Biomedical subjects

A T Willemsen

Publications and source records attributed to A T Willemsen.

At least 19 recordsLinked to original sources

PubMed1999

55Cobalt (Co) as a PET-tracer in stroke, compared with blood flow, oxygen metabolism, blood volume and gadolinium-MRI.

Several studies have shown the feasibility of divalent cobalt (Co)-isotopes (55Co and 57Co) in imaging of neuronal damage in stroke, multiple sclerosis, cerebral tumors and traumatic brain injury. Little is known how regional Co uptake relates to other pathophysiological changes after stroke. Therefore, we compared 55Co-PET with functional parameters such as regional cerebral blood flow (rCBF) using C(15)O(2), regional oxygen metabolism (rCMRO(2)) using 15O(2), regional cerebral blood volume (rCBV) and post-gadolinium (Gd) T(1)w-MRI to assess the permeability of the blood-brain-barrier (BBB). Sixteen patients (10 female; six male) aged 43 to 84 (mean 69) years with first ever stroke, as shown by CT or MRI, were examined with 55Co-PET and C(15)O(2)-, 15O(2)- and C(15)O-PET in one single session, in a period varying from 0 to 30 days after stroke-onset. Regions of infarction on C(15)O(2)- and 15O(2)-PET (defined by rCMRO(2)<65% or rCBF<45% of the contralateral value) were subsequently superimposed on the 55Co-PET scan. Clinical status was established using the Orgogozo stroke scale, which was assessed both at day 1 and at discharge (at least 6 weeks after day 1). Accumulation of 55Co was seen in eight out of 16 patients, occurring in areas showing a diminished oxygen metabolism, was only partially related to blood flow, and was located mainly outside the extent of the infarction or luxury perfusion as seen on post-Gd T(1)w-MRI. Statistical analysis showed a negative correlation between the Orgogozo score at discharge and the uptake of radioactive cobalt.

Adult↗

PubMed1999

A new in vivo method to study P-glycoprotein transport in tumors and the blood-brain barrier.

Drug resistance is a major cause of chemotherapy failure in cancer treatment. One reason is the overexpression of the drug efflux pump P-glycoprotein (P-gp), involved in multidrug resistance (MDR). In vivo pharmacokinetic analysis of P-gp transport might identify the capacity of modulation by P-gp substrate modulators, such as cyclosporin A. Therefore, P-gp function was measured in vivo with positron emission tomography (PET) and [11C]verapamil as radiolabeled P-gp substrate. Studies were performed in rats bearing tumors bilaterally, a P-gp-negative small cell lung carcinoma (GLC4) and its P-gp-overexpressing subline (GLC4/P-gp). For validation, in vitro and biodistribution studies with [11C]daunorubicin and [11C]verapamil were performed. [11C]Daunorubicin and [11C]verapamil accumulation were higher in GLC4 than in GLC4/P-gp cells. These levels were increased after modulation with cyclosporin A in GLC4/P-gp. Biodistribution studies showed 159% and 185% higher levels of [11C]daunorubicin and [11C]verapamil, respectively, in GLC4 than in GLC4/P-gp tumors. After cyclosporin A, [11C]daunorubicin and [11C]verapamil content in the GLC4/P-gp tumor was raised to the level of GLC4 tumors. PET measurements demonstrated a lower [11C]verapamil content in GLC4/P-gp tumors compared with GLC4 tumors. Pretreatment with cyclosporin A increased [11C]verapamil levels in GLC4/P-gp tumors (184%) and in brains (1280%). This pharmacokinetic effect was clearly visualized with PET. These results show the feasibility of in vivo P-gp function measurement under basal conditions and after modulation in solid tumors and in the brain. Therefore, PET and radiolabeled P-gp substrates may be useful as a clinical tool to select patients who might benefit from the addition of a P-gp modulator to MDR drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Brain activation related to the change between bimanual motor programs.

