Publications by authors named "Gustav J Strijkers"

200 Publications

Confirmatory factor analysis including MRI-derived adipose tissues quantification improves associations of metabolic dysregulation to diastolic dysfunction.

J Diabetes Complications 2022 Jun 21;36(6):108202. Epub 2022 Apr 21.

Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.

Aims: To quantify metabolic impairment via a one-factor approach with confirmatory factor analysis (CFA) including MRI-derived visceral and subcutaneous adipose tissues and to associate it with diastolic dysfunction.

Methods: In this cross-sectional analysis, 916 participants (53% female, mean age (SD): 56 (6)) underwent abdominal and cardiovascular MRI. With CFA a metabolic-load factor of metabolic-syndrome variables and visceral and subcutaneous adipose tissues was constructed. A piecewise structural equation model approach with adjustment for confounding factors was used to determine associations with left-ventricular diastolic function, cardiac morphology and hemodynamics.

Results: Model fitting excluding blood pressure and waist circumference but including visceral and subcutaneous adipose tissues, fasting glucose, HDL-c and triglycerides was used to construct the metabolic-load factor. Evaluating measurement invariance demonstrated sex-specificity. Change in mitral early/late peak filling rate ratio was -0.12 for both males [-0.20; -0.05, p > 0.05] and females [-0.17; -0.07, p > 0.001] per SD of metabolic-load factor. Change in deceleration time of mitral early filling was -11.83 ms in females [-17.38; -6.27] per SD of metabolic-load factor.

Conclusion: A single latent metabolic-load factor via CFA including MRI-derived adipose tissues increased sensitivity for metabolic impairment obsoleting waist circumference and is associated with a decreased left-ventricular diastolic function, more apparent in females than in males.
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http://dx.doi.org/10.1016/j.jdiacomp.2022.108202DOI Listing
June 2022

Combination of Radiological and Clinical Baseline Data for Outcome Prediction of Patients With an Acute Ischemic Stroke.

Front Neurol 2022 1;13:809343. Epub 2022 Apr 1.

Department of Biomedical Engineering and Physics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.

Background: Accurate prediction of clinical outcome is of utmost importance for choices regarding the endovascular treatment (EVT) of acute stroke. Recent studies on the prediction modeling for stroke focused mostly on clinical characteristics and radiological scores available at baseline. Radiological images are composed of millions of voxels, and a lot of information can be lost when representing this information by a single value. Therefore, in this study we aimed at developing prediction models that take into account the whole imaging data combined with clinical data available at baseline.

Methods: We included 3,279 patients from the MR CLEAN Registry; a prospective, observational, multicenter registry of patients with ischemic stroke treated with EVT. We developed two approaches to combine the imaging data with the clinical data. The first approach was based on radiomics features, extracted from 70 atlas regions combined with the clinical data to train machine learning models. For the second approach, we trained 3D deep learning models using the whole images and the clinical data. Models trained with the clinical data only were compared with models trained with the combination of clinical and image data. Finally, we explored feature importance plots for the best models and identified many known variables and image features/brain regions that were relevant in the model decision process.

Results: From 3,279 patients included, 1,241 (37%) patients had a good functional outcome [modified Rankin Scale (mRS) ≤ 2] and 1,954 (60%) patients had good reperfusion [modified Thrombolysis in Cerebral Infarction (eTICI) ≥ 2b]. There was no significant improvement by combining the image data to the clinical data for mRS prediction [mean area under the receiver operating characteristic (ROC) curve (AUC) of 0.81 vs. 0.80] above using the clinical data only, regardless of the approach used. Regarding predicting reperfusion, there was a significant improvement when image and clinical features were combined (mean AUC of 0.54 vs. 0.61), with the highest AUC obtained by the deep learning approach.

Conclusions: The combination of radiomics and deep learning image features with clinical data significantly improved the prediction of good reperfusion. The visualization of prediction feature importance showed both known and novel clinical and imaging features with predictive values.
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http://dx.doi.org/10.3389/fneur.2022.809343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010547PMC
April 2022

Editorial for "Accelerating Cardiac Diffusion Imaging With a U-Net Based Model: Towards Single Breath-Hold".

J Magn Reson Imaging 2022 Apr 13. Epub 2022 Apr 13.

Department of Biomedical Engineering and Physics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.

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http://dx.doi.org/10.1002/jmri.28197DOI Listing
April 2022

Reply to Stöllberger et al.

J Anat 2022 Jun 1;240(6):1207-1209. Epub 2022 Feb 1.

Department of Medical Biology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1111/joa.13625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119612PMC
June 2022

A diffusion tensor-based method facilitating volumetric assessment of fiber orientations in skeletal muscle.

PLoS One 2022 27;17(1):e0261777. Epub 2022 Jan 27.

Department of Biomedical Engineering and Physics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Background: The purpose of this study was to develop a DTI-based method to quantitatively assess fiber angles and changes therein in leg muscles in order to facilitate longitudinal studies on muscle fiber architectural adaptations in healthy subjects.

Methods: The upper legs of five volunteers were scanned twice on the same day. The right lower legs of five volunteers were scanned twice with the ankle in three positions, i.e. -15° dorsiflexion, 0° neutral position, and 30° plantarflexion. The MRI protocols consisted of a noise scan, a 3-point mDixon scan and a DTI scan. Fiber-angle color maps were generated for four muscles in the upper legs and two muscles in the lower leg. Voxel-wise fiber angles (θ) were calculated from the angle between the principal eigenvector of the diffusion tensor and a reference line defined between the origo and insertion points of each muscle. Bland-Altman analysis, intraclass correlation coefficient (ICC), coefficient of variation (CV%), minimal detectable change (MDC), standard error (SE) and Friedman test were used for assessing the feasibility of this method and in order to have an indication of the repeatability and the sensitivity.

