XRays Compton Detectors For Biomedical Application

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efficiency, and hence a larger encumbrance of the camera. Moreover, the measurement of electron tracks in space requires a 3D sophisticated detector, which is.
XRays Compton Detectors For Biomedical Application Paolo Rossi, Giuseppe Baldazzi, Andrea Battistella, Michele Bello, Dante Bollini et al. Citation: AIP Conf. Proc. 1336, 356 (2011); doi: 10.1063/1.3586119 View online: http://dx.doi.org/10.1063/1.3586119 View Table of Contents: http://proceedings.aip.org/dbt/dbt.jsp?KEY=APCPCS&Volume=1336&Issue=1 Published by the American Institute of Physics.

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X-Rays Compton Detectors For Biomedical Application Paolo Rossia, Giuseppe Baldazzib,c, Andrea Battistellad, Michele Bellod, Dante Bollinic, Valter Bonvicinie, Cristiano Lino Fontanaa, Gisella Gennarof, Giuliano Moschinia, Francesco Navarriab,c, Alexander Rashevskye, Nikolay Uzunovd,g, Gianluigi Zampae, Nicola Zampae, Andrea Vacchie a

Department of Physics of the Universityof Padua and INFN, via Marzolo 8, Padua 35131, Italy b Department of Physics, University , Bologna, Italy c INFN, Bologna, Italy d National Laboratories of Legnaro, INFN, Legnaro (Padua), Italy e INFN, Trieste, Italy f Veneto Institute of Oncology IOV – IRCCS, Padua, Italy g Faculty of Natural Sciences, Shumen University, Shumen, Bulgaria

Collimators are usually needed to image sources emitting X-rays that cannot be focused. Alternately, one may employ a Compton Camera (CC) and measure the direction of the incident X-ray by letting it interact with a thin solid, liquid or gaseous material (Tracker) and determine the scattering angle. With respect to collimated cameras, CCs allow higher gamma-ray efficiency in spite of lighter geometry, and may feature comparable spatial resolution. CCs are better when the X-ray energy is high and small setups are required. We review current applications of CCs to Gamma Ray Astronomy and Biomedical systems stressing advantages and drawbacks. As an example, we focus on a particular CC we are developing, which is designed to image small animals administered with marked pharmaceuticals, and assess the bio-distribution and targeting capability of these latter. This camera has to address some requirements: relatively high activity of the imaged objects; detection of gamma-rays of different energies that may range from 140keV (Tc99m) to 511 keV; presence of gamma and beta radiation with energies up to 2MeV in case of 188Re. The camera consists of a thin position-sensitive Silicon Drift Detector as Tracker, and a further downstream position-sensitive system employing scintillating crystals and a multi-anode photo-multiplier (Calorimeter). The choice of crystal, pixel size, and detector geometry has been driven by measurements and simulations with the tracking code GEANT4. Spatial resolution, efficiency and scope are discussed.

Abstract.

Keywords: Compton camera, Gamma detectors, Molecular imaging, Small animals SPET PACS: 87.58.-b, 87.58.Ce, 87.58.Pm

singling out the radiation coming from an astronomical source of given angular direction. The tight requirement of having a light apparatus in a satellite together with a reasonable angular resolution discourages application of this method to high energy penetrating X-rays needing large screen thickness that moreover entails reduced detection efficiency. In this domain the Compton Telescope application is gaining momentum, being the preferred tool today. However, the Compton Concept has not yet proved to be the best solution in terrestrial detectors. We may quote for example only a quite few research projects aimed at demonstrating the adequacy of this concept to what is

INTRODUCTION The Compton Concept has been rather extensively applied to satellite X-ray astronomy above all when energetic X-ray sources, above 100 keV, have to be imaged [1, 2, 3]. Focusing energetic X-rays is not possible and collimators or masks have to be employed. In satellite astronomy “coded mask telescopes” are largely used for low energy X-rays of less than 100 keV [3, 4], where a mask with a known, although arbitrary, pattern of opaque and transparent areas is projected on a downstream detector plane,

