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Biomedical subjects

K Brechtel

Publications and source records attributed to K Brechtel.

At least 19 recordsLinked to original sources

[Evaluation of different breathing and contrast-protocols concerning quality and alignment in 18F-FDG PET/CT].

PURPOSE: The purpose of this study was to establish a reliable and simple parameter for alignment evaluation and the evaluation and optimization of state-of-the-art contrast-enhanced examination protocols for (18)F FDG-PET/CT. MATERIALS AND METHODS: 44 consecutive patients were referred to 4 examination protocols. Group A and B underwent single-phase, contrast-enhanced CT (90 s delay) performed either during free shallow breathing (FA; group A) or normal expiration (NormExp; group B). Groups C and D underwent arterial and portal venous multiphase examinations performed during FA (group C) or during NormExp (group D) followed by a low-dose CT scan for attenuation correction. Organ displacement in the cranio-caudal direction was correlated with a 3D-vectorial shift. For alignment evaluation discrepancies with respect to size and liver location, the spleen and kidneys were calculated. Additionally, the groups were compared with regard to the presence of CT artifacts. RESULTS: Cranio-caudal organ shift and 3D-vectorial shift showed a high correlation (r > 0.8). Single-phase CT scans performed during NormExp yielded better image quality (p < 0.001) and alignment (p < 0.01 for liver, spleen and right kidney) than those performed during FA. Differences in organ size did not differ during FA and NormExp. Depending on the evaluated organ, breathing and contrast protocol misalignment was in the cranio-caudal direction 0-27 mm (mean: 6.8; standard deviation: +/- 4.9) in multiphase CT compared to 0 - 11 mm (mean: 4.5 +/- 2.3) in single-phase examinations. CONCLUSION: 1. Organ shift in the cranio-caudal direction is a good and simple parameter for alignment evaluation. 2. Alignment and CT quality are best in expiration protocols. 3. Despite comparatively low alignment quality, integrated multiphase CT examinations show acceptable quality and alignment.

Aged↗

Intrinsic locomotor outcome in dorsal transection of rat spinal cord: predictive value of minimal incision depth.

STUDY DESIGN: Experimental, prospective, blinded, animal study. OBJECTIVES: Subtotal transection models in rodents are widely used in spinal cord injury (SCI) research. In this model, we investigate the effect of the dorso-ventral incision depth (ID) of the spinal cord on functional locomotor outcome using the Basso, Beattie, Bresnahan (BBB) scale. We introduce the minimal incision depth (ID(min)) and the average lesion depth (ID(mean)) as reliable, fast and easily available predictive parameters for intrinsic locomotor function. SETTING: Tuebingen, Germany. METHODS: Dorsal over-hemisection at the level of T8 was performed in male Lewis rats. Functional outcome 4 weeks after SCI and histological analysis of the lesion were studied and correlated in 36 animals. Animals reaching weight support (BBB> or =9) were considered as having reached functional recovery. Data analysis was performed in linear (ordinary least squares; OLS) and nonlinear (logistic) regression models for correlation of histological parameters and functional outcome. RESULTS: BBB scores revealed a strong correlation with ID(mean) and ID(min), showing a higher value in predicting functional outcome for the latter parameter. Based on logistic regression analysis, animals with an ID(min) of 69% would have a 95% probability of reaching weight support. CONCLUSION: These results demonstrate that histological analysis is crucial when functional outcome parameters are used in the dorsal over-hemisection SCI model. A simple and feasible histological evaluation can reliably predict spontaneous functional locomotor recovery in dorsal transection models and could provide a simple tool to identify treatment effects of new experimental therapeutic approaches.

Animals↗

[Large vessel vasculitis as cause of fever of unknown origin (FUO) or systemic inflammation. Diagnosis using 18-F-fluor-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)].

