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CdTe detectors in medicine: a review of current applications and future perspectives
WJear instruments and Methods in Physics Research A322 (1992) 604-614 North-Holland
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INST 11
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in medicine : a review of current applications ture perspectives C. Scheiber and J. Cambron
Serrice de .,Ujdecine Nucijaire, histitut de Pkysique Biok)gique, Faculti de Midecine . 6708-5 Strasbourg Cedex, France
Cadmium telluride (CdTe) semiconductor sensors have been evaluated for medical applications for 15 years owing to their high stopping power, convenient energy resolution and operating conditions at room temperature . Most of the applications herein re,iewed concern medical imaging procedures, i .e ., nuclear medicine, including positron emission tomography and radiology with computerized tomography (XCT). Despite their attractive physical characteristics, their preliminary commercial development has been _Nlowed down in the early 80s because of technical problems, particularly when large arrays were considered, and because of the competition with the more available and less expensive scintillators or xenon chambers which are still mounted in most modern medical imaging systems. Nowadays the characteristics of new materials have allowed the development of restricted but more specific domains of CdTe medical applications i .e . miniaturized nuclear probes dedicated to per-operative tumor detection or ambulatory, monitoring of physiological (renal, cardiac) functions and bone absorptiometry using either planar or miniature tomographic systems. Supported by these features and encouraged by the growing competition between ionising and non-ionizing imaging modalities (US, MRD, research work is presently conducted with a view to using CdTe detectors in XCT. troduction A considerable increase in medical imaging diagnostic performance and number of investigations has been noted in the last decade. Beside ionising radiations techniques (RX), i.e . nuclear medicine (NM) and radiology, high spatial resolution non-ionising methods such as ultrasound (US) and magnetic resonance imaging (MRI) have been developed and are in a very fast growing stage . NM ar.j RX a,c the main man-made sources of populatiA, exposure [1] but their indications are at first governed by their diagnostic performance . Me fatal=e of MA and RX lies in their specificity, but a!,,o depends on a diminution of the doses administered to the patients . CdTe sensors may contribute to achieve these goals: in NM by spreading its applications with the use of miniaturized probes and L; dose reduction in computerized tomography [2] . Despite suitable physical characteristics CdTe sensors are still at an early stage of their medical applications . For a realistic approach it is useful to review sensor specifications m(.unted in commercially available systca-as ire parallel with present CdTe medical applications and/or development .
. Radiology Radiology is based upon X-ray attenuation by the human body that assumes a mnonocxponential decay of the monochromatic beam. In fact, breinsstrahlung and
K lines are filtered to improve beam uniformity and narrow the spectrum . As far as sensors are concerned we can describe separately conventional radiology (CR) and computerized tomography (XCT), conventional tomography procedures becoming progressively obsolete . Other quantitative transmission techniques such as osteodensitometry may figure in the same chapter since most of the commercially available systems use an X-ray generator . 2.1 . Conventional radiology Digital CR is rapidly developing, X-ray films being replaced by light-intensifiers that are read either by TV cameras or CCD units . Digital imaging improves diagnostic performance together with data transmission and storage . This technological evolution has already been achieved for vascular investigations and is in progress for bone and abdominal techniques . Digital chest plane imaging is still problematic because of the large field of view (FOV) and physiological motion, as well as the high resolution which it requires . Semiconductor sensors are rarely used in CR to determine film exposition where conventional ionisation chamber-, arc too cumbersome . 2.2. Computed tomography The precise determination of body attenuation by X-rays requires to determine a space density distribution from its known projections onto one or more
01680002/92/$05AO (0 1992 - Elsevier Science Publishers B .V . All rights reserved
C. Scheiber, J. Chambron / CdTe detectors in medicine Table l Irradiation data for XCT detectors X-ray [kV] Tube current [mA] Dose flux detector [R/s] Typical attenuation Quanta flux [s -1 cm - `] Quanta rate per detector element [s -I cm -Z ] Sampling interval [ms] Quantum noise [variance %]
Head scan
Thorax
120 200-600 <3 90 3 .7 x 10 x 1 .1x10" 3 .7 x 10 7 1 .1 x 10 1° 1 0.3-3
137 80-220 <3 300 2 x 10 8 6x10' ° 2 x 10 7 _ 6x l0" 1 0 .3-5
planes . Solving this problem involves taking slices through the distribution and considering the projected densities to be line integrals through the slices. The image reconstruction (density distribution in the slice) is obtained by applying a Fourier transform or an orthogonal expansion of the line integrals [3] . The finite number of measurements and the polychromatic nature of the X-ray beam induced artefacts [41 . improvement of XCT [5] has led to a huge improvement of image quality through the optimization of data collection and the narrowing of slice thickness, but at the cost of higher photon fluxes and data sampl ;ng which determine sensors operating conditions (table 1). With the third generation XCT type, data are acquired in 1-2 s using a continuously rotating measurement system (fig . 1) which consists of an X-ray tube emitting a diverging beam (40° fan beam) and a large array of detectors (n = 768). Uniformity of detector response is assumed and all drifts are corrected by automatic computer-controlled calibration . The system resolution at
605
Table 2 Dose value in mGy for one slice of a brain scan (120 kV and 300 mAAs) Slice thickness [mm] Skin dose [mGy] CTDI [mGy]
10 20 37
5 19 31
1 15 28
high contrast is largely determined by the beam spacing (i .e . the detector grid projected to the isocenter), and modulation transfer functions (MTF) at 2% of 8-16 line paris/cm Op/cm) are obtained . Soft tissues have very similar X-ray attenuation and the diagnostic performance of the XCT is related to the resolution at low contrast which is strongly dose dependent. Table 2 illustrates typical skin and brain dose, averaged for 14 slices and normalized to a slice thickness (CTDI index) . Although many other parameters are involved (including collimators, electronics) dose reduction and/or further improvements of image quality can be achieved through detector improvement XCT sensors are either scintillators coupled to photodiodes or xenon chambers (25 bar) (table 3) . Research is conducted to increase detector efficiency while keeping the afterglow as short as nossihle and to increase their density (number/degree). The mechanical motion induces septa vibrations and the detector should have a low microphonic sensitivity. The stability (both short and long term) should be very high and its availability compatible with large industrial diffusion . A spectrometer should be used to reduce the "beam hardening" artefact (in posterior and temporal fossa of the brain) and diffusion (body scan) . The dual-energy absorption densitometry technique (see below) is another potential application of spectrometry. CdTe detectors have theoretical advantages due to the lower energy required to produce a charge pair (4 .5 eV) compared to other sensors (30 eV) and due to their solid state which provides excellent stability . The difficulties which must yet be overcome are both eco-
Table 3 Important detector properties for XCT applications
Fig. 1 . Third generation XCT principle : the 40° fan beam consists of 768 xenon chambers (25 bar) detectors . (Reprint from ref. [4], p 118 with permission .)
Signal to noise ratio X-ray energy absorption [%] Speed of response (afterglow) [ms] Reproducibility of response Detector dimensions [mm] Availability and costs
Xenon
CdIA1 04
Ceramic
CdTc
++
+++
+ ++
+
70
95
99
95
<1
<3
<2
-
++
+
++
-
+ ++
+ +
+ +
+ -
V . APPLICATIONS
C. Scheiber, J. Chambron / CdTe detectors in medicine nomic (availability, cost) as well as technical (time response, linearity under high photon flux, sensitivity to vibrations). As far as we know, CdTe detectors are presently evaluated in company research centers but no published data are available . 23'. Borte densâtometty A decrease in the total mass of bone, a normal concomitant in the aging process, is accelerated in ost-oporotic patients. The most striking loss, of calcium occurs in the trabecular bone of vertebral bodies but also in the neck of the femur, the upper humerus and the dis-,al radius . The diagnosis used to be based upon C. : : :;z ,-. n advanced stage of the disease when the vertebr`._ bodies had collapsed because of a loss of calcium, the rate r f which had fallen beneath the '-vel required for bon_- matrix stability . Absorptiometric techniques designed to measure quantitatively and noninvasively bone density at an early stage of the disease when medical treatment is more efficient . Bone densitometrv is even more useful for treatment followup which requires a high reproducibility (1 170 of measurement . Absorptiometry is based upon monoexponential attenuation of a monochromatic beam. Radioactive source ("1 (gamma-ray 27.5 keV, 15 GBq) or ';;Gd (K X-ray -12--f8 keV tnd gamma-ray 97, 103 keV)) have been replaced by an X-ray tube (50-90 keV) for higher sensitivity and practical use . Both planar and tomographic techniques are described further on. Planar techniques must be corrected for soft tissue attenuation using a dual-energy subtraction technique [6,7]. This method utilizes the different energy dependences of Compton- and photoabsorption cross sections. A specific element can be distinguished from its matrix and its density evaluated if its atomic number differs signs icantly from that of its matrix . Similarly a group of heavy elements can be distinguished from a group of lighter elements. When known bone standards are measured in the same conditions, the experimental data can be converted to grams of bone mineral per
Discriminatorl Counterl VL
H. V.
VH
Discriminatorl Counter2 Fig . 2. Diagram of the detector element of the CdTe X-ray imaging sensor . (Reprint from ref . [9J, p . 97 with permission .)
