Publications by authors named "Florian von Knobelsdorff-Brenkenhoff"

67 Publications

Influence of motion correction on the visual analysis of cardiac magnetic resonance stress perfusion imaging.

MAGMA 2021 Oct 11;34(5):757-766. Epub 2021 Apr 11.

Department of Cardiology, Academic Teaching Hospital Agatharied of the Ludwig-Maximilians-University Munich, Agatharied, Germany.

Objective: Image post-processing corrects for cardiac and respiratory motion (MoCo) during cardiovascular magnetic resonance (CMR) stress perfusion. The study analyzed its influence on visual image evaluation.

Materials And Methods: Sixty-two patients with (suspected) coronary artery disease underwent a standard CMR stress perfusion exam during free-breathing. Image post-processing was performed without (non-MoCo) and with MoCo (image intensity normalization; motion extraction with iterative non-rigid registration; motion warping with the combined displacement field). Images were evaluated regarding the perfusion pattern (perfusion deficit, dark rim artifact, uncertain signal loss, and normal perfusion), the general image quality (non-diagnostic, imperfect, good, and excellent), and the reader's subjective confidence to assess the images (not confident, confident, very confident).

Results: Fifty-three (non-MoCo) and 52 (MoCo) myocardial segments were rated as 'perfusion deficit', 113 vs. 109 as 'dark rim artifacts', 9 vs. 7 as 'uncertain signal loss', and 817 vs. 824 as 'normal'. Agreement between non-MoCo and MoCo was high with no diagnostic difference per-patient. The image quality of MoCo was rated more often as 'good' or 'excellent' (92 vs. 63%), and the diagnostic confidence more often as "very confident" (71 vs. 45%) compared to non-MoCo.

Conclusions: The comparison of perfusion images acquired during free-breathing and post-processed with and without motion correction demonstrated that both methods led to a consistent evaluation of the perfusion pattern, while the image quality and the reader's subjective confidence to assess the images were rated more favorably for MoCo.
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http://dx.doi.org/10.1007/s10334-021-00923-2DOI Listing
October 2021

Quantification of myocardial strain assessed by cardiovascular magnetic resonance feature tracking in healthy subjects-influence of segmentation and analysis software.

Eur Radiol 2021 Jun 4;31(6):3962-3972. Epub 2020 Dec 4.

Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, a Joint Cooperation Between the Charité - Universitätsmedizin Berlin, Department of Internal Medicine and Cardiology and the Max-Delbrueck Center for Molecular Medicine, and HELIOS Klinikum Berlin Buch, Department of Cardiology and Nephrology, Berlin, Germany.

Objectives: Quantification of myocardial deformation by feature tracking is of growing interest in cardiovascular magnetic resonance. It allows the assessment of regional myocardial function based on cine images. However, image acquisition, post-processing, and interpretation are not standardized. We aimed to assess the influence of segmentation procedure such as slice selection and different types of analysis software on values and quantification of myocardial strain in healthy adults.

Methods: Healthy volunteers were retrospectively analyzed. Post-processing was performed using CVI and TomTec. Longitudinal and radial strain were quantified using 4-chamber-view, 3-chamber-view, and 2-chamber-view. Circumferential and radial strain were assessed in basal, midventricular, and apical short-axis views and using full coverage. Global and segmental strain values were compared to each other regarding their post-processing approach and analysis software package.

Results: We screened healthy volunteers studied at 1.5 or 3.0 T and included 67 (age 44.3 ± 16.3 years, 31 females). Circumferential and radial strain values were different between a full coverage approach vs. three short slices (- 17.6 ± 1.8% vs. - 19.2 ± 2.3% and 29.1 ± 4.8% vs. 34.6 ± 7.1%). Different analysis software calculated significantly different strain values. Within the same vendor, different field strengths (- 17.0 ± 2.1% at 1.5 T vs. - 17.0 ± 1.7% at 3 T, p = 0.845) did not influence the calculated global longitudinal strain (GLS), and were similar in gender (- 17.4 ± 2.0% in females vs. - 16.6 ± 1.8% in males, p = 0.098). Circumferential and radial strain were different in females and males (circumferential strain - 18.2 ± 1.7% vs. - 17.1 ± 1.8%, p = 0.029 and radial strain 30.7 ± 4.7% vs. 27.8 ± 4.6%, p = 0.047).

Conclusions: Myocardial deformation assessed by feature tracking depends on segmentation procedure and type of analysis software. Circumferential and radial depend on the number of slices used for feature tracking analysis. As known from other imaging modalities, GLS seems to be the most stable parameter. During follow-up studies, standardized conditions should be warranted. Trial registration Retrospectively registered KEY POINTS: • Myocardial deformation assessed by feature tracking depends on the segmentation procedure. • Global myocardial strain values differ significantly among vendors. • Standardization in post-processing using CMR feature tracking is essential.
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http://dx.doi.org/10.1007/s00330-020-07539-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128822PMC
June 2021

Impact of sequence type and field strength (1.5, 3, and 7T) on 4D flow MRI hemodynamic aortic parameters in healthy volunteers.

Magn Reson Med 2021 02 4;85(2):721-733. Epub 2020 Aug 4.

Department of Cardiology and Nephrology, Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine and HELIOS Hospital Berlin Buch, Berlin, Germany.

Purpose: 4D flow magnetic resonance imaging (4D-MRI) allows time-resolved visualization of blood flow patterns, quantification of volumes, velocities, and advanced parameters, such as wall shear stress (WSS). As 4D-MRI enters the clinical arena, standardization and awareness of confounders are important. Our aim was to evaluate the equivalence of 4D flow-derived aortic hemodynamics in healthy volunteers using different sequences and field strengths.

Methods: 4D-MRI was acquired in 10 healthy volunteers at 1.5T using three different prototype sequences, at 3T and at 7T (Siemens Healthineers). After evaluation of diagnostic quality in three segments (ascending-, descending aorta, aortic arch), peak velocity, flow volumes, and WSS were investigated. Equivalence limits for comparison of field strengths/sequences were based on the limits of Bland-Altman analyses of the intraobserver variability.

Results: Non-diagnostic quality was found in 10/144 segments, 9/10 were obtained at 7T. Apart for the comparison of forward flow between sequence 1 and 3, the differences in measurements between field strengths/sequences exceeded the range of agreement. Significant differences were found between field strengths/sequences for forward flow (1.5T vs. 3T, 3T vs. 7T, sequence 1 vs. 3, 2 vs. 3 [P < .001]), WSS (1.5T vs. 3T [P < .05], sequence 1 vs. 2, 1 vs. 3, 2 vs. 3 [P < .001]), and peak velocity (1.5T vs. 7T, sequence 1 vs. 3 [P > .001]). All parameters at all field strengths/with all sequences correlated moderately to strongly (r ≥ 0.5).

Conclusion: Data from all sequences could be acquired and resulting images showed sufficient quality for further analysis. However, the variability of the measurements of peak velocity, flow volumes, and WSS was higher when comparing field strengths/sequences as the equivalence limits defined by the intraobserver assessments.
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http://dx.doi.org/10.1002/mrm.28450DOI Listing
February 2021

Assessment of diastolic dysfunction: comparison of different cardiovascular magnetic resonance techniques.

ESC Heart Fail 2020 10 20;7(5):2637-2649. Epub 2020 Jul 20.

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max Delbrueck Center for Molecular Medicine, Lindenberger Weg 80, Berlin, 13125, Germany.

Aims: Heart failure with preserved ejection fraction is still a diagnostic and therapeutic challenge, and accurate non-invasive diagnosis of left ventricular (LV) diastolic dysfunction (DD) remains difficult. The current study aimed at identifying the most informative cardiovascular magnetic resonance (CMR) parameters for the assessment of LVDD.

