The goal of this proposal is to develop and clinically test a real-time optical imaging modality based on confocal reflectance microscopy, with enhancement of nuclear-to-dermal contrast using acetic acid and crossed polarization, to intra-operatively examine basal cell cancers to guide Mohs micrographic surgery. Basal cell cancers (BCCs) are among the fastest growing cancers (>1.2 million new USA cases/year); because they occur most frequently on older people and in high risk anatomical sites (near or on the eyes, mouth, nose, ears), precise microsurgery is necessary with minimum damage to the surrounding normal tissue. Mohs surgery is time-consuming (one to several hours) and tedious because several (2-20) excisions must be made, and frozen histology sections carefully prepared and examined for each. Realtime confocal reflectance imaging may make Mohs surgery significantly more efficient by enabling direct intraoperative examination for cancer nests and cancer-to-normal tissue margins on the patient; this will reduce the number of excisions and avoid frozen histology. Both the patient and surgeon will save several hours per procedure in the operating room. Although proposed for Mohs surgery of BCCs, this real-time intra-operative imaging modality may, in fact, prove useful in a variety of other microsurgical settings. The research will be a collaboration between Northeastern University (Boston) and Memorial Sloan-Kettering Cancer Center (New York). This project will be implemented in two phases: (1) an ex vivo study using freshly excised skin specimens from Mohs surgeries, to (a) design a confocal microscope that mimics the Mohs surgeon's examination of frozen histology: rapid low-resolution examination of BCC nests in wide fields-of-view followed by high-resolution inspection of nuclear morphology in small fields-of-view, and develop (b) optimum contrast enhancement methods using topical acetic acid (induces condensation of chromatin that increases light backscatter from nuclei) and optical crossed polarization (suppresses light backscatter from the surrounding normal dermis), (c) optimum hemostasis methods using either topical aluminum chloride or electrocautery, (d) image understanding by detailed correlation of images to histology; and (2) an intraoperative study, involving (a) design of a specialized confocal articulated telescope, to enable (b) imaging of BCCs on patients during surgery, to evaluate the optimum contrast enhancement and hemostasis methods, correlate confocal images to histology and quantitatively determine diagnostic/screening accuracy. The overall goal is to develop an optical (confocal) intra-operative imaging instrument for Mohs and other modes of microsurgery.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB002715-02
Application #
6801944
Study Section
Special Emphasis Panel (ZRG1-SRB (53))
Program Officer
Haller, John W
Project Start
2003-09-20
Project End
2007-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
2
Fiscal Year
2004
Total Cost
$307,224
Indirect Cost
Name
Northeastern University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
001423631
City
Boston
State
MA
Country
United States
Zip Code
02115
Jain, Manu; Rajadhyaksha, Milind; Nehal, Kishwer (2017) Implementation of fluorescence confocal mosaicking microscopy by ""early adopter"" Mohs surgeons and dermatologists: recent progress. J Biomed Opt 22:24002
Mu, Euphemia W; Lewin, Jesse M; Stevenson, Mary L et al. (2016) Use of Digitally Stained Multimodal Confocal Mosaic Images to Screen for Nonmelanoma Skin Cancer. JAMA Dermatol 152:1335-1341
Longo, Caterina; Ragazzi, Moira; Rajadhyaksha, Milind et al. (2016) In Vivo and Ex Vivo Confocal Microscopy for Dermatologic and Mohs Surgeons. Dermatol Clin 34:497-504
Mancebo, Silvia E; Cordova, Miguel; Myskowski, Patricia L et al. (2016) Reflectance confocal microscopy features of mycosis fungoides and Sézary syndrome: correlation with histopathologic and T-cell receptor rearrangement studies. J Cutan Pathol 43:505-15
Gareau, Daniel S; Jeon, Hana; Nehal, Kishwer S et al. (2012) Rapid screening of cancer margins in tissue with multimodal confocal microscopy. J Surg Res 178:533-8
Bini, Jason; Spain, James; Nehal, Kishwer et al. (2011) Confocal mosaicing microscopy of human skin ex vivo: spectral analysis for digital staining to simulate histology-like appearance. J Biomed Opt 16:076008
Scope, A; Mahmood, U; Gareau, D S et al. (2010) In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins. Br J Dermatol 163:1218-28
Karen, J K; Gareau, D S; Dusza, S W et al. (2009) Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy. Br J Dermatol 160:1242-50
Gareau, Daniel S; Karen, Julie K; Dusza, Stephen W et al. (2009) Sensitivity and specificity for detecting basal cell carcinomas in Mohs excisions with confocal fluorescence mosaicing microscopy. J Biomed Opt 14:034012
Rajadhyaksha, Milind (2009) Confocal microscopy of skin cancers: translational advances toward clinical utility. Conf Proc IEEE Eng Med Biol Soc 2009:3231-3

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