Technical Summaries - SPIE8565E: Diagnostic and Therapeutic Applications of Light in ... Clinical...

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Conferences & Courses2–7 February 2013

ExhibitionBiOS Expo: 2–3 February 2013Photonics West: 5–7 February 2013

Technical Summarieswww.spie.org/pw

2–7 February 2013

LocationThe Moscone CenterSan Francisco, California, USA


Symposium Chairs

James FujimotoMassachusetts Institute of Technology (USA)

R. Rox Anderson M.D.Wellman Ctr. for Photomedicine, Massachusetts General Hospital (USA) and Harvard School of Medicine (USA)

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Contents8565A: Photonics in Dermatology and Plastic Surgery . . . . . . . . . . . . . . 3

8565B: Therapeutics and Diagnostics in Urology: Lasers, Robotics, Minimally Invasive, and Advanced Biomedical Devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

8565C: Optical Imaging, Therapeutics, and Advanced Technology in Head and Neck Surgery and Otolaryngology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

8565D: Optical Techniques in Pulmonary Medicine . . . . . . . . . . . . . . . . 27

8565E: Diagnostic and Therapeutic Applications of Light in Cardiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

8565F: Optical Techniques in Neurosurgery, Brain Imaging, and Neurobiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

8565G: Neurophotonics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

8565H: Optics in Bone Surgery and Diagnostics . . . . . . . . . . . . . . . . . . 60

8566: Lasers in Dentistry XIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

8567: Ophthalmic Technologies XXIII . . . . . . . . . . . . . . . . . . . . . . . . . . 71

8568: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXII . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92

8569: Mechanisms for Low-Light Therapy VIII . . . . . . . . . . . . . . . . . . 105

8570: Frontiers in Biological Detection: From Nanosensors to Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112

8571: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XVII . . . . . . . . . . . . . 119

8572: Advanced Biomedical and Clinical Diagnostic Systems XI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150

8573: Design and Quality for Biomedical Technologies V . . . . . . . . . 164

8574: Multimodal Biomedical Imaging VIII . . . . . . . . . . . . . . . . . . . . . 171

8575: Endoscopic Microscopy VIII . . . . . . . . . . . . . . . . . . . . . . . . . . . 178

8576: Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XIII . . . . . . . . . . . . . . 187

8577: Optical Biopsy X . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195

8578: Optical Tomography and Spectroscopy of Tissue X . . . . . . . . 203

8579: Optical Interactions with Tissue and Cells XXIV . . . . . . . . . . . . 233

8580: Dynamics and Fluctuations in Biomedical Photonics VIII . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243

8581: Photons Plus Ultrasound: Imaging and Sensing 2013 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256

8582: Biophotonics and Immune Responses VIII . . . . . . . . . . . . . . . . 301

8583: Design and Performance Validation of Phantoms Used in Conjunction with Optical Measurement of Tissue V . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309

8584: Energy-Based Treatment of Tissue and Assessment VII . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315

8585: Terahertz and Ultrashort Electromagnetic Pulses for Biomedical Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325

8586: Optogenetics and Hybrid-Optical Control of Cells . . . . . . . . . . 334

8587: Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XI . . . . . . . . . . . . . . . . . . . . . 342

8588: Multiphoton Microscopy in the Biomedical Sciences XIII . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362

8589: Three-Dimensional and Multidimensional Microscopy: Image Acquisition and Processing XX . . . . . . . . . . . . . . . . . . . 390

8590: Single Molecule Spectroscopy and Superresolution Imaging VI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404

8591: Optical Diagnostics and Sensing XIII: Toward Point-of-Care Diagnostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 416

8592: Biomedical Applications of Light Scattering VIII . . . . . . . . . . . . 424

8593: Optical Methods in Developmental Biology . . . . . . . . . . . . . . . 437

8594: Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications IX . . . . . . . . . . . . . . . . . . . . . . . . . . . . 444

8595: Colloidal Nanoparticles for Biomedical Applications VIII . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451

8596: Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications . . . . . . . . . . . . 467

8597: Plasmonics in Biology and Medicine X . . . . . . . . . . . . . . . . . . . 478

8598: Bioinspired, Biointegrated, Bioengineered Photonic Devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 488


Conference 8565A: Photonics in Dermatology and Plastic SurgerySaturday - Sunday 2 –3 February 2013Part of Proceedings of SPIE Vol . 8565 Photonic Therapeutics and Diagnostics IX

8565-1, Session 1

Confocal microscopy to guide laser ablation of non-melanoma skin cancers: a preliminary feasibility studyBjorg A. Larson, Jason C. Chen, Milind Rajadhyaksha, Memorial Sloan-Kettering Cancer Ctr. (United States)Laser ablation may be a promising method for removal of skin lesions, with the potential for better cosmetic outcomes and reduced pain, scarring and infection and may be a good choice for patients who are susceptible to cancerous lesions, such as those with nevoid basal cell carcinoma (BCC) syndrome, widespread actinic damage, or immunosuppression. However, an obstacle to implementing laser ablation is that the treatment leaves no tissue for histopathological analysis, which is routinely performed to examine for residual tumor. Confocal microscopy offers noninvasive optical sectioning of intact tissue, and has been shown to detect BCCs with high sensitivity and specificity, both in vivo as well as in excised tissue. Thus, pre-operative mapping of the depth and extent of BCCs may guide the initial ablation of the tumor, and subsequent intra-operative imaging may guide further ablation until all tumor is removed. We demonstrate preliminary feasibility of confocal microscopy to guide laser ablation of BCCs in freshly excised tissue from Mohs surgery. A pulsed Er: YAG laser, operating at 2940 nm wavelength, provides efficient ablation of tumor with reduced thermal damage to the surrounding tissue. Varying fluence up to 25 J/cm2 determines the ablation depth, up to 100 um. Tissue was examined for tumor before and after ablation using a confocal microscope with the imaging results confirmed by histopathology. A key challenge for this technique will be the development of contrast agents for vital staining of nuclear morphology to enable imaging of residual BCC tumors, ultimately on patients.

8565-2, Session 1

Automated localization of wrinkles and the dermo-epidermal junction in obliquely-oriented reflectance confocal microscopic images of human skinJamshid Sourati, Northeastern Univ. (United States); Milind Rajadhyaksha, Memorial Sloan-Kettering Cancer Ctr. (United States); Jennifer G. Dy, Deniz Erdogmus, Dana H. Brooks, Northeastern Univ. (United States)Reflectance confocal microscopic (RCM) imaging of obliquely-oriented optical sections, rather than with traditional z-stacks, shows depth information that more closely mimics the appearance of skin in orthogonal sections of histology. This approach may considerably reduce the amount of data that must be acquired and processed. However, as with z-stacks, purely visual detection of certain structures, such as the dermal-epidermal junction (DEJ), in oblique images remains challenging due to low contrast in reflectance and textural variability in epidermal and dermal layers. We previously developed a machine learning approach to locating the DEJ in z-stacks. We have now extended that approach for obliquely-oriented sections. In addition we have developed a new algorithm to locate wrinkles in oblique sections. Since wrinkles are known to effectively change the local shape of DEJ, this algorithm, in addition to its intrinsic merit, gives useful information for localization of the DEJ. Automatically finding such morphological structures is not straightforward due to factors which include imaging artifacts, reflectance from the floor of wrinkles and the so-called “horny-plug” feature. As with our original algorithm, the approach combines feature sets based on image processing techniques and machine learning methods devised to cope with these difficulties.

8565-3, Session 1

Investigating the metastatic potential and pigment chemistry of melanomas using pump-probe imaging (Invited Paper)Mary Jane Simpson, Jesse W. Wilson, Francisco E. Robles, Maria A. Selim, Marshall Phipps, Duke Univ. (United States); Warren S. Warren, Duke Univ. (United States) and Duke Univ. Medical Ctr. (United States)Pump-probe microscopy non-destructively differentiates eumelanin and pheomelanin and can be used to quantify melanin distributions in thin biopsy slices. The nature of the technique makes it compatible with stained slides and suitable for in vivo imaging of moles. Monitoring the intensity and phase of the modulation transferred as a function of interpulse delay gives unique spectroscopic signatures to eumelanin and pheomelanin. Here we have extended that work for imaging melanin heterogeneity on a sub-cellular scale, investigating melanin degradation, and identifying features of metastatic melanomas. We have found that melanin heterogeneity, characteristic of melanomas, persists on the sub-cellular scale, particularly in nested melanocytes. Other cells such as benign keratinocytes, do not have as much variation in pigment type in individual cells. High resolution melanin imaging has also allowed a comparison of the size of melanin granules in different types of cells. We have also found spectral changes associated with melanin undergoing oxidative degradation, which breaks the biopolymer into monomers. This may be useful for differentiating melanophages from melanocytes and identifying pigmented cells experiencing oxidative stress due to malignancy or other damage.We have analyzed a collection of archived melanomas with known sentinel lymph node biopsy results to avoid the uncertainty associated with a melanoma diagnosis by a pathologist. This study has revealed differences between the melanomas that had positive sentinel lymph node biopsies and the melanomas that showed no evidence of metastases following the excision of the primary tumor.

