Publications by authors named "Bernd Jung"

77 Publications

Radial self-navigated native magnetic resonance angiography in comparison to navigator-gated contrast-enhanced MRA of the entire thoracic aorta in an aortic patient collective.

J Cardiovasc Magn Reson 2021 07 12;23(1):94. Epub 2021 Jul 12.

Department of Diagnostic, Interventional and Pediatric Radiology (DIPR), Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 10, 3010, Bern, Switzerland.

Background: The native balanced steady state with free precession (bSSFP) magnetic resonance angiography (MRA) technique has been shown to provide high diagnostic image quality for thoracic aortic disease. This study compares a 3D radial respiratory self-navigated native MRA (native-SN-MRA) based on a bSSFP sequence with conventional Cartesian, 3D, contrast-enhanced MRA (CE-MRA) with navigator-gated respiration control for image quality of the entire thoracic aorta.

Methods: Thirty-one aortic native-SN-MRA were compared retrospectively (63.9 ± 10.3 years) to 61 CE-MRA (63.1 ± 11.7 years) serving as a reference standard. Image quality was evaluated at the aortic root/ascending aorta, aortic arch and descending aorta. Scan time was recorded. In 10 patients with both MRA sequences, aortic pathologies were evaluated and normal and pathologic aortic diameters were measured. The influence of artifacts on image quality was analyzed.

Results: Compared to the overall image quality of CE-MRA, the overall image quality of native-SN-MRA was superior for all segments analyzed (aortic root/ascending, p < 0.001; arch, p < 0.001, and descending, p = 0.005). Regarding artifacts, the image quality of native-SN-MRA remained superior at the aortic root/ascending aorta and aortic arch before and after correction for confounders of surgical material (i.e., susceptibility-related artifacts) (p = 0.008 both) suggesting a benefit in terms of motion artifacts. Native-SN-MRA showed a trend towards superior intraindividual image quality, but without statistical significance. Intraindividually, the sensitivity and specificity for the detection of aortic disease were 100% for native-SN-MRA. Aortic diameters did not show a significant difference (p = 0.899). The scan time of the native-SN-MRA was significantly reduced, with a mean of 05:56 ± 01:32 min vs. 08:51 ± 02:57 min in the CE-MRA (p < 0.001).

Conclusions: Superior image quality of the entire thoracic aorta, also regarding artifacts, can be achieved with native-SN-MRA, especially in motion prone segments, in addition to a shorter acquisition time.
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http://dx.doi.org/10.1186/s12968-021-00774-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274024PMC
July 2021

The blood oxygen level dependent (BOLD) effect of in-vitro myoglobin and hemoglobin.

Sci Rep 2021 06 1;11(1):11464. Epub 2021 Jun 1.

Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

The presence of deoxygenated hemoglobin (Hb) results in a drop in T2 and T2* in magnetic resonance imaging (MRI), known as the blood oxygenation level-dependent (BOLD-)effect. The purpose of this study was to investigate if deoxygenated myoglobin (Mb) exerts a BOLD-like effect. Equine Met-Mb powder was dissolved and converted to oxygenated Mb. T1, T2, T2*-maps and BOLD-bSSFP images at 3Tesla were used to scan 22 Mb samples and 12 Hb samples at room air, deoxygenation, reoxygenation and after chemical reduction. In Mb, T2 and T2* mapping showed a significant decrease after deoxygenation (- 25% and - 12%, p < 0.01), increase after subsequent reoxygenation (+ 17% and 0% vs. room air, p < 0.01), and finally a decrease in T2 after chemical reduction (- 28%, p < 0.01). An opposite trend was observed with T1 for each stage, while chemical reduction reduced BOLD-bSSFP signal (- 3%, p < 0.01). Similar deflections were seen at oxygenation changes in Hb. The T1 changes suggests that the oxygen content has been changed in the specimen. The shortening of transverse relaxation times in T2 and T2*-mapping after deoxygenation in Mb specimens are highly indicative of a BOLD-like effect.
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http://dx.doi.org/10.1038/s41598-021-90908-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169704PMC
June 2021

Magnetization-prepared 2 Rapid Gradient-Echo MRI for B Insensitive 3D T1 Mapping of Hip Cartilage: An Experimental and Clinical Validation.

Radiology 2021 04 23;299(1):150-158. Epub 2021 Feb 23.

From the Department of Diagnostic, Interventional and Pediatric Radiology (F.S., T.D.L., M.I., J.L.C., B.J.) and Department of Orthopaedic Surgery (K.A.S., M.T.), Inselspital, University Hospital Bern, University of Bern, Freiburgstrasse, 3010 Bern, Switzerland; Departments of Orthopaedic Surgery (F.S., Y.J.K., E.N.N.) and Radiology (O.A., S.D.B.), Boston Children's Hospital, Harvard Medical School, Boston, Mass; Advanced Clinical Imaging Technology, Siemens Healthcare, Lausanne, Switzerland (T.K.); Department of Radiology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland (T.K.); LTS5, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland (T.K.); Siemens Healthcare, Zürich, Switzerland (M.K.); and Department of Orthopaedic Surgery, Cantonal Hospital, University of Fribourg, Fribourg, Switzerland (M.T.).

Background Often used for T1 mapping of hip cartilage, three-dimensional (3D) dual-flip-angle (DFA) techniques are highly sensitive to flip angle variations related to B inhomogeneities. The authors hypothesized that 3D magnetization-prepared 2 rapid gradient-echo (MP2RAGE) MRI would help provide more accurate T1 mapping of hip cartilage at 3.0 T than would 3D DFA techniques. Purpose To compare 3D MP2RAGE MRI with 3D DFA techniques using two-dimensional (2D) inversion recovery T1 mapping as a standard of reference for hip cartilage T1 mapping in phantoms, healthy volunteers, and participants with hip pain. Materials and Methods T1 mapping at 3.0 T was performed in phantoms and in healthy volunteers using 3D MP2RAGE MRI and 3D DFA techniques with B field mapping for flip angle correction. Participants with hip pain prospectively (July 2019-January 2020) underwent indirect MR arthrography (with intravenous administration of 0.2 mmol/kg of gadoterate meglumine), including 3D MP2RAGE MRI. A 2D inversion recovery-based sequence served as a T1 reference in phantoms and in participants with hip pain. In healthy volunteers, cartilage T1 was compared between 3D MP2RAGE MRI and 3D DFA techniques. Paired tests and Bland-Altman analysis were performed. Results Eleven phantoms, 10 healthy volunteers (median age, 27 years; range, 26-30 years; five men), and 20 participants with hip pain (mean age, 34 years ± 10 [standard deviation]; 17 women) were evaluated. In phantoms, T1 bias from 2D inversion recovery was lower for 3D MP2RAGE MRI than for 3D DFA techniques (mean, 3 msec ± 11 vs 253 msec ± 85; < .001), and, unlike 3D DFA techniques, the deviation found with MP2RAGE MRI did not correlate with increasing B deviation. In healthy volunteers, regional cartilage T1 difference (109 msec ± 163; = .008) was observed only for the 3D DFA technique. In participants with hip pain, the mean T1 bias of 3D MP2RAGE MRI from 2D inversion recovery was -23 msec ± 31 ( < .001). Conclusion Compared with three-dimensional (3D) dual-flip-angle techniques, 3D magnetization-prepared 2 rapid gradient-echo MRI enabled more accurate T1 mapping of hip cartilage, was less affected by B inhomogeneities, and showed high accuracy against a T1 reference in participants with hip pain. © RSNA, 2021.
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http://dx.doi.org/10.1148/radiol.2021200085DOI Listing
April 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

Effect of Hyperoxia on Myocardial Oxygenation and Function in Patients With Stable Multivessel Coronary Artery Disease.

