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The acquisition of radiotherapy planning scans on positron emission tomography (PET)-CT scanners requires the involvement of radiotherapy radiographers. This study assessed the radiation dose received by these radiographers during this process. Radiotherapy planning (18)F-fluorodeoxyglucose ((18)F-FDG) PET-CT scans were acquired for 28 non-small cell lung cancer patients. In order to minimise the radiation dose received, a two-stage process was used in which the most time-consuming part of the set-up was performed before the patient received their (18)F-FDG injection. Throughout this process, the radiographers wore electronic personal dosemeters and recorded the doses received at different stages of the process. The mean total radiation dose received by a radiotherapy radiographer was 5.1+/-2.6 microSv per patient. The use of the two-stage process reduced the time spent in close proximity to the patient by approximately a factor of four. The two-stage process was effective in keeping radiation dose to a minimum. The use of a pre-injection set-up session reduces the radiation dose to the radiotherapy radiographers because of their involvement in PET-CT radiotherapy treatment planning scans by approximately a factor of three.

The introduction of functional data into the radiotherapy treatment planning process is currently the focus of significant commercial, technical, scientific and clinical development. The potential of such data from positron emission tomography (PET) was recognized at an early stage and was integrated into the radiotherapy treatment planning process through the use of image fusion software. The combination of PET and CT in a single system (PET/CT) to form an inherently fused anatomical and functional dataset has provided an imaging modality which could be used as the prime tool in the delineation of tumour volumes and the preparation of patient treatment plans, especially when integrated with virtual simulation. PET imaging typically using 18F-Fluorodeoxyglucose (18F-FDG) can provide data on metabolically active tumour volumes. These functional data have the potential to modify treatment volumes and to guide treatment delivery to cells with particular metabolic characteristics. This paper reviews the current status of the integration of PET and PET/CT data into the radiotherapy treatment process. Consideration is given to the requirements of PET/CT data acquisition with reference to patient positioning aids and the limitations imposed by the PET/CT system. It also reviews the approaches being taken to the definition of functional/tumour volumes and the mechanisms available to measure and include physiological motion into the imaging process. The use of PET data must be based upon a clear understanding of the interpretation and limitations of the functional signal. Protocols for the implementation of this development remain to be defined, and outcomes data based upon clinical trials are still awaited.

The purpose of this study was to undertake an audit of the quantitative characteristics of single photon emission computed tomography software using projection data from an analytically generated software phantom and a measured line source. The phantom consisted of three structures. A uniformly filled cylinder, a series of cylindrical rods of various diameters in a background activity with a rod to background ratio of 2:1 and lastly, a set of three concentric rings of activity in the ratio 1:0:1. The phantom contained no added statistical noise. No attenuation was imposed on the data. The phantom was generated analytically and projections were distributed at six different count densities. A single set of projections from a thin line source was also distributed. These data were distributed to centres throughout the UK. Centres were asked to reconstruct the data using a 'ramp only' reconstruction with no additional smoothing function applied. Data were requested for mean and standard deviation in the uniform cylinder, the maximum counts for each cylindrical rod and the mean counts in regions placed within the concentric rings. For the measured line source, centres were asked to measure the full width at half maximum and peak pixel counts for a profile through the reconstructed line. Results from 115 systems were obtained from 100 centres throughout the UK. These provided data from 12 software providers, 11 of these being commercial companies. Data were compared with the known input values and histograms of the distribution of results obtained. Significant differences in quantitative parameters were noted for the different input count densities as well as between suppliers and revisions of software from single suppliers.

The purpose of this study was to perform an audit of quantitative values obtained from gamma camera renography in the UK. Ten patient image sequences representing normal and pathological renal function were obtained from archived studies and distributed to hospitals in the UK. Hospitals were asked to measure five parameters: relative function, renogram time-to-peak (left and right), and whole kidney mean transit time (left and right). Details of methodology, software used and operator experience were requested. This allowed the influence of operational factors on variations in reported values to be examined. A total of 180 responses from 81 hospitals were received. Values reported for the parameters, together with other details supplied, were entered into Excel and SPSS for statistical analysis. Histograms representing the distribution of values were produced for each parameter. The largest variations were found for mean transit time and occasionally for time-to-peak. The effect of factors was assessed using nonparametric statistical tests applied independently to each renogram. For all the parameters, the hospital, UK region, supplier, computer and software version influenced variations in the reported values. Algorithm and site of background region were influencing factors for relative function, the background subtraction method influenced time-to-peak, and curve smoothing influenced mean transit time.