8565-4, Session 1

State-of-the-art clinical in vivo multiphoton tomographyKarsten Koenig, Univ. des Saarlandes (Germany) and JenLab GmbH (Germany)Clinical multiphoton tomography based on femtosecond near infrared laser pulses for in vivo high-resolution skin imaging has been employed to thousands of volunteers and patients. The novel multimodal multiphoton tomograph MPTflex with its mechano-optical arm, active beam control, dual detector and wide-field imaging (up to 5x5 mm2) is in use in clinics in Japan, California, and Europe. Two-photon cellular autofluorescence and second harmonic generation of collagen can be detected with single-photon sensitivity and submicron spatial resolution. Using TCSPC, clinical two-photon FLIM has been used to distinguish fluorophores and to control therapeutical effects on patients suffering from dermatitis. Also in vivo clinical CARS has been realized to image intratissue lipids and water. Novel developments focus on multimodal hybrid imaging to generate optical tissue biopsies with subcellular resolution, deep-tissue information, and chemical fingerprints. Wide-field imaging tools such as dermoscopes, optical coherence tomographs as well as ultrasound and photoacoustics devices can be integrated. The hybrid tomographs have the potential to detect cosmetics and pharmaceutical components such as sunscreen nanoparticles and anti-aginging products in humans. Skin cancer such as malignant melanoma as well as dermatitis can be detected at an early stage and the efficiency


of the treatment can be monitored. Multiphoton tomographs will become biopsy-free and label-free imaging tools in personalized medicine, pharmacy, biotechnology as well as cosmetic research.

8565-5, Session 2

Comparison of single-photon and two-photon fluorescence properties of human skin and skin fluorophoresJianhua Zhao, The BC Cancer Agency Research Ctr. (Canada); Mengzhe Shen, The Univ. of British Columbia (Canada); Edward Yu, The BC Cancer Agency Research Ctr. (Canada); Shuo Tang, Harvey Lui, The Univ. of British Columbia (Canada); Haishan Zeng, The BC Cancer Agency Research Ctr. (Canada)Fluorescence spectroscopy is one of the most sensitive optical techniques for in vivo measurement of tissue biochemical and morphological properties. There is considerable interest in developing fluorescence-based spectroscopic and imaging techniques in biomedicine, particularly for early diagnosis of cancers and other diseases. Recently, two-photon fluorescence (TPF) imaging has gained popularity in biological and biomedical studies because of its advantages over single-photon fluorescence (SPF). Significant endogenous fluorophores in biological tissues include collagen, keratin, elastin, nicotinamide adenine dinucleotide (NADH), and flavin adenine dinucleotide (FAD). Understanding the fluorescence properties, concentrations and distributions of these fluorophores within tissue is important in optimizing the spectroscopic and imaging techniques and algorithms. It is believed that the TPF properties of these endogenous fluorophores are close to their SPF counterparts. However, there is no systematic compared study on the TPF and SPF properties of these endogenous fluorophores as of to date, due partially to the limitation of instrumentation. Very recently, we developed a video-rate TPF imaging system with the capability of measuring the two-photon excitation-emission matrix (EEM) spectroscopy. In this paper, we will present the SPF and TPF properties of the above mentioned biological fluorophores and human skin using single-photon EEM and two-photon EEM systems. We find that there are similarities and differences between SPF and TPF for these fluorophores and these differences demonstrate that caution must be exercised when interpreting tissue TPF properties based on the source of SPF reference spectra or vice versa.

8565-6, Session 2

Differential diagnosis of pigmented skin lesions based on harmonic generation microscopyMing-Rung Tsai, National Taiwan Univ. (Taiwan); Yi-Hua Liao M.D., National Taiwan Univ. Hospital (Taiwan); Chi-Kuang Sun, National Taiwan Univ. (Taiwan)In clinical diagnosis, pigmented lesions are usually diagnosed using the naked eye and are with similar appearance. This may result in misdiagnosis and differential diagnosis of benign versus malignant lesions is thus important to ensure proper prognosis and treatment. Biopsy is currently the gold standard to make the definitive diagnosis, but this medical procedure is invasive and painful for patients. Recently in vivo harmonic generation microscopy (HGM) has been reported to have a superior performance on healthy human skin and oral mucosa. With the noninvasive nature, high penetration capability, and a high resolution, HGM could serve as an ideal virtual biopsy tool for in vivo, in situ, and immediate differential diagnosis of pigmented skin lesions. It is thus critical to investigate if the endogenous contrast provided by the HGM enough to diagnose the differences between the pigmented skin lesions. In this paper, we summarize our current clinical trial to perform in vivo and ex vivo HGM on pigmented skin lesions, including melanoma, pigmented basal cell carcinoma (BCC), nevocellular nevus, and

seborrheic keratosis. Based on ex vivo study, histopathological correlated HGM imaging criteria for differential diagnosis were established. Three features of melanoma and four features of BCC were specified and statistically evaluated. Sensitivity values up to 100% (87-100%) and specificity values up to 99% (95-99%) were achieved for diagnostic classification. HGM presents a great potential to become a noninvasive diagnostic tool for the disease prescreening and clinical management of malignant diseases.

8565-7, Session 2

Video-rate in vivo human skin imaging using co-registered multiphoton and reflectance confocal microscopyHequn Wang, Anthony M. Lee, Zack Frehlick, The BC Cancer Agency Research Ctr. (Canada); Harvey Lui M.D., David I. McLean M.D., The BC Cancer Agency Research Ctr. (Canada) and The Univ. of British Columbia (Canada) and Vancouver Coastal Health Research Institute (Canada); Shuo Tang, The Univ. of British Columbia (Canada); Haishan Zeng, The BC Cancer Agency Research Ctr. (Canada) and The Univ. of British Columbia (Canada) and Vancouver Coastal Health Research Institute (Canada)

Combining reflectance confocal microscopy (RCM) and multiphoton microscopy (MPM) imaging potentially allows greater clinical diagnostic utility as complementary information can be revealed using these two techniques. Here we present a multimodal in vivo skin imaging instrument that is capable of simultaneously acquiring multiphoton and reflectance confocal images at up to 27 fps with 256?256 pixel resolution. A tunable (720-950nm) 80MHz femtosecond Ti:Sa laser was scanned into the back aperture of a 60X (NA=1.0) long working distance water immersion objective using a paired resonance/galvanometer scanner. A combination of beamsplitters, dichroic mirrors, and filters separated and directed the reflectance confocal (RCM), two-photon fluorescence (TPF) and second harmonic generation (SHG) signals onto their respective detectors. Images from all channels were simultaneously captured by a multichannel frame grabber. Imaging all channels with only one excitation laser source ensures perfect image registration between the RCM, TPF, and SHG images. Images and videos acquired with our system show that the three imaging channels provide complementary information in in vivo human skin measurements. In the epidermis, cell boundaries are clearly seen in the RCM channel, while cytoplasm is better seen in the TPF imaging channel; in the dermis, SHG and TPF channels show collagen bundles and elastin fibers, respectively. The demonstrated fast imaging speed and multimodal imaging capabilities of this MPM/RCM instrument are essential features for future clinical noninvasive applications of this technique.

8565-8, Session 2

Modeling semiconductor lasers for In vivo confocal-laser-scanning-microscopy in dermatologyMeng-Mu Shih, Univ. of Florida (United States)Different lasers have clinical and research applications in dermatology and plastic surgery. Semiconductor lasers have attractive features such as small-size, low-power, and various wavelengths. Grating-embedded semiconductor lasers make not only the size more compact but the emitting wavelength more stable and precise. This talk promotes applications of such lasers in this biomedical field. A skin-imaging technique using in vivo confocal-laser-scanning-microscopy (CLSM) serves as an example. The modeling results related to structures and materials of lasers are presented numerically by the optical and the photonic approaches. Interpretations based on numerical results provide insights into the modeling and design of laser-based applications.

Conference 8565: Photonics in Dermatology and Plastic Surgery


8565-9, Session 3

Investigation of fractional laser photothermolysis and visualization of microthermal zone with optical coherence tomographyFeng-Yu Chang, Cheng-Hsing Fan, Cheng-Kuang Lee, Meng-Tsan Tsai, Chang Gung Univ. (Taiwan); Chih-Hsung Yang M.D., Chang-Gung Memorial Hospital (Taiwan)Laser photothermal therapy is an effective method for skin resurfacing, including using ablative CO2 pulsed laser or non-ablative Er: Glass laser. However, it is difficult to evaluate the effect of laser treatment in real-time since the parameters including the density of incident beams, the penetration depth and the beam diameter cannot be obtained immediately. Therefore, in this study, we propose to use a noninvasive optical imaging technique, optical coherence tomography (OCT), to investigate the effect of laser treatment with three-dimensional imaging. In our experiments, the phantom and human skin including facial and belly skin were scanned with our SS-OCT system after laser treatments. From the scanning results, several parameters can be obtained such as the penetration depth, the zone of thermal damage, and the recovery time. Also, the treatment effects are compared by using CO2 pulsed laser and Er: Glass laser. With OCT scanning, it can provide the real-time information to evaluate the parameters of microthermal zones and penetration depth of optical beams, enabling to help the physicians determine the treatment parameters.

