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

Baowei Fei, Guolan Lu, Xu Wang, Hongzheng Zhang, James V Little, Mihir R Patel, Christopher C Griffith, Mark W El-Diery, Amy Y Chen, Baowei Fei, Guolan Lu, Xu Wang, Hongzheng Zhang, James V Little, Mihir R Patel, Christopher C Griffith, Mark W El-Diery, Amy Y Chen

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.

Keywords: cancer detection; head and neck cancer; hyperspectral imaging; image classification; image quantification; image-guided surgery; label-free; tumor margin assessment.

(2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Figures

Fig. 1
Fig. 1
Study design for the HSI of surgical specimens of H&N cancer patients.
Fig. 2
Fig. 2
Flowchart of the machine-learning-based quantification pipeline for hyperspectral images.
Fig. 3
Fig. 3
Surgical specimens of tumor, normal tissue, and tumor with adjacent normal tissue from a tongue cancer patient. Left: tissue and corresponding histological slides. Right: 2-NBDG and proflavine fluorescence images for each tissue.
Fig. 4
Fig. 4
Tumor margin detection of surgical specimens from an H&N cancer patient. After hyperspectral image acquisitions, the tissue was processed histologically, and tumor margins were outlined on the pathology image (bottom right) by a pathologist (J.V.L.), which was used to validate the results of the classification (top-right). The average spectral curves are shown at the bottom left for each type of tissue, i.e., tumor, normal, and tumor with adjacent normal tissue.