Methods And Results: We prospectively included 50 patients and classified them into three groups: with DD (DD+, n = 15), without (DD-, n = 26), and uncertain (DD±, n = 9). Diagnosis of DD was based on echocardiographic E/E', invasive LV end-diastolic pressure, and N-terminal pro-brain natriuretic peptide. CMR was performed at 1.5 T to assess LV and left atrial (LA) morphology, LV diastolic strain rate (SR) by tissue tracking and tagging, myocardial peak velocities by tissue phase mapping, and transmitral inflow profile using phase contrast techniques. Statistics were performed only on definitive DD+ and DD- (total number 41). DD+ showed enlarged LA with LA end-diastolic volume/height performing best to identify DD+ with a cut-off value of ≥0.52 mL/cm (sensitivity = 0.71, specificity = 0.84, and area under the receiver operating characteristic curve = 0.75). DD+ showed significantly reduced radial (inferolateral E peak: DD-: -14.5 ± 6.5%/s vs. DD+: -10.9 ± 5.9%/s, P = 0.04; anterolateral A peak: DD-: -4.2 ± 1.6%/s vs. DD+: -3.1 ± 1.4%/s, P = 0.04) and circumferential (inferolateral A peak: DD-: 3.8 ± 1.2%/s vs. DD+: 2.8 ± 0.8%/s, P = 0.007; anterolateral A peak: DD-: 3.5 ± 1.2%/s vs. DD+: 2.5 ± 0.8%/s, P = 0.048) SR in the basal lateral wall assessed by tissue tracking. In the same segments, DD+ showed lower peak myocardial velocity by tissue phase mapping (inferolateral radial peak: DD-: -3.6 ± 0.7 ms vs. DD+: -2.8 ± 1.0 ms, P = 0.017; anterolateral longitudinal peak: DD-: -5.0 ± 1.8 ms vs. DD+: -3.4 ± 1.4 ms, P = 0.006). Tagging revealed reduced global longitudinal SR in DD+ (DD-: 45.8 ± 12.0%/s vs. DD+: 34.8 ± 9.2%/s, P = 0.022). Global circumferential and radial SR by tissue tracking and tagging, LV morphology, and transmitral flow did not differ between DD+ and DD-.

Conclusions: Left atrial size and regional quantitative myocardial deformation applying CMR identified best patients with DD.
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http://dx.doi.org/10.1002/ehf2.12846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524101PMC
October 2020

Influence of contrast agent and spatial resolution on myocardial strain results using feature tracking MRI.

Eur Radiol 2020 Nov 29;30(11):6099-6108. Epub 2020 May 29.

Department of Cardiology, Clinic Agatharied, Ludwig-Maximilians-University of Munich, Norbert-Kerkel-Platz, Hausham, Agatharied, 83734, Munich, Germany.

Objectives: Feature tracking for assessing myocardial strain from cardiac magnetic resonance (CMR) cine images detects myocardial deformation abnormalities with prognostic implication, e.g., in myocardial infarction and cardiomyopathy. Standards for image acquisition and processing are not yet available. Study aim was analyzing the influence of spatial resolution and contrast agent on myocardial strain results.

Methods: Seventy-five patients underwent CMR for analyzing peak systolic circumferential, longitudinal, and radial strain. Group A included n = 50 with normal left ventricular ejection fraction, no wall motion abnormality, and no fibrosis on late enhancement imaging. Group B included n = 25 with chronic myocardial infarct. For feature tracking, steady-state free precession cine images were acquired repeatedly. (1) Native standard cine (spatial resolution 1.4 × 1.4 × 8 mm). (2) Native cine with lower spatial resolution (2.0 × 2.0 × 8 mm). (3) Cine equal to variant 1 acquired after administration of gadoteracid.

Results: Lower spatial resolution was associated with elevated longitudinal strain (- 21.7% vs. - 19.8%; p < 0.001) in viable myocardium in group A, and with elevated longitudinal (- 17.0% vs. - 14.3%; p = 0.001), circumferential (- 18.6% vs. - 14.6%; p = 0.002), and radial strain (36.8% vs. 31.0%; p = 0.013) in infarcted myocardium in group B. Gadolinium administration was associated with reduced circumferential (- 21.4% vs. - 22.3%; p = 0.001) and radial strain (44.4% vs. 46.9%; p = 0.016) in group A, whereas strain results of the infarcted tissue in group B did not change after contrast agent administration.

Conclusions: Variations in spatial resolution and the administration of contrast agent may influence myocardial strain results in viable and partly in infarcted myocardium. Standardized image acquisition seems important for CMR feature tracking.

Key Points: • Feature tracking is used for calculating myocardial strain from cardiac magnetic resonance (CMR) cine images. • This prospective study demonstrated that CMR strain results may be influenced by spatial resolution and by the administration of gadolinium-based contrast agent. • The results underline the need for standardized image acquisition for CMR strain analysis, with constant imaging parameters and without contrast agent.
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http://dx.doi.org/10.1007/s00330-020-06971-xDOI Listing
November 2020

Standardized image interpretation and post-processing in cardiovascular magnetic resonance - 2020 update : Society for Cardiovascular Magnetic Resonance (SCMR): Board of Trustees Task Force on Standardized Post-Processing.

J Cardiovasc Magn Reson 2020 03 12;22(1):19. Epub 2020 Mar 12.

Institute for Experimental and Translational Cardiovascular Imaging, DZHK (German Centre for Cardiovascular Research) Centre for Cardiovascular Imaging, partner site RheinMain, University Hospital Frankfurt, Frankfurt am Main, Germany.

With mounting data on its accuracy and prognostic value, cardiovascular magnetic resonance (CMR) is becoming an increasingly important diagnostic tool with growing utility in clinical routine. Given its versatility and wide range of quantitative parameters, however, agreement on specific standards for the interpretation and post-processing of CMR studies is required to ensure consistent quality and reproducibility of CMR reports. This document addresses this need by providing consensus recommendations developed by the Task Force for Post-Processing of the Society for Cardiovascular Magnetic Resonance (SCMR). The aim of the Task Force is to recommend requirements and standards for image interpretation and post-processing enabling qualitative and quantitative evaluation of CMR images. Furthermore, pitfalls of CMR image analysis are discussed where appropriate. It is an update of the original recommendations published 2013.
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http://dx.doi.org/10.1186/s12968-020-00610-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066763PMC
March 2020

Cardiorenal sodium MRI at 7.0 Tesla using a 4/4 channel H/ Na radiofrequency antenna array.

Magn Reson Med 2019 12 30;82(6):2343-2356. Epub 2019 Jun 30.

Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.

Purpose: Cardiorenal syndrome describes disorders of the heart and the kidneys in which a dysfunction of 1 organ induces a dysfunction in the other. This work describes the design, evaluation, and application of a 4/4-channel hydrogen-1/sodium ( H/ Na) RF array tailored for cardiorenal MRI at 7.0 Tesla (T) for a better physiometabolic understanding of cardiorenal syndrome.

Methods: The dual-frequency RF array is composed of a planar posterior section and a modestly curved anterior section, each section consisting of 2 loop elements tailored for Na MR and 2 loopole-type elements customized for H MR. Numerical electromagnetic field and specific absorption rate simulations were carried out. Transmission field ( ) uniformity was optimized and benchmarked against electromagnetic field simulations. An in vivo feasibility study was performed.

Results: The proposed array exhibits sufficient RF characteristics, homogeneity, and penetration depth to perform Na MRI of the heart and kidney at 7.0 T. The mean field for sodium in the heart is 7.7 ± 0.8 µT/√kW and in the kidney is 6.9 ± 2.3 µT/√kW. The suitability of the RF array for Na MRI was demonstrated in healthy subjects (acquisition time for Na MRI: 18 min; nominal isotropic spatial resolution: 5 mm [kidney] and 6 mm [heart]).

Conclusion: This work provides encouragement for further explorations into densely packed multichannel transceiver arrays tailored for Na MRI of the heart and kidney. Equipped with this technology, the ability to probe sodium concentration in the heart and kidney in vivo using Na MRI stands to make a critical contribution to deciphering the complex interactions between both organs.
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http://dx.doi.org/10.1002/mrm.27880DOI Listing
December 2019

Correction to: Subclinical myocardial injury in patients with Facioscapulohumeral muscular dystrophy 1 and preserved ejection fraction - assessment by cardiovascular magnetic resonance.