8565-10, Session 3

Microvasculature imaging for clinical scar assessment (Invited Paper)Yih Miin Liew, Robert A. McLaughlin, Peijun Gong, The Univ. of Western Australia (Australia); Fiona M. Wood M.D., The Univ. of Western Australia (Australia) and Burns Service of Western Australia, Royal Perth Hospital (Australia); David D. Sampson, The Univ. of Western Australia (Australia)Pathological scarring, such as hypertrophic scars and keloids, can result in major functional, cosmetic and psychosocial impairment of patients. Examination of scar progression is important in assessing response to treatment, and in early identification of pathological scarring. Redness of scarring is a commonly graded clinical indicator, indicating the level of scar vascularity. Angiogenesis occurs at an early stage of wound healing and may progress under pathological conditions long after wound closure, therefore causing pathological scars (keloid and hypertrophic) to appear very red. Scar vascularity is expected to reduce towards maturation as indicated by the reduction in their redness comparable to the surrounding normal skin. However, manual assessment of scar appearance can be subjective and suffer significant inter-observer variability. We demonstrate the first clinical application of optical coherence tomography (OCT) for in vivo, non-invasive and contrast agent-free quantification of the microvasculature network in human skin scars. In OCT imaging, vascular areas have been shown to undergo rapid speckle decorrelation, and this was used to delineate the microvasculature. Automatic techniques were then developed to quantify the degree of vasculature, including estimates of average vessel diameter and total amount of vasculature. Measurements were performed on eight human burns scar patients, comparing scar tissue with contralateral healthy tissue. Results showed a substantial difference between the scar and the normal tissue, with a significant increase in the measured density of vasculature present in scarred tissue.

8565-11, Session 3

Optical coherence tomography demonstrates epidermal thinning of human forearm volar skin after 2 weeks application of a topical corticosteroid.Stephen J. Matcher, Zenghai Lu, Michael Cork, The Univ. of Sheffield (United Kingdom)The use of topical corticosteroids (TCS) to treat inflammatory skin disorders such as atopic dermatitis is clinically established. However there is a strong interest in developing non-steroidal alternatives to TCS because the latter compounds are known to have strong effects on, for example, skin barrier function. In this report we present a human volunteer study in which optical coherence tomography (OCT) was used to non-invasively quantify the effects of a potent TCS on the structure of volar forearm skin and compare this with a non-steroidal alternative eczema treatment. Methods: two matching sites were chosen on the left and right forearm of a human volunteer. The sites were recorded using nearby skin features and baseline OCT images recorded. OCT imaging was performed using a 1300 nm swept-source OCT system. 4x2 mm B-scans were recorded, revealing the epidermis and dermis as dark and bright band respectively. One arm was then treated using a potent TCS (betamethasone valerate 0.1%) whilst the other was treated using a non-steroidal immunosuppressant eczema treatment (Tacrolimus). After 14 days OCT images were collected at the same sites. Results: The OCT images of the Tacrolimus-treated skin showed no discernible difference between pre- and post-treatment. In contrast the skin treated with bethamethasone valerate showed a substantial (~50%) decrease in the epidermal thickness as measured from the OCT image. Conclusion: OCT is capable of detecting changes in skin structure induced by clinically approved eczema treatments. It is thus a viable tool for assessing the physical effects of alternative treatments.

8565-12, Session 3

Quantitative monitoring of tissue rejuvenation using 3D OCTAreun Kim, Jeonghyeon Lee, Taeho Kim, Ulsan National Institute of Science and Technology (Korea, Republic of); Haekwang Lee, Sunghoon Lee, AmorePacific Corp. (Korea, Republic of); Woonggyu Jung, Ulsan National Institute of Science and Technology (Korea, Republic of)Nowadays, laser therapy is a common method for treating various dermatological troubles, because it provides effective care of acne, pigmentation and wrinkle etc. in the skin. Although laser treatment becomes a routine procedure in medical and cosmetic fields, there are few studies investigating laser-tissue interaction and the prevention of side effect such as hyperpigmentation, redness and burning. This results from the lack of optimal imaging modality enabling fast feedback and quantitative information of tissue during therapeutic procedure. In this study, we introduce a quantitative tissue monitoring tool using 3D optical coherence tomography (OCT) to observe tissue rejuvenation after laser irradiation. OCT has been used to image skin in dermatology, but previous approach was mostly focused on the diagnosis of disease with 2D image which has restriction to explore large area of tissue dynamically. In order to overcome these limit, we fabricated video integrated high speed 3D OCT which is capable of large field of cross-sectional imaging as well as surface imaging. Automatic segmentation software enabling the calculation of 3D volume was also developed accordingly. Engineered skins were irradiated by fractional laser, and analyzed by developed system and software. The experiment was repeated every two hours to observe the tissue rejuvenation for five days. Through this experiment, we found that laser irradiated engineered skin was mostly recovered within two days which has similar tendency with



histological evaluation. Our result shows that 3D OCT could be promising tool to be used in laser therapeutic procedure to monitor and quantify skin.

8565-13, Session 4

Effective dermal heating with temporal squared millisecond Nd:YAG pulses visualized using subsurface thermo imagingRudolf M. Verdaasdonk, Vrije Univ. Medical Ctr. (Netherlands) and Free Univ. Amsterdam (Netherlands); Albert Van der Veen, Divya Chandrabose, Vrije Univ. Medical Ctr. (Netherlands); Vladimir Lemberg, BonCheol L. Goo M.D., Lutronic Corp. (Korea, Republic of)Various non-ablative treatment strategies have been introduced for effective skin rejuvenation. A wide beam millisecond long pulse Nd:YAG laser (CLARIA, Lutronic) was used to deliver thermal energy inside the dermis preserving the epidermis. The temporal pulse shape could contribute significantly to the heat accumulation inside the tissue. The heat accumulation of ‘square’ and ‘non-squared’ pulses were compared in relation to beam diameter (5-20 mm), pulse length (1-100 ms, at 5 Hz) and energy (5-20 J) using thermal imaging in a model tissue simulating the treatment technique. A layer of chicken skin was position on an IR absorbing polyacrylamide gel and imaged from the side ( ‘underneath the surface’) with a thermo camera showing the absolute temperature dynamics in a ‘2 ? D geometry’. The squared pulse showed to be more effective in heat accumulation (~25 %) compared to the non-squared pulse. A maximum temperature increase of 50 degree C occurred around 1 mm underneath the surface after 5 s exposure. Thermal relaxation was in the order of 30 seconds (however, in a model without perfusion). Larger spot sizes provide a more homogeneous temperature distribution inside the tissue. Thermo imaging in a ‘subsurface’ geometry provided an insight in the temperature dynamics of non-ablative skin rejuvenation therapy showing that temporal square shaped pulses are more effective in heating tissue.

8565-14, Session 4

Comparative analysis of the thermal distribution of a radio frequency fractional system using high speed thermo imaging techniques Rudolf M. Verdaasdonk, Vrije Univ. Medical Ctr. (Netherlands) and Free Univ. Amsterdam (Netherlands); Albert Van der Veen, Divya Chandrabose, Vrije Univ. Medical Ctr. (Netherlands); Vladimir Lemberg, BonCheol L. Goo M.D., Lutronic Corp. (Korea, Republic of)Fractional RF treatment has become the effective skin rejuvenation procedure. The RF energy build up in the skin dermis creates the fractionated thermal damage and collagen denature. To control the clinical effect and adverse effects, it is important to know the thermal distribution in the dermis created by RF pulses. High speed (Schlieren) imaging techniques were applied to study the thermo dynamic effects in transparent tissue models (polyacrylamide gel or pig cornea) imaging from the side ( ‘underneath the surface’) of a RF Fractional System (INFINI, Lutronic) complimented with a standard thermo imaging. The RF system consisted either of a array of 7x7 surface electrodes or an array of 7 x 7 RF needles that are spring loaded injected 1-4 mm into the tissue to expose the tissue for 100 - 500 ms. The dynamic images of the localized heating around the tip of the electrode at several mm depth in the tissue and consequent thermal relaxation gave good insight in heating mechanism (10 ms resolution). Additionally, the ‘subsurface’ thermal images showed local temperature

rise of 50 degree C and relaxation times in the order of 1-2 seconds.High speed thermo imaging in a ‘subsurface’ geometry provided an insight in the temperature dynamics during the application of RF electrodes to control and improve of non-ablative skin rejuvenation therapy .

8565-15, Session 4

Preclinical in vivo evaluation of combination photodynamic therapy and pulsed dye laser treatment on normal vasculatureWesley Moy, Justin Moy, Kristen M. Kelly M.D., Bernard Choi, Beckman Laser Institute and Medical Clinic (United States)Port wine stain (PWS) is a congenital birth mark commonly found on the face and neck regions. It consists of abnormally-enlarged vasculature in the dermis. Current treatments typically involve the use of a pulsed dye laser (PDL) combined with cryogenic cooling of the skin. Yellow light, from 585-595 nm wavelengths, is strongly absorbed by hemoglobin. The clinical goal is to achieve photocoagulation of the targeted vasculature in a selective manner.Based on past studies, we postulate that PDL therapy is ineffective to acute consistent photocoagulation of smaller vasculature. Over the past decade, we studied the use of photodynamic therapy (PDT) as an alternate treatment option, either as a standalone procedure or in combination with PDL therapy. We hypothesize that combined use of PDT and PDL therapy can achieve photocoagulation of targeted vessels while reducing the radiant energies required for each therapy, resulting in a safer, more effective treatment option.We devised a protocol that involves use of an intravascular photosensitizer followed by PDL treatments. To assess therapeutic efficacy, we used the mouse dorsal window chamber model and laser speckle imaging to monitor blood-flow dynamics. We defined a successful treatment outcome as achieving persistent vascular shutdown within the window, seven days following the combined PDT and PDL treatment.With our preclinical data, we applied dose response curve analysis to identify a characteristic radiant exposure to achieve a successful treatment. We studied PDT threshold radiant exposures with the PDL treatments to achieve successful outcomes. Our preliminary data suggest that the combination PDT and PDL therapy is a viable treatment option for PWS vasculature.