Results: Bland-Altman analysis showed good repeatability (CV%<10 and 0.7≤ICC≤0.9) with exception of the Tibialis Anterior (TA) muscle in dorsiflexion position(CV%: 12.2) and the Semitendinosus (ST) muscle (left leg) (CV%: 11.4). The best repeatability metrics were found for the SOL muscle in neutral position (CV%: 2.6). Changes in average θ in TA and SOL with ankle positions were observed in accordance with expected agonist and antagonist functions of both muscles. For example, for the anterior left compartment the change in fiber angle Δθ with respect to the neutral position Δθ = -1.6° ± 0.8° and 2.2° ± 2.8° (p = 0.008), for dorsiflexion and plantarflexion, respectively.

Conclusion: Our method facilitates fast inspection and quantification of muscle fiber angles in the lower and upper leg muscles in rest and detection of changes in lower-leg muscle fiber angles with varying ankle angles.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261777PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8794095PMC
February 2022

Comparative Analysis of Blood T Values Measured by T -TRIR and TRUST.

J Magn Reson Imaging 2022 Jan 25. Epub 2022 Jan 25.

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam, The Netherlands.

Background: Venous blood oxygenation (Yv), which can be derived from venous blood T (T b), combined with oxygen-extraction fraction (OEF) and cerebral metabolic rate of oxygen, is considered indicative for tissue viability and brain functioning and frequently assessed in patients with sickle cell disease. Recently, T -Prepared-Blood-Relaxation-Imaging-with-Inversion-Recovery (T -TRIR) was introduced allowing for simultaneous measurements of blood T and T (T b), potentially improving Yv estimation by overcoming the need to estimate hematocrit.

Purpose: To optimize and compare T -TRIR with T -relaxation-under-spin-tagging (TRUST) sequence.

Study Type: Prospective.

Population: A total of 12 healthy volunteers (six female, 27 ± 3 years old) and 7 patients with sickle cell disease (five female, 32 ± 12 years old).

Field Strength/sequence: 3 T; turbo field echo planar imaging (TFEPI), echo planar imaging (EPI), and fast field echo (FFE).

Assessment: T b, Yv, and OEF from TRUST and T -TRIR were compared and T -TRIR-derived T b was assessed. Within- and between-session repeatability was quantified in the controls, whereas sensitivity to hemodynamic changes after acetazolamide (ACZ) administration was assessed in the patients.

Statistical Tests: Shapiro-Wilk, one-sample and paired-sample t-test, repeated measures ANOVA, mixed linear model, Bland-Altman analysis and correlation analysis. Sidak multiple-comparison correction was performed. Significance level was 0.05.

Results: In controls, T b from T -TRIR (70 ± 11 msec) was higher compared to TRUST (60 ± 8 msec). In patients, T b values were lower pre- compared to post-ACZ administration (TRUST: 80 ± 15 msec and 106 ± 23 msec and T -TRIR: 95 ± 21 msec and 125 ± 36 msec). Consequently, Yv and OEF were lower and higher pre- compared to post-ACZ administration (TRUST Yv: 68% ± 7% and 77% ± 8%, T -TRIR Yv: 74% ± 8% and 80% ± 6%, TRUST OEF: 30% ± 7% and 21% ± 8%, and T -TRIR OEF: 25% ± 8% and 18% ± 6%).

Data Conclusion: TRUST and T -TRIR are reproducible, but T -TRIR-derived T b values are significantly higher compared to TRUST, resulting in higher Yv and lower OEF estimates. This bias might be considered when evaluating cerebral oxygen homeostasis.

Evidence Level: 2 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.28066DOI Listing
January 2022

Multi-parametric quantitative magnetic resonance imaging of the upper arm muscles of patients with spinal muscular atrophy.

NMR Biomed 2022 Jan 20:e4696. Epub 2022 Jan 20.

UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Quantitative magnetic resonance imaging (qMRI) is frequently used to map the disease state and disease progression in the lower extremity muscles of patients with spinal muscular atrophy (SMA). This is in stark contrast to the almost complete lack of data on the upper extremity muscles, which are essential for carrying out daily activities. The aim of this study was therefore to assess the disease state in the upper arm muscles of patients with SMA in comparison with healthy controls by quantitative assessment of fat fraction, diffusion indices, and water T2 relaxation times, and to relate these measures to muscle force. We evaluated 13 patients with SMA and 15 healthy controls with a 3-T MRI protocol consisting of DIXON, diffusion tensor imaging, and T2 sequences. qMRI measures were compared between groups and related to muscle force measured with quantitative myometry. Fat fraction was significantly increased in all upper arm muscles of the patients with SMA compared with healthy controls and correlated negatively with muscle force. Additionally, fat fraction was heterogeneously distributed within the triceps brachii (TB) and brachialis muscle, but not in the biceps brachii muscle. Diffusion indices and water T2 relaxation times were similar between patients with SMA and healthy controls, but we did find a slightly reduced mean diffusivity (MD), λ1, and λ3 in the TB of patients with SMA. Furthermore, MD was positively correlated with muscle force in the TB of patients with SMA. The variation in fat fraction further substantiates the selective vulnerability of muscles. The reduced diffusion tensor imaging indices, along with the positive correlation of MD with muscle force, point to myofiber atrophy. Our results show the feasibility of qMRI to map the disease state in the upper arm muscles of patients with SMA. Longitudinal data in a larger cohort are needed to further explore qMRI to map disease progression and to capture the possible effects of therapeutic interventions.
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http://dx.doi.org/10.1002/nbm.4696DOI Listing
January 2022

Coronary Flow Assessment Using Accelerated 4D Flow MRI With Respiratory Motion Correction.

Front Bioeng Biotechnol 2021 17;9:725833. Epub 2021 Aug 17.

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, Netherlands.

