Cluster analysis of 100 Marfan patients based on aortic 4D flow MRI and Z-score: insights into disease heterogeneity and stratification of subgroups.

OBJECTIVES: 4D flow MRI-derived variables from Marfan patients are highly heterogeneous. Our aim was to identify distinct Marfan patient subgroups based on aortic 4D flow MRI and Z-score for stratification of distinct hemodynamic profiles and clinical features by means of hierarchical cluster analysis. MATERIALS AND METHODS: One hundred Marfan patients underwent baseline aortic 4D flow MRI at 3 T. Z-scores, degree of helical and vortical flow, wall shear stress, flow displacement, and peak velocity were determined in the ascending aorta. Sex, age, BMI, antihypertensive medication, and dural ectasia were recorded. Hierarchical cluster analysis was performed using 4D flow MRI variables and Z-scores as input. RESULTS: Cluster analysis resulted in three distinct clusters characterized by different Z-scores (mean ± SD); cluster 1: 0.4 ± 1.1 vs. cluster 2: 3.1 ± 1.1 vs. cluster 3: 3.6 ± 1.9. The three clusters delivered differences in helical and vortical flow patterns (global p = 0.003 and p < 0.001, respectively), wall shear stress (0.49 ± 0.11 vs. 0.44 ± 0.12 vs. 0.37 ± 0.09 N/m2, global p < 0.001), flow displacement (0.11 ± 0.05 vs. 0.16 ± 0.08 vs. 0.15 ± 0.07, global p = 0.006), and peak velocity (76.3 ± 9.0 vs. 60.1 ± 7.3 vs. 56.0 ± 7.8 cm/s, global p < 0.001). Patients in cluster 1 and 2 were relevantly younger than in cluster 3 (32.3 ± 13.8 vs. 32.8 ± 12.6 vs. 40.2 ± 15.0 years, all pairwise ∆p < 0.0297). CONCLUSION: Hierarchical cluster analysis based on aortic 4D flow MRI and Z-score revealed three distinct subgroups of Marfan patients, each characterized by specific hemodynamic profiles and clinical features. Follow-up of our patients is warranted to assess if 4D flow MRI- and Z-score-based stratification can predict future aortic diameter growth and ultimately improve outcomes. CLINICAL RELEVANCE STATEMENT: A combination of Z-score and 4D flow MRI-derived parameters may help identify subgroups of Marfan patients representing different stages or phenotypes of aortic disease, which require specific management strategies. KEY POINTS: Four-dimensional (4D) flow MRI-derived variables of Marfan patients are highly heterogeneous across varying Z-scores. Cluster analysis based on 4D flow MRI and Z-score revealed three distinct subgroups of Marfan patients. A combination of Z-score and 4D flow MRI-derived parameters may identify different stages of aortic disease in Marfan patients.

Value of patient-reported outcome measures for evaluating the benefit of speech processor upgrading in patients with cochlear implants.

BACKGROUND: Patients with a cochlear implant (CI) should be evaluated for a new speech processor every 6 years. The aim of this analysis was to assess the subjective and audiological benefit of upgrades. METHODS: Speech understanding and subjective benefit were analyzed in 99 patients with the old and the new speech processor after 4 weeks of wearing. Speech understanding was assessed using the Freiburg monosyllabic test in quiet (FBE) at 65 dB and 80 dB, and the Oldenburg Sentence Test (OLSA) at 65 dB noise with adaptive speech sound level. The Abbreviated Profile of Hearing Aid Benefit (APHAB) was used to assess subjective hearing impairment, and the Audio Processor Satisfaction Questionnaire (APSQ) was used to assess subjective satisfaction. RESULTS: The speech processor upgrade resulted in a significant improvement of speech understanding in quiet at 65 dB (mean difference 8.9 ± 25.9 percentage points, p < 0.001) and 80 dB (mean difference 8.1 ± 29.7 percentage points, p < 0.001) and in noise (mean difference 3.2 ± 10.7 dB signal-to-noise ratio [S/N], p = 0.006). Using the APHAB, a significant improvement (mean difference 0.07 ± 0.16, p < 0.001) in hearing impairment was demonstrated in all listening situations. The APSQ showed significantly higher patient satisfaction with the new speech processor (mean difference 0.42 ± 1.26, p = 0.006). A comparative assessment of the benefit based on subjective and speech audiometric results identified a proportion of patients (35-42%) who subjectively benefited from the upgrade but had no measurable benefit based on speech audiometry. CONCLUSION: There was a significant improvement in audiologically measurable and subjectively reflected speech understanding and patient satisfaction after the upgrade. In patients with only a small improvement in audiologically measurable speech understanding, the subjective benefit should also be assessed with validated measurement instruments in order to justify an upgrade to the payers in the health sector.

