Publications by authors named "Aart J Nederveen"

236 Publications

Gender- and Age-Associated Differences in Bone Marrow Adipose Tissue and Bone Marrow Fat Unsaturation Throughout the Skeleton, Quantified Using Chemical Shift Encoding-Based Water-Fat MRI.

Authors:
Kerensa M Beekman Martine Regenboog Aart J Nederveen Nathalie Bravenboer Martin den Heijer Peter H Bisschop Carla E Hollak Erik M Akkerman Mario Maas

Front Endocrinol (Lausanne) 2022 27;13:815835. Epub 2022 Apr 27.

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

Bone marrow adipose tissue (BMAT) is a dynamic tissue which is associated with osteoporosis, bone metastasis, and primary bone tumors. The aim of this study is to determine region-specific variations and age- and gender-specific differences in BMAT and BMAT composition in healthy subjects. In this cross-sectional study, we included 40 healthy subjects (26 male: mean age 49 years, range 22-75 years; 14 female: mean age 50 years, range 29-71) and determined the bone marrow signal fat fraction and bone marrow unsaturation in the spine (C3-L5), pelvis, femora, and tibiae using chemical shift encoding-based water-fat imaging (WFI) with multiple gradient echoes (mGRE). Regions of interest covered the individual vertebral bodies, pelvis and proximal epimetaphysis, diaphysis, and distal epimetaphysis of the femur and tibia. The spinal fat fraction increased from cervical to lumbar vertebral bodies (mean fat fraction ( ± SD or (IQR): cervical spine 0.37 ± 0.1; thoracic spine 0.41 ± 0.08. lumbar spine 0.46 ± 0.01; p < 0.001). The femoral fat fraction increased from proximal to distal (proximal 0.78 ± 0.09; diaphysis 0.86 (0.15); distal 0.93 ± 0.02; p < 0.001), while within the tibia the fat fraction decreased from proximal to distal (proximal 0.92 ± 0.01; diaphysis 0.91 (0.02); distal 0.90 ± 0.01; p < 0.001). In female subjects, age was associated with fat fraction in the spine, pelvis, and proximal femur (ρ = 0.88 p < 0.001; ρ = 0.87 p < 0.001; ρ = 0.63 p = 0.02; ρ = 0.74 p = 0.002, respectively), while in male subjects age was only associated with spinal fat fraction (ρ = 0.40 p = 0.04). Fat fraction and unsaturation were negatively associated within the spine (r = -0.40 p = 0.01), while in the extremities fat fraction and unsaturation were positively associated (distal femur: r = 0.42 p = 0.01; proximal tibia: r = 0.47, p = 0.002; distal tibia: r = 0.35 p = 0.03), both independent of age and gender. In conclusion, we confirm the distinct, age- and gender-dependent, distribution of BMAT throughout the human skeleton and we show that, contradicting previous animal studies, bone marrow unsaturation in human subjects is highest within the axial skeleton compared to the appendicular skeleton. Furthermore, we show that BMAT unsaturation was negatively correlated with BMAT within the spine, while in the appendicular skeleton, BMAT and BMAT unsaturation were positively associated.
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http://dx.doi.org/10.3389/fendo.2022.815835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9094426PMC
May 2022

Assessment of functional shunting in patients with sickle cell disease.

Authors:
Liza Afzali-Hashemi Lena Václavů John C Wood Bart J Biemond Aart J Nederveen Henk J M M Mutsaerts Anouk Schrantee

Haematologica 2022 May 12. Epub 2022 May 12.

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

Silent cerebral infarcts (SCIs) are common in patients with sickle cell disease (SCD) and are thought to be caused by a mismatch between oxygen delivery and consumption. Functional cerebrovascular shunting is defined as reduced oxygen offloading due to the rapid transit of blood through the capillaries caused by increased flow and has been suggested as a potential mechanism underlying reduced oxygenation and SCI. We investigated the venous arterial spin labeling signal (VS) in the sagittal sinus as a proxy biomarker of cerebral functional shunting, and its association with hemodynamic imaging and hematological laboratory parameters. We included 28 children and 38 adults with SCD, and 10 healthy race-matched adult controls. VS, cerebral blood flow (CBF), velocity in the brain feeding arteries, oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) were measured before and after acetazolamide administration. VS was higher in patients with SCD compared to controls (p.
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http://dx.doi.org/10.3324/haematol.2021.280183DOI Listing
May 2022

Dynamic MR imaging of cerebral perfusion during bicycling exercise.

Authors:
Isa H Mast Koen P A Baas Harald T Jørstad John C Wood Aart J Nederveen Adrianus J Bakermans

Neuroimage 2022 04 1;250:118961. Epub 2022 Feb 1.

