The Moscone Center
San Francisco, California, United States
28 January - 2 February 2017
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Translational Research Presentations

Photonic Therapeutics and Diagnostics
(ordered chronologically by start date and time)


Sub-diffuse structured light imaging provides macroscopic maps of microscopic tissue structure
Paper 9696-1

Author(s):  Stephen C. Kanick, Thayer School of Engineering at Dartmouth (United States), et al.
Conference 9696: Molecular-Guided Surgery: Molecules, Devices, and Applications II
Session 1: Advanced Molecular Imaging Methods I
Date and Time: Saturday, February 13, 2016, 8:00 AM

This study uses structured light imaging to provide quantitative wide-field maps of tissue ultrastructural biomarkers. A model based approach is developed and validated to interpret reflectance in terms of spatial frequency, reduced scattering coefficient, absorption coefficient, and a metric of the scattering phase function that is related to the fractal dimension of the scatterers. This multi-scale scatter imaging approach used in a pilot clinical study to characterize differences in the spatial distributions among tissue types in breast lumpectomy samples.


Imaging and modeling of collagen architecture in living tissue with polarized light transfer
Paper 9696-2

Author(s):  Jessica C. Ramella-Roman, Florida International Univ. (United States), et al.
Conference 9696: Molecular-Guided Surgery: Molecules, Devices, and Applications II
Session 1: Advanced Molecular Imaging Methods I
Date and Time: Saturday, February 13, 2016, 8:30 AM

Monitoring of collagen arrangement and cross-linking has been utilized to diagnose a variety of medical conditions and guide surgical intervention. We have developed a suite of tools and models based on polarized light transfer for the assessment of collagen presence, cross-linking, and orientation in living tissue. Here we will present some example of such approach applied to the human cervix. We will illustrate a novel Mueller Matrix imaging system for the study of cervical tissue; furthermore we will show how our model of polarized light transfer through cervical tissue compares to the experimental findings. Finally we will show validation of the methodology through histological results and Second Harmonic imaging microscopy.


Noncontact diffuse optical assessment of blood flow changes in head and neck free tissue transfer flaps
Paper 9689-67

Author(s):  Guoqiang Yu, Univ. of Kentucky (United States), et al.
Conference 9689C: Optical Imaging, Therapeutics, and Advanced Technology in Head and Neck Surgery and Otolaryngology
Session 1: Clinical and Operative Head and Neck Cancer Imaging
Date and Time: Saturday, February 13, 2016, 8:50 AM

Knowledge of tissue blood flow (BF) changes after free tissue transfer may enable surgeons to early predict the failure of flap thrombosis. This study used our recently developed noncontact diffuse correlation spectroscopy to monitor BF changes in free flaps without getting in contact with the targeted tissue. Eight free flaps were elevated in patients with head and neck cancer; one of the flaps failed. The BF recoveries over the seven successful flaps were found to be significantly higher than the unsuccessful flap. Measurement of BF recovery after flap anastomosis holds the potential to act early to salvage ischemic flaps.


Three-photon imaging of ovarian cancer
Paper 9689-131

Author(s):  Jennifer K. Barton, The Univ. of Arizona (United States), et al.
Conference 9689E: Diagnosis and Treatment of Diseases in the Breast and Reproductive System II
Session 1: Gynecology
Date and Time: Saturday, February 13, 2016, 8:50 AM

Three-photon microscopy enables high resolution, deep tissue imaging, and is now feasible in endoscopic configurations due to the development of fiber-coupled femtosecond laser systems. We imaged surgical discard ovarian and fallopian tube tissue of patients without disease and with ovarian adenocarcinoma, to determine the mechanisms of contrast. These images were compared to optical coherence tomography and frozen sections stained for various tissue constituents. Three-photon excited fluorescence and third harmonic generation signal came strongly from lipids and connective tissue. There was limited overlap with two-photon information, suggesting that three-photon microscopy can provide additional information for early diagnosis of ovarian cancer.


Diagnosis of female genital tract melanocytic lesions based on pigment chemistry using pump-probe laser microscopy
Paper 9689-2

Author(s):  Francisco E. Robles, Duke Univ. (United States), et al.
Conference 9689A: Photonics in Dermatology and Plastic Surgery
Session 2: Skin Cancer I
Date and Time: Saturday, February 13, 2016, 9:00 AM

Melanoma of the vulva is the second most common type of malignancy afflicting that organ, and caries poor prognosis. This potentially life-threatening disease is also clinically similar to nonmalignant lesions known as melanotic macules, which have high prominence (c.a., 10%) among the general female population. In this work we apply a novel nonlinear optical method, pump-probe microscopy, to quantitatively analyze female genitalia tract melanocytic lesions. Pump-probe microscopy provides chemical information of endogenous pigments with subcellular resolution. We find significant quantitative chemical and morphological differences in melanin pigmentation between invasive melanoma, melanoma in-situ and non-malignant melanocytic lesions.


New imaging-based biomarkers for melanoma diagnosis using CARS microscopy
Paper 9689-3

Author(s):  Hequn Wang, Wellman Ctr. for Photomedicine (United States), et al.
Conference 9689A: Photonics in Dermatology and Plastic Surgery
Session 2: Skin Cancer I
Date and Time: Saturday, February 13, 2016, 9:20 AM

Recent studies suggest pheomelanin may play an important role in melanomagenesis. Here, we show for the first time that coherent anti-Stokes Raman scattering (CARS) microscopy system could visualize and characterize pheomelanin in cultured siRNA knockdown melanoma cells, melanocytes extracted from redhead mice, ex vivo and in vivo ear tissue from redhead mice. We also demonstrate the capability of CARS to identify pheomelanin inside amelanotic melanoma patient samples. We believe these pheomelanotic CARS features can be used as potential new biomarkers for melanoma detection, especially for amelanotic melanomas.


4D microscope-integrated OCT improves accuracy of ophthalmic surgical manuevers
Paper 9693-5

Author(s):  Oscar Carrasco-Zevallos, Duke Univ. (United States), et al.
Conference 9693: Ophthalmic Technologies XXVI
Session 2: Ophthalmic Imaging: Clinical and Surgical
Date and Time: Saturday, February 13, 2016, 9:30 AM

While ophthalmic microsurgery has benefitted from rapid advances in instrumentation and techniques, the basic principles of the operating microscope have not changed since the 1930’s. Our 4D microscope integrated OCT (MIOCT) system can record and display the surgical field stereoscopically through the microscope oculars using a dual-channel heads-up display (HUD) at up to 10 micron-scale volumes per second. Here, we demonstrate that 4D MIOCT guidance improves the accuracy of depth-based microsurgical maneuvers in mock surgery trials. Additionally, 4D MIOCT in 52 human eye surgeries revealed to the surgeon in real-time previously unrecognized lesions that were invisible through the operating microscope.


First clinical pilot study with intravascular polarization sensitive OCT
Paper 9689-94

Author(s):  Martin Villiger, Harvard Medical School (United States), et al.
Conference 9689D: Diagnostic and Therapeutic Applications of Light in Cardiology
Session 1: Advanced OCT
Date and Time: Saturday, February 13, 2016, 9:30 AM

Polarization sensitive (PS) OCT provides measures of tissue birefringence and depolarization in addition to the structural OCT signal. Ex vivo studies have demonstrated that birefringence and depolarization can identify important aspects of the mechanical integrity and vulnerability of atherosclerotic plaques. To evaluate the potential of PS-OCT in the clinical setting we performed a pilot study in 30 patients. Comparing consecutive pullbacks of the same coronary artery validated the repeatability and robustness of PS-OCT in the clinical setting. In addition we observed that the birefringence and depolarization features vary significantly across lesions with identical structural OCT appearance, suggesting morphological subtypes.


A portable cross-shape near-infrared spectroscopic detector for bone marrow lesions diagnosis
Paper 9689-165

Author(s):  Ting Li, Univ. of Electronic Science and Technology of China (China), et al.
Conference 9689F: Optics in Bone Surgery and Diagnostics
Session 1: Musculoskeletal Imaging and Diagnostics I
Date and Time: Saturday, February 13, 2016, 9:50 AM

Bone marrow lesions (BMLs) is an incidence-increasing disease which seriously hazard to human health and the patients always suffered from invasive, painful, and high health risk biopsy/aspiration diagnosis. It is highly in need of a noninvasive and safe BMLs detector. We attempted to develop a noninvasive, real-time, continuous measurement, easy-operated optical device aimed at detecting bone marrow diseases and carried out both phantom and in-vivo experiments to testify the feasibility of our device in BMLs diagnosis and during-surgery guidance.