Lateral attenuation in single-photon emission tomography (SPET) myocardial perfusion imaging (MPI) has been attributed to the left arm if it is held by the patient's side during data acquisition. As a result MPI data are conventionally acquired with the arms held above the head. The aims of this study were to determine the effect of imaging arms down on reconstructed tomographic images depicting regional myocardial thallium-201 distribution and to assess whether attenuation-corrected (AC) myocardial perfusion images acquired arms down could replace uncorrected (NC) images acquired arms up for routine clinical service. Twenty-eight patients referred for routine MPI underwent sequential 180 degrees emission/transmission imaging for attenuation correction using an L-shaped dual-headed gamma camera (GE Optima) fitted with two gadolinium-153 scanning line sources. Delay data were acquired twice: once supine with the arms up and then supine with the arms down. Detector radius of rotation (ROR) for arms up and arms-down studies was recorded. For each data set, count density was measured in 17 segments of a polar plot and segmental uptake expressed relative to study maximum. Oblique images were assessed qualitatively by two observers blinded to study type for tracer distribution and overall quality. Transmission maps were assessed for truncation. Mean detector ROR was 190 mm for arms-up studies and 232 mm for arms-down studies (P<0.05). Population mean segmental relative uptake values for NC arms-up studies were higher than for NC arms-down studies, with the greatest difference seen anterolaterally. Nevertheless, the majority (24/28) of oblique NC arms-up and NC arms-down images appeared similar and only four (14%) NC arms-down studies showed additional areas of reduced count density (one anterior and three lateral). Corresponding AC arms-down studies showed that count density within the anterior defect improved to normal but the lateral reductions persisted, and in two of these three studies the arms-down transmission map was distorted. Population mean segmental relative uptake values for NC arms-down studies were lower than for AC arms-down studies apart from three anterolateral segments where NC arms-down values were higher. Of 28 AC arms-down studies, 11 (39%) were of reduced quality compared with NC arms-up studies because of poorer spatial resolution and because AC enhances liver activity compared with NC. It is concluded that arm positioning influences reconstructed tomographic images depicting regional 201T1 distribution, particularly anterolaterally. There is lateral undercorrection in approximately 10% of AC arms-down studies, possibly because of attenuation map truncation. Image quality is reduced in about one-third of AC armsdown studies compared with NC arms-up studies. These data suggest that this attenuation correction method is not sufficiently robust to allow routine acquisition of MPI data with the arms down.

A variety of software is used to determine quantitative parameters from radionuclide imaging procedures. Knowledge of the variability of parameter values found in different hospitals is an important aspect of clinical audit of these techniques. This study investigated the variation in relative renal function measurement from static DMSA scintigraphy in the UK. Ten studies representing a range of ages and relative function values were distributed in digital form to 100 hospitals with the assistance of the gamma camera computer suppliers and regional audit coordinators. The studies were analysed at each participating hospital and details of the different techniques and computer systems used were documented. The median value of relative percentage function was assessed for each of the studies. Methods varied in terms of the view used for analysis (54% geometric mean, 46% posterior), the type of background subtraction (single region 32%, separate regions 60%, none 8%) and the definition of the renal regions of interest (73% manual, 27% semi-automatic). Eighty-eight percent of results were within two percentage points of the study median and 98% within five percentage points. There were statistically significant differences observed in the results arising from the view used for the analysis and the background subtraction protocol. The results indicate that relative renal function assessment from static DMSA scintigraphy in the UK is essentially a reliable procedure, although improvements could be made by standardizing the technique used.

The aim of this study was to assess the status of acquisition and reporting of myocardial perfusion tomography in the UK. Centres were asked to provide an expert panel with clinical and technical information, digital and hard copy of raw data and reconstructed tomograms, as well as their report (optional) for five randomly selected studies. Ninety studies were received from 18 centres; report text was provided for 66 studies. Six parameters (stress technique, radiopharmaceutical usage, image acquisition and processing, report images and text) were scored as good (2), adequate (1) or poor (0) by consensus. Centres received the quality scores for each study and a consensus clinical report from the panel. Stress technique was scored as inadequate in 10 (11%) studies, radiopharmaceutical usage and image acquisition as inadequate in 5 (6%) studies, image processing as inadequate in 8 (10%) studies and report images as inadequate in 2 (3%) studies. Report text was felt to be inadequate in 21 of 66 (32%) studies; in 11 of these (52%), the report text was judged to be incorrect and in 10 (48%) it was essentially correct but misleading because of poor phraseology. The mean quality score per study was 1.3 (range 0.5-2.0). Seventeen of 88 (19%) studies scored less than 1.0 and were considered to be of poor quality. In conclusion, a large variation in standards of myocardial perfusion tomography was seen. Data acquisition was generally satisfactory, but 32% of reports were inadequate.

For attenuation correction (AC) of 201Tl myocardial perfusion images, an accurate attenuation map is required. This study assessed whether prolonged transmission scanning is required in obese compared to normal-sized patients. Twenty-nine obese patients (mean body mass index 33 kg m-2) underwent sequential emission/transmission imaging for AC using an L-shaped, dual-headed gamma camera fitted with two 153Gd scanning line sources. Transmission data were acquired for 5 s per view (scan time for normal-sized patients) and for 10 s per view and used to reconstruct individual attenuation maps. Emission data were reconstructed using each attenuation map in turn to produce attenuation-corrected images (AC5 and AC10). Tracer distribution in the AC5 and AC10 images was compared by two observers blinded to study type. For each data set, count density was measured in 17 segments of a polar plot and segmental uptake expressed relative to study maximum. Although myocardial count density was low on the 5 s per view transmission images (0.5-13.0 and 3.0-14.0 counts per pixel in the anteroposterior and lateral projections respectively), no significant differences in tracer distribution were seen between the AC5 and AC10 images and these were reported identically. In addition, the mean segmental relative uptake values were similar (P > 0.05) for corresponding segments of the AC5 and AC10 images. We conclude that prolonged transmission scanning is not required in obese compared to normal-sized patients. The transmission scanning protocol used in normal-sized patients is applicable across a wide patient weight range.

