Publications by authors named "Joachim Wildberger"

274 Publications

A novel risk score for contrast-associated acute kidney injury: the heart of the matter.

Lancet 2021 Nov 15;398(10315):1941-1943. Epub 2021 Nov 15.

Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre, Maastricht 6202 AZ, Netherlands.

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http://dx.doi.org/10.1016/S0140-6736(21)02445-4DOI Listing
November 2021

The impact of dark-blood versus conventional bright-blood late gadolinium enhancement on the myocardial ischemic burden.

Eur J Radiol 2021 Nov 8;144:109947. Epub 2021 Oct 8.

School of Biomedical Engineering & Imaging Sciences, King's College London, London, United Kingdom. Electronic address:

Purpose: In perfusion cardiovascular magnetic resonance (CMR), ischemic burden predicts adverse prognosis and is often used to guide revascularization. Ischemic scar tissue can cause stress perfusion defects that do not represent myocardial ischemia. Dark-blood late gadolinium enhancement (LGE) methods detect more scar than conventional bright-blood LGE, however, the impact on the myocardial ischemic burden estimation is unknown and evaluated in this study.

Methods: Forty patients with CMR stress perfusion defects and ischemic scar on both dark-blood and bright-blood LGE were included. For dark-blood LGE, phase sensitive inversion recovery imaging with left ventricular blood pool nulling was used. Ischemic scar burden was quantified for both methods using >5 standard deviations above remote myocardium. Perfusion defects were manually contoured, and the myocardial ischemic burden was calculated by subtracting the ischemic scar burden from the perfusion defect burden.

Results: Ischemic scar burden by dark-blood LGE was higher than bright-blood LGE (13.3 ± 7.4% vs. 10.3 ± 7.1%, p < 0.001). Dark-blood LGE derived myocardial ischemic burden was lower compared with bright-blood LGE (15.6% (IQR: 10.3 to 22.0) vs. 19.3 (10.9 to 25.5), median difference -2.0%, p < 0.001) with a mean bias of -2.8% (95% confidence intervals: -4.0 to -1.6%) and a large effect size (r = 0.62).

Conclusion: Stress perfusion defects are associated with higher ischemic scar burden using dark-blood LGE compared with bright-blood LGE, which leads to a lower estimation of the myocardial ischemic burden. The prognostic value of using a dark-blood LGE derived ischemic burden to guide revascularization is unknown and warrants further investigation.
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http://dx.doi.org/10.1016/j.ejrad.2021.109947DOI Listing
November 2021

Dark-blood late gadolinium enhancement cardiovascular magnetic resonance for improved detection of subendocardial scar: a review of current techniques.

J Cardiovasc Magn Reson 2021 07 22;23(1):96. Epub 2021 Jul 22.

Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, PO Box 616, Maastricht, 6200 MD, The Netherlands.

For almost 20 years, late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has been the reference standard for the non-invasive assessment of myocardial viability. Since the blood pool often appears equally bright as the enhanced scar regions, detection of subendocardial scar patterns can be challenging. Various novel LGE methods have been proposed that null or suppress the blood signal by employing additional magnetization preparation mechanisms. This review aims to provide a comprehensive overview of these dark-blood LGE methods, discussing the magnetization preparation schemes and findings in phantom, preclinical, and clinical studies. Finally, conclusions on the current evidence and limitations are drawn and new avenues for future research are discussed. Dark-blood LGE methods are a promising new tool for non-invasive assessment of myocardial viability. For a mainstream adoption of dark-blood LGE, however, clinical availability and ease of use are crucial.
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http://dx.doi.org/10.1186/s12968-021-00777-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296731PMC
July 2021

Influence of Contrast Material Temperature on Patient Comfort and Image Quality in Computed Tomography of the Abdomen: A Randomized Controlled Trial.

Invest Radiol 2021 Jul 2. Epub 2021 Jul 2.

From the Department of Radiology and Nuclear Medicine, Maastricht University Medical Center CARIM School for Cardiovascular Diseases, Maastricht University Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center Department of Internal Medicine, Division of Medical Oncology GROW-School for Oncology and Developmental Biology, Maastricht UMC+, Maastricht, the Netherlands.

Background: International guideline recommendations on safe use of contrast media (CM) are conflicting regarding the necessity to prewarm iodinated CM.

Purpose: Aim of the study was to evaluate the effects of room temperature CM compared with prewarmed CM on image quality, safety, and patient comfort in abdominal computed tomography (CT).

Methods: CATCHY (Contrast Media Temperature and Patient Comfort in Computed Tomography of the Abdomen) is a double-blinded, randomized noninferiority trial. Between February and August 2020, 218 participants referred for portal venous abdominal CT were prospectively and randomly assigned to 1 of 2 groups. All patients received iopromide at 300 mg I/mL: group 1 at room temperature (~23°C [~73°F]) and group 2 prewarmed to body temperature (37°C [99°F]). A state-of-the-art individualized CM injection protocol was used, based on body weight and adapted to tube voltage. Primary outcome was absolute difference in mean liver attenuation between groups, calculated with a 2-sided 95% confidence interval. The noninferiority margin was set at -10 HU. Secondary outcomes were objective (signal-to-noise ratio and contrast-to-noise ratio) and subjective image quality; CM extravasations and other adverse events; and participant comfort (5-point scale questionnaire) and pain (numeric rating scale). This trial is registered with ClinicalTrials.gov (NCT04249479).

Results: The absolute difference in mean attenuation between groups was + 4.23 HU (95% confidence interval, +0.35 to +8.11; mean attenuation, 122.2 ± 13.1 HU in group 1, 118.0 ± 15.9 HU in group 2; P = 0.03). Signal-to-noise ratio, contrast-to-noise ratio, and subjective image quality were not significantly different between groups (P = 0.53, 0.23, and 0.99 respectively). Contrast extravasation occurred in 1 patient (group 2), and no other adverse events occurred. Comfort scores were significantly higher in group 1 than in group 2 (P = 0.03); pain did not significantly differ (perceived P > 0.99; intensity P = 0.20).

Conclusions: Not prewarming iodinated CM was found noninferior in abdominal CT imaging. Prewarming conferred no beneficial effect on image quality, safety, and comfort, and might therefore no longer be considered a prerequisite in state-of-the art injection protocols for parenchymal imaging.
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http://dx.doi.org/10.1097/RLI.0000000000000807DOI Listing
July 2021

Impact of Field Strength in Clinical Cardiac Magnetic Resonance Imaging.

