An International Research Journal

AJP

SSN : 0971 - 3093

Vol  24, No. 7, July, 2015

Optical Diagnostics: Bench to Bedside

Guest Editorial

            Optical diagnostics, also variously and interchangeably referred to as optical pathology, optical diagnosis, optical biopsy, spectral diagnosis, spectromics, describe applications of spectroscopic and/or optical based methods in disease diagnosis- one of the highly attractive, active and vigorously  pursued areas of biomedical applications of spectroscopy and optical methods. Conventionally, diseases are diagnosed by clinical examination followed by relevant biochemical/micorobiological/pathological/imaging investigations. Such approaches, relying on symptoms, are considered to diagnose an existing disease, could be a late diagnosis which often lead to  poor prognosis. Early stage diagnosis can almost always provide better prognosis. Since morphological changes could be rather late, diagnostics should be sensitive to biochemical changes happening much earlier, for early diagnosis. In this context, opical spectroscopy methods are being pursued as potential alternatives/adjuncts, mainly due to the attributes such as sensitivity to biochemical composition, less time consuming, no external labeling or sample processing, more objective, and most importantly feasible in vivo/in situ on line diagnosis. Laser-induced-fluorescene, FTIR, FT-Raman and diffuse reflectance are some of the most widely pursued optical methods. In the present issue articles are selected to showcase some of the latest development in disease diagnosis by optical spectroscopy methods – otpical diagnostics.

            As discussed earlier, objective diagnosis is one of the major attributes of optical diagnostics, besides noninvasive/in vivo/in situ applications. As spectral data are amenable mathematical data processing, multivariate analyses offer a suitable approach through various unsupervised and supervised methods in achieving objective and on line decision making. The opening paper Disease diagnosis by optical spectroscopy: Role of multivariate analysis’ by N Tayal et al  reviews several data processing and preprocessing tools that are being widely employed, and also presents typical optical diagnostics protocols. This could be useful starting step for enthusiasts who like to venture into this promising field. Conventionally, experimental models, mostly rodents, have been used for development of diagnostics and therapeutics, especially in early phases or more commonly known as Proof-of-Concepts studies. In the case of optical diagnosis, ex vivo samples, tissues, or body fluids are also investigated to develop proof of concept. This can be attributed to the fact that spectral investigations are mostly non-interventional, unlike drug or other clinical trials. Accessibility, both ethical and practical point of view, of these samples could be other driving point. Nevertheless, there have been several pioneering spectroscopy based disease diagnosis studies on animal models. Therefore, it is pertinent to present the role of animal models in development of spectral diagnosis.  Hence the article entitled ‘Animal models in disease diagnosis: Raman spectroscopic explorations, by P Kumar and Murali Krishna  presents an overview, though limited to Raman spectroscopic studies, of this field. The ultimate aim/goal of optical pathology is noninvasive screening and diagnosis. Screening of oral cancer, most common among Indian and south Asian population, is a daunting task, from the logistic point of view. Higher incidence, large population, coupled with lack of reliable early diagnosis and screening, are known reasons for high mortality. In view of this, several groups have actively pursued spectral diagnostics using laser-induced-fluorscence, Raman and many other methods. The Manipal Group (India) of  Laser Spectroscopy, established by Prof  V B  Kartha, presently lead by Prof  C Santosh, is one of the pioneers in optical diagnostics applications, especially towards oral cancer screening and diagnosis. In their article, entitled ‘Optical Biopsy: Journey from laboratory system to rural health-care’, they share their observations and experiences in bench to bed-side translation towards rural set up. Another poineering laser spectroscopy group is one lead by Dr R Jaysree at Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India. This group has been actively pursuing spectral diagnostic applications in several cancers, including oral, liver and brain. In the article Pathological fingerprinting of tissue observed through the window of fluorescence spectroscopy’,  they overview cancer diagnosis using home-built fluorescence spectrometer, besides lucid description of fundamentals of spectroscopy. Raman spectroscopy is the other widely explored optical spectroscopy technique in disease diagnosis. Among cancers, treatment (surgery) of brain cancer is very critical and often tricky. As majority of these tumors are highly infiltrative gliomas, wherein demarcation of surgical margins are very crucial for better prognosis. Keeping importance of brain, conservative surgeries are often carried out leaving residual tumor, hence recurrence. There have been several Raman spectroscopic investigations reporting its utility. The article entitled ‘Raman spectroscopy in biomedical diagnosis: Brain cancers’ by Hole and Murali Krishna  summarizes  the literature on Raman spectroscopic explorations in brain cancers. Radiotherapy is the choice of treatment for many cancers such cervix and laropharynx, usually combination of surgery, radiotherapy, chemotherapy employed in a typical cancer thereapetuic regimen. Unfortuately radiation resistance is a major hurdle in radiotherapy. In the next article, Goyal et al describe basic mechanisms involved in radioresistance, assays to predict tumor radioresponse. Authors also provide insights on  emerging  optical based technologies in the article entitled Mechanistics of tumour radioresistance and predictive techniques to assess tumour response’. Mutlimodal approach, i.e., two or more optical methods, is the other widely pursued approach in disease (cancer) diagnosis. Most commonly employed methods are combination of Raman + IR- complementary vibrational spectroscopy methods, fluorescence + diffused reflectance. There also exist several reports exploring combination of opical imaging tools such as OCT with spectroscopy tools.  In this context, the paper entitled ‘Multimodal spectroscopic applications in cancer diagnosis: Combined Raman spectroscopy and optical coherence tomography’, by P Kumar et al provides insights on combined Raman + OCT explorations in cancer diagnosis. These  authors also describe some of  their findings on hamster buccal pouch models. As mentioned earlier, there have been significant advancements in spectral diagnosis using less invasive samples such bodyfluids –plasma, serum, CSF, semen- and exfoliated cells. These explorations were  necessitated due to the fact that, though in vivo/in situ applications are very attractive and useful, they are limited by on-site instrumentation and rather stringent experimental requirements – controlled environment and a dark room. Such facilities may be difficult in rural areas of under developed and developing countries. On the other hand, body fluids such as serum and plasma are more easily accessible and transferable to centralized facilities. The article entitled Serum Raman spectroscopy and applications in disease diagnosis by Sahu and Murali Krishna summarizes advancements in this area of research.

