Recent silent infarcts do not increase the risk of haemorrhage after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Haemorrhagic transformation (HT) is one of the main risks of intravenous thrombolysis (IVT) for acute ischaemic stroke. Contraindications serve to exclude patients at high risk of HT after IVT. One of these contraindications is a stroke within the preceding 3 months. It is unclear if this contraindication should include recent clinically silent infarcts (RSIs). The aim of this study was to investigate whether RSIs are associated with a higher risk of HT and a worse clinical outcome after IVT for acute ischaemic stroke. METHODS: In a retrospective monocentric cohort study, all patients who received IVT for acute ischaemic stroke based on magnetic resonance imaging were assessed over 5 years. RSIs were defined as lesions with diffusion restriction and positive signal on fluid attenuated inversion recovery sequences. Patients with RSIs (RSI+) were compared to patients without RSIs (RSI-) regarding HT after IVT and clinical outcome. RESULTS: In all, 981 patients who had received IVT for acute ischaemic stroke demonstrated by magnetic resonance imaging were identified. RSIs were detected in 115 patients (11.5%). HT after IVT was observed in 32 (28.3%) RSI+ and 56 (25.8%) RSI- patients (P = 0.624). Symptomatic intracerebral haemorrhage was noted in two (1.8%) RSI+ and five (2.3%) RSI- patients (P = 1.000). No differences in clinical outcome were observed. CONCLUSIONS: The detection of RSIs in patients treated with IVT for acute ischaemic stroke was not associated with a higher risk of HT or a worse clinical outcome. The results of this study argue against considering RSIs as a contraindication for IVT.

Myocardial edema in acute myocarditis: relationship of T2 relaxometry and late enhancement burden by using dual-contrast turbo spin-echo MRI.

To quantify myocardial edema by using a T2 relaxometry approach with a dual-contrast turbo spin-echo (dcTSE) sequence in patients with acute myocarditis regarding focal late gadolinium enhancement (LGE) burden. CMR T2 relaxometry was performed in 39 patients (age 41 ± 19 years; 36% women) with LGE in a typical myocarditis pattern and in ten healthy volunteers (age 46 ± 12; 60% woman). dcTSE sequence (echo time 29 and 75 ms, respectively) was used for T2 mapping, analysis were performed on the basis of region of interest (ROI). Myocardial T2 relaxation times (T2 RT) in patients-ROI with focal LGE were significantly (p < 0.001) higher than T2 RT in patients-ROI without apparent LGE pattern (65 ms (IQR 36-95) vs. 60 ms (IQR 26-88), respectively). T2 RT in healthy volunteers [55 ms (IQR 35-71)] were significantly lower than in patients ROI with or without focal LGE-pattern (p < 0.001, respectively). T2 RT assessed by dcTSE are significantly higher in patients segments with and without focal LGE compared to normal controls, supporting a global myocardial inflammatory process in acute myocarditis. Furthermore, this quantitative T2-mapping approach highlights the potential to identify patients with diffuse myocarditis.

R2* relaxometry for the quantification of hepatic iron overload: biopsy-based calibration and comparison with the literature.

PURPOSE: We compared the calibration of hepatic iron based on R2* relaxometry and liver biopsy with similar studies that have already been published to investigate the transferability of published calibration curves. MATERIALS AND METHODS: 17 patients with clinically suspected hepatic iron overload (HIO) were enrolled. All patients underwent liver biopsy and MRI of the liver using a multi-echo gradient echo sequence (TR = 200 ms; TE-initial 0.99 ms; Delta-TE 1.41 ms; 12 echos; flip-angle: 20 °). R2* parameter maps were analyzed using manually placed regions of interest and R2* values were correlated with liver iron concentration (LIC) obtained from liver biopsy. In addition, the results of our study were compared with 6 similar, already published studies. RESULTS: A linear relationship between R2* and LIC was found. Regression analysis yielded a correlation coefficient of 0.926, a slope of 0.024 (s mg/g) [95 % CI 0.013 - 0.024] and an intercept of 0.277 (mg/g) [95 % CI -0.328 - 2.49]. We found a significant correlation between the calibration curves obtained from our study in comparison to 3/6 similar studies. The other 3 studies used a different reference standard or sequence parameters which lead to a significant difference for slope, intercept or both in comparison to our data. CONCLUSION: Calibration curves from published studies that are based on a correlation of liver biopsy and R2* can be used for the estimation of liver iron concentration, although different scanning parameters and post-processing protocols were used. Low initial TEs might be a prerequisite for pooling data for liver iron quantification. KEY POINTS: • Calibration curves from different studies can be used for liver iron quantification• For that purpose calibration curves from published studies should be based on liver biopsy• Low initial TEs might be a prerequisite for pooling data for liver iron quantification.