Application of Accelerators in Research and Industry AIP Conf. Proc. 1336, 356-360 (2011); doi: 10.1063/1.3586119 © 2011 American Institute of Physics 978-0-7354-0891-3/$30.00

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material (Tracker) and measure the scattering angle (Figure 1). Finally the total energy of the scattered gamma is determined by a downstream Calorimeter. CCs allow higher gamma-ray efficiency and feature millimeter resolution also at higher energies, like those coming from I-131 (364 keV), beta+ emitters (511 keV) or even Co-58 (810 keV), where CAC would require a very large septa thickness. Higher energy gamma-rays are appealing because they feature reduced scattering in the animal body and hence a better imaging. Compton tomography luckily requires only a few views (for example rotating the apparatus in just four positions around the subject), as the "electronic collimation" that takes place in each position already extracts X-rays coming from many directions. Finally the compact geometry and lighter setup are suited for “small” subjects, like prostate, thyroid and of course mice. Differences between solid (or even liquid) and gaseous tracker in a CC can be summarized as follows: recoiling electrons travel very little in solid, a few tens of microns, and their direction cannot be measured. On the other hand, one needs a large gaseous volume (about 1000 times more) to have comparable detection efficiency, and hence a larger encumbrance of the camera. Moreover, the measurement of electron tracks in space requires a 3D sophisticated detector, which is demanding in cost and operation [8]. On the other hand as solid or liquid Cameras are concerned, the image reconstruction from “incomplete” Compton scattered data, with no information on the recoiling electron, requires special algorithms. In fact we merely obtain the gamma-ray’s outgoing direction and scattering angle and with them a “cone” of possible solutions of the incoming direction. At least three different cones are needed to have a unique solution. A special Filtered Back-Projection algorithm has been developed for this kind of image reconstruction in case of small animal tomography [9]. We shall consider henceforth a CC prototype [10] consisting of a Tracker based on the SDD (Silicon Drift Detector) built for the LHC-Alice experiment [11, 12], and a Calorimeter based on a scintillating crystal and a position sensitive multi-anode photomultiplier, model Hamamatsu H8500. Application to higher energy gamma-rays (usually up to 511 keV) has to be taken into account, and calorimeter thickness has to be sized accordingly.

by large the most widespread application of gamma detection: i.e. the bio-medical imaging related to either human diagnostics or research in the field of new pharmaceuticals [5, 6, 7]. In this domain one may employ gammas with an energy in the range 100-1000 keV coming from a family of radioisotopes which are named “medical”. This paper is concerned with the Compton Concept in general, the bio-medical application of it, and the development of an innovative Compton Camera for small animal imaging.

THE COMPTON CONCEPT The bio-distribution and targeting capability of pharmaceuticals may be assessed in small animals by imaging gamma-rays emitted from radio-isotope markers. Anger C: -rays selection

Coll. Scint. Position. Sens. PM system. Direct Imaging

Compton C: -rays measurement

PT , ET Tracker



PC , EC

Calorimeter

Computed Imaging

FIGURE 1. Compton concept (down) compared to the traditional Anger method employing collimators (up).

Orthogonal projections of this bio-distribution are traditionally obtained by employing lead collimators featuring a dense matrix of millimeter holes separated by septa, which involve the rejection of an extremely large fraction of gammas (CAC, Collimated Anger Cameras). Alternately, one may have a Compton Camera (CC) and establish the direction of the gamma by letting it interact with a thin solid, liquid or gaseous

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Being RC, Ri and RT respectively the Collimator, the Intrinsic (of the detector) and Total resolution. Figure 3 shows the comparison of a CAC with a CC for a CC’s typical efficiency of 10%. In this case, to

