Ernst Moser

Impaired Endothelium-Dependent Vasodilation of Coronary Resistance Vessels Is Associated With Exercise-Induced Myocardial Ischemia

BACKGROUND The release of endothelium-derived relaxing factors has been shown experimentally to be of pivotal importance for the maintenance of coronary blood flow during increased demand. In humans with coronary atherosclerosis, endothelial vasodilator dysfunction is not confined only to epicardial conductance vessels but may also extend into the coronary microcirculation. We therefore tested the hypothesis that endothelial vasodilator dysfunction of the coronary resistance vasculature is associated with myocardial ischemia during exercise in patients without hemodynamically significant epicardial artery stenoses. METHODS AND RESULTS Coronary vasodilator function was assessed by subselective infusion of the endothelium-dependent dilator acetylcholine (0.036 to 3.6 micrograms/mL) and the endothelium-independent dilator papaverine (7 mg). Coronary blood flow responses were evaluated by intracoronary Doppler flow velocity recordings and quantitative angiography. Exercise-induced myocardial perfusion was determined by 201Tl single photon emission computed tomographic imaging. Thirteen patients had exercise-induced myocardial perfusion defects suggestive of myocardial ischemia, whereas 14 patients had normal thallium imaging during exercise. In patients with exercise-induced thallium perfusion defects, coronary blood flow responses to acetylcholine were significantly (P < .005) blunted compared with patients with normal thallium imaging during exercise. In contrast, coronary blood flow reserve to the endothelium-independent smooth muscle relaxant papaverine was similar in the two groups. Patients with exercise-induced thallium perfusion defects exhibited a significantly (P < .005) reduced (23.9 +/- 9.0% [mean +/- SD]) endothelium-mediated coronary vasodilator capacity compared with patients with normal thallium testing (56.2 +/- 27.8%). Epicardial artery vasoreactivity to acetylcholine did not differ between the two groups. CONCLUSIONS Impaired endothelium-dependent vasodilation of the coronary microcirculation is associated with exercise-induced myocardial ischemia in patients without hemodynamically significant epicardial artery lesions. Endothelial vasodilator dysfunction extending into the coronary microcirculation may thus contribute to the ischemic manifestations of coronary artery disease during times of increased myocardial demand.

18F-DOPA positron emission tomography for tumour detection in patients with medullary thyroid carcinoma and elevated calcitonin levels

Abstract. In spite of the availability of numerous procedures, diagnostic imaging of tumour manifestations in patients with medullary thyroid carcinoma and elevated calcitonin levels is often difficult. In the present study, the new procedure of fluorine-18 dihydroxyphenylalanine positron emission tomography (18F-DOPA PET) was compared with the established functional and morphological imaging methods. After evaluation of the normal distribution of 18F-DOPA, 11 patients with medullary thyroid carcinoma were examined using 18F-DOPA PET. Results of 18F-fluorodeoxyglucose (18F-FDG) PET, somatostatin receptor scintigraphy (SRS) and morphological tomographic imaging (CT/MRI) were available for all patients. All individual procedures were evaluated without reference to prior information. Data assessment for each patient was based on cooperation between experienced radiologists and specialists in nuclear medicine, who considered all the available findings (histological results, imaging, follow-up studies). This cooperation served as the gold standard against which the results of the individual procedures were evaluated. A total of 27 tumours were studied [three primary tumours (PT)/local recurrence (LR), 16 lymph node metastases (LNM) and eight organ metastases (OM)]. 18F-DOPA PET produced 17 true-positive findings (2 PT/LR, 14 LNM, 1 OM), 18F-FDG PET 12 (2 PT/LR, 7 LNM, 3 OM), SRS 14 (2 PT/LR, 8 LNM, 4 OM) and morphological imaging 22 (3 PT/LR, 11 LNM, 8 OM). The following sensitivities were calculated with respect to total tumour manifestations: 18F-DOPA PET 63%, 18F-FDG PET 44%, SRS 52%, morphological imaging 81%. Thus, the morphological imaging procedures produce the best overall sensitivity, but the specificity for PT/LR (55%) and LNM (57%) was low. With respect to lymph node staging, the best results were obtained with 18F-DOPA PET. 18F-DOPA PET is a new functional imaging procedure for medullary thyroid carcinoma that seems to provide better results than SRS and 18F-FDG PET. Moreover, the data indicate that no single procedure provides adequate diagnostic certainty. Therefore, 18F-DOPA PET is a useful supplement to morphological diagnostic imaging, improving lymph node staging and enabling a more specific diagnosis of primary tumour and local recurrence.