Fig . 3. (a) Low-energy image; (b) high-energy image and (c) computed bone density image of a hand phantom on 13 cm acrylic plate . (Reprint from ref. [9), p. 100 with permission .)
cm-' since the value of the attenuation coefficient is determined . Although the usefulness of CdTe detectors was described in 1977 using a single energy method [8] their application with regards to the dual-energy absorption technique is still under development . A Japanese research center has developed a 64 CdTe linear imaging sensor [9] which operated in the pulse counting mode. The photon source is an X-ray tube (100 kV) with a IC-edge filter separating the continuous beam into two energy levels at about 60 keV . Each detector channel comprises a CdTe crystal (2 x 2 x 0.5 mm), a current-voltage conversion amplifier and two sets of discriminators (fig. 2). The output pulses of height greater than the discrimination voltage VL (noise level) and HL (separation energy level : 60 keV) were counted separately. The two X-ray photon counting images (low-energy and high-energy) of a hand phantom in acrylic were taken simultaneously by single synchronous scanning of both the sensor and the X-ray tube (fig. 3). The bone density image was derived by image subtraction according to densitometry theory equations . Bone phantoms were measured and bone mineral densities corresponded to their true values . CdTe sensor count-rate linearity was tested up to 50
C Scheiber, J. Chambron / CdTe detectors in medicine
07
to test all organs and tissue functions . These investigations are noninvasive owing to external detection of organ radioactivity . NM studies are devoted to the investigation of dynamic metabolic processes using mathematical (often compartmental) analysis of the time activity curves derived from the volume of interest WOD. In most cases, data are represented as a bidimensional image of count distribution in the FOV of the detector . As far as radionuclide emitting particles are concerned, conventional NM should be distinguished from positron emission tomography (PET). 3. 1. Positron einission tonzography Fig . 4 . A miniature tomographic for peripheral bone densito metry . The distal radius bone density is measured with a 1 17 .r reproducibility . (Courtesy of Stratec company .)
kcounts/s (kcps), with an 18171 energy resolution (FWHM) . A complete high resolution (1 mm) data set is obtained by a single scanning within one minute of acquisition time . Planar methods are easy to implement but the measurements are blurred by geometric artefacts, and they cannot discriminate vertebral bones from other calcified structures (arthrosis, vessels) . These factors affect not only the absolute mineral density (gcm -2 ) but also the reproducibility of the measurement . Computerized tomography allows direct measurement of trabccular bone mineral density in gcm- 3. A whole-body XCT may be advantageously replaced by a dedicated system developed by a German University [101 . This miniature (scale 1/8) first generation type XCT (translation-rotation) uses six CdTe detectors (fig. 4). The X-ray beam is almost monochromatic (38 keV, FWHM : 8 kcV) . After careful selection (planar image) of the 2 .5 mm slice of interest the image (128 2 ) is obtained after 7 min (acquisition time) . In these conditions the radius exposition is 0 .1 mSv. A 15 cm FOV is available to determine the mineral density of distal radius with a reproducibility of 1% [11] . It has been demonstrated [12] that peripheral bone measurements have a higher sensitivity and specificity in predicting axial fracture risk than dual-energy X-ray absorptiometry performed on the vertebral bodies which was taken as the reference method.
3 . Nuclear medicine The main goal of NM is the physiological studies of tissues by using specific radioactive tracers . The labeled molecule is injected in negligible amounts, and detected owing to its high specific activity . A large variety of radiopharmaccuticals are currently available
PET makes possible the quantization of the rugional distribution of positron-emitting radioisotopes in a selected organ owing to the unique characteristics of positron annihilation in tissues . Since a large variety of physiological substances can be labeled with positron emitters ("F, "C, ' I N, 1 *1 0) this lechi ;ique can be used to monitor various biochemical and physiological processes in living tissues [13] . After a short distance (1-2 mm) the annihilation with an electron produces simultaneously two 511 keV gamma rays in directions nearly opposite to each other . The presence of a positron is assessed by the simultaneous detection of two annihilation gamma photons interacting with two radiation detectors . Events are registered in coincidence if they are detected within a 5 ns time window. Coincidence detection of positrons emitted outside the volume delimited by the two detectors is not registered owing to electronic collimation . In order to optimize detection, each detector in a PET camera is coupled in coincidence with many others . Typically the detectors are arranged around the body in multiple rings to obtain multiple slices of the organ at one time . The spatial resolution is degraded by some factors such as : the positron range, angle deviation, photon interactions, scattered radiations, attenuation of photons, and random coincidences implying adequate corrections [14]. Currently available high spatial resolution cameras use small scintillation crystals and PM tubes. A high density and a very short decay time are required . Usually BGO (bismuth germanate oxide) is used . The main characteristics of a EGO detector are summarized in table 4 . Gd .,SiO 5 crystals are being evaluated for their short scintillation time (60 ns) but Table 4 Main characteristics of a typical BGO-PM detector for PET camera Coincidence photopeak efficiency Timing resolution [s] Energy resolution for 511 key FWHM Scintillation decay constant [s] Block intrinsic spatial resolution MTF (5 1-c) line paris c .ii - 1
41 3X 10 -9 13 300X 10 - " 3
V . APPLICATIONS
C SchAer; I Chanibron / CdTe detectors in medicine
bps
fable 5 Main characteristics of a typical gamma-camera Detection efficiency for 140 keV Energy resolution FWHM [%] (50 cm d . FOV) Count rate linearity (50 cm d . FO") Uniformity [%] (50 cm d . FOV) Spatial resolution MTF (5%) at 5 mm 0 cm - I Spatial resolution MTF (5 %,) at 100 mm lp cm - I
95 >11 > 105 >4
3-2 Conventional NM The gamma-camera [17] is widely used for both planar or single photon emission computerized tomography (SPELT) [18] procedures instead of the conventional nuclear probe .
Fig . 5 . Block element. of a modem AGO based PET camera : 64 crystals are coupled to four miniature PM tubes. (Courtesy of Siemens company .)
33. The gamnia -camera remain expensive. The geometry of the crystal is an important feature and the detectors are used in the form of a block detector 30 mm thick. Each BGO crystal is divided in 64 crystal segments (6.8 min apart with a 0 .6 mm gap) [15]. The blocks are placed in modules of four (fig . 5) and ten units are mounted in each of the sixteen detector rings (8192 crystals). The linearity (10% loss) of a PET camera is 500 kcps for a specific activity of 200 kBq/ml . m-operating semiconductor detectors are very attractive because their excellent stopping power: they, can be assembled into position sensitive arrays . Unfortunately . their properties are such that thick detectors yield poor spectral response where events register at a lower than true energy. this tailing effect is not uniform either as a function of energy or among detectors- CdTe detectors 2-5 mm thick have been evaluated : the spectral response was such that a majority of the stopped 511 keV register above a threshold of 100 keV . The detector efficiency was 30% . Coincidence resolution was found to be 50-100 ns depending on the detector thickness [16].
This stationary detector basically consists of a parallel holes collimator and a large Nal scintillator (60 X 40 X 10 cm) . This large FOV is the main feature of the gamma camera and the determinant factor in the development of NM. The spatial localization of the scintillation light is achieved by 90 photomultiplier tubes and a calibrated resistance network . Signal numerisation allows computer controlled corrections for system imperfections (energy, linearity, uniformity). The main characteristics of a gamma-camera are summarized in table 5 . It ;- reminded that for clinical dose and examination time, it is not useful to design a very high spatial resolution detector, the corresponding collimator transparency being so low that the image quality is spoiled by the statistical fluctuations of each image point . In practice, radiopharmaceuticals designed for human studies can be labeled with a limited number of radioisotopes (table 6) among which 99 'Tc (140 keV) represents more than 70% of routine NM investigations . Quantitative studies, based on the proportional relationship existing between organ activity and the
a
TAW 6 List of main radioisotopes in NM Isotope
Half-life
Energy [keV]
""'Tc 2m -I'1 1 '- ; I 67 Ga MI
6 .02 h 73 .5 h 13 .2 h 78 .1 yr 8 yr 53 yr 60 yr 1 .50 h
140 69-83 (X) 156 296,184,93 364 81 27 .5 393
Xe lu i Is 113
In
Clinical use
Availability ++
+ +
+++
+
+++
Cost
C Scheiber, J. Chambron / CdTe detectors in medicine
609
to that of gamma-cameras. Although the field of their medical applications is relatively limited it consists of unique nuclear medicine procedures ; thus it is an important potential development for NM . Conventional Nal probes are still cumbersome and should be advantageously replaced by miniaturized CdTe probes especially in two ranges of applications: the peroperative localization of small masses and the continuous monitoring of physiological functions . 3.5. hitraoperative probes
Fig. 6 . A new two-heads rotating gamma-camera . The large FOV (60 X 40 X I cm) of the Nal based Anger camera was a determinant factor in the development of nuclear medicine . (Courtesy of Eiscint company .)