 

We would like to acknowledge the whole-hearted cooperation from all the authors who have contributed to this issue. Special mention goes to Prof V B Kartha for his suggestions. We gratefully acknowledge the help of Dr Dominque Bertrand, France, for his valuable suggestions and ideas in preparing the article entitled, ‘Disease Diagnosis by optical spectroscopy: Role of multivariate analysis’.

We would also like to express our sincere thanks to the Editor in Chief  of Asian journal of Physics, Prof Vinod Rastogi for giving me the opportunity to edit and his  enthusiasm in presenting this special issue to the scientific community during International Year of Light. Finally, thanks are due to Er Manoj Kumar, Managing Editor AJP, for preparing the Press Copy of the articles.

June 30, 2015

C Murali Krishna


Asian Journal of Physics                                                                                                            Vol. 24, No 7 (2015) 00-00


Dispersion in twisted PMC clad optical fibers


M A Baqir and P K Choudhury

Institute of Microengineering and Nanoelectronics 

Universiti Kebangsaan Malaysia 

43600 UKM Bangi, Selangor, Malaysia

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The paper reports dispersion characteristics of twisted clad optical fibers under the situation when a sheath helix, composed of perfect magnetic conductor (PMC), is introduced in the core-clad interface. For this purpose, the allowed values of wave propagation constants corresponding to the sustained modes are deduced by the use of eigenvalue relation, as developed by implementing suitable feld continuity conditions. Moreover, modes corresponding to the slow- and the fast-waves in the guide are analyzed by investigating the dispersion characteristics. © Anita Publications. All rights reserved.

Total Refs : 30

Dispersion in twisted PMC clad optical fbers.pdf
M A Baqir and P K Choudhury

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Asian Journal of Physics                                                                                                          Vol. 24, No 7 (2015) 00-00


Disease diagnosis by optical spectroscopy: Role of multivariate analysis


N Tayal, P  Kumar and C Murali Krishna

Chilakapati Laboratory

Advanced Centre for Treatment Research and Education in Cancer (ACTREC)                                        

Tata Memorial Centre (TMC), Kharghar, Sector '22', Navi Mumbai-410 210, India.