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

Habitual physical activity is beneficial for cerebrovascular health and cognitive function. Physical exercise therefore constitutes a clinically relevant cerebrovascular stimulus. This study demonstrates the feasibility of quantitative cerebral blood flow (CBF) measurements during supine bicycling exercise with pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging (MRI) at 3 Tesla. Twelve healthy volunteers performed a steady-state exercise-recovery protocol on an MR-compatible bicycle ergometer, while dynamic pCASL data were acquired at rest, during moderate (60% of the age-predicted supine maximal heart rate (HR)) and vigorous (80% of supine HR) exercise, and subsequent recovery. These CBF measurements were compared with 2D phase-contrast MRI measurements of blood flow through the carotid arteries. Procedures were repeated on a separate day for an assessment of measurement repeatability. Whole-brain (WB) CBF was 41.2 ± 6.9 mL/100 g/min at rest (heart rate 63 [57-71] beats/min), remained similar at moderate exercise (102 [97-107] beats/min), decreased by 10% to 37.1 ± 5.7 mL/100 g/min (p = 0.001) during vigorous exercise (139 [136-142] beats/min) and decreased further to 34.2 ± 6.0 mL/100 g/min (p < 0.001) during recovery. Hippocampus CBF decreased by 12% (p = 0.001) during moderate exercise, decreased further during vigorous exercise (-21%; p < 0.001) and was even lower during recovery (-31%; p < 0.001). In contrast, motor cortex CBF increased by 12% (p = 0.027) during moderate exercise, returned to resting-state values during vigorous exercise, and decreased by 17% (p = 0.006) during recovery. The inter-session repeatability coefficients for WB CBF were approximately 20% for all stages of the exercise-recovery protocol. Phase-contrast blood flow measurements through the common carotid arteries overestimated the WB CBF because of flow directed to the face and scalp. This bias increased with exercise. We have demonstrated the feasibility of dynamic pCASL-MRI of the human brain for a quantitative evaluation of cerebral perfusion during bicycling exercise. Our spatially resolved measurements revealed a differential response of CBF in the motor cortex as well as the hippocampus compared with the brain as a whole. Caution is warranted when using flow through the common carotid arteries as a surrogate measure for cerebral perfusion.
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http://dx.doi.org/10.1016/j.neuroimage.2022.118961DOI Listing
April 2022

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

Authors:
Laura Secondulfo Melissa T Hooijmans Joep J Suskens Valentina Mazzoli Mario Maas Johannes L Tol Aart J Nederveen Gustav J Strijkers

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.

Authors:
Koen P A Baas Bram F Coolen Esben T Petersen Bart J Biemond Gustav J Strijkers Aart J Nederveen

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.

Authors:
Melissa T Hooijmans Laura E Habets Sandra A M van den Berg-Faay Martijn Froeling Fay-Lynn Asselman Gustav J Strijkers Jeroen A L Jeneson Bart Bartels Aart J Nederveen W Ludo van der Pol

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.

Authors:
Carmen P S Blanken Eric M Schrauben Eva S Peper Lukas M Gottwald Bram F Coolen Diederik F van Wijk Jan J Piek Gustav J Strijkers R Nils Planken Pim van Ooij Aart J Nederveen

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

Magnetic resonance reveals mitochondrial dysfunction and muscle remodelling in spinal muscular atrophy.

Authors:
Laura E Habets Bart Bartels Fay-Lynn Asselman Melissa T Hooijmans Sandra van den Berg Aart J Nederveen W Ludo van der Pol Jeroen A L Jeneson

Brain 2021 Nov 11. Epub 2021 Nov 11.

Centre for Child Development, Exercise and Physical Literacy, Wilhelmina Children's Hospital, University Medical Centre Utrecht, P.O. Box 85090 3508 AB Utrecht, The Netherlands.

Genetic therapy has changed the prognosis of hereditary proximal spinal muscular atrophy, although treatment efficacy has been variable. There is a clear need for deeper understanding of underlying causes of muscle weakness and exercise intolerance in patients with this disease to further optimize treatment strategies. Animal models suggest that in addition to motor neuron and associated musculature degeneration, intrinsic abnormalities of muscle itself including mitochondrial dysfunction contribute to the disease etiology. To test this hypothesis in patients, we conducted the first in vivo clinical investigation of muscle bioenergetics. We recruited 15 patients and 15 healthy age and gender-matched control subjects in this cross-sectional clinico-radiological study. MRI and 31phosphorus magnetic resonance spectroscopy, the modality of choice to interrogate muscle energetics and phenotypic fiber type makeup, was performed of the proximal arm musculature in combination with fatiguing arm-cycling exercise and blood lactate testing. We derived bioenergetic parameter estimates including: blood lactate, intramuscular pH and inorganic phosphate accumulation during exercise, and muscle dynamic recovery constants. Linear correlation was used to test for associations between muscle morphological and bioenergetic parameters and clinico-functional measures of muscle weakness. MRI showed significant atrophy of triceps but not biceps muscles in patients. Maximal voluntary contraction force normalized to muscle cross-sectional area for both arm muscles was 1.4-fold lower in patients than in controls, indicating altered intrinsic muscle properties other than atrophy contributed to muscle weakness in this cohort. In vivo 31phosphorus magnetic resonance spectroscopy identified white-to-red remodeling of residual proximal arm musculature in patients on basis of altered intramuscular inorganic phosphate accumulation during arm-cycling in red versus white and intermediate myofibers. Blood lactate rise during arm-cycling was blunted in patients and correlated with muscle weakness and phenotypic muscle makeup. Post-exercise metabolic recovery was slower in residual intramuscular white myofibers in patients demonstrating mitochondrial ATP synthetic dysfunction in this particular fiber type. This study provides first in vivo evidence in patients that degeneration of motor neurons and associated musculature causing atrophy and muscle weakness in 5q spinal muscular atrophy type 3 and 4 is aggravated by disproportionate depletion of myofibers that contract fastest and strongest. Our finding of decreased mitochondrial ATP synthetic function selectively in residual white myofibers provides both a possible clue to understanding the apparent vulnerability of this particular fiber type in 5q spinal muscular atrophy type 3 and 4 as well as a new biomarker and target for therapy.
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http://dx.doi.org/10.1093/brain/awab411DOI Listing
November 2021

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

Authors:
Luuk Voskuilen Jasper Schoormans Oliver J Gurney-Champion Alfons J M Balm Gustav J Strijkers Ludi E Smeele Aart J Nederveen

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

Phase I/II Study of LDE225 in Combination with Gemcitabine and Nab-Paclitaxel in Patients with Metastatic Pancreatic Cancer.

Authors:
Esther N Pijnappel Nienke P M Wassenaar Oliver J Gurney-Champion Remy Klaassen Koen van der Lee Marjolein C H Pleunis-van Empel Dick J Richel Marie C Legdeur Aart J Nederveen Hanneke W M van Laarhoven Johanna W Wilmink

Cancers (Basel) 2021 Sep 28;13(19). Epub 2021 Sep 28.

