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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 by conference and paper number)


Quantitative assessment of graded burn wounds using a commercial and research grade laser speckle imaging (LSI) system
Paper 10037-18

Author(s):  Adrien Ponticorvo, Beckman Laser Institute and Medical Clinic, Univ. of California, Irvine (United States), et al.
Conference 10037: Photonics in Dermatology and Plastic Surgery
Session : Wide-Field Imaging

Accurately diagnosing burn severity in a timely manner is critical for improving patient outcomes by dictating the correct wound management strategy as early as possible. To address this challenge, research groups have studied the use of commercial laser Doppler (LDI) and laser speckle imaging (LSI) systems to provide objective characterization of burn-wound severity. Here we studied the performance of a commercial LSI system (Pericam PSI, Perimed AB) and a research grade LSI system in a controlled environment and an animal study to quantitatively compare the performance of both systems and also better understand the “Perfusion Unit” output of commercial systems.


Spectral biopsy for skin cancer diagnosis: initial clinical results
Paper 10037-2

Author(s):  Austin Moy, The Univ. of Texas at Austin (United States), et al.
Conference 10037: Photonics in Dermatology and Plastic Surgery
Session 1: Skin Cancer I: Spectroscopy and Wide-Field Imaging

Skin cancer diagnosis typically involves an invasive and expensive biopsy of the suspicious lesion followed by histopathology. An unmet critical need exists to develop a non-invasive and inexpensive screening method that can eliminate the need for unnecessary biopsies of suspicious skin lesions. We report our progress on the continued development of a multimodal spectroscopy system towards the goal of a “spectral biopsy” of skin. We describe the first results from an extensive clinical study (n = 250) to evaluate our approach.


Combined multimodal photoacoustic tomography, optical coherence tomography (OCT) and OCT based angiography system for in vivo imaging of multiple skin disorders in human
Paper 10037-29

Author(s):  Mengyang Liu, Medizinische Univ. Wien (Austria), et al.
Conference 10037: Photonics in Dermatology and Plastic Surgery
Session 8: OCT Angiography

In this work, we combine an all optical photoacoustic tomography (PAT) system with an optical coherence tomography (OCT) system with angiography extension. This multimodal PAT/OCT/OCT-angiography system provides co-registered human skin vasculature information as well as the structural information of cutaneous. The scanning probe is mounted onto a portable rack, allowing the probe to access nearly all regions of human body. Fused PAT/OCT-angiography volume shows the complete blood vessel network in human skin, which is further embedded in the morphology provided by OCT. Our results demonstrate the clinical translational value of this multimodal optical imaging system in dermatology.


Development of an integrated skin marking tool for use with optical coherence tomography for skin diseases.
Paper 10037-33

Author(s):  Andrew J. Coleman, Guy's and St Thomas' NHS Foundation Trust (United Kingdom), et al.
Conference 10037: Photonics in Dermatology and Plastic Surgery
Session 9: OCT

Non-invasive imaging is an emerging field in dermatology with valuable application in diagnosis and in assessing the pre-surgical margins of skin cancer. Optical Coherence Tomography (OCT), for example, provides sufficient resolution to the depth of the dermis to reveal sub-clinical spread of disease. Accurate OCT image-guided delineation of the disease margin is currently degraded in practice by the need to remove the OCT probe to physically mark the skin. We have developed a device that integrates with the probe allowing the skin to be marked whist simultaneously imaging. We present data on the performance and clinical accuracy of the system.


Physiological basis for noninvasive skin cancer diagnosis using diffuse reflectance spectroscopy
Paper 10037-5

Author(s):  Yao Zhang, The Univ. of Texas at Austin (United States), et al.
Conference 10037: Photonics in Dermatology and Plastic Surgery
Session 1: Skin Cancer I: Spectroscopy and Wide-Field Imaging

To provide physiological basis for spectral diagnoses, we used the Monte Carlo look-up table (MCLUT) model to extract physiological parameters from reflectance spectra acquired in the clinic. We built logistic regression classifiers and compared our classification results with histopathology of tissue. Higher sensitivity and specificity were achieved for most of classifications compared to our previous principal component analysis (PCA) results. Physiological parameters show that cancerous skin tissue has lower oxygen saturation, higher hemoglobin concentration, lower scattering, and larger vessel radius, compared to normal tissue. These results demonstrate the potential of our model for detection of early precancerous changes in tissue.


Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels
Paper 10037-6

Author(s):  Jianhua Zhao, The Univ. of British Columbia (Canada), et al.
Conference 10037: Photonics in Dermatology and Plastic Surgery
Session 2: Skin Cancer II: Raman and Fluorescence Spectroscopy

We proposed a method for wavenumber selection in Raman spectroscopy analysis for skin cancer diagnosis. It was implemented using windows of wavenumber and leave-one-out cross-validated stepwise regression or least and shrinkage selection operator (LASSO). The diagnostic algorithms were generated from the selected windows of wavenumber using principal component and general discriminant analysis (PC-GDA) or partial least squares (PLS). For a cohort of 645 confirmed lesions, the area under the receiver operating characteristic curve (ROC) was improved from 0.861–0.891 to 0.891–0.911 and the diagnostic specificity was improved from 0.17–0.65 to 0.20–0.75 for sensitivity levels 0.99–0.90 respectively.


Characterization of UV irradiation damage in skin fibroblasts using Raman Spectroscopy
Paper 10037-8

Author(s):  Surya P. Singh, Massachusetts Institute of Technology (United States), et al.
Conference 10037: Photonics in Dermatology and Plastic Surgery
Session 2: Skin Cancer II: Raman and Fluorescence Spectroscopy

Minimizing morbidities in skin cancer cases requires sustained research with the goal of obtaining improved diagnostic methods and new safe regimen strategies. The present study aims at predicting radiation induced damage by specific markers and transition of spectroscopic methods for in vivo analyses. Using Raman spectroscopy, we have shown that both morphological and biochemical changes due to UV irradiation induced can be identified in a dose dependent manner. The findings are expected to provide an accurate understanding of different markers associated with radiation damage and would assist in providing a quantitative base to our future studies on designing alternate diagnostic tools.


Skin cancer margin analysis within minutes with FFOCT
Paper 10037-9

Author(s):  Eugénie Dalimier, LLTech SAS (France), et al.
Conference 10037: Photonics in Dermatology and Plastic Surgery
Session 3: Skin Cancer III: Optical Microscopy and OCT

Full-field optical coherence tomography (FFOCT) offers a fast and non-destructive method of obtaining images of biological tissues at ultrahigh resolution approaching traditional histological sections. There is a current need for a fast intra-operative skin cancer margin assessment during skin cancer treatment. FFOCT imaging of skin cancer margins shows good concordance with histology and does not introduce artifacts on traditional frozen section histology. FFOCT shows good promise as a valuable fast intra-operative margin assessment tool. It can potentially reduce recurrence rates, surgery time, and optimize clinical workflow.


In vivo fluorescence imaging of an orthotopic rat bladder tumor model indicates differential uptake of intravesically instilled near-infrared labeled 2-deoxyglucose analog by neoplastic urinary bladder tissues
Paper 10038-1

Author(s):  Daqing Piao, Oklahoma State Univ. (United States), et al.
Conference 10038: Therapeutics and Diagnostics in Urology
Session 1: Fluorescence Imaging

Differential uptake of intravesically administered IRDye800CW-DG in an orthotopic rat bladder tumor model was explored. Twenty-five female Fischer rats were randomly grouped to group-1) no-tumor-control treated with intravesical saline (n=3), group-2) no-tumor-control intravesically instilled with IRDye800CW-DG (n=6), group-3) rats bearing GFP-labeled AY-27 rat bladder urothelial cell carcinoma cells and washed with saline (n=5), and group-4) rats treated with AY-27 and intravesically instilled with IRDye800CW-DG ( n=11). There is no significant difference of the fluorescence intensity among the group 1-3. When compared to that of the group-2, the fluorescence intensity of group-4 was remarkably stronger (3.34 folds of the former) (p<0.0001).


