- Email: [email protected]
The high resolution gamma imager (HRGI): a CCD based camera for medical imaging
ARTICLE IN PRESS
Nuclear Instruments and Methods in Physics Research A 513 (2003) 23–26
The high resolution gamma imager (HRGI): a CCD based camera for medical imaging John. E. Leesa,*, George.W. Frasera, Adam Keaya, David Bassforda, Robert Ottb, William Ryderb a
Bio Imaging Unit, Space Research Centre, Department of Physics and Astronomy, University of Leicester, Leicester, LE1 7RH, UK b Institute of Cancer Research and Royal Marsden Hospital Downs Rd, Sutton, Surrey SM2 5PT, UK
Abstract We describe the High Resolution Gamma Imager (HRGI): a Charge Coupled Device (CCD) based camera for imaging small volumes of radionuclide uptake in tissues. The HRGI is a collimated, scintillator-coated, low cost, high performance imager using low noise CCDs that will complement whole-body imaging Gamma Cameras in nuclear medicine. Using 59.5 keV radiation from a 241Am source we have measured the spatial resolution and relative efficiency of test CCDs from E2V Technologies (formerly EEV Ltd.) coated with Gadox (Gd2O2S(Tb)) layers of varying thicknesses. The spatial resolution degrades from 0.44 to 0.6 mm and the detection efficiency increases ( 3) as the scintillator thickness increases from 100 to 500 mm. We also describe our first image using the clinically important isotope 99mTc. The final HRGI will have intrinsic sub-mm spatial resolution (B0.7 mm) and good energy resolution over the energy range 30–160 keV. r 2003 Elsevier B.V. All rights reserved. PACS: 85.25.Oj; 87.58.Pm Keywords: CCDs; Medical imaging; Gadox;
241
Am
1. Introduction Commercially available gamma cameras designed for whole body imaging are large and expensive. A standard gamma camera has an intrinsic spatial resolution of B4 mm but a system resolution in the order of B10 mm after the necessary collimator is taken into account [1].
*Corresponding author. Tel.: +44-116-252-5519; fax: +44116-252-2464. E-mail address: [email protected] (J.E. Lees).
There is an increasing demand for small, dedicated gamma cameras that offer higher spatial resolution at reasonable cost. Such cameras would be very useful for imaging sentinel nodes, small organs such as the thyroid and would find application in radio-guided surgery. Menard et al. [2] have developed a camera using CsI scintillators and position sensitive photomultiplier tube (PSPMT) technology for intra-operative gamma-ray imaging, specifically for sentinel node imaging, having a spatial resolution between 1 and 2 mm depending on the type of collimator. Porras et al. [3] have also developed a similar mini
0168-9002/$ - see front matter r 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0168-9002(03)02129-6
ARTICLE IN PRESS 24
J.E. Lees et al. / Nuclear Instruments and Methods in Physics Research A 513 (2003) 23–26
gamma camera and report system spatial resolution of B3 mm. Our aim is to produce a small hand-held gamma camera that would have intrinsic sub-mm spatial resolution (B0.5 mm), good efficiency and excellent energy resolution over the energy range 30– 160 keV. In this paper, we report on our first measurement of spatial resolution and relative efficiency using 241Am (59.5 keV X-rays) and 99m Tc (140 keV) sources.
2. Devices Our initial device was a standard dental Charge Coupled Device (CCD) obtained gratis from E2V Technologies [4]. These devices, designated CCD38-20, are designed as full-frame X-ray imaging sensors for intra-oral dental applications (see Fig. 1). They have 44 mm square pixels and a 456 684 pixel image area with a 100 mm thick Gadox (Gd2O2S) scintillator layer in direct contact with the input surface. The CCD and scintillator are hermetically sealed within a plastic sheath. A 2 m long cable and a 14-pin DDK connector bring clock and bias supplies to the CCD. Two further devices, adapted CCD38-20 s, were later procured from E2V having thicker scintillator layers of 300 and 500 mm, respectively. The
CCD38 operates in Advanced Inverted Mode Operation (AIMO) mode and for this application is read out at a speed of 650 kHz.
