Self-rating scales assessing subjective well-being and distress correlate with rCBF in PTSD-sensitive regions.

BACKGROUND: The aim of this study was to investigate the distribution of the regional cerebral blood flow (rCBF) in occupational-related post-traumatic stress disorder (PTSD) subjects and to seek possible correlations between brain perfusion and self-rating scales (SRS) in order to cross-check their diagnostic value and to look for their neural correlates. METHOD: A total of 13 traumatized underground and long-distance train drivers developing (S) and 17 not developing (NS) PTSD who had experienced a 'person under train' accident or who had been assaulted at work underwent clinical assessment and 99mTc-HMPAO SPECT imaging during autobiographical trauma scripts. Statistical parametric mapping was applied to analyse rCBF changes in S as compared with NS and to search for correlations between rCBF and the administered SRS scores, modelling age, months to SPECT and the ratio 'grey matter/intra-cranial volume' as nuisance variables. RESULTS: Significantly higher activity was observed during trauma script in left posterior and anterior insula, posterior cingulate, inferior parietal lobule, precuneus, caudate and putamen in PTSD subjects as compared with the trauma-exposed control group. Impact of Event Scale and World Health Organisation (10) Well-Being Index scores highly correlated with tracer uptake to a great extent in the same regions in which rCBF differences between S and NS were found. CONCLUSIONS: These findings support the involvement of insular, cingulate and parietal cortices (as well as the basal ganglia) in the pathogenesis of PTSD and in the processing of related subjective well-being and distress.

Feasibility and quality of biological banking of human normal and tumor tissue specimens as sources of DNA for the Malmö Diet and Cancer Study.

Human tumor and normal tissue specimens, which were collected from autopsy material 1-6 days postmortem, were compared with similar tissue specimens collected within 2 h after surgical resection and transport to the pathology department. The end point criteria used to evaluate the quality of the specimens for biological banking purposes were the extractability and yield of high molecular weight DNA and UV absorption ratios at 260:280 after collection and immediate storage of the specimens at -80 degrees C. The data demonstrated that autopsy material was a quality source of DNA, although of not such high quality as surgical biopsy specimens <2 h after resection. The advantages of using autopsy material to supplement surgical specimen collection sent to pathology, as opposed to using specimen collection at surgery wards or formalin-fixed material, as sources of DNA are: (a) large amounts of tumor and normal tissues from a variety of organ sites can be obtained without regard to the patient's health status; (b) a higher percentage of retrieval of incident cases of cancer in prospective designed trials is more likely to be achieved; and (c) the extractable DNA is of sufficiently high enough quality to permit direct analyses by molecular hybridization and sequence methodologies.

Collimator design for improved spatial resolution in SPECT and planar scintigraphy.

UNLABELLED: This paper evaluates the design of a new planar-concave collimator with nonuniform response that better matches the body shape than conventional collimators. METHODS: The collimator properties are evaluated and assessed by means of both a stimulation program and an experimental test using a prototype planar-concave collimator. RESULTS: The results, for points located 150 mm from the axis of rotation, demonstrate that the ratio of radial and tangential spatial resolution in SPECT with the new collimator decreased by 40%, as compared to SPECT with a standard collimator. In planar scintigraphy, the spatial resolution improved correspondingly from 10.9 mm (FWHM) to 7.8 mm in lateral areas of the body. CONCLUSION: The new collimator reduces nonisotropic blurring in SPECT in addition to improving spatial resolution in both planar scintigraphy and in SPECT.

Generalized scatter correction method in SPECT using point scatter distribution functions.

A new two-dimensional (2-D) scatter correction technique in single photon emission computed tomography (SPECT) based on convolution or frequency filtering with a 2-D scatter distribution function is described. A scatter distribution function of the form A exp(-Br), has been derived from measurements of a point source in a water phantom. Both the amplitude A and the slope B of this function, were approximately invariant with source position except near phantom surface. The accuracy of the 2-D correction technique was compared with that of the previous one-dimensional (1-D) scatter correction technique. As could be expected the latter technique was shown to be less accurate due to its dependence on axial distribution of radioactivity. Phantom SPECT studies showed a clear superiority of the 2-D over the 1-D scatter correction in quantitative imaging. Images derived from clinical studies of regional bloodflow with 99mTc-HM-PAO and liver uptake showed significant contrast improvement by both techniques.

