Maggie A Flower

Imaging metastatic testicular germ cell tumours with 18FDG positron emission tomography: prospects for detection and management

The aim of this study was to investigate the role of positron emission tomography (PET) with [18F]fluoro-2-deoxyglucose (18FDG) in metastatic testicular germ cell tumours. Twenty-one patients with stage II–IV testicular germ cell tumours were imaged by PET with a multiwire proportional chamber PET system and18FDG. Avid18FDG uptake was seen in metastatic disease from primary seminoma and malignant teratoma. Normal tissue uptake was seen in differentiated teratoma or necrotic, fibrotic tissue.18FDG standard uptake values and tumour to normal tissue ratios were 6.0±1.4 and 1.7±0.4 (mean ± 1SD), respectively, for malignant tissue. Reduction of18FDG tumour to normal tissue ratios from pre-treatment to on-treatment scans was predictive of response (n=3). No significant reduction in18FDG uptake was seen in patients not responding to therapy (n=2). These results suggest a role for18FDG PET in the detection and management of metastatic testicular germ cell tumours.

RMDP: a dedicated package for 131I SPECT quantification, registration and patient-specific dosimetry.

The limitations of traditional targeted radionuclide therapy (TRT) dosimetry can be overcome by using voxel-based techniques. All dosimetry techniques are reliant on a sequence of quantitative emission and transmission data. The use of (131)I, for example, with NaI or mIBG, presents additional quantification challenges beyond those encountered in low-energy NM diagnostic imaging, including dead-time correction and additional photon scatter and penetration in the camera head. The Royal Marsden Dosimetry Package (RMDP) offers a complete package for the accurate processing and analysis of raw emission and transmission patient data. Quantitative SPECT reconstruction is possible using either FBP or OS-EM algorithms. Manual, marker- or voxel-based registration can be used to register images from different modalities and the sequence of SPECT studies required for 3-D dosimetry calculations. The 3-D patient-specific dosimetry routines, using either a beta-kernel or voxel S-factor, are included. Phase-fitting each voxels activity series enables more robust maps to be generated in the presence of imaging noise, such as is encountered during late, low-count scans or when there is significant redistribution within the VOI between scans. Error analysis can be applied to each generated dose-map. Patients receiving (131)I-mIBG, (131)I-NaI, and (186)Re-HEDP therapies have been analyzed using RMDP. A Monte-Carlo package, developed specifically to address the problems of (131)I quantification by including full photon interactions in a hexagonal-hole collimator and the gamma camera crystal, has been included in the dosimetry package. It is hoped that the addition of this code will lead to improved (131)I image quantification and will contribute towards more accurate 3-D dosimetry.

62Cu-PTSM and PET used for the assessment of angiotensin II-induced blood flow changes in patients with colorectal liver metastases

Abstract. The aim of this study was to establish a quantitative positron emission tomography (PET) method for investigating angiotensin II (AII)-induced changes in blood flow distribution in the liver. This was in order to evaluate the role of vascular manipulation applied to locoregional chemotherapy treatment in patients with colorectal liver metastases. The tracer selected was copper-62 (II) pyruvaldehyde bis-(N4-methyl)thiosemicarbazone (62Cu-PTSM), which exhibits high first-pass extraction and tissue retention following intra-arterial administration. The short half-life of the tracer and its availability from a 62Zn/62Cu generator enabled short-interval repeat PET scans on patients in a single imaging session. Distribution of tracer within the liver was imaged in a single view using a PET camera with rotating large-area detectors. By optimisation of the acquisition protocol, it was possible to acquire sufficient data to produce good-quality images and to quantify tracer uptake with an accuracy of ≤10%. Reproducibility of the imaging method was assessed in a single patient in whom three consecutive 62Cu-PTSM PET scans were obtained, and in whom no vascular manipulation was performed. Sets of scans (before, during and immediately after a 45-min AII infusion) were obtained in nine patients to assess blood flow changes associated with prolonged vascular manipulation. Significant individual responses, varying in both the magnitude and the duration of flow change, were observed in the majority of cases (7/11 lesions; 7/9 patients). These findings illustrate the potential of 62Cu-PTSM and PET for pharmacological studies. The wide range of individual patient responses to AII infusion suggests that PET blood flow assessment would be of value for selecting patients in whom this procedure may be effective.

Estimation and implications of random errors in whole-body dosimetry for targeted radionuclide therapy

For targeted radionuclide therapy, the level of activity to be administered is often determined from whole-body dosimetry performed on a pre-therapy tracer study. The largest potential source of error in this method is due to inconsistent or inaccurate activity retention measurements. The main aim of this study was to develop a simple method to quantify the uncertainty in the absorbed dose due to these inaccuracies. A secondary aim was to assess the effect of error propagation from the results of the tracer study to predictive absorbed dose estimates for the therapy as a result of using different radionuclides for each. Standard error analysis was applied to the MIRD schema for absorbed dose calculations. An equation was derived to describe the uncertainty in the absorbed dose estimate due solely to random errors in activity-time data, requiring only these data as input. Two illustrative examples are given. It is also shown that any errors present in the dosimetry calculations following the tracer study will propagate to errors in predictions made for the therapy study according to the ratio of the respective effective half-lives. If the therapy isotope has a much longer physical half-life than the tracer isotope (as is the case, for example, when using 123I as a tracer for 131I therapy) the propagation of errors can be significant. The equations derived provide a simple means to estimate two potentially large sources of error in whole-body absorbed dose calculations.

Absorbed dose ratios for repeated therapy of neuroblastoma with I-131 mIBG.

