Concept and setup for intraoperative imaging of tumorous tissue via Attenuated Total Reflection spectrosocopy with Quantum Cascade Lasers

A major challenge in tumor surgery is the differentiation between normal and malignant tissue. Since an incompletely resected tumor easily leads to recidivism, the gold standard is to remove malignant tissue with a sufficient safety margin and send it to pathology for examination with patho-histological techniques (rapid section diagnosis). This approach, however, exhibits several disadvantages: The removal of additional tissue (safety margin) means additional stress to the patient; the correct interpretation of proper tumor excision relies on the pathologist’s experience and the waiting time between resection and pathological result can be more than 45 minutes. This last aspect implies unnecessary occupation of cost-intensive operating room staff as well as longer anesthesia for the patient. Various research groups state that hyperspectral imaging in the mid-infrared, especially in the so called "fingerprint region", allows spatially resolved discrimination between normal and malignant tissue. All these experiments, though, took place in a laboratory environment and were conducted on dried, ex vivo tissue and on a microscopic scale. It is therefore our aim to develop a system incorporating the following properties: Intraoperatively and in vivo applicable, measurement time shorter than one minute, based on mid infrared spectroscopy, providing both spectral and spatial information and no use of external fluorescence markers. Theoretical assessment of different concepts and experimental studies show that a setup based on a tunable Quantum Cascade Laser and Attenuated Total Reflection seems feasible for in vivo tissue discrimination via imaging. This is confirmed by experiments with a first demonstrator.

[1]  K. Mai,et al.  Resection margin status in lumpectomy specimens of infiltrating lobular carcinoma , 2000, Breast Cancer Research and Treatment.

[2]  Antonella I. Mazur,et al.  Molecular pathology via IR and Raman spectral imaging , 2013, Journal of biophotonics.

[3]  Yaw-Bin Huang,et al.  Characterization of human cervical precancerous tissue through the fourier transform infrared microscopy with mapping method. , 2003, Gynecologic oncology.

[4]  Wolfgang Petrich,et al.  Quantum cascade laser–based hyperspectral imaging of biological tissue , 2014, Journal of biomedical optics.

[5]  K. Horst,et al.  Association of Clinical and Pathologic Variables with Lumpectomy Surgical Margin Status after Preoperative Diagnosis or Excisional Biopsy of Invasive Breast Cancer , 2007, Annals of Surgical Oncology.

[6]  R. Salzer,et al.  Raman spectroscopic imaging for in vivo detection of cerebral brain metastases , 2010, Analytical and bioanalytical chemistry.

[7]  Max Diem,et al.  Imaging of colorectal adenocarcinoma using FT-IR microspectroscopy and cluster analysis. , 2004, Biochimica et biophysica acta.

[8]  Gabriele Schackert,et al.  Classification of human gliomas by infrared imaging spectroscopy and chemometric image processing , 2005 .

[9]  M. Diem,et al.  Fourier transform infrared (FTIR) spectral mapping of the cervical transformation zone, and dysplastic squamous epithelium. , 2004, Gynecologic oncology.

[10]  Gabriele Schackert,et al.  Distinguishing and grading human gliomas by IR spectroscopy. , 2003, Biopolymers.

[11]  Yuan-fu Zhang,et al.  The Use of FTIR-ATR Spectrometry for Evaluation of Surgical Resection Margin in Colorectal Cancer: A Pilot Study of 56 Samples , 2014 .

[12]  K. McMasters,et al.  Lumpectomy margins are affected by tumor size and histologic subtype but not by biopsy technique. , 2004, American journal of surgery.

[13]  C. Balleyguier,et al.  Ultrasound of renal tumors , 2001, European Radiology.

[14]  Christopher H Contag,et al.  Fiber-optic probes enable cancer detection with FTIR spectroscopy. , 2010, Trends in biotechnology.

