Fiber Optic RS-OCT probe Advisors: Dr. Patil Dr. Mahadevan-Jansen John Acevedo Kelly Thomas Chris Miller

Epithelial cancer types Epithelium – cells that line hollow organs and make up the outer surface of the body (skin) Basal Cell Carcinoma: 1 million new cases are diagnosed each year in the U.S. The basal cells line the deepest layer of the epidermis Squamous Cell Carcinoma: More than 700,000 new cases are diagnosed every year. Chronic exposure to sunlight is the cause of most squamous cell carcinoma and basal cell carcinoma. Optical imaging such as Optical Coherence Tomography (OCT) can noninvasively serve as a diagnostic and monitoring tool of epithelial cancers, and can evaluate therapeutic responses http://www.skincancer.org/Basal-Cell-Carcinoma/ http://www.skincancer.org/basal-cell-carcinoma.html Almost all basal cell carcinomas occur on parts of the body excessively exposed to the sun — especially the face, ears, neck, scalp, shoulders, and back. On rare occasions, however, tumors develop on unexposed areas. In a few cases, contact with arsenic, exposure to radiation, open sores that resist healing, chronic inflammatory skin conditions, and complications of burns, scars, infections, vaccinations, or even tattoos are contributing factors.

RS and OCT are complimentary Raman Spectroscopy Strengths Biochemical Specificity Limitations No spatial Information Susceptible to sampling error Optical Coherence Tomography Strengths Micron-scale structural resolution Real-time imaging speeds Limitations Insensitive to tissue biochemical composition

Procedure Turn on OCT component Acquire tomographical map Detect area of interest Turn off OCT component Turn on RS component Acquire biochemical composition of area of interest Turn off RS component

Dr. Patil’s RS-OCT probe Problem statement and take out schematic How it works…

Reason for fiber optic RS-OCT probe Improve detection and diagnosis of cancer Hand held device will facilitate the use RS-OCT probe A fiber optic probe will decrease the size of the current probe Potential endoscopic use, non-invasive Cost effective Current skin probe~$4000 Our design ~$700 Product Price Fiber Optics $100 Platinum Alloy coil Focusing Lens $200 Polymer block Electrodes All Products $700

Miniaturizing sample arm of current RS-OCT probe Problem Statement Miniaturizing sample arm of current RS-OCT probe 5” 8” Therefore, additional diagnostic tools are sought to aid the endoscopist with the identification of pre-cancerous changes so that appropriate treatment can be targeted at an early stage. Ideally these tools would be used in vivo, providing non-invasive, reproducible, real time information on the disease state of the tissue. Such tools could also lead to improved targeting of excisional biopsy, or resection margins, and minimise the number of normal samples collected, thus reducing the burden on busy histopathology departments. Raman spectroscopy is an inelastic scattering technique which provides a biochemical fingerprint of a tissue sample under interrogation. Requirements of Raman probes for in vivo endoscopic applications include biocompatibility, miniaturisation to fit down the biopsy channel, well defined depth of field, low backgroun signal and high collection efficiency to enable routine application with spectral acquisition periods of a few seconds. Due to the cost of optical components the probes should be robust enough to withstand sterilisation procedures

Design Criteria Meet existing RS-OCT probe performance and functionality Decrease size of probe to < 1 cm in diameter Reach a scan rate of RS and OCT to 4 frames per second Reach a scan range of at least 3 mm depth OCT sensitivity of -95 dB RS collection efficiency of 10 seconds Spot size for OCT should be < 50 microns Determined by depth of focus Beat existing probe performance and beat what current 2 probes do independently

RS and OCT existing designs Raman Spectroscopy Current Probe Design Direct light source surrounded by 7 detection fibers Optical Coherence Tomography Current Probe Design Forward facing Bundle-based MEMS mirror BP filter Notch filters 785 nm Spectrograph 7 300 mm fibers CCD Psample = 80 mW tacq < 5 sec

Challenges Quality compensation from combining RS and OCT RS requires narrow band of light source and multi- mode fibers for optimum specificity OCT requires broad band of light source and single- mode fibers for optimum specificity Develop scanning technique for the OCT probe in such a small area Spatial registration of RS and OCT data sets Obtaining material for tests Generalize. Getting materials.

Current Design Forward facing Electrostatic scanning probe for OCT component Located in the center Fiber-optic array for RS component 270 um 300 um 125 um inner diam

Electrostatic OCT component 125 µm diameter single mode fiber illuminates and detects elastic scattering in the area of interest Fiber placed in 250 µm diameter platinum alloy coil Placed in the center of 400 µm diameter lumen of a triple lumen catheter Two peripheral lumens contain 270 µm diameter wires One serves as electrode and the other serves as ground leads Driven by DC power supply, <5 µA, 1-3 kV 1310 nm light source - broadband Diameter of glass was 125 um. Single mode fiber is 9 um. Munce, N.R. and Yang, V.X.D. et al. (2008).

Electrostatic OCT component Electrostatic driven cantilever to create a compact, wide angle, rapid scanning forward viewing probe Cantilever is neutral and is attracted to electrode Cantilever touches electrode and acquires the same potential Charge dissipates through the polymer from the cantilever and repels from electrode Cantilever touches ground and becomes neutral again Process restarts enacting a scanning motion

Fiber Optic Array RS Component Multi-mode fibers (200 µm)set on either side of the OCT scanning fiber One narrow band (785 nm) light sources on one side Light source Figure out how to describe it Collection OCT Highest concentration of collection

Future work Build prototype Test prototype Evaluate effectiveness Improve design by adding more collection fibers Modifying SolidWorks 3D design Prepare poster presentation

Current Progress Voltage source and optical fibers have been obtained Dissipative Polymer has been ordered Platinum coil or suitable replacement is needed Find a suitable replacement for dissipative polymer if polymer is not effective Capacitor, resistor, inductor

References Patil, C.A. (2009). Development combined raman spectroscopy-optical coherence tomograpgy for the detection of skin cancer. Disertation submitted to faculty of Graduate school of Vanderbilt University. Munce, N.R. and Yang, V.X.D. et al.(2008). Electrostatic forward-viewing scanning probe for doppler optical coherence tomography using a dissipative polymer catheter. Optical letters, 33, 7, 657-60.

Questions?

Specific Aims Combine RS-OCT techniques into a fiber optic device to replace sample arm of current probe Maximize Raman detection time efficiency Integrate multi-mode and single-mode fibers into probe without compromising RS-OCT functionality

Raman Spectroscopy Inelastic scattering (Stokes and Anti-Stokes) Occurs 1 in 10 million compared to elastic Frequency of light scattered from a molecule dependent on structural characteristics of molecular bonds Able to determine malignant from non-malignant tissue Gives no spatial information All sorts of epithelial diseases Next slide: existing raman probes. CURRENTLY THE BEST WAY IS WITH FIBER OPTIC PROBES..DIRECT LIGHT (picture on experimental methods slide). Problem: no info about space n0 n1 Raman Shift (cm-1) = f ( ) – f ( )

Optical Coherence Tomography (OCT) Sensitivity to microstructural features of disease Measures tissue reflectivity as function of depth Detects elastic scattering Ability to image over transverse areas of tissue of greater than 5mm Micron scale resolution (>25µm) Real-time speed Current oct design