The incidence of skin cancer has been on the rise in recent years and as in most cancers, early diagnosis and thorough treatment (i.e., complete resection) are the keys to gain a favorable prognosis. Current diagnostic methods for skin cancers rely on physical examination in conjunction with skin biopsy, methods that have limited accuracy in early diagnosis. Hence there is considerable interest in developing a non-invasive diagnostic and screening tool, which can accurately recognize skin cancer in its early stages. Such a tool would not only detect early signs of malignancy, it will also reduce unnecessary diagnostic surgical procedures, facilitate complete excision of skin cancers by accurately delineating the skin cancer margins prior to and during the surgery, and allow treated patients to be monitored for recurrence. In this proposal we present a method that combines Optical Coherence Tomography (OCT), an imaging technique that visualizes tissue microstructure, with Raman spectroscopy, a spectroscopy technique that provides a tissue biochemical map in a single portable instrument for the effective detection of skin lesions. The real-time non-invasive nature of this combined technique can enable a """"""""see and treat"""""""" protocol that would decrease the number of return clinic visits and patient anxiety as the long waits for histopathology diagnoses would be eliminated. Thus, the technology has the potential to increase access to underserved populations where follow-up to screening may not be available. The technology poses no known risks to the patient, and therefore could be a safe alternative to current screening methods.

Public Health Relevance

The incidence of skin cancer has been on the rise in recent years and as in most cancers, early diagnosis and thorough treatment (i.e., complete resection) are the keys to gain a favorable prognosis. Current diagnostic methods for skin cancers rely on physical examinations in conjunction with skin biopsy, methods that have limited accuracy for early diagnosis. Hence there is considerable interest in developing a non- invasive diagnostic and screening tool, which can accurately recognize skin cancer in its early stages. Such a tool would not only detect early signs of malignancy, it could also reduce unnecessary diagnostic surgical procedures, facilitate complete excision of skin cancers by accurately delineating the skin cancer margins prior to and during the surgery, and allow treated patients to be monitored for recurrence. Initial reports have identified the practical limitations of non-invasive optical devices using either imaging or spectroscopy to evaluate the diverse clinical appearance of normal skin, benign lesions, and malignancy. In this proposal, we describe the design of a device that is specifically geared towards thorough non-invasive analysis of both the underlying microstructure and biochemical composition of the skin. The challenge presented by the variability of skin and skin cancers present the ideal test organ and pathology for the proposed multi-modal device. This R21 proposal seeks to validate the hypothesis that a device that combines morphological imaging with optical coherence tomography (OCT) and biochemical evaluation with Raman spectroscopy (RS) increases the diagnostic information available to the physician and could improve the diagnostic performance of each technique alone. The feasibility phase of this project is designed towards the development of a combined RSOCT system and the validation of such a combined imaging method for the detection of skin cancers.
The specific aims are designed towards quantifiable and achievable milestones that will demonstrate the potential of such an approach towards cancer diagnosis in general and skin cancer detection in particular.
Specific Aim #1 : Develop and test a benchtop combined RS-OCT system: A benchtop version of the combined system will be developed on the platform of a Fourier Domain-OCT spectral radar system consisting of two sources but a single detector and sample arm. The performance of both OCT and RS will each be compared with benchmark values of existing in vivo systems.
Specific Aim #2 : Develop an RSOCT handheld probe for in vivo application: In order to test the utility of such a multi-modal system in vivo, a handheld probe will be developed and the entire system made portable to allow for flexibility of measurements from hard to reach lesion sites. The performance of both OCT and RS will each be compared with benchmark values of the benchtop system.
Specific Aim #3 : Conduct a pilot study on 30 patients with suspected basal cell carcinomas (BCCs) to demonstrate the utility RS-OCT: A small pilot study will evaluate the validity of the combined device in clinical practice where lesions suspected of BCCs will be assessed with RS alone, OCT alone, and combined RS-OCT. The ability of RS to discriminate between normal benign and malignant lesions will be compared with OCT guided RS.
The specific aims described above will demonstrate the potential of RSOCT for the diagnosis and possible screening of skin cancers. The proposed work will have a significant impact on health care by providing the potential for complete disease management with a single detection tool. This would result in improved patient care and cost-effectiveness. With the success of this technique, RSOCT can be applied to other organ sites such as the breast, prostate and ovary as well as other diseases thus impacting a broader field in medicine.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA133477-02
Application #
7623181
Study Section
Special Emphasis Panel (ZRG1-SBIB-J (90))
Program Officer
Nordstrom, Robert J
Project Start
2008-06-01
Project End
2011-05-31
Budget Start
2009-06-01
Budget End
2011-05-31
Support Year
2
Fiscal Year
2009
Total Cost
$131,197
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Surgery
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Patil, Chetan A; Kirshnamoorthi, Harish; Ellis, Darrel L et al. (2011) A clinical instrument for combined raman spectroscopy-optical coherence tomography of skin cancers. Lasers Surg Med 43:143-51
Patil, Chetan A; Kalkman, Jeroen; Faber, Dirk J et al. (2011) Integrated system for combined Raman spectroscopy-spectral domain optical coherence tomography. J Biomed Opt 16:011007
Patil, Chetan A; Bosschaart, Nienke; Keller, Matthew D et al. (2008) Combined Raman spectroscopy and optical coherence tomography device for tissue characterization. Opt Lett 33:1135-7