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Radionuclide angiography with technetium-99m ethyl cysteinate dimer (ECD) allows non-invasive estimation of absolute cerebral blood flow (CBF), either by graphical Patlak-Gjedde analysis (PGA) or by spectral analysis (SA). Other methods estimate CBF by means of single-point arterial or venous sampling. The aim of this study was to evaluate radionuclide scanning and single-point venous sampling as potential clinical non- to minimally invasive methods for CBF determination in a large set of carefully screened healthy volunteers over the adult age range. Eighty-three carefully screened healthy volunteers (20-81 years, 43 males, 40 females) underwent planar radionuclide angiography with 925 MBq 99mTc-ECD. After correction for camera dead-time loss, hemispheric CBF was calculated from brain perfusion indices (BPI): BPI(G) for PGA and BPI(S) for SA. Of the volunteers, 49 also underwent venous sampling 6 min post injection, from which the lipophilic octanol extraction fraction and hemispheric brain fractionation index (BFI) were determined. All datasets were correlated and evaluated as a function of age and gender. Intrasubject variability for the BPI measurements was assessed in 11 volunteers by repeat study within 2 weeks of the first acquisition. Graphical and spectral analysis BPIs were strongly correlated (R=0.846, P<0.00001). This correlation coefficient increased to R=0.903 for the 74 cases in which graphical analysis was not hampered by temporal tracer retention in cervicobrachial venous valves. The BFI was weakly correlated to both BPI indices (BPI(G): R=0.34, P=0.02; BPI(S): R=0.31, P=0.04). The right hemisphere showed significant asymmetry for BPI(S) (AI=2.7%+/-4.3%, P<0.001), in correspondence with previous 99mTc-ECD data. BPI(G), BPI(S) and BFI were all inversely related to age, with an increased gradient after the age of 55 years, while there was no significant gender difference. The ratio of BPI(G) to BIP(S), which is a measure of the cerebral extraction fraction for 99mTc-ECD, was not dependent on age. Intersubject variability was 15.5% for both radionuclide scanning-based methods and 18.2% for venous sampling, and in all cases was independent of age. A much lower intrasubject variability was observed for BPI(S) (7.2%) than for BPI(G) (12.6%). This study provides reference values for normal perfusion indices assessed by graphical and spectral analysis. The results also indicate that spectral analysis allows the most reproducible estimate of hemispheric perfusion by means of an operator-independent and objective approach. Whereas accurate calibration of normal BPI(S) values to hemispheric CBF with established methods needs to be performed, non-invasive calculation of regional absolute CBF using 99mTc-ECD is possible by application of a linearisation algorithm.

A stereotactic, normal perfusion database is imperative for optimal clinical brain single-photon emission tomography (SPET). However, interdepartmental use of normal data necessitates accurate transferability of these data sets. The aim of this study was to investigate transfer of three normal perfusion databases obtained in the same large population of healthy volunteers who underwent sequential scanning using multihead gamma cameras with different resolution. Eighty-nine healthy adults (46 females, 43 males; aged 20-81 years) were thoroughly screened by history, biochemistry, physical and full neurological examination, neuropsychological testing and magnetic resonance imaging. After injection of 925 MBq technetium-99m labelled ethyl cysteinate dimer (ECD) under standard conditions, 101 scans were acquired from all subjects (12 repeat studies) on a triple-head Toshiba GCA-9300A (measured average FWHM 8.1 mm). Ninety-one sequential scans were performed on a dual-head Elscint Helix camera (FWHM 9.6 mm) and 22 subjects also underwent imaging on a triple-head Prism 3000 (FWHM 9.6 mm). Images were transferred to the same processing platform and reconstructed by filtered back-projection with the same Butterworth filter (order 8, cut-off 0.9 cycles/cm) and uniform Sorensen attenuation correction (mu = 0.09). After automated rigid intrasubject registration, all subjects were automatically reoriented to a stereotactic template by a nine-parameter affine transformation. The databases were analysed using 35 predefined volumes of interest (VOIs) with normalisation on total VOI counts. For comparison, the high-resolution data were smoothed with a 3D Gaussian kernel to achieve more similar spatial resolution. Hoffman phantom measurements were conducted on all cameras. Partial volume effects after smoothing varied between -6.5% and 10%, depending on VOI size. Between-camera reproducibility was 2.5% and 2.7% for the Toshiba camera versus the Helix and the Prism database, respectively. The highest reduction in between-camera variability was achieved by resolution adjustment in combination with linear washout correction and a Hoffman phantom-based correction. In conclusion, transfer of normal perfusion data between multihead gamma cameras can be accurately achieved, thereby enabling widespread interdepartmental use, which is likely to have a positive impact on the diagnostic capabilities of clinical brain perfusion SPET.