J Cardiovasc Magn Reson 2019 Jun 3;21(1):32. Epub 2019 Jun 3.

Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center a joint cooperation between the Charité - Universitätsmedizin Berlin, Department of Internal Medicine and Cardiology and the Max-Delbrueck Center for Molecular Medicine, and HELIOS Klinikum Berlin Buch,Department of Cardiology and Nephrology, Berlin, Germany.

In the original version of this article [1], published on 29 April 2019, there is 1 error in the 'Method' section of the article.
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http://dx.doi.org/10.1186/s12968-019-0541-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545672PMC
June 2019

Subclinical myocardial injury in patients with Facioscapulohumeral muscular dystrophy 1 and preserved ejection fraction - assessment by cardiovascular magnetic resonance.

J Cardiovasc Magn Reson 2019 04 29;21(1):25. Epub 2019 Apr 29.

Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center a joint cooperation between the Charité - Universitätsmedizin Berlin, Department of Internal Medicine and Cardiology and the Max-Delbrueck Center for Molecular Medicine, and HELIOS Klinikum Berlin Buch,Department of Cardiology and Nephrology, Berlin, Germany.

Background: Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is an autosomal dominant and the third most common inherited muscle disease. Cardiac involvement is currently described in several muscular dystrophies (MD), but there are conflicting reports in FSHD1. Mostly, FSHD1 is recognized as MD with infrequent cardiac involvement, but sudden cardiac deaths are reported in single cases. The aim of this study is to investigate whether subclinical cardiac involvement in FSHD1 patients is detectable in preserved left ventricular systolic function applying cardiovascular magnetic resonance (CMR).

Methods: We prospectively included patients with genetically confirmed FSHD1 (n = 52, 48 ± 15 years) and compared them with 29 healthy age-matched controls using a 1.5 T CMR scanner. Myocardial tissue differentiation was performed qualitatively using focal fibrosis imaging (late gadolinium enhancement (LGE)), fat imaging (multi-echo sequence for fat/water-separation) and parametric T2- and T1-mapping for quantifying inflammation and diffuse fibrosis. Extracellular volume fraction was calculated. A 12-lead electrocardiogram and 24-h Holter were performed for the assessment of MD-specific Groh-criteria and arrhythmia.

Results: Focal fibrosis by LGE was present in 13 patients (25%,10 men), fat infiltration in 7 patients (13%,5 men). T2 values did not differ between FSHD1 and healthy controls. Native T1 mapping revealed significantly higher values in patients (global native myocardial T1 values basal: FSHD1: 1012 ± 26 ms vs. controls: 985 ± 28 ms, p < 0.01, medial FSHD1: 994 ± 37 ms vs. controls: 982 ± 28 ms, p = 0.028). This was also evident in regions adjacent to focal fibrosis, indicating diffuse fibrosis. Groh-criteria were positive in 1 patient. In Holter, arrhythmic events were recorded in 10/43 subjects (23%).

Conclusions: Patients with FSHD1 and preserved left ventricular ejection fraction present focal and diffuse myocardial injury. Longitudinal multi-center trials are needed to define the impact of myocardial changes as well as a relation between myocardial injury and arrhythmias on long-term prognosis and therapeutic decision-making.

Trial Registration: ISRCTN registry with study ID ISRCTN13744381 .
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http://dx.doi.org/10.1186/s12968-019-0537-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487526PMC
April 2019

Porous medium 3D flow simulation of contrast media washout in cardiac MRI reflects myocardial injury.

Magn Reson Med 2019 08 16;82(2):775-785. Epub 2019 Apr 16.

DZHK, German Center for Cardiovascular Research, Berlin, Germany.

Purpose: Myocardial blood-flow simulation based on laws of fluid mechanics is a valuable tool for understanding tissue behavior. Our aim is to evaluate the ability of a porous-media flow model approach to reflect disturbed washout of contrast media (CM) from the myocardium as observed by cardiovascular MR.

Methods: A coupled advection-diffusion model is used to describe the CM flow in the vascular and extravascular space as separate compartments. Their exchange of CM is controlled by the exchange rate , which in turn determines the washout behavior. We fitted simulations to CM concentration measurements, derived from T maps of the midventricular slice. The CM concentration was extracted from 18 patients with myocarditis in the acute phase and during follow-up after 6 months. The results were compared with 18 sex- and age-matched controls. For each subject, the measurements were acquired before and during the first 10 minutes at 5 time points after CM administration, representing CM washout. Image registration was applied to compensate for motion between different time points.

Results: Eight matched data sets had to be excluded due to low registration quality. Processing was successful in n = 10 matched data sets of acute and healed myocarditis as well as controls. Significant differences in were observed when comparing patients with acute myocarditis to controls (P < .001), to their follow-up (P < .05), and the follow-up to controls (P < .05).

Conclusion: Our study suggests the feasibility of using the proposed porous-medium flow framework for the simulation of pathologic myocardial tissue.
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http://dx.doi.org/10.1002/mrm.27756DOI Listing
August 2019

Native myocardial T1 time can predict development of subsequent anthracycline-induced cardiomyopathy.

ESC Heart Fail 2018 08 19;5(4):620-629. Epub 2018 Apr 19.

Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center - a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Germany.

Aims: This study aims to assess subclinical changes in functional and morphological myocardial magnetic resonance parameters very early into an anthracycline treatment, which may predict subsequent development of anthracycline-induced cardiomyopathy (aCMP).

Methods And Results: Thirty sarcoma patients with planned anthracycline-based chemotherapy (360-400 mg/m doxorubicin-equivalent) were recruited. Median treatment time was 19.1 ± 2.1 weeks. Enrolled individuals received three cardiovascular magnetic resonance studies (before treatment, 48 h after first anthracycline treatment, and upon completion of treatment). Native T1 mapping (modified Look-Locker inversion recovery 5s(3s)3s), T2 mapping, and extracellular volume maps were acquired in addition to a conventional cardiovascular magnetic resonance with steady-state free precession cine imaging at 1.5 T. Patients were given 0.2 mmol/kg gadoteridol for extracellular volume quantification and late gadolinium enhancement imaging. Development of relevant aCMP was defined as drop of left ventricular ejection fraction (LVEF) by >10%. For analysis, 23 complete data sets were available. Nine patients developed aCMP with LVEF reduction >10% until end of chemotherapy. Baseline LVEF was not different between patients with and without subsequent aCMP. When assessed 48 h after first dose of antracyclines, patients with subsequent aCMP had significantly lower native myocardial T1 times compared with before therapy (1002.0 ± 37.9 vs. 956.5 ± 29.2 ms, P < 0.01) than patients who did not develop aCMP (990.9 ± 56.4 vs. 978.4 ± 57.4 ms, P > 0.05). Patients with aCMP had decreased left ventricular mass upon completion of therapy (86.9 ± 24.5 vs. 81.1 ± 22.3 g; P = 0.02), while patients without aCMP did not show a change in left ventricular mass (81.8 ± 21.0 vs. 79.2 ± 18.1 g; P > 0.05). No patient developed new myocardial scars or compact myocardial fibrosis under chemotherapy.

Conclusions: Early decrease of T1 times 48 h after first treatment with anthracyclines can predict the development of subsequent aCMP after completion of chemotherapy.
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http://dx.doi.org/10.1002/ehf2.12277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073029PMC
August 2018

Comparison of fast multi-slice and standard segmented techniques for detection of late gadolinium enhancement in ischemic and non-ischemic cardiomyopathy - a prospective clinical cardiovascular magnetic resonance trial.

J Cardiovasc Magn Reson 2018 02 19;20(1):13. Epub 2018 Feb 19.

Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center - a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine and HELIOS Hospital Berlin-Buch, Department of Cardiology and Nephrology, Lindenberger Weg 80, 13125, Berlin, Germany.