By using positron emission tomography, we aimed to identify cerebral foci of neuronal activation associated with the initiation of a specific motor program. To that end, a state of repeatedly alternating in- and antiphase of bimanual flexion and extension movements was compared with similar movement responses except phase changing. This comparison provided the opportunity to eliminate confounding effects of attention and simple movements. Change between the two bimanual motor programs was related with activation at the posterior border of the left angular gyrus, the right precuneus, and the right premotor and right medial prefrontal cortex. In a subsequent experiment, with attention and random movements as additional variables, activation at the posterior border of the left angular gyrus was found at the same significance level. This posterior parietal activation may indicate an equivalence with the coding of intention in monkey posterior parietal cortex. Lesion of the left posterior parietal cortex in human gives rise to left-right disorientation and ideomotor apraxia. Our results may support the view that these symptoms reflect the inability to transpose a motor plan to the representation of a personal body scheme. Activation of the right premotor and right medial prefrontal cortex was related both to the change between motor programs and to the condition with strictly regular movement in which no additional responses were made to randomly presented signals. This is consistent with the concept that motor preparation is associated with both the selection of internally instructed movements and the suppression of irrelevant environmental stimuli.

Adult↗

PubMed1999

The distribution of cerebral activity related to visuomotor coordination indicating perceptual and executional specialization.

The distribution of increased regional cerebral blood flow (rCBF) related to visuomotor coordination was studied by means of positron emission tomography (PET) in normal subjects. An experimental condition, in which a vertically presented zigzag figure had to be copied in a horizontal orientation, was compared with a control condition in which the same horizontal drawing was made, guided by a horizontally presented example. Cognitive components dealing with the mismatch in visual orientation resulted in activation of (i) right dorsal premotor cortex, (ii) right posterior parietal cortex, (iii) visual cortex (area V1) and (iv) left fusiform gyrus. In a second experiment, conditions were compared in which the same horizontal zigzag figure was copied in either a vertical or a horizontal orientation. Now, the motor components of the transformation of orientation appeared to be associated only with left premotor cortex activation. The differential distribution of activations is regarded to reflect the selective effort to cope with either the visual or the motor component of spatial incongruity, and indicates specialization for perceptual and executive components in visuomotor control. We propose that the perceptual component of visuomotor transformation in our experiment relates to a realignment of the coordinates of a percept to an internally defined coordinate system. The executive component relates to guidance of movement within an internal representation of space. In a preceding behavioural experiment, a majority of patients with Parkinson's disease (PD) failed on the task in which they had to make a horizontal copy of a vertically presented picture. This finding may suggest a deficit in the maintenance of an internal spatial representation to guide movement.

Adolescent↗

PubMed1999

Parametric polar maps of regional myocardial beta-adrenoceptor density.

UNLABELLED: Quantification of myocardial beta-adrenoceptor density (Bmax) is of interest in cardiac diseases in which altered function of the sympathetic nervous system is thought to play a pathophysiological role. PET provides an unrivaled means of taking regional measurements of cardiac microcirculatory function, tissue metabolism and autonomic nervous system activity. Measurements in small regional areas may be biased because of increased noise levels. This study examined the parametric polar map approach for the regional quantification of Bmax. METHODS: Dynamic PET with parametric polar map imaging was performed in 10 healthy volunteers and 4 patients with hypertrophic cardiomyopathy using (S)-[11C]-(4-(3-tertiarybutylamino-2-hydroxypropoxy)-benzidimaz ole-2)-on hydrochloride (CGP)-12177 and a double-injection protocol. Time-activity curves were corrected for partial volume, spill-over and wall motion effects. The mean Bmax of the left ventricle was calculated in two ways. First, the average time-activity curve of all segments, having the highest achievable signal-to-noise ratio, was used to calculate Bmax(mTAC) (the myocardial beta-adrenoceptor density of the left ventricle calculated using the average time-activity curve). The bias in Bmax(mTAC) introduced by noise is minimal. Second, an estimate of whole-heart receptor density was calculated using the polar map method by averaging the values of Bmax obtained for 576 individual segments. In these calculations, three different filters (3 x 5, 3 x 9 and 3 x 13 segments) were used to smooth the time-activity curves before calculating Bmax. Mean values of whole-left-ventricular receptor density obtained by averaging regional values using the different filters (Bmax(PMF1/2/3)) were compared with Bmax(mTAC) to assess bias introduced by the polar map approach. Segments with a calculated Bmax outside the range 0.1-50 pmol/g were considered unreliable and were excluded from the analysis. RESULTS: The differences between the two methods of calculating Bmax were small (7.8%, 4.8% and 3.2%, with the three filters, respectively). Reliable results were obtained in >95% of the segments and in 9 volunteers and all 4 patients. CONCLUSION: When using PET for the quantification of beta-adrenoceptor density, the regional variation in Bmax can be reliably assessed using the parametric polar map approach.

