-Oxidase (CCO), the mitochondrial enzyme responsible for the last step of the electron transport chain. Changes in CCO redox reflect changes in respiratory flux, and thus changes in the rate of oxidative adenosine triphosphate (ATP) synthesis. In other words, changes in CCO reflect brain cell’s metabolic activity more directly than the traditional blood oxygenation measurement methods. To non-invasively measure changes in CCO as well as blood oxygenation, we have developed a SuperContinuum Infrared Spectroscopy of Cytochrome-C-Oxidase (SCISCCO) system that uses an all-fiber integrated, supercontinuum light source to simultaneously measure both of the new (CCO) and the traditional (blood oxygenation) markers of neural metabolism. The SCISCCO system is validated by confirming the near-infrared spectrum of CCO in vitro. To demonstrate in vivo feasibility, the measured responses of oxygenation and CCO responses to acute ischemia (e.g., blood pressure tests) in human participants are compared to data from the literature. Furthermore, we show that the new device’s measurements of oxygenated (HbO) and deoxygenated (HbR) hemoglobin in response to breath hold challenges are principled and consistent with previously reported findings. The validated SCISCCO system is finally applied to measure cerebral oxygenation and the redox state of CCO in participants during an attention test protocol. Twenty-five healthy adults completed an attention task that included nine 60-second periods of attention task, interleaved with 60-s periods of resting baseline. It has been well established that the frontal lobe of the human brain is active during tasks of attention. We therefore predicted that attention task should elicit an increase in HbO concentration accompanied by a decrease in redox state of CCO (e.g., ratio of oxidized CCO to reduced CCO) in frontal lobe brain regions as measured with the SCISCCO system. Our findings are consistent with our predictions: HbO concentration increases while CCO concentration decreases during the attention blocks relative to the resting baseline, thereby indicating an increase in oxidative metabolism of the frontal lobe brain regions of interest. Our systematic, multi-method approach thus validates the new device as well as the validity of the metabolic biomarkers that it measures. The SCISCCO system could be a new tool for monitoring brain and organ metabolism, which could be invaluable for screening concussion patients or use in an operating or emergency room to gauge patient’s organ response to treatments.

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.

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.

Non-invasive optical techniques on the basis of quenching of phosphorescence by molecular oxygen represent a powerful tool to perform mapping of oxygen content in biological systems. The development of phosphorescent oxygensensitive probes suitable for biological applications, especially in vivo, remains a challenging task. In this paper we applied for biological investigations one novel and one previously published Ir(III)-based complexes. This complexes demonstrate low cytotoxicity at the concentrations ≤70 μM and good uptake by cultured cancer cells. Both compounds were primarily located within the cytoplasm. Using TCSPC-based phosphorescence lifetime macro-imaging in vivo, we found that IR-2 complex shows detectable phosphorescence in tumor tissue in mice upon local injection. These results illustrate the high potential of organometallic complexes under study for mapping of oxygen level in cells and tissues.

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 vortex (CVV) beams among them are the Laguerre-Gaussian 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 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.

Alzheimer’s disease, being a major societal burden, demands improvement of current techniques for its treatment and diagnostics. Currently only autopsy histology is able to provide the definite diagnosis for Alzheimer’s disease. However, the procedure is rather time consuming and costly. In the current study, we utilized Stokes and Mueller polarimetry techniques to screen for amyloid-β (Aβ) deposits in formalin-fixed, paraffin-embedded mouse brain tissue at different stages of Alzheimer’s disease. The study has shown that the presence of Aβ plaques influences the properties of scattered polarized light. The Poincaré sphere was used as a graphical tool for the visualization of the alterations of the Stokes vector, obtained with Stokes polarimetry, whereas statistical moments were used for the analysis of depolarization distributions that were acquired with Mueller polarimetry. We demonstrate the sensitivity of the last component of the Stokes vector, the degree of polarization and high-order statistical moments of depolarization to the structural alterations in brain tissue, which correspond to the disease progression. The described approach has a potential to improve the existing pathology screening methods and facilitates Aβ detection in AD research.

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.