Magnetic resonance imaging (MRI) can potentially be used for non-invasive screening of patients with stable angina pectoris to identify probable obstructive coronary artery disease. MRI-based coronary blood flow quantification has to date only been performed in a 2D fashion, limiting its clinical applicability. In this study, we propose a framework for coronary blood flow quantification using accelerated 4D flow MRI with respiratory motion correction and compressed sensing image reconstruction. We investigate its feasibility and repeatability in healthy subjects at rest. Fourteen healthy subjects received 8 times-accelerated 4D flow MRI covering the left coronary artery (LCA) with an isotropic spatial resolution of 1.0 mm. Respiratory motion correction was performed based on 1) lung-liver navigator signal, 2) real-time monitoring of foot-head motion of the liver and LCA by a separate acquisition, and 3) rigid image registration to correct for anterior-posterior motion. Time-averaged diastolic LCA flow was determined, as well as time-averaged diastolic maximal velocity (V) and diastolic peak velocity (V). 2D flow MRI scans of the LCA were acquired for reference. Scan-rescan repeatability and agreement between 4D flow MRI and 2D flow MRI were assessed in terms of concordance correlation coefficient (CCC) and coefficient of variation (CV). The protocol resulted in good visibility of the LCA in 11 out of 14 subjects (six female, five male, aged 28 ± 4 years). The other 3 subjects were excluded from analysis. Time-averaged diastolic LCA flow measured by 4D flow MRI was 1.30 ± 0.39 ml/s and demonstrated good scan-rescan repeatability (CCC/CV = 0.79/20.4%). Time-averaged diastolic V (17.2 ± 3.0 cm/s) and diastolic V (24.4 ± 6.5 cm/s) demonstrated moderate repeatability (CCC/CV = 0.52/19.0% and 0.68/23.0%, respectively). 4D flow- and 2D flow-based diastolic LCA flow agreed well (CCC/CV = 0.75/20.1%). Agreement between 4D flow MRI and 2D flow MRI was moderate for both diastolic V and V (CCC/CV = 0.68/20.3% and 0.53/27.0%, respectively). In conclusion, the proposed framework of accelerated 4D flow MRI equipped with respiratory motion correction and compressed sensing image reconstruction enables repeatable diastolic LCA flow quantification that agrees well with 2D flow MRI.
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http://dx.doi.org/10.3389/fbioe.2021.725833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634777PMC
August 2021

Dynamic MRI of swallowing: real-time volumetric imaging at 12 frames per second at 3 T.

MAGMA 2021 Nov 15. Epub 2021 Nov 15.

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.

Objective: Dysphagia or difficulty in swallowing is a potentially hazardous clinical problem that needs regular monitoring. Real-time 2D MRI of swallowing is a promising radiation-free alternative to the current clinical standard: videofluoroscopy. However, aspiration may be missed if it occurs outside this single imaged slice. We therefore aimed to image swallowing in 3D real time at 12 frames per second (fps).

Materials And Methods: At 3 T, three 3D real-time MRI acquisition approaches were compared to the 2D acquisition: an aligned stack-of-stars (SOS), and a rotated SOS with a golden-angle increment and with a tiny golden-angle increment. The optimal 3D acquisition was determined by computer simulations and phantom scans. Subsequently, five healthy volunteers were scanned and swallowing parameters were measured.

Results: Although the rotated SOS approaches resulted in better image quality in simulations, in practice, the aligned SOS performed best due to the limited number of slices. The four swallowing phases could be distinguished in 3D real-time MRI, even though the spatial blurring was stronger than in 2D. The swallowing parameters were similar between 2 and 3D.

Conclusion: At a spatial resolution of 2-by-2-by-6 mm with seven slices, swallowing can be imaged in 3D real time at a frame rate of 12 fps.
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http://dx.doi.org/10.1007/s10334-021-00973-6DOI Listing
November 2021

Right atrial function is associated with RV diastolic stiffness: RA-RV interaction in pulmonary arterial hypertension.

Eur Respir J 2021 Nov 11. Epub 2021 Nov 11.

Pulmonary Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Background: Pulmonary arterial hypertension (PAH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness. This study assessed the impact of RV diastolic stiffness on RA-RV interaction.

Methods: Low or high end-diastolic elastance (E) PAH patients (n=94) were compared to controls (n=31). Treatment response was evaluated in n=62 patients. RV and RA longitudinal strain, RA emptying and RV filling were determined and diastole was divided in a passive and active phase. Vena cava backflow was calculated as RV active filling-RA active emptying; RA stroke work as RA active emptying*RV end-diastolic pressure.

Results: With increased E, RA and RV passive strain were reduced while active strain was preserved. In comparison to controls, patients had lower RV passive filling, but higher RA active emptying and RA stroke work. RV active filling was lower in high E patients, resulting in higher vena cava backflow. Upon treatment, E reduced in half of high Epatients, which coincided with larger reductions in afterload, RV mass and vena cava backflow and greater improvements in RV active filling and stroke volume in comparison to patients in whom E remained high.

Conclusions: In PAH, RA function is associated with changes in RV function. Despite increased RA stroke work, severe RV diastolic stiffness is associated with reduced RV active filling and increased vena cava backflow. In 50% of high baseline E patients, diastolic stiffness remains high, despite treatment. E reduction coincided with a large reduction in afterload, increased RV active filling and decreased vena cava backflow.
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http://dx.doi.org/10.1183/13993003.01454-2021DOI Listing
November 2021

Higher spatial resolution improves the interpretation of the extent of ventricular trabeculation.

J Anat 2022 02 26;240(2):357-375. Epub 2021 Sep 26.

Department of Medical Biology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.