Adrenergic beta-Antagonists↗

PubMed1999

Detection of muscarinic receptors in the human lung using PET.

UNLABELLED: The characterization of pulmonary muscarinic receptors with PET is still in its infancy. Because approximately 70% of the lungs consists of air and pulmonary muscarinic receptor densities are low, ligands with high receptor affinity are required to obtain reasonable signal-to-noise ratios on PET images. Therefore, the potent 11C-labeled muscarinic antagonist N-methyl-piperidin-4-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate methiodide ([R]-VC-002) was developed. We administered this radioligand to four healthy human volunteers to examine its suitability for studying pulmonary muscarinic receptors in vivo. METHODS: [11C]VC-002 (185 MBq, specific activity > 7.4 TBq/mmol) was intravenously injected on 2 separate days, with an interval of at least 1 wk. On the first day the volunteers were not pretreated, but on the second day they received the anticholinergic glycopyrronium bromide (Robinul; 2 x 0.1 mg intravenous) 25 and 30 min before the injection of the radiopharmaceutical. C[15O]O scans (approximately 740 MBq [20 mCi] by inhalation) were acquired before the receptor scan to calculate pulmonary blood volume. RESULTS: On PET images of the thorax, the lungs were clearly visible. After the volunteer was pretreated with glycopyrronium bromide, pulmonary uptake of the radioligand was reduced to 32%+/-12% of the control value at 60 min postinjection and the lungs could no longer be seen. (R)-[11C]-VC-002 was rapidly cleared from plasma and was slowly metabolized during the time course (60 min) of the PET scan. The fraction of radioligand representing parent compound decreased from 99.9% at the time of injection to 82% at 40-60 min postinjection, both in the presence and absence of Robinul. Pulmonary tissue-to-plasma ratios, calculated on a count-per-minute-per-gram basis, reached a plateau value of 17.8+/-1.2 at 40-50 min postinjection. CONCLUSION: [11C]VC-002 appears to be suitable for in vivo studies of pulmonary cholinoceptors.

Carbon Radioisotopes↗

PubMed1998

Validation of S-1'-[18F]fluorocarazolol for in vivo imaging and quantification of cerebral beta-adrenoceptors.

S-1'-[18F]fluorocarazolol (S-(-)-4-(2-hydroxy-3-(1'-[18F]fluoroisopropyl)-aminopropoxy)carba zole, a non-subtype-selective beta-adrenoceptor antagonist) has been investigated for in vivo studies of beta-adrenoceptors. Previous results indicated that uptake of this radioligand in heart and lung can be inhibited by beta-adrenoceptor agonists and antagonists. In the present study, blocking, displacement and saturation experiments were performed in rats, in combination with metabolite analysis to investigate the suitability of this radioligand for in vivo positron emission tomography (PET) imaging and quantification of beta-adrenoceptors in the brain. The results demonstrate that, (i) the uptake of S-1'-[18F]fluorocarazolol reflects specific binding to beta-adrenoceptors, (ii) binding of S-1'-[18F]fluorocarazolol to atypical or non-beta-adrenergic sites is negligible, (iii) uptake of radioactive metabolites in the brain is less than 25% of total radioactivity, 60 min after injection, (iv) in vivo measurements of receptor densities (Bmax) in cortex, cerebellum, heart, lung and erythrocytes are within range of densities determined from in vitro assays, (v) binding of S-1'-[18F]fluorocarazolol can be displaced. In conclusion, S-1'-[18F]fluorocarazolol seems to possess the appropriate characteristics to visualize and quantify beta-adrenoceptors in vivo in the central nervous system using PET.

