Delayed inhibition of angiotensin II receptor type 1 reduces secondary brain damage and improves functional recovery after experimental brain trauma*.

OBJECTIVE: To investigate the regulation of the cerebral renin-angiotensin system and the effect of angiotensin II receptor type 1 inhibition on secondary brain damage, cerebral inflammation, and neurologic outcome after head trauma. DESIGN: The expression of renin-angiotensin system components was determined at 15 mins, 3 hrs, 6 hrs, 12 hrs, and 24 hrs after controlled cortical impact in mice. Angiotensin II receptor type 1 was inhibited using candesartan (0.1, 0.5, 1 mg/kg) after trauma to determine its effect on secondary brain damage, brain edema formation, and inflammation. The window of opportunity was tested by delaying angiotensin II receptor type 1 inhibition for 30 mins, 1 hr, 2 hrs, and 4 hrs. The long-term effect was tested by single and daily repeated treatment with candesartan for 5 days after controlled cortical impact. SETTING: University research laboratory. SUBJECTS: Male C57Bl/6N mice. INTERVENTIONS: Brain trauma by use of a controlled cortical impact device. MEASUREMENTS AND MAIN RESULTS: Expression of angiotensin II receptor type 1A decreased by 42% within 24 hrs after controlled cortical impact, whereas angiotensin II receptor type 1B expression increased to 220% between 6 and 12 hrs. Blockage of angiotensin II receptor type 1 with 0.1 mg/kg candesartan within 4 hrs of injury significantly reduced secondary brain damage (30 mins: 25 mm vs. vehicle: 41 mm) and improved neurologic function after 24 hrs but failed to reduce brain edema formation. Daily treatment with candesartan afforded sustained reduction of brain damage and improved neurologic function 5 days after traumatic brain injury compared with single and vehicle treatment. Inhibition of angiotensin II receptor type 1 significantly attenuated posttraumatic inflammation (interleukin-6: -56%; interleukin-1ß: -42%; inducible nitric oxide synthase: -36%; tumor necrosis factor-α: -35%) and microglia activation (vehicle: 163 ± 25/mm vs. candesartan: 118 ± 13/mm). Higher dosages (0.5 and 1 mg/kg) resulted in prolonged reduction in blood pressure and failed to reduce brain lesion. CONCLUSIONS: The results indicate that angiotensin II receptor type 1 plays a key role in the development of secondary brain damage after brain trauma. Inhibition of angiotensin II receptor type 1 with a delay of up to 4 hrs after traumatic brain injury effectively reduces lesion volume. This reduction makes angiotensin II receptor type 1 a promising therapeutic target for reducing cerebral inflammation and limiting secondary brain damage.

Three-dimensional simulator: training for beginners in endovascular embolization with liquid agents.

BACKGROUND: To design a simulator for novices without prior experience in embolization with liquid agents such as n-Butyl cyanoacrylate (n-BCA) and to evaluate the simulator using surveys and post hoc video analysis. MATERIALS AND METHODS: The simulator was created using computer-aided design software and three-dimensionally printed. Before an embolization, trainees completed questionnaires regarding their level of expertise and self-reported confidence level. The participants were shown an instruction video and each participant performed four embolizations on the simulator. Subsequently, the participants completed surveys on self-reported confidence level and assessed the simulator's face and content validity. RESULTS: Five experts and twelve novices trained on the simulator. The experts were radiology residents and fellows with at least 5 years of work experience in interventional radiology. The novices were medical students and radiology residents without any previous experience with embolization. Based on the surveys, the experts assessed the simulator as very useful for embolization training. Performance, e.g. mean duration embolization between experts (mean ± standard deviation = 189 ± 42 s) and novices (mean ± standard deviation = 235 ± 66 s) were significantly different (p = .001). The overall simulation of the embolization process, simulated complications, and educational capabilities of the simulator were evaluated positively. In the novice group the self-reported confidence level significantly increased (p = .001). CONCLUSION: The liquid embolization simulator proposed here is a suitable educational tool for training embolization procedures. It reduces the duration of embolization procedures and improves the confidence level of beginners in embolization.

