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1 Q J NUCL MED 2002;46:3-7 Since Nuclear Medicine diagnostic applications are growing fast, room temperature semiconductor detectors such CdTe and CdZnTe either in the form of single detectors or as segmented monolithic detectors have been investigated aiming to replace the NaI scintillator. These detectors have inherently better energy resolution that scintillators coupled to photodiodes or photomultiplier tubes leading to compact imaging systems with higher spatial resolution and enhanced contrast. Advantages and disadvantages of CdTe and CdZnTe detectors in imaging systems are discussed and efforts to develop semiconductor-based planar and tomographic cameras as well as nuclear probes are presented. KEY WORDS: Semiconductors - Cadmium compounds - Gamma cameras - Nuclear medicine. In Nuclear Medicine a γ-ray emitting radiotracer is usually injected intravenously in the body and its distribution is imaged using either a large-area γ camera or a single-detector probe. The main task of Nuclear Medicine as an imaging modality is to provide us with functional information with respect to a specific organ, e.g. brain or heart, as well as to the behaviour of particular molecules directed against tissues containing pathological cells. Other imaging modalities such as computed tomography, magnetic resonance imaging and ultrasound are capable of mainly imaging anatomy, while nuclear medicine is extremely sensitive to physiologically relevant studies. As a result, today nuclear medicine is a well-established Solid state detectors in Nuclear Medicine Address reprint requests to: D. G. Darambara, Department of Medical Physics and Bioengineering, University College London, Capper Street, London WC1E 6JA, UK. dimitrad@medphys.ucl.ac.uk - atoddpok@medphys.ucl.ac.uk D. G. DARAMBARA, A. TODD-POKROPEK From the Department of Medical Physics and Bioengineering University College London, London, UK imaging modality in many fields like neurology, cardiology and oncology leading to a demand of an even more rapid expansion. The most commonly used γ camera for single photon emitters is based on a design originally developed by Anger 1 nearly 40 years ago. An image is obtained by using a detector consisting of a large-area NaI(Tl) scintillator viewed by an array of photomultiplier tubes. In this type of detector, the scintillator absorbs the radiation and emits visible light in proportion to the energy absorbed. The focusing of the γ rays emitted from the body is achieved by several types of collimators. The most commonly used collimators include parallel, converging, diverging and pinhole. The position of interaction in the crystal is derived by comparing the light yield in various photomultiplier tubes. The intrinsic spatial resolution of current γ cameras is typically 3-4 mm. However the existing scintillation γ cameras reach fundamental performance limitations imposed by the detection systems and collimators presently used. The energy resolution is rather poor, in particular in energies lower that 150 kev, affecting both the intrinsic spatial resolution and the intrinsic efficiency, and therefore, a significant fraction of scattered photons contributes to decrease the image contrast. An increase in crystal thickness as well as statistical fluctuations in the light distribution play a significant role in further reducing the spatial resolution. The γ cameras are also quite Vol No. 1 THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE 3

2 DARAMBARA SOLID STATE DETECTORS FOR USE IN NUCLEAR MEDICINE bulky and immobile due to the shielding needed to reject scattered radiation. Therefore, attempts have been made to replace the NaI scintillators with semiconductor detectors with better spectroscopic characteristics to improve contrast and quantitative measurements. Room temperature semiconductor detectors Room temperature solid-state detectors have paved the way for their wider use in research, industrial and medical applications by achieving better energy resolution at room temperature without loss of detection efficiency. In particular for imaging devices, their good energy resolution and the ability to fabricate compact arrays are very attractive characteristics in comparison with inorganic scintillation detectors coupled to either photodiodes or photomultiplier tubes. The system spatial resolution however is expected to be similar to scintillation cameras, because this parameter depends primarily on the geometric characteristics of the collimator. The best two semiconductor detectors, silicon (Si) and germanium (Ge), exhibit excellent energy resolution and charge transport properties. Nevertheless, their low stopping power for high-energy photons as well as the small bandgap of germanium, which forces us to operate the detectors at cryogenic temperatures, limit their applications. Therefore, room temperature semiconductors with high atomic numbers and wide bandgaps have long been under development as X- and γ-ray detectors. The most attractive and promising solid-state detector materials for room temperature X- and γ-ray detection are CdTe, CdZnTe (CZT) and possibly HgI 2. In particular, both CdTe and Cd 1-x Zn x Te can be considered from their favourable physical properties as very good candidates for medical imaging applications because of their high density, the high atomic number of their components and a wide bandgap. 