Cervical Intraepithelial Neoplasia treatment: a non-invasive translational technology
Paper 9689-135

Author(s):  Natalia M. Inada, Univ. de São Paulo (Brazil), et al.
Conference 9689E: Diagnosis and Treatment of Diseases in the Breast and Reproductive System II
Session 1: Gynecology
Date and Time: Saturday, February 13, 2016, 9:50 AM

This is a minimally invasive and translational technology presenting a new device under approval. Was tested a clinical protocol using topical MAL-PDT of over than 60 patients with low-grade CIN by Human Papilloma Virus (HPV) infection. The safety and efficacy were evaluated and based on these results a multicenter study is ongoing for high-grade CIN diagnosis and treatment.


Intraoperative detection and elimination of microscopic tumors in head and neck
Paper 9689-70

Author(s):  Dmitri Lapotko, Rice Univ. (United States), et al.
Conference 9689C: Optical Imaging, Therapeutics, and Advanced Technology in Head and Neck Surgery and Otolaryngology
Session 1: Clinical and Operative Head and Neck Cancer Imaging
Date and Time: Saturday, February 13, 2016, 9:50 AM


Defining a path for critical dosimetry measures and surrogate tools that can facilitate clinical success
Paper 9694-4

Author(s):  Brian W. Pogue, Thayer School of Engineering at Dartmouth (United States), et al.
Conference 9694: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV
Session 2: Photodynamic Therapy II
Date and Time: Saturday, February 13, 2016, 10:50 AM

Photodynamic therapy can be a highly complex treatment with more than one parameter to control, or in some cases it is easily implemented with little control other than prescribed drug and light values. The role of measured dosimetry as related to clinical adoption has not been as successful as it could have been, and part of this may be from the conflicting goals of advocating for as many measurements as possible for accurate control, versus companies and clinical adopters advocating for as few measurements as possible, to keep it simple. An organized approach to dosimetry selection is required, which shifts from mechanistic measurements in pre-clinical and early phase I trials, towards just those essential dose limiting measurements and a focus on possible surrogate measures in phase II/III trials. This essential and surrogate approach to dosimetry should help successful adoption of clinical PDT if successful. The examples of essential dosimetry points and surrogate dosimetry tools which might be implemented in phase II and higher trials are discussed for solid tissue PDT with verteporfin and skin lesion treatment with aminolevulinc acid.


Blood coagulation profiling in patients using optical thromboelastography (OTEG)
Paper 9689-98

Author(s):  Markandey M. Tripathi, Wellman Ctr. for Photomedicine (United States), et al.
Conference 9689D: Diagnostic and Therapeutic Applications of Light in Cardiology
Session 2: Blood
Date and Time: Saturday, February 13, 2016, 11:00 AM

In this clinical study, we investigate Optical Thromboelastography (OTEG), a novel technique for real-time blood coagulation profiling in 269 patients, and demonstrate its capability in detecting coagulation defects rapidly using a few drops of whole blood. In OTEG, temporal laser speckle intensity fluctuations from a clotting blood are analyzed and changes in blood viscoelastic modulus during coagulation are measured. Our results show that coagulation parameters derived using OTEG are strongly correlated with standard Thromboelastography (TEG), demonstrating the potential of OTEG for rapid evaluation blood coagulation status in cardiovascular patients at the point of care.


Intraoperative assessment of breast tumor margins using a multimodal photoacoustic tomography system
Paper 9689-137

Author(s):  Rui Li, Purdue Univ. (United States), et al.
Conference 9689E: Diagnosis and Treatment of Diseases in the Breast and Reproductive System II
Session 2: Tumor Margin Assessment
Date and Time: Saturday, February 13, 2016, 11:00 AM

Achieving time-efficient and highly-sensitive intraoperative evaluation of breast cancer margins is essential for accurate removal of the tumor. Photoacoustic tomography, inherently compatible with ultrasound imaging, provides chemical specific contrast and centimeter penetration depth with high-speed; thus it offers a compelling method of breast tumor margin evaluation intraoperatively. We demonstrate assessment of intraoperative breast tumor margins using a multimodal imaging system with multi-wavelength photoacoustic mode, ultrasound mode, and ultrasound radio frequency spectrum analysis. Consistent with histopathology, the results highlight the potential of multimodal photoacoustic tomography as a high-speed and accurate method for real-time intraoperative tumor margin evaluation in breast-conserving surgeries.


In-situ photopolymerized and monitored implants: successful application to an intervertebral disc replacement
Paper 9689-168

Author(s):  Andreas Schmocker, Ecole Polytechnique Fédérale de Lausanne (Switzerland), et al.
Conference 9689F: Optics in Bone Surgery and Diagnostics
Session 2: Bone Surgery and Diagnostics
Date and Time: Saturday, February 13, 2016, 11:20 AM

Currently implants or tissue replacements are inserted either as a whole implant or by injecting a liquid which polymerizes to form a solid implant at the appropriate location. This is either highly invasive or not controllable. We developed a tool to perform such surgeries in a minimally invasive and controllable way. It combines photopolymerization and fluorescence spectroscopy in a surgical apparatus. The device was successfully tested in-vitro to replace the core of intervertebral discs where it fulfilled the functionality of the tissue over more than 0.5 million loading cycles.


Optical profiling of anticoagulation status
Paper 9689-99

Author(s):  Diane M. Tshikudi, Massachusetts General Hospital (United States), et al.
Conference 9689D: Diagnostic and Therapeutic Applications of Light in Cardiology
Session 2: Blood
Date and Time: Saturday, February 13, 2016, 11:20 AM

Anticoagulant drugs, commonly administered to prevent and treat thrombotic disorders such as stroke and myocardial infarction, are often associated with bleeding complications requiring frequent anticoagulation testing. Here we describe OTEG, a new tool that measures temporal speckle intensity fluctuations to rapidly assess a patient’s coagulation status. Our current studies conducted using a drop of anticoagulated whole blood demonstrate a close correspondence between OTEG and standard-reference TEG with dose-dependents prolongation of clotting time and unaltered maximum clot stiffness. We conclude that OTEG has the potential for accurately monitoring anticoagulation in patients in the clinic or the home setting.


A compact bio-inspired visible/NIR imager for image-guided surgery
Paper 9696-9

Author(s):  Viktor Gruev, Washington Univ. in St. Louis (United States), et al.
Conference 9696: Molecular-Guided Surgery: Molecules, Devices, and Applications II
Session 2: Advanced Molecular Imaging Methods II
Date and Time: Saturday, February 13, 2016, 11:45 AM

Near-infrared (NIR) fluorescent imaging system has been widely used for intraoperative image-guided application. In this paper, we present a compact and ultra-sensitive bio-inspired imaging system capable of simultaneously capturing visible and NIR information. The single imaging device combines pixelated spectral filters with an array of CCD imaging elements. The system has been validated with tumor targeted agent, LS301, in PyMT murine model of breast cancer. We also used our imaging sensor to locate sentinel lymph nodes (SLNs) in patients with breast cancer using indocyanine green tracer.


In-vivo continuous monitoring of mixed venous oxygen saturation by photoacoustic transesophageal echocardiography
Paper 9689-101

Author(s):  Li Li, Harvard Medical School (United States), et al.
Conference 9689D: Diagnostic and Therapeutic Applications of Light in Cardiology
Session 2: Blood
Date and Time: Saturday, February 13, 2016, 12:00 PM

Mixed venous oxygen saturation (SvO2) is a gold-standard measure of the body’s dynamic oxygen sufficiency. Traditionally, SvO2 is measured by pulmonary artery catheters (PAC), which require a risky invasive insertion procedure. We are developing a new technology termed photoacoustic transesophageal echocardiography (PA-TEE), which integrates transesophageal echocardiography with photoacoustic oximetry to address the unmet clinical need for a non-invasive SvO2 monitor. A clinically translatable prototype was developed and has now been used to evaluate SvO2 in living swine. We will present statistic comparison between SvO2 measurements from PA-TEE in vivo and the gold-standard laboratorial analysis on blood samples drawn from PACs.