Diagnosis of Left Ventricular Diastolic Dysfunction Using Cardiac Magnetic Resonance Imaging: Comparison of Volume-Time Curves Derived from Long- and Short-Axis Cine Steady-State Free Precession Datasets.

PURPOSE: To evaluate the diagnostic performance of diastolic function parameters derived from long-axis (LAX) planimetry compared with short-axis (SAX) volumetry in cardiac magnetic resonance imaging. MATERIALS AND METHODS: Cine steady-state free precession (SSFP) datasets of 15 healthy participants (8 young and 7 middle aged) and 25 patients with echocardiographically proven diastolic dysfunction (9 mild, 9 moderate, and 7 severe) were retrospectively included. Volume-time curves for assessing left ventricular (LV) function were obtained by manually contouring the LV endocardial borders in SAX and LAX datasets. The time needed for contouring was recorded for each dataset. The following LV parameters were determined: end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), myocardial mass (MM), time to peak filling rate (TPFR), normalized peak filling rate (nPFR), and the ratio of early to late peak filling rate (E/A ratio). A Wilcoxon signed-rank test was used to compare subgroups based on age and severity of diastolic dysfunction for statistical differences. Intraclass correlation coefficients were used to assess intermethod and interobserver reliability. RESULTS: Accuracy for the diagnosis of diastolic dysfunction was highest for E/A (mild diastolic dysfunction) and nPFR (any stage of diastolic dysfunction) derived from LAX datasets (E/A: area under the curve (AUC) = 0.97, sensitivity of 68 % and specificity of 100 %; nPFR: AUC = 0.84, sensitivity of 84 % and specificity of 80 %). Diastolic parameters showed a moderate to good intraclass correlation between both methods. The mean differences in EDV, ESV, EF, and MM were 5.3 ml, 1.9 ml, 3.5 %, and 11 g, respectively (each p < 0.001). Significantly less time was needed to derive volume-time curves from LAX images (median 14:45 min, interquartile range 14:15-15:53 min versus median 29:25 min, interquartile range 28:12-32:22 min; p = 0.001). The interobserver reliability was generally good to excellent. CONCLUSION: Diastolic function parameters derived from left ventricular LAX planimetry have high diagnostic performance and can be obtained in significantly less time compared with SAX volumetry. These findings may pave the way for routine use of LAX planimetry in the clinical diagnosis of diastolic dysfunction. KEY POINTS: · Diastolic function parameters derived from long-axis datasets have high diagnostic performance.. · Generation of volume-time curves using long-axis datasets requires significantly less time.. · This time savings may allow use of cardiac MRI for the diagnosis of diastolic dysfunction in the clinical routine.. CITATION FORMAT: · Schaafs LA, Wyschkon S, Elgeti M et al. Diagnosis of Left Ventricular Diastolic Dysfunction Using Cardiac Magnetic Resonance Imaging: Comparison of Volume-Time Curves Derived from Long- and Short-Axis Cine Steady-State Free Precession Datasets. Fortschr Röntgenstr 2020; 192: 764 - 775.

Evaluation of left ventricular function in patients with acute ischaemic stroke using cine cardiovascular magnetic resonance imaging.

AIMS: Heart failure (HF) is frequent in patients with acute ischaemic stroke (AIS) and associated with higher morbidity and mortality. Assessment of cardiac function in AIS patients using cardiovascular MRI (CMR) may help to detect HF. We report the rate of systolic and diastolic dysfunction in a cohort of patients with AIS using CMR and compare cine real-time (CRT) sequences with the reference of segmented cine steady-state free precession sequences. METHODS AND RESULTS: Patients with AIS without known atrial fibrillation were prospectively enrolled in the HEart and BRain Interfaces in Acute Ischemic Stroke (HEBRAS) study (NCT02142413) and underwent CMR at 3 Tesla within 7 days after AIS. Validity of CRT sequences was determined in 50 patients. A total of 229 patients were included in the analysis (mean age 66 years; 35% women; HF 2%). Evaluation of cardiac function was successful in 172 (75%) patients. Median time from stroke onset to CMR was 82 h (interquartile range 56-111) and 54 h (interquartile range 31-78) from cerebral MRI to CMR. Systolic dysfunction was observed in 43 (25%) and diastolic dysfunction in 102 (59%) patients. Diagnostic yield was similar using CRT or segmented cine imaging (no significant difference in left ventricular ejection fraction, myocardial mass, time to peak filling rate, and peak filling rate ratio E/A). Intraobserver and interobserver agreement was high (κ = 0.78-1.0 for all modalities). CONCLUSIONS: Cardiovascular MRI at 3 Tesla is an appropriate method for the evaluation of cardiac function in a selected cohort of patients with AIS. Systolic and diastolic dysfunction is frequent in these patients. CRT imaging allows reliable assessment of systolic and diastolic function.

