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Clinical trials of the prototype Rutherford Appleton Laboratory MWPC positron camera at the Royal Marsden Hospital
350
Nuclear Instruments and Methods in Physics Research A269 (1988) 350-353 North-Holland, Amsterdam
CLINICAL TRIALS OF THE PROTOTYPE RUTHERFORD APPLETON LABORATORY MWPC POSITRON CAMERA AT THE ROYAL MARSDEN HOSPITAL M.A . FLOWER, R.J . OTT, S. WEBB, M.O . LEACH, P.K . MARSDEN, R. CLACK, O . KHAN, V. BATTY, V.R. McCREADY and J.E . BATEMAN') The Royal Marsden Hospital and Institute of Cancer Research, Sutton, Surrey, England The Rutherford Appleton Laboratory, Chilton, Didcot, Oxfordshire, England
Two clinical trials of the prototype RAL multiwire proportional chamber (MWPC) positron camera were carried out prior to the development of a clinical system with large-area detectors . During the first clinical trial, the patient studies included skeletal imaging using 18 F, imaging of brain glucose metabolism using t8 F FDG, bone marrow imaging using 52 Fe citrate and thyroid imaging with Na'z° I. Longitudinal tomograms were produced from the limited-angle data acquisition from the static detectors. During the second clinical trial, transaxial, coronal and sagittal images were produced from the multiview data acquisition. A more detailed thyroid study was performed in which the volume of the functioning thyroid tissue was obtained from the 3D PET image and this volume was used in estimating the radiation dose achieved during radioiodine therapy of patients with thyrotoxicosis. Despite the small field of view of the prototype camera, and the use of smaller than usual amounts of activity administered, the PET images were in most cases comparable with, and in a few cases visually better than, the equivalent planar view using a state-of-the-art gamma camera with a large field of view and routine radiopharmaceuticals .
1. Introduction This paper reviews two clinical trials which were carried out using the prototype RAL MWPC positron camera [1,2], which consisted of two opposing 30 cm X 30 cm chambers . During the initial trial period (October to December 1982) the detectors were positioned either side of a patient couch (fig. 1) and longitudinal tomograms were produced from the limited-angle data acquisition . During the second trial period (March 1984 to March 1985) the detectors were mounted on a raised gantry and positioned on either side of a rotating chair (fig. 2) so that transaxial tomograms were produced from data acquired with the patient at eight different angular orientations at 22 .5' intervals.
function . The properties of the prototype PET camera at the time of the first clinical trial are listed in table 1 . Note that the useful field of view was limited to the central 15 cm X 15 cm area so that the PSRF could be considered spatially invariant for the deconvolution process. During the 2-month evaluation period, 25 patients were imaged and 44 studies were performed. These studies included skeletal imaging using ' 8 17, brain imaging using 18 F fluorodeoxyglucose (FDG) and bone-mar-
2. First clinical trial A full report on the evaluation of this positron camera for longitudinal tomography has already been presented [3]. Hence only a brief summary is given here . The image reconstruction method was a two-stage process. Firstly, the acquired data from the pair of detectors operating in coincidence were back-projected into five image planes parallel to the face of the detector with an interplane spacing of typically 3-5 cm. Secondly, the back-projected images (represented by five 64 X 64 matrices with a pixel size of 2.3 mm) were deconvolved with a 2-dimensional point source response 0168-9002/88/$03 .50 (~) Elsevier Science Publishers B.V . (North-Holland Physics Publishing Division)
Fig. 1. The prototype RAL MWPC positron camera set up for the first clinical trial with the two 30 cm X 30 cm detectors positioned either side of the patient couch.
35 1
M.A . Flower et al. / Clinical trials of a MWPC positron camera
Table 1 Properties of the prototype RAL MWPC PET camera Physical sensitive volume Usable sensitive volume Efficiency Count rate limit Point source sensitivity Spatial resolution Resolving time
Fig. 2. The prototype RAL MWPC positron camera set up for the second clinical trial with the detectors positioned either side of a rotating chair. row imaging with 52 Fe . These positron-emitting radiopharmaceuticals were provided by the MRC cyclotron at Hammersmith. In addition to these radiopharmaceuticals, Na1241 for thyroid imaging was obtained from the Birmingham University Nuffield cyclotron and purified in the Department of Medical Biophysics at the University of Manchester . Patients were selected from those attending the Nuclear Medicine Department for single-photon imaging and the quality of the PET images was compared with the planar images and, in some cases, SPECT tomograms as well . Some of the details of the scanning parameters used for these studies are listed in table 2. More than half of the patients imaged were those examined to identify suspected skeletal metastases . The most impressive images were the 18 F tomograms of the skull on patients with metastatic deposits from Ca breast, where a marked increase in 18 F uptake was seen at the site of each lesion in addition to the normal uptake in the skeleton . 18 F tomograms of patients with skeletal metastases in sites other than the skull also showed increased uptake at the lesion site, but were less impressive than the skull images due to the limited field of view of the prototype camera (- 20 cm X 20 cm).
