PET imaging with yttrium-86: comparison of phantom measurements acquired with different PET scanners before and after applying background subtraction.

Quantitative imaging with the positron emitter (86)Y is the method of choice to determine the uptake and dosimetry of (90)Y-labelled radiopharmaceuticals. To examine the quantitative accuracy of positron emission tomography findings with (86)Y, this non-pure positron emitter was evaluated in a cylindrical phantom with rods of Teflon, water and air and measured with three different scanners: ECAT EXACT (2D/3D), ECAT HR+ (2D/3D) and PC4096+ (2D). After standard reconstruction, (86)Y radioactivity measured with the ECAT EXACT and related to the true radioactivity varied between 0.84 and 0.99 in 2D and between 0.93 and 1.20 in 3D from the first to the last acquisition (eight half-life times later). The water and Teflon rods exhibited considerable amounts of reconstructed radioactivity-21% in 2D and 67% in 3D for water and 65% and 147%, respectively, for Teflon-compared with the actual (86)Y radioactivity of the phantom. For the ECAT HR+ similar results were obtained in 3D, but there were even greater overestimations in 2D. Measurements with the PC4096+ showed rather small errors, with 10% for water and 20% for Teflon. To correct for the background of gamma-coincidences, sinograms were analysed and an experimental percentage of the background was subtracted from the sinograms. In order to minimise the errors in reconstructed radioactivity, the subtraction value had to be different for the individual scanners and modes. Our results demonstrate that (90)Y/(86)Y-based dosimetry for bone and red marrow must be regarded with caution if it is derived from regions of interest over the bone, the density of which is similar to that of Teflon. To obtain more reliable estimates, an appropriate background correction must be applied and tailored individually with respect to the scanner and acquisition mode.

Somatostatin-receptor scintigraphy in Graves' disease: reproducibility and variance of orbital activity.

Somatostatin-receptor (SSTR) scintigraphy using the single photon emission computed tomography (SPECT) technique allows the assessment of orbital inflammation in patients with Graves' disease. Previous studies showed differences in orbital octreotide uptake already 4 hr after injection. In this study, analysis of inter-/intra-observer variance and reproducibility in the evaluation of orbital SPECT images was performed. First, SPECT data of one representative female patient with clinically active Graves' ophthalmopathy (GO), obtained 4 hr after intravenous injection of 110 MBq 111In-pentetreotide and processed by filtered backprojection, were analyzed. Transverse SPECT images were reconstructed, an optimal orbital image was selected and predetermined regions of interests (ROIs) for both orbits were positioned by three independent observers 15 to 19 times each. In a second step, SPECT data of 8 different patients with GO were evaluated in the same manner by four independent observers 3 to 4 times each. Variance component partitioning was used to compare the order of intra- and inter-observer variation. For the right and the left orbit, the inter-observer variance proportion was 90% and 79%, whereas intra-observer variance partition was 10% and 21%, respectively. The corresponding ratios 0.11 and 0.27 summarize the comparison of sources of variance. The overall reliability was 84%, representing the patients influence on the total variance. Intra-observer reliability for both orbits was 88%, 89%, 97% and 98% (mean over orbits), respectively for observers I to IV. Using the Spearman Brown prophecy formula it follows that two replications per patient are sufficient to ensure a minimum reproducibility of 90%, which is also confirmed by the low intra-observer variation. Furthermore, intra-class correlation as a measure of (multiple) observer reproducibility was 94%. In conclusion, due to the increased inter-observer variance proportion and the high variation in intra-observer reliability, evaluations of orbital SSTR scintigraphy have to be done by the same and experienced observer leading to comparable data. But an automatic and quantitative computerized technique for evaluation of these SPECT data should be exactly reproducible and probably lead to more accurate and representative results.

Occupancy of striatal D(2)-like dopamine receptors after treatment with the sigma ligand EMD 57445, a putative atypical antipsychotic.

