Constantinos Pitris

Handbook of Biomedical Optics

Preface David A. Boas, Constantinos Pitris, Nimmi Ramanujam I. Background Geometrical Optics Ting-Chung Poon Diffraction Optics Colin Sheppard Optics: Basic Physics Raghuveer Parthasarathy Light Sources, Detectors, and Irradiation Guidelines Carlo Amadeo Alonzo, Malte C. Gather, Jeon Woong Kang, Giuliano Scarcelli, Seok-Hyun Yun Tissue Optical Properties Alexey N. Bashkatov, Elina A. Genina, Valery V. Tuchin II. Spectroscopy and Spectral Imaging Reflectance Spectroscopy Sasha McGee, Jelena Mirkovic, Michael Feld Multi/Hyper-Spectral Imaging Costas Balas, Christos Pappas, George Epitropou Light Scattering Spectroscopy Le Qiu, Irving Itzkan, Lev T. Perelman Broadband Diffuse Optical Spectroscopic Imaging Bruce J. Tromberg, Albert E. Cerussi, So-Hyun Chung, Wendy Tanamai, Amanda Durkin Near Infrared Diffuse Correlation Spectroscopy for Assessment of Tissue Blood Flow Guoqiang Yu, Turgut Durduran, Chao Zhou, Ran Cheng, Arjun G. Yodh Fluorescence Spectroscopy Darren Roblyer, Richard A. Schwarz, Rebecca Richards-Kortum Raman, SERS and FTIR Spectroscopy Andrew J. Berger III. Tomographic Imaging Optical Coherence Tomography: Introduction and Theory Yu Chen, Evgenia Bousie, Constantinos Pitris, James G. Fujimoto Functional Optical Coherence Tomography in Preclinical Models Melissa C. Skala, Yuankai K. Tao, Anjul M. Davis, Joseph A. Izatt Optical Coherence Tomography: Clinical Applications Brian D. Goldberg, Melissa J. Suter, Guillermo J. Tearney, Brett E. Bouma Forward Models of Light Transport in Biological Tissue Andreas H. Hielscher, Hyun Keol Kim, Alexander K. Klose Inverse Models of Light Transport Simon Arridge, Martin Schweiger, John C. Schotland Laminar Optical Tomography Sean A. Burgess, Elizabeth M. C. Hillman Diffuse Optical Tomography using Continuous Wave and Frequency Domain Imaging Systems Subhadra Srinivasan, Scott C. Davis, Colin M. Carpenter Diffuse Optical Tomography: Time Domain Juliette Selb, Adam Gibson Photoacoustic Tomography and Ultrasound-Modulated Optical Tomography Changhui Li, Chulhong Kim, Lihong V. Wang Optical and Photoacoustic Molecular Tomography of Small Animals Vasilis Ntziachristos IV. Microscopic Imaging Assesing Microscopic Structural Features Using Fourier-Domain Low Coherence Interferometry Robert N. Graf, Francisco E. Robles, Adam Wax Phase Imaging Microscopy: Beyond Darkfield, Phase and Differential Interference Contrast Microscopy Chrysanthe Preza, Sharon V. King, Nicoleta M. Dragomir, Carol J. Cogswell Confocal Microscopy William C. Warger II, Charles A. DiMarzio, Milind Rajadhyaksha Fluorescence Microscopy with Structured Excitation Illumination Alexander Brunner, Gerrit Best, Roman Amberger, Paul Lemmer, Thomas Ach, Stefan Dithmar, Rainer Heintzmann, Christoph Cremer Nonlinear Optical Microscopy for Biology and Medicine Daekeun Kim, Heejin Choi, Jae Won Cha, Peter T. C. So Fluorescence Lifetime Imaging Microscopy, Endoscopy and Tomography James McGinty, Clifford Talbot, Dylan Owen, David Grant, Sunil Kumar, Neil Galletly, Bebhinn Treanor, Gordon Kennedy, Peter M. P. Lanigan, Ian Munro, Daniel S. Elson, Anthony Magee, Dan Davis, Gordon Stamp, Mark Neil, Christopher Dunsby, Paul W. M. French Application of Digital Holographic Microscopy in Biomedicine Christian Depeursinge, Pierre Marquet, Nicolas Pavillon Polarized Light Imaging of Biological Tissues Steven L. Jacques V. Molecular Probe Development Molecular Reporter Systems for Optical Imaging Walter J. Akers, Samuel Achilefu Nanoparticles for Targeted Therapeutics and Diagnostics Timothy Larson, Kort Travis, Pratixa Joshi, Konstantin Sokolov Plasmonic Nanoprobes for Biomolecular Diagnostics of DNA Targets Tuan Vo-Dinh, Hsin-Neng Wang VI. Phototherapy Photodynamic Therapy Jarod C. Finlay, Keith Cengel, Theresa M. Busch, Timothy C. Zhu Low Level Laser and Light Therapy Ying-Ying Huang, Aaron C-H Chen, Michael R. Hamblin

