Juvenile idiopathic arthritis of the knee: is contrast needed to score disease activity when using an augmented MRI protocol comprising PD-weighted sequences?

OBJECTIVE: To compare unenhanced versus enhanced knee joint magnetic resonance imaging (MRI) to assess disease activity of juvenile idiopathic arthritis (JIA). METHODS: Fifty-three knee joint MRI examinations were performed on a 3-Tesla system in 27 patients (age: 11.40 ± 3.61 years; 21 females, 6 males). MRI protocols comprised PD-weighted sequences in addition to the widely used standard protocol. JIA subgroups comprised oligoarticular arthritis (n = 16), extended oligoarthritis (n = 6), rheumatoid factor-negative polyarticular arthritis (n = 3), enthesitis-related arthritis (n = 1), and psoriatic arthritis (n = 1). MR images were retrospectively analyzed by 3 experienced radiologists in two readings, using JAMRIS (juvenile arthritis MRI scoring) system and a modified IPSG (international prophylaxis study group) classification. In the first reading session, only unenhanced MR images were evaluated. In a second reading session, all images before and after contrast medium application were included. In order to avoid bias, an interval of at least 2 weeks was set between the two readings. The clinical JADAS10 (juvenile arthritis disease activity score) was calculated including clinical assessment and laboratory workup and correlated with MRI scores. Statistical analysis comprised Pearson's correlation for correlating two scoring results of unenhanced and the enhanced MRI, intra-class correlation coefficient (ICC) for inter- and intra-reader agreement. Diagnostic accuracy was calculated using ROC (receiver operating characteristics) curve analysis. RESULTS: Inter-reader agreement determined by ICC for unenhanced and enhanced MRI scores for IPSG was moderate (0.65, 95% CI 0.51-0.76, and 0.62, 95% CI 0.48-0.75) and high for JAMRIS (0.83, 95% CI 0.75-0.89, and 0.82, 95% CI 0.74-0.89). Intra-reader agreement was good to very good for JAMRIS (0.85 95% CI 0.81-0.88, 0.87 95% CI 0.83-0.89 and 0.96 95% CI 0.92-0.98) and IPSG (0.76 95% CI 0.62-0.86, 0.86 95% CI 0.77-0.92 and 0.92 95% CI 0.86-0.96). Scores of unenhanced MRI correlated with contrast-enhanced MRI: JAMRIS (r = 0.97, R2 = 0.93, p < 0.01), modified IPSG (r = 0.95, R2 = 0.91, p < 0.01). When using JADAS10 as a reference standard, moderate accuracy for both unenhanced and enhanced MRI scores was noted: JAMRIS (AUC = 0.68, 95% CI 0.51-0.85, and AUC = 0.66, 95% 0.49-0.82), IPSG score (AUC = 0.68, 95% 0.50-0.86, and AUC = 0.61, 95% 0.41-0.81). CONCLUSIONS: Our results suggest that contrast agent application could be omitted in JIA patients with an augmented knee MRI protocol comprising PD-weighted sequence. KEY POINTS: • Unenhanced MRI can detect disease activity of the knee joint in patients with JIA with equally high accuracy compared to contrast-enhanced MRI. • The intra- and inter-reader agreement was high for unenhanced and enhanced MRI JAMRIS scores, which indicate relatively good applicability of the scoring system, even for less experienced readers. • When using the clinical JADAS10 as a reference standard for the detection of disease activity, moderate accuracy for both unenhanced and enhanced MRI scores, both JAMRIS and IPSG, was noted, which might be caused by the fact that the majority of patients had either no or minimal clinical disease activity.

[Imaging of tumor predisposition syndromes]. / Bildgebung bei Tumorprädispositionssyndromen.