[15]  R. Soloway,et al.  Distinguishing malignant from normal oral tissues using FTIR fiber-optic techniques. , 2001, Biopolymers.

[16]  K. Yano,et al.  Direct measurement of human lung cancerous and noncancerous tissues by fourier transform infrared microscopy: can an infrared microscope be used as a clinical tool? , 2000, Analytical biochemistry.

[17]  S. Rehman,et al.  Fourier Transform Infrared (FTIR) Spectroscopy of Biological Tissues , 2008 .

[18]  Tim May,et al.  Fourier transform infrared spectromicroscopy and hierarchical cluster analysis of human meningiomas. , 2008, International journal of molecular medicine.

[19]  Abdelilah Beljebbar,et al.  Modeling and quantifying biochemical changes in C6 tumor gliomas by Fourier transform infrared imaging. , 2008, Analytical chemistry.

[20]  H. M. Heise,et al.  Epidermal in vivo and in vitro studies by attenuated total reflection mid-infrared spectroscopy using flexible silver halide fibre-probes , 2003 .

[21]  Peter Lasch,et al.  Characterization of Colorectal Adenocarcinoma Sections by Spatially Resolved FT-IR Microspectroscopy , 2002 .

[22]  Abraham Katzir,et al.  Fiber-optic and microscopic infrared biodiagnostics , 2003 .

[23]  J. Fahrenfort,et al.  Attenuated total reflection: A new principle for the production of useful infra-red reflection spectra of organic compounds , 1989 .

[24]  Benjamin Bird,et al.  Detection of breast micro-metastases in axillary lymph nodes by infrared micro-spectral imaging. , 2009, The Analyst.

[25]  E. Papavassiliou,et al.  Phosphodiester Stretching Bands in the Infrared Spectra of Human Tissues and Cultured Cells , 1991 .

[26]  Rohit Bhargava,et al.  Towards a practical Fourier transform infrared chemical imaging protocol for cancer histopathology , 2007, Analytical and bioanalytical chemistry.

[27]  M. Milosevic,et al.  Internal Reflection and ATR Spectroscopy , 2004 .

[28]  Z L Gokaslan,et al.  A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. , 2001, Journal of neurosurgery.

[29]  Paul Bassan,et al.  Large scale infrared imaging of tissue micro arrays (TMAs) using a tunable Quantum Cascade Laser (QCL) based microscope. , 2014, The Analyst.

[30]  Virgilia Macias,et al.  High-resolution Fourier-transform infrared chemical imaging with multiple synchrotron beams , 2011, Nature Methods.

[31]  L. Jacobs,et al.  Annals of Surgical Oncology 15(5):1271–1272 DOI: 10.1245/s10434-007-9766-0 Positive Margins: The Challenge Continues for Breast Surgeons , 2008 .

[32]  C Dener,et al.  Interoperative frozen section for margin assessment in breast conserving energy. , 2009, Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society.

[33]  M. Milosevic,et al.  Internal Reflection and ATR Spectroscopy: Milosovic/Internal Reflection , 2012 .

[34]  Sergei G. Kazarian,et al.  Micro- and Macro-Attenuated Total Reflection Fourier Transform Infrared Spectroscopic Imaging , 2010 .

[35]  P H Watson,et al.  Beware of connective tissue proteins: assignment and implications of collagen absorptions in infrared spectra of human tissues. , 1995, Biochimica et biophysica acta.

[36]  Christoph Krafft,et al.  Classification of malignant gliomas by infrared spectroscopic imaging and linear discriminant analysis , 2007, Analytical and bioanalytical chemistry.

[37]  Matthias Kirsch,et al.  Optical spectroscopic methods for intraoperative diagnosis , 2013, Analytical and Bioanalytical Chemistry.

[38]  C. Dener,et al.  Intraoperative Frozen Section for Margin Assessment in Breast Conserving Surgery , 2009 .

[39]  Werner Mäntele,et al.  Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy , 2011 .

