[Confusion and abdominal pain after COVID-19 vaccination]. / Verwardheid en buikpijn na covid-19-vaccinatie.

BACKGROUND: Vaccine-induced immune thrombotic trombocytopenia (VITT) is a rare phenomenon, that may present with diffuse and atypical symptoms. CASE DESCRIPTION: We present a case of 63 years old female patient with abdominal pain, confusion and tromboctytopenia. CT scan shows sinustrombosis and trombosis of the vena renalis. The diagnosis VITT was confirmed by a positive HIT test. After initiating treatment with immunoglobulines and a non-heparinoid anticoagulans, symptoms improved and platelet count increased. CONCLUSION: This case illustrates that awareness in case of atypical symptoms and a history of vaccination is important to recognize this phenomenon.

Online adaptive MR-guided radiotherapy for rectal cancer; feasibility of the workflow on a 1.5T MR-linac: clinical implementation and initial experience.

BACKGROUND AND PURPOSE: Daily online adaptation of the clinical target volume (CTV) using MR-guided radiotherapy enables margin reduction of the planning target volume (PTV). This study describes the implementation and initial experience of MR-guided radiotherapy on the 1.5T MR-linac and evaluates treatment time, patient compliance, and target coverage, including an initial assessment of margin reduction. MATERIALS AND METHODS: Patients were treated on a 1.5T MR-linac (7MV, FFF). At each fraction a 3D T2 weighted (T2w) MR-sequence was acquired on which the CTV was adapted after a deformable registration of the contours from the pre-planning CT scan. Based on the new contours a full online replanning was done after which a new 3D T2w MR-sequence was acquired for position verification. A 5 field Intensity Modulated Radiotherapy (IMRT) plan was delivered. RESULTS: Forty-three patients with rectal cancer were treated with 25 Gy in 5 fractions of which 18 with reduced margins. In total, 204 of 215 fractions were delivered on the MR-linac all of which obtained a clinically acceptable treatment plan. Median in-room time per fraction was 48 min (interquartile range 8). No fractions were canceled or interrupted because of patient intolerance. CTV coverage after margin reduction was good on all post-treatment scans but one due to passing gas. CONCLUSION: MR-guided radiotherapy using daily full online recontouring and replanning on a 1.5T MR-linac for rectal cancer is feasible and currently takes about 48 min per fraction.

Technical feasibility of magnetic resonance fingerprinting on a 1.5T MRI-linac.

Hybrid MRI-linac (MRL) systems enable daily multiparametric quantitative MRI to assess tumor response to radiotherapy. Magnetic resonance fingerprinting (MRF) may provide time efficient means of rapid multiparametric quantitative MRI. The accuracy of MRF, however, relies on adequate control over system imperfections, such as eddy currents and [Formula: see text], which are different and not as well established on MRL systems compared to diagnostic systems. In this study we investigate the technical feasibility of gradient spoiled 2D MRF on a 1.5T MRL. We show with phantom experiments that the MRL generates reliable MRF signals that are temporally stable during the day and have good agreement with spin-echo reference measurements. Subsequent in-vivo MRF scans in healthy volunteers and a patient with a colorectal liver metastasis showed good image quality, where the quantitative values of selected organs corresponded with the values reported in literature. Therefore we conclude that gradient spoiled 2D MRF is feasible on a 1.5T MRL with similar performance as on a diagnostic system. The precision and accuracy of the parametric maps are sufficient for further investigation of the clinical utility of MRF for online quantitatively MRI-guided radiotherapy.

The Absorb bioresorbable vascular scaffold in real-world practice: long-term follow-up of the AMC Single Centre Real World PCI Registry.

BACKGROUND: Bioresorbable scaffolds have been introduced to overcome the shortcomings of drug-eluting stents. Higher rates of device thrombosis, however, have been reported up to 3 years after implantation of the Absorb bioresorbable vascular scaffold (BVS). In the current article, we therefore report long-term clinical outcomes of the AMC Absorb Registry. METHODS AND RESULTS: In the AMC Absorb Registry, all patients who underwent a percutaneous coronary intervention with Absorb BVS implantation between 30 August 2012 and 5 August 2013 at the Amsterdam University Medical Centre-Academic Medical Centre were included. The composite endpoint of this analysis was target-vessel failure (TVF). The median follow-up of the study cohort of the AMC Absorb Registry was 1534 days. At the time of the cross-sectional data sweep the clinical status at 4 years was known in 124 of 135 patients (91.9%). At long-term follow-up, the composite endpoint of TVF had occurred in 27 patients. The 4­year Kaplan-Meier estimate of TVF was 19.8%. At 4 years cardiac death had occurred in 4 patients (3.2%) and target-vessel myocardial infarction in 9 (6.9%) patients. Definite scaffold thrombosis occurred in 5 (3.8%) patients. We found 1 case of very late scaffold thrombosis that occurred at 911 days after device implantation in a patient who was not on dual anti-platelet therapy. CONCLUSION: In a patient population reflecting routine clinical practice, we found that cases of TVF continued to accrue beyond 2 years after Absorb BVS implantation.

The noise navigator: a surrogate for respiratory-correlated 4D-MRI for motion characterization in radiotherapy.