30 x 30 x 30 cm3 15 x15 x20 cm3 5%/photon (0 .25% coincidence) 500 kcps singles (5 kcps coincidence) 100 cps/MBq. 5 mm in planes parallel to detectors 30 mm in planes perpendicular to detectors 20 ns
Nevertheless, images of the ribs, spine and pelvis did not appear to be degraded by the extra scattering from these larger parts of the body . Other successful studies involving "small" organs, which were well matched to the field of view of the prototype camera, involved the use of 18F FDG and Na124 1 to provide information on glucose and iodine metabolism of the brain and thyroid respectively. In one patient, suffering from multiple brain metastases from Ca bronchus, increased glucose metabolism was seen at the site of a known metastatic deposit, which was also identified on the 99 Tc m glucoheptonate SPECT image of this patient. High resolution PET images of the thyroid, using Na 1241, were obtained in three patients who presented with thyroid lumps or thyrotoxic symptoms . The PET thyroid images were compared with 99 Tc m pertechnetate images taken with a pinhole camera and with ultrasound images . There was no doubt that the PET images provided improved localisation for space-occupying lesions of the thyroid. The only study which was considered to be unsuccessful was the 52 Fe bone-marrow imaging. Four patients were scanned during the clinical trial, and tomograms were obtained of the sternum, spine and liver. However, due to the low activity injected (3 MBq), the PET images were limited by photon noise and were of poor quality. In addition to the clinical studies described above, a study was carried out to assess the feasibility of cardiac imaging using 92 Rb from a 200 MBq 82 Sr/82 Rb genera-
Table 2 Studies performed during first clinical trial Study
Radiopharmaceutical
Skeleton Brain Thyroid Bone-marrow
18 F 18F FDG
Na 1241 52 Fe citrate
Activity administered (MBq) 75 40 4 3
Total number of coincidence events - 750k 500k 75k 150k-250k
Duration of study (min) 20 25 30
up
to 30
35 2
M.A . Flower et al. / Clinical trials of a MWPC positron camera
tor . The 82 Rb was infused into a heart phantom (comprising a beaker containing two Perspex cylinders which represented two cardiac chambers) for 10 min . Data collection was started 14 min after the end of the infusion to simulate the emptying of the cardiac vessels . The initial coincidence count-rate of 1800 fell to 25 counts/s after 10 min and the total number of coincidence events during this period was 270k. Unfortunately, the generator was not suitable for clinical use at the time of the trial . In summary, the results of the first clinical trial were very encouraging. The images obtained, although limited by the small field of view of the prototype camera, were comparable in quality to conventional images . It should be noted that in some cases, equivalent single-photon studies were not possible since the radiopharmaceuticals themselves result in different biodistributions . For example, there is no 99 Tc m equivalent of FDG. Hence the introduction of a low-cost MWPC PET camera into a routine Nuclear Medicine Department would offer not just the opportunity of performing high resolution imaging, but the chance to expand the range of radiopharmaceuticals, currently dominated by 99 Tc', to include other, more useful, positron emitting radionuclides . It was concluded at the end of the first trial that a MWPC PET camera could be used for routine organ imaging, and the results justified further development of the RAL system .