Invest Radiol 2021 11;56(11):764-772

Abstract: Cardiac magnetic resonance imaging (MRI) is widely applied for the noninvasive assessment of cardiac structure and function, and for tissue characterization. For more than 2 decades, 1.5 T has been considered the field strength of choice for cardiac MRI. Although the number of 3-T systems significantly increased in the past 10 years and numerous new developments were made, challenges seem to remain that hamper a widespread clinical use of 3-T MR systems for cardiac applications. As the number of clinical cardiac applications is increasing, with each having their own benefits at both field strengths, no "holy grail" field strength exists for cardiac MRI that one should ideally use. This review describes the physical differences between 1.5 and 3 T, as well as the effect of these differences on major (routine) cardiac MRI applications, including functional imaging, edema imaging, late gadolinium enhancement, first-pass stress perfusion, myocardial mapping, and phase contrast flow imaging. For each application, the advantages and limitations at both 1.5 and 3 T are discussed. Solutions and alternatives are provided to overcome potential limitations. Finally, we briefly elaborate on the potential use of alternative field strengths (ie, below 1.5 T and above 3 T) for cardiac MRI and conclude with field strength recommendations for the future of cardiac MRI.
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http://dx.doi.org/10.1097/RLI.0000000000000809DOI Listing
November 2021

Transforming a pre-existing MRI environment into an interventional cardiac MRI suite.

J Cardiovasc Electrophysiol 2021 08 4;32(8):2090-2096. Epub 2021 Jul 4.

Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands.

Aims: To illustrate the practical and technical challenges along with the safety aspects when performing MRI-guided electrophysiological procedures in a pre-existing diagnostic magnetic resonance imaging (MRI) environment.

Methods And Results: A dedicated, well-trained multidisciplinary interventional cardiac MRI team (iCMR team), consisting of electrophysiologists, imaging cardiologists, radiologists, anaesthesiologists, MRI physicists, electrophysiological (EP) and MRI technicians, biomedical engineers, and medical instrumentation technologists is a prerequisite for a safe and feasible implementation of CMR-guided electrophysiological procedures (iCMR) in a pre-existing MRI environment. A formal dry run "mock-up" to address the entire spectrum of technical, logistic, and safety issues was performed before obtaining final approval of the Board of Directors. With this process we showed feasibility of our workflow, safety protocol, and bailout procedures during iCMR outside the conventional EP lab. The practical aspects of performing iCMR procedures in a pre-existing MRI environment were addressed and solidified. Finally, the influence on neighbouring MRI scanners was evaluated, showing no interference.

Conclusion: Transforming a pre-existing diagnostic MRI environment into an iCMR suite is feasible and safe. However, performing iCMR procedures outside the conventional fluoroscopic lab, poses challenges with technical, practical, and safety aspects that need to be addressed by a dedicated multi-disciplinary iCMR team.
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http://dx.doi.org/10.1111/jce.15128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456838PMC
August 2021

Serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with SARS-CoV-2 infection; the prospective Maastricht intensive care COVID cohort.

Thromb J 2021 May 31;19(1):35. Epub 2021 May 31.

Department of Intensive Care Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Background: The incidence of pulmonary thromboembolism is high in SARS-CoV-2 patients admitted to the Intensive Care. Elevated biomarkers of coagulation (fibrinogen and D-dimer) and inflammation (c-reactive protein (CRP) and ferritin) are associated with poor outcome in SARS-CoV-2. Whether the time-course of fibrinogen, D-dimer, CRP and ferritin is associated with the occurrence of pulmonary thromboembolism in SARS-CoV-2 patients is unknown. We hypothesise that patients on mechanical ventilation with SARS-CoV-2 infection and clinical pulmonary thromboembolism have lower concentrations of fibrinogen and higher D-dimer, CRP, and ferritin concentrations over time compared to patients without a clinical pulmonary thromboembolism.

Methods: In a prospective study, fibrinogen, D-dimer, CRP and ferritin were measured daily. Clinical suspected pulmonary thromboembolism was either confirmed or excluded based on computed tomography pulmonary angiography (CTPA) or by transthoracic ultrasound (TTU) (i.e., right-sided cardiac thrombus). In addition, patients who received therapy with recombinant tissue plasminogen activator were included when clinical instability in suspected pulmonary thromboembolism did not allow CTPA. Serial data were analysed using a mixed-effects linear regression model, and models were adjusted for known risk factors (age, sex, APACHE-II score, body mass index), biomarkers of coagulation and inflammation, and anticoagulants.

Results: Thirty-one patients were considered to suffer from pulmonary thromboembolism ((positive CTPA (n = 27), TTU positive (n = 1), therapy with recombinant tissue plasminogen activator (n = 3)), and eight patients with negative CTPA were included. After adjustment for known risk factors and anticoagulants, patients with, compared to those without, clinical pulmonary thromboembolism had lower average fibrinogen concentration of - 0.9 g/L (95% CI: - 1.6 - - 0.1) and lower average ferritin concentration of - 1045 μg/L (95% CI: - 1983 - - 106) over time. D-dimer and CRP average concentration did not significantly differ, 561 μg/L (- 6212-7334) and 27 mg/L (- 32-86) respectively. Ferritin lost statistical significance, both in sensitivity analysis and after adjustment for fibrinogen and D-dimer.

Conclusion: Lower average concentrations of fibrinogen over time were associated with the presence of clinical pulmonary thromboembolism in patients at the Intensive Care, whereas D-dimer, CRP and ferritin were not. Lower concentrations over time may indicate the consumption of fibrinogen related to thrombus formation in the pulmonary vessels.
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http://dx.doi.org/10.1186/s12959-021-00286-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165953PMC
May 2021

The Effects of In-Plane Spatial Resolution on CT-Based Radiomic Features' Stability with and without ComBat Harmonization.

Cancers (Basel) 2021 Apr 13;13(8). Epub 2021 Apr 13.

Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

While handcrafted radiomic features (HRFs) have shown promise in the field of personalized medicine, many hurdles hinder its incorporation into clinical practice, including but not limited to their sensitivity to differences in acquisition and reconstruction parameters. In this study, we evaluated the effects of differences in in-plane spatial resolution (IPR) on HRFs, using a phantom dataset (n = 14) acquired on two scanner models. Furthermore, we assessed the effects of interpolation methods (IMs), the choice of a new unified in-plane resolution (NUIR), and ComBat harmonization on the reproducibility of HRFs. The reproducibility of HRFs was significantly affected by variations in IPR, with pairwise concordant HRFs, as measured by the concordance correlation coefficient (CCC), ranging from 42% to 95%. The number of concordant HRFs (CCC > 0.9) after resampling varied depending on (i) the scanner model, (ii) the IM, and (iii) the NUIR. The number of concordant HRFs after ComBat harmonization depended on the variations between the batches harmonized. The majority of IMs resulted in a higher number of concordant HRFs compared to ComBat harmonization, and the combination of IMs and ComBat harmonization did not yield a significant benefit. Our developed framework can be used to assess the reproducibility and harmonizability of RFs.
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http://dx.doi.org/10.3390/cancers13081848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103509PMC
April 2021

The Diagnostic Value of an X-ray-based Scoring System for Degeneration of the Cervical Spine: A Reproducibility and Validation Study.