8565-16, Session 4

Blue LED treatment of superficial abrasionsDomenico Alfieri, Light4Tech Firenze S.r.l. (Italy); Stefano Bacci, Univ. degli Studi di Firenze (Italy); Riccardo Cicchi, Istituto Nazionale di Ottica (Italy) and European Lab. for Non-linear Spectroscopy (Italy); Gaetano De Siena, Univ. degli Studi di Firenze (Italy); Francesco S. Pavone, European Lab. for Non-linear Spectroscopy (Italy); Roberto Pini, Francesca Rossi, Francesca Tatini, Istituto di Fisica Applicata Nello Carrara (Italy)

A compact and easy-to-handle photocoagulation device was used for inducing an immediate coagulation effect in skin large superficial abrasions, reducing the recovering time and improving the wound healing process. The handheld illumination device consists of a high power LED, emitting in the blue region of the spectrum, mounted in a suitable and ergonomic case, together with power supply, electronics, and batteries. The working principle of the LED-based photocoagulator is a photothermal effect: the blue light (420 nm) is selectively absorbed by the haemoglobin content of the blood and then converted into heat. Here we present an in vivo study performed on animal models. 10 Sprague Dawley rats (Harlan, Italy, weighing 200-250 g) were used to study the wound healing process. On the back of each rat, four large



abrasions were mechanically produced: two of them were used as a control, while the other two were treated with the photocoagulator, keeping it at a constant distance (2 mm) from the target, in continuous slow motion (treatment time: tens of seconds). The induced photothermal effect was monitored by an infrared thermocamera in order to avoid accidental thermal damage and to control the temperature dynamics during treatment. Objective observations, histopathological analysis and non-linear microscopy performed in a 8 days follow-up study showed no adverse reactions and no thermal damage in the treated areas and surrounding tissues. Moreover, a faster healing process and a better recovered morphology was evidenced in the treated tissue.

8565-18, Session 5

Elimination of single-beam substitution error in diffuse reflectance measurements using an integrating sphereLuka Vidovic, Jo?ef Stefan Institute (Slovenia); Boris Majaron, Jo?ef Stefan Institute (Slovenia) and Univ. of Ljubljana (Slovenia)Diffuse reflectance spectroscopy (DRS) is a popular approach to objective characterization of various skin test sites. A common DRS setup involves an integrating sphere (IS), in which spectrally broad illumination light is multiply scattered and homogenized. To account for illumination spectrum, each measurement begins by placing a highly reflective “white standard” against the IS sample opening and collecting the reflected light at the signal output port. After replacing the white standard with skin site of interest, DRS of the latter is determined by dividing the two signals at each involved wavelength. However, because skin samples are invariably less reflective than the white standard, such a substitution modifies the illumination field inside the IS. This is known as a “single-beam substitution error” (SBSE) and leads to underestimation of skin’s reflectivity and distortion of measured DRS, with adverse consequences for subsequent quantitative analysis. Barring the use of much more complex dual-beam experimental setups, involving dedicated IS, literature states that only approximate corrections of SBSE are possible, e.g., by using look-up tables generated with lower-reflectivity standards.We have established a way to eliminate SBSE by using IS equipped with an additional “reference” output port (e.g., ISP-REF by Ocean Optics). In a theoretical derivation, we show that two additional measurements performed at this port (of the white standard and skin sample, respectively) enable accurate compensation of the IS throughput alteration, thereby eliminating SBSE. We also demonstrate that the difference between DRS measured with and without such correction (reaching 7%) behaves according to theoretical predictions.

8565-19, Session 5

Characterization of a multi-modal probe for early skin cancer detection using Raman, reflectance and fluorescence spectroscopiesManu Sharma, Liang Lim, The Univ. of Texas at Austin (United States); Eric Marple, EmVision, LLC (United States); William Riggs, DermDx (United States); James W. Tunnell, The Univ. of Texas at Austin (United States)The development of technologies which focus on noninvasive pathology detection and diagnosis are imperative as their noninvasive nature improves patient care and their early detection capabilities reduce patient morbidity and mortality. The combination of different spectroscopic techniques, with each modality providing complementary information, has proven to be a very successful and relatively cheap option. Here we describe the design and testing of a novel optical fiber probe, which combines three optical spectroscopy modalities, and forms a key component in the development of a system to be used for the early detection of skin cancer.

Our probe collects light for fluorescence, Raman and reflectance spectroscopies. An effective multi-modal probe design must cater to the specifics of each technique such as a high Raman collection efficiency and the source-detector geometry for physiological measurements from reflectance spectra. Our solution involves an innovative gradient-index (GRIN) lens configuration to focus and collect light from the same area. We have tested our prototype in both tissue-simulating phantoms and on human skin. Diagnostically important spectral features (Amide I/III, Q/Soret bands) can be identified and physiologically important parameters have been extracted, demonstrating adequate Raman collection efficiency and appropriate source-detector separation. Results from our clinical trial demonstrate that a multi-modal approach is a superior skin cancer diagnostic tool compared to any one single modality. These initial results suggest that our multi-modal probe offers considerable promise for early skin cancer detection purposes. Our probe performance indicates that it could be well-applied to any biomedical multi-modal application.

8565-20, Session 5

Quantitative assessment of response of generalized Argyria to Nd:YAG treatment using diffuse optical spectroscopyRolf B. Saager, Beckman Laser Institute and Medical Clinic (United States); Khaled M. Hassan, Univ. of California, Irvine (United States); Clement Kondru, Anthony J. Durkin, Beckman Laser Institute and Medical Clinic (United States); Kristen M. Kelly, Univ. of California, Irvine School of Medicine (United States)Generalized argyria is a blue-gray hyperpigmentation of the skin resulting from repeated ingestion of products as silver colloid. While some case reports have noted improvement after Q-Switched 1064nm Nd:YAG laser treatment to small surface areas, no reports have objectively monitored laser treatment of generalized argyria over large areas of skin, nor have long-term outcomes been evaluated.We have developed a novel fiber probe which can be used in combination with diffuse optical spectroscopic (DOS) methods, to noninvasively determine full spectrum optical properties of superficial in-vivo skin in the wavelength range from 650-1000nm. This probe uses a highly scattering layer to diffuse photons emitted from a collimated light source, and relies on a two-layer diffusion model to determine tissue absorption coefficient ?a and reduced scattering coefficient ?s’. This technique was used to quantify the concentration of silver particles in the skin prior to laser treatment, as well as multiple time intervals up to 1 year thereafter. We were able to estimate from the quantitative absorption data that there was, on average, a 0.042 mg/mL concentration of silver in the tissue prior to treatment through direct comparison of reference measurements of silver colloid in solution (H2O) taken in a spectrophotometer. There was no detectable presence of silver after a single treatment of the tissue area and no indication of recurrence up to one year. Additionally, the tissue optical properties indicated that there was no collateral tissue damage that resulted from these treatments, in agreement with clinical observation.

8565-21, Session 5

Non-invasive, in vivo fluorescence monitoring as an objective tool to examine wound healing progression following low level laser therapyVijendra Prabhu, Edward M. Fernandes, Satish B. S. Rao, Krishna K. Mahato, Manipal Univ. (India)Collagen represents major protein component of the extracellular



matrix (ECM) and hence it could be used as an ideal tool for assessing wound healing following any therapy. Presently, there is a great need to develop quick, objective, non-destructive method to monitor collagen levels during progression of wound healing. The applicability of the laser induced fluorescence (LIF) towards wound healing monitoring by measuring collagen levels at different stages of the healing progression is the main idea behind the current work. Six to eight weeks old Swiss albino mice with ccircular wounds of 15 mm diameter were illuminated with single exposure of 2 J/cm2 from He-Ne laser (632.8 nm; 7 mW power; 4.02 mW/cm2 power density) along with un-illuminated and un-wounded controls. Spectroscopic changes were monitored by recording in vivo fluorescence spectra from each animal under anesthesia at different post-wounding days (5th, 10th, 30thday) by exciting wound granulation tissue/skin with 325 nm He-Cd laser. The autofluorescence from the tissue/skin was recorded from four different sites and four spectra were recorded from each. A total of 2160 spectra were recorded from 45 animals and analysed. The present study have shown significant increase (P


8565-25, Session 6

Diffuse reflectance imaging system for spectral analysis of skin cancer in vivoSheldon F. Bish, Youmin Wang, Manu Sharma, Nicholas Triesault, The Univ. of Texas at Austin (United States); Jason Reichenberg M.D., Univ. Medical Ctr. Brackenridge (United States); Xiaojing Zhang, James W. Tunnell, The Univ. of Texas at Austin (United States)Diffuse reflectance spectroscopy provides a noninvasive means to determine tissue optical properties and has been used as a diagnostic tool for early cancer detection in several organ sites including the skin, cervix, and oral cavity. Until recently, these measurements were made on a single point of tissue, missing the spatial context to investigate critical features such as margins and shape. To expand on these point measurements, we have developed a diffuse reflectance spectroscopy imaging (DRSI) system capable of acquiring wide field optical property maps of tissue. This system uses a white light source and a portable spectrometer to acquire high resolution UV-VIS spectra. Currently, image acquisition time is approximately 10 seconds for a 50x50 pixel image. A nonlinear optimization fitting routine was used to fit a look-up table (LUT) model to the DRSI spectral images resulting in spatially resolved fits for reduced scattering, hemoglobin and melanin concentration. The system was validated across biologically relevant levels of reduced scattering (7% Error) and absorption (10% Error) using tissue simulating phantoms. DRSI optical property maps of suspected basal cell carcinoma and melanoma were acquired in vivo. These quantitative maps showed consistency with the known optical properties found in literature such as decreased reduced scattering within lesion margins. Here we have presented the latest edition of our DRSI system, demonstrating the potential as an effective tumor margin delineation tool for clinicians.

