Influence of a 7-day Transalpine Trail Run on cardiac biomarkers and myocardial function.

Intense physical exercise is known to increase cardiac biomarkers; however, it is unclear, whether this phenomenon is physiological, or if it indicates myocardial tissue injury. The aim of our study was to investigate the effects of seven consecutive days of excessive endurance exercise on continuous assessment of cardiac biomarkers, function, and tissue injury. During a 7-day trail-running competition (Transalpine Run, distance 267.4 km, altitude ascent/descent 15556/14450 m), daily blood samples were obtained for cardiac biomarkers (hs-TnT, NT-proBNP, and suppression of tumorigenicity-2 protein (ST2)) at baseline, after each stage and 24-48 h post-race. In addition, echocardiography was performed every second day, cardiac magnetic resonance imaging (CMR) before (n = 7) and after (n = 16) the race. Twelve (eight males) out of 17 healthy athletes finished all seven stages (average total finish time: 43 ± 8 h). Only NT-proBNP increased significantly (3.6-fold, p = 0.009) during the first stage and continued to increase during the race. Hs-TnT revealed an incremental trend during the first day (2.7-fold increase, p = 0.098) and remained within the pathological range throughout the race. ST2 levels did not change during the race. All cardiac biomarkers completely returned to physiological levels post-race. NT-proBNP kinetics correlated significantly with mild transient reductions in right ventricular function (assessed by TAPSE, tricuspid annular plane systolic function; r = -0.716; p = 0.014). No significant echocardiographic changes in LV dimensions, LV function, or relevant alterations in CMR were observed post-race. In summary, this study shows that prolonged, repetitive, high-volume exercise induced a transient, significant increase in NT-proBNP associated with right ventricular dysfunction without corresponding left ventricular functional or structural impairment.

MRI-based Neuropathy Score Reporting And Data System (NS-RADS): multi-institutional wider-experience usability study of peripheral neuropathy conditions among 32 radiology readers.

OBJECTIVE: To determine the inter-reader reliability and diagnostic performance of classification and severity scales of Neuropathy Score Reporting And Data System (NS-RADS) among readers of differing experience levels after limited teaching of the scoring system. METHODS: This is a multi-institutional, cross-sectional, retrospective study of MRI cases of proven peripheral neuropathy (PN) conditions. Thirty-two radiology readers with varying experience levels were recruited from different institutions. Each reader attended and received a structured presentation that described the NS-RADS classification system containing examples and reviewed published articles on this subject. The readers were then asked to perform NS-RADS scoring with recording of category, subcategory, and most likely diagnosis. Inter-reader agreements were evaluated by Conger's kappa and diagnostic accuracy was calculated for each reader as percent correct diagnosis. A linear mixed model was used to estimate and compare accuracy between trainees and attendings. RESULTS: Across all readers, agreement was good for NS-RADS category and moderate for subcategory. Inter-reader agreement of trainees was comparable to attendings (0.65 vs 0.65). Reader accuracy for attendings was 75% (95% CI 73%, 77%), slightly higher than for trainees (71% (69%, 72%), p = 0.0006) for nerves and comparable for muscles (attendings, 87.5% (95% CI 86.1-88.8%) and trainees, 86.6% (95% CI 85.2-87.9%), p = 0.4). NS-RADS accuracy was also higher than average accuracy for the most plausible diagnosis for attending radiologists at 67% (95% CI 63%, 71%) and for trainees at 65% (95% CI 60%, 69%) (p = 0.036). CONCLUSION: Non-expert radiologists interpreted PN conditions with good accuracy and moderate-to-good inter-reader reliability using the NS-RADS scoring system. CLINICAL RELEVANCE STATEMENT: The Neuropathy Score Reporting And Data System (NS-RADS) is an accurate and reliable MRI-based image scoring system for practical use for the diagnosis and grading of severity of peripheral neuromuscular disorders by both experienced and general radiologists. KEY POINTS: • The Neuropathy Score Reporting And Data System (NS-RADS) can be used effectively by non-expert radiologists to categorize peripheral neuropathy. • Across 32 different experience-level readers, the agreement was good for NS-RADS category and moderate for NS-RADS subcategory. • NS-RADS accuracy was higher than the average accuracy for the most plausible diagnosis for both attending radiologists and trainees (at 75%, 71% and 65%, 65%, respectively).