J Am Heart Assoc 2020 03 22;9(5):e014739. Epub 2020 Feb 22.

Department of Anaesthesiology and Pain Medicine Inselspital Bern University Hospital University of Bern Switzerland.

Background The impact of hyperoxia, that is, supraphysiological arterial partial pressure of O, on myocardial oxygen balance and function in stable multivessel coronary artery disease (CAD) is poorly understood. In this observational study, we assessed myocardial effects of inhalational hyperoxia in patients with CAD using a comprehensive cardiovascular magnetic resonance exam. Methods and Results Twenty-five patients with stable CAD underwent a contrast-free cardiovascular magnetic resonance exam in the interval between their index coronary angiography and subsequent revascularization. The cardiovascular magnetic resonance exam involved T1 and T2 mapping for tissue characterization (fibrosis, edema) as well as function imaging, from which strain analysis was derived, and oxygenation-sensitive cardiovascular magnetic resonance imaging. The latter modalities were both acquired at room air and after breathing pure O by face mask at 10 L/min for 5 minutes. In 14 of the 25 CAD patients (56%), hyperoxia induced poststenotic myocardial deoxygenation with a subsequent oxygenation discordance across the myocardium. Extent of deoxygenation was correlated to degree of stenosis (=-0.434, =0.033). Hyperoxia-associated poststenotic deoxygenation was accompanied by ipsiregional reduction of diastolic strain rate (1.39±0.57 versus 1.18±0.65; =0.045) and systolic radial velocity (37.40±17.22 versus 32.88±13.58; =0.038). Increased T2, as well as lower cardiac index, and defined abnormal strain parameters on room air were predictive for hyperoxia-induced abnormalities (<0.05). Furthermore, in patients with prolonged native T1 (>1220 ms), hyperoxia reduced ejection fraction and peak strain. Conclusions Patients with CAD and pre-existent myocardial injury who respond to hyperoxic challenge with strain abnormalities appear susceptible for hyperoxia-induced regional deoxygenation and deterioration of myocardial function. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02233634.
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http://dx.doi.org/10.1161/JAHA.119.014739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335579PMC
March 2020

Automated Quantitative Extraction and Analysis of 4D flow Patterns in the Ascending Aorta: An intraindividual comparison at 1.5 T and 3 T.

Sci Rep 2020 02 19;10(1):2949. Epub 2020 Feb 19.

Department of Diagnostic and Interventional Radiology, University of Leipzig - Heart Centre, Leipzig, Germany.

4D flow MRI enables quantitative assessment of helical flow. Current methods are susceptible to noise. To evaluate helical flow patterns in healthy volunteers and patients with bicuspid aortic valves (BAV) at 1.5 T and 3 T using pressure-based helix-extraction in 4D flow MRI. Two intraindividual 4D flow MRI examinations were performed at 1.5 T and 3 T in ten healthy volunteers (5 females, 32 ± 3 years) and 2 patients with BAV using different acceleration techniques (kt-GRAPPA and centra). Several new quantitative parameters for the evaluation of volumes [ml], lengths [mm] as well as temporal parameters [ms] of helical flow were introduced and analyzed using the software tool Bloodline. We found good correlations between measurements in volunteers at 1.5 T and 3 T regarding helical flow volumes (R = 0.98) and temporal existence (R = 0.99) of helices in the ascending aorta. Furthermore, we found significantly larger (11.7 vs. 77.6 ml) and longer lasting (317 vs. 769 ms) helices in patients with BAV than in volunteers. The assessed parameters do not depend on the magnetic field strength used for the acquisition. The technique of pressure-based extraction of 4D flow MRI pattern is suitable for differentiation of normal and pathological flow.
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http://dx.doi.org/10.1038/s41598-020-59826-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031260PMC
February 2020

Comparison of two accelerated 4D-flow sequences for aortic flow quantification.

Sci Rep 2019 06 14;9(1):8643. Epub 2019 Jun 14.

Department of Diagnostic and Interventional Radiology, University of Leipzig - Heart Centre, Leipzig, Germany.

To compare two broadly used 4D-flow- with a 2D-flow-sequence in healthy volunteers, regarding absolute flow parameters, image quality (IQ), and eddy current correction (ECC). Forty volunteers (42 ± 11.8 years, 22 females) were examined with a 3T scanner. Thoracic aortic flow was assessed using a 3D-T2w-SPACE-STIR-sequence for morphology and two accelerated 4D-flow sequences for comparison, one with k-t undersampling and one with standard GRAPPA parallel-imaging. 2D-flow was used as reference standard. The custom-made software tool Bloodline enabled flow measurements for all analyses at the same location. Quantitative flow analyses were performed with and without ECC. One reader assessed pathline IQ (IQ-PATH) and occurrence of motion artefacts (IQ-ART) on a 3-point grading scale, the higher the better. k-t GRAPPA allowed a significant mean scan time reduction of 46% (17:56 ± 5:26 min vs. 10:40 ± 3:15 min) and provided significantly fewer motion artefacts than standard GRAPPA (IQ-ART 1.57 ± 0.55 vs. 0.84 ± 0.48; p < 0.001). Neither 4D-flow sequence significantly differed in flow volume nor peak velocity results with or without ECC. Nevertheless, the correlation between both 4D-flow sequences and 2D-flow was better with ECC; the k-t GRAPPA sequence performed best (R = 0.96 vs. 0.90). k-t GRAPPA 4D-flow was not inferior to a standard GRAPPA-sequence, showed fewer artefacts, comparable IQ and was almost two-fold faster.
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http://dx.doi.org/10.1038/s41598-019-45196-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572772PMC
June 2019

Validation of two accelerated 4D flow MRI sequences at 3 T: a phantom study.

Eur Radiol Exp 2019 Feb 26;3(1):10. Epub 2019 Feb 26.

Department of Diagnostic and Interventional Radiology, University of Leipzig - Heart Centre, Leipzig Strümpellstrasse 39, 04289, Leipzig, Germany.

Background: Four-dimensional (4D) flow magnetic resonance imaging (MRI) sequences with advanced parallel imaging have the potential to reduce scan time with equivalent image quality and accuracy compared with standard two-dimensional (2D) flow MRI. We compared 4D flow to standard 2D flow sequences using a constant and pulsatile flow phantom at 3 T.

Methods: Two accelerated 4D flow sequences (GRAPPA2 and k-t-GRAPPA5) were evaluated regarding the concordance of flow volumes, flow velocities, and reproducibility as well as dependency on measuring plane and velocity encoding (V). The calculated flow volumes and peak velocities of the phantom were used as reference standard. Flow analysis was performed using the custom-made software "Bloodline".