Iterative reconstruction algorithms produce accurate images without streak artifacts as in filtered backprojection. They allow improved incorporation of important corrections for image degrading effects, such as attenuation, scatter and depth-dependent resolution. Only some corrections, which are important for accurate reconstruction in positron emission tomography and single photon emission computed tomography, can be applied to the data before filtered backprojection. The main limitation for introducing iterative algorithms in nuclear medicine has been computation time, which is much longer for iterative techniques than for filtered backprojection. Modern algorithms make use of acceleration techniques to speed up the reconstruction. These acceleration techniques and the development in computer processors have introduced iterative reconstruction in daily nuclear medicine routine. We give an overview of the most important iterative techniques and discuss the different corrections that can be incorporated to improve the image quality.

This paper will review the recent advances and future developments in the field of coincidence imaging of positron emitters with a conventional Anger-type gamma camera. FDG imaging has shown high clinical importance in cardiology, neurology and especially oncology. Since access to full ring PET is mainly limited to university hospitals, there have been new developments allowing PET imaging on the standard Anger gamma camera. First the principles of coincidence imaging on a gamma camera will be reviewed. We will discuss the limitations of this technique, and the techniques used to partly overcome these limitations. The different configurations of the gamma camera operating in coincidence mode are pointed out. Different corrections for image degrading effects and reconstruction methods are evaluated in the final part.

Among the factors contributing to optimal image quality in single-photon emission computed tomography (SPECT), image filtering is an important, though mostly subjectively applied, image-processing parameter. We have aimed at giving an overview of current available SPECT filtering options. Current SPECT applications are discussed and practical guidelines to choose optimal filter parameters for a given situation are provided. It is shown that Hann and Butterworth filters allow accurate approximations to most filter types. The authors support the use of limited filter types in an attempt to standardise image-processing approaches, which may lead to better diagnostic compatibility and interpretation of interdepartmental results.

This overview takes a look at different correction techniques for Single Photon Emission Computed Tomography (SPECT). We discuss the influence of the detection system followed by the scatter and attenuation caused by the object of investigation. When possible we describe how the correction methods for the different physical effects can be incorporated in the reconstruction method, being either filtered backprojection or iterative reconstruction.

Due to the limited resolution of single-photon emission computed tomography (SPECT) imaging devices, tissue interfaces are not well defined in the reconstructed image, even though resolution recovery techniques may be used during reconstruction. Therefore, segmentation of a particular region and quantification of the tracer uptake in that region is critical due to spillover effects, when based on the SPECT image only. In this study, we present two methods for quantification of tracer uptake in a SPECT image, defined by a matched high resolution structural magnetic resonance image. We show preliminary results of both techniques, when applied for quantifying regional uptake in the different compartments of a phantom simulating the basal ganglia. These results indicate that the quantification method, which takes into account the blurring by the SPECT imaging device, promises to be perform better in the presence of background activity.

