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.

The PETRRA positron camera: design, characterization and results of a physical evaluation.

The PETRRA positron camera is a large-area (600 mm x 400 mm sensitive area) prototype system that has been developed through a collaboration between the Rutherford Appleton Laboratory and the Institute of Cancer Research/Royal Marsden Hospital. The camera uses novel technology involving the coupling of 10 mm thick barium fluoride scintillating crystals to multi-wire proportional chambers filled with a photosensitive gas. The performance of the camera is reported here and shows that the present system has a 3D spatial resolution of approximately 7.5 mm full-width-half-maximum (FWHM), a timing resolution of approximately 3.5 ns (FWHM), a total coincidence count-rate performance of at least 80-90 kcps and a randoms-corrected sensitivity of approximately 8-10 kcps kBq(-1) ml. For an average concentration of 3 kBq ml(-1) as expected in a patient it is shown that, for the present prototype, approximately 20% of the data would be true events. The count-rate performance is presently limited by the obsolete off-camera read-out electronics and computer system and the sensitivity by the use of thin (10 mm thick) crystals. The prototype camera has limited scatter rejection and no intrinsic shielding and is, therefore, susceptible to high levels of scatter and out-of-field activity when imaging patients. All these factors are being addressed to improve the performance of the camera. The large axial field-of-view of 400 mm makes the camera ideally suited to whole-body PET imaging. We present examples of preliminary clinical images taken with the prototype camera. Overall, the results show the potential for this alternative technology justifying further development.

Statistical pixelwise inference models for planar data analysis: an application to gamma-camera uniformity monitoring.

In this paper two tests based on statistical models are presented and used to assess, quantify and provide positional information of the existence of bias and/or variations between planar images acquired at different times but under similar conditions. In the first test a linear regression model is fitted to the data in a pixelwise fashion, using three mathematical operators. In the second test a comparison using z-scoring is used based on the assumption that Poisson statistics are valid. For both tests the underlying assumptions are as simple and few as possible. The results are presented as parametric maps of either the three operators or the z-score. The z-score maps can then be thresholded to show the parts of the images which demonstrate change. Three different thresholding methods (naive, adaptive and multiple) are presented: together they cover almost all the needs for separating the signal from the background in the z-score maps. Where the expected size of the signal is known or can be estimated, a spatial correction technique (referred to as the reef correction) can be applied. These tests were applied to flood images used for the quality control of gamma camera uniformity. Simulated data were used to check the validity of the methods. Real data were acquired from four different cameras from two different institutions using a variety of acquisition parameters. The regression model found the bias in all five simulated cases and it also found patterns of unstable regions in real data where visual inspection of the flood images did not show any problems. In comparison the z-map revealed the differences in the simulated images from as low as 1.8 standard deviations from the mean, corresponding to a differential uniformity of 2.2% over the central field of view. In all cases studied, the reef correction increased significantly the sensitivity of the method and in most cases the specificity as well. The two proposed tests can be used either separately or in combination and are capable of showing trends and/or the magnitude of difference between images acquired under similar conditions with high positional and statistical precision. In addition to gamma camera quality control, they could be applied to any pair (or set) of registered planar images to detect subtle changes, e.g. a set of scintigrams or conventional radiographs of a patient before, during and after treatment.

Scaling images using their background ratio. An application in statistical comparisons of images.

Comparison of two medical images often requires image scaling as a pre-processing step. This is usually done with the scaling-to-the-mean or scaling-to-the-maximum techniques which, under certain circumstances, in quantitative applications may contribute a significant amount of bias. In this paper, we present a simple scaling method which assumes only that the most predominant values in the corresponding images belong to their background structure. The ratio of the two images to be compared is calculated and its frequency histogram is plotted. The scaling factor is given by the position of the peak in this histogram which belongs to the background structure. The method was tested against the traditional scaling-to-the-mean technique on simulated planar gamma-camera images which were compared using pixelwise statistical parametric tests. Both sensitivity and specificity for each condition were measured over a range of different contrasts and sizes of inhomogeneity for the two scaling techniques. The new method was found to preserve sensitivity in all cases while the traditional technique resulted in significant degradation of sensitivity in certain cases.

Continuous angiotensin II infusion increases tumour: normal blood flow ratio in colo-rectal liver metastases.