detected counts, arc hampered by the activity of nonselected tissues both within and without the FOV, and gamma-ray attenuation . Dosimetry is another limiting factor and in most clinical studies poor statistics are encountered . At the present time these problems [19] have not been solved by using SPELT, either with one rotating head camera or multidetector systems. Compton diffusion (particularly primary photons emitted outside of the VOI and having undergone a Compton interaction in the FOV) has a strong incidence on NM data, resulting in a lower image signal/noise ratio, and thus compromises quantification . Spectrometry allows a significant reduction of the Compton component at the cost of a lower count rate . Using multiple windows and tracers labeled with distinct energy emitters enables one to study simultaneously two biological functions. Semiconductors arrays have been considered [20,21] for improved energy resolution, counting rate, and mechanical convenience . McCready et at . [20] have built and evaluated a GOLD camera based on the multiwire chamber principle (fig . 6) (a row of parallel line electrodes on top of the crystal and another row (but perpendicular) electrode array on the bottom). The energy resolution was reasonably good (10 keV) but the sensitive area was limited . CdTe arrays were evaluated [22] but at the time dispersion of crystal characteristics and polarization problems were too large to allow the realization of a convemional whoic-body camera . 3.4. Nuclear probes Nuclear probes are still being used for their higher sensitivity, portability and relatively low cost compared
In oncology, loco-regional tumor extension and lymph nodes involvement are essential elements for diagnosis and treatment . High spatial resolution methods (US, XCT, MI I) are very efficient with regards to the localization of 0 .5 cm lymph nodes but fail to demonstrate their tumoral involvement . NM may contribute to achieve this goal by using specific tumoral tracers . At the present time, only few specific tracers are available (antibodies, antimitotic drugs, hormone precursors) for routine investigations and tracers with only nonspecific femoral affinity are still employed (0Ga, 2° "T0 . The tracer is injected I to 3 days before the investigation in order to decrease nonspecific activity by clearance . The signal/noise is a function of the tumor uptake (volume, vascularization, metabolism) and background activity. Usually the lesion is small and located so deep inside the body that external detection with the gamma-camera is unsuccessful. The point of using a miniaturized probe is that one can get closer to the pathological site . This can be achieved either during surgery or by insertion of the probe in the body (during broncho-, gastro- or recto scopy). The use of both INa(TD and CdTe probes have been described and recently reviewed [23] . A typical hand-held gamma detecting probe is 15 cm long, 4 cm in diameter, is gas-sterilizable, made in stainless steel, very sensitive to decrease the count integration time, but collimated to be directional (fig . 7) . Nonimaging probes are subject to localization errors . The detection of an unknown region of interest with a single-hole collimated probe is difficult when a nonspecific uptake arises from healthy tissues, the localization of the lesion being dependent on small changes in probe orientation . In order to overcome I,'i;.E problem a multidetector system should be used and a low energy emitter, like 1251 (27 .5 keV), should be preferred . The gamma photons detected are transformed into both a digital readout and an auditory signal after being discriminated from background activity .
Peroperative detection of subclinical tismoral mass or involved lymph nodes has been applied in thyroid highly differentiated cancer surgery . This tumor concentrates iodine in the same way as a healthy thyroid V . APPLICATIONS
C. Scheiber, J. Chambrcn / CdTe detectors in medicine
Fig . 7. CdTe surgical probe and associated electronics. The probe is IS cm lone and 2 cm in diameters . The battery-operated, gas-sterilisable probe is designed for intraoperative use with ' 2~1 monoclonal antibodies. (Courtesy of Neoprobe company.)
gland does . Twentv patients referred to surgery for thivroid cancer have been injected with 20 MBq ' -'I intravenously, 24 hours before the operation [241. After removal of all macroscopically visible thyroid tissue and metastatic growth. the operative field was examined with a CdTe probe . Iodine uptake was found in 16 out of the 2 patients. Recording over different-sized tissue fragments showed the detector to be very highly sensitive, and capable to detect tissue fragments weighing less than 2 me. These results indicate that intraoperative scintigraphy significantly reduces the need of postoperative radiciodine ablation (3 .7 GBq, ' 3 '1), a very high exposure for such young patients . Another CdTe probe has been used in the precise localization of two malignant pheochromocytoma after the injection of I mg meta-iodo-benzyl-guanidine (mIBG, 74 1v1Bq, ' -'I) [251, the tumor background count ratio was 10. Since 1986, Cd"fe probes [261 have been used in extensive clinical evaluation for radioimmunolocalization of colorectal carcinoma . In another study from the same research group a ' 2 'I-MAb B72 .3 IgG [271 was used . Thirty-one patients with primary or recurrent colorectal carcinoma were examined during surgery : 83% of re,:urrent sites were detected . The procedure did alter the surgical approach in 26% (8/31) of the patients with recurrent colorectal cancer . A further report noted that 68% (21/31) [281 of the rumor sites had probe counts at least twice those of normal tissue . In 2 out of 32 patients the only tumor found was localized by the probe . These results have been confirmed by Lecouffe [291 using another CdTe probe [30] . Feistel et al . [311 have shown in a study of women with ovarian carcinoma, using "' I-OC-125 F(ab')2, that 66%
of the probe guided biopsies were positive compared with only 15% of the blind biopsies, when the disease was not clinically evident . Some of the inherent limitations of the nonimaging probes can be overcome by using two NaI(Tl) crystals [321 or imaging-detector systems . A planar array of 21 CdTe was evaluated with regards to thyroid imaging [231 . The detector has a parallel hole collimator with a FOV of 2 .5 cm in diameter and was able to generate scintigraphy . The spatial resolution at the face of the probe was 3 mm but unfortunately with a low efficiency . Probes have been used inside the body for a variety of applications other than malignant tumor detection . These include the precise localization of osteoid osteoma [33,341, a benign bone lesion, which remains symptomatic when a nidus has been incompletely removed during surgery . The osteoma concentrate the bone tracer ("'Tc-methylene-phosphonate) . More recently [351 both Nal and CdTe probes have been used in a series of 30 patients ; the CdTe probe has proved to be a more durable, more reliable (solid/hygroscopic), more sensitive (10 times more so than Nal probes) and sterilisable probe . These CdTe probes have been used for intraoperative localization of benign parathyroid ailenonia after an Injection of °" TI [361 . CdTe detectors are small enough to be incorporated in medical probes that are inserted into the upper or lower gastrointestinal tract in the immediate vicinity of the tumor . In this situation, the localization is not helped by visual inspection and probe angulation as in intraoperative investigation . Imaging CdTe probes can determine the size, distance and anatomical location of tumors . One of these probes consists of an array of seven CdTe stacked detectors, one detector having a different 51° FOV through a separate, nonoverlapping azimuthal aperture [371 . The detector was designed to image mediastinal lymph nodes, as it is withdrawn through the oesophagus . A scan of the mediastinum takes approximately 20 min . 3.5. Continuous monitoring of patients's physiological functions Continuous monitoring of electrocardiogram (ECG) is largely indicated both in intensive care units, to detect symptoms of cardiac dysfunction in real time, or during patients' daily activities (ambulatory) for a better understanding of transient troubles of the cardiac rythm or ischaernic episodes. NM procedures are suitable for the continuous monitoring of physiological parameters . At the present time, the acquisition period is limited to one physical period of the tracer used, 6 h in the case of '9mTc . Ambulatory measurements are more difficult to achieve than bedside monitoring because of patients' motion .
C Scheiber, J. Chambron / CdTe detectors ira medicine
Two miniaturized portable and autonomous CdTe probes were used for blood-flow measurements in adipose and muscle tissue by local clearance studies with 133 Xe [38,39]. 133 Xe is injected in the anterior tibial muscle ; the decrease of local radioactivity with time, assumed to be a perfusion-dependent process, indicates the effective blood flow in the muscle . Transient pathological decrease of the renal function may occur in the course of a patient's normal life, due for example to a mobile kidney. The renal function can be assessed by measuring the plasma clearance of a chemical compound which is selectively eliminated by the kidneys. Itadiopharmaceuticals were developed to study both the glomerular (99mTc-DTPA) [40) and the tubular ( 123 1-I3ippuran) [41] renal function. In practice, the time activity curve recorded by the CdTe probe in the precordial area is assimilated to the plasma activity curve. At equilibrium with the extravascular space the monoexponential decay of the physical decay corrected curve reflects the renal function. Long term monitoring allows several values to be computed and assessment of any significant modification of the renal clearance . CdTe probes were used for glomerular filtration measurement using a P-type CdTe (resistivity : 104-106 11 cm', 0.8 mm thickness), the noise level was set at 40 keV, the results being concordant with the reference method using s1 Cr-EDTA and the multiple plasma sample technique (r = 0.97 ; n = 21) [42]. The value of biotelemetry measurement was clearly demonstrated : in the last 30 min period of muscular exercise the clearance has decreased by a factor of 5. The same detection system was used for the continuous monitoring of the renal graft function [43]: a significant decrease of DTPA clearance was considered an early sign of transplant rejection 24 h before elevation of plasma creatinine (reference method). A small CdTe probe with a chlorine doped high resistivity crystal (10 8-109 fl cm -') was found well adapted to pediatric studies with some modifications of the collimation in order to decrease high background activity of the bladder. The spectrometric characteristics of the probe permitted double-isotope studies using 99 'Tc-DTPA and 51 CrEDTA [44]. Another group of workers have built a CdTe based (P type, chlorine doped, 3 mm thickness, 4 min 2) detection system which was used to measure the tubular function (2MBq, 123 T-fiiopuran) in 20 patients : the results correlated well with the simultaneous measurements using the gamma-camera [45]. Tubular/ glomerular clearance ratio is 5; this higher clearance indicates the tubular tracer when global renal function is severely impaired. The reliability of these CdTe probes in the medical environment was found ilisufficient [46] and preliminary attempts of commercialization have been stopped . Presently this work has been resumed, with new CdTe materials .