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Spectroscopic techniques in conjunction with chemometrics tools offer a perspective which can distinguish subtle but significant changes in the complex biological environment and thus provide an adjunct to existing disease diagnostic modalities. In view of levels of complexity in living organisms, multivariate analyses offer a suitable approach through various unsupervised and supervised methods. Robust estimators are used to trained and evaluate models which can be used to test independent data set.© Anita Publications. All rights reserved.                                               

Keywords: Spectroscopic techniques, Chemometrics tools, Optical spectroscopy

Total Ref: 30

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Asian Journal of Physics                                                                                                          Vol. 24, No 7 (2015) 00-00


Animal models in disease diagnosis: Exploration using Raman spectroscopy


Piyush Kumar, and C Murali Krishna

Chilakapati Laboratory,

Advanced Centre for Treatment Research and Education in Cancer (ACTREC)

Tata Memorial Centre (TMC), Kharghar, Sector '22', Navi Mumbai – 410 210, India

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Experimental models, mostly rodent models have been used in experiments which have been precursors in development of diagnostics and therapeutics. In recent decades, spectroscopic techniques are being explored as adjuncts to the existing methods of diagnosis, especially in cancer diagnosis, to reduce the existing work load on health personnel. Raman spectroscopy (RS) has been emerging as a potential tool as major bands are not influenced by the presence of water, a major constituent of organisms and thus can be adapted for in vivo applications. This review focuses on application of RS on animal models for diagnosis of disease conditions, including cancers. © Anita Publications. All rights reserved.

Keywords: Animal models, Spectroscopic techniques, Cancer diagnosis, Raman spectroscopy.

Total Ref: 95

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Asian Journal of Physics                                                                                                          Vol. 24, No 7 (2015) 00-00


Optical Biopsy: Journey from laboratory system to rural health-care


Ajeetkumar Patil1,V K Unnikrishnan1, Keerthilatha M Pai2, Ravikiran Ongole4, Kanthilatha Pai5, V B Kartha1,3 and Santhosh Chidangil1*

1Department of Atomic and Molecular Physics, Manipal University, Manipal-576 104, India

2Department of Oral Medicine and Radiology, Manipal University, Manipal-5761 04, India

321, Udayagiri, Sion, Trombay, Mumbai-400 088, India

4Department of Oral Medicine and Radiology, Mangalore-575 001, India

5Department of Pathology, Kasturba Medical College Manipal, Manipal University, Manipal-576 104, India

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85 % of the world population exists in the under-developed countries and almost 80% of them live in rural areas. This number constitutes a large fraction of the world population- more than 60%- who are living in conditions of grossly inadequate health care, without any modern medical facilities for therapy, or relief from conditions like coronary problems, various types of cancers, diabetes etc., diseases which remain clinically silent for long periods. For all these diseases, overt symptoms start appearing only in the final stages, by which time therapy is almost always unsuccessful, and serves only palliative purposes. The solution for this is provided by development of screening and diagnostic methods, which are cost-effective, can be used even in small hospitals and community health-care centers, or medical camps organized in rural areas. The present paper discusses the possibility of using Optical methods for early detection of clinically silent diseases of the type discussed. The paper presents results of the successful development of an "Optical Biopsy" system, which is non-invasive, capable of repeated application, highly cost-effective, can be used in small clinics and hospitals in rural areas, and even by health-care workers in community medical camps, to screen large susceptible population groups (tobacco users) for oral premalignancy and malignancy condition. © Anita Publications. All rights reserved.

Keywords : Cancers, Diabetes, Optical Biopsy, Alzheimer's and Parkinsons, Pulsed Laser LIF System, Nd-YAG laser

Total Refs: 19

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Asian Journal of Physics                                                                                                      Vol. 24, No 7 (2015) 933-950


Pathological fingerprinting of tissue observed through the window of fluorescence spectroscopy


Shaiju S Nazeer and  Ramapurath S Jayasree

Biophotonics and Imaging Lab, Biomedical Technology Wing

Sree Chitra Tirunal Institute for Medical Sciences & Technology,

Poojappura, Thiruvananthapuram - 695 012, India.

