Vanderbilt University
Grant Proposal
Fiber Optic RS-OCT Probe
Proposed by: John Acevedo
Kelly Thomas
Chris Miller
Proposal date: October 28, 2010
Abstract
Reducing invasive procedures is important in cancer diagnoses since it reduces risks while
providing accurate results. Cancer detection at an early stage is crucial since treatment at this stage has a
higher rate of effectiveness. Optical Coherence Tomography (OCT) is a technique that utilizes optical
interferometry to rapidly visualize the micro-structural irregularities associated with the disease. To
compensate for the drawbacks of OCT, Raman Spectroscopy (RS) can perform direct multi-class
identification of cancers, pre-cancers, non-malignant lesions and normal tissue with accuracy. By
combining RS and OCT techniques, cancer detection will be less invasive and more efficient. Currently,
the smallest probe combination can only detect skin cancer. However reducing the size of the probe will
enable this device to be used to diagnose cancer in internal tissues. By reducing the size of the sample arm
to a fiber optic level, the probe will be able to be used endoscopically. The team is made up of three
Biomedical Engineers that attend Vanderbilt University. Each member has experience with the various
aspects that the project calls for. They will be working with Dr. Mahadevan-Jansen and Chetan Patil,
whom have developed the novel approach of combining RS and OCT. The design of the miniaturized
RS-OCT probe will be finalized by January and testing will begin in February.
Objectives
1. Miniaturize RS-OCT probe for potential endoscopic use in disease diagnosis
2. Develop novel approach for fiber optic RS-OCT
3. Increase sensitivity and specificity of probe
Introduction
Non-invasive or minimally-invasive cancer detection is an important tool in diagnosing diseased
tissues and cancer. The advantages of imaging instead of biopsy are that no surgical procedure is needed
for diagnoses, results will be attained much quicker and tissue will not need to be removed from the
patient. Optical coherence tomography (OCT) and Raman spectroscopy (RS) are minimally-invasive
techniques used to detect disease based on the analysis of tissue microstructure and biochemical
composition. To improve cancer detection OCT and RS can be used simultaneously so that the
advantages of both techniques can be used (Vo-Dinh, 2003).
OCT is a technique that utilizes optical interferometry to rapidly visualize the micro-structural
irregularities associated with the disease. This technique is advantageous because it has a micrometerresolution that produces three-dimensional images of internal tissues. This is possible since OCT uses
light instead of sound to achieve resolutions on the scale of 3-20 µm. Images are obtained by low
coherence infrared light being directed onto a tissue sample, which allows the intensity of the reflections
to be measured and compared to a reference beam. Penetration depths are on the order of 2-3 mm. Thus
OCT is preferable to confocal microscopy, since it provides deeper tissue penetration. This relaying of
morphological information is an important aspect in tissue diagnosis since it is useful for staging disease
and guiding treatment. However OCT cannot identify disease type or separate non-malignant regions with
malignant regions (Munce, 2008).
To compensate for the drawbacks of OCT, RS can perform direct multi-class identification of
cancers, pre-cancers, non-malignant lesions and normal tissue with accuracy. RS is a spectroscopic
technique used to study variational, rotational and other low frequency modes. RS is the measurement of
the wavelength and intensity of inelastically scattered light from molecules. This technique involves a
laser beam to be focused on a tissue sample. The molecules within the sample scatter the light. The elastic
scattering, which has the same frequency as the incident laser, is filtered out and the remaining scattered
light is collected. The remaining light is not at the incident frequency since energy was lost due to a
change in vibrational, rotational or electronic energy of a molecule. Once this data is sent to a computer,
the computer shows how much the frequency of the scattered light was shifted from the incident light and
therefore identifies the particular elements and structures that are present in the sample. OCT is a faster
procedure than RS because RS can take up to thirty seconds to acquire data. However RS results in
quantitative evaluation of the sample’s chemical composition which is related to the tissue pathology for
diagnosis (Lyon et al., 1998).
The sequential acquisition of RS and OCT along a common optical axis allow both the tissue
microstructure and biochemical composition to be viewed simultaneously. This enables the diagnosis of
the biochemical composition of tissues at specific locations. Currently the combination of RS and OCT
can only be used to diagnose skin cancer due to its large size (Patil et Al, 2008). By miniaturizing the
sample arm of the RS-OCT probe the probe will be used endoscopically to perform measurements in
internal tissues such as those in the gastrointestinal tract or respiratory system to detect disease such as
colon and lung cancer.
History and Context
An RS-OCT probe has already been developed by Dr. Mahadevan-Jansen of Vanderbilt
University but is too bulky to be used endoscopically. Research has been done to gain a further
understanding of the interworkings of Raman spectroscopy and Optical Coherence Tomography and the
drawbacks of combining them. The main drawback of combining Raman Spectroscopy and Optical
Coherence Tomography is that Raman spectroscopy limits OCT with respect to time to acquire data and
uses monochromatic light whereas OCT uses a broadband light source. The detection arms and the light
sources must be prevented from over-lapping to avoid interference of detection from the other part of the
probe. Also, OCT uses a beam splitter so the probe must avoid interference of light from Raman
Spectroscopy.
