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  • Advanced optical-molecular imaging applied to surgical guidance has emerged over the last decade as a major sector of Biomedical Optics with a growing impact and increasing numbers of clinical devices and procedures. Molecular-guided surgery relies on imaging specific markers in vivo, whether exogenous (e.g. fluorescence) or endogenous (e.g. hemoglobin), and allows healthcare practitioners to visualize features and function of tissue, in addition to the standard anatomical structures. This field requires a broad range of expertise including instrumentation, chemistry, biology, physics, tracer kinetics and clinical translation.

    The number of investigators working in this specific field has grown from just a few individuals to hundreds of research groups today. This new conference aims to consoildate related work into one forum with the goals of pooling expertise and allowing the community to follow and contribute to the field's progress while offering strong potential for discussions and collaborations.

    Submissions are solicited in the following and related areas: ;
    In progress – view active session
    Conference 11943

    Molecular-Guided Surgery: Molecules, Devices, and Applications VIII

    In person: 22 - 23 January 2022
    All sponsors
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    View Session ∨
    • 1: Endogenous Molecular Contrast
    • 2: Fluorescence Imaging Systems and Methods
    • 3: Contrast Agent Development and Preclinical Applications
    • 4: Contrast Agent Clinical Translation
    • 5: Clinically Approved Contrast Agents
    • 6: Clinical Trials
    • 7: Industry Perspective
    • Posters


    • Submissions are accepted through 06-December
    • Notification of acceptance by 20-December

    View Call for Papers PDF Flyer
    Session 1: Endogenous Molecular Contrast
    Author(s): Anita M. Mahadevan-Jansen, Vanderbilt Univ. (United States)
    Author(s): Baowei Fei, The Univ. of Texas at Dallas (United States)
    Author(s): Calum Williams, Univ. of Cambridge (United Kingdom); George S. D. Gordon, The Univ. of Nottingham (United Kingdom); Travis W. Sawyer, The Univ. of Arizona (United States); Sarah E. Bohndiek, Univ. of Cambridge (United Kingdom)
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    White-light imaging remains indispensable as the standard of care, from ophthalmoscopy to endoscopy, yet the ability to capture multispectral imaging (MSI) data without changing the instrument form factor would dramatically enhance our visualization of tissue biochemistry. We introduce a custom MSI sensor that combines standard white-light with narrowband imaging and enables quantitative assessment of changes in tissue blood supply. The MSI sensor is realized by patterning a custom filter array atop a CMOS image sensor using a single-step grayscale-to-color lithographic process. By augmenting the ubiquitous Bayer mosaic with complementary narrowband filters, biomedical MSI is achieved using a single image sensor.
    Author(s): Marcelo Saito Nogueira, Michael Raju, Jacqueline E. Gunther, Siddra Maryam, Michael Amissah, Huihui Lu, Tyndall National Institute (Ireland); Shane Killeen, Mercy Univ. Hospital (Ireland); Micheal O’Riordain, Stefan Andersson-Engels, Tyndall National Institute (Ireland)
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    Developing new technologies for accurate colorectal cancer detection and delineation for resection requires unveiling biochemical and microstructural changes associated with carcinogenesis. These changes can be probed by diffuse reflectance spectroscopy (DRS). In this study, we probed such changes by extracting tissue parameters based on an extended wavelength range (450–1590 nm) compared previous CRC studies and on DRS spectral fitting using a Monte Carlo reflectance look-up table. By combining spectral fitting and machine learning algorithms, we found that total lipid content, reduced scattering amplitude, Mie scattering power and microvascular parameters are the most important parameters for CRC detection/delineation using DRS.