Insufficient blood flow within colo-rectal hepatic metastases is a factor which may limit drug delivery to, and thus the response of, these tumours to regional chemotherapy. Loco-regional flow may be manipulated pharmacologically to enhance the tumour blood flow relative to that of the normal liver. However, as yet, only transient effects have been studied. Patients receiving regional chemotherapy for unresectable hepatic disease were given a 45 min regional infusion of the vasoconstrictor Angiotensin II. Intrahepatic blood flow distribution was assessed serially by Positron Emission Tomography (PET) imaging together with the trapping tracer copper(II) pyruvaldehyde bis(N-4-methylthiosemicarbazone) (Cu-PTSM) labelled using copper-62. Eleven lesions in nine patients were studied, with no adverse effects. Prior to Angiotensin II administration tumour blood flow was generally found to be greater than that of liver (10/11 lesions; 8/9 patients; median TNR 1.3, iqr 0.9-2.5). A significant increase in relative flow to tumour was seen in response to 10 min Angiotensin II infusion in most cases (7/11 lesions; 7/9 patients; median TNR 2.1, iqr 1.4-4.1; P = 0.008), which appeared to be sustained throughout the 45 min infusion period (median TNR 1.85, iqr 1.3-3.8; P = 0.03). These effects were accompanied by transient elevation of mean arterial pressure, but no change in pulse rate. These observations suggest that prolonged regional vasoconstrictor administration could prove useful in the management of unresectable colo-rectal hepatic metastases, and that further development of vascular manipulation to enhance tumour targeting and drug delivery is warranted.

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.

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

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.

Automated CT marker segmentation for image registration in radionuclide therapy.

In this paper a novel, automated CT marker segmentation technique for image registration is described. The technique, which is based on analysing each CT slice contour individually, treats the cross sections of the external markers as protrusions of the slice contour. Knowledge-based criteria, using the shape and dimensions of the markers, are defined to enable marker identification and segmentation. Following segmentation, the three-dimensional (3D) markers' centroids are localized using an intensity-weighted algorithm. Finally, image registration is performed using a least-squares fit algorithm. The technique was applied to both simulated and patient studies. The patients were undergoing 131I-mIBG radionuclide therapy with each study comprising several 99mTc single photon emission computed tomography (SPECT) scans and one CT marker scan. The mean residual 3D registration errors (+/- 1 SD) computed for the simulated and patient studies were 1.8 +/- 0.3 mm and 4.3 +/- 0.5 mm respectively.

Effects of cellular repair and proliferation on targeted radionuclide therapy: a modelling study.

A previous targeted radionuclide therapy modelling study has been extended to include the radiobiological effects of cellular repair and proliferation. Dose distributions have been converted into biologically effective dose (BED) distributions using a previously published formulation. With suitable estimated parameters, corrected tumour control probability (TCP) values were derived. The dependence of BED on the physical half-life of the radionuclide was also modelled. Results indicate that the TCP is greater when a shorter physical half-life is employed.

Intercomparison of four reconstruction techniques for positron volume imaging with rotating planar detectors.

Four reconstruction techniques for positron volume imaging have been evaluated for scanners based on rotating planar detectors using measured and simulated data. The four techniques compared are backproject then filter (BPF), the 3D reprojection (3D RP) method for 3D filtered backprojection (FBP), Fourier rebinning (FORE) in conjunction with 2D FBP (FORE + 2D FBP) and 3D ordered subsets expectation maximization (3D OSEM). The comparison was based on image resolution and on the trade-off between contrast and noise. In general FORE + 2D FBP offered a better contrast-noise trade-off than 3D RP, whilst 3D RP offered a better trade-off than BPF. Unlike 3D RP, FORE + 2D FBP did not suffer any contrast degradation effect at the edges of the axial field of view, but was unable to take as much advantage from high-accuracy data as the other methods. 3D OSEM gave the best contrast at the expense of greater image noise. BPF, which demonstrated generally inferior contrast-noise behaviour due to use of only a subset of the data, gave more consistent spatial resolution over the field of view than the projection-data based methods, and was best at taking full advantage of high-accuracy data.

Fast accurate iterative reconstruction for low-statistics positron volume imaging.

A fast accurate iterative reconstruction (FAIR) method suitable for low-statistics positron volume imaging has been developed. The method, based on the expectation maximization-maximum likelihood (EM-ML) technique, operates on list-mode data rather than histogrammed projection data and can, in just one pass through the data, generate images with the same characteristics as several ML iterations. Use of list-mode data preserves maximum sampling accuracy and implicitly ignores lines of response (LORs) in which no counts were recorded. The method is particularly suited to systems where sampling accuracy can be lost by histogramming events into coarse LOR bins, and also to sparse data situations such as fast whole-body and dynamic imaging where sampling accuracy may be compromised by storage requirements and where reconstruction time can be wasted by including LORs with no counts. The technique can be accelerated by operating on subsets of list-mode data which also allows scope for simultaneous data acquisition and iterative reconstruction. The method is compared with a standard implementation of the EM-ML technique and is shown to offer improved resolution, contrast and noise properties as a direct result of using improved spatial sampling, limited only by hardware specifications.

Thyroid volume measurement in thyrotoxic patients: comparison between ultrasonography and iodine-124 positron emission tomography.