Antibiotic resistance is a burgeoning global public health threats of our time. Antibiotic resistance is a multifactorial and complex problem which cannot be solved by only developing stronger and better antibiotic compounds. Rapid detection and characterization of pathogenic bacteria are critical for effectively treating bacterial infections without exacerbating the resistance problem. Here, we present a novel highly-sensitive and label-free platform, Rapid-Ultra-Sensitive-Detector (RUSD), that utilizes the high reflectance coefficient of light at the interface between low-refractive-index and high-refractive-index media. The sensitivity of RUSD is three to four orders of magnitude higher than conventional optical density-based methods. Utilizing RUSD, we can detect as low as ~20 bacterial cells or a single fungal cell. This technique does not require any sophisticated signal processing steps and it enables growth rate measurements in less than an hour. Finally, we can now measure antibiotics resistance of several gram-negative and gram-positive bacteria, including Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, within two hours.

Time-resolved (TR) near-infrared spectroscopy (NIRS) offers non-invasive clinical applications in monitoring the blood oxygenation, where absolute values of oxygenated and deoxygenated hemoglobin, and absorption and scattering coefficient, can be obtained. 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 the lateral electric field-charge modulator (LEFM) to achieve high time resolution. Preliminary experiments based on the reflectance of an agar phantom with varying absorption coefficient have been conducted and the ability to detect the changes in the absorption coefficient has been demonstrated. The reflectance of the agar phantom is directly observed by the image sensor, which was operated at a time-window of 900 ps with a sensor detection area of 2.9mm² . The results suggest that a NIRS device using CIS is feasible, which opens the potential of a miniature wearable time-resolved NIRS device.

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.

Surgery is the usual treatment for removing malformations and tumours in brain; however, the lack of contrast between diseased tissues and normal brain is a major problem. Magnetic Resonance Imaging (MRI) can be used to detect them, but brain shifts may severely reduce the accuracy of surgical removal procedures. In this framework, optical spectroscopy – being a fast and label-free method for analysing tissue composition – has the potential for improving detection and diagnosis of diseased areas. In this study, we used a quadrifurcated optical fibre-probe system combining multiple spectroscopic techniques for analysing ex vivo human brain freshly excised biopsies taken from both tumour and dysplastic tissues. All spectral recordings were done immediately after surgical resection, requiring less than 2 minutes for each sample. The recorded data were analysed using Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) for obtaining an automated classification of the examined samples based on the intrinsic spectral information provided by all three techniques. Significant differences were observed between dysplastic and tumour spectra, resulting in high sensitivity (83%) and specificity (73%). In particular, diffuse reflectance and UVexcited fluorescence spectroscopies provided the highest accuracies in discriminating different tissue types (78% and 75%, respectively) in good agreement with the corresponding histopathological examination; moreover, their combination with Raman spectroscopy resulted in a further improve of the classification capability up to 85%. The presented method demonstrates the huge potential of multimodal spectroscopy for the examination of brain tissues and opens the way for possible applications in surgical environment.

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 sparse particles of RDX, caffeine, and acetaminophen deposited on substrates consisting of smooth aluminum, silicon, and glass substrates at a distance of 3.6 m using a mid-infrared supercontinuum FTIR sensor. The measured spectra show that molecular fingerprint regime contains reflectance peaks that can be used for chemical identification and the mid-wave infrared provides information for target orientation. Furthermore, we demonstrate that spectra obtained using our supercontinuum FTIR sensor can be accurately simulated using a Bobbert-Vlieger model. The Bobbert-Vlieger model can then be used to create a library that can account for the trace chemical, underlying substrate, and target orientation, for stand-off chemical identification.

We demonstrate an all-fiber super-continuum (SC) laser based near infrared (1160nm to 2350nm) spectroscopy system that is capable of measuring protein (gluten) levels in wheat flour, at a stand-off distance. We show that reflectance spectrum between 1160nm and 2350nm can be used to measure protein levels in wheat flour. The measured 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. Our system could be used for non-destructive, real-time determination of the protein level of wheat flour at a stand-off distance in industrial settings such as food factories or flour milling plants.

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.

Indocyanine green (ICG) is a United States Food and Drug Administration approved near-infrared (NIR) chromophore used in clinics for the last six decades. It has been used for cardiac output, hepatic function measurements, NIR imaging, and anticancer therapy. ICG is known for its NIR optical properties. in addition to the well-known NIR absorption, ICG also shows an absorption band with a peak maximum at ~400 nm. However, insignificant information is available about its optical properties in the visible wavelength range. The absorption peak at ~400 nm could be referred to as the transition of the electrons from the ground (S₀) state to second excited (S₂) state. After excitation to the S2 state, these electrons could directly relax to S₀ state, this transition causes an emission with a maximum at ~557 nm. ICG is an optically unstable molecule, its NIR absorption and emission deteriorate upon optical exposure. However, optical exposure does not seem to affect the higher energy transitions of ICG adversely. Unlike the NIR emission, the fluorescence emission of ICG at ~557 nm increases upon continuous optical exposure. To the best of our knowledge, this is the first report on the S₂ state mediated emission enhancement due to the light exposure of ICG in the visible wavelength range. Improvement in the optical properties of the ICG due to optical exposure might open several exciting areas of research where its application could be broadened.

