This PDF file contains the front matter associated with SPIE Proceedings Volume 10340, including the Title Page, Copyright information, Table of Contents, Introduction, and Conference Committee listing.

The international health care costs associated with Alzheimer’s disease (AD) and dementia have been predicted to reach $2 trillion USD by 2030. As such, there is urgent need to develop new treatments and diagnostic methods to stem an international health crisis. A major limitation to therapy and diagnostic development is the lack of complete understanding about the disease mechanisms. Spectroscopic methods at synchrotron light sources, such as FTIR, XRF, and XAS, offer a “multi-modal imaging platform” to reveal a wealth of important biochemical information in situ within ex vivo tissue sections, to increase our understanding of disease mechanisms.

Background: In excess of 60% of all cancers are detected in low and middle-income countries, with breast cancer (BC) the dominant malignancy for women. Incidence rates continue to climb, most noticeably in the less than 50-year-old population. Expansion of mammography infrastructure and resources is lacking, resulting in over 60% of women diagnosed with stage III/IV BC in the majority of these countries. Optical Breast Spectroscopy (OBS) was shown to correlate well with mammographic breast density (MBD). OBS could aid breast screening programs in low- and middle-income countries by lowering the number of mammographs required for complete population coverage. However, its performance needs to be tested in large population trails to ensure high sensitivity and acceptable specificity. Methods: For the planned studies in low- and middle-income countries in different continents, online methods need to be implemented to monitor the performance and data collection by these devices, operated by trained nurses. Based on existing datasets, procedures were developed to validate an individual woman's data integrity and to identify operator errors versus system malfunctions. Results: Using a dataset comprising spectra from 360 women collected by 2 instruments in different locations and with 3 different trained operators, automated methods were developed to identify 100% of the source or photodetector malfunctions as well as incorrect calibrations and 96% of instances of insufficient tissue contact. Conclusions: Implementing the dataset validation locally in each instrument and tethered to a cloud database will allow the planned clinical trials to proceed.

Background: The majority of de novo cancers are diagnosed in low and middle-income countries, which often lack the resources to provide adequate therapeutic options. None or minimally invasive therapies such as Photodynamic Therapy (PDT) or photothermal therapies could become part of the overall treatment options in these countries. However, widespread acceptance is hindered by the current empirical training of surgeons in these optical techniques and a lack of easily usable treatment optimizing tools. Methods: Based on image processing programs, ITK-SNAP, and the publicly available FullMonte light propagation software, a work plan is proposed that allows for personalized PDT treatment planning. Starting with, contoured clinical CT or MRI images, the generation of 3D tetrahedral models in silico, execution of the Monte Carlo simulation and presentation of the 3D fluence rate, Φ, [mWcm^-2] distribution a treatment plan optimizing photon source placement is developed. Results: Permitting 1-2 days for the installation of the required programs, novices can generate their first fluence, H [Jcm^-2] or Φ distribution in a matter of hours. This is reduced to 10th of minutes with some training. Executing the photon simulation calculations is rapid and not the performance limiting process. Largest sources of errors are uncertainties in the contouring and unknown tissue optical properties. Conclusions: The presented FullMonte simulation is the fastest tetrahedral based photon propagation program and provides the basis for PDT treatment planning processes, enabling a faster proliferation of low cost, minimal invasive personalized cancer therapies.

We propose a simple, numerical procedure for dispersion mapping of an object, which can be easily used for every OCT data set acquired from a Fourier domain system employing light source of sufficiently broad spectral bandwidth. The mapped value is Group Velocity Dispersion and its determination is based on the estimation of the difference in material’s thickness calculated from two images obtained for different spectral ranges. Instead of using two separate light sources to achieve that, we propose to apply a filter-based, numerical procedure that synthesizes two spectra centered around different wavelengths from one sufficiently broadband spectrum.

