Novel automated non invasive detection of ocular surface squamous neoplasia using multispectral autofluorescence imaging.

PURPOSE Diagnosing Ocular surface squamous neoplasia (OSSN) using newly designed multispectral imaging technique. METHODS Eighteen patients with histopathological diagnosis of Ocular Surface Squamous Neoplasia (OSSN) were recruited. Their previously collected biopsy specimens of OSSN were reprocessed without staining to obtain auto fluorescence multispectral microscopy images. This technique involved a custom-built spectral imaging system with 38 spectral channels. Inter and intra-patient frameworks were deployed to automatically detect and delineate OSSN using machine learning methods. Different machine learning methods were evaluated, with K nearest neighbor and Support Vector Machine chosen as preferred classifiers for intra- and inter-patient frameworks, respectively. The performance of the technique was evaluated against a pathological assessment. RESULTS Quantitative analysis of the spectral images provided a strong multispectral signature of a relative difference between neoplastic and normal tissue both within each patient (at p < 0.0005) and between patients (at p < 0.001). Our fully automated diagnostic method based on machine learning produces maps of the relatively well circumscribed neoplastic-non neoplastic interface. Such maps can be rapidly generated in quasi-real time and used for intraoperative assessment. Generally, OSSN could be detected using multispectral analysis in all patients investigated here. The cancer margins detected by multispectral analysis were in close and reasonable agreement with the margins observed in the H&E sections in intra- and inter-patient classification, respectively. CONCLUSIONS This study shows the feasibility of using multispectral auto-florescence imaging to detect and find the boundary of human OSSN. Fully automated analysis of multispectral images based on machine learning methods provides a promising diagnostic tool for OSSN which can be translated to future clinical applications.

[1]  Edward P. Markowski,et al.  Conditions for the Effectiveness of a Preliminary Test of Variance , 1990 .

[2]  Marti J. Anderson,et al.  A new method for non-parametric multivariate analysis of variance in ecology , 2001 .

[3]  A. Visser,et al.  Fluorescence lifetime imaging microscopy in life sciences , 2010 .

[4]  Ruth Etzioni,et al.  Early detection: The case for early detection , 2003, Nature Reviews Cancer.

[5]  Ewa M. Goldys,et al.  Statistically strong label-free quantitative identification of native fluorophores in a biological sample , 2017, Scientific Reports.

[6]  D. Char,et al.  20 MHz high frequency ultrasound assessment of scleral and intraocular conjunctival squamous cell carcinoma , 2002, The British journal of ophthalmology.

[7]  H. Weiss,et al.  Clinical Presentation of Ocular Surface Squamous Neoplasia in Kenya. , 2015, JAMA ophthalmology.

[8]  K. T. Moesta,et al.  Protoporphyrin IX occurs naturally in colorectal cancers and their metastases. , 2001, Cancer research.

[9]  I. Schwab,et al.  Pterygium and associated ocular surface squamous neoplasia. , 2009, Archives of ophthalmology.

[10]  J. A. Gomes,et al.  Predictive index to differentiate invasive squamous cell carcinoma from preinvasive ocular surface lesions by impression cytology , 2008, British Journal of Ophthalmology.

[11]  Enrico Gratton,et al.  Metabolic trajectory of cellular differentiation in small intestine by Phasor Fluorescence Lifetime Microscopy of NADH , 2012, Scientific Reports.

[12]  John R. Anderson,et al.  MACHINE LEARNING An Artificial Intelligence Approach , 2009 .

[13]  D. Sarraf,et al.  Clinical applications of fundus autofluorescence in retinal disease , 2016, International Journal of Retina and Vitreous.

[14]  N. Ramanujam,et al.  In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia , 2007, Proceedings of the National Academy of Sciences.

[15]  Juan C Cassano,et al.  Functional hyperspectral imaging captures subtle details of cell metabolism in olfactory neurosphere cells, disease-specific models of neurodegenerative disorders. , 2016, Biochimica et biophysica acta.

[16]  Mohamed-Jalal Fadili,et al.  Wavelets, Ridgelets, and Curvelets for Poisson Noise Removal , 2008, IEEE Transactions on Image Processing.