A special cut-off gamma camera for high-resolution SPECT of the head.

A modern system for single photon emission computerized tomography has been modified in order to optimize examinations of the head. By cutting off part of the detector housing and collimators at one edge, it is possible to rotate the camera close to the skull while still covering the entire brain and the skull base. The minimum radius of revolution used in 32 patients was thereby reduced from about 20 cm to 12.7 +/- 0.8 cm. This, combined with an adjustment of the 64 X 64 matrix to a 26- by 26-cm field of view, resulted in an improvement of the spatial resolution from about 19 mm to 12.6 +/- 0.3 mm with a low-energy, all-purpose collimator, and to 10.4 +/- 0.3 mm (FWHM) with a low-energy, high-resolution collimator. The improved spatial resolution offers several clinical advantages in studies of the brain, the cerebrospinal fluid space, and the skull base.

A new method for granulocyte labeling with technetium-99m: preliminary results in abscess detection.

A new method for 99mTc-labeling of granulocytes for clinical routine use has been developed. The labeling is simple to perform by means of a kit of radiopharmaceutical quality, utilizing dihydroxy-benzoic acid. Pretinning techniques are avoided. The technique has been applied clinically in 15 patients with indications of intra-abdominal abscess. In six patients, [99mTc]granulocyte scintigraphy at 3 hr and/or 24 hr after i.v. administration, correctly depicted the abscess, as verified by subsequent surgery. In the remaining patients, who were negative at surgery or recovered without operation, all scans were negative.

Development of "resistance" in beta-adrenergic receptors of asthmatic patients.

Complete in vitro dose-response curves for (see article) -isoproterenol (isoprenaline) sulfate showed no functional defects in bronchial muscular beta-adrenergic receptors in three patients with chronic intrinsic asthma, as compared to 60 patients with normal pulmonary function. Complete in vivo dose-response curves for intravenously infused isoproterenol were obtained in eight outpatients with chronic intrinsic asthma to register effects on bronchial muscle (forced expiratory volume in one second), heart rate, blood pressure, and skeletal muscular tremor. The isoproterenol test was performed before and also during oral treatment with a long-acting selective beta-adrenergic stimulator (terbutaline sulfate, 5 mg three times daily). The study was performed over 12 months to avoid seasonal variation in basal levels of obstruction and was concluded by adding inhaled terbutaline (two inhalations four times daily) to oral therapy. No "resistance" developed in bronchial beta-adrenergic receptors during this prolonged treatment. Inhalation therapy in addition to oral therapy improved bronchodilation without causing resistance. Even six inhalations given four times daily (four- to five-hour intervals) did not cause any bronchial resistance; however, resistance developed in skeletal muscles with decreased tremor and in cardiac beta-adrenergic receptors.

NCQ 298, a new selective iodinated salicylamide ligand for the labelling of dopamine D2 receptors.