Molecular imaging modalities, like multimodal imaging, e.g. the combination of coherent-anti-Stokes Raman scattering (CARS), second-harmonic generation (SHG) and two-photon-excited fluorescence (TPEF), feature a unique potential for disease diagnostics and treatment monitoring. In order to use the full potential of multi-modal imaging for diagnostic tasks powerful image analysis methods are necessary, which translate the physical measurements into medical meaningful information. This translation process requires standardization, correction procedures and statistical models like regression or classification models. With the help of these techniques medical relevant information can be extracted and used for the diagnostics of cancer or inflammation related diseases.

Lattice light-sheet (LLS) microscopy provides ultrathin light sheets of a two-dimensional optical lattice that allows us imaging three-dimensional (3D) objects for hundreds of time points at sub-second intervals and at or below the diffraction limit. Galectin-3 (Gal3), a carbohydrate-binding protein, triggers glycosphingolipid (GSL)-dependent biogenesis of morphologically distinct endocytic vesicles that are cargo specific and clathrin independent. In this study, we apply LLS microscopy to study the dynamics of Gal3 dependent endocytosis in live T cells. This will allow us to observe Gal3-mediated endocytosis at high temporal and excellent 3D spatial resolution, which may shed light on our understanding of the mechanism and physiological function of Gal3-induced endocytosis.

Protein phosphorylation controls fundamental biological processes. Dysregulation of protein kinase is associated with a series of human diseases including cancer. Protein kinase A (PKA) activity has been reported to serve as a potential prognostic marker for cancer. To this end, we developed a non-radioactive, rapid, cheap and robust scheme based on surface-enhanced Raman spectroscopy (SERS) for label-free detection of PKA phosphorylation using gold nanostars (AuNS) functionalized with BSA-kemptide. While bovine serum albumin (BSA) proteins stabilized the AuNS, kemptide, which is a high affinity substrate peptide specific for PKA, were phosphorylated in vitro to generate Raman signals that were identified by performing principal component analysis (PCA) on the acquired SERS spectra.

Contact between a medical device and tissue accounts for approximately a third of damage to soft tissue in hospitals. The use of sensors at the interface between the device and tissue can be used to maintain the optimum pressure and reduce such injuries. A sensorised endotracheal tube has been developed and is proposed as a method of reducing soft tissue damage and improving design of future devices. Optical fibre sensing is used to monitor both cuff contact pressure (via a fibre Bragg grating) and tissue perfusion (via reflectance photoplethysmography). The monitoring system developed has been used in an animal study and demonstrates reliable measurement of contact pressure and perfusion.

We have developed a high-resolution optical coherence elastography system capable of estimating Young’s modulus in tissue volumes with an isotropic resolution of 15 μm over a 1 mm lateral field of view and a 100 μm axial depth of field. We demonstrate our technique on healthy and hypertensive, freshly excised and intact mouse aortas. Our technique has the capacity to delineate the individual mechanics of elastic lamellae and vascular smooth muscle. Further, we observe global and regional vascular stiffening in hypertensive aortas, and note the presence of local micro-mechanical signatures, characteristic of fibrous and lipid-rich regions.

The ever-increasing spread and emergence of antibiotic resistance poses a serious threat to global public health. With the existence of Carbapenem-resistant Enterobacteriaceae (CRE) produced by the Klebsiella Pneumoniae bacteria, it renders the use of carbapenems, the last-resort class of β-lactam antibiotics, useless against combating against bacterial infections. Such infections reduce the ability to treat complex infections due to the lack of antibiotic options for treatment, leading to CRE-associated mortalities. Current methods of detection, like CarbaNP test and Modified Hodge’s Test, have significant limitations in that the time taken for detection of carbapenemase activity ranges between hours to days, and are non-specific in detecting the specific phenotype, making it challenging to isolate patients rapidly and to devise appropriate treatment for infected patients. We propose a methodology by utilising Surface Enhanced Raman Spectroscopy (SERS) to study bacterial β-lactamase activity. This is done via the use of gold nanostars (AuNS), which have reported excellent SERS properties, conjugated with a β-lactam antibiotic ceftriaxole, as a proof-of-concept study to analyse the changes in the SERS spectra associated with cleavage of the β-lactam ring upon interaction with the New Delhi Metalloproteinase (NDM)- producing Escherichia coli (Class B β-lactamase). We are able to obtain detection of carbapenemase activity within 25 minutes, with the associated changes in SERS spectra being diminishing of SERS peaks at 1358cm^-1 and 1495cm^-1. This project can be further extended to study the activity of other classes of β-lactamases and other β-lactam antibiotics to improve this state of technology for potential adoption by healthcare institutions.