If I had a magic wand....A dermatology photonics wish list
Paper 9689-8

Author(s):  Kristen M. Kelly, Univ. of California, Irvine (United States), et al.
Conference 9689A: Photonics in Dermatology and Plastic Surgery
Session 4: Clinical Perspective
Date and Time: Saturday, February 13, 2016, 1:20 PM

Challenges in dermatology that can be addressed by photonics research will be explored. Non-invasive, real-time diagnosis of skin lesions would eliminate biopsy risks, minimize patient anxiety by providing more rapid answers and allow diagnosis and treatment in a single visit. Photonics can also be used for treatment assessment to determine if intervention is adequate or if further treatment is needed. Monitoring for potential adverse effects can greatly improve treatment safety. Light based therapies can also be improved by increasing photon penetration and selectivity for targeted cells or skin structures. Scientist and clinician collaboration can greatly improve patient care.


Photoacoustic Imaging to predict photodynamic therapy efficacy
Paper 9694-9

Author(s):  Srivalleesha Mallidi, Harvard Medical School (United States), et al.
Conference 9694: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV
Session 3: Photodynamic Therapy III
Date and Time: Saturday, February 13, 2016, 1:40 PM


Quantitative assessment of optical properties in healthy cartilage and repair tissue by optical coherence tomography and histology
Paper 9689-170

Author(s):  Sanne M. A. Jansen, Academisch Medisch Centrum (Netherlands), et al.
Conference 9689F: Optics in Bone Surgery and Diagnostics
Session 3: Musculoskeletal Imaging and Diagnostics II
Date and Time: Saturday, February 13, 2016, 2:00 PM

Accurate imaging of early damage to articular cartilage that lines the joints is an important clinical challenge. Optical Coherence Tomography has shown promising results in high-resolution imaging of articular cartilage. For clinical implementation, quantification of the OCT signal is an important step toward clinical implementation of a diagnostic tool in cartilage imaging. OCT signal attenuation (μOCT) was used to distinguish between healthy cartilage, repair tissue and bone in a goat model. To relate morphological differences to variation in μOCT, histological parameters (nucleus count, -size and inter-nucleus distance) were assessed and collagen content was imaged using polarization microscopy.


Development of low-cost devices for image-guided photodynamic therapy treatment of oral cancer in global health settings
Paper 9694-11

Author(s):  Hui Liu, Univ. of Massachusetts Boston (United States), et al.
Conference 9694: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV
Session 3: Photodynamic Therapy III
Date and Time: Saturday, February 13, 2016, 2:20 PM

Photodynamic therapy (PDT) is a light-based modality that shows promises as a cancer treatment technology for global health. Recently we demonstrated a low-cost prototype battery-powered LED source for ALA-PpIX PDT achieves tumoricidal efficacy comparable to a commercial laser. We discuss here light delivery, and dosimetry considerations to enable clinical translation of low-cost, portable, battery-powered sources for lesions in the oral cavity. To leverage PpIX tumor imaging under the same resource constraints, we tested a simple smartphone-based imaging fluorescence device that showed tumor contrast and PpIX quantitation. Together, we build an integrated simple-to-use PDT platform with embedded imaging and dosimetry control.


Imaging of skin surface architecture with out of plane polarimetry
Paper 9689-11

Author(s):  Jessica C. Ramella-Roman, Florida International Univ. (United States), et al.
Conference 9689A: Photonics in Dermatology and Plastic Surgery
Session 5: Wide-Field Imaging I
Date and Time: Saturday, February 13, 2016, 2:30 PM

Knowledge of skin surface topography is of great importance when establishing environmental and age related skin damage. We utilized an out-of-plane polarimeter for the characterization of skin surface profile non-invasively. The system consists of an imaging Stokes vector polarimeter where the light source is allowed to rotate about the normal to the sample. For each position of the incident beam the principal angle of polarization is calculated. This parameter relates indirectly to surface profile and architecture. The system was used to image the forehead and hands of healthy volunteers between eighteen and sixty years of age. A clear separation appeared among the different age groups establishing out-of-plane polarimetry as a promising technique for skin topography quantification.


In vivo optical coherence tomography (OCT) examination of living kidney
Paper 9689-57

Author(s):  Zheng Huang, Fujian Normal Univ. (China), et al.
Conference 9689B: Therapeutics and Diagnostics in Urology
Session 3: Tissue imaging
Date and Time: Saturday, February 13, 2016, 2:40 PM

In this pilot study, living animal and human donor kidneys were imaged using swept source OCT (SS OCT). The light source used in the OCT system was a wavelength swept laser light source centered at approximately 1,300 nm with a full width at half maximum bandwidth of 100 nm, yielding approximately 10 μm axial and lateral image resolution in tissue. In vivo imaging was carried out using an OCT microscope setup and by placing the imaging probe gently on the surface of the kidney. The imaging acquisition was performed at a frame rate of 150 frames per second. The laser operated at a 100 kHz sweep repetition rate with 20 mW average output power. The system detection sensitivity was measured to be 105 dB. A semi-quantitative analysis of the OCT images was performed to evaluate the size, shape, density and uniformity of the tubule.


Reliability analysis of instrument design of noninvasive bone marrow disease detector
Paper 9689-172

Author(s):  Ting Li, Univ. of Electronic Science and Technology of China (China), et al.
Conference 9689F: Optics in Bone Surgery and Diagnostics
Session 3: Musculoskeletal Imaging and Diagnostics II
Date and Time: Saturday, February 13, 2016, 2:40 PM

Bone marrow lesions(BMLs)may cause a variety of complications with high death rate and short survival time. Early detection and follow up care are particularly important and the current technique rely on invasive and high-risk bone marrow biopsy/puncture. We attempted to design a near infrared spectroscopy based device aimed for detecting bone marrow lesions and carried out the series of reliability experiments to test the sensitivity, specificity, signal-to-noise ratio (SNR), stability, and etc. Finally, these reliability-test data supported the promising diagnosis and surgery guidance of our novel instrument in detection of BMLs.


Visualization of tumor vascular reactivity in response to respiratory challenges by optical coherence tomography
Paper 9689-141

Author(s):  Hoon Sup Kim, Gwangju Institute of Science and Technology (Korea, Republic of), et al.
Conference 9689E: Diagnosis and Treatment of Diseases in the Breast and Reproductive System II
Session 3: Optical Coherence Tomography and Fluorescence Imaging
Date and Time: Saturday, February 13, 2016, 2:40 PM

In this study, we utilized a spectral domain optical coherence tomography (OCT) system to visualize vascular reactivity of tumor and normal vasculature during respiratory challenges in a mouse model. We adapted intensity based Doppler variance algorithm to draw angiogram from the mouse ear (8-week-old Balb/c nu/nu). The vasoconstriction effect of hyperoxic gas on vasculature was in the range of 1 to 12% depending on arterial, capillary, or venous blood vessel. The vascular reactivity change during breast tumor progression and post chemotherapy will be monitored by OCT angiography.


Porphyrin lipid nanoparticles for enhanced photothermal therapy (PTT) in a patient-derived orthotopic pancreas xenograft cancer model
Paper 9696-14

Author(s):  Christina MacLaughlin, Univ. Health Network (Canada), et al.
Conference 9696: Molecular-Guided Surgery: Molecules, Devices, and Applications II
Session 3: Molecular Contrast Agents
Date and Time: Saturday, February 13, 2016, 3:15 PM

Light-based therapies are advantageous for pancreatic cancer treatment because surgery is highly invasive and radiotherapy cannot be delivered in curative doses. Despite the promise of PTT for ablation of pancreatic tumors, current studies lack clinical relevance for absence of a realistic model. Theranostic porphyrin lipid nanoparticles (porphysomes) were employed as photothermal sensitizers to study the specificity and efficacy of PTT in a clinically relevant patient-derived orthotopic pancreas xenograft tumor model. Fluorescence was used to confirm porphysome tumor uptake, PTT progress monitored using IR optical imaging, and histological analyses used to determine heat-induced effects on tumor morphology and remaining tissue viability.


Redox subpopulations and the risk of breast cancer progression
Paper 9689-145

Author(s):  Lin Z. Li, The Univ. of Pennsylvania Health System (United States), et al.
Conference 9689E: Diagnosis and Treatment of Diseases in the Breast and Reproductive System II
Session 4: Breast Cancer
Date and Time: Saturday, February 13, 2016, 3:30 PM

Based on the fluorescence signals of NADH and oxidized flavoproteins (Fp) and their ratios, i.e., the redox ratios, we have identified multiple redox subpopulations in both mouse xenografts and clinical specimens of breast cancer. Our data from pilot studies indicate that redox deviations may be predictive of breast cancer invasive/metastatic potential and poor prognosis.


