Progetto MATISSE MAmmographic and Tomographic Imaging with Silicon detectors and Synchrotron radiation at Elettra Tomografia Digitale per la diagnosi di tumori al seno Fascio Monocromatico presso la Sorgente di Luce di Sincrotrone Elettra a Trieste Rivelatore a Stato Solido (Si): Geometria “Edge-On” Elettronica di Lettura Intergrata a “Single Photon Counting” Dimensioni Pixel 100x300 mm2

Mammografia e Tomografia con Luce di Sincrotrone Vantaggi dati dalla Luce di Sincrotrone in Mammografia: Alta flussi su largo spettro energetico Utilizzo fascio monocromatico scelta dell’energia ottimale riduzione della dose Fascio laminare riduzione della radiazione diffusa necessaria scansione Sorgente di piccole dimensioni in Tomografia: Fascio monocromatico nessun arteffatto da hardening del fascio determinazione dei coeff. m dei tessuti Fascio laminare riduzione della radiazione diffusa Divergenza Trascurabile semplici algoritmi di ricostruzione 28 keV, 0.16 mGy 22 keV, 0.2 mGy Ottimi risultati ottenuti con campioni in vitro The fesibility of breast tomography has been already indagated at the SYRMEP beam line at Elettra, with very promising results. The images show a mammogram and a tomographic slice. Comparing the 2 images we ca see that while in the planar image all the structures are superimposed, in the tomography we can clearly distinguish the various tissues. The fat tissue is dark, the glandular is white and a microcalcification is clearly visible. Tomography is performed at higher energies than planar mammography and this implies that the dose increment isn’t so high. It is particulary suggested for thick and dense breasts when the dose needed is usually higher and the superimposition of structures is more critical. The shape of the lesions can be reconstructed and this can be very important for differentiating benignant from malignant lesions. This technique can help to reduce the number of women needing to undergo a biopsy after an ambiguous screening mammogram.

SYRMEP beam-line Radiazione da magnete curvante campione camera ionizzazione sorgente fenditure monocromatore filtri rivelatore Radiazione da magnete curvante sorgente = 1100m x140m Caratteristiche monocromatore: Area del fascio nella sala sperimentale: 140x4 mm2 Divergenza : orizzontale 7 mrad verticale 0.155 mrad FWHM Distanza sorgente-sala sperimentale: 23 m Flusso a 17 keV, 2GeV, 300mA: 1.6 108 ph mm-2 s-1 diffrazione alla Bragg su un cristallo di Si (1,1,1) intevallo energia 10 ÷ 35 keV risoluzione energetica : 10-3

Sistema allineamento per il rivelatore Il Setup Clinico Sala Paziente Sala Sperimentale Al II piano Sala Controllo ed apparati Supporto rotante per il paziente Sala Radiologo Since the beam is stationary the examination is performed by moving the patient. An innovative patient support has been developed in order to move the patient, laying in prone position with pendulant breast. The movement resolutions is of few microns and the velocity is highly constant. The rotational movement is also implemented in order to acquire images at various projections and for tomographic examinations. The tomographic setup is completed by a precision alignement system for the detector, since even a slight misalignement between beam, detector and axis of rotation can lead to artifacts in the image. Sistema allineamento per il rivelatore

Il Rivelatore MATISSE Larghezza pari a quella del fascio (20 cm ) 2 Strati con PCB ‘back-to-back’ 100 x300 m2 dimesioni pixel Efficienza 80% Elettronica di lettura: High Speed Single Photon Counting The MATISSE detector consists of a side illuminated silicon microstrip detector with single photon counting read out electronics. The drawing shows how the detector will look like. Since the organ has to lay in the field of view of the detector during each step of the rotation in order to reconstruct the image, the detector has to bee at least 20 cm wide, which is needed in order to image the whole organ rotating in front of the detector. Since the maximum size of our detectors is about 13 cm, 2 detectors need to be aligned on the side in order to reach such a width. 2 layers will be piled up misaligning the junction region on the 2 layers so that a full set of data needed for image reconstruction will be obtained by summing up the information from the 2 layers.

Requisiti del rivelatore Rivelare calcificazioni di poche centinaia di m Rivelare lesioni a basso contrasto acquisendo proiezioni con alcune centinaia di fotoni/pixel ognuna  Pixel size E  1.5 t t Elettronica di lettura: a basso rumore singolo conteggio di fontone Rivelazione con conversione diretta Microstrip di silicio in configurazione edge-on Range d’energie 25-32 keV QSi/QSe10

Sensori microsrip di silicio principio di funzionamento electronica di read-out conversione diretta fotoni/carica alta efficienza grazie all’edge-on facile rimozione della radiazione diffusa Raggi X area ‘morta’ p+ n+ n regione ‘morta’ necessaria scansione A microstrip detector is given by p-doped silicon strips implanted on a n-doped bulk. A negative voltage is applied to the strips and a positive one to the backplane, so that the detector is depleted from free charge carriers. When a charged particle crosses the detector or an X-ray is absorbed in it, the charge created is collected by the closer strip and by the backplane. If we oriented the detector with the radiation impinging on the large surface of the silicon crystal, the absorption effiiciency for X-rays would be very low, since the thickness is usually of about 300um. The edge on configuration consists in orienting the detector with the strips parallel to the radiation and the absorption efficiency results very high. The charge absorbed in the undepleted region between the border of the detector and the beginning of the strip implants isn’t collected and leads thus to a loss of efficiency. It will be important to try to reduce this thickness, however the total absorbtion efficiency is given by the two components and generally increases with energy. The sensor results in a line of pixels of size defined by the stip pitch times the wafer thickness.