Longitudinal follow-up by MR angiography reveals progressive dilatation of the distal aorta after aortic root replacement in Marfan syndrome.

OBJECTIVES: To define and compare growth rates of the distal aorta in Marfan patients with and without aortic root replacement using serial MR angiography (MRA). METHODS: We retrospectively included 136 Marfan patients with a total of 645 MRAs who underwent a median of five MRAs (range: 2-13) at 1.5 T and 3 T in annual intervals. Of these, 41 patients (34.8 ± 12 years) had undergone aortic root replacement. The remaining 95 patients (29.0 ± 17 years) still had a native aorta and served as the control group. Thoracic aortic diameters were independently measured at eleven predefined levels. Estimated growth rates were calculated using a mixed effects model adjusted for sex, age, BMI, and medication. RESULTS: Marfan patients with aortic root replacement revealed the highest mean estimated growth rate in the proximal descending aorta (0.77 mm/year, CI: 0.31-1.21). Mean growth rates at all levels of the distal thoracic aorta were significantly higher in patients with aortic root replacement (0.28-0.77 mm/year) when compared to patients without aortic root replacement (0.03-0.07 mm/year) (all p < 0.001). Antihypertensive medication, gender, and BMI had no significant impact on the distal aortic growth rates. CONCLUSION: Distal thoracic aortic diameters increase at a significantly higher rate in Marfan patients with aortic root replacement compared to Marfan patients without aortic root replacement. Further studies are warranted to investigate if the increased growth rate of the distal thoracic aorta after aortic root replacement is caused by altered hemodynamics due to the rigid aortic root graft or due to the general genetic disposition of post-operative Marfan patients. CLINICAL RELEVANCE STATEMENT: High growth rates of the distal aorta after aortic root replacement underline the need for careful life-long aortic imaging of Marfan patients after aortic root replacement. KEY POINTS: • Aortic growth rates in Marfan patients with aortic root replacement are highest in the mid-aortic arch, the proximal- and mid-descending aorta. • Growth rates of the distal thoracic aorta are significantly higher in Marfan patients with aortic root replacement compared to Marfan patients without aortic root replacement. • Antihypertensive medication, gender, and BMI have no significant impact on distal aortic growth rates in Marfan patients.

Assessment of aortic diameter in Marfan patients: intraindividual comparison of 3D-Dixon and 2D-SSFP magnetic resonance imaging.

OBJECTIVES: To compare the accuracy and precision of 3D-Dixon and 2D-SSFP MR-imaging for assessment of aortic diameter in Marfan patients. METHODS: This prospective single-center study investigated respiratory-gated 3D-Dixon and breath-hold 2D-SSFP non-contrast MR-imaging at 3 T in 47 Marfan patients (36.0 ± 13.2 years, 28♀,19♂). Two radiologists performed individual diameter measurements at five levels of the thoracic aorta and evaluated image quality on a four-grade scale (1 = poor, 4 = excellent) and artifacts (1 = severe, 4 = none). Aortic root diameters acquired by echocardiography served as a reference standard. Intraclass correlation coefficient, Bland-Altman analyses, F-test, t-test, and regression analyses were used to assess agreement between observers and methods. RESULTS: Greatest aortic diameters were observed at the level of the sinuses of Valsalva (SOV) for 3D-Dixon (38.2 ± 6.8 mm) and 2D-SSFP (38.3 ± 7.1 mm) (p = 0.53). Intra- and interobserver correlation of diameter measurements was excellent at all aortic levels for both 3D-Dixon (r = 0.94-0.99 and r = 0.94-0.98) and 2D-SSFP (r = 0.96-1.00 and r = 0.95-0.99). 3D-Dixon-derived and 2D-SSFP-derived diameter measurements at the level of the SOV revealed a strong correlation with echocardiographic measurements (r = 0.92, p < 0.001 and r = 0.93, p < 0.001, respectively). The estimated mean image quality at the level of SOV was higher for 2D-SSFP compared to that for 3D-Dixon (3.3 (95%-CI: 3.1-3.5) vs. 2.9 (95%-CI: 2.7-3.1)) (p < 0.001). Imaging artifacts were less at all aortic levels for 3D-Dixon compared to 2D-SSFP (3.4-3.8 vs. 2.8-3.1) (all p < 0.002). CONCLUSION: Respiratory-gated 3D-Dixon and breath-hold 2D-SSFP MR-imaging provide accurate and precise aortic diameter measurements. We recommend 3D-Dixon imaging for monitoring of aortic diameter in Marfan patients due to fewer imaging artifacts and the possibility of orthogonal multiplanar reformations of the aortic root. KEY POINTS: • Respiratory-gated 3D-Dixon and breath-hold 2D-SSFP imaging provide accurate and precise aortic diameter measurements in patients suffering from Marfan syndrome. • Imaging artifacts are stronger in 2D-SFFP imaging than in 3D-Dixon imaging. • We recommend 3D-Dixon imaging for monitoring of aortic diameter in Marfan patients due to fewer imaging artifacts and the possibility of orthogonal multiplanar reformations.