    Session 2: Fluorescence Imaging Systems and Methods
    Author(s): Viktor Gruev, Univ. of Illinois (United States)
    Author(s): Arthur Pétusseau, Petr Bruza, Thayer School of Engineering at Dartmouth (United States); Arin Ulku, Ecole Polytechnique Fédérale de Lausanne (Switzerland); Samuel Streeter, Thayer School of Engineering at Dartmouth (United States); Kimberley S. Samkoe, Geisel School of Medicine (United States); Claudio Bruschini, Edoardo Charbon, Ecole Polytechnique Fédérale de Lausanne (Switzerland); Brian W. Pogue, Thayer School of Engineering at Dartmouth (United States)
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    Classical fluorescence guided surgery uses long laser pulses to excite fluorescent tracers, only providing the practitioner with 2D information. In this work, we develop and test a 3D imaging technique using LiDAR technology to sense target tissue depths up to 5 mm below the surface. Imaging through highly scattering medium like tissues implies that temporal information used for 3D reconstruction is convolved with diffuse dynamics of the medium. Using diffuse reflectance as an indicator of the medium’s optical properties, correction of the time-of-flight is made possible. Time-of-flight fluorescence imaging, captures intensity as well as temporal profile of fluorescence excited by ultra-short pulses.
    Author(s): Xiangnan Zhou, Silvia N. Anbunesan, Alba Alfonso García, Julien Bec, Lisanne Kraft, Roberto P. Frusciante, Orin Bloch, Laura Marcu, Univ. of California, Davis (United States)
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    5-ALA induced PpIX is increasingly used for guiding brain tumor resection surgery. The current intensity-based approach fails at detecting lower concentrations of PpIX found in low-grade gliomas or the infiltrative edge of glioblastomas. Here, we report the first results in patients of real-time, PpIX fluorescence lifetime measurements using a hand-held fiber probe. Fluorescence from different spectral channels (390/40 nm (Collagen), 470/28 nm (NADH), 629/53 nm (PPIX)), is augmented onto a video stream of the surgical field-of-view to provide intraoperative tumor visualization in real-time. In-vivo data reveals strong contrast between regions of high PpIX accumulation associated with tumor (>8 ns) and healthy brain tissue (<4 ns).
    Author(s): Youbo Zhao, Mark Scimone, Gopi Maguluri, Physical Sciences Inc. (United States); Brian W. Pogue, Dartmouth College (United States); Nicusor Iftimia, Physical Sciences Inc. (United States)
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    We report a unique imaging technology to suppress the ambient light interference during intraoperative fluorescence imaging. The technology uses a novel temporally gated and spatially modulated illumination scheme, which significantly reduces the negative impact of the ambient light background. Based on a simple and low-cost hardware platform, rejection of ambient light background by a factor of >16,000 was achieved. Such a high background suppression rate enabled in vivo imaging of visible fluorophores with the presence of a high-brightness surgical lamp illumination. The presented imaging results demonstrate the potential of capturing background-free fluorescence images using the tempo-spatially modulated imaging technology.
    Author(s): Michael J. Daly, Murtuza V. Rajkotwala, Arjun Jagota, Yasmeen El-Rayyes, Sharon Tzelnick, Axel Sahovaler, Brian C. Wilson, Jonathan C. Irish, Univ. Health Network (Canada)
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    A spatial frequency domain imaging (SFDI) system is under development to quantify the depth of tissue invasion in oral cancer tumors. Depth-resolved imaging is implemented by exploiting changes in optical sampling depth with spatial frequency. Fluorescence quantification is enabled by compensating for profile-corrected optical properties. A digital catalogue of clinically realistic oral cancer tumors is under development to fabricate surgical phantoms for imaging evaluation and clinical education. Fluorescence tomography results show performance across a range of simulated tumor diameters, depths, and shapes. Ex vivo tissue models with infiltrative inclusions and tissue heterogeneities assess fluorescence quantification and depth recovery accuracy.
    Session 3: Contrast Agent Development and Preclinical Applications
    Author(s): Martin Schnermann, National Cancer Institute (United States)
    Author(s): Brook K. Byrd, Thayer School of Engineering at Dartmouth (United States); Dennis J. Wirth, Dartmouth-Hitchcock Medical Ctr. (United States); Rendall R. Strawbridge, Scott C. Davis, Thayer School of Engineering at Dartmouth (United States)
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    Gadolinium-based MRI plays a central role in the management of glioblastomas. Preoperative MRI-guidance is commonly used to guide resection, with the tumor outline directly projected onto the surgical microscope. However, intraoperative brain shift can cause misregistration between pMRI and the surgical field. To address this challenge, we aim to identify a fluorescent agent which behaves analogously to MRI-Gd uptake in glioma models. Using a whole-body imaging cryo-macrotome, we compare mutual information between Gd-MR and 3D cryo-volumes to screen multiple fluorescent contrast agents simultaneously. Translation of a suitable optical Gd-analog could place this familiar information directly in the surgical field.