Pain Pract 2021 09 18;21(7):766-777. Epub 2021 May 18.

Division of Medical Imaging and Clinical Laboratories, Department of Radiology and Nuclear Medicine, University Medical Centre Maastricht, Maastricht, The Netherlands.

Background: In interventional pain medicine, cervical facet joint (CFJ) pain is commonly treated with CFJ denervation techniques, almost automatically assuming degeneration of the CFJs as an important cause of CFJ pain. A standard cervical X-ray is still commonly used in the clinical evaluation of patients suspected for CFJ degeneration. Although degenerative features can be visualized by different radiological imaging techniques, the relation between radiological degenerative features of the cervical spine and pain remains controversial. Paramount in order to estimate the clinical usefulness of a radiological imaging is to establish the reproducibility of the radiological scoring system. A reproducible and clinically feasible diagnostic scoring system was developed to estimate cervical degeneration on standard cervical X-rays.

Materials And Methods: A reproducibility study for the interpretation of degenerative abnormalities on standard cervical X-rays was performed, using a dichotomous outcome (degenerative abnormalities present Yes/No). The estimation of intervertebral disc height loss on standard cervical X-rays was validated with computed tomography (CT) scan measurements.

Results: Five radiological degenerative features on standard cervical X-rays (disc height loss, anterior vertebral osteophytes, posterior vertebral osteophytes, vertebral end plate sclerosis, and uncovertebral osteoarthritis) showed a substantial to excellent reproducibility (kappa value ≥ 0.60). The qualitative definition of disc height loss used in the reproducibility study showed a substantial agreement with the actual measurements of disc height loss on CT scan (kappa value = 0.69).

Conclusion: Subjective judgment of a cervical standard X-ray is a reproducible method to demonstrate degenerative abnormalities of the cervical spine.
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http://dx.doi.org/10.1111/papr.13013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518644PMC
September 2021

Cardiovascular magnetic resonance accurately detects obstructive coronary artery disease in suspected non-ST elevation myocardial infarction: a sub-analysis of the CARMENTA Trial.

J Cardiovasc Magn Reson 2021 03 22;23(1):40. Epub 2021 Mar 22.

Department of Cardiology, Maastricht UMC+, Maastricht, The Netherlands.

Background: Invasive coronary angiography (ICA) is still the reference test in suspected non-ST elevation myocardial infarction (NSTEMI), although a substantial number of patients do not have obstructive coronary artery disease (CAD). Early cardiovascular magnetic resonance (CMR) may be a useful gatekeeper for ICA in this setting. The main objective was to investigate the accuracy of CMR to detect obstructive CAD in NSTEMI.

Methods: This study is a sub-analysis of a randomized controlled trial investigating whether a non-invasive imaging-first strategy safely reduced the number of ICA compared to routine clinical care in suspected NSTEMI (acute chest pain, non-diagnostic electrocardiogram, high sensitivity troponin T > 14 ng/L), and included 51 patients who underwent CMR prior to ICA. A stepwise approach was used to assess the diagnostic accuracy of CMR to detect (1) obstructive CAD (diameter stenosis ≥ 70% by ICA) and (2) an adjudicated final diagnosis of acute coronary syndrome (ACS). First, in all patients the combination of cine, T2-weighted and late gadolinium enhancement (LGE) imaging was evaluated for the presence of abnormalities consistent with a coronary etiology in any sequence. Hereafter and only when the scan was normal or equivocal, adenosine stress-perfusion CMR was added.

Results: Of 51 patients included (63 ± 10 years, 51% male), 34 (67%) had obstructive CAD by ICA. The sensitivity, specificity and overall accuracy of the first step to diagnose obstructive CAD were 79%, 71% and 77%, respectively. Additional vasodilator stress-perfusion CMR was performed in 19 patients and combined with step one resulted in an overall sensitivity of 97%, specificity of 65% and accuracy of 86%. Of the remaining 17 patients with non-obstructive CAD, 4 (24%) had evidence for a myocardial infarction on LGE, explaining the modest specificity. The sensitivity, specificity and overall accuracy to diagnose ACS (n = 43) were 88%, 88% and 88%, respectively.

Conclusion: CMR accurately detects obstructive CAD and ACS in suspected NSTEMI. Non-obstructive CAD is common with CMR still identifying an infarction in almost one-quarter of patients. CMR should be considered as an early diagnostic approach in suspected NSTEMI.

Trial Registration: The CARMENTA trial has been registered at ClinicalTrials.gov with identifier NCT01559467.
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http://dx.doi.org/10.1186/s12968-021-00723-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983380PMC
March 2021

Characterization of Ascending Aortic Flow in Patients With Degenerative Aneurysms: A 4D Flow Magnetic Resonance Study.

Invest Radiol 2021 08;56(8):494-500

Department of Radiology, Leiden University Medical Center.

Objectives: Degenerative thoracic aortic aneurysm (TAA) patients are known to be at risk of life-threatening acute aortic events. Guidelines recommend preemptive surgery at diameters of greater than 55 mm, although many patients with small aneurysms show only mild growth rates and more than half of complications occur in aneurysms below this threshold. Thus, assessment of hemodynamics using 4-dimensional flow magnetic resonance has been of interest to obtain more insights in aneurysm development. Nonetheless, the role of aberrant flow patterns in TAA patients is not yet fully understood.

Materials And Methods: A total of 25 TAA patients and 22 controls underwent time-resolved 3-dimensional phase contrast magnetic resonance imaging with 3-directional velocity encoding (ie, 4-dimensional flow magnetic resonance imaging). Hemodynamic parameters such as vorticity, helicity, and wall shear stress (WSS) were calculated from velocity data in 3 anatomical segments of the ascending aorta (root, proximal, and distal). Regional WSS distribution was assessed for the full cardiac cycle.

Results: Flow vorticity and helicity were significantly lower for TAA patients in all segments. The proximal ascending aorta showed a significant increase in peak WSS in the outer curvature in TAA patients, whereas WSS values at the inner curvature were significantly lower as compared with controls. Furthermore, positive WSS gradients from sinotubular junction to midascending aorta were most prominent in the outer curvature, whereas from midascending aorta to brachiocephalic trunk, the outer curvature showed negative WSS gradients in the TAA group. Controls solely showed a positive gradient at the inner curvature for both segments.

Conclusions: Degenerative TAA patients show a decrease in flow vorticity and helicity, which is likely to cause perturbations in physiological flow patterns. The subsequent differing distribution of WSS might be a contributor to vessel wall remodeling and aneurysm formation.
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http://dx.doi.org/10.1097/RLI.0000000000000768DOI Listing
August 2021

Probability of receiving a high cumulative radiation dose and primary clinical indication of CT examinations: a 5-year observational cohort study.