RATIONALE: EMD 57445 (panamesine) is a high affinity sigma ligand with the profile of an atypical antipsychotic in animal studies. It has been reported recently to have antipsychotic activity in schizophrenia. However, its metabolite, EMD 59983, binds also to D(2) and D(3) dopamine (DA) receptors. OBJECTIVES: The aim of this study was to test, using single photon emission computed tomography (SPECT) and [(123)I]iodobenzamide (IBZM) as the radiotracer, whether EMD 59983 would pass the blood-brain barrier and to what extent it would contribute to the effects of EMD 57445 in schizophrenia. METHODS: Two IBZM SPECT-scans were performed in five neuroleptic-free schizophrenic patients (DSM IV), one before and one after treatment with 60 mg panamesine daily for a treatment duration of 12-26 days. RESULTS: A high occupancy of striatal D(2)-like DA receptors similar to that induced by typical neuroleptics was observed in all patients treated with EMD 57445. CONCLUSIONS: Our results suggest that a possible antipsychotic activity of EMD 57445 in schizophrenia is not necessarily attributable to its affinity for sigma receptors, but could be simply due to the potent antidopaminergic effects of EMD 59983, its main metabolite.

Isolated dysarthria due to extracerebellar lacunar stroke: a central monoparesis of the tongue.

OBJECTIVES: The pathophysiology of dysarthria can preferentially be studied in patients with the rare lacunar stroke syndrome of "isolated dysarthria". METHODS: A single study was carried out on seven consecutive patients with sudden onset of isolated dysarthria due to single ischaemic lesion. The localisation of the lesion was identified using MRI. The corticolingual, cortico-orofacial, and corticospinal tract functions were investigated using transcranial magnetic stimulation. Corticopontocerebellar tract function was assessed using 99mTc hexamethylpropylene amine oxime-single photon emission computerised tomography (HMPAO-SPECT) in six patients. Sensory functions were evaluated clinically and by somatosensory evoked potentials. RESULTS: Brain MRI showed the lesions to be located in the corona radiata (n=4) and the internal capsule (n=2). No morphological lesion was identified in one patient. Corticolingual tract function was impaired in all patients. In four patients with additional cortico-orofacial tract dysfunction, dysarthria did not differ from that in patients with isolated corticolingual tract dysfunction. Corticospinal tract functions were normal in all patients. HMPAO-SPECT showed no cerebellar diaschisis, suggesting unimpaired corticopontocerebellar tract function. Sensory functions were not affected. CONCLUSION: Interruption of the corticolingual pathways to the tongue is crucial in the pathogenesis of isolated dysarthria after extracerebellar lacunar stroke.

[123I]IBZM SPECT in patients treated with typical and atypical neuroleptics: relationship to drug plasma levels and extrapyramidal side effects.

[123I]Iodobenzamide (IBZM) is an iodine-labeled dopamine receptor ligand and can be used to visualize brain D2 receptors in humans with single photon emission computerized tomography (SPECT). The ratio of striatal IBZM uptake to uptake in frontal cortex (ST/FC ratio) represents a semiquantitative measure of D2 receptor binding in the striatum. Our study sample included six patients treated with haloperidol (3.0-8.0 mg/day orally; one patient with an average of 0.9 mg/day intramuscularly), five patients with benperidol (9.0-15.0 mg/day orally) and nine patients treated with clozapine (200.0-600.0 mg/day orally). Typical neuroleptics (TNs) and atypical neuroleptics (ANs) were significantly different in their ST/FC ratios. The ST/FC ratios indicated that patients treated with benperidol exhibited the lowest ST/FC ratios, with increasingly higher ratios in patients on haloperidol or clozapine. We found a curvilinear relationship between the ST/FC ratios and the dose/kg body wt. of TNs and ANs on the basis of a dose-normalization according to Ki-values of the neuroleptic at D2 receptors and a weaker, but also curvilinear relationship between ST/FC ratios and normalized dosages according to clinically defined chlorpromazine equivalents. The specific uptake of IBZM did not correlate with the plasma levels of the TN haloperidol at the present dose range (0-12.4 ng/ml). For clozapine, a meaningful negative correlation between plasma levels and ST/FC ratio could be established. There was a negative continuous correlation between uptake of IBZM and extrapyramidal side effects, which is different from the threshold-based relationship between extrapyramidal side effects and IBZM uptake reported previously.