Rivelatore a microstrip (Si) Distanza di Taglio Fino a 240 m Guard Ring Bias Line Fascio Incidente Pitch 100 m Lunghezza Strip 2 cm Dark Current < 0.1 nA/strip Efficienza: The detector is oriented in edge on configuration, which means that the radiation impinges parallel to the strips. The strip length of 2 cm leads to the total asorption of the X-rays in the detector bulk. A loss of efficiency is due to the presence of an undepleted region in the entrance window of the detector. In order to limit the distance between the scribe line of the detector and the beginning of the strips, the guard ring is present on only 3 sides, as can be seen in the detail in the picture. The distance between the border and the bias ring has been reduced down to 240 um. This doesn’t increase the leakage current of the detector, which is still 0.1 nA/strip, like in the detectors with standard cutting distance. The overall efficiency is higher than 80% at all tomographic energies, as can be seen in the plot on the right. The pixel size is determined in the vertical direction by the wafer thickness, wich is 300 um, and by the strip pitch in the horizontal one.

Elettronica di Front-End Soglia Amplificatore e filtro Comparatore +1 Dal rivelatore Single Photon Counting Guadagno 100 mV/fC 500 e- ENC 75 ns Peaking Time 64 Canali Uscite Digitali Parallele Read-Out con FPGA The read out is carried out by two application specific integrated circuit manifactured by IDEAS. The VA64_tap chip performs the amplification and discrimination operation, while the LS works as output buffer. Each input channel is connected to a strip of the detector, and the parallel outputs of the chip are the digital signals from the comparators. High gain and low noise are needed in order to discriminate the charge created by the x-rays, which is of the order of 1 fC. The ENC of the chip allows a signal-to noise ratio higher than 10:1. A high speed is required in order to limit the time duration of the examination to a few seconds without loss of contrast and the design peaking time of the chip is very good. VA64_tap LS64

Matisse: Primo Prototipo a 64 Canali rivelatore Perdita nel rate  Perdita di contrasto VA64TAP LS64 FPGA The first prototype has been assembled. It is made of only one ASIC, 64 channels, 6.4mm sensitive region. It contains several devices: the ASICs, THE PLD, the EPROM reprogram the PLD every time it is turned on and several devices to adjust the power supplies and the signal levels, since every device works with a different standard. The integrated circuits have signals and power supplies in +-2 CMOS, the digital outputs are in LVTTL, while the signals from the VME are in TTL standard and the FPGA has a core voltage of 1.8V. Segnali di Test iniettati attraverso la capacita’ di calibrazione Linearita’ fino a 3.5 MHz

Prime Immagini Visibili contrasti <1% 104 ph/pixel 28 keV Fantoccio CD C = IOUT - IIN IOUT SNR = IOUT - IIN IOUT + IIN Finally the prototype has been used to acquire images of a mammographic phantom at the SYRMEP beam line at Elettra. The phantom is made of plexiglas discs of different thickness and their theoric contrast can be calculated from their geometrical characteristics. The statistics acquired is of about 10000 photons per pixel and in the image we can see discs with a contrast lower than 1% (0.96 at 28 keV, 0.83 at 32keV). Visibili contrasti <1% 104 ph/pixel

Prototipo a 384 canali: MATSIX Prime misure ad Elettra The new 6 asic prototype has been designed and is now in the manifacturing phase. It has 3.84 cm sensitive width and its design presents a high grade of complexity, due to the high number of channels of the detector and to the low space occupancy requirements. This problem has been solved by using a ball grid array logic device, but many signal planes are then needed in order to route all the lines. Great care has been taken in the design since it will constitue the module to build up ther final 2000 channels detector. In one month we hope to start the tests on the new prototype and we should have the first tomographic images befor the summer. Fantoccio CD a 20 keV Presenza di artefatti: Problemi di stabilità e rumore da risolvere Larghezza sensibile 3.84 cm Candidato a divenire un modulo per il riveltore finale

Conclusioni L’uso di Luce di Sincrotrone per immagini al seno e’ considerata un potente mezzo per la diagnosi precoce di tumori in casi non risolti con tecniche tradizionali La mammografia digitale e’ un importante campo per lo sviluppo di rivelatori Setup per la tomografia clinica alla beam line SYRMEP @ Elettra in fase di test Primi risultati ottenuti con il prototipo a 384 canali Avvio di studio estensivo per l’ottimizzazione dei parametri dell’elettronica di front-end Summarizing what we’ve said so far, the first MATISSE detector prototype for synchrotron radiation breast tomography has been tested and satisfied all the design requirements. New prototypes with a larger sensitive region and upgraded readout logic are being developed and at the same time the integration of the detector in the SYRMA beam line for clinical examination is being carried on. The first tomographic images are expected during the next months.