Nuclear medicine has a large domain of cardiac applications . The left ventricular function can be evaluated by the ejection fraction (LVEF) which is the fraction of blood contained i 1.h c left ventricular chamber at the end of the diastolic phase ejected during heart systolic contraction, the normal value range being 60-80% at rest. The ability to continuously monitor LVEF in addition to ECG : wasurements would be of great value for the assessment of the ventricular function in both the critically ill, as well as the ambulatory cardiac patients. For instance, it can contribute to detect transient ischemic cardiac episodes which present neither ECG abnormalities nor pain (silent ischaemia) [47], and it has been reported that ECG signs of ischaemia (ST depression) must be interpreted cautiously in the case of patients with known obstructive coronary disease [48]. e cardiac investigation [49] is based on the isotopic dilution principle : the detector count rate being proportional to the l is labeled ventricular volume. Today, the blood with 500 Bq "Tc [50]. At equilibrium, the background activity, i.e. non-left-ventricular counts, is as high as 55-75% . Most of the time the study is perservice formed with the gamma-camera in the N allowing a precise and reproducible (automatic) determination of the ventricular border and background measurements . Owing to the low sensitivity inherent in the device, several hundred (600) cardiac cycles must be averaged in phase with ECG synchronization [51] to produce a high-quality data set consisting of 24 (40 ms each) 642 frames . The LVEF is derived from the background subtracted ventricular time activity curve . The gamma-camera method is not sensitive enough to detect rapidly changing events and is too cumbersome for evaluating serial function at the bedside. Nonimaging probes can provide high temporal resolution activity curves and were evaluated in the mid-1970s with the e madevelopment of the nuclear stethoscope [52]. jor assumption of this nonimaging approach is that the ventricular region can be isolated from other cardiac structures so that changes in radionuclide counts reflect the changes in ejection fraction and volumes. Breisblatt has reviewed [5.3,54] tine advantages and problems related to nonimaging devices for LVEF measurements and summarized the main characteristics of an ideal cardiac probe for continuous monitoring. Although the first CdTe system described was an array [55], the first clinical results published were about a system using a single crystal, 1.5 cm2 sensitive area, 2 mm thick probe. The results correlated with those from the camera method (n = 18, r = 074) or tho NATO probe (r = 0.76) [56,57]. Another study using a detector with higher spectrometric capabilities [58] have shown similar results. The background is higher (75-81%) V. APPLICATIONS
61 2
C. Scheiber, J. Chambron / CdTe detectors in medicine
Fig. S . The `, EST: this autonomous and portable Nat miniature detector is designed for ambulatory monitoring of cardiac function b)9 measurement of the left ventricul- ?;action fraction. (Courtesy of Capintec Corp.)
compared to that measured with the Nal probe in
relation to the large collimation rather than the scatter faction. For all groups the results have shown too large a variance (> 10%) in the range of interest (VEF : 50-60 1x) precluding the medical use. The sensitive area was too small (maximum of 1 .5 cm - ); thus the geometry was not adapted to ever' ventricular shape and the sensitivity was too love for rapid serial measurements [59]. A CdTe array of seven detectors,
connected in parallel, has been evaluated in 1983 [60] . The results have shown the expected improvements (n = 37, r = 0.95) due to the increased active area and higher sensitivity, but technical problems have be--n encountered an :] a INa miniature probe was finally chosen . At the same period of time a l-lgl, probe was evaluated [61] but has been recently replaced by a Csl(Tl) scintillator [62] . Today there is only one commercial system available [63]. The VEST* consists of a 5 .6 cm diameter NATO crystal coupled with a miniature PM tube (Fig. 8). Despite encouraging clinical results both during muscular exercise [64] and ambulatory monitoring [65] this nonimaging probe does not have the expected commercial diffusion considering its medical interest. Nonimaging probes require a gammacamera to be positioned exactly in front of the left ventricular region ; moreover, as far as ambulatory monitoring is concerned, stability of detection geometry needs to be perfectly assessed, a difficult task for a nonimaging device . New developments are implemented in the latest CdTe array [66]. The current prototype consists of 12 (10 x 10 x 2 mm) CdTe, which operate in the counting mode, each detector having independent electronics . The geometry is controlled by 10 x 10 mm cylindrical collimators ; the total sensitive area is 36 cm-' . Miniaturized and low consumption electronics was designed. Acquisition and data processing are performed by a commercial microcomputer and application sufiware . A typical set of time activity ventricular curves is shown in fig . 9 . These curves were
W4 . @a m
Fig . 9. Twelve regional ventricular activity curves as recorded by a twelve CdTe prototype designed for cardiac monitoring . These curves reflect the cardiac activity (5n cycles were acquired with ECG triggering) along the cardiac cycle after appropriate background correction . The left ventricular function ca .i be derived from these data .
C Scheiber, J. Chambron / CdTe defectors in medicine
obtained after the acquisition of 50 cardiac cycles with a temporal resolution of 40 ms/point . The background was set at 75% of the diastolic counts . The characteristic shape of the ventricular curve can be recognized . The first clinical results demonstrated good correlation with the reference method (r = 0.87, n = 25). A reproducibility of 5% was found, based on nine successive measurements . Most important, the detector is now very stable and no detection problems have been noied. These preliminary results arc encouraging but sensitivity must be optimized. A portable and ;-!utonomous system is currently being deveioped.
4 . Conclusion
Although CdTe detectors have very attractive physical characteristics with regards to their utilization in NM and RX, they are still at an early stage of commercial diffusion. They were extensively evaluated during the late 70s and a variety of medical applications were envisaged. Specific technical problems (reliability, polarization, electronics, availability, cost) have slowed down their medical use for the past ten years. Today, workable materials have now overcome most of these problems and developments in electronics have allowed dedicated multidetector probes to be built which can compete with scintillators. At the present time industrial medical applications are more oriented towards probe miniaturization rather than detection efficiency with the development of intraoperative probes, and tomographic bone absorptiometry, where these detectors have demonstrated their superiority . Continuous radionuclide monitoring of the renal or cardiac function is promising but still at a stage of clinical evaluation . The potential CdTe applications in high spatial resolution devices like XCT are presently being reevaluated, with regards to the new materials, encouraged by the competition beiween ionising and nonionising imaging methods.
eferences [1] A. Marchetti, M. Paganin i-Fioratti, A. Susanna, A. Calicchia, P.L. Indovina and P. Salvadori, Proc . Symp. on Patient Exposure to Radiation in Medical X-ray Diagnosis, EUR 7438, A. G. Drexler (Commission of the European Community, Luxembourg, 1981) p. 107. [2] G. Entine, Rev. de Phys . Appl . 12 (1977) 356. [3] M.A. Cormack, Phys . Mod. Biol . 18 (1973) 195. [4] E. Krestel, in : Bildgebende Systeme für die medizinische Diagnostik (Siemens, Erlangen, 1988) p . 89 . [51 G .N . Hounsfield, J. Ambrose and J. Perry, Brit . J Radio] . 46 (1973) 1016 . [6] G.W. Resd, Phys . Med. Biol . It (1966) 1174.
61 3
W.L. Dunn, H.W. Wahner and B.L. Riggs, Radiology 136 (1980) 485. [8] J. Vogel and J. Ullman, Rev. de Phys . Appl . 12 (1977) 375 . [9] T. Ohtsushi, H. Tsutsui, K_ Ohmori and S. Baba, Technical Digest of the 10th Sensor Symp ., Arcadia Ichigaya (shigaku Kaitran, Tokyo, ed . T. Nakamura (institute of Electrical Engineers of Japan, Tokyo, Japan, 1991) p. 97. [10] P. Schneider, Thesis, Bayersichen J. Maximilians-Universität zu Würzburg (RFA) (1984) . [11] P. Schneider and W. Bbrner, Fortschr . Rdntgenstr. 154 (1991) 292. [12] P. Schneider and W. Bbrner, Fortschr . R6ntgenstr . (Thieme, Stuttgart, New York) 154 (3) (1991) 292. [13] M.E . Phelps, in : Positron Emission Tomography and Audioradiography (Raven, New York, 1986) p. 237. [14] N.D . Volkow, N.A. Mullani and B. Bendriem, Am . J. Physiol. Imaging 3 (1988) 142. [15] S.E. Derenzo, IEEE Trans. Nucl . Sci. NS-28 (1981) 81 . [16] L. Kaufman and S.H . William, IEEE Trans Nucl . Sci. NS-26 (1979) 648. [171 H.O . Anger, Rev. Sci. Instr. 29 (1958) 27 . (18) D.E . Kuhl and R.Q. Edwards, Radiology 80 (1963) 653. [191 M.E . Phelps, Sem. Nucl . Med. 4 (1977) 337. [20] V.R . McCready. R.P . Parker. E.M . Gunnersen, R. Ellis, E. Moss, W.G . Gore and J_ Bell, Brit . J. Radiology 44 (1971) 58 . [211 J.F. Detko, Radiology 104 (1972) 461 . [22] R. Allemand, P. Bouteiller and M. Laval, Rev. de Phys . Appl . 12 (1977) 365 [23] J.M. Woolfenden and H.B . Barber, AJR 153 (1989) 35. [24] S. Lennquist, J. Persliden and S. Smeds, World J. Surg. 10 (1986) 711 . [25] M. Ricard, R. Regal, M. Schlumberger, J.P . Travagli, B. Malassagne, D. Elias and C. Parmentier, J. Med. Nucl . Biophys. 1 4 (1990) 151. [26] E.W. Martin, S.E. Tuttle, M. Rousseau, C.M . Mojzisik, P.J . O'Dwyer and G.H . Hinkle, Hybridoma 5 (suppl .) (1986) p. 97. [27] B.J . Sickle-Santanello, P.J . O'Dwyer, C., Mojzisik. R.N . Tuttle, G.H . Hinkle and M. Rousseau . Dis. Colon Rectum 30 (1987) 761 . [281 S.E. Tuttle, S.D . Jewell, C.M . Mojzisik, G.H. Hinkle, D. Colcher, J. Schlorr and E.W. Martin, Int. J. Cancer 42 (1988)352 [29] P. Lecouffe, B. Carnaille, C. Hossein-Foucher, J.P. Triboulet, H. Venel, C. Prove and X. Marchandise, in : Trends and Possibilities in Nuclear Medicine (Shattauer, Stuttgart, New York, 1989) p. 2. [30] C. Hossein-Foucher, J. Rousseau, P. Lecouffe and R. Regal, Eur. J. Nucl . Med . 1 4 (1988) 226. [31] H. Feistel, F . Wolf, W. Jäger, E.M . Paterok and N. Lang, in : Radioactiv Isotop in Klinik und Forschung (Schattauer, Stuttgart, 1988) p. 63 . [32] T.S . Hickernell, H.B . Barber, H.H. Barett and J.M . Woolfenden, J. Nucl . Med. 29 (1988) 1101 . [33] B. Ghelman, F.M . Thompson and W.D. Arnold, J. Bone Joint Surgery 63 (1981) 826. [34] H.T. Harcke, J.J . Conway, M.O . Tachdjian, L.S . Dias, H.B. Noble, G.D . Mac Ewen, and R.T . Weiss. Skeletal Radiol . 13 (1985) 211 . [7]
V. APPLICATIONS
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1351 E.P. Szpryt, J.G . Hardy and C.L . Cotton, J. Bone Joint Sur- . 58 (1986) 642. [.,t,] C.S . Uhbi . J .G . Hardy and C.A. Pegg, Brit . J. Surg . 71 (11)84) 859. 1371 H.B . Barber, H.H . Barett, W.J . Wild and J.M . Woolfenden. IEEE Trans. Nucl . Sci. NS-31 (1984) 599. [381 J. Bojsen, N. Rossing, 0. Soeberg and S. Vadstrup, Rev. PhNs . Appl . 12 (1977) 361 . 1391 P. Ceretelli, M. Blau, D. Pendergast, C. Eisenhardt and .W. Rennie, IEEE Trans. Nucl . Sci. NS-25 (1978) 620. 1401 J.F. Klopper. W. Hauser and H.L . Atkins, J. Nucl . Med. 21 (1972) 107. 1411 G.C. Chisholm . M.D . Shor t and ß+1.I . Glass, Brit . J . Urol . 46 (1974) 591. 1,121 N. Rossing, J . Bojsen and P.L. Frederiksen, Scan. 1. Clin . Lab- Invest . 38 (1978) 23 . 14311 W.F. Sampson. D.J . Warren and .A . Mc Leod. J. Nue! . .22 (198 1) 411. Nie 141 H. R. Ham. A. Piepsz, NI . Hall, lei . Ectors and A. tibbeleir. Proc. 3rd World Cong. Nucl . Med. and Biol . Paris (19S2) ed . C. Raynaud (Pergamon) p. -*384. 1451 C . Scheîber, NLA. NIolinari. A. Gallmann and J. Chambrom oil, P. 588. j4r~j C. Scheiber. N .A . N-Iolinari, A. Gallmann and J. Chambron . Euir . J. Nucl . Med. 8 (1983) 138. 1471 NI .J . O'Hara . R.J- Jones. A. Lahiri and E.B . Raftery, Brit . Heart J. 55 (1986) 148. [-IS] R.S. Kohli. P.NI. Cashman. A. Lahiri and E.B. Raftery, Brit - Heart J. 60 (1988) 4. 4, M. Prinzinelal. E. Corday and H.C . Bergman. Science 108 (1948) 141).