3. Spatial resolution The spatial resolution of each device was measured using a 1 cm thick lead block having a 3 mm wide by 21 mm long slit illuminated by an 241 Am source (73 MBq). The line images gave two well-defined edges from which to calculate the modulation transfer function (MTF). The edge spread response is differentiated to derive the line spread function (LSF), and the absolute value of the Fourier transform gives an estimate of the MTF for the system. The variation of spatial resolution with scintillator thickness at a MTF of 4% is given in Table 1. The spatial resolution degrades as expected with increasing scintillator thickness. However, even for the thickest layer, 500 mm, we have still achieved our goal of sub-mm spatial resolution.
4. Relative efficiency The scintillator coating is screen-printed to the desired thickness (usually up to 100 mm) on the front of the CCD. Fig. 2 shows the calculated efficiencies for coated CCDs with various thicknesses of the Gadox scintillator: Also shown is the efficiency of direct detection in a 30 mm depletion depth typical of a high resistivity CCDs that have been evaluated for direct detection of hard X-rays [5]. A 100 mm thick Gadox layer, Fig. 2, corresponds to a standard dental chip, optimised for X-rays Table 1 Spatial resolution for each device as a function of scintillator thickness
Fig. 1. A CCD38-20, dental imaging detector (courtesy E2V Technologies).
Gadox thickness (mm)
Spatial resolution (mm) FWHM
100 300 500
0.44 0.57 0.61
ARTICLE IN PRESS J.E. Lees et al. / Nuclear Instruments and Methods in Physics Research A 513 (2003) 23–26
Absorption (%)
100.0
25
100 um 300 um 500 um Direct absorption in CCD
10.0
1.0
I-125
0.1 10
35
Am-241
59.5
Co-57 Tc-99m
100 122 140 Energy (keV)
1000
Fig. 2. Absorption in Gadox layers and directly in a silicon CCD. Emission energies of named isotopes indicated by broken vertical lines. 99m
Tc data
Table 2 Relative efficiency versus scintillator thickness at 59.5 keV
5.
Gadox thickness (mm)
The CCD with 100 mm thick Gadox layer was taken to The Leicester Royal Infirmary to evaluate its performance with 140 keV gamma rays from 99m Tc. The hospital made up a sample of liquid containing 99mTc held in a 1 mm wide capillary. The activity of the source was 14.2 MBq. We then placed the CCD package on top of the vessel, approximately 0.5 mm above the source. Fig. 3 shows the line shape recorded during a 300 s integration, and a slice taken through the image, Fig. 4, shows the resolution of the CCD. In this case the resolution was found to be 0.770.2 mm.
100 300 500
Relative efficiency Predicted
Measured
0.5 0.85 1.0
0.25 0.75 1.0
The predicted figures derive from the absorption probabilities in bulk density GADOX.
with a mean energy of 30 keV. The principal emission energies of four common hard X-ray/ gamma-ray sources are indicated by the broken vertical lines. The data in the figure indicates that the efficiency at 99mTc (140 keV) can be increased from 8% to 35% by using a thicker Gadox coating. The relative efficiency of our devices was measured using a 241Am source. Images were obtained by illuminating the CCD through the lead slit (Section 3) with an integration time of 150 s Relative efficiencies were estimated by taking a slice through the image of the slit and calculating mean levels for the illuminated and noise sections. Table 2 shows the relative efficiency for 241Am. The efficiency increases, as expected, for thicker Gadox layers and the trend is in agreement with our calculated efficiencies for 241Am X-rays, Fig. 2.
6. Conclusions We have shown that scintillatorcoated CCDs can be used to image hard X-ray/gamma ray sources and still offer sub-mm spatial resolution. However, to realize the goal of a gamma camera for clinical use we need to address the following: *
Operation of the CCD in photon-counting mode in order to provide pulse height resolution for scatter rejection and maximum sensitivity for low-activity emitting regions.