EFFICIENCY AND SPATIAL RESOLUTION The

efficiency of a CC is:  tr  Ca where P is the probability that a Tr E ff  Ptr   4 4 gamma-ray interacts with the tracker, and Tr/4 and Ca/4 are the “solid angle fraction” covered by the Tracker and the Calorimeter. In Table 1 we have collected gamma detection efficiencies for some simplified configurations of interest relative to a silicon Tracker. As far as the detectors coverage is concerned, we have considered two cases: 1)a full “square” lateral cylindrical coverage:  (1  cos  )  1 2  0.71,  45  4 2 2) a module 5x5 cm2 again placed at 2.5 cm from the mouse center:

Detector L x

t

d

 z 4

d t+d

t Object Further Detector Plane

 (1  cos  )   0.15,   45  4 2

FIGURE 2. Imaging with a Collimated Anger Camera.

This latter case roughly corresponds to a module consisting of a SDD Tracker detector and a scintillating crystal calorimeter read by a multi-anode PMT Hamamatsu 8500. Furthermore we have considered the solid angle fractions of Tracker and Calorimeter as equal. PTr in Table 1 is the probability that a gamma-ray does interact with a Silicon wafer of thickness L and has been roughly set equal to 1-exp(L/) where  is the interaction length of gamma-rays of given energy.

Resolution & Efficiency

res(mm) & 100*Efficiency

20 18

140 keV - 1/Res

16

140 keV - Eff

14

CC-Eff

12 10 8 6 4

CAC

2 0 0

RC

2

res(mm) & 100*Efficiency

18

511 keV - 1/Res

16

5

511 keV - Eff

14 12

CC-Eff

10 8 6 4

CAC

2 0 0

2

4

6

8

10

hole diameter d (mm)

FIGURE 3. Resolution and efficiency curves as a function of the collimator hole diameter for a full coverage Collimated Anger Camera, “sandwiching” the subject and comparison with a Compton Camera for gamma-rays of 140 keV (left) and 511 keV (right). Distance mouse-coll=20 mm, thickness = 5 (20) mm, septa = 2 mm, , intrinsic res. = 1 mm. The green straight line refers to a typical CC efficiency.

2 C

  d2   Efficiency  2   FArea     4 2  L  (t  d ) 

4

Resolution & Efficiency

R R R 2 i

3

20

One has to compare these values with those of a Collimated AC, where efficiency actually depends on the hole-septum geometry and the spatial resolution. From Figure 2 one can easily obtain the resolution and efficiency curves for a full coverage CAC camera consisting of two planes “sandwiching” the subject: 2 T

2

hole diameter d (mm)

TABLE 1. Gamma detection efficiencies for some simplified configurations of interest relative to a silicon Tracker Eff Tr-Th L PTr  En /4  mm keV mm 1.0 140 0.71 3 0.28 0.142 1.0 511 0.71 5 0.18 0.091 1.0 140 0.15 3 0.28 0.006 1.0 511 0.15 5 0.18 0.004 0.3 140 0.71 3 0.10 0.048 0.3 511 0.71 5 0.06 0.029 0.3 140 0.15 3 0.10 0.002 0.3 511 0.15 5 0.06 0.001

d 2  (L  Z )  L

1

2

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reach a similar efficiency with a CAC, one should have a resolution of 12 mm FWHM for the favorable case of 140 keV, and even a worse one for higher energies, and substantially worse of what one can get with a CC. In fact the resolution of this latter can be kept to less than 6-8 mm for most of the cases (at energy of 511 keV) .