Automated two-point dixon screening for the evaluation of hepatic steatosis and siderosis: comparison with R2-relaxometry and chemical shift-based sequences.

OBJECTIVES: To evaluate the automated two-point Dixon screening sequence for the detection and estimated quantification of hepatic iron and fat compared with standard sequences as a reference. METHODS: One hundred and two patients with suspected diffuse liver disease were included in this prospective study. The following MRI protocol was used: 3D-T1-weighted opposed- and in-phase gradient echo with two-point Dixon reconstruction and dual-ratio signal discrimination algorithm ("screening" sequence); fat-saturated, multi-gradient-echo sequence with 12 echoes; gradient-echo T1 FLASH opposed- and in-phase. Bland-Altman plots were generated and correlation coefficients were calculated to compare the sequences. RESULTS: The screening sequence diagnosed fat in 33, iron in 35 and a combination of both in 4 patients. Correlation between R2* values of the screening sequence and the standard relaxometry was excellent (r = 0.988). A slightly lower correlation (r = 0.978) was found between the fat fraction of the screening sequence and the standard sequence. Bland-Altman revealed systematically lower R2* values obtained from the screening sequence and higher fat fraction values obtained with the standard sequence with a rather high variability in agreement. CONCLUSIONS: The screening sequence is a promising method with fast diagnosis of the predominant liver disease. It is capable of estimating the amount of hepatic fat and iron comparable to standard methods. KEY POINTS: • MRI plays a major role in the clarification of diffuse liver disease. • The screening sequence was introduced for the assessment of diffuse liver disease. • It is a fast and automated algorithm for the evaluation of hepatic iron and fat. • It is capable of estimating the amount of hepatic fat and iron.

Association of aortic stiffness with biomarkers of myocardial wall stress after myocardial infarction.

BACKGROUND: Aortic pulse wave velocity (PWV) was linked to LV-geometry and -function in patients with kidney disease and non-ischemic cardiomyopathy. The role of aortic compliance after acute STEMI is so far unknown. In the present study, we prospectively investigated the relationship of increased aortic stiffness with biomarkers of myocardial wall stress 4 months after STEMI. METHODS: 48 STEMI patients who were reperfused by primary coronary angioplasty underwent cardiovascular magnetic resonance (CMR) at baseline and at 4-month follow-up. The CMR protocol comprised cine-CMR as well as gadolinium contrast-enhanced CMR. Aortic PWV was determined by velocity-encoded, phase-contrast CMR. Blood samples were routinely drawn at baseline and follow-up to determine N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a subgroup of patients, mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-A-type natriuretic peptide (MR-proANP) levels were determined. RESULTS: Patients with a PWV above median (>7.0m/s) had significantly higher NT-proBNP, MR-proADM and MR-proANP concentrations at 4-month follow-up than patients with a PWV below median (all p<0.02). PWV showed moderate to good correlation with NT-proBNP, MR-proAMD and MR-proANP levels 4 months after STEMI (all p<0.05). Multivariate analysis revealed PWV, beside myocardial infarct size, as an independent predictor of 4-month NT-proBNP levels after correction for age, creatinine and LV ejection fraction (model r: 0.781, p<0.001). CONCLUSION: Aortic stiffness is directly associated with biomarkers of myocardial wall stress 4 months after reperfused STEMI, suggesting a role for aortic stiffness in chronic LV-remodelling.

Effects of a 10-week conventional strength training program on lower leg muscle performance in adolescent boys compared to adults.