Combination photodynamic therapy using 5-fluorouracil and aminolevulinate enhances tumor-selective production of protoporphyrin IX and improves treatment efficacy of squamous skin cancers
Paper 9694-18

Author(s):  Edward V. Maytin, Cleveland Clinic Lerner Research Institute (United States), et al.
Conference 9694: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV
Session 4: Photodynamic Therapy IV
Date and Time: Saturday, February 13, 2016, 3:50 PM

Combination approaches for photodynamic therapy (PDT) include the use of simple drugs (methotrexate; 5-fluorouracil, 5-FU; or vitamin D) prior to aminolevulinic acid (ALA) to enhance therapeutic effectiveness of PDT. Only 5-FU is currently FDA-approved for skin cancers. Here we describe studies on mechanisms of action whereby 5-FU pretreatment leads to PpIX accumulation and improves the selectivity and clinical responses in early/advanced squamous cell carcinoma (SCC). 5-FU alters heme enzymes, enhances tumor cell differentiation, and selectively increases tumor cell death via enhanced expression of p53. We propose that 5-FU is a useful clinical adjuvant to ALA-PDT for SCC of the skin


Assessing idiopathic pulmonary fibrosis with bronchoscopic optical coherence tomography
Paper 9691-43

Author(s):  Lida P. Hariri, Massachusetts General Hospital (United States), et al.
Conference 9691B: Optical Techniques in Pulmonary Medicine III
Session 11: New Techniques for Clinical Imaging
Date and Time: Saturday, February 13, 2016, 4:00 PM

Idiopathic pulmonary fibrosis (IPF) must be distinguished from other forms of fibrotic lung disease due to its significantly worse prognosis and new therapeutic options FDA-approved only for use in IPF. Often, patients must undergo surgical tissue resection for diagnosis, which has risks of adverse effects. Bronchoscopic OCT has potential to provide a low-risk, non-surgical method for IPF diagnosis. We performed bronchoscopic OCT imaging in lung specimens from pulmonary fibrosis patients, and demonstrated that OCT can visualize characteristic IPF features, including dense peripheral fibrosis and microscopic honeycombing. We conclude that OCT has potential as a minimally-invasive method for IPF diagnosis.


Optical surgical navigation for nodal staging: to see or not to see?
Paper 9696-15

Author(s):  Eva M Sevick-Muraca, The Univ. of Texas Health Science Ctr. at Houston (United States), et al.
Conference 9696: Molecular-Guided Surgery: Molecules, Devices, and Applications II
Session 4: Imaging Systems
Date and Time: Saturday, February 13, 2016, 4:00 PM


Raman spectroscopy and oral exfoliative cytology: investigating misclassifications between contralateral normal and tumor sites
Paper 9689-81

Author(s):  C. Murali Krishna, Advanced Ctr. for Treatment, Research & Education in Cancer (India), et al.
Conference 9689C: Optical Imaging, Therapeutics, and Advanced Technology in Head and Neck Surgery and Otolaryngology
Session 3: Endocrine Imaging and Spectroscopy
Date and Time: Saturday, February 13, 2016, 4:00 PM

Raman spectroscopic (RS) studies have been explored for early oral cancer diagnosis, where misclassification between contralateral normal and tumors was observed. In this study, RS of oral exfoliated cells coupled with cytopathological evaluation was carried out to understand the origin of such misclassifications. Principal-component-linear-discriminant-analysis (PC-LDA) followed by Leave-one-out-cross-validation (LOOCV) indicate ~27% misclassifications between the contralateral and tumor groups. Cytopathological results for misclassified contralateral samples demonstrate cytological changes like mild dysplasia, dyskeratosis and increased number of parakeratotic and anucleate squames. Thus, the present study demonstrates definite cytological changes in contralateral normal sites and the potential of RS in detecting these changes.


Combination strategy in photodynamic therapy of skin diseases
Paper 9694-14

Author(s):  Zheng Huang, Fujian Normal Univ. (China), et al.
Conference 9694: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV
Session 4: Photodynamic Therapy IV
Date and Time: Saturday, February 13, 2016, 4:20 PM

In recent years, topical photodynamic therapy (PDT) has been widely used in dermatology and beyond oncological indications. Our clinical study suggests that the combination of PDT with other therapeutic modalities could further improve clinical outcomes inn the treatment of several common skin disorders. This presentation will demonstrate our experience in: (i) treating skin cancers using surgery combined with ALA-PDT, (ii) treating flat wart, condyloma acuminate, and refractory plantar wart using cryotherapy combined with ALA-PDT, (iii) treating severe acne in combination with clearing procedure and ALA-PDT, and (iv) treating the rosacea using fractional laser combined with ALA-PDT. The optimization of combination treatment protocols and outcomes will be discussed.


Analysis of the variation in OCT measurements of a structural bottle neck for eye-brain transfer of visual information from 3D-volumes of the optic nerve head, PIMD(0-2pi)
Paper 9693-23

Author(s):  Per G. Söderberg, Uppsala Univ. (Sweden), et al.
Conference 9693: Ophthalmic Technologies XXVI
Session 5: Ophthalmic Image Processing and Analysis
Date and Time: Saturday, February 13, 2016, 4:30 PM

The aim of this study was to establish if measurements of PIMD (0-2Pi) can be used for follow up of glaucoma. PIMD (0-2Pi) was iteratively estimated in iterated 3D captures of the optic nerve head at iterated occsions in patients clinically diagnosed with early phase glaucoma. The sources of variation in PIMD (0-2Pi) were quantified with an analysis of variance. It was found that if five 3D captures are averaged and PIMD (0-2Pi) is measured once in each capture, the variation coefficient for a 0.2 relative change from baseline is 0.15.


Design and validation of the ball lens-based intravascular catheter for fluorescence lifetime imaging microscopy of atherosclerosis
Paper 9689-109

Author(s):  Xi Chen, Texas A&M Univ. (United States), et al.
Conference 9689D: Diagnostic and Therapeutic Applications of Light in Cardiology
Session 4: Photacoustics and Spectroscopy
Date and Time: Saturday, February 13, 2016, 4:40 PM

We report the design and validation of a ball lens-based imaging catheter and broadband rotary joint for fluorescence lifetime imaging microscopy of atherosclerosis. The 4 Fr catheter can be rotated by a custom built lensless rotary joint with high coupling efficiency (>90%) over a broad UV to near-IR range. Experiments conducted using a resolution target, a fluorescein phantom, and a segment of ex vivo pig coronary artery demonstrate the system performance for fluorescence lifetime imaging including a lateral resolution of 0.08 radians (80 μm at 1 mm lens-to-sample distance) and pullback velocities in excess of 8mm/s.


Using polarization-sensitive optical coherence tomography to identify tumor stromal fibrosis and increase tumor biopsy yield
Paper 9691-45

Author(s):  Lida P. Hariri, Massachusetts General Hospital (United States), et al.
Conference 9691B: Optical Techniques in Pulmonary Medicine III
Session 11: New Techniques for Clinical Imaging
Date and Time: Saturday, February 13, 2016, 4:40 PM

Biopsy is the principal method used to diagnose tumors in a variety of organ systems, but inadvertent biopsy of stromal fibrosis can impede diagnosis. Polarization sensitive OCT (PS-OCT) measures tissue birefringence and could distinguish tumor from fibrosis for biopsy guidance. In this study, PS-OCT was obtained in lung nodules from surgical resection specimens containing varying ratios of tumor and fibrosis. PS-OCT demonstrated strong birefringence in regions of dense fibrosis, moderate birefringence in tumors with early, loosely-organized fibrosis, and negligible birefringence in tumors with minimal fibrosis. Our findings support the potential use of PS-OCT to increase tumor yield during biopsy.


Goggle augmented imaging and navigation system (GAINS) for real-time fluorescence image-guided oncologic surgery
Paper 9696-17

Author(s):  Suman B. Mondal, Washington Univ. in St. Louis (United States), et al.
Conference 9696: Molecular-Guided Surgery: Molecules, Devices, and Applications II
Session 4: Imaging Systems
Date and Time: Saturday, February 13, 2016, 4:45 PM

Oncologic surgery often suffers from incomplete tumor removal necessitating repeat surgery. We have developed a wearable goggle augmented imaging and navigation system (GAINS) that can provide real-time intraoperative visualization of tumors and sentinel lymph nodes without disrupting the surgical workflow. GAINS projects near-infrared fluorescence from tumor-avid contrast agents and color tissue images to a head-mounted display worn by the surgeon in real-time. GAINS guided complete tumor resection in mouse models of cancer with high accuracy and detected sentinel lymph nodes in human breast cancer and melanoma patients with high sensitivity. GAINS may improve outcomes in oncologic surgery.