The ventricular walls of the human heart comprise an outer compact layer and an inner trabecular layer. In the context of an increased pre-test probability, diagnosis left ventricular noncompaction cardiomyopathy is given when the left ventricle is excessively trabeculated in volume (trabecular vol >25% of total LV wall volume) or thickness (trabecular/compact (T/C) >2.3). Here, we investigated whether higher spatial resolution affects the detection of trabeculation and thus the assessment of normal and excessively trabeculated wall morphology. First, we screened left ventricles in 1112 post-natal autopsy hearts. We identified five excessively trabeculated hearts and this low prevalence of excessive trabeculation is in agreement with pathology reports but contrasts the prevalence of approximately 10% of the population found by in vivo non-invasive imaging. Using macroscopy, histology and low- and high-resolution MRI, the five excessively trabeculated hearts were compared with six normal hearts and seven abnormally trabeculated and excessive trabeculation-negative hearts. Some abnormally trabeculated hearts could be considered excessively trabeculated macroscopically because of a trabecular outflow or an excessive number of trabeculations, but they were excessive trabeculation-negative when assessed with MRI-based measurements (T/C <2.3 and vol <25%). The number of detected trabeculations and T/C ratio were positively correlated with higher spatial resolution. Using measurements on high resolution MRI and with histological validation, we could not replicate the correlation between trabeculations of the left and right ventricle that has been previously reported. In conclusion, higher spatial resolution may affect the sensitivity of diagnostic measurements and in addition could allow for novel measurements such as counting of trabeculations.
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http://dx.doi.org/10.1111/joa.13559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742974PMC
February 2022

Whole-Heart 4D Flow MRI for Evaluation of Normal and Regurgitant Valvular Flow: A Quantitative Comparison Between Pseudo-Spiral Sampling and EPI Readout.

J Magn Reson Imaging 2022 Apr 12;55(4):1120-1130. Epub 2021 Sep 12.

Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.

Background: Pseudo-spiral Cartesian sampling with compressed sensing reconstruction has facilitated highly accelerated 4D flow magnetic resonance imaging (MRI) in various cardiovascular structures. However, unlike echo planar imaging (EPI)-accelerated 4D flow MRI, it has not been validated in whole-heart applications.

Hypothesis: Pseudo-spiral 4D flow MRI (PROUD [PROspective Undersampling in multiple Dimensions]) is comparable to EPI in robustness of valvular flow measurements and remains comparable as the undersampling factor is increased and scan time reduced.

Study Type: Prospective.

Population: Twelve healthy subjects and eight patients with valvular regurgitation.

Field Strength/sequence: 3.0 T; PROUD and EPI 4D flow sequences, 2D flow and balanced steady-state free precession sequences.

Assessment: Valvular blood flow was quantified using valve tracking. PROUD- and EPI-based measurements of aortic (AV) and pulmonary (PV) flow volumes and left and right ventricular stroke volumes were tested for agreement with 2D MRI-based measurements. PROUD reconstructions with undersampling factors (R) of 9, 14, 28, and 56 were tested for intervalve consistency (per valve, compared to the other valves) and preservation of peak velocities and E/A ratios.

Statistical Tests: We used repeated measures ANOVA, Bland-Altman, Wilcoxon signed rank, and intraclass correlation coefficients. P < 0.05 was considered statistically significant.

Results: PROUD and EPI intervalve consistencies were not significantly different both in healthy subjects (valve-averaged mean difference [limits of agreement width]: 3.2 ± 0.8 [8.7 ± 1.1] mL/beat for PROUD, 5.5 ± 2.9 [13.7 ± 2.3] mL/beat for EPI, P = 0.07) and in patients with valvular regurgitation (2.3 ± 1.2 [15.3 ± 5.9] mL/beat for PROUD, 0.6 ± 0.6 [19.3 ± 2.9] mL/beat for EPI, P = 0.47). Agreement between EPI and PROUD was higher than between 4D flow (EPI or PROUD) and 2D MRI for forward flow, stroke volumes, and regurgitant volumes. Up to R = 28 in healthy subjects and R = 14 in patients with valvular regurgitation, PROUD intervalve consistency remained comparable to that of EPI. Peak velocities and E/A ratios were preserved up to R = 9.

Conclusion: PROUD is comparable to EPI in terms of intervalve consistency and may be used with higher undersampling factors to shorten scan times further.

Level Of Evidence: 1 TECHNICAL EFFICACY STAGE: 2.
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http://dx.doi.org/10.1002/jmri.27905DOI Listing
April 2022

Quantification of Mouse Heart Left Ventricular Function, Myocardial Strain, and Hemodynamic Forces by Cardiovascular Magnetic Resonance Imaging.

J Vis Exp 2021 05 24(171). Epub 2021 May 24.

Department of Biomedical Engineering & Physics, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, University of Amsterdam.

Mouse models have contributed significantly to understanding genetic and physiological factors involved in healthy cardiac function, how perturbations result in pathology, and how myocardial diseases may be treated. Cardiovascular magnetic resonance imaging (CMR) has become an indispensable tool for a comprehensive in vivo assessment of cardiac anatomy and function. This protocol shows detailed measurements of mouse heart left ventricular function, myocardial strain, and hemodynamic forces using 7-Tesla CMR. First, animal preparation and positioning in the scanner are demonstrated. Survey scans are performed for planning imaging slices in various short- and long-axis views. A series of prospective ECG-triggered short-axis (SA) movies (or CINE images) are acquired covering the heart from apex to base, capturing end-systolic and end-diastolic phases. Subsequently, single-slice, retrospectively gated CINE images are acquired in a midventricular SA view, and in 2-, 3-, and 4-chamber views, to be reconstructed into high-temporal resolution CINE images using custom-built and open-source software. CINE images are subsequently analyzed using dedicated CMR image analysis software. Delineating endomyocardial and epicardial borders in SA end-systolic and end-diastolic CINE images allows for the calculation of end-systolic and end-diastolic volumes, ejection fraction, and cardiac output. The midventricular SA CINE images are delineated for all cardiac time frames to extract a detailed volume-time curve. Its time derivative allows for the calculation of the diastolic function as the ratio of the early filling and atrial contraction waves. Finally, left ventricular endocardial walls in the 2-, 3-, and 4-chamber views are delineated using feature-tracking, from which longitudinal myocardial strain parameters and left ventricular hemodynamic forces are calculated. In conclusion, this protocol provides detailed in vivo quantification of the mouse cardiac parameters, which can be used to study temporal alterations in cardiac function in various mouse models of heart disease.
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http://dx.doi.org/10.3791/62595DOI Listing
May 2021

Double delay alternating with nutation for tailored excitation facilitates banding-free isotropic high-resolution intracranial vessel wall imaging.

