Real-time in-vivo μ-imaging with Medipix2

Abstract An X-ray micro-radiographic system based on the Medipix2 semiconductor pixel detector for dynamic high spatial resolution and for high contrast imaging has been developed. Our system is based on a micro-focus and nano-focus X-ray tube and the hybrid single-photon counting silicon pixel detector Medipix2 (matrix 256×256 sq. pixels of 55 μm pitch). This compact table-top system stands promising as a new tool in the field of small animal imaging as well as in the in-vivo observation of dynamic processes inside living organisms. The main advantages of these Medipix2 pixel detectors include: high sensitivity to low-energy X-ray photons; position sensitive and noiseless single-photon detection with preselected photon energies; single-quantum counting in each pixel performed by digital counter (therefore there is no dark current); digital integration (providing unlimited dynamic range and absolute linearity in device response to number of photons, high sensitivity and high contrast); real-time digital information, high-speed digital communication and data transfer. We improve the picture quality with the help of statistical data analysis and extended the calibration of individual pixels response. 2D and 3D radiographic images of samples demonstrate the potential and applicability of our system for precise in-vivo X-ray high-resolution dynamic diagnostic and biological studies. Obtained results are shown on small animal and organic samples

Monitoring of hadrontherapy treatments by means of charged particle detection

The interaction of the incoming beam radiation with the patient body in hadrontherapy treatments produces secondary charged and neutral particles, whose detection can be used for monitoring purposes and to perform an on-line check of beam particle range. In the context of ion-therapy with active scanning, charged particles are potentially attractive since they can be easily tracked with a high efficiency, in presence of a relatively low background contamination. In order to verify the possibility of exploiting this approach for in-beam monitoring in ion-therapy, and to guide the design of specific detectors, both simulations and experimental tests are being performed with ion beams impinging on simple homogeneous tissue-like targets (PMMA). From these studies, a resolution of the order of few millimeters on the single track has been proven to be sufficient to exploit charged particle tracking for monitoring purposes, preserving the precision achievable on longitudinal shape. The results obtained so far show that the measurement of charged particles can be successfully implemented in a technology capable of monitoring both the dose profile and the position of the Bragg peak inside the target and finally lead to the design of a novel profile detector. Crucial aspects to be considered are the detector positioning, to be optimized in order to maximize the available statistics, and the capability of accounting for the multiple scattering interactions undergone by the charged fragments along their exit path from the patient body. The experimental results collected up to now are also valuable for the validation of Monte Carlo simulation software tools and their implementation in Treatment Planning Software packages

Towards a Radio-guided Surgery with β−\beta^{-} Decays: Uptake of a somatostatin analogue (DOTATOC) in Meningioma and High Grade Glioma

A novel radio guided surgery (RGS) technique for cerebral tumors using $\beta^{-}$ radiation is being developed. Checking the availability of a radio-tracer that can deliver a $\beta^{-}$ emitter to the tumor is a fundamental step in the deployment of such technique. This paper reports a study of the uptake of 90Y labeled (DOTATOC) in the meningioma and the high grade glioma (HGG) and a feasibility study of the RGS technique in these cases.Comment: 21 pages, 5 figure