[Automatic setting of the contrast range of whole body scintigrams using a histogram method]. / Automatische Kontrasteinstellung von Ganzkörperszintigrammen mit einer Histogramm-Methode.

AIM: To get standardised results on the display of whole body scintigrams regarding an optimal contrast setting (using linear scaling), an algorithm was developed, which can be used for an automatic setting of an upper intensity truncation value. METHODS: From the integral of the gray level histogram of 30 randomly selected whole body images upper threshold values LA were defined, where a certain area percentage A (80% < or = A < or = 99.5%) of all pixels with intensity > 0 are contained in the intensity range. Independently an interactive upper level Lvis of the contrast range was determined by two observers to get an optimal visual appearance of the image. RESULTS: For the threshold levels with an area percentage A of 92% ... 98% (L92 ... L98) a very close linear correlation (r > 0.9) was found to the visual levels. Levels resulting to area percentages A < 92% or A > 98% correlated worse to the interactive values. Based on our results we propose as a good definition for an upper threshold on whole body scintigrams with dual intensity ranges: Range 1 (high activities): Upper threshold = min (2.5 x L95, 100%), Range 2 (low activities): Upper threshold = min (1.25 x L95, 100%). CONCLUSION: The procedure is well suited for an automatic definition of the contrast settings of whole body scintigrams. It can be implemented easily; its use gives a substantial contribution to the standardisation of the documentation of scintigrams.

Prolactin plasma levels and D2-dopamine receptor occupancy measured with IBZM-SPECT.

By the application of 123([123I]IBZM), an iodine-labelled dopamine D2-receptor antagonist, brain D2 receptors in humans can be visualized with single photon emission computed tomography (SPECT). The ratio of IBZM binding to striatal regions versus binding to frontal cortex (ST/FC ratio) provided a semiquantitative measurement of D2 receptor binding in the striatum. This study investigated the relationship between receptor occupancy and plasma prolactin levels in 12 male patients treated with haloperidol, benperidol or clozapine. Prolactin levels were positively correlated with D2 receptor occupancy, reflecting at least in part a comparable dopamine receptor antagonism in different dopaminergic pathways.

Regional cerebral blood flow in depression: associations with psychopathology.

Regional cerebral blood flow (rCBF) was measured during rest and cognitive activation in 21 patients with a major depressive episode and 21 healthy subjects. Depressive patients had significantly lower rCBF during rest in the right global, frontal, parietal, occipital and temporal regions and in the left global and frontal regions. During mental activation patients showed significantly lower values in all right and left parietal regions. rCBF was correlated with the scores of the Brief Psychiatric Rating Scale (BPRS), the parietal regions. rCBF was correlated with the scores of the Brief Psychiatric Rating Scale (BPRS), the Bech-Rafaelsen Melancholia Scale (BRMS), the Hamilton Depression Scale (HAM-D) and the Hamilton Anxiety Scale (HAM-A). The most significant negative correlations were obtained with the BPRS. Correlation analyses between each single item of the BPRS and CBF values revealed the strongest associations between emotional withdrawal and decreased CBF. Patients with 'reactive' features had higher CBF than patients without 'reactive' symptoms. Only patients without 'reactive' symptoms had a lower CBF than controls. 'Endogenous' features had no impact on CBF.

SPECT bone scintigraphy of benign and malignant lesions of the spine.

70 patients were examined with planar and SPECT bone scintigraphy. SPECT proved to be superior over planar bone scanning for imaging of traumatic, inflammatory, and malignant bone lesions. SPECT provides three-dimensional information and, therefore, delineates the exact location and extension of lesions. It also has a higher sensitivity than planar bone scintigraphy. The three-dimensional bone scan generates complementary diagnostic information which often facilitates an adequate therapy protocol.

RCBF-quantification with 99mTc-HMPAO-SPECT: theory and first results.