Unlabelled: Intra- or intersubject registration of anatomically poorly defined SPECT data, such as in neuroreceptor imaging, is important for longitudinal or group analysis. However, accurate registration is difficult with only emission CT (ECT) data. We investigated fully automated registration using transmission CT (TCT) data as an intermediary image set., Methods: The accuracy of TCT registration was compared to that of ECT registration for four types of data: gray-matter distribution (with [99mTc]ethylcysteinate dimer (ECD)), neocortical distribution (with [123I]R91150, a highly specific 5-HT2a receptor ligand), and striatal distribution of the D2-receptor ligand (with [123I]iodobenzamide (IBZM)) and the dopamine transporter ligand (with [123I]2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CIT)). In total, 10 datasets of the various study types were used, all collected on a Toshiba GCA9300 gamma camera with super-high-resolution fanbeam collimators and 3 x 370 MBq of 153Gd transmission sources (4-min sequential TCT scanning for receptor studies and 20-min simultaneous scanning for [99mTc]ECD studies). Per dataset, 15 random misalignments of 9 rigid-body parameters (translation, rotation, and anisotropic scaling) were conducted. All coregistrations were done twice, both to the subject's original scan and to a study-specific template. This was done manually by two independent experienced observers and with three automated voxel similarity algorithms: mutual information (M.I.), count difference (C.D.), and uniformity index (U.I.). As an outcome measure, the impact of misregistration on semiquantification for the various study types was established., Results: TCT matching allowed registration within 3.3 mm, 2.4 degrees, and 1.2% scaling (mean squared values for all directions) with an overall accuracy decrease in the following order: C.D. > M.I. > manual > U.I. For [99mTc]ECD and [123I]IBZM, TCT registration was as accurate as ECT registration, while it was far superior for the other receptor data types, especially for abnormal studies. The automated TCT registration accuracy corresponded to average quantification errors of 2.9% ([99mTc]ECD), 4.2% ([123I]BZM), 5.7% ([123I]R91150), and 6.1% ([123I]beta-CIT)., Conclusion: Fully automated registration through intermediary TCT images is clinically feasible, fast, and accurate. In addition to nonuniform attenuation correction, TCT scanning therefore allows coregistration for group comparisons of SPECT receptor data on a standardized or pixel-by-pixel basis.

Although non-uniform attenuation correction (NUAC) can supply more accurate absolute quantification, it is not entirely clear whether NUAC provides clear-cut benefits in the routine clinical practice of brain SPET imaging. The aim of this study was to compare the effect of NUAC versus uniform attenuation correction (UAC) on volume of interest (VOI)-based semi-quantification of a large age- and gender-stratified brain perfusion normal database. Eighty-nine healthy volunteers (46 females and 43 males, aged 20-81 years) underwent standardised high-resolution single-photon emission tomography (SPET) with 925 MBq 99mTc-ethyl cysteinate dimer (ECD) on a Toshiba GCA-9300A camera with 153Gd or 99mTc transmission CT scanning. Emission images were reconstructed by filtered back-projection and scatter corrected using the triple-energy window correction method. Both non-uniform Chang attenuation correction (one iteration) and uniform Sorenson correction (attenuation coefficient 0.09 cm(-1)) were applied. Images were automatically reoriented to a stereotactic template on which 35 predefined VOIs were defined for semi-quantification (normalisation on total VOI counts). Small but significant differences between relative VOI uptake values for NUAC versus UAC in the infratentorial region were found. VOI standard deviations were significantly smaller for UAC, 4.5% (range 2.6-7.5), than for NUAC, 5.0% (2.3-9.0) (P<0.01). Higher filter roll-off values of the transmission reconstruction filter increased noise in the emission images and altered estimated cortical attenuation coefficients as well as uptake values. In conclusion, semi-quantification based upon reconstruction with UAC results in very similar 99mTc-ECD uptake values in healthy volunteers to those obtained with NUAC, although values for the infratentorial region are slightly lower. NUAC produces a slight increase in inter-subject variability. Further study is necessary in various patient populations to establish the full clinical impact of NUAC in brain perfusion SPET.