Diagnosis of joint invasion in patients with malignant bone tumors: value and reproducibility of direct and indirect signs on MR imaging.

OBJECTIVES: To evaluate the performance and reproducibility of MR imaging features in the diagnosis of joint invasion (JI) by malignant bone tumors. METHODS: MR images of patients with and without JI (n = 24 each), who underwent surgical resection at our institution, were read by three radiologists. Direct (intrasynovial tumor tissue (ITT), intraarticular destruction of cartilage/bone, invasion of capsular/ligamentous insertions) and indirect (tumor size, signal alterations of epiphyseal/transarticular bone (bone marrow replacement/edema-like), synovial contrast enhancement, joint effusion) signs of JI were assessed. Odds ratios, sensitivity, specificity, PPV, NPV, and reproducibilities (Cohen's and Fleiss' κ) were calculated for each feature. Moreover, the diagnostic performance of combinations of direct features was assessed. RESULTS: Forty-eight patients (28.7 ± 21.4 years, 26 men) were evaluated. All readers reliably assessed the presence of JI (sensitivity = 92-100 %; specificity = 88-100%, respectively). Best predictors for JI were direct visualization of ITT (OR = 186-229, p < 0.001) and destruction of intraarticular bone (69-324, p < 0.001). Direct visualization of ITT was also highly reliable in assessing JI (sensitivity, specificity, PPV, NPV = 92-100 %), with excellent reproducibility (κ = 0.83). Epiphyseal bone marrow replacement and synovial contrast enhancement were the most sensitive indirect signs, but lacked specificity (29-54%). By combining direct signs with high specificity, sensitivity was increased (96 %) and specificity (100 %) was maintained. CONCLUSION: JI by malignant bone tumors can reliably be assessed on preoperative MR images with high sensitivity, specificity, and reproducibility. Particularly direct visualization of ITT, destruction of intraarticular bone, and a combination of highly specific direct signs were valuable, while indirect signs were less predictive and specific. KEY POINTS: • Direct visualization of intrasynovial tumor was the single most sensitive and specific (92-100%) MR imaging sign of joint invasion. • Indirect signs of joint invasion, such as joint effusion or synovial enhancement, were less sensitive and specific compared to direct signs. • A combination of the most specific direct signs of joint invasion showed best results with perfect specificity and PPV (both 100%) and excellent sensitivity and NPV (both 96 %).

Ultrasound-based examination of the medial ligament complex shows gender- and age-related differences in laxity.

PURPOSE: Ultrasound (US) examination of the medial joint space of the knee has played a subordinate diagnostic role up till now. The purpose of the present study was to describe mean values of medial joint width and to investigate the impact of gender, age, and body mass index (BMI) on medial joint laxity in healthy knees using modern, dynamic US in a standardized fashion in unloaded and standardized loaded conditions. METHODS: A total of 65 subjects with 79 healthy knees were enrolled in this study. All volunteers underwent clinical examination of the knee. The medial knee joint width was determined using US in a supine position at 0° and 30° of knee flexion in unloaded and standardized loaded (= 15 Dekanewton, daN) conditions using a specific device. Mean values were described and correlations between medial knee joint width and gender, age, and BMI were assessed. RESULTS: Thirty-two females and 33 males were enrolled in this study. The mean medial joint width in 0° unloaded was 5.7 ± 1.2 mm and 7.4 ± 1.4 mm loaded. In 30° of knee flexion, the mean medial joint width was 6.1 ± 1.1 mm unloaded and 7.8 ± 1.2 mm loaded. The average change between unloaded and loaded conditions in 0° was 1.7 ± 1.0 mm and in 30° 1.7 ± 0.9 mm. A significant difference between genders was evident for medial joint width in 0° and 30° of flexion in unloaded and loaded conditions (p < 0.05). With rising age, a significant increased change of medial joint space width between unloaded and loaded conditions could be demonstrated in 0° (p = 0.032). No significant correlation between BMI and medial joint width in US could be found. CONCLUSION: Mean values of medial joint width in unloaded and standardized loaded conditions using a fixation device could be demonstrated. Based on the results of this study, medial knee joint width in US is gender- and age-related in healthy knees. These present data may be useful for evaluating patients with acute or chronic pathologies to the medial side of the knee. LEVEL OF EVIDENCE: III.