Results: No significant differences in flow volume were found between the 2D, both 4D flow MRI sequences, and the pump reference (p = 0.994) or flow velocities (p = 0.998) in continuous and pulsatile flow. An excellent correlation (R = 0.99-1.0) with a reference standard and excellent reproducibility of measurements (R = 0.99) was achieved for all sequences. A V overestimated by up to two times had no impact on flow measurements. However, misaligned measuring planes led to an increasing underestimation of flow volume and mean velocity in 2D flow accuracy, while both 4D flow measurements were not affected. Scan time was significantly shorter for k-t-GRAPPA5 (1:54 ± 0:01 min, mean ± standard deviation) compared to GRAPPA2 (3:56 ± 0:02 min) (p = 0.002).

Conclusions: Both 4D flow sequences demonstrated equal agreement with 2D flow measurements, without impact of V overestimation and plane misalignment. The highly accelerated k-t-GRAPPA5 sequence yielded results similar to those of GRAPPA2.
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http://dx.doi.org/10.1186/s41747-019-0089-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391502PMC
February 2019

Relationship between myocardial oxygenation and blood pressure: Experimental validation using oxygenation-sensitive cardiovascular magnetic resonance.

PLoS One 2019 16;14(1):e0210098. Epub 2019 Jan 16.

Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Background: The relationship between mean arterial pressure (MAP) and coronary blood flow is well described. There is autoregulation within a MAP range of 60 to 140 mmHg providing near constant coronary blood flow. Outside these limits flow becomes pressure-dependent. So far, response of myocardial oxygenation to changes in pressure and flow has been more difficult to assess. While established techniques mostly require invasive approaches, Oxygenation-Sensitive (OS) Cardiovascular Magnetic Resonance (CMR) is a technique that can non-invasively assess changes in myocardial tissue oxygenation. The purpose of this study was to follow myocardial oxygenation over a wide range of blood pressure variation within and outside known coronary autoregulatory limits using OS-CMR, and to relate these data to coronary hemodynamics.

Methods: Ten anaesthetized swine (German Large White) underwent left-sided thoracotomy and attachment of a perivascular flow probe to the proximal left anterior descending (LAD) coronary artery for continuous measurement of blood flow (QLAD). Thereafter, animals were transferred into a 3T MRI scanner. Mean arterial pressure (MAP) was varied in 10-15 mmHg steps by administering alpha1-receptor agents phenylephrine or urapidil. For each MAP level, OS-CMR images as well as arterial and coronary sinus blood gas samples were obtained simultaneously during brief periods of apnea. Relative changes (Δ) of coronary sinus oxygen saturation (ScsO2), oxygen delivery (DO2) and demand (MVO2), extraction ratio (O2ER) and excess (Ω) from respective reference levels at a MAP of 70 mmHg were determined and were compared to %change in OS-signal intensity (OS-SI) in simultaneously acquired OS-CMR images.

Results: QLAD response indicated autoregulation between MAP levels of 52 mmHg (lower limit) and127 mmHg (upper limit). OS-CMR revealed a global myocardial oxygenation deficit occurring below the lower autoregulation limit, with the nadir of OS-SI at -9.0%. With MAP values surpassing 70 mmHg, relative OS-SI increased to a maximum of +10.6%. Consistent with this, ΔScsO2, ΔDO2, ΔMVO2, ΔO2ER and ΔΩ responses indicated increasing mismatch of oxygenation balance outside the autoregulated zone. Changes in global OS-CMR were significantly correlated with all of these parameters (p≤0.02) except with ΔMVO2.

Conclusion: OS-CMR offers a novel and non-invasive route to evaluate the effects of blood pressure variations, as well as of cardiovascular drugs and interventions, on global and regional myocardial oxygenation, as demonstrated in a porcine model. OS-CMR identified mismatch of O2 supply and demand below the lower limit of coronary autoregulation. Vasopressor induced acute hypertension did not compromise myocardial oxygenation in healthy hearts despite increased cardiac workload and O2 demand. The clinical usefulness of OS-CMR remains to be established.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210098PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334913PMC
September 2019

Electro-mechanical (dys-)function in long QT syndrome type 1.

Int J Cardiol 2019 Jan 9;274:144-151. Epub 2018 Jul 9.

Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address:

Background: Prolonged repolarization is the hallmark of long QT syndrome (LQTS), which is associated with subclinical mechanical dysfunction. We aimed at elucidating mechanical cardiac function in LQTS type 1 (loss of I) and its modification upon further prolongation of the action potential (AP) by I-blockade (E-4031).

Methods: Transgenic LQT1 and wild type (WT) rabbits (n = 12/10) were subjected to tissue phase mapping MRI, ECG, and epicardial AP recording. Protein and mRNA levels of ion channels and Ca handling proteins (n = 4/4) were determined. In silico single cell AP and tension modeling was performed.

Results: At baseline, QT intervals were longer in LQT1 compared to WT rabbits, but baseline systolic and diastolic myocardial peak velocities were similar in LQT1 and WT. E-4031 prolonged QT more pronouncedly in LQT1. Additionally, E-4031 increased systolic and decreased diastolic peak velocities more markedly in LQT1 - unmasking systolic and diastolic LQT1-specific mechanical alterations. E-4031-induced alterations of diastolic peak velocities correlated with the extent of QT prolongation.

Conclusion: While baseline mechanical function is normal in LQT1 despite a distinct QT prolongation, further prolongation of repolarization by I-blocker E-4031 unmasks mechanical differences between LQT1 and WT with enhanced systolic and impaired diastolic function only in LQT1. These data indicate an importance of the extent of QT prolongation and the contribution of different impaired ion currents for conveying mechanical dysfunction.
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http://dx.doi.org/10.1016/j.ijcard.2018.07.050DOI Listing
January 2019

Feasibility of cardiovascular magnetic resonance to detect oxygenation deficits in patients with multi-vessel coronary artery disease triggered by breathing maneuvers.

J Cardiovasc Magn Reson 2018 05 7;20(1):31. Epub 2018 May 7.

Department of Anaesthesiology and Pain Medicine, Bern University Hospital, Inselspital, University of Bern, 3010, Bern, Switzerland.

Background: Hyperventilation with a subsequent breath-hold has been successfully used as a non-pharmacological vasoactive stimulus to induce changes in myocardial oxygenation. The purpose of this pilot study was to assess if this maneuver is feasible in patients with multi-vessel coronary artery disease (CAD), and if it is effective at detecting coronary artery stenosis > 50% determined by quantitative coronary angiography (QCA).

Methods: Twenty-six patients with coronary artery stenosis (QCA > 50% diameter stenosis) underwent a contrast-free cardiovascular magnetic resonance (CMR) exam in the time interval between their primary coronary angiography and a subsequent percutaneous coronary intervention (PCI, n = 24) or coronary artery bypass (CABG, n = 2) revascularization procedure. The CMR exam involved standard function imaging, myocardial strain analysis, T2 mapping, native T1 mapping and oxygenation-sensitive CMR (OS-CMR) imaging. During OS-CMR, participants performed a paced hyperventilation for 60s followed by a breath-hold to induce a vasoactive stimulus. Ten healthy subjects underwent the CMR protocol as the control group.

