Label-free reflectance hyperspectral imaging for tumor margin assessment: a pilot study on surgical specimens of cancer patients

Abstract. A label-free, hyperspectral imaging (HSI) approach has been proposed for tumor margin assessment. HSI data, i.e., hypercube (x,y,λ), consist of a series of high-resolution images of the same field of view that are acquired at different wavelengths. Every pixel on an HSI image has an optical spectrum. In this pilot clinical study, a pipeline of a machine-learning-based quantification method for HSI data was implemented and evaluated in patient specimens. Spectral features from HSI data were used for the classification of cancer and normal tissue. Surgical tissue specimens were collected from 16 human patients who underwent head and neck (H&N) cancer surgery. HSI, autofluorescence images, and fluorescence images with 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) and proflavine were acquired from each specimen. Digitized histologic slides were examined by an H&N pathologist. The HSI and classification method were able to distinguish between cancer and normal tissue from the oral cavity with an average accuracy of 90%±8%, sensitivity of 89%±9%, and specificity of 91%±6%. For tissue specimens from the thyroid, the method achieved an average accuracy of 94%±6%, sensitivity of 94%±6%, and specificity of 95%±6%. HSI outperformed autofluorescence imaging or fluorescence imaging with vital dye (2-NBDG or proflavine). This study demonstrated the feasibility of label-free, HSI for tumor margin assessment in surgical tissue specimens of H&N cancer patients. Further development of the HSI technology is warranted for its application in image-guided surgery.

[1]  Zhen Luo,et al.  Widefield Optical Imaging of Changes in Uptake of Glucose and Tissue Extracellular pH in Head and Neck Cancer , 2014, Cancer Prevention Research.

[2]  M. Soloway,et al.  Intraoperative T staging in radical retropubic prostatectomy: is it reliable? , 2001, Urology.

[3]  D. Mohr Current Clinical Practice , 1987 .

[4]  Umberto Veronesi,et al.  Global cancer surgery: delivering safe, affordable, and timely cancer surgery. , 2015, The Lancet. Oncology.

[5]  Cecelia E Schmalbach,et al.  A ratiometric threshold for determining presence of cancer during fluorescence‐guided surgery , 2015, Journal of surgical oncology.

[6]  M. Varvares,et al.  Surgical margin determination in head and neck oncology: Current clinical practice. The results of an International American Head and Neck Society Member Survey , 2005, Head & neck.

[7]  V. Tuchin Tissue Optics: Light Scattering Methods and Instruments for Medical Diagnosis , 2000 .

[8]  Guolan Lu,et al.  Hyperspectral imaging of neoplastic progression in a mouse model of oral carcinogenesis , 2016, SPIE Medical Imaging.

[9]  I Ihse,et al.  Influence of Resection Margins on Survival for Patients With Pancreatic Cancer Treated by Adjuvant Chemoradiation and/or Chemotherapy in the ESPAC-1 Randomized Controlled Trial , 2001, Annals of surgery.

[10]  John V. Frangioni,et al.  The Value of Intraoperative Near-Infrared Fluorescence Imaging Based on Enhanced Permeability and Retention of Indocyanine Green: Feasibility and False-Positives in Ovarian Cancer , 2015, PloS one.

[11]  D R Walker,et al.  Fate of patients with residual tumour at the bronchial resection margin. , 1994, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[12]  H. Lynch,et al.  Psychologic Aspects of Cancer Genetic Testing: A Research Update for Clinicians , 1997 .

[13]  Guolan Lu,et al.  Medical hyperspectral imaging: a review , 2014, Journal of biomedical optics.

[14]  Alexander F. H. Goetz,et al.  Three decades of hyperspectral remote sensing of the Earth: a personal view. , 2009 .

[15]  Dongsheng Wang,et al.  A Minimum Spanning Forest-Based Method for Noninvasive Cancer Detection With Hyperspectral Imaging , 2016, IEEE Transactions on Biomedical Engineering.

[16]  Michael Hünerbein,et al.  An Experimental Study to Evaluate the Fluobeam 800 Imaging System for Fluorescence-Guided Lymphatic Imaging and Sentinel Node Biopsy , 2013, Surgical innovation.

[17]  Costas Balas,et al.  Multi/Hyper-Spectral Imaging , 2011 .

[18]  Judith Sandbank,et al.  A device for real-time, intraoperative margin assessment in breast-conservation surgery. , 2007, American journal of surgery.