CLINICAL ISSUE: Tumor predisposition syndromes (TPS) are a heterogeneous group of genetic cancers. About 10% of the approximately 2200 malignancies in the childhood in Germany develop due to an inherited disposition, whereby TPS may be underdiagnosed. The focus of this review is set on imaging of Li-Fraumeni syndrome, neurofibromatoses, tuberous sclerosis, overgrowth, and neuroendocrine syndromes. STANDARD RADIOLOGICAL METHODS: In order to detect tumors at an early stage, screening at specific time intervals for each TPS are required. Ultrasonography and magnetic resonance imaging (MRI), especially whole-body MRI, are particularly important imaging modalities. METHODOLOGICAL INNOVATIONS: Innovative MRI techniques can increase image quality and patient comfort. MRI acquisition time can be significantly reduced through optimized acceleration factors, motion robust radial sequences and joint acquisition and readout of multiple slices during excitation. Thus, shorter MRI examinations can be performed in younger children without anesthesia. PRACTICAL RECOMMENDATION: Regular screening with ultrasound and MRI can reduce the morbidity and mortality of the patients affected with TPS.

Spectral CT and its specific values in the staging of patients with non-small cell lung cancer: technical possibilities and clinical impact.

AIM: To investigate how spectral computed tomography (SCT) values impact the staging of non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: One hundred and thirteen patients with confirmed NSCLC were included in a prospective cohort study. All patients underwent single-phase contrast-enhanced SCT (using the fast tube voltage switching technique, 80-140 kV). SCT values (iodine content [IC], spectral slope pitch, and radiodensity increase) of malignant tissue (primary and metastases) and lymph nodes (LNs) were measured. Adrenal masses were evaluated in a virtual non-contrast series (VNS). If pulmonary embolism was present, pulmonary perfusion was analysed as an additional finding. RESULTS: Fifty-two untreated primary NSCLC lesions were evaluable. Lung adenocarcinoma had significantly higher normalised IC (NIC: 19.37) than squamous cell carcinoma (NIC: 12.03; p=0.035). Pulmonary metastases were not significantly different from benign lung nodules. A total of 126 LNs were analysed and histologically proven metastatic LNs (2.08 mg/ml) had significantly lower IC than benign LNs (2.58 mg/ml; p=0.023). Among 34 adrenal masses, VNS identified adenomas with high sensitivity (91%) and specificity (100%). In two patients, a perfusion defect due to pulmonary embolism was detected in the iodine images. CONCLUSION: SCT may contribute to the differentiation of histological NSCLC subtypes and improve the identification of LN metastases. VNS differentiates adrenal adenoma from metastasis. In case of pulmonary embolism, iodine imaging can visualise associated pulmonary perfusion defects.

[Imaging of abdominal tumors in childhood and adolescence : Part II: relevant intra-abdominal and retroperitoneal tumor entities]. / Bildgebung bei abdominellen Tumoren im Kindes- und Jugendalter : Teil II: Relevante intraabdominale und retroperitoneale Tumorentitäten.

Abdominal and pelvic tumors in children and adolescents can be manifested intra-abdominally and also often in the retroperitoneum. The most important pediatric primary retroperitoneal space-occupying lesions are nephroblastoma (Wilms' tumor) and neuroblastoma, whereby imaging plays a decisive role in the diagnostics and differentiation of the two entities. Benign tumors of the mesentery and gastrointestinal tract occur more frequently in children than malignant lesions. The benign entities include lipoma, polyps and vascular tumors, such as lymphatic malformations. Of the malignant sarcomas, abdominal rhabdomyosarcomas (RMS) occur relatively often in childhood and adolescence. The most frequent pediatric abdominal lymphoma is Burkitt's lymphoma, an aggressive subtype of non-Hodgkin's lymphoma. Relevant tumor entities in childhood are also germ cell tumors, which originate from the genitals (gonadal) or can be extragonadally manifested. The benignancy or malignancy of germ cell tumors ranges from benign teratomas to highly malignant entities, such as yolk sac tumors. The germ cell tumors, just as all pediatric abdominal mass lesions, show a broad spectrum of tumor aggressiveness, malignancy and therefore also prognosis and mortality for the affected children and adolescents.

[Imaging of abdominal tumors in childhood and adolescence : Part I: Background, hepatic, splenic and pancreatic tumors]. / Bildgebung bei abdominellen Tumoren im Kindes- und Jugendalter : Teil I: Hintergründe, Leber­, Milz- und Pankreastumoren.