BACKGROUND: Diagnosis and treatment of FUO or systemic inflammation with unknown reason are still a great challenge for the treating physician. We used (18)F-FDG-PET for further diagnostic work in patients in whom a diagnosis could not be established despite intensive diagnostic efforts. METHODS/RESULTS: We studied nine patients with (18)F-FDG-PET. Two female patients with known Takayasu's arteritis but undefined disease activity, and seven patients with the clinical suspicion of an underlying large vessel vasculitis. The diagnosis of active vasculitis could be confirmed by the PET-results in eight patients. Active vasculitis could be nearly ruled out in one. The diagnoses could be confirmed by follow-up visits. CONCLUSION: (18)F-FDG-PET is a useful diagnostic tool in patients with unclear systemic inflammation and FUO. Especially when large vessel vasculitis is suspected, further diagnostic work by PET seems to be of benefit. Furthermore, it offers the opportunity to evaluate disease activity and to check which vessels are involved.

Adult↗

The LPS receptor (CD14) links innate immunity with Alzheimer's disease.

To rapidly respond to invading microorganisms, humans call on their innate immune system. This occurs by microbe-detecting receptors, such as CD14, that activate immune cells to eliminate the pathogens. Here, we link the lipopolysaccharide receptor CD14 with Alzheimer's disease, a severe neurodegenerative disease resulting in dementia. We demonstrate that this key innate immunity receptor interacts with fibrils of Alzheimer amyloid peptide. Neutralization with antibodies against CD14 and genetic deficiency for this receptor significantly reduced amyloid peptide induced microglial activation and microglial toxicity. The observation of strongly enhanced microglial expression of the LPS receptor in brains of animal models of Alzheimer's disease indicates a clinical relevance of these findings. These data suggest that CD14 may significantly contribute to the overall neuroinflammatory response to amyloid peptide, highlighting the possibility that the enormous progress currently being made in the field of innate immunity could be extended to research on Alzheimer's disease.

Alzheimer Disease↗

Effects of statins on human cerebral cholesterol metabolism and secretion of Alzheimer amyloid peptide.

Cerebral cholesterol metabolism has been linked with production of amyloid peptide (Abeta) crucial in AD. The association between use of cholesterol-lowering drugs (statins) and AD disease is currently being intensely discussed. In this case-control study on elderly nondemented subjects, the authors provide the first evidence that statins in clinically relevant dosages indeed affect cerebral cholesterol metabolism. However, these changes were not associated with altered intrathecal secretion of Alzheimer Abeta.

Aged↗

Perivenous expression of the mRNA of the three hypoxia-inducible factor alpha-subunits, HIF1alpha, HIF2alpha and HIF3alpha, in rat liver.

The cDNAs of three hypoxia-inducible factor (HIF) alpha-subunits were cloned from RNA of primary rat hepatocytes by reverse transcriptase PCR. All three cDNAs encoded functionally active proteins, of 825, 874 and 662 amino acids. After transfection they were able to activate luciferase activity of a luciferase gene construct containing three HIF-responsive elements. The mRNAs of the rat HIF alpha-subunits were expressed predominantly in the perivenous zone of rat liver tissue; the nuclear HIFalpha proteins, however, did not appear to be zonated.

Amino Acid Sequence↗

Fast elevation of the intramyocellular lipid content in the presence of circulating free fatty acids and hyperinsulinemia: a dynamic 1H-MRS study.

The influence of a short-term elevation of free fatty acids (FFAs) on intramyocellular lipids (IMCL) under hyperinsulinemic conditions was monitored in five healthy male subjects in the course of a 5-hr hyperinsulinemic glucose clamp. During the glucose clamp a lipid emulsion (Intralipid 20(R)) and heparin were administered intravenously. IMCL was quantified in the tibialis anterior (TA) and the soleus (SOL) muscle by (1)H-MRS. A rapid elevation of the IMCL pool was found in both muscles (61% in TA and 22% in SOL) in the 5-hr time period. A control hyperinsulinemic glucose clamp in the same study group, repeated without elevation of circulating FFAs, did not lead to significant changes in IMCL for both muscles. The present study shows for the first time that only the combination of high concentrations of FFAs and insulin lead to marked storage of lipids in skeletal muscle cells in humans. Magn Reson Med 45:179-183, 2001.

