Axel Bossuyt

Dopamine D2 receptors in depression measured with single photon emission computed tomography

Psychobiological theories of mood disorders have been concerned mainly with noradrenaline and serotonin. There exists, however, a recent upsurge of interest in dopamine. We have used single photon emission computed tomography and 123I-iodobenzamide, a high-affinity ligand for D2 receptors, to study these receptors in depression. Subjects were 21 (unipolar) depressed inpatients and 11 normal controls. The mean basal ganglia/cerebellum uptake ratio was 1.94 (+/- 0.27) in the depressed patients versus 1.74 (+/- 0.17) in the controls. This difference was statistically significant (Mann-Whitney U test, p = 0.025). These data could indicate an increase of D2 receptor density in depression.

SPECT imaging of serotonin2 receptors in depression

Changes of serotonin2 (5HT2) receptors have been described in depression, and long-term antidepressant treatment has been shown to decrease the number of 5HT2 receptors. In this study, single photon emission computed tomography (SPECT), with 2-123I-ketanserin as a ligand, was used to investigate 5HT2 receptors in vivo in the brain of depressed patients and normal volunteers. A higher uptake of the tracer was observed in the parietal cortex of the patients, and there was a right greater than left asymmetry in the infero-frontal region of the depressed subjects and not in that of the control subjects. These findings could indicate changes in 5HT2 receptors in major depression.

Interest of the ordered subsets expectation maximization (OS-EM) algorithm in pinhole single-photon emission tomography reconstruction : A phantom study

Abstract.Pinhole single-photon emission tomography (SPET) has been proposed to improve the trade-off between sensitivity and resolution for small organs located in close proximity to the pinhole aperture. This technique is hampered by artefacts in the non-central slices. These artefacts are caused by truncation and by the fact that the pinhole SPET data collected in a circular orbit do not contain sufficient information for exact reconstruction. The ordered subsets expectation maximization (OS-EM) algorithm is a potential solution to these problems. In this study a three-dimensional OS-EM algorithm was implemented for data acquired on a single-head gamma camera equipped with a pinhole collimator (PH OS-EM). The aim of this study was to compare the PH OS-EM algorithm with the filtered back-projection algorithm of Feldkamp, Davis and Kress (FDK)and with the conventional parallel-hole geometry as a whole,using a line source phantom, Picker’s thyroid phantom and a phantom mimicking the human cervical column. Correction for the angular dependency of the sensitivity in the pinhole geometrywas based on a uniform flood acquisition. The projection data were shifted according to the measured centre of rotation. No correction was made for attenuation, scatter or distance-dependent camera resolution. The resolution measured with the line source phantom showed a significant improvement with PH OS-EM as compared with FDK, especially in the axial direction. Using Picker’s thyroid phantom, one iteration with eight subsets was sufficient to obtain images with similar noise levels in uniform regions of interest to those obtained with the FDK algorithm. With these parameters the reconstruction time was 2.5 times longer than for the FDK method. Furthermore, there was a reduction in the artefacts caused by the circular orbit SPET acquisition. The images obtained from the phantom mimicking the human cervical column indicated that the improvement in image quality with PH OS-EM is relevant for future clinical useand that the improvements obtained using the OS-EM algorithm are more significant for the pinhole geometry than for the conventional parallel-hole geometry. We conclude that PH OS-EM is a practical and promising alternative for pinhole SPET reconstruction.

Comparison of 99mTc HMPAO SPECT Scan between Chronic Fatigue Syndrome, Major Depression and Healthy Controls: An Exploratory Study of Clinical Correlates of Regional Cerebral Blood Flow

An explorative analysis of the relationship between symptomatology and cerebral blood flow in the chronic fatigue syndrome (CFS) as assessed with 99mTc HMPAO SPECT scan reveals statistically significant positive correlations between frontal blood flow on the one hand and objectively and subjectively assessed cognitive impairment, self-rating of physical activity limitations and total score on Hamilton Depression Rating Scale on the other. A pathophysiological role of frontal blood flow in the cognitive impairment and physical activity limitations in CFS is hypothesized. A comparison of cerebral blood flow between CFS, major depression (MD) and healthy controls (HC) has been performed. A lower superofrontal perfusion index is demonstrated in MD as compared with both CFS and HC. There is neither a global nor a marked regional hypoperfusion in CFS compared with HC. Asymmetry (R > L) of tracer uptake at parietotemporal level is demonstrated in CFS as compared with MD.