Investigations on Ho:YAG-laser induced lithrotripsy
Paper 10038-13

Author(s):  Max Eisel, Laser-Forschungslabor (Germany), et al.
Conference 10038: Therapeutics and Diagnostics in Urology
Session 4: Laser Lithotripsy

This study of Ho:YAG laser lithotripsy focussed on the investigation of different laser parameters in relation to the stone dusting efficiency. Reproducible experiments were performed on Bego-Stones of different hardness. Dusting (dfrag<1mm) can be reached most efficient by using low energy/pulse and high repetition rate. Higher energy/pulse showed strong repulsion and thereby increased mobility. Dusting and fragmentation process depends not only on the energy/pulse and repetition rate of a Ho:YAG-laser system.


Optical monitoring of kidney oxygenation and hemodynamics using a miniaturized near-infrared sensor
Paper 10038-17

Author(s):  Babak Shadgan, The Univ. of British Columbia (Canada), et al.
Conference 10038: Therapeutics and Diagnostics in Urology
Session 5: Spectroscopy I

We report the feasibility of near-infrared spectroscopy (NIRS) monitoring of the kidney to detect renal tissue ischemia and hypoxia in an animal model. We have shown that a customized NIRS sensor can detect renal ischemia and tissue hypoxia induced by renal artery ligation. A modification of our optical method may contribute to early detection of renal vascular complications.


Prostate cancer diagnosis with fluorescence lifetime imaging
Paper 10038-2

Author(s):  Shamira Sridharan, Univ. of California, Davis (United States), et al.
Conference 10038: Therapeutics and Diagnostics in Urology
Session 1: Fluorescence Imaging


Orthotopic AY-27 rat bladder urothelial cell carcinoma model presented an elevated methemoglobin proportion in the increased total hemoglobin content when evaluated in vivo by single-fiber reflectance spectroscopy
Paper 10038-20

Author(s):  Tengfei Sun, Oklahoma State Univ. (United States), et al.
Conference 10038: Therapeutics and Diagnostics in Urology
Session 5: Spectroscopy I

In vivo single-fiber reflectance spectroscopy (SfRS) was performed on an orthotopic rat bladder tumor model to explore potential spectroscopic features revealing neoplastic changes. AY-27 bladder urothelial cell carcinoma cells were intravesically instilled in four rats. A total of 107 SfRS measurements were taken from 80 sites on four AY-27 instilled bladders and 27 sites on two controls. The spectral profiles obtained from AY-27 instilled bladders revealed various levels of a methemoglobin characteristic feature around 635nm. The elevation of the methemoglobin proportion in the total hemoglobin correlated with the increase of total hemoglobin concentration.


Optical monitoring of testicular torsion using a miniaturized near infrared spectroscopy sensor
Paper 10038-22

Author(s):  Babak Shadgan, The Univ. of British Columbia (Canada), et al.
Conference 10038: Therapeutics and Diagnostics in Urology
Session 6: Spectroscopy II

In this study an animal model of testicular torsion was used to examine the feasibility and sensitivity of a spatially-resolved near infrared spectroscopy (SR-NIRS) system with a custom-made miniaturized optical sensor probe to detect and study changes in testicular hemodynamics and oxygenation during and after three degrees of induced testicular torsion (360, 720, 1080 degrees) and after detorsion. This study offers the potential for SR-NIRS using a miniaturized sensor to be explored as for rapid and noninvasive means of detecting testicular torsion in children.


Discrimination of Malignant and Benign Kidney tissue with 1064 nm dispersive Raman spectroscopy
Paper 10038-23

Author(s):  Miki Haifler, Fox Chase Cancer Ctr. (United States), et al.
Conference 10038: Therapeutics and Diagnostics in Urology
Session 6: Spectroscopy II

Many kidney masses are misclassified as malignant and removed surgically. Raman spectroscopy (RS) has been widely demonstrated for disease discrimination. A 1064nm excitation dispersive RS system demonstrated the ability to collect spectra with superior quality from kidney tissue. Our objective is to develop a 1064 nm dispersive detection RS system capable of differentiating normal and malignant renal tissue. A total of 93 measurements were collected from 12 specimens (6 Renal Cell Carcinoma, 6 Normal ). Spectral classification was performed using sparse multinomial logistic regression (SMLR). Correct classification was obtained in 78%. This indicates the potential for accurately separating healthy and cancerous tissues.


Investigations on the fluorescence of urinary stones
Paper 10038-3

Author(s):  Ronald Sroka, Laser-Forschungslabor (Germany), et al.
Conference 10038: Therapeutics and Diagnostics in Urology
Session 1: Fluorescence Imaging


Quality control and primo-diagnosis of transurethral bladder resections with full-field OCT
Paper 10038-4

Author(s):  Eugénie Dalimier, LLTech SAS (France), et al.
Conference 10038: Therapeutics and Diagnostics in Urology
Session 2: OCT/DOT

Full-field optical coherence tomography (FFOCT) offers a fast and non-destructive method of obtaining images of biological tissues at ultrahigh resolution, approaching traditional histological sections. In the context of bladder cancer diagnosis and treatment, there is a current need for an intra-operative tool for transurethral bladder resections. FFOCT imaging of transurethral bladder resections showed very good concordance with histology and no artefacts for the histological preparation. FFOCT shows good promise to be a valuable quality control and primo-diagnosis tool for transurethral bladder resections in the urology suite.


Using optical coherence tomography to detect bacterial biofilm on foley catheters
Paper 10038-5

Author(s):  Andrew E. Heidari, Beckman Laser Institute and Medical Clinic (United States), et al.
Conference 10038: Therapeutics and Diagnostics in Urology
Session 2: OCT/DOT

Urinary tract infections(UTI) caused by indwelling foley catheters pose a serious problem for hospital patients accounting for 33% of all hospital acquired(nosocomial) infections. The presence of an indwelling foley catheter provides a scaffolding for circulating planktonic bacteria to adhere to and to form microbial biofilm communities that would typically be hindered by the body’s innate immune system response. It is these bacterial communities in the biofilms that are the main pathogenesis of urinary catheter-associated infections. By utilizing Optical Coherence Tomography, a minimally invasive high resolution imaging technique, we will build a better understanding of biofilm formation in-vitro.


Micro-optical coherence tomography imaging of cochlear cells and nerve fibers
Paper 10039-1

Author(s):  Janani Iyer, Harvard-MIT Health Sciences and Technology (United States), et al.
Conference 10039: Optical Imaging, Therapeutics, and Advanced Technology in Head and Neck Surgery and Otolaryngology
Session 1: OCT and Related Technologies for Middle and Inner Ear Imaging

Due to its small size, complex 3D structure, and deeply embedded location, the cochlea has historically resisted attempts at clinical imaging for assessing structural integrity. As a result, little is know about the relationship between cochlear pathology and hearing deterioration, significantly hindering otologists’ ability to personalize patient diagnosis and therapy. Here we demonstrate the ability of micro-optical coherence tomography (µOCT), a non-invasive, low-coherence interferometric imaging technique, to capture critical intracochlear anatomical structures at micron-level resolution in the guinea pig cochlea in situ, motivating further investigation into µOCT’s potential utility as an imaging tool in otology research and clinical practice.