Impact of [18F]FDG-PET on the primary staging of small-cell lung cancer

PurposeThe purpose of this study was to evaluate the impact of [18F]fluorodeoxy-d-glucose positron emission tomography (FDG-PET) on the primary staging of patients with small-cell lung cancer (SCLC).MethodsFDG-PET was performed in 120 consecutive patients with SCLC during primary staging. In addition, brain examinations with both FDG-PET and cranial magnetic resonance imaging (MRI) or computed tomography (CT) were performed in 91 patients. Results of FDG-PET were compared with those of conventional staging procedures. FDG-PET detected markedly increased FDG uptake in the primary tumours of all 120 patients (sensitivity 100%).ResultsComplete agreement between FDG-PET results and other staging procedures was observed in 75 patients. Differences occurred in 45 patients at 65 sites. In 47 sites the FDG-PET results were proven to be correct, and in ten, incorrect. In the remaining eight sites, the discrepancies could not be clarified. In 14/120 patients, FDG-PET caused a stage migration, correctly upstaging ten patients to extensive disease and downstaging three patients by not confirming metastases of the adrenal glands suspected on the basis of CT. Only 1/120 patients was incorrectly staged by FDG-PET, owing to failure to detect brain metastases. In all cases the stage migration led to a significant change in the treatment protocol. Sensitivity of FDG-PET was significantly superior to that of CT in the detection of extrathoracic lymph node involvement (100% vs 70%, specificity 98% vs 94%) and distant metastases except to the brain (98% vs 83%, specificity 92% vs 79%). However, FDG-PET was significantly less sensitive than cranial MRI/CT in the detection of brain metastases (46% vs 100%, specificity 97% vs 100%).ConclusionThe introduction of FDG-PET in the diagnostic evaluation of SCLC will improve the staging results and affect patient management, and may reduce the number of tests and invasive procedures.

FDG-PET imaging for the staging and follow-up of small cell lung cancer

Abstract. The staging procedures for small cell lung cancer do not differ appreciably from those for other forms of lung cancer. For practical purposes, the TNM stages are usually collapsed into a simple binary classification: limited disease and extensive disease. This study was performed to answer the question of whether fluorine-18 labelled 2-deoxy-2-D-glucose positron emission tomography (FDG-PET) imaging permits appropriate work-up (including both primary and follow-up staging) of patients presenting with small cell lung cancer, as compared with currently recommended staging procedures. Thirty-six FDG-PET examinations were performed in 30 patients with histologically proven small cell lung cancer. Twenty-four patients were examined for primary staging while four were imaged for therapy follow-up only. Two patients underwent both primary staging and up to four examinations for therapy follow-up. Static PET imaging was performed according to a standard protocol. Image reconstruction was based on an ordered subset expectation maximization algorithm including post-injection segmented attenuation correction. Results of FDG-PET were compared with those of the sum of other staging procedures. Identical results from FDG-PET and the sum of the other staging procedures were obtained in 23 of 36 examinations (6× limited disease, 12× extensive disease, 5× no evidence of disease). In contrast to the results of conventional staging, FDG-PET indicated extensive disease resulting in an up-staging in seven patients. In one patient in whom there was no evidence for tumour on conventional investigations following treatment, FDG-PET was suggestive of residual viability of the primary tumour. Furthermore, discordant results were observed in five patients with respect to lung, bone, liver and adrenal gland findings, although in these cases the results did not affect staging as limited or extensive disease. Moreover, FDG-PET appeared to be more sensitive for the detection of metastatic mediastinal and hilar lymph nodes and bone metastases. Finally, all findings considered suspicious for tumour involvement on the other staging procedures were also detected by FDG-PET. It is concluded that FDG-PET has potential for use as a simplified staging tool for small cell lung cancer.

Activation of a residual cortical network during painful stimulation in long-term postanoxic vegetative state: a 15O–H2O PET study

Survivors of prolonged cerebral anoxia often remain in the persistent vegetative state (PVS). In this study, long-term PVS patients were investigated by 15O-H(2)O PET to analyze their central processing of pain. The study was approved by the local Ethics Committee, the experiments were performed in accordance with the Helsinki Declaration of 2000. Seven patients remaining in PVS of anoxic origin for a mean of 1.6 years (range 0.25-4 years) were investigated. We performed functional PET of the brain using 15O-labelled water during electrical nociceptive stimulation. Additionally, a brain metabolism study using 18F-fluorodeoxyglucose (FDG) PET and multi-sequence MRI (including a 3-D data set) were acquired in all patients. PET data were analyzed by means of Statistical Parametric Mapping (SPM99) and coregistered to a study-specific brain template. MRI and FDG PET showed severe cortical impairment at the structural and the functional level, that is, general atrophy of various degrees and a widespread significant hypometabolism, respectively. Pain-induced activation (hyperperfusion) was found in the posterior insula/secondary somatosensory cortex (SII), postcentral gyrus/primary somatosensory cortex (SI), and the cingulate cortex contralateral to the stimulus and in the posterior insula ipsilateral to the stimulus (P<0.05, small-volume-corrected). No additional areas of the complex pain-processing matrix were significantly activated. In conclusion, the regional activity found at the cortical level indicates that a residual pain-related cerebral network remains active in long-term PVS patients.