3. Second clinical trial One of the limitations of the prototype camera used in the first clinical trial was the limited angle of acceptance obtained by the single pair of parallel-opposed detectors . This resulted in poor tomography and although the acquired data could be reconstructed into five image planes parallel to the face of the detectors, there was considerable interference between these neighbouring planes . This limitation was overcome in the second clinical trial when multiview data acquisition was made possible with the patient sitting on a rotating chair between the two detectors. The acquired data were reconstructed by backprojection and deconvolution of a 3-dimensional point source response function into a 64 x 64 x 64 matrix (with a pixel size of 3 mm) . The data were displayed as 2D transaxial, sagittal or coronal images or as a 3D model using a contouring technique to find the surface of the radioactive distribution . During the second clinical trial, 39 patients were imaged and two types of study were performed : either thyroid imaging using Na1241 or brain imaging using 68 Ga EDTA . In 22 patients undergoing radioiodine therapy for thyrotoxicosis, measurements were made of the functioning volume of the thyroid tissue, using the prototype
RAL MWPC positron camera with multiview acquisition. A full report of these measurements has already been presented [4] so again only a brief summary is given here . The high-resolution PET camera made it possible to measure the functioning thyroid volume to an accuracy of ±4% to ±14% . No attempt was made to determine the thyroid uptake with the PET camera since no correction for photon attenuation was incorporated in the reconstruction software at this time . Using a simple scintillation detector, the radioiodine uptake was found to vary from 28% to 98% in the 22 patients studied . The functioning volumes of these thyroids were found to be in the range 21-79 cm3 . A value of 6 days was assumed for the effective half-life of radioiodine in hyperactive thyroids [5,6] . The radiation doses for these patients, who received a mixed dose of 25 MBq 1241 plus 55 MBq 1311, (which is equivalent to a standard 75 MBq 1311 therapy dose) were calculated to vary between 11 and 48 Gy . This range needs to be compared with the recommended range of 50-70 Gy. [6] . These results showed that an unsatisfactory therapeutic effect could be obtained in many cases and that the administered activity of 131 1 should be matched to the size and uptake of the gland being treated . In addition to the measurement of the functioning volume, the PET images were compared to those obtained with planar scintigraphy using a gamma camera with a pinhole collimator . As a result of the higher resolution and tomographic capability of the MWPC positron camera, it was found that in five cases PET imaging revealed a non-uniform distribution of radioiodine in thyroids which were thought to have uniform uptake from the conventional scintigram. The 68 Ga EDTA for brain imaging was obtained from an in-house 68 Ge/ 68 Ga generator . This radio-
Fig . 3 . The clinical prototype multiwire proportional chamber PET camera (MUP-PET), with the detectors rotating around the patient couch .
M.A . Flower et al. / Clinical trials of a MWPC positron camera pharmaceutical is used for studying the integrity of the blood/brain barrier (BBB). Patients attending the Nuclear Medicine department for brain imaging using the equivalent single-photon emitting radiopharma-
ceutical, 99 Tc' glucoheptonate, were selected for additional PET scanning. Although a high-quality BBB image was obtained from a normal volunteer, the 11 images from patients with brain tumours were disap-
pointing due to the inability to keep the patients immobilised for the duration of the acquisition . Although
abnormal uptake was identified in most cases, the image quality was unacceptable as a result of the patient movement . This problem will hopefully be overcome in future studies with the clinical prototype camera (MUP-
PET) [7] in which the new large-area detectors (60 cm x 30 cm) are mounted on a gantry which enables
rotation about a horizontal axis around a patient couch (fig . 3) .
References [1] J.E. Bateman, J.F. Connolly, R. Stephenson and A.C . Flesher, Nucl . Instr. and Meth . 176 (1980) 83 .
35 3
[2] J.E. Bateman, J.F . Connolly, R. Stephenson, G.J . Tappern and A.C. Flesher, Rutherford Laboratory report R1-83-113, Chilton, Oxon . (1983). M.A. Flower, R.J. Ott, S. Webb, M.O . Leach, P. Marsden, O. Khan, V.R. McCready, J.E . Bateman, A.C . Flesher, H.L. Sharma and A.G . Smith, Brit. J. Radiol. 57 (1984) 1103 . [4] R.J . Ott, V. Batty, S. Webb, M.A . Flower, M.O . Leach, R. Clack, P.K . Marsden, V.R . McCready, J.E. Bateman, H. Sharma and A. Smith, Brit. J. Radio] . 60 (1987) 245. J. Harbert and A.F.G . da Rocha, Textbook of Nuclear Medicine, Vol. 11 Clinical Applications (Lea and Febiger, Philadelphia, 1984) pp . 30-35. [6] M.K. O'Connor, M.J. Cullen and J.F . Malone, Brit . J. Radiol. 59 (1979) 719. R.J . Ott, P.K . Marsden, M.A . Flower, S. Webb, S. Cherry and V.R . McCready, these Proceedings (Int . Symp . on the Use of Wire Chambers in Medical Imaging, Corsendonk Belgium, 1987) Nucl . Instr. and Meth. A269 (1988) 436.