Diffuse reflectance spectroscopy from 400-1600 nm to evaluate tumor resection margins during head and neck surgery
Paper 10039-12

Author(s):  Susan G. Brouwer de Koning, The Netherlands Cancer Institute (Netherlands), et al.
Conference 10039: Optical Imaging, Therapeutics, and Advanced Technology in Head and Neck Surgery and Otolaryngology
Session 3: Multimodal Imaging Technologies in Head and Neck Tumor Detection, Staging and Follow-Up

This ex vivo study evaluates the feasibility of diffuse reflectance spectroscopy (DRS) for discriminating tumor from healthy oral tissue, with the aim to develop a technique that can be used to determine a complete excision of tumor through intraoperative margin assessment. DRS spectra were acquired on fresh surgical specimens from patients with an oral squamous cell carcinoma. Preliminary results showed that the diffuse light reflection at 650-750 nm contains sufficient spectral information to discriminate tumor from healthy tissue in an ex vivo setting. More analyses have been performed to further evaluate this technique, prior to in vivo patient measurements.


In vivo nasopharyngeal carcinoma staging using rapid fiber-optic Raman endoscopy
Paper 10039-16

Author(s):  Zhiwei Huang, National Univ. of Singapore (Singapore), et al.
Conference 10039: Optical Imaging, Therapeutics, and Advanced Technology in Head and Neck Surgery and Otolaryngology
Session 3: Multimodal Imaging Technologies in Head and Neck Tumor Detection, Staging and Follow-Up

We evaluate the diagnostic performance of a rapid simultaneous fingerprint and high wavenumber (HW) fiber-optic Raman endoscopy platform for in vivo real-time nasopharyngeal carcinoma (NPC) staging during clinical endoscopy. The integrated FP and HW Raman spectra were acquired from 26 cancerous sites from 10 NPC patients. Multivariate diagnostic algorithms based on principal component analysis (PCA) and linear discriminate analysis (LDA) yield an encouraging accuracy of ~84% for discrimination early and advanced NPC stage. This result reveal the great potential of the FP/HW Raman endoscopic technique developed for monitoring different NPC stages in vivo during routine endoscopic examination.


The mechanism for welding with a green laser: revisited
Paper 10039-20

Author(s):  Claus-Peter Richter, Northwestern Univ. (United States), et al.
Conference 10039: Optical Imaging, Therapeutics, and Advanced Technology in Head and Neck Surgery and Otolaryngology
Session 4: Advances in Photodynamic Therapy, Tissue Reduction and Joining in Head and Neck Surgery


Longitudinal intravital imaging in the murine bone marrow
Paper 10040-1

Author(s):  David Reismann, Deutsches Rheuma-Forschungszentrum Berlin (Germany), et al.
Conference 10040: Endoscopic Microscopy XII
Session 1: New Techniques

To date, intravital imaging in the murine bone marrow (BM) by 2PM is limited to a few hours and depths < 150 µm. We developed a reproducible microendoscopy technique based on GRIN lenses that allows for longitudinal intravital multiphoton microendoscopy in BM (LIMB). A titanium implant precisely guides a 350 µm thin microendoscope into the marrow cavity. This implant is fixed to the femur, allowing repeated access over more than 100 days without further surgical procedures. We use this approach to study immune reactions and elucidate the role of immune and bone cells in fracture models.


In vivo multiplexed molecular endoscopy of esophageal cancer in an orthotopic rat model with topically applied SERS nanoparticles
Paper 10040-10

Author(s):  Yu Wang, Univ. of Washington (United States), et al.
Conference 10040: Endoscopic Microscopy XII
Session 2: Spectroscopy/Polarization

In order to improve the biological investigation and early detection of esophageal cancers, we demonstrate that the topical application and endoscopic imaging of biomarker-targeted SERS NPs, in which various “flavors” of SERS NPs may be identified by their unique spectral signatures, enables the rapid detection of tumors in an orthotopic rat model of esophageal cancer.


Optimizing the villi visualization by tethered capsule OCT endomicroscopy for comprehensive imaging of human duodenum
Paper 10040-12

Author(s):  Jing Dong, Wellman Ctr. for Photomedicine (United States), et al.
Conference 10040: Endoscopic Microscopy XII
Session 3: Tethered Capsule Endomicroscopy

The diagnosis of celiac disease in the duodenum is made by random endoscopic biopsy, which is a gold standard that is flawed by sampling error. In this abstract, we report on a new tethered capsule OCT endomicroscopy (TCE) device that is optimized to enable clear visualization of villi throughout the entire human duodenum. The primary change over other OCT TCE devices is additional structure added to the outer surface of capsule that improves visualization of villus height and crypt depth.


Clinical utility of ultrahigh speed endoscopic optical coherence tomography and angiography in gastroenterology
Paper 10040-25

Author(s):  Osman O. Ahsen, Massachusetts Institute of Technology (United States), et al.
Conference 10040: Endoscopic Microscopy XII
Session 5: Optical Coherence Tomography

We report our clinical studies performed with an ultrahigh speed endoscopic swept source OCT system with 600kHz axial scan rate. In combination with distal scanning micromotor devices, this technology enables depth resolved en face visualization of tissue microstructure, i.e. pit patterns, as well as OCT angiography (OCTA) to visualize microvasculature in 3D without contrast agents. We will present examples of cross-sectional and en face OCT and OCTA data that show characteristic hallmarks of a range of upper and lower GI pathologies. In addition, we will present the results of our diagnostic studies on identifying dysplasia in Barrett’s esophagus.


A handheld MEMS-based line-scanned dual-axis confocal microscope for early cancer detection and surgical guidance
Paper 10040-31

Author(s):  Ye Chen, Univ. of Washington (United States), et al.
Conference 10040: Endoscopic Microscopy XII
Session 7: MEMS-based Endoscopic Imaging: Joint Session with Conferences 10040 and 10116

A miniature MEMS-based line-scanned dual-axis confocal (LS-DAC) microscope, with a 12-mm diameter distal tip, has been developed for the early detection of oral cancers and for guiding brain tumor resection. We will discuss the design of the LS-DAC microscope device, which features a high frame rate of >15 frames/sec, and preclinical validation with phantoms and animal models.


Differential Structured Illumination Microendoscopy for in vivo imaging of molecular contrast agents and cervical dysplasia
Paper 10040-4

Author(s):  Pelham Keahey, Rice Univ. (United States), et al.
Conference 10040: Endoscopic Microscopy XII
Session 1: New Techniques

Fiber-optic microendoscopes have shown promise as an imaging tool capable of visualizing molecular contrast agents used to study disease in vivo. However, image contrast can be severely limited when imaging highly scattering tissue. Here we present differential structured illumination microendoscopy (DSIMe) capable of performing structured illumination in a fiber-optic microendoscope. Sectioning can be performed at video rates without the need for opto-mechanical components on the distal end of the fiber-bundle. We demonstrate contrast enhancement using DSIMe to image cervical tissue in patients diagnosed with cervical precancer and an improved ability to identify cellular changes associated with neoplasia in vivo.


Spectral and lifetime endoscopic measurements using one and two-photon excitation
Paper 10040-9

Author(s):  Darine Abi Haidar, IMNC Lab., Institut National de Physique Nucléaire et de Physique des Particules (France), et al.
Conference 10040: Endoscopic Microscopy XII
Session 2: Spectroscopy/Polarization

Eliminating time-consuming process of conventional biopsy is a clinical need, as well as increasing the accuracy of tissue diagnostics and patient comfort. We propose to address these needs by developing a multimodal nonlinear endomicroscope that allow real-time optical biopsies during surgery. In this work we present the first spectral and fluorescence lifetime measurements taken by this endomicroscopic system based on a new homemade optical fiber. This investigation was made with one and two photons excitation on freshly and fixed human brain tissues.