8565-26, Session 6

An initial development of laser speckle imaging for application in the inflammatory arthritis diseaseTaeyoon Son, Won Hyuk Jang, Jihoon Park, Byungjo Jung, Yonsei Univ. (Korea, Republic of)Rheumatoid arthritis (RA) is one of most common inflammatory joint disease. RA leads to damage to the articular cartilage, bony erosion and, finally, articular destruction. As the treatment in RA moves toward early and aggressive therapy more sensitive imaging techniques are needed to evaluate the effectiveness of early therapy. Common joint imaging modalities to diagnosis arthritis are conventional and digital radiography, CT, US, MRI and nuclear imaging. But, there exist some drawbacks. That is low soft tissue contrast and patient exposure to ionizing radiation expensive and not as widely available as US or CR for CT, difficulty to assess the structural changes within the bone, performance is highly dependent on the skills of operator for US, high cost, need for contrast agent long data acquisition time, in some cases impossible to use for MRI and poor spatial resolution and limitation of anatomical information for nuclear imaging. Optical imaging such as Laser speckle imaging (LSI) offers unique advantages - nonionizing noninvasive method - over existing imaging methods for medical imaging and diagnosis of arthritis. In this study, adjuvant-induced arthritis model was used and mouse feet were imaged. The mouse was divided into two groups – control (with no arthritis) and test (with inflammatory arthritis). The acquired images were analyzed into speckle contrast index and erythema index and compared conventional diagnosis method. The results show that the test group represent higher index for both LSI and erythema imaging compared to control group. From the results, LSI shows the potential of early diagnosis for inflammatory arthritis

8565-27, Session 7

Assessment of reconstructive flap occlusion in a preclinical model: A comparison of spatial frequency domain imaging to conventional digital color imagingEren Taydas, Beckman Laser Institute and Medical Clinic (United States); Adrien Ponticorvo, Beckman Laser Institute and Medical Clinic, University of California Irvine (United States); Amaan Mahzar, Modulated Imaging, Inc. (United States) and Beckman Laser Institute Photonics Incubator (United States); Thomas Scholz M.D., Jonathan Rimler M.D., Hak-Su Kim, Univ. of California, Irvine Medical Ctr. (United States); June Tong, Beckman Laser Institute and Medical Clinic (United States) and Univ. of California, Irvine (United States); Gregory R. D. Evans M.D., Univ. of California, Irvine Medical Ctr. (United States); David J. Cuccia, Modulated Imaging, Inc. (United States) and Beckman Laser Institute Photonics Incubator (United States); Anthony J. Durkin, Beckman Laser Institute and Medical Clinic (United States) and Univ. of California, Irvine (United States)

Tissue transfer techniques are commonly used in reconstructive surgery to replace damaged tissue. While typically successful, there is a 40-60% failure rate for tissue flaps that require additional surgery. The current technique for diagnosing tissue flap failure is to monitor the flap on an hourly basis and look for signs of discoloration. Because the chances of salvaging a tissue flap improve the earlier a problem becomes apparent, a technique that is capable of detecting changes before they are clinically noticeable has the potential to improve post-operative flap management. The research presented here aims to compare clinical appearance as recorded via digital camera with spatial frequency domain imaging (SFDI), a non-invasive imaging technique utilizing wide field patterned illumination at multiple wavelengths to generate images of tissue oxygen saturation. To mimic different levels of tissue failure, flaps were created in a swine model where blood flow was monitored with ultrasound probes and controlled with vascular occlusion cuffs. Blood flow was reduced by 25%, 50%, 75%, and 100% of baseline values in each of the flaps. The color changes recorded in the digital camera images were quantified in order to predict which occlusion conditions were visible to the human eye. The results of the color change analysis are compared to the oxygen saturation images generated by the SFDI system. Results indicate that while the human eye can reliably perceive changes at 100% occulsion, SFDI is able to detect changes as small as 50%, thereby improving the potential response time and reducing the potential for flap failure.

8565-28, Session 7

Quantitative longitudinal measurement in a rat model of controlled burn severity using spatial frequency domain imaging (Invited Paper)John Quan M. Nguyen, Tuan Mai, Christian Crouzet, Beckman Laser Institute and Medical Clinic (United States); Nicole Bernal, Univ. of California, Irvine (United States); Bernard Choi, Anthony J. Durkin, Beckman Laser Institute and Medical Clinic (United States)Despite an estimated 500,000 burn injuries reported each year in the United States, clinical diagnosis of burn wound severity still remains a challenge. Whether an injury will be able to heal by itself or require surgical excision and grafting is highly dependent on the wound’s burn depth. In particular, partial thickness burn wounds are very difficult for clinicians to identify, and as such, result in delays in grafting and extended hospital stays. Here, we present a multi-day pre-clinical study in which we utilized a non-invasive wide-field functional imaging



modality known as Spatial Frequency Domain Imaging (SFDI) in order to quantitatively evaluate burn wound severities in a rat model. Imaging was conducted at 17 evenly spaced wavelengths from 650 to 970 nm using a broadband tungsten light source and liquid crystal tunable filter. Three groups of rats were given three categories of burn injuries (superficial, partial-thickness, and full thickness) according to a controlled burn protocol. Imaging and biopsy were conducted before and after burn injury, then on days 2, 3, and 7. Over the course of the one week healing period, we were able to map quantitative changes in spatially resolved tissue oxygen saturation, oxy/deoxy hemoglobin concentration, and reduced scattering coefficient. Overall, the results of this study suggest that SFDI can provide a quantitative means for tracking burn related tissue changes in a pre-clinical animal model.

8565-29, Session 7

Development of a wide-field fluorescence imaging system for evaluation of wound re-epithelializationWalfre Franco, Enoch Gutierrez-Herrera, Martin Purschke, Ying Wang, Joshua Tam, R. Rox Anderson M.D., Apostolos G. Doukas, Massachusetts General Hospital (United States)Normal skin barrier function depends on having a viable epidermis, an epithelial layer formed by keratinocytes. The transparent epidermis, which is less than a 100 mum thick, is nearly impossible to see. Thus, the clinical evaluation of re-epithelialization is difficult, which hinders selecting appropriate therapy for promoting wound healing. An imaging system was developed to evaluate epithelialization by detecting endogenous fluorescence emissions of cellular proliferation over a 10 mm x 10 mm field of view. A custom-made 295 nm ultraviolet (UV) light source was used for excitation. Detection was done by integrating a near-UV camera with sensitivity down to 300 nm, a 12 mm quartz lens with iris and focus lock for the UV regime, and a fluorescence bandpass filter with 340 nm center wavelength. To demonstrate that changes in fluorescence are related to cellular processes, the epithelialization of skin substitute constructs was monitored in vitro. Skin substitute constructs were made by embedding microscopic live porcine skin tissue columns, 700 mum in diameter and spaced 1 mm apart, in acellular porcine dermis. Surface images after embedding show circular profiles of the microscopic skin columns clearly defined by the UV signals. Images on a weekly basis show the extent of radial surface proliferation of keratinocytes and, eventually, full surface coverage. Functional validation of UV images was done by comparison to histology at the same time points. A simple, user-friendly way of imaging the presence of skin epithelium would improve wound care in civilian burns, ulcers and surgeries.

8565-30, Session 7

A novel spectral imaging system for quantitative analysis of hypertrophic scarPejhman Ghassemi, The Catholic Univ. of America (United States); Jeffrey W. Shupp M.D., Lauren T. Moffatt, Washington Hospital Ctr. (United States) and MedStar Health Research Institute (United States); Jessica C. Ramella-Roman, The Catholic Univ. of America (United States)Scarring can lead to significant cosmetic, psychosocial, and functional consequences in patients with hypertrophic scars from burn injuries. Therefore, quantitative assessment of scar is needed in clinical diagnosis and treatment. The Vancouver Scar Scale (VSS), the accepted clinical scar assessment tool, was introduced in the nineties and relies only on the physician subjective evaluation of skin pliability, height, vascularity, and pigmentation. To date, no entirely objective method has been available for scar assessment yet there is a continued need for better techniques to monitor patients with scars. We introduce a new spectral imaging system combining out-of-plane Stokes

polarimetry, Spatial Frequency Domain Imaging (SFDI), and three-dimensional (3D) reconstruction. The main idea behind this system is to estimate hemoglobin and melanin contents of scar using SFDI technique, roughness features with Stokes polarimetry, and height and general shape with 3D reconstruction. Our proposed tool has several advantages compared to current methodologies. First and foremost, it is non-contact and non-invasive and thus can be used at any stage in a wound healing without causing harm to the patient. Secondarily, the height, pigmentation, and hemoglobin assessments are co-registered and are based on imaging and not point measurement, allowing for more meaningful interpretation of the data. Finally, the algorithms used in the data analysis are physics based which will be very beneficial in the standardization of the technique. A swine model has also been developed for hypertrophic scarring and an ongoing pre-clinical evaluation of the technique is being conducted.