150~ D.G . PaveL A.M . Zimmer and V.N . Patterson, J. Nucl . deal . 18, (1977) 305. i5l] G. Hoffmann and N. Kleine . Nuclearmedizin 7 (1968) 351) .
[52] H.N . Wagner, R. Wake, E. Nickoloff and F. Natarajan, Am . J. Cardiol. 38 (1976) 747. [531 W.M . Breisblatt and D. Schulman . Am . J. Noninvas . Cardiol . 3 (I(,t-9) 359. [54] W.M . Breisblatt, J. Nucl . Med. 32 (1991) 44 [55] J.L Lazewatsky, N.M . Alpen, R.H. Moore, C.A. Boucher, H.W . Strauss and G. Entine, IEEE Trans. Nucl . Sci. NS-27 (1980) 524. [56] P.B . Hoffer, H.J . Berger, J. Steidley, A.F . Brandet, A. Gottschalk and B .L. Zaret, Radiology 138 (1981) 477. [571 K.S . Harisson, X. Lice, S. Han, E.E . Camargo and H.N. Wagner. Eur. J. Nucl . Med. 7 (1982) 204. [58] C. Scheiber, M.A . Molinari, A. Gallmann and J. Chambron, Proc . Symp . Nucl . Cardiology, Vienna (1982) !) . 24 . (Europ . Soc. of Cardiology) . [591 C. Scheiber, M.A. Molinari, A. Gallmann and J. Chambron, Eur. J. Nucl . Med. 14 (1988) 281 . [60] R.A . Wilson, P.J. Sullivan, R.H . Moore, J.S . Zielonka, N.M . Alpen, C.A . Boucher. K.A . McKusick and H.W . Strauss, Am . J. Cardiol. 52 (1983) 601 . [61] A. Lahm, J.C . Crawley, R.I . Jones, M.J . Bowies and E.B . Raftery, Clin . Sci. 66 (1984) 551 [62] P. Broadhurst . P. Cashman, J.C . Crawley. E.B . Raftery and A. Lahm, J. Nucl . Med. 32 (1991) 37. [63] N. Tarnaki, J.B . Gill, R.H . Moore, T. Yasuda. C.A . Bouche r and H.W . Strauss. Am . J. Cardiol. 59 (1987) 1164 . 1641 M. Pfisterer, S. Regenass, J. Müller-Brand and F. Barkart, Eur. Heart J. 9 (1988) 98. [65] L. Yang, C.N . Bairey . D.S . Bairey, . .J Nichols, T. K Odom-Maryon and A. Rozanski, J. Nucl. Med. 32 (1991) 796. [661 C. Scheiber, Regall, P. Siffert and J. Chambron, Eur. J. Nucl . Med. 18 (1991) 603.
CLE
ENTS S SICS ESEARC
INST 11
T
SedwnA
in medicine : a review of current applications ture perspectives C. Scheiber and J. Cambron
Serrice de .,Ujdecine Nucijaire, histitut de Pkysique Biok)gique, Faculti de Midecine . 6708-5 Strasbourg Cedex, France
Cadmium telluride (CdTe) semiconductor sensors have been evaluated for medical applications for 15 years owing to their high stopping power, convenient energy resolution and operating conditions at room temperature . Most of the applications herein re,iewed concern medical imaging procedures, i .e ., nuclear medicine, including positron emission tomography and radiology with computerized tomography (XCT). Despite their attractive physical characteristics, their preliminary commercial development has been _Nlowed down in the early 80s because of technical problems, particularly when large arrays were considered, and because of the competition with the more available and less expensive scintillators or xenon chambers which are still mounted in most modern medical imaging systems. Nowadays the characteristics of new materials have allowed the development of restricted but more specific domains of CdTe medical applications i .e . miniaturized nuclear probes dedicated to per-operative tumor detection or ambulatory, monitoring of physiological (renal, cardiac) functions and bone absorptiometry using either planar or miniature tomographic systems. Supported by these features and encouraged by the growing competition between ionising and non-ionizing imaging modalities (US, MRD, research work is presently conducted with a view to using CdTe detectors in XCT. troduction A considerable increase in medical imaging diagnostic performance and number of investigations has been noted in the last decade. Beside ionising radiations techniques (RX), i.e . nuclear medicine (NM) and radiology, high spatial resolution non-ionising methods such as ultrasound (US) and magnetic resonance imaging (MRI) have been developed and are in a very fast growing stage . NM ar.j RX a,c the main man-made sources of populatiA, exposure [1] but their indications are at first governed by their diagnostic performance . Me fatal=e of MA and RX lies in their specificity, but a!,,o depends on a diminution of the doses administered to the patients . CdTe sensors may contribute to achieve these goals: in NM by spreading its applications with the use of miniaturized probes and L; dose reduction in computerized tomography [2] . Despite suitable physical characteristics CdTe sensors are still at an early stage of their medical applications . For a realistic approach it is useful to review sensor specifications m(.unted in commercially available systca-as ire parallel with present CdTe medical applications and/or development .
. Radiology Radiology is based upon X-ray attenuation by the human body that assumes a mnonocxponential decay of the monochromatic beam. In fact, breinsstrahlung and
K lines are filtered to improve beam uniformity and narrow the spectrum . As far as sensors are concerned we can describe separately conventional radiology (CR) and computerized tomography (XCT), conventional tomography procedures becoming progressively obsolete . Other quantitative transmission techniques such as osteodensitometry may figure in the same chapter since most of the commercially available systems use an X-ray generator . 2.1 . Conventional radiology Digital CR is rapidly developing, X-ray films being replaced by light-intensifiers that are read either by TV cameras or CCD units . Digital imaging improves diagnostic performance together with data transmission and storage . This technological evolution has already been achieved for vascular investigations and is in progress for bone and abdominal techniques . Digital chest plane imaging is still problematic because of the large field of view (FOV) and physiological motion, as well as the high resolution which it requires . Semiconductor sensors are rarely used in CR to determine film exposition where conventional ionisation chamber-, arc too cumbersome . 2.2. Computed tomography The precise determination of body attenuation by X-rays requires to determine a space density distribution from its known projections onto one or more
01680002/92/$05AO (0 1992 - Elsevier Science Publishers B .V . All rights reserved
C. Scheiber, J. Chambron / CdTe detectors in medicine Table l Irradiation data for XCT detectors X-ray [kV] Tube current [mA] Dose flux detector [R/s] Typical attenuation Quanta flux [s -1 cm - `] Quanta rate per detector element [s -I cm -Z ] Sampling interval [ms] Quantum noise [variance %]
Head scan
Thorax
120 200-600 <3 90 3 .7 x 10 x 1 .1x10" 3 .7 x 10 7 1 .1 x 10 1° 1 0.3-3
137 80-220 <3 300 2 x 10 8 6x10' ° 2 x 10 7 _ 6x l0" 1 0 .3-5
planes . Solving this problem involves taking slices through the distribution and considering the projected densities to be line integrals through the slices. The image reconstruction (density distribution in the slice) is obtained by applying a Fourier transform or an orthogonal expansion of the line integrals [3] . The finite number of measurements and the polychromatic nature of the X-ray beam induced artefacts [41 . improvement of XCT [5] has led to a huge improvement of image quality through the optimization of data collection and the narrowing of slice thickness, but at the cost of higher photon fluxes and data sampl ;ng which determine sensors operating conditions (table 1). With the third generation XCT type, data are acquired in 1-2 s using a continuously rotating measurement system (fig . 1) which consists of an X-ray tube emitting a diverging beam (40° fan beam) and a large array of detectors (n = 768). Uniformity of detector response is assumed and all drifts are corrected by automatic computer-controlled calibration . The system resolution at
605
Table 2 Dose value in mGy for one slice of a brain scan (120 kV and 300 mAAs) Slice thickness [mm] Skin dose [mGy] CTDI [mGy]
10 20 37
5 19 31
1 15 28
high contrast is largely determined by the beam spacing (i .e . the detector grid projected to the isocenter), and modulation transfer functions (MTF) at 2% of 8-16 line paris/cm Op/cm) are obtained . Soft tissues have very similar X-ray attenuation and the diagnostic performance of the XCT is related to the resolution at low contrast which is strongly dose dependent. Table 2 illustrates typical skin and brain dose, averaged for 14 slices and normalized to a slice thickness (CTDI index) . Although many other parameters are involved (including collimators, electronics) dose reduction and/or further improvements of image quality can be achieved through detector improvement XCT sensors are either scintillators coupled to photodiodes or xenon chambers (25 bar) (table 3) . Research is conducted to increase detector efficiency while keeping the afterglow as short as nossihle and to increase their density (number/degree). The mechanical motion induces septa vibrations and the detector should have a low microphonic sensitivity. The stability (both short and long term) should be very high and its availability compatible with large industrial diffusion . A spectrometer should be used to reduce the "beam hardening" artefact (in posterior and temporal fossa of the brain) and diffusion (body scan) . The dual-energy absorption densitometry technique (see below) is another potential application of spectrometry. CdTe detectors have theoretical advantages due to the lower energy required to produce a charge pair (4 .5 eV) compared to other sensors (30 eV) and due to their solid state which provides excellent stability . The difficulties which must yet be overcome are both eco-
Table 3 Important detector properties for XCT applications
Fig. 1 . Third generation XCT principle : the 40° fan beam consists of 768 xenon chambers (25 bar) detectors . (Reprint from ref. [4], p 118 with permission .)