Multimodal ophthalmic imaging using swept source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography
Paper 9693-25

Author(s):  Joseph Malone, Cleveland Clinic (United States), et al.
Conference 9693: Ophthalmic Technologies XXVI
Session 6: Ophthalmic OCT and SLO Technology
Date and Time: Saturday, February 13, 2016, 5:00 PM

We demonstrate swept source spectrally encoded scanning laser ophthalmoscope and OCT (SS-SESLO-OCT) human retinal imaging at 1060 nm. SS-SESLO-OCT uses a shared 100 kHz Axsun swept source, shared scanner and imaging optics, and are detected simultaneously on a shared, dual channel high-speed digitizer. SESLO illumination and detection were performed using the single mode core and multimode inner cladding of a double clad fiber coupler, respectively, to preserve lateral resolution while improving collection efficiency and reducing speckle contrast at the expense of confocality. En face SESLO and cross-sectional OCT images were acquired with 1376 x 500 pixels at 200 frames-per-second concurrently.


Localization analysis of lipid core plaques detected by a near infrared spectroscopy system as compared to histological finding: intracoronary imaging application
Paper 9689-110

Author(s):  Zhihua He, InfraReDx, Inc. (United States), et al.
Conference 9689D: Diagnostic and Therapeutic Applications of Light in Cardiology
Session 4: Photacoustics and Spectroscopy
Date and Time: Saturday, February 13, 2016, 5:00 PM

A catheter-based near infrared spectroscopy (NIRS) imaging system has been approved by FDA for detection of coronary lipid core plaques (LCP) in patients. The NIRS detection results are summarized as a 2D Chemogram map, with LCP presence highlighted by predefined pseudo-color. An enhanced Chemogram map with less/no outliers and less diffused LCP clustering could enable better clinical use with easier access to LCP objects (LO). The localized ROC analysis against histology golden standard, using both location ROC (LROC) and free response ROC (FROC), suggest good AUC values for fibroatheroma presence and promising localized LCP detection within an artery.


Fluorescence guided lymph node biopsy in large animals using direct image projection device
Paper 9696-19

Author(s):  Walter J. Akers, Washington Univ. School of Medicine in St. Louis (United States), et al.
Conference 9696: Molecular-Guided Surgery: Molecules, Devices, and Applications II
Session 4: Imaging Systems
Date and Time: Saturday, February 13, 2016, 5:15 PM

The use of fluorescence imaging two aiding oncologic surgery is a fast growing field and biomedical imaging, revolutionizing open and minimally invasive surgery practices. We have designed, constructed, and tested a system for fluorescence image acquisition and direct display on the surgical field for fluorescence guided surgery. After verification of accurate alignment, feasibility for clinical application was demonstrated in large animal models of sentinel lymph node biopsy. Fluorescence was detected by the camera system during operations and projected onto the imaging field, accurately identifying tissues containing the fluorescent tracer at up to 15 frames per second.


Home-use cancer detecting plaster
Paper 9694-17

Author(s):  Zeev Zalevsky, Bar-Ilan Univ. (Israel), et al.
Conference 9694: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV
Session 4: Photodynamic Therapy IV
Date and Time: Saturday, February 13, 2016, 5:20 PM

In this paper we present a novel concept in which special plaster is developed for early detection of cancer. The plaster contains an array of micro needles with small detection array connected to each needle which inspects the color of the surface of the skin versus time after being pinched with the needles. We were able to show in pre-clinical trials that the color varies differently if the skin is close to tumor tissue. Such a device can be affordable for the end user and can make our life significantly better as it may significantly reduce the probability of missing malignant tissues or discovering malignant tissue in its “too late” progress stage. In addition to the home use of the proposed plaster, it can also be used by medical surgeons in the stage they are preparing the patient for the medical operation and need to properly identify the exact borders of the tumor, which is to be removed.


Intraoperative vascular imaging with augmented microscopy
Paper 9696-20

Author(s):  Jeffrey R. Watson, The Univ. of Arizona (United States), et al.
Conference 9696: Molecular-Guided Surgery: Molecules, Devices, and Applications II
Session 4: Imaging Systems
Date and Time: Saturday, February 13, 2016, 5:30 PM

A common difficulty in intracranial vascular angiography is the inability to simultaneously visualize and manipulate vascular anatomy upon near-infrared contrast injection. We developed the augmented microscope to improve surgical image guidance. Vascular imaging under augmented microscopy guidance was compared to current surgical image guidance technique, i.e., standard bright-field microscopy. The augmented fluorescence channel improved accuracy of locating vessels of interest and reduced surgical time through a more efficient image guidance system. Though the vascular system remains the main route for delivering contrasts and therapies, we envision augmented microscopy being applied to agents that extravasate or localize to various solid tissues.


Fluorophore-conjugated antibodies for imaging and resection of GI tumors
Paper 9696-22

Author(s):  Michael Bouvet, Univ. of California, San Diego (United States), et al.
Conference 9696: Molecular-Guided Surgery: Molecules, Devices, and Applications II
Session 5: Preclinical Applications and Clinical Translation I
Date and Time: Sunday, February 14, 2016, 8:00 AM

Negative surgical margins are critical to prevent recurrence in cancer surgery. This is because with current technology in many cases negative margins are impossible due the inability of the surgeon to detect the margin. Our laboratory has developed fluorophore-labeled monoclonal antibodies to aid in cancer visualization in orthotopic nude mouse models of human gastrointestinal (GI) cancer in order to achieve negative margins in fluorescence-guided surgery (FGS). The technologies described herein have the potential to change the paradigm of surgical oncology to engender significantly improved outcomes.


Multimodal in vivo imaging of lung cancer and its microenvironment
Paper 9691-47

Author(s):  Lida P. Hariri, Massachusetts General Hospital (United States), et al.
Conference 9691B: Optical Techniques in Pulmonary Medicine III
Session 12: New Approaches, Advancements and Techniques
Date and Time: Sunday, February 14, 2016, 8:30 AM

Despite advances in lung cancer therapies, prognosis remains poor. Tumor growth and drug response are progressive processes involving tumor cells and their microenvironment. We developed a multimodal optical imaging protocol to serially assess tumor and its microenvironment in mice implanted with human lung carcinoma. Structural OCT assessed tumor viability and necrosis, polarization-sensitive OCT measured tissue birefringence for collagen detection, and Doppler OCT assessed tumor vasculature. Confocal imaging provided high-resolution visualization of GFP-labeled tumor cells. Our results demonstrated that stromal support and vascular growth are essential to tumor progression. Multimodal imaging provides informative assessments of tumor and its microenvironment over time.


Photodynamic therapy for targeting extracellular biophysical regulators of tumor growth and invasive behavior in pancreatic cancer
Paper 9694-13

Author(s):  Jonathan P. Celli, Univ. of Massachusetts Boston (United States), et al.
Conference 9694: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV
Session V: Photodynamic Therapy V
Date and Time: Sunday, February 14, 2016, 8:50 AM

The mechanical properties of the tumor microenvironment play a significant role in regulating growth behavior. This is particularly relevant to pancreatic tumors associated with an abundance of rigid, fibrotic stroma. Here, we use 3D tumor models with customized stromal composition combined with particle tracking microrheology to correlate mechanical changes associated with phenotypic alteration and therapeutic interventions. We use this approach to study altered matrix remodeling in chemotherapy-resistant populations that show elevated sensitivity to photodynamic therapy (PDT). We also examine the impact of PDT on stromal components and consider the broader applicability of this methodology for screening therapeutics targeting tumor-stroma interactions.


Optical coherence tomography imaging to analyze biofilm thickness from distal to proximal regions of endotracheal tubes
Paper 9691-48

Author(s):  Robert E. Dunn, Univ. of California, Irvine (United States), et al.
Conference 9691B: Optical Techniques in Pulmonary Medicine III
Session 12: New Approaches, Advancements and Techniques
Date and Time: Sunday, February 14, 2016, 8:50 AM

The development of nosocomial ventilator-associated pneumonia (VAP) has been linked to the presence of specific bacteria found in the biofilm that develops in intubated endotracheal tubes of critical care patients. Presence of biofilm has been difficult to assess clinically. Here, we use Optical coherence tomography (OCT), to visualize the biofilm at both the proximal and distal tips. Ultimately, the goal will be to determine if OCT can be a tool to visualize biofilm development and potential interventions to reduce the incidence of VAP.