    Author(s): Veronica C. Torres, Sassan Hodge, Eunice Chen, Louis Vaickus, Matthew LeBoeuf, Kimberley S. Samkoe, Dartmouth College (United States)
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    A rapid method of tumor margin analysis for Mohs micrographic surgery is presented here. Fluorescence paired-agent imaging (PAI) was applied to mouse models of head and neck squamous cell carcinoma, and positive tumor burden was detected and localized in deep tissue margins up to 1.3 mm thick. Serial sections of pathological stains and binding potential from fluorescence images showed good correlation and confirmed the presence of deep cancer cells.
    Author(s): Thinzar M. Lwin, Univ. of California, San Diego (United States), Dana Farber Cancer Ctr. (United States); Michael A. Turner, Hiroto Nishino, Univ. of California, San Diego (United States); Sophie Hernot, Vrije Univ. Brussel (Belgium); Michael Bouvet, Univ. of California, San Diego (United States)
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    Tumor-specific targeting with fluorescent probes can enhance contrast for identification cancer during surgical resection and visualize otherwise invisible tumor margins. Fluorescent probes derived from nanobodies, the smallest naturally occurring antigen binding molecules, can be used for in-vivo labeling with rapid pharmacokinetics. The present work demonstrates the efficacy of a fluorescent anti-CEA nanobody conjugated to an IR800 dye to target and label patient derived pancreatic cancer xenografts. After intravenous administration, the probe clearly localized to the pancreatic cancer tumors and had a tumor-to-background ratio of 2 or greater by 1 hour. Tumor-specific fluorescent nanobodies are clinically promising molecules for same-day labeling and imaging of tumors.
    Author(s): Matthew Bogyo, Stanford Univ. School of Medicine (United States)
    Author(s): Aditi Sahu, Ucalene Harris, Memorial Sloan-Kettering Cancer Ctr. (United States); Melissa Gill, SUNY Downstate Medical Ctr. (United States); Cecelia Lezcano, Allan Halpern, Anthony Rossi, Klaus Busam, Memorial Sloan-Kettering Cancer Ctr. (United States); Thomas Reiner, Novartis International AG (Switzerland); Ashfaq Marghoob, Manu Jain, Milind Rajadhyaksha, Memorial Sloan-Kettering Cancer Ctr. (United States)
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    Melanoma is the most aggressive skin cancer with the highest associated mortality, early diagnosis ensures high survival rates. Currently, in vivo morphological imaging such as reflectance confocal microscopy (RCM) is associated with high sensitivity but moderate specificity. Addition of molecular imaging using PARPi-FL (PARP1-targeted fluorophore) can improve distinction between malignant/potentially malignant lesions. Towards multimodal imaging in vivo, we first investigated differential PARP1 expression in the spectrum of melanocytic lesions. Higher PARP area positivity and intensity were found in melanoma as compared to benign nevi. Thus, PARPi-FL in association with RCM can potentially improve melanoma diagnosis non-invasively in patients.
    Author(s): Michael A. Turner, Hiroto Nishino, Siamak Amirfakhri, Univ. of California, San Diego (United States), Veterans Affairs Hospital (United States); Sukhwinder Kaur, Kavita Mallya, Univ. of Nebraska Medical Ctr. (United States); Robert Hoffman, Univ. of California, San Diego (United States), AntiCancer, Inc. (United States); Surinder Batra, Univ. of Nebraska Medical Ctr. (United States); Michael Bouvet, Univ. of California, San Diego (United States), Veterans Affairs Hospital (United States)
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    Patient derived pancreatic tumor fragments were subcutaneously implanted in nude mice. After the tumors grew, mice were injected with a fluorescently labeled antibody (MUC4-IR800). MUC4-IR800 selectively imaged the pancreatic tumors over normal tissue. This present study demonstrated the successful targeting of a patient hepatic metastatic pancreatic cancer murine model with MUC4-IR800. This has potential to improve metastatic pancreatic cancer detection. Future studies will be conducted with orthotopic models.
