Photodiagnosis and Photodynamic Therapy 17 (2017) 65–74 Contents lists available at ScienceDirect Photodiagnosis and Photodynamic Therapy journal homepage: www.elsevier.com/locate/pdpdt Biochemical assessment of human uterine cervix by micro-Raman mapping Amuthachelvi Daniel a,∗ , Aruna P. a , S. Ganesan a , Leena Joseph b a Department of Medical Physics, Anna University, Sardar Patel Road, Chennai, 600025, India b Department of Pathology, SriRamachandra Medical University, Chennai, 600116, India a r t i c l e i n f o Article history: Received 19 May 2016 Received in revised form 26 July 2016 Accepted 31 August 2016 Available online 23 September 2016 Keywords: Raman mapping Cervical cancer Cancer diagnosis Biochemical assessment a b s t r a c t Raman spectroscopy and mapping are capable of probing the molecular changes due to oncogenesis. Here Raman maps of cervical tissues under different pathological conditions were studied. Multivariate analytical methods were utilized to reconstruct these Raman maps and were compared with Hematoxylin and Eosin stained histological images. The maps showed clear differences between the different regions of the tissue and there were spectral changes associated with neoplasia and malignancy. A semi-quantitative biochemical modeling was carried out to quantify these spectral changes and the relative contributions of the biochemicals. This method revealed gradual biochemical changes (nucleus to cytoplasm ratio, glycogen, collagen, lipids, protein and carotene) associated with the progression of cervical cancer. These biomolecules extracted for the disease prognosis would have greater significance for cervical cancer diagnosis. © 2016 Elsevier B.V. All rights reserved. 1. Introduction Globally cervical carcinoma is the second most common malig- nancy affecting women with a high mortality rate of 52% [1]. The estimated deaths worldwide due to cervical cancer every year is 270000, of this an unprecedented >85% of the deaths occur in the developing countries. Hence it is of immense importance to diag- nose this disease early for treatment and for better therapeutic prognosis. The currently available mass screening method for cer- vical pre-cancerous and cancerous lesions is the Pap smear test, the reliability and accuracy of it is still debatable. Of the 10% cases detected with abnormal smear, only 0.1% turn out to be having cancerous lesions [2]. The next widely used method of cervical diagnosis for Cervical Intraepithelial Neoplasia (CIN) is the col- poscopy and the sensitivity of colposcopy for the detection of CIN 1 or CIN 2 is 58.0–74.7% and specificity is 57.5–92.9% [3]. Although the histopathological study is regarded as the golden standard method for cervical pre-cancerous and cancerous conditions, it is invasive and subjective. Therefore, the high mortality rate can be reduced by novel and effective screening programmes. In this context, optical spectroscopic techniques have been intensively explored for cancer diagnosis at molecular level for ∗ Corresponding author. E-mail address: amydany1011@gmail.com (A. Daniel). the past two decades. Among the various optical spectroscopic techniques, Raman spectroscopy is regarded as a valuable and non- destructive tool for probing molecular vibrations of the biochemical composition of molecules and provides a specific fingerprint for structure and morphology of tissue without labeling. Furthermore, the growth of key technologies like small and stable lasers, holo- graphic gratings and filters and electronically cooled CCD detectors have enabled the rapid expansion of Raman spectroscopy and imag- ing. Based on these, many have reported both in vitro and in vivo characteristics of cervical malignancy and found that the finger- print region (600–1800 cm −1 ) as well as high wavenumber region (2600–4000 cm −1 ) in conjunction with various multivariate sta- tistical techniques diagnose pre-malignancy and malignancy with appreciable accuracy [4–11]. Due to the advancements in technology, the Raman spec- troscopy of tissues has also been extended for mapping/imaging studies. Puppels and his co-workers have mapped bronchial tis- sues to understand the biochemical changes associated with the malignancy of lung [12]. They have also extended the same to brain tissues for discriminating vital tumor from necrotic regions to aid real time in vivo intra-operative brain biopsy guidance [13]. Kirsch et al. have performed in vivo brain surface mapping for intracerebral tumors in animal model [14] and Amharref et al. have also reported the mapping of glioma tissues in animal model [15]. Tan et al. [16] and Rashid et al. [17] have reported the Raman imaging of normal http://dx.doi.org/10.1016/j.pdpdt.2016.08.011 1572-1000/© 2016 Elsevier B.V. All rights reserved.