Selection of endogenous control genes for normalization of gene expression analysis after experimental brain trauma in mice.

Quantitative measurements of gene expression require correction for tissue sample size, RNA quantity, and reverse transcription efficiency. This can be achieved by normalization with control genes. The study was designed to identify candidates not altered after brain trauma. Male C57Bl/6 mice were anesthetized with isoflurane, and a pneumatic brain trauma was induced by controlled cortical impact (CCI) on the right parietal cortex. Brains were removed at 15 min, and 3, 6, 12 and 24 h after CCI and from naive animals (n = 6 each). Absolute copies of six control genes (beta-2-microglobin [B2M], cyclophilin A, beta-actin, hypoxanthine ribosyltransferase [HPRT], porphobilinogen deaminase [PBGD], and glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) and one example target gene (iNOS) were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR; Lightcycler) in the traumatic focus and contralateral tissue. Control gene expression was stable until 12 h after CCI. At 24 h after CCI expression of B2M, cyclophilin A and HPRT remained stable in the contusion, while expression of beta-actin, GAPDH, and PBGD increased. Due to variations between animals (+/-85%), increases in beta-actin (+64%) and GAPDH (+59%) did not reach the level of significance. In non-contused tissue, expression of all genes dropped 24 h after CCI (range, -17% to -61%). Due to low variations between animals and stable expression after CCI, B2M and cyclophilin A seem to be suitable to serve as single normalizer. Normalization of the example target gene iNOS resulted in varying relative expression extending from onefold (PBDG) to 10-fold (HPRT). The results suggest that the knowledge of the temporal profile of control genes is essential to properly interpret results of mRNA quantification.

Pulmonary MRI at 3T: Non-enhanced pulmonary magnetic resonance Imaging Characterization Quotients for differentiation of infectious and malignant lesions.

OBJECTIVE: To investigate 3T pulmonary magnetic resonance imaging (MRI) for characterization of solid pulmonary lesions in immunocompromised patients and to differentiate infectious from malignant lesions. MATERIALS AND METHODS: Thirty-eight pulmonary lesions in 29 patients were evaluated. Seventeen patients were immunocompromised (11 infections and 6 lymphomas) and 12 served as controls (4 bacterial pneumonias, 8 solid tumors). Ten of the 15 infections were acute. Signal intensities (SI) were measured in the lesion, chest wall muscle, and subcutaneous fat. Scaled SIs as Non-enhanced Imaging Characterization Quotients ((SILesion-SIMuscle)/(SIFat-SIMuscle)*100) were calculated from the T2-weighted images using the mean SI (T2-NICQmean) or the 90th percentile of SI (T2-NICQ90th) of the lesion. Simple quotients were calculated by dividing the SI of the lesion by the SI of chest wall muscle (e.g. T1-Qmean: SILesion/SIMuscle). RESULTS: Infectious pulmonary lesions showed a higher T2-NICQmean (40.1 [14.6-56.0] vs. 20.9 [2.4-30.1], p<0.05) and T2-NICQ90th (74.3 [43.8-91.6] vs. 38.5 [15.8-48.1], p<0.01) than malignant lesions. T1-Qmean was higher in malignant lesions (0.85 [0.68-0.94] vs. 0.93 [0.87-1.09], p<0.05). Considering infections only, T2-NICQ90th was lower when anti-infectious treatment was administered >24h prior to MRI (81.8 [71.8-97.6] vs. 41.4 [26.6-51.1], p<0.01). Using Youden's index (YI), the optimal cutoff to differentiate infectious from malignant lesions was 43.1 for T2-NICQmean (YI=0.42, 0.47 sensitivity, 0.95 specificity) and 55.5 for T2-NICQ90th (YI=0.61, 0.71 sensitivity, 0.91 specificity). Combining T2-NICQ90th and T1-Qmean increased diagnostic performance (YI=0.72, 0.77 sensitivity, 0.95 specificity). CONCLUSION: Considering each quotient alone, T2-NICQ90th showed the best diagnostic performance and could allow differentiation of acute infectious from malignant pulmonary lesions with high specificity. Combining T2-NICQ90th with T1-Qmean increased overall performance, especially regarding sensitivity.