In-vitro investigation on the interaction of thulium-laser irradiation with bronchial stents
Paper 10041-19

Author(s):  Ronald Sroka, Laser-Forschungslabor (Germany), et al.
Conference 10041: Optical Techniques in Pulmonary Medicine IV
Session 4: Novel Techniques for Pulmonary Imaging

Granulation and tumor regrowth in the area of bronchi stent implants may result in restenosis. Although a controlled ablation and reduction of the tissue within the stent could be performed using TFL investigation of potential risk factors are necessary. Clinical used stents fixed to pig trachea tissue underwent laser exposure under different parameters. Appearance of ruptures, perforations, burns and flames were dependent on light application parameter. In clinical TFL-irradiation distance should be ≥5mm, power level should be reduced to ≤6W, oxygen conc. should not exceed 30% and short term continuous irradiation texposition< 15s should be considered. Contamination should be avoided.


Fluorescence lifetime intravascular ultrasound (FL-IVUS) and the quest to discriminate between early and advanced lipid cores in atherosclerosis
Paper 10042-11

Author(s):  Jennifer E. Phipps, Univ. of California, Davis (United States), et al.
Conference 10042: Diagnostic and Therapeutic Applications of Light in Cardiology
Session 2: Multimodality Imaging

FL-IVUS combines intravascular ultrasound with fluorescence lifetime imaging to obtain morphologic and biochemical details from the arterial wall. We focused on the ability of FL-IVUS to differentiate between early and advanced lipid cores—advanced cores are vulnerable to rupture. We imaged N=12 ex vivo human coronary arteries. IVUS was able to observe the increased plaque burden and calcification of the advanced and deep necrotic cores, but could not identify early lipid cores, foam cell infiltration or discriminate between deep necrotic cores and TCFA. The addition of FLIm to IVUS allowed the TCFA to be discriminated from early lipid accumulation.


Machine learning voxel-based coronary artery plaque classification from IVOCT images
Paper 10042-19

Author(s):  David L. Wilson, Case Western Reserve Univ. (United States), et al.
Conference 10042: Diagnostic and Therapeutic Applications of Light in Cardiology
Session 4: Optical Coherence Tomography

Visual interpretation of a 500-image, IVOCT coronary artery pullback is difficult, especially during a stressful intervention. We created a multi-class machine learning method to automatically classify plaque tissues as calcified, lipid-rich, or fibrous. We trained and tested on manually labeled sub-volumes from 35 clinical pullbacks (9485 images), and obtained better than 87% correct voxel classification. Results generalized with similar accuracy on independent, ex-vivo data accurately annotated using registered 3D microscopic cryo-imaging. Since voxel-wise classification is noisy with greater resolution than needed, we applied sector plurality voting to improve accuracy. Visualizations of plaque allow one to rapidly review results and make informed treatment decisions.


Contact optical rotary junction for multi-modality optical coherence tomography and near-infrared fluorescence/autofluorescence imaging
Paper 10042-8

Author(s):  Zhonglie Piao, Harvard Medical School (United States), et al.
Conference 10042: Diagnostic and Therapeutic Applications of Light in Cardiology
Session 2: Multimodality Imaging

Fiber based multimodality endoscopic imaging techniques such as intravascular OCT-NIRF, OCT-NIRAF imaging have been widely investigated. One of the main challenges of multimodal imaging is transmit the optical signal in different wavelength band high efficiently through the optical rotary junction. In this work, we present a compact rotary junction with an optical contact design. The insertion loss with angle variation was measured and analyzed. The proposed RJ was validated by OCT-NIRF and OCT-NIRAF imaging of coronary arteries ex vivo. Results show that a stable and high signal to noise ratio OCT and fluorescence data can be achieved with the device.


Detection and characterization of atherosclerotic plaques by Raman probe spectroscopy and optical coherence tomography
Paper 10042-9

Author(s):  Christian Matthäus, Leibniz-Institut für Photonische Technologien e.V. (Germany), et al.
Conference 10042: Diagnostic and Therapeutic Applications of Light in Cardiology
Session 2: Multimodality Imaging

Visualization and characterization of inner arterial plaque depositions is of vital diagnostic interest, especially for early recognition of vulnerable plaques. Established intravascular imaging techniques provide valuable morphological information, but cannot deliver information about the chemical composition of individual plaques. Probe based Raman spectroscopy offers the possibility for a biochemical characterization of atherosclerotic plaque formations during an intravascular intervention. In combination with OCT imaging the obtained spectral information can provide substantial information supporting on on-site diagnosis of various plaque types and therefor an improved risk assessment. Here, the feasibility of combining OCT with Raman spectroscopy is demonstrated.


Breast cancer margin delineation with fluorescence lifetime imaging
Paper 10043-10

Author(s):  Jennifer E. Phipps, Univ. of California, Davis (United States), et al.
Conference 10043: Diagnosis and Treatment of Diseases in the Breast and Reproductive System III
Session 3: Tumor Margin Assessment

The current standard of care for early stages of breast cancer is breast-conserving surgery (BCS). Currently there is no method to determine if cancer cells exist at the margins of lumpectomy specimens aside from time-intensive histology methods that result in reoperations in up to 38% of cases. We used fluorescence lifetime imaging (FLIm) to measure time-resolved autofluorescence from N=13 ex vivo human breast cancer specimens (N=10 patients undergoing lumpectomy or mastectomy) and compared our results to histology. Tumor (both invasive and ductal carcinoma in situ), fibrous tissue, fat and fat necrosis have unique fluorescence signatures.


Spatial frequency domain imaging (SFDI) as a new tool for monitoring chemotherapy response and resistance
Paper 10043-12

Author(s):  Darren M. Roblyer, Boston Univ. (United States), et al.
Conference 10043: Diagnosis and Treatment of Diseases in the Breast and Reproductive System III
Session 4: Breast Cancer

SFDI was used to track chemotherapy response and treatment resistance in a preclinical tumor model. The effects of key parameters including the choice of imaging spatial frequency and inverse model were evaluated. Baseline chromophore values and intratumor heterogeneity were evaluated over 25 tumors, and chemotherapy response and resistance was tracked over a 45 day longitudinal study. Optical scattering and oxygen saturation increased as much as 70% and 25% respectively in treated tumors, and substantial differences were observed between cytotoxic and antiangiogenic therapies during initial response and treatment rebound. SFDI may aid in the translation of new therapeutic strategies.


Detecting breast cancer using contrast-enhanced multimodal optical imaging
Paper 10043-38

Author(s):  Anna N. Yaroslavsky, Univ. of Massachusetts Lowell (United States), et al.
Conference 10043: Diagnosis and Treatment of Diseases in the Breast and Reproductive System III
Session PSun: Posters-Sunday

Demarcation of cancer is required during surgery. We evaluated a pH low insertion peptide(pHLIP) for the detection of breast cancer and compared the results with those yielded by Methylene Blue(MB). Experiments demonstrated increased pHLIP-Alexa 532 emission and high MB polarization of fluorescence in cancer. Both pHLIP-Alexa532 and MB accumulated in cancer cells. MB also stained nuclei of normal cells. Fluorescence emission of MB highlights morphology of breast tissue. pHLIP-Alexa532 stained the cytoplasm of cancer cells. The results indicate that fluorescence emission imaging of pHLIP-Alexa 532 exhibits high specificity for breast cancer and can be used for detecting malignant cancers.