Regional variation of tracer distribution is seen in uncorrected thallium-201 images of normal hearts. This study evaluates the effect of attenuation correction on myocardial 201T1 distribution in patients with low risk of coronary artery disease. An L-shaped dual-detector single-photon emission tomographic system equipped with a pair gadolinium-153 scanning line sources was used for sequential emission/transmission imaging in 36 patients (14 men and 22 women) with less than 5% risk for coronary artery disease. Uncorrected emission images were reconstructed using filtered back-projection (FBP) whereas the attenuation corrected (AC) images were iteratively reconstructed using the attenuation map computed from the transmission data. Both sets of images were reorientated into short axis, vertical long axis and horizontal long axis images. For quantification data were reconstructed into polar plots and count density estimated in 17 myocardial segments. The population % standard deviation for each segment of AC data was significantly smaller than that for FBP data, indicating improved homogeneity of tracer distribution. In men the anterior-basal inferior activity ratio improved from 1.20 for FBP to 0.96 for AC (stress) and from 1.23 for FBP to 0.98 for AC (delay) (P < 0.0001). In women the anterior-basal inferior activity ratio changed from 1.08 for FBP to 0.94 for AC (stress) and from 1.08 for FBP to 0.93 for AC (delay) (P < 0.001). These ratios reflect appropriate compensation for basal attenuation but a lack of scatter correction. The lateral-septal activity ratio in men changed from 1.05 for FBP to 0.99 for AC (stress) and from 1.02 for FBP to 0.96 for AC (delay), while in women it changed from 1.05 for FBP to 0.98 for AC (stress) and from 1.04 for FBP to 0.98 for AC (delay) (P < 0.005 in all cases). The apex of AC images showed a decrease in activity consistent with wall thining at this site. It is concluded that the use of attenuation correction yields improved homogeneity of myocardial tracer distribution in patients with low risk of coronary artery disease. The diagnostic benefits of attenuation correction are yet to be fully assessed.

Optimized positron emission tomographs have begun to demonstrate an ever widening range of clinical applications for positron labelled pharmaceuticals. This potential has led to a renewed interest in the use of the more widely available Anger gamma camera detectors for imaging the 511 keV photons from the positron decay process. Two forms of detection can be considered: either the detection of the 511 keV photons as single events or the detection of coincidence events from the opposed pair annihilation photons. The widespread availability of dual, opposed-pair, large field-of-view detectors has promoted the development of coincidence detection without collimation. With detector rotation, positron emission tomography (PET) can be performed. An alternative and lower cost option has been the universal development of ultra high-energy collimators to perform single photon emission tomography (SPET) with 511 keV photons. This review outlines the currently available performance characteristics of these two approaches and compares them with those from two- and three-dimensional PET optimized systems. The limitations on the development of these systems is discussed through the analysis of the principles underlying both single photon and coincidence detection. Preliminary clinical experience indicates that limitations in the performance characteristics of these systems has implications for their potential role, although applications in cardiology and oncology are being pursued.

Unlabelled: Technetium-99m tetrofosmin is a recently developed compound that clears from background organs rapidly. Tetrofosmin has a good correlation with 201Tl. This study assesses the feasibility and diagnostic accuracy of a combined protocol involving rest 201Tl SPECT and stress imaging with 99mTc-tetrofosmin., Methods: Twenty-five patients (23 men, 2 women; aged 36-73 yr) with known coronary artery disease underwent the combined protocol. Twenty minutes after the resting injection of 201Tl, resting SPECT data were acquired using low-energy, high-resolution collimators. A stress test using adenosine infusion combined with low-level dynamic exercise was performed. The stress data were collected 20 min later. The reconstructed vertical long-axis, horizontal long-axis and short-axis slices were analyzed qualitatively. Analysis was carried out using nine segments of the left ventricle. The segments were reported either as fixed or reversible. The results were compared to coronary angiography results., Results: The sensitivity and specificity for the detection of diseased coronary vessels were 85% and 70% for the left anterior descending territory, respectively, 78% and 71% for the right coronary artery, and 69% and 70% for the left circumflex. Overall, the sensitivity was 80% and the specificity 70%., Conclusion: Combined rest 201Tl/stress 99mTc-tetrofosmin SPECT provides a protocol of short duration which displays similar diagnostic accuracy to a protocol using tetrofosmin as a single agent.

Planar renal scintigraphy with Tc-99m DMSA has become established as a standard diagnostic test to determine if a kidney has been scarred by infection. It has been suggested that high resolution SPECT may improve the sensitivity of detection of renal scars. To determine if it is possible to produce good quality renal SPECT with a short acquisition time, 10 adults were examined with a new multi-detector gamma camera using 8 minute, 16 minute, and 32 minute acquisitions. The number of defects seen (N = 16) with an 8 minute acquisition was not significantly different from the defects (N = 15) seen using a 16 minute and a 32 minute acquisition. In adults when imaging with a multi-detector gamma camera there was no clinical advantage in using an acquisition of longer than 8 minutes.