NMR Biomed 2021 09 2;34(9):e4567. Epub 2021 Jun 2.

Department of Radiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

The purpose of this study was to evaluate the use of a double delay alternating with nutation for tailored excitation (D-DANTE)-prepared sequence for banding-free isotropic high-resolution intracranial vessel wall imaging (IC-VWI) and to compare its performance with regular DANTE in terms of signal-to-noise ratio (SNR) as well as cerebrospinal fluid (CSF) and blood suppression efficiency. To this end, a D-DANTE-prepared 3D turbo spin echo sequence was implemented by interleaving two separate DANTE pulse trains with different RF phase-cycling schemes, but keeping all other DANTE parameters unchanged, including the total number of pulses and total preparation time. This achieved a reduction of the banding distance compared with regular DANTE enabling banding-free imaging up to higher resolutions. Bloch simulations assuming static vessel wall and flowing CSF spins were performed to compare DANTE and D-DANTE in terms of SNR and vessel wall/CSF contrast. Similar image quality measures were assessed from measurements on 13 healthy middle-aged volunteers. Both simulation and in vivo results showed that D-DANTE had only slightly lower vessel wall/CSF and vessel wall/blood contrast-to-noise ratio values compared with regular DANTE, which originated from a 10%-15% reduction in vessel wall SNR but not from reduced CSF or blood suppression efficiency. As anticipated, IC-VWI acquisitions showed that D-DANTE can successfully remove banding artifacts compared with regular DANTE with equal scan time or DANTE preparation length. Moreover, application was demonstrated in a patient with an intracranial aneurysm, indicating improved robustness to slow flow artifacts compared with clinically available 3D turbo spin echo scans. In conclusion, D-DANTE provides banding artifact-free IC-VWI up to higher isotropic resolutions compared with regular DANTE. This allows for a more flexible choice of DANTE preparation parameters in high-resolution IC-VWI protocols.
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http://dx.doi.org/10.1002/nbm.4567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459252PMC
September 2021

The Antibiotic Doxycycline Impairs Cardiac Mitochondrial and Contractile Function.

Int J Mol Sci 2021 Apr 15;22(8). Epub 2021 Apr 15.

Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

Tetracycline antibiotics act by inhibiting bacterial protein translation. Given the bacterial ancestry of mitochondria, we tested the hypothesis that doxycycline-which belongs to the tetracycline class-reduces mitochondrial function, and results in cardiac contractile dysfunction in cultured H9C2 cardiomyoblasts, adult rat cardiomyocytes, in and in mice. Ampicillin and carbenicillin were used as control antibiotics since these do not interfere with mitochondrial translation. In line with its specific inhibitory effect on mitochondrial translation, doxycycline caused a mitonuclear protein imbalance in doxycycline-treated H9C2 cells, reduced maximal mitochondrial respiration, particularly with complex I substrates, and mitochondria appeared fragmented. Flux measurements using stable isotope tracers showed a shift away from OXPHOS towards glycolysis after doxycycline exposure. Cardiac contractility measurements in adult cardiomyocytes and hearts showed an increased diastolic calcium concentration, and a higher arrhythmicity index. Systolic and diastolic dysfunction were observed after exposure to doxycycline. Mice treated with doxycycline showed mitochondrial complex I dysfunction, reduced OXPHOS capacity and impaired diastolic function. Doxycycline exacerbated diastolic dysfunction and reduced ejection fraction in a diabetes mouse model vulnerable for metabolic derangements. We therefore conclude that doxycycline impairs mitochondrial function and causes cardiac dysfunction.
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http://dx.doi.org/10.3390/ijms22084100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071362PMC
April 2021

Retrospective Camera-Based Respiratory Gating in Clinical Whole-Heart 4D Flow MRI.

J Magn Reson Imaging 2021 08 10;54(2):440-451. Epub 2021 Mar 10.

Radiology and Nuclear Medicine, Amsterdam, Amsterdam University Medical Centers, location AMC, The Netherlands.

Background: Respiratory gating is generally recommended in 4D flow MRI of the heart to avoid blurring and motion artifacts. Recently, a novel automated contact-less camera-based respiratory motion sensor has been introduced.

Purpose: To compare camera-based respiratory gating (CAM) with liver-lung-navigator-based gating (NAV) and no gating (NO) for whole-heart 4D flow MRI.

Study Type: Retrospective.

Subjects: Thirty two patients with a spectrum of cardiovascular diseases.

Field Strength/sequence: A 3T, 3D-cine spoiled-gradient-echo-T1-weighted-sequence with flow-encoding in three spatial directions.

Assessment: Respiratory phases were derived and compared against each other by cross-correlation. Three radiologists/cardiologist scored images reconstructed with camera-based, navigator-based, and no respiratory gating with a 4-point Likert scale (qualitative analysis). Quantitative image quality analysis, in form of signal-to-noise ratio (SNR) and liver-lung-edge (LLE) for sharpness and quantitative flow analysis of the valves were performed semi-automatically.

Statistical Tests: One-way repeated measured analysis of variance (ANOVA) with Wilks's lambda testing and follow-up pairwise comparisons. Significance level of P ≤ 0.05. Krippendorff's-alpha-test for inter-rater reliability.

Results: The respiratory signal analysis revealed that CAM and NAV phases were highly correlated (C = 0.93 ± 0.09, P < 0.01). Image scoring showed poor inter-rater reliability and no significant differences were observed (P ≥ 0.16). The image quality comparison showed that NAV and CAM were superior to NO with higher SNR (P = 0.02) and smaller LLE (P < 0.01). The quantitative flow analysis showed significant differences between the three respiratory-gated reconstructions in the tricuspid and pulmonary valves (P ≤ 0.05), but not in the mitral and aortic valves (P > 0.05). Pairwise comparisons showed that reconstructions without respiratory gating were different in flow measurements to either CAM or NAV or both, but no differences were found between CAM and NAV reconstructions.