8565-17, Session PSun

Fiber 1.56-1.9 µm lasers in treatment of vascular malformations in children and adults Ivan A. Abushkin, Valeriy A. Privalov, Chelyabinsk State Medical Academy (Russian Federation); Alexander V. Lappa, Chelyabinsk State Univ. (Russian Federation); Vladimir P. Minaev, IRE-Polus Co. (Russian Federation) Our many years’ experience (Proc. SPIE 7883, 78830H, 2011) of successful treatment of hemangiomas with NIR diode lasers (920-1060 nm) allowed us to take attempts to apply the experience to treatment other vascular pathologies: malformations. But the used lasers failed in these applications. Analysis of the failure reasons led us to fiber lasers of 1.5-2 µm wavelength. Four new low invasive technologies with using these lasers were developed for treatment of:• capillary malformations (port-wine stains),• venous and venous-arterial malformations,• micro and small cystic lymphangiomas,• large cystic lymphangiomas.1st technology is based on distant blood photocoagulation with the help of 1.56 µm fiber laser (for anatomically complicated parts of strains) and high intensive light (IPL) (for simple large areas). About 150 patients (children - 87%) were treated, good cosmetic effect have been achieved in 95% cases.2nd technology uses endovascular blood photocoagulation with 1.56 µm laser or that in combination with 1.9 µm laser excision. More than 100 patients (children - 50%) with venous malformations and 5 children with venous-arterial ones were treated; excelent and good results have been achieved in all cases.3rd technology uses laser actions of 2 types: distant ablation and interstitial thermotherapy with 1.9 µm laser. 6 children were treated, all with good result.4th technology uses endocystic ablation and excision with 1.9 µm laser. 3 newborns with very extensive large cystic lymphangiomas were treated. Results are good.


Treatment of toe nail fungus infection using an AO Q-switched eye-safe erbium glass laser at 1534 nmMichael J. Myers, Jeffrey A. Myers, Baoping Guo, Christopher R. Hardy, Sean Myers, Angelo Carrabba, Kigre, Inc. (United States); Carmen Trywick, May River Dermatology, LLC (United States); Stewart Bryant, Clemson Univ. (United States); John Robert Griswold, Ave Maria Univ. (United States); Aggie Mazzochi,



Beauty & the Beach (United States); Franziska Roth, Kigre, Inc. (United States)We report on “eye-safe” erbium glass laser operating at Short-Wave Infra-Red (SWIR) region at 1534nm, to treat Onychomycosis or toenail fungus. Infected toenails of 12 patients were treated over a 3 month period using both long pulse and Q-switched laser output pulses. Our results compared favorably to Neodymium Yittrium Aluminum Garnet (Nd:YAG) laser fungus treatment studies as reported in literature. Nd:YAG laser devices, operating in the Near Infra-Red, (NIR) region at 1064nm, have recently become an effective alternative treatment to traditional oral medications used to treat nail fungal infections. Conventional nail infection treatments employ medications such as allylamines, azoles and other classes of antifungal drugs that are unpopular due to numerous side-affects and drug interactions. Side-effects of these drugs include headache, itching, loss of sense of taste, nausea, diarrhea, heart failure and even potential death from liver failure. The effectiveness of conventional oral antifungal medications varies. In addition, antifungal prescription drugs are administered for long periods ranging from 6 weeks to 18 months. Nd:YAG antifungal laser treatment reports claim high success rates (65-95%) in eradicating toenail fungus and without adverse side-affects. Multiple laser treatments are administered over a 3 to 6 month period. Our initial treatments performed with the Er:glass laser on toenail fungus patients required only 1 to 2 treatments for cure. This same SWIR laser was used in experiments to treat Athlete’s Foot fungal infections. The 1534nm Er:glass laser emission has been found to be well optimized for dermatological treatments due high transmission properties of human skin in the SWIR region. Increased depth of tissue penetration is well-tolerated and provides for effective treatment of various skin conditions. “Eye-safe” Class I lasers provide for practical skin and nail tissue treatment without the need for eye-protection goggles. Laser safety filters may inhibit a practitioner’s vision and ability to distinguish skin and nail regions exhibiting different colors and textures. The laser is “eye-safe” due to the fact that Megawatt peak power Q-switched lasers operating at 1.54um in the narrow spectral window between 1.4um and 1.6um are approximately 8000 times more eye-safe than other laser devices operating in the visible and near infrared. Long-pulse or free running lasers operating in this wavelength range are ~ 2000 times more eye-safe.


Phenylalanine gas phase and solvated models applied to skin NMF simulation by DFT calculationsBruna G. Carvalho, Leandro Raniero, Airton A. Martin, Priscila P. Favero, Univ. do Vale do Paraíba (Brazil)The L-phenylalanine is an essential amino acid to the organism. It is the precursor of tyrosine molecule participating in the synthesis of melanin. In the skin, it is one of the amino acids which compose the Natural Moisturizing Factor (NMF) that is responsible for the hydration of the skin. Thus, in medicine, the phenylalanine plays a relevant role when applied in topical and systemic therapy against diseases such as vitiligo. Based on this motivation, we present electronic proprieties analysis. We calculate the electronic density of state spectra, charge density plot for HOMO and LUMO states and energies of the systems. The data were obtained using the Vienna Ab-initio Simulation Package (VASP) program that is based on the density of functional theory (DFT). The molecule was modeled in vacuum and water, in nonionic and zwitterionic forms, this evaluation shows characteristics as hydrophilicity and hydrophobicity. In order to understand the environment dependence, the models were made with ammonia and urea which are molecules found in the NMF of the stratum corneum of the skin. Our data were validated with the calculation of the vibrational modes and the errors calculation between theoretical and experimental data obtained by FT-IR and Raman spectroscopy. The results show that the vibrational modes can be calculated with a difference between experiment and theory lower than 3% for any model. However electronic properties, like charge density, depend on

the adopted model and environment. In the case of optical or electronic evaluation the most complete model (solvated) is the recommended.


Discriminating model for skin cancer diagnosis in vivo through Raman spectroscopyFabrício L. Silveira, Univ. Camilo Castelo Branco (Brazil); Landulfo Silveira Jr., Camilo Castelo Branco Univ. (Brazil); Benito Bodanese M.D., Univ. Comunitária da Região de Chapecó (Brazil); Renato A. Zângaro M.D., Marcos T. T. Pacheco, Univ. Camilo Castelo Branco (Brazil)The incidence and mortality rates of skin cancer have increased dramatically over the last decade in Brazil, mainly due to prolonged exposure of workers/farmers in the countryside to solar radiation, and general population in leisure time (especially beaches). The early diagnosis of precancerous and cancerous lesions through non-invasive diagnostic techniques such as Raman spectroscopy can help to reduce this incidence. The objective of this work is to develop a discriminating model, using near-infrared Raman spectroscopy, based on the estimated concentration of selected biochemical components presented in skin tissues, in order to discriminate normal and benign skin lesions from malignant tissues in vivo. Raman spectra were collected in patients who underwent excision surgery of suspicious lesions at the lesion site and at a normal circumjacent site, right before tissue withdrawn. A spectral model was developed in order to estimate the relative amount of selected biochemical compounds presented in skin, such as actin, collagen, elastin, nucleic acids, triolein, phenylalanine, ceramide and melanin, using least squares fitting. This amount was used to discriminate tissues according to the pathological condition. The results showed that the Raman spectra of normal skin, benign and malignant lesions have differences in the spectral regions of proteins and lipids (800-1000, 1200-1350 and 1450-1670 cm-1), indicating different biochemical constitution. The spectral model showed changes in the relative amount of the basal constituents, such as reduction in collagen and increase in actin and triolein for normal, benign and malignant tissues, which could be used to discriminate these tissues in vivo.



Conference 8565B: Therapeutics and Diagnostics in Urology: Lasers, Robotics, Minimally Invasive, and Advanced Biomedical DevicesSaturday 2 –2 February 2013Part of Proceedings of SPIE Vol . 8565 Photonic Therapeutics and Diagnostics IX

8565-34, Session 1

Optical diagnosis of painful bladder syndrome/interstitial cystitisBabak Shadgan M.D., Andrew J. Macnab M.D., Lynn Stothers M.D., The Univ. of British Columbia (Canada)Painful bladder syndrome/interstitial cystitis (PBS/IC) is defined as a syndrome of urgency, frequency, and suprapubic pain in the absence of positive urine culture or obvious bladder pathology. As no specific etiology has been identified yet, no specific methodology exists for diagnosis of this condition. One potential etiology of PBS/IC is bladder mucosa inflammation associated with abnormal angiogenesis and ulcerative lesions in bladder mucosa. A method capable of evaluating bladder wall metabolism may therefore be relevant for diagnosis of PBS/IC. Near infrared spectroscopy (NIRS) is a noninvasive optical technique using light to monitor tissue oxygenation and hemodynamics. The purpose of this study was to examine ability of NIRS to differentiate subjects identified as PBS/IC from other marked bladder conditions.Twenty four adult patients with lower urinary tract dysfunction were divided into two groups, PBS/IC (4 male) and non-PBS/IC (8 male and 12) after standard diagnostic investigations. Detrusor oxygen saturation percentage (TSI%), were studied in all subjects using a spatially-resolved (SR) NIRS instrument, simultaneous to UDS study. After one minute baseline measurement in rest position, the detrusor TSI% was recorded by the NIRS instrument that was placed over the bladder. Statistical difference of the detrusor TSI% values between two groups were studied. Mean resting values of detrusor TSI% were significantly different (P