[19]  Job Kievit,et al.  Intraoperative near‐infrared fluorescence imaging of parathyroid adenomas with use of low‐dose methylene blue , 2014, Head & neck.

[20]  Andreas Kirschbaum,et al.  Frequency of local recurrence following segmentectomy of stage IA non-small cell lung cancer is influenced by segment localisation and width of resection margins--implications for patient selection for segmentectomy. , 2007, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[21]  R. Gandour-Edwards,et al.  Accuracy of intraoperative frozen section diagnosis in head and neck surgery: Experience at a university medical center , 1993, Head & neck.

[22]  Eben L. Rosenthal,et al.  Putting Numbers to Fluorescent Guided Surgery , 2013, Molecular Imaging and Biology.

[23]  Miriam Scadeng,et al.  Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival , 2010, Proceedings of the National Academy of Sciences.

[24]  Dongsheng Wang,et al.  Spectral-spatial classification for noninvasive cancer detection using hyperspectral imaging , 2014, Journal of biomedical optics.

[25]  D. Ferris,et al.  Multimodal Hyperspectral Imaging for the Noninvasive Diagnosis of Cervical Neoplasia , 2001, Journal of lower genital tract disease.

[26]  Rebecca Richards-Kortum,et al.  Vital-dye-enhanced multimodal imaging of neoplastic progression in a mouse model of oral carcinogenesis , 2013, Journal of biomedical optics.

[27]  G. Zonios,et al.  Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo. , 1999, Applied optics.

[28]  J. Frangioni,et al.  An Operational Near-Infrared Fluorescence Imaging System Prototype for Large Animal Surgery , 2003, Technology in cancer research & treatment.

[29]  R. Tsien,et al.  Fluorescence-guided surgery with live molecular navigation — a new cutting edge , 2013, Nature Reviews Cancer.

[30]  Guolan Lu,et al.  Spectral-spatial classification using tensor modeling for cancer detection with hyperspectral imaging , 2014, Medical Imaging.

[31]  Tin Kam Ho,et al.  The Random Subspace Method for Constructing Decision Forests , 1998, IEEE Trans. Pattern Anal. Mach. Intell..

[32]  Guolan Lu,et al.  Framework for hyperspectral image processing and quantification for cancer detection during animal tumor surgery , 2015, Journal of biomedical optics.

[33]  Shuming Nie,et al.  Nanotechnology applications in surgical oncology. , 2010, Annual review of medicine.

[34]  Zhuo Georgia Chen,et al.  Biodistribution study of nanoparticle encapsulated photodynamic therapy drugs using multispectral imaging , 2013, Medical Imaging.

[35]  Alexandros D. Polydorides,et al.  Discrimination of Benign and Neoplastic Mucosa with a High-Resolution Microendoscope (HRME) in Head and Neck Cancer , 2012, Annals of Surgical Oncology.

[36]  Luma V. Halig,et al.  Hyperspectral imaging and quantitative analysis for prostate cancer detection. , 2012, Journal of biomedical optics.

[37]  A. Vahrmeijer,et al.  Clinical trial of combined radio‐ and fluorescence‐guided sentinel lymph node biopsy in breast cancer , 2013, The British journal of surgery.

[38]  Vijayashree S. Bhattar,et al.  Accuracy of In Vivo Multimodal Optical Imaging for Detection of Oral Neoplasia , 2012, Cancer Prevention Research.

[39]  Alexander L. Vahrmeijer,et al.  Optical Image-guided Surgery—Where Do We Stand? , 2010, Molecular Imaging and Biology.

[40]  Joshua S Richman,et al.  Safety and Tumor Specificity of Cetuximab-IRDye800 for Surgical Navigation in Head and Neck Cancer , 2015, Clinical Cancer Research.

[41]  Dongsheng Wang,et al.  Hyperspectral imaging for cancer surgical margin delineation: registration of hyperspectral and histological images , 2014, Medical Imaging.

[42]  Merrick I Ross,et al.  Positive surgical margins and ipsilateral breast tumor recurrence predict disease‐specific survival after breast‐conserving therapy , 2003, Cancer.

[43]  Xu Wang,et al.  Tumor margin assessment of surgical tissue specimen of cancer patients using label-free hyperspectral imaging , 2017, BiOS.

[44]  Walter J. Riker A Review of J , 2010 .