Data Conclusion: Camera-based respiratory gating performed as well as conventional liver-lung-navigator-based respiratory gating. Quantitative image quality analysis showed that both techniques were equivalent and superior to no-gating-reconstructions. Quantitative flow analysis revealed local flow differences (tricuspid/pulmonary valves) in images of no-gating-reconstructions, but no differences were found between images reconstructed with camera-based and navigator-based respiratory gating.

Level Of Evidence: 3 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.27564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359364PMC
August 2021

Iron Oxide Nanoparticle Uptake in Mouse Brachiocephalic Artery Atherosclerotic Plaque Quantified by T-Mapping MRI.

Pharmaceutics 2021 Feb 19;13(2). Epub 2021 Feb 19.

Department of Biomedical Engineering and Physics, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

The purpose of our study was to monitor the iron oxide contrast agent uptake in mouse brachiocephalic artery (BCA) atherosclerotic plaques in vivo by quantitative T-mapping magnetic resonance imaging (MRI). Female ApoE mice ( = 32) on a 15-week Western-type diet developed advanced plaques in the BCA and were injected with ultra-small superparamagnetic iron oxides (USPIOs). Quantitative in vivo MRI at 9.4 T was performed with a Malcolm-Levitt (MLEV) prepared T-mapping sequence to monitor the nanoparticle uptake in the atherosclerotic plaque. Ex vivo histology and particle electron paramagnetic resonance (pEPR) were used for validation. Longitudinal high-resolution in vivo T-value maps were acquired with consistent quality. Average T values in the plaque decreased from a baseline value of 34.5 ± 0.6 ms to 24.0 ± 0.4 ms one day after injection and partially recovered to an average T of 27 ± 0.5 ms after two days. T values were inversely related to iron levels in the plaque as determined by ex vivo particle electron paramagnetic resonance (pEPR). We concluded that MRI T mapping facilitates a robust quantitative readout for USPIO uptake in atherosclerotic plaques in arteries near the mouse heart.
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http://dx.doi.org/10.3390/pharmaceutics13020279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922981PMC
February 2021

Correction to: Early impairment of coronary microvascular perfusion capacity in rats on a high fat diet.

Cardiovasc Diabetol 2021 Feb 22;20(1):51. Epub 2021 Feb 22.

Department of Physiology, CARIM School for Cardiovascular Diseases, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.

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http://dx.doi.org/10.1186/s12933-021-01239-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901173PMC
February 2021

Quantification of Myocardial Creatine and Triglyceride Content in the Human Heart: Precision and Accuracy of in vivo Proton Magnetic Resonance Spectroscopy.

J Magn Reson Imaging 2021 08 10;54(2):411-420. Epub 2021 Feb 10.

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.

Background: Proton magnetic resonance spectroscopy ( H-MRS) of the human heart is deemed to be a quantitative method to investigate myocardial metabolite content, but thorough validations of in vivo measurements against invasive techniques are lacking.

Purpose: To determine measurement precision and accuracy for quantifications of myocardial total creatine and triglyceride content with localized H-MRS.

Study Type: Test-retest repeatability and measurement validation study.

Subjects: Sixteen volunteers and 22 patients scheduled for open-heart aortic valve replacement or septal myectomy.

Field Strength/sequence: Prospectively ECG-triggered respiratory-gated free-breathing single-voxel point-resolved spectroscopy (PRESS) sequence at 3 T.

Assessment: Myocardial total creatine and triglyceride content were quantified relative to the total water content by fitting the H-MR spectra. Precision was assessed with measurement repeatability. Accuracy was assessed by validating in vivo H-MRS measurements against biochemical assays in myocardial tissue from the same subjects.

Statistical Tests: Intrasession and intersession repeatability was assessed using Bland-Altman analyses. Agreement between H-MRS measurements and biochemical assay was tested with regression analyses.

Results: The intersession repeatability coefficient for myocardial total creatine content was 41.8% with a mean value of 0.083% ± 0.020% of the total water signal, and 36.7% for myocardial triglyceride content with a mean value of 0.35% ± 0.13% of the total water signal. Ex vivo myocardial total creatine concentrations in tissue samples correlated with the in vivo myocardial total creatine content measured with H-MRS: n = 22, r = 0.44; P < 0.05. Likewise, ex vivo myocardial triglyceride concentrations correlated with the in vivo myocardial triglyceride content: n = 20, r = 0.50; P < 0.05.

Data Conclusion: We validated the use of localized H-MRS of the human heart at 3 T for quantitative assessments of in vivo myocardial tissue metabolite content by estimating the measurement precision and accuracy.

Level Of Evidence: 2 TECHNICAL EFFICACY STAGE: 2.
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http://dx.doi.org/10.1002/jmri.27531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277665PMC
August 2021

Ultra-high resolution, 3-dimensional magnetic resonance imaging of the atherosclerotic vessel wall at clinical 7T.

PLoS One 2020 14;15(12):e0241779. Epub 2020 Dec 14.

BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.