Milk cloud appearance-a characteristic sign of fibrous dysplasia on contrast-enhanced MR imaging.

OBJECTIVE: To evaluate contrast-enhanced T1-weighted magnetic resonance (MR) images in histologically proven fibrous dysplasia (FD) for the prevalence of "milk cloud appearance" and its association with ground-glass appearance (GGA) on radiography or computed tomography (CT). METHODS: For this retrospective cohort study, 37 patients with histologically proven FD imaged preoperatively with contrast-enhanced MR imaging and radiography or CT were identified at our institution. Three radiologists independently evaluated MR images for the presence of milk cloud appearance on T1-weighted contrast-enhanced images, sites of skeletal involvement, type of bone involved, uni- vs. multifocality, mono- vs. polyostotic disease, maximum diameter, proportion of bone involved, expansile remodeling, and T2 homogeneity. The presence or absence of GGA on radiography or CT was determined in consensus. Inter-reader agreement was evaluated for milk cloud appearance using Cohen's kappa, and associations between milk cloud appearance and other imaging parameters were tested using Spearman's rho. RESULTS: Among the 37 histologically proven FD lesions, GGA was identified in 70% of the lesions, while milk cloud appearance was found in 82% of the lesions. Inter-reader agreement for milk cloud appearance on MR imaging was good to excellent (κ 0.65, 0.82, and 0.8). A significant correlation was found between milk cloud appearance and GGA (ρ = 0.31, p < 0.001). CONCLUSION: Milk cloud appearance is a characteristic sign of FD on contrast-enhanced T1-weighted MR images. Recognition of this feature may be helpful when radiographs are equivocal or unremarkable or when MR imaging is performed as the primary imaging modality in cases of FD. KEY POINTS: • Fibrous dysplasia displays a characteristic feature on contrast-enhanced T1-weighted MR imaging: milk cloud appearance. • Milk cloud appearance correlates well with the radiographic or CT finding of ground-glass appearance. • Recognition of milk cloud appearance on contrast-enhanced MR imaging may be helpful when radiographs are equivocal or unremarkable or when MR imaging is performed as the primary imaging modality in cases of fibrous dysplasia.

4D-Flow MRI: Technique and Applications. / 4D-MR-Flussmessung: Technik und Anwendungen.

BACKGROUND: Blood flow through the cavities of the heart and great vessels is pulsatile and is subject to time and multidirectional variations. To date, the recording of blood flow in multiple directions and phases has been limited. 4D-flow MRI offers advantages for the recording, visualization and analysis of blood flow. METHOD: The status quo of the method was summarized through analysis with the PubMed database using the keywords "4D-flow MRI, phase-contrast magnetic resonance imaging, MR flow imaging/visualization, MR flow quantification, 3 D cine (time-resolved) phase-contrast CMR, three-directional velocity-encoding MRI". RESULTS/CONCLUSION: This review summarizes the current status of the technical development of 4D-flow MRI, discusses its advantages and disadvantages and describes clinical applications. Finally, the most important principles and parameters are explained to give the reader relevant information about clinical indications, postprocessing methods and limitations of the method. KEY POINTS: · 4D-Fluss-MRT. · 3-dimensionale zeitaufgelöste Phasenkontrast-MRT. · Flussanalyse-MRT (Wall-Shear-Stress/Druckgradienten-Messung/Vortex-Fluss/turbulente kinetische Energie/Flussgeschwindigkeit/Flussrate). CITATION FORMAT: · Sträter A, Huber A, Rudolph J et al. 4D-Flow MRI: Technique and Applications. Fortschr Röntgenstr 2018; 190: 1025 - 1035.

Improved detection rates and treatment planning of head and neck cancer using dual-layer spectral CT.