The clinical experience with the Toshiba GCA-9300A single photon emission tomography (SPET) system is discussed along with typical acquisition protocols for various SPET studies. The system was used to perform SPET studies in normals and in a variety of brain and body disorders. Its three Anger-type gamma cameras forming a triangular aperture offer a substantial increase in sensitivity compared to a single rotating gamma camera. This has allowed the routine use of lead fanbeam super high-resolution collimators (SHR FB) for 99Tcm-hexamethylpropyleneamine oxime (HMPAO) brain SPET studies and high-resolution parallel-hole collimators (HR PH) for cardiac and other body studies. The resulting improvement in spatial resolution coupled with the ease of patient positioning and the greater patient throughput compared to a conventional tomographic gamma camera, will enhance the role of brain and body SPET for both routine and research purposes.

201Tl myocardial perfusion single photon emission tomography (SPET) with pharmacological coronary vasodilatation using adenosine is now often used in the investigation of a patient with ischaemic heart disease (IHD). In this study, we present data from two groups of patients. Group A (n = 40) experienced 201Tl SPET with adenosine only as the pharmacological stress test, using an infusion rate of 140 micrograms kg-1 min-1. Group B patients (n = 50) had the same test combined with low-level dynamic exercise. The side effects were noted for both groups and 201Tl SPET studies were acquired for stress and redistribution images. There was a lesser degree of non-cardiac side effects in patients of group B. There was a significant difference in the haemodynamic parameters between the two groups. There was no significant difference in overall sensitivity (87% versus 90%) and specificity (84% versus 88%) in the detection of IHD between the two groups. In conclusion, addition of low-level dynamic exercise with adenosine is to be preferred to adenosine infusion alone, as this protocol is better tolerated and may enhance the detection of right coronary artery disease (sensitivity = 82% versus 90%, n.s.).

The physical performance of the Toshiba GCA-9300A triple-headed SPECT system has been assessed. Using a water-filled cylinder containing 99mTc, the tomographic volume sensitivity was 33.8 and 34.8 kcps/(MBq/ml)/cm for the high-resolution, parallel-hole (HR-PH) collimator and the super high-resolution, lead fanbeam (SHR-FB) collimator, respectively, excluding the rotation time(s) during scanning when data are not acquired. The tomographic spatial resolution at the center, in air, with 132 mm radius of rotation was 10.2 and 7.8 mm FWHM with the HR-PH and SHR-FB collimators, respectively; in water it was 11.0 and 7.8 mm. Reconstructed relative activity concentrations were accurate for both collimator sets if attenuation correction was used. With the SHR-FB collimators, the average peak-to-valley ratio of five-line sources in water improved significantly when an asymmetric energy window was used. Using the three-dimensional Hoffman brain phantom which simulates a 4:1 grey matter-to-white matter ratio and the usual choice of acquisition and processing parameters for brain studies, the reconstructed grey matter-to-white matter ratio was only about 1.7 for total counts typically acquired in a 99mTc-HMPAO study (4.0 M counts) and only 2.3 for 40 M counts. There was a qualitative improvement with an asymmetric energy window.

Planar skeletal scintigraphy has become established as a standard diagnostic test performed within the nuclear medicine department. Since the 1970s good quality images have been produced using an Anger gamma camera and 99Tcm-labelled diphosphonates. Single photon emission tomography (SPET) has improved the sensitivity of detection and the ability to localize bony pathology, particularly benign bone disease in the spine. Recently multi-detector gamma cameras dedicated to SPET have become available. One such system, the Toshiba GCA-9300A, has been used to perform routine clinical skeletal SPET in 81 patients. Good quality images have been obtained using an 8 min acquisition in the axial skeleton and a 16 min acquisition protocol in the peripheral skeleton. Multiple sites can be tomographed in the same patient during the same examination using two or more 8 min acquisitions. Such a multi-detector gamma camera offers advantages over the standard single-headed rotating camera for skeletal SPET in terms of both imaging time and image quality. A cost analysis was performed which demonstrated that the additional cost of purchasing such a multidector gamma camera was less than 30.00 pounds per SPET study.

The definition of viable myocardium after an acute myocardial infarction (MI) is important as it will determine which therapeutic option will be best for the patient. In 201Tl scintigraphy it has been shown that late redistribution (8-24 h) or reinjection may help to identify viable myocardium which does not appear to reperfuse on the 4 h redistribution image. In a prospective study 20 patients with a persistent defect seen on both stress and redistribution images were imaged after reinjection of 201Tl. On visual analysis a total of 180 segments were studied, 85 were normal, 18 reperfused at redistribution and a further nine (in six patients) after reinjection. Bull's-eye analysis at stress demonstrated a mean defect size of 279 pixels, S.D. +/- 74. After redistribution, there was no significant change in mean defect size (227 +/- 96 pixels). At reinjection, there was a significant reduction in mean defect size (189 +/- 107 pixels) (P < 0.05, paired 't'-test). Quantification shows a significant reduction in defect size between stress and reinjection. The use of the 201Tl reinjection technique in patients with a fixed perfusion deficit on stress and redistribution images improves the detection of viable myocardium and is to be preferred to a method of redistribution analysis alone.