Adrenergic beta-Antagonists↗

PubMed1998

Skeletal muscle perfusion measured by positron emission tomography during exercise.

The applicability of H215O-positron emission tomographic (PET) imaging for the assessment of skeletal muscle perfusion during exercise was investigated in five healthy subjects performing intermittent isometric contractions on a calf ergometer. The workload of the left calf muscles was kept constant in all exercises, while that of the right calf muscles was varied. During exercise H215O distribution in the calf muscles was measured by PET. Radioactivity measured in the left calf muscles was used as a reference for the radioactivity measured in the right calf muscles. In all studies, muscles were delineated by uptake of radioactivity. Four subjects demonstrated high radioactivity in the gastrocnemius medialis muscle, in one subject high radioactivity was distributed over the triceps surae muscles. The observed muscles demonstrated also local foci of radioactivity indicating regionally enhanced tissue perfusion. The right-left ratio of radioactivity in the active muscles increased as a function of the load. We conclude that inter- and intramuscle perfusion differences can be measured during exercise by H215O-PET imaging.

Adult↗

PubMed1998

Complete in vivo reversal of P-glycoprotein pump function in the blood-brain barrier visualized with positron emission tomography.

1. Homozygously mdr1a gene disrupted mice (mdr1a(-/-) mice) and wild type mice (mdr1a(+/+) mice) were used to develop a method for P-glycoprotein (P-gp) function imaging non-invasively and to study the effect of a P-gp reversal agent on its function in vivo. 2. [11C]verapamil (0.1 mg/kg) was administered and the changes in tissue concentrations were determined ex vivo by organ extirpation and in vivo with PET. To block P-gp function, cyclosporin A was administered. 3. Biodistribution studies revealed 9.5-fold (P < 0.001) and 3.4-fold (P < 0.001) higher [11C]verapamil in the brain and testes of mdr1a(-/-) mice than in mdr1a(+/+) mice. Cyclosporin A (25 mg/kg) increased [11C]verapamil levels in the brain and testes of mdr1a(+/+) mice in both cases 3.3-fold (P < 0.01 (brain); P < 0.001 (testes)). Fifty mg/kg cyclosporin A increased [11C]verapamil in the brain 10.6-fold (P < 0.01) and in the testes 4.1-fold (P < 0.001). No increases were found in the mdr1a(-/-) mice. This indicates complete inhibition of P-gp mediated [11C]verapamil efflux. 4. Positron camera data showed lower [11C]verapamil levels in the brain of mdr1a(+/+) mice compared to those in mdr1a(-/-) mice. [11C]verapamil accumulation in the brain of mdr1a(+/+) mice was increased by cyclosporin A to levels comparable with those in mdr1a(-/-) mice, indicating that reversal of P-gp mediated efflux can be monitored by PET. 5. We conclude that cyclosporin A can fully block the P-gp function in the blood brain barrier and the testes and that PET enables the in vivo measurement of P-gp function and reversal of its function non-invasively.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

A mathematical model for the heterogeneity of myocardial perfusion using nitrogen-13-ammonia.