RIVELATORE SECTRA http://www.sectra.se/medical/ MicroDose Mammography™ Efficienza assorbimento (sensori Si in ‘edge-on’), Front-end a conteggio di fotone Tesi dottorato M.Lundqvist Silicon strip detectors for scanned multi-slit X-ray imaging Campo visuale 24x26 cm

Risoluzione spaziale verticale Sensori con pixel 200x300 mm: Tecniche di miglioramento della risoluzione Acquisizione con passo pari alle dimensioni del pixel (300 µm) Acquisizione con passo inferiore alle dimensioni del pixel (50 µm)

MTF Sensori con pixel 200x300 mm: MTF (theoretical) 300 µm 0,2 0,4 0,6 0,8 1 1,2 4 8 12 16 20 24 MTF (theoretical) 300 µm MTF (theoretical) 20 µm MTF estimated from the reconstructed image

EVENTUALI DOMANDE

Un Canale di MATISSE Secondo Stadio di Amplificazione selezionabile Charge Preamplifier Counter with Loadable Shift register Level Shifter Gain stage Shaper + Comparator Global Threshold 4 bit DAC VA64_tap LS64 APEX20K Readout Logic Here we can see the layout of an channel of the frontend electronics. The charge preamplifier is followed by a selectable gain stage, a shaper followed by a high pass filter and a comparator. The threshold can be finely tuned on a channel by channel by channel basis thanks to a 4 bit DAC. The va output is open drain and is then sent to the LS that operates as level shifter. The outputs are then sent to an Altera FPGA programmed with a counter per channel with a loadable shift register for serial read out. Several test modalities have been implemented and the read out can be performed with negligible dead time. Secondo Stadio di Amplificazione selezionabile Soglia fine con 4 bit Uscita Global Trigger Disabilitazione del Canale

Imaging Tomografico Informazioni sulla profondita’ delle lesioni Tomografia clinica con Tubo a Raggi X Ricostruzione dell’Immagine Tomografia con Luce di Sincrotrone A tomographic image is obtained acquiring planar images of an object with different angular projections. This can be obtained or rotating detector and source around the sample, like in common clinical practice, or by rotating the sample, like in the case of synchrotron radiation imaging when the beam is stationary. The planar data are then filtered and backprojected in order to obtain a section of the sample. This technique allows to detect the lesions without superimposition effects, collecting information also about their depth and shape. Informazioni sulla profondita’ delle lesioni Nessuna sovraposizione di strutture

SELEZIONE FLUSSO E GEOMETRIA SYRMA Vacuum slits Monochromator Al filters Air Slits Beam stopper Fast shutters Ionization chambers BEAM SS Mammographic station SELEZIONE ENERGIA SELEZIONE FLUSSO E GEOMETRIA La SYRMEP pressi Elettra e’ stata modificata per effettuare esami clinici Primi pazienti??? A beam line dedicated to medical physics has been active at Elettra since 1996 and in the last few years it has been modified in order to perform experimentations on patients, wich are expected to start later this year. The beam line has been implemented in order to satisfy all the safety rules necessary for clinical examinations and in the first phase planar mammography with traditional films will be performed. The possibility of rotating the bed has been implemented in order to perform also tomographic examinations The use of synchrotron radiation allow to monochromzie the X-ray beam thus optimizing the energy for the specific sample to be radiographed. The monochromator allows us to select x-rays in the energy range 8-35 keV with a resolution better than %. For what concerns tomography the monochromaticity prevents the hardening of the beam avoiding the presence of artifacts. The negligible divergence of the beam makes the image reconstruction simpler, while its laminarity reduces the presence of scattered radiation in the images.

Sistema di Acquisizione PC Linux GUI, Image preview Crate VME 16 bit I/O register SERIAL VME Allineamento Rivelatore GPIB Inizializzazione Amplificatore e Comparatore Generatore d’onde Repeater The data acquisition is controlled by a PC Linux and the acqusisiton program is written in C with a Tcl/tk graphical interface. An image preview is also provided. The computer controls the sample movement through a GPIB interface, while the read out is carried out with a VME I/O register. A Printed circuit, indicated as repeater provides the power supplies and logic signals to the readout electronics. It is possible to initialize the integrated circuits and perform the readout operations. Alimentazione Elettronica Logica di Lettura Motori Scheda Rivelatore Alimentazione Rivelatore

Amplifier and Shaper +1 threshold From detector Comparator