Optical fibre sensing is a platform technology for applications in biomedical and environmental monitoring. Fibre Bragg Gratings can be used to monitor parameters such as pressure and temperature. Alternatively, coating the fibres with functional layers, either at the tip of the fibre, on a U-shaped fibre, or a long period grating enables sensing of analytes in liquids and gases. This paper describes the application of optical fibre sensing techniques during mechanical ventilation via an endotracheal tube in critical care. Functional coatings on the fibres are used to monitor humidity of inspired air and can be used to monitor other analytes.

During the last decade, endoluminal laser treatment (ELT) has been rapidly developing. Protocols using radially emitting ELT fibres in combination with infrared laser light show clinical advantages over the bare-fibre technique and near infrared irradiation. Although the clinical response rate is high several side effects occurred. Innovative light application systems and feedback systems are therefore being under development to potentially improve the clinical situation. The irradiation patterns of bare fibres and radially emitting 1-ring and 2-ring fibres were measured using the goniometer technique. The device robustness, device handling and tissue effects were investigated using the established ox-foot-model. Furthermore, temperature measurements were performed either intraluminal within the irradiation field using a tiny temperature sensor and on the outer surface of the vessel wall by means of a thermocamera. All fibres showed sufficient mechanical and thermal robustness. The destruction threshold is far beyond the light powers employed during clinical application. The 1-ring fibre showed very high peak temperatures for a short time, while the 2-ring-fibre hold its somewhat lower maximum temperature for a longer time. Both forms of energy application resulted in the desired shrinkage and destruction effect. In this regard, the handling of the 2-ring fibre appears subjectively more convenient with reduced sticking-related problems. Acute tissue effects could be investigated to improve the understanding especially of the interaction between handling, maneuvers and tissue effects. The 2-ring radially emitting fibre in combination with IR laser light and specific application parameters showed improved handling and safety features.

Malignant gliomas are a devastating brain tumor disease with very poor prognosis. Stereotactic biopsy sampling is routinely used in larger neurosurgical centers to confirm the diagnosis of a suspected brain tumor. This procedure is associated with risk of blood vessel rupture as well as false-negative results. Recent investigations suggest a potential of light-based techniques to improve both therapy and diagnosis of GBM. Optical guidance can be utilized to improve the biopsy sampling procedure in terms of safety, reliability, and efficacy. Recording of optical signals (transmission, remission, fluorescence) can be potentially integrated into a biopsy needle for providing optical detection of tumor tissue and blood vessel recognition during the biopsy sampling. Optical signals can also be used for monitoring purposes during photodynamic therapy. Here, fluorescence signals recorded before the treatment indicate the presence and accumulation level of photosensitizer, while photobleaching of the photosensitizer fluorescence during the treatment can be used as a measure of the effectiveness of the therapy. Finally, transmitted light can reveal problematic tissue-optical conditions as well as changes of the optical properties of the treated tissue, which may be relevant with regard to treatment prognosis and strategy. Different optical concepts for interstitial PDT monitoring and optical tissue property assessment are presented.

A spatial structure for which mirror reflection cannot be represented by rotations and translations is chiral. For photonic crystals and metamaterials, chirality implies the possibility of circular dichroism, that is, that the propagation of left-circularly polarized light may differ from that of right-circularly polarized light. Here we draw attention to chiral sheet- or surface-like geometries based on chiral triply-periodic minimal surfaces. Specifically we analyse two photonic crystal designs based on the C(Y) minimal surface, by band structure analysis and by scattering matrix calculations of the reflection coefficient, for high-dielectric contrasts.