In comparison to adult patients, other specific entities of abdominal tumors occur in childhood and adolescence. These include malignant tumors originating from embryonic tissue, such as hepatoblastoma. Some of the abdominal tumors are already diagnosed prenatally or in neonates. Sonography functions as the primary radiological basic diagnostics of pediatric abdominal space-occupying lesions, if necessary supplemented by administration of ultrasound contrast medium or the implementation of novel techniques (e.g. innovative Doppler and elastography procedures). Magnetic resonance imaging (MRI) is used for a comprehensive and detailed depiction of the tumors including the question of resectability and vascular supply. Various weighting and different MRI sequences are used in order to be able to assess the signal behavior of the tumor and therefore the possible presence of calcification, necrosis or hemorrhage, the behavior of dynamic contrast enhancement, and the presence and extent of diffusion disorders. This information is decisive in order to be able to assess the entity and malignancy of the abdominal space-occupying lesion. Rare but relevant tumors with respect to the entity occur in childhood and adolescence in the abdominal organs liver, spleen and pancreas.

MRI of cystic fibrosis lung manifestations: sequence evaluation and clinical outcome analysis.

AIM: To evaluate different magnetic resonance imaging (MRI) sequences for diagnosis of pulmonary manifestations of cystic fibrosis (CF) in comparison to chest computed tomography (CT), including an extended outcome analysis. MATERIALS AND METHODS: Twenty-eight patients with CF (15 male, 13 female, mean age 30.5±9.4 years) underwent CT and MRI of the lung. MRI (1.5 T) included different T2- and T1-weighted sequences: breath-hold HASTE (half Fourier acquisition single shot turbo spin echo) and VIBE (volumetric interpolated breath-hold examination, before and after contrast medium administration) sequences and respiratory-triggered PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) sequences with and without fat signal suppression, and perfusion imaging. CT and MRI images were evaluated by the modified Helbich and the Eichinger scoring systems. The clinical follow-up analysis assessed pulmonary exacerbations within 24 months. RESULTS: The highest concordance to CT was achieved for the PROPELLER sequences without fat signal suppression (concordance correlation coefficient CCC of the overall modified Helbich score 0.93 and of the overall Eichinger score 0.93). The other sequences had the following concordance: PROPELLER with fat signal suppression (CCCs 0.91 and 0.92), HASTE (CCCs 0.87 and 0.89), VIBE (CCCs 0.84 and 0.85) sequences. In the outcome analysis, the combined MRI analysis of all five sequences and a specific MRI protocol (PROPELLER without fast signal suppression, VIBE sequences, perfusion imaging) reached similar correlations to the number of pulmonary exacerbations as the CT examinations. CONCLUSION: An optimum lung MRI protocol in patients with CF consists of PROPELLER sequences without fat signal suppression, VIBE sequences, and lung perfusion analysis to enable high diagnostic efficacy and outcome prediction.

Dose reduction in paediatric cranial CT via iterative reconstruction: a clinical study in 78 patients.

AIM: To assess how adaptive statistical iterative reconstruction (ASIR) contributes to dose reduction and affects image quality of non-contrast cranial computed tomography (cCT) in children. MATERIALS AND METHODS: Non-contrast cranial CT acquired in 78 paediatric patients (age 0-12 years) were evaluated. The images were acquired and processed using four different protocols: Group A (control): 120 kV, filtered back projection (FBP), n=18; Group B: 100 kV, FBP, n=22; Group C: 100 kV, scan and reconstruction performed with 20% ASIR, n=20; Group D1: 100 kV, scan and reconstruction performed with 30% ASIR, n=18; Group D2: raw data from Group D1 reconstructed using a blending of 40% ASIR and 60% FBP, n=18. The effective dose was calculated and the image quality was assessed quantitatively and qualitatively. RESULTS: Compared to Group A, Groups C and D1/D2 showed a significant reduction of the dose-length product (DLP) by 34.4% and 64.4%, respectively. All experimental groups also showed significantly reduced qualitative levels of noise, contrast, and overall diagnosability. Diagnosis-related confidence grading showed Group C to be adequate for everyday clinical practice. Quantitative measures of Groups B and C were comparable to Group A with only few parameters compromised. Quantitative scores in Groups D1 and D2 were mainly lower compared to Group A, with Group D2 performing better than Group D1. Group D2 was considered adequate for follow-up imaging of severe acute events such as bleeding or hydrocephalus. DISCUSSION: The use of ASIR combined with low tube voltage may reduce radiation significantly while maintaining adequate image quality in non-contrast paediatric cCT.