8565-37, Session 1

Full-field OCT can distinguish tumor from benign in human kidney and bladder tissue and assess kidney fibrosis in a rat modelJonathan Caron, INSERM (France) and Univ. Paris VI (France); Sushmita Mukherjee, Manu Jain, Bekheit Salomoon, Maria M. Shevchuk, Douglas S. Scherr, Weill Cornell Medical College (United States); Isabelle Brocheriou, Hôpital Tenon (France); Jean-Jacques Boffa, INSERM (France) and Univ. Paris VI (France) and Hôpital Tenon (France); Katharine Grieve, Institut Langevin (France); Fabrice Harms, Bertrand Le Conte de Poly, LLTECH SAS (France); Albert C. Boccara, Institut Langevin (France) and LLTECH SAS (France)

Full-Field Optical Coherence Tomography (FF-OCT) is an alternative approach to Fourier-domain OCT, allowing parallel acquisition of en-face optical sections. Using medium numerical aperture objectives, isotropic resolution of approximately 1x1x1 µm is achieved. In this study, FF-OCT was used to image human kidney and bladder, consisting of both benign and malignant specimens. Additionally, in rat kidney, a quantitative assessment of the state of fibrosis of the tissue was possible. In benign bladder specimens, all normal tissue components such as urothelial cells, connective tissue and muscle bundles were readily identified. In tumor-free kidney, renal tubules, glomeruli, vasculature and interstitial tissue were clearly recognized. Features of the injured kidney such as sclerotic glomeruli and interstitial fibrosis defined as increased collagen fiber density were clearly visible. In bladder tumors, we could differentiate flat from papillary lesions. Furthermore, increased nuclear-cytoplasmic (N:C) ratio was seen in high-grade tumors. In kidney tumors, we saw a complete loss of normal architecture, associated with increased cellularity. At this time, we cannot confidently distinguish cellular clusters as inflammatory versus malignant. In the rat model of hypertensive nephropathy, we present images in control, early fibrosis and advanced fibrosis states, and report on a quantitative method to assess renal fibrosis. Our preliminary results show that FF-OCT is a valuable method to rapidly assess sclerotic glomeruli in depth of fresh kidney tissue. The sum of serial images allows highlighting of peritubular capillaries which are not visible on histological analysis. We believe that FF-OCT could have clinical applications in fibrosis assessment in various tissues.

8565-38, Session 2

in vivo photoacoustic imaging of urinary bladders with dye-enhanced carbon nanotubesJasung Koo, Hyun Wook Kang, Pukyong National Univ. (Korea, Republic of); Jeehyun Kim, Kyungpook National Univ. (Korea, Republic of); Chulhong Kim, Univ. at Buffalo (United States); Junghwan Oh, Pukyong National Univ. (Korea, Republic of)Photoacoustic tomography (PAT) is a nonionizing and noninvasive imaging technique with high ultrasonic resolution and functional information. Visualizing bladders (cystography) is a key procedure for diagnosing bladder-related diseases such as bladder cancer. However, the organ is clinically imaged by harmful ionizing imaging tools that induce significant damage on connective tissues. The purpose of the study was to demonstrate the feasibility of mapping a urinary bladder in small animals by using modified single-walled carbon nanotubes (SWNTs) as a nonionizing photoacoustic (PA) contrast agent. To improve the PA sensitivity of the SWNTs, indocyanine green (ICG) was conjugated to SWNTs and the optical absorption of SWNTs-ICG was enhanced by ~4 times compared to that of plain SWNTs at the concentration of 0.3 ?M. In vivo PA imaging results showed that the bladder was clearly visualized

due to accumulation of SWNTs-ICG. A clinical PAT system with higher sensitivity may be able to use relatively low concentration of SWNTs-ICT with sub-nM sensitivity and sub-mm spatial resolution. The current results demonstrated that SWNTs-ICG could be potentially utilized to track vesicoureteral reflux (VUR) in combination with PA imaging due to its high optical contrast and good ultrasonic resolution without any ionizing radiation and invasiveness.

8565-39, Session 2

Subsurface optical stimulation of the rat prostate cavernous nerves using a 1490-nm diode laser Serhat Tozburun, Charlotte D. Stahl, Thomas C. Hutchens, The Univ. of North Carolina at Charlotte (United States); Gwen A. Lagoda, Arthur L. Burnett M.D., Johns Hopkins Medical Institutions (United States); Nathaniel M. Fried, The Univ. of North Carolina at Charlotte (United States)Introduction: Successful identification and preservation of the cavernous nerves (CN’s), which are responsible for sexual function, during prostate cancer surgery, requires detecting CN’s through a thin layer of overlying fascia. Subsurface optical nerve stimulation (ONS) of CN’s has been previously reported in a rat model in which fascia is placed over CN’s, using 1455 and 1550 nm infrared lasers. This study explores an alternative intermediate wavelength laser at 1490 nm, which combines advantages of both 1455 and 1550 nm lasers. Methods: A 150-mW, single-mode, narrow linewidth, 1490-nm diode laser was used to stimulate the CN in continuous-wave mode in 8 rats through a fiber optic probe with 1-mm-diameter spot. This wavelength provides an optical penetration depth of ~520 micrometers, sufficient to penetrate typical thicknesses of both fascia and nerve for successful stimulation. ONS was measured by an intracavernous pressure response (ICP) in the rat penis. Results: ONS was observed at 1490 nm through fascia layers up to 380 micrometers using a minimum incident laser power of ~53 mW. ICP response times averaged 10.4 + 1.8 s near the stimulation threshold and 4.6 + 0.2 s using higher laser powers (~75 mW) just below the thermal damage threshold. ICP signal-to-noise ratios of 3:2 were recorded.Conclusions: The 1490-nm laser is capable of stimulating the CN at 2-3 times depth of 1455-nm laser, and it is also a lower cost, higher power, and higher quality laser alternative to the 1550-nm laser, for easy integration into a compact and inexpensive all-single-mode-fiber ONS system.

8565-40, Session 2

Temperature-controlled optical stimulation of the rat prostate cavernous nervesSerhat Tozburun, The Univ. of North Carolina at Charlotte (United States); Gwen A. Lagoda, Johns Hopkins Medical Institutions (United States); Michael A. McLain, The Univ. of North Carolina at Charlotte (United States); Arthur L. Burnett M.D., Johns Hopkins Medical Institutions (United States); Nathaniel M. Fried, The Univ. of North Carolina at Charlotte (United States)

Introduction: Optical nerve stimulation (ONS) may be useful for intra-operative identification and preservation of the prostate cavernous nerves (CN’s), responsible for erectile function, during prostate cancer surgery. ONS relies on a photothermal mechanism of laser-tissue interaction in which elevating nerve temperature to within a narrow range (~ 42-45 C) is critical to successful nerve activation without thermal damage. Closed-feedback loops utilizing an infrared (IR) sensor for real-time control of tissue surface temperatures during laser therapy have previously been reported (e.g. for laser tissue welding/soldering). This preliminary study explores a prototype temperature-controlled laser system for maintaining

Conference 8565B: Therapeutics and Diagnostics in Urology: Lasers, Robotics, Minimally Invasive, and Advanced Biomedical Devices


a constant nerve temperature during short-term ONS of the rat prostate CN’s. Methods: A 150-mW, 1455-nm diode laser was operated in continuous-wave mode during stimulation of the rat CN’s for 30 s through a fiber optic probe with 1-mm-diameter spot. The all-single-mode ONS system was controlled by a computer which opened and closed an in-line mechanical shutter in response to an IR sensor, with a temperature set-point of 45 C. Thermal camera temperature measurements and ONS without temperature control were performed for comparison. Results: Strong correlation was observed between IR sensor and camera temperatures. With temperature control, CN temperature was maintained at 45.0 +/- 1.5 C. Without IR sensor feedback, CN temperatures continued to rise during ONS, reaching unsafe levels of ~50 C.Conclusions: With further development, temperature-controlled ONS may provide a rapid, stable, and safe method for stimulation of the prostate cavernous nerves.

8565-41, Session 2

A new optical method enables fluorescence guided diagnosis of bladder tumours in the outpatient department and reveals significant photo bleaching problems in established inpatients photo dynamic diagnostics (PDD) techniques.Lars R. Lindvold, Risø National Lab. (Denmark); Gregers G. Hermann, Frederiksberg Hospital (Denmark)Photo dynamic diagnosis (PDD) is a convenient and well-documented procedure for diagnosis of bladder cancer and tumours using endoscopic techniques. At present, this procedure is available only for use in an operating room (OR) and often with substantial photobleaching effects of the photosensitizer.We present a novel optical design of the endoscopic PDD procedure that allows the procedure to be performed in the outpatient department (OPD) and not only in the OR. Thereby, inpatient procedures lasting 1-2 days may be replaced by a few hours lasting procedure in the OPD.Urine blurs the fluorescence during PDD used in the OPD. Urine contains fluorescent metabolites that are excited by blue light giving an opaque green fluorescence confounding the desired red fluorescence (PDD) from the tumour tissue. Measurements from the clinical situation has shown that some systems for PPD based on blue light illumination (PDD mode) and white light illumination used for bladder tumour diagnosis and surgery suffers some inherent disadvantages, i.e., photo bleaching in white light that impairs the possibility for PDD as white light usually is used before the blue light for PDD. Based on spectroscopic observations of urine and the photoactive dye Protoporphyrin IX used in PDD, a novel optical system for use with the cystoscope has been devised that solves the problem of green fluorescence from urine. This and the knowledge of photo-bleaching pitfalls in established systems make it possible to perform PDD of bladder tumours in the OPD and to improve PDD in the OR.