Cancer Center Amsterdam, Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, 1012 Amsterdam, The Netherlands.

Background: Desmoplasia is a central feature of the tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC). LDE225 is a pharmacological Hedgehog signaling pathway inhibitor and is thought to specifically target tumor stroma. We investigated the combined use of LDE225 and chemotherapy to treat PDAC patients.

Methods: This was a multi-center, phase I/II study for patients with metastatic PDAC establishing the maximum tolerated dose of LDE225 co-administered with gemcitabine and nab-paclitaxel (phase I) and evaluating the efficacy and safety of the treatment combination after prior FOLFIRINOX treatment (phase II). Tumor microenvironment assessment was performed with quantitative MRI using intra-voxel incoherent motion diffusion weighted MRI (IVIM-DWI) and dynamic contrast-enhanced (DCE) MRI.

Results: The MTD of LDE225 was 200 mg once daily co-administered with gemcitabine 1000 mg/m and nab-paclitaxel 125 mg/m. In phase II, six therapy-related grade 4 adverse events (AE) and three grade 5 were observed. In 24 patients, the target lesion response was evaluable. Three patients had partial response (13%), 14 patients showed stable disease (58%), and 7 patients had progressive disease (29%). Median overall survival (OS) was 6 months (IQR 3.9-8.1). Blood plasma fraction (DCE) and diffusion coefficient (IVIM-DWI) significantly increased during treatment. Baseline perfusion fraction could predict OS (>222 days) with 80% sensitivity and 85% specificity.

Conclusion: LDE225 in combination with gemcitabine and nab-paclitaxel was well-tolerated in patients with metastatic PDAC and has promising efficacy after prior treatment with FOLFIRINOX. Quantitative MRI suggested that LDE225 causes increased tumor diffusion and works particularly well in patients with poor baseline tumor perfusion.
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http://dx.doi.org/10.3390/cancers13194869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507646PMC
September 2021

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

Authors:
Carmen P S Blanken Lukas M Gottwald Jos J M Westenberg Eva S Peper Bram F Coolen Gustav J Strijkers Aart J Nederveen R Nils Planken Pim van Ooij

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

Cardiac Biomarker Kinetics and Their Association With Magnetic Resonance Measures of Cardiomyocyte Integrity Following a Marathon Run: Implications for Postexercise Biomarker Testing.

Authors:
Vincent L Aengevaeren Roland R J van Kimmenade Jordi Ordóñez-Llanos Álvaro García-Osuna Thomas E Kaier Michael Marber Martijn Froeling Sandra van den Berg-Faay Melissa T Hooijmans Jithsa R Monte Maria T E Hopman Gustav J Strijkers Aart J Nederveen Adrianus J Bakermans Thijs M H Eijsvogels

J Am Heart Assoc 2021 07 26;10(13):e020039. Epub 2021 Jun 26.

Department of Physiology Radboud Institute for Health SciencesRadboud University Medical Center Nijmegen The Netherlands.

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http://dx.doi.org/10.1161/JAHA.120.020039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403309PMC
July 2021

Editorial for "Quantification of Regional Cerebral Blood Flow Using Diffusion Imaging With Phase-Contrast".

Authors:
Matthan W A Caan Aart J Nederveen

J Magn Reson Imaging 2021 11 23;54(5):1687-1688. Epub 2021 Jun 23.

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

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http://dx.doi.org/10.1002/jmri.27785DOI Listing
November 2021

Clinical intra-cardiac 4D flow CMR: acquisition, analysis, and clinical applications.

Authors:
Ahmet Demirkiran Pim van Ooij Jos J M Westenberg Mark B M Hofman Hans C van Assen Linda J Schoonmade Usman Asim Carmen P S Blanken Aart J Nederveen Albert C van Rossum Marco J W Götte

Eur Heart J Cardiovasc Imaging 2022 01;23(2):154-165

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

Identification of flow patterns within the heart has long been recognized as a potential contribution to the understanding of physiological and pathophysiological processes of cardiovascular diseases. Although the pulsatile flow itself is multi-dimensional and multi-directional, current available non-invasive imaging modalities in clinical practice provide calculation of flow in only 1-direction and lack 3-dimensional volumetric velocity information. Four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) has emerged as a novel tool that enables comprehensive and critical assessment of flow through encoding velocity in all 3 directions in a volume of interest resolved over time. Following technical developments, 4D flow CMR is not only capable of visualization and quantification of conventional flow parameters such as mean/peak velocity and stroke volume but also provides new hemodynamic parameters such as kinetic energy. As a result, 4D flow CMR is being extensively exploited in clinical research aiming to improve understanding of the impact of cardiovascular disease on flow and vice versa. Of note, the analysis of 4D flow data is still complex and accurate analysis tools that deliver comparable quantification of 4D flow values are a necessity for a more widespread adoption in clinic. In this article, the acquisition and analysis processes are summarized and clinical applications of 4D flow CMR on the heart including conventional and novel hemodynamic parameters are discussed. Finally, clinical potential of other emerging intra-cardiac 4D flow imaging modalities is explored and a near-future perspective on 4D flow CMR is provided.
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http://dx.doi.org/10.1093/ehjci/jeab112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787996PMC
January 2022

Improved unsupervised physics-informed deep learning for intravoxel incoherent motion modeling and evaluation in pancreatic cancer patients.

Authors:
Misha P T Kaandorp Sebastiano Barbieri Remy Klaassen Hanneke W M van Laarhoven Hans Crezee Peter T While Aart J Nederveen Oliver J Gurney-Champion

Magn Reson Med 2021 10 9;86(4):2250-2265. Epub 2021 Jun 9.

Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Purpose: Earlier work showed that IVIM-NET , an unsupervised physics-informed deep neural network, was faster and more accurate than other state-of-the-art intravoxel-incoherent motion (IVIM) fitting approaches to diffusion-weighted imaging (DWI). This study presents a substantially improved version, IVIM-NET , and characterizes its superior performance in pancreatic cancer patients.

Method: In simulations (signal-to-noise ratio [SNR] = 20), the accuracy, independence, and consistency of IVIM-NET were evaluated for combinations of hyperparameters (fit S0, constraints, network architecture, number of hidden layers, dropout, batch normalization, learning rate), by calculating the normalized root-mean-square error (NRMSE), Spearman's ρ, and the coefficient of variation (CV ), respectively. The best performing network, IVIM-NET was compared to least squares (LS) and a Bayesian approach at different SNRs. IVIM-NET 's performance was evaluated in an independent dataset of 23 patients with pancreatic ductal adenocarcinoma. Fourteen of the patients received no treatment between two repeated scan sessions and nine received chemoradiotherapy between the repeated sessions. Intersession within-subject standard deviations (wSD) and treatment-induced changes were assessed.

Results: In simulations (SNR = 20), IVIM-NET outperformed IVIM-NET in accuracy (NRMSE(D) = 0.177 vs 0.196; NMRSE(f) = 0.220 vs 0.267; NMRSE(D*) = 0.386 vs 0.393), independence (ρ(D*, f) = 0.22 vs 0.74), and consistency (CV (D) = 0.013 vs 0.104; CV (f) = 0.020 vs 0.054; CV (D*) = 0.036 vs 0.110). IVIM-NET showed superior performance to the LS and Bayesian approaches at SNRs < 50. In vivo, IVIM-NET showed significantly less noisy parameter maps with lower wSD for D and f than the alternatives. In the treated cohort, IVIM-NET detected the most individual patients with significant parameter changes compared to day-to-day variations.

Conclusion: IVIM-NET is recommended for accurate, informative, and consistent IVIM fitting to DWI data.
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http://dx.doi.org/10.1002/mrm.28852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362093PMC
October 2021

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

Authors:
Bram F Coolen Jasper Schoormans Guillaume Gilbert Ernst S Kooreman Naomi de Winter Olivia Viessmann Jaco J M Zwanenburg Charles B L M Majoie Gustav J Strijkers Aart J Nederveen Jeroen C W Siero

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

Assessment of Imaging Modalities Against Liver Biopsy in Nonalcoholic Fatty Liver Disease: The Amsterdam NAFLD-NASH Cohort.

Authors:
Marian A Troelstra Julia J Witjes Anne-Marieke van Dijk Anne L Mak Oliver Gurney-Champion Jurgen H Runge Diona Zwirs Daniela Stols-Gonçalves Aelko H Zwinderman Marije Ten Wolde Houshang Monajemi Sandjai Ramsoekh Ralph Sinkus Otto M van Delden Ulrich H Beuers Joanne Verheij Max Nieuwdorp Aart J Nederveen Adriaan G Holleboom

J Magn Reson Imaging 2021 12 15;54(6):1937-1949. Epub 2021 May 15.

Department of Internal and Vascular Medicine, Amsterdam University Medical Centres, Amsterdam, The Netherlands.

Background: Noninvasive diagnostic methods are urgently required in disease stratification and monitoring in nonalcoholic fatty liver disease (NAFLD). Multiparametric magnetic resonance imaging (MRI) is a promising technique to assess hepatic steatosis, inflammation, and fibrosis, potentially enabling noninvasive identification of individuals with active and advanced stages of NAFLD.

Purpose: To examine the diagnostic performance of multiparametric MRI for the assessment of disease severity along the NAFLD disease spectrum with comparison to histological scores.

Study Type: Prospective, cohort.

Population: Thirty-seven patients with NAFLD.

Field Strength/sequence: Multiparametric MRI at 3.0 T consisted of magnetic resonance (MR) spectroscopy (MRS) with multi-echo stimulated-echo acquisition mode, magnitude-based and three-point Dixon using a two-dimensional multi-echo gradient echo, MR elastography (MRE) using a generalized multishot gradient-recalled echo sequence and intravoxel incoherent motion (IVIM) using a multislice diffusion weighted single-shot echo-planar sequence.

Assessment: Histological steatosis grades were compared to proton density fat fraction measured by MRS (PDFF ), magnitude-based MRI (PDFF ), and three-point Dixon (PDFF ), as well as FibroScan® controlled attenuation parameter (CAP). Fibrosis and disease activity were compared to IVIM and MRE. FibroScan® liver stiffness measurements were compared to fibrosis levels. Diagnostic performance of all imaging parameters was determined for distinction between simple steatosis and nonalcoholic steatohepatitis (NASH).

Statistical Tests: Spearman's rank test, Kruskal-Wallis test, Dunn's post-hoc test with Holm-Bonferroni P-value adjustment, receiver operating characteristic curve analysis. A P-value <0.05 was considered statistically significant.

Results: Histological steatosis grade correlated significantly with PDFF (r  = 0.66, P < 0.001), PDFF (r  = 0.68, P < 0.001), and PDFF (r  = 0.67, P < 0.001), whereas no correlation was found with CAP. MRE and IVIM diffusion and perfusion significantly correlated with disease activity (r  = 0.55, P < 0.001, r  = -0.40, P = 0.016, r  = -0.37, P = 0.027, respectively) and fibrosis (r  = 0.55, P < 0.001, r  = -0.46, P = 0.0051; r  = -0.53, P < 0.001, respectively). MRE and IVIM diffusion had the highest area-under-the-curve for distinction between simple steatosis and NASH (0.79 and 0.73, respectively).