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There is a high demand for non invasive, non hazardous and fast techniques for the disease diagnose at its early onset which are affordable to common man. The background of the demand is the fact that an early stage diagnosis helps the physician or surgeon to intervene with effective therapeutic strategies to reduce morbidity and mortality. When considering the already prevailing techniques, each modality has its own merits and demerits. The advancement in the properties of light sources and supporting technologies and the potential of optical based techniques give a strong indication that optical pathology and non invasive optical diagnostics will replace the conventional techniques in next generation diagnostics. Spectral information are capable of providing biochemical and metabolic fingerprinting which is very essential for an early stage diagnosis, but lacks among the currently available techniques. Most useful spectroscopic techniques which have proven to be useful in diseases diagnosis are Raman spectroscopy, Infrared spectroscopy, Magnetic resonance spectroscopy and fluorescence spectroscopy. This review focuses on the fluorescence spectroscopy and the supporting statistical tools, the most economic and fast technique from the above list. Details on the instrumentation for in vitro and in vivo studies have also been reviewed. Case studies based on oral cavity disorders, brain tumor and liver abnormalities have been discussed in detail. © Anita Publications. All rights reserved

Keywords: Non invasive, fluorescence spectroscopy, Raman spectroscopy

Total Refs: 88

Pathological fingerprinting of tissue observed through the window of fluorescence spectroscopy.pdf
Shaiju S Nazeer and Ramapurath S Jayasree

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Asian Journal of Physics                                                                                                          Vol. 24, No 7 (2015) 00-00


Raman spectroscopy in biomedical diagnosis: Brain cancers


Arti R Hole and C Murali Krishna

Chilakapati Laboratory,

Advanced Centre for Treatment Research and Education in Cancer (ACTREC)

Tata Memorial Centre (TMC), Kharghar, Navi Mumbai - 410 210, India

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Around 45% of brain tumours are gliomas, which are currently diagnosed by a combination of CT scanning and magnetic resonance imaging (MRI). The standard treatment of gliomas is surgical resection along with adjuvant radiotherapy and chemotherapy. Surgical resection, largely guided by visual inspection and pre-operative MRI is a tricky process. Residual invasive cancer cells may cause recurrence of brain cancers while the removal of healthy tissue can cause serious cognitive deficits. Thus prognosis in brain cancers is poor. Optical techniques may play an important role in diagnosis as well as in situ surgical demarcations..© Anita Publications. All rights reserved.

Keywords:  Brain tumours, Gliomas, CT scanning, Magnetic resonance imaging (MRI). Optical spectroscopy techniques.

Total Refs: 20.

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Asian Journal of Physics                                                                                                          Vol. 24, No 7 (2015) 00-00


Mechanistics of tumour radioresistance and predictive techniques to assess tumour response 


Nisha Goyal1, C Murali Krishna1 and Jayant S Goda2

                   1Chilakapati lab, TMC- ACTREC, Kharghar, Navi Mumbai- 410 210, India

      2Department of Radiation Oncology, TMC-ACTREC, Kharghar, Navi Mumbai 410 210, India

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Radiotherapy plays an important role in the curative and palliative management of malignant tumours. Radiotherapy along with chemotherapy and surgery is a major cancer treatment modality and is used to treat approximately 50% of all cancer patients, with varying success. For decades, most research on improving treatment outcomes has focused on modulating radiation-induced biological effects on cancer cells. However, cellular resistance in tumour to different therapeutic approaches has been a limiting factor in curative treatment of cancer. Resistance to therapeutic radiation is a common phenomenon which significantly reduces treatment options and impacts survival. The mechanistic basis of radiation resistance in tumours is considered to be multifactorial. The present review summarizes current knowledge on underlying mechanisms of radioresistance in tumours and techniques to predict the factors responsible for radiation resistance and tumour response. © Anita Publications. All rights reserved.

Keywords : Radiation resistance, Radiotherapy, Malignant tumours, Cancer cells, Cellular resistance

Total Refs: 71

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Asian Journal of Physics                                                                                                          Vol. 24, No 7 (2015) 00-00


Multimodal spectroscopic applications in cancer diagnosis: Combined Raman spectroscopy

 and optical coherence tomography


Piyush Kumar1,C Murali Krishna1, N K Sahoo2 and K Divakar Rao3

1Chilakapati Laboratory, Advanced Centre for Treatment Research and Education in Cancer (ACTREC)

Tata Memorial Centre (TMC), Kharghar, Navi Mumbai – 410 210, India

2Atomic & Molecular Physics Division, Bhabha Atomic Research Centre, Trombay, Mumbai- 400 085, India

