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Experimental Dosimetry of High Dose Rates X-Ray Microbeams Fields for the MRT Program

Curing cancers in all their different forms have been, till nowadays, one of the most difficult challenges for medicine. In order to improve the life expectancy and or quality in palliative cases, several physics techniques have been developed based on the use of ionizing radiation. As an example, X-rays have been used to treat a cancer patient only few years after their discovery in 1895 [1].
All these techniques are known with the general name of “Radiotherapy”
The use of different forms of ionizing radiation (i.e. the protons and carbon ions), the born of new powerful and precise techniques as the Gating Intensity Modulated Radiation Therapy (IMRT) and new kind of machines like the Cyberknife are just few selected examples of the technical developments in Radiotherapy in the last two decades.
However, all these techniques have to face the same problems in terms of preserving the normal tissues close to the tumor. These ones are exposed to a large amount of dose that could cause their definitive damage or necrosis, potentially causing severe collateral effects to the patient. Those effects can be dramatic when organs in the central nervous system are involved.
Since several years, at the ID17 Biomedical Beamline of the ESRF (European Synchrotron Radiation Facility) intense research program in radiotherapy is carried out in preclinical and clinical models using a powerful source of ionizing radiations, the Synchrotron Radiation.[2]
One of recently developed techniques is the Microbeam Radiation Therapy (MRT) [3].
MRT has been invented in the 90’s at Brookhaven National Laboratories (Upton, New York), with the aim of finding a treatment for brain gliomas, for which at that time (and still nowadays!) only palliative treatments could be applied. In MRT, the dose is delivered by microbeams, i.e. the ionizing radiation is spatially fractionated before delivery to the tissues.
MRT uses extremely high doses rates (~10000 Gy/s) to avoid that the cardiosynchronous movements of tissues can destroy the spatial structure of the microbeams within the tissues; the ideal source to create an array of identical microbeams is synchrotron radiation, because of the very high flux density, but also for its intrinsic low divergence, that allow an “easy” spatial fractionation of the radiation.
Due to the extremely high tolerance to the dose that healthy tissues show to dose delivered in microbeams, using MRT it is possible to deliver strong dose to the cancerous tissues without destroying the healthy ones. The results of the preclinical studies support the idea that MRT could be a suitable technique for the treatment of the cerebral tumors that represent the 30 % of the tumors that affects childhood in Europe.
It is clear that one of the key-word in MRT is Microdosimetry [4]. The aim of this Thesis work is that to explore two of the most important aspects of dosimetry in MRT: the calibration of dosimeters and the interpretation of the results of the dose measurements.
In fact, due to the very specific characteristics of MRT, in terms of spectrum (broad and at lower energy 50-35 keV with respect to standard radiotherapy using ~6 MeV photons), high dose rate (10000 Gy/s to be compared with 1 Gy/minute of conventional therapy), spatial fractionation (25-100 micron wide beams) no one of the standard procedures applied in clinical dosimetry can be used.
It is not possible even to imagine the clinical application of MRT without a complete management of all these aspects.
In the first part of this work is presented a description of the different available dosimeters, in particular of the HD-810 Gafchromic films (used at the Biomedical Beamline at ESRF) and of the two instruments used for the film reading: an Epson Flat Panel Scanner v750 and a Microdensitometer J.L Automation 3CS.

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7 2- Microbeam Radiation Therapy 2.1 Principles and history The first studies about the effect of microbeams on the human body were made during the 50’s, with the aim of understanding the effect of the cosmic rays on human beings (the space programs were just starting in those days!). Microbeams were used to simulate the effect of cosmic rays, the latter being a radiation arriving in small and spatially separated bunches; deuteron beams of energy 22 MeV and width of about 25 µm were chosen as a radiation model delivered to rodents. These pioneer works were made by H.J Curtis and his team at the Brookhaven National Laboratory, Upton, New York [5]. The results of this work were surprising: Curtis and his team discovered that they had to use a much higher amount of dose, using microbeams of 25 micron, to obtain the same biological effect (damage of the visual cortex in mice) than that caused by beams of 1 mm width. These results were indicated as the Dose Volume Effect: the smallest is the irradiated volume the highest is the dose tolerated by normal tissues. In particular, Curtis’ team realized that depositing several thousands of Grays in ~ 25 micron microbeams, only cell nuclei along the microbeams path were destroyed, while the tissue structure, the organ architecture and function remained intact. They also proposed the first hypothesis to explain this phenomenon in the fast repair of radio-biological microscopic damages [6].

Laurea liv.II (specialistica)

Facoltà: Scienze Matematiche, Fisiche e Naturali

Autore: Maurizio Morri Contatta »

Composta da 108 pagine.

 

Questa tesi ha raggiunto 876 click dal 14/04/2011.

Disponibile in PDF, la consultazione è esclusivamente in formato digitale.