AIM: The use of resistance training by adolescents has been an area of controversy. The aim of the present work was therefore to evaluate the degree of strength trainability in adolescents compared to adults. METHODS: Thirteen healthy male adolescents (AL) and eight adults (AD) volunteered to participate in a 10-week training program. Subjects performed supervised exercises for the legs, calf raise, leg curl and leg extension three times a week. Maximal strength, explosive power and anaerobic power were assessed prior and after the 10-week training program. RESULTS: Significant interaction effects (time * age group) were found only for explosive strength as improvements of squat jump and counter movement jump performance (P<0.05) in favor of the AL group. No between-group changes were found for maximal strength and anaerobic power. However, significant time effects were observed for these parameters within both groups. CONCLUSION: Taken together, adolescents show distinct muscular adaptations by a higher gain in explosive power in response to resistance training when compared to adults. This might be related to peak height velocity (PHV) which is a "sensitive" period of trainability and accelerated adaptation to resistance training in adolescents.

Relation of plasma adiponectin levels and aortic stiffness after acute ST-segment elevation myocardial infarction.

BACKGROUND: Pulse wave velocity is a measure of aortic stiffness and an independent predictor of cardiovascular morbidity and mortality. Adiponectin is involved in atherosclerosis and inflammation. In the present study we aimed to explore the association between plasma adiponectin concentrations and pulse wave velocity in the acute phase after ST-segment elevation myocardial infarction (STEMI). METHODS: Forty-six consecutive STEMI patients (mean age 57 ± 11 years) treated with primary percutaneous coronary intervention (PCI) were enrolled in this cross-sectional study. Plasma adiponectin was measured 2 days after index event by enzyme-linked immunosorbent assay. Aortic pulse wave velocity (PWV) was calculated by the transit-time method with the use of a velocity-encoded, phase-contrast cardiac magnetic resonance protocol. RESULTS: Median plasma adiponectin concentration was 2385 ng/ml (interquartile range 1735-5403). Males had lower plasma adiponectin values than females and current smokers had lower values than non-smokers (all p<0.02). Adiponectin was significantly associated with PWV (r=0.505, p<0.001), age (r=0.437, p=0.002), and total cholesterol (r=0.468, p=0.001). Multiple linear regression analysis revealed adiponectin as a predictor of PWV independently of age, sex, smoking status, total cholesterol, and N-terminal pro-B-type natriuretic peptide (p=0.027). CONCLUSIONS: Plasma adiponectin concentrations are strongly associated with aortic stiffness in patients after acute STEMI treated with primary PCI. Our data support a possible role for adiponectin as an independent risk marker for increased aortic stiffness in STEMI patients.

High-dose intravenous interferon-beta in multiple sclerosis patients with high-titer neutralizing antibodies (HINABS II) - A pilot study.

BACKGROUND: Neutralizing antibodies (NAb) against interferon-beta (IFNß) affect its treatment efficacy. So far, there are no anti-NAb strategies available. OBJECTIVES: To investigate if the repeated administration of high-dose IFNß-1b intravenous in NAb positive multiple sclerosis (MS) patients induces tolerance and establishes IFNß bioavailability as measured by the induction of myxovirus protein A (MxA). METHODS: Nine MS patients with NAb titers >500 10-fold reduction units (TRU) received 1500µg IFNß-1b intravenously once weekly over three months. Blood samples were collected at screening, monthly during the treatment period (before and four hours after IFNß administration), and at follow-up after 6 months for determination of NAbs and MxA expression. RESULTS: Median NAb titer at baseline was 1429TRU. NAb titers determined before each infusion did not significantly change over the treatment period and were not different at follow-up compared to baseline. However, NAb titers were significantly decreased four hours after IFNß infusions (by roughly 50%) and MxA mRNA levels were significantly elevated reaching a median value of 206. CONCLUSIONS: Weekly intravenous administration of IFNß in patients with high NAb titers established its bioavailability, but failed to induce tolerance towards IFNß.

Ewing sarcoma versus osteomyelitis: differential diagnosis with magnetic resonance imaging.