3Photonics and Nanotechnology Section, Bhabha Atomic Research Centre Facility, Visakhapatnam-530 012, India

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In contrast to current diagnostics in cancers, optical techniques are non invasive, rapid and objective. Spectroscopic techniques like Raman spectroscopy (RS) may detect biochemical changes associated with disease conditions, especially cancers while Optical Coherence Tomography (OCT) reveals morphological features in tissues. Simultaneous application of both techniques may lead to better prognosis as both morphological and biochemical changes may be explored, overcoming limitations of both techniques. Such a study may be informative in conditions like cancer where massive changes in tissues architecture and biochemistry are involved. Such developments may act as adjunct to existing screening, diagnostic and therapeutic response modalities.© Anita Publications. All rights reserved.

Keywords:  Cancer, Optical techniques, Raman spectroscopy (RS), Optical coherence tomography (OCT), Tissues.

Total Refs: 83

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Asian Journal of Physics                                                                                                          Vol. 24, No 7 (2015) 00-00


Serum Raman spectroscopy and applications in disease diagnosis

 

Aditi Sahu and C Murali Krishna

Chilakapati Laboratory 

Advanced Centre for Treatment Research and Education in Cancer (ACTREC),

Tata Memorial Centre (TMC), Kharghar, Sector '22', Navi Mumbai – 410 210, India

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Biofluids like blood may reflect metabolic disturbances due to onset of disease in the body and are known to be one of the ideal samples for disease diagnosis in clinics. Detection of individual disease-specific markers is a laborious, time-consuming and cost-ineffective procedure. Raman spectroscopy is a vibrational spectroscopic method based on inelastic scattering of light. Raman spectroscopy is a holistic approach: it yields a global profile representing the total biochemical components of the sample under consideration. Because of attributes like being rapid, objective, non-destructive and no requirement of sample preparation or external reagents, it has the potential to serve as a useful adjunct for disease diagnosis in clinics. Raman spectroscopy of biofluids like blood (serum/plasma) is more practical for clinical use. Hence, this technique has been extensively investigated for diagnosis of several diseases, including cancers. Some examples include detection of sepsis, asthma, dengue, Alzheimer’s disease and cancers like breast, cervical, colorectal, ovarian and head and neck cancers. This review summarizes some important applications of serum Raman spectroscopy in disease diagnosis.   © Anita Publications. All rights reserved.

Key words: Serum Raman spectroscopy,Inelastic scattering, Biofluids, Alzheimer’s disease.

Total Refs: 64

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Asian Journal of Physics                                                                                                          Vol. 24, No 7 (2015) 00-00


Influence of Cd0.99Ni0.01SiO3 nanofiller on structural and optical properties of spin coated

poly(vinylidene fluoride) nanocomposites flexible films


G Shireesha1,2, C Manjunatha3, Anjana Jain4, and M C Radhakrishna5

1Department of Physics, Bangalore University, Bangalore-560 056, India.

2Department of Physics, R V College of Engineering, Bangalore-560 059, India.

3Department of Chemistry, R V College of Engineering, Bangalore-560 059, India.

4 Material Science Division, National Aerospace Laboratories, Bangalore-560 017, India.

5Department of Physics, Dayanand Academy of Technology and Management, Bangalore-560 082, India

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PVDF-Cd0.99Ni0.01SiO3 nanocomposite flexible films were prepared for the first time by spin coating technique. Nanocomposites of varying concentration (1, 3 and 5 wt %) were prepared and the thickness of the films was measured and found to be ~40μm. The crystal structure, morphology, composition and optical properties of the flexible films were investigated. Peaks in the X-ray diffraction pattern of the formed nanocomposite indicate the successful incorporation of Cd0.99Ni0.01SiO3 nanoparticles in PVDF matrix which is also confirmed by SEM micrographs and EDX analysis. The shift in the optical edges as observed by UV-Vis spectra of the developed composites has been co-related to optical band gap using Tauc’s expression. The composite indicates an increasing trend in the optical band gap and activation energy with the increase in the concentration of the nanofillers. It is also found that the fluoroscence of the nanocomposites increased with the increase in the concentration of the nanoinclusions. © Anita Publications. All rights reserved.

Total Refs: 23

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