Unlabelled: Nonuniform attenuation correction in brain SPECT can be done routinely by means of additional gamma transmission CT (TCT) measurements, using different commercially available line-source isotopes, 201Tl, 153Gd, and 99mTc are among the most commonly used isotopes, depending on practical and cost-effectiveness issues. We have measured additional radiation burden from static uncollimated brain SPECT transmission sources for these isotopes. The influence of the transmission isotope on brain quantification was also measured and compared with uniform attenuation correction for phantom and human data. Full iterative transmission and emission reconstruction were compared with filtered backprojection techniques., Methods: Rod sources with 201Tl, 153Gd, and 99mTc were used on a triple-head gamma camera. Dosimetry was performed using LiF TLD-100 pellets and an anthropomorphic RANDO phantom. Effective dose equivalents were calculated on the basis of measured and extrapolated absorbed doses. For brain activity measurements, a Hoffman phantom was used. Images were corrected for scatter (triple-energy window) and were reconstructed by Chang attenuation correction and filtered backprojection as well as full iterative reconstruction (ordered-subsets expectation maximization [OSEM]). To study the effect of inhomogeneous bone attenuation, realistic measurements were performed on 10 young, healthy volunteers with 153Gd TCT. After stereotactic image realignment, a volume-of-interest analysis normalized to total counts was performed., Results: Brain SPECT-TCT using 201Tl, 153Gd, and 99mTc produced total effective dose-rate equivalents of 50.3 +/- 11.2, 32.0 +/- 2.7, and 71.1 +/- 7.1 microSv/GBq x h, respectively, representing dose equivalents of 18.6, 11.9, and 26.3 microSv for a typical 20-min brain SPECT scan at maximal used source strength. Standardized quantification resulted in insignificant differences between the isotopes and methods (Chang versus OSEM) used for nonuniform correction. Iterative reconstruction enhanced image contrast and provided more accurate gray-to-white matter ratios. Between nonuniform and uniform attenuation with an optimized attenuation coefficient, slight central discrepancies were found for volunteer studies. Significantly lower intersubject variation was found for nonuniform corrected values in infratentorial and posterior brain regions., Conclusion: Brain transmission scanning using 201Tl, 153Gd, or 99mTc results in limited effective radiation dose equivalents compared with the typical radiation burden. Relative brain perfusion quantification is not significantly different for the various nonuniform TCT isotopes. Iterative reconstruction improves gray-to-white contrasts but has no significant influence on brain perfusion semiquantification. Nonuniform attenuation correction decreases intersubject variability in the posterior brain regions that were compared, which may lead to improved sensitivity toward clinical applications.

Aims: To investigate the importance of venous pooling and variation in venous tone during nitrate-stimulated tilt testing in patients., Methods: Ten patients with a history of vasovagal syncope underwent an upright tilt test after an injection of 99mTc-labelled albumin. A gamma camera was positioned at the level of the lower legs. The patients were tilted to 90 degrees for 30 min or until symptoms developed. In those subjects who did not show any symptoms before the end of the 30-min period, isosorbide dinitrate (ISDN) 5 mg was given sublingually and the test was prolonged for a maximum of 15 min., Results: Nine of 10 patients needed nitrate stimulation to develop symptoms, and one patient remained symptom free following ISDN administration. Measurement of radioactivity revealed no significant increase in calf volume after nitrate stimulation (the mean volume increase was 77% before ISDN stimulation and a further 0.9% afterwards)., Conclusions: The higher sensitivity for vasovagal syncope during upright tilt testing after administration of sublingual ISDN is not due to an increase in venous pooling in the lower extremities.