Results: All CAD patients completed the breathing maneuvers with an average breath-hold duration of 48 ± 23 s following hyperventilation and without any complications or adverse effects. In comparison to healthy subjects, CAD patients had a significantly attenuated global myocardial oxygenation response to both hyperventilation (- 9.6 ± 6.8% vs. -3.1 ± 6.5%, p = 0.012) and apnea (11.3 ± 6.1% vs. 2.1 ± 4.4%, p < 0.001). The breath-hold maneuver unmasked regional oxygenation differences in territories subtended by a stenotic coronary artery in comparison to remote territory within the same patient (0.5 ± 3.8 vs. 3.8 ± 5.3%, p = 0.011).

Conclusion: Breathing maneuvers in conjunction with OS-CMR are clinically feasible in CAD patients. Furthermore, OS-CMR demonstrates myocardial oxygenation abnormalities in regional myocardium related to CAD without the use of pharmacologic vasodilators or contrast agents. A larger trial appears warranted for a better understanding of its diagnostic utility.

Trial Registration: Clinical Trials Identifier: NCT02233634 , registered 8 September 2014.
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http://dx.doi.org/10.1186/s12968-018-0446-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937049PMC
May 2018

Segmental biventricular analysis of myocardial function using high temporal and spatial resolution tissue phase mapping.

MAGMA 2018 Feb 15;31(1):61-73. Epub 2017 Nov 15.

Institute of Diagnostic, Interventional and Pediatric Radiology, University Hospital Bern, Bern, Switzerland.

Objective: Myocardial dysfunction of the right ventricle (RV) is an important indicator of RV diseases, e.g. RV infarction or pulmonary hypertension. Tissue phase mapping (TPM) has been widely used to determine function of the left ventricle (LV) by analyzing myocardial velocities. The analysis of RV motion is more complicated due to the different geometry and smaller wall thickness. The aim of this work was to adapt and optimize TPM to the demands of the RV.

Materials And Methods: TPM measurements were acquired in 25 healthy volunteers using a velocity-encoded phase-contrast sequence and kt-accelerated parallel imaging in combination with optimized navigator strategy and blood saturation. Post processing was extended by a 10-segment RV model and a detailed biventricular analysis of myocardial velocities was performed.

Results: High spatio-temporal resolution (1.0 × 1.0 × 6 mm, 21.3 ms) and the optimized blood saturation enabled good delineation of the RV and its velocities. Global and segmental velocities, as well as time to peak velocities showed significant differences between the LV and RV. Furthermore, complex timing of the RV could be demonstrated by segmental time to peak analysis.

Conclusion: High spatio-temporal resolution TPM enables a detailed biventricular analysis of myocardial motion and might provide a reliable tool for description and detection of diseases affecting left and right ventricular function.
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http://dx.doi.org/10.1007/s10334-017-0661-9DOI Listing
February 2018

Phase-contrast magnet resonance imaging reveals regional, transmural, and base-to-apex dispersion of mechanical dysfunction in patients with long QT syndrome.

Heart Rhythm 2017 09 4;14(9):1388-1397. Epub 2017 May 4.

Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Institute for Experimental Cardiovascular Medicine, Heart Center, University of Freiburg, Freiburg, Germany. Electronic address:

Background: Regional dispersion of prolonged repolarization is a hallmark of long QT syndrome (LQTS). We have also revealed regional heterogeneities in mechanical dysfunction in transgenic rabbit models of LQTS.

Objective: In this clinical pilot study, we investigated whether patients with LQTS exhibit dispersion of mechanical/diastolic dysfunction.

Methods: Nine pediatric patients with genotyped LQTS (12.2 ± 3.3 years) and 9 age- and sex-matched healthy controls (10.6 ± 1.5 years) were subjected to phase-contrast magnetic resonance imaging to analyze radial (Vr) and longitudinal (Vz) myocardial velocities during systole and diastole in the left ventricle (LV) base, mid, and apex. Twelve-lead electrocardiograms were recorded to assess the heart rate-corrected QT (QTc) interval.

Results: The QTc interval was longer in patients with LQTS than in controls (469.1 ± 39.4 ms vs 417.8 ± 24.4 ms; P < .01). Patients with LQTS demonstrated prolonged radial and longitudinal time-to-diastolic peak velocities (TTP), a marker for prolonged contraction duration, in the LV base, mid, and apex. The longer QTc interval positively correlated with longer time-to-diastolic peak velocities (correlation coefficient 0.63; P < .01). Peak diastolic velocities were reduced in LQTS in the LV mid and apex, indicating impaired diastolic relaxation. In patients with LQTS, regional (TTPmax-min) and transmural (TTPVz-Vr) dispersion of contraction duration was increased in the LV apex (TTPVz_max-min: 38.9 ± 25.5 ms vs 20.2 ± 14.7 ms; P = .07; TTPVz-Vr: -21.7 ± 14.5 ms vs -8.7 ± 11.3 ms; P < .05). The base-to-apex longitudinal relaxation sequence was reversed in patients with LQTS compared with controls (TTPVz_base-apex: 14.4 ± 14.9 ms vs -10.1 ± 12.7 ms; P < .01).

Conclusion: Patients with LQTS exhibit diastolic dysfunction with reduced diastolic velocities and prolonged contraction duration. Mechanical dispersion is increased in LQTS with an increased regional and transmural dispersion of contraction duration and altered apicobasal longitudinal relaxation sequence. LQTS is an electromechanical disorder, and phase-contrast magnetic resonance imaging Heterogeneity in mechanical dysfunction enables a detailed assessment of mechanical consequences of LQTS.
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http://dx.doi.org/10.1016/j.hrthm.2017.04.045DOI Listing
September 2017

Magnetic resonance tissue phase mapping demonstrates altered left ventricular diastolic function in children with chronic kidney disease.

Pediatr Radiol 2017 Feb 13;47(2):169-177. Epub 2016 Dec 13.

Department of Pediatric and Congenital Cardiology, University Hospital Heidelberg, Heidelberg, Germany.

Background: Echocardiographic examinations have revealed functional cardiac abnormalities in children with chronic kidney disease.

Objective: To assess the feasibility of MRI tissue phase mapping in children and to assess regional left ventricular wall movements in children with chronic kidney disease.

Materials And Methods: Twenty pediatric patients with chronic kidney disease (before or after renal transplantation) and 12 healthy controls underwent tissue phase mapping (TPM) to quantify regional left ventricular function through myocardial long (Vz) and short-axis (Vr) velocities at all 3 levels of the left ventricle.

Results: Patients and controls (age: 8 years-20 years) were matched for age, height, weight, gender and heart rate. Patients had higher systolic blood pressure. No patient had left ventricular hypertrophy on MRI or diastolic dysfunction on echocardiography. Fifteen patients underwent tissue Doppler echocardiography, with normal z-scores for mitral early diastolic (V), late diastolic (V) and peak systolic (V) velocities. Throughout all left ventricular levels, peak diastolic Vz and Vr (cm/s) were reduced in patients: Vz -10.6 ± 1.9 vs. -13.4 ± 2.0 (P < 0.0003), Vz -7.8 ± 1.6 vs. -11 ± 1.5 (P < 0.0001), Vz -3.8 ± 1.6 vs. -5.3 ± 1.6 (P = 0.01), Vr -4.2 ± 0.8 vs. -4.9 ± 0.7 (P = 0.01), Vr -4.7 ± 0.7 vs. -5.4 ± 0.7 (P = 0.01), Vr -4.7 ± 1.4 vs. -5.6 ± 1.1 (P = 0.05).