Nuclear Instruments and Methods in Physics Research A269 (1988) 350-353 North-Holland, Amsterdam
CLINICAL TRIALS OF THE PROTOTYPE RUTHERFORD APPLETON LABORATORY MWPC POSITRON CAMERA AT THE ROYAL MARSDEN HOSPITAL M.A . FLOWER, R.J . OTT, S. WEBB, M.O . LEACH, P.K . MARSDEN, R. CLACK, O . KHAN, V. BATTY, V.R. McCREADY and J.E . BATEMAN') The Royal Marsden Hospital and Institute of Cancer Research, Sutton, Surrey, England The Rutherford Appleton Laboratory, Chilton, Didcot, Oxfordshire, England
Two clinical trials of the prototype RAL multiwire proportional chamber (MWPC) positron camera were carried out prior to the development of a clinical system with large-area detectors . During the first clinical trial, the patient studies included skeletal imaging using 18 F, imaging of brain glucose metabolism using t8 F FDG, bone marrow imaging using 52 Fe citrate and thyroid imaging with Na'z° I. Longitudinal tomograms were produced from the limited-angle data acquisition from the static detectors. During the second clinical trial, transaxial, coronal and sagittal images were produced from the multiview data acquisition. A more detailed thyroid study was performed in which the volume of the functioning thyroid tissue was obtained from the 3D PET image and this volume was used in estimating the radiation dose achieved during radioiodine therapy of patients with thyrotoxicosis. Despite the small field of view of the prototype camera, and the use of smaller than usual amounts of activity administered, the PET images were in most cases comparable with, and in a few cases visually better than, the equivalent planar view using a state-of-the-art gamma camera with a large field of view and routine radiopharmaceuticals .
1. Introduction This paper reviews two clinical trials which were carried out using the prototype RAL MWPC positron camera [1,2], which consisted of two opposing 30 cm X 30 cm chambers . During the initial trial period (October to December 1982) the detectors were positioned either side of a patient couch (fig. 1) and longitudinal tomograms were produced from the limited-angle data acquisition . During the second trial period (March 1984 to March 1985) the detectors were mounted on a raised gantry and positioned on either side of a rotating chair (fig. 2) so that transaxial tomograms were produced from data acquired with the patient at eight different angular orientations at 22 .5' intervals.
function . The properties of the prototype PET camera at the time of the first clinical trial are listed in table 1 . Note that the useful field of view was limited to the central 15 cm X 15 cm area so that the PSRF could be considered spatially invariant for the deconvolution process. During the 2-month evaluation period, 25 patients were imaged and 44 studies were performed. These studies included skeletal imaging using ' 8 17, brain imaging using 18 F fluorodeoxyglucose (FDG) and bone-mar-
2. First clinical trial A full report on the evaluation of this positron camera for longitudinal tomography has already been presented [3]. Hence only a brief summary is given here . The image reconstruction method was a two-stage process. Firstly, the acquired data from the pair of detectors operating in coincidence were back-projected into five image planes parallel to the face of the detector with an interplane spacing of typically 3-5 cm. Secondly, the back-projected images (represented by five 64 X 64 matrices with a pixel size of 2.3 mm) were deconvolved with a 2-dimensional point source response 0168-9002/88/$03 .50 (~) Elsevier Science Publishers B.V . (North-Holland Physics Publishing Division)
Fig. 1. The prototype RAL MWPC positron camera set up for the first clinical trial with the two 30 cm X 30 cm detectors positioned either side of the patient couch.
35 1
M.A . Flower et al. / Clinical trials of a MWPC positron camera
Table 1 Properties of the prototype RAL MWPC PET camera Physical sensitive volume Usable sensitive volume Efficiency Count rate limit Point source sensitivity Spatial resolution Resolving time
Fig. 2. The prototype RAL MWPC positron camera set up for the second clinical trial with the detectors positioned either side of a rotating chair. row imaging with 52 Fe . These positron-emitting radiopharmaceuticals were provided by the MRC cyclotron at Hammersmith. In addition to these radiopharmaceuticals, Na1241 for thyroid imaging was obtained from the Birmingham University Nuffield cyclotron and purified in the Department of Medical Biophysics at the University of Manchester . Patients were selected from those attending the Nuclear Medicine Department for single-photon imaging and the quality of the PET images was compared with the planar images and, in some cases, SPECT tomograms as well . Some of the details of the scanning parameters used for these studies are listed in table 2. More than half of the patients imaged were those examined to identify suspected skeletal metastases . The most impressive images were the 18 F tomograms of the skull on patients with metastatic deposits from Ca breast, where a marked increase in 18 F uptake was seen at the site of each lesion in addition to the normal uptake in the skeleton . 18 F tomograms of patients with skeletal metastases in sites other than the skull also showed increased uptake at the lesion site, but were less impressive than the skull images due to the limited field of view of the prototype camera (- 20 cm X 20 cm).