Can magnetic resonance imaging be an alternative to computed tomography in immunocompromised patients with suspected fungal infections? Feasibility of a speed optimized examination protocol at 3 Tesla.

OBJECTIVE: To prospectively evaluate a short MRI examination protocol for the detection of nodular pulmonary infiltrates in immunocompromised patients with hematologic diseases and suspected invasive fungal infections. METHODS: Patients with nodular infiltrates on CT scans were examined on a 3T MRI scanner. The standardized protocol included axial T2-weighted fast spin echo (FSE) sequences +/- fat saturation (FS), and axial T1-weighted gradient echo (GRE) sequences. Long and short axis diameters of nodular infiltrates and visibility were assessed on MR images at least six months after the CT scan, blinded to patient and examination data. Inter- and intra-reader reliability was assessed in two patients. Statistical testing included Wilcoxon-test, Cohen's kappa, and intra-class correlation coefficients. Bland-Altman plots were created to visualize differences in the measurements. RESULTS: In all 13 patients MRI examinations were completed successfully (average examination time 12 min and maximum breath-hold time of 8s). CT detected 409 nodules. Sensitivity of MRI was 93.2% when using all sequences in combination; considering nodules >5mm, sensitivity increased to 97.9%. Reliability analysis showed excellent correlations with an intra-class correlation coefficient of at least 0.89 for T2 FSE (95% CI 0.79-0.93, p<0.01) images for the intra-, and the lowest of 0.77 for T2 FSE (95% CI 0.55-0.89, p<0.01) images for the inter-reader comparison. Agreement on nodule visibility was at least kappa=0.95 (p<0.01) for the intra- and 0.72 (p<0.01) for the inter-reader analysis. CONCLUSION: With an average examination time of 12 min, pulmonary MRI at 3T is feasible in immunocompromised patients with hematologic diseases and suspected invasive fungal infections. MRI might serve as an alternative diagnostic tool during follow-up examinations.

Apparent migration of implantable port devices: normal variations in consideration of BMI.

PURPOSE: To evaluate the extent of normal variation in implantable port devices between supine fluoroscopy and upright chest x-ray in relation to body mass index (BMI) based on three different measurement methods. METHODS: Retrospectively, 80 patients with implanted central venous access port systems from 2012-01-01 until 2013-12-31 were analyzed. Three parameters (two quantitative and one semi-quantitative) were determined to assess port positions: projection of port capsule to anterior ribs (PCP) and intercostal spaces, ratio of extra- and intravascular catheter portions (EX/IV), normalized distance of catheter tip to carina (nCTCD). Changes were analyzed for males and females and normal-weight and overweight patients using analysis of variance with Bonferroni-corrected pairwise comparison. RESULTS: PCP revealed significantly greater changes in chest x-rays in overweight women than in the other groups (p<0.001, F-test). EX/IV showed a significantly higher increase in overweight women than normal-weight women and men and overweight men (p<0.001). nCTCD showed a significantly greater increase in overweight women than overweight men (p = 0.0130). There were no significant differences between the other groups. Inter- and intra-observer reproducibility was high (Cronbach alpha of 0.923-1.0) and best for EX/IV. CONCLUSIONS: Central venous port systems show wide normal variations in the projection of catheter tip and port capsule. In overweight women apparent catheter migration is significantly greater compared with normal-weight women and with men. The measurement of EX/IV and PCP are straightforward methods, quick to perform, and show higher reproducibility than measurement of catheter tip-to-carina distance.