Development of multifunctional optical coherence tomography and application to mouse myocardial infarction model in vivo
Paper 9689-115

Author(s):  Sun-Joo Jang, KAIST (Korea, Republic of), et al.
Conference 9689D: Diagnostic and Therapeutic Applications of Light in Cardiology
Session 5: Myocardium
Date and Time: Sunday, February 14, 2016, 9:00 AM

We demonstrate a multifunctional OCT system for a beating mouse heart with high spatiotemporal resolution and deep tissue imaging. Angiographic imaging and polarization-sensitive (PS) imaging were implemented with the electrocardiogram (ECG)-triggered beam scanning scheme on the high-speed OCT platform (A-line rate: 240 kHz). Depth-resolved local birefringence and local orientation of myocardial fiber were visualized from the PS-OCT. ECG-triggered angiographic OCT (AOCT) with the motion stabilization imaging window provided myocardial vasculature of a beating mouse heart. AOCT and PS-OCT visualize change of functionality of coronary vessels and myocardium respectively at different phases (acute and chronic) of the myocardial infarction.


Optical coherence tomography based microangiography in dermatology applications
Paper 9689-20

Author(s):  Ruikang K. Wang, Univ. of Washington (United States), et al.
Conference 9689A: Photonics in Dermatology and Plastic Surgery
Session 9: OCT
Date and Time: Sunday, February 14, 2016, 9:00 AM

Optical coherence tomography (OCT) based microangiography (OMAG) is a new imaging technique enabling the visualization of blood flow within microcirculatory tissue beds in vivo with high resolution. In this talk, the concept and advantages of OMAG will be discussed and its potential clinical applications in the dermatology will be shown, demonstrating its usefulness in the clinical monitoring and therapeutic treatment of various skin pathologies, e.g. acne, port wine stain and wound healing.


Vitamin D for combination photodynamic therapy of skin cancer in individuals with vitamin D deficiency: Insights from a preclinical study in a mouse model of squamous cell carcinoma
Paper 9694-19

Author(s):  Sanjay Anand, Cleveland Clinic Lerner Research Institute (United States), et al.
Conference 9694: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV
Session V: Photodynamic Therapy V
Date and Time: Sunday, February 14, 2016, 9:10 AM


Direct administration of nerve-specific fluorophores to guide nerve-sparing radical prostatectomy
Paper 9696-25

Author(s):  Connor Barth, Oregon Health & Science Univ. (United States), et al.
Conference 9696: Molecular-Guided Surgery: Molecules, Devices, and Applications II
Session 5: Preclinical Applications and Clinical Translation I
Date and Time: Sunday, February 14, 2016, 9:15 AM

Prostate cancer cure is the primary goal of radical prostatectomy, however preserving the nerve structures responsible for continence and potency are vital for maintained quality of life. Nerve damage following radical prostatectomy plagues surgical treatment and is reported in up to 60% of patients. Nerve-specific fluorophores have the potential to improve nerve visualization, but the prostate is a highly innervated organ, where direct labeling of the cavernous nerve and neurovascular bundle would provide significantly improved imaging contrast over systemic labeling of all nerve structures in the gland. In the current work, a direct administration protocol was optimized for application of a nerve-specific fluorophore during nerve-sparing radical prostatectomy.


Adapting biomodulatory approaches to enhance photodynamic therapy outcomes in new contexts: pancreatic and oral cancers
Paper 9694-21

Author(s):  Sriram R. Anbil, Harvard Medical School (United States), et al.
Conference 9694: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV
Session V: Photodynamic Therapy V
Date and Time: Sunday, February 14, 2016, 9:50 AM

Overcoming obstacles associated with cancer therapy will require a multifaceted approach that includes modulating the pathways that cancer cells use to progress and evade treatment. Biomodulation enhanced photodynamic therapy (PDT) is promising in this regard, but its broader potential in context of PDT with exogenous photosensitizers as well as in low resource settings remain unrealized. Using two low-cost agents, we assess the ability of biomodulation-enhanced PDT to improve outcomes in challenging disease contexts.


A novel automated instrument designed to determine photosensitivity thresholds
Paper 9693-35

Author(s):  Mariela C. Aguilar, Bascom Palmer Eye Institute (United States), et al.
Conference 9693: Ophthalmic Technologies XXVI
Session 8: Vision Assessment and Correction
Date and Time: Sunday, February 14, 2016, 10:30 AM

As there is no clinically available instrument to systematically and reliably determine photosensitivity thresholds, a computer-controlled optoelectronics system was designed. The BPEI Photosensitivity System provides a light stimuli with varying intensity emitted from a bi-cupola concave, 210 white LED array. The subject is instructed to indicate discomfort by pressing a hand-held button. The threshold is calculated after 10 response reversals. In a preliminary study, we demonstrated that subjects suffering from Achromatopsia experienced lower photosensitivity thresholds than normal subjects. Hence, the system can safely determine the photosensitivity thresholds of healthy and light sensitive subjects by detecting and quantifying the individual differences.


Tethered capsule OCT endomicroscopy: from bench to bedside at the primary care office
Paper 9691-1

Author(s):  Michalina J. Gora, CNRS (France), et al.
Conference 9691A: Endoscopic Microscopy XI
Session 2: OCT I
Date and Time: Sunday, February 14, 2016, 10:30 AM

We have developed a swallowable tethered capsule OCT endomicroscopy (TCE) device that acquires microscopic images of the entire esophagus in unsedated subjects in a quick and comfortable procedure. To test its capabilities of TCE to become a population-based screening device, we conducted a clinical feasibility study in the primary care office. Twenty primary care subjects were enrolled and high-resolution images of the esophagus were obtained in 17/20 subjects that swallowed the capsule. Our clinical experience in this cohort, subject feedback, image quality, and recommendations for future technological adaptations for efficient utilization in this setting will be presented.


Broadband rotary joint for high speed ultrahigh resolution endoscopic OCT imaging
Paper 9691-3

Author(s):  Milad Alemohammad, Johns Hopkins Univ. (United States), et al.
Conference 9691A: Endoscopic Microscopy XI
Session 2: OCT I
Date and Time: Sunday, February 14, 2016, 11:10 AM


Laser ablation of basal cell carcinomas guided by confocal microscopy
Paper 9689-26

Author(s):  Heidy Sierra, Memorial Sloan-Kettering Cancer Ctr. (United States), et al.
Conference 9689A: Photonics in Dermatology and Plastic Surgery
Session 10: Therapeutics
Date and Time: Sunday, February 14, 2016, 11:40 AM

Laser ablation offers fast and precise removal of basal cell carcinomas (BCCs). However, the lack of histological confirmation after ablation has been a limitation. Reflectance confocal microscopy (RCM) imaging combined with a contrast agent provides cellular-level histology-like feedback on the patient. An ex-vivo study shows that for an Er:YAG laser with 6 passes of 25 J/cm2, the thermal coagulation can be controlled, to allow removal of BCCs and uptake of contrast agent for imaging post- ablation. Similar results were obtained for a CO2 laser with 3 passes of 6.5 J/cm2. In-vivo testing on 38 patients show feasibility of RCM to guide laser ablation of BCCs.


Optical extended depth of focus lens design for children myopia control
Paper 9693-40

Author(s):  Zeev Zalevsky, Bar-Ilan Univ. (Israel), et al.
Conference 9693: Ophthalmic Technologies XXVI
Session 8: Vision Assessment and Correction
Date and Time: Sunday, February 14, 2016, 11:45 AM

The mechanism that causes to the progress of children myopia is not completely clear yet but the predominant recent speculation is that it is related to hyperopic blurring in the periphery of the retina. In our article we discuss a proof of concept to an innovative optical design that can control the focal plane of any lens and to extend its depth of focus and as a result to cause the focal plane to conjugate with the fovea also in its peripheral region (note that the trials made so far to solve the problem did not use extended depth of focus lenses) and therefore to assist in resolving the children myopia control problem. In our article we focused on the optical design with respect to all others articles that suggested optical elements that can do myopic shift but didn’t show simulations results to prove it.