Contrast-enhanced spectral mammography versus MRI: Initial results in the detection of breast cancer and assessment of tumour size.

OBJECTIVES: To compare mammography (MG), contrast-enhanced spectral mammography (CESM), and magnetic resonance imaging (MRI) in the detection and size estimation of histologically proven breast cancers using postoperative histology as the gold standard. METHODS: After ethical approval, 80 women with newly diagnosed breast cancer underwent MG, CESM, and MRI examinations. CESM was reviewed by an independent experienced radiologist, and the maximum dimension of suspicious lesions was measured. For MG and MRI, routine clinical reports of breast specialists, with judgment based on the BI-RADS lexicon, were used. Results of each imaging technique were correlated to define the index cancer. Fifty-nine cases could be compared to postoperative histology for size estimation. RESULTS: Breast cancer was visible in 66/80 MG, 80/80 CESM, and 77/79 MRI examinations. Average lesion largest dimension was 27.31 mm (SD 22.18) in MG, 31.62 mm (SD 24.41) in CESM, and 27.72 mm (SD 21.51) in MRI versus 32.51 mm (SD 29.03) in postoperative histology. No significant difference was found between lesion size measurement on MRI and CESM compared with histopathology. CONCLUSION: Our initial results show a better sensitivity of CESM and MRI in breast cancer detection than MG and a good correlation with postoperative histology in size assessment. KEY POINTS: • Contrast-enhanced spectral mammography (CESM) is slowly being introduced into clinical practice. • Access to breast MRI is limited by availability and lack of reimbursement. • Initial results show a better sensitivity of CESM and MRI than conventional mammography. • CESM showed a good correlation with postoperative histology in size assessment. • Contrast-enhanced spectral mammography offers promise, seemingly providing information comparable to MRI.

Topographic analysis and evaluation of anatomical landmarks for placement of central venous catheters based on conventional chest X-ray and computed tomography.

BACKGROUND: Positioning central venous catheters (CVCs) in the proper part of the superior vena cava (SVC) is difficult. The aim of this exploratory study was to analyse topographic relationships of the extrapericardial SVC using chest X-ray (CXR) and computed tomography (CT). This included an appraisal of rules for optimal CVC tip placement. METHODS: We retrospectively evaluated 100 patients with CVCs who underwent bedside CXR and CT on the same day. Distances between the sternoclavicular joint (SCJ), tracheal carina, SVC origin, pericardial reflection, and CVC tip were analysed on CT and, if visible, on CXR. These measurements served to locate the extrapericardial SVC in relation to anatomical landmarks. Different strategies for CVC tip positioning were evaluated. RESULTS: The mean (standard deviation) extrapericardial length of the SVC was 26 (12) mm. The average position of the pericardial reflection was 5 mm below the carina (range, 29 mm below to 25 mm above). In our patient population, the best results in terms of tip positions in the extrapericardial SVC would have been achieved by using 85% of the SCJ-to-carina distance (in 86%) or by positioning the CVC tip 9 mm above the carina (in 84% of patients). CONCLUSIONS: The extrapericardial part of the SVC varies considerably in length and position, and rules of thumb based on anatomical landmarks should be used cautiously. In our series, using 85% of the SCJ-to-carina distance or placing the CVC tip 9 mm above the carina would have resulted in a high percentage of positions in the extrapericardial SVC.

Photon-counting detector CT (PCD-CT) generated iodine maps to characterize parenchymal lung disease: A feasibility study.