The GE/CGR Neurocam is a triple-headed single photon emission tomography (SPET) system dedicated to multi-slice brain tomography. We have assessed its physical performance in terms of sensitivity and resolution, and its clinical efficacy in comparison with a modern, single rotating gamma-camera (GE 400XCT). Using a water-filled cylinder containing technetium-99m, the tomographic volume sensitivity of the Neurocam was 30.0 and 50.7 kcps/MBq.ml.cm for the high-resolution (HR) and general-purpose (GP) collimators, respectively; the corresponding values for the single rotating camera were 7.6 and 12.8 kcps/(MBq/ml)/cm. Tomographic resolution was measured in air and in water. In air, the Neurocam resolution at the cente of the field-of-view (FOV) is 9.0 and 10.7 mm full width at half-maximum (FWHM) with the HR and GP collimators, respectively, and is isotropic in the three orthogonal planes; the resolution of the GE 400XCT with 13 cm radius of rotation is 10.3 and 11.7 mm, respectively. For the Neurocam with the HR collimator, the transaxial FWHM values in water were 9.7 mm at the centre and 9.5 mm radial (6.6 mm tangential) at 8 cm from the centre. The physical characteristics of the Neurocam enable the routine acquisition of brain perfusion data with technetium-99m hexamethyl-propylene amine oxime (99mTc-HMPAO) in about 14 min, yielding better image quality than with a single rotating camera in 40 min.

We report the validation of a new delivery system--aerosol production equipment (known by the acronym APE), which generates a particulate aerosol of technetium 99m diethylene triamine penta-acetic acid (DTPA) with a mass-median aerodynamic diameter of 0.35 microns and a geometric standard deviation of 1.8 Twenty subjects were studied; in group 1 were 12 healthy men with normal spirometry; in group 2 were 8 men with AIDS who had mildly abnormal lung function following an episode of pneumocystis pneumonia-spirometry FEV1 3.08 (0.73) L, FVC 4.83 (0.82) L [mean (SD)]. The APE nebulizer was used to form a particulate aerosol with 200 MBq of 99mTc DTPA, which was collected in a 35 1 reservoir of air, which was subsequently inhaled. The mean (SD) inhalation time was 4.7 (0.44) min. The output of the nebulizer (% of activity inhaled) was 82%. Using planar imaging, the penetration index (right lung) in group 1 was 0.93 (0.18), mean (SD), and in group 2 it was 0.91 (0.12). There was virtually no tracheal deposition and extrapulmonary deposition (oropharynx and stomach) was less than 5% of the aerosol delivered. Single-photon emission tomography (SPET) studies carried out in five patients from group 1 confirmed homogeneous intrapulmonary deposition of 99mTc-DTPA. In view of the excellent intrapulmonary deposition of 99mTc-DTPA produced by the APE nebulizer, it may provide an alternative to conventional ventilation studies using radioactive gases.

The need for a reliable non-invasive investigation in osteoradionecrosis (ORN) of the mandible is discussed. The results of 99mTc-methylene diphosphonate bone scans using single photon emission tomography, and measuring dynamic uptake in 13 patients are presented. These suggest that sites of osteoradionecrosis may be defined by a paradoxically increased uptake of 99mTc-methylene diphosphonate.

Relative and absolute 99Tcm-DMSA uptake measurements were carried out on 25 adult patients among whom there were 23 normal and 25 malfunctioning kidneys. Data were collected at 3 and 6 h post intravenous tracer injection. Four methods of calculating absolute uptake were investigated and evaluated. These were based on: (1) posterior view and measured kidney depth; (2) posterior view and Raynauld's depth; (3) geometric mean assuming kidney thickness is small enough not to introduce self attenuation of counts in the kidney itself; (4) geometric mean taking kidney thickness into account. Whilst (1) and (2) were found to overestimate and underestimate renal uptake by up to 5 and 14%, respectively, (3) and (4) were found to be more accurate and comparable. The measurement of relative DMSA uptake (right to left) showed no change between the 1 and 6 h measurements for both obstructed and non-obstructed kidneys. Based on the results from method 4, the absolute renal DMSA uptake had a mean value of 25.4%, S.D. 8.9% and 30.0%, S.D. 9.2% at 3 and 6 h, respectively, for normal/non obstructed kidneys. For obstructed kidneys (responding to frusemide), the mean uptake was 23.0%, S.D. 7.2 and 25.6%, S.D. 6.7% at 3 and 6 h, respectively. For obstructed kidneys not responding to frusemide, the mean uptake was 16.8%, S.D. 3.9 and 20.6%, S.D. 4.8% at 3 and 6 h, respectively. No correlation was found between absolute DMSA uptake and degree of renal obstruction.

Emission tomography has the potential to be developed into a clinically useful technique. Its clinical applications, however, will be limited and not in the main stream of space occupying disease detection but in the definition of quantitative information particularly relevant in those disease processes where the metabolic component is the most important one. Special purpose designed instrumentation may prove to be the best of several possible compromises.

The intracellular localization and relative distribution of 99Tcm-hexamethylpropyleneamine-oxime (99Tcm-d, l-HMPAO) and 201Tl-diethyldithiocarbamate (201Tl-DDC), which have been used to assess regional cerebral blood flow (rCBF) in man, were investigated in rat brain. 99Tcm-d, l-HMPAO was found attached mainly to cell organelles whilst 201Tl-DDC was localized mainly in free state in the cytosolic fraction. Isolation of neuronal and glial nuclei showed that there is higher uptake of 99Tcm-d, l-HMPAO in neuronal nuclei than in glial nuclei for all the different regions of the rat brain investigated. These data demonstrate a different subcellular localization of the two lipophilic agents studied. In view of their proposed clinical utility, this difference merits further investigation.