    Author(s): Hiroto Nishino, Michael A. Turner, Siamak Amirfakhri, Hannah M. Hollandsworth, Thinzar M. Lwin, Jun Yamamoto, Univ. of California, San Diego (United States); Bérénice Framery, Françoise Cailler, SurgiMab (France); Bernhard B. Singer, Univ. Duisburg-Essen (Germany); Robert M. Hoffman, AntiCancer, Inc. (United States); Michael Bouvet, Univ. of California, San Diego (United States)
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    Indocyanine green (ICG) labeling has been used to visualize liver tumors and liver segment, but it is difficult to distinguish between a tumor and its adjacent liver segment with conventional use of ICG alone. In the present study, we developed a novel method to discriminate between a liver metastasis and adjacent liver segment in orthotopic mouse models. Imaging on the 700 nm channel visualized the metastatic liver tumor with a tumor-specific near-infrared fluorescent conjugated antibody. The adjacent liver segment labeled with ICG was imaged on the 800 nm channel.
    Author(s): Max J. Witjes, Univ. Medical Ctr. Groningen (Netherlands)
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    The ICON trial concers the study of the diagnostic value of targeted fluorescence imaging with cetuximab-800CW in surgical margin asessment. The tracer was pre operatively administered in a total of 57/70 patients undergoing surgical treatment for oral cancer. The data show a benefit for identifying positve or close margins. The challenges in image analysis and the effect on decision making will be shown.
    Author(s): Connor W. Barth, Lei G. Wang, Antonio Montano, Vidhiben Shah, Oregon Health & Science Univ. (United States); Adam Alani, Oregon State Univ. (United States); Alexander L. Antaris, Johnathan Sorger, Intuitive Surgical, Inc. (United States); Summer L. Gibbs, Oregon Health & Science Univ. (United States)
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    Nerve damage plagues surgical outcomes, significantly affecting post-surgical quality of life. Intraoperative nerve detection is difficult since neuroanatomy is varilable between patients, and nerves are typically protected deep within the tissue. Fluorescence-guided surgery (FGS) offers a potential means for enhanced intraoperative nerve identification and preservation. We have developed the first near infrared (NIR) nerve-specific fluorophores for use during FGS. Lead optimization has yielded water soluble derivatives with excellent safety and pharmacology parameters. Work is underway to plan and execute preclinical toxicity testing to enable first-in-human clincial trials. Additionally, this technology has application to reconstructive surgery, where identification of intact and viable nerve tissue is of utmost importance to obtaining positive outcomes.
    Author(s): Kendra A. Hebert, Thayer School of Engineering at Dartmouth (United States)
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    In this work, we compare the accuracy of radiological axial imaging-guided surgical navigation (computed tomography (CT) and magnetic resonance (MR)) with and without the use of subsurface fluorescence guidance. We tested this by utilizing a validated tissue-simulating phantom model of various tissue types with a randomly placed tumor inclusion and then dissecting the phantoms using different combinations of navigation modalities. Results demonstrated that fluorescence guidance improves the accuracy of radiological imaging-guided surgery with significant improvements in margin consistency and tumor inclusion alignment.
    Session 4: Contrast Agent Clinical Translation
    Author(s): Kimberley S. Samkoe, Dartmouth-Hitchcock Medical Ctr. (United States)
    Author(s): Hak Soo Choi, Massachusetts General Hospital (United States)
    Author(s): Eric R. Henderson, Xiaochun Xu, Dartmouth-Hitchcock Medical Ctr. (United States); Keith D. Paulsen, Dartmouth College (United States); Lesley Jarvis, P. Jack Hoopes, Dartmouth-Hitchcock Medical Ctr. (United States); Eben L. Rosenthal, Stanford Univ. School of Medicine (United States); Brian W. Pogue, Kimberley S. Samkoe, Dartmouth College (United States)
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    The aim of this work was to determine if standard neoadjuvant therapies for human sarcomas reduce expression of the epidermal growth factor receptor (EGFR) and subsequent binding of an EGFR-targeted fluorophore. Documentation of this finding would potentially jeopardize the advancement of fluorescence-guided surgery using EGFR-targeted reporters. We grew five cell lines in mice randomized to receive scaled and validated treatments mimicking standard preoperative sarcoma therapies. Our results show that human sarcoma xenografts subjected to therapy do not demonstrate a change in EGFR expression or in fluorescence, indicating that EGFR-targeted FGS should be feasible under normal therapeutic conditions in the clinic.