30 x 30 x 30 cm3 15 x15 x20 cm3 5%/photon (0 .25% coincidence) 500 kcps singles (5 kcps coincidence) 100 cps/MBq. 5 mm in planes parallel to detectors 30 mm in planes perpendicular to detectors 20 ns
Nevertheless, images of the ribs, spine and pelvis did not appear to be degraded by the extra scattering from these larger parts of the body . Other successful studies involving "small" organs, which were well matched to the field of view of the prototype camera, involved the use of 18F FDG and Na124 1 to provide information on glucose and iodine metabolism of the brain and thyroid respectively. In one patient, suffering from multiple brain metastases from Ca bronchus, increased glucose metabolism was seen at the site of a known metastatic deposit, which was also identified on the 99 Tc m glucoheptonate SPECT image of this patient. High resolution PET images of the thyroid, using Na 1241, were obtained in three patients who presented with thyroid lumps or thyrotoxic symptoms . The PET thyroid images were compared with 99 Tc m pertechnetate images taken with a pinhole camera and with ultrasound images . There was no doubt that the PET images provided improved localisation for space-occupying lesions of the thyroid. The only study which was considered to be unsuccessful was the 52 Fe bone-marrow imaging. Four patients were scanned during the clinical trial, and tomograms were obtained of the sternum, spine and liver. However, due to the low activity injected (3 MBq), the PET images were limited by photon noise and were of poor quality. In addition to the clinical studies described above, a study was carried out to assess the feasibility of cardiac imaging using 92 Rb from a 200 MBq 82 Sr/82 Rb genera-
Table 2 Studies performed during first clinical trial Study
Radiopharmaceutical
Skeleton Brain Thyroid Bone-marrow
18 F 18F FDG
Na 1241 52 Fe citrate
Activity administered (MBq) 75 40 4 3
Total number of coincidence events - 750k 500k 75k 150k-250k
Duration of study (min) 20 25 30
up
to 30
35 2
M.A . Flower et al. / Clinical trials of a MWPC positron camera
tor . The 82 Rb was infused into a heart phantom (comprising a beaker containing two Perspex cylinders which represented two cardiac chambers) for 10 min . Data collection was started 14 min after the end of the infusion to simulate the emptying of the cardiac vessels . The initial coincidence count-rate of 1800 fell to 25 counts/s after 10 min and the total number of coincidence events during this period was 270k. Unfortunately, the generator was not suitable for clinical use at the time of the trial . In summary, the results of the first clinical trial were very encouraging. The images obtained, although limited by the small field of view of the prototype camera, were comparable in quality to conventional images . It should be noted that in some cases, equivalent single-photon studies were not possible since the radiopharmaceuticals themselves result in different biodistributions . For example, there is no 99 Tc m equivalent of FDG. Hence the introduction of a low-cost MWPC PET camera into a routine Nuclear Medicine Department would offer not just the opportunity of performing high resolution imaging, but the chance to expand the range of radiopharmaceuticals, currently dominated by 99 Tc', to include other, more useful, positron emitting radionuclides . It was concluded at the end of the first trial that a MWPC PET camera could be used for routine organ imaging, and the results justified further development of the RAL system .