Left ventricular ejection fraction from gated SPET myocardial perfusion studies: a method based on the radial distribution of count rate density across the myocardial wall

Left ventricular ejection fraction (LVEF) can be derived from gated single-photon emission tomographic (SPET) myocardial perfusion studies using either manual or edge detection techniques. In the presence of severe perfusion defects, however, difficulties may be encountered. In this article a method based on the assumption that the average position of the myocardial wall can be localized by means of statistical analysis of the distribution count density, and not on edge detection, is used to measure LVEF. SPET myocardial perfusion images, gated in eight time bins, were recorded in 50 patients 60 min after the injection of 925 MBq technetium-99m tetrofosmin. Masking of non-myocardial structures and thresholding resulted in images in which only myocardial walls had significant non-zero values. The distance of the wall relative to the centre of the cavity was calculated in the three-dimentional space as the first moment of the count rate distribution along radii originating in the centre of the cavity. LVEF was calculated using, for each time bin, the sum of the cube of all distances as an estimate of the cavity volume. The method required minimal operator interventions and was successful in all patients, including those with severe perfusion defects. Intraobserver and interobserver variability was excellent, with regression coefficients of 0.97 and standard deviations of 4.5% and 4.7%, respectively. For 30 patients, the measurements were validated against planar equilibrium radionuclide angiography (ERNA) that was obtained within an interval of 1 week. LVEF ranged from 12% to 88%. Agreement between the two methods was excellent (LVEFEERNA=1.05+0.92 LVEFGSPET,r=0.93,P=0.023, SEE=7.06). The Bland-Altman analysis did not show any apparent trend in the differences between ERNA and gated SPET over a wide range of ejection fractions. The standard deviation of the differences was 3.1%. In addition no relationship was found between the two methods and the severity of perfusion defects. In conclusion, accurate measurements of LVEF are obtained from gated SPET perfusion images using a method based on statistical analysis of the count rate density. This method did not deteriorate even in the presence of severe perfusion defects and could therefore be used in following patients after myocardial infarction.

Evaluation of the radiation dose in micro-CT with optimization of the scan protocol

INTRODUCTION Micro-CT provides non-invasive anatomic evaluation of small animals. Serial micro-CT measurements are, however, hampered by the severity of ionizing radiation doses cumulating over the total period of follow-up. The dose levels may be sufficient to influence experimental outcomes such as animal survival or tumor growth. AIM This study was designed to evaluate the radiation dose of micro-CT and to optimize the scanning protocol for longitudinal micro-CT scans. METHODS AND MATERIALS Normal C57Bl/6 mice were euthanized. Radiation exposure was measured using individually calibrated lithium fluoride thermoluminescent dosimeters (TLDs). Thirteen TLDs were placed in the mice at the thyroid, lungs, liver, stomach, colon, bladder and near the spleen. Micro-CT (SkyScan 1178) was performed using two digital X-ray cameras which scanned over 180 degrees at a resolution of 83 microm, a rotation step of 1.08 degrees , 50 kV, 615 microA and 121 s image acquisition time. The TLDs were removed after each scan. CTDI(100) was measured with a 100 mm ionization chamber, centrally positioned in a 2.7 cm diameter water phantom, and rotation steps were increased to reduce both scan time and radiation dose. RESULTS Internal TLD analysis demonstrated median organ dose of 5.5 +/- 0.6 mGy per mA s, confirmed by CTDI(100) with result of 6.6 mGy per mA s. A rotation step of 2.16 resulted in qualitatively accurate images. At a resolution of 83 microm the scan time is reduced to 63 s with an estimated dose of 2.9 mGy per mA s. At 166 microm resolution, the scan time is limited to 27 s, with a concordant dose of 1.2 mGy per mA s. CONCLUSIONS The radiation dose of a standard micro-CT scan is relatively high and could influence the experimental outcome. We believe that the presented adaptation of the scan protocol allows for accurate imaging without the risk of interfering with the experimental outcome of the study.

Relationship between blood flow and fatty acid metabolism in subacute myocardial infarction: a study by means of 99mTc-Sestamibi and 23I-β-methyl-iodo-phenyl pentadecanoic acid

Contradictory data have been published on the relative behaviour of fatty acids and flow tracers during the subacute stage of myocardial infarction. Therefore, the present study was set up (1) to investigate the potential occurrence of mismatches between β-methyl-iodophenyl pentadecanoic acid (BMIPP), a fatty acid analogue, and Sestamibi, and to describe their nature, and (2) to relate these mismatches to clinical characteristics such as whether or not thrombolysis or percutaneous transluminal coronary angioplasty (PTCA) had been performed. Twenty-six patients were studied within 2 weeks after myocardial infarction. Sestamibi and BMIPP single-photon emission tomography (SPET) were performed within 4 days of one another. Activity of both tracers was scored in 16 basal, 16 midventricular and 8 apical segments, using a four-point grading system: 3 = normal (≥65% of maximum activity), 2 = mildly decreased (45%–64%), 1 = moderately decreased (25%–44%), 0 = severely decreased (0%–24%). Coronary arteriography was obtained during the same hospital stay. Four hundred and seventy-seven segments out of 1040 studied were abnormal for at least one tracer: 197 with higher Sestamibi activity (group I), 226 with equal scores for Sestamibi and BMIPP (group II) and 54 with higher BMIPP activity (group III). Seventy-five percent of group I segments and 84% of group III segments were found in infarct-related artery territories. Group I segments were associated with acute thrombolysis and/or PTCA (P < 0.01), and with the absence of prior infarction in the territory of the infarct-related artery (P < 0.001). Group III segments were associated with the absence of thrombolysis or PTCA (P < 0.001), with occlusion of the infarct-related artery (P < 0.001), with previous infarction in the same territory (P < 0.001) and with a- or dyskinesia in this territory (P < 0.001). These data could support the interpretation that areas in which the uptake of BMIPP is more decreased than that of Sestamibi (group I) are due to delayed recovery of fatty acid metabolism after reperfusion, whereas those with higher BMIPP than Sestamibi activity (group III) are accounted for by the enhanced metabolism induced by passive systolic wall stretch.