Background: Segmented phase-sensitive inversion recovery (PSIR) cardiovascular magnetic resonance (CMR) sequences are reference standard for non-invasive evaluation of myocardial fibrosis using late gadolinium enhancement (LGE). Several multi-slice LGE sequences have been introduced for faster acquisition in patients with arrhythmia and insufficient breathhold capability. The aim of this study was to assess the accuracy of several multi-slice LGE sequences to detect and quantify myocardial fibrosis in patients with ischemic and non-ischemic myocardial disease.

Methods: Patients with known or suspected LGE due to chronic infarction, inflammatory myocardial disease and hypertrophic cardiomyopathy (HCM) were prospectively recruited. LGE images were acquired 10-20 min after administration of 0.2 mmol/kg gadolinium-based contrast agent. Three different LGE sequences were acquired: a segmented, single-slice/single-breath-hold fast low angle shot PSIR sequence (FLASH-PSIR), a multi-slice balanced steady-state free precession inversion recovery sequence (bSSFP-IR) and a multi-slice bSSFP-PSIR sequence during breathhold and free breathing. Image quality was evaluated with a 4-point scoring system. Contrast-to-noise ratios (CNR) and acquisition time were evaluated. LGE was quantitatively assessed using a semi-automated threshold method. Differences in size of fibrosis were analyzed using Bland-Altman analysis.

Results: Three hundred twelve patients were enrolled (n = 212 chronic infarction, n = 47 inflammatory myocardial disease, n = 53 HCM) Of which 201 patients (67,4%) had detectable LGE (n = 143 with chronic infarction, n = 27 with inflammatory heart disease and n = 31 with HCM). Image quality and CNR were best on multi-slice bSSFP-PSIR. Acquisition times were significantly shorter for all multi-slice sequences (bSSFP-IR: 23.4 ± 7.2 s; bSSFP-PSIR: 21.9 ± 6.4 s) as compared to FLASH-PSIR (361.5 ± 95.33 s). There was no significant difference of mean LGE size for all sequences in all study groups (FLASH-PSIR: 8.96 ± 10.64 g; bSSFP-IR: 8.69 ± 10.75 g; bSSFP-PSIR: 9.05 ± 10.84 g; bSSFP-PSIR free breathing: 8.85 ± 10.71 g, p > 0.05). LGE size was not affected by arrhythmia or absence of breathhold on multi-slice LGE sequences.

Conclusions: Fast multi-slice and standard segmented LGE sequences are equivalent techniques for the assessment of myocardial fibrosis, independent of an ischemic or non-ischemic etiology. Even in patients with arrhythmia and insufficient breathhold capability, multi-slice sequences yield excellent image quality at significantly reduced scan time and may be used as standard LGE approach.

Trial Registration: ISRCTN48802295 (retrospectively registered).
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http://dx.doi.org/10.1186/s12968-018-0434-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819178PMC
February 2018

Quantification of the left atrium applying cardiovascular magnetic resonance in clinical routine.

Scand Cardiovasc J 2018 04 5;52(2):85-92. Epub 2018 Jan 5.

a Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, a joint cooperation between the Charité - Universitätsmedizin Berlin, Department of Internal Medicine and Cardiology and the Max-Delbrueck Center for Molecular Medicine, and HELIOS Klinikum Berlin Buch, Department of Cardiology and Nephrology , Berlin , Germany.

Objectives: In recent years the impact of the left atrium (LA) has become more evident in different cardiovascular pathologies. We aim to provide LA parameters in healthy volunteers for cardiovascular magnetic resonance (CMR) using a fast approach.

Design: We analyzed 203 healthy volunteers (mean age 44.6 years (y), range 19y-76y) at 1.5 and 3.0 Tesla (T) using steady-state free precession (SSFP) cine in routine long axis view. Left atrial enddiastolic volume (LA-EDV), endsystolic volume (LA-ESV), stroke volume (LA-SV) and ejection fraction (LA-EF) were quantified and indexed to body-surface-area (BSA). Dependency on age and sex was analyzed.

Results: 21 subjects had to be excluded. In the remaining, there was no significant difference between 1.5 T and 3.0 T. Absolut LA-EDV and LA-ESV were larger in men than in women (LA-EDV: male 70 ± 19 ml vs. female 61 ± 16 ml (p = .001); LA-ESV: male 24 ± 9 ml vs. female 21 ± 8 ml (p = .01)). These differences disappeared after indexing to BSA (LA-EDV/BSA: male 34 ± 10 ml/m vs. female 33 ± 9 ml/m (p = .65) and LA-ESV/BSA: male 12 ± 4 ml/m vs. female 11 ± 4 ml/m (p = .71)). LA-EDV/BSA decreased with older age.

Conclusions: Reference values for LA size and function based on a fast approach are provided. LA size decreases with older age. Normalization to body size overcomes sex-dependency. Reports should be related to body size.
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http://dx.doi.org/10.1080/14017431.2017.1423107DOI Listing
April 2018

Effect of candesartan and metoprolol on myocardial tissue composition during anthracycline treatment: the PRADA trial.

Eur Heart J Cardiovasc Imaging 2018 05;19(5):544-552

Department of Cardiology, Division of Medicine, Akershus University Hospital, Sykehusveien 25, 1478 Lørenskog, Norway.

Aims: Anthracycline treatment may cause myocyte loss and expansion of the myocardial extracellular volume (ECV) fraction by oedema and fibrosis. We tested the hypotheses that adjuvant treatment for early breast cancer with the anthracycline epirubicin is dose dependently associated with increased ECV fraction and total ECV, as well as reduced total myocardial cellular volume, and that these changes could be prevented by concomitant angiotensin or beta-adrenergic blockade.

Methods And Results: PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA) was a 2 × 2 factorial, placebo-controlled, double-blinded trial of candesartan and metoprolol. Sixty-nine women had valid ECV measurements. ECV fraction, total ECV, and total cellular volume were measured by cardiovascular magnetic resonance before and at the completion of anthracycline therapy. ECV fraction increased from 27.5 ± 2.7% to 28.6 ± 2.9% (P = 0.002). A cumulative doxorubicin equivalent dose of 268 mg/m2 was associated with greater increase in ECV fraction than doses <268 mg/m2 (mean change 3.4% [95% confidence interval (CI) 1.2, 5.5] vs. 0.7% [95% CI 0.0, 1.5], P = 0.006), as well as greater increase in total ECV (1.9 mL [95% CI 0.4, 3.5] vs. 0.1 mL [95% CI -0.6, 0.8], P = 0.04). In patients receiving candesartan, total cellular volume decreased (-3.5 mL [95% CI - 4.7, -2.2], P < 0.001) while in patients not receiving candesartan, it remained unchanged (P = 0.45; between group difference P = 0.003).

Conclusions: Anthracycline therapy is associated with dose-dependent increase in ECV fraction and total ECV. Concomitant treatment with candesartan reduces left ventricular total cellular volume.
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http://dx.doi.org/10.1093/ehjci/jex159DOI Listing
May 2018

Myocardial tissue characterization by contrast-enhanced cardiac magnetic resonance imaging in subjects with prediabetes, diabetes, and normal controls with preserved ejection fraction from the general population.

Eur Heart J Cardiovasc Imaging 2018 06;19(6):701-708

Department of Diagnostic and Interventional Radiology, University of Tuebingen, Hoppe-Seyler-Straße 3, 72076 Tuebingen, Germany.

Aims: To characterize changes in the myocardium in subjects with prediabetes, diabetes, and healthy controls with preserved left ventricular ejection fraction (LVEF) by using cardiac magnetic resonance imaging (CMR) in a sample from the general population.

