A real time in vivo dosimeter integrated in the radiation protection disk for IORT breast treatment 1G. Felici, 2M. Iori , 3A. Montanari , 3N. Tosi, 2E. Cagni, 2A. Botti, 1A. Ciccotelli, 4L. Strigari 1 )Sordina IORT Technologies Spa, Aprilia, Italy 2) S. Maria Nuova Hospital - IRCCS, Reggio Emilia, Italy 3) National Institute of Nuclear Physics - Section of Bologna, Italy 4) National Cancer Istitute Regina Elena, Roma, Italy

IORT: current practice with linacs An electron beam (4-12 MeV) is delivered in one session by a mobile LINAC. A protection disc is inserted under tissue to be treated. The correct alignment of the protection disc is verified by surgeon by touch when the disc is no more visible. The entrance dose is measured in one point (MOSFET) at applicator output. The dose delivered to the target is measured offline (radiochromic film) above the protection disc.

Critical points The blackened area of the gafcromic film also allows to check the centering of the protections disc during the IORT treatment delivery. The monitoring of the dose on the target is done in one or two points just at the end of the treatments (MOSFET) or hours, on the entire beam region, by the end of treatment session. This could causes uncertainties on the dose delivered to tissue during the treatment. Healthy tissues that are posed under the target (ribs, lung, etc..) need to be protected, but correct positioning of the protection disc is verified .. when it is too late & the fraction of acceptable alignments is far from 100%. Some examples of wrong alignment: Usiamo le GAF del tipo EBT3, 1cGy – 40Gy, Scanner Epson 10000XL, film a double layer, 24h, le leggiamo nel red. surgical stitches

Plastic scintillator Cast sheet of polyvinyl toluene or polystyrene doped with organic scintillating molecules; emits violet light proportionally to the dose deposited in the detector volume; light collection with Wave Length Shifting (WLS) fiber (green light); WLS fiber coupled to photodetector. Main properties: water equivalent, no perturbation of beam; no energy dependence, linear to dose; high rates capability; negligible temperature dependence; high radiation tolerance; low cost. Materiale plastico (like PMMA) drogato con molecole organiche, se ne sono di due tipi, il nostro era toluene, il più sensibile, l’altro lo è meno. Con le radiazioni le molecole si eccitano e poi subuto si diseccitano, emettendo una luce nel violetto o ultravioletto. La luce dell’intero blocco, viene raccolta da una singola fibra ottica (WLS) [anche questa è drogata si eccita e si diseccita ad energia più bassa, riceve luce nel violetto e la emette nel verde, e guida la luce ai suoi estremi, a più bassa energia e quindi frequenza]. La luce raccolta è solo in parte di quella generata nel rivelatore, ma nonostante il doppio passaggio la luce prodotta è proporzionale alla dose rilasciata nel rivelatore plastico. E’ una raccolta di energia in due step. I tempi in gioco per emissione e raccolta sono dell’ordine dei nano-secondi, mentre in una IC sono dell’ordine dei micro-sec. Il rivelatore plastico è pressochè equivalente all’acqua, può avere ampie dimensioni rispetto alle fibre, nel nostro range di uso non satura, non dipende dalla temperatura ed attorno agli 80° fonde, con dosi superiori a 1000Gy i centri di colore lo fanno ingiallire, sotto variazione inferiore ad 1%, cambia risposta in quano centri di colore o molecole droganti cambiano si rompono ecc.. - Nelle fibre scintillanti, diametri di 1 o 2mm, stesso drogaggio di molecole organiche, ma luce prodotta dalla fibra e guidata dalla fibra con riflessione totale in quanto chiusa. Case Trap

Proposed solution Insert a scintillator detector between the metallic disc and its PTFE cover that compose the protection disk. Detector formed by 4 leaves, with independent WLS fibers. If the beam is centered on the disc, each leaf produces the same light output. Beam PTFE cover 4-leaves detector Metallic disc PTFE – Teflon Steel 3mm Teflon 3mm Up to 8MeV, less than 1% below From 10 to 12 MeV we can arrive at 1 – 2% Not used for boost (< 10Gy), used always for radical treatment 21Gy Dose that cause a broken of the rib is 6Gy, used the PDD in water for calculating the dose in the other organ Thickness ?? Patent application A new dosimeter is proposed that provides in real time (IT Patent TO2014A000943): the correct centering of the protective metallic disc. the on-line measurement of the integral dose. Wrong beam centering

First prototype & preliminary tests Light  Photodiode  analog signal  Fast ADC  digital pulse shape (20 ns sampling time). Each pulse shape is visible online and recorded for offline analysis. UNDER BEAM: plastic scintillator tile & optical fiber REMOTE READOUT: photodiode & fast ADC The prototype was irradiated with a LIAC 10 MeV model (SIT) at ASMN-IRCCS in order to: measure the linearity of scintillator response under the electron beam; compare its dose measurements with a calibrated ionization chamber (Advanced Markus, PTW). - Tile (piastrella ricoperta da una copertura plastica nera) – collegata ad una fibra – spessore 1 cm La IORT ha 1 impulso ogni 10 Hz, il campionamento del rivelatore ottico è a 50 MHz (ecco perchè è rapido) Advanced Markus, poca dipendenza da rateo, punto sensibile in superficie, diametro di 5mm x 1mm di spessore Tile - mattonella