Accurate quantification and characterization of atherosclerotic plaques with MRI requires high spatial resolution acquisitions with excellent image quality. The intrinsically better signal-to-noise ratio (SNR) at high-field clinical 7T compared to the widely employed lower field strengths of 1.5 and 3T may yield significant improvements to vascular MRI. However, 7T atherosclerosis imaging also presents specific challenges, related to local transmit coils and B1 field inhomogeneities, which may overshadow these theoretical gains. We present the development and evaluation of 3D, black-blood, ultra-high resolution vascular MRI on clinical high-field 7T in comparison lower-field 3T. These protocols were applied for in vivo imaging of atherosclerotic rabbits, which are often used for development, testing, and validation of translatable cardiovascular MR protocols. Eight atherosclerotic New Zealand White rabbits were imaged on clinical 7T and 3T MRI scanners using 3D, isotropic, high (0.63 mm3) and ultra-high (0.43 mm3) spatial resolution, black-blood MR sequences with extensive spatial coverage. Following imaging, rabbits were sacrificed for validation using fluorescence imaging and histology. Image quality parameters such as SNR and contrast-to-noise ratio (CNR), as well as morphological and functional plaque measurements (plaque area and permeability) were evaluated at both field strengths. Using the same or comparable imaging parameters, SNR and CNR were in general higher at 7T compared to 3T, with a median (interquartiles) SNR gain of +40.3 (35.3-80.1)%, and a median CNR gain of +68.1 (38.5-95.2)%. Morphological and functional parameters, such as vessel wall area and permeability, were reliably acquired at 7T and correlated significantly with corresponding, widely validated 3T vessel wall MRI measurements. In conclusion, we successfully developed 3D, black-blood, ultra-high spatial resolution vessel wall MRI protocols on a 7T clinical scanner. 7T imaging was in general superior to 3T with respect to image quality, and comparable in terms of plaque area and permeability measurements.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241779PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735577PMC
January 2021

Predicting Poor Outcome Before Endovascular Treatment in Patients With Acute Ischemic Stroke.

Front Neurol 2020 15;11:580957. Epub 2020 Oct 15.

Department of Biomedical Engineering and Physics, University of Amsterdam, Amsterdam, Netherlands.

Although endovascular treatment (EVT) has greatly improved outcomes in acute ischemic stroke, still one third of patients die or remain severely disabled after stroke. If we could select patients with poor clinical outcome despite EVT, we could prevent futile treatment, avoid treatment complications, and further improve stroke care. We aimed to determine the accuracy of poor functional outcome prediction, defined as 90-day modified Rankin Scale (mRS) score ≥5, despite EVT treatment. We included 1,526 patients from the MR CLEAN Registry, a prospective, observational, multicenter registry of ischemic stroke patients treated with EVT. We developed machine learning prediction models using all variables available at baseline before treatment. We optimized the models for both maximizing the area under the curve (AUC), reducing the number of false positives. From 1,526 patients included, 480 (31%) of patients showed poor outcome. The highest AUC was 0.81 for random forest. The highest area under the precision recall curve was 0.69 for the support vector machine. The highest achieved specificity was 95% with a sensitivity of 34% for neural networks, indicating that all models contained false positives in their predictions. From 921 mRS 0-4 patients, 27-61 (3-6%) were incorrectly classified as poor outcome. From 480 poor outcome patients in the registry, 99-163 (21-34%) were correctly identified by the models. All prediction models showed a high AUC. The best-performing models correctly identified 34% of the poor outcome patients at a cost of misclassifying 4% of non-poor outcome patients. Further studies are necessary to determine whether these accuracies are reproducible before implementation in clinical practice.
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http://dx.doi.org/10.3389/fneur.2020.580957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593486PMC
October 2020

Supervised segmentation framework for evaluation of diffusion tensor imaging indices in skeletal muscle.

NMR Biomed 2021 01 1;34(1):e4406. Epub 2020 Oct 1.

Department of Biomedical Engineering and Physics, Amsterdam University Medical Centers, University of Amsterdam, The Netherlands.

Diffusion tensor imaging (DTI) is becoming a relevant diagnostic tool to understand muscle disease and map muscle recovery processes following physical activity or after injury. Segmenting all the individual leg muscles, necessary for quantification, is still a time-consuming manual process. The purpose of this study was to evaluate the impact of a supervised semi-automatic segmentation pipeline on the quantification of DTI indices in individual upper leg muscles. Longitudinally acquired MRI datasets (baseline, post-marathon and follow-up) of the upper legs of 11 subjects were used in this study. MR datasets consisted of a DTI and Dixon acquisition. Semi-automatic segmentations for the upper leg muscles were performed using a transversal propagation approach developed by Ogier et al on the out-of-phase Dixon images at baseline. These segmentations were longitudinally propagated for the post-marathon and follow-up time points. Manual segmentations were performed on the water image of the Dixon for each of the time points. Dice similarity coefficients (DSCs) were calculated to compare the manual and semi-automatic segmentations. Bland-Altman and regression analyses were performed, to evaluate the impact of the two segmentation methods on mean diffusivity (MD), fractional anisotropy (FA) and the third eigenvalue (λ ). The average DSC for all analyzed muscles over all time points was 0.92 ± 0.01, ranging between 0.48 and 0.99. Bland-Altman analysis showed that the 95% limits of agreement for MD, FA and λ ranged between 0.5% and 3.0% for the transversal propagation and between 0.7% and 3.0% for the longitudinal propagations. Similarly, regression analysis showed good correlation for MD, FA and λ (r = 0.99, p < 60; 0.0001). In conclusion, the supervised semi-automatic segmentation framework successfully quantified DTI indices in the upper-leg muscles compared with manual segmentation while only requiring manual input of 30% of the slices, resulting in a threefold reduction in segmentation time.
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http://dx.doi.org/10.1002/nbm.4406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757256PMC
January 2021

Marathon running transiently depletes the myocardial lipid pool.

Physiol Rep 2020 09;8(17):e14543

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.