Single Photon Counting X Ray Micro Imaging of Biological Samples

In this thesis, performed in the framework of the interdisciplinary research of the Italian National Institute of Physics (INFN) and within a collaboration with Prof. S. Pospisil at Czech Technical University in Prague, Institute of Experimental and Applied Physics, we compared the experimental technique of Single Photon Counting (SPC) imaging to the charge integrating Flat Panel (FP) detector imaging, for X-ray biomedical imaging applications. In particular, we investigated the application of SPC detector for the X ray micro-imaging and X-ray volumetric Computed Tomography (CT) technique. The motivation for such a research arises from the potential advantages of the single photon counting technology. In fact, this detection modality allows to have an efficient suppression of the electronic noise, scatter radiation rejection and immunity for afterglow effect of scintillator-based detectors, thanks to a read-out scheme able to discriminate photons with energy above a chosen threshold. This means that, during the exposure, the signal increases but not the noise, leading to excellent values of the image quality parameters such as the Signal-to-Noise Ratio (SNR) and the Contrast-to-Noise Ratio (CNR). In SPC imaging, each interacting photon is counted as one single event, independently of its energy, so that soft X-rays are equally weighted compared to the harder ones. This results into a high Contrast (C) also for low attenuating objects, such as soft tissues in an organism or small biological samples. On the contrary, charge integrating detectors (and FP detector among this class of devices) integrate both signal and noise, and high energy photons bring a larger weight than low energy ones. These high energy photons, however, contribute less to the detectability (SNR) and to the visibility (C) of low contrast samples, since material attenuation generally decreases with increasing energy. Theoretical models and computer simulations [1] [3] show that energy sensitive detectors and SPC detectors as particular representatives of this class of devices may perform better than charge integrating systems in terms of SNR, for X-ray 2D and 3D imaging. The significance of such result is also related to the possibility of a high image quality for a satisfactory visualization of the sample with a lower radiation dose, because the same image SNR can be achieved with a lower exposure level. The above described aspects of the SPC technology are most important in medical imaging, where the patient absorbed dose and the low contrast image quality for the soft tissues detection are the fundamental parameters to take into account. In fact, the harder task in X-rays imaging is to visualize small and low-attenuating structures in an organism, using X-rays of energies neither too low (because they result in a high absorbed dose) or too high (because they result in loss of contrast for softer tissues). SPC detectors may provide an accurate representation of the beam hardening effect with compared to charge integrating devices [4]. In fact, charge integration decreases the relative weight of the low energy part of the spectrum thus giving less importance to the loss of the soft photons as the beam is transmitted through the sample. On the other hand, SPC devices assign the same weight to all the detected photons, leading to a higher but more correct expression of the beam hardening effect. The aim of this thesis is to experimentally demonstrate the feasibility of planar, real time and tomographic X-ray imaging utilizing an SPC detector in the field of Medical Physics. Since the use of this technology is regarded as an alternative to the more commonly employed charge integrating systems, a comparison with an FP detector, in terms of image quality parameters (SNR, C, CNR) evaluation has also been done. The thesis is organized as follows. In the first chapter, the basic concepts of the SPC technology are described, with a particular attention to the analysis of advantages and drawbacks of its use in Medical Imaging. The CT technique and the more common reconstruction algorithms have also been described in their general features. Finally, an overview of the state of the art of the SPC application in CT is presented. In the second chapter, the experimental systems employed for the experimental part of this work are described, with particular attention to the SPC detector used: the Medipx2 SPC hybrid pixel detector, developed within the Medipix2 European Collaboration (designed at CERN, Geneva, Switzerland) to which University & INFN Napoli belong [5]. The characterization of the measurements setups is presented. Moreover, two kinds of detector pixels efficiency equalizations have been described: the standard Flat Field Correction (FFC) and the Signal to Thickness Calibration (STC) [6] [7]. In the third chapter are reported the experimental tests and images relative to the application of the Medipix2 SPC detector for planar, tomographic and real-time X-ray imaging of small biological samples. Then, its performance in terms of image quality parameters has been compared to a commercially available FP charge integrating detector used in the same experimental conditions. Moreover, two kinds of detector pixels efficiency equalizations have been compared in terms of image parameters, on images of both phantoms and biological samples

Accreditamento di un Laboratorio di Taratura per le Radiazioni Ionizzanti e successiva implementazione di una procedura di irraggiamento per dosimetri personali a termoluminescenza