References

    1. Sullivan R., et al. , “Global cancer surgery: delivering safe, affordable, and timely cancer surgery,” Lancet Oncol. 16(11), 1193–1224 (2015).10.1016/S1470-2045(15)00223-5
    1. Singhal S., Nie S. M., Wang M. D., “Nanotechnology applications in surgical oncology,” Annu. Rev. Med. 61, 359–373 (2010).10.1146/annurev.med.60.052907.094936
    1. De Grand A. M., Frangioni J. V., “An operational near-infrared fluorescence imaging system prototype for large animal surgery,” Technol. Cancer Res. Treat. 2(6), 553–562 (2003).10.1177/153303460300200607
    1. Vaidya A., et al. , “Intraoperative T staging in radical retropubic prostatectomy: is it reliable?” Urology 57(5), 949–954 (2001).10.1016/S0090-4295(01)00904-9
    1. Nguyen Q. T., Tsien R. Y., “Fluorescence-guided surgery with live molecular navigation—a new cutting edge,” Nat. Rev. Cancer 13(9), 653–662 (2013).NRCAC410.1038/nrc3566
    1. Gebitekin C., et al. , “Fate of patients with residual tumour at the bronchial resection margin,” Eur. J. Cardio-Thorac. Surg. 8(7), 339–342 (1994).EJCDBR10.1016/1010-7940(94)90025-6
    1. Meric F., et al. , “Positive surgical margins and ipsilateral breast tumor recurrence predict disease-specific survival after breast-conserving therapy,” Cancer 97(4), 926–933 (2003).CANCAR10.1002/(ISSN)1097-0142
    1. Sienel W., 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,” Eur. J. Cardio-Thorac. Surg. 31(3), 522–528 (2007).EJCDBR10.1016/j.ejcts.2006.12.018
    1. Karni T., et al. , “A device for real-time, intraoperative margin assessment in breast-conservation surgery,” Am. J. Surg. 194(4), 467–473 (2007).10.1016/j.amjsurg.2007.06.013
    1. Neoptolemos J. P., 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,” Ann. Surg. 234(6), 758–768 (2001).10.1097/00000658-200112000-00007
    1. Keereweer S., et al. , “Optical image-guided surgery—where do we stand?” Mol. Imaging Biol. 13(2), 199–207 (2011).10.1007/s11307-010-0373-2
    1. Nguyen Q. T., et al. , “Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival,” Proc. Natl. Acad. Sci. U. S. A. 107(9), 4317–4322 (2010).10.1073/pnas.0910261107
    1. Meier J. D., Oliver D. A., Varvares M. A., “Surgical margin determination in head and neck oncology: current clinical practice. The results of an International American Head and Neck Society Member Survey,” Head Neck 27(11), 952–958 (2005).10.1002/(ISSN)1097-0347
    1. Gandour-Edwards R. F., Donald P. J., Wiese D. A., “Accuracy of intraoperative frozen section diagnosis in head and neck surgery: experience at a university medical center,” Head Neck 15(1), 33–38 (1993).10.1002/(ISSN)1097-0347
    1. Warram J. M., et al. , “A ratiometric threshold for determining presence of cancer during fluorescence-guided surgery,” J. Surg. Oncol. 112(1), 2–8 (2015).JSONAU10.1002/jso.23946
    1. Rosenthal E. L., et al. , “Safety and tumor specificity of Cetuximab-IRDye800 for surgical navigation in head and neck cancer,” Clin. Cancer Res. 21(16), 3658–3666 (2015).10.1158/1078-0432.CCR-14-3284
    1. Hirche C., et al. , “An experimental study to evaluate the Fluobeam 800 imaging system for fluorescence-guided lymphatic imaging and sentinel node biopsy,” Surg. Innov. 20(5), 516–523 (2013).10.1177/1553350612468962
    1. van der Vorst J. R., et al. , “Intraoperative near-infrared fluorescence imaging of parathyroid adenomas with use of low-dose methylene blue,” Head Neck 36, 853–858 (2014).10.1002/hed.v36.6
    1. Schaafsma B. E., et al. , “Clinical trial of combined radio- and fluorescence-guided sentinel lymph node biopsy in breast cancer,” Br. J. Surg. 100(8), 1037–1044 (2013).10.1002/bjs.9159
    1. Tummers Q., 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,” PLoS One 10(6), e0129766 (2015).POLNCL10.1371/journal.pone.0129766
    1. Rosenthal E. L., Zinn K. R., “Putting numbers to fluorescent guided surgery,” Mol. Imaging Biol. 15(6), 647–648 (2013).10.1007/s11307-013-0662-7
    1. Goetz A. F. H., “Three decades of hyperspectral remote sensing of the Earth: a personal view,” Remote Sens. Environ. 113(Suppl. 1), S5–S16 (2009).RSEEA710.1016/j.rse.2007.12.014
    1. Lu G., Fei B., “Medical hyperspectral imaging: a review,” J. Biomed. Opt. 19(1), 010901 (2014).JBOPFO10.1117/1.JBO.19.1.010901
    1. Zonios G., et al. , “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Appl. Opt. 38(31), 6628–6637 (1999).APOPAI10.1364/AO.38.006628
    1. Wang L. V., Wu H.-I., “Introduction,” in Biomedical Optics, pp. 1–15, John Wiley and Sons, Inc., Hoboken, New Jersey: (2009).
    1. Costas B., Christos P., George E., “Multi/hyper-spectral imaging,” in Handbook of Biomedical Optics, pp. 131–164, CRC Press, Boca Raton, Florida: (2011).
    1. Tuchin V. V., Tuchin V., Tissue Optics: Light Scattering Methods and Instruments for Medical Diagnosis, SPIE Press, Bellingham, Washington: (2007).
    1. Ferris D. G., et al. , “Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia,” J. Lower Genital Tract Dis. 5(2), 65–72 (2001).10.1046/j.1526-0976.2001.005002065.x
    1. Pierce M. C., et al. , “Accuracy of in vivo multimodal optical imaging for detection of oral neoplasia,” Cancer Prev. Res. 5(6), 801–809 (2012).10.1158/1940-6207.CAPR-11-0555
    1. Akbari H., et al. , “Hyperspectral imaging and quantitative analysis for prostate cancer detection,” J. Biomed. Opt. 17(7), 076005 (2012).JBOPFO10.1117/1.JBO.17.7.076005
    1. Lu G., et al. , “Spectral-spatial classification for noninvasive cancer detection using hyperspectral imaging,” J. Biomed. Opt. 19(10), 106004 (2014).JBOPFO10.1117/1.JBO.19.10.106004
    1. Pike R., et al. , “A minimum spanning forest-based method for noninvasive cancer detection with hyperspectral imaging,” IEEE Trans. Biomed. Eng. 63(3), 653–663 (2016).IEBEAX10.1109/TBME.2015.2468578
    1. Lu G., et al. , “Hyperspectral imaging of neoplastic progression in a mouse model of oral carcinogenesis,” Proc. SPIE 9788, 978812 (2016).PSISDG10.1117/12.2216553
    1. Lu G., et al. , “Framework for hyperspectral image processing and quantification for cancer detection during animal tumor surgery,” J. Biomed. Opt. 20(12), 126012 (2015).JBOPFO10.1117/1.JBO.20.12.126012
    1. Fei B., et al. , “Tumor margin assessment of surgical tissue specimen of cancer patients using label-free hyperspectral imaging,” Proc. SPIE 10054, 100540E (2017).PSISDG10.1117/12.2249803
    1. Lu G., et al. , “Spectral-spatial classification using tensor modeling for cancer detection with hyperspectral imaging,” Proc. SPIE 9034, 903413 (2014).PSISDG10.1117/12.2043796
    1. Lu G., et al. , “Hyperspectral imaging for cancer surgical margin delineation: registration of hyperspectral and histological images,” Proc. SPIE 9036, 90360S (2014).PSISDG10.1117/12.2043805
    1. Halig L. V., et al. , “Biodistribution study of nanoparticle encapsulated photodynamic therapy drugs using multispectral imaging,” Proc. SPIE 8672, 867218 (2013).PSISDG10.1117/12.2006492
    1. Hellebust A., et al. , “Vital-dye-enhanced multimodal imaging of neoplastic progression in a mouse model of oral carcinogenesis,” J. Biomed. Opt. 18(12), 126017 (2013).JBOPFO10.1117/1.JBO.18.12.126017
    1. Ho T. K., “The random subspace method for constructing decision forests,” IEEE Trans. Pattern Anal. Mach. Intell. 20(8), 832–844 (1998).ITPIDJ10.1109/34.709601
    1. Luo Z., et al. , “Widefield optical imaging of changes in uptake of glucose and tissue extracellular pH in head and neck cancer,” Cancer Prev. Res. 7(10), 1035–1044 (2014).10.1158/1940-6207.CAPR-14-0097
    1. Vila P., et al. , “Discrimination of normal and neoplastic mucosa with a high-resolution microendoscope (HRME) in head and neck cancer,” Ann. Surg. Oncol. 19(11), 3534–3539 (2012).10.1245/s10434-012-2351-1
    1. Lu G., et al. , “Hyperspectral imaging of neoplastic progression in a mouse model of oral carcinogenesis,” Proc. SPIE 9788, 978812 (2016).10.1117/12.2216553

Source: PubMed

3
Subskrybuj