BACKGROUND: With photon-counting CT, spectral imaging is always available, and iodine maps with high spatial and spectral resolution can be generated. OBJECTIVES: The aim of this study was to investigate whether iodine uptake in different parenchymal patterns can be used to characterise parenchymal disease with increased lung attenuation. METHODS: 325 patients were scanned with a photon-counting CT using four scan protocols, all with lung parenchymal contrast. Lesions were classified into three basic patterns: consolidation, ground-glass opacities (GGO), and reticular pattern. Lesion classification was performed by 2 of 3 radiologists who were blinded to the diagnosis. Classification was performed twice using a 5-point Likert scale (with and without iodine maps). In case of disagreement, a third reader was consulted, and the decision was made by consensus. RESULTS: 206 lesions were found with a confirmed diagnosis (83 consolidations, 72 GGO, and 51 reticular). Diagnostic confidence improved when iodine maps were included in the evaluation. The mean Likert score increased significantly for all three basic patterns (consolidations: 3.3 vs. 3.9, GGO: 3.4 vs. 4.1, and reticular: 3.6 vs. 4.4, p < 0.001). However, the score for GGO and reticular pattern was downgraded in three and one cases, respectively. The downgrading occurred for morphologically uncertain GGO findings (3) and atelectasis (1) with inhomogeneous iodine uptake. In 29 lesions, the classification was changed when the iodine maps were included in the evaluation. CONCLUSION: Including iodine maps adds contrast uptake information and improves the diagnostic confidence of radiologists in the characterization of parenchymal pathologies. CLINICAL IMPACT: Iodine maps have the potential to provide complementary information for the interpretation of lung opacities with overlapping morphology.

Cost comparison of nerve root infiltration of the lumbar spine under MRI and CT guidance.

OBJECTIVES: To compare the costs of CT- and MR-guided lumbosacral nerve root infiltration for minimally invasive treatment of low back pain and radicular pain. METHODS: Ninety patients (54 men, 36 women; mean age, 45.5 ± 12.8 years) underwent MR-guided single-site periradicular lumbosacral nerve root infiltration with 40 mg of triamcinolone acetonide. A further 91 patients (48 men, 43 women; mean age, 59.1 ± 13.8 years) were treated under CT fluoroscopy guidance. Prorated costs of equipment use (purchase, depreciation and maintenance), staff costs based on involvement times and expenditure for disposables were identified for MR- and CT-guided procedures. RESULTS: Mean intervention time was 20.6 min (14-30 min) for MR-guided and 14.3 min (7-32 min) for CT-guided treatment. The average total costs per patient were €177 for MR-guided and €88 for CT-guided interventions. These consisted of (MR/CT guidance) €93/29 for equipment use, €43/35 for staff and €41/24 for disposables. CONCLUSIONS: Lumbosacral nerve root infiltration using MRI guidance is still about twice as expensive as infiltration using CT guidance. Given the advantages of no radiation exposure and possible future decrease in prices for MRI devices and MR-compatible injection needles, MR-guided nerve root infiltration may become a promising alternative to the CT-guided procedure. KEY POINTS: • MR-guided nerve root infiltration therapy is now technically and clinically established. • Costs using MRI guidance are still about double those for CT guidance. • MR guidance involves no radiation exposure to patients and personnel. • MR-guided nerve root infiltration may become a promising alternative to CT.

Diffusion-weighted imaging (DWI) in MR mammography (MRM): clinical comparison of echo planar imaging (EPI) and half-Fourier single-shot turbo spin echo (HASTE) diffusion techniques.

Diffusion-weighted imaging (DWI) techniques have shown potential to differentiate between benign and malignant neoplasms. However, the diagnostic significance of using DWI under routine conditions remains unclear. This study investigated the use of echo planar imaging (EPI) and half-Fourier acquired single-shot turbo spin echo (HASTE)-DWI with respect to the three parameters: lesion visibility, apparent diffusion coefficient (ADC) measurements, and size estimation. Following MRM (1.5 T), EPI- and HASTE-DWI were applied in 65 patients. Lesion visibility on DWI was compared with lesion visibility on subtracted contrast-enhanced T1w images (CE-T1w). Statistical tests were applied to diameter, visibility, and ADC value measurements. Seventy-four lesions were identified. ADC value measurements did not differ significantly between the two DWI sequences. The sensitivity and specificity of routine diagnostics (97.4% and 85.7%) were superior to EPI-DWI (87.2% and 82.9%) and HASTE-DWI (76.9% and 88.6%). Selecting only nonmass lesions, DWI did not prove to be of diagnostic value. Lesion demarcation by DWI was significantly lower compared with that by CE-T1w, with EPI-DWI showing the better performance (p < 0.001). No significant differences were found for size measurements between CE-T1w and DWI. Although clearly inferior compared with CE-T1w imaging, both DWI techniques are applicable for lesion assessment and size measurements.