Endoscopic optical coherence tomography

Optical coherence tomography (OCT) is a recently developed optical imaging technique that uses low coherence interferometry to perform high resolution, cross-sectional imaging in biological systems. While in vitro studies have been performed to demonstrate the feasibility of performing optical biopsy in human tissues, key technologies must be developed to extend this technique to in vivo internal organ systems. These advances include improvements in image acquisition speed, and the development of an OCT compatible catheter-endoscope. A fast scanning OCT system has recently been constructed. This system employs a high power (200 mW) chromium doped forsterite laser as the low coherence source and a piezoelectric fiber stretcher to induce reference arm optical path length delay. The fast scanning system acquires OCT images with an acquisition rate of four images per second, an axial resolution of 15 micrometers, and a signal to noise ratio of 112 dB. When incorporated with the recently constructed OCT compatible catheter-endoscope, this system is capable of obtaining high resolution endoscopic diagnostic images of tissue microstructure in vivo.

An Approach for Preoperative Planning and Performance of MR-guided Interventions Demonstrated With a Manual Manipulator in a 1.5T MRI Scanner

PurposeThe aim of this work was to develop and test a general methodology for the planning and performance of robot-assisted, MR-guided interventions. This methodology also includes the employment of software tools with appropriately tailored routines to effectively exploit the capabilities of MRI and address the relevant spatial limitations.MethodsThe described methodology consists of: (1) patient-customized feasibility study that focuses on the geometric limitations imposed by the gantry, the robotic hardware, and interventional tools, as well as the patient; (2) stereotactic preoperative planning for initial positioning of the manipulator and alignment of its end-effector with a selected target; and (3) real-time, intraoperative tool tracking and monitoring of the actual intervention execution. Testing was performed inside a standard 1.5T MRI scanner in which the MR-compatible manipulator is deployed to provide the required access.ResultsA volunteer imaging study demonstrates the application of the feasibility stage. A phantom study on needle targeting is also presented, demonstrating the applicability and effectiveness of the proposed preoperative and intraoperative stages of the methodology. For this purpose, a manually actuated, MR-compatible robotic manipulation system was used to accurately acquire a prescribed target through alternative approaching paths.ConclusionsThe methodology presented and experimentally examined allows the effective performance of MR-guided interventions. It is suitable for, but not restricted to, needle-targeting applications assisted by a robotic manipulation system, which can be deployed inside a cylindrical scanner to provide the required access to the patient facilitating real-time guidance and monitoring.

OCT imaging of osteoarthritic cartilage: structure, polarization sensitivity, and clinical feasibility

This work demonstrates the feasibility of OCT for identifying early osteoarthritic pathology. In addition to structural abnormalities, changes in collagen fiber organization, an indicator of very early osteoarthritis, were assessed with a polarization sensitive OCT system. A portable, real time, modular OCT system, suitable for both laboratory and clinical settings, has been developed. Preliminary in vivo imaging results obtained during partial knee replacement surgery are discussed.

Axial resolution improvement by modulated deconvolution in Fourier domain optical coherence tomography.

Abstract. A novel technique for axial resolution improvement in Fourier domain optical coherence tomography (FDOCT) is presented. The technique is based on the deconvolution of modulated optical coherence tomography signals. In FDOCT, the real part of the Fourier transform of the interferogram is modulated by a frequency which depends on the position of the interferogram in k space. A slight numerical k shift results in a different modulation frequency. By adding two shifted signals, beating can appear in the A-scan. When the amount of shifting is appropriately selected, deconvolution of the resulting depth profile, using suitable modulated kernels, yields a narrower resolution width. A resolution improvement by a factor of ∼7 can be achieved without the need for a broader bandwidth light source.