Lipids, stored as intracellular triacylglycerol droplets within the myocardium, serve as an important source of energy, particularly in times of prolonged increased energy expenditure. In only a few studies, the acute effects of exercise on such ectopic myocardial lipid storage were investigated. We studied the dynamic behavior of the myocardial lipid pool in response to completing the 2017 Amsterdam Marathon using proton magnetic resonance (MR) spectroscopy ( H-MRS). We hypothesized that the prolonged increased myocardial energy demand of running a marathon could shift the balance of myocardial triacylglycerol turnover from triacylglycerol synthesis toward lipolysis and mitochondrial fatty acid β-oxidation, and decrease the myocardial lipid pool. We employed two 3 Tesla MR systems in parallel to noninvasively examine endurance-trained healthy men (n = 8; age 50.7 [50.1-52.7] y) at 1 week prior (baseline), <6 hr after finishing the marathon (post-marathon), and 2 weeks thereafter (recovery). Exercise intensity was 89 ± 6% of the age-predicted maximal heart rate, with a finish time of 3:56 [3:37-4:42] h:min. Myocardial lipid content was 0.66 [0.58-0.87]% of the total myocardial water signal at baseline, was lower post-marathon (0.47 [0.41-0.63]% of the total myocardial water signal), and had restored to 0.55 [0.49-0.83]% of the total myocardial water signal at recovery, representing a transient marathon running-induced depletion of 29 ± 24% (p = .04). The magnitude of this myocardial lipid pool depletion did not correlate with exercise intensity (r = -0.39; p = .39), nor with marathon finishing time (ρ = 0.57; p = .15). Our data show that prolonged high-intensity exercise can induce a transient depletion of the myocardial lipid pool, reinforcing the dynamic nature of ectopic triacylglycerol storage under real-life conditions of extreme endurance exercise.
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http://dx.doi.org/10.14814/phy2.14543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460059PMC
September 2020

Altered brain fluid management in a rat model of arterial hypertension.

Fluids Barriers CNS 2020 Jun 26;17(1):41. Epub 2020 Jun 26.

Department of Biomedical Engineering and Physics, Amsterdam Cardiovascular Sciences, Amsterdam Neuroscience, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Background: Proper neuronal function is directly dependent on the composition, turnover, and amount of interstitial fluid that bathes the cells. Most of the interstitial fluid is likely to be derived from ion and water transport across the brain capillary endothelium, a process that may be altered in hypertension due to vascular pathologies as endothelial dysfunction and arterial remodelling. In the current study, we investigated the effects of hypertension on the brain for differences in the water homeostasis.

Methods: Magnetic resonance imaging (MRI) was performed on a 7T small animal MRI system on male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) of 10 months of age. The MRI protocol consisted of T2-weighted scans followed by quantitative apparent diffusion coefficient (ADC) mapping to measure volumes of different anatomical structures and water diffusion respectively. After MRI, we assessed the spatial distribution of aquaporin 4 expression around blood vessels.

Results: MRI analysis revealed a significant reduction in overall brain volume and remarkably higher cerebroventricular volume in SHR compared to WKY. Whole brain ADC, as well as ADC values of a number of specific anatomical structures, were significantly lower in hypertensive animals. Additionally, SHR exhibited higher brain parenchymal water content. Immunohistochemical analysis showed a profound expression of aquaporin 4 around blood vessels in both groups, with a significantly larger area of influence around arterioles. Evaluation of specific brain regions revealed a decrease in aquaporin 4 expression around capillaries in the corpus callosum of SHR.

Conclusion: These results indicate a shift in the brain water homeostasis of adult hypertensive rats.
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http://dx.doi.org/10.1186/s12987-020-00203-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318739PMC
June 2020

Subclinical effects of long-chain fatty acid β-oxidation deficiency on the adult heart: A case-control magnetic resonance study.

J Inherit Metab Dis 2020 09 5;43(5):969-980. Epub 2020 Jun 5.

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.

Cardiomyopathy can be a severe complication in patients with long-chain fatty acid β-oxidation disorders (LCFAOD), particularly during episodes of metabolic derangement. It is unknown whether latent cardiac abnormalities exist in adult patients. To investigate cardiac involvement in LCFAOD, we used proton magnetic resonance imaging (MRI) and spectroscopy ( H-MRS) to quantify heart function, myocardial tissue characteristics, and myocardial lipid content in 14 adult patients (two with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD); four with carnitine palmitoyltransferase II deficiency (CPT2D); and eight with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD)) and 14 gender-, age-, and BMI-matched control subjects. Examinations included cine MRI, MR tagging, native myocardial T and T mapping, and localized H-MRS at 3 Tesla. Left ventricular (LV) myocardial mass (P = .011) and the LV myocardial mass-to-volume ratio (P = .008) were higher in patients, while ejection fraction (EF) was normal (P = .397). LV torsion was higher in patients (P = .026), whereas circumferential shortening was similar compared with controls (P = .875). LV hypertrophy was accompanied by high myocardial T values (indicative of diffuse fibrosis) in two patients, and additionally a low EF in one case. Myocardial lipid content was similar in patients and controls. We identified subclinical morphological and functional differences between the hearts of LCFAOD patients and matched control subjects using state-of-the-art MR methods. Our results suggest a chronic cardiac disease phenotype and hypertrophic LV remodeling of the heart in LCFAOD, potentially triggered by a mild, but chronic, energy deficiency, rather than by lipotoxic effects of accumulating lipid metabolites.
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http://dx.doi.org/10.1002/jimd.12266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539973PMC
September 2020

Probing myeloid cell dynamics in ischaemic heart disease by nanotracer hot-spot imaging.

Nat Nanotechnol 2020 05 20;15(5):398-405. Epub 2020 Apr 20.

BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Ischaemic heart disease evokes a complex immune response. However, tools to track the systemic behaviour and dynamics of leukocytes non-invasively in vivo are lacking. Here, we present a multimodal hot-spot imaging approach using an innovative high-density lipoprotein-derived nanotracer with a perfluoro-crown ether payload (F-HDL) to allow myeloid cell tracking by F magnetic resonance imaging. The F-HDL nanotracer can additionally be labelled with zirconium-89 and fluorophores to detect myeloid cells by in vivo positron emission tomography imaging and optical modalities, respectively. Using our nanotracer in atherosclerotic mice with myocardial infarction, we observed rapid myeloid cell egress from the spleen and bone marrow by in vivo F-HDL magnetic resonance imaging. Concurrently, using ex vivo techniques, we showed that circulating pro-inflammatory myeloid cells accumulated in atherosclerotic plaques and at the myocardial infarct site. Our multimodality imaging approach is a valuable addition to the immunology toolbox, enabling the study of complex myeloid cell behaviour dynamically.
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http://dx.doi.org/10.1038/s41565-020-0642-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416336PMC
May 2020
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