Metallic dental artifact reduction in computed tomography (Smart MAR): Improvement of image quality and diagnostic confidence in patients with suspected head and neck pathology and oral implants.

PURPOSE: We determined whether the Smart MAR metal artifact reduction tool - a three-stage, projection-based, post processing algorithm - improves subjective and objective image quality and diagnostic confidence in patients with dental artifacts and suspected head and neck pathology compared to standard adaptive statistical iterative reconstructions (ASIR V) alone. METHOD: The study included 100 consecutive patients with nonremovable oral implants or dental fillings and suspected oropharyngeal cancer or abscess. CT raw data of a single-source multislice CT scanner were postprocessed using ASIR V alone and with additional Smart MAR reconstruction. Image quality of baseline ASIR V and Smart MAR-based reconstruction series was compared both quantitatively (5 regions of interest, ROIs) and qualitatively (two independent raters). RESULTS: Additional Smart MAR reconstruction significantly seems to improve both attenuation and noise adjacent to implants and in more distant areas (all p < 0.001) compared to standard ASIR V reconstructions alone. Signal-to-noise ratio (SNR; p = 0.001) and contrast-to-noise ratio were improved significantly (CNR; p = 0.001). Smart MAR improved visualization of tumor/abscess (detected in 36 of 100 patients, 36%) and representative oropharyngeal tissue (p < 0.001). In 8 of 36 patients (22%), tumor was only detected in Smart MAR series. Mean total DLP was 506.8mGy*cm; average CTDIvol was 5.5 mGy. CONCLUSIONS: The supplementary use of the Smart MAR post-processing tool seems to significantly improve both subjective and objective image quality as well as diagnostic confidence and lesion detection in CT of the head and neck. In 22% of cases, the tumor was detected only in Smart MAR reconstructed images.

Effects of long-term immobilisation on cortical bone mass after traumatic amputation of the phalanges estimated by digital X-ray radiogrammetry.

UNLABELLED: Osteopenia of the cortical and trabecular bone partition is a common finding after immobilisation. Digital X-ray radiogrammetry (DXR) seems to quantify cortical demineralisation caused by circular saw amputation already few days after accident. INTRODUCTION: The study analyses the extent of demineralisation caused by immobilisation in patients with digital amputation after a circular saw injury, and elucidates the period of time which discloses a significant deprivation of bone mineral density estimated at the metacarpalia II-IV using DXR. METHODS: Twenty-eight patients with digital amputations underwent measurements of bone mineral density, cortical thickness, bone width and metacarpal index using DXR-technology in a follow-up up to 902 days. RESULTS: The data showed a significant decline of bone mineral density (-10.47%), the metacarpal index (-4.38%), the bone width (-12.06%) and the cortical thickness (-7.04%) after trauma-related amputation. The cortical demineralisation of the metacarpals could already be revealed in two patients after the second day, according to the amputation of phalanges (-3.65%). CONCLUSIONS: The inhibition of the periosteal bone formation detected by DXR-technique seems to be a specific finding caused by amputation, which thus differs from normal age-related (i.e., endosteal) bone loss and from demineralisation following acute immobilisation (i.e., trabecular osteopenia).

Reducing Radiation Dose in Adult Head CT using Iterative Reconstruction - A Clinical Study in 177 Patients.