The activity concentrations of 99mTc-HMPAO in brain after intravenous injection were evaluated in 25 patients using SPECT. With additional first pass studies of heart and brain with the short lived isotope 195mAu, the cardiac output and the mean cerebral transit times of the patients were measured a short time before the HMPAO injection. The time dependence of 99mTc-HMPAO activity in the brain was registered during the first 5 min after injection over both hemispheres. Using a simplified three compartment model it was possible to calculate the mean retention fraction of HMPAO in brain from the time activity curves. It could be shown that the regional cerebral blood flow in ml/min per 100 g can be calculated from the activity concentration of HMPAO in the brain, the cardiac output and the retention fraction. In 15 of the 25 cases the rCBF was measured using the planar 133Xe inhalation method as a reference. We found a significant correlation between the mean hemisphere CBF from our method and the mean hemisphere grey matter CBF from the Xenon method with a correlation coefficient of 0.73.

Non invasive assessment of regional diastolic left ventricular function with first pass radionuclide functional imaging in ischaemic heart disease.

Functional images of regional distribution of rapid filling (RF) rates have been developed and applied at rest and on exercise for regional analysis of 301 coronary artery territories (103 compromised by coronary narrowings, 198 normal). The observed time-interval of RF averaged 209 ms at rest (range 200 to 280) and 172 ms on exercise (range 125 to 200 ms). Normal RF is directed to the apex, and it is deviated from territories with reduced compliance to normal territories. Sensitivity in detection and localization of territories compromised by coronary narrowings exceeds 90% at rest for the anterior and infero-posterior wall and is higher than that obtained from systolic functional images. Specificity amounts also to over 90% and is much higher than that observed with systolic functional images. During RF, moderate to severe loss in compliance results in initial regional paradoxical inward motion in 40 to 45% of anterior or postero-inferior segments eventually accompanied by significant inward displacement of blood. Thus, with functional imaging of regional RF rates one can establish dysfunction and functional significance of coronary narrowings.

New nuclear medical technologies for pediatrics.

Nuclear medicine is very helpful for pediatric diagnostics because it provides noninvasive methods for the evaluation of physiologic functions and for the imaging of tumours, metastases and inflammatory diseases. These examinations can be done with very low risk and with low radiation burden for the children. New technologies help us to get more detailed diagnostic information and to reduce further the radiation. The most important developments in this field allow the clinical use of radioisotopes with extremely short lifetimes combined with a very low radiation exposure, imaging of tumours by new radioactive labelled tumour-markers, the measurement of heart functions and blood flow through the use of computerized gammacameras with digital imaging processing capabilities and the three-dimensional imaging of radioactive tracers within the body.

[Radioisotope study (first pass) of left ventricular function in 2 oblique projections using gold-195m after myocardial infarction]. / Studio radioisotopico (primo transito) della funzione ventricolare sinistra in due proiezioni oblique con l'uso di oro 195m nell'infarto miocardico pregresso.

The radioisotope 195Aum because of its short halflife of 30 seconds and reduced radiation exposure allows routine first pass examinations in two oblique projections, i.e. right anterior and left anterior oblique. The value of the additional left anterior oblique projection has been examined in 30 patients after previous myocardial infarction by functional imaging in two oblique projections. The multicrystal gamma camera connected with a microprocessor and a contrast injector have been used. For assessment of left ventricular function the following functional images have been adopted: the regional ejection fractions (rEF), the regional ejection rates (rEJR) and the regional mean transit times (rMTT). The right anterior oblique view resulted diagnostic for miocardial infarction in 26 of 30 patients (86,6%). The left anterior oblique view was informative with respect of septal extension 17 times (58,6%), lateral extension 9 times (31%), septal and lateral extension 3 times. With regard of the different functional images the rMTT showed the severe dysfunction in the infarcted zones in all patients (100%), the rEJR in 29 patients (96,6%), the rEF in 28 cases (93,3%). In 4 cases dyskinesia was observed, twice in the left anterior oblique view and also twice in the right anterior oblique view. In patients with previous MI it is necessary to record the second left anterior oblique projection which can be done routinely by the use of 195Aum and first pass technique. On functional images, maximum information is obtained by the rMTT which visualizes the zones of severe dysfunction and its extension.