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

[41]  Christine Desmedt,et al.  Discrimination between healthy and tumor tissues on formalin-fixed paraffin-embedded breast cancer samples using IR imaging , 2010 .

[42]  S. Hewitt,et al.  Infrared spectroscopic imaging for histopathologic recognition , 2005, Nature Biotechnology.

[43]  P. Lasch,et al.  Diagnosing benign and malignant lesions in breast tissue sections by using IR-microspectroscopy. , 2006, Biochimica et biophysica acta.

[44]  M. Kon,et al.  Infrared spectral histopathology (SHP): a novel diagnostic tool for the accurate classification of lung cancer , 2012, Laboratory Investigation.

[45]  I. W. Levin,et al.  Fourier transform infrared vibrational spectroscopic imaging: integrating microscopy and molecular recognition. , 2005, Annual review of physical chemistry.

[46]  Christoph Herwig,et al.  Reagent-free monitoring of multiple clinically relevant parameters in human blood plasma using a mid-infrared quantum cascade laser based sensor system. , 2013, The Analyst.

[47]  Abdelilah Beljebbar,et al.  Brain tissue characterisation by infrared imaging in a rat glioma model. , 2006, Biochimica et biophysica acta.

[48]  Michel Manfait,et al.  IR spectral imaging of secreted mucus: a promising new tool for the histopathological recognition of human colonic adenocarcinomas , 2010, Histopathology.

[49]  Y Liu,et al.  Detection of cervical metastatic lymph nodes in papillary thyroid carcinoma by Fourier transform infrared spectroscopy , 2011, The British journal of surgery.

[50]  Li Zhang,et al.  In vivo and in situ detection of colorectal cancer using Fourier transform infrared spectroscopy. , 2005, World journal of gastroenterology.

[51]  Uwe Bindig,et al.  Fibre-optic IR-spectroscopy for biomedical diagnostics , 2003 .

[52]  Michel Manfait,et al.  Infrared imaging as a cancer diagnostic tool: Introducing a new concept of spectral barcodes for identifying molecular changes in colon tumors , 2013, Cytometry Part A.

[53]  Francis L Martin,et al.  Diagnostic segregation of human brain tumours using Fourier-transform infrared and/or Raman spectroscopy coupled with discriminant analysis. , 2013, Analytical methods : advancing methods and applications.

[54]  J Dwyer,et al.  Applications of Fourier transform infrared microspectroscopy in studies of benign prostate and prostate cancer. A pilot study , 2003, The Journal of pathology.

[55]  Uwe Bindig,et al.  Fiber-optical and microscopic detection of malignant tissue by use of infrared spectrometry. , 2002, Journal of biomedical optics.

[56]  Nicholas Stone,et al.  FTIR of touch imprint cytology: a novel tissue diagnostic technique. , 2008, Journal of photochemistry and photobiology. B, Biology.

[57]  Elena Mazza,et al.  Anaplastic astrocytoma in adults. , 2007, Critical reviews in oncology/hematology.

[58]  Edmund Koch,et al.  Intra-operative optical diagnostics with vibrational spectroscopy , 2011, Analytical and bioanalytical chemistry.

[59]  Kazuyuki Yano,et al.  Applications of Fourier transform infrared spectroscopy, Fourier transform infrared microscopy and near-infrared spectroscopy to cancer research , 2003 .

[60]  Christoph Krafft,et al.  Suitability of infrared spectroscopic imaging as an intraoperative tool in cerebral glioma surgery , 2009, Analytical and bioanalytical chemistry.

[61]  P. Griffiths Fourier Transform Infrared Spectrometry , 2007 .

[62]  Natalia I. Afanasyeva,et al.  Minimally invasive and ex-vivo diagnostics of breast cancer tissues by fiber optic evanescent-wave Fourier transform IR (FEW-FTIR) spectroscopy , 1998, Photonics West - Biomedical Optics.