Radiobiology with laser-driven electron accelerators

Transcription

1 Radiobiology with laser-driven electron accelerators L. Labate1,2, M.G. Andreassi3, F. Baffigi1, R. Bizzarri4, A. Borghini3, G. Bussolino1, G. Candiano5, C. Casarino5, F. Di Martino6, L. Fulgentini1, P. Koester1, F. Ghetti4, M.C. Gilardi5, A. Giulietti1, D. Lamia5, T. Levato1, G. Russo5, A. Sgarbossa4, C. Traino6, L.A. Gizzi1,2 1 ILIL, Istituto Nazionale di Ottica, Consiglio Nazionale delle Ricerche, Pisa, Italy Istituto Nazionale di Fisica Nucleare, Sezione di Pisa e Laboratori Nazionali di Frascati, Italy 3 Istituto di Fisiologia Clinica, Consiglio Nazionale delle Ricerche, Pisa, Italy 4 Istituto di Nanoscienze, Consiglio Nazionale delle Ricerche, Pisa, Italy 5 Laboratorio di Tecnologie Oncologiche HSR-Giglio, Istituto di Bioimmagini e Fisiologia Molecolare, Consiglio Nazionale delle Ricerche, Cefalu', Italy 6 U.O. Fisica Sanitaria, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy 2

2 The Intense Laser Irradiation Laboratory group PEOPLE Leonida A. GIZZI (CNR)* (Resp.) Giancarlo BUSSOLINO (CNR) Gabriele CRISTOFORETTI (CNR) Luca LABATE (CNR)* Fernando BRANDI (CNR), Ric. TD. Petra KOESTER (CNR), Ric. Contr. Tadzio LEVATO (CNR), Ric. Contr. Federica BAFFIGI (CNR), A.R. Paolo FERRARA (CNR), A. R. Lorenzo FULGENTINI (CNR), A.R. Antonio GIULIETTI(CNR), Assoc Danilo GIULIETTI (Univ. Pisa), Ass.* Daniele PALLA, PhD student * Antonella ROSSI (CNR) Tech. * Also at INFN Main fields - Laser-driven acceleration of electrons and related secondary sources - Laser-plasma interaction studies relevant for ICF

3 Outline Overview of the Laser WakeField (LWFA) technique Why using LWFA for radiotherapy A taste of the first radiobiology studies with LWF-accelerated electrons

4 The Laser WakeField Acceleration concept Electron plasma waves meet the requirements for charged particle acceleration: - intense longitudinal electric fields - phase velocity close to the speed of light Analogy with a surfer How to create a high amplitude plasma wave? Ponderomotive force (laser pulse) Coulomb force (charged particle bunches) Laser Wakefield Acceleration use the first approach, made possible by ultrashort and ultraintense laser pulses Analogy with a boat F -grad I Electron density perturbation Laser pulse

5 RF-based vs. laser-driven plasma accelerators Classical (RF-based) accelerators limits Maximum E-field ~few tens of MV/m (due to breakdown) Synchrotron radiation losses large radius Laser-driven plasma accelerators Plasma is an ionized medium no structural limits to the E-field Electric field amplitude in a plasma wave: E~ E ~ 0.3 GV/m E ~ 300 GV/m n for 1% density perturbation at n ~ 1017cm-3 for 100% density perturbation at n ~ 1019 cm-3

6 LWFA: the basic setup and accelerator footprint Basic arrangement The laser pulse is focused in the proximity of the entrance edge of the gas-jet Electrons are accelerated in the forward direction Gas-jet nozzle e- bunch La s er

7 A glance at the (now historical ) literature 1979: proposal by Tajima&Dawson 2004: Dream beam front cover of Nature (3 papers reporting highquality e- bunch production) End of noughties: routine production of stable e- bunch 2006: GeV energy reported

8 Table-top e- accelerators for medicine Using laser-driven (table-top) electron accelerators for radiotherapy is attracting increasing attention of the international scientific community Limits of conventional accelerators: - large footprint and reduced operational flexibility - the available electron energy is limited by the LINAC size - need for UHV (with possible failures) - need for a large radioprotected area Laser-driven accelerator Conventional (RF) accelerator A laser-driven electron accelerator - exhibits a reduced footprint, due to the fact that a single ultrashort laser system can be used for different treatment areas - the active source (to be hosted in a radioprotected area) can be as small as a few tens of cm - higher energy bunches could be available - no need for UHV, high power supplies,...