PURPOSE: The aim of this study was to evaluate the advantages of dual-layer spectral CT (DLSCT) in detection and staging of head and neck cancer (HNC) as well as the imaging of tumour margins and infiltration depth compared to conventional contrast enhanced CT (CECT). MATERIALS AND METHODS: Thirty-nine patients with a proven diagnosis of HNC were examined with a DLSCT scanner and retrospectively analysed. An age-matched healthy control group of the same size was used. Images were acquired in the venous phase. Virtual monoenergetic 40keV-equivalent (MonoE40) images were compared to CECT-images. Diagnostic confidence for tumour identification and margin detection was rated independently by four experienced observers. The steepness of the Hounsfield unit (HU)-increase at the tumour margin was analysed. External carotid artery branch image reconstructions were performed and their contrast compared to conventional arterial phase imaging. Means were compared using a Student's t-test. ANOVA was used for multiple comparisons. RESULTS: MonoE40 images were superior to CECT-images in tumour detection and margin delineation. MonoE40 showed significantly higher attenuation differences between tumour and healthy tissue compared to CECT-images (p < 0.001). The HU-increase at the boundary of the tumour was significantly steeper in MonoE40 images compared to CECT-images (p < 0.001). Iodine uptake in the tumour was significantly higher compared to healthy tissue (p < 0.001). MonoE40 compared to conventional images allowed visualisation of external carotid artery branches from the venous phase in a higher number of cases (87% vs. 67%). CONCLUSION: DLSCT enables improved detection of primary and recurrent head and neck cancer and quantification of tumour iodine uptake. Improved contrast of MonoE40 compared to conventional reconstructions enables higher diagnostic confidence concerning tumour margin detection and vessel identification. KEY POINTS: • Sensitivity concerning tumour detection are higher using dual-layer spectral-CT than conventional CT. • Lesion to background contrast in DLSCT is significantly higher than in CECT. • DLSCT provides sufficient contrast for evaluation of external carotid artery branches.

Medial meniscus extrusion increases with age and BMI and is depending on different loading conditions.

PURPOSE: Meniscus extrusion has always been described as an indirect sign of meniscus pathology and is associated with a loss of function of the affected meniscus. The current cut-off value of 3 mm displacement is indicated as abnormal and has been determined on magnetic resonance images (MRI) and ultrasound (US). However, it has to be considered that there is no description of the physiological meniscus extrusion in healthy knees depending on age or different weight-bearing conditions. It was hypothesized that in healthy knees there is a physiological age and BMI dependent meniscal extrusion, and meniscus extrusion depends on different loading conditions. METHODS: Healthy volunteers with non-symptomatic knee, and no history of knee injuries or operations were included in this prospective cross-sectional study. Exclusion criteria were age < 18years, subjective or objective instability, malalignment and positive medial meniscus test. Secondary exclusion criteria were osteoarthritis ICRS grade 3-4 or signs of meniscus tear on MRI. Every patient underwent standard knee examination following measurement of medial meniscus extrusion (MME) using US. In US extrusion was determined in supine position (unloaded) and in standing position with full weight-bearing and 20° of flexion (loaded). MRI was performed in a neutral knee position to compare ultrasound measurements with the current gold standard. Based on the power calculation of preliminary results a minimum of 70 volunteers was needed. RESULTS: 75 patients were enrolled to this study. The mean US MME was 1.1 mm ± 0.5 mm in supine position and 1.9 mm ± 0.9 mm under full weight-bearing. The mean US Δ-extrusion was 0.8 mm ± 0.6 mm. With rising age, a significant increased MME in US and MRI could be demonstrated (p < 0.001). Furthermore, elevated BMI was significantly correlated to increased US MME under full weight-bearing (p = 0.002) and to US Δ-extrusion (p = 0.003). CONCLUSION: Based on the results of this study, medial meniscus extrusion is an age-depending phenomenon in healthy knees and depends on various load-bearing conditions. Ultrasound examination of the MME might be favorable compared to MRI due to the ability of dynamic evaluation. As a consequence, the current cut-off value of 3 mm for meniscus pathologies should be reconsidered. LEVEL OF EVIDENCE: III.

Evaluation of an iterative model-based CT reconstruction algorithm by intra-patient comparison of standard and ultra-low-dose examinations.