Cost-effective triaging of prostatectomy specimens using light sheet microscopy
Paper 10043-8

Author(s):  Nicholas P. Reder, Univ. of Washington Medical Ctr. (United States), et al.
Conference 10043: Diagnosis and Treatment of Diseases in the Breast and Reproductive System III
Session 3: Tumor Margin Assessment

Pathology laboratories must balance competing pressures to keep tissue processing low versus the need to provide high quality patient care. Many surgical resection specimens, including prostatectomy specimens, require extensive sampling due to the absence of grossly visible carcinoma. We describe the use of an inverted light sheet microscope (LSM) system for non-destructive imaging of prostatectomy specimens. Images produced by the LSM system are compared to corresponding H&E-stained slides. We demonstrate the potential of the LSM system to decrease laboratory workload and costs while increasing tissue sampling to maintain high quality care.


Performance comparison of optical coherent tomography and thermophotonic lock-in imaging for early detection of dental caries
Paper 10044-2

Author(s):  Nima Tabatabaei, York Univ. (Canada), et al.
Conference 10044: Lasers in Dentistry XXIII
Session 1: OCT in Dental Tissues and Early Caries Detection

Many optics-based early detection technologies have recently been developed for early detection of dental caries. The contrast mechanism in these technologies relies on enhancement of either light scattering (e.g., optical coherent tomography/OCT) or light absorption (e.g., thermophotonic lock-in imaging/TPLI) in early caries. In this paper, we present a systematic comparison between the detection performance of OCT and TPLI through imaging of inception and progression of artificially-induced early proximal and occlusal caries in human teeth. Key performance parameters such as early caries detection threshold, maximum inspection depth, detection sensitivity, and imaging time will be presented and discussed.


1050 nm diagnostic imaging of pediatric retinoblastoma patients with a novel handheld optical coherence tomography system
Paper 10045-47

Author(s):  Oleg Nadiarnykh, Vrije Univ. Amsterdam (Netherlands), et al.
Conference 10045: Ophthalmic Technologies XXVII
Session 8: Ophthalmic Imaging: Technology

We have implemented a novel handheld 1050nm optical coherence tomography system specifically designed and validated for clinical imaging of retinoblastoma tumors in pediatric patients. The more detailed visualization of three-dimensional morphology than achieved by the clinically established optical modalities improves sensitivity of real-time diagnostics; helps determine vitality of suspect masses; improves the treatment strategy. Our design accommodates for the range of optical parameters of infants’ eyes. The findings of the ongoing clinical study will be discussed, specifically the images of early, active, and treated retinoblastoma tumors, differentially diagnosed disorders, and follow-up observations.


The relationship between 3D morphology of optic disc and spatial patterns of visual field loss in glaucoma
Paper 10045-66

Author(s):  Mengyu Wang, Schepens Eye Research Institute, Harvard Medical School (United States), et al.
Conference 10045: Ophthalmic Technologies XXVII
Session PSun: Posters-Sunday

In this work, we study the impact of optic cup depth (OCD) on spatial patterns of visual field loss in glaucoma. The OCD was automatically calculated on OCT B-scan. For all severities glaucoma (424 eyes), there was no significant correlation between OCD and the mean sector PD in glaucoma hemifield test (GHT). For mild glaucoma (346 eyes), OCD was uniquely correlated to the vision loss of the inferior pericentral sector (r=-0.18, p=0.01) in GHT. Future advancement of OCT imaging techniques may provide better clinical diagnosis for early glaucoma by focusing on 3D morphological variation of the optic disc.


Direct visualization of functional heterogeneity in hepatobiliary metabolism
Paper 10046-11

Author(s):  Chen-Yuan Dong, National Taiwan Univ. (Taiwan), et al.
Conference 10046: Visualizing and Quantifying Drug Distribution in Tissue
Session 3: FLIM/Multi-Photon/Two-Photon Imaging


Mass spectrometry imaging applications to characterize and quantify drug distribution in tissue from animal models and clinical trials
Paper 10046-14

Author(s):  Nathalie Agar, Brigham and Women's Hospital (United States), et al.
Conference 10046: Visualizing and Quantifying Drug Distribution in Tissue
Session 4: Multimodal/Linear Scattering/Mass Spectroscopy/RNA Tools

An effective targeted therapeutic must both meet criteria for potency, and reach cancer cells at therapeutic levels. In solid tumors of the brain, reaching therapeutic drug levels is limited by the blood-brain barrier, but detailed characterization of drug distribution in the brain has been limited by the lack of tools to directly image small molecules without altering their chemistry with the use of molecular probes. Matrix Assisted Laser Desorption Ionization (MALDI) Fourier Transform Ion Cyclotron Resonance (FTICR) Mass Spectrometry Imaging (MSI) can now be used to characterize and quantitate the distribution of intact small molecules and their metabolites in tissue.


Advanced imaging approaches for characterizing nanoparticle delivery and dispersion in skin
Paper 10046-6

Author(s):  Tarl W. Prow, The Univ. of Queensland (Australia), et al.
Conference 10046: Visualizing and Quantifying Drug Distribution in Tissue
Session 1: Raman Imaging

The purpose of this research was to develop advanced imaging approaches to characterise the combination of elongated silica microparticles (EMP) and nanoparticles to control topical delivery of drugs and peptides. The microparticles penetrate through the epidermis and stop at the dermal-epidermal junction (DEJ). In this study we incorporated a fluorescent lipophilic dye, DiI, as a hydrophobic drug surrogate into the nanoparticle for visualization with microscopy. In another nanoparticle-based approach we utilized a chemically functionalized melanin nanoparticle for peptide delivery. These nanoparticles were imaged by coherent anti-Stoke Raman scattering (CARS) microscopy to characterize the delivery of these nanoparticles into freshly excised human skin. The resulting data show that advanced imaging techniques can give unique, label free data that shows promise for clinical investigations.


Combining imaging with microbiopsy enables a more comprehensive approach for topical drug research
Paper 10046-7

Author(s):  Tarl W. Prow, The Univ. of Queensland (Australia), et al.
Conference 10046: Visualizing and Quantifying Drug Distribution in Tissue
Session 2: Fluorescence Imaging

There is a largely unmet need for non- and minimally invasive approaches to evaluate topical drug delivery and efficacy in excised and volunteer skin. We are meeting this need by using fluorescent dermoscopy, fluorescence scanning and confocal microscopy. Minimally invasive microbiopsies are being used to extract drug concentrations from tiny pieces of skin without the need for local anaesthetics and without scars. This combined strategy enables us to collect drug disposition information in addition to skin morphology and molecular characterisation which provides a more dynamic and comprehensive way to examine drug deliver, effects of enhancement technologies and efficacy.


Modulating inflammation-mediated activation of growth factor/survival pathways: a novel mechanism to improve outcomes in patients undergoing intraoperative adjuvant photodynamic therapy?
Paper 10047-16

Author(s):  Keith A. Cengel, Perelman Ctr. for Advanced Medicine (United States), et al.
Conference 10047: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVI
Session 3: Photodynamic Therapy III

Adjuvant intraoperative photodynamic therapy (PDT) is used after surgical resection of serosal malignancies. Here, we found that activation of EGFR/IL6/STAT3/Cox-2 pathways is associated with poor prognosis in patients undergoing surgery/PDT and that inhibiting either EGFR or IL-6-mediated Cox-2 activation abrogated this negative effect in a murine model. Using 3D cell culture system, we found that activation of these pathways significantly decreased PDT mediated cellular cytotoxicity and inhibition of these pathways enhanced PDT efficacy. These observations suggest that surgically mediated activation of inflammatory signaling pathways results in STAT3-dependent crosstalk to growth/survival pathways that impairs the potential efficacy of intraoperative/post-operative PDT.