BMJ Open 2021 01 17;11(1):e041883. Epub 2021 Jan 17.

Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Objective: High radiation exposure is a concern because of the association with cancer. The objective was to determine the probability of receiving a high radiation dose from CT (from one or more examinations within a 5-year period) and to assess the clinical context by evaluating clinical indications in the high-dose patient group.

Design: Observational cohort study. Effective radiation dose received from one or more CT examinations within a predefined 5-year calendar period was assessed for each patient.

Setting: Hospital setting.

Participants: All patients undergoing a diagnostic CT examination between July 2013 and July 2018 at the Maastricht University Medical Center.

Primary And Secondary Outcome Measures: The primary outcome was the probability of receiving a high effective dose, defined as ≥100 mSv, from one or more CT examinations within 5 years as derived from a time-to-event analysis. Secondary outcomes were the clinical indication for the initial scan of patients receiving a high effective dose.

Results: 100 672 CT examinations were performed among 49 978 patients including 482 (1%) who received a high radiation dose. The estimated probability of a high effective dose from a single examination is low (0.002% (95% CI 0.00% to 0.01%)). The 4.5-year probability of receiving a high cumulative effective dose was 1.9% (95% CI 1.6% to 2.2%) for women and 1.5% (95% CI 1.3% to 1.7%) for men. The probability was highest in age categories between 51 and 74 years. A total of 2711 (5.5%) of patients underwent more than six CT examinations, and the probability of receiving a high effective dose was 16%. Among patients who received a high effective dose, most indications (80%) were oncology related.

Conclusions: The probability of receiving a high radiation dose from CT examinations is small but not negligible. In the majority (80%) of high effective dose receiving patients, the indication for the initial CT scan was oncology related.
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http://dx.doi.org/10.1136/bmjopen-2020-041883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813417PMC
January 2021

Post-Contrast Acute Kidney Injury and Intravenous Prophylactic Hydration: An Update.

Rofo 2021 Feb 16;193(2):151-159. Epub 2020 Dec 16.

Radiology & Nuclear Medicine, Maastricht University Medical Centre+, Maastricht, Netherlands.

Background:  Despite tremendous improvement in molecular properties over the last century, intravascular injection of iodinated contrast material may still have systemic and hemodynamic consequences. Patients with pre-existing renal insufficiency may be at risk for acute kidney injury, which may be associated with an increased risk of the need for dialysis and mortality in the long term. Many questions as to the physiological pathways, optimal definition, and incidence of contrast-induced acute kidney injury remain open. These uncertainties are reflected in the changing landscape of this field in terms of nomenclature, research, and clinical practice.

Methods:  Clinical practice guidelines for the prevention of post-contrast acute kidney injury all recommend giving prophylaxis in the form of intravenous hydration to high-risk patients. Solid evidence for this strategy is lacking. This article gives an overview of the changing landscape of post-contrast acute kidney injury and prophylactic intravenous hydration, with the aim of supporting informed decision-making in clinical practice.

Results:  Recent data have caused a shift in guideline recommendations: 90 % of patients formerly considered high-risk for contrast-induced acute kidney injury no longer qualify for prophylaxis. The remaining high-risk patients, with severe chronic kidney disease, represent a vulnerable population for whom intravenous hydration may provide some benefits but also carries risk.

Conclusion:  Intravenous hydration may benefit 'new' high-risk patients. However, it also confers risk. A dual approach to screening patients will help avoid this risk in clinical practice.

Key Points:   · Intravenous hydration is the cornerstone for preventing contrast-induced acute kidney injury. · Solid evidence is lacking; recent data caused a shift in guideline recommendations. · Intravenous hydration may benefit 'new' high-risk patients with severe chronic kidney disease; however, it also confers risk. · A dual approach to screening patients will help avoid this risk in clinical practice.

Citation Format: · Nijssen E, Rennenberg R, Nelemans P et al. Post-Contrast Acute Kidney Injury and Intravenous Prophylactic Hydration: An Update. Fortschr Röntgenstr 2021; 193: 151 - 159.
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http://dx.doi.org/10.1055/a-1248-9178DOI Listing
February 2021

Steadily Increasing Inversion Time Improves Blood Suppression for Free-Breathing 3D Late Gadolinium Enhancement MRI With Optimized Dark-Blood Contrast.

Invest Radiol 2021 05;56(5):335-340

Philips Healthcare, Guildford, United Kingdom.

Materials And Methods: Fifty consecutive patients with previous cardiac arrhythmias, scheduled for high-resolution 3D LGE MRI, were prospectively enrolled between October 2017 and February 2020. Free-breathing 3D dark-blood LGE MRI with high isotropic resolution (1.6 × 1.6 × 1.6 mm) was performed using a conventional fixed TI (n = 25) or a dynamic TI (n = 25). The average increase in blood nulling TI per minute was obtained from Look-Locker scans before and after the 3D acquisition in the first fixed TI group. This average increment in TI was used as input to calculate the dynamic increment of the initial blood nulling TI value as set in the second dynamic TI group. Regions of interest were drawn in the left ventricular blood pool to assess mean signal intensity as a measure for blood pool suppression. Overall image quality, observer confidence, and scar demarcation were scored on a 3-point scale.

Results: Three-dimensional dark-blood LGE data sets were successfully acquired in 46/50 patients (92%). The calculated average TI increase of 2.3 ± 0.5 ms/min obtained in the first fixed TI group was incorporated in the second dynamic TI group and led to a significant decrease of 72% in the mean blood pool signal intensity compared with the fixed TI group (P < 0.001). Overall image quality (P = 0.02), observer confidence (P = 0.02), and scar demarcation (P = 0.01) significantly improved using a dynamic TI.

Conclusions: A steadily increasing dynamic TI improves blood pool suppression for optimized dark-blood contrast and increases observer confidence in free-breathing 3D dark-blood LGE MRI with high isotropic resolution.
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http://dx.doi.org/10.1097/RLI.0000000000000747DOI Listing
May 2021

An international multi-center investigation on the accuracy of radionuclide calibrators in nuclear medicine theragnostics.

EJNMMI Phys 2020 Nov 23;7(1):69. Epub 2020 Nov 23.

Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, P.O. Box 5800, 6202, AZ, Maastricht, The Netherlands.

Background: Personalized molecular radiotherapy based on theragnostics requires accurate quantification of the amount of radiopharmaceutical activity administered to patients both in diagnostic and therapeutic applications. This international multi-center study aims to investigate the clinical measurement accuracy of radionuclide calibrators for 7 radionuclides used in theragnostics: Tc, In, I, I, I, Lu, and Y.