NCQ 298 ((S)-3-iodo-N-[(l-ethyl-2-pyrrolidinyl)methyl]-5,6- dimethoxysalicylamide) has an iodine substituent. We have labelled NCQ 298 with 123I and 125I, and used the radioligands as tracers in receptor studies in vitro, in vivo in autoradiography and in SPECT studies on Cynomolgus monkeys. [125I]NCQ 298 bound in vitro to a single binding site with a KD = 19 pM. NCQ 298 has thus a 10-fold higher affinity for the dopamine D2 receptors than the corresponding des-5-methoxy compound FLA 961 (IBZM), previously used in SPECT studies. The binding of [125I]NCQ 298 was entirely reversible (T1/2 = 17.5 min at 37 degrees C). Autoradiographical studies in vitro on rat and monkey brain tissue sections showed a distinct binding in caudate-putamen, nucleus accumbens, substantia nigra, and in layer 5 of the cerebral cortex. In vivo binding studies in mice showed a ratio of 10 between [125I]NCQ 298 binding in striatum and cerebellum. Binding was displaced by the selective dopamine D2 receptor antagonist raclopride. In SPECT studies with [123I]NCQ 298 in two Cynomolgus monkeys, radioactivity accumulated in the basal ganglia. The measured striatum to cerebellum ratio was about 15 after 3 h. A monkey brain phantom was constructed for the determination of conversion factors from pixel events to actual radioactivity. The resulting, corrected striatum to cerebellum ratio obtained was 30. After administration of 12 mg raclo-pride to one of the monkeys there was a substantial decrease in striatal radioactivity. [125I]NCQ 298 is a suitable ligand for the labelling of dopamine D2 receptors in vitro and in vivo. The specific properties of [123I]NCQ 298 suggest that this compound is a useful ligand for quantitative SPECT studies of dopamine D2 receptors in man.

Z-IQNP: a potential radioligand for SPECT imaging of muscarinic acetylcholine receptors in Alzheimer's disease.

RATIONALE: The density of the M2 subtype of muscarinic acetylcholine receptors (mAChR) has been shown to be reduced in the brain of patients with Alzheimer's disease (AD). It is therefore of interest to develop a brain imaging method for diagnostic purposes. Z-(R,R)-1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo1-propen-3-yl)-alpha-phenylacetat e (Z-IQNP) is a muscarinic antagonist with high affinity for the M2 subtype. OBJECTIVE: The pharmacological characteristics and topographic distribution of radiolabelled Z-IQNP as a radioligand for the M2 mAChR subtype were examined in vitro and in vivo. METHODS: Z-IQNP was labelled with 1251 and 123I. Autoradiography was performed on whole-hemisphere cryosections from human post mortem brains. SPECT was performed in a cynomolgus monkey. RESULTS: Autoradiography showed binding of [125I]Z-IQNP in all brain regions, which was inhibited by the non-selective muscarinic antagonist scopolamine. The addition of BIBN 99, a compound with high affinity for the M2 subtype, inhibited [125I]Z-IQNP binding particularly in the cerebellum, which has a high density of the M2 subtype. SPECT demonstrated high uptake of [123I]Z-IQNP in all brain regions. The binding was markedly reduced in all brain regions after pretreatment with the non-selective muscarinic antagonist dexetimide and also the M1 antagonist biperiden. Dexetimide markedly inhibited [123I]Z-IQNP binding in the cerebellum, which is consistent with a high density of M2-receptors in this region. The sigma receptor binding compound DuP 734 had no effect on Z-IQNP binding either in vitro or in vivo. CONCLUSIONS: This study indicates that radiolabelled Z-IQNP has high specificity for mAChR with higher affinity for the M2 than the M1 subtype and negligible affinity for sigma recognition sites both in vitro and in vivo. [123I]Z-IQNP should be useful for future SPECT studies in AD for examination of the density of M2 receptors particularly in the cerebellum.

Pulmonary perfusion is more uniform in the prone than in the supine position: scintigraphy in healthy humans.

The main purpose of this study was to find out whether the dominant dorsal lung perfusion while supine changes to a dominant ventral lung perfusion while prone. Regional distribution of pulmonary blood flow was determined in 10 healthy volunteers. The subjects were studied in both prone and supine positions with and without lung distension caused by 10 cmH2O of continuous positive airway pressure (CPAP). Radiolabeled macroaggregates of albumin, rapidly trapped by pulmonary capillaries in proportion to blood flow, were injected intravenously. Tomographic gamma camera examinations (single-photon-emission computed tomography) were performed after injections in the different positions. All data acquisitions were made with the subject in the supine position. CPAP enhanced perfusion differences along the gravitational axis, which was more pronounced in the supine than prone position. Diaphragmatic sections of the lung had a more uniform pulmonary blood flow distribution in the prone than supine position during both normal and CPAP breathing. It was concluded that the dominant dorsal lung perfusion observed when the subjects were supine was not changed into a dominant ventral lung perfusion when the subjects were prone. Lung perfusion was more uniformly distributed in the prone compared with in the supine position, a difference that was more marked during total lung distension (CPAP) than during normal breathing.