2, 3 The high atomic number of these materials, Z cd =48 and Z Te =52, gives a high quantum efficiency, in comparison with Si, for relatively low photon energies even at thickness smaller than 3 mm. A large bandgap energy of E g =1.5 ev allows us to operate these detectors at room temperature. They allow direct conversion of the energy absorbed to charge leading to much better energy resolution compared to scintillator-based systems, which improves Compton scatter suppression. Additionally, they can operate in low voltage bias. Finally, it is possible to segment these detectors into pixel arrays with very fine pitch allowing high spatial resolution. 4 However, a considerable amount of charge loss in these detectors, due to incomplete charge collection caused by the low mobility and short lifetime of holes, produces a reduced energy resolution. Incomplete charge collection could limit the thickness and therefore the volume of detectors, which in turn limits the usefulness of the detector. Significant improvements have been recently achieved to improve the spectral properties based on the advances in the production of crystals and in the design of electrodes. 5 After continuous efforts, a technique for growing large single CdTe with good charge transport properties and compensation of native defects with Cl seems to be established: the travelling heater method (THM). 6 Very recently, CdZnTe grown by the high-pressure Bridgman (HPB) technique 7 possesses several advantages over CdTe, mainly higher resistivity (nearly two orders of magnitude larger), and therefore, lower leakage currents and low-noise characteristics. As a result, CZT detectors can be implemented, in large area and thickness, as single element detectors or as segmented monolithic pad or strip detectors at low photon energies. However, at present, the yield of HPB CdZnTe dies suitable for X- and γ-ray imaging devices is very low, as well as the hole collection in CdZnTe detectors is almost one order of magnitude smaller than that of the recent CdTe detector. This is probably due to some degradation in properties introduced by adding Zn. Many methods have been proposed and used to overcome the hole-trapping problem for both types of detectors in order to correct for variations in charge losses at different depths of interaction within the detector and therefore to improve their charge collection properties. 5 One approach is to use the information contained in the pulse shape by means of specially designed electronics. 2, 8 Another approach is to design detectors and/or electrodes of various geometries. For example, in hemispherical 2 or cylindrical detectors the induced charge is dominated by electron transport. Further, new ideas based on the concept of single charge collection have been proposed utilising techniques to form strip or pixel electrodes on the surface of the material and to process many channels by means of high-density analogue LSI in the form of ASICs Coplanar grids, small pixels and control electrode, 3D configuration are some examples of these novel electrode designs. 4 THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE March 2002

3 SOLID STATE DETECTORS FOR USE IN NUCLEAR MEDICINE DARAMBARA CdTe and CdZnTe detectors in Nuclear Medicine Due to a considerable research work on material, contacts and dedicated electronics, CdTe and CdZnTe detectors in the form of single elements or as segmented monolithic sensors have been shown to be useful in nuclear medicine imaging systems These detectors possess inherently better energy resolution than scintillators coupled to either photodiodes or photomultipliers and together with application specific integrated circuits lead to compact imaging systems with higher spatial resolution and enhanced contrast. Since the clinical demand for improved systems is increasing as nuclear medicine applications are expanding, CdTe and CZT detectors are now widely accepted and used. CdTe and CZT-based intraoperative probes are well established and have great impact on patient management in surgical oncology, particularly for sentinel node localisation (breast cancer and cutaneous melanoma). Although today a large field γ camera based on multi-element detector array is very expensive for clinical systems, small field of view, compact pixellated γ cameras with improved energy resolution have been developed and already on market. Affordable, high-performance, mobile small-field dedicated systems are very attractive, since they are more patient friendly, can be used closer to the patient and can be brought in areas such as operating theatres and intensive care units or can be used in hospitals, which do not have nuclear medicine sections. CZT detectors with high resistivity and low leakage current can be promising candidates for computerised tomography (CT) systems at a reasonable cost. However, potential problem, there, is the long afterglow of the CZT varying widely from a few µs to months, which might reduce the contrast sensitivity and the dynamic range. Regarding the position emission tomography (PET) systems, CdTe and CZT have better energy resolution compared to BGO and LSO scintillators currently used; though the latter have higher atomic number, higher densities, and therefore, higher efficiency than CdTe and CZT. The main limitation arises from the thickness of the semiconductor material presently available. CdTe and CZT detectors are currently been investigated if they can successfully compete with BGO and LSO scintillators. The first CdTe medical imaging system, NUCAM, was presented by Eisen et al. 18 aiming to replace the Anger type γ cameras. NUCAM is a small field cm camera equipped with CdTe:Cl detectors with Pt contacts and a pixel size of 4 4 mm, each one connected to a low-noise pre-amplifier and an amplifier-shaper. Continuous clinical trials of the NUCAM camera were carried out for more than 2 years in various hospitals in Israel and USA for different clinical procedures, such as cardiac Tl and Tc perfusion, Tc MIBI gated perfusion, Tc MUGA, thyroid, breast, and children organs. The performance of the NUCAM was comparable to that of the Anger camera, with contrast resolution due to scatter rejection better for the NUCAM camera. Digital Corporation (San Diego, USA) has developed the first small γ-camera based on CZT detectors, Digirad 2020t Imager, which is on market. It has an active area of cm made of mm CZT detector modules. Each module is an 8 8 array of pixels with an electrode configuration that reduces trapping problems. 19 The system can be mounted on a special rotation chair to carry out heart SPECT studies. Initial results show that Digirad camera has comparable or better performance than that of conventional Anger cameras allowing better imaging geometries in some clinical procedures such as breast imaging. Under the umbrella of BIOMED II European programme, a CdTe:Tl camera has been built (15 15 cm, 3 mm pixel) and images of test objects were obtained. These images were better when compared to those taken by a Helix γ camera, but the whole system suffered from low sensitivity. A CZD γ camera that provides an array of CZT pixels and associated front-end electronics has been designed permitting γ camera measurements using the method patented by CEA-LETI and reported by Verger et al. 20 Electron response in each CZT pixel is registered by correcting pulse height for position of interaction based on fast rise time information bringing advantage of high scatter rejection while allowing high detection efficiency. The project, named PEGASE, 21 has been developed at CEA-LETI in an exclusive joint development with BICRON and CRIS- MATEC, which in turn are commercialising the technology. The initial system is implemented in an array framework with 1920 pixels, approximately mm 2 in dimension, but the system architecture expands readily to 4096 pixels, and up to 8 boards can be combined to provide up to pixels without changes in system logic. Another example of small camera is the ELGEMS Vol No. 1 THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE 5

4 DARAMBARA SOLID STATE DETECTORS FOR USE IN NUCLEAR MEDICINE (Israel) prototype camera based on IMARAD mm CZT detector modules indium doped (2.5 mm pixel) and equipped with a modified collimator. Finally, Siemens Medical systems has an R&D collaborative project with IMARAD to design and build a large field of view γ camera. However, there are inherent limitations in planar imaging which restrict the further development of planar cameras based on semiconductor detectors. It is known that the spatial resolution and efficiency compromise in γ cameras is mainly controlled by the collimator. Therefore the use of solid-sate detectors in multiple-pinhole SPECT imaging could be proved more advantageous than in planar imaging. It has been shown in simulations by Rogulski et al. 22 that it is possible to have substantial improvement in both spatial resolution and counting efficiency over conventional systems, if a combination of multiple-pinhole imaging system and high-resolution semiconductor detector arrays is used. A prototype system (ultra high resolution brain SPECT system, Tuscon