Methods: In total, 32 radionuclide calibrators from 8 hospitals located in the Netherlands, Belgium, and Germany were tested. For each radionuclide, a set of four samples comprising two clinical containers (10-mL glass vial and 3-mL syringe) with two filling volumes were measured. The reference value of each sample was determined by two certified radioactivity calibration centers (SCK CEN and JRC) using two secondary standard ionization chambers. The deviation in measured activity with respect to the reference value was determined for each radionuclide and each measurement geometry. In addition, the combined systematic deviation of activity measurements in a theragnostic setting was evaluated for 5 clinically relevant theragnostic pairs: I/I, I/I, Lu/In, Y/Tc, and Y/In.

Results: For Tc, I, and Lu, a small minority of measurements were not within ± 5% range from the reference activity (percentage of measurements not within range: Tc, 6%; I, 14%; Lu, 24%) and almost none were outside ± 10% range. However, for In, I, I, and Y, more than half of all measurements were not accurate within ± 5% range (In, 51%; I, 83%; I, 63%; Y, 61%) and not all were within ± 10% margin (In, 22%; I, 35%; I, 15%; Y, 25%). A large variability in measurement accuracy was observed between radionuclide calibrator systems, type of sample container (vial vs syringe), and source-geometry calibration/correction settings used. Consequently, we observed large combined deviations (percentage deviation > ± 10%) for the investigated theragnostic pairs, in particular for Y/In, I/I, and Y/Tc.

Conclusions: Our study shows that substantial over- or underestimation of therapeutic patient doses is likely to occur in a theragnostic setting due to errors in the assessment of radioactivity with radionuclide calibrators. These findings underline the importance of thorough validation of radionuclide calibrator systems for each clinically relevant radionuclide and sample geometry.
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http://dx.doi.org/10.1186/s40658-020-00338-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683758PMC
November 2020

The prevalence of pulmonary embolism in patients with COVID-19 and respiratory decline: A three-setting comparison.

Thromb Res 2020 12 15;196:486-490. Epub 2020 Oct 15.

Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre+, Maastricht, the Netherlands; Thrombosis Expert Centre Maastricht and Department of Internal Medicine, Section Vascular Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands.

Background: The risk of pulmonary embolism (PE) in patients with Coronavirus Disease 2019 (COVID-19) is recognized. The prevalence of PE in patients with respiratory deterioration at the Emergency Department (ED), the regular ward, and the Intensive Care Unit (ICU) are not well-established.

Objectives: We aimed to investigate how often PE was present in individuals with COVID-19 and respiratory deterioration in different settings, and whether or not disease severity as measured by CT-severity score (CTSS) was related to the occurrence of PE.

Patients/methods: Between April 6th and May 3rd, we enrolled 60 consecutive adult patients with confirmed COVID-19 from the ED, regular ward and ICU who met the pre-specified criteria for respiratory deterioration.

Results: A total of 24 (24/60: 40% (95% CI: 28-54%)) patients were diagnosed with PE, of whom 6 were in the ED (6/23: 26% (95% CI: 10-46%)), 8 in the regular ward (8/24: 33% (95% CI: 16-55%)), and 10 in the ICU (10/13: 77% (95% CI: 46-95%)). CTSS (per unit) was not associated with the occurrence of PE (age and sex-adjusted OR 1.06 (95%CI 0.98-1.15)).

Conclusion: The number of PE diagnosis among patients with COVID-19 and respiratory deterioration was high; 26% in the ED, 33% in the regular ward and 77% in the ICU respectively. In our cohort CTSS was not associated with the occurrence of PE. Based on the high number of patients diagnosed with PE among those scanned we recommend a low threshold for performing computed tomography angiography in patients with COVID-19 and respiratory deterioration.
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http://dx.doi.org/10.1016/j.thromres.2020.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557291PMC
December 2020

Serial measurements in COVID-19-induced acute respiratory disease to unravel heterogeneity of the disease course: design of the Maastricht Intensive Care COVID cohort (MaastrICCht).

BMJ Open 2020 09 29;10(9):e040175. Epub 2020 Sep 29.

Department of Intensive Care, Maastricht University Medical Center+, Maastricht, The Netherlands.

Introduction: The course of the disease in SARS-CoV-2 infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort (MaastrICCht). We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with a SARS-CoV-2 infection.

Methods And Analysis: Mechanically ventilated patients admitted to the intensive care with a SARS-CoV-2 infection will be included. We will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, ECGs, echocardiography as well as other imaging modalities to assess heterogeneity of the course of a SARS-CoV-2 infection in critically ill patients. The MaastrICCht is also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national intensive care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence. The spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS-CoV-2 infection in mechanically ventilated patients. Our study design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of the MaastrICCht.

Ethics And Dissemination: Ethical approval has been obtained from the medical ethics committee (Medisch Ethische Toetsingscommissie 2020-1565/3 00 523) of the Maastricht University Medical Centre+ (Maastricht UMC+), which will be performed based on the Declaration of Helsinki. During the pandemic, the board of directors of Maastricht UMC+ adopted a policy to inform patients and ask their consent to use the collected data and to store serum samples for COVID-19 research purposes. All study documentation will be stored securely for fifteen years after recruitment of the last patient. The results will be published in peer-reviewed academic journals, with a preference for open access journals, while particularly considering deposition of the manuscripts on a preprint server early.

Trial Registration Number: The Netherlands Trial Register (NL8613).
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http://dx.doi.org/10.1136/bmjopen-2020-040175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526030PMC
September 2020

L-carnitine infusion does not alleviate lipid-induced insulin resistance and metabolic inflexibility.

PLoS One 2020 25;15(9):e0239506. Epub 2020 Sep 25.

Departments of Radiology and Nuclear Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.

Background: Low carnitine status may underlie the development of insulin resistance and metabolic inflexibility. Intravenous lipid infusion elevates plasma free fatty acid (FFA) concentration and is a model for simulating insulin resistance and metabolic inflexibility in healthy, insulin sensitive volunteers. Here, we hypothesized that co-infusion of L-carnitine may alleviate lipid-induced insulin resistance and metabolic inflexibility.

Methods: In a randomized crossover trial, eight young healthy volunteers underwent hyperinsulinemic-euglycemic clamps (40mU/m2/min) with simultaneous infusion of saline (CON), Intralipid (20%, 90mL/h) (LIPID), or Intralipid (20%, 90mL/h) combined with L-carnitine infusion (28mg/kg) (LIPID+CAR). Ten volunteers were randomized for the intervention arms (CON, LIPID and LIPID+CAR), but two dropped-out during the study. Therefore, eight volunteers participated in all three intervention arms and were included for analysis.

Results: L-carnitine infusion elevated plasma free carnitine availability and resulted in a more pronounced increase in plasma acetylcarnitine, short-, medium-, and long-chain acylcarnitines compared to lipid infusion, however no differences in skeletal muscle free carnitine or acetylcarnitine were found. Peripheral insulin sensitivity and metabolic flexibility were blunted upon lipid infusion compared to CON but L-carnitine infusion did not alleviate this.