PURPOSE: To assess how ASIR (adaptive statistical iterative reconstruction) contributes to dose reduction and affects image quality of non-contrast cranial computed tomography (cCT). MATERIALS AND METHODS: Non-contrast emergency CT scans of the head acquired in 177 patients were evaluated. The scans were acquired and processed using four different protocols: Group A (control): 120 kV, FBP (filtered back projection) n = 71; group B1: 120 kV, scan and reconstruction performed with 20 % ASIR (blending of 20 % ASIR and 80 % FBP), n = 86; group B2: raw data from group B1 reconstructed using a blending of 40 % ASIR and 60 % FBP, n = 74; group C1: 120 kV, scan and reconstruction performed with 30 % ASIR, n = 20; group C2: raw data from group C1 reconstructed using a blending of 50 % ASIR and 50 % FBP, n = 20. The effective dose was calculated. Image quality was assessed quantitatively and qualitatively. RESULTS: Compared to group A, groups B1/2 and C1/2 showed a significantly reduced effective dose of 40.4 % and 73.3 % (p < 0.0001), respectively. Group B1 and group C1/2 also showed significantly reduced quantitative and qualitative image quality parameters. In group B2, quantitative measures were comparable to group A, and qualitative scores were lower compared to group A but higher compared to group B1. Diagnostic confidence grading showed groups B1/2 to be adequate for everyday clinical practice. Group C2 was considered acceptable for follow-up imaging of severe acute events such as bleeding or subacute stroke. CONCLUSION: Use of ASIR makes it possible to reduce radiation significantly while maintaining adequate image quality in non-contrast head CT, which may be particularly useful for younger patients in an emergency setting and in follow-up. KEY POINTS: ASIR may reduce radiation significantly while maintaining adequate image quality. cCT protocol with 20 % ASIR and 40 %ASIR/60 %FBP blending is adequate for everyday clinical use. cCT protocol with 30 % ASIR and 50 %ASIR/50 %FBP blending is adequate for follow-up imaging

Transcriptional silencing of human Alu sequences and inhibition of protein binding in the box B regulatory elements by 5'-CG-3' methylation.

In earlier work, we demonstrated that 5'-CG-3' methylation inhibits the transcriptional activity of human Alu elements associated with the alpha 1-globin and the angiogenin genes in a cell-free transcription system from HeLa nuclear extracts. These studies have been extended to different Alu sequences and to investigations on the mechanism involved in transcriptional silencing by methylation. By comparing the results of DNase I and dimethyl sulfate (DMS) in vitro footprinting on a consensus sequence in the RNA polymerase III promoter control B region between the unmethylated and the 5'-CG-3' methylated B box, evidence has been adduced for effects of 5'-CG-3' methylation on the interaction of specific nuclear proteins with DNA sequences in the B control region of the Alu elements. These results are consistent with the interpretation that the 5'-CG-3' methylation interferes with the binding of proteins that are essential for the function of the B control region in these RNA polymerase III-transcribed elements, and that promoter methylation thus inhibits transcription.

DNA methylation in the promoter of ribosomal RNA genes in human cells as determined by genomic sequencing.

Many RNA polymerase II- or III-transcribed genes are inactive when their promoter is methylated at critical CpG dinucleotides. We have applied the genomic sequencing method and a direct DNA blotting technique to analyze the extent of DNA methylation in the 5'-CpG-3' rich promoter region of the RNA polymerase I-transcribed ribosomal RNA genes (rDNA) in DNA from primary human cells, primary human tumor cells and human cell lines. In none of the analyzed primary human cells and primary human tumor cells was the DNA in the rDNA promoter region found to be detectably methylated. In contrast, in some of the cell lines this promoter is methylated in all 5'-CpG-3' dinucleotides in the majority of the approximately 200 ribosomal RNA gene copies. In actively growing cells, rDNA gene activity is a prerequisite for cell viability. The high levels of DNA methylation in the promoter region of rDNA in the human cell lines raise questions on the role of promoter methylation in these RNA polymerase I-transcribed genes. It is, however, conceivable that a subset of the about 200 rDNA copies per haploid genome have escaped methylation and account for the rRNA synthesis in these cell lines. Alternatively, complete 5'-CpG-3' promoter methylation may be compatible with promoter activity as demonstrated for certain viral genomes.

Hypothermia abolishes hypoxia-induced hyperpermeability in brain microvessel endothelial cells.