Patients undergoing targeted radionuclide therapy (TRT) may receive a series of two or more treatment administrations at varying intervals. However, the level of activity administered and the frequency of administration can vary widely from centre to centre for the same therapy. Tumour dosimetry is seldom employed to determine the optimum treatment plan mainly due to the potential inaccuracies of image quantification. In this work 3D dose distributions obtained from repeated therapies have been registered to enable the dose ratios to be determined. These ratios are independent of errors in image quantification and, since the same target volume can be transferred from one distribution to the next, independent of inconsistencies in outlining these volumes. These techniques have initially been applied to ten sets of I-131 mIBG therapy scan data from five patients, each undergoing two therapies. It was found that where a similar level of activity was administered for the second therapy, a similar tumour dose was delivered, and in two cases where a higher level of activity was administered for the second treatment, a correspondingly higher absorbed dose was delivered. This justifies an approach of administering activities based on individual patient kinetics rather than administering standard activities to all patients.

An automated technique for SPECT marker-based image registration in radionuclide therapy.

An automated technique for marker-based image registration in radionuclide therapy is described. This technique is based on localization of the centroids of external markers and on establishing correspondence between the individual markers of the two studies to be registered. Localization of the centroids of markers relies on segmenting the markers using iterative thresholding. Thresholding is locally adaptive in order to account for study-dependent conditions (e.g. crossover between adjacent markers and markers with varying radioactive concentrations). Following marker segmentation, the centroids of the markers are computed based on an intensity-weighted method. Finally, prior to the least-squares fit registration, the markers of the two sets are matched to achieve one-to-one correspondence. The technique was applied to both simulated and patient studies resulting in mean residual three-dimensional registration errors (+/- 1SD) of 1.7 +/- 0.1 mm and 3.5 +/- 0.3 mm respectively. The technique was compared with a semi-automated approach and no significant difference was found between the mean residual three-dimensional registration errors (t = 0.281. p = 0.8). This automated marker-based image registration technique provides robust and accurate registration. Although it was developed as part of a programme to generate three-dimensional dose distributions for radionuclide therapy, it could be useful for other clinical applications.

Radiation dosimetry for therapy of neuroblastoma

This paper describes the methodology which can be used to determine whole-body, red marrow, blood, bladder, liver, and tumour doses delivered during 131I-mIBG therapy of neuroblastoma. The methodology is based on the Physics Protocol used in a multi-centre study undertaken by the United Kingdom Childrens Cancer Study Group (UKCCSG). In this study, the estimates of the doses delivered, using 2.4-12.1 GBq 131I-mIBG, were in the following ranges: whole body, 0.14-0.65 mGy MBq-1; red marrow, 0.17-0.63 mGy MBq-1; blood, 0.04-0.17 mGy MBq-1; bladder, 2.2-5.3 mGy MBq-1; liver, 0.3-1.9 mGy MBq-1; and tumour, 0.2-16.6 mGy MBq-1.

Estimation of random coincidences from the prompt PET data

Currently the most widely implemented method for estimating the random events present in PET prompt data is the delayed-coincidence-channel method. The delayed randoms are usually subtracted from the prompts. However, the acquired randoms suffer from poor statistics and post processing variance reduction techniques are often used prior to the subtraction. We have developed a new method of estimating the randoms from the PET prompt data acquired in list or sinogram mode (LM or SM respectively). In both cases random events were obtained by swapping the detection coordinates of prompt events. The statistics of the estimated randoms could virtually be unlimited. For LM data the process was straightforward and easily implemented, but for SM data a multi-step algorithm was developed.

A novel four-dimensional image registration method for radionuclide therapy dosimetry

A novel method for registering sequential SPECT scans (4DRRT) is described, whereby all sequential scans acquired in the course of a therapy or a pre-therapy tracer study may be registered in one pass. The method assumes that a monoexponential decay function can be fitted to the series of sequential SPECT scans. Multiple volumes, presenting with different decay rates, are fitted with different mono-exponential functions. The MSSE (mean sum of squared errors in the least-squares fit algorithm), over the volume used for registration, is the cost function minimized at registration. Simulated data were used to assess the effect of thresholding, smoothing, noise and the multi-exponential nature of the four-dimensional (4D) SPECT studies on the performance of 4DRRT, resulting in three-dimensional (3D) residual registration errors <3.5 mm. The 4DRRT method was then compared to the following 3D registration methods: the correlation coefficient, the sum of absolute differences, the variance of image ratios and the mutual information. The comparisons, using both simulated and clinical data, were based on the standard deviation of the effective decay time distribution, generated from the registered 4D dataset, and showed that image registration using 4DRRT is simpler and more robust compared to the 3D techniques, especially when multiple tumour sites with different decay rates are present.

Image intensity normalisation by maximising the Siddon line integral in the joint intensity distribution space

This paper presents a novel data-driven method for image intensity normalisation, which is a prerequisite step for any kind of image comparison. The method involves a novel application of the Siddon algorithm that was developed initially for fast reconstruction of tomographic images and is based on a linear normalisation model with either one or two parameters. The latter are estimated by maximising the line integral, computed using the Siddon algorithm, in the 2D joint intensity distribution space of image pairs. The proposed normalisation method, referred to as Siddon Line Integral Maximisation (SLIM), was compared with three other methodologies, namely background ratio (BAR) scaling, linear fitting and proportional scaling, using a large number of synthesised datasets. SLIM was also compared with BAR normalisation when applied to phantom data and two clinical examples. The new method was found to be more accurate and less biased than its counterparts for the range of characteristics selected for the synthesised data. These findings were in agreement with the results from the analysis of the experimental and clinical data.