Conclusion: Acute L-carnitine infusion could not alleviated lipid-induced insulin resistance and metabolic inflexibility and did not alter skeletal muscle carnitine availability. Possibly, lipid-induced insulin resistance may also have affected carnitine uptake and may have blunted the insulin-induced carnitine storage in muscle. Future studies are needed to investigate this.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239506PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518598PMC
November 2020

Tailoring Contrast Media Protocols to Varying Tube Voltages in Vascular and Parenchymal CT Imaging: The 10-to-10 Rule.

Invest Radiol 2020 10;55(10):673-676

The latest technical developments in CT have created the possibility for individualized scan protocols at variable kV settings. Lowering tube voltages closer to the K-edge of iodine increases attenuation. However, the latter is also influenced by patient characteristics such as total body weight. To maintain a robust contrast enhancement throughout the patient population in both vascular and parenchymal CT scans, one must adapt the contrast media administration protocols to both the selected kV setting and patient body habitus. This article proposes a simple rule of thumb for how to adapt the contrast media protocol to any kV setting: the 10-to-10 rule.
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http://dx.doi.org/10.1097/RLI.0000000000000682DOI Listing
October 2020

A Solution for Homogeneous Liver Enhancement in Computed Tomography: Results From the COMpLEx Trial.

Invest Radiol 2020 10;55(10):666-672

Department of Internal Medicine, Division of Medical Oncology, GROW-School for Oncology and Developmental Biology, Maastricht UMC+, Maastricht, the Netherlands.

Objectives: The aim of the study was to reach homogeneous enhancement of the liver, irrespective of total body weight (TBW) or tube voltage. An easy-to-use rule of thumb, the 10-to-10 rule, which pairs a 10 kV reduction in tube voltage with a 10% decrease in contrast media (CM) dose, was evaluated.

Materials And Methods: A total of 256 patients scheduled for an abdominal CT in portal venous phase were randomly allocated to 1 of 4 groups. In group 1 (n = 64), a tube voltage of 120 kV and a TBW-adapted CM injection protocol was used: 0.521 g I/kg. In group 2 (n = 63), tube voltage was 90 kV and the TBW-adapted CM dosing factor remained 0.521 g I/kg. In group 3 (n = 63), tube voltage was reduced by 20 kV and CM dosing factor by 20% compared with group 1, in line with the 10-to-10 rule (100 kV; 0.417 g I/kg). In group 4 (n = 66), tube voltage was decreased by 30 kV paired with a 30% decrease in CM dosing factor compared with group 1, in line with the 10-to-10 rule (90 kV; 0.365 g I/kg). Objective image quality was evaluated by measuring attenuation in Hounsfield units (HU), signal-to-noise ratio, and contrast-to-noise ratio in the liver. Overall subjective image quality was assessed by 2 experienced readers by using a 5-point Likert scale. Two-sided P values below 0.05 were considered significant.

Results: Mean attenuation values in groups 1, 3, and 4 were comparable (118.2 ± 10.0, 117.6 ± 13.9, 117.3 ± 21.6 HU, respectively), whereas attenuation in group 2 (141.0 ± 18.2 HU) was significantly higher than all other groups (P < 0.01). No significant difference in attenuation was found between weight categories 80 kg or less and greater than 80 kg within the 4 groups (P ≥ 0.371). No significant differences in subjective image quality were found (P = 0.180).

Conclusions: The proposed 10-to-10 rule is an easily reproducible method resulting in similar enhancement in portal venous CT of the liver throughout the patient population, irrespective of TBW or tube voltage.
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http://dx.doi.org/10.1097/RLI.0000000000000693DOI Listing
October 2020

Pericardial fat and its influence on cardiac diastolic function.

Cardiovasc Diabetol 2020 08 17;19(1):129. Epub 2020 Aug 17.

NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands.

Background: Pericardial fat (PF) has been suggested to directly act on cardiomyocytes, leading to diastolic dysfunction. The aim of this study was to investigate whether a higher PF volume is associated with a lower diastolic function in healthy subjects.

Methods: 254 adults (40-70 years, BMI 18-35 kg/m, normal left ventricular ejection fraction), with (a)typical chest pain (otherwise healthy) from the cardiology outpatient clinic were retrospectively included in this study. All patients underwent a coronary computed tomographic angiography for the measurement of pericardial fat volume, as well as a transthoracic echocardiography for the assessment of diastolic function parameters. To assess the independent association of PF and diastolic function parameters, multivariable linear regression analysis was performed. To maximize differences in PF volume, the group was divided in low (lowest quartile of both sexes) and high (highest quartile of both sexes) PF volume. Multivariable binary logistic analysis was used to study the associations within the groups between PF and diastolic function, adjusted for age, BMI, and sex.

Results: Significant associations for all four diastolic parameters with the PF volume were found after adjusting for BMI, age, and sex. In addition, subjects with high pericardial fat had a reduced left atrial volume index (p = 0.02), lower E/e (p < 0.01) and E/A (p = 0.01), reduced e' lateral (p < 0.01), reduced e' septal p = 0.03), compared to subjects with low pericardial fat.

Conclusion: These findings confirm that pericardial fat volume, even in healthy subjects with normal cardiac function, is associated with diastolic function. Our results suggest that the mechanical effects of PF may limit the distensibility of the heart and thereby directly contribute to diastolic dysfunction. Trial registration NCT01671930.
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http://dx.doi.org/10.1186/s12933-020-01097-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430122PMC
August 2020

Biomarkers Associated With Aortic Valve Calcification: Should We Focus on Sex Specific Processes?

Front Cell Dev Biol 2020 10;8:604. Epub 2020 Jul 10.

Department of Biochemistry and CARIM, Maastricht University, School for Cardiovascular Diseases, Maastricht, Netherlands.

Objective: Circulating biomarkers are useful in detection and monitoring of cardiovascular diseases. However, their role in aortic valve disease is unclear. Mechanisms are rapidly elucidated and sex differences are suggested to be involved. Therefore, we sought to identify biomarkers involved in aortic valve calcification (AVC) stratified by sex.

Methods: Blood samples of 34 patients with AVC (without further overt cardiovascular disease, including absence of hemodynamic consequences of valvular calcification) were compared with 136 patients without AVC. AVC was determined using computed tomography calcium scoring. Circulating biomarkers were quantified using a novel antibody-based method (Olink Proseek Multiplex Cardiovascular Panel I) and 92 biomarkers were compared between patients with and without AVC.