Fusion imaging: Combined visualization of 3D reconstructed coronary artery tree and 3D myocardial scintigraphic image in coronary artery disease

Background: In patients with coronary artery disease, coronary angiography is performed for assessment of epicardial coronary artery stenoses. In addition, myocardial scintigraphy is commonly used to evaluate regional myocardial perfusion. These two-dimensional (2D) imaging modalities are typically reviewed through a subjective, visual observation by a physician. Even though on the analysis of 2D display scintigraphic myocardial perfusion segments are arbitrarily assigned to three major coronary artery systems, the standard myocardial distribution territories of the coronary tree correspond only in 50–60% of patients. On the other hand, the mental integration of both 2D images of coronary angiography and myocardial scintigraphy does not allow an accurate assignment of particular myocardial perfusion regions to the corresponding vessels. To achieve an objective assignment of each vessel segment of the coronary artery tree to the corresponding myocardial regions, we have developed a 3D ‘fusion image’ technique and applied it to patients with coronary artery disease. The morphological data (coronary angiography) and perfusion data (myocardial scintigraphy) are displayed in a 3D format, and these two 3D data sets are merged into one 3D image. Results: Seventy-eight patients with coronary artery disease were studied with this new 3D fusion technique. Of 162 significant coronary lesions, 120 (74%) showed good coincidence with regional myocardial perfusion abnormality on 3D fusion image. No regional myocardial perfusion abnormality was found in 44 (26%) lesions. Furthermore, the 3D fusion image revealed 24 ischemic myocardial regions that could not be related to angiographically significant coronary artery lesions. Conclusion: The results of this study demonstrate that our newly developed 3D fusion technique is useful for an accurate assignment of coronary vessel segments to the corresponding myocardial perfusion regions, and suggest that it may be helpful to improve the interpretative and decision-making process in the treatment of patients with coronary artery disease.

Validation of FDG positron emission tomography for differentiation of unknown pulmonary lesions

OBJECTIVE The impact of the (2-(fluorine-18)-fluoro-2-2deoxy-D-glucose)-positron emission tomography ((18)F-FDG-PET) for discrimination of pulmonary lesions was evaluated in a single centre prospective study. METHODS In the study, 109 patients with pulmonary lesions of unknown origin verified by computed tomography were enrolled consecutively (April 1999--May 2000). They were subject to (18)F-FDG-PET diagnostics. (18)F-FDG-PET images were interpreted by two independent nuclear medicine physicians who were blinded to the results of other imaging procedures. In 87 patients, surgery was applied followed by histological investigation, which served as the gold standard. In 22 other patients, extensive tumour load or assumed benign dignity of the lesions prevented surgery. RESULTS Overall sensitivity of (18)F-FDG-PET in 87 resected patients was 0.86. Differentiation in malignant (n = 69) and benign lesions (n = 18) revealed sensitivities of 0.9 and 0.72, respectively. Sensitivity of (18)F-FDG-PET in inflammatory lesions was markedly lower (0.43) than in benign tumours (0.91). Standard uptake values were significantly increased in malignant tumours compared with benign lesions (9.9 and 1.6, respectively; P = 0.035). There was a clear correlation of sensitivity with tumour size with a failure rate of 27% in lesions < or = 1cm (n = 15), 10% (n = 20) in lesions between 1 and 2 cm and 12% (n = 45) above 2 cm. In primary bronchial carcinoma, a clear correlation of sensitivity was observed with regard to tumour grading (G1, three out of five; G2, 24 out of 27; G3, 26 out of 26; and G4, one out of one). Lymph node involvement was correctly suggested in 10 out of 19 (52.6%) patients. However, false positive lymph node enhancement was indicated in one out of 18 (5.5%) operated patients with benign lesions and eight out of 39 (20.5%) with bronchial carcinoma. CONCLUSION (18)F-FDG-PET at present does not serve as the gold standard for early detection of small and well-differentiated tumours. However, it contributes efficiently to the detection of malignancy in tumours >1cm, which are moderately or poorly differentiated. Positive lymph node imaging must not preclude surgery but requires histological proof. Discrimination of benign and malignant pulmonary tumours by (18)F-FDG-PET appears to be hampered in inflammatory lesions.