Signal to noise ratio X-ray energy absorption [%] Speed of response (afterglow) [ms] Reproducibility of response Detector dimensions [mm] Availability and costs
Xenon
CdIA1 04
Ceramic
CdTc
++
+++
+ ++
+
70
95
99
95
<1
<3
<2
-
++
+
++
-
+ ++
+ +
+ +
+ -
V . APPLICATIONS
C. Scheiber, J. Chambron / CdTe detectors in medicine nomic (availability, cost) as well as technical (time response, linearity under high photon flux, sensitivity to vibrations). As far as we know, CdTe detectors are presently evaluated in company research centers but no published data are available . 23'. Borte densâtometty A decrease in the total mass of bone, a normal concomitant in the aging process, is accelerated in ost-oporotic patients. The most striking loss, of calcium occurs in the trabecular bone of vertebral bodies but also in the neck of the femur, the upper humerus and the dis-,al radius . The diagnosis used to be based upon C. : : :;z ,-. n advanced stage of the disease when the vertebr`._ bodies had collapsed because of a loss of calcium, the rate r f which had fallen beneath the '-vel required for bon_- matrix stability . Absorptiometric techniques designed to measure quantitatively and noninvasively bone density at an early stage of the disease when medical treatment is more efficient . Bone densitometrv is even more useful for treatment followup which requires a high reproducibility (1 170 of measurement . Absorptiometry is based upon monoexponential attenuation of a monochromatic beam. Radioactive source ("1 (gamma-ray 27.5 keV, 15 GBq) or ';;Gd (K X-ray -12--f8 keV tnd gamma-ray 97, 103 keV)) have been replaced by an X-ray tube (50-90 keV) for higher sensitivity and practical use . Both planar and tomographic techniques are described further on. Planar techniques must be corrected for soft tissue attenuation using a dual-energy subtraction technique [6,7]. This method utilizes the different energy dependences of Compton- and photoabsorption cross sections. A specific element can be distinguished from its matrix and its density evaluated if its atomic number differs signs icantly from that of its matrix . Similarly a group of heavy elements can be distinguished from a group of lighter elements. When known bone standards are measured in the same conditions, the experimental data can be converted to grams of bone mineral per
Discriminatorl Counterl VL
H. V.
VH
Discriminatorl Counter2 Fig . 2. Diagram of the detector element of the CdTe X-ray imaging sensor . (Reprint from ref . [9J, p . 97 with permission .)
Fig . 3. (a) Low-energy image; (b) high-energy image and (c) computed bone density image of a hand phantom on 13 cm acrylic plate . (Reprint from ref. [9), p. 100 with permission .)
cm-' since the value of the attenuation coefficient is determined . Although the usefulness of CdTe detectors was described in 1977 using a single energy method [8] their application with regards to the dual-energy absorption technique is still under development . A Japanese research center has developed a 64 CdTe linear imaging sensor [9] which operated in the pulse counting mode. The photon source is an X-ray tube (100 kV) with a IC-edge filter separating the continuous beam into two energy levels at about 60 keV . Each detector channel comprises a CdTe crystal (2 x 2 x 0.5 mm), a current-voltage conversion amplifier and two sets of discriminators (fig. 2). The output pulses of height greater than the discrimination voltage VL (noise level) and HL (separation energy level : 60 keV) were counted separately. The two X-ray photon counting images (low-energy and high-energy) of a hand phantom in acrylic were taken simultaneously by single synchronous scanning of both the sensor and the X-ray tube (fig. 3). The bone density image was derived by image subtraction according to densitometry theory equations . Bone phantoms were measured and bone mineral densities corresponded to their true values . CdTe sensor count-rate linearity was tested up to 50
C Scheiber, J. Chambron / CdTe detectors in medicine
07
to test all organs and tissue functions . These investigations are noninvasive owing to external detection of organ radioactivity . NM studies are devoted to the investigation of dynamic metabolic processes using mathematical (often compartmental) analysis of the time activity curves derived from the volume of interest WOD. In most cases, data are represented as a bidimensional image of count distribution in the FOV of the detector . As far as radionuclide emitting particles are concerned, conventional NM should be distinguished from positron emission tomography (PET). 3. 1. Positron einission tonzography Fig . 4 . A miniature tomographic for peripheral bone densito metry . The distal radius bone density is measured with a 1 17 .r reproducibility . (Courtesy of Stratec company .)
kcounts/s (kcps), with an 18171 energy resolution (FWHM) . A complete high resolution (1 mm) data set is obtained by a single scanning within one minute of acquisition time . Planar methods are easy to implement but the measurements are blurred by geometric artefacts, and they cannot discriminate vertebral bones from other calcified structures (arthrosis, vessels) . These factors affect not only the absolute mineral density (gcm -2 ) but also the reproducibility of the measurement . Computerized tomography allows direct measurement of trabccular bone mineral density in gcm- 3. A whole-body XCT may be advantageously replaced by a dedicated system developed by a German University [101 . This miniature (scale 1/8) first generation type XCT (translation-rotation) uses six CdTe detectors (fig. 4). The X-ray beam is almost monochromatic (38 keV, FWHM : 8 kcV) . After careful selection (planar image) of the 2 .5 mm slice of interest the image (128 2 ) is obtained after 7 min (acquisition time) . In these conditions the radius exposition is 0 .1 mSv. A 15 cm FOV is available to determine the mineral density of distal radius with a reproducibility of 1% [11] . It has been demonstrated [12] that peripheral bone measurements have a higher sensitivity and specificity in predicting axial fracture risk than dual-energy X-ray absorptiometry performed on the vertebral bodies which was taken as the reference method.
3 . Nuclear medicine The main goal of NM is the physiological studies of tissues by using specific radioactive tracers . The labeled molecule is injected in negligible amounts, and detected owing to its high specific activity . A large variety of radiopharmaccuticals are currently available
PET makes possible the quantization of the rugional distribution of positron-emitting radioisotopes in a selected organ owing to the unique characteristics of positron annihilation in tissues . Since a large variety of physiological substances can be labeled with positron emitters ("F, "C, ' I N, 1 *1 0) this lechi ;ique can be used to monitor various biochemical and physiological processes in living tissues [13] . After a short distance (1-2 mm) the annihilation with an electron produces simultaneously two 511 keV gamma rays in directions nearly opposite to each other . The presence of a positron is assessed by the simultaneous detection of two annihilation gamma photons interacting with two radiation detectors . Events are registered in coincidence if they are detected within a 5 ns time window. Coincidence detection of positrons emitted outside the volume delimited by the two detectors is not registered owing to electronic collimation . In order to optimize detection, each detector in a PET camera is coupled in coincidence with many others . Typically the detectors are arranged around the body in multiple rings to obtain multiple slices of the organ at one time . The spatial resolution is degraded by some factors such as : the positron range, angle deviation, photon interactions, scattered radiations, attenuation of photons, and random coincidences implying adequate corrections [14]. Currently available high spatial resolution cameras use small scintillation crystals and PM tubes. A high density and a very short decay time are required . Usually BGO (bismuth germanate oxide) is used . The main characteristics of a EGO detector are summarized in table 4 . Gd .,SiO 5 crystals are being evaluated for their short scintillation time (60 ns) but Table 4 Main characteristics of a typical BGO-PM detector for PET camera Coincidence photopeak efficiency Timing resolution [s] Energy resolution for 511 key FWHM Scintillation decay constant [s] Block intrinsic spatial resolution MTF (5 1-c) line paris c .ii - 1
41 3X 10 -9 13 300X 10 - " 3
V . APPLICATIONS
C SchAer; I Chanibron / CdTe detectors in medicine
bps
fable 5 Main characteristics of a typical gamma-camera Detection efficiency for 140 keV Energy resolution FWHM [%] (50 cm d . FOV) Count rate linearity (50 cm d . FO") Uniformity [%] (50 cm d . FOV) Spatial resolution MTF (5%) at 5 mm 0 cm - I Spatial resolution MTF (5 %,) at 100 mm lp cm - I
95 >11 > 105 >4
3-2 Conventional NM The gamma-camera [17] is widely used for both planar or single photon emission computerized tomography (SPELT) [18] procedures instead of the conventional nuclear probe .