The effect of mild (32 degrees C) and deep (22 degrees C) hypothermia on hypoxia-induced hyperpermeability was examined using an in vitro model of brain derived microvascular endothelial cells (BMEC). It was shown that hypoxia-induced hyperpermeability to inulin across the BMEC monolayer was completely abolished at 32 degrees C and 22 degrees C for up to 24 h of hypoxia. During normoxia, no influence of hypothermia on BMEC monolayer permeability was observed. The hypoxia-induced decrease of the cyclic AMP level after 6 h was abolished at 32 degrees C as well as at 22 degrees C of hypoxia. But after 24 h of hypoxia, hypothermia did no longer prevent the hypoxia-induced decrease of the cAMP level, which suggests that the effect of hypothermia on hypoxia-induced hyperpermeability is not caused by maintenance of the cAMP level. Because vascular endothelial growth factor (VEGF) has been shown to be the mediator of hypoxia-induced permeability changes of BMEC via the release of nitric oxide (NO), the effect of hypothermia on the VEGF expression was evaluated. During normoxia, hypothermia did not change the VEGF expression significantly but the hypoxia-induced increase in VEGF mRNA and protein expression was completely abolished at 32 degrees C and 22 degrees C respectively. Accordingly, the hypoxia-induced increase of the cGMP level was depressed by hypothermia, which demonstrates that also the amount of NO released during hypoxia is decreased at lower temperatures. Results suggest that deep as well as mild hypothermia decreased hypoxia-induced hyperpermeability by lowering the expression of the permeability-increasing protein VEGF and with it the release of NO.

Barbiturates decrease the expression of vascular endothelial growth factor in hypoxic cultures of porcine brain derived microvascular endothelial cells.

Vascular endothelial growth factor (VEGF) is known to be produced in higher amounts during hypoxia by a variety of cell types and has been shown to increase the permeability of brain derived microvascular endothelial cells (BMEC) during hypoxia by an autocrine mechanism. Because the barbiturates, methohexital (MH) and thiopental (TP), induced a dose-dependent reduction in hypoxia-induced permeability changes of BMEC, the effect of both barbiturates on the VEGF expression during hypoxia was investigated. Both barbiturates decreased the hypoxia-induced expression of VEGF in BMEC in a concentration-dependent manner. This effect is partly caused by the impairment of the hypoxia-induced VEGF mRNA stabilization. VEGF-induced permeability changes during normoxia were unaffected by the barbiturates suggesting that MH and TP are directly reducing hypoxia-induced VEGF synthesis. In conclusion, the inhibiting effect of these barbiturates on the hypoxia-induced VEGF expression results in the decreased permeability of the BMEC monolayer during hypoxia, which may contribute to the described neuroprotective action of barbiturates by reduction of brain edema formation.

Role of adenosine in the hypoxic induction of vascular endothelial growth factor in porcine brain derived microvascular endothelial cells.

Hypoxia induced the mRNA expression of vascular endothelial growth factor (VEGF) in porcine brain derived microvascular endothelial cells (BMEC) in a time-dependent manner. Corresponding to the mRNA induction the protein level of VEGF was elevated during hypoxia. The adenosine A1 receptor antagonist 8-phenyltheophylline (8-PT) reduced the hypoxia-induced VEGF mRNA and protein expression significantly. The treatment of BMEC with cobalt chloride-known to activate an oxygen sensing mechanism similar to the one used by the erythropoietin gene-also induced the VEGF mRNA expression, but 8-PT did not reduce this VEGF induction. Although, earlier studies revealed that agents like phorbolester induced the VEGF mRNA expression, the specific inhibitor of the proteinkinase C (PKC) bisindolylmaleimide (BIM) did not reduce but enhanced the hypoxia-induced VEGF mRNA expression. These results indicate that the VEGF induction in BMEC can proceed through PKC-dependent and -independent pathways (like those acting via the putative oxygen sensor). Hypoxia in BMEC probably activates the PKC-dependent pathway mainly via adenosine which might be formed during hypoxia and thereby inhibits activation of PKC-independent, oxygen sensing, pathways. This suggestion was supported by the fact that hypoxia as well as adenosine increased the VEGF mRNA expression post-transcriptionally by enhancing the stability of the VEGF mRNA [corrected].