We demonstrate label-free multimodal multiphoton microscopy in human skin tissue with an ultrafast Er:fiber-laserbased source that emits femtosecond pulses at 775 nm and 1250 nm. This novel two-color fiber-based source enables second-harmonic generation, third-harmonic generation, and two-photon excitation fluorescence, which serves as a potential solution to optical virtual skin biopsy with compactness, robustness, and cost-effectiveness.

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.

Antibiotic resistance is a burgeoning global public health threats of our time. Antibiotic resistance is a multifactorial and complex problem which cannot be solved by only developing stronger and better antibiotic compounds. Rapid detection and characterization of pathogenic bacteria are critical for effectively treating bacterial infections without exacerbating the resistance problem. Here, we present a novel highly-sensitive and label-free platform, Rapid-Ultra-Sensitive-Detector (RUSD), that utilizes the high reflectance coefficient of light at the interface between low-refractive-index and high-refractive-index media. The sensitivity of RUSD is three to four orders of magnitude higher than conventional optical density-based methods. Utilizing RUSD, we can detect as low as ~20 bacterial cells or a single fungal cell. This technique does not require any sophisticated signal processing steps and it enables growth rate measurements in less than an hour. Finally, we can now measure antibiotics resistance of several gram-negative and gram-positive bacteria, including Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, within two hours.

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.

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.

Laser-based diagnostics and therapeutics show promise for many neurological disorders. However, the poor transparency of the 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 (ncYSZ). In addition, we have also explored the use of optical clearing agents (OCAs) to achieve a local, reversible and temporal 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 recurrent craniotomies or scalp removal.

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.

In vivo Native Fluorescence spectroscopic characterization of oral tissue and saliva of same group of normal, and patients with oral squamous cell carcinoma conditions were studied at 350 nm excitation. The measured fluorescence emission spectra exhibit broad emission with peaks due to NADH, FAD and Porphyrin. To resolve the emission from individual fluorophores, the measured fluorescence spectra were subjected to spectral deconvolution. Further, the variations in relative distribution, peak shifts and spectral broadening were analyzed with respect to the fluorophores, NADH, FAD, and porphyrin. The changes in the above photophysical characteristics of various native fluorophores between normal and cancer group in both tissue and saliva confirms that there is a significant molecular level changes during the transformation of normal into cancer. The extracted spectral signatures of tissues and saliva were also subjected to linear discriminant analysis and the diagnostic accuracy between tissue and saliva were compared.

The aim of the study was to compare the metabolic activity of brain cortex after the acute hypoxia caused by the impairment of breathing or blood circulation. Male Wistar rats were randomized in two groups: impaired breathing and blood circulation failure groups. Fluorescence under 365 and 450 nm excitation and diffuse reflectance intensity at 550-820 nm range were estimated. We found that after long-term hypoxic conditions, notable metabolic changes occur. We suppose that oxygen deficiency causes an activation of the GABA shunt mechanism. In cases of blood circulation failure, fluorescence intensity changes faster than in cases of breathing impairment.