Fig . 5 . Block element. of a modem AGO based PET camera : 64 crystals are coupled to four miniature PM tubes. (Courtesy of Siemens company .)
33. The gamnia -camera remain expensive. The geometry of the crystal is an important feature and the detectors are used in the form of a block detector 30 mm thick. Each BGO crystal is divided in 64 crystal segments (6.8 min apart with a 0 .6 mm gap) [15]. The blocks are placed in modules of four (fig . 5) and ten units are mounted in each of the sixteen detector rings (8192 crystals). The linearity (10% loss) of a PET camera is 500 kcps for a specific activity of 200 kBq/ml . m-operating semiconductor detectors are very attractive because their excellent stopping power: they, can be assembled into position sensitive arrays . Unfortunately . their properties are such that thick detectors yield poor spectral response where events register at a lower than true energy. this tailing effect is not uniform either as a function of energy or among detectors- CdTe detectors 2-5 mm thick have been evaluated : the spectral response was such that a majority of the stopped 511 keV register above a threshold of 100 keV . The detector efficiency was 30% . Coincidence resolution was found to be 50-100 ns depending on the detector thickness [16].
This stationary detector basically consists of a parallel holes collimator and a large Nal scintillator (60 X 40 X 10 cm) . This large FOV is the main feature of the gamma camera and the determinant factor in the development of NM. The spatial localization of the scintillation light is achieved by 90 photomultiplier tubes and a calibrated resistance network . Signal numerisation allows computer controlled corrections for system imperfections (energy, linearity, uniformity). The main characteristics of a gamma-camera are summarized in table 5 . It ;- reminded that for clinical dose and examination time, it is not useful to design a very high spatial resolution detector, the corresponding collimator transparency being so low that the image quality is spoiled by the statistical fluctuations of each image point . In practice, radiopharmaceuticals designed for human studies can be labeled with a limited number of radioisotopes (table 6) among which 99 'Tc (140 keV) represents more than 70% of routine NM investigations . Quantitative studies, based on the proportional relationship existing between organ activity and the
a
TAW 6 List of main radioisotopes in NM Isotope
Half-life
Energy [keV]
""'Tc 2m -I'1 1 '- ; I 67 Ga MI
6 .02 h 73 .5 h 13 .2 h 78 .1 yr 8 yr 53 yr 60 yr 1 .50 h
140 69-83 (X) 156 296,184,93 364 81 27 .5 393
Xe lu i Is 113
In
Clinical use
Availability ++
+ +
+++
+
+++
Cost
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to that of gamma-cameras. Although the field of their medical applications is relatively limited it consists of unique nuclear medicine procedures ; thus it is an important potential development for NM . Conventional Nal probes are still cumbersome and should be advantageously replaced by miniaturized CdTe probes especially in two ranges of applications: the peroperative localization of small masses and the continuous monitoring of physiological functions . 3.5. hitraoperative probes
Fig. 6 . A new two-heads rotating gamma-camera . The large FOV (60 X 40 X I cm) of the Nal based Anger camera was a determinant factor in the development of nuclear medicine . (Courtesy of Eiscint company .)
detected counts, arc hampered by the activity of nonselected tissues both within and without the FOV, and gamma-ray attenuation . Dosimetry is another limiting factor and in most clinical studies poor statistics are encountered . At the present time these problems [19] have not been solved by using SPELT, either with one rotating head camera or multidetector systems. Compton diffusion (particularly primary photons emitted outside of the VOI and having undergone a Compton interaction in the FOV) has a strong incidence on NM data, resulting in a lower image signal/noise ratio, and thus compromises quantification . Spectrometry allows a significant reduction of the Compton component at the cost of a lower count rate . Using multiple windows and tracers labeled with distinct energy emitters enables one to study simultaneously two biological functions. Semiconductors arrays have been considered [20,21] for improved energy resolution, counting rate, and mechanical convenience . McCready et at . [20] have built and evaluated a GOLD camera based on the multiwire chamber principle (fig . 6) (a row of parallel line electrodes on top of the crystal and another row (but perpendicular) electrode array on the bottom). The energy resolution was reasonably good (10 keV) but the sensitive area was limited . CdTe arrays were evaluated [22] but at the time dispersion of crystal characteristics and polarization problems were too large to allow the realization of a convemional whoic-body camera . 3.4. Nuclear probes Nuclear probes are still being used for their higher sensitivity, portability and relatively low cost compared
In oncology, loco-regional tumor extension and lymph nodes involvement are essential elements for diagnosis and treatment . High spatial resolution methods (US, XCT, MI I) are very efficient with regards to the localization of 0 .5 cm lymph nodes but fail to demonstrate their tumoral involvement . NM may contribute to achieve this goal by using specific tumoral tracers . At the present time, only few specific tracers are available (antibodies, antimitotic drugs, hormone precursors) for routine investigations and tracers with only nonspecific femoral affinity are still employed (0Ga, 2° "T0 . The tracer is injected I to 3 days before the investigation in order to decrease nonspecific activity by clearance . The signal/noise is a function of the tumor uptake (volume, vascularization, metabolism) and background activity. Usually the lesion is small and located so deep inside the body that external detection with the gamma-camera is unsuccessful. The point of using a miniaturized probe is that one can get closer to the pathological site . This can be achieved either during surgery or by insertion of the probe in the body (during broncho-, gastro- or recto scopy). The use of both INa(TD and CdTe probes have been described and recently reviewed [23] . A typical hand-held gamma detecting probe is 15 cm long, 4 cm in diameter, is gas-sterilizable, made in stainless steel, very sensitive to decrease the count integration time, but collimated to be directional (fig . 7) . Nonimaging probes are subject to localization errors . The detection of an unknown region of interest with a single-hole collimated probe is difficult when a nonspecific uptake arises from healthy tissues, the localization of the lesion being dependent on small changes in probe orientation . In order to overcome I,'i;.E problem a multidetector system should be used and a low energy emitter, like 1251 (27 .5 keV), should be preferred . The gamma photons detected are transformed into both a digital readout and an auditory signal after being discriminated from background activity .
Peroperative detection of subclinical tismoral mass or involved lymph nodes has been applied in thyroid highly differentiated cancer surgery . This tumor concentrates iodine in the same way as a healthy thyroid V . APPLICATIONS
C. Scheiber, J. Chambrcn / CdTe detectors in medicine
Fig . 7. CdTe surgical probe and associated electronics. The probe is IS cm lone and 2 cm in diameters . The battery-operated, gas-sterilisable probe is designed for intraoperative use with ' 2~1 monoclonal antibodies. (Courtesy of Neoprobe company.)
gland does . Twentv patients referred to surgery for thivroid cancer have been injected with 20 MBq ' -'I intravenously, 24 hours before the operation [241. After removal of all macroscopically visible thyroid tissue and metastatic growth. the operative field was examined with a CdTe probe . Iodine uptake was found in 16 out of the 2 patients. Recording over different-sized tissue fragments showed the detector to be very highly sensitive, and capable to detect tissue fragments weighing less than 2 me. These results indicate that intraoperative scintigraphy significantly reduces the need of postoperative radiciodine ablation (3 .7 GBq, ' 3 '1), a very high exposure for such young patients . Another CdTe probe has been used in the precise localization of two malignant pheochromocytoma after the injection of I mg meta-iodo-benzyl-guanidine (mIBG, 74 1v1Bq, ' -'I) [251, the tumor background count ratio was 10. Since 1986, Cd"fe probes [261 have been used in extensive clinical evaluation for radioimmunolocalization of colorectal carcinoma . In another study from the same research group a ' 2 'I-MAb B72 .3 IgG [271 was used . Thirty-one patients with primary or recurrent colorectal carcinoma were examined during surgery : 83% of re,:urrent sites were detected . The procedure did alter the surgical approach in 26% (8/31) of the patients with recurrent colorectal cancer . A further report noted that 68% (21/31) [281 of the rumor sites had probe counts at least twice those of normal tissue . In 2 out of 32 patients the only tumor found was localized by the probe . These results have been confirmed by Lecouffe [291 using another CdTe probe [30] . Feistel et al . [311 have shown in a study of women with ovarian carcinoma, using "' I-OC-125 F(ab')2, that 66%
of the probe guided biopsies were positive compared with only 15% of the blind biopsies, when the disease was not clinically evident . Some of the inherent limitations of the nonimaging probes can be overcome by using two NaI(Tl) crystals [321 or imaging-detector systems . A planar array of 21 CdTe was evaluated with regards to thyroid imaging [231 . The detector has a parallel hole collimator with a FOV of 2 .5 cm in diameter and was able to generate scintigraphy . The spatial resolution at the face of the probe was 3 mm but unfortunately with a low efficiency . Probes have been used inside the body for a variety of applications other than malignant tumor detection . These include the precise localization of osteoid osteoma [33,341, a benign bone lesion, which remains symptomatic when a nidus has been incompletely removed during surgery . The osteoma concentrate the bone tracer ("'Tc-methylene-phosphonate) . More recently [351 both Nal and CdTe probes have been used in a series of 30 patients ; the CdTe probe has proved to be a more durable, more reliable (solid/hygroscopic), more sensitive (10 times more so than Nal probes) and sterilisable probe . These CdTe probes have been used for intraoperative localization of benign parathyroid ailenonia after an Injection of °" TI [361 . CdTe detectors are small enough to be incorporated in medical probes that are inserted into the upper or lower gastrointestinal tract in the immediate vicinity of the tumor . In this situation, the localization is not helped by visual inspection and probe angulation as in intraoperative investigation . Imaging CdTe probes can determine the size, distance and anatomical location of tumors . One of these probes consists of an array of seven CdTe stacked detectors, one detector having a different 51° FOV through a separate, nonoverlapping azimuthal aperture [371 . The detector was designed to image mediastinal lymph nodes, as it is withdrawn through the oesophagus . A scan of the mediastinum takes approximately 20 min . 3.5. Continuous monitoring of patients's physiological functions Continuous monitoring of electrocardiogram (ECG) is largely indicated both in intensive care units, to detect symptoms of cardiac dysfunction in real time, or during patients' daily activities (ambulatory) for a better understanding of transient troubles of the cardiac rythm or ischaernic episodes. NM procedures are suitable for the continuous monitoring of physiological parameters . At the present time, the acquisition period is limited to one physical period of the tracer used, 6 h in the case of '9mTc . Ambulatory measurements are more difficult to achieve than bedside monitoring because of patients' motion .
