Harald Fricke

Resting regional cerebral glucose metabolism in advanced Parkinson's disease studied in the off and on conditions with [18F]FDG-PET

Studies of resting regional cerebral glucose consumption (rCMRGlc) in nondemented patients with Parkinsons disease (PD) have produced conflicting results, reporting both reduced and normal metabolism in advanced disease and reduced or normal metabolism after dopaminergic therapy. To investigate these issues, [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed in 11 nondemented PD patients with advanced disease and 10 age‐matched controls. PD patients were studied after withdrawal of all dopaminergic medication to produce a practically defined off condition, and a second time 1 hour after levodopa, resulting in a clinical on state. Dynamic PET scans and simultaneous arterialised venous blood samples of [18F] acticvity were obtained. A graphical approach was used to generate parametric images of rCMRGlc and statistical parametric mapping to localise significant metabolic changes in PD. Compared with controls, global rCMRGlc was reduced in the on but not in the off condition in PD. In both states, significant regional reductions of glucose uptake were found in the parietal, frontal, temporal cortex, and caudate nucleus. Reductions correlated with the severity of disability in frontal and temporal cortex. Direct comparison between on and off conditions revealed relatively greater reductions of uptake in the ventral/orbital frontal cortex and the thalamus during on. Results suggest that cortical and caudate hypometabolism are common in advanced PD and that caution is mandatory if [18F]FDG PET is being used to differentiate advanced PD from dementia and progressive supranuclear palsy where similar reductions are seen. Furthermore, in PD, administration of levodopa is associated with further hypometabolism in orbitofrontal cortex; an area known to be relevant for reversal learning where performance is typically impaired after dopaminergic treatment.

Correlates of local cerebral blood flow (CBF) in normal pressure hydrocephalus patients before and after shunting—A retrospective analysis of [15O]H2O PET-CBF studies in 65 patients

OBJECTIVES Findings in local cerebral blood flow (rCBF) in Normal pressure hydrocephalus (NPH) have always been challenged by the variable and inconsistent relation to clinical symptoms before and after shunt treatment. [(15)O]H(2)O PET data from a consecutive cohort of 65 idiopathic NPH patients were retrospectively analyzed questioning whether the functional status before and after shunt treatment might correlate with local blood flow. PATIENTS AND METHODS Using statistical parametric mapping (SPM99, Wellcome Department of Cognitive Neurology, London), the [(15)O]H(2)O uptake was correlated with the preoperative clinical scores, graded according to a modified Stein and Langfitt score. Furthermore, differences in the uptake in the pre-and post-shunt treatment study after seven to 10 days in patients with and without clinical improvement were studied. RESULTS A higher clinical score significantly correlated with a reduced tracer uptake in mesial frontal (k=1,239 voxel, Z=4.41) and anterior temporal (k=469, Z=4.07) areas. In the mesial frontal areas, tracer uptake showed significant reciprocal changes in the clinically improved vs. the unimproved patients. CONCLUSION Matched with the existing literature, the regional blood flow alterations are suggested relevant to the NPH syndrome and to post-treatment functional changes. The present rCBF findings warrant prospective studies on the accuracy of neuroimaging studies as they may provide a more specific insight into disease mechanisms.

Myocardial Sympathetic Innervation in Patients with Symptomatic Coronary Artery Disease: Follow-up After 1 Year with Neurostimulation

In both diabetic and nondiabetic patients, there is a loose correlation between coronary flow reserve (CFR) and sympathetic innervation in viable myocardial segments. The loose correlation implies that sympathetic innervation may be preserved even with major impairment of myocardial blood supply. In some patients, denervation is due to repetitive episodes of ischemia in areas with severely reduced CFR. We investigated the long-term effect of reduced CFR on myocardial sympathetic innervation in diabetic and nondiabetic patients with spinal cord stimulation. Methods: We analyzed 23 patients (10 diabetic and 13 nondiabetic) with coronary artery disease and without known cardiac autonomic neuropathy. At baseline, we determined quantitative myocardial blood flow using 13N-ammonia PET, myocardial viability using 18F-FDG PET, and cardiac innervation using 11C-hydroxyephedrine (HED) PET. At the 1-y follow-up we measured CFR and 11C-HED retention. During follow-up, no cardiac intervention was performed and no myocardial infarction occurred. In all patients, spinal cord stimulation was performed for relief of angina. Results: There was no significant difference in segmental 11C-HED retention between baseline and follow-up in the whole patient group. In diabetic patients, as well as in segments with severely reduced CFR (<1.5), 11C-HED retention showed a small but significant decrease (P < 0.05). Linear regression of segmental 11C-HED retention between baseline and follow-up was high (r2 = 0.81), confirming good reproducibility of the investigation on the one hand and little change in regional sympathetic innervation on the other hand. Conclusion: In patients with stable chronic coronary artery disease, sympathetic innervation of the myocardium is almost unchanged in both diabetic and nondiabetic patients in a 1-y follow-up. In myocardial segments with severely altered blood supply, a small but significant decrease in 11C-HED retention most probably reflects ischemic neuronal damage. The prognostic relevance of sympathetic denervation in viable myocardium still has to be determined.