1. The effect of iron binding on the conformation of transferrins has been studied using analytical gel filtration and differential velocity sedimentation. 2. In all cases where bicarbonate is the anion the transferrin molecules undergo changes in Stokes' radius and sedimentation coefficient of the same order of magnitude, but of opposite sign. 3. Replacement of the bicarbonate ion with oxalate results in smaller changes in these two parameters. 4. In all cases except ovotranferrin, sheep serum transferrin, and human transferrin with oxalate as the anion, changes in Stokes' radius for the addition of the first and second iron atoms are similar. 5. For ovotransferrin and sheep transferrin it is necessary to postulate interaction between the iron-binding sites to account for the change in Stokes' radius caused by the second iron atom binding being greater than for the first. 6. Human transferrin with oxalate as the anion shows a greater change for the first atom bound than for the second which is consistent with the increased size of the oxalate ion compared with bicarbonate.

A new approach to the radionuclide imaging of the lungs is illustrated in this paper, describing four patients who were subjected to section scanning of the chest in addition to conventional planar imaging. The significance of this new method in the investigation of patients suspected of having pulmonary embolism is discussed. The main advantages of the new approach include increased information with depth, clearer definition of the mediastinal space, and the detection in some instances of new lesions not seen by conventional means.

1. A competitive dialysis technique has been used to study the relative affinities of the two iron-binding sites on transferrin molecules and the relative binding strengths of transferrins isolated from plasma of different species. 2. The comparisons were extended to include desialylated human transferrin, ovotransferrin, and a cyanogen bromide fragment of the latter. 3. Although the results of bilateral experiments could generally be accounted for in terms of the theory of independent sites, there were some exceptions, and cyclic comparisons were inconsistent. 4. All the comparisons made were compatible with a model in which site-interaction occurred, but it was not possible to decide whether the sites were intrinsically identical or not. For most species this corresponded to positive cooperativity, but for rabbit it was negative. 5. The average affinity of transferrin for iron depended on species, but the variation was never more than about one order of magnitude. 6. No effect on the binding constants for human transferrin could be detected when the sialic acid residues were removed. 7. The fragment of ovotransferrin competed fairly effectively with the native molecule for iron, although the average relative affinity was only about 1:15. 8. The relative binding of iron by ovotranferrin and human transferrin was affected little when bicarbonate anion was replaced by oxalate, although the ratio of the two binding constants for ovotranferrin increased.

Thirteen patients with left ventricular aneurysms complicating myocardial infarction were studied by contrast angiography and by first pass radionuclide ventriculography. The ejection fraction of the contractile segment (EFCS) was measured from both studies using a double hemishperoid model, and the values correlated closely. There was a monotonic relation between EFCS and stroke volume index measured from thermodilution cardiac outputs carried out simultaneously with the radionuclide study. When radionuclide ventriculography was performed at submaximal supine exercise, changes in EFCS paralleled changes in the total left ventricular ejection fraction in 10 of the 13 cases. In nine patients, changes in EFCS paralleled changes in stroke volume index and the relation between EFCS and stroke volume index was maintained at exercise. After administration of the vasodilator isosorbide dinitrate to 12 patients, repeat exercise radionuclide ventriculography showed an improvement in left ventricular ejection fraction and in eight patients EFCS improved. First pass radionuclide ventriculography can accurately estimate EFCS, which may be an important factor in predicting the likely response to aneurysmectomy. Changes in EFCS on exercise are reflected in changes in total left ventricular ejection fraction and stroke volume index. Isosorbide dinitrate may improve contractile segment function on exercise.

Physical and clinical data on a new emission transverse-section scanner are given. Comparative data from an earlier tomoscanner and a rotating gamma-camera system yield the following information for the three imagers. Resolution at the center of the field is 9 mm for this tomoscanner, 18 mm for the earlier tomoscanner, and 11 mm for the rotating camera; sensitivity (cps/muCi-ml) 36K, 15.4K, 1.9K; crystal area (cm2) 3096, 619, 490, respectively. The quantification of images is discussed. Clinical emission section scans of the brain, liver, chest and skull are presented and discussed. Forty brain scans were analyzed in conjunction with x-ray transmission tomography. No false positives were found. From a total of 15 lesions seen by the CT x-ray scanner, 14 were detected by the emission tomographic scanner, 12 by standard gamma-camera imaging. One false negative case (cyst) was seen by the transmission x-ray scanner but not by the emission scanner.

The distribution of 99Tcm-HM-PAO is described in normal man. Since our initial report on the clinical potential of this new radiopharmaceutical in 1984, a number of clinical trials are in progress worldwide. As the tracer has been designed to enable the in vivo assessment of the distribution of cerebral blood flow in man, significant interest in this new 99Tcm-labelled compound can be detected not only in the nuclear medicine practice in general, but in the more specialist areas of medicine such as neurology and psychiatry. In this paper we report findings which should aid in the evaluation of this compound in normal individuals.