Data Conclusion: Multiparametric MRI is a promising method for noninvasive, accurate, and sensitive distinction between simple hepatic steatosis and NASH, as well as for the assessment of steatosis and fibrosis severity.

Level Of Evidence: 2 TECHNICAL EFFICACY: 2.
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http://dx.doi.org/10.1002/jmri.27703DOI Listing
December 2021

Impairment of Cerebrovascular Hemodynamics in Patients With Severe and Milder Forms of Sickle Cell Disease.

Authors:
Liza Afzali-Hashemi Koen P A Baas Anouk Schrantee Bram F Coolen Matthias J P van Osch Stefan M Spann Erfan Nur John C Wood Bart J Biemond Aart J Nederveen

Front Physiol 2021 20;12:645205. Epub 2021 Apr 20.

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

In patients with sickle cell disease (SCD), cerebral blood flow (CBF) is elevated to counteract anemia and maintain oxygen supply to the brain. This may exhaust the vasodilating capacity of the vessels, possibly increasing the risk of silent cerebral infarctions (SCI). To further investigate cerebrovascular hemodynamics in SCD patients, we assessed CBF, arterial transit time (ATT), cerebrovascular reactivity of CBF and ATT (CVR and CVR ) and oxygen delivery in patients with different forms of SCD and matched healthy controls. We analyzed data of 52 patients with severe SCD (HbSS and HbSβ-thal), 20 patients with mild SCD (HbSC and HbSβ-thal) and 10 healthy matched controls (HbAA and HbAS). Time-encoded arterial spin labeling (ASL) scans were performed before and after a vasodilatory challenge using acetazolamide (ACZ). To identify predictors of CBF and ATT after vasodilation, regression analyses were performed. Oxygen delivery was calculated and associated with hemoglobin and fetal hemoglobin (HbF) levels. At baseline, severe SCD patients showed significantly higher CBF and lower ATT compared to both the mild SCD patients and healthy controls. As CBF was linearly related to CBF , CVR decreased with disease severity. CVR was also significantly affected in severe SCD patients compared to mild SCD patients and healthy controls. Considering all groups, women showed higher CBF than men ( < 0.01) independent of baseline CBF. Subsequently, post ACZ oxygen delivery was also higher in women ( < 0.05). Baseline, but not post ACZ, GM oxygen delivery increased with HbF levels. Our data showed that baseline CBF and ATT and CVR and CVR are most affected in severe SCD patients and to a lesser extent in patients with milder forms of SCD compared to healthy controls. Cerebrovascular vasoreactivity was mainly determined by baseline CBF, sex and HbF levels. The higher vascular reactivity observed in women could be related to their lower SCI prevalence, which remains an area of future work. Beneficial effects of HbF on oxygen delivery reflect changes in oxygen dissociation affinity from hemoglobin and were limited to baseline conditions suggesting that high HbF levels do not protect the brain upon a hemodynamic challenge, despite its positive effect on hemolysis.
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http://dx.doi.org/10.3389/fphys.2021.645205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093944PMC
April 2021

Reduced global cerebral oxygen metabolic rate in sickle cell disease and chronic anemias.

Authors:
Chau Vu Adam Bush Soyoung Choi Matthew Borzage Xin Miao Aart J Nederveen Thomas D Coates John C Wood

Am J Hematol 2021 08 12;96(8):901-913. Epub 2021 May 12.

Department of Biomedical Engineering, University of Southern California, Los Angeles, California, USA.

Anemia is the most common blood disorder in the world. In patients with chronic anemia, such as sickle cell disease or major thalassemia, cerebral blood flow increases to compensate for decreased oxygen content. However, the effects of chronic anemia on oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO ) are less well understood. In this study, we examined 47 sickle-cell anemia subjects (age 21.7 ± 7.1, female 45%), 27 non-sickle anemic subjects (age 25.0 ± 10.4, female 52%) and 44 healthy controls (age 26.4 ± 10.6, female 71%) using MRI metrics of brain oxygenation and flow. Phase contrast MRI was used to measure resting cerebral blood flow, while T -relaxation-under-spin-tagging (TRUST) MRI with disease appropriate calibrations were used to measure OEF and CMRO . We observed that patients with sickle cell disease and other chronic anemias have decreased OEF and CMRO (respectively 27.4 ± 4.1% and 3.39 ± 0.71 ml O /100 g/min in sickle cell disease, 30.8 ± 5.2% and 3.53 ± 0.64 ml O /100 g/min in other anemias) compared to controls (36.7 ± 6.0% and 4.00 ± 0.65 ml O /100 g/min). Impaired CMRO was proportional to the degree of anemia severity. We further demonstrate striking concordance of the present work with pooled historical data from patients having broad etiologies for their anemia. The reduced cerebral oxygen extraction and metabolism are consistent with emerging data demonstrating increased non-nutritive flow, or physiological shunting, in sickle cell disease patients.
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http://dx.doi.org/10.1002/ajh.26203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273150PMC
August 2021

Quantification of Mitral Valve Regurgitation from 4D Flow MRI Using Semiautomated Flow Tracking.

Authors:
Carmen P S Blanken Jos J M Westenberg Jean-Paul Aben Geertruida P Bijvoet Steven A J Chamuleau S Matthijs Boekholdt Aart J Nederveen Tim Leiner Pim van Ooij R Nils Planken

Radiol Cardiothorac Imaging 2020 Oct 15;2(5):e200004. Epub 2020 Oct 15.

Departments of Radiology and Nuclear Medicine (C.P.S.B., A.J.N., P.v.O., R.N.P.) and Cardiology (S.M.B.), Amsterdam University Medical Centers, Location Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (J.J.M.W.); Department of Research and Development, Pie Medical Imaging BV, Maastricht, the Netherlands (J.P.A.); and Departments of Cardiology (G.P.B., S.A.J.C.) and Radiology (T.L.), University Medical Center Utrecht, Utrecht, the Netherlands.