Results: In the overall population, Interleukin-1 Receptor Antagonist and pappalysin-1 were associated with increased and decreased odds of having AVC. These differences were driven by the male population [IL1RA: OR 2.79 (1.16-6.70), = 0.022; PAPPA: OR 0.30 (0.11-0.84), = 0.021]. Furthermore, TNF-related activation-induced cytokine (TRANCE) and fibroblast growth factor-23 were associated decreased odds of having AVC, and monocyte chemotactic protein-1 was associated with increased odds of having AVC [TRANCE: OR 0.32 (0.12-0.80), = 0.015; FGF23: OR 0.41 (0.170-0.991), = 0.048; MCP1: OR 2.64 (1.02-6.81), = 0.045]. In contrast, galanin peptides and ST2 were associated with increased odds of having AVC in females [GAL: OR 12.38 (1.31-116.7), = 0.028; ST2: OR13.64 (1.21-153.33), = 0.034].

Conclusion: In this exploratory study, we identified biomarkers involved in inflammation, fibrosis and calcification which may be associated with having AVC. Biomarkers involved in fibrosis may show higher expression in females, whilst biomarkers involved in inflammation and calcification could associate with AVC in males.
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http://dx.doi.org/10.3389/fcell.2020.00604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366171PMC
July 2020

Hounsfield's Legacy.

Invest Radiol 2020 09;55(9):556-558

Department of Radiology, Nuclear Medicine, and Anatomy, Radboud University Medical Center, Nijmegen, the Netherlands.

Computed tomography (CT) has evolved over decades, offering superb morphologic imaging with isotropic resolution at rapid acquisition times. The latest developments in hardware, such as photon-counting and ultrahigh-resolution detectors, together with breakthroughs in software technology have further improved spatial and temporal resolution while steadily reducing radiation exposure. These achievements enable CT for functional imaging and make high-quality imaging more accessible through workflow automation. Radiomics, integrated diagnostics, and data science will further push CT applications beyond their current limits.
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http://dx.doi.org/10.1097/RLI.0000000000000680DOI Listing
September 2020

CT in relation to RT-PCR in diagnosing COVID-19 in The Netherlands: A prospective study.

PLoS One 2020 9;15(7):e0235844. Epub 2020 Jul 9.

Department of Internal Medicine, Division of General Internal Medicine, Section Acute Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.

Introduction: Early differentiation between emergency department (ED) patients with and without corona virus disease (COVID-19) is very important. Chest CT scan may be helpful in early diagnosing of COVID-19. We investigated the diagnostic accuracy of CT using RT-PCR for SARS-CoV-2 as reference standard and investigated reasons for discordant results between the two tests.

Methods: In this prospective single centre study in the Netherlands, all adult symptomatic ED patients had both a CT scan and a RT-PCR upon arrival at the ED. CT results were compared with PCR test(s). Diagnostic accuracy was calculated. Discordant results were investigated using discharge diagnoses.

Results: Between March 13th and March 24th 2020, 193 symptomatic ED patients were included. In total, 43.0% of patients had a positive PCR and 56.5% a positive CT, resulting in a sensitivity of 89.2%, specificity 68.2%, likelihood ratio (LR)+ 2.81 and LR- 0.16. Sensitivity was higher in patients with high risk pneumonia (CURB-65 score ≥3; n = 17, 100%) and with sepsis (SOFA score ≥2; n = 137, 95.5%). Of the 35 patients (31.8%) with a suspicious CT and a negative RT-PCR, 9 had another respiratory viral pathogen, and in 7 patients, COVID-19 was considered likely. One of nine patients with a non-suspicious CT and a positive PCR had developed symptoms within 48 hours before scanning.

Discussion: The accuracy of chest CT in symptomatic ED patients is high, but used as a single diagnostic test, CT can not safely diagnose or exclude COVID-19. However, CT can be used as a quick tool to categorize patients into "probably positive" and "probably negative" cohorts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235844PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347219PMC
July 2020

Application of a BIlinear Rotation Decoupling (BIRD) filter in combination with J-difference editing for indirect C measurements in the human liver.

Magn Reson Med 2020 12 3;84(6):2911-2917. Epub 2020 Jul 3.

Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.

Purpose: Recently, we introduced a quantum coherence based method (ge-HSQC) for indirect C-MRS in the liver to track C-labeled lipids into the hepatic lipid pool in vivo. This approach is more robust in case of respiratory motion, however, inherently leads to a signal loss of 50% when compared with a conventional J-difference editing technique (JDE). Here, we intend to improve the robustness of a regular JDE (STEAM-ACED) with the use of a BIlinear Rotation Decoupling (BIRD) filter to achieve 100% higher signal gain when compared with ge-HSQC.

Methods: To determine the efficiency of the BIRD filter H-[ C] lipid spectra were acquired on 3T from a peanut oil phantom, with three different MR sequences: ge-HSQC, STEAM-ACED, and the BIRD filter together with STEAM-ACED (BIRD-STEAM-ACED). Finally, our proposed method is tested in vivo in five healthy volunteers with varying liver fat content. In these subjects we quantified the H-[ C]-signal from the hepatic lipid pool and determined C enrichment, which is expected to be 1.1% according to the natural abundance of C.

Results: The application of the proposed BIRD filter reduces the subtraction artifact of H-[ C] lipid signal efficiently in JDE experiments, which leads to a signal gain of 100% of H-[ C]-lipid signals when compared with the ge-HSQC. Phase distortions in vivo were minimal with the use of BIRD compared with STEAM-ACED, which enabled us to robustly quantify the C-enrichment in all five subjects.

Conclusion: The BIRD-STEAM-ACED sequence is an efficient and promising tool for C-tracking experiments in the human liver in vivo.
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http://dx.doi.org/10.1002/mrm.28394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540382PMC
December 2020

Retrospectively ECG-gated helical vs. non-ECG-synchronized high-pitch CTA of the aortic root for TAVI planning.

PLoS One 2020 12;15(5):e0232673. Epub 2020 May 12.

Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.

Background: Multidetector computed tomography (MDCT) plays a key role in patient assessment prior to transcatheter aortic valve implantation (TAVI). However, to date no consensus has been established on what is the optimal pre-procedural imaging protocol. Variability in pre-TAVI acquisition protocols may lead to discrepancies in aortic annulus measurements and may potentially influence prosthesis size selection.

Purpose: The current study evaluates the magnitude of differences in aortic annulus measurements using max-systolic, end-diastolic, and non-ECG-synchronized imaging, as well as the impact of method on prosthesis size selection.

Material And Methods: Fifty consecutive TAVI-candidates, who underwent retrospectively-ECG-gated CT angiography (CTA) of the aortic root, directly followed by non-ECG-synchronized high-pitch CT of the entire aorta, were retrospectively included. Aortic root dimensions were assessed at each 10% increment of the R-R interval (0-100%) and on the non-ECG-synchronized scan. Dimensional changes within the cardiac cycle were evaluated using a 1-way repeated ANOVA. Agreement in measurements between max-systole, end-diastole and non-ECG-synchronized scans was assessed with Bland-Altman analysis.

