Aloke Chatterjee

Computer simulation of initial events in the biochemical mechanisms of DNA damage

Understanding the systematic and quantitative correlation between the physical events of energy deposition by ionizing radiation and the ensuing chemical and biochemical processes leading to DNA damage is one of the goals in radiation research. Significant progress has been made toward achieving the stated goal by using theoretical modeling techniques. These techniques are strongly dependent on computer simulation procedures. A review of such techniques with details of various stages of simulation development, including a comparison with available experimental data, is presented in this article.

Radiation chemistry of heavy-particle tracks. 2. Fricke dosimeter system

LBL-10283 Preprint Submitted to the Journal of Physical Chemistry RADIATION CHEMISTRY OF HEAVY PARTICLE TRACKS. II. THE FRICKE DOSIMETER SYSTEM Aloke Chatterjee and John L. Magee March 1980 TWO-WEEK LOAN COPY This is a Library Circulating Copy which may be borrowed for two weeks. For a personal retention copy, call . Info. Division, Ext. 6782. Prepared for the U.S. Department of Energy under Contract W-7405-ENG-48

Particle radiography and autoactivation

Abstract Two new techniques are being developed using accelerated heavy-ion beams that will allow better localization of deep-seated tumors and diagnostic imaging adjustment of therapy beams. Both depend on the unique physical characteristics of the interaction of heavy particles with matter. Heavy-ion radiography uses monoenergetic particle beams for imaging the distribution of electron densities in tissue with very high sensitivity for small density differences. It is based on the exact range-energy relationship of heavy particles. Images are obtained of the pattern of stopping heavy ions in a stack of plastic nuclear detector foils. Differences as small as 0.2% in tissue stopping power have been detected and measured. Work is in progress on computerized tomography. 260 MeV/nucleon carbon ions give considerably better depth and lateral resolution than protons or helium ions at low doses. When ordinary heavy-ion beams pass through matter, some of the particles become radioactive and form an “autoradioactive” component of the beam. Following deposition of the radioactive particles, γ-ray coincidence techniques have been used to measure the depth penetration of the beam in tissue. Work is in progress on a special γ-ray camera to image the distribution of beam stopping regions; since measurements are made between beam pulses, this technique can be used to alter by feedback methods the range penetration of the therapy beams. 11 6 C, 15 8 O and 19 20 Ne isotopes have been used. In the future, it may be feasible to use pure radioactive heavy-ion beams for therapy with simultaneous imaging of the therapy distribution.

High energy beams of radioactive nuclei and their biomedical applications

Abstract It is possible to produce energetic beam of radioactive nuclei, as secondary beams, from the heavy-particle compound accelerator called BEVALAC. These beam can be focused into experimental areas without significant contamination using suitable magnetic filters and proper beam-optics. Properly selected high-energy beam of radioactive nuclei (those which decay by positron emission) can provide a truly unique opportunity to evaluate the effectiveness of these beam in localizing the Bragg peak on a tumor volume—necessary in heavy-particle therapy. Preliminary data are presented here to demonstrate the possible use of these beam in radiotherapy treatment-planning verification.

A spur unfolding model for the radiolysis of water

Abstract A previous treatment of the theory of the chemical action of high energy electrons contains the spur yield, Gsp, as a parameter. Use of this theory allows one to obtain Gsp for any reaction for which sufficient experimental data are available. A model for the spur in dilute aqueous solution is considered here with the aim to provide some reaction details in that track entity. From the detailed considerations presented here, it appears that the size of the spurs must be taken as decreasing with the number of radical pairs initially present, if the radiation chemical yields are to be compatible with experiments. There is an unavoidable lack of uniqueness in such treatments which has led to the question of further comparison with experiments. This important question is also discussed.

An Imaging Instrument for Positron Emitting Heavy Ion Beam Injection

The design and performance of an instrument for the imaging of coincidence annihilation gamma rays emitted from the end point of the trajectories of radioactive high-energy heavy ions is described. The positron-emitting heavy ions are the result of nuclear fragmentation of accelerated heavy ions used in cancer theraphy or diagnostic medicine. The instrument constructed is capable of locating the ion beam trajectory end point within 1 mm for an injected activity of 200 nanoCi in a measurement time of 1 sec. in some favorable conditions. Limited imaging in three dimensions is also demonstrated.

Monte Carlo approach in assessing damage in higher order structures of DNA

We have developed a computer monitor of nuclear DNA in the form of chromatin fibre. The fibres are modeled as a ideal solenoid consisting of twenty helical turns with six nucleosomes per turn. The chromatin model, in combination with are Monte Carlo theory of radiation damage induces by charged particles, based on general features of tack structure and stopping power theory, has been used to evaluate the influence of DNA structure on initial damage. An interesting has emerged from our calculations. Our calculated results predict the existence of strong spatial correlations in damage sites associated with the symmetries in the solenoidal model. We have calculated spectra of short fragments of double stranded DNA produced by multiple double strand breaks induced by both high and low LET radiation. The spectra exhibit peaks at multiples of approximately 85 base pairs (the nucleosome periodicity), and approximately 1000 base pairs (solenoid periodicity). Preliminary experiments to investigate the fragment distributions from irradiated DNA, made by B. Rydberg at Lawrence Berkeley Laboratory, confirm the existence of short DNA fragments and are in substantial agreement with the predictions of our theory.

A Computational Approach to the Relationship between Radiation Induced Double Strand Breaks and Translocations

A theoretical framework is presented which provides a quantitative analysis of radiation induced translocations between the ab1 oncogene on CH9q34 and a breakpoint cluster region, bcr, on CH 22q11. Such translocations are associated frequently with chronic myelogenous leukemia. The theory is based on the assumption that incorrect or unfaithful rejoining of initial double strand breaks produced concurrently within the 200 kbp intron region upstream of the second abl exon, and the 16.5 kbp region between bcr exon 2 and exon 6 interact with each other, resulting in a fusion gene. for an x-ray dose of 100 Gy, there is good agreement between the theoretical estimate and the one available experimental result. The theory has been extended to provide dose response curves for these types of translocations. These curves are quadratic at low doses and become linear at high doses.

On The Applicability Of The Maximum Likelihood Estimator Algorithm For Image Recovery In Accelerated Positron Emitter Beam Injection

The Maximum Likelihood Estimator (MLE) algorithm for tomographic image reconstruction is being investigated in substantial detail by a number of research groups, as it appears to promise images with very low noise and increased sharpness when compared with filtered backprojection techniques. Recently, however, it has been found that the reconstruction of data from uniform activity distributions exhibits strong peaks and valleys when the number of iterations increases toward a maximum in the likelihood function. This problem has now been investigated with our Positron Emitter Beam Analyzer (PEBA) camera, which, because of its small size and favorable geometry, has allowed an analysis with enough detail to find the origin of that apparent instability. The findings can be summarized as follows: 1) The very low noise of the MLE reconstructions comes about by the ability of the Poisson-based MLE algorithm to generate an image which favors the matching of experimental data (detector pairs) containing few counts. 2) The image instability at a high number of iterations is a direct consequence of the above characteristic. 3) The matrix of probability elements needed for the MLE reconstruction provides the link between the two above observed phenomena. It appears that, by proper system design, it is possible to obtain the favorable low noise characteristic without the instability. The applicability of the above findings to true tomography (PEBA does not carry out a true tomographic reconstruction) seems direct, but confirmation should be obtained by further research on the question.