ARTICLE IN PRESS 26
J.E. Lees et al. / Nuclear Instruments and Methods in Physics Research A 513 (2003) 23–26
*
Fig. 3. Image of a 1 mm diameter
99m
Tc line source.
reduction of up to 30 C using a simple air flow heat exchanger. Theoretically, a DT of 30 C would reduce the dark current by approximately 20 times. Design and optimisation of a collimator.
We have begun a programme to address these issues as well as investigating other scintillating materials. We plan to investigate the performance of the High Resolution Gamma Imager (HRGI) in the context of sentinel lymph node imaging, focusing in particular, on breast and vulvar cancer treatment in collaboration with the Leicester Royal Infirmary and the Royal Marsden Hospital.
Acknowledgements The authors would like to thank Mike Early and his colleagues at the Leicester Royal Infirmary for supplying the 99mTc. Nick Nelms and Andrew Holland for advice. E2V Technologies Ltd for supplying our initial device and supporting the production of the later devices. This work has been part funded by the MRC and PPARC through a Discipline Hopping Award (G0100705). W. Ryder is funded by EPSRC. Fig. 4. Slice through
99m
Tc image shown in Fig. 3.
References *
*
Reduction of CCD read noise from the B150 electrons rms of our current dental CCDs to the o 10 electrons representative of CCDs used for direct X-ray detection in astronomy (to achieve optimal energy resolution). Cooling of the CCD, without condensation onto the chip. This could be achieved by a small Peltier-effect cooler to provide a temperature
[1] S. Webb, The Physics of Medical Imaging, Hilger, Bristol, 1988. [2] L. Menard, et al., IEEE Trans. Nucl. Sci. NS-46 (1999) 2068. [3] E. Porras, et al., Nucl. Instr. and Meth. A 486 (2002) 186. [4] E2V Technologies Ltd., Waterhouse Lane, Chemlsford, Essex, CM1 2QU, UK. [5] D.H. Lumb, A.D. Holland, IEEE Trans. Nucl. Sci. NS-45 (1988) 534.
Nuclear Instruments and Methods in Physics Research A 513 (2003) 23–26
The high resolution gamma imager (HRGI): a CCD based camera for medical imaging John. E. Leesa,*, George.W. Frasera, Adam Keaya, David Bassforda, Robert Ottb, William Ryderb a
Bio Imaging Unit, Space Research Centre, Department of Physics and Astronomy, University of Leicester, Leicester, LE1 7RH, UK b Institute of Cancer Research and Royal Marsden Hospital Downs Rd, Sutton, Surrey SM2 5PT, UK
Abstract We describe the High Resolution Gamma Imager (HRGI): a Charge Coupled Device (CCD) based camera for imaging small volumes of radionuclide uptake in tissues. The HRGI is a collimated, scintillator-coated, low cost, high performance imager using low noise CCDs that will complement whole-body imaging Gamma Cameras in nuclear medicine. Using 59.5 keV radiation from a 241Am source we have measured the spatial resolution and relative efficiency of test CCDs from E2V Technologies (formerly EEV Ltd.) coated with Gadox (Gd2O2S(Tb)) layers of varying thicknesses. The spatial resolution degrades from 0.44 to 0.6 mm and the detection efficiency increases ( 3) as the scintillator thickness increases from 100 to 500 mm. We also describe our first image using the clinically important isotope 99mTc. The final HRGI will have intrinsic sub-mm spatial resolution (B0.7 mm) and good energy resolution over the energy range 30–160 keV. r 2003 Elsevier B.V. All rights reserved. PACS: 85.25.Oj; 87.58.Pm Keywords: CCDs; Medical imaging; Gadox;
241
Am
1. Introduction Commercially available gamma cameras designed for whole body imaging are large and expensive. A standard gamma camera has an intrinsic spatial resolution of B4 mm but a system resolution in the order of B10 mm after the necessary collimator is taken into account [1].