Validation of 4D flow cardiovascular magnetic resonance in TIPS stent grafts using a 3D-printed flow phantom.

BACKGROUND: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) is feasible for portal blood flow evaluation after placement of transjugular intrahepatic portosystemic shunts (TIPS) in patients with liver cirrhosis. However, clinical acceptance of 4D flow CMR in TIPS patients is limited due to the lack of validation studies. The purpose of this study was to validate 4D flow CMR-derived measurements in TIPS stent grafts using a three-dimensional (3D)-printed flow phantom. METHODS: A translucent flow phantom of the portal vasculature was 3D-printed. The phantom consisted of the superior mesenteric vein and the splenic vein draining into the portal vein, the TIPS-tract, and the hepatic vein. A TIPS stent graft (Gore® Viatorr®) was positioned within the TIPS-tract. Superior mesenteric vein and splenic vein served as inlets for blood-mimicking fluid. 4D flow CMR acquisitions were performed at 3T at preset flow rates of 0.8 to 2.8 l/min using velocity encoding of both 1.0 and 2.0 m/s. Flow rates and velocities were measured at predefined levels in the portal vasculature and within the stent graft. Accuracy of 4D flow CMR was assessed through linear regression with reference measurements obtained by flow sensors and two-dimensional (2D) phase contrast (PC) CMR. Intra- and interobserver agreement were assessed through Bland-Altman analyses. RESULTS: At a velocity encoding of 2.0 m/s, 4D flow CMR-derived flow rates and velocities showed an excellent correlation with preset flow rates and 2D PC CMR-derived flow velocities at all vascular levels and within the stent graft (all r ≥ 0.958, p ≤ 0.003). At a velocity encoding of 1.0 m/s, aliasing artifacts were present within the stent graft at flow rates ≥ 2.0 l/min. 4D flow CMR-derived measurements revealed high intra- and interobserver agreement. CONCLUSIONS: The in vitro accuracy and precision of 4D flow CMR is unaffected by the presence of TIPS stent grafts, suggesting that 4D flow CMR may be used to monitor TIPS patency in patients with liver cirrhosis.

Liver cirrhosis in children - the role of imaging in the diagnostic pathway.

Liver cirrhosis in children is a rare disease with multifactorial causes that are distinct from those in adults. Underlying reasons include cholestatic, viral, autoimmune, hereditary, metabolic and cardiac disorders. Early detection of fibrosis is important as clinical stabilization or even reversal of fibrosis can be achieved in some disorders with adequate treatment. This article focuses on the longitudinal evaluation of children with chronic liver disease with noninvasive imaging tools, which play an important role in detecting cirrhosis, defining underlying causes, grading fibrosis and monitoring patients during follow-up. Ultrasound is the primary imaging modality and it is used in a multiparametric fashion. Magnetic resonance imaging and computed tomography are usually applied second line for refined tissue characterization, clarification of nodular lesions and full delineation of abdominal vessels, including portosystemic communications.