Adult↗

Utilisation of intramyocellular lipids (IMCLs) during exercise as assessed by proton magnetic resonance spectroscopy (1H-MRS).

Recently, a 1H-MRS method became available to quantify intramyocellular lipids (IMCL) non-invasively. Currently, little is known about the regulation of this lipid pool. During prolonged exercise of moderate intensity, non-plasma-derived fatty acids play an important role as an energy source; lipids located within the skeletal muscle are considered to be a major source for these fatty acids. To see whether IMCL are reduced by exercise, 12 male runners were studied before and after exercising at different workloads and duration. Six subjects participated in a non-competitive run (NCR), three runners in a competitive half marathon (HM, 21 km) and another three in a competitive marathon (M, 42 km). Intra- and extramyocellular lipids were quantified by 1H-MR spectroscopy in the tibialis anterior (TA) and soleus (SOL) muscles prior to and after the exercise bout. Moderate intensity (MI; 60-70% VO2max in NCR) with a mean exercise time (MET) ranging between 105-110 min decreased IMCL by 10 - 36% in both muscles. Prolonged MI exercise (MET 210-240 min; 68-70% VO2max in M) reduced IMCL by 42-57% in TA and 27 - 56% in SOL. In contrast, high intensity exercise (HI; MET 80-120 min; 83-85% VO2max in HM) did not alter IMCL in either muscle. Extramyocellular lipids (EMCL) did not show any significant change in any group. The data show that one bout of moderate-intensity (60-70% VO2max) aerobic exercise markedly reduces the IMCL in TA and SOL muscles in a time-dependent fashion as assessed by 1H-MRS. However, exercise of similar duration but higher workload (> 80% VO2max) does not reduce IMCL. These data suggest that both exercise duration and workload are important factors in determining the reduction of IMCL.

Adult↗

[2D-phase contrast flow evaluation and contrast-enhanced MR angiography for perioperative assessment of internal mammary artery grafts].

PURPOSE: To evaluate LV functional parameters, graft flow and patency in patients with IMA grafts using a combined MR protocol with phase-contrast technique and contrast enhanced MR angiography. MATERIAL AND METHODS: Using a 1.5 T MR system 27 patients with 27 left internal mammary artery (LIMA) and 41 venous grafts were examined before and 6 months after CABG surgery. A T(1)w-TSE sequence (slice thickness 5 mm) was applied for morphological imaging. LV function (EF, CO) was evaluated on cine images (segmented FLASH 2D, TR(eff) 11 ms, TE 4.8 ms, flip angle 25 degrees ). A phase-contrast FLASH 2D (TR 24 ms, TE 5 ms, flip angle 20 degrees ) sequence was applied for aortic and IMA flow measurements. Postoperatively, a contrast enhanced FLASH 3D MR angiography (TR 3.8 ms, TE 1.4 ms, flip angle 30 degrees ) with 25 ml Gd-DTPA was performed to assess bypass patency. RESULTS: In patients with reduced LV function (ejection fraction < 50 %) an improvement of the ejection fraction from 38.4 +/- 10.3 % to 49.8 +/- 15.3 % (p < 0.05) was found postoperatively. LIMA grafts were occluded in 1/27 patients, while 6/41 venous grafts were occluded. Distal LIMA anastomoses were demonstrated in 33 % by MRA. Flow of LIMA decreased from 21.2 +/- 11 ml/min/m(2) preoperatively to 14.4 +/- 9.6 ml/min/m(2) postoperatively (p < 0.01). CONCLUSION: MR imaging allows accurate combined assessment of LV function, bypass patency and flow. The protocol of this study may be applicable for perioperative follow-up studies in patients after CABG surgery.