Conclusion: Tissue phase mapping is feasible in children and adolescents. Children with chronic kidney disease show significantly reduced peak diastolic long- and short-axis left ventricular wall velocities, reflecting impaired early diastolic filling. Thus, tissue phase mapping detects chronic kidney disease-related functional myocardial changes before overt left ventricular hypertrophy or echocardiographic diastolic dysfunction occurs.
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http://dx.doi.org/10.1007/s00247-016-3741-5DOI Listing
February 2017

High resolution CBV assessment with PEAK-EPI: k-t-undersampling and reconstruction in echo planar imaging.

Magn Reson Med 2017 06 25;77(6):2153-2166. Epub 2016 Jun 25.

Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Purpose: Achieving higher spatial resolution and improved brain coverage while mitigating in-plane susceptibility artifacts in the assessment of perfusion parameters, such as cerebral blood volume, in echo planar imaging (EPI)-based dynamic susceptibility contrast weighted cerebral perfusion measurements.

Methods: PEAK-EPI, an EPI sequence with interleaved readout trajectories and three different strategies for autocalibration-signal acquisition (inplace, dynamic extra and extra) is presented. Performance of each approach is analyzed in vivo based on flip angle variation induced dynamics, assessing temporal fidelity, temporal SNR and g-factors. All approaches are compared with conventional GRAPPA reconstructions. PEAK-EPI with inplace autocalibration-signal at R = 5 is then compared with the standard clinical EPI protocol in six patients, using two half-dose dynamic susceptibility contrast weighted cerebral perfusion measurements per subject.

Results: PEAK-EPI acquisition facilitates a substantial increase of spatial resolution at a higher number of slices per TR and provides improved SNR compared to conventional GRAPPA. High dependency of the resulting reconstruction quality on the type of autocalibration-signal acquisition is observed. PEAK-EPI with inplace autocalibration-signal achieves high temporal fidelity and initial feasibility is shown.

Conclusion: The obtained high resolution cerebral blood volume maps reveal more detailed information than in corresponding standard EPI measurements and facilitate detailed delineation of tumorous tissue. Magn Reson Med 77:2153-2166, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
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http://dx.doi.org/10.1002/mrm.26298DOI Listing
June 2017

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

Left ventricular mass and systolic function in children with chronic kidney disease-comparing echocardiography with cardiac magnetic resonance imaging.

Pediatr Nephrol 2016 Feb 5;31(2):255-65. Epub 2015 Sep 5.

Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg, Germany.

Background: Increased left ventricular mass (LVM) is an important risk marker of uremic cardiovascular disease. Calculation of LVM by echocardiography (Echo) relies on geometric assumptions and in adults on hemodialysis overestimates LVM compared to cardiac magnetic resonance (CMR). We compare both techniques in children with chronic kidney disease (CKD).

Methods: Concurrent Echo and CMR was performed in 25 children with CKD (14 after kidney transplantation) aged 8-17 years.

Results: Compared to normal children, CMR-LVM was increased (standard deviation score (SDS) 0.39 ± 0.8 (p = 0.03)), stroke volume and cardiac output decreased (SDS -1.76 ± 1.1, p = 0.002 and -1.11 ± 2.0, p = 0.001). CMR-LVM index but not Echo-LVMI correlated to future glomerular filtration rate (GFR) decline (r = -0.52, p = 0.01). Mean Echo-LVM was higher than CMR-LVM (117 ± 40 vs. 89 ± 29 g, p < 0.0001), with wide limits of agreement (-6.2 to 62.8 g). The Echo-CMR LVM difference increased with higher Echo-LVMI (r = 0.77, p < 0.0001). Agreement of classifying left ventricular hypertrophy was poor with Cohen's kappa of 0.08. Mean Echo and CMR-ejection fraction differed by 1.42% with wide limits of agreement (-12.6 to 15.4%).

Conclusions: Echo overestimates LVM compared to CMR, especially at higher LVM. Despite this, CMR confirms increased LVM in children with CKD. Only CMR-LVMI but not Echo-LVMI correlated to future GFR decline.
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http://dx.doi.org/10.1007/s00467-015-3198-zDOI Listing
February 2016

Acquisition of 3D temperature distributions in fluid flow using proton resonance frequency thermometry.

Magn Reson Med 2016 07 24;76(1):145-55. Epub 2015 Aug 24.

Department of Radiology, University Medical Center Freiburg, Medical Physics, Freiburg, Germany.

Purpose: Proton resonance frequency thermometry is well established for monitoring small temperature changes in tissue. Application of the technique to the measurement of complex temperature distributions within fluid flow is of great interest to the engineering community and could also have medical applications. This work presents an experimental approach to reliably measure three-dimensional (3D) temperature fields in fluid flow using proton resonance frequency thermometry.

Methods: A velocity-compensated three-dimensional gradient echo sequence was used. A flexible pumping system was attached to an MR compatible double pipe heat exchanger. The temperature of two separate flow circuits could be adjusted to produce various three-dimensional spatial temperature distributions within the fluid flow. Validation was performed using MR compatible temperature probes in a uniformly heated flow. A comparative study was conducted with thermocouples in the presence of a spatially varying temperature distribution.

Results: In uniformly heated flow, temperature changes were accurately measured to within 0.5 K using proton resonance frequency thermometry, while spatially varying temperature changes measured with MR showed good qualitative agreement with pointwise measurements using thermocouples.

Conclusion: Proton resonance frequency thermometry can be used in a variety of complex flow situations to address medical as well as engineering questions. This work makes it possible to gain new insights into fundamental heat transfer phenomena. Magn Reson Med 76:145-155, 2016. © 2015 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/mrm.25874DOI Listing
July 2016

Pre-procedural assessment of aortic annulus dimensions for transcatheter aortic valve replacement: comparison of a non-contrast 3D MRA protocol with contrast-enhanced cardiac dual-source CT angiography.

Eur Heart J Cardiovasc Imaging 2016 Apr 27;17(4):458-66. Epub 2015 Jul 27.

Department of Radiology, Section of Cardiovascular Radiology, University of Freiburg, Südring 15, Bad Krozingen 79189, Germany

Aims: To evaluate the feasibility of a non-contrast three-dimensional (3D)-FLASH magnetic resonance angiography (MRA) protocol for pre-procedural aortic annulus assessment for transcatheter aortic valve replacement (TAVR) in comparison with cardiac dual-source computed tomography angiography (CTA).

Methods And Results: In this prospective study, 69 of 104 consecutive patients (mean age 81.8 ± 5.4 years, 37.7% arrhythmic) with severe aortic stenosis who had undergone pre-TAVR cardiac CTA received a respiratory and ECG-triggered, non-contrast 3D-FLASH MRA at 3 T. Annular area measurements were obtained at mid-diastole for both modalities whereas maximum systolic area was assessed by CTA only. Systolic MRA dimensions were modelled, by adding the relative difference of systolic and diastolic CTA area dimensions as a corrective factor. Hypothetical prosthesis sizing was performed based on systolic CTA, diastolic, and modelled systolic MRA area measurements. MR image quality and degree of annular calcifications were evaluated using 4-point-grading scales. The mean acquisition time was 14 ± 4.2 min. The mean image quality was 3.1 ± 0.9 with only two examinations rated non-diagnostic. The mean degree of calcifications was equal. As assessed by Bland-Altman analysis, there was no relevant systematic difference between area measurements for modelled systolic MRA and systolic CTA [the mean difference -3.1 mm(2) (limits of agreement -44.4 mm(2); 38.2 mm(2))]. Agreement for hypothetical prosthesis sizing was found in 63 of 67 (94%) patients for systolic CTA and modelled systolic MRA.