L’Azienda USL 6 di Livorno è dotata – unica tra tutte le USL del Servizio Sanitario Nazionale – di un Laboratorio Accreditato di Taratura, a cui è stata assegnata la sigla di LAT N° 222 e sede fisica presso l’Unità Operativa di Fisica Sanitaria dell’Azienda livornese. I lavori per il LAT N° 222 sono ufficialmente partiti il 21 ottobre 2008 grazie al Decreto N° 4972 col quale la Regione Toscana approvava il progetto biennale denominato “Centro Regionale di Taratura per le radiazioni ionizzanti”. Nei successivi anni 2009, 2010 e 2011, grazie ai fondi assegnati, è stato possibile attrezzare il Laboratorio con la strumentazione opportuna e, in un secondo momento, approntare una serie di procedure sia tecniche che gestionali che rendessero possibile all’Ente preposto (ACCREDIA) di deliberarne accreditamento, avvenuto nel luglio 2011. Questa tesi descrive il lavoro svolto, a partire dal maggio 2010, per portare all’accreditamento il LAT N° 222 e per le successive implementazioni relative all’estensione del range di accreditamento e all’introduzione di un’ulteriore grandezza di taratura . Il progetto trova la sua motivazione nella imprescindibilità della taratura effettuata su qualsiasi tipo di strumentazione utilizzata per la valutazione del rischio da radiazioni ionizzanti ovvero per: - misure atte a verificare il rispetto dei limiti e dei vincoli di dose sia preliminarmente alla messa in atto di una nuova pratica che nel corso del tempo; - misure effettuate nel caso di esposizioni di emergenza; - monitoraggio ambientale dell’esposizione; - dosimetria individuale. In particolare, nel campo della Radioprotezione, l’ultimo punto, la dosimetria individuale, risulta di altissima rilevanza, in quanto consente di conoscere i livelli di esposizione alla radiazione ionizzante di lavoratori o di pazienti sottoposti ad esami radiologici. In tutti questi casi, è necessario l’utilizzo di strumenti di misura calibrati, per i quali, cioè, sia noto il coefficiente che consenta di passare dalla lettura dello strumento al valore effettivo della grandezza fisica da misurare, e di assegnare a tale valore un’incertezza nota. Il processo di taratura serve a determinare sia tale coefficiente che l’incertezza ad esso associata. Tale processo si attua utilizzando un termine sorgente, riconducibile alla grandezza da misurare (Kerma in aria, attività superficiale, equivalente di dose in profondità, ecc.), di cui si conosca a priori il valore e la relativa incertezza, e misurando tale valore con lo strumento da tarare. Il confronto tra la lettura dello strumento e il valore noto consente di determinare il coefficiente di taratura. La taratura è quindi un elemento fondamentale nel processo di valutazione del rischio associato all’esposizione da radiazioni ionizzanti, in quanto fa sì che le letture dei diversi strumenti di misura vengano ricondotte - entro un’incertezza nota - ai valori effettivi delle grandezze fisiche necessarie per la valutazione. Per questo motivo, la taratura periodica degli strumenti utilizzati nei settori sopra elencati è considerata elemento imprescindibile da tutte le norme di buona tecnica che trattano di misure proteximetriche. In particolare, nel decreto legislativo 230/95, modificato successivamente dal D.Lgs 241/2000 , che in Italia regola le problematiche generali inerenti la protezione sanitaria della popolazione e dei lavoratori contro i rischi derivanti dalle radiazioni ionizzanti, si ritiene necessaria la taratura adeguatamente certificata dei dosimetri per il monitoraggio personale e ambientale (art. 107 del D.Lgs. 230/95 e s.m.i.). Nello specifico, nel settore della dosimetria ambientale e individuale, il sistema qualità del servizio di dosimetria deve necessariamente prevedere l’irraggiamento periodico di una partita di dosimetri a un valore noto di equivalente di dose profondo per una o più qualità della radiazione, al fine di stabilire una corrispondenza tra la lettura del dosimetro e la dose assorbita dal lavoratore. Questa tesi, suddivisa in 4 capitoli, è così strutturata: 1. il primo capitolo rappresenta una panoramica sul mondo dell’accreditamento, sui Laboratori Accreditati di Taratura che rappresentano gli unici Enti (oltre agli Istituti Primari) abilitati a rilasciare a terzi certificati di taratura accreditati e sull’organizzazione specifica del LAT N° 222 di Livorno; 2. il secondo capitolo, cuore di questo lavoro, entra nello specifico delle procedure tecniche sviluppate per la corretta caratterizzazione dei fasci di radiazione del Laboratorio, descrive le apparecchiature utilizzate, i controlli preliminari da effettuare sul sistema prima della taratura, le verifiche di tipo metrologico da effettuare regolarmente per mantenere la Qualità del Laboratorio e, argomento di imprescindibile importanza, illustra le modalità di calcolo delle incertezze sulle grandezze misurate; 3. nel terzo capitolo è affrontato il tema della dosimetria personale in termini di normativa e delle sue applicazioni; in particolare, viene descritto un particolare tipo di dosimetro personale, quello a termoluminescenza, che è, sicuramente, il più utilizzato per la dosimetria personale e nel Servizio Sanitario Nazionale e in tutti i luoghi di lavoro in cui, per legge, l’esposizione a radiazione ionizzante dei lavoratori deve essere monitorata; 4. il quarto capitolo è dedicato alla procedura sviluppata per l’irraggiamento dei dosimetri personali a termoluminescenza (descritti, appunto, nel capitolo terzo) e alla loro parziale caratterizzazione, quest’ultima finalizzata a definire in maniera chiara le modalità di irraggiamento per elaborare la procedura presentata in questa tesi e che è stata validata dall’Ente accreditante. In particolare, il lavoro di caratterizzazione è stato svolto su cristalli di LiF:Mg, Cu P Gr 200 A, i dosimetri a termoluminescenza utilizzati dalla ASL 6 di Livorno e distribuiti dal servizio di dosimetria della Fisica Sanitaria dell’ospedale livornese. La tesi si conclude con un’appendice A che presenta un breve excursus su tre tra i più comuni tipi di dosimetri personali passivi ad integrazione per irradiazione esterna ed un’appendice B in cui vengono raccolte le definizioni dei concetti chiave esposti e assunti noti durante la stesura