[Value of patient-reported outcome measures for evaluating the benefit of speech processor upgrading in patients with cochlear implants. German version]. / Wertigkeit von Patient-Reported Outcome Measures zur Bewertung des Versorgungsvorteils der Sprachprozessorumversorgung bei Patient/-innen mit Cochleaimplantaten.

BACKGROUND: Patients with a cochlear implant (CI) should be evaluated for a new speech processor every 6 years. The aim of this analysis was to assess the subjective and audiological benefit of upgrades. METHODS: Speech understanding and subjective benefit were analyzed in 99 patients with the old and the new speech processor after 4 weeks of wearing. Speech understanding was assessed using the Freiburg monosyllabic test in quiet (FBE) at 65 dB and 80 dB, and the Oldenburg Sentence Test (OLSA) at 65 dB noise with adaptive speech sound level. The Abbreviated Profile of Hearing Aid Benefit (APHAB) was used to assess subjective hearing impairment, and the Audio Processor Satisfaction Questionnaire (APSQ) was used to assess subjective satisfaction. RESULTS: The speech processor upgrade resulted in a significant improvement of speech understanding in quiet at 65 dB (mean difference 8.9 ± 25.9 percentage points, p < 0.001) and 80 dB (mean difference 8.1 ± 29.7 percentage points, p < 0.001) and in noise (mean difference 3.2 ± 10.7 dB signal-to-noise ratio [S/N], p = 0.006). Using the APHAB, a significant improvement (mean difference 0.07 ± 0.16, p < 0.001) in hearing impairment was demonstrated in all listening situations. The APSQ showed significantly higher patient satisfaction with the new speech processor (mean difference 0.42 ± 1.26, p = 0.006). A comparative assessment of the benefit based on subjective and speech audiometric results identified a proportion of patients (35-42%) who subjectively benefited from the upgrade but had no measurable benefit based on speech audiometry. CONCLUSION: There was a significant improvement in audiologically measurable and subjectively reflected speech understanding and patient satisfaction after the upgrade. In patients with only a small improvement in audiologically measurable speech understanding, the subjective benefit should also be assessed with validated measurement instruments in order to justify an upgrade to the payers in the health sector.

Fetal dynamic magnetic resonance imaging using Doppler ultrasound gating for the assessment of the aortic isthmus: A feasibility study.

INTRODUCTION: Cardiovascular magnetic resonance imaging (MRI) is established in cardiac evaluation in postnatal life, but its application to the fetus has been hampered by technical limitations. We aimed to investigate the feasibility of dynamic MRI of the fetal aortic isthmus using a magnetic resonance-compatible Doppler ultrasound device for cardiac gating. MATERIAL AND METHODS: This prospective study included 19 fetuses at a median gestational age of 32.3 weeks (range 26-38 weeks). Imaging of the fetal aortic isthmus was assessed by (a) dynamic steady-state free precession MRI using a magnetic resonance-compatible Doppler ultrasound device for cardiac gating and (b) echocardiography. Diameters of the aortic isthmus were compared by two blinded observers. Magnetic resonance image quality was assessed independently by two observers using a four-point scale (1 = low quality, 4 = high quality). Furthermore, we performed four-dimensional flow MRI of the fetal aorta in three of these fetuses. RESULTS: The Doppler ultrasound device for cardiac gating allowed successful dynamic MRI examinations of the aortic isthmus in 18/19 (95%) fetuses. Evaluation of the fetal aortic isthmus was possible by both MRI (15/18, 83%) and echocardiography (16/18, 89%) (P < .05). Diameters of the aortic isthmus were concordant for MRI (3.8 ± 0.9 mm) and echocardiography (4.0 ± 1.1 mm), with a variability of 10.8% (bias -2.3%, 95% limits of agreement -23.9% to 19.3%). Overall magnetic resonance image quality was good (score 4 in 67% and score 3 in 23%) with good inter-observer agreement (κ = 0.75; 95% CI 0.5-1). Fetal four-dimensional flow MRI allowed visualization of aortic flow dynamics. CONCLUSIONS: Doppler ultrasound-gating allows dynamic MRI of the fetal aorta with the potential to serve as a complementary imaging tool in cases where echocardiography is inconclusive.

4D flow cardiovascular magnetic resonance for monitoring of aortic valve repair in bicuspid aortic valve disease.