Purpose: To compare the accuracy of semiautomated flow tracking with that of semiautomated valve tracking in the quantification of mitral valve (MV) regurgitation from clinical four-dimensional (4D) flow MRI data obtained in patients with mild, moderate, or severe MV regurgitation.

Materials And Methods: The 4D flow MRI data were retrospectively collected from 30 patients (21 men; mean age, 61 years ± 10 [standard deviation]) who underwent 4D flow MRI from 2006 to 2016. Ten patients had mild MV regurgitation, nine had moderate MV regurgitation, and 11 had severe MV regurgitation, as diagnosed by using semiquantitative echocardiography. The regurgitant volume (Rvol) across the MV was obtained using three methods: indirect quantification of Rvol (Rvol), semiautomated quantification of Rvol using valve tracking (Rvol), and semiautomated quantification of Rvol using flow tracking (Rvol). A second observer repeated the measurements. Aortic valve flow was quantified as well to test for intervalve consistency. The Wilcoxon signed rank test, orthogonal regression, Bland-Altman analysis, and coefficients of variation were used to assess agreement among measurements and between observers.

Results: Rvol was higher (median, 24.8 mL; interquartile range [IQR], 14.3-45.7 mL) than Rvol (median, 9.9 mL; IQR, 6.0-16.9 mL; < .001). Both Rvol and Rvol differed significantly from Rvol (median, 19.1 mL; IQR, 4.1-47.5 mL; = .03). Rvol agreed more with Rvol ( = 0.78 + 12, = 0.88) than with Rvol ( = 0.16 + 8.1, = 0.53). Bland-Altman analysis revealed underestimation of Rvol in severe MV regurgitation. Interobserver agreement was excellent for Rvol ( = 0.95, coefficient of variation = 27%) and moderate for Rvol ( = 0.72, coefficient of variation = 57%). Orthogonal regression demonstrated better intervalve consistency for flow tracking ( = 1.2 - 13.4, = 0.82) than for valve tracking ( = 2.7 - 92.4, = 0.67).

Conclusion: Flow tracking enables more accurate 4D flow MRI-derived MV regurgitation quantification than valve tracking in terms of agreement with indirect quantification and intervalve consistency, particularly in severe MV regurgitation.© RSNA, 2020.
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http://dx.doi.org/10.1148/ryct.2020200004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977692PMC
October 2020

Calibration of T oximetry MRI for subjects with sickle cell disease.

Authors:
Adam Bush Chau Vu Soyoung Choi Matthew Borzage Xin Miao Wenbo Li Qin Qin Aart J Nederveen Thomas D Coates John C Wood

Magn Reson Med 2021 08 14;86(2):1019-1028. Epub 2021 Mar 14.

Department of Biomedical Engineering, University of Southern California, Los Angeles, California, USA.

Purpose: Cerebral T oximetry is a non-invasive imaging method to measure blood T and cerebral venous oxygenation. Measured T values are converted to oximetry estimates using carefully validated and potentially disease-specific calibrations. In sickle cell disease, red blood cells have abnormal cell shape and membrane properties that alter T oximetry calibration relationships in clinically meaningful ways. Previous in vitro works by two independent groups established potentially competing calibration models.

Methods: This study analyzed pooled datasets from these two studies to establish a unified and more robust sickle-specific calibration to serve as a reference standard in the field.

Results: Even though the combined calibration did not demonstrate statistical superiority compared to previous models, the calibration was unbiased compared to blood-gas co-oximetry and yielded limits of agreement of (-10.1%, 11.6%) in non-transfused subjects with sickle cell disease. In transfused patients, this study proposed a simple correction method based on individual hemoglobin S percentage that demonstrated reduced bias in saturation measurement compared to previous uncorrected sickle calibrations.

Conclusion: The combined calibration is based on a larger range of hematocrit, providing greater confidence in the hematocrit-dependent model parameters, and yielded unbiased estimates to blood-gas co-oximetry measurements from both sites. Additionally, this work also demonstrated the need to correct for transfusion in T oximetry measurements for hyper-transfused sickle cell disease patients and proposes a correction method based on patient-specific hemoglobin S concentration.
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http://dx.doi.org/10.1002/mrm.28757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076101PMC
August 2021

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

Authors:
Lukas M Gottwald Carmen P S Blanken João Tourais Jouke Smink R Nils Planken S Matthijs Boekholdt Lilian J Meijboom Bram F Coolen Gustav J Strijkers Aart J Nederveen Pim van Ooij

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

Fully quantitative mapping of abnormal aortic velocity and wall shear stress direction in patients with bicuspid aortic valves and repaired coarctation using 4D flow cardiovascular magnetic resonance.

Authors:
Pim van Ooij Emile S Farag Carmen P S Blanken Aart J Nederveen Maarten Groenink R Nils Planken S Matthijs Boekholdt

J Cardiovasc Magn Reson 2021 02 15;23(1). Epub 2021 Feb 15.

Department of Cardiology, Amsterdam University Medical Center, location AMC, Amsterdam, The Netherlands.

Background: Helices and vortices in thoracic aortic blood flow measured with 4D flow cardiovascular magnetic resonance (CMR) have been associated with aortic dilation and aneurysms. Current approaches are semi-quantitative or when fully quantitative based on 2D plane placement. In this study, we present a fully quantitative and three-dimensional approach to map and quantify abnormal velocity and wall shear stress (WSS) at peak systole in patients with a bicuspid aortic valve (BAV) of which 52% had a repaired coarctation.