Methods And Results: Subjects without history of cardiovascular disease and preserved LVEF but established diabetes, prediabetes, and controls from a population-based cohort underwent contrast-enhanced CMR. Obtained parameters included left ventricular (LV) function and morphology, late gadolinium enhancement as well as T1-mapping and derivation of extracellular volume fraction (ECV) by modified Look-Locker inversion recovery for diffuse fibrosis in a subset of patients. Fibrosis volume and cell volume were calculated and LV remodelling index was calculated by dividing the LV mass by its end-diastolic volume. Among 343 subjects (56.1 ± 9.2 years, 57% males), 47 subjects were classified as diabetes, 78 as prediabetes, and 218 as controls. Haematocrit values and thus ECV parameters were available in 251 subjects. LV remodelling index was significantly higher in participants with prediabetes and diabetes, independent of body mass index (BMI), hypertension, age, and sex. ECV was decreased in subjects with prediabetes and diabetes compared with healthy controls (23.1 ± 2.4% and 22.8 ± 3.0%, both P < 0.007). In contrast, cell volume was significantly higher in subjects with prediabetes and diabetes as compared with controls (109.1 ± 23.8 and 114.9 ± 32.3 mL vs. 96.5 ± 26.9 mL, both P < 0.03, respectively). However, differences in ECV and cell volume attenuated after the adjustment for cardiometabolic risk factors, including age, sex, BMI, and hypertension.

Conclusion: Subjects with prediabetes and diabetes but preserved LVEF had higher LV remodelling indices, suggesting early detectable changes in the disease process, while diffuse myocardial fibrosis appears to be less relevant at this stage.
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http://dx.doi.org/10.1093/ehjci/jex190DOI Listing
June 2018

Representation of cardiovascular magnetic resonance in the AHA / ACC guidelines.

J Cardiovasc Magn Reson 2017 Sep 25;19(1):70. Epub 2017 Sep 25.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany.

Background: Whereas evidence supporting the diagnostic value of cardiovascular magnetic resonance (CMR) has increased, there exists significant worldwide variability in the clinical utilization of CMR. A recent study demonstrated that CMR is represented in the majority of European Society for Cardiology (ESC) guidelines, with a large number of specific recommendations in particular regarding coronary artery disease. To further investigate the gap between the evidence and clinical use of CMR, this study analyzed the role of CMR in the guidelines of the American College of Cardiology (ACC) and American Heart Association (AHA).

Methods: Twenty-four AHA/ACC original guidelines, updates and new editions, published between 2006 and 2017, were screened for the terms "magnetic", "MRI", "CMR", "MR" and "imaging". Non-cardiovascular MR examinations were excluded. All CMR-related paragraphs and specific recommendations for CMR including the level of evidence (A, B, C) and the class of recommendation (I, IIa, IIb, III) were extracted.

Results: Twelve of the 24 guidelines (50.0%) contain specific recommendations regarding CMR. Four guidelines (16.7%) mention CMR in the text only, and 8 (33.3%) do not mention CMR. The 12 guidelines with recommendations for CMR contain in total 65 specific recommendations (31 class-I, 23 class-IIa, 6 class-IIb, 5 class-III). Most recommendations have evidence level C (44/65; 67.7%), followed by level B (21/65; 32.3%). There are no level A recommendations. 22/65 recommendations refer to vascular imaging, 17 to congenital heart disease, 8 to cardiomyopathies, 8 to myocardial stress testing, 5 to left and right ventricular function, 3 to viability, and 2 to valvular heart disease.

Conclusions: CMR is represented in two thirds of the AHA/ACC guidelines, which contain a number of specific recommendations for the use of CMR. In a simplified comparison with the ESC guidelines, CMR is less represented in the AHA/ACC guidelines in particular in the field of coronary artery disease.
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http://dx.doi.org/10.1186/s12968-017-0385-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5611635PMC
September 2017

Advanced Assessment of Aortic Stenosis Reflecting the Complex Interplay of Valve, Ventricle, Vessel, and Flow.

Circ Cardiovasc Imaging 2017 06;10(6)

From the Department of Cardiology, Clinic Agatharied, Ludwig Maximilian University of Munich, Hausham, Germany; and Working Group Cardiovascular MR, Experimental and Clinical Research Center, Joint Cooperation Between Charité and Max-Delbrueck Center for Molecular Medicine, Berlin, Germany.

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http://dx.doi.org/10.1161/CIRCIMAGING.117.006594DOI Listing
June 2017

Cardiac Fibrosis in Aortic Stenosis and Hypertensive Heart Disease Assessed by Magnetic Resonance T1 Mapping.

J Heart Valve Dis 2016 09;25(5):527-533

German Center for Cardiovascular Research (DZHK), partner site Berlin, Germany.

Background: Continuous pressure overload may lead to subclinical myocardial tissue changes in patients with hypertensive heart disease (HHD) and aortic stenosis (AS). The study aim was to detect interstitial fibrosis using quantitative cardiovascular magnetic resonance.

Methods: Fifteen patients with HHD (arterial hypertension + septal wall thickness ≥13 mm), 33 with AS (eight mild, 15 moderate, 10 severe), and 60 healthy controls were enrolled. Native T1 maps (modified Look-Locker inversion recovery) were obtained in a basal, mid-ventricular, and apical shortaxis slice of the left ventricle to assess cardiac fibrosis. Focal fibrosis was assessed with late gadolinium enhancement (LGE).

Results: Patients with HHD and controls did not differ regarding the native myocardial T1 values, both per slice and per segment. In AS patients, apical native T1 values were lower than in controls, and there was a trend towards higher T1 values in the septum in severe AS (1172.6 ± 62.0 ms versus 1152.9 ± 43.9 ms). Five HHD patients and 11 AS patients had non-ischemic fibrosis in LGE images. Native T1 times did not differ between LGE-positive and LGEnegative groups (both with inclusion and exclusion of segments with LGE).

Conclusions: T1 mapping did not reveal any evidence of abnormal interstitial fibrosis in HHD subjects with mild hypertrophy. In severe AS, a trend towards more interstitial fibrosis was present, but absolute differences were small for decision making.
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September 2016

Detection and Monitoring of Acute Myocarditis Applying Quantitative Cardiovascular Magnetic Resonance.

Circ Cardiovasc Imaging 2017 Feb;10(2)

From the Working Group Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine; and HELIOS Klinikum Berlin Buch, Department of Cardiology and Nephrology, Germany (F.v.K.-B., J.S., S.D., A.R., J.S.-M.); Clinic Agatharied, Department of Cardiology, Ludwig-Maximilians-University Munich, Hausham, Germany (F.v.K.-B.); Siemens Healthcare, Erlangen, Germany (M.A.D., A.G.); National Institute of Health, Bethesda, MD (P.K.); and German Center for Cardiovascular Research (DZHK), partner site Berlin, Germany (J.S.-M.).

Background: Cardiovascular magnetic resonance based on the Lake Louise Criteria is used to make the diagnosis of acute myocarditis. Novel quantitative parametric mapping techniques promise to overcome some of its limitations. We aimed to evaluate quantitative cardiovascular magnetic resonance to detect and monitor acute myocarditis.

Methods And Results: Eighteen patients with clinical diagnosis of acute myocarditis (25 years [23-38 years]; 78% males) were prospectively enrolled and repeatedly underwent cardiovascular magnetic resonance at 1.5 T seven days (5-10 days) after symptom onset (FU0), after 5 weeks (FU1), and after 6 months (FU2). Eighteen age- and sex-matched healthy subjects served as controls. Cardiovascular magnetic resonance included imaging of edema, hyperemia, necrosis, and fibrosis using semiquantitative T2-weighted spin echo, T2 mapping, and T1 mapping before and 3 and 10 minutes after gadobutrol administration. Extracellular volume for diffuse and late gadolinium enhancement for focal fibrosis were assessed. Compared with controls, patients had significantly higher global T2 times at FU0 (55.1 ms [53.3-57.2 ms] versus 50.2 ms [49.2-52.0 ms]; <0.001) and at FU1 (52.0 ms [52.0-53.2 ms]; =0.007), which normalized at FU2 (50.9 ms [49.6-53.3 ms]; =0.323). Global native T1 times in patients were elevated acutely (1004 ms [988-1048 ms] versus 975 ms [957-1004 ms]; =0.002) and remained elevated throughout the follow-up (FU1: 998 ms [990-1027 ms]; =0.014; FU2: 1000 ms [972-1027 ms]; =0.044). Global extracellular volume fraction was statistically not different between patients and controls (=0.057). 77.8% (14/18) of patients had focal late gadolinium enhancement. T2 ratio was significantly elevated in patients with myocarditis at FU0 (2.2 [2.0-2.3] versus 1.6 [1.5-1.7]; <0.001). The difference decreased during follow-up (FU1: 1.9 [1.7-1.9]; =0.001 and FU2: 1.7 [1.7-1.8]; =0.053). The diagnostic accuracy to discriminate between patients with acute myocarditis and healthy controls was 86% for T2>52 ms, 78% for native T1>981 ms, 74% for extracellular volume fraction >0.24, and 100% for T2 ratio >1.9.

