Deep learning data augmentation for Raman spectroscopy cancer tissue classification.

Recently, Raman Spectroscopy (RS) was demonstrated to be a non-destructive way of cancer diagnosis, due to the uniqueness of RS measurements in revealing molecular biochemical changes between cancerous vs. normal tissues and cells. In order to design computational approaches for cancer detection, the quality and quantity of tissue samples for RS are important for accurate prediction. In reality, however, obtaining skin cancer samples is difficult and expensive due to privacy and other constraints. With a small number of samples, the training of the classifier is difficult, and often results in overfitting. Therefore, it is important to have more samples to better train classifiers for accurate cancer tissue classification. To overcome these limitations, this paper presents a novel generative adversarial network based skin cancer tissue classification framework. Specifically, we design a data augmentation module that employs a Generative Adversarial Network (GAN) to generate synthetic RS data resembling the training data classes. The original tissue samples and the generated data are concatenated to train classification modules. Experiments on real-world RS data demonstrate that (1) data augmentation can help improve skin cancer tissue classification accuracy, and (2) generative adversarial network can be used to generate reliable synthetic Raman spectroscopic data

Review of Modern Techniques for the Assessment of Skin Hydration

Skin hydration is a complex process that influences the physical and mechanical properties of skin. Various technologies have emerged over the years to assess this parameter, with the current standard being electrical probe-based instruments. Nevertheless, their inability to provide detailed information has prompted the use of sophisticated spectroscopic and imaging methodologies, which are capable of in-depth skin analysis that includes structural and composition details. Modern imaging and spectroscopic techniques have transformed skin research in the dermatological and cosmetics disciplines, and are now commonly employed in conjunction with traditional methods for comprehensive assessment of both healthy and pathological skin. This article reviews current techniques employed in measuring skin hydration, and gives an account on their principle of operation and applications in skin-related research

Single-shot two-dimensional full-range optical coherence tomography achieved by dispersion control

We present a full-range Fourier-domain optical coherence tomography (OCT) system that is capable of acquiring two-dimensional images of living tissue in a single shot. By using line illumination of the sample in combination with a two-dimensional imaging spectrometer, 1040 depth scans are performed simultaneously on a sub-millisecond timescale. Furthermore, we demonstrate an easy and flexible real-time single-shot technique for full-range (complex-conjugate cancelled) OCT imaging that is compatible with both two-dimensional as well as ultrahighresolution OCT. By implementing a dispersion imbalance between reference and sample arms of the interferometer, we eliminate the complex-conjugate signal through numerical dispersion compensation, effectively increasing the useful depth range by a factor of two. The system allows us to record 6.7 × 3.2 mm images at 5 μm depth resolution in 0.2 ms. Data postprocessing requires only 4 s. We demonstrate the capability of our system by imaging the anterior chamber of a mouse eye in vitro, as well as human skin in vivo. © 2009 Optical Society of America

High-speed polarization sensitive optical frequency domain imaging with frequency multiplexing

Polarization sensitive optical coherence tomography (PS-OCT) provides a cross-sectional image of birefringence in biological samples that is complementary in many applications to the standard reflectance-based image. Recent ex vivo studies have demonstrated that birefringence mapping enables the characterization of collagen and smooth muscle concentration and distribution in vascular tissues. Instruments capable of applying these measurements percutaneously in vivo may provide new insights into coronary atherosclerosis and acute myocardial infarction. We have developed a polarization sensitive optical frequency domain imaging (PS-OFDI) system that enables high-speed intravascular birefringence imaging through a fiber-optic catheter. The novel design of this system utilizes frequency multiplexing to simultaneously measure reflectance of two incident polarization states, overcoming concerns regarding temporal variations of the catheter fiber birefringence and spatial variations in the birefringence of the sample. We demonstrate circular cross-sectional birefringence imaging of a human coronary artery ex vivo through a flexible fiber-optic catheter with an A-line rate of 62 kHz and a ranging depth of 6.2 mm