BACKGROUND: Aortic valve repair has become a treatment option for adults with symptomatic bicuspid (BAV) or unicuspid (UAV) aortic valve insufficiency. Our aim was to demonstrate the feasibility of 4D flow cardiovascular magnetic resonance (CMR) to assess the impact of aortic valve repair on changes in blood flow dynamics in patients with symptomatic BAV or UAV. METHODS: Twenty patients with adult congenital heart disease (median 35 years, range 18-64; 16 male) and symptomatic aortic valve regurgitation (15 BAV, 5 UAV) were prospectively studied. All patients underwent 4D flow CMR before and after aortic valve repair. Aortic valve regurgitant fraction and systolic peak velocity were estimated. The degree of helical and vortical flow was evaluated according to a 3-point scale. Relative flow displacement and wall shear stress (WSS) were quantified at predefined levels in the thoracic aorta. RESULTS: All patients underwent successful aortic valve repair with a significant reduction of aortic valve regurgitation (16.7 ± 9.8% to 6.4 ± 4.4%, p < 0.001) and systolic peak velocity (2.3 ± 0.9 to 1.9 ± 0.4 m/s, p = 0.014). Both helical flow (1.6 ± 0.6 vs. 0.9 ± 0.5, p < 0.001) and vortical flow (1.2 ± 0.8 vs. 0.5 ± 0.6, p = 0.002) as well as both flow displacement (0.3 ± 0.1 vs. 0.25 ± 0.1, p = 0.031) and WSS (0.8 ± 0.2 N/m2 vs. 0.5 ± 0.2 N/m2, p < 0.001) in the ascending aorta were significantly reduced after aortic valve repair. CONCLUSIONS: 4D flow CMR allows assessment of the impact of aortic valve repair on changes in blood flow dynamics in patients with bicuspid aortic valve disease.

Non-contrast MR angiography at 1.5 Tesla for aortic monitoring in Marfan patients after aortic root surgery.

BACKGROUND: Contrast-enhanced cardiovascular magnetic resonance angiography (CE-CMRA) is the established imaging modality for patients with Marfan syndrome requiring life-long annual aortic imaging before and after aortic root replacement. Contrast-free CMRA techniques avoiding side-effects of contrast media are highly desirable for serial imaging but have not been evaluated in the postoperative setup of Marfan patients. The purpose of this study was to assess the feasibility of non-contrast balanced steady-state free precession (bSSFP) magnetic resonance imaging for aortic monitoring of postoperative patients with Marfan syndrome. METHODS: Sixty-four adult Marfan patients after aortic root replacement were prospectively included. Fourteen patients (22%) had a residual aortic dissection after surgical treatment of type A dissection. bSSFP imaging and CE-CMRA were performed at 1.5 Tesla. Two radiologists evaluated the images regarding image quality (1 = poor, 4 = excellent), artifacts (1 = severe, 4 = none) and aortic pathologies. Readers measured the aortic diameters at defined levels in both techniques. Statistics included observer agreement for image scoring and diameter measurements and ROC analyses for comparison of the diagnostic performance of bSSFP and CE-CMRA. RESULTS: Both readers observed no significant differences in image quality between bSSFP and CE-CMRA and found a median image quality score of 4 for both techniques (all p > .05). No significant differences were found regarding the frequency of image artifacts in both sequences (all p > .05). Sensitivity and specificity for detection of aortic dissections was 100% for both readers and techniques. Compared to bSSFP imaging, CE-CMRA resulted in higher diameters (mean bias, 0.9 mm; p < .05). The inter-observer biases of diameter measurements were not significantly different (all p > .05), except for the distal graft anastomosis (p = .001). Using both techniques, the readers correctly identified a graft suture dehiscence with aneurysm formation requiring surgery. CONCLUSION: Unenhanced bSSFP CMR imaging allows for riskless aortic monitoring with high diagnostic accuracy in Marfan patients after aortic root surgery.

Current Imaging Strategies in Patients with Abdominal Aortic Aneurysms.