Methods: 4D flow CMR was performed in 48 patients with BAV and in 25 healthy subjects at a spatiotemporal resolution of 2.5 × 2.5 × 2.5mm/ ~ 42 ms and TE/TR/FA of 2.1 ms/3.4 ms/8° with k-t Principal Component Analysis factor R = 8. A 3D average of velocity and WSS direction was created for the normal subjects. Comparing BAV patient data with the 3D average map and selecting voxels deviating between 60° and 120° and > 120° yielded 3D maps and volume (in cm) and surface (in cm) quantification of abnormally directed velocity and WSS, respectively. Linear regression with Bonferroni corrected significance of P < 0.0125 was used to compare abnormally directed velocity volume and WSS surface in the ascending aorta with qualitative helicity and vorticity scores, with local normalized helicity (LNH) and quantitative vorticity and with patient characteristics.

Results: The velocity volumes > 120° correlated moderately with the vorticity scores (R ~ 0.50, P < 0.001 for both observers). For WSS surface these results were similar. The velocity volumes between 60° and 120° correlated moderately with LNH (R = 0.66) but the velocity volumes > 120° did not correlate with quantitative vorticity. For abnormal velocity and WSS deviating between 60° and 120°, moderate correlations were found with aortic diameters (R = 0.50-0.70). For abnormal velocity and WSS deviating > 120°, additional moderate correlations were found with age and with peak velocity (stenosis severity) and a weak correlation with gender. Ensemble maps showed that more than 60% of the patients had abnormally directed velocity and WSS. Additionally, abnormally directed velocity and WSS was higher in the proximal descending aorta in the patients with repaired coarctation than in the patients where coarctation was never present.

Conclusion: The possibility to reveal directional abnormalities of velocity and WSS in 3D provides a new tool for hemodynamic characterization in BAV disease.
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http://dx.doi.org/10.1186/s12968-020-00703-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885343PMC
February 2021

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

Authors:
Adrianus J Bakermans S Matthijs Boekholdt Dylan K de Vries Yolan J Reckman Emile S Farag Paul de Heer Laween Uthman Simone W Denis Coert J Zuurbier Riekelt H Houtkooper David R Koolbergen Jolanda Kluin R Nils Planken Hildo J Lamb Andrew G Webb Gustav J Strijkers Daniel A Beard Jeroen A L Jeneson Aart J Nederveen

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

Longitudinal relation between blood pressure, antihypertensive use and cerebral blood flow, using arterial spin labelling MRI.

Authors:
Jan Willem van Dalen Henri Jmm Mutsaerts Jan Petr Matthan Wa Caan Eric P Moll van Charante Bradley J MacIntosh Willem A van Gool Aart J Nederveen Edo Richard

J Cereb Blood Flow Metab 2021 07 16;41(7):1756-1766. Epub 2020 Dec 16.

Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Consistent cerebral blood flow (CBF) is fundamental to brain function. Cerebral autoregulation ensures CBF stability. Chronic hypertension can lead to disrupted cerebral autoregulation in older people, potentially leading to blood pressure levels interfering with CBF. This study tested whether low BP and AHD use are associated with contemporaneous low CBF, and whether longitudinal change in BP is associated with change in CBF, using arterial spin labelling (ASL) MRI, in a prospective longitudinal cohort of 186 community-dwelling older individuals with hypertension (77 ± 3 years, 53% female), 125 (67%) of whom with 3-year follow-up. Diastolic blood pressure, systolic blood pressure, mean arterial pressure, and pulse pressure were assessed as blood pressure parameters. As additional cerebrovascular marker, we evaluated the ASL signal spatial coefficient of variation (ASL SCoV), a measure of ASL signal heterogeneity that may reflect cerebrovascular health. We found no associations between any of the blood pressure measures and concurrent CBF nor between changes in blood pressure measures and CBF over three-year follow-up. Antihypertensive use was associated with lower grey matter CBF (-5.49 ml/100 g/min, 95%CI = -10.7|-0.27,  = 0.04) and higher ASL SCoV (0.32 SD, 95%CI = 0.12|0.52,  = 0.002). These results warrant future research on the potential relations between antihypertensive use and cerebral perfusion.
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http://dx.doi.org/10.1177/0271678X20966975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217888PMC
July 2021

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

Authors:
Martin J Willemink Bram F Coolen Hadrien Dyvorne Philip M Robson Ilda Bander Seigo Ishino Alison Pruzan Arthi Sridhar Bei Zhang Priti Balchandani Venkatesh Mani Gustav J Strijkers Aart J Nederveen Tim Leiner Zahi A Fayad Willem J M Mulder Claudia Calcagno

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

Hepatic Insulin Resistance Is Not Pathway Selective in Humans With Nonalcoholic Fatty Liver Disease.

Authors:
Kasper W Ter Horst Daniel F Vatner Dongyan Zhang Gary W Cline Mariette T Ackermans Aart J Nederveen Joanne Verheij Ahmet Demirkiran Bart A van Wagensveld Geesje M Dallinga-Thie Max Nieuwdorp Johannes A Romijn Gerald I Shulman Mireille J Serlie

Diabetes Care 2021 02 8;44(2):489-498. Epub 2020 Dec 8.

Department of Endocrinology and Metabolism, Amsterdam University Medical Center, Amsterdam, the Netherlands

Objective: Both glucose and triglyceride production are increased in type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). For decades, the leading hypothesis to explain these paradoxical observations has been selective hepatic insulin resistance wherein insulin drives de novo lipogenesis (DNL) while failing to suppress glucose production. Here, we aimed to test this hypothesis in humans.

Research Design And Methods: We recruited obese subjects who met criteria for bariatric surgery with ( = 16) or without ( = 15) NAFLD and assessed ) insulin-mediated regulation of hepatic and peripheral glucose metabolism using hyperinsulinemic-euglycemic clamps with [6,6-H]glucose, ) fasting and carbohydrate-driven hepatic DNL using deuterated water (HO), and ) hepatocellular insulin signaling in liver biopsy samples collected during bariatric surgery.