Conclusion: The employed non-contrast 3D-FLASH MRA protocol allows for reliable assessment of aortic annulus dimensions and calcifications even in the presence of arrhythmias in an all-comers pre-TAVR population. Implementation of this technique appears legitimate in patients at an increased risk for contrast-induced nephropathy.
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http://dx.doi.org/10.1093/ehjci/jev188DOI Listing
April 2016

Investigation of hemodynamics in an in vitro system simulating left ventricular support through the right subclavian artery using 4-dimensional flow magnetic resonance imaging.

J Thorac Cardiovasc Surg 2015 Jul 28;150(1):200-7. Epub 2015 Feb 28.

Cardiovascular Surgery, Heart Center Freiburg University, Freiburg, Germany.

Objectives: Left ventricular assist devices are an important treatment option for patients with heart failure alter the hemodynamics in the heart and great vessels. Because in vivo magnetic resonance studies of patients with ventricular assist devices are not possible, in vitro models represent an important tool to investigate flow alterations caused by these systems. By using an in vitro magnetic resonance-compatible model that mimics physiologic conditions as close as possible, this work investigated the flow characteristics using 4-dimensional flow-sensitive magnetic resonance imaging of a left ventricular assist device with outflow via the right subclavian artery as commonly used in cardiothoracic surgery in the recent past.

Methods: An in vitro model was developed consisting of an aorta with its supra-aortic branches connected to a left ventricular assist device simulating the pulsatile flow of the native failing heart. A second left ventricular assist device supplied the aorta with continuous flow via the right subclavian artery. Four-dimensional flow-sensitive magnetic resonance imaging was performed for different flow rates of the left ventricular assist device simulating the native heart and the left ventricular assist device providing the continuous flow. Flow characteristics were qualitatively and quantitatively evaluated in the entire vessel system.

Results: Flow characteristics inside the aorta and its upper branching vessels revealed that the right subclavian artery and the right carotid artery were solely supported by the continuous-flow left ventricular assist device for all flow rates. The flow rates in the brain-supplying arteries are only marginally affected by different operating conditions. The qualitative analysis revealed only minor effects on the flow characteristics, such as weakly pronounced vortex flow caused by the retrograde flow via the brachiocephalic artery.

Conclusions: The results indicate that, despite the massive alterations in natural hemodynamics due to the retrograde flow via the right subclavian and brachiocephalic arteries, there are no drastic consequences on the flow in the brain-feeding arteries and the flow characteristics in the ascending and descending aortas. It may be beneficial to adjust the operating condition of the left ventricular assist device to the residual function of the failing heart.
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http://dx.doi.org/10.1016/j.jtcvs.2015.02.048DOI Listing
July 2015

A g-factor metric for k-t SENSE and k-t PCA based parallel imaging.

Magn Reson Med 2016 Feb 24;75(2):562-71. Epub 2015 Mar 24.

Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland.

Purpose: To propose and validate a g-factor formalism for k-t SENSE, k-t PCA and related k-t methods for assessing SNR and temporal fidelity.

Methods: An analytical gxf -factor formulation in the spatiotemporal frequency domain is derived, enabling assessment of noise and depiction fidelity in both the spatial and frequency domain. Using pseudoreplica analysis of cardiac cine data the gxf -factor description is validated and example data are used to analyze the performance of k-t methods for various parameter settings.

Results: Analytical gxf -factor maps were found to agree well with pseudoreplica analysis for 3x, 5x, and 7x k-t SENSE and k-t PCA. While k-t SENSE resulted in lower average gxf values (gx (avg) ) in static regions when compared with k-t PCA, k-t PCA yielded lower gx (avg) values in dynamic regions. Temporal transfer was better preserved with k-t PCA for increasing undersampling factors.

Conclusion: The proposed gxf -factor and temporal transfer formalism allows assessing noise performance and temporal depiction fidelity of k-t methods including k-t SENSE and k-t PCA. The framework enables quantitative comparison of different k-t methods relative to frame-by-frame parallel imaging reconstruction.
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http://dx.doi.org/10.1002/mrm.25606DOI Listing
February 2016

Prevalence of potential retrograde embolization pathways in the proximal descending aorta in stroke patients and controls.

Cerebrovasc Dis 2014 3;38(6):410-7. Epub 2014 Dec 3.

Department of Neurology, University Medical Center Freiburg, Freiburg, Germany.

Background: Retrograde diastolic blood flow in the proximal descending aorta (DAo) connecting complex plaques (≥4 mm thick) with brain-supplying supra-aortic arteries may constitute a source of stroke. Yet, data only from high-risk populations (cryptogenic stroke patients with aortic atheroma≥3 mm) regarding the prevalence of this potential stroke mechanism are available. We aimed to quantify the frequency of this mechanism in unselected patients with cryptogenic stroke after routine diagnostics and controls without a history of stroke.

Methods: 88 patients (67 stroke patients, 21 cardiac controls) were prospectively included. 3D T1-weighted bright blood MRI of the aorta was applied for the detection of complex DAo atheroma. ECG-triggered and navigator-gated 4D flow MRI allowed measuring time-resolved 3D blood flow in vivo. Potential retrograde embolization pathways were defined as the co-occurrence of complex plaques and retrograde blood flow in the DAo reaching the outlet of (a) the left subclavian artery, (b) the left common carotid artery, or/and (c) the brachiocephalic trunk. The frequency of these pathways was analyzed by importing 2D plaque images into 3D blood flow visualization software.

Results: Complex DAo plaques were more frequent in stroke patients (44 in 31/67 patients (46.3%) vs. 5 in 4/21 controls (19.1%); p=0.039), especially in older patients (29/46 (63.04%) patients≥60 years of age with 41 plaques vs. 2/21 (9.14%) patients<60 years of age with 3 plaques; p<0.001). Contrary to our assumption, retrograde diastolic blood flow at the DAo occurred in every patient irrespective of the existence of plaques with a similar extent in both groups (26±14 vs. 32±18 mm; p=0.114). Therefore, only the higher prevalence of complex DAo plaques in stroke patients resulted in a three times higher frequency of potential retrograde embolization pathways compared to controls (22/67 (32.8%) vs. 2/21 (9.5%) controls; p=0.048).

Conclusions: This study revealed that retrograde flow in the descending aorta is a common phenomenon not only in stroke patients. The existence of potential retrograde embolization pathways depends mainly on the occurrence of complex plaques in the area 0 to ∼30 mm behind the outlet of the left subclavian artery, which is exposed to flow reversal. In conclusion, we have shown that the frequency of potential retrograde embolization pathways was significantly higher in stroke patients suggesting that this mechanism may play a role in retrograde brain embolism.
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http://dx.doi.org/10.1159/000369001DOI Listing
September 2015

Analysis of left ventricular function of the mouse heart during experimentally induced hyperthyroidism and recovery.

NMR Biomed 2015 Jan 13;28(1):116-23. Epub 2014 Nov 13.

Department of Radiology, Medical Physics, University Medical Center Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany.