9 Conventional vs. laser-driven e- bunches Comparable figures as for electron energy, bunch charge, rep rate, average current Bunch duration ( peak current) of laser-driven accelerators much shorter An assessment of the effects of such high-current e- bunches on biological samples is needed at a pre-clinical stage (and new applications in perspectives?) Biological Effects of laser-accelerated Electrons for Medicine

10 Setup for irradiation of in-vitro Bio samples position e- bunch Gas-jet target Biological samples are irradiated in air Driver laser beam An ad hoc collimator and vacuum-air window for the e- bunches were designed, simulated and tested using GEANT4 The e- bunch was fully characterized, in terms of energy, charge and divergence by means of calibrated stacks of RadioChromic Film detectors and MonteCarlo simulations

11 Typical e- spectrum and beam transverse profile Typical spectrum selected for radiobiology studies extends up to ~20MeV However, dosimetric measurements and comparison with GEANT4 simulations show that a strong low-energy (~MeV) component exists The transverse profile of the dose distribution in air shows a variation of the order of 10% across a 20mm size spatial region

12 Dosimetric characterization The dose/shot on the sample was retrieved by comparing experimental measurements performed using suitable stacks of GAFchromic films with GEANT4 MonteCarlo simulations of the electron beam transport/interactions Retrieved dose ~100mGy/shot Cumulated doses up to 1 10 Gy were provided at 1Hz rep rate in a few 10s of seconds Scattering/interactions processes make the bunch last for a few picoseconds at the sample position

13 Example of DNA damage studies Micronuclei induction in cytokinesis-blocked human blood lymphocytes The micronuclei assay was used to evaluate DNA damages in human blood lymphocites at different doses (the doseresponse curve was obtained by scoring 1000 cells of two donors (each on two replicated experiments). Rates of MNs were significantly higher than baseline from 0.20 Gy ( p=0.04) and 0.5 Gy (p=0.009) for first and second donors, respectively. MN/1000 cells p<0.001 First donor (m ale) was carried out; a comparison with e- bunches from a LINAC is also ongoing p= p=0.004 p= Baseline A comparison with damage from X-rays at the same doses Dose (Gy) 14 52

14 Example of membrane damage studies [1/2] Cell organization: barrier, signalling,... τr Fluorescence microscopy of suitable fluorophores targeting specific cell region is a powerful tool to investigate cell biochemistry: - poorly invasive - high sensitivity (down to single molecule) - high spatial resolution (down to nm)

15 Example of membrane damage studies [2/2] Targeting cell membrane The molecule Ge1 was used to study the dielectric constant of the cell membrane after irradiation at different doses Significant increase in membrane hydrophobicity upon irradiation: biological mechanism to be investigated further

16 Summary and conclusions Laser-driven electron accelerators (based on the Laser WakeField Acceleration concept) have now entered a mature phase and are rapidly going toward real applications in medicine (in particular, radiotherapy) The group operating at the ILIL laboratory is carrying out a long term study of laser-driven electron accelerators and high energy photon sources based on them In particular, a project is ongoing aimed at assessing, at a pre-clinical stage, the possibility of using small-scale, TW-class laser systems to produce electron bunches at a few tens of MeV energy, of interest for radiotherapy An ad hoc setup has been studied, simulated and tested, allowing irradiation of in vitro samples in air The first tests show a biological response similar to the one expected from the literature for irradiation using conventional (RF linacs) electron bunches

17 The ILIL laboratory Laser main figures -energy: up to 450mJ on target -pulse duration <40fs -ASE contrast > 109 -M2 < 1.5 -intensity: up to 2x1019 W/cm2 Target area equipment -2 dedicated vacuum chambers ( gas-jet and solid targets) -optical and X-ray diagnostics -electron diagnostics -integrated environment for diagnostic data automatic collection