Team
We will be working under the direction of Dr. Anita Mahadevan-Jansen and Chetan Patil. Dr.
Mahadevan is an expert in laser spectroscopy to identify brain tumors. Chetan Patil is a research associate
in Biomedical Engineering who has published a dissertation based on novel approach to combine RS and
OCT techniques. Our advisors will guide us towards completion of this project to miniaturize the sample
arm of the RS-OCT probe.
The team members include Chris Miller, John Acevedo and Kelly Thomas. We are all senior
biomedical engineering students. We are all working together on this project because we share a common
interest of using advanced techniques for disease tissue diagnosis. Chris has taken a BioMEMS class and
BioMEMS laboratory offered at Vanderbilt that has increased his interest in methods of spectroscopy to
count and sort individual cells. Chris has also had experience working with the University of Pittsburgh
Medical Center in studying and imaging cells in the Cardiovascular Research Lab. John has taken
BioMEMs and Nanobiotech classes at Vanderbilt that has enabled him to gain an insight on the field of
miniaturizing medical devices. He wishes to put this knowledge into practice. As a member of the
Vanderbilt NROTC program, John shows great organizational, time management and leadership skills.
Kelly has volunteered for University of Pittsburgh Medical Center to gain experience with analysing
images from endoscopies and colonoscopies. She also worked with Roche Diagnostics as their Product
Support Intern which enabled her to develop organizational skills such as project timeline management to
ensure that tasks are complete in time.
Since John shows strong leadership skills from experience in NROTC, he was chosen to be the
team leader and point of contact. Other than this, each individual on the team does not have a defined
role. The team will collaborate on every issue. Each member will work together to gain better
understanding of the topic. The team will work to design the probe, design the web site, make the final
poster and make the final oral report. Each member must participate in every milestone so that every
individual will have a complete understanding of the project and so that synergy can be used to develop
ideas to create and improve the device design.
Work Plan and Outcomes
The educational outcomes we hope to achieve are to understand the use of laser detection of
molecules and location. We must gain knowledge on how to develop and follow a design process that will
allow the miniaturizing of the RS-OCT probe that will accurately detect irregularities in tissues. We will
gain experience with project timeline management since written/oral reports are required, along with a
final presentation in April. By working together to miniaturize the RS-OCT device, we will gain
experience in working as a team member.
The ideal commercial outcomes of this project are to develop a device that is appealing to doctors
and beneficial to patients in comparison to current diagnosis techniques. The device must be easy to use
and minimally or non-invasive for the patient. This device must be created to have the capability to be
used in hospitals nationwide for disease cancer detection.
If this cancer detection device is successful, it will be easier and less invasive than current
techniques. The project will succeed based on prior experience of Dr. Mahadevan-Jansen and Chetan Patil
This would lead patenting this design, gaining FDA approval and then manufacturing these devices on a
large scale so doctors can use these devices in hospitals everywhere.
*Gantt chart attached
Evaluation and Sustainability
The measures for success of a miniaturized RS-OCT probe is as follows: decrease size of probe to
less than 1 cm, reach a scan rate of RS and OCT to 4 frames per second, reach a scan range of at least 3
mm depth and reach an OCT sensitivity of -95 dB and RS collection efficiency of 10 seconds.
Appendix 1
Product
Price
Fiber Optics
$100
Scan Beam
$500
Focusing Lens
$200
Probe Housing
$500
Phantom
$100
All Products
$1,400
Appendix 2
Resumes attached
References
Lyon, Andrew L., Christine D. Keating, Audrey P. Fox, Bonnie E. Baker, Lin He, Sheila R, Nicewarner,
Shawn P. Mulvaney and Michael J. Natan. Raman Spectroscopy. The Pennylvania State
University. PA, 1998.
Mahadevan-Jansen et al. USPTO Patent Full-Text and Image Database. United States Patent, 2009.
Munce, Nigel R, Adrian Mariampillai, Beau A. Standish, Mihaela Pop, Kevan J. Anderson, George Y.
Liu, Tim Luk, Brian K. Courtney, Graham A. Wright, I. Alex Vitkin and Victor X. D. Yang.
Electrostatic forward-viewing scanning probe for Doppler optical coherence tomography using a
dissipative polymer catheter. Vol. 33. Optics Letters, 2008.
Patil, Chetan A., Nienke Bosschaart, Matthew D. Keller, Ton G. van Leeuwen, and Anita MahadevanJansen. Combined Raman spectroscopy and optical coherence tomography device for tissue
characterization. Vol. 33. Optics Letters, 2008.
Vo-Dinh Tuan. Biomedical Photonics Handbook. Raman Spectroscopy: From Benchtop to Bedside. DRD
Press, 2003.