C Scheiber, J. Chambron / CdTe detectors ira medicine
Two miniaturized portable and autonomous CdTe probes were used for blood-flow measurements in adipose and muscle tissue by local clearance studies with 133 Xe [38,39]. 133 Xe is injected in the anterior tibial muscle ; the decrease of local radioactivity with time, assumed to be a perfusion-dependent process, indicates the effective blood flow in the muscle . Transient pathological decrease of the renal function may occur in the course of a patient's normal life, due for example to a mobile kidney. The renal function can be assessed by measuring the plasma clearance of a chemical compound which is selectively eliminated by the kidneys. Itadiopharmaceuticals were developed to study both the glomerular (99mTc-DTPA) [40) and the tubular ( 123 1-I3ippuran) [41] renal function. In practice, the time activity curve recorded by the CdTe probe in the precordial area is assimilated to the plasma activity curve. At equilibrium with the extravascular space the monoexponential decay of the physical decay corrected curve reflects the renal function. Long term monitoring allows several values to be computed and assessment of any significant modification of the renal clearance . CdTe probes were used for glomerular filtration measurement using a P-type CdTe (resistivity : 104-106 11 cm', 0.8 mm thickness), the noise level was set at 40 keV, the results being concordant with the reference method using s1 Cr-EDTA and the multiple plasma sample technique (r = 0.97 ; n = 21) [42]. The value of biotelemetry measurement was clearly demonstrated : in the last 30 min period of muscular exercise the clearance has decreased by a factor of 5. The same detection system was used for the continuous monitoring of the renal graft function [43]: a significant decrease of DTPA clearance was considered an early sign of transplant rejection 24 h before elevation of plasma creatinine (reference method). A small CdTe probe with a chlorine doped high resistivity crystal (10 8-109 fl cm -') was found well adapted to pediatric studies with some modifications of the collimation in order to decrease high background activity of the bladder. The spectrometric characteristics of the probe permitted double-isotope studies using 99 'Tc-DTPA and 51 CrEDTA [44]. Another group of workers have built a CdTe based (P type, chlorine doped, 3 mm thickness, 4 min 2) detection system which was used to measure the tubular function (2MBq, 123 T-fiiopuran) in 20 patients : the results correlated well with the simultaneous measurements using the gamma-camera [45]. Tubular/ glomerular clearance ratio is 5; this higher clearance indicates the tubular tracer when global renal function is severely impaired. The reliability of these CdTe probes in the medical environment was found ilisufficient [46] and preliminary attempts of commercialization have been stopped . Presently this work has been resumed, with new CdTe materials .
Nuclear medicine has a large domain of cardiac applications . The left ventricular function can be evaluated by the ejection fraction (LVEF) which is the fraction of blood contained i 1.h c left ventricular chamber at the end of the diastolic phase ejected during heart systolic contraction, the normal value range being 60-80% at rest. The ability to continuously monitor LVEF in addition to ECG : wasurements would be of great value for the assessment of the ventricular function in both the critically ill, as well as the ambulatory cardiac patients. For instance, it can contribute to detect transient ischemic cardiac episodes which present neither ECG abnormalities nor pain (silent ischaemia) [47], and it has been reported that ECG signs of ischaemia (ST depression) must be interpreted cautiously in the case of patients with known obstructive coronary disease [48]. e cardiac investigation [49] is based on the isotopic dilution principle : the detector count rate being proportional to the l is labeled ventricular volume. Today, the blood with 500 Bq "Tc [50]. At equilibrium, the background activity, i.e. non-left-ventricular counts, is as high as 55-75% . Most of the time the study is perservice formed with the gamma-camera in the N allowing a precise and reproducible (automatic) determination of the ventricular border and background measurements . Owing to the low sensitivity inherent in the device, several hundred (600) cardiac cycles must be averaged in phase with ECG synchronization [51] to produce a high-quality data set consisting of 24 (40 ms each) 642 frames . The LVEF is derived from the background subtracted ventricular time activity curve . The gamma-camera method is not sensitive enough to detect rapidly changing events and is too cumbersome for evaluating serial function at the bedside. Nonimaging probes can provide high temporal resolution activity curves and were evaluated in the mid-1970s with the e madevelopment of the nuclear stethoscope [52]. jor assumption of this nonimaging approach is that the ventricular region can be isolated from other cardiac structures so that changes in radionuclide counts reflect the changes in ejection fraction and volumes. Breisblatt has reviewed [5.3,54] tine advantages and problems related to nonimaging devices for LVEF measurements and summarized the main characteristics of an ideal cardiac probe for continuous monitoring. Although the first CdTe system described was an array [55], the first clinical results published were about a system using a single crystal, 1.5 cm2 sensitive area, 2 mm thick probe. The results correlated with those from the camera method (n = 18, r = 074) or tho NATO probe (r = 0.76) [56,57]. Another study using a detector with higher spectrometric capabilities [58] have shown similar results. The background is higher (75-81%) V. APPLICATIONS
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C. Scheiber, J. Chambron / CdTe detectors in medicine
Fig. S . The `, EST: this autonomous and portable Nat miniature detector is designed for ambulatory monitoring of cardiac function b)9 measurement of the left ventricul- ?;action fraction. (Courtesy of Capintec Corp.)
compared to that measured with the Nal probe in
relation to the large collimation rather than the scatter faction. For all groups the results have shown too large a variance (> 10%) in the range of interest (VEF : 50-60 1x) precluding the medical use. The sensitive area was too small (maximum of 1 .5 cm - ); thus the geometry was not adapted to ever' ventricular shape and the sensitivity was too love for rapid serial measurements [59]. A CdTe array of seven detectors,
connected in parallel, has been evaluated in 1983 [60] . The results have shown the expected improvements (n = 37, r = 0.95) due to the increased active area and higher sensitivity, but technical problems have be--n encountered an :] a INa miniature probe was finally chosen . At the same period of time a l-lgl, probe was evaluated [61] but has been recently replaced by a Csl(Tl) scintillator [62] . Today there is only one commercial system available [63]. The VEST* consists of a 5 .6 cm diameter NATO crystal coupled with a miniature PM tube (Fig. 8). Despite encouraging clinical results both during muscular exercise [64] and ambulatory monitoring [65] this nonimaging probe does not have the expected commercial diffusion considering its medical interest. Nonimaging probes require a gammacamera to be positioned exactly in front of the left ventricular region ; moreover, as far as ambulatory monitoring is concerned, stability of detection geometry needs to be perfectly assessed, a difficult task for a nonimaging device . New developments are implemented in the latest CdTe array [66]. The current prototype consists of 12 (10 x 10 x 2 mm) CdTe, which operate in the counting mode, each detector having independent electronics . The geometry is controlled by 10 x 10 mm cylindrical collimators ; the total sensitive area is 36 cm-' . Miniaturized and low consumption electronics was designed. Acquisition and data processing are performed by a commercial microcomputer and application sufiware . A typical set of time activity ventricular curves is shown in fig . 9 . These curves were
W4 . @a m
Fig . 9. Twelve regional ventricular activity curves as recorded by a twelve CdTe prototype designed for cardiac monitoring . These curves reflect the cardiac activity (5n cycles were acquired with ECG triggering) along the cardiac cycle after appropriate background correction . The left ventricular function ca .i be derived from these data .
C Scheiber, J. Chambron / CdTe defectors in medicine
obtained after the acquisition of 50 cardiac cycles with a temporal resolution of 40 ms/point . The background was set at 75% of the diastolic counts . The characteristic shape of the ventricular curve can be recognized . The first clinical results demonstrated good correlation with the reference method (r = 0.87, n = 25). A reproducibility of 5% was found, based on nine successive measurements . Most important, the detector is now very stable and no detection problems have been noied. These preliminary results arc encouraging but sensitivity must be optimized. A portable and ;-!utonomous system is currently being deveioped.
4 . Conclusion
Although CdTe detectors have very attractive physical characteristics with regards to their utilization in NM and RX, they are still at an early stage of commercial diffusion. They were extensively evaluated during the late 70s and a variety of medical applications were envisaged. Specific technical problems (reliability, polarization, electronics, availability, cost) have slowed down their medical use for the past ten years. Today, workable materials have now overcome most of these problems and developments in electronics have allowed dedicated multidetector probes to be built which can compete with scintillators. At the present time industrial medical applications are more oriented towards probe miniaturization rather than detection efficiency with the development of intraoperative probes, and tomographic bone absorptiometry, where these detectors have demonstrated their superiority . Continuous radionuclide monitoring of the renal or cardiac function is promising but still at a stage of clinical evaluation . The potential CdTe applications in high spatial resolution devices like XCT are presently being reevaluated, with regards to the new materials, encouraged by the competition beiween ionising and nonionising imaging methods.
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