Myocardial perfusion after one year of spinal cord stimulation in patients with refractory angina.

AIM Spinal cord stimulation (SCS) is recommended for patients with coronary artery disease (CAD) and refractory angina. We used positron emission tomography (PET) to investigate the long-term effect of SCS on regional myocardial perfusion in patients suffering from angina pectoris refractory to medical treatment and without option for coronary intervention. PATIENTS, METHODS We analyzed data of 44 patients with stable CAD (91% three vessel disease). At baseline, we determined coronary flow reserve (CFR) using 13N-ammonia-PET and myocardial viability with 18F-FDG. SCS was performed for one year (Medtronic Itrell III or Synergy, Düsseldorf, Germany). During follow-up, no cardiac interventions were necessary and no myocardial infarctions occurred. At one year follow-up, CFR was measured again. RESULTS In the majority of patients (77%), SCS led to an improvement of clinical symptoms. CFR did not change significantly during follow-up. Subjective improvement did not correlate with an increase of CFR. CONCLUSIONS Despite its clinical effect, SCS does not have a direct impact on CFR in patients with stable CAD. According to our results, the pain relief is not due to an improvement of the myocardial blood supply.

Performance evaluation of PET scanners: testing of geometric arc correction by off-centre uniformity measurement

Abstract.The aim of this study was to demonstrate the necessity of an off-centre uniformity measurement during performance evaluation and acceptance testing of a positron emission tomography (PET) system. To this end, the effect of different methods of geometric arc correction on image uniformity was considered. The arc correction routine of the system software of a particular PET scanner family was tested in computer simulations, phantom measurements and a patient study. Various methods of geometric arc correction – nearest neighbour interpolation, linear interpolation and cubic smoothing spline interpolation – were applied to the same data. Uniformity was evaluated both visually and quantitatively using intensity profiles and regions of interest. The arc correction routine of the PET scanner family produced significant ring artefacts and led to overestimation of tracer uptake by up to 15%. Since uniformity measurements are usually performed using a cylindrical phantom at the centre of the transverse field of view, these artefacts are not detected. In conclusion, the standards for performance evaluation of a PET scanner should be extended by inclusion of an off-centre uniformity measurement at the edge of the transverse field of view. On the basis of our comparison of different methods for geometric arc correction, we suppose that cubic smoothingspline interpolationmight improve the relation between statistical noise reduction and spatial resolution as compared with conventional linear interpolation.

Respiratory resistance of patients during cardiac stress testing with adenosine: Is dyspnea a sign of bronchospasm?

BackgroundA denosine is widely used for stress-testing in myocardial perfusion imaging. During adenosine infusion, dyspnea is one of the main complaints of patients. The aim of this study was to determine whether dyspnea during adenosine infusion is caused by bronchospasm.MethodsFifty-four patients were enrolled in the study. Seven of these 54 suffered from mild chronic obstructive pulmonary disease (COPD). We continuously measured respiratory resistance (Rrs), using impulse oscillometry. Respiratory resistance was measured before, during, and after a continuous infusion of 140 μg/kg/min adenosine.ResultsSixty-seven percent of patients suffered from dysnea during adenosine infusion. In patients with mild COPD, Rrs was higher compared with other patients (0.48 vs 0.27 kPa/L/s, P<.05). Neither patients with COPD nor those without COPD exhibited a significant increase in Rrs during adenosine infusion. The Rrs of patients with dyspnea was insignificantly lower compared with patients without dyspnea(P=.469).ConclusionsDyspnea as a side effect of adenosine infusion is not correlated with impaired respiratory resistance in nonasthmatic pattents and in patients with mild COPD. Thus bronchospasm is ruled out as cause of this clinical symptom. Despite the small number of COPD patients enrolled in the study, adenosine infusion might be possible in patients with mild COPD.

Ein dynamisches Herzphantom für die Qualitätskontrolle in der nuklearkardiologischen Funktionsdiagnostik

Zusammenfassung Ein dynamisches Herzphantom fur die Qualitatskontrolle tomographischer Systeme, wie sie in der nuklearkardiologischen Funktionsdiagnostik zum Einsatz kommen, wurde als Prufkorper entwickelt, aufgebaut und erprobt. Anatomisch wird mit dem Phantom der linke Ventrikel des Herzens nachgebildet. Das dynamische Herzphantom kann uber das Fullvolumen, den zeitlichen Verlauf des Fullvorganges und die Frequenz, mit der das Fullen des Ventrikels vorgenommen wird, variabel angesteuert werden. Mit diesen Stellgrosen konnen Wandbewegung, Wanddickenzunahme, linksventrikulare Auswurffraktion und Schlagvolumen des linken Ventrikels leicht simuliert werden.