Many of the clinical manifestations of hyperthyroidism are due to the ability of thyroid hormones to alter myocardial contractility and cardiovascular hemodynamics, leading to cardiovascular impairment. In contrast, recent studies highlight also the potential beneficial effects of thyroid hormone administration for clinical or preclinical treatment of different diseases such as atherosclerosis, obesity and diabetes or as a new therapeutic approach in demyelinating disorders. In these contexts and in the view of developing thyroid hormone-based therapeutic strategies, it is, however, important to analyze undesirable secondary effects on the heart. Animal models of experimentally induced hyperthyroidism therefore represent important tools for investigating and monitoring changes of cardiac function. In our present study we use high-field cardiac MRI to monitor and follow-up longitudinally the effects of prolonged thyroid hormone (triiodothyronine) administration focusing on murine left ventricular function. Using a 9.4 T small horizontal bore animal scanner, cinematographic MRI was used to analyze changes in ejection fraction, wall thickening, systolic index and fractional shortening. Cardiac MRI investigations were performed after sustained cycles of triiodothyronine administration and treatment arrest in adolescent (8 week old) and adult (24 week old) female C57Bl/6 N mice. Triiodothyronine supplementation of 3 weeks led to an impairment of cardiac performance with a decline in ejection fraction, wall thickening, systolic index and fractional shortening in both age groups but with a higher extent in the group of adolescent mice. However, after a hormonal treatment cessation of 3 weeks, only young mice are able to partly restore cardiac performance in contrast to adult mice lacking this recovery potential and therefore indicating a presence of chronically developed heart pathology.
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http://dx.doi.org/10.1002/nbm.3233DOI Listing
January 2015

In vitro study to simulate the intracardiac magnetohydrodynamic effect.

Magn Reson Med 2015 Sep 15;74(3):850-7. Epub 2014 Sep 15.

Department of Radiology, University Medical Center Freiburg, Medical Physics, Freiburg, Germany.

Purpose: Blood flow causes induced voltages via the magnetohydrodynamic (MHD) effect distorting electrograms (EGMs) made during magnetic resonance imaging. To investigate the MHD effect in this context MHD voltages occurring inside the human heart were simulated in an in vitro model system inside a 1.5 T MR system.

Methods: The model was developed to produce MHD signals similar to those produced by intracardiac flow and to acquire them using standard clinical equipment. Additionally, a new approach to estimate MHD distortions on intracardiac electrograms is proposed based on the analytical calculation of the MHD signal from MR phase contrast data.

Results: The recorded MHD signals were similar in magnitude to intracardiac signals that would be measured by an electrogram of the left ventricle. The dependency of MHD signals on magnetic field strength and electrode separation was well reflected by an analytical model. MHD signals reconstructed from MR flow data were in excellent agreement with the MHD signal measured by clinical equipment.

Conclusion: The in vitro model allows investigation of MHD effects on intracardiac electrograms. A phase contrast MR scan was successfully applied to characterize and estimate the MHD distortion on intracardiac signals allowing correction of these effects.
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http://dx.doi.org/10.1002/mrm.25456DOI Listing
September 2015

K-t GRAPPA-accelerated 4D flow MRI of liver hemodynamics: influence of different acceleration factors on qualitative and quantitative assessment of blood flow.

MAGMA 2015 Apr 7;28(2):149-59. Epub 2014 Aug 7.

Department of Radiology, Feinberg School of Medicine, Northwestern University, 737 N Michigan Avenue Suite 1600, Chicago, IL, 60611, USA,

Objective: We sought to evaluate the feasibility of k-t parallel imaging for accelerated 4D flow MRI in the hepatic vascular system by investigating the impact of different acceleration factors.

Materials And Methods: k-t GRAPPA accelerated 4D flow MRI of the liver vasculature was evaluated in 16 healthy volunteers at 3T with acceleration factors R = 3, R = 5, and R = 8 (2.0 × 2.5 × 2.4 mm(3), TR = 82 ms), and R = 5 (TR = 41 ms); GRAPPA R = 2 was used as the reference standard. Qualitative flow analysis included grading of 3D streamlines and time-resolved particle traces. Quantitative evaluation assessed velocities, net flow, and wall shear stress (WSS).

Results: Significant scan time savings were realized for all acceleration factors compared to standard GRAPPA R = 2 (21-71 %) (p < 0.001). Quantification of velocities and net flow offered similar results between k-t GRAPPA R = 3 and R = 5 compared to standard GRAPPA R = 2. Significantly increased leakage artifacts and noise were seen between standard GRAPPA R = 2 and k-t GRAPPA R = 8 (p < 0.001) with significant underestimation of peak velocities and WSS of up to 31 % in the hepatic arterial system (p <0.05). WSS was significantly underestimated up to 13 % in all vessels of the portal venous system for k-t GRAPPA R = 5, while significantly higher values were observed for the same acceleration with higher temporal resolution in two veins (p < 0.05).

Conclusion: k-t acceleration of 4D flow MRI is feasible for liver hemodynamic assessment with acceleration factors R = 3 and R = 5 resulting in a scan time reduction of at least 40 % with similar quantitation of liver hemodynamics compared with GRAPPA R = 2.
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http://dx.doi.org/10.1007/s10334-014-0456-1DOI Listing
April 2015

A g-factor metric for k-t-GRAPPA- and PEAK-GRAPPA-based parallel imaging.

Magn Reson Med 2015 Jul 18;74(1):125-135. Epub 2014 Jul 18.

Department of Diagnostic Radiology, Medical Physics, University Medical Center, University of Freiburg, Freiburg, Germany.

Purpose: The aim of this work is to derive a theoretical framework for quantitative noise and temporal fidelity analysis of time-resolved k-space-based parallel imaging methods.

Theory: An analytical formalism of noise distribution is derived extending the existing g-factor formulation for nontime-resolved generalized autocalibrating partially parallel acquisition (GRAPPA) to time-resolved k-space-based methods. The noise analysis considers temporal noise correlations and is further accompanied by a temporal filtering analysis.

Methods: All methods are derived and presented for k-t-GRAPPA and PEAK-GRAPPA. A sliding window reconstruction and nontime-resolved GRAPPA are taken as a reference. Statistical validation is based on series of pseudoreplica images. The analysis is demonstrated on a short-axis cardiac CINE dataset.

Results: The superior signal-to-noise performance of time-resolved over nontime-resolved parallel imaging methods at the expense of temporal frequency filtering is analytically confirmed. Further, different temporal frequency filter characteristics of k-t-GRAPPA, PEAK-GRAPPA, and sliding window are revealed.

Conclusion: The proposed analysis of noise behavior and temporal fidelity establishes a theoretical basis for a quantitative evaluation of time-resolved reconstruction methods. Therefore, the presented theory allows for comparison between time-resolved parallel imaging methods and also nontime-resolved methods. Magn Reson Med 74:125-135, 2015. © 2014 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/mrm.25386DOI Listing
July 2015

Comparison of two fiber-optical temperature measurement systems in magnetic fields up to 9.4 Tesla.

Magn Reson Med 2015 May 19;73(5):2047-51. Epub 2014 Jun 19.

University Medical Center Freiburg, Radiology - Medical Physics, Freiburg, Germany.