[Computer-aided evaluation of ultrasonic images of the thyroid]. / Rechnerunterstützte Auswertung von Ultraschallbildern der Schilddrüse.

Forty-two patients are described. The ultrasound patterns of normal and pathologically changed thyroid glands have been analysed with the aid of a computer. Using several parameters such as run-length histograms, brightness-histograms, middle run length and standard deviation, we are able to classify the patterns of a thyroid lobe or of a part of it into 4 or 5 major groups. The estimation of the benign or malignant character of the lesions with the used parameters must be controlled by further investigation.

[Noninvasive first-pass study of the heart with the short-lived radionuclide gold 195m]. / Nichtinvasive First Pass-Untersuchung des Herzens mit dem kurzlebigen Radionuklid Aurum 195m.

The new shortlived radionuclide Aurum 195 m (T1/2: 30.5 sec) has been used for 1,596 first-pass examinations of 792 patients. During first-pass the same maximum count rates of an average of 300,000 cts/sec and after background subtraction the same enddiastolic counts over the left ventricle averaging 10,000 cts/sec can be achieved as with the previously used Tc-99 m pertechnetate injections. The short half-life and fast regeneration of Au-195 m within 3 minutes allow repeated, subsequent injections with significant reduction in radiation exposure. Half of the studies were done at rest and exercise, one third in two oblique projections, RAO and LAO. Examinations in two projections improve the information facilitating the localization of ischemic or infarcted LV-regions particularly with respect of septal and/or lateral extension. Strictly lateral dysfunction may sometimes be only recognizable in the second LAO-projection. The RAO-view best discriminates the extension along the anterior and infero-posterior wall.

[Global and regional left ventricular myocardial function following aorto-coronary multiple (5-, 6-, 7-) bypass. Non-invasive determination with technetium 99m-pertechnetate scintigraphy]. / Globale und regionale linksventrikuläre Myokardfunktion nach aortokoronarem Mehrfach-(5-, 6-, 7-)Bypass. Nicht-invasive Bestimmung mit der Technetium-99m-Pertechnetat-Szintigraphie.

In 19 patients (mean age 55.3 years) with severe, diffuse coronary artery disease and stable angina pectoris, coronary artery bypass surgery was performed with an average of 5.36 anastomoses per patient. At 15.5 +/- 8 months postoperatively, radionuclide ventriculograms were obtained in the RAO projection (first-pass-technique) at rest and during maximal exercise by means of a multicrystal camera. To assess the effects of revascularization on the myocardial function, analysis was performed for global ejection fraction (GEF) as well as three regional ejection fraction (GEF) as well as three regional ejection fractions (REF) corresponding to the vascular beds of the three major coronary arteries. During exercise global ejection fraction increased in 13 patients (68.4%) an average of 9.5%-points from 51.5 to 61.0%, in one patient (5.2%) remained unchanged and in five patients (26.3%) decreased an average of 9.6% %-points from 62.6 to 53.0% (all changes p less than 0.05). The classification of the various myocardial regions was based on the preoperative coronary angiogram as well as intraoperative in-situ findings according to the status of the coronary vessels, the extent of revascularization and the presence of remote myocardial infarctions. Regions of group I had a significantly higher fraction of complete revascularizations, that is 79.9%. 61.1% of group-II-territories were incompletely revascularized. The weighted balance of the three regions supplied by the left anterior descending artery, the circumflex and the right coronary artery explains the postoperative response of the global ejection fraction to exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Parametric imaging of regional cerebral blood flow with the short-lived isotope 195mAu.