BACKGROUND: An abdominal aortic aneurysm (AAA) is defined as a localized dilatation of the abdominal aorta of ≥ 3 cm. With a prevalence of 4-8 %, AAA is one of the most common vascular diseases in Western society. Radiological imaging is an elementary component in the diagnosis, monitoring, and treatment planning of AAA patients. METHOD: This is a narrative review article on preoperative imaging strategies of AAA, incorporating expert opinions based on the current literature and standard-of-care practices from our own center. Examples are provided to illustrate clinical cases from our institution. RESULTS AND CONCLUSION: Radiological imaging plays a pivotal role in the initial diagnosis and monitoring of patients with AAA. Ultrasound is the mainstay imaging modality for AAA screening and surveillance. Contrast-enhanced CT angiography is currently considered the gold standard for preoperative imaging and image-based treatment planning in AAA repair. New non-contrast MR angiography techniques are robustly applicable and allow precise determination of aortic diameters, which is of critical importance, particularly with regard to current diameter-based surgical treatment guidelines. 3D imaging with multiplanar reformation and automatic centerline positioning enables more accurate assessment of the maximum aortic diameter. Modern imaging techniques such as 4D flow MRI have the potential to further improve individualized risk stratification in patients with AAA. KEY POINTS: · Ultrasound is the mainstay imaging modality for AAA screening and monitoring. · Contrast-enhanced CT angiography is the gold standard for preoperative imaging in AAA repair. · Non-contrast MR angiography allows for accurate monitoring of aortic diameters in AAA patients. · Measurement of aortic diameters is more accurate with 3D-CT/MRI compared to ultrasound. · Research seeks new quantitative imaging biomarkers for AAA risk stratification, e. g., using 4D flow MRI.

Towards multimodal graph neural networks for surgical instrument anticipation.

PURPOSE: Decision support systems and context-aware assistance in the operating room have emerged as the key clinical applications supporting surgeons in their daily work and are generally based on single modalities. The model- and knowledge-based integration of multimodal data as a basis for decision support systems that can dynamically adapt to the surgical workflow has not yet been established. Therefore, we propose a knowledge-enhanced method for fusing multimodal data for anticipation tasks. METHODS: We developed a holistic, multimodal graph-based approach combining imaging and non-imaging information in a knowledge graph representing the intraoperative scene of a surgery. Node and edge features of the knowledge graph are extracted from suitable data sources in the operating room using machine learning. A spatiotemporal graph neural network architecture subsequently allows for interpretation of relational and temporal patterns within the knowledge graph. We apply our approach to the downstream task of instrument anticipation while presenting a suitable modeling and evaluation strategy for this task. RESULTS: Our approach achieves an F1 score of 66.86% in terms of instrument anticipation, allowing for a seamless surgical workflow and adding a valuable impact for surgical decision support systems. A resting recall of 63.33% indicates the non-prematurity of the anticipations. CONCLUSION: This work shows how multimodal data can be combined with the topological properties of an operating room in a graph-based approach. Our multimodal graph architecture serves as a basis for context-sensitive decision support systems in laparoscopic surgery considering a comprehensive intraoperative operating scene.

Discrimination of benign, atypical, and malignant peripheral nerve sheath tumors in neurofibromatosis type 1 using diffusion-weighted MRI.

Background: Neurofibromatosis type 1 (NF1) is associated with the development of benign (BPNST) and malignant (MPNST) peripheral nerve sheath tumors. Recently described atypical neurofibromas (ANF) are considered pre-malignant precursor lesions to MPNSTs. Previous studies indicate that diffusion-weighted magnetic resonance imaging (DW-MRI) can reliably discriminate MPNSTs from BPNSTs. We therefore investigated the diagnostic accuracy of DW-MRI for the discrimination of benign, atypical, and malignant peripheral nerve sheath tumors. Methods: In this prospective explorative single-center phase II diagnostic study, 44 NF1 patients (23 male; 30.1 ±â€…11.8 years) underwent DW-MRI (b-values 0-800 s/mm²) at 3T. Two radiologists independently assessed mean and minimum apparent diffusion coefficients (ADCmean/min) in areas of largest tumor diameters and ADCdark in areas of lowest signal intensity by manual contouring of the tumor margins of 60 BPNSTs, 13 ANFs, and 21 MPNSTs. Follow-up of ≥ 24 months (BPNSTs) or histopathological evaluation (ANFs + MPNSTs) served as diagnostic reference standard. Diagnostic ADC-based cut-off values for discrimination of the three tumor groups were chosen to yield the highest possible specificity while maintaining a clinically acceptable sensitivity. Results: ADC values of pre-malignant ANFs clustered between BPNSTs and MPNSTs. Best BPNST vs. ANF + MPNST discrimination was obtained using ADCdark at a cut-off value of 1.6 × 10-3 mm2/s (85.3% sensitivity, 93.3% specificity), corresponding to an AUC of 94.3% (95% confidence interval: 85.2-98.0). Regarding BPNST + ANF vs. MPNST, best discrimination was obtained using an ADCdark cut-off value of 1.4 × 10-3 mm2/s (83.3% sensitivity, 94.5% specificity). Conclusions: DW-MRI using ADCdark allows specific and noninvasive discrimination of benign, atypical, and malignant nerve sheath tumors in NF1.