Aims: To evaluate the impact of second harmonic (SH) compared to fundamental mode (FM) imaging on the echocardiographic determination of ejection fraction (EF) and wall motion score index (WMSI), using MIBI gated SPECT as an independent reference., Methods: Sixty-two consecutive patients underwent an echocardiography study and a MIBI gated SPECT over 24 hours. EF was estimated visually (estimated-E) and was calculated with the Simpson biplane method (Tracing-T), for both FM and SH. WMSI was determined by two independent echo-readers blinded to the nuclear imaging results. The same segmentation and scoring system was used for WMSI determined by MIBI gated SPECT., Results: The percentages of unscored segments because of suboptimal endocardial border detection were 19.5% (FM) and 9.0% (SH). The correlation coefficients (r) between SPECT-EF and echo-EF were: FM (E)=0.705, FM (T)=0.546, SH (E)=0.771, SH (T)=0.743. Agreement between SPECT-EF and echo-EF was acceptable for both imaging modalities (mean of the difference +/- 2 S.D.): -2.8 +/- 18.5 (FM) and -3.5 +/- 16.4 (SH). Correlation coefficients (r) between WMSI calculated by SPECT and by echo were 0.715 (FM) and 0.789 (SH). Agreement between SPECT-WMSI and echo-WMSI was good for all imaging modes but better with SH compared to FM: 0.12 +/- 0.91 (FM), 0.10 +/- 0.77 (SH). The interobserver correlation coefficients (r) for the WMSI were 0.939 (FM) and 0.996 (SH). The agreement between the two observers was better for SH compared to FM. The systematic differences (mean differences) were 0.21 (FM) and -0.01 (SH), and the random differences between both observers (2 S.D.) decreased from 1.55 (FM) to 0.29 (SH)., Conclusions: The use of SH echocardiography decreases the number of unscored segments. This results in an important gain in correlation and agreement for EF determination between echo and SPECT, and in a considerable decline of the interobserver variability for the echo-determined WMSI. WMSI determined by MIBI gated SPECT correlated closely with the SH WMSI, and agreement between both methods was excellent.

We report a case of recurrent pacemaker lead endocarditis as the cause of acquired tricuspid stenosis. The diagnosis was made noninvasively by 2-dimensional Doppler echocardiography. The case was further complicated by a paradoxical septic embolism through a patent foramen ovale. This cascade of rear events after a pacemaker implantation has never been described in the literature before.

A PACS (Picture Archiving and Communication System) is a system that is able to store, exchange, display and manipulate images and associated diagnoses from any modality within a hospital in a timely and cost-effective way. Several developments, such as the DICOM standard, fast and convenient networking, and new storage solutions for large amounts of data, make the setup of such a PACS system possible. As the information acquired with various imaging modalities is then available and often complementary, it is desirable for the clinician to have a point-by-point spatial co-registration of images from different modalities in order to enable a synergistic use of the multimodality imaging of a patient for increased diagnostic accuracy. Various types of algorithms are available for the matching of medical images from the same or from different modalities. Co-registration algorithms based on voxel properties consist of a similarity or dissimilarity measure and an iterative or non-iterative method minimizing the dissimilarity or maximizing the similarity between the two images by a transformation of one image relative to the other.

The aim of this study was to assess the accuracy and computing time needed for MRI-SPET and SPET-SPET brain co-registration using eight different algorithms (Hermes software from Nuclear Diagnostics Ltd run on a SUN Ultra Sparc 2) to determine the clinically most suitable algorithm. MRI-SPET co-registration was evaluated using phantom studies. To approximate clinical dual-headed SPET studies, a Hoffman brain phantom was filled with 99Tcm. For MRI imaging (1.5 Tesla), the phantom was filled with water and doped with Gd-DTPA for contrast enhancement. For both modalities, phantom images were acquired and reconstructed using a routine clinical protocol. MRI and SPET images were matched by Downhill Simplex minimization of the sum of absolute Count Differences (CD), the sum of the Square Root of absolute count differences (SR), the Difference in Shape between the binary masks (SD), the number of Sign Changes in the subtracted image (SC), the Variance of intensities between corresponding pixels (VAR), the sum of absolute count differences between the 2D- and 3D-Gradient images (2DG-3DG) and, finally, the standard deviation of the Uniformity Index (UI), that is the intensity ratio between spatially corresponding voxels. Six degrees of freedom were allowed (three translation and three rotation parameters, three scaling parameters were constrained). The accuracy of the matching process with these different similarity measures was evaluated via the residual mismatch between external markers. We found that CD, SR, VAR nad UI give the most accurate registration compared with the other similarity measures. For the evaluation of SPET-SPET co-registration, five 99Tcm-ECD brain perfusion SPET scans were performed with a dual-headed gamma camera. These studies were then manually misaligned, and subsequently re-aligned using the methods outlined above. For this application, CD, SR and VAR were also found to give the most accurate registration. For all of these algorithms, the computing time required was clinically acceptable (i.e. less than 10 min).