UNLABELLED: Heterogeneity of left ventricular myocardial perfusion is an important clinical characteristic. Different aspects of this heterogeneity were analyzed. METHODS: The coefficient of variation (v), characterizing heterogeneity, was modeled as a function of the number of segments (n), characterizing spatial resolution of the measurement, using two independent pairs of mutually dependent parameters: the first pair describes v as a power function of n, and the second pair adds a correction for n small. n was varied by joining equal numbers of neighboring segments. Local similarity of the perfusion was characterized by the correlation between the perfusions of neighboring segments. Genesis of the perfusion distribution was modeled by repeated asymmetric subdivision of the perfusion into a volume among two equal subvolumes. These analyses were applied to study the differences between 16 syndrome X patients and 16 age- and sex-matched healthy volunteers using 13N-ammonia parametric PET perfusion data with a spatial resolution of 480 segments. RESULTS: The heterogeneity of patients is higher for the whole range of spatial resolutions considered (2 < or = n < or = 480; for n = 480, v = 0.22 +/- 0.03 and 0.18 +/- 0.02; p < 0.005). This is because the first pair of parameters differs between patients and volunteers (p < 0.005), whereas the second pair does not (p > 0.1). For both groups of subjects there is a significant positive local correlation for distances up to 30 segments. This correlation is a formal description of the patchy nature of the perfusion distribution. CONCLUSION: When comparing values of v, these should be based on the same value of n. The model makes it possible to calculate v for all values of n < or = 480. Mean perfusion together with the two pairs of parameters are necessary and sufficient to describe all aspects of the perfusion distribution. For n small, heterogeneity estimation is less reliable. Patients have a higher heterogeneity because their perfusion distribution is more asymmetrical from the third to the seventh generation of subdivision (8 < or = n < or = 128). Therefore, a spatial resolution of n > or = 128 is recommended for parametric imaging of perfusion with PET. Patients have only a very slightly more patchy distribution than volunteers. The differences in perfusion between areas with low perfusion and areas with high perfusion is larger in patients.

Ammonia↗

PubMed1997

Coronary vasomotion in patients with syndrome X: evaluation with positron emission tomography and parametric myocardial perfusion imaging.

The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [13N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127+/-31 ml.min-1.100 g-1; group B, 124+/-30 ml.min-1.100 g-1 normal subjects, 105+/-21 ml.min-1.100 g-1 (groups A and B vs normals, P<0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20+/-0.23; group B, 1.24+/-0.22; normal subjects, 1.23+/-0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71+/-0.67; group B, 2.77+/-1.29; normal subjects, 2. 91+/-1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1+/-4.5 vs 17.0+/-3.0, P<0.05). In group B (coefficient of variation 19.4+/-3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X.

Adult↗

PubMed1997

Cobalt-55 positron emission tomography in ischemic stroke.

After acute cerebral stroke, the (peri-) infarct tissue is characterized by calcium (Ca)-mediated neuronal damage and inflammatory processes. Monitoring Ca-mediated damage using the isotope cobalt-55 (Co) as a Ca-tracer may enable PET-imaging of this tissue. Since the fate of (peri-) infarct tissue determines clinical outcome, Co-PET may have prognostic value in stroke. Six stroke patients were examined with Co-PET, MRI and a middle cerebral artery (mca) stroke scale (Orgogozo). In every patient, specific Co-accumulation in the appropriate brain region was seen, irrespective of the integrity of the blood-brain barrier. This pilot study suggests Co-PET as a diagnostic tool in stroke, which may provide additional information on the clinical outcome. Validation of method in larger patient series is necessary.

Aged↗

PubMed1997

Regional cerebral blood flow changes related to affective speech presentation in persistent vegetative state.

A story told by his mother was presented on tape to a trauma patient in persistent vegetative state (PVS). During auditory presentation, measurements of regional cerebral blood flow (rCBF) were performed by means of positron emission tomography (PET). Changes in rCBF related to this stimulus condition, as compared to presenting non-word sound, were evaluated by means of statistical parametric mapping (SPM). This analysis indicated activation of rostral anterior cingulate, right middle temporal and right premotor cortices, which may reflect appropriate cortical involvement in processing emotional attributes of sound or speech.