A study was undertaken to evaluate the role of positive infarct scintigraphy in the diagnosis of acute myocardial infarction (AMI), using Technetium99m stannous pyrophosphate (Tc-PYP) and a portable gamma camera. Sixty-one patients admitted to the Coronary Care Unit (CCU) with a presumptive diagnosis of AMI or ischaemic cardiac pain were studied. Positive scans were present in 24/25 (96%) patients with AMI and new Q waves, and in 10/12 (83%) patients with AMI and no Q waves. Nine of eleven (82%) patients with chest pain and no infarction had negative scans. Of thirteen patients with unstable angina, ten (77%) had positive scans. A further eight patients undergoing coronary artery bypass surgery for angina pectoris were studied pre- and postoperatively. Two patients had strongly positive postoperative scans. The Tc-PYP scan is valuable in the detection of peri-operative infarction following coronary artery surgery, and in patients with unstable angina the technique may detect small amounts of myocardial necrosis undetectable by more conventional means. When the diagnosis of infarction is obvious from the ECG, enzymes, or a combination of the two, the Tc-PYP scan provides no extra information helpful in patient management.

Seventy subjects with suspected coronary artery disease were studied by radionuclide angiocardiography. Delayed or paradoxically emptying regions of the left ventricle were detected by a relatively new nuclear technique--phase imaging. The results were assessed in the light of cardiac catheterisation findings. Compared with 19 normals, regions with abnormally high phase (and therefore late emptying) were found in 42 of 61 subjects with coronary disease. High phase values were associated with total occlusion of a major coronary artery, low ejection fraction, and extensive wall motion abnormalities. The phase image greatly facilitated the calculation of contractile segment ejection fraction in 14 cases of left ventricular aneurysm. In three of these postoperative left ventricular ejection fraction agreed closely with preoperative contractile segment ejection fraction and there was a distinct improvement in the phase image after aneurysmectomy.

The data from 84 patients with suspected embolic lung disease who underwent radionuclide section scanning of the chest is reported. All underwent additional conventional planar imaging; specific angiographic evidence of embolic disease was available in 12 cases. A good correlation between the section scans and angiography was obtained. Greater sensitivity in lesion detection was obtained by multiplane section imaging, which should reduce the number of diagnostic uncertainties in embolic lung disease.

The use of multiple gated cardiac imaging in the diagnosis of left ventricular pseudo-aneurysm is reported and the clinical and therapeutic implications are discussed. Complemented with myocardial perfusion imaging, it is the method of choice for screening patients following infarction or chest trauma who may develop this potentially treatable complication of myocardial necrosis.

The radionuclide tracer method is unique amongst all other imaging methodologies in its ability to trace organ or tissue function and metabolism. It derives this advantage from the nature of the signal used for image generation, and its single interaction with the organ or system under examination. Physical processes such as electron or proton density assessment or resonance, edge identification, electrical or ultrasonic impedence, do not pertain to the image generation process in nuclear medicine, and if so, only in a rather secondary manner. The nuclear medicine imaging study is primarily a study of the chemical nature, distribution and interaction of the tracer/radiopharmaceutical utilised with the cellular system which requires investigation: the thyroid cells with sodium iodide, the recticular endothelial cells with colloidal particles, the adrenal medulla cells with metaiodobenzylguanidine, and so on. In the two most recent areas of nuclear medicine expansion, oncology (with labelled monoclonal antibodies) and neurology and psychiatry (with a whole new series of lipid soluble radiopharmaceuticals), specific cell systems can also be targeted and hence imaged and investigated. The study of structure as masterly performed by Virchow and all his successors over more than a century, is now definitely the prerogative of such imaging systems which excel with spatial and contrast resolution (x-ray computed transmission tomography, nuclear magnetic resonance imaging, diagnostic ultrasound). However the investigation of function and metabolism (as performed by Claude Bernard, Georg von Hevesy, and so many others), has clearly passed from the laboratory animal protocol and experiment to the direct investigation in man, this being the achievement of the radionuclide tracer methodology. In this article, we review present interest and developments in that part of nuclear medicine activity which is aimed at the study of the neurological or psychiatric patient.

Electrocardiogram gated single photon emission computed tomography of the intracardiac blood pools is a recent development that involves the acquisition of images in multiple projections after in vivo erythrocyte labelling with technetium-99m and reconstruction of these images into tomographic sections in any desired plane. The technique was used in 25 subjects to measure left ventricular volume, by summing the areas of the ventricle in each of the tomographic sections, and the results compared with those using a counts based (non-geometric) technique from planar radionuclide ventriculography. Endocardium was defined with the aid of a contour at 43% of maximum left ventricular counts, and this contour was validated for a left ventricular phantom. Correlation between tomographic and counts based left ventricular volume was close. Similarly, ejection fraction correlated well. The technique is therefore an accurate method for determining left ventricular volume and ejection fraction, avoiding the assumptions about shape made by other geometric methods.

Eighteen patients with a history of previous anterior myocardial infarction and suspected left ventricular aneurysms were studied both by contrast left ventriculography and by first pass radionuclide ventriculography using Technetium99m and a computerised multicrystal gamma camera. The radionuclide study successfully identified all 14 patients with aneurysms and all 4 with diffusely hypo-kinetic ventricles. Ejection fraction calculated from the change in radioactive counts in the left ventricle correlated well with that calculated from the area-length method from the contrast angiogram (r = 0.83). Ventricular volumes calculated from the area-length formula for both contrast and radionuclide angiograms correlated closely (r = 0.85 and r = 0.89 for end-systolic and end-diastolic volumes, respectively). In the patients with aneurysms, there was a close correlation between the extent of akinesis, as assessed by the two methods (r = 0.94). The ability of the radionuclide ventriculogram to provide accurate information on global and segmental ventricular function, and to differentiate between segmental and diffuse ventricular dysfunction, enables the method to act as a screening procedure in the investigation of patients with suspected left ventricular aneurysms.