Respiratory-correlated 4D-MRI can characterize respiratory-induced motion of tumors and organs-at-risk for radiotherapy treatment planning and is a necessity for image guidance of moving tumors treated on an MRI-linac. Essential for 4D-MRI generation is a robust respiratory surrogate signal. We investigated the feasibility of the noise navigator as respiratory surrogate signal for 4D-MRI generation. The noise navigator is based on the respiratory-induced modulation of the thermal noise variance measured by the receive coils during MR acquisition and thus is inherently present and synchronized with MRI data acquisition. Additionally, the noise navigator can be combined with any rectilinear readout strategy (e.g. radial and cartesian) and is independent of MR image contrast and imaging orientation. For radiotherapy applications, the noise navigator provides a robust respiratory signal for patients scanned with an elevated coil setup. This is particularly attractive for widely used cartesian sequences where currently a non-interfering self-navigation means is lacking for MRI-based simulation and MRI-guided radiotherapy. The feasibility of 4D-MRI generation with the noise navigator as respiratory surrogate signal was demonstrated for both cartesian and radial readout strategies in radiotherapy setup on four healthy volunteers and two radiotherapy patients on a dedicated 1.5 T MRI scanner and two radiotherapy patients on a 1.5 T MRI-linac system. Moreover, the respiratory-correlated 4D-MR images showed liver motion comparable to a reference 2D cine MRI series for the volunteers. For 2D cartesian cine MRI acquisitions, both the noise navigator and respiratory bellows were benchmarked against an image navigator. Respiratory phase detection based on the noise navigator agreed 1.4 times better with the image navigator than the respiratory bellows did. For a 3D Stack-of-Stars acquisitions, the noise navigator was compared to radial self-navigation and a 1.7 times higher respiratory phase detection agreement was observed than for the respiratory bellows compared to radial self-navigation.

Assessment of 3D motion modeling performance for dose accumulation mapping on the MR-linac by simultaneous multislice MRI.

Hybrid MR-linac systems enable intrafraction motion monitoring during radiation therapy. Since time-resolved 3D MRI is still challenging, various motion models have been developed that rely on time-resolved 2D imaging. Continuous validation of these models is important for accurate dose accumulation mapping. In this study we used 2D simultaneous multislice (SMS) imaging to improve the PCA-based motion modeling method developed previously (Stemkens et al 2016 Phys. Med. Biol. 61 5335-55). From the additional simultaneously acquired slices, several independent motion models could be generated, which allowed for an assessment of the sensitivity of the motion model to the location of the time-resolved 2D slices. Additionally, the best model could be chosen at every time-point, increasing the method's robustness. Imaging experiments were performed in six healthy volunteers using three simultaneous slices, which generated three independent models per volunteer. For each model the motion traces of the liver tip and both kidneys were estimated. We found that the location of the 2D slices influenced the model's error in five volunteers significantly with a p -value <0.05, and that selecting the best model at every time-point can improve the method. This allows for more accurate and robust motion characterization in MR-guided radiotherapy.

Nuts and bolts of 4D-MRI for radiotherapy.

Magnetic resonance imaging (MRI) is increasingly being used in the radiotherapy workflow because of its superior soft tissue contrast and high flexibility in contrast. In addition to anatomical and functional imaging, MRI can also be used to characterize the physiologically induced motion of both the tumor and organs-at-risk. Respiratory-correlated 4D-MRI has gained large interest as an alternative to 4D-CT for the characterization of respiratory motion throughout the thorax and abdomen. These 4D-MRI data sets consist of three spatial dimensions and the respiratory phase or amplitude over the fourth dimension (opposed to time-resolved 4D-MRI that represents time in the fourth dimension). Over the last 15 years numerous methods have been presented in literature. This review article provides a comprehensive overview of the various 4D-MRI techniques, and describes the differences in MRI data acquisition and 4D data set generation from a methodological point of view. The current status and future perspective of these techniques are highlighted, and the requirements for safe introduction into the clinic (e.g. method validation) are discussed.

Emerging role of MRI in radiation therapy.

Advances in multimodality imaging, providing accurate information of the irradiated target volume and the adjacent critical structures or organs at risk (OAR), has made significant improvements in delivery of the external beam radiation dose. Radiation therapy conventionally has used computed tomography (CT) imaging for treatment planning and dose delivery. However, magnetic resonance imaging (MRI) provides unique advantages: added contrast information that can improve segmentation of the areas of interest, motion information that can help to better target and deliver radiation therapy, and posttreatment outcome analysis to better understand the biologic effect of radiation. To take advantage of these and other potential advantages of MRI in radiation therapy, radiologists and MRI physicists will need to understand the current radiation therapy workflow and speak the same language as our radiation therapy colleagues. This review article highlights the emerging role of MRI in radiation dose planning and delivery, but more so for MR-only treatment planning and delivery. Some of the areas of interest and challenges in implementing MRI in radiation therapy workflow are also briefly discussed. Level of Evidence: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;48:1468-1478.

Characterization of imaging latency for real-time MRI-guided radiotherapy.

Hybrid MR-linac systems can use fast dynamic MR sequences for tumor tracking and adapt the radiation treatment in real-time. For this the imaging latency must be as short as possible. This work describes how different acquisition parameters influence this latency. First, the latency was measured for Cartesian readouts with phase encode orderings linear, reverse-linear, and high-low. Second, the latency was measured for radial readouts with linear and golden angle profile orderings. To reduce the latency, a spatio-temporal (k-t) filter that suppresses the k-space center of earlier acquired spokes was implemented for the golden angle sequence. For Cartesian readouts a high-low ordering achieved a three times lower latency compared to a linear ordering with our sampling parameters. For radial readouts the filter was able to reduce the acquisition latency from half the acquisition time to a quarter of the acquisition time. The filter did not compromise the signal-to-noise ratio and the artifact power.

Respiratory motion model based on the noise covariance matrix of a receive array.

PURPOSE: Tracking of the internal anatomy by means of a motion model that uses the MR-derived motion fields and noise covariance matrix (NCM) dynamic as a surrogate signal. METHODS: A 2D respiratory motion model was developed based on the MR-derived motion fields and the NCM of a receive array used in MRI. Temporal dