PUBLISHED BY THE

DEPARTMENT OF ATOMIC ENERGY

GOVERNMENT OF INDIA

VOL. 36/NO.1-2/July-August 2002

 

 

Tata Memorial Centre (TMC), grant-in-aid institute under the aegis of the Department of Atomic Energy, has now brought the state-of-the-art cancer diagnosis and treatment at the doorsteps of villagers.The Telepathology Programme of the Tata Memorial Hospital of TMC, which uses the latest strength of Information Technology, has taken shape at Barshi - a small town in district Sholapur of Maharashtra, which is one of thousands of rural Indian towns. The tele-link between Barshi and TMH exchange images of cytology smears and histology sections using the telecommunication link, for expert opinion, ensuring high quality expertise to rural areas.

From a small beginning and with the support from the Tata Memorial Hospital, Barshi has now become an important centre for cancer detection and treatment of patients, which caters to a large number of surrounding villages and towns.

Dr. Suresh H. Advani	Dr. Chaitanyamoy Ganguly
Shri H.S. Kamath	Shri VK Sharma

On the occasion of National Technology Day - May 11, 2002, Department of Atomic Energy in a function held at Anushaktinagar, Mumbai, felicitated its four Padmashri Awardees. The officials felicitated were - Dr. S. H. Advani ( Tata Memorial Hospital, Mumbai ), Dr. C. Ganguly ( Chief Executive, Nuclear Fuel Complex, Hyderabad ), Shri H. S. Kamath ( Chief Executive, Heavy Water Board, Mumbai ) and Shri V. K. Sharma ( Senior Executive Director, Nuclear Power Corporation of India Limited, Mumbai ). Chief Guest Dr. R. Chidambaram, Principal Scientific Advisor to Government of India and DAE-Homi Bhabha Chair Professor, felicitated the awardees by offering them Shawls, Shrifals (coconuts) and Silver plaques. Dr. Chidambaram in his address observed that over the years Department of Atomic Energy has "grown into a unique organisation with diverse activities and is equipped with probably world’s greatest collection of science and technology experts". Dr. Anil Kakodkar, Chairman, Atomic Energy Commission, in his presidential remarks said that DAE has acquired comprehensive ability across the entire chain of its activities. He further said that at DAE "we translate our R & D efforts into technological reality and ultimate commercial success".

The function was attended by senior scientists and engineers from various units of DAE. Former AEC Chairmen Dr. H. N. Sethna and Dr. P. K. Iyengar and many former senior officers of the Department graced the function with their presence.

Shri R. M. Premkumar, Additional Secretary, DAE, while welcoming the guests remarked that in the recent years DAE has set a tradition of getting such national awards in clusters and this is a recognition of the tremendous strides the department has made in its scientific and technical achievements.

In a separate function, DAE released a film on the Uranium Corporation of India Limited.
 

Heavy Water :Alternative applications in

biology, medicine and industry

 

Dr. P.S. Chauhan

ICMR Emeritus Medical Scientist & Honorary Visiting Scientist

Heavy Water Board

(Formerly, Head, Cell Biology Division & Project Manager, MSP)

Bhabha Atomic Research Centre

Heavy Water exhibits different chemical and physical properties compared to normal water due to difference in the zero point energy arising out of the isotope effects. The isotope effect gives rise to difference in bond energies and this leads to the different chemical behavior of heavy water. Due to the difference in bond energy, D2O exhibit different deuterium bonding effects also (hydrogen bonding in case of normal water) giving rise to changes in composite molecular structure and behavior. In broader sense, the effects of D2O on living systems can be categorized into two types:

(i) "Solvent Isotope Effect," based on the properties of D2O molecule as a whole, in particular its effects on the structure of water and the biological macromolecules.

(ii) "Deuterium Isotope Effect" (DIE), resulting from the ability of D2O to replace H with D in biological molecules. The C-D bond is several times stronger than the C-H bond and thus more resistant to enzymatic and even to chemical cleavage.

In mammals, investigations in the past have concentrated on identifying the effects of D2O, following the replacement of body water by D2O. In humans, studies on the use of D2O as a tracer in clinical nutrition and for determining normal parameters of human physiology, among infants, pregnant and lactating mothers as well as healthy adults have been continued over the decades and profoundly increased in recent years. The major advantages of D2O as a tracer are that it is non-radioactive and more importantly with almost instant access to all body compartments, tissues and cell types. A number of methods based on nuclear magnetic resonance, and spectrophotometry have increased the sensitivity of detection and deuterium is now a well-accepted tracer in humans. These investigations establish the safety of D2O in humans at low-level exposures.

The biological and therapeutical potential of D2O began to be recognized right during the 1950s-60s phase of biological studies. During the recent decades, interest has spread widely in several areas of basic biology, medicine and industry. Focus has been on deuteration of drugs to slow down the pathway(s) of their metabolism. The altered metabolism of some of the drugs may lead to increased duration of their pharmacological action and/or reduction of toxic manifestations. About two dozens of drugs, already in use in clinical practice, have been deuterated and their therapeutic efficacy found to be greatly enhanced. Recently, two of such drugs have been approved for clinical trials by Canadian and US regulatory agencies. This opens up new opportunities of enormous potential for use of deuterated drugs in health care system. It has been reported that D2O can reduce salt and ethanol-induced hypertension in rats. Likewise, there are reports on anti-genotoxic and radio protective effects of D2O in mice. These claims need to be confirmed and investigated in detail.

Another unique property of D2O relates to the enhancement of thermal stability of macromolecules, cells and tissues. This property has been utilized to enhance the thermostability of certain vaccines e.g., oral polio vaccine or other macromolecules, which need freezing temperature. A French Group had shown D2O based thermostabili-zation of Oral Polio Vaccine (OPV). Recently, Despande et.al of Enterovirus Research Centre, an ICMR Institution at Mumbai in collaboration with the Heavy Water Board (HWB) have improved the process and a distinct advantage of D2O based OPV has been demonstrated. Thus, Oral Polio Vaccine remains biologically active, even if the cold chain is disturbed for a while. This technology has enormous potential in tropical countries and can serve as a support system for cold chain in far remote areas where it is difficult to maintain the desired temperature. Likewise, several tissues/ organs e.g., kidneys and other biological material can be preserved without degradation or decay.

D2O is more toxic to malignant than normal animal cells, but higher concentrations are required. Therefore, new modalities are required to be explored for regular therapeutic use. It has been shown to control the invasiveness of several types of malignant cells including those of pancreas, which are difficult to treat. In boron neutron capture therapy (BNCT), D2O has been found to increase neutron penetration to boron compounds bound to malignant cells. Deuteration of anticancer drugs reduces side effects while retaining their therapeutic efficacy, while, D2O enhances therapeutical potential of photosensitizers. Thus, there is wider interest in exploring the application of D2O in cancer therapy employing different approaches.

Future Perspective

D2O exhibits several biological effects, independent of H2O and some of these have enormous possibilities of application in medicine and technology. Some of the areas of interest are mentioned briefly here.

Shelf-life Extension

Thermostabilization of vaccines being used in the country, is an important field with enormous possibilities and deserves to be considered on priority. Since regulatory obligations may be relatively less stringent, the vaccines currently in use in poultry or for cattle, farm and domestic animals form the areas of choice. Likewise, preservation of cells, organs, and industrial enzymes is another area of profound interest worth exploring.

Drug Development and Therapy

The recent approval of clinical trials by the Canadian and US Agencies for deuterated drugs opens up enormous avenues for deuteration of drugs already in use in the country. This includes all classes of drugs, whose biological efficacy can be enhanced. A comprehensive programme for synthesis of deuteration of drugs, their pharmacokinetic profile and detailed pharmaco-therapeutic studies can be very rewarding. Likewise, in the area of cancer therapy, several strategies such as deuteration of anti-cancer drugs to enhance efficacy and reduce side effects, use of D2O to slow down proliferation of malignant cells and enhance BNCT or photo dynamic therapy are promising. The anti- hypertensive effects of D2O are dramatic and make a case for a detailed pharmacological evaluation of D2O.

Biotechnology

Lower organisms including algae and bacteria can adapt to grow almost in 100% D2O. Since, distinct morphological features are associated with microbial adaptation, the phenomenon is an excellent model to explore the basic biology of stress and adaptive responses. Some of these organisms are being explored as sources of a number of deuterated molecules for industrial, biotechnological and medical applications. To illustrate the point, deuterated glycerol has interesting potential uses as a precursor of transparent plastics and other compounds. Deuterated glycerol can be produced by Dunaliella spp, a salt-tolerant algae growing in D2O at high NaCl concentrations. Thus, indicating an interesting biotechnological potential for such organisms and several groups are engaged to exploit these possibilities.

Industry

The different behavior arising out of the isotope & deuterium bonding effects have found potential use in various industrial activities. Using some of the fundamental differences between hydrogen and deuterium, a number of applications have been developed in the high technology area. Some of these are in the field of optical fibres [improved intensity and better transmission characteristics of deuterated PMMA (Poly methyl meta acrylate) compared to conventional one], optical recording systems (improved storage capacity as a result of sharper and uniform optical recording density with deuterated polymeric substance) and better quality semi-conductors with reduced stress induced leakage currents across the metal oxide gates. Deuterated compounds like lubricant additives have also been reported to provide excellent properties vis-à-vis the normal lubricants. The deuterated polymers exhibit interesting physico–chemical properties providing enormously better features for future technology.

The potential for deuterated compounds in the industry is enormous and needs a dedicated effort in some of the fundamental and applied area of research work .

Low-dose exposure and homeostatic benefits

An area, yet to be explored, relates to the effect of lower concentrations of D2O on mammalian physiology and its health implications. D2O slows down physiological processes. The beneficial health effects of the physiological slowing either by caloric restriction, or through central nervous system control, are now being increasingly recognized. It is no wonder that several companies in North America are marketing D2O as a health promoter and cosmetic marvel. It would be worthwhile to examine, if there is a scientific basis of beneficial health effects of D2O at lower doses.

Probing biological phenomena

D2O provides highly unique avenues for exploring basic mechanisms of biological phenomenon. As said earlier, D2O has access to all body organs, cellular components and molecules. Merely, withdrawing D2O from feeding water removes deuterium from the body as H replaces D. This is a unique property, practically, not shared by any other agent and provides extremely interesting avenues of delineating the mysteries of biological processes. For instance, cell division can be inhibited but cells recover completely on withdrawal of D2O. Thus, the sequence of array of genes involved in the process can be investigated with ease. With the use of new technology, a large number of the genes or proteins and the basic events of translation can be investigated, simultaneously.

Rush for Patenting

About two dozen patents had been granted or filed in the Western World and Japan up to 1995. However, from 1995 to 2000, as many as 189 patents have been filed or granted on biomedical and technological applications of D2O which is a clear indication of the potential being perceived in the technologically advanced world about the applications of D2O in industry and health care system. Development of alternate applications of heavy water in all the above fields through a national level programme involving R&D, academic institutions and industries can have a tremendous potential in this country. This is especially so in view of the fact that Heavy Water Board is a leading producer of heavy water and can produce any quantity of heavy water for such a programme. HWB can also appropriately support collaborative efforts in all the above-mentioned field of work.

R. Natarajan

Associate Director, Reprocessing Group,

Indira Gandhi Centre for Atomic Research, Kalpakkam

Cell piping during erection	a - tight container in a shielded cask (yellow colour) brings fuel from Post Irradiation Examination Facility to LMC Facility
Lead Mini Cell facility comprises lead shielded hot cells with 250 mm or 200 mm thick lead shielding (depending upon the b,g radioactivity in different zones). The facility is a compact one and constructed on an area of 10,950 mm in length and 2050 mm. in width. The overall height is 2550 mm. An a-tight stainless steel containment box of 10,100 mm long, 1200 mm wide and 1500 mm high is housed inside this lead shielding. It is provided with six radiation shielding windows and six pairs of master slave manipulators with articulated arms to facilitate remote operation and maintenance of different equipment and systems. In addition, an a tight blister box provides access for direct maintenance of small gadgets, which can be brought out of the cell. The high level of plutonium in the fuel poses a criticality problem, which has been addressed fully with adequate design features. Specially designed tanks (annular or slab type) have been installed to store solutions containing fissile material to meet the safety requirements of criticality. Around 2 km of intricate stainless steel piping involving 3000 bends and 2000 X-Radiography weld joints, has been successfully completed within the limited area of the facility. The density of piping was a challenging task for the manipulation of welder. Around 35 process vessels and 30 equipment are installed in the hot cell.

Lead Mini Cell Facility (LMC) is designed to demonstrate reprocessing of the mixed carbide fast reactor fuel. In this cell, mixed carbide fuel with high plutonium content (upto max of 70% Pu) with a high burn up (100 GWD/T and above) and short cooling period (180 days) will be processed in a phased manner. This is an unique experience and a very challenging task. High radioactivity (12000 curies/kg), large content of plutonium and the carbide matrix of the fuel, pose a multifaceted challenge in the development of the technology of reprocessing the spent fuel of Fast Breeder Test Reactor (FBTR). The larger plutonium content, provides a challenge from the point of view of second organic phase formation of the loaded solvent during solvent extraction; the mixed carbide spent fuel raises difficulties arising due to the dissolution and the undestroyed carbon during stripping in the extraction process. At Reprocessing Development Laboratory (RDL), IGCAR, process flow sheet and equipment have been developed to meet the challenges. Though the process is based on the PUREX flow sheet, major modifications are made to meet the above requirements. The flow sheet parameters have been analysed with extensive mathematical modeling of the extraction process. The demonstration of the process and equipment will be done at the Lead Mini Cell Facility.
 
 

LMC is a mini test bed where the basic flow sheet will be tested so as to provide the operating parameters for the future fast reactor fuel reprocessing plants. Since large concentrations of plutonium are handled, the hot cell facility is designed providing criticality control measures and a-shielding.
 
 

Apart from the shielded cell, a re-conversion laboratory converts Plutonium solution to solid, a second reconversion laboratory converts depleted Uranium in to solid, a control laboratory provides the required analytical services, a centralized control panel provides means to operate and to effectively interface with the facility. An underground storage vault houses tanks for storing the liquid wastes.
 
 

Process solution is transferred from one tank to another by vacuum aided airlifts. Process instrumentation provides the level, density and pressure details of the tanks through air purge type measurements and DP transmitters. PC based data acquisition system and a PLC based logic control system aid the operator to carry out the required process operations.
 
 

A schematic of the process is given in figure. The spent fuel subassembly from FBTR is disassembled into individual pins and stacked in magazines in the DPEND hot cells. The fuel pins are then transported to LMC in special a-tight containers and a lead shielded cask. The container is engaged with a matching a tight door at one end of the LMC facility and the fuel pins are transferred to the cell. The fuel pins are then chopped using a single pin chopper. The dissolution of the chopped pieces in nitric acid is carried out in an electrolytic dissolver manufactured from titanium. EODT (Electro Oxidative Dissolution Technique) process is used for the dissolution. This technique aids in the dissolution of mixed carbide fuel and as well as in the destruction of the organic acids produced during dissolution. The dissolver solution, after clarification in a high speed air operated centrifuge for the removal of small fines, is purified by solvent extraction using 30% Tri Butyl Phosphate (TBP) in a hydrocarbon diluent. Three solvent extraction cycles are used to achieve the required decontamination of uranium and plutonium from the fission products. Plutonium is separated from uranium by insitu electrolytic partitioning process.
 
 

The heart of the processing is solvent extraction. Three cycles of solvent extraction are used for getting decontamination factors as high as 107 with respect to fission products. The solvent extraction process is mathematically modeled to predict the concentration profiles. This helps in ensuring that second organic phase formation is avoided in the extraction unit, which is possible in the concentration regimes of plutonium encountered in the FBR fuel reprocessing.

A typical centrifugal extractor being tested in the engineering laboratory	Equipment in the containment box during erection

Since solvent undergoes radiation damage because of the high radiation levels of the solution, extractors with short contact time, namely, centrifugal extractors are used. The centrifugal extractors are designed and developed in house. After detailed testing, the extractors have been installed in the LMC facility. Three types of CEs are used in LMC:

a) electrically driven with adjustable interface

b) electrically driven with fixed interface

c) air motor driven with adjustable interface.

LMC will be used as the test bed for validating the centrifugal extractor designs. Insitu electrolytic mixer settler is used for separating plutonium from uranium. plutonium is precipitated as Plutonium oxalate and uranium as ammonium diuranate. These are calcined into their respective oxides in the re-conversion boxes.

Most of the important equipment, namely, single pin chopper, electrolytic dissolver, centrifugal extractors and electrolytic partitioner were developed in RDL. All the equipment have been installed in the LMC. The re-conversion boxes, wherePlutonium would be converted to oxide powder, are located by the side of the cell. Uranium conversion is carried out in a separate laboratory. Samples with high activity are analysed in the cell itself whereas other samples are analysed in the control laboratory.

High active liquid storage tanks in the waste vault

The high active liquid waste from the plant is stored in two large stainless tanks each having a capacity of 7200 litres which are housed in an underground waste vault. The floor and the walls (up to 1.25 metre) of the vault have been provided with stainless steel lining to prevent the seepage of active waste to the earth. The walls and roof of the vault have been provided with shielding using concrete of sufficient thickness. Organic wastes are stored in two stainless steel tanks each having a capacity of 1600 litres. These waste solutions will be transferred to Waste Immobilization Plant (WIP) for treatment and immobilization to provide a safe environment to the public. Alpha bearing solid wastes will be stored separately for treatment and disposal by WIP. Other wastes will be treated and disposed by the Central Waste Management Facility (CWMF).

All the equipment and systems have been installed in the cell. Commissioning trialsare in progress. It is proposed to process fuels having low burnup initially and then progressively process fuels with higher burnup and shorter cooling periods.
 

Single pin chopper being tested with uranium carbide pins in air atmosphere

 

A four step approach is adopted to establish fast reactor fuel reprocessing technology: The first step is the demonstration of LMC facility so as to establish the process and equipment; the second step is to operate the Fast Reactor Fuel Reprocessing Plant (FRFRP) (under construction) to optimize the plant operating conditions, to reduce the waste volumes and manrem exposures; the third step is to operate FRFRP with a few Prototype Fast Breeder Reactor (PFBR) to optimize the operating conditions for the oxide fuel and the fourth step is to operate the PFBR Reprocessing plant (PFRP) economically.
 
 

With the hot commissioning of LMC a major milestone in closing the FBR fuel cycle will be achieved.
 

Dr.(Ms.) Sangita Desai, T.K. Ghosh, Dr.(Ms.) R. Chinoy,

Dr. Ashok Mohan and Dr. (Ms.) K. A. Dinshaw

Tata Memorial Centre, Parel, Mumbai

Telepathology diagnosis: Extensive squamous metsplasia (H&E,10x)

Telemedicine is a practice of medicine at a distance. Telepathology, a subset of telemedicine, involves viewing slides under a microscope, capturing images in a suitable format, transmitting them to a distant site over a communication medium and viewing them on a video monitor. With the increasing sophistication in computer and communication technology the transmission of voice, video and text has become a reality. The results have good reliability and reproducibility. Declining costs of equipment and increasing availability of infrastructure in our country has further fueled the development in Tele-medicine.

The motivating force for this activity is that it is not always possible to provide the best expertise everywhere, specially in remote areas. For a country like India this is particularly significant. While the highest quality of expertise is available within the country, it is not available to a large section of population in the rural areas. It is particularly true for a super speciality hospital like Tata Memorial Hospital. While it has the highest level of expertise it cannot keep increasing its patient load due to various constraints. Improved telecommunication infrastructure now provides an opportunity to reach the expertise to these remote areas rather than move the patients to overcrowded urban facilities with associated hardships for the patient and the family.

Telepathology can be used for remote primary diagnosis, consultations, second opinion, remote presentation, quality assurance, consensus diagnosis for pathological review in clinical trials and education. The use of tele-pathology in management of patients is important since it allows faster diagnosis and consultations among remotely located specialist pathologists The benefits stem from easy accessibility to speciality consultants and timeliness of consultation. Needless to mention, this application is operable only in those rural and semi urban areas where a minimum standard of telecommunication infrastructure is available. However, such areas are growing in the country.
 
 

Technical requirements: The basic requirements include a microscope, an image capturing device mounted on a microscope, (preferably a charge-coupled-device camera) a computer with image editing software, communication mechanism between sending and receiving sites and a computer at the receiving site with a good quality monitor for viewing the images. In the present context the top of the bracket equipment required would cost approximately 4 lakhs (including PC but excluding the microscope), which is affordable for most organisations.

Telepathology system can be dynamic, static or hybrid. In the dynamic system the robotic microscope at the transmitting site is tele controlled by the consulting pathologist at the receiving site as though it is a microscope at the receiving end, permitting remote panning, magnification control etc.. While this could be the ideal arrangement and preferred in some western countries, there is a high cost involved and hence not the most suitable for a developing country. Specially as the nominal expertise required at the remote location in a static system can be easily developed through training which would have an additional advantage of upgrading knowledge at the remote locations as well.

In static telepathology the receiving end relies on the images prepared by the transmitting end where the operators have to learn to capture quality images with different magnification and transmit. They have also to learn proper sampling.
 
 
 

Sophisticated technology at the door step of Barshi

 

Telepathology at TMH: TMH’s experience in Telepathology revolves around Barshi- a rural landscape in interior Maharashtra, located around 500km away from Mumbai. Barshi prototypes typical rural India. The Nargis Dutt Memorial Cancer Hospital (NDMCH) is located in Barshi. With constant support and guidance from Tata Memorial Hospital (TMH), NDMCH has become an important cancer center for delivering health care to a sizable population from a number of villages and towns surrounding it in the districts of Solapur, Osmanabad and Latur.

Recognizing the merit of the work, the Bill and Melinda Gates Foundation have funded a prestigious project - Cervical Cancer Prevention Program (CCPP). The work is being carried out by NDMCH, Barshi, in collaboration with TMH/WHO/IARC, Lyon, France. It is estimated that more than 1,50,000 women will be screened under the project.

This project required pathologists in Barshi to carry out primary screening and quality assurance of surgical pathology and cytology material. Since the necessary expertise exists with TMH & since NDMCH is also a valued and proven partner, this provided a strong impetus for the development of telepathology link between the two institutions. Besides, the regular hospital cases are also included in the ambit of this exercise.

The basic equipment for the Barshi Centre was procured through Tata Memorial Hospital funds. Considering various factors such as telecommunication facility available at Barshi, daily load factor, economic viability, versatility, turn around time etc., it was felt that the store - forward methodology of transmission using simple telephone lines and Internet facility was the best option. Specially as ISDN line was not available at Barshi. Lease lines or V-SAT transmission are costly proposition in view of the number of cases expected to be refered. We opted for the cheapest means of communication viz. telephone and the ubiquitous Internet. The Internet connection at Barshi was through a 56 kbps dial-up modem. Barshi telephone exchange in turn is connected to Solapur district telephone exchange via a microwave link.

When everything was more or less in place and the initial experiment in transmitting pathology slides also succeeded, we found that connection was tripping too often. This did not permit images to be transmitted fully. Through interaction of TMH with the engineers at BSNL and District Engineer, Telecom, Barshi, the problem was identified as that of exchange synchronization for data transmission. DOT/MTNL/BSNL were persuaded and the problem was finally got over with the installation of appropriate hardware in the telephone exchange. This has led to remarkable improvement in communication reliability. With this we could achieve not only picture transmission but also transmission of large text files. The exercise is viewed as providing additional benefit from the interaction between an organisation like TMH & sub-urban services. This has benefited the e-mail users of the area as well, who could not transmit large image files earlier.

The image files, on an average were of the order of 600-800kb each. The quality of images received at TMH are good and of diagnosable grade.

The benefits of telepathology have now started accruing to the TMH/Barshi complex.
 

Laser induced fluorescence spectroscopy of

human tissues for cancer diagnosis

Dr. P K Gupta

Head, Biomedical Applications Section

Centre for Advanced Technology, Indore, Madhya Pradesh

In-vivo Autofluorescence setup for cancer diagnosis

Cancer is one of the most dreaded diseases of our time and has a very high incidence. Many cancers are curable if detected sufficiently early. Development of techniques to detect cancer at an early stage before the disease becomes difficult to manage is therefore an urgent current need. Early tumours often arise from tissue which have a rapid turnover of cells and are active in repair, like transformed mucosa on the surface of hollow organs (oral cavity, gastrointestinal tract, female reproductive organs etc.). These are often difficult to detect by the currently available techniques like X-ray computerised tomography, magnetic resonance imaging etc.. Further, there do not exist satisfactory methods to detect pre-malignant alterations, which precede many invasive cancers. Laser spectroscopic techniques hold considerable promise to solve both these problems. Further, these techniques have the potential for in-situ, near real time diagnosis and the use of non-ionizing radiation ensures that the diagnosis can be made repeatedly without any adverse side effects.

For optical diagnosis one mostly makes use of the light scattered from the tissue. Most of the scattered light is scattered without any change in frequency but it also has a very weak component which is scattered in-elastically i.e. with a change in frequency via processes like fluorescence, Raman scattering etc.. This inelastically scattered light is characteristic of the chemical composition and morphology of the tissue and may therefore help monitor onset and progression of a disease like cancer which is often associated with biochemical and morphological changes in the tissue. However, since the inelastically scattered light is a very small fraction of the incident light, practical applications based on this component require use of high spectral brightness source like lasers and appropriate light delivery and collection systems.

Laser Induced Fluorescence (LIF) has been used for diagnosing cancer in two ways. One approach involves systemic administration of a drug like haemaotoporphyrin derivative (HpD) which is selectively retained by the tumour. When photoexcited with light of appropriate wavelength, the drug localized in the tumour fluoresces. This fluorescence is used for detection and imaging of the tumour. Photoexcitation also leads to populating the triplet state via intersystem crossing. The molecule in excited triplet state can directly react with biomolecules or lead to generation of singlet oxygen, which is toxic to the host tissue. The resulting destruction of the host tissue is exploited for photodynamic therapy of tumour. From the point of view of use in diagnosis this approach has two drawbacks; a possible dark toxicity of the drug and the possibility of drug induced photosensitization. There is therefore interest in developing tumour markers where the triplet state is rapidly quenched and thereby photosensitization is avoided. The other approach, the one that has received more attention in recent years, does not use any exogenous tumour markers. Instead it exploits for diagnosis the subtle changes in the spectrum as well as the decay time of fluorescence from native tissues as it transforms from normal to the malignant state. The studies carried out over the last few years have shown considerable promise of this approach for diagnosis of the cancer of various organs like uterine cervix, esophagus, lung, breast, and oral cavity.

At Biomedical Applications Section, CAT, several studies have been carried out towards development and evaluation of laser induced fluorescence (LIF) spectroscopy for the diagnosis of cancer. In the initial phase of this work, studies were carried out on tissues resected at surgery or biopsy from patients with cancer of different organs - uterus, breast and oral cavity. The objectives for these studies were to establish the potential of the approach, find the excitation wavelength(s), which result in significant differences in the fluorescence from normal and diseased tissue and develop algorithms, which can exploit these differences for diagnosis. These studies revealed that nitrogen laser operating at 337nm was a good choice for exciting tissue fluorescence. Algorithms developed to quantify the spectral differences in the nitrogen laser excited fluorescence from malignant, benign tumour and normal tissue sites provided good discrimination with sensitivity and specificity towards cancer of ~ 90% in general and up to 100% in favourable cases. Another important finding of these studies was that while the malignant breast tissue sites (invasive ductal carcinoma) were considerably more fluorescent than the benign tumour (fibroadenoma) and normal tissue sites (uninvolved region of the resected tissue), reverse was the case with tissue from oral cavity. For the latter the malignant sites (squamous cell carcinoma) were considerably less fluorescent than the normal tissue. Various measurements on tissue fluorescence (excitation-emission spectroscopy, synchronous scan and time resolved measurements) were carried out to unravel the reasons for the observed difference in the fluorescence from normal and malignant sites. These suggest a significant variation in the concentration of the fluorophores in the different tissue types. In particular, the studies showed that while concentration of NADH (reduced nicotinamide adenine dinucleotide) is higher in malignant breast tissues compared to benign tumour and normal breast tissues the reverse is true for tissues from oral cavity where NADH concentration is higher in normal oral tissues. These results have been confirmed by enzymatic measurements of NADH concentration in malignant and normal tissues from breast and oral cavity. The differences in fluorophore concentration inferred from spectroscopic studies not only account qualitatively for the observed spectral differences in the autofluorescence spectra of the normal and diseased oral and breast tissues but also explain why nitrogen laser is a good excitation source.

In principal a quantitative evaluation of the concentration of fluorophores is also possible from the measured fluorescence spectra at a given excitation wavelength. This however requires measurement of tissue optical parameters and modeling of light transport in tissue. Work in this direction is also being carried out at CAT. Our measurements on breast tissue showed that the absorption and scattering coefficients are larger in malignant sites as compared to normal. The larger scattering coefficient of malignant sites has an interesting consequence. Whereas for thin tissue sections (thickness < optical transport length) the depolarization of fluorescence was observed to be smaller in malignant tissues compared to normal the reverse was observed for thicker tissue section. The latter effect has been shown to arise due to larger scattering in malignant tissue.

Prototype systems suitable for evaluation of the LIF technique for in-vivo diagnosis of cancer have also been developed. These comprise a sealed-off N2 laser (7ns, 10mJ, 10Hz), an optical fibre probe, and a gateable intensified-charge-coupled-device (ICCD) detector. A pilot study on 25 patients, with histopathologically confirmed squamous cell carcinoma of oral cavity, has been carried out using one of the set up. The discrimination algorithm developed could differentiate the squamous cell carcinoma of the oral cavity from normal squamous tissue with a sensitivity and specificity towards cancer of 86% and 63%, respectively. The reason for the relatively lower specificity values appears to be the fact that most of the patients who participated in this study were at an advanced stage of malignancy. Some of the visually uninvolved sites assumed to be normal might therefore not be truly normal, since it is known that the cancerous tumour may have some biochemical changes occurring due to the field effect of malignancy. Indeed, when the discrimination analysis was carried out on the basis of two tissue spectra per patient one averaged over all the malignant sites and the other averaged over all the normal tissue sites, sensitivity and specificity towards cancer of ~100% were obtained. The unit has now been installed at the local Government cancer hospital for a detailed clinical evaluation of the technique.
 

 News ....
 

Film on UCIL released
 

Dr. Anil Kakodkar, Chairman, AEC releasing the film. On the dias are Shri B. Bhattacharjee, Director, BARC (left) and Shri R. Gupta, CMD, UCIL.

Shri R. Gupta, CMD, UCIL informed that in view of the upcoming PHWR’s and the ambitious plan of reaching installed capacity of 20,000 megawatt (e) by the year 2020, UCIL is engaged in expansion of its activities which include deepening of its existing mines and increasing the ore processing capacity. He emphasized that the impact of mining operations and processing of uranium ore on environment is kept much below the limits prescribed by the statutory bodies and there is no adverse effect on the health of UCIL’s employees or the people living in the surrounding areas.

Shri Rajeev Shah, the director of the film recollected his pleasant experiences while making the film. He complimented and appreciated the support of UCIL and DAE in making the film. The function ended with the screening of the film.

Symposium ......
 
 

National Symposium on Environment
 
 

Dr. Anil Kakodkar, Chairman, Atomic Energy Commission, delivering inaugural address

The Board of Research in Nuclear Sciences (BRNS) sponsored the 11th National Symposium on Environment (NSE-11) was held at Rajasthan College of Agriculture, Udaipur during June 5-7, 2002. The Symosium was jointly organized by Rajasthan College of Agriculture and Rajasthan Atomic Power Station, Kota.

Dr. Anil Kakodkar, Chairman, Atomic Energy Commission, in his inaugural address stressed on sustainable development without impairing the environment. He spoke about the increase in green house gases and the predicted changes in climate. He was of the opinion that the environmental issues should be tackled at three levels - local, national & international. Shri K.P. Ojha, Station Director, Rajasthan Atomic Power Station (RAPS), in his introductory remarks, dwelled on the importance of the World Environment Day and recounted the efforts of nuclear power industry towards preservation and improvement of environment. Prof. A.K. Singh, Vice Chancellor, Mohan Lal Sukhadia University, in his address called for an attitudinal change in education to bring about an awareness of the importance of environmental quality. Prof. A.S. Faroda, Vice Chancellor, Maharana Pratap University of Agriculture and Technology, presided over the function and spoke about the need for eternal vigilance on environmental issues. Prof. G.S. Sharma, Dean, Rajasthan College of Agriculture, and Chairman, Symposium Organising Committee welcomed the gathering and Dr. L.L. Sharma, Secretary of the Organising Committee proposed a vote of thanks.

This symposium series has attracted increasing attention in the country. Response to the call for papers this year was overwhelming and 140 papers covering the specified topics were received. However, because of paucity of time, only 82 papers could be accommodated for presentation in 10 technical sessions including one poster session which had 26 poster presentations. There were 9 invited talks on important environmental issues. Shri P.M. Wagh, Director, Health, Safety & Environment Group, NPCIL, described the safety features adopted in nuclear industry. In view of the changing perceptions in environmental management, he reiterated the fact that nuclear power will have to play an important role in the long term management of the country’s power needs. Dr. K. S. Parthasarathy, Secretary, Atomic Energy Regulatory Board, gave a lucid account of the evolution of the atomic energy regulatory programme. He also mentioned about the safety programs adopted in the various fields where radioactivity is handled. Dr. S. Krishnaswamy highlighted the use of U-Th series in studies for particle dynamics, estimating ground water discharge into sea, sediment accumulation rates in lakes etc. Dr. K. Raghu (ex-BARC), Jai Research Foundation, Gujarat, talked on phyto-remediations of soils polluted with pesticides and waste waters. Dr. R.V. Singh from Rajasthan College of Agriculture, Udaipur talked on remedial measures for protection of ground water from pollution. Dr. N.C. Aery from University College, Udaipur, explained various aspects of phyto-remediations of metalliferrous wastes. His study concentrated on zinc and copper tailings from Zawar and Khetri plants. The 82 contributed papers covered broadly the areas : Air pollution, Water pollution, Waste management, Radioactivity (Natural and man-made), Environment and biological aspects and Air quality monitoring and Modeling. The Symposium Sessions were well attended.
 

 TECHNOLOGY TRANSFER....