Swept source / Fourier domain polarization sensitive optical coherence tomography with a passive polarization delay unit

Polarization sensitive optical coherence tomography (PS-OCT) is a functional imaging method that provides additional contrast using the light polarizing properties of a sample. This manuscript describes PS-OCT based on ultrahigh speed swept source / Fourier domain OCT operating at 1050nm at 100kHz axial scan rates using single mode fiber optics and a multiplexing approach. Unlike previously reported PS-OCT multiplexing schemes, the method uses a passive polarization delay unit and does not require active polarization modulating devices. This advance decreases system cost and avoids complex synchronization requirements. The polarization delay unit was implemented in the sample beam path in order to simultaneously illuminate the sample with two different polarization states. The orthogonal polarization components for the depth-multiplexed signals from the two input states were detected using dual balanced detection. PS-OCT images were computed using Jones calculus. 3D PS-OCT imaging was performed in the human and rat retina. In addition to standard OCT images, PS-OCT images were generated using contrast form birefringence and depolarization. Enhanced tissue discrimination as well as quantitative measurements of sample properties was demonstrated using the additional contrast and information contained in the PS-OCT images.National Institutes of Health (U.S.) (NIH R01-EY011289-25)National Institutes of Health (U.S.) (R01-EY013178-12)National Institutes of Health (U.S.) (R01-EY013516-09)National Institutes of Health (U.S.) (R01-EY019029-04)National Institutes of Health (U.S.) (R01-EY018184-05)National Institutes of Health (U.S.) (R01-CA075289-14)National Institutes of Health (U.S.) (R01-HL095717-03)National Institutes of Health (U.S.) (R01-NS057476-05)United States. Air Force Office of Scientific Research (AFOSR FA9550-10-1-0063)United States. Dept. of Defense. Medical Free Electron Laser Program (FA9550-07-1-0101

Alternative Splicing Events Are a Late Feature of Pathology in a Mouse Model of Spinal Muscular Atrophy

Spinal muscular atrophy is a severe motor neuron disease caused by inactivating mutations in the SMN1 gene leading to reduced levels of full-length functional SMN protein. SMN is a critical mediator of spliceosomal protein assembly, and complete loss or drastic reduction in protein leads to loss of cell viability. However, the reason for selective motor neuron degeneration when SMN is reduced to levels which are tolerated by all other cell types is not currently understood. Widespread splicing abnormalities have recently been reported at end-stage in a mouse model of SMA, leading to the proposition that disruption of efficient splicing is the primary mechanism of motor neuron death. However, it remains unclear whether splicing abnormalities are present during early stages of the disease, which would be a requirement for a direct role in disease pathogenesis. We performed exon-array analysis of RNA from SMN deficient mouse spinal cord at 3 time points, pre-symptomatic (P1), early symptomatic (P7), and late-symptomatic (P13). Compared to littermate control mice, SMA mice showed a time-dependent increase in the number of exons showing differential expression, with minimal differences between genotypes at P1 and P7, but substantial variation in late-symptomatic (P13) mice. Gene ontology analysis revealed differences in pathways associated with neuronal development as well as cellular injury. Validation of selected targets by RT–PCR confirmed the array findings and was in keeping with a shift between physiologically occurring mRNA isoforms. We conclude that the majority of splicing changes occur late in SMA and may represent a secondary effect of cell injury, though we cannot rule out significant early changes in a small number of transcripts crucial to motor neuron survival

Polarization-sensitive optical frequency domain imaging based on unpolarized light