The aim of this paper was to compare ultrasound (US) assessment of thyroid volume with that obtained by positron emission tomography (PET), in patients scheduled for adaptive radioiodine therapy, in which 50 Gy was prescribed to the functional PET volume. Firstly a pilot study was performed to ascertain the optimum method for US assessment of thyroid volume. Then 17 comparative measurements of thyroid volume by US and PET were made on 15 patients (two male and thirteen female, ages 28-73 years) with suspected Graves' disease. This comparison showed that in normal sized and enlarged thyroid glands (n=13), the ratio of functional PET to anatomical US volume was approximately 2:3. However, using the same ellipsoid model, PET and US assessment of anatomical volume agreed within the measurement errors. Owing to the presence of nodules and non-uniform distribution of radioiodine, the functional PET volume and anatomical US volume are often not equivalent. If high-resolution emission tomography (e.g. PET) is unavailable, the comparative data presented in this paper could be used to derive the functional volume from the US volume for calculating functional thyroid dose in hyperthyroid patients undergoing radioiodine therapy.

Radiation dosimetry for 131I-mIBG 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 Children's 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.

A prototype rotating slat collimator for single photon emission computed tomography.

A collimator consisting of a series of highly attenuating parallel slats has been constructed and used in conjunction with a gamma-camera to approximately measure planar projections of a given radionuclide distribution. The enlarged solid angle of acceptance afforded by the slat collimator gave rise to an increased geometric efficiency of between 12 and 28 times that observed with a low-energy high-resolution (LEHR) parallel-hole collimator. When the slats rotated over the face of the detector and the camera gantry turned about the object, sufficient projections were acquired to reconstruct a three-dimensional (3-D) image using the inversion of the 3-D radon transform. The noise behavior of an algorithm for implementing this inversion was studied analytically and the resulting relationship has been verified by computer simulation. The substantially improved geometric efficiency of the slat collimator translated to improvements in reconstructed signal-to-noise ratio (SNR) by, at best, up to a factor of 2.0 with respect to standard parallel-hole collimation. The spatial resolution achieved with the slat collimator was comparable to that obtained with a LEHR collimator and no significant differences were observed in terms of scatter response. Accurate image quantification was hindered by the spatially variant response of the slat collimator.

Absolute 99Tcm-DMSA renal uptake in children: optimum time to scan.

Absolute renal uptake was measured at 2, 4 and 6 h in 27 patients in order to determine a more convenient time for uptake compared with the 6-h measurement proposed by other authors. Measurements made at 2 and 4 h would need to be increased by 20 and 6%, respectively, to convert to the value at 6 h. Measurements at 4 h are a reasonable compromise to achieve a high-count/low-background image in a reasonable time and to obtain a good estimate of the predicted 6 h uptake at a single scanning session. The percent renal uptake at 6 h, U(6), can be derived from the percent uptake measured at t hours after injection, U(t), using the following formula: U(6) = U(t) x CF(t), where CF(t) = 1.0 + 0.03 (6 - t) for 4 < or = t < or = 6.

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 and 18FDG. Avid 18FDG 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 of 18FDG tumour to normal tissue ratios from pre-treatment to on-treatment scans was predictive of response (n = 3). No significant reduction in 18FDG uptake was seen in patients not responding to therapy (n = 2). These results suggest a role for 18FDG PET in the detection and management of metastatic testicular germ cell tumours.

The experimental evaluation of a prototype rotating slat collimator for planar gamma camera imaging.

A collimator consisting of a series of parallel slats has been constructed and used in conjunction with a conventional gamma camera to collect one-dimensional projections of the radioisotope distribution being imaged. With the camera remaining stationary, the collimator was made to rotate continuously over the face of the detector and the projections acquired were used to reconstruct a planar image by the theory of computed tomography. The propagation of noise on image reconstruction was largely offset by the increased geometric efficiency that resulted from the enlarged solid angle of acceptance afforded by the slat collimator. For a uniform disc of activity the signal to noise ratio (SNR) at a point in an image reconstructed by convolution and backprojection is shown to be given by [formula:see text] and Q1(xi) is the one-dimensional filter function in Fourier space. Improved noise behaviour was observed for images acquired with the slat collimator compared to those acquired with a low-energy high-resolution (LEHR) collimator for small distributions of activity. Spatial resolution with the slat collimator was approximately equal to that obtained with an LEHR collimator and improved contrast was observed in images of small hot regions.

Blood flow measurement in extremity soft tissue sarcoma with technetium-99m hexamethyl-propyleneamineoxime and single photon emission computed tomography.

Blood flow measurements were made in 28 patients with soft tissue sarcoma of the extremities to investigate the prognostic significance of tumour vascularity. Four patients with benign tumours also underwent blood flow measurement. Mean and maximum tumour blood flow was calculated from technetium-99m hexamethyl-propyleneamineoxime uptake measured using single photon emission computed tomography (SPECT), tumour volume measured from SPECT transaxial image reconstructions and cardiac output assessed with Doppler ultrasonography. Twenty-seven malignant lesions and one benign tumour showed increased uptake of isotope relative to surrounding tissues. Mean sarcoma blood flow varied between 1 and 33 ml per 100 ml tumour per min, and maximum flow between 5 and 57 ml per 100 ml per min. Fourteen patients developed progressive disease during the first year of follow-up. Eight of 11 patients with a high isotope uptake ratio, eight of 12 with a high mean blood flow and eight of 14 with a high maximum blood flow relative to the respective medians for the series showed disease progression.