University of Arizona, USA) using CZT focal-plane arrays is under development 23 consisting of 256 modular detectors in a full 3D-SPECT approach. The detector is a hybrid CZT detector array interfaced to a multiplexer readout chip custom designed for this application. Another application of semiconductor detectors concerns the Compton camera or electronically collimated SPECT, which has the potential for dramatic improvement in sensitivity without sacrificing spatial resolution. The standard Compton camera is a twodetector coincidence system. Several approaches of Compton camera have been developed based on segmented Ge detectors, Si-pad or microstrip Si detectors Most recently, feasibility studies of using CdTe and CZT detectors for Compton camera have been presented. 28, 29 However, even though CZT has a better energy resolution than most scintillators, its value is still below that of Ge. It is expected that this type of Compton camera will work better at higher energies such as 511 kev. A medical imaging system providing both X-ray transmission and radionuclide measurements would allow correlation of structural and functional information. Most recently systems based on pixellated CZT detector for combined X-ray computed tomography (CT) and single photon emission computed tomography (SPECT) imaging modalities have been designed and are currently evaluated. Preliminary results suggest that CZT detector is capable of performing both X-ray CT and SPECT with fast photon counting electronics. 30, 31 Most of the tumours clinically detected by scintillator-based γ cameras may be investigated by intraoperative detection when they require surgical treatment. The intraoperative detection has been so far evaluated in the case of several pathologies including osteoid osteoma, colorectal cancer, neuroblastoma, re-operation of differentiated thyroid carcinoma and localisation of sentinel node in breast cancer and cutaneous melanoma. This means that the development of miniaturised nuclear probes presents potential interest. Depending upon the type of application some particular probes and electronic devices have been designed to provide the surgeon with the best information. Manufacturers of intraoperative probes use either scintillators or semiconductors, which are well adapted for the range of energies covered by nuclear medicine. Four commercially available probes based on CdTe, CZT, NaI, CdTe or CsI have been developed and evaluated. 32, 33 These are: 1) the Auto Suture Navigator system based on CdTe detector; 2) the CareWise C-Trak system based on NaI(Tl) scintillator and photomultiplier tube; 3) the Eurorad system: EURO- PROBE; this device can accommodate two probes: a CdTe detector for low- and middle-energy range and a CsI(Tl) with a Si photodiode for middle- and highenergy range; and 4) the Neoprobe system (1500 and neo2000); at the beginning Neoprobe worked with CdTe detectors, now replaced by CZT with significant improvements in spectroscopic capabilities. The CZTand NaI-based probes are preferred due to their higher sensitivity in the kev energy range. All these commercial probes for intraoperative use are based either on a single scintillation crystal or single semiconductor detector having a size ranging between 5 and 20 mm in diameter. However, small multi-detector CZT devices are under development. Conclusions Overall, due to the significant progress in producing high-quality CdTe and CdZnTe crystals, these materials are now regarded as promising candidates for X- and γ-ray detectors for medical applications. In particular, it is demonstrated that these room temperature detectors are capable of improving the spatial resolution and imaging performance of nuclear medicine cameras. However, the widespread use of 6 THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE March 2002

5 SOLID STATE DETECTORS FOR USE IN NUCLEAR MEDICINE DARAMBARA these detectors depends on the production and availability of low-cost large-area semiconductor substrates as well as on further advances in ASICs for the fabrication of fine pitch pixel detectors. Work currently under way by research laboratories and industry will take forward the further development of these promising detectors. References 1. Anger HO. Scintillation camera. Rev Sci Instr 1958;29: Siffert P. Cadmium telluride and related materials as X- and γ-ray detectors: a review of recent progress. Proc SPIE 1994;2305: Takahashi T, Watanabe S, Kouda M, Sato G, Okada Y, Kubo S et al. High-resolution CdTe detector and applications to imaging devices. IEEE Trans Nucl Sci 2001;NS-48: Eisen Y. Current state-of-the-art industrial and research applications using room-temperature CdTe and CdZnTe solid state detectors. Nucl Inst Meth Phys Res 1996;A380: Takahashi T, Watanabe S. Recent progress in CdTe and CdZnTe detectors. 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