Polarization-sensitive optical coherence tomography (PS-OCT) is an augmented form of OCT, providing 3D images of both tissue structure and polarization properties. We developed a new method of polarization-sensitive optical frequency domain imaging (PS-OFDI), which is based on a wavelength-swept source. In this method the sample was illuminated with unpolarized light, which was composed of two orthogonal polarization states (i.e., separated by 180° in the Poincaré sphere) that are uncorrelated to each other. Reflection of these polarization states from within the sample was detected simultaneously and independently using a frequency multiplexing scheme. This simultaneous sample probing with two polarization states enabled determination of the depth-resolved Jones matrices of the sample. Polarization properties of the sample were obtained by analyzing the sample Jones matrices through eigenvector decomposition. The new PS-OFDI system ran at 31K wavelength-scans/s with 3072 pixels per wavelength-scan, and was tested by imaging a polarizer and several birefringent tissues such as chicken muscle and human skin. Lastly the new PS-OFDI was applied to imaging two cancer animal models: a mouse model by injecting cancer cells and a hamster cheek pouch model. These animal model studies demonstrated the significant differences in tissue polarization properties between cancer and normal tissues in vivo. © 2011 Optical Society of America

Optical coherence tomography for the diagnosis of skin cancer in adults

Background: Early accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell carcinoma (SCC) are high-risk skin cancers, which have the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised, with potential to infiltrate and damage surrounding tissue. Anxiety around missing early cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Optical coherence tomography (OCT) is a microscopic imaging technique, which magnifies the surface of a skin lesion using near-infrared light. Used in conjunction with clinical or dermoscopic examination of suspected skin cancer, or both, OCT may offer additional diagnostic information compared to other technologies. Objectives: To determine the diagnostic accuracy of OCT for the detection of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants, basal cell carcinoma (BCC), or cutaneous squamous cell carcinoma (cSCC) in adults. Search methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; EMBASE; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles. Selection criteria: Studies evaluating OCT in adults with lesions suspicious for invasive melanoma and atypical intraepidermal melanocytic variants, BCC or cSCC, compared with a reference standard of histological confirmation or clinical follow-up. Data collection and analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Our unit of analysis was lesions. Where possible, we estimated summary sensitivities and specificities using the bivariate hierarchical model. Main results: Five studies including 529 cutaneous lesions (273 malignant lesions) were included, providing nine datasets for OCT, two for visual inspection alone, and two for visual inspection plus dermoscopy. Studies were of moderate to poor quality using data driven thresholds for test positivity and giving poor accounts of reference standard interpretation and blinding. Studies may not be representative of populations eligible for OCT in practice, for example due to high disease prevalence in study populations, and may not reflect how OCT is used in practice, for example by using previously acquired OCT images. It is not possible to make summary statements regarding accuracy of detection of melanoma or of cSCC because of the paucity of studies, small sample sizes, and for melanoma differences in the OCT technologies used (high-definition versus conventional resolution OCT), and differences in the degree of testing performed prior to OCT (i.e. visual inspection alone or visual inspection plus dermoscopy). Pooled data from two studies using conventional swept-source OCT alongside visual inspection and dermoscopy for the detection of BCC estimated the sensitivity and specificity of OCT as 95% (95% CI: 91, 97%) and 77% (95% CI: 69, 83%), respectively. When applied to a hypothetical population of 1000 lesions at the mean observed BCC prevalence of 60%, OCT would miss 31 BCCs (91 fewer than would be missed by visual inspection alone and 53 fewer than would be missed by visual inspection and dermoscopy), and OCT would lead to 93 false positive results for BCC (a reduction in unnecessary excisions of 159 compared to using visual inspection alone and of 87 compared to visual inspection and dermoscopy). Authors' conclusions: Insufficient data are available on the use of OCT for the detection of melanoma or cSCC. Initial data suggests conventional OCT may have a role for the diagnosis of BCC in clinically challenging lesions, our meta-analysis showing a higher sensitivity and higher specificity when compared to visual inspection and dermoscopy. However the small number of studies and varying methodological quality means implications to guide practice cannot currently be drawn. Appropriately designed prospective comparative studies are required, given the paucity of data comparing OCT with dermoscopy and indeed other similar diagnostic aids such as reflectance confocal microscopy