Comparative diagnostic accuracy of magnetic resonance imaging and immunoscintigraphy for detection of bone marrow involvement in patients with malignant lymphoma.

PURPOSE To compare the diagnostic accuracy of magnetic resonance imaging (MRI) and immunoscintigraphy (IS) for detection of bone marrow infiltration in malignant lymphoma. PATIENTS AND METHODS In 32 patients with Hodgkins disease (HD) or non-Hodgkins lymphoma (NHL), MRI of the axial skeleton and whole-body IS using technetium-99m (99mTc)-labeled monoclonal antibodies were reviewed and compared with iliac crest biopsies. Criterion for marrow infiltration was a positive biopsy or concordant positive results of MRI and IS. RESULTS In 16 patients (50%), MRI, IS, and iliac crest biopsies were negative for marrow infiltration. Iliac crest biopsy showed infiltration in only four patients (13%). Infiltration was missed in two of 32 patients with IS and in one patient with MRI. In one additional patient, MRI was false-positive because of pelvic hematopoietic hyperplasia. A subset of nine patients (28%) with negative biopsies had bone marrow involvement according to MRI and IS with identical location and pattern of infiltration. In eight of these nine patients, diagnostic imaging indicated marrow involvement only in noncrest marrow. Subsequent biopsy confirmed infiltration in five patients. The clinical course suggested true-positive imaging results in the remaining four patients. Two patients (6%) remained equivocal. Overall concordance of MRI and IS for marrow infiltration was 88% (28 of 32 patients). CONCLUSION Diagnostic imaging is essential for optimal staging in malignant lymphoma, as blind biopsies appear to have low sensitivity for bone marrow infiltration because of frequent involvement in noncrest marrow. both imaging modalities show a high rate of detection of bone marrow infiltration.

Comparative diagnostic value and therapeutic relevance of magnetic resonance imaging and bone marrow scintigraphy in patients with metastatic solid tumors of the axial skeleton

PURPOSE To evaluate the comparative impact of magnetic resonance imaging (MRI) and bone marrow scintigraphy (BMS) in bone marrow metastases of solid tumors. METHODS In 20 patients with solid tumors MRI of the axial skeleton and whole-body BMS were retrospectively reviewed. Detectability of metastases, extent of disease and therapeutic implications were assessed. RESULTS In 15/20 (75%) patients MRI and BMS concordantly revealed bone marrow metastases of the axial skeleton. In nine of these 15 patients (60%) MRI showed more metastases. Local radiotherapy or surgery was performed in seven of these cases (78%). BMS detected additional metastases of the appendicular skeleton in 8/15 (53%) patients. In 4/20 cases (20%) the imaging findings were discordant. In three patients with degenerative changes (n=2) or lipoma (n=1) BMS was false positive. In another patient BMS failed to detect metastases proven by MRI and clinical follow-up resulting in subsequent radiation therapy. One patient had normal bone marrow. CONCLUSION MRI appears to be more sensitive and specific in the detection of bone marrow metastases in the axial skeleton and is of clinical importance for subsequent local therapy.

Klinische Wertigkeit der Positronen-Emissions-Tomographie in der Neuromedizin Positionspapier zu den Ergebnissen einer interdisziplinären Konsensuskonferenz

ZusammenfassungDie Positronen-Emissions-Tomographie (PET) ist das derzeit leistungsfähigste Verfahren zur In-vivo-Untersuchung des zerebralen Stoffwechsels. Neben einem breitgefächerten Einsatz von PET in der neuromedizinischen Forschung findet die PET zunehmend auch Eingang in die klinische Diagnostik. Dieser Entwicklung entgegen stehen die relativ hohen Kosten, die mit diesem Verfahren verbunden sind. Die vorliegende Arbeit begründet die, in einer interdisziplinären Konferenz erarbeiteten Konsensusindikationen für den klinischen Einsatz der PET in der Neurologie, Neurochirurgie und Psychiatrie durch Aufarbeitung der einschlägigen Literatur.SummaryTo date, positron emission tomography (PET) is the most powerful method for the in-vivo investigation of human brain metabolism. Besides extensive application of this technology in the neurosciences, PET is also being increasingly used as a clinical tool. However, despite its acceptance in clinical practice, a major obstacle is its high costs. The present article reviews the literature on the clinical use of PET in neurology, neurosurgery, and psychiatry in order to substantiate the clinical indications for PET in these specialties as established by an interdisciplinary conference.