Background The explosive growth of computer tomography (CT) has led to a growing public health concern about patient and population radiation dose. A recently introduced technique for dose reduction, which can be combined with tube-current modulation, over-beam reduction, and organ-specific dose reduction, is iterative reconstruction (IR). Purpose To evaluate the quality, at different radiation dose levels, of three reconstruction algorithms for diagnostics of patients with proven liver metastases under tumor follow-up. Material and Methods A total of 40 thorax-abdomen-pelvis CT examinations acquired from 20 patients in a tumor follow-up were included. All patients were imaged using the standard-dose and a specific low-dose CT protocol. Reconstructed slices were generated by using three different reconstruction algorithms: a classical filtered back projection (FBP); a first-generation iterative noise-reduction algorithm (iDose4); and a next generation model-based IR algorithm (IMR). Results The overall detection of liver lesions tended to be higher with the IMR algorithm than with FBP or iDose4. The IMR dataset at standard dose yielded the highest overall detectability, while the low-dose FBP dataset showed the lowest detectability. For the low-dose protocols, a significantly improved detectability of the liver lesion can be reported compared to FBP or iDose4 ( P = 0.01). The radiation dose decreased by an approximate factor of 5 between the standard-dose and the low-dose protocol. Conclusion The latest generation of IR algorithms significantly improved the diagnostic image quality and provided virtually noise-free images for ultra-low-dose CT imaging.

Aldehyde dehydrogenase 1A1--a new mediator of resistance to temozolomide in glioblastoma.

Implementation of chemotherapy with the drug temozolomide increased the overall survival of patients with glioblastoma multiforme (GBM; WHO grade IV), in particular when the O(6)-methylguanine DNA methyltransferase (MGMT) promoter is epigenetically silenced. Nevertheless, the prognosis remains poor, and relapse in GBM occurs regularly. This clinical behavior seems to be due to the existence of a therapy-resistant subpopulation of cells that induce tumor regrowth. The objective of this work was to analyze the role of aldehyde dehydrogenase (ALDH) 1A1 in mediating temozolomide resistance and its value as a predictor of clinical outcome in GBM patients. Nine GBM cell lines were treated with temozolomide alone or in combination with 4-diethylaminobenzaldehyde (DEAB), an inhibitor of ALDH1A1, or with ALDH1A1 short hairpin (sh)RNA. ALDH1A1 expression and MGMT status of 70 primary GBM patients were correlated with median survival. ALDH1A1 overexpression predicted temozolomide resistance in vitro. Sensitivity of ALDH1A1 positive/MGMT-positive cells to temozolomide could be restored by inhibition of ALDH1A1 by DEAB or by knockdown with shRNA, as indicated by increased cytotoxicity, reduced clonogenicity, and accumulation in the G2/M cell-cycle phase. The prognosis of patients with a high level of ALDH1A1 expression was poor compared with that of patients with low levels (P < .0001). ALDH1A1 is a new mediator for resistance of GBM to temozolomide and a reliable predictor of clinical outcome and may serve as a potential target to improve treatment of human GBM.

Aldehyde dehydrogenase 1 positive glioblastoma cells show brain tumor stem cell capacity.

Glioblastoma (GBM) is the most aggressive primary brain tumor and is resistant to all therapeutic regimens. Relapse occurs regularly and might be caused by a poorly characterized tumor stem cell (TSC) subpopulation escaping therapy. We suggest aldehyde dehydrogenase 1 (ALDH1) as a novel stem cell marker in human GBM. Using the neurosphere formation assay as a functional method to identify brain TSCs, we show that high protein levels of ALDH1 facilitate neurosphere formation in established GBM cell lines. Even single ALDH1 positive cells give rise to colonies and neurospheres. Consequently, the inhibition of ALDH1 in vitro decreases both the number of neurospheres and their size. Cell lines without expression of ALDH1 do not form tumor spheroids under the same culturing conditions. High levels of ALDH1 seem to keep tumor cells in an undifferentiated, stem cell-like state indicated by the low expression of beta-III-tubulin. In contrast, ALDH1 inhibition induces premature cellular differentiation and reduces clonogenic capacity. Primary cell cultures obtained from fresh tumor samples approve the established GBM cell line results.