Cerenkov radiation-induced phototherapy for depth-independent cancer treatment
Paper 10047-21

Author(s):  Walter J. Akers, Washington Univ. School of Medicine in St. Louis (United States), et al.
Conference 10047: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVI
Session 3: Photodynamic Therapy III

Light emitted as the result of high-energy particle transport through biological tissues (Cerenkov radiation) can be exploited for noninvasive diagnostic imaging using high sensitivity scientific cameras. We have investigated the energy transfer potential of Cerenkov radiation, discovering a new phototherapeutic technique for treatment of localized and disseminated cancers. Titanium oxide nanoparticles, which produce cytotoxic reactive oxygen species upon irradiation with UV light, were targeted to tumor tissue by surface decoration with transferrin. Subsequent administration of tumor-avid radiotracer, 18-fluorodeoxyglucose (18FDG) provided localized UV light source via Cerenkov radiation. Treatment of tumor-bearing mice with the combination of Titanium nanoparticles and 18FDG resulted in effective reduction in tumor growth, while individual agents were not therapeutic. This new strategy in cancer therapy extends the reach of phototherapy beyond what was previously possible, with potential for treatment of cancer metastases and rescue from treatment resistance.


Simple and optimum background-free estimation method of PPIX fluorescence for 5-ALA-based fluorescence diagnosis of malignant lesions
Paper 10047-28

Author(s):  Takeo Minamikawa, The Univ. of Tokushima (Japan), et al.
Conference 10047: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVI
Session 4: Photodynamic Therapy IV

In this study, we proposed and experimentally demonstrated background-free protoporphyrin IX (PPIX) fluorescence estimation method for accurate 5-aminolevulinic-based fluorescence diagnosis of malignant lesions. To realize background-free PPIX fluorescence estimation, we computationally optimized observation wavelength regions in terms of minimizing prediction error of PPIX fluorescence intensity in the presence of typical chromophores. We verified the fundamental detection capability of our method by using known-chemical mixtures. Furthermore, we applied our method to lymph node metastasis, and successfully realized background-free histopathological evaluation of metastatic lesions of lymph node metastasis.


Cypate-mediated thermosensitive nanoliposomes for nir imaging and photothermal triggered drug release
Paper 10047-32

Author(s):  Yueqing Gu, China Pharmaceutical Univ. (China), et al.
Conference 10047: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVI
Session 4: Photodynamic Therapy IV

In this work, we developed a kind of multifunctional photo-thermal sensitive drug-loading system, with cypate doped in the hydrophobic layer and doxorubicin(DOX) entrapped in the hydrophilic layer of liposomes for multi-mechanism diagnosis and treatment of tumor diseases. A series of characterize experiments, cell and animal experiments were conducted focusing on the DOX@PTSL. In general, the DOX@PTSL was demonstrated tumor-targeted abilities, enhanced antitumor activities, minimal side effects and significant improved capability to combat with free DOX as results of the comprehensive therapeutic effectiveness of chemotherapy, thermotherapy and cypate-mediated photochemical internalization.


Singlet oxygen explicit dosimetry to predict local tumor control for HPPH-mediated photodynamic therapy
Paper 10047-36

Author(s):  Rozhin Penjweini, Univ. of Pennsylvania (United States), et al.
Conference 10047: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVI
Session PMon: Posters-Monday

In this study, concentration of the reacted singlet oxygen ([1O2]rx) for 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH)-mediated photodynamic therapy (PDT) is calculated using a macroscopic model based on the explicit dosimetry of light fluence (rate), initial tissue oxygenation, and photosensitizer concentration. Assessing long-term local control rate (LCR) of radiation-induced fibrosarcoma (RIF) tumor model across four dosimetric quantities, light fluence, photosensitizer photobleaching ratio, PDT dose, and [1O2]rx, demonstrates that [1O2]rx is the most reliable dosimetric metric.


Singlet oxygen explicit dosimetry to predict long-term local tumor control for Photofrin-mediated photodynamic therapy
Paper 10047-37

Author(s):  Rozhin Penjweini, Univ. of Pennsylvania (United States), et al.
Conference 10047: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVI
Session PMon: Posters-Monday

Although photodynamic therapy (PDT) is an established modality for the cancer treatment, the medical application of this technique has been limited due to inaccurate PDT dosimetric methods. In this study we suggest a calculated singlet oxygen concentration ([1O2]rx) based on the explicit dosimetry of the photosensitizer concentration, tissue optical properties, tissue oxygenation, and blood flow during PDT to predict complete tumor response and local control rate (LCR). Assessing LCR across four dosimetric quantities, light fluence, photobleaching rate, PDT dose, and [1O2]rx in the radiaion-induced fibrosarcoma (RIF) tumor model demonstrates that [1O2]rx is the most reliable dosimetric metric for Photofrin-mediated PDT.


Impact of photodynamic therapy on extracellular matrix components (and vice versa) in 3D pancreatic tumor models
Paper 10047-4

Author(s):  Jonathan P. Celli, Univ. of Massachusetts Boston (United States), et al.
Conference 10047: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVI
Session 1: Photodynamic Therapy I

The development of abundant stroma with collagen-rich extracellular matrix (ECM) is a common feature of invasive solid tumors. Building on our recent work showing that phenotypic changes driven by ECM interactions can determine response to photodynamic therapy (PDT), we examine here the inverse effect, focusing on the impact of PDT on the ECM. Bulk rheology analysis shows that changes in ECM are strongly dependent on PDT dose, with increasing rigidity at low doses giving way to photodestruction of ECM (decreased rigidity) at higher doses. We further examine downstream effects on cell phenotype and motility concomitant with these changes in ECM.


Comparison of doses delivered in daylight versus regular light delivery in ALA-PDT in the treatment of skin cancer
Paper 10047-41

Author(s):  Ana Luiza Ribeiro de Souza, Thayer School of Engineering at Dartmouth (United States), et al.
Conference 10047: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVI
Session PMon: Posters-Monday


In vivo wide-field multispectral dosimeter for use in ALA-PpIX based photodynamic therapy
Paper 10047-5

Author(s):  Ethan LaRochelle, Thayer School of Engineering at Dartmouth (United States), et al.
Conference 10047: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVI
Session 1: Photodynamic Therapy I

Photodynamic therapy (PDT) for Actinic Kertoses (AK) using aminoluvelinic acid (ALA) is an FDA-approved treatment, which is generally effective, yet response rates vary. The origin of the variability may be related to inter-patient variability in the production of protoporphyrin IX (PpIX). In an effort to improve dosimetry and treatment it is important to develop a robust system that accounts for spatial variability and reduces the chance of operator errors. To address this need, a wide-field multispectral imaging system was developed that is capable of quantifying maps of PpIX in both liquid phantoms and in vivo experiments.