    Author(s): Yue Tang, Dartmouth College (United States); Jessica M. Sin, I. Leah Gitajn, Dartmouth-Hitchcock Medical Ctr. (United States); Xu Cao, Xinyue Han, Dartmouth College (United States); Jonathan T. Elliott, Dartmouth-Hitchcock Medical Ctr. (United States); Xiaohan Yu, Dartmouth College (United States); Melanie L. Christian, Eric R. Henderson, Dartmouth-Hitchcock Medical Ctr. (United States); Brian W. Pogue, Shudong Jiang, Dartmouth College (United States)
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    ICG-based dynamic contrast-enhanced fluorescence imaging (DCE-FI) and intraoperative DCE- magnetic resonance imaging (MRI) have been carried out nearly simultaneously in three tibia bone infection cases to investigate the relationship between these two imaging modalities for assessing bone blood perfusion during open orthopedic surgeries. Time-intensity curves in the corresponding regions of interest of two modalities were derived for comparison. The results demonstrated that ICG-based DCE-FI has higher sensitivity to perfusion changes while DCE-MRI provides superior and supplemental depth-related perfusion information. The study of using the depth-related perfusion information to improve the overall analytic modeling of intraoperative DCE-FI is ongoing.
    Author(s): Yao Chen, Cheng Wang, Samuel Streeter, Brian W. Pogue, Kimberley S. Samkoe, Dartmouth College (United States)
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    Optimal discrimination between tumor and normal tissues using epidermal growth factor receptor targeted fluorescence guided surgery (FGS) of head and neck cancer (HNC) is complicated by the presence of target receptor in the normal surrounding tissues. We propose the use of radiomics feature analysis to increase the accuracy and efficiency of tumor tissue discrimination based on machine-learning algorithms. Radiomics analysis demonstrates that sub-image misclassification mainly focused at the margins of the different tissues, and normal tissue with positive EGFR expression. The identification accuracy using radiomics analysis of ABY-029 reaches 94.9% in the preclinical mouse and 84.1% in the human data. PAI demonstrated higher area-under-curve (AUC) of receiver operator characteristic (ROC) curves as compared to ABY-029 alone. The study supports the use of radiomics analysis as an accurate and efficient method for identifying and discriminating tumor and healthy tissue.
    Session 5: Clinically Approved Contrast Agents
    Author(s): Philip Low, Purdue Univ. (United States)
    Author(s): Keith D. Paulsen, Thayer School of Engineering at Dartmouth (United States)
    Author(s): John Y. K. Lee, Penn Medicine (United States)
    Session 6: Clinical Trials
    Clinical Trials I (Invited Paper)
    Author(s): Alexander L. Vahrmeijer, Leiden Univ. Medical Ctr. (Netherlands)
    Clinical trials II (Invited Paper)
    Author(s): Gooitzen M. van Dam, Univ. Medical Ctr. Groningen (Netherlands)
    Clinical trials III (Invited Paper)
    Author(s): Eben L. Rosenthal, Stanford Univ. School of Medicine (United States)
    Clinical trials IV (Invited Paper)
    Author(s): Jonathan T. Elliott, Thayer School of Engineering at Dartmouth (United States)
    Session 7: Industry Perspective
    Industry perspective I (Invited Paper)
    Author(s): Adrian Taruttis, SurgVision GmbH (Germany)
    Industry perspective II (Invited Paper)
    Author(s): Ethan Philip M. LaRochelle, Quel Imaging, LLC (United States)
    Industry perspective III (Invited Paper)
    Author(s): Françoise Cailler, SurgiMab (France)
    Industry perspective IV (Invited Paper)
    Author(s): Hao Nguyen, Univ. of California, San Francisco (United States)
    Conference attendees are invited to attend the BiOS poster session. Come view the posters, enjoy light refreshments, ask questions, and network with colleagues in your field.