OBJECTIVE: To find and evaluate characteristic magnetic resonance imaging (MRI) patterns for the differentiation between Ewing sarcoma and osteomyelitis. MATERIALS AND METHODS: We identified 28 consecutive patients referred to our department for MRI (1.5 T) of an unclear bone lesion with clinical symptoms suggestive of Ewing sarcoma or osteomyelitis. MRI scans were re-evaluated by two experienced radiologists, typical MR imaging features were documented and a diagnostic decision between Ewing sarcoma and osteomyelitis was made. Statistical significance of the association between MRI features and the biopsy-based diagnosis was assessed using Fisher's exact test. RESULTS: The most clear-cut pattern for determining the correct diagnosis was the presence of a sharp and defined margin of the bone lesion, which was found in all patients with Ewing sarcoma, but in none of the patients with osteomyelitis (P < 0.0001). Contrast enhancing soft tissue was present in all cases with Ewing sarcoma and absent in 4 patients with osteomyelitis (P = 0.0103). Cortical destruction was found in all patients with Ewing sarcoma, 4 patients with osteomyelitis did not present any cortical reaction (P = 0.0103). Cystic or necrotic areas were identified in 13 patients with Ewing sarcoma and in 1 patient with osteomyelitis (P = 0.004). Interobserver reliability was very good (kappa = 1) in Ewing sarcoma and moderate (kappa = 0.6) in patients with osteomyelitis. CONCLUSIONS: A sharp and defined margin, optimally visualized on T1-weighted images in comparison to short tau inversion recovery (STIR) images, is the most significant feature of Ewing sarcoma in differentiating from osteomyelitis.

Different metabolic responses during incremental exercise assessed by localized 31P MRS in sprint and endurance athletes and untrained individuals.

Until recently, assessment of muscle metabolism was only possible by invasive sampling. 31P magnetic resonance spectroscopy (31P MRS) offers a way to study muscle metabolism non-invasively. The aim of the present study was to use spatially-resolved 31P MRS to assess the metabolism of the quadriceps muscle in sprint-trained, endurance-trained and untrained individuals during exercise and recovery. 5 sprint-trained (STA), 5 endurance-trained (ETA) and 7 untrained individuals (UTI) completed one unlocalized 31P MRS session to measure phosphocreatine (PCr) recovery, and a second session in which spatially-resolved 31P MR spectra were obtained. PCr recovery time constant (τ) was significantly longer in STA (50±17 s) and UTI (41±9 s) than in ETA (30±4 s), (P<0.05). PCr changes during exercise differed between the groups, but were uniform across the different components of the quadriceps within each group. pH during recovery was higher for the ETA than for the UTI (P<0.05) and also higher than for the STA (P<0.01). Muscle volume was greater in STA than in UTI (P<0.05) but not different from ETA. Dynamic 31P MRS revealed considerable differences among endurance and sprint athletes and untrained people. This non-invasive method offers a way to quantify differences between individual muscles and muscle components in athletes compared to untrained individuals.

Evaluation of MR imaging with T1 and T2* mapping for the determination of hepatic iron overload.

OBJECTIVES: To evaluate MRI using T1 and T2* mapping sequences in patients with suspected hepatic iron overload (HIO). METHODS: Twenty-five consecutive patients with clinically suspected HIO were retrospectively studied. All underwent MRI and liver biopsy. For the quantification of liver T2* values we used a fat-saturated multi-echo gradient echo sequence with 12 echoes (TR = 200 ms, TE = 0.99 ms + n × 1.41 ms, flip angle 20°). T1 values were obtained using a fast T1 mapping sequence based on an inversion recovery snapshot FLASH sequence. Parameter maps were analysed using regions of interest. RESULTS: ROC analysis calculated cut-off points at 10.07 ms and 15.47 ms for T2* in the determination of HIO with accuracy 88 %/88 %, sensitivity 84 %/89.5 % and specificity 100 %/83 %. MRI correctly classified 20 patients (80 %). All patients with HIO only had decreased T1 and T2* relaxation times. There was a significant difference in T1 between patients with HIO only and patients with HIO and steatohepatitis (P = 0.018). CONCLUSIONS: MRI-based T2* relaxation diagnoses HIO very accurately, even at low iron concentrations. Important additional information may be obtained by the combination of T1 and T2* mapping. It is a rapid, non-invasive, accurate and reproducible technique for validating the evidence of even low hepatic iron concentrations. KEY POINTS: • Hepatic iron overload causes fibrosis, cirrhosis and increases hepatocellular carcinoma risk. • MRI detects iron because of the field heterogeneity generated by haemosiderin. • T2* relaxation is very accurate in diagnosing hepatic iron overload. • Additional information may be obtained by T1 and T2* mapping.