Aged↗

Effects of intravenous and dietary lipid challenge on intramyocellular lipid content and the relation with insulin sensitivity in humans.

An increased intramyocellular lipid (IMCL) content, as quantified by (1)H-magnetic resonance spectroscopy ((1)H-MRS), is associated with reduced insulin sensitivity. At present, it is unclear which factors determine IMCL formation and how rapidly IMCL accumulation can be induced. We therefore studied the impact of hyperinsulinemia and elevated circulating nonesterified fatty acid (NEFA) levels on IMCL formation and insulin sensitivity. We further evaluated the influence of a high-fat diet on IMCL storage. In the infusion protocol, 12 healthy male subjects underwent a 6-h hyperinsulinemic-euglycemic glucose clamp with concomitant infusion of Intralipid plus heparin. IMCL was quantified by (1)H-MRS in soleus (SOL) and tibialis anterior (TA) muscle at baseline and then every hour. IMCL levels started to increase significantly after 2 h, reaching a maximum of 120.8 +/- 3.4% (SOL) and 164.2 +/- 13.8% (TA) of baseline after 6 h (both P < 0.05). In parallel, the glucose infusion rate (GIR) decreased progressively, reaching a minimum of 60.4 +/- 5.4% of baseline after 6 h. Over time, the GIR was strongly correlated with IMCL in TA (r = -0.98, P < or = 0.003) and SOL muscle (r = -0.97, P < or = 0.005). In the diet protocol, 12 male subjects ingested both a high-fat and low-fat diet for 3 days each. Before and after completion of each diet, IMCL levels and insulin sensitivity were assessed. After the high-fat diet, IMCL levels increased significantly in TA muscle (to 148.0 +/- 16.9% of baseline; P = 0.005), but not in SOL muscle (to 114.4 +/- 8.2% of baseline; NS). Insulin sensitivity decreased to 83.3 +/- 5.6% of baseline (P = 0.033). There were no significant changes in insulin sensitivity or IMCL levels after the low-fat diet. The effects of the high-fat diet showed greater interindividual variation than those of the infusion protocol. The data from the lipid infusion protocol suggest a functional relationship between IMCL levels and insulin sensitivity. Similar effects could be induced by a high-fat diet, thereby underlining the physiological relevance of these observations.

Adult↗

Persistent accumulation of cyclooxygenase-1 (COX-1) expressing microglia/macrophages and upregulation by endothelium following spinal cord injury.

Acute inflammation following spinal cord injury results in secondary injury and pathological reorganisation of the central nervous system (CNS) architecture. Cyclooxygenases (Prostaglandin Endoperoxide H Synthases, PGH) are key enzymes in the conversion of arachidonic acid into prostanoids which mediate immunomodulation, mitogenesis, apoptosis, blood flow, secondary injury (lipid peroxygenation) and inflammation. Here, we report cyclooxygenase-1 (COX-1) expression following spinal cord injury. In control spinal cords, COX-1 expression was localized by immunohistochemistry to ependymal cells, some neurons, inclusive dorsal and ventral root ganglion cells, few endothelial cells but rarely to brain microglia/macrophages. In injured spinal cords, COX-1(+) microglia/macrophages accumulated highly significantly (P<0.0001) at peri-lesional areas and in the developing necrotic core early after injury. Here numbers of COX-1(+) cells remained persistently elevated up to 4 weeks following injury. Further, COX-1(+) cells were located in perivascular Virchow-Robin spaces, between spared axons and in areas of Wallerian degeneration. Double labeling experiments confirmed co-expression of COX-1 by ED-1(+) and OX-42(+) microglia/macrophages. Transiently after infarction most COX-1(+) microglia/macrophages coexpress the activation antigen OX-6 (MHC class II). However, the prolonged accumulation of COX-1(+) microglia/macrophages at the lesion site enduring the acute post injury inflammatory response points to a role of COX-1 in tissue remodeling or secondary injury. We have identified and localized persistent accumulation of COX-1 expressing cells which might be a potential pharmacological target following spinal cord injury. Therefore, we suggest that approaches based on: (i) short-term; and (ii) selective COX-2 blocking alone might not be a sufficient tool to suppress the local synthesis of prostanoids.