Subcellular optical coherence tomography with a Kerr lens mode-locked Ti:Al2O3 laser

The longitudinal resolution of optical coherence tomography (OCT) is currently limited by the optical bandwidth of the light source, typically a superluminescent diodes, to approximately 10-15 micrometers . This resolution is insufficient to identify individual cells or to assess subcellular structures such as nuclei or mitotic figures. The ability to perform subcellular imaging with OCT could greatly enhance the detection of early neoplastic changes and improve early cancer diagnosis or the imaging of developing biological morphology. Higher resolution OCT would also improve specificity of diagnosis for several ocular diseases, such as glaucoma, which require precise, detailed imaging and measurement of retinal nerve fiber layer thickness. State of the art Kerr-lens mode-locked Ti:Al2O3 lasers using double chirped dispersion compensating mirrors can generate pulse durations of < 7 fs and bandwidths of 200 nm or more at 800 nm center wavelength. These pulse durations and bandwidths can be used for OCT, resulting in longitudinal resolutions of less than 2 micrometers . The use of such broad bandwidths also enables the extraction of localized, wavelength dependent absorption and scattering tissue characteristic by detecting the full interferometric fringe signa and using Fourier signal processing. In this paper we demonstrate an ultra-high-subcellular level resolution, spectroscopic OCT system based on a mode-locked Ti:Al2O3 laser. In vivo imaging of development biology specimens as well as preliminary in vivo spectroscopic OCT result are demonstrated.

Infrared Fluorescence-Based Cancer Screening Capsule for the Small Intestine

Infrared fluorescence endoscopy (IRFE), in conjunction with an infrared fluorescent-labelling contrast agent, is a well known technique used for efficient early-stage cancer detection. In this paper we present a cost-effective ( <;

Consideration of geometric constraints regarding MR-compatible interventional robotic devices

500) screening capsule prototype, which is able to detect infrared (IR) fluorescence emitted by indocyanine green (ICG) fluorophore dye. Rather than image, the capsule works as a high-sensitivity fluorometer that records fluorescence levels throughout the small intestine. The presented mixed-signal system has a small size, consumes very little power ( ≈6.3 mA) and does not require an external belt and hardware for data collection. By determining fluorescence levels in the intestine, rather than collecting images, we avoid the need for labour intensive video analysis. The whole system is contained within a compact ingestible capsule, that is sized so as to come into close contact with the intestine walls during peristalsis. Ex-vivo experiments, on ICG-impregnated swine intestine, have shown that the prototype system is able to detect low concentrations of ICG in the nanomolar and micromolar region, which is required to detect early cancer in the small intestine.

Classification of Raman Spectra using Support Vector Machines

The design of MR-compatible robotic systems is a challenging task given the magnetic nature of the scanning environment but also the limitations imposed by the geometric characteristics of the imaging modality. The latter issue is often referred to as geometric MR-compatibility and was treated through image-based analyses as part of the design of a new interventional robotic device. Examinations on geometric MR-compatibility focused on ways to quantify the available space inside a cylindrical scanner, considerations regarding the effective field-of-view of an MR scanner, representations of the attainable anatomical region as defined for needle targeting applications, and computer simulations using three-dimensional digital models representing the patient. Geometric considerations are relevant both to the design of an MR-compatible robotic device but also its operation, as for example when using patient-specific data for intervention planning purposes. A preoperative planning procedure developed for the new robotic device will also be described.

Design of MR-compatible robotic devices: magnetic and geometric compatibility aspects

The classification of Raman Spectra is useful in identification and diagnosis applications. We have obtained Raman Spectra from bacterial samples using three different species of bacteria. Before any form of classification can be carried out on the Raman Spectra it is important that some form of normalization is used. This is due to the nature of the readings obtained by the acquisition equipment. The method used for normalization greatly affects the accuracy of the results. We have carried out experiments using Support Vector Machines and the correlation kernel. Our observations have led us to the hypothesis that the correlation kernel is “self-normalizing” and gives satisfactory results without the need of any other normalization technique.