(intersections of the horizontal lines with the curves in Figure 5). These values are there referred to as ShortTail and Long-Tail errors. Here we report some conclusions drawn from the simulations: 1) DIST may have substantial tails even without any added error, as illustrated by the curves in Figure 5. This means that the unavoidable smearing-out of the Compton angle due both to Doppler Broadening and the scattering in the materials upstream the tracker, and which GEANT4 accounts for, puts a lower limit on the overall accuracy of the method, and that a DIST smaller than 0.9 mm for 140 keV and 0.5 mm for 511 keV is not obtainable. 2) The Short-Tail does not depend much on both Tracker and Calorimeter spatial accuracy. 3) Cutting off gamma-rays with energy lower than the initial energy reduces the Long-Tail errors of both 140 keV (considerably) and 511 keV (slightly) gamma-rays, while leaving the Short-Tails values unaffected. 4) The Long-Tail is somehow sensible only to changes in the Calorimeter, but this is because the Calorimeter positioning is intrinsically much less accurate than that of the Tracker (a resolution in the worst case of 0.2 mm for the Tracker compared to 10 mm of the Calorimeter). 5) Both Short-Tail (slightly) and Long-Tail (significantly) values depend on the energy resolution of both Tracker and Calorimeter, because these resolutions largely affect the scattering angle). 6) As expected, 511 keV gammas allow for higher accuracy.

SIMULATION AND DETECTOR PERFORMANCE The Compton Camera design has been developed with the help of a numerical simulation [10]. To this aim we have used the GEANT4 library (http://geant4.web.cern.ch/geant4/) and the Livermore low-energy package. The latter is based on a model of electromagnetic processes down to 250 eV and up to 100 GeV, which also describes scintillation and recoiling electrons coming from Compton scattering. Gamma-rays of 140 keV and 511 keV have been tracked from a point in the center of a tissue cylinder, 30 mm in diameter, representing a mouse, through air, Tracker (1 mm Si), air again and the calorimeter, as described in Figure 4. The calorimeter is a total absorber. Gaussian errors on the Tracker and Calorimeter energy and position values have been added externally. Compton scattering in mouse and air before the Tracker has been included. The trajectory of the incident gamma was estimated from the energies and angles provided by GEANT4 and the added errors. Finally the distance (DIST) of this trajectory from the source point was calculated. Reproducing what a reconstruction program would do, we have employed the Compton formula for free electrons (with E1 and E2 energies of incoming and outgoing gamma-ray into and from the tracker):

LaBr3, YAP, GSO (50x50x5 mm3)

1 1 cos   1  mc (  ) E2 E1 2

which unavoidably lacks high accuracy when applied to electrons that are bound to atoms (due to the Doppler Broadening). DIST has been plotted for different values of the initial energy (140 keV, 511 keV), the Tracker spatial resolution (0, 30, 100, 200 microns) and the Calorimeter spatial resolution (0,1, 2, 5, 10, and 20 mm). Figure 5 shows the histograms of DIST in logarithmic scale for the 511 keV case. They have been obtained by varying the Calorimeter position error and normalizing the initial value to 105. Distributions are far from being Gaussian, featuring a very large tail. Different “tail” contributions have been parameterized by two numbers (in mm) that give the DIST values for which the histogram height is respectively 1/10 and 1/100 of the initial, highest value

P1 0.5 cm



4

H8 5 c 50 m 0 64 P2 ch cm

7 cm

3 cm DIST

E1= Incident Energy E2=Scattered Energy Measured: E1, E2, P1, P2 cos   1  mc 2 (1 / E 2  1 / E1 )

NI-6025-PCI Front-End Card 8x (MPX-08) TRACKER (SDD–TS) (70x75x0.3 mm3) 512 R/O anodes High Sensitivity, Low Dyn. Range 8x(32 chans ASIC) NI PCI 6133

FIGURE 4. Imaging with a Collimated Anger Camer. Small Animal Compton Camera Prototype. Dimensions used in the GEANT4 simulation.