*Corresponding author. Tel.: +44-116-252-5519; fax: +44116-252-2464. E-mail address: [email protected] (J.E. Lees).
There is an increasing demand for small, dedicated gamma cameras that offer higher spatial resolution at reasonable cost. Such cameras would be very useful for imaging sentinel nodes, small organs such as the thyroid and would find application in radio-guided surgery. Menard et al. [2] have developed a camera using CsI scintillators and position sensitive photomultiplier tube (PSPMT) technology for intra-operative gamma-ray imaging, specifically for sentinel node imaging, having a spatial resolution between 1 and 2 mm depending on the type of collimator. Porras et al. [3] have also developed a similar mini
0168-9002/$ - see front matter r 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0168-9002(03)02129-6
ARTICLE IN PRESS 24
J.E. Lees et al. / Nuclear Instruments and Methods in Physics Research A 513 (2003) 23–26
gamma camera and report system spatial resolution of B3 mm. Our aim is to produce a small hand-held gamma camera that would have intrinsic sub-mm spatial resolution (B0.5 mm), good efficiency and excellent energy resolution over the energy range 30– 160 keV. In this paper, we report on our first measurement of spatial resolution and relative efficiency using 241Am (59.5 keV X-rays) and 99m Tc (140 keV) sources.
2. Devices Our initial device was a standard dental Charge Coupled Device (CCD) obtained gratis from E2V Technologies [4]. These devices, designated CCD38-20, are designed as full-frame X-ray imaging sensors for intra-oral dental applications (see Fig. 1). They have 44 mm square pixels and a 456 684 pixel image area with a 100 mm thick Gadox (Gd2O2S) scintillator layer in direct contact with the input surface. The CCD and scintillator are hermetically sealed within a plastic sheath. A 2 m long cable and a 14-pin DDK connector bring clock and bias supplies to the CCD. Two further devices, adapted CCD38-20 s, were later procured from E2V having thicker scintillator layers of 300 and 500 mm, respectively. The
CCD38 operates in Advanced Inverted Mode Operation (AIMO) mode and for this application is read out at a speed of 650 kHz.
3. Spatial resolution The spatial resolution of each device was measured using a 1 cm thick lead block having a 3 mm wide by 21 mm long slit illuminated by an 241 Am source (73 MBq). The line images gave two well-defined edges from which to calculate the modulation transfer function (MTF). The edge spread response is differentiated to derive the line spread function (LSF), and the absolute value of the Fourier transform gives an estimate of the MTF for the system. The variation of spatial resolution with scintillator thickness at a MTF of 4% is given in Table 1. The spatial resolution degrades as expected with increasing scintillator thickness. However, even for the thickest layer, 500 mm, we have still achieved our goal of sub-mm spatial resolution.
4. Relative efficiency The scintillator coating is screen-printed to the desired thickness (usually up to 100 mm) on the front of the CCD. Fig. 2 shows the calculated efficiencies for coated CCDs with various thicknesses of the Gadox scintillator: Also shown is the efficiency of direct detection in a 30 mm depletion depth typical of a high resistivity CCDs that have been evaluated for direct detection of hard X-rays [5]. A 100 mm thick Gadox layer, Fig. 2, corresponds to a standard dental chip, optimised for X-rays Table 1 Spatial resolution for each device as a function of scintillator thickness
Fig. 1. A CCD38-20, dental imaging detector (courtesy E2V Technologies).
Gadox thickness (mm)
Spatial resolution (mm) FWHM
100 300 500
0.44 0.57 0.61
ARTICLE IN PRESS J.E. Lees et al. / Nuclear Instruments and Methods in Physics Research A 513 (2003) 23–26
Absorption (%)
100.0
25
100 um 300 um 500 um Direct absorption in CCD
10.0
1.0
I-125
0.1 10
35
Am-241
59.5
Co-57 Tc-99m
100 122 140 Energy (keV)
1000
Fig. 2. Absorption in Gadox layers and directly in a silicon CCD. Emission energies of named isotopes indicated by broken vertical lines. 99m
Tc data
Table 2 Relative efficiency versus scintillator thickness at 59.5 keV
5.