[17]  B. Wilson,et al.  In Vivo Fluorescence Spectroscopy and Imaging for Oncological Applications , 1998, Photochemistry and photobiology.

[18]  Wei-Yin Loh,et al.  Classification and regression trees , 2011, WIREs Data Mining Knowl. Discov..

[19]  H. Weiss,et al.  Topical fluorouracil after surgery for ocular surface squamous neoplasia in Kenya: a randomised, double-blind, placebo-controlled trial , 2016, The Lancet. Global health.

[20]  Michael Kalloniatis,et al.  Multispectral Pattern Recognition Reveals a Diversity of Clinical Signs in Intermediate Age-Related Macular Degeneration. , 2018, Investigative ophthalmology & visual science.

[21]  A. Maćkiewicz,et al.  Principal Components Analysis (PCA) , 1993 .

[22]  Long Wang,et al.  Registration of images with affine geometric distortion based on Maximally Stable Extremal Regions and phase congruency , 2015, Image Vis. Comput..

[23]  M. Baker,et al.  Multiphoton fluorescence lifetime imaging microscopy reveals free-to-bound NADH ratio changes associated with metabolic inhibition. , 2014, Journal of biomedical optics.

[24]  Martin E. Gosnell,et al.  Fluorescence quenching of free and bound NADH in HeLa cells determined by hyperspectral imaging and unmixing of cell autofluorescence. , 2017, Biomedical optics express.

[25]  Sarah E Bohndiek,et al.  Fluorescence hyperspectral imaging (fHSI) using a spectrally resolved detector array , 2017, Journal of biophotonics.

[26]  Sander R. Dubovy,et al.  Predictors of ocular surface squamous neoplasia recurrence after excisional surgery. , 2012, Ophthalmology.

[27]  Martin E. Gosnell,et al.  Quantitative non-invasive cell characterisation and discrimination based on multispectral autofluorescence features , 2016, Scientific Reports.

[28]  H. Weiss,et al.  Diagnosing Ocular Surface Squamous Neoplasia in East Africa , 2014, Ophthalmology.

[29]  Preeya K Gupta,et al.  Anterior Segment Imaging in Ocular Surface Squamous Neoplasia , 2016, Journal of ophthalmology.

[30]  K. Colby,et al.  Topical Medical Therapies for Ocular Surface Tumors , 2006, Seminars in ophthalmology.

[31]  J. Lowe,et al.  Corneal intraepithelial neoplasia: in vivo confocal microscopic study with histopathologic correlation. , 2011, American journal of ophthalmology.

[32]  Faith G. Davis,et al.  Factors associated with survival in patients with meningioma , 1998 .

[33]  Karen Drukker,et al.  Mammographic quantitative image analysis and biologic image composition for breast lesion characterization and classification. , 2014, Medical physics.

[34]  W. Pych A Fast Algorithm for Cosmic‐Ray Removal from Single Images , 2003, astro-ph/0311290.

[35]  En-Bing Lin,et al.  Image compression and denoising via nonseparable wavelet approximation , 2003 .

[36]  A. Balestrazzi,et al.  Corneal invasion of ocular surface squamous neoplasia after clear corneal phacoemulsification: in vivo confocal microscopy analysis. , 2008, Journal of cataract and refractive surgery.

[37]  Alina A. von Davier,et al.  Cross-Validation , 2014 .

[38]  J M Buatti,et al.  Benign meningiomas: primary treatment selection affects survival. , 1997, International journal of radiation oncology, biology, physics.

[39]  W. Wee,et al.  Conjunctival granuloma with necrosis associated with exposed suture in upper double lid masquerading as ocular surface squamous neoplasia: a case report , 2017, BMC Ophthalmology.

[40]  H. Weiss,et al.  Epidemiology of ocular surface squamous neoplasia in Africa , 2013, Tropical medicine & international health : TM & IH.

[41]  N. Tananuvat,et al.  Role of Impression Cytology in Diagnosis of Ocular Surface Neoplasia , 2008, Cornea.

[42]  Benjamin Schmid,et al.  Hyperspectral light sheet microscopy , 2015, Nature Communications.