The short wavelength infrared (SWIR) region (1000-2500 nm) has three near-infrared (NIR) windows (1100-1350 nm, 1600-1870 and 2100-2350 nm). These windows have received increased attention in imaging and spectroscopy. We investigated the total attenuation lengths (lt) (based on absorption and scattering properties of light) through human normal and malignant prostate and breast tissues. It was found, using window III (at a wavelength of 1700 nm), that l_t from prostate normal and cancerous tissues were 589 and 216 microns, whereas l_t from breast normal and cancerous tissues were 271 and 106 microns. This non-invasive SWIR technique can show how prostate and breast cancer are different from normal prostate and breast. This could be important for patients who have hundreds of potential tumors, in which numerous biopsies are not possible. Important examples include patients with multiple skin, lung or bowel lesions. For example, patients with Von Recklinghausen’s Disease (neurofibromatosis), which occurs in about one in 2800 people, may have multiple (perhaps hundreds) of benign tumors, but have a markedly increased risk of developing cancer. These lesions are far too many to biopsy. Patients may be multiple lipomas. Many patients have numerous polyps in the small or large bowel which are not malignant, but may become so. It is very common in parts of the country that many inhabitants there have multiple “cannonball” lesions on chest x-ray that may be cancer, sarcoidosis or areas of fungal (coccidioidomycosis, histoplasmosis, aspergillosis etc.) accumulation. In addition, when patient has multiple lesions, they can also be monitored at frequent intervals to see if there are changes in any suspicious lesions.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumour in adults, and the survival rate of patients affected by this disease is strongly dependent on the successful resection of the tumour. In this framework, multimodal optical spectroscopy could provide a fast and label-free tool for improving tumour detection and guiding the surgical removal of diseased tissues. In this study, we used an optical fibre-probe system combining multiple spectroscopic techniques for in vivo examination of normal and GBM tissues in mouse brain. Spectroscopic measurements based on fluorescence, Raman, and diffuse reflectance spectroscopy were performed on anesthetized animals through two optical windows implanted on the head of each mouse. Then, the recorded data were analysed using Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) for obtaining an automated classification of the examined tissues based on the intrinsic spectral information provided by Raman and reflectance spectroscopy. These techniques provided 77% and 97% classification accuracy, respectively, by taking advantage of the intrinsic molecular content of the examined tissues. In particular, the high sensitivity and specificity achieved by means of reflectance spectroscopy indicate that such technique is the most suited for in vivo detection of GBM. The presented results demonstrate the potential of our method for improving the diagnosis of suspicious brain areas during surgery through a very fast spectroscopic inspection, thus helping the surgeon in removing all tumour tissues and reducing the probability of GBM recurrence.

Functional near-infrared spectroscopy techniques, in the form of either optical topography (OT) or diffuse optical tomography (DOT), can non-invasively recover the hemodynamic changes occurring in the activated cerebral cortex. In comparison with the traditional OT that provides a less quantitative absorption perturbation map along the subject domain surface, a successful DOT has ability to quantify depth-resolved information that relies on abundant boundary overlapping measurements using a high-density (HD) source-detector array. To achieve a trade-off between the temporal resolution and sensitivity by channel cross-talk suppression, a hybrid frequency- and time-division-multiplexing strategy have to be normally adopted to the HD-DOT implementation, where the temporal resolution degradation due to the multi-field illuminations might still prevent from capturing the high frequency information. In this work, a deep-learning based pre-OT method has been proposed to improve the temporal resolution of HD-DOT. The pre-OT could provide prior information on activation regions to exclude measurements of non-sensitive data. We have performed simulation and phantom experiments to evaluate the performances of the proposed method, and demonstrated its superiority over the stand-alone HD-DOT in improving both the temporal resolution and localization accuracy.

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-τ -design and NIR-sensitive avalanche photodiode detectors. The flow-velocity resolution, measurement fidelity and imaging depth of the system were evaluated by phantom experiments. In vivo experiments on human arm were then performed that accurately imaged the shape and position of the blood vessels and demonstrated the ability of the proposed methodology to capture blood flow changes.

We have developed a real-time multi-wavelength spatial frequency domain (SFD) diffuse optical tomography (DOT) to characterize the optical properties of biological tissues, using single-pixel imaging based on lock-in photon-counting. In our approach, three laser diodes at wavelengths of 450 nm, 520 nm and 635 nm, are intensity-modulated by square waves of three frequencies (temporal-encoding), respectively, and focused into the first digital micromirror device (DMD) to generate a sinusoidal illumination pattern at selected spatial frequencies. The reflected light from the surface of turbid medium are spatially integrated by the second DMD, successively using sampling patterns based on the two- dimensional discrete cosine transform (DCT) bases around the spatial modulation frequencies (spatial-compressing). The temporally encoded and spatially compressed multi-wavelength signals that are detected from photomultiplier tube are firstly demodulated by a highly-sensitive lock-in photon-counting module for temporal-decoding, and then uncompressed into the spatial frequency domain images by the inverse DCT, from which tomographic images of the absorption coefficient are finally reconstructed using the first-order Rytov approximation of the diffusion equation. The phantom experiments show that the proposed method can achieve a reconstruction error within 10%, and a temporal resolution of less than 10 s.

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-formylL-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, Brodmann’s Area 9), but not in minimally-affected areas such as Brodmann’s Area 17. Since ALZ develops only in areas of the brain where excess kynurenines are produced, it is possible ALZ is caused by abnormal tryptophan metabolism rather than protein aggregation.