Regional cerebral hypoperfusion in long-term type 1 (insulin-dependent) diabetic patients: relation to hypoglycaemic events.

Regional distribution of cerebral blood flow was determined semi-quantitatively with 99Tcm-HMPAO brain SPET under basal conditions in Type 1 (insulin-dependent) diabetic patients of recent onset and longer disease duration, and related to metabolic control and history of hypoglycaemic events. Long-term diabetic patients showed significantly more alterations in regional cerebral blood flow than diabetics of recent onset and healthy controls. Regional hypoperfusion, predominantly localized in the fronto-temporal cortex, was almost exclusively observed in patients with long-term diabetes. The latter finding was related to lower HbA1c levels (i.e. better metabolic control) and to the frequency of impending hypoglycaemia, but not to age of the patient, duration of diabetes or to chronic diabetes complications. The incidence of hypoperfusion was comparable in patient groups with or without a medical history of hypoglycaemic coma. However, regions of hypoperfusion were larger in the patients who had experienced hypoglycaemic coma. It is concluded that regional cerebral hypoperfusion in long-term Type 1 (insulin-dependent) diabetics, as evidenced by HMPAO-SPET can be related to the frequency and degree of hypoglycaemic events and to tight metabolic control, which is however at the expense of an increased risk of recurrent hypoglycaemia.

Optimal collimator choice for sequential iodine-123 and technetium-99m imaging

Dual-isotope studies with technetium-99m and iodine-123 may be useful for various organs, including brain and myocardium. For the images obtained with each of the tracers to be comparable, it is important that activity ratios (activity in one part of the image/reference activity in the image) are preserved by the imaging method. We have used a Rollo phantom to study how collimator response affects such ratios. All investigations were performed with123I(p,5n) and on a Siemens Orbiter 3700 camera fitted with either a low-energy high-resolution (LEHR) or a medium-energy (ME) collimator. Images were made of a Rollo phantom filled with an aqueous solution of either99Tc or123I, and placed on the collimator surface with 8 cm of methyl-methacrylate interposed. Count densities were measured in ROIs drawn in each cell of the phantom, and normalised to the maximal ROI value in the image. The mean square error (MSE) was used to assess how well the ratios of count densities approximated the known activity ratios based on the dimensions of the cells of the phantom. For99mTc, regardless of the collimator used, the count density ratios approximated the activity ratios fairly well (LEHR: MSE=0.008; ME: MSE=0.020). For123I, count density ratios obtained with the LEHR were consistently higher than activity ratios (MSE=0.235), whereas the differences between the measured and the theoretical values were less with the ME collimator (MSE=0.013). Contrast fidelity of the123I images obtained with the LEHR collimator could be improved with Jaszczak scatter correction withk=1, but this led to unfavourable signal-to-noise ratios. For sequential99mTc/123I studies with extended sources, ME is to be preferred because of its higher contrast accuracy. Spatial resolution is less for the ME than for the LEHR collimator (FWHM with scatter: LEHR/99mTc=6.9 mm, LEHR/123I=7.4 mm, ME/99mTc=10.1 mm, ME/123I=11.1 mm), but remains similar for both tracers when the ME is used.

Reconstruction of gated myocardial perfusion SPET incorporating temporal information during iterative reconstruction

Abstract. Reconstruction of gated single-photon emission tomography (gSPET) is intrinsically a four-dimensional (4D) problem. In practice, the time frames are reconstructed independently as a sequence of frame-by-frame reconstructions. This approach is not optimal since the strong signal correlations among the individual time frames are not exploited. In this study we propose a simple but efficient algorithm to improve the image quality of myocardial perfusion gSPET by incorporating the cyclic temporal information within the reconstruction using Fourier filtering. The gSPET images were reconstructed using the Ordered Subsets Expectation Maximisation (OSEM) algorithm employing six iterations with eight subsets. Temporal filtering was applied either before (PreOSEM) or after image reconstruction (PostOSEM) or was incorporated within the OSEM algorithm (OSEM4D). The effect of temporal filtering was compared with conventional frame-by-frame OSEM using clinical data. Image quality was evaluated by estimating the systematic and statistical error. The results indicated that temporal filtering introduces a small (<1%) systematic error, while the statistical error was reduced from 15.0%±3.1% when conventional frame-by-frame OSEM was applied to 12.6%±2.7%, 12.0%±2.5% and 9.3%±2.4% when PreOSEM, PostOSEM and OSEM4D were used, respectively. It is concluded that temporal filtering incorporated within OSEM reconstruction dramatically reduces noise in gated SPET myocardial images.