A summary of light dose distribution using an IR navigation system for Photofrin-mediated Pleural PDT
Paper 10047-8

Author(s):  Timothy C. Zhu, The Univ. of Pennsylvania Health System (United States), et al.
Conference 10047: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVI
Session 2: Photodynamic Therapy II

Uniform delivery of light fluence is an important goal for photodynamic therapy. We present summary results for an infrared (IR) navigation system to deliver light dose uniformly during intracavitory PDT by tracking the movement of the light source and providing real-time feedback on the light fluence rate on the entire cavity surface area. In the current intrapleural PDT protocol, 8 detectors placed in selected locations in the pleural cavity monitor the light doses. To improve the delivery of light dose uniformity, an IR camera system is used to track the motion of the light source as well as the surface contour of the pleural cavity. A MATLAB-based GUI program is developed to display the light dose in real-time during PDT to guide the PDT treatment delivery to improve the uniformity of the light dose. We have developed an improved model for direct light calculation that accounts for the anisotropy of the light from the light sources. A comprehensive analysis of the distribution of light fluence during PDT is presented in both phantom conditions and in clinical cases.


Low-level light treatment ameliorates immune thrombocytopenia
Paper 10048-13

Author(s):  Mei X. Wu, Harvard Medical School (United States), et al.
Conference 10048: Mechanisms of Photobiomodulation Therapy XII
Session 4: Mechanisms of Photobiomodulation Therapy IV

Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized with abnormally low platelet counts. There is currently no standard, safe and effective therapy for this disorder. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The LLLT is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP.


Laser-induced immune modulation inhibits tumor growth in vivo
Paper 10048-14

Author(s):  Giulia Ottaviani, The International Ctr. for Genetic Engineering and Biotechnology (Italy), et al.
Conference 10048: Mechanisms of Photobiomodulation Therapy XII
Session 4: Mechanisms of Photobiomodulation Therapy IV

Photobiomodulation is becoming an effective supportive therapy for oncological patients. We assessed the effect of laser light on cancer cell proliferation in vitro and in vivo. While metabolism and proliferation were increased in cultured cells, the overall effect in vivo was a reduced tumor growth and progression, paralleled by increased recruitment and activity of immune cells. A similar capacity of laser light to activate the immune response was also revealed in a model of vaccination. These data support the safe use of laser light in cancer patients and open the way to novel therapeutic opportunities to boost the immune response.


3D Monte Carlo simulation of light propagation for laser acupuncture and optimazation of illumination paramters
Paper 10048-16

Author(s):  Ting Li, Univ. of Electronic Science and Technology of China (China), et al.
Conference 10048: Mechanisms of Photobiomodulation Therapy XII
Session 4: Mechanisms of Photobiomodulation Therapy IV

Laser acupuncture refers to the effective photochemical and nonthermal stimulation of traditional acupuncture points with low-intensity laser irradiation. Laser acupuncture is painless, sterile, and safe compared to traditional acupuncture. The use of LED devices for phototherapy is a good choice as the laser source for this technology, and the wavelength of LED is taken into account during 600~800nm by MonteCarlo method using MCVM soft. In order to protect viability of cells and tissue, and get better therapeutic effect, it’s best to control the output power varied at 10mW~30mW range. As to the irradiation time, which is influenced by optical parameters, especially in this study, it’s about 10 minutes every time to irradiate.


Effect of LED phototherapy on blood lactate level in Taekwondo contest
Paper 10048-17

Author(s):  Sungkyoo Lim, Dankook Univ. (Korea, Republic of), et al.
Conference 10048: Mechanisms of Photobiomodulation Therapy XII
Session 4: Mechanisms of Photobiomodulation Therapy IV

The effect of LED phototherapy on blood lactate level in the muscle was studied. A 450cm2 large red and near infrared LED pad with its irradiance of 10mW/cm2 was applied for 10 minutes to brachial muscle and quadriceps muscle of thigh before the Taekwondo contest for one group of players and after the contest for the other group. Blood samples from the players were taken at 5 minutes and 10 minutes after the contest. The test results showed that the LED phototherapy before and after the contest had a significant effect on the decrease of blood lactate level.


Near infrared phototherapy and EEG biofeedback in the treatment of cognitive and behavioral symptoms of Alzheimer's disease
Paper 10048-3

Author(s):  Marvin H. Berman, Quietmind Foundation (United States), et al.
Conference 10048: Mechanisms of Photobiomodulation Therapy XII
Session 1: Mechanisms of Photobiomodulation Therapy I

The presentation proposes a safe, low-cost, scalable, easily deployed model for noninvasive treatment of neurodegenerative disorders employing brainwave biofeedback (NFB) and near-infrared photobiomodulation (NPBM). Pilot study data being presented evaluated the efficacy of brief, repeated exposure to 1060-1080nm transcranial NIR stimulation to remediate cognitive and behavioral symptoms associated with early to mid-stage dementia. An additional trial utilized brainwave biofeedback training to determine if subjects with dementia could, through operant conditioning, remediate cognitive and behavior symptoms by modifying the amplitude of specific EEG frequencies. Results suggest that NIR stimulation supports both repair and protects against further neuronal damage, while EEG biofeedback training can substantively improve neural connectivity.


Ultra-fast frequency domain Diffuse Optical Spectroscopy using miniaturized sources and detectors towards quantitative wearables
Paper 10049-1

Author(s):  Darren M. Roblyer, Boston Univ. (United States), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session 1: Advanced Molecular Imaging Methods I

Frequency domain Diffuse Optical Spectroscopy (DOS) allows for quantitative extraction of endogenous tissue optical properties and chromophore concentrations. We will present our most recent work on ultra-fast frequency-domain digital DOS which can perform simultaneous six wavelength 50 – 400MHz sweeps at a 97Hz repetition rate, a speed sufficient for capturing hemodynamics of the cardiac cycle in peripheral vasculature. We will show how we are combining fast digital DOS with new multi-wavelength VCSEL sources and miniaturized PMTs and APDs to fabricate frequency-domain wearables towards real-time tracking of quantitative tissue metabolism with applications in oncology, neuroscience, and fitness.


Setup for testing cameras for image guided surgery using an controlled NIR fluorescence mimicking light source and tissue phantom
Paper 10049-13

Author(s):  Rudolf M. Verdaasdonk, Vrije Univ. Medical Ctr. (Netherlands), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session 3: Imaging Systems I

A setup was developed to test cameras for fluorescence guided surgery using a µW NIR LED light source in an tissue phantom to measure the sensitivity and resolution by analyzing captured images with ImageJ software. Enhanced CCD night vision cameras were the most sensitive, however, NIR sensitive DSLR cameras proved relative less sensitive but are preferred for clinical use by full control of gain and exposure time in combination with wifi remote control. The NIR fluorescence testing setup proved to be useful for camera testing and can be used for development and quality control of new NIR fluorescence guided surgery equipment.


Raman-encoded molecular imaging (REMI) with topically applied SERS nanoparticles for intraoperative guidance of breast cancer lumpectomy
Paper 10049-15

Author(s):  Yu Wang, Univ. of Washington (United States), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session 3: Imaging Systems I

In order to identify residual tumors at the surgical margin surface of lumpectomy specimens, we have developed a Raman-encoded molecular imaging (REMI) technology for the simultaneous imaging of 4 biomarkers at the surfaces of fresh tissues following a rapid topical-staining (5-min) protocol with targeted SERS NPs, in which various “flavors” of SERS NPs may be identified by their unique spectral signatures. A ratiometric method is employed to quantify biomarker expression. Correlation studies with histopathology indicate that REMI is capable of comprehensively imaging large biopsy shavings (>4 cm2) under time-constrained intraoperative conditions with sub-millimeter resolution for the detection of residual tumors.