Pulse shape & integrated charge The ADC samples (every 20 ns) the pulse shape corresponding to the light output of the scintillator (proportional to dose) for each bunch of Linac electrons The histogram of the integrated charge of 2000 pulses gives an indication on the uniformity of dose delivered by each pulse Less single pulse dose uniformity at higher beam energies 1.5 μs 6 MeV Pion o Ksat sono la stessa cosa Il grigio rappresenta un impulso lungo 1.5us che viene campionato ogni 20 ns, la sua area è proporzionale alla dose, è il numero di elettroni che compone un impulso. Fatte selezionando lo stesso tempo o lo stesso numero di impulsi si ottengono le stesse misure. Tra 4 – 10 MeV, la durata di 1 impulso varia tra 1 – 2 microsec, la dose per inpulso varia tra 0.5 – 3 cGy. La macchina lavora in un range di frequenza tra 10 – 25Hz. L’integrale di quello istogramma è la distribuzione degli impulsi. La dose per impulso nella IORT varia con l’energia ed il diametro dei coni: Al crescere dell’energia la dose per impulso cresce (4MV -> 0,5 cGy/p, 10MV -> 3 cGy/p) Al crescere del diametro dei coni la dose per impulso diminuisce (cono 4cm -> 100%, cono 10cm -> 50%). La dose per impulso nei LINAC per gli elettroni è bassa < 0,1 cGy/p ma high dose-per-pulse FFF beams arriva a 0,2 cGy/p. Variando la dose per impulso, non posso calcolare ksat con il metodo delle tue correnti per le camere a ionizzazione a piatti paralleli. SAD = 71,3cm, energie 4 – 10 MeV, campi con coni da 3 – 10cm, angoli dei coni da 0, 15, 30 e 45°, dose in superficie 85% (4MeV) - 92% (10MeV), ratei da 1-10 Gy/min (4MeV) a 1-30Gy/min (10MeV), isodose 80% da 1,3 a 3cm, contaminazione dei raggi x è < 0,7% per cono 10cm a 10MeV, corrente fascio 1,5 mA. SSD = 71,3cm, 28,5 MU/Gy, 2,3 cGy/imp (p) (23 mGy/p). 1 burst (scoppio) del linac è 1 cGy 6 MeV The area of the pulse shape (integrated charge) correspond to the dose delivered to scintillator by a single burst of the Linac (~ 1 cGy) The integral of the histogram is proportional to the total dose

Results: linearity & correlation Measure the dose delivered in various runs with different numbers of pulses: Dose measured by the scintillator & chamber at different energies and d/p (2000 pulses): IONIZATION CHAMBER (total charge read out by electrometer) SCINTILLATOR (sum of the integrated charges of all pulses) 10 MeV 8 MeV Grafico 1 Rappresenta la linearità della risposta con l’energia per la camera a ionizzazione, ventilata, ed il grafico 2 lo steso per lo scintillatore Grafico 3 rappresenta una correlazione tra le letture, normalizzate entrambe a dose 6MeV, dei due rivelatori. Seppure le aree dei due disposotivi siano diverse, entrambe sono correlate nel misurare lo stesso fenomeno, sono coerenti nel misurare la stessa cosa - Measurements are dose in a contemporary way 6 MeV 6 MeV 6 MeV The response of scintillator is linear, as in the case of ionization chamber, and both detectors show a very good correlation.

Monte Carlo simulations Translation effects of the IORT applicator on the four-leaf detector: MC code EGSnrc / BEAMnrc [Iaccarino G, PMB 2011], beam energy of 10MeV, cone of 60 mm, detector diameter of 70 mm (1 mm thick), depth in tissue of 27mm, light blue isodose of 90%. 1 2 4 3 1 2 4 3 1 2 4 3 Lateral translation Translation along a leaf-diagonal 1  2 3  4 1 4 2  3 1mm Monte Carlo simulation of electron beams generated by a 12 MeV dedicated mobile IORT accelerator The aim of this study was to investigate the dosimetric characteristics of the electron beams generated by the light intraoperative accelerator, Liac® (SORDINA, Italy), using Monte Carlo (MC) calculations. Moreover we investigated the possibility of characterizing the Liac® dosimetry with a minimal set of dosimetric data. In fact accelerator commissioning requires measurements of both percentage depth doses (PDDs) and off-axis profiles for all the possible combinations of energy, applicator diameter and bevelled angle. The Liac® geometry and water phantom were simulated in a typical measurement setup, using the MC code EGSnrc/BEAMnrc. A simulated annealing optimization algorithm was used in order to find the optimal non-monoenergetic spectrum of the initial electron beam that minimizes the differences between calculated and measured PDDs. We have concluded that, for each investigated nominal energy beam, only the PDDs of applicators with diameters of 30, 70 and 100 mm and the PDD without an applicator were needed to find the optimal spectra. Finally, the output factors of the entire set of applicator diameters/bevelled angles were calculated. The differences between calculated and experimental output factors were better than 2%, with the exception of the smallest applicator which gave differences between 3% and 4% for all energies. The code turned out to be useful for checking the experimental data from various Liac®beams and will be the basis for developing a tool based on MC simulation to support the medical physicist in the commissioning phase. Each leaf has its own pattern of response

Conclusions The proposed plastic scintillator for in vivo dosimeter improves the IORT clinical practice since it makes: a check of the right position of the protection disc with very small dose (~ 1 cGy); the surgeon could correct the positioning of the disc before delivering the treatment. a real time check of the protection disk position; a real time check of the dose delivery over the whole treatment. First one-leaf prototype tested with positive results (sensitivity, linearity, absolute dose measurement,..). Next steps: engineering and validation; Certification – fourth quarter 2016/first quarter 2017 10MeV, A 90°, 30uSv/10Gy a 1m, 120uSv/10Gy a 50cm, 120uSv/1000cGy = 0,12uSv/cGy (cioè per inpulso); se uso 45% in basso, 300uSv/1000cGy a 1m diventano 1.2uSv/cGy per impulso (between 1 – 4uSv/p)