Diagnosing sternal wound infections with 99mTc-labeled monoclonal granulocyte antibody scintigraphy.

BACKGROUND: Postoperative mediastinitis is a serious complication of thoracic operations. The diagnosis can sometimes be difficult, especially in cases with subacute clinical presentation. The aim of this study was to assess the clinical use of granulocyte scintigraphy and tomography in the diagnosis of postoperative wound infection and mediastinitis. METHODS: Twenty-nine patients after cardiothoracic operations were included, of whom 5 patients with a normal postoperative course formed the control group. We injected technetium 99m-monoclonal antigranulocyte antibodies and performed single-photon emission computed tomography after 4 and 20 hours. RESULTS: Twenty-three patients had both the early and the later scan; the remaining 6 had only the early scan. Seven scans indicated infection: 3 cases of mediastinitis, 2 cases of superficial wound infection, 1 case of infection in a synthetic aortic graft, and 1 case of osteitis. All were verified by bacterial culture. There was one false-negative scan; this patient had only the early registration and then was explored. CONCLUSIONS: This method when combined with the tomographic scan option is able to distinguish between deep and superficial infections. Two registrations must be made for optimal results.

Detection of extrathoracic manifestations in sarcoidosis with somatostatin analogue scintigraphy.

BACKGROUND AND AIM OF WORK: Scintigraphy using a long lived radiolabelled somatostatin analogue [111In-DTPA-D-Phe1]-octreotide (OctreoScan) has previously been shown to be useful in the detection and management of neuroendocrine tumours, as well as in the imaging of various other malignant tumours. It was recently reported that the radiopharmaceutical accumulates also in the granulomatous lesions in Wegener's disease and in sarcoidosis. The present study was undertaken in order to evaluate the usefulness of the technique in detection of extrathoracic manifestations. METHODS: OctreoScan scintigraphy was performed in 5 patients with biopsy-proven sarcoidosis. A patient with a familial history of multiple endocrine neoplasia served as control. RESULTS: In 4/5 patients previously unknown granulomas were registered, and in the remaining subject the findings at the physical examination were confirmed. CONCLUSIONS: We conclude that somatostatin analogue scintigraphy may be helpful in finding extrathoracic granulomatous lesions in sarcoidosis, thus providing good prerequisites for focused biopsy attempts.

A spatially varying compton scatter correction for SPECT utilizing the integral Klein-Nishina cross section.

An algorithm correcting for the fraction of scattered events in SPECT and planar imaging is proposed. The algorithm utilizes a pixel-based multi-channel analyser for data acquisition. The method was designed to operate on a local level by three subtraction steps: (a) Subtracting a modified Klein-Nishina single scatter distribution, pixel by pixel, from the events obtained experimentally in the upper half of the photo-peak window. (b) Subtracting a mirrored distribution of the unscattered events hence obtained from that of total events in the lower half of the window, thus giving the scatter distribution in this part of the window. (c) Subtracting the sum of the scatter distributions in both window halves from the corresponding sum of total events in order to obtain the unscattered photons within the photo-peak window. The accuracy of the method was validated experimentally, using a new rCBF phantom allowing for imaging in matter corresponding to soft tissue and approximately in air, respectively. After correction for photon scattering and attenuation, the regional difference in SPECT values in soft tissue equivalent matter and in low-density matter (simulating air) was only 1.5 +/- 7.2% (mean +/- 1 SD), thus indicating a high accuracy of the correction method. Provided that an accurate and stable pixel peak-alignment routine is available, the method can be applied using a minimum of three windows.

Optimal design of planar-concave collimators for SPECT--an analytical approach.