    View poster presentation guidelines and set-up instructions at:
    Author(s): Leonid Shmuylovich, Samuel Achilefu, Christine M. O'Brien, Karen Nwosu, Washington Univ. in St. Louis (United States)
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    Near infrared (NIR) in-vivo fluorescence imaging is a powerful modality capable of interrogating biological tissue in real time, at high spatial resolution, without the need for ionizing radiation, and at depths exceeding visible light imaging modalities. Several fluorescence guided surgery (FGS) imaging systems have been developed, but their complexity and cost effectively excludes low resource settings from this technology. To help make NIR FGS available globally, we developed a fluorescence imaging augmented reality Raspberry Pi-based goggle system (FAR-Pi), open-source-hardware-inspired low cost, fully wearable, compact, and battery powered redesign of our previously described goggle-based FGS system.
    Author(s): Cyril Saudan, Ivan Michel Antolović, Harald A. R. Homulle, Pi Imaging Technology SA (Switzerland)
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    We present a 512x512 high resolution single-photon avalanche diode (SPAD) camera with 100 kfps 1-bit imaging rate and 18 ps temporal resolution. The application of this detector to widefield FLIM enables close-to-ideal photon efficiency as well as real-time (above 30 fps) acquisition and processing of FLIM images with a fast and fit-free phasor analysis method. With optimization of the time-gate sequence, the mono-exponential lifetime standard deviation can be reduced by up to 38.7% while keeping the same frame rate. Applying this time-gate sequence, a lifetime relative precision under 10% can be reached while using only 7 gate positions.
    Author(s): Xinyue Han, Dartmouth College (United States); Valentin Demidov, Dartmouth Hitchcock Medical Ctr. (United States), Dartmouth College (United States); Dennis J. Wirth, Dartmouth-Hitchcock Medical Ctr. (United States); Brook K. Byrd, Scott C. Davis, Dartmouth College (United States); I. Leah Gitajn, Jonathan T. Elliott, Dartmouth-Hitchcock Medical Ctr. (United States), Dartmouth College (United States)
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    In this study, we aim to establish a repeatable and accurate fluorescent microsphere-based blood flow measurement approach to validate our earlier developed dynamic contrast-enhanced fluorescence imaging technique for femur periosteal and endosteal blood flow detection. We successfully determined that FMs of four different colors could be accurately detected in controlled phantoms and evaluated their detection accuracy in real blood samples. These experiments allowed to initiate the third phase of this study to validate the blood flow detection capability of DCE-FI technique in a pre-clinical animal model.
    Conference Chair
    Intuitive Surgical, Sàrl (Switzerland)
    Conference Chair
    Oregon Health & Science Univ. (United States)
    Conference Co-Chair
    Thayer School of Engineering at Dartmouth (United States)
    Program Committee
    Univ. of California, San Diego (United States)
    Program Committee
    Modulated Imaging, Inc. (United States)
    Program Committee
    The Institute of Image-Guided Surgery of Strasbourg (France)
    Program Committee
    Fernando Dip
    Consultant (United States)
    Program Committee
    Oregon Health & Science Univ. (United States)
    Program Committee
    National Cancer Institute (United States)
    Program Committee
    Ecole Polytechnique de Montréal (Canada)
    Program Committee
    Univ. of Washington (United States)
    Program Committee
    Helmholtz Zentrum München GmbH (Germany), Technical Univ. of Munich (Germany)
    Program Committee
    Thayer School of Engineering at Dartmouth (United States)
    Program Committee
    Stanford Health Care (United States)
    Program Committee
    Jonathan M. Sorger
    Intuitive Surgical, Inc. (United States)
    Program Committee
    Illinois Institute of Technology (United States)
    Program Committee
    Leiden Univ. Medical Ctr. (Netherlands)
    Program Committee
    Univ. of Michigan (United States)
    Program Committee
    Ontario Cancer Institute (Canada)
    Additional Information