Reliability of constant-load treadmill testing in patients with intermittent claudication.

AIM: Constant-load treadmill testing is frequently used to estimate walking ability of patients with peripheral arterial disease and to assess changes in functional capacity following therapeutic interventions or through disease progression. The value of this test has frequently been disputed based on doubts concerning its reproducibility. The aim of this study was to investigate the reliability of treadmill testing at a speed of 3 km/h and a constant inclination of 12%. METHODS: Sixty-eight patients with stable peripheral arterial disease who were familiar with treadmill testing underwent two sessions of walking exercise at 3 km/h and 12% inclination within three weeks. Initial claudication distance (ICD) and maximum walking distance (MWD) on the treadmill as well as reported walking distances on level ground at individual speed were recorded. RESULTS: Correlation coefficients of 0.8 and within-subject variation coefficients of 15% for ICD and 13% for MWD demonstrated low variability of walking distances between visits. No learning effects were observed. Intra-class correlation coefficients of 0.78 for ICD and 0.83 for MWD proved good reproducibility of treadmill testing. Correlation of measured and reported walking distances was poor. CONCLUSION: Constant-load treadmill testing at 3km/h and 12% inclination is a well reproducible method to investigate walking capacity of patients with stable intermittent claudication who are familiar with this test method. From treadmill walking distances, no conclusions should be drawn concerning the actual walking range of the patient.

The run-off resistance (ROR) assessed on MR angiograms may serve as a valid scoring system in patients with symptomatic peripheral arterial disease (PAD) and correlates with the ankle-brachial pressure index (ABI).

OBJECTIVE: To investigate the correlation between the hemodynamic parameter ankle-brachial pressure index (ABI) and the run-off resistance (ROR) assessed on MR angiograms (MRA) in patients with peripheral arterial disease (PAD) Fontaine Stage I and II and its potential as reliable reporting system in clinical routine. METHODS: Contrast-enhanced MRA was performed in 321 PAD patients using a 1.5T MR scanner with moving bed technique. The ROR and resting ABI were determined in each patient's leg and correlation analysis was performed using the Pearson test. RESULTS: A significant negative correlation (r = -.513; p<.001) between ROR (mean 11.03±5.42) and resting ABI (mean .81±.26) was identified. An even more pronounced correlation was found in patients younger than median age who had higher ABI values (r = -.608; p<.001). CONCLUSION: The ROR scoring system evaluated in this series correlates better with the ABI than previously published scoring systems and could be suggested as reporting system for routine MRA evaluation.

Ventilation-limited exercise capacity in a 59-year-old athlete.

Aerobic exercise performance may be limited by the respiratory system in fit elderly adults whose lungs undergo the normal ageing process or who develop lung diseases but can maintain high pulmonary blood flows and ventilatory requirements. Here we describe a 59-year-old athlete demonstrating high aerobic exercise performance limited by his relatively low ventilatory capacity. The male hobby cyclist (59 years, 176 cm, 83 kg), undergoing cardiopulmonary exercise testing, reported no complaints except a history of dyspnoea and exercise intolerance at high altitude (> 2000 m). Lung function testing indicated mild airway obstruction (FEVC: 4.22 l, FEV1: 2.91 l, FEV1/FEVC: 69%) which was not reversed post-bronchodilator. However, FEV1/FEVC was slightly above the 5th percentile and thus not confirming the diagnosis of COPD. The athlete completed 300 W (3.6 W/kg) and his maximal oxygen uptake was 45 ml/min/kg (156% predicted!). Above 250 W he was unable further increasing minute ventilation, and oxygen pulse and oxygen uptake even decreased. The related changes of the respiratory pattern (increase of breathing frequency, decreases of inspiratory capacity and tidal volume) indicated dynamic lung hyperinflation resulting in cardiac output constraint, arterial oxygen desaturation, severe dyspnoea and exercise limitation. This case report delineates the pathophysiological situation of ventilation-limited exercise capacity in a well-trained middle-aged subject. However, beneficial adaptations to regular exercise may have helped maintain high aerobic performance without any adverse symptoms during submaximal exercise.