Photodynamic therapy for skin rejuvenation
Paper 9689-28

Author(s):  Zheng Huang, Fujian Normal Univ. (China), et al.
Conference 9689A: Photonics in Dermatology and Plastic Surgery
Session 10: Therapeutics
Date and Time: Sunday, February 14, 2016, 12:20 PM

Although mechanisms are not fully understood, recently, it has been demonstrated that topical photodynamic therapy (PDT) can offer certain beneficial effects in skin rejuvenation. Our clinical study shows that low-dose topical PDT medicated with 5-aminolevulinic acid (ALA) and red light can achieve better result than conventional photorejuvenation modalities. This presentation will summarize the progress in the application of PDT in skin rejuvenation and our clinical experience in utilizing topical PDT in the treatment of skin photoaging.


A novel piezoelectric microstage with embedded sensor for dual axes confocal endomicroscopy
Paper 9691-5

Author(s):  Jongsoo Choi, Univ. of Michigan (United States), et al.
Conference 9691A: Endoscopic Microscopy XI
Session 3: Confocal and Multimodality Imaging
Date and Time: Sunday, February 14, 2016, 1:20 PM

A new class of piezoelectric microactuators has recently been developed that meets two primary challenges for mirror scanning in dual axes confocal endomicroscopy imaging: large out-of-plane actuation (~500μm) and a relatively high bandwidth (>100Hz). This paper reports results on the development of on-chip sensing and calibration for the actuators to further achieve stage positioning error better than a desired imaging resolution of 5 μm and to improve the robustness of actuator performance by the use of a closed-loop controller. The experimental outputs of the piezoelectric sensor and an analytical model developed to estimate the deflections of actuation beams are presented.


A prospective cohort: probe based confocal laser endomicroscopy for peripheral pulmonary lesions
Paper 9691-7

Author(s):  Yuji Matsumoto, National Cancer Ctr. Hospital East (Japan), et al.
Conference 9691A: Endoscopic Microscopy XI
Session 3: Confocal and Multimodality Imaging
Date and Time: Sunday, February 14, 2016, 2:00 PM

Probe based confocal laser endomicroscopy (pCLE) is a novel technique which provides in vivo real-time image of the contacted surface structures. However, its findings have not been established yet. We prospectively enrolled 19 consecutive patients who have underwent bronchoscopy for peripheral pulmonary lesions (PPLs) with pCLE. As a results, discontinuous, crushed or aggregated alveolar structures accompanied by thickened and distorted elastic fibers were detected as pCLE findings in PPLs. Some cases showed dark hollow with fragmented or granular fluorescence. Meanwhile, 11 cases (57.9%) needed the position change despite an adequate positional image had been obtained by radial endobronchial ultrasound.


Performance of combined OCT/MFI microendoscope for ovarian cancer detection
Paper 9691-8

Author(s):  Molly Keenan, The Univ. of Arizona (United States), et al.
Conference 9691A: Endoscopic Microscopy XI
Session 3: Confocal and Multimodality Imaging
Date and Time: Sunday, February 14, 2016, 2:20 PM

To improve early detection of ovarian cancer, we have designed and built a microendoscope that combines optical coherence tomography (OCT) and multispectral fluorescence imaging (MFI) into a 0.7 mm diameter package. An endoscope of this size allows access to the ovaries through the fallopian tubes creating a minimally invasive procedure. We characterize the falloposcope’s imaging behavior and show that this system provides contrast on ex vivo surgical samples of ovary and fallopian tube. In addition, we show the mechanical performance of the endoscope in an anatomically correct model of the female reproductive treatment.


Space travel thins skin as multiphoton tomography shows
Paper 9689-30

Author(s):  Karsten König, Univ. des Saarlandes (Germany), et al.
Conference 9689A: Photonics in Dermatology and Plastic Surgery
Session 11: Optical Microscopy I
Date and Time: Sunday, February 14, 2016, 2:20 PM

Skin impairments belong to the most frequent health problems during space missions. The multiphoton tomograph MPTflex. which provides non-invasively and label-free high resolution optical biopsies, was employed to study skin modifications of astronauts. This flexible clinical imaging system with its optomechanical arm measured pre-flight and post-flight the epidermis and upper dermis on six different sites of the volar left forearm of three European astronauts. The results of multiphoton sectioning based on two-photon autofluorescence and SHG of the collagen network demonstrate a thinning of the epidermis, a reduction of melanin and an increased collagen level after 6month space trips.


Two-photon autofluorescence/FLIM/SHGendoscopy to study the oral cavity and wound healing in humans
Paper 9691-9

Author(s):  Karsten König, Univ. des Saarlandes (Germany), et al.
Conference 9691A: Endoscopic Microscopy XI
Session 3: Confocal and Multimodality Imaging
Date and Time: Sunday, February 14, 2016, 2:40 PM

Monitoring the oral cavity noninvasively with superior 3D resolution is realized by clinical multiphoton tomography and high NA two-photon endoscopy without the need of additional contrast agents. The technology behind this investigation is based on nonlinear optical contrast of the multiphoton tomograph MPTflex®. Furthermore, the miniaturized GRIN endoscope was used to realize more accessibility for more demanding wound conditions in skin. The MPTflex® distinguishes autofluorescence (AF) signals from second harmonic generation (SHG) signals simultaneously. Fluorescence lifetime imaging (FLIM) based on time correlated single photon counting (TCSPC) technology offers additional information on the functional level of the intratissue fluorophores, their binding status, and the contribution of SHG signals in chronic wounds.


Intraoperative optical imaging of peritoneal carcinomatosis of colorectal origin using a vegf-targeted fluorescent tracer: results of the hi-light study, a first in human imaging study
Paper 9696-35

Author(s):  Marjory Koller, Univ. Medical Ctr. Groningen (Netherlands), et al.
Conference 9696: Molecular-Guided Surgery: Molecules, Devices, and Applications II
Session 7: Clinical Applications
Date and Time: Sunday, February 14, 2016, 2:45 PM

Optimal cytoreduction in addition to a Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) procedure is of essential value in the curative treatment of peritoneal carcinomatosis of colorectal origin. Currently, the surgeon is dependent on visual inspection and palpation, so malignant lesions can be easily missed. Intraoperative optical imaging can be of essential value for better detection of malignant lesions. This study shows the feasibility of the the detection of peritoneal metastases of colorectal origin using a VEGF-A targeted near-infrared tracer: Bevacizumab-800CW.


Mechanistic exploration of a bi-directional photochemotherapeutic combination for pancreatic cancer
Paper 9694-30

Author(s):  Huang-Chiao Huang, Massachusetts General Hospital (United States), et al.
Conference 9694: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV
Session 8: Photodynamic Therapy VIII
Date and Time: Sunday, February 14, 2016, 3:30 PM

It is increasingly evident that the most effective cancer treatments will involve interactive regimens that target multiple non-overlapping pathways, preferably such that each component enhances the others to improve outcomes while minimizing systemic toxicities. Toward this goal, we developed a combination of photodynamic therapy and irinotecan, which mechanistically cooperate with each other, beyond their individual tumor destruction pathways, to cause synergistic reduction in orthotopic pancreatic tumor burden. The mechanistic basis of the observed the synergism and the clinical translation potential of the combination will be discussed.


Parafoveal retinal cone mosaic imaging in children with ultra-compact switchable SLO/OCT handheld probe
Paper 9693-52

Author(s):  Francesco LaRocca, Duke Univ. (United States), et al.
Conference 9693: Ophthalmic Technologies XXVI
Session 10: Adaptive Optics and Cellular Imaging
Date and Time: Sunday, February 14, 2016, 4:45 PM

In vivo photoreceptor imaging has enhanced the way vision scientists and ophthalmologists understand the retinal structure, function, and etiology of numerous retinal pathologies. However, the large footprint of current systems capable of resolving photoreceptors is not suitable for imaging an important fraction of patients including bedridden patients and small children. Here, we show that our handheld probe, weighing only 94 g, can visualize photoreceptors in supine children (14 months to 12 years). This work lays the foundation for pediatric research, which will improve understanding of retinal development, maldevelopment and early onset of diseases during the beginning stages of human growth.