Adolescent↗

PubMed1997

A PET study on brain control of micturition in humans.

Although the brain plays a crucial role in the control of micturition, little is known about the structures involved. Identification of these areas is important, because their dysfunction is though to cause urge incontinence, a major problem in the elderly. In the cat, three areas in the brainstem and diencephalon are specifically implicated in the control of micturition: the dorsomedial pontine tegmentum, the periaqueductal grey, and the preoptic area of the hypothalamus. PET scans were used to test whether these areas are also involved in human micturition. Seventeen right-handed male volunteers were scanned during the following four conditions: (i) 15 min prior to micturition during urine withholding: (ii) during micturition; (iii) 15 min after micturition; (iv) 30 min after micturition. Ten of the 17 volunteers were able to micturate during scanning. micuturition was associated with increased blood flow in the right dorsomedial pontine tegmentum, the periaqueductal grey, the hypothalamus and the right inferior frontal gyrus. Decreased blood flow was found in the right anterior cingulate gyrus when urine was withheld. The other seven volunteers were not able to micturate during scanning, although they had a full bladder and tried vigorously to do so. In this group, during these unsuccessful attempts to micturate, increased blood flow was found in the right ventral pontine tegmentum, which corresponds with the hypothesis, formulated from results in cats, that this area controls the motor neurons of the pelvic floor. Increased blood flow was also found in the right inferior frontal gyrus during unsuccessful attempts at micturition, and decreased blood flow in the right anterior cingulate gyrus was found during the withholding of urine. The results suggest that, as that of the cat, the human brainstem contains specific nuclei responsible for the control of micturition, and that the cortical and pontine micturition sites are predominantly on the right side.

Adult↗

PubMed1997

Characterization of pulmonary and myocardial beta-adrenoceptors with S-1'-[fluorine-18]fluorocarazolol.

UNLABELLED: S-1'-[18F]fluorocarazolol was administered to healthy volunteers to assess its potential for noninvasive measurement of regional pulmonary and myocardial beta-adrenoceptor densities. METHODS: High-specific activity fluorocarazolol was intravenously injected on two separate occasions within a 1-wk interval. The initial injection was without pretreatment, but before the second injection, the volunteers either inhaled salbutamol (2 x 200 micrograms aerosol) or they ingested pindolol (3 x 5 mg during a 12-hr interval). Twenty-eight PET time frames of 31 planes were acquired over a period of 60 min after each injection. Blood samples were drawn and analyzed for the presence of fluorocarazolol and radioactive metabolites. RESULTS: Uptake of fluorocarazolol in the target tissues was hardly affected by salbutamol but was strongly depressed by pindolol. Pulmonary and myocardial tissue-to-plasma concentration ratios of fluorocarazolol reached plateau values of 11.6 +/- 0.6 (lungs) and 18.1 +/- 1.0 (heart) at 45-50 min postinjection. These values were reduced to 2.0 +/- 0.4 and 2.0 +/- 0.6 after treatment with pindolol. CONCLUSION: These data indicate that: 1. Pulmonary and myocardial uptake of radioactivity after intravenous administration of S-1'-[18F]fluorocarazolol represents radioligand binding to beta-adrenoceptors. 2. Pulmonary binding occurs mainly in alveoli rather than in airway smooth muscle under these conditions. 3. Binding kinetics do not preclude quantification of receptors with compartment models.

Adrenergic beta-Agonists↗

PubMed1997

Imaging beta-adrenoceptors in the human brain with (S)-1'-[18F]fluorocarazolol.