3. Second clinical trial One of the limitations of the prototype camera used in the first clinical trial was the limited angle of acceptance obtained by the single pair of parallel-opposed detectors . This resulted in poor tomography and although the acquired data could be reconstructed into five image planes parallel to the face of the detectors, there was considerable interference between these neighbouring planes . This limitation was overcome in the second clinical trial when multiview data acquisition was made possible with the patient sitting on a rotating chair between the two detectors. The acquired data were reconstructed by backprojection and deconvolution of a 3-dimensional point source response function into a 64 x 64 x 64 matrix (with a pixel size of 3 mm) . The data were displayed as 2D transaxial, sagittal or coronal images or as a 3D model using a contouring technique to find the surface of the radioactive distribution . During the second clinical trial, 39 patients were imaged and two types of study were performed : either thyroid imaging using Na1241 or brain imaging using 68 Ga EDTA . In 22 patients undergoing radioiodine therapy for thyrotoxicosis, measurements were made of the functioning volume of the thyroid tissue, using the prototype
RAL MWPC positron camera with multiview acquisition. A full report of these measurements has already been presented [4] so again only a brief summary is given here . The high-resolution PET camera made it possible to measure the functioning thyroid volume to an accuracy of ±4% to ±14% . No attempt was made to determine the thyroid uptake with the PET camera since no correction for photon attenuation was incorporated in the reconstruction software at this time . Using a simple scintillation detector, the radioiodine uptake was found to vary from 28% to 98% in the 22 patients studied . The functioning volumes of these thyroids were found to be in the range 21-79 cm3 . A value of 6 days was assumed for the effective half-life of radioiodine in hyperactive thyroids [5,6] . The radiation doses for these patients, who received a mixed dose of 25 MBq 1241 plus 55 MBq 1311, (which is equivalent to a standard 75 MBq 1311 therapy dose) were calculated to vary between 11 and 48 Gy . This range needs to be compared with the recommended range of 50-70 Gy. [6] . These results showed that an unsatisfactory therapeutic effect could be obtained in many cases and that the administered activity of 131 1 should be matched to the size and uptake of the gland being treated . In addition to the measurement of the functioning volume, the PET images were compared to those obtained with planar scintigraphy using a gamma camera with a pinhole collimator . As a result of the higher resolution and tomographic capability of the MWPC positron camera, it was found that in five cases PET imaging revealed a non-uniform distribution of radioiodine in thyroids which were thought to have uniform uptake from the conventional scintigram. The 68 Ga EDTA for brain imaging was obtained from an in-house 68 Ge/ 68 Ga generator . This radio-
Fig . 3 . The clinical prototype multiwire proportional chamber PET camera (MUP-PET), with the detectors rotating around the patient couch .
M.A . Flower et al. / Clinical trials of a MWPC positron camera pharmaceutical is used for studying the integrity of the blood/brain barrier (BBB). Patients attending the Nuclear Medicine department for brain imaging using the equivalent single-photon emitting radiopharma-
ceutical, 99 Tc' glucoheptonate, were selected for additional PET scanning. Although a high-quality BBB image was obtained from a normal volunteer, the 11 images from patients with brain tumours were disap-
pointing due to the inability to keep the patients immobilised for the duration of the acquisition . Although
abnormal uptake was identified in most cases, the image quality was unacceptable as a result of the patient movement . This problem will hopefully be overcome in future studies with the clinical prototype camera (MUP-
PET) [7] in which the new large-area detectors (60 cm x 30 cm) are mounted on a gantry which enables
rotation about a horizontal axis around a patient couch (fig . 3) .
References [1] J.E. Bateman, J.F. Connolly, R. Stephenson and A.C . Flesher, Nucl . Instr. and Meth . 176 (1980) 83 .
35 3
[2] J.E. Bateman, J.F . Connolly, R. Stephenson, G.J . Tappern and A.C. Flesher, Rutherford Laboratory report R1-83-113, Chilton, Oxon . (1983). M.A. Flower, R.J. Ott, S. Webb, M.O . Leach, P. Marsden, O. Khan, V.R. McCready, J.E . Bateman, A.C . Flesher, H.L. Sharma and A.G . Smith, Brit. J. Radiol. 57 (1984) 1103 . [4] R.J . Ott, V. Batty, S. Webb, M.A . Flower, M.O . Leach, R. Clack, P.K . Marsden, V.R . McCready, J.E. Bateman, H. Sharma and A. Smith, Brit. J. Radio] . 60 (1987) 245. J. Harbert and A.F.G . da Rocha, Textbook of Nuclear Medicine, Vol. 11 Clinical Applications (Lea and Febiger, Philadelphia, 1984) pp . 30-35. [6] M.K. O'Connor, M.J. Cullen and J.F . Malone, Brit . J. Radiol. 59 (1979) 719. R.J . Ott, P.K . Marsden, M.A . Flower, S. Webb, S. Cherry and V.R . McCready, these Proceedings (Int . Symp . on the Use of Wire Chambers in Medical Imaging, Corsendonk Belgium, 1987) Nucl . Instr. and Meth. A269 (1988) 436.