Conclusions: Although both T2 and T1 mapping reliably detected acute myocarditis, only T2 mapping discriminated between acute and healed stages, underlining the incremental value of T2 mapping.
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http://dx.doi.org/10.1161/CIRCIMAGING.116.005242DOI Listing
February 2017

Effects of heart valve prostheses on phase contrast flow measurements in Cardiovascular Magnetic Resonance - a phantom study.

J Cardiovasc Magn Reson 2017 Jan 16;19(1). Epub 2017 Jan 16.

Working Group on Cardiovascular Magnetic Resonance Imaging, Experimental and Clinical Research Center, joint cooperation of the Max-Delbrück-Centrum and Charité -Medical University Berlin, Berlin, Germany.

Background: Cardiovascular Magnetic Resonance is often used to evaluate patients after heart valve replacement. This study systematically analyses the influence of heart valve prostheses on phase contrast measurements in a phantom trial.

Methods: Two biological and one mechanical aortic valve prostheses were integrated in a flow phantom. B maps and phase contrast measurements were acquired at a 1.5 T MR scanner using conventional gradient-echo sequences in predefined distances to the prostheses. Results were compared to measurements with a synthetic metal-free aortic valve.

Results: The flow results at the level of the prosthesis differed significantly from the reference flow acquired before the level of the prosthesis. The maximum flow miscalculation was 154 ml/s for one of the biological prostheses and 140 ml/s for the mechanical prosthesis. Measurements with the synthetic aortic valve did not show significant deviations. Flow values measured approximately 20 mm distal to the level of the prosthesis agreed with the reference flow for all tested all prostheses.

Conclusions: The tested heart valve prostheses lead to a significant deviation of the measured flow rates compared to a reference. A distance of 20 mm was effective in our setting to avoid this influence.
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http://dx.doi.org/10.1186/s12968-016-0319-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5238524PMC
January 2017

Effect of Nitroglycerin on the Performance of MR Coronary Angiography.

J Magn Reson Imaging 2017 05 12;45(5):1419-1428. Epub 2016 Oct 12.

Clinic Agatharied, Department of Cardiology, Academic Teaching Hospital, University of Munich, Hausham, Germany.

Purpose: To systematically investigate the effect of sublingual glyceryl trinitrate (nitroglycerin=nitro=glyceryl trinitrate=GTN=C H N O [NTG]) on the diagnostic performance of MR coronary artery imaging (MRCA) to detect relevant coronary artery disease (CAD).

Materials And Methods: Thirty-five healthy volunteers and 25 patients with suspected or proven CAD (all in sinus rhythm) underwent MRCA before and after NTG using a contrast-agent free, three-dimensional, navigator-based, steady state free precession acquisition (voxel size 1.0 × 0.7 × 0.7 mm ) at 1.5 Tesla. Target parameters were stenosis detection (>50%), visible vessel length (straightened planar reconstruction) and vessel diameter (curved planar reconstruction, measured proximal/medial/distal). In patients, invasive coronary angiography served as reference.

Results: NTG led to increase of the coronary diameter both in healthy volunteers (right coronary artery [RCA]: 3.2 to 3.7 mm, P < 0.001; left anterior descending coronary artery [LAD]: 2.9 to 3.4 mm, P = 0.009; left circumflex coronary artery [LCx]: 2.8 to 3.3 mm, P < 0.001) and patients (RCA 3.5 to 4.0 mm, P = 0.01; LAD 3.3 to 3.7 mm, P = 0.008; LCx: 2.9 to 3.3 mm, P = 0.03). Visible vessel length increased after NTG for the LAD (volunteers: 72 to 84 mm, P = 0.03; patients: 56 to 78 mm, P = 0.01) and for LCx (volunteers: 48 to 60 mm, P = 0.02). Sensitivity to detect > 50% stenosis improved after NTG from 88.0 to 96%, specificity from 46.5 to 69.8%, diagnostic accuracy from 61.8 to 79.4% and positive/negative predictive value from 48.9 to 64.9% and 87.0 to 96.8%, respectively.

Conclusion: Sublingual administration of NTG significantly enhanced the visibility of the coronary arteries and improved the detection of coronary artery stenosis.

Level Of Evidence: 2 J. MAGN. RESON. IMAGING 2017;45:1419-1428.
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http://dx.doi.org/10.1002/jmri.25483DOI Listing
May 2017

Influence of spatial resolution and contrast agent dosage on myocardial T1 relaxation times.

MAGMA 2017 Feb 20;30(1):85-91. Epub 2016 Aug 20.

Working Group Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, A Joint Cooperation Between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Lindenberger Weg 80, 13125, Berlin, Germany.

Objective: Our aim was to study the influence of small variations in spatial resolution and contrast agent dosage on myocardial T1 relaxation time.

Materials And Methods: Twenty-nine healthy volunteers underwent cardiovascular magnetic resonance at 3T twice, including a modified look-locker inversion recovery (MOLLI) technique-3(3)3(3)5-for T1 mapping. Native T1 was assessed in three spatial resolutions (voxel size 1.4 × 1.4 × 6, 1.6 × 1.6 × 6, 1.7 × 1.7 × 6 mm), and postcontrast T1 after 0.1 and 0.2 mmol/kg gadobutrol. Partition coefficient was calculated based on myocardial and blood T1. T1 analysis was done per segment, per slice, and for the whole heart.

Results: Native T1 values did not differ with varying spatial resolution per segment (p = 0.116-0.980), per slice (basal: p = 0.772; middle: p = 0.639; apex: p = 0.276), and globally (p = 0.191). Postcontrast T1 values were significantly lower with higher contrast agent dosage (p < 0.001). The global partition coefficient was 0.43 ± 0.3 for 0.2 and 0.1 mmol gadobutrol (p = 0.079).

Conclusion: Related to the tested MOLLI technique at 3T, very small variations in spatial resolution (voxel sizes between 1.4 × 1.4 × 6 and 1.7 × 1.7 × 6 mm) remained without effect on the native T1 relaxation times. Postcontrast T1 values were naturally shorter with higher contrast agent dosage while the partition coefficient remained constant. Further studies are necessary to test whether these conclusions hold true for larger matrix sizes and in larger cohorts.
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http://dx.doi.org/10.1007/s10334-016-0581-0DOI Listing
February 2017

Cardiac Involvement in Myotonic Dystrophy Type 2 Patients With Preserved Ejection Fraction: Detection by Cardiovascular Magnetic Resonance.

Circ Cardiovasc Imaging 2016 07;9(7)

From the Working Group on Cardiovascular Magnetic Resonance, Experimental, and Clinical Research Center, a joint cooperation between the Charité University Medicine Berlin and the Max-Delbrueck Center for Molecular Medicine, and HELIOS Klinikum Berlin Buch, Department of Cardiology and Nephrology, Germany (L.S., J.T., W.U., M.A.D., E.B., F.v.K.-B., J.S.-M.); DZHK (German Center for Cardiovascular Research), partner site Berlin, Germany (L.S., F.v.K.-B, J.S.-M.); Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (U.G., S.S.); and Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (P.K.).