UNLABELLED: We evaluated the suitability of fluorocarazolol for in vivo studies of cerebral beta-adrenoceptors because (S)-1'-[18F]fluorocarazolol has a higher affinity to beta-adrenoceptors than to serotonergic receptors (pKi beta 1 9.4, beta 2 10.0, 5HT1A 7.4, 5HT1B 8.1) and rapidly crosses the blood-brain barrier. METHODS: The (S)-[18F]fluorocarazolol (74 MBq, > 37 TBq/mmol) was intravenously administered to healthy volunteers on two separate occasions with an interval of at least 1 wk. The initial injection was without pretreatment, but before the second injection, the volunteers received the beta blocker (+/-)-pindolol (3 x 5 mg orally, during 18 hr). The brain was studied with a PET camera in dynamic mode. RESULTS: Uptake of radioactivity delineated gray matter and was particularly high in the posterior cingulate, precuneus and striatum. Low uptake occurred in the thalamus, whereas the lowest uptake was observed in the white matter of the corpus callosum. After pindolol pretreatment, uptake was reduced and its distribution became homogeneous throughout the brain. The ratio of total-to-nonspecific binding was about 2 at 60 min, increasing to 2.5-2.75 at longer intervals. CONCLUSION: Fluorocarazolol is the first radioligand that can visualize cerebral beta-adrenoceptors and may enable monitoring of these binding sites during disease.

Adrenergic beta-Antagonists↗

PubMed1997

55Co-PET in stroke: relation to bloodflow, oxygen metabolism and gadolinium-MRI.

BACKGROUND: Several studies have shown the feasibility of Co-isotopes (55Co and 57Co) in imaging of neuronal damage in stroke, multiple sclerosis, cerebral tumors and trauma. These studies indicate that Co-isotopes allow visualization of brain pathology related to inflammatory processes, reactive gliosis and cell death. Until now, it is not clear if 55Co accumulation occurs in the core of infarction or in the penumbra. Therefore, in the present study, we compared 55Co-PET with functional parameters such as cerebral bloodflow (rCBF) using C15O2, oxygen metabolism (rCMRO2) using 15O2 and cerebral bloodvolume (CBV) using C15O in PET and with the anatomical parameter Gd-MRI. PATIENTS AND METHODS: Seventeen patients (11 male; 6 female) age 43 to 84 (mean 69) with middle cerebral artery (mca) stroke, as proven by CT or MRI, were examined with 55Co-PET (0.5-1.0 mCi 55CoCl2), C15O2-, 15O2- and C15O-PET in one session 0-30 days after stroke-onset. Regions of infarction were defined by rCMRO2 being smaller than 65% or rCBF below 45% of the contralateral value and were subsequently superimposed on the cobalt scan. To compare the Cobalt uptake with the Gd-MRI, a realignment program was used that matches the MRI with the bloodflow images. Clinical status was established using the Orgogozo stroke scale at admission and at discharge (at least 6 weeks after admission) and the Barthel index. RESULTS: Eight patients showed a positive Co-PET scan and were used for further analysis. It appeared that Co accumulates in areas with a diminished oxygen metabolism and with a preserved bloodflow. We found Co-uptake in only a part of the Gd enhanced brain tissue with a tendency to be located peripherally or outside the Gd demarcated brain tissue. CONCLUSION: The results of the present study suggest that Co accumulates into infarcted brain tissue with a rather preserved flow independently of blood-brain barrier breakdown.

Adult↗

PubMed1996

Brain activity related to serial cognitive performance resembles circuitry of higher order motor control.

Differences between two states of cerebral activation were studied in eight subjects by positron emission tomography (PET) of regional cerebral blood flow (rCBF) and subsequent statistical parameter mapping. Subjects had to respond to a row of numbers presented on tape. In one condition they had to repeat each number. In the other condition the last heard number had to be added to the number presented before. Cerebral activity specifically related to the serial addition task was distributed over supplementary motor area (SMA), left premotor cortex and superior dorsal parietal cortex bilaterally, without significant involvement of prefrontal cortex. This indicated circuitry related to mental performance characterised by a fixed strategy of executing serial manipulation of numbers within "internal space". The main aim of this communication is to discuss the similarity between circuitry underlying higher order motor control and pure cognitive performance.

Adult↗