Intuitive teaching of medical device operation to clinical assistance robots.

PURPOSE: The adjustment of medical devices in the operating room is currently done by the circulating nurses. As digital interfaces for the devices are not foreseeable in the near future and to incorporate legacy devices, the robotic operation of medical devices is an open topic. METHODS: We propose a teleoperated learning from demonstration process to acquire the high-level device functionality with given motion primitives. The proposed system is validated using an insufflator as an exemplary medical device. RESULTS: At the beginning of the proposed learning period, the teacher annotates the user interface to obtain the outline of the medical device. During the demonstrated interactions, the system observes the state change of the device to generalize logical rules describing the internal functionality. The combination of the internal logics with the interface annotations enable the robotic system to adjust the medical device autonomously. To interact with the device, a robotic manipulator with a finger-like end-effector is used while relying on haptic feedback from torque sensors. CONCLUSION: The proposed approach is a first step towards teaching a robotic system to operate medical devices. We aim at validating the system in an extensive user study with clinical personnel. The logical rule generalization and the logical rule inference based on computer vision methods will be focused in the future.

4D flow MRI-guided treatment of portal-hypertensive complications in a patient with multiple extrahepatic arterioportal shunts.

Portal hypertension is the underlying reason for complications like ascites or gastrointestinal varices in end-stage liver disease. On rare occasions, portal hypertension may be caused by extrahepatic arterioportal shunts. This report illustrates an outstanding case of extrahepatic arterioportal shunting as an uncommon cause of TIPS-refractory portal hypertension. Four-dimensional flow magnetic resonance imaging (4D flow MRI) is a novel non-invasive technique that enables the visualization of complex vascular disorders but has not been put into daily clinical practice in hepatology. In this case, 4D flow MRI enabled the visualization of three abdominal arterioportal shunts as the reason for TIPS-refractory portal hypertension. The quantification of individual shunt flow rates by 4D flow MRI guided our treatment strategy consisting of embolization during interventional angiography and surgical resection of all three arterioportal shunts. In conclusion, this case highlights the usefulness of 4D flow MRI for evaluating shunt flow in cases of complex vascular disorders and portal-hypertensive complications, thus helping to guide therapeutic decisions and monitoring the therapeutic success.

Cardiac T1 mapping enables risk prediction of LV dysfunction after surgery for aortic regurgitation.

Background: To assess whether cardiac T1 mapping for detecting myocardial fibrosis enables preoperative identification of patients at risk for early left ventricular dysfunction after surgery of aortic regurgitation. Methods: 1.5 Tesla cardiac magnetic resonance imaging was performed in 40 consecutive aortic regurgitation patients before aortic valve surgery. Native and post-contrast T1 mapping was performed using a modified Look-Locker inversion-recovery sequence. Serial echocardiography was performed at baseline and 8 ± 5 days after aortic valve surgery to quantify LV dysfunction. Receiver operating characteristic analysis was performed to determine the diagnostic accuracy of native T1 mapping and extracellular volume for predicting postoperative LV ejection fraction decrease >-10% after aortic valve surgery. Results: Native T1 was significantly increased in patients with a postoperatively decreased LVEF (n = 15) vs. patients with a preserved postoperative LV ejection fraction (n = 25) (i.e., 1,071 ± 67 ms vs. 1,019 ± 33 ms, p = .001). Extracellular volume was not significantly different between patients with preserved vs. decreased postoperative LV ejection fraction. With a cutoff-of value of 1,053 ms, native T1 yielded an area under the curve (AUC) of .820 (95% CI: .683-.958) for differentiating between patients with preserved vs. reduced LV ejection fraction with 70% sensitivity and 84% specificity. Conclusion: Increased preoperative native T1 is associated with a significantly higher risk of systolic LV dysfunction early after aortic valve surgery in aortic regurgitation patients. Native T1 could be a promising tool to optimize the timing of aortic valve surgery in patients with aortic regurgitation to prevent early postoperative LV dysfunction.