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limit in the obtainable spatial resolution due to the Doppler Broadening; 2) the measurement of the recoiling electron, if decided, would require demanding 3D tracking gaseous detector; 3) Tomography reconstruction applied to small subjects is more demanding and less effective when the recoiling electron is not known; 4) spatial resolution and efficiency favorably compete with those of collimated cameras only for energies higher than some hundreds of keV. To support the measurements and help the design of a CC, 140 and 511 keV gammas have been simulated with GEANT4 and tracked from a point-like source inside a mouse through the Compton Camera. The performance has been evaluated by calculating the distance of the reconstructed trajectory from the pointlike source. Detailed conclusions have been drawn before. Here we stress that no matter how small the detector’s error is, Doppler Broadening and scattering in materials upstream the detector entail an unavoidable “blurring” that brings the overall best spatial accuracy to 0.9 mm for the 140 keV gammas and 0.5 mm for the 511 keV gamma-rays. Segmented crystals with a stride comparable to the profitable accuracy, i.e. ~2 mm, coupled to a position sensitive detector with millimeter resolution provide the best solution when gamma-rays of a wide energy range have to be imaged.

FIGURE 5. Distribution of the distance (DIST) of the reconstructed gamma trajectory from a point like source for the 511 keV case. The lowest Curv refers to a “no error” situation, including only Doppler Broadening and Compton Scattering in mouse and air. The others have: E/E (Tracker) = 4%, E/E (Cal.) = 7% , P (Tracker) = 0.030 mm, and different spatial accuracies for the Calorimeter. Lines at a DIST probability of 1/10 and 1/100 are drawn, permitting the definition of “Short-Tail” and “Long-Tail” errors. The ShortTail error for the lowest curve is 0.9 mm for 140 keV, and 0.5 for 511 keV gammas.

Crystals like NaI, LaBr3, GSO and CsI, in “continuous” or segmented geometry have been considered. They have been optically coupled to a multi-anode detector Hamamatsu H8500, allowing measurements of spatial resolution and efficiency. Measurements were performed using a Tc-99*, 0.5 mCi “Flat Field”, obtained by elution from a standard Mo-99 generator. Although “Continuous” geometry in “integral configuration” that optimizes the optical coupling has been proven to reach millimeter resolution for 5 mm thick crystals [13], nevertheless segmented geometry looks the best when thicker crystals are employed to absorb higher energy gammarays. This is our choice for a detector that seeks to be a general purpose tool suitable for a wide range of energies, up to 511 keV.

REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

CONCLUSION

11.

The “Compton” concept has been already fruitfully demonstrated in satellite astronomy for measuring cosmic X-rays, above all when their energy is higher than 1 MeV, while conclusive assessment is lacking when this detection method is applied to small subject bio-medical imaging and actual studies are still under way. Positive facets are: 1) low encumbrance and weight of equipment, and 2) high detection efficiency. However, there are weak points such as: 1) physical

12. 13.

Imaging Compton Telescope (COMPTEL); http://www.gro.unh.edu/comptel/ A. Takada, et al. (SMILE), J. Phys. Soc. Jpn. 78 (2009) Suppl. A, pp. 161. M. Forot et al. (INTEGRAL), The Astrophysical Journal, 668:1259Y1265, 2007 October 20 M. Feroci et al. (AGILE), Nucl. Instrum. And Meth. A 581(2007) 728-754 R. Pani et al, Nucl. Instrum. And Meth. A 571(2007)187 G. Moschini, et al., The Scintirad Project, Nat. Lab. of Legnaro (Italy), INFN-LNL-221 (2007) R. Pani et al., AIP, CP1099 (2009) 488-491 A. Takada et al., NIM A 546 (2005) 258–262 C. Fontana et al., Communication to CAARI 2010. P. Rossi, et al., Nucl Instr. And Meth. A (2010), doi:10.1016/j.nima.1010.07.018 A. Vacchi, et al., Nucl. Instr. And Meth. A 306 (1991) 187. A. Rashevsky, et al., Nucl. Instr. And Meth. A 485 (2002) 54. R. Pani et al., Nucl. Instrum. And Meth. A 572 (2007) 268

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