Results: Compared with subjects without NAFLD, those with NAFLD demonstrated impaired insulin-mediated suppression of glucose production and attenuated-not increased-glucose-stimulated/high-insulin lipogenesis. Fructose-stimulated/low-insulin lipogenesis was intact. Hepatocellular insulin signaling, assessed for the first time in humans, exhibited a proximal block in insulin-resistant subjects: Signaling was attenuated from the level of the insulin receptor through both glucose and lipogenesis pathways. The carbohydrate-regulated lipogenic transcription factor was increased in subjects with NAFLD.

Conclusions: Acute increases in lipogenesis in humans with NAFLD are not explained by altered molecular regulation of lipogenesis through a paradoxical increase in lipogenic insulin action; rather, increases in lipogenic substrate availability may be the key.
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http://dx.doi.org/10.2337/dc20-1644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818337PMC
February 2021

Carotid plaque composition in persons with hemophilia: An explorative study with multi-contrast MRI.

Authors:
Hilde Hop Jan-Hendrik Potze Sandra van den Berg-Faaij Ronald J H Borra Kang H Zheng Aart J Nederveen Karina Meijer Pieter Willem Kamphuisen

Thromb Res 2021 01 6;197:138-140. Epub 2020 Nov 6.

Department of Internal Medicine, University Medical Center Groningen, University of Groningen, the Netherlands; Department of Internal Medicine, Tergooi Hospital, location Hilversum, the Netherlands.

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http://dx.doi.org/10.1016/j.thromres.2020.10.036DOI Listing
January 2021

Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis.

Authors:
Julia J Witjes Loek P Smits Ceyda T Pekmez Andrei Prodan Abraham S Meijnikman Marian A Troelstra Kristien E C Bouter Hilde Herrema Evgeni Levin Adriaan G Holleboom Maaike Winkelmeijer Ulrich H Beuers Krijn van Lienden Judith Aron-Wisnewky Ville Mannisto Jacques J Bergman Jurgen H Runge Aart J Nederveen Lars O Dragsted Prokopis Konstanti Erwin G Zoetendal Willem de Vos Joanne Verheij Albert K Groen Max Nieuwdorp

Hepatol Commun 2020 Nov 7;4(11):1578-1590. Epub 2020 Oct 7.

Department of Internal and Vascular Medicine Amsterdam University Medical Centers Location AMC Amsterdam the Netherlands.

The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant-based, low-animal-protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. We therefore performed a double-blind randomized controlled proof-of-principle study in which individuals with hepatic steatosis on ultrasound were randomized to two study arms: lean vegan donor (allogenic n = 10) or own (autologous n = 11) FMT. Both were performed three times at 8-week intervals. A liver biopsy was performed at baseline and after 24 weeks in every subject to determine histopathology (Nonalcoholic Steatohepatitis Clinical Research Network) classification and changes in hepatic gene expression based on RNA sequencing. Secondary outcome parameters were changes in intestinal microbiota composition and fasting plasma metabolomics. We observed a trend toward improved necro-inflammatory histology, and found significant changes in expression of hepatic genes involved in inflammation and lipid metabolism following allogenic FMT. Intestinal microbial community structure changed following allogenic FMT, which was associated with changes in plasma metabolites as well as markers of . Allogenic FMT using lean vegan donors in individuals with hepatic steatosis shows an effect on intestinal microbiota composition, which is associated with beneficial changes in plasma metabolites and markers of steatohepatitis.
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http://dx.doi.org/10.1002/hep4.1601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603524PMC
November 2020

Cerebral Blood Flow in Patients with Severe Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Implantation.

Authors:
Wieneke Vlastra Astrid C van Nieuwkerk Anne-Sophie G T Bronzwaer Adriaan Versteeg Esther E Bron Wiro J Niessen Henk J M M Mutsaerts Björn J P van der Ster Charles B L M Majoie Geert J Biessels Aart J Nederveen Mat J A P Daemen Matthias J P van Osch Jan Baan Jan J Piek Johannes J Van Lieshout Ronak Delewi

J Am Geriatr Soc 2021 02 17;69(2):494-499. Epub 2020 Oct 17.

Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Heart Center, Amsterdam, the Netherlands.

Background: Transcatheter aortic valve implantation (TAVI) is a minimally invasive, life-saving treatment for patients with severe aortic valve stenosis that improves quality of life. We examined cardiac output and cerebral blood flow in patients undergoing TAVI to test the hypothesis that improved cardiac output after TAVI is associated with an increase in cerebral blood flow.

Design: Prospective cohort study.

Setting: European high-volume tertiary multidisciplinary cardiac care.

Participants: Thirty-one patients (78.3 ± 4.6 years; 61% female) with severe symptomatic aortic valve stenosis.

Measurements: Noninvasive prospective assessment of cardiac output (L/min) by inert gas rebreathing and cerebral blood flow of the total gray matter (mL/100 g per min) using arterial spin labeling magnetic resonance imaging in resting state less than 24 hours before TAVI and at 3-month follow-up. Cerebral blood flow change was defined as the difference relative to baseline.

Results: On average, cardiac output in patients with severe aortic valve stenosis increased from 4.0 ± 1.1 to 5.4 ± 2.4 L/min after TAVI (P = .003). The increase in cerebral blood flow after TAVI strongly varied between patients (7% ± 24%; P = .41) and related to the increase in cardiac output, with an 8.2% (standard error = 2.3%; P = .003) increase in cerebral blood flow per every additional liter of cardiac output following the TAVI procedure.

Conclusion: Following TAVI, there was an association of increase in cardiac output with increase in cerebral blood flow. These findings encourage future larger studies to determine the influence of TAVI on cerebral blood flow and cognitive function.
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http://dx.doi.org/10.1111/jgs.16882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894507PMC
February 2021
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