Gadox thickness (mm)
The CCD with 100 mm thick Gadox layer was taken to The Leicester Royal Infirmary to evaluate its performance with 140 keV gamma rays from 99m Tc. The hospital made up a sample of liquid containing 99mTc held in a 1 mm wide capillary. The activity of the source was 14.2 MBq. We then placed the CCD package on top of the vessel, approximately 0.5 mm above the source. Fig. 3 shows the line shape recorded during a 300 s integration, and a slice taken through the image, Fig. 4, shows the resolution of the CCD. In this case the resolution was found to be 0.770.2 mm.
100 300 500
Relative efficiency Predicted
Measured
0.5 0.85 1.0
0.25 0.75 1.0
The predicted figures derive from the absorption probabilities in bulk density GADOX.
with a mean energy of 30 keV. The principal emission energies of four common hard X-ray/ gamma-ray sources are indicated by the broken vertical lines. The data in the figure indicates that the efficiency at 99mTc (140 keV) can be increased from 8% to 35% by using a thicker Gadox coating. The relative efficiency of our devices was measured using a 241Am source. Images were obtained by illuminating the CCD through the lead slit (Section 3) with an integration time of 150 s Relative efficiencies were estimated by taking a slice through the image of the slit and calculating mean levels for the illuminated and noise sections. Table 2 shows the relative efficiency for 241Am. The efficiency increases, as expected, for thicker Gadox layers and the trend is in agreement with our calculated efficiencies for 241Am X-rays, Fig. 2.
6. Conclusions We have shown that scintillatorcoated CCDs can be used to image hard X-ray/gamma ray sources and still offer sub-mm spatial resolution. However, to realize the goal of a gamma camera for clinical use we need to address the following: *
Operation of the CCD in photon-counting mode in order to provide pulse height resolution for scatter rejection and maximum sensitivity for low-activity emitting regions.
ARTICLE IN PRESS 26
J.E. Lees et al. / Nuclear Instruments and Methods in Physics Research A 513 (2003) 23–26
*
Fig. 3. Image of a 1 mm diameter
99m
Tc line source.
reduction of up to 30 C using a simple air flow heat exchanger. Theoretically, a DT of 30 C would reduce the dark current by approximately 20 times. Design and optimisation of a collimator.
We have begun a programme to address these issues as well as investigating other scintillating materials. We plan to investigate the performance of the High Resolution Gamma Imager (HRGI) in the context of sentinel lymph node imaging, focusing in particular, on breast and vulvar cancer treatment in collaboration with the Leicester Royal Infirmary and the Royal Marsden Hospital.
Acknowledgements The authors would like to thank Mike Early and his colleagues at the Leicester Royal Infirmary for supplying the 99mTc. Nick Nelms and Andrew Holland for advice. E2V Technologies Ltd for supplying our initial device and supporting the production of the later devices. This work has been part funded by the MRC and PPARC through a Discipline Hopping Award (G0100705). W. Ryder is funded by EPSRC. Fig. 4. Slice through
99m
Tc image shown in Fig. 3.
References *
*
Reduction of CCD read noise from the B150 electrons rms of our current dental CCDs to the o 10 electrons representative of CCDs used for direct X-ray detection in astronomy (to achieve optimal energy resolution). Cooling of the CCD, without condensation onto the chip. This could be achieved by a small Peltier-effect cooler to provide a temperature
[1] S. Webb, The Physics of Medical Imaging, Hilger, Bristol, 1988. [2] L. Menard, et al., IEEE Trans. Nucl. Sci. NS-46 (1999) 2068. [3] E. Porras, et al., Nucl. Instr. and Meth. A 486 (2002) 186. [4] E2V Technologies Ltd., Waterhouse Lane, Chemlsford, Essex, CM1 2QU, UK. [5] D.H. Lumb, A.D. Holland, IEEE Trans. Nucl. Sci. NS-45 (1988) 534.