Background: Myotonic dystrophy type 2 (DM2) is a genetic disorder characterized by skeletal muscle symptoms, metabolic changes, and cardiac involvement. Histopathologic alterations of the skeletal muscle include fibrosis and fatty infiltration. The aim of this study was to investigate whether subclinical cardiac involvement in DM2 is already detectable in preserved left ventricular function by cardiovascular magnetic resonance.

Methods And Results: Twenty-seven patients (mean age, 54±10 years; 20 females) with a genetically confirmed diagnosis of DM2 were compared with 17 healthy age- and sex-matched controls using a 1.5 T magnetic resonance imaging. For myocardial tissue differentiation, T1 and T2 mapping, fat/water-separated imaging, focal fibrosis imaging (late gadolinium enhancement [LGE]), and (1)H magnetic resonance spectroscopy were performed. Extracellular volume fraction was calculated. Conduction abnormalities were diagnosed based on Groh criteria. LGE located subepicardial basal inferolateral was detectable in 22% of the patients. Extracellular volume was increased in this region and in the adjacent medial inferolateral segment (P=0.03 compared with healthy controls). In 21% of patients with DM2, fat deposits were detectable (all women). The control group showed no abnormalities. Myocardial triglycerides were not different in LGE-positive and LGE-negative subjects (P=0.47). Six patients had indicators for conduction disease (60% of LGE-positive patients and 12.5% of LGE-negative patients).

Conclusions: In DM2, subclinical myocardial injury was already detectable in preserved left ventricular ejection fraction. Extracellular volume was also increased in regions with no focal fibrosis. Myocardial fibrosis was related to conduction abnormalities.
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http://dx.doi.org/10.1161/CIRCIMAGING.115.004615DOI Listing
July 2016

Current T₁ and T₂ mapping techniques applied with simple thresholds cannot discriminate acute from chronic myocadial infarction on an individual patient basis: a pilot study.

BMC Med Imaging 2016 Apr 29;16:35. Epub 2016 Apr 29.

Working Group Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine and HELIOS Klinikum Berlin Buch, Department of Cardiology and Nephrology, Lindenberger Weg 80, Berlin, 13125, Germany.

Background: Studying T1- and T2-mapping for discrimination of acute from chronic myocardial infarction (AMI, CMI).

Methods: Eight patients with AMI underwent CMR at 3 T acutely and after >3 months. Imaging techniques included: T2-weighted imaging, late enhancement (LGE), T2-mapping, native and post-contrast T1-mapping. Myocardial T2- and T1-relaxation times were determined for every voxel. Abnormal voxels as defined by having T2- and T1-values beyond a predefined threshold (T2 > 50 ms, native T1 > 1250 ms and post-contrast T1 < 350 ms) were highlighted and compared with LGE as the reference.

Results: Abnormal T2-relaxation times were present in the voxels with AMI (=> delete acute infarction; unfortunately this is not possible in your web interface) acute infarction only in half of the subjects. Abnormal T2-values were also present in subjects with CMI, thereby matching the chronically infarcted territory in some. Abnormal native T1 times were present in voxels with AMI in 5/8 subjects, but also remote from the infarcted territory in four. In CMI, abnormal native T1 values corresponded with infarcted voxels, but were also abnormal remote from the infarcted territory. Voxels with abnormal post-contrast T1-relaxation times agreed well with LGE in AMI and CMI.

Conclusions: In this pilot-study, T2- and T1-mapping with simple thresholds did not facilitate the discrimination of AMI and CMI.
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http://dx.doi.org/10.1186/s12880-016-0135-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850633PMC
April 2016

Evaluation of Aortic Blood Flow and Wall Shear Stress in Aortic Stenosis and Its Association With Left Ventricular Remodeling.

Circ Cardiovasc Imaging 2016 Mar;9(3):e004038

From the Working Group Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, a Joint Cooperation Between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine and HELIOS Klinikum Berlin Buch, Department of Cardiology and Nephrology, Berlin, Germany (F.v.K.-B., A.K., R.F.T., E.B., J.S.-M.); Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Chicago, IL (A.J.B., M.M.); and Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.M.).

Background: Aortic stenosis (AS) leads to variable stress for the left ventricle (LV) and consequently a broad range of LV remodeling. The aim of this study was to describe blood flow patterns in the ascending aorta of patients with AS and determine their association with remodeling.

Methods And Results: Thirty-seven patients with AS (14 mild, 8 moderate, 15 severe; age, 63±13 years) and 37 healthy controls (age, 60±10 years) underwent 4-dimensional-flow magnetic resonance imaging. Helical and vortical flow formations and flow eccentricity were assessed in the ascending aorta. Normalized flow displacement from the vessel center and peak systolic wall shear stress in the ascending aorta were quantified. LV remodeling was assessed based on LV mass index and the ratio of LV mass:end-diastolic volume (relative wall mass). Marked helical and vortical flow formation and eccentricity were more prevalent in patients with AS than in healthy subjects, and patients with AS exhibited an asymmetrical and elevated distribution of peak systolic wall shear stress. In AS, aortic orifice area was strongly negatively associated with vortical flow formation (P=0.0274), eccentricity (P=0.0070), and flow displacement (P=0.0021). Bicuspid aortic valve was associated with more intense helical (P=0.0098) and vortical flow formation (P=0.0536), higher flow displacement (P=0.11), and higher peak systolic wall shear stress (P=0.0926). LV mass index and relative wall mass were significantly associated with aortic orifice area (P=0.0611, P=0.0058) and flow displacement (P=0.0058, P=0.0283).

Conclusions: In this pilot study, AS leads to abnormal blood flow pattern and peak systolic wall shear stress in the ascending aorta. In addition to aortic orifice area, normalized flow displacement was significantly associated with LV remodeling.
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http://dx.doi.org/10.1161/CIRCIMAGING.115.004038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772425PMC
March 2016

Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol.

Eur Heart J 2016 06 21;37(21):1671-80. Epub 2016 Feb 21.

Department of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway Center for Heart Failure Research and K.G. Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway

Aims: Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation.

Methods And Results: In a 2 × 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the β-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI -0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed.

Conclusion: In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function.
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http://dx.doi.org/10.1093/eurheartj/ehw022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887703PMC
June 2016

High Spatial Resolution Cardiovascular Magnetic Resonance at 7.0 Tesla in Patients with Hypertrophic Cardiomyopathy - First Experiences: Lesson Learned from 7.0 Tesla.

PLoS One 2016 10;11(2):e0148066. Epub 2016 Feb 10.

Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrueck Center for Molecular Medicine, Berlin, Germany.

Background: Cardiovascular Magnetic Resonance (CMR) provides valuable information in patients with hypertrophic cardiomyopathy (HCM) based on myocardial tissue differentiation and the detection of small morphological details. CMR at 7.0T improves spatial resolution versus today's clinical protocols. This capability is as yet untapped in HCM patients. We aimed to examine the feasibility of CMR at 7.0T in HCM patients and to demonstrate its capability for the visualization of subtle morphological details.

Methods: We screened 131 patients with HCM. 13 patients (9 males, 56 ±31 years) and 13 healthy age- and gender-matched subjects (9 males, 55 ±31years) underwent CMR at 7.0T and 3.0T (Siemens, Erlangen, Germany). For the assessment of cardiac function and morphology, 2D CINE imaging was performed (voxel size at 7.0T: (1.4x1.4x2.5) mm3 and (1.4x1.4x4.0) mm3; at 3.0T: (1.8x1.8x6.0) mm3). Late gadolinium enhancement (LGE) was performed at 3.0T for detection of fibrosis.

Results: All scans were successful and evaluable. At 3.0T, quantification of the left ventricle (LV) showed similar results in short axis view vs. the biplane approach (LVEDV, LVESV, LVMASS, LVEF) (p = 0.286; p = 0.534; p = 0.155; p = 0.131). The LV-parameters obtained at 7.0T where in accordance with the 3.0T data (pLVEDV = 0.110; pLVESV = 0.091; pLVMASS = 0.131; pLVEF = 0.182). LGE was detectable in 12/13 (92%) of the HCM patients. High spatial resolution CINE imaging at 7.0T revealed hyperintense regions, identifying myocardial crypts in 7/13 (54%) of the HCM patients. All crypts were located in the LGE-positive regions. The crypts were not detectable at 3.0T using a clinical protocol.

