Detection limits of intraoperative near infrared imaging for tumor resection.
OBJECTIVE
The application of fluorescent molecular imaging to surgical oncology is a developing field with the potential to reduce morbidity and mortality. However, the detection thresholds and other requirements for successful intervention remain poorly understood. Here we modeled and experimentally validated depth and size of detection of tumor deposits, trade-offs in coverage and resolution of areas of interest, and required pharmacokinetics of probes based on differing levels of tumor target presentation.


METHODS
Three orthotopic tumor models were imaged by widefield epifluorescence and confocal microscopes, and the experimental results were compared with pharmacokinetic models and light scattering simulations to determine detection thresholds.


RESULTS
Widefield epifluorescence imaging can provide sufficient contrast to visualize tumor margins and detect tumor deposits 3-5  mm deep based on labeled monoclonal antibodies at low objective magnification. At higher magnification, surface tumor deposits at cellular resolution are detectable at TBR ratios achieved with highly expressed antigens.


CONCLUSIONS
A widefield illumination system with the capability for macroscopic surveying and microscopic imaging provides the greatest utility for varying surgical goals. These results have implications for system and agent designs, which ultimately should aid complete resection in most surgical beds and provide real-time feedback to obtain clean margins.
Thurber
Greg M
GM
Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Figueiredo
Jose-Luiz
JL
Weissleder
Ralph
R
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000601:surgery; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000601:surgery; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000601:surgery; D003198:Computer Simulation; D003952:Diagnostic Imaging; D005260:Female; D006801:Humans; D057230:Limit of Detection; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000601:surgery; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008962:Models, Theoretical; D016343:Monitoring, Intraoperative; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000601:surgery; D041623:Tomography, Optical Coherence; D014407:Tumor Cells, Cultured