Results: Maximal dimensions of the aortic root structures and minimum annulus-coronary ostia distances were measured during systole. Max-systolic measurements were significantly and substantially larger than end-diastolic (p<0.001) and non-ECG-synchronized measurements (p<0.001). Due to these discrepancies, the three methods resulted in the same prosthesis size selection in only 48-62% of patients.

Conclusions: The systematic differences between max-systolic, end-diastolic and non-ECG-synchronized measurements for relevant aortic annular dimensions are both statistically significant and clinically relevant. Imaging strategy impacts prosthesis size selection in nearly half the TAVI-candidates. End-diastolic and non-ECG-synchronized imaging does not provide optimal information for prosthesis size selection. Systolic image acquisition is necessary for assessment of maximal annular dimensions and minimum annulus-coronary ostia distances.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232673PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217477PMC
August 2020

Evaluating the diagnostic accuracy of maximal aortic diameter, length and volume for prediction of aortic dissection.

Heart 2020 06 8;106(12):892-897. Epub 2020 Mar 8.

Department of Cardiothoracic Surgery, Maastricht University Medical Center, Maastricht, Limburg, The Netherlands.

Objective: Management of thoracic aortic aneurysms (TAAs) comprises regular diameter follow-up until the indication criterion for prophylactic surgery is reached. However, this approach is unable to predict the majority of acute type A aortic dissections (ATAADs). The current study aims to evaluate the diagnostic accuracy of ascending aortic diameter, length and volume for occurrence of ATAAD.

Methods: This two-centre observational cohort study retrospectively screened 477 consecutive patients who presented with ATAAD between 2009 and 2018. Of those, 25 (5.2%) underwent CT angiography (CTA) within 2 years before dissection onset. Aortic diameter, length and volume of these patients ('pre-ATAAD') were compared with those of TAA controls (n=75). Receiver operating curve analysis was performed to evaluate the predictive accuracy of the three different measurements.

Results: 96% of patients with pre-ATAAD did not meet the surgical diameter threshold of 55 mm before dissection onset. Maximal aortic diameters (45 (40-49) mm vs 46 (44-49) mm, p=0.075) and volume (126 (95-157) cm vs 124 (102-136) cm, p=0.909) were comparable between patients with pre-ATAAD and TAA controls. Conversely, ascending aortic length (84±9 mm vs 90±16 mm, p=0.031) was significantly larger in patients with pre-ATAAD. All three parameters had an area under the curve of >0.800. At the 55 mm cut-off point, the maximal diameter yielded a positive predictive value (PPV) of 20%. While maintaining same specificity levels, measurements of aortic volume and length showed superior diagnostic accuracy (PPV 55% and 70%, respectively).

Conclusion: Measurements of aortic volume and length have superior diagnostic accuracy compared with the maximal diameter and could improve the timely identification of patients at risk for ATAAD.
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http://dx.doi.org/10.1136/heartjnl-2019-316251DOI Listing
June 2020

Gonad shielding in pelvic radiography: modern optimised X-ray systems might allow its discontinuation.

Insights Imaging 2020 Feb 7;11(1):15. Epub 2020 Feb 7.

Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, P. Debijelaan 25, 6229 HX, Maastricht, The Netherlands.

Objective: As gonad shielding is currently under debate, this study evaluates the practice, from its introduction in about 1905 until today.

Methods: The literature was searched for developments in shielding and insights into the effects of ionising radiation on gonads. Based on own pre-1927 dose reconstructions, reported doses after 1927, a 2015-report from the European Union and recent own measurements, the effects of technological evolution and optimisation on radiation dose and hereditary risk were assessed.

Results: In the 1900s, gonad shielding was first applied to prevent male sterility, but was discontinued when instrumental developments led to reduced radiation doses. In the 1950s, concerns about hereditary risks intensified and gonad shielding was recommended again, becoming routine worldwide. Imaging-chain improvements over time were considerable: in 2018, the absorbed dose was 0.5% of its 1905 value for the testes and 2% for the ovaries, our optimised effective dose a factor five lower than the value corresponding to the current EU diagnostic reference level, and the reduction in detriment-adjusted risk by shielding less than 1 × 10 for women and 5 × 10 for men.

Conclusions: Assessment of pelvic doses revealed a large reduction in radiation risks facilitated by technological developments. Optimisation likewise contributed, but unfortunately, its potential was never adequately exploited. Today, using a modern and optimised X-ray system, gonad shielding can be safely discontinued for women. For men, there might be a marginal benefit, but potential negative side-effects may well dominate. Discontinuation of gonad shielding seems therefore justifiable.
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http://dx.doi.org/10.1186/s13244-019-0828-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005227PMC
February 2020

Nitroglycerin as a radiosensitizer in non-small cell lung cancer: Results of a prospective imaging-based phase II trial.

Clin Transl Radiat Oncol 2020 Mar 13;21:49-55. Epub 2019 Dec 13.

The D-Lab & The M-Lab, Department of Precision Medicine, GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.

Background: Nitroglycerin is proposed as an agent to reduce tumour hypoxia by improving tumour perfusion. We investigated the potential of nitroglycerin as a radio-sensitizer in non-small cell lung cancer (NSCLC) and the potential of functional imaging for patient selection.

Material And Methods: Trial NCT01210378 is a single arm phase II trial, designed to detect 15% improvement in 2-year overall survival (primary endpoint) in stage IB-IV NSCLC patients treated with radical (chemo-) radiotherapy and a Transiderm-Nitro 5 patch during radiotherapy. Patients underwent dynamic contrast-enhanced CTs (DCE-CT) and HX4 (hypoxia) PET/CTs before and after nitroglycerin. Secondary endpoints were progression-free survival, toxicity and the prognostic value of tumour perfusion/hypoxia at baseline and after nitroglycerin.

Results: The trial stopped after a futility analysis after 42 patients. At median follow-up of 41 months, two-year and median OS were 58% (95% CI: 44-78%) and 38 months (95% CI: 22-54 months), respectively. Nitroglycerin could not reduce tumour hypoxia. DCE-CT parameters did not correlate with OS, whereas hypoxic tumours had a worse OS (p = 0.029). Changes in high-uptake fraction of HX4 and tumour blood flow were negatively correlated (r = -0.650, p = 0.022). The heterogeneity in treatment modalities and patient characteristics combined with a small sample size made further subgroup analysis of survival results impossible. Toxicity related to nitroglyerin was limited to headache (17%) and hypotension (2.4%).

Conclusion: Nitroglycerin did not improve OS of NSCLC patients treated with (chemo-)radiotherapy. A general ability of nitroglycerin to reduce hypoxia was not shown.
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http://dx.doi.org/10.1016/j.ctro.2019.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993056PMC
March 2020
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