CdTe compact gamma camera for coded aperture imaging in radioguided surgery

The aim of this work was to assess the performance of a prototype compact gamma camera (MediPROBE) based on a CdTe semiconductor hybrid pixel detector, for coded aperture imaging. This probe can be adopted for various tasks in nuclear medicine such as preoperative sentinel lymph node localization, breast imaging with 99mTc radiotracers and thyroid imaging, and in general in radioguided surgery tasks. The hybrid detector is an assembly of a 1-mm thick CdTe semiconductor detector bump-bonded to a photon-counting CMOS readout circuit of the Medipix2 series or energy-sensitive Timepix detector. MediPROBE was equipped with a set of two coded aperture masks with 0.07-mm or 0.08-mm diameter holes. We performed laboratory measurements of field of view, system spatial resolution, and signal-difference-to-noise ratio, by using gamma-emitting radioactive sources (109Cd, 125I, 241Am, 99mTc). The system spatial resolution in the lateral direction was 0.56 mm FWHM (coded aperture mask with holes of 0.08 mm and a 60 keV source) at a source-collimator distance of 50 mm and a field of view of 40 mm by side. Correspondingly, the longitudinal resolution in 3D source localization tasks was about 3 mm. MediPROBE showed a significant improvement in terms of spatial resolution when equipped with the high-resolution coded apertures, with respect to the performance previously reported with 1–2 mm pinhole apertures as well as with respect to adopting a 0.35 mm pinhole aperture

Preliminary evaluation of the tomographic performance of the MediSPECT small animal imaging system

We report on the tests of a prototype (MediSPECT) system developed at University & INFN Napoli, for Single Photon Emission Computed Tomography (SPECT) imaging on small animals with a small Field of View (FoV) and high spatial resolution. MediSPECT is a SPECT imaging system based on a 1-mm-thick CdTe pixel detector, bump-bonded to the Medipix2 CMOS readout circuit operating in single-photon counting. The CdTe detector has 256X256 square array of pixels arranged with a 55 micron pitch, for a sensitive area of 14X14mm^2. In its present version, this system implements a single detector head, mounted on a rotating gantry. For preliminary testing and calibration of the acquisition equipment and image reconstruction algorithms, 90 projections of a gamma-ray point source (109-Cd) through a single pinhole (diameter 0.4 mm; radius of rotation about 2.5 cm; focal length about 4.5 cm) were acquired for 20 min each in a stepand- shoot mode. Capillaries, 800 mm in diameter, were arranged in a Y-shape to form a more complex phantom (125-I, 1mm pinhole diameter, 45 projections, each acquired for 25 min). Images were reconstructed with a custom algorithm implementing standard OS-EM with center of rotation correction and spatial resolution of 0.2mm over a FoV of 2mm was obtained