Feasibility of [18F]-2-Fluoro-A85380-PET imaging of human vascular nicotinic acetylcholine receptors in vivo.

OBJECTIVES: The aim of this feasibility study was to evaluate [(18)F]-2-Fluoro-A85380 for in vivo imaging of arterial nicotinic acetylcholine receptors (nAChRs) in humans. Furthermore, potentially different vascular uptake patterns of this new tracer were evaluated in healthy volunteers and in patients with neurodegenerative disorders. BACKGROUND: [(18)F]-2-Fluoro-A85380 was developed for in vivo positron emission tomography (PET) imaging of nAChR subunits in the human brain. These nAChRs are also found in arteries and seem to mediate the deleterious effects of nicotine as a part of tobacco smoke in the vasculature. It has been previously shown that uptake patterns of the radiotracer in the brain differs in patients with neurodegenerative disorders compared with healthy controls. METHODS: [(18)F]-2-Fluoro-A85380 uptake was quantified in the ascending and descending aorta, the aortic arch, and the carotids in 5 healthy volunteers and in 6 patients with either Parkinson's disease or multiple system atrophy, respectively, as the maximum target-to-background ratio. The maximal standardized uptake value values, the single hottest segment, and the percent active segments of the [(18)F]-2-Fluoro-A85380 uptake in the arteries were also assessed. RESULTS: [(18)F]-2-Fluoro-A85380 uptake was clearly visualized and maximum target-to-background ratio uptake values corrected for the background activity of the tracer showed specific tracer uptake in the arterial walls. Significantly higher uptake values were found in the descending aorta. Comparison between volunteers and patients revealed significant differences, with lower [(18)F]-2-Fluoro-A85380 uptake in the patient group when comparing single arterial territories but not when all arterial territories were pooled together. CONCLUSIONS: [(18)F]-2-Fluoro-A85380 can provide specific information on the nAChR distribution in human arteries. Vascular nAChR density seems to be lower in patients with Parkinson's disease or multiple system atrophy. Once confirmed in larger study populations and in the experimental setting, this approach might provide insights into the pathogenic role of nAChRs in the human vasculature.

Resting-state perfusion in nonmedicated schizophrenic patients: a continuous arterial spin-labeling 3.0-T MR study.

PURPOSE: To determine whether well-described patterns of altered perfusion in schizophrenia can be identified by using continuous arterial spin labeling (CASL) with a whole-brain imaging sequence. MATERIALS AND METHODS: This study was approved by the ethics committee of the local institutional review board, and written informed consent was obtained from all subjects. CASL was used to compare cerebral perfusion between 11 nonmedicated patients with schizophrenia and 25 healthy control subjects. Since antipsychotic medication may affect perfusion, only drug-free subjects were examined. Resting-state perfusion, as measured in terms of regional cerebral blood flow, was compared voxel wise by using an analysis of variance design in a statistical parametric mapping program, with patient age and sex as covariates. RESULTS: Compared with the healthy control subjects, the schizophrenic patients had extensive areas of hypoperfusion in the frontal lobes bilaterally, in the anterior and medial cingulate gyri, and in the parietal lobes bilaterally. Increased perfusion was observed in the cerebellum, brainstem, and thalamus of the schizophrenic patients as compared with the perfusion in these areas in the control subjects. CONCLUSION: CASL in schizophrenia revealed patterns of hypo- and hyperperfusion similar to the perfusion patterns in previously published positron emission tomographic and single photon emission computed tomographic studies. The advantages of CASL, including independence from injected contrast agents, no irradiation, and fast acquisition time, may facilitate intensive perfusion studies of the early recognition of schizophrenia and other psychiatric disorders, as well as longitudinal disease-monitoring research of these conditions.

Whole-body high-field-strength (3.0-T) MR imaging in clinical practice. Part II. Technical considerations and clinical applications.

This is the second part of a two-part series on the clinical applications of high-field-strength (3.0-T) magnetic resonance (MR) imaging and spectroscopy. In this part, the current level of evidence regarding the use of higher magnetic field strengths for cardiac imaging techniques (including the assessment of cardiac anatomy and function), breast and pelvic imaging, musculoskeletal applications, pediatric imaging, and MR spectroscopy is presented. Published data are interpreted from the perspective of the clinical radiologist. Specific difficulties associated with high-field-strength MR for body imaging and for spectroscopic applications are reviewed and compared with the expected or documented added value of high-field-strength MR for clinical patient care. The overall number of studies published on clinical body high-field-strength MR is still small, and there is evidence for a clinical advantage for selected, but not all, body MR imaging applications. Even without published evidence, clinical experience suggests substantial clinical advantages for musculoskeletal and pediatric applications.

Feasibility of 18F-fluoromethylcholine PET/CT for imaging of vessel wall alterations in humans--first results.

PURPOSE: Recently published data indicated (18)F-fluorocholine to be feasible for imaging vulnerable atherosclerotic plaques in an animal model. METHODS: Five patients undergoing whole-body (18)F-fluoromethylcholine-((18)F-FMCH-) PET/CT for imaging of prostate cancer disease were retrospectively evaluated. Whole-body PET scans were started immediately after i.v. injection of (18)F-FMCH. About 5-15 min after tracer injection, acquisition of scans of the pelvis and abdomen was performed. PET, CT, and PET/CT slices were generated for review and visual analyses of the abdominal aorta and the common iliac arteries were performed. Vascular findings in examined arteries and surrounding structures due to artifacts were excluded from further analysis. The lower threshold of (18)F-FMCH uptake was set above the background activity within the examined vessels. Morphological classification of vessel wall alterations (WA) included structural wall alterations without additional calcification (SWA), structural wall alterations associated with calcifications (SWC), and solely calcified lesions (CL). They were correlated with (18)F-FMCH uptake qualified as present and vice versa. RESULTS: A total of 31 WA were identified. Positive (18)F-FMCH uptake was found in 14 lesions (SWA: n = 5; SWC: n = 9). Sixteen of 17 (18)F-FMCH negative lesions were identified as CL without additional structural vessel wall alteration. One SWA did not show any (18)F-FMCH accumulation. None of the CLs as well as unaltered parts of the vessel wall showed (18)F-FMCH uptake. CONCLUSIONS: Our initial data in five patients with a total of 31 vessel wall alterations show promising results indicating for the first time the feasibility of (18)F-FMCH for in vivo imaging of structural WA in humans.

Myocardial uptake characteristics of three 99mTc-labeled tracers for myocardial perfusion imaging one hour after rest injection.

OBJECTIVE: 99mTc-tetrofosmin and 99mTc-sestamibi are approved tracers for myocardial perfusion studies. Recently, a 99mTc-MIBI preparation from a different manufacturer (99mTc-cardiospect-MIBI) has been introduced to the market. Therefore, the aim of this study was the evaluation of 99mTc-tetrofosmin as well as of two different 99mTc-labeled MIBI tracers with regard to differences in imaging quality under resting conditions. METHODS: Sixty patients (mean age 63.8 years +/- 1.25) with known or suspected coronary artery disease but without evidence of rest-ischemia were included. Twenty patients in each group were examined by a two-day-rest-stress protocol using the three 99mTc-labeled tracers. Visual analysis of all images was performed by two experienced physicians blinded with regard to the applied tracer. Regions of interest (ROI) were defined over the heart, lung and whole body only in the rest imaging in order to calculate heart-to-lung, lung-to-whole body-, and heart-to-whole body-ratios. RESULTS: The heart-to-lung ratio was statistically significant higher for 99mTc-cardiospect-MIBI as compared to 99mTc-sestamibi as well as to 99mTc-tetrofosmin. Furthermore, a significantly higher heart-to-lung ratio was found for 99mTc-sestamibi as compared to 99mTc-tetrofosmin. The heart-to-whole body-ratio and the lung-to-whole body-ratio were equivalent between all tracers. Visual analysis revealed only slight differences regarding image quality between all tracers. CONCLUSIONS: ROI analysis surprisingly revealed a significant higher myocardial uptake and consequently a higher heart-to-lung ratio for 99mTc-cardiospect-MIBI. Whether this leads to a better visual image quality has to be evaluated in future studies with larger study populations as well as semiquantitative segmental analysis of the myocardial perfusion images.

[A case of arteria cerebri aneurysm, sepsis, and miliary lung infiltrates in a 32-year-old woman]. / Arteria-cerebri-Aneurysma, Sepsis und miliare Lungenrundherde bei einer 32-jährigen Patientin.

BACKGROUND: Miliary tuberculosis is a rare manifestation of tuberculosis with a high mortality rate. Diagnosis may easily be missed when severe neurologic symptoms are the first clinical manifestation. A typical case of miliary tuberculosis is reported, with special regard to the problems of diagnostic work-up. The need for an early empirical therapy for suspected military tuberculosis is emphasized in particular. CASE REPORT: A 32-year-old Moroccan woman was admitted to the hospital with aphasia and a hemiparesis due to an intracerebral hemorrhage caused by a ruptured septic A. cerebri media aneurysm. Despite intensive work-up no septic focus could be found. Chest radiograph and computerized tomography (CT) showed miliary consolidations in the lungs. Skin testing (Tuberkulin Behring GT5) and smears for acid-fast bacilli and polymerase chain reaction (PCR) for tuberculosis of bronchoalveolar lavage (BAL) were negative. A four-drug antituberculous regimen (rifampicin [RMP], isoniazid [INH], pyrazinamide [PZA], ethambutol [EMB]) was initiated, and resulted in normalization of temperature, blood pressure, and C-reactive protein. Subsequently, cultures of BAL yielded Mycobacterium tuberculosis. The patient was discharged, a two-drug regimen was conducted (RMP, INH) after 2 months. Follow-up of the patient showed a significant improvement of the miliary lung consolidations after 5 months in CT of the lung. Only minor neurologic symptoms persisted after cessation of the therapy. CONCLUSION: In developed countries, miliary tuberculosis is a very rare cause of septic infiltrative lung disease. However, due to the nonspecific nature of the presentation and despite improved diagnostic techniques, a high clinical suspicion is essential for successful treatment.

Three-dimensional dynamic susceptibility-weighted perfusion MR imaging at 3.0 T: feasibility and contrast agent dose.

PURPOSE: To prospectively investigate if T2*-weighted dynamic susceptibility-weighted first-pass perfusion magnetic resonance (MR) imaging is feasible at 3.0 T and which dose of contrast agent is suitable for high-field-strength imaging. MATERIALS AND METHODS: Informed consent was obtained from all participants; study protocol was approved by the institutional review board. Study included three volunteers (two men, one woman aged 35, 39, and 52 years) and 26 patients (mean age, 49 years +/- 12.8 [standard deviation]; range, 19-76 years). Volunteers underwent 3.0-T perfusion MR imaging with 0.20, 0.10, and 0.05 mmol per kilogram body weight of gadopentetate dimeglumine; patients underwent imaging with 0.10- and 0.05-mmol doses. Perfusion MR imaging was performed with three-dimensional echo-shifted echo-planar imaging (repetition time msec/echo time msec, 14/21; isotropic 4 mm3 voxels; 50 dynamic volumes with 30 sections each, covering entire brain at temporal resolution of 1.5 seconds per MR image). Quality of source echo-planar images and perfusion maps was assessed; perfusion maps obtained at studies with different contrast media doses were compared. Quantitative perfusion values and diagnostic sensitivity of perfusion studies with 0.10-mmol dose were compared with results with 0.05-mmol dose. Image quality scores were compared with marginal homogeneity test for multinomial variables (Mantel-Haenszel statistics for ordered categorized values). Signal-to-noise ratio and baseline signal intensity in perfusion studies were tested (Student t test for paired samples). Mean transit time (MTT), negative integral (NI), and maximum T2* effect from region-of-interest analysis were compared (one-tailed Student t test for paired samples). Quantitative data on number of gamma-fitted pixels were compared (t test for paired samples). Difference with P=.05 (t test for paired samples) was considered significant. RESULTS: Perfusion image quality was satisfactory even in areas close to skull base (47 of 52 images, minor distortions; remaining images, marked distortions). Perfusion imaging with 0.20-mmol dose caused almost complete signal cancellation during first pass, particularly in cortical gray matter, since mean maximum T2* effect of 98%, 99%, and 98% for gray matter was reached such that the accurate calculation of perfusion maps was impossible. With 0.10-mmol dose, the NI and maximum T2* effect were comparable to published data for 1.5-T perfusion imaging with 0.20- and 0.05-mmol doses; perfusion maps of sufficient diagnostic quality were obtained. For gray matter, mean maximum T2* effect was 25.4% +/- 9.8 with 0.10-mmol dose and 17.5% +/- 9.0 with 0.05-mmol dose. For white matter, mean maximum T2* effect was 15.2% +/- 4.5 with 0.10-mmol dose and 7.7% +/- 2.9 with 0.05-mmol dose. Difference in maximum signal intensity decrease was significant (P <.01). For NI, the difference between 0.10- and 0.05-mmol doses was significant: For gray matter, mean NI was 3.1 +/- 1.60 for 0.10-mmol dose and 1.56 +/- 1.16 for 0.05-mmol dose. For white matter, mean NI was 1.35 +/- 0.59 with 0.1-mmol dose and 0.59 +/- 0.30 with 0.05-mmol dose. CONCLUSION: With echo-shifted multishot echo-planar imaging, dynamic susceptibility-weighted perfusion MR imaging at high field strength is feasible without relevant image distortions. Compared with contrast agent dose for 1.5 T imaging, the dose for 3.0 T can be reduced to 0.10 mmol.

Novelty detection and repetition suppression in a passive picture viewing task: a possible approach for the evaluation of neuropsychiatric disorders.

The applicability of functional magnetic resonance imaging (fMRI) in patients with Alzheimer's disease (AD) or schizophrenia is frequently limited by cognitive impairment, which prevents the adequate execution of complex tasks. An experimental design that puts only minor demands on the patients' cognitive ability but engages disease-relevant brain structures would be of benefit. Novelty detection and repetition suppression are two basic components of memory that might be used to investigate specific brain areas under these conditions. Novelty detection has been related to hippocampal activation increases. Stimulus repetition related activation decreases (suppression) have been observed in the extrastriate cortex and have been related to perceptual priming. Both processes have been examined primarily in neuroimaging studies with complex cognitive tasks. We used event-related fMRI to investigate novelty- and repetition-related effects in an attended but passive picture-viewing task in healthy subjects. The differential activation, detected in the novel vs. repeated contrast, was located in the bilateral anterior hippocampus and in bilateral occipital and inferior-temporal areas. The hippocampal activation is of interest because medial temporal lobe lesions are key features in AD and schizophrenia. The repetition-related activation decreases in the extrastriate areas are of potential value in investigating the conflicting results regarding perceptual priming impairment in both disorders. Our results indicate that activation of disease-relevant brain regions under passive task conditions is possible. This might increase the utility of functional imaging in cognitively impaired patients.

Regional N-acetylaspartate reduction in the hippocampus detected with fast proton magnetic resonance spectroscopic imaging in patients with Alzheimer disease.

OBJECTIVE: To detect regional metabolic changes that resemble the expected spatial pattern of neuronal loss in patients with Alzheimer disease (AD). METHODS: Thirty-four patients with AD and 22 healthy control subjects were included in the study. Single-slice fast proton spectroscopic imaging was performed in parallel angulation to the temporal lobes. Proton spectra were selected from the hippocampus, the lateral temporal lobe, and the occipital lobe of both hemispheres to determine metabolite concentration of N-acetylaspartate (NAA), total creatine (tCr), including phosphocreatine and creatine, and choline-containing compounds (Cho). The metabolic ratios of NAA/tCr and Cho/tCr were calculated and compared between patients with AD and healthy volunteers. RESULTS: The NAA/tCr ratios were significantly reduced in the left (F(1,1) = 4.34, P =.04) and right hippocampus (F(1,1) = 9.96, P =.003) in patients with AD. The Cho/tCr ratios remained unchanged in both hippocampi. There was no significant change of either NAA/tCr or Cho/tCr in the lateral temporal and occipital lobes of patients with AD. CONCLUSION: This study provides evidence that fast proton spectroscopic imaging may detect the regional pattern of disturbed neuronal integrity in patients with AD with high spatial resolution in a short acquisition time.