Light-sheet microscopy for rapid 3D digital pathology of fresh tissue specimens
Paper 10049-19

Author(s):  Adam K. Glaser, Univ. of Washington (United States), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session 4: Imaging Systems II

We describe the design, characterization, and imaging performance of a two-color LSM system that can image nuclear and cytoplasmic features of fresh tissue surfaces at high speed (


Intraoperative visualization of plasmon resonant liposomes using augmented microscopy
Paper 10049-20

Author(s):  Jeffrey R. Watson, The Univ. of Arizona (United States), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session 4: Imaging Systems II

Plasmon resonance associated with nanoparticles of gold enables photothermal ablation of tissues, controlled drug release, or interrogation of individual cells, all with exquisite temporal and spatial control. These technologies may support many applications of precision medicine. However, their clinical implementations will require new methods of intraoperative imaging and guidance. Here we describe application of augmented microscopy in guiding surgical procedures employing plasmon resonant gold-coated liposomes.


Sprayable enzyme-activatable fluorescent probes: kinetic mapping using dynamic fluorescence imaging can help detecting tiny cancer foci.
Paper 10049-23

Author(s):  Hisataka Kobayashi, National Cancer Institute (United States), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session 5: Contrast Agents

Optical fluorescence-guided imaging is increasingly used to guide surgery and endoscopic procedures. Sprayable enzyme-activatable probes are particularly useful because of high target-to-background ratios that increase sensitivity for tiny cancer foci. Dynamic imaging followed by the kinetic analysis could be detected local enzyme activity and used to differentiate specific fluorescence arising from an activated probe in a tumor from autofluorescence in background tissues especially when low concentrations of the dye are applied to detect tiny cancer foci. Especially at lower concentrations, kinetic maps derived from dynamic fluorescence imaging were clearly superior to unprocessed images for detection small cancer foci.


Evaluation of contrast and intratumoral heterogeneity for ABY-029 in glioma, with pre-doses of unlabeled cetuximab as a receptor 'cold dose'
Paper 10049-25

Author(s):  Ana Luiza Ribeiro de Souza, Thayer School of Engineering at Dartmouth (United States), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session 5: Contrast Agents


Intraoperative fluorescence diffuse optical tomography using spatial frequency domain techniques
Paper 10049-3

Author(s):  Sang Hoon Chong, Univ. of Pennsylvania (United States), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session 1: Advanced Molecular Imaging Methods I

Fluorescence image guided surgery is an emerging technique for tumor resection surgery. Its current level of clinical use is largely limited to 2D near-surface imaging. We have constructed a compact fluorescence imaging system for 3D volumetric imaging of tumor in the reflectance geometry that permits quasi real-time visualization in an operating room. This new instrument provides depth-sensitive tumor location information at depths up to 1 cm. We present results from an extensive range of characterization experiments using Indocynanine Green in tissue phantoms and in a pilot in-vivo measurement.


Novel applications of near-infrared fluorescence imaging in orthopedic surgery
Paper 10049-31

Author(s):  Eric R. Henderson, Dartmouth Hitchcock Medical Ctr. (United States), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session 7: Clinical Translation and Clinical Applications II

Sarcomas are cancers of the bones, muscles, nerves, and fat that require complete surgical removal for cure. At present, surgeons rely on radiologic imaging and visual and tactile clues to gauge cancer depth and guide surgical excision. This can result in removal of too much or too little tissue, which can lead to unnecessary removal of vital structures or incomplete cancer removal. Near-infrared (NIR) fluorescence probes are molecules that emit a distinct frequency of light and can label specific tissues. We seek to use NIR fluorescence to label tumors and make surgical removal safer and more effective.


A laparoscopic applicator probe for real-time en-face mapping of near-surface optical sources of heterogeneity over a 1cm instrument-tip-size field-of-view
Paper 10049-41

Author(s):  Daqing Piao, Oklahoma State Univ. (United States), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session PSun: Posters-Sunday

We demonstrate a laparoscopic applicator probe and a method thereof for real-time mapping of near-surface optical heterogeneity for potential use towards intraoperative margin assessment. The probe fits a 12mm port and houses 128 fibers of 750µm in diameter that form radially alternating illumination and detection channels. By simultaneously illuminating all source channels and concurrently measuring the light diffusely propagated to the detector channels using a camera, visualization of subsurface margin formed by a strong attenuation contrast at a depth up to 3mm over an en-face 9.5mm FOV is demonstrated at one wavelength at 1.25Hz.


Pre-clinical evaluation of fluorescent ABY-029 in 3 mouse sarcoma models, to assess enhanced contrast in fluorescence guided surgery relative to fluorescent perfusion contrast
Paper 10049-43

Author(s):  Kayla A. Marra, Thayer School of Engineering at Dartmouth (United States), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session PSun: Posters-Sunday


Dexamethasone enhances 5-ALA/PpIX contrast but degrades ABY-029 contrast at glioma margins during fluorescence guided resection
Paper 10049-45

Author(s):  Jonathan T. Elliott, Thayer School of Engineering at Dartmouth (United States), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session PSun: Posters-Sunday


Pre-clinical development and safety testing of GMP produced ABY-029, fluorescent anti-EGFR affibody, for use in surgical resection
Paper 10049-46

Author(s):  Jason R. Gunn, Thayer School of Engineering at Dartmouth (United States), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session PSun: Posters-Sunday


Moving beyond single-point Raman spectroscopy: development of a hand-held Raman imaging probe for intraoperative tumor margin assessment
Paper 10049-48

Author(s):  Karl St-Arnaud, Ecole Polytechnique de Montréal (Canada), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session PSun: Posters-Sunday

Tissue interrogation using Raman spectroscopy has been exploited to develop surgical guidance tools that can help improve the safety of tissue resection procedures. In the past, hand-held Raman probes have shown great potential to help surgeons discriminate between cancerous and normal tissue/cells. Here, we present the development of a hand-held macroscopic Raman spectroscopy imaging probe with a larger field of view of 16mm² and a spatial resolution of 100µm. The hand-held probe was tested ex vivo on calf brain and human prostates. The ability of the system to recreate tissues maps of molecular content was validated using Neural Network classification.


Sub-diffusive spatial frequency domain imaging provides wide-field visualization and quantification of light scattering as an endogenous biomarker for morphological change in tissue
Paper 10049-5

Author(s):  David M. McClatchy, Thayer School of Engineering at Dartmouth (United States), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session 1: Advanced Molecular Imaging Methods I

With sub-diffusive SFDI, very high (>0.5 mm-1) spatial modulation frequencies are projected yielding sensitivity to the directionality of light scattering with only few scattering events occurring and sub-millimeter penetration depth and spatial resolution. To test sensitivity to changes in human breast tissue morphology, a cohort of over 30 freshly excised human breast tissue specimens, including adipose, fibroglandular, fibroadenoma, and invasive carcinoma, have been imaged and co-registered to whole specimen histology. Statistical analysis of the distributions of both textual raw reflectance parameters and model based optical properties for each type of tissue will be presented.


Addressing the challenges of translating laser speckle imaging to the clinic
Paper 10049-6

Author(s):  Bernard Choi, Beckman Laser Institute and Medical Clinic (United States), et al.
Conference 10049: Molecular-Guided Surgery: Molecules, Devices, and Applications III
Session 2: Advanced Molecular Imaging Methods II

Since the seminal publication in 2001 by Dunn et al., several research groups have adopted laser speckle imaging (LSI) to map blood flow in laboratory studies. Due to the simplicity of the components involved in a LSI device, scientists and engineers naturally have applied LSI in studies involving human subjects. In this talk, I will describe seminal efforts, from Beckman Laser Institute and from other research groups, designed to translate LSI from the lab to the clinic. I will emphasize the design considerations from an engineering perspective, and give specific examples of efforts to integrate LSI within specific clinics.


Important Dates

Author Notification
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.