Large area 3-D optical coherence tomography imaging of lumpectomy specimens for radiation treatment planning
Paper 9689-151

Author(s):  Mark C. Pierce, Rutgers, The State Univ. of New Jersey (United States), et al.
Conference 9689E: Diagnosis and Treatment of Diseases in the Breast and Reproductive System II
Session PSun: Posters-Sunday
Date and Time: Sunday, February 14, 2016, 5:30 PM

We have assembled a benchtop spectral-domain optical coherence tomography (SD-OCT) system for comprehensive assessment of tissue removed during lumpectomy procedures. Multiple sub-volumes are acquired and en face images spanning the entire specimen (up to 40 mm x 25 mm) are reconstructed. These en face OCT images are compared to established disease markers on corresponding histopathology sections. We are currently assessing the accuracy of tissue classification based on OCT image features. Ongoing work includes developing algorithms for mapping OCT image volumes to clinical CT and MRI images to guide post-operative treatment planning.


Metal-clad waveguide characterization for contact-based light transmission into tissue
Paper 9689-40

Author(s):  Jeff A. Chininis, Univ. of Missouri (United States), et al.
Conference 9689A: Photonics in Dermatology and Plastic Surgery
Session PSun: Posters-Sunday
Date and Time: Sunday, February 14, 2016, 5:30 PM

Contemporary laser dermatology applications have been steadily increasing in popularity, but are nevertheless consistently subject to problems of over-exposure, ocular injury, and excessive thermal damage. Transmitting the laser light through metal-clad planar waveguides promises to circumvent these issues by reducing the operating distance between the laser source and the tissue to 0, thereby enclosing the beam path, eliminating back-reflections, and allowing for the easy incorporation of contact cooling technologies. Cladding glass substrates with titanium and silver forces light to propagate along the length of the waveguide, while also encouraging evanescent leaking through designated active areas in contact with tissue.


Safety and efficacy of photo modulation therapy for weight loss
Paper 9695-19

Author(s):  Ambereen Ahmed, A&M Assorted Therapy, LLC (United States), et al.
Conference 9695: Mechanisms of Photobiomodulation Therapy XI
Session PSun: Posters-Sunday
Date and Time: Sunday, February 14, 2016, 5:30 PM

Photomodulation therapy uses light from a laser and is, therefore, a non-invasive, non-thermal treatment that is also being explored as an alternative to lipoplasty for fat removal. Based on the studies reported in this review, photo modulation therapy is a safe technique that showed promising results in reducing the circumference of treated body parts.. The mechanism of action of how photo modulation therapy removes fat from the mammalian cells is controversial and requires further investigation. Moreover, additional studies demonstrating the efficacy of photo modulation therapy in larger groups would be helpful in establishing this technique for regular clinical use.


The lavender procedure: how we do it
Paper 9689-157

Author(s):  Phillip Bretz, The Visionary Breast Ctr. (United States), et al.
Conference 9689E: Diagnosis and Treatment of Diseases in the Breast and Reproductive System II
Session PSun: Posters-Sunday
Date and Time: Sunday, February 14, 2016, 5:30 PM

If the National Cancer Institute prediction is correct that the number of breast cancers will double in the U.S. by 2030, other diagnostic and therapeutic capabilities need to be researched. Heterogeneity is the cause of treatment failure. Visionary Breast Centers has developed an alternative to current diagnostic and treatment methods using non-radiation modalities including infrared and liquid nitrogen. The key is to preempt heterogeneity. The Lavender Procedure is an in office 20 minute procedure and under certain conditions it is definitive treatment for breast cancer. The Lavender Procedure can eliminate the need for surgery, chemotherapy and radiation.


A fiber-delivered optoacoustic guide for precise breast-conserving surgery
Paper 9689-158

Author(s):  Ji-Xin Cheng, Purdue Univ. (United States), et al.
Conference 9689E: Diagnosis and Treatment of Diseases in the Breast and Reproductive System II
Session PSun: Posters-Sunday
Date and Time: Sunday, February 14, 2016, 5:30 PM


Reducing the cost of tethered capsule endomicroscopy for Barrett's esophagus screening
Paper 9691-21

Author(s):  Rohith Reddy, Massachusetts General Hospital (United States), et al.
Conference 9691A: Endoscopic Microscopy XI
Session 6: OCT II
Date and Time: Monday, February 15, 2016, 10:30 AM

Optical coherence tomography (OCT) is an imaging technology that forms depth-resolved images by using interferometry to measure the optical delay of backscattered light from a sample. It has been shown in prior studies to be capable of accurately diagnosing Barrett’s Esophagus (BE), a metaplastic change that conveys an increased risk of developing esophageal adenocarcinoma (EAC). Tethered capsule endomicroscopy (TCE) using OCT is a technology developed in our lab where a tethered opto-mechanical capsule that is 11mm x 24.5mm in size obtains 10 µm resolution cross-sectional OCT images of the entire esophageal wall as it traverses the esophagus via peristalsis. Recent work1 improved on this technology by replacing the TCE rotary junction (RJ) and driveshaft by a micro-motor. While this has several advantages, the cost of the motor and consequently that of the capsule is relatively high for a disposable device, hindering wide adoption for BE screening. In this work we develop a new generation TCE device that is significantly less expensive in both fixed and disposable costs while producing better, quantitative data at the same time. The expensive RJ is replaced by an inexpensive cell-phone micro-motor that costs less than $10. We mitigate challenges arising out of the relatively poor speed characteristics of the inexpensive motors and obtain imaging performance comparable to that from a RJ by performing image segmentation on OCT data, estimating speed characteristics of the micro-motor and using a feedback-loop to correct for imperfections arising from using the inexpensive micro-motor. Consequently, the fixed and disposable costs of the TCE device are reduced dramatically facilitating wide adoption of TCE for BE screening in primary care settings. 1 Liang et. al. Ultrahigh speed en face OCT capsule for endoscopic imaging, Biomed Opt Express. 6(4): 1146–1163, 2015


Tethered capsule OCT endomicroscopy for upper gastrointestinal tract imaging by using ball lens based probe
Paper 9691-22

Author(s):  Jing Dong, Wellman Ctr. for Photomedicine, Massachusetts General Hospital (United States), et al.
Conference 9691A: Endoscopic Microscopy XI
Session 6: OCT II
Date and Time: Monday, February 15, 2016, 10:50 AM

In this abstract, we report on the new design of simplified tethered capsule OCT endomicroscopy (TCE) optics, where an angle-polished ball lens design was adopted instead of GRIN lens-based configuration which has been previously presented by our lab. The new optics includes a single mode optical fiber, a glass spacer and an angle polished ball lens. The tethered capsule with ball lens design renders 30µm (lateral) × 7 µm (axial) resolutions as it travels through the gastrointestinal (GI) tract, while it decreases the cost and improved the manufacturability of the capsule’s optical configuration.


Feasibility of optical coherence tomography to detect radiation-induced esophageal damage in small animal models
Paper 9691-23

Author(s):  Pouya Jelvehgaran, Academisch Medisch Centrum (Netherlands), et al.
Conference 9691A: Endoscopic Microscopy XI
Session 6: OCT II
Date and Time: Monday, February 15, 2016, 11:10 AM

Lung cancer radiotherapy is hampered by toxicity to nearby healthy organs. Improved knowledge of the effect of irradiation on the organs at risk is required. Current techniques are limited in determination of radiation-induced esophageal damage. In this study we investigated the feasibility of optical coherence tomography (OCT) to detect radiation-induced esophageal damage in a small animal model. We compared toxicity based on the histopathology reports with OCT. The results indicate the feasibility of OCT to detect the radiation-induced damage, which occurred primarily at high-radiation-dose regions (16Gy and 20Gy delivered in a single fraction).


Tethered capsule endomicroscopy with capsule position localization for diagnosis of diseases of the upper gastrointestinal tract
Paper 9691-27

Author(s):  Oriane Poupart, Wellman Ctr. for Photomedicine, Massachusetts General Hospital (United States), et al.
Conference 9691A: Endoscopic Microscopy XI
Session PMon: Posters-Monday
Date and Time: Monday, February 15, 2016, 5:30 PM

Tethered capsule endomicroscopy (TCE) is a newly developed technique that involves swallowing a capsule that performs in vivo microscopy. We are currently unable to track the position of the capsule, which limits our ability to study the organ in three dimensions and evaluate disease progression. In this paper, we describe the incorporation of a 6DOF miniature electromagnetic sensor that communicates with a transmitter and an electronic unit. Testing results show that the precision is better than 1 mm over a range of -30cm to +30cm from the transmitter. These results suggest that electromagnetic position tracking technology will be suitable for TCE capsule position localization.


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26 September 2016

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Journal of Biomedical Optics

Journal of Biomedical OpticsPublishes peer-reviewed papers that utilize modern optical technology for improved health care and biomedical research.