[43]  M. Macsai,et al.  Ocular surface squamous neoplasia: a review. , 2003, Cornea.

[44]  Amita Pal,et al.  Generalized quadratic discriminant analysis , 2015, Pattern Recognit..

[45]  P. Zoroquiaín,et al.  High frequency of squamous intraepithelial neoplasia in pterygium related to low ultraviolet light exposure , 2016, Saudi journal of ophthalmology : official journal of the Saudi Ophthalmological Society.

[46]  M. Ringnér,et al.  Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks , 2001, Nature Medicine.

[47]  G. Latifi,et al.  Changes in in vivo confocal microscopic findings of ocular surface squamous neoplasia during treatment with topical interferon alfa-2b. , 2018, The ocular surface.

[48]  Mengyan Wang,et al.  Rapid, Label-Free, and Highly Sensitive Detection of Cervical Cancer With Fluorescence Lifetime Imaging Microscopy , 2016, IEEE Journal of Selected Topics in Quantum Electronics.

[49]  Jayashree Kalpathy-Cramer,et al.  Machine Learning Has Arrived! , 2017, Ophthalmology.

[50]  L. Hirst,et al.  Ocular surface squamous neoplasia. , 1995, Survey of ophthalmology.

[51]  A. Galor,et al.  Subconjunctival/perilesional recombinant interferon α2b for ocular surface squamous neoplasia: a 10-year review. , 2010, Ophthalmology.

[52]  Shu-Sen Xie,et al.  Autofluorescence excitation-emission matrices for diagnosis of colonic cancer. , 2005, World journal of gastroenterology.

[53]  José Manuel Amigo,et al.  Pre-processing of hyperspectral images. Essential steps before image analysis , 2012 .

[54]  J. Hanley,et al.  The meaning and use of the area under a receiver operating characteristic (ROC) curve. , 1982, Radiology.

[55]  F. Liu,et al.  The clinical value of in vivo confocal microscopy for diagnosis of ocular surface squamous neoplasia , 2012, Eye.

[56]  Sarah Jane Delany k-Nearest Neighbour Classifiers , 2007 .

[57]  Y. Shildkrot,et al.  Outcomes in 15 patients with conjunctival melanoma treated with adjuvant topical mitomycin C: complications and recurrences. , 2011, Ophthalmology.

[58]  R. Kalaivani,et al.  Fluorescence spectra of blood components for breast cancer diagnosis. , 2008, Photomedicine and laser surgery.

[59]  F. Leung Incomplete resection after macroscopic radical endoscopic resection of T1 colorectal cancer-should a paradigm-changing approach to address the risk be considered? , 2017, Translational gastroenterology and hepatology.

[60]  P. Finger,et al.  Eye cancer related glaucoma: current concepts. , 2009, Survey of ophthalmology.

[61]  Jiong Ma,et al.  Rapid diagnosis and intraoperative margin assessment of human lung cancer with fluorescence lifetime imaging microscopy , 2017, BBA clinical.

[62]  P. Siersema,et al.  Risk for Incomplete Resection after Macroscopic Radical Endoscopic Resection of T1 Colorectal Cancer: A Multicenter Cohort Study , 2017, The American Journal of Gastroenterology.

[63]  Nello Cristianini,et al.  Support vector machine classification and validation of cancer tissue samples using microarray expression data , 2000, Bioinform..

[64]  H. Girish,et al.  Risk of tumor cell seeding through biopsy and aspiration cytology , 2014, Journal of International Society of Preventive & Community Dentistry.

[65]  Volkan Hurmeric,et al.  Ultra high-resolution anterior segment optical coherence tomography in the evaluation of anterior corneal dystrophies and degenerations. , 2011, Ophthalmology.

[66]  Yolanda Diebold,et al.  Impression cytology of the ocular surface: a review. , 2004, Experimental eye research.

[67]  James V. Little,et al.  Detection of Head and Neck Cancer in Surgical Specimens Using Quantitative Hyperspectral Imaging , 2017, Clinical Cancer Research.

[68]  L. Cantley,et al.  Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation , 2009, Science.