Impact of a Higgs boson at a mass of 126 GeV on the standard model with three and four fermion generations.

We perform a comprehensive statistical analysis of the standard model (SM) with three and four generations using the latest Higgs search results from LHC and Tevatron, the electroweak precision observables measured at LEP and SLD, and the latest determinations of M(W), m(t), and α(s). For the three-generation case we analyze the tensions in the electroweak fit by removing individual observables from the fit and comparing their predicted values with the measured ones. In particular, we discuss the impact of the Higgs search results on the deviations of the electroweak precision observables from their best-fit values. Our indirect prediction of the top mass is m(t) =175.7(-2.2)(+3.0) GeV at 68.3% C.L., which is in good agreement with the direct measurement. We also plot the preferred area in the M(W)-m(t) plane. The best-fit Higgs boson mass is 126.0 GeV. For the case of the SM with a perturbative sequential fourth fermion generation (SM4) we discuss the deviations of the Higgs signal strengths from their best-fit values. The H → γγ signal strength now disagrees with its best-fit SM4 value at more than 4σ. We perform a likelihood-ratio test to compare the SM and SM4 and show that the SM4 is excluded at 5.3σ. Without the Tevatron data on H → bb the significance drops to 4.8σ.

Impact of glyphosate-based herbicide on early embryonic development of the amphibian Xenopus laevis.

BACKGROUND: Worldwide, amphibian populations are declining drastically. One reason might be the use of pesticides including herbicides. The herbicide glyphosate is an inhibitor of the 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase of the plant shikimate pathway, preventing the formation of aromatic amino acids and thus inducing plant death. Due to this specific action, GBH are considered nontoxic to non-target organisms. However, GBH impairs embryonic development of chickens, amphibians and fishes. So far, no detailed tissue- and organ-specific analysis of the effects of GBH during development in amphibians has been performed. RESULTS: We demonstrated that GBH Roundup® LB plus has a negative effect on embryonic development of the South African clawed frog Xenopus laevis. GBH treatment with sublethal concentrations resulted in a reduced body length and mobility of embryos. Furthermore, incubation with GBH led to smaller eyes, brains and cranial cartilages in comparison to untreated embryos. GBH incubation also resulted in shorter cranial nerves and had an effect on cardiac development including reduced heart rate and atrium size. On a molecular basis, GBH treatment led to reduced expression of marker genes in different tissues and developmental stages. CONCLUSION: GBH leads to disturbed embryonic development of Xenopus laevis.

Radiation dose reduction during adrenal vein sampling using a new angiographic imaging technology.

To compare the patient radiation doses during angiographic selective adrenal vein sampling (AVS) before and after an imaging technology upgrade. In this retrospective single-center-study, cumulative air kerma (AK), cumulative dose area product (DAP), fluoroscopy time and contrast agent dosage were recorded from 70 patients during AVS. 35 procedures were performed before and 35 after an imaging processing technology upgrade. Mean values were calculated and compared using an unpaired student's t-test. DSA image quality was assessed independently by two blinded readers using a four-point Likert scale (1 = poor; 4 = excellent) and compared using Wilcoxon signed-rank test. After the technology upgrade we observed a significant reduction of 35% in AK (1.7 ± 0.7 vs. 1.1 ± 0.7 Gy, p = 0.01) and a significant reduction of 28% in DAP (235.1 ± 113 vs. 170.1 ± 94 Gy*cm2, p = 0.01) in comparison to procedures before the upgrade. There were no significant differences between the number of exposure frames (143 ± 86 vs. 132 ± 61 frames, p = 0.53), fluoroscopy time (42 ± 23 vs. 36 ± 18 min, p = 0.22), or the amount of contrast medium used (179.5 ± 84 vs. 198.1 ± 109 ml, p = 0.41). There was also no significant difference regarding image quality (3 (2-4) vs. 3 (2-4), p = 0.67). The angiographic imaging technology upgrade significantly decreases the radiation dose during adrenal vein sampling without increasing time of fluoroscopy or contrast volume and without compromising image quality.