We performed a prospective study to establish the optimal background correction algorithm for the determination of differential renal function (DRF), using 99Tc(m)-diethylenetriamine pentaacetate (99Tc(m)-DTPA) in the presence of unilateral hydronephrosis, with 24 h 99Tc(m)-dimercaptosuccinic acid (99Tc(m)-DMSA) uptake as the 'gold standard'. From September 1996 to June 1997, 12 males and 4 females (mean age 10 years, range 1 month to 72 years), presenting with unilateral hydronephrosis, were studied. All patients underwent both DTPA renography and quantitative DMSA scintigraphy within 24 h. In all patients, using a surface method, the DRF of the obstructed kidney was determined using infrarenal, suprarenal and perirenal background correction, time intervals of 60-180 s (t1), 120-180 s (t2) and 80-140 s (t3), and the application or non-application of a Rutland-Patlak correction (RPC). In the absence of RPC, for all three types of background correction, no difference in DTPA DRF for any of the three time intervals was noted; higher DTPA DRF values were found (mean +/- S.D.: overestimates of 7.8+/-24.4%, 6.5+/-9.5% and 3.3+/-14.9% for suprarenal, infrarenal and perirenal background correction, respectively). Application of RPC resulted in an overall decrease in both the mean and standard deviation values, which was most pronounced with infrarenal background correction: -0.38+/-6.5% for t1, 0.31+/-6.3% for t2 and -1.3 +/-6.9% for t3 (t1 vs t2, P = 0.06; t3 vs t1 or t2, P = 0.04). Our results suggest that infrarenal background correction using t1 or t2 and RPC is the best algorithm for DRF estimation using 99Tc(m)-DTPA renography.

Recent and future evolutions in neuroSPECT apply to radiopharmaceuticals techniques and the synergistic use of different imaging modalities in the work-up of neurological disorders. The introduction of Technetium labelled perfusion tracers, which could pass the intact blood-brain barrier, together with the implementation of the tomographic principle, by making the conventional gamma camera rotating, enabled estimation of regional cerebral blood flow and indirectly of local brain metabolism. In addition at present Thallium-201 and Tc-99m sestaMIBI allow functional detection of viable tumor tissue, without interference from previous surgery or radiotherapy as seen using CT-scan or MRI. In neurology this has led to the recognition of SPECT by the American Academy of Neurology (Therapeutics and technology subcommittee) as an established or promising tool in major neurological disorders such as dementia, stroke and epilepsy, while other domains such as brain oncology are considered investigational. With regard to radiopharmaceuticals, recent evolutions mainly include the development of mostly Iodine-123 labelled receptor ligands, some of which are already commercially available. For instrumentation advances consist e.g. of multidetector systems equipped with fanbeam collimators, attenuation and scatter correction or coincidence detection. Given the present role for nuclear neurology it may be expected that these additional radiopharmaceutical and technical innovations will continue to stimulate the development of SPECT of the brain. The synergistic use of several imaging techniques such as CT, (functional) MRI, source imaging, SPECT and PET represents a multimodal holistic approach to probe cerebral functions for research and clinical purposes. Clinical indications, in which this synergistic use is illustrated include e.g. support of the clinical diagnosis of dementia of the Alzheimer type, presurgical ictal detection of seizure focus, detection of acute ischemia and differential diagnosis between radiation necrosis and brain tumor recurrence. The synergistic use of imaging modalities, optimally applied using image fusion, allows to overcome the intrinsic limitations and to enhance the specific advantages of the different approaches as it leads to increased precision and accuracy, as well for spatial anatomofunctional correlation as for quantification.