Polarization-sensitive OCT (PS-OCT) has proven useful in determining the stress-induced birefringence of non-biological materials, but such utility in biological tissues subjected to stress has not been well studied yet. To study stress-induced birefringence of biological tissues, we use a swept-source PS-OCT system with passively depth-encoded, orthogonal polarization states in the illumination path and polarization-diversity detection and a Mueller formalism in post-processing. We present measurements of stress-induced changes in the birefringence of non-biological and biological samples that provide useful benchmarks in further assessing the utility of this approach.

We examined the impact of axial length on superficial retinal vessel density (SRVD) and foveal avascular zone area (FAZA) measurement using optical coherence tomography angiography. The SRVD and FAZA were quantified before and after correction for magnification error associated with axial length variation. Although SRVD did not differ before and after correction for magnification error in the parafoveal region, change in foveal SRVD and FAZA were significant. This has implications for clinical trials outcome in diseased eyes where significant capillary dropout may occur in the parafovea.

Label-free imaging of the blood and lymphatic vessel networks of the conjunctiva of the eye is important in assessing the drainage pathways affected by glaucoma. We utilize the characteristically low signal in optical coherence tomography (OCT) provided by such vessels in ex vivo tissue to characterize their morphology in two and three dimensions. We demonstrate this method on conjunctiva from six porcine eyes, showing the ready visualization of both vessel networks. Such ex vivo characterization is a necessary precursor for future in vivo studies directed towards improving glaucoma surgery.

A fibre-based full-range polarisation-sensitive optical coherence tomography system is developed to enable complete capture of the structural and birefringence properties of the anterior segment of the human eye in a single acquisition. The system uses a wavelength swept source centered at 1.3 μm, passively depth-encoded, orthogonal polarisation states in the illumination path and polarisation-diversity detection. Off-pivot galvanometer scanning is used to extend the imaging range and compensate for sensitivity drop-off. A Mueller matrix-based method is used to analyse data. We demonstrate the performance of the system and discuss issues relating to its optimisation.

We report a new type of all-optical ultrafast laser-scanning microscopy( (at a line-scan rate of 20 MHz) based on a phenomenon called free-space angular-chirp-enhanced delay (FACED). It results in the generation of a reconfigurable array of spatiotemporally encoded virtual pulsed sources, which acts as a scanning laser beam. We demonstrate its application in high-throughput multivariate image-based single-cell analysis (10,000 cells/sec).

Quantitative assessment of upper airway geometry using optical coherence tomography in burns patients could provide physicians with the information needed to make critical decisions. We have developed a high speed catheter based OCT system capable of real time imaging in airways up to 3cm in diameter. Preliminary scans of inhalation injured airways are presented to demonstrate the feasibility of aOCT as a diagnostic tool for assessing burns patients.

Publisher’s Note: This paper, originally published on 29 April 2017, was withdrawn per author request.

Fetal Alcohol Syndrome (FAS) refers to the broad spectrum of developmental and behavioral effects caused due to prenatal alcohol exposure (PAE).

Wide range of abnormalities vary depending on the amount of alcohol consumed and the period of consumption during gestation.

PAE during early stages of pregnancy is very common. However a large number of women continue to consume alcohol even during the second trimester, a critical period for fetal neurogenesis and angiogenesis.

Optical coherence tomography (OCT) has shown to be extremely useful in embryonic imaging.

Our previous work showed that OCT is capable of quantitative assessment of ventriculomegaly caused by maternal alcohol consumption.

Although structural changes and changes in blood flow in the fetal brain after maternal alcohol consumption have been studied, acute vasculature changes are not well documented.

Speckle variance OCT (SVOCT), is a functional extension of OCT that has been used to study vasculature development in embryos.

We use SVOCT, to detect vasculature changes in the embryonic brain in utero, minutes after maternal alcohol consumption.