Purpose: Precise temperature measurements in the magnetic field are indispensable for MR safety studies and for temperature calibration during MR-guided thermotherapy. In this work, the interference of two commonly used fiber-optical temperature measurement systems with the static magnetic field B0 was determined.

Methods: Two fiber-optical temperature measurement systems, a GaAs-semiconductor and a phosphorescent phosphor ceramic, were compared for temperature measurements in B0 . The probes and a glass thermometer for reference were placed in an MR-compatible tube phantom within a water bath. Temperature measurements were carried out at three different MR systems covering static magnetic fields up to B0  = 9.4T, and water temperatures were changed between 25°C and 65°C.

Results: The GaAs-probe significantly underestimated absolute temperatures by an amount related to the square of B0 . A maximum difference of ΔT = -4.6°C was seen at 9.4T. No systematic temperature difference was found with the phosphor ceramic probe. For both systems, the measurements were not dependent on the orientation of the sensor to B0 .

Conclusion: Temperature measurements with the phosphor ceramic probe are immune to magnetic fields up to 9.4T, whereas the GaAs-probes either require a recalibration inside the MR system or a correction based on the square of B0.
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http://dx.doi.org/10.1002/mrm.25314DOI Listing
May 2015

Cold ischaemic time and time after transplantation alter segmental myocardial velocities after heart transplantation.

Eur J Cardiothorac Surg 2014 Mar 11;45(3):502-8. Epub 2013 Sep 11.

Department of Cardiology and Angiology I, University Heart Centre Freiburg, Freiburg, Germany.

Objectives: The aim of this study was to investigate changes in segmental, three-directional left ventricular (LV) velocities in patients after heart transplantation (Tx).

Methods: Magnetic resonance tissue phase mapping was used to assess myocardial velocities in patients after Tx (n = 27) with normal LV ejection fraction (63 ± 5%) and those without signs of rejection. Regional wall motion and dyssynchrony were analysed in relation to cold ischaemic time (150 ± 57 min, median = 154 min), age of the donor heart (35 ± 13 years, median = 29 years), time after transplantation (32 ± 26 months, median = 31 months) and global LV morphology and function.

Results: Segmental myocardial velocities were significantly altered in patients with cold ischaemic times >155 min resulting in an increase in peak systolic radial velocities (2 of 16 segments, P = 0.03-0.04) and reduced segmental diastolic long-axis velocities (5 of 16 segments, P = 0.01-0.04). Time after transplantation (n = 8 patients <12 months after Tx vs n = 19 >12 months) had a significant influence on systolic radial velocities (increased in 2 of 16 segments, P = 0.01-0.04) and diastolic long-axis velocities (reduced in 5 of 16 segments, P = 0.02-0.04). Correlation analysis and multiple regression revealed significant relationships of cold ischaemic time (R = -0.384, P = 0.048), the donor heart's age (β= 0.9, P = 0.01) and time from transplantation (β= -0.36, P = 0.03) with long-axis diastolic dyssynchrony.

Conclusions: Time after transplantation and cold ischaemic time strongly affect segmental systolic and diastolic motion in patients after Tx. The understanding of alterations in regional LV motion in the transplanted heart under stable conditions is essential in order to utilize this methodology in the future as a potentially non-invasive means of diagnosing transplant rejection.
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http://dx.doi.org/10.1093/ejcts/ezt448DOI Listing
March 2014

Reproducibility study of four-dimensional flow MRI of arterial and portal venous liver hemodynamics: influence of spatio-temporal resolution.

Magn Reson Med 2014 Aug 9;72(2):477-84. Epub 2013 Sep 9.

Department of Radiology, Northwestern University, Chicago, Illinois, USA; Department of Biomedical Engineering, Northwestern University, Chicago, Illinois, USA; Department of Diagnostic Radiology and Medical Physics, University Medical Center Freiburg, Freiburg, Germany.

Purpose: To evaluate influence of variation in spatio-temporal resolution and scan-rescan reproducibility on three-dimensional (3D) visualization and quantification of arterial and portal venous (PV) liver hemodynamics at four-dimensional (4D) flow MRI.

Methods: Scan-rescan reproducibility of 3D hemodynamic analysis of the liver was evaluated in 10 healthy volunteers using 4D flow MRI at 3T with three different spatio-temporal resolutions (2.4 × 2.0 × 2.4 mm(3), 61.2 ms; 2.5 × 2.0 × 2.4 mm(3), 81.6 ms; 2.6 × 2.5 × 2.6 mm(3), 80 ms) and thus different total scan times. Qualitative flow analysis used 3D streamlines and time-resolved particle traces. Quantitative evaluation was based on maximum and mean velocities, flow volume, and vessel lumen area in the hepatic arterial and PV systems.

Results: 4D flow MRI showed good interobserver variability for assessment of arterial and PV liver hemodynamics. 3D flow visualization revealed limitations for the left intrahepatic PV branch. Lower spatio-temporal resolution resulted in underestimation of arterial velocities (mean 15%, P < 0.05). For the PV system, hemodynamic analyses showed significant differences in the velocities for intrahepatic portal vein vessels (P < 0.05). Scan-rescan reproducibility was good except for flow volumes in the arterial system.

Conclusion: 4D flow MRI for assessment of liver hemodynamics can be performed with low interobserver variability and good reproducibility. Higher spatio-temporal resolution is necessary for complete assessment of the hepatic blood flow required for clinical applications.
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http://dx.doi.org/10.1002/mrm.24939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950306PMC
August 2014

k-t GRAPPA accelerated four-dimensional flow MRI in the aorta: effect on scan time, image quality, and quantification of flow and wall shear stress.

Magn Reson Med 2014 Aug 4;72(2):522-33. Epub 2013 Sep 4.

Department of Radiology, Northwestern University, Chicago, Illinois, USA.

Purpose: The purpose of this study was to evaluate the utility of k-t parallel imaging for accelerating aortic four-dimensional (4D)-flow MRI. The aim was to systematically investigate the impact of different acceleration factors and number of coil elements on acquisition time, image quality and quantification of hemodynamic parameters.

Methods: k-t accelerated 4D-flow MRI (spatial/temporal resolution = 2.1 × 2.5 × 2.5 mm/40.0 ms) was acquired in 10 healthy volunteers with acceleration factors R = 3, 5, and 8 using 12- and 32-channel receiver coils. Results were compared with conventional parallel imaging (GRAPPA [generalized autocalibrating partial parallel acquisition], R = 2). Data analysis included radiological grading of three-dimensional blood flow visualization quality as well as quantification of blood flow, velocities and wall shear stress (WSS).

Results: k-t GRAPPA significantly reduced scan time by 28%, 54%, and 68%, for R = 3, 5, and 8, respectively, while maintaining image quality as demonstrated by overall similar image quality grading. Significant differences in peak WSS (diff12ch = -5.9%, diff32ch = 18.5%) and mean WSS (diff32ch = 13.9%) were found at the descending aorta for both receiver coils for R = 5 (PWSS < 0.04). Peak velocity differed for R=8 at the aortic root (-7.4%) and descending aorta (-12%) with PpeakVelo < 0.03.

Conclusion: k-t GRAPPA acceleration with a 12- or 32-channel receiver coil and an acceleration of 3 or 5 can compete with a standard GRAPPA R = 2 acceleration.
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http://dx.doi.org/10.1002/mrm.24925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414256PMC
August 2014
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