99mTc-labelled phosphates (PyP, IDP and MDP) were compared for their usefulness for the diagnosis of myocardial infarction. The results indicated the superiority of 99mTc-labelled imidodiphosphonate over the other 99mTc-labelled phosphates. At the same time, two mobile gamma cameras were compared with respect to their instrumental characteristics and clinical versalitity and their advantages and disadvantages are reported.

The first clinical data is given on 99Tcm-hexamethylpropyleneamine oxime (HM-PAO) in normal subjects and patients with established stroke. Regional cerebral blood flow maps (rCBF) have been recorded and displayed in tomographic mode with this new radiopharmaceutical. Good images were obtained, comparable to those achieved with 123I-isopropylamphetamine (IMP).

ECG-gated single-photon emission-computed tomography of the intracardiac blood pool is a new technique that has not previously been widely applied. It involves the acquisition of ECG-gated images of the intracardiac blood pools labelled with sodium pertechnetate Tc 99m in 32 projections around the left-anterior hemithorax using a rotating gamma camera. From these images, tomographic sections are reconstructed orthogonal to the long axis of the left ventricle. The heart is therefore imaged three dimensionally, and more extensive information is obtained than in planar radionuclide ventriculography where imaging is usually restricted to only a single projection. Both structure and function can be studied, and the left-ventricular volume and ejection fraction, and wall motion are obtained. Of 50 patients studied, 7 cases are illustrated in order to show normal findings, examples of wall motion that were not shown by planar-contrast and radionuclide ventriculography, examples of the localisation of ventricular hypertrophy, and a comparison between blood-pool and 201TI myocardial tomography.

The cerebral distribution of a new class of 123I radiopharmaceuticals was determined by emission tomography after the isotope had been injected intravenously into 20 patients with a variety of neurological disorders. Regional cerebral blood flow images of diagnostic quality were obtained in all cases. Early and late ischaemic stroke showed up as areas of impaired perfusion, and gliomas and secondary deposits as areas of increased or reduced blood flow. A hyperaemic focus was clearly seen in an epileptic patient in whom other imaging techniques, including CT scanning and electroencephalography, had been uninformative. This new technique promises to be an extremely useful addition to the range of radioisotope brain scanning methods.

Emission computed tomography (emission CT) and conventional planar gamma-camera imaging of the liver were compared in 242 patients with suspected metastatic spread to liver. Concordant data were obtained in 171 patients (71%). Single large lesions, multiple small lesions, and diffuse disease were accurately defined with this new radionuclide tomographic technique. The smallest lesion detected by emission CT was 8 mm. Emission CT, planar gamma-camera imaging, and transmission (x-ray) CT were compared in 107 patients. All three methods gave identical results in 76 patients (71%). Assessed against other criteria, such as histological findings and follow-up data, emission CT yielded the highest range of accuracy (92-96%), while transmission CT and planar gamma-camera imaging had similar but lower accuracies (78-81%). Emission CT had a false-positive rate of 2.8% and a false-negative rate of less than 1%. Thus emission CT is highly sensitive in detecting space-occupying disease in the liver.

Thirty-three subjects were studied by first pass radionuclide angiography. The extrapolated monoexponential tracer washout slopes from septal, lateral, and apical segments of the left ventricle were measured. In 13 subjects with normal left ventricles, as assessed by ejection fraction estimation and phase analysis, there was no difference between septal and lateral segments but, in each case, apical washout was significantly prolonged. In 20 subjects with abnormal ventricles washouts were, in general, slower than those of the normal ventricles. Apical washout was still the slowest but the difference between base and apex was less pronounced. In contrast to the normal ventricles, differences appeared between septal and lateral segments. The left ventricle is a poor mixing chamber. Pools of relative stasis exist at the apex of both normal and abnormal ventricles and within the body of the chamber in the latter.

Fifty-two subjects with suspected coronary artery disease were studied by first pass radionuclide angiocardiography using a single crystal gamma camera. Phase analysis, a new technique which can detect ventricular regions with abnormal emptying patterns, was applied to the resulting left ventricular radionuclide angiocardiograms. Eighteen turned out be normal and in these subjects the variation of phase values in each of eight ventricular segments was established. Thirty-four had coronary artery disease. By comparison with the normal subjects, 21 had at least one segment with an abnormally high phase value. Such high values were associated with low values of ejection fraction, as determined by a radionuclide technique, total occlusion of a major coronary artery and significant wall motion abnormalities on the radiographic ventriculogram. A comparison between phase analysis and wall motion on a regional basis disclosed progressively high phase values with increasing severity of wall motion abnormality. Particularly high values were found in association with ventricular aneurysm. Phase analysis of first pass radionuclide angiocardiograms is a valid method for the detection of regional abnormalities of ventricular contraction in coronary artery disease.