[Differential diagnosis of parkinsonian syndromes using MRI]. / Differenzialdiagnose der Parkinson-Syndrome mittels MRT.

The differential diagnosis of parkinsonian syndromes is considered one of the most challenging in clinical neurology. Despite published consensus operational criteria for the diagnosis of Parkinson's disease (PD) and the various atypical parkinsonian disorders (APD), such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal degeneration (CBD), the clinical separation of APDs from PD carries a high rate of misdiagnosis. However, the early differentiation between APD and PD, each characterized by a very different natural history, is crucial for determining the prognosis and choosing a treatment strategy. Despite limitations the various modern magnetic resonance imaging (MRI) techniques have undoubtedly added to the differential diagnosis of neurodegenerative parkinsonism. In clinical practice conventional MRI with visual assessment of T2 and T1-weighted imaging is a well established method for the exclusion of symptomatic parkinsonism due to other pathologies and may also point to the diagnosis of APD. Furthermore, advances in MRI techniques, such as diffusion-weighted imaging (DWI), have enabled abnormalities in the basal ganglia and infratentorial brain structures in APD to be quantitatively illustrated.

The Innsbruck hand transplant program: update at 8 years after the first transplant.

We herein provide an update on two bilateral hand and one bilateral forearm transplants with emphasis on immunosuppression (IS), function, morphology, and graft vascular changes at 8 years and 2 years after bilateral hand and 5 years after bilateral forearm transplantation. Between March 2000 and May 2006, three patients underwent bilateral hand or forearm transplantation at our institution. Following induction therapy with antithymocyte globulin (ATG) (n = 2) or alemtuzumab (n = 1), tacrolimus, prednisolone +/- mycophenolate mofetil (MMF) were given for maintenance IS. Later, tacrolimus (n = 1) or MMF (n = 1) was replaced by sirolimus/everolimus for long-term IS. Clinical follow-ups with evaluation of hand function, skin biopsies, X-ray, ultrasound, angiography, computed tomography angiography, electrophysiological studies, and somatosensory evoked potentials were performed at regular intervals. Three, six, and three rejection episodes were successfully treated with bolused steroids, anti-CD25 or anti-CD52 antibodies. Subsequently, skin histology remained normal without any evidence of chronic rejection. Hand function continuously improved during the first 3 years and since then remained stable with minor improvements. Investigation of hand arteries revealed no signs of occlusion or stenosis. Motor and intrinsic hand muscle function continues to improve in all patients. Protective sensation was observed in all patients; however, discriminative sensation was only accomplished after hand but not forearm transplantation. No life-threatening adverse events occurred. Despite immunologic challenging postoperative courses, patients are now free of rejection with moderate levels of IS and good functional results. No signs indicating chronic rejection have been encountered.

High-energy phosphate metabolism in the exercising muscle of patients with peripheral arterial disease.

Patients with peripheral arterial disease (PAD) suffer from impaired muscle function due to insufficient oxygen supply during exercise, mitochondrial damages, unfavourable muscle fibre type distribution and impaired exercise tolerance. These factors influence the symptoms as well as the quality of life in PAD patients and are closely connected to failures of high-energy phosphate metabolism. At onset of muscle exercise, the mitochondrial capacity cannot match the increased demand. The oxygen supply via blood flow must be increased. Meanwhile, anaerobic glycolysis and internal stores of oxygen like mixed venous blood and myoglobin as well as internal stores of high-energy phosphates like phosphocreatine (PCr) are adducted for the provision of additional adenosine-triphosphate (ATP), which is consumed by the ATPase at the myofibrils in order to fuel muscle contraction. Since the ATP production is insufficient, this phase (anaerobic phase) is characterized by a progressive decrease in PCr, which can be accurately measured by phosphorus 31 magnetic resonance spectroscopy (31p MRS). If the oxygen supply is improved, the mitochondrial capacity can match the increased metabolic demand. This phase is the aerobic phase, which is indicated by a steady-state of PCr hydrolysis. In PAD patients or experimental models of peripheral ischemia, the anaerobic phase is prolonged or does not pass into the aerobic phase resulting in exercise abortion. This review summarizes the results of 31p MRS studies investigating the high-energy phosphate metabolism during ischemic exercise in healthy humans and during ramp or incremental exercise in PAD patients.