Conclusions: CMR at 7.0T is feasible in patients with HCM. High spatial resolution gradient echo 2D CINE imaging at 7.0T allowed the detection of subtle morphological details in regions of extended hypertrophy and LGE.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148066PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749213PMC
July 2016

Role of cardiovascular magnetic resonance in the guidelines of the European Society of Cardiology.

J Cardiovasc Magn Reson 2016 Jan 22;18. Epub 2016 Jan 22.

Working Group Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine; and HELIOS Klinikum Berlin Buch, Department of Cardiology and Nephrology, Berlin, Germany.

Background: Despite common enthusiasm for cardiovascular magnetic resonance (CMR), its application in Europe is quite diverse. Restrictions are attributed to a number of factors, like limited access, deficits in training, and incomplete reimbursement. Aim of this study is to perform a systematic summary of the representation of CMR in the guidelines of the European Society of Cardiology (ESC).

Methods: Twenty-nine ESC guidelines were screened for the terms "magnetic", "MRI", "CMR", "MR" and "imaging". As 3 topics were published twice (endocarditis, pulmonary hypertension, NSTEMI), 26 guidelines were finally included. MRI in the context of non-cardiovascular examinations was not recognized. The main CMR-related conclusions and, if available, the level of evidence and the class of recommendation were extracted.

Results: Fourteen of the 26 guidelines (53.8%) contain specific recommendations regarding the use of CMR. Nine guidelines (34.6%) mention CMR in the text, and 3 (11.5%) do not mention CMR. The 14 guidelines with recommendations regarding the use of CMR contain 39 class-I recommendations, 12 class-IIa recommendations, 10 class-IIb recommendations and 2 class-III recommendations. Most of the recommendations have evidence level C (41/63; 65.1%), followed by level B (16/63; 25.4%) and level A (6/63; 9.5%). The four guidelines, which absolutely contained most recommendations for CMR, were stable coronary artery disease (n = 14), aortic diseases (n = 9), HCM (n = 7) and myocardial revascularization (n = 7).

Conclusions: CMR is represented in the majority of the ESC guidelines. They contain many recommendations in favour of the use of CMR in specific scenarios. Issues regarding access, training and reimbursement have to be solved to offer CMR to patients in accordance with the ESC guidelines.
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http://dx.doi.org/10.1186/s12968-016-0225-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724113PMC
January 2016

Myocardial dysfunction in patients with aortic stenosis and hypertensive heart disease assessed by MR tissue phase mapping.

J Magn Reson Imaging 2016 07 21;44(1):168-77. Epub 2015 Dec 21.

Working Group Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine; and HELIOS Klinikum Berlin Buch, Department of Cardiology and Nephrology, Berlin, Germany.

Purpose: To identify abnormalities of myocardial velocities in patients with left ventricular pressure overload using magnetic resonance tissue phase mapping (TPM).

Material And Methods: Thirty-three patients (nine with hypertensive heart disease [HYP], 24 with aortic stenosis [AS]) and 41 healthy controls were enrolled. To assess left ventricular motion, a basal, midventricular, and apical slice were acquired using three-directional velocity-encoded phase-contrast MR with a 3T system. Target parameters were peak longitudinal (Vz ) and radial (Vr ) velocity in systole and diastole (Peaksys , Peakdias ). Analysis was done on each myocardial segment. In a subgroup (n = 7 HYP, n = 12 AS, n = 24 controls), measurement was repeated during handgrip exercise.

Results: AS had significantly lower Vz -Peaksys in the inferolateral and inferoseptal wall (P = 0.003-0.029) and Vr -Peaksys in the septum and anterior wall (P = 0.001-0.013) than controls. Vz -Peakdias and Vr -Peakdias were lower in AS than in controls in almost all segments (P < 0.001-0.028). HYP showed reduced Vz -Peakdias compared to controls in all basal segments as well as in the lateral midventricular wall (P < 0.001-0.045), and reduced Vr -Peakdias compared to controls predominantly in the midventricular and apical segments (P = 0.004-0.042). AS patients with focal fibrosis had significantly reduced myocardial velocities (P = 0.001-0.047) in segments without late enhancement. During exercise, Vz -Peaksys , Vr -Peaksys , and Vz -Peakdias remained unchanged in AS and HYP, but decreased in the lateral wall in controls (P < 0.001-0.043).

Conclusion: Even with preserved left ventricle (LV) ejection fraction, peak longitudinal and radial velocities of the LV are reduced in AS and HYP, indicating early functional impairment. J. Magn. Reson. Imaging 2016;44:168-177.
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http://dx.doi.org/10.1002/jmri.25125DOI Listing
July 2016

Quantitative, Organ-Specific Interscanner and Intrascanner Variability for 3 T Whole-Body Magnetic Resonance Imaging in a Multicenter, Multivendor Study.

Invest Radiol 2016 Apr;51(4):255-65

From the *Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg; †Department of Clinical Radiology, Campus Grosshadern, Ludwig-Maximilians University, Munich; ‡Fraunhofer Institute for Medical Image Computing MEVIS, Bremen; §Institute of Neuroscience and Medicine, Jülich Research Centre, Jülich; ∥Department of Cardiology and Nephrology, HELIOS Clinic Berlin Buch, Berlin; ¶Institute for Community Medicine, Ernst-Moritz-Arndt University, Greifswald; #Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen; **Institute of Diagnostic Radiology, and ††Department of Epidemiology and Preventive Medicine, University Hospital Regensburg, Regensburg; ‡‡Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Aachen; §§Department of Epidemiology, Helmholtz Centre for Infection Research, Braunschweig; ∥∥Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover; ¶¶O. Vogt Institute for Brain Research, Heinrich-Heine-University Düsseldorf, Düsseldorf; ##Department of Diagnostic and Interventional Radiology, University Hospital Klinikum rechts der Isar, Munich; ***Department of Radiology and Neuroradiology,University Medicine Greifswald, Ernst-Moritz-Arndt University, Greifswald; and †††Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen, Germany.

Introduction: Whole-body magnetic resonance (MR) imaging is increasingly implemented in population-based cohorts and clinical settings. However, to quantify the variability introduced by the different scanners is essential to make conclusions about clinical and biological data, and relevant for internal/external validity. Thus, we determined the interscanner and intrascanner variability of different 3 T MR scanners for whole-body imaging.

Methods: Thirty volunteers were enrolled to undergo multicentric, interscanner as well intrascanner imaging as part of the German National Cohort pilot studies. A comprehensive whole-body MR protocol was installed at 9 sites including 7 different MR scanner models by all 4 major vendors. A set of quantitative, organ-specific measures (n = 20; eg, volume of brain's gray/white matter, pulmonary trunk diameter, vertebral body height) were obtained in blinded fashion. Reproducibility was determined using mean weighted relative differences and intraclass correlation coefficients.

Results: All participants (44 ± 14 years, 50% female) successfully completed the imaging protocol except for two because of technical issues. Mean scan time was 2 hours and 32 minutes and differed significantly across scanners (range, 1 hour 59 minutes to 3 hours 12 minutes). A higher reproducibility of obtained measurements was observed for intrascanner than for interscanner comparisons (intraclass correlation coefficients, 0.80 ± 0.17 vs 0.60 ± 0.31, P = 0.005, respectively). In the interscanner comparison, mean relative difference ranged from 1.0% to 53.2%. Conversely, in the intrascanner comparison, mean relative difference ranged from 0.1% to 15.6%. There were no statistical differences for intrascanner and interscanner reproducibility between the different organ foci (all P ≥ 0.24).

Conclusions: While whole-body MR imaging-derived, organ-specific parameters are generally associated with good to excellent reproducibility, smaller differences are obtained when using identical MR scanner models by a single vendor.
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http://dx.doi.org/10.1097/RLI.0000000000000237DOI Listing
April 2016
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