The use of the short-lived (30 s) isotope 195mAu in brain perfusion studies has been tested on 40 patients and 8 volunteers. The activity of the eluate from the 195mHg/195Au generator was high enough to give good image statistics of brain perfusion after a single bolus injection. The examinations can be repeated after 3 min giving the same quality and without significant background. The use of a low-energy photon peak at 68 keV (Au-K alpha) allows the imaging of brain perfusion in both lateral views with almost no look-through effect. With a modified height-over-area formula for the calculation of regional cerebral blood flow parametric images were obtained of high diagnostic value. The sensitivity and reproducibility of the method has been demonstrated by mental stimulation tests on eight volunteers: after optical stimulation a clear increase of blood flow could be shown in the visual cortex.

Quantitative activation patterns of cerebral blood flow during mental stimulation after intravenous injection of 195mAu.

A previously reported theory for quantitative cerebral blood flow measurement for nondiffusible radiotracers has been applied to patients after stroke and to volunteers undergoing a mental stimulation exercise. Quantitative measurements of cerebral blood flow pattern in p-a and lateral projections of the brain are obtained using the short lived (30s) isotope 195mAu from the recently developed generator. The energy spectrum of the eluate from the generator shows two strong photon peaks, one at an energy level of 68 KeV and a second at 262 KeV. The low-energy peak is suitable for perfusion studies of the cerebral hemispheres in lateral projection, being without "look through" effect. The high-energy level is good for studies in the p-a-projection. Studies last less than 1 min and can be repeated after 3 min. Parametric images for quantitative regional cerebral blood flow can be generated, in which the avascular region following stroke can be detected. Quantitative activation patterns of cerebral blood flow during mental stimulation can be generated. The results show that it is possible to measure cerebral blood-flow patterns not only with freely diffusible indicators like Xenon but also with nondiffusible indicators.

Scintigraphic measurement of left-ventricular volumes from the count-density distribution.

An experimental model was developed using ellipsoidal balloons of different volumes to derive an empirical formula linking the "normalized" total count rates on gamma-camera images to volume. The normalized total count rate (NTC) is defined as the total count rate divided by the maximum count density. If an object is at a constant distance from the collimator, the NTC is found to be a linear function of volume. This formula was then applied to calculate left-ventricular end-diastolic volume from scintigraphic images obtained by radionuclide ventriculography in 71 consecutive patients. The distance from the left ventricle to the collimator was estimated from the patient's height and weight. The volumes calculated by the radionuclide method were compared with angiographic volumes obtained at cardiac catheterization, and good correlation was found (r = 0.95).

Regional left ventricular function in the three main coronary artery territories at rest and during exercise.

Twenty consecutive patients (mean age 51.6 years) with persistent severe angina pectoris underwent aorto-coronary bypass surgery receiving an overall of 60 anastomosis. On an average, 9.4 +/- 1.5 months p.o. first pass radionuclide ventriculograms (18 to 24 mCi 99m Technetium-Pertechnetate i.v.) were performed at rest and after exercise. Besides measurement of global ejection fraction (GEF), regional ejection fraction (REF) was assessed employing for the first time a new technique: each RAO-view of p.o. radionuclide left ventriculogram was subdivided into three regions according to supply of the three main coronary arteries and their branches as visualized on pre-operative coronary angiogram. GEF improved after maximum exercise in 13 cases by 8.1% points (from 50.4 to 58.5%), remained unchanged three times and decreased four times by 7.1 points (from 51.6 to 44.5%; all changes p less than 0.05). In completely revascularized regions (n = 35) REF improved 24 times by 9.7 points (from 51.1 to 60.8%), did not differ from rest REF six times and decreased in three case by 7.3 points (from 48.6 to 41.3%; all changes p less than 0.05). completely revascularized regions responded to exercise like normally perfused areas (increase 7.8 points (from 50.6 to 58.4%; n = 7; p less than 0.05). REF deteriorated in incompletely revascularized regions (n = 9) six times by 12.8 points (from 58.0 to 45.2%), remained unchanged twice and improved once by 4.5 points. Total group's REF decreased by 7.3 points (from 56.8 to 49.5%; p less than 0.05). Exercise REF of incompletely revascularized regions was highly significant inferior to that of completely revascularized regions (49.5 to 58.4%; p less than 0.01). GEF is a weighted balanced of the three regional ejection fractions. The most important parameter is REF of LAD territory.