8565-42, Session 3

Fiber optic suctioning of urinary stone phantoms during laser lithotripsyRichard L. Blackmon, The Univ. of North Carolina at Charlotte (United States); Jason Case, Susan Trammell, Univ of North Carolina at Charlotte (United States); Pierce B. Irby M.D., Carolinas Medical Ctr. (United States); Nathaniel M. Fried, The Univ. of North Carolina at Charlotte (United States)

Introduction: Fiber optic attraction of urinary stones during laser lithotripsy may be exploited to pull stone fragments inside the urinary tract without insertion of mechanical grasping tools, thus saving the urologist time and space in the working channel of the ureteroscope. In this study, we compare the experimental Thulium fiber laser (TFL) high pulse rate/low pulse energy operation to conventional Holmium:YAG low pulse rate/high pulse energy operation for fiber optic suctioning and manipulation of stone phantoms. Methods: A TFL with wavelength of 1908 nm, pulse energy of 35 mJ, pulse duration of 500 microseconds, and pulse rate of 10-350 Hz, and Holmium laser with wavelength of 2120 nm, pulse energy of 35-350 mJ, pulse duration of 300 microseconds, and pulse rate of 20 Hz were tested, using 270-micrometer-core fibers. Plaster-of-Paris, 4-mm-diameter, stone phantoms were used. Stone drag speed was calculated by video recording distance moved per unit time. Five samples were averaged for each laser parameter set.Results: A peak drag speed of ~2.5 mm/s was measured for both TFL at 35 mJ and 150-250 Hz and Holmium laser at 210 mJ and 20 Hz. However, TFL provided more stable manipulation over larger range of laser parameters.Conclusions: Fiber optic “suctioning” of urinary stone phantoms is feasible. TFL operation at high pulse rates/low pulse energies is superior to Holmium operation at low pulse rates/high pulse energies for rapid and stable stone pulling. With further development, this technique may be useful for manipulation of stone fragments inside the urinary tract.

8565-43, Session 3

Dependence of laser-induced bubble collapse shockwave and fluence during Q-switched Tm:YAG laser lithotripsyDanop Rajabhandharaks, Jian J. Zhang, Hui Wang, Jason R. Xuan, Ray Chia, Thomas Hasenberg, American Medical Systems (United States); Hyun Wook Kang, Pukyong National Univ. (Korea, Republic of)Q-switched Tm:YAG laser ablation mechanisms on urinary calculi are still unclear to researchers. In this study, two parameters that may affect calculus ablation performance were investigated: laser-induced bubble collapse shockwave and laser fluence. For the effect of laser-induced bubble collapse shockwave study, calculus phantoms (Plaster of Paris) were ablated at single pulse and contact mode in air and in water. Ablation volume was obtained 0.006 mm3 and 0.008 mm3 in air and water group, respectively. High-speed photography showed formation of half-spherical bubble in contact mode with associated minimal collapse shockwave pressure, captured by a hydrophone. When a phantom was placed 1 mm away from the fiber tip to allow construction of full-spherical bubble, calculus ablation was very minimal and negligible compared with that obtained from the contact mode. Bubble collapse shockwave may not be the primary mechanism for calculus ablation during Q-switched Tm:YAG laser lithotripsy. Water surrounding calculus and fiber can help cool down the fiber tip to avoid catastrophic melting of the fiber and can help soften the calculus phantom to reduce the damage threshold. However, it may not significantly enhance calculus ablation volume. For dependence of fluence on calculus ablation study, calculus phantoms were ablated at single pulse and in contact mode with various pulse energies and fiber core sizes. Ablation was initiated at 12 J/cm2 (threshold) and became saturated after 28 J/cm2. The efficacy of using Q-switched Tm:YAG laser for urinary calculus lithotripsy is still under investigation and more feasibility experiments will be conducted in the future.

Conference 8565B: Therapeutics and Diagnostics in Urology: Lasers, Robotics, Minimally Invasive, and Advanced Biomedical Devices


8565-44, Session 3

Comparison of detachable and tapered fiber optic tips for use in thulium fiber laser lithotripsyThomas C. Hutchens, Richard L. Blackmon, The Univ. of North Carolina at Charlotte (United States); Pierce B. Irby M.D., Carolinas Medical Ctr. (United States); Nathaniel M. Fried, Univ. of North Carolina at Charlotte (United States)Introduction: The single-mode Thulium fiber laser (TFL) beam profile has previously been shown to allow coupling of higher power laser radiation into smaller fibers than the conventional multimode Holmium laser beam profile without proximal fiber tip degradation. This is significant because larger, more rigid optical fibers inserted into the working channel of a flexible ureteroscope may hinder ureteroscope deflection and prevent easy access to the upper urinary tract during lithotripsy. Furthermore, Holmium laser lithotripsy is typically performed with expensive, single-use optical fibers due to fiber tip degradation and sterilization issues. In this study, we propose use of inexpensive, detachable, and disposable large-core-diameter fiber tips in combination with a flexible, small-core “trunk” fiber. Methods: A TFL with wavelength of 1908 nm, pulse energy of 40 mJ, pulse duration of 500 microseconds, and pulse rate of 100 Hz was used. A disposable, spring-loaded, twist-lock, 300-micrometer-core silica fiber optic tip was manually inserted and self-aligned with a 150-micrometer-core, 1-m-long trunk silica fiber. Fiber optic transmission tests and ex vivo stone ablation studies were performed using human urinary stone samples. Results: The fiber optic system provided a transmission rate of ~77%. Human calcium oxalate monohydrate stones were ablated without damage to the trunk/tip interface, and the fiber probe delivered greater than 30,000 pulses without distal fiber tip degradation. Conclusion: A novel fiber optic design incorporating an inexpensive, detachable, and disposable fiber optic tip was successfully tested. Future work will involve further miniaturization of the fiber optic design for potential integration into a flexible ureteroscope.

8565-45, Session 3

Laser lithotripsy retropulsion varies with stone massJoel M. Teichman M.D., St. Paul’s Hospital (Canada); Michael E. Robinson, The Univ. of British Columbia (Canada)INTRODUCTION AND OBJECTIVES: The Ho:YAG laser fragments stones by a photothermal mechanism. As fragment debris is ejected off the stone surface, it exerts a force in the opposite direction producing retropulsion. As pulse energy is increased, ablation crater volumes and retropulsion both increase. A recent study using 6 mm stone phantoms showed an overall benefit using low pulse energy at high pulse frequency. However, retropulsion has not been characterized for larger stones. We hypothesize that retropulsion would be minimal if treating a large bladder or renal calculus even at high pulse energy.MATERIALS AND METHODS: Stone phantoms were constructed to uniform cube sizes of 0.5 cm to 2.0 cm. Stones were positioned in a cylindrical tube in a water bath, and irradiated with a 365 um fiber using Ho:YAG pulse energies 0.5 to 3.5 J to a constant total energy applied. Displacement was measured. Analysis of variance was used for statistics.RESULTS: At any given pulse energy, retropulsion decreased as stone size increased, p


fluorescence from a substantial distance within the body, the emission wavelength must be in the NIR wavelength window in which light passing through tissue is less likely to be absorbed or scattered. Over the past decade, cyanine dyes have been investigated as contrast agents for optical detection of tumors because their emission range is in the tissue “optical window”. Indocyanine Green (ICG), the only clinically approved NIR dye by FDA, is one of the most investigated. As a small ICG-derivative dye-peptide, Cybesin, was synthesized and used as a contrast agent to detect the over-express bombesin receptor in pancreas tumors in an animal model a few years ago. It was observed that the bombesin receptors are over-expressed on the membranes of human prostate cancer cells.In this study, Cybesin was used to target over-expressed bombesin receptors in human prostate cancer tissue. We report on the NIR spectral polarization imaging study using Cybesin as an optical smart contrast agent marker to differentiate human prostate cancerous and normal tissues. The absorption and fluorescence spectra of Cybesin were studied in the wavelength region from 650 nm to 900 nm. The model prostate samples consisting of a small piece of normal prostate tissue and a small piece of prostate cancer tissues stained with Cybesin were imaged. The results indicate that this receptor-targeted Cybesin was preferentially taken up by prostate cancerous tissue compared to prostate normal tissues.

8565-51, Session P1

Magnetic nanoparticles-assisted cellular imaging for cervical cancer: preliminary studyJasung Koo, Hyun Wook Kang, Pukyong National Univ. (Korea, Republic of); Jeehyun Kim, Kyungpook National Univ. (Korea, Republic of); Junghwan Oh, Pukyong National Univ. (Korea, Republic of)Optical coherence tomography (OCT) has been applied to detect the movement of magnetic nanoparticles uptaken by cells and tissues under externally high-strength continuous magnetic fields, referred to as magneto-motive OCT (MM-OCT). The current study investigated the feasibility of PMM-OCT to track the mechanical movement of the remote magnetically-labeled cells eventually for early detection of cervical cancer. For non-contact cellular imaging, pulsed magneto-motive optical coherence tomography (PMM-OCT) was developed to reduce environmental temperature in the measurement volume and to expand the effective magnetic field distance from a pulse source. The PMM-OCT system consisted of a spectral-domain OCT system and a customarily-designed electrical pulse generator. Pulsed and sinusoidal modes were compared along with presence and non-presence of an iron core in the generator. Temperature as well as magnetization was quantitatively characterized for each condition in terms of distance and time. Due to the characteristics of

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