In this paper we present an analytical tool for the design and optimization of planar-concave collimators for SPECT. We conclude that a single general planar-concave collimator that eliminates the non-isotropic blurring for all SPECT applications does not exist. On the other hand, it is possible to achieve pseudo-optimal collimators for different clinical applications by a careful choice of the design parameters. By classifying the clinical applications into two groups, for instance body and brain studies, the non-isotropic blurring for most SPECT situations may be dramatically reduced by means of planar-concave collimators. The results based on Monte Carlo simulations show that the shape of the point source response function of the reconstructed image obtained from the planar-concave collimator is more isotropic than that obtained from a conventional parallel-hole collimator. Specifically, the ratio of the FWHM of the reconstructed point response function in the radial and tangential direction is increased from 0.5 for the parallel-hole to 0.85 for the planar-concave collimator for sources 200 mm away from the centre of rotation.

Some physical factors influencing the accuracy of convolution scatter correction in SPECT.

Some important physical factors influencing the accuracy of convolution scatter correction techniques in SPECT are presented. In these techniques scatter correction in the projection relies on filter functions, QF, evaluated by Fourier transforms, from measured scatter functions, Qp, obtained from point spread functions. The spatial resolution has a marginal effect on Qp. Thus a single QF can be used in the scatter correction of SPECT measurements acquired with the low energy high resolution or the low energy general purpose collimators and over a wide range of patient-collimator distances. However, it is necessary to examine the details of the shape of point spread functions during evaluation of Qp. QF is completely described by scatter amplitude AF, slope BF and filter sum SF. SF is obtained by summation of the values of QF occupying a 31 x 31 pixels matrix. Regardless of differences in amplitude and slope, two filter functions are shown to be equivalent in terms of scatter correction ability, whenever their sums are equal. On the basis of filter sum, the observed small influence of ellipticity on QF implies that an average function can be used in scatter correcting SPECT measurements conducted with elliptic objects. SF is shown to increase with a decrease in photon energy and with an increase in window size. Thus, scatter correction by convolution may be severely hampered by photon statistics when SPECT imaging is done with low-energy photons. It is pointless to use unnecessarily large discriminator windows, in the hope of improving photon statistics, since most of the extra events acquired will eventually be subtracted during scatter correction. Regardless of the observed moderate reduction in SF when a lung-equivalent material replaces a portion of a water phantom, further studies are needed to develop a technique that is capable of handling attenuation and scatter corrections simultaneously. Whenever superficial and inner radioactive distributions coexist the observed reduction of SF close to the phantom surface indicates that scatter correction of such distributions has to rely on two distinct filter functions. Corrections based on a surface function produce accurate results in the superficial region, while the central distributions are substantially overestimated. Surface radioactive distributions introduce appreciable errors in the determination of central distributions when corrections are based on central filter function. This function introduces a reduction of about 40% in the measured surface concentration.

Effect of food intake on liver and spleen volume: assessment with single photon emission computed tomography.

RATIONALE AND OBJECTIVES: The authors evaluated the influence of food intake on liver and spleen size. The rationale was that since a meal induces a marked increase in splanchnic blood flow, organ volume might also be affected. This could influence conclusions made at clinical examination. METHODS: Single photon emission computed tomography (SPECT) was performed in 20 healthy volunteers after administration of technetium-99m albumin colloid before and after ingestion of a standardized meal. A semiautomatic technique was used to determine liver and spleen size. RESULTS: There was a nonsignificant reduction in liver volume of 1.5% (P = .063) and a significant reduction in spleen volume of 3.2% (P = .00033) after food intake. CONCLUSION: Liver and spleen volume are marginally affected by food intake, and the changes are within the methodologic error of radiologic modalities.

The application of single photon emission computed tomography to the diagnosis of ankylosing spondylitis of the spine.

Single Photon Emission Computed Tomography (SPECT) has been used to examine the spine in a prospective long-term study with the aim of assessing the value of bone scintigraphy in the detection and diagnosis of ankylosing spondylitis (AS). Sites of increased uptake of 99Tcm-MDP were observed in three of the eleven patients examined so far. By carefully optimising the SPECT system (rotating gamma camera), as well as the examination procedure, with respect to high spatial resolution, it was possible to relate these sites precisely to anatomical sites in sectional images of the spine. The advantages of SPECT are demonstrated in all three cases in which the areas of increased uptake in sagittal and transverse sections can be related to specific anatomical sites of the spine characteristically affected by AS. The findings in each of these cases are quite distinct from those of a normal case and correlate with the radiographic appearances. It is concluded that SPECT will make it easier to observe, localise and evaluate regions of increased uptake in patients with AS compared with conventional scintigraphy.

Localization of sentinel nodes in head and neck tumours by combined lymphoscintigraphy and bone scintigraphy.

Sentinel node scintigraphy in tumours of the head and neck region was combined with bone scintigraphy to provide anatomical landmarks in order to better locate the lymph node uptake. 99Tc(m)-nanocolloid (40 MBq) was injected in the peritumour region 1 h after the administration of bone-seeking 99Tc(m)-methylene diphosphonate (200 MBq). After 5 min, A-P and lateral projections of the head and neck region were acquired. In all the 26 patients examined, the surrounding anatomy was clearly depicted. In 23 patients, the lymphatic drainage was identified within 30 min. In these patients, all hot spots appearing outside the deposited activity could be located according to the neck region classification system of the Memorial Sloan-Kettering Hospital. No lymphatic drainage was visualized in the remaining three patients. The injection of bone-seeking activity 1 h before deposition of the radiocolloid provided images visualizing soft tissues as well as skeletal structures, thus improving the topical diagnosis. Correlation with the results of surgery was not performed. The administration of a small amount of bone-seeking activity prior to sentinel node scintigraphy of head and neck tumours improves the anatomical localization of the lymph node activity.

A comparison of 99Tcm-MDP and 99Tcm-MIBI in the detection of breast cancer.

In this study, we made an intra-individual comparison of the uptake of 99Tcm-MDP and 99Tcm-MIBI in breast cancer. Twenty women with large breast masses (one dimension > or = 3 cm on mammography) underwent SPET in the supine position with both agents. All transverse sections demonstrating tumour activity were added together and the net (total) tumour uptake in a region of interest was compared to that of surrounding tissue activity (background). We also evaluated maximum tumour uptake versus background activity. Tumour uptake was observed in all examinations. In contrast to MIBI, eight MDP examinations showed increased uptake in normal breast parenchyma in addition to tumour uptake. There was no significant difference in net tumour uptake between the two tracers and non-parenchymal (indifferent) background activity, but the maximum tumour activity of MIBI was significantly higher than that of MDP. In the eight MDP examinations with parenchymal activity, mammograms were required to identify tumour uptake correctly. In conclusion, MDP may provide similar images to MIBI in postmenopausal women not receiving hormone replacement therapy. For other patients, MIBI gives better tumour depiction.

Reproducibility and repeatability of 99Tcm-HMPAO rCBF SPET in normal subjects at rest using brain atlas matching.

The aim of this study was to assess regional cerebral blood flow (rCBF) in normal subjects at rest using 99Tcm-HMPAO single photon emission tomography (SPET). Analysis of reproducibility and repeatability was performed both before and after normalization of flow data. Six healthy volunteers were examined, three times each, according to a routine rCBF protocol. A computerized brain atlas was used to evaluate flow data in eight selected regions. The overall reproducibility of rCBF was evaluated from two scans performed at an average interval of 3 months. Repeatability was evaluated from two scans, 3 h apart and without re-injection of 99Tcm-HMPAO. For the normalized (relative) flow data, the reproducibility was +/- 1.3% and the repeatability +/- 2.2% (i.e. methodological errors dominate). For the non-normalized flow data, the corresponding values were +/- 14.8% and +/- 5.9%. rCBF SPET with 99Tcm-HMPAO is highly reproducible provided that the flow data are normalized. The variation in flow between individuals at one point in time and 3 months later was less than +/- 5% for all brain regions.