Animals↗

Acquired generalized lipoatrophy (AGL): highly selective MR lipid imaging and localized (1)H-MRS.

Frequency-selective chemical shift magnetic resonance (MR) imaging was applied on the calf musculature and the abdomen of a patient with acquired generalized lipoatrophy (AGL; Lawrence syndrome), a very rare syndrome affecting selectively several types of adipose tissue accompanied by alterations in glucose and energy metabolism. In addition, (1)H-MRS was used for assessment of intra- (IMCL) and extramyocellular lipid stores (EMCL) in the skeletal musculature of the calf. Results from the AGL patient were compared with an age-matched group of five healthy volunteers. Fat-selective imaging of the calf revealed a total lack of subcutaneous adipose tissue. No EMCL signal was found in the spectra from the soleus muscle of the AGL patient. IMCL signals were present in the spectra but were clearly lower than in the controls (14% of normal value in the soleus muscle). In abdominal images, subcutaneous fat signal was not detectable, as in the calf, but nearly normal conditions were shown for visceral adipose tissue between abdominal organs. Fat-selective images showed the liver with high signal intensity, indicating hepatic steatosis combined with hepatosplenomegaly. Modern chemical shift-selective MR imaging and localized spectroscopy allow a noninvasive and quantitative assessment of tissue composition in patients with disorders of carbohydrate and lipid metabolism.

Adipose Tissue↗

[Variability in the MR tomographic determination of myocardial function and perfusion parameters in health subjects].

PURPOSE: The aim of the study was to evaluate myocardial function and perfusion patterns using magnetic resonance imaging in normal subjects. MATERIALS AND METHODS: 22 healthy volunteers were examined. Cine-mode acquisitions along all three axes of the heart were generated and perfusion was measured on a mid-ventricular short-axis view. Myocardial wall thickening was scored and contrast enhancement during the first pass was analysed. RESULTS: For myocardial wall thickening increasing values from base (24-86%) to apex (63-106%) were found. Contrast enhancement patterns showed regional variability. In addition marked individual differences were detectable. CONCLUSION: Perfusion patterns should be interpreted only in combination with functional parameters. Standard values for perfusion measurements cover very large range as a result of the high individual variability.

Adult↗

Fat- and water-selective MR cine imaging of the human heart: assessment of right ventricular dysplasia.

RATIONALE AND OBJECTIVES: The purpose of this study was to develop and implement MR sequences for chemical shift-selective breath-hold cine imaging of the heart. Fibroadipose conversion of myocardium in cases suspected of right ventricular dysplasia should be revealed in fat- and water-selective MR images of high quality. METHODS: Frequency-selective saturation of one chemical shift component was applied in modified k-space-segmented, electrocardiography-gated sequences, allowing high-quality cine imaging of the human heart in a single breath-hold. Phantom studies and human examinations in eight normal subjects (aged 24-62 years) and in seven patients (aged 31-47 years) with suspected right ventricular dysplasia were performed. The patients showed suspicious findings, such as a dyskinetic and dilated right ventricle combined with ventricular arrhythmia, and underwent MR imaging after exclusion of other possible reasons (eg, coronary artery disease or pulmonary hypertension). RESULTS: High selectivity to the desired chemical shift component was confirmed by test measurements in a phantom containing water and lipids. In the human subjects, minor problems with magnetic field inhomogeneities appeared in the thoracic walls only. Four patients with suspected right ventricular dysplasia showed clearly abnormal signal behavior of the right myocardial wall in both fat- and water-selective cine images. Bright transmural structures were exhibited in fat-selective images, but the origin of the fat (epicardium or infiltrated myocardium) was often difficult to assess. CONCLUSIONS: Right ventricular areas with fibrosis and fatty degeneration often show normal signal intensity in standard T1-weighted images but can be differentiated from normal tissue by the new chemical shift-selective breath-hold cine techniques.

Adipose Tissue↗

[Optimization of numerical measurement parameters for ECG-triggered MRI snapshot-FLASH myocardial perfusion studies].

BACKGROUND AND AIMS: In MR examinations of myocardial perfusion by the use of Snapshot-FLASH sequences it is of major importance that the achievable signal difference between pre- and normal postcontrast myocardium be maximized. METHODS: In ECG-triggered Snapshot-FLASH sequences the signal intensity of the myocardium depends on the flip angle alpha, the inversion time TI and the trigger delay TD (both depending on the cardiac frequency f) for unchanged slice thickness (SL), matrix size (MA), repetition time (TR) and echo time (TE). Therefore a simulation of the signal behavior of pre- and postcontrast myocardium based on Bloch's equations was performed by varying the flip angle alpha, TI and TD for different cardiac frequencies in order to determine an optimized combination of the measurement parameters. RESULTS: In normal heart rates (50-70 beats/min) maximal signal differences between pre- and normal postcontrast myocardium can be reached for inversion times TI = 170-200 ms and a flip angle alpha = 11 degrees. For higher heart rates again alpha = 11 degrees and TI = 200-220 ms with shortened TD (TD = 0 for f > 90 beats/min) were found to be optimal. The calculated values were semiquantitatively confirmed in phantom and volunteer measurements. CONCLUSIONS: The described method allows cardiac frequency dependent optimization of the Snapshot-FLASH measurement parameters alpha, TI and TD in order to reach a maximum in signal contrast between normal and malperfused myocardium.

Computer Graphics↗

Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects.

Insulin resistance plays an important role in the pathogenesis of type 2 diabetes; however, the multiple mechanisms causing insulin resistance are not yet fully understood. The aim of this study was to explore the possible contribution of intramyocellular lipid content in the pathogenesis of skeletal muscle insulin resistance. We compared insulin-resistant and insulin-sensitive subjects. To meet stringent matching criteria for other known confounders of insulin resistance, these individuals were selected from an extensively metabolically characterized group of 280 first-degree relatives of type 2 diabetic subjects. Some 13 lean insulin-resistant and 13 lean insulin-sensitive subjects were matched for sex, age, BMI, percent body fat, physical fitness, and waist-to-hip ratio. Insulin sensitivity was determined by the hyperinsulinemic-euglycemic clamp method (for insulin-resistant subjects, glucose metabolic clearance rate [MCR] was 5.77+/-0.28 ml x kg(-1) x min(-1) [mean +/- SE]; for insulin-sensitive subjects, MCR was 10.15+/-0.7 ml x kg(-1) x min(-1); P<0.002). Proton magnetic resonance spectroscopy (MRS) was used to measure intramyocellular lipid content (IMCL) in both groups. MRS studies demonstrated that in soleus muscle, IMCL was increased by 84% (11.8+/-1.6 vs. 6.4+/-0.59 arbitrary units; P = 0.008 ), and in tibialis anterior muscle, IMCL was increased by 57% (3.26+/-0.36 vs. 2.08+/-0.3 arbitrary units; P = 0.017) in the insulin-resistant offspring, whereas the extramyocellular lipid content and total muscle lipid content were not statistically different between the two groups. These data demonstrate that in these well-matched groups of lean subjects, IMCL is increased in insulin-resistant offspring of type 2 diabetic subjects when compared with an insulin-sensitive group matched for age, BMI, body fat distribution, percent body fat, and degree of physical fitness. These results indicate that increased IMCL represents an early abnormality in the pathogenesis of insulin resistance and suggest that increased IMCL may contribute to the defective glucose uptake in skeletal muscle in insulin-resistant subjects.

Adult↗