Intraoperative Delineation of Tumor-resection Margins

Brain tumors

A critical need for neurosurgeons operating on infiltrative glial neoplasms is the ability to distinguish between normal brain and glial tumor. Moreover, difficulties in differentiating tumor from radiation injury complicate treatment of post-radiation therapy (RT) patients with tumor recurrence.  There are no effective tools for real-time assessment of tumor resection margins or irradiated tissue during neurosurgical interventions. Our lab is developing fluorescence lifetime techniques that have potential to analyze the brain tissue molecular makeup and to resolve distinct types of brain tumors from the surrounding normal or radiation necrosis during surgical interventions.

Wide-field Fluorescence lifetime imaging in patients

FLIM image of (left) Normal Brain (cortex) and (right) tumor (high grade glioma) infiltrated in brain cortex.

FLIM image of (left) Normal Brain (cortex) and (right) tumor (high grade glioma) infiltrated in brain cortex.

Head and Neck tumors

Head and Neck Squamous Cell Carcinoma (HNSCC) is the 6th most common cancer worldwide. Despite advances in surgical and nonsurgical treatment, overall survival for these tumors has not improved significantly. ~600,000 people will be diagnosed this year with HNSCC of the oral cavity, oropharynx, larynx, hypopharynx, and nasopharynx. Only 40-50% of these patients will survive for 5 years. Challenges in improving these statistics are multiple and include tumor recurrence at the local and regional level, distant metastasis, and second tumors.

The fluorescence lifetime techniques developed in our laboratory target noninvasive and possibly earlier and more accurate diagnosis and detection of the extent of the neoplastic area in the pre- and intra-operative setting. This could guide more restricted surgical procedures and less aggressive nonsurgical treatment, thus improving survival and reducing morbidity.

Photo of the operating room compatible cart that accommodated the TRFS and FLIM systems used for patients studies. (b) Image-bundle probe for FLIM integrating a single fiber illumination channel, a 0.5 mm diameter image-bundle (10,000 fibers), and a sterilizable spacer that allows for positioning of probe in the oral cavity as depicted in (d). Bifurcated fiberoptic probe for excitation and collection of fluorescence in the TRFS system. Inset: Distal end configuration. (e) Example of time-resolved fluorescence emission spectra from of an advance stage tumor.

Photo of the operating room compatible cart that accommodated the TRFS and FLIM systems used for patients studies. (b) Image-bundle probe for FLIM integrating a single fiber illumination channel, a 0.5 mm diameter image-bundle (10,000 fibers), and a sterilizable spacer that allows for positioning of probe in the oral cavity as depicted in (d). Bifurcated fiberoptic probe for excitation and collection of fluorescence in the TRFS system. Inset: Distal end configuration. (e) Example of time-resolved fluorescence emission spectra from of an advance stage tumor.

FLIM imaging of oral carcinoma in patients

FLIM – in-vivo head and neck cancer patients. Representative intensity images of (a) normal and (b) tumor, and (e) intensity histogram versus the corresponding lifetime images (c) normal, (d) tumor, and (f) lifetime histograms. Results for 460 nm emission band (NADH fluorescence)

FLIM – in-vivo imaging in head and neck cancer patients. Representative intensity images of (a) normal and (b) tumor, and (e) intensity histogram versus the corresponding lifetime images (c) normal, (d) tumor, and (f) lifetime histograms. Results for 460 nm emission band (NADH fluorescence)

Breast tumors

We investigate the prospects of using time-resolved fluorescence spectroscopy (TRFS) to assess the breast cancer margins, after breast conserving surgery (BCS). Current studies demonstrate that fluorescence lifetime presents the prospect to discriminate between fibrotic tissue (FT), adipose tissue (AT) and invasive ductal carcinoma (IDC), while fluorescent intensity based measurements fail to provide any significant differentiation between FT and IDC.

Related Publications

L. Marcu, J. A. Jo, P. V. Butte, W.H. Yong, B. K. Pikul, K. L. Black, R. C. Thompson, Fluorescence lifetime spectroscopy of glioblastoma multiforme, Photochemistry and Photobiology, 80(1): 98-103, 2004. (Link) (PDF)

W. H. Yong, P. V. Butte, Brian K. Pikul, J. A. Jo, K. L. Black, MD, L. Marcu, Distinction of Brain tissue, low grade and high grade glioma with time-resolved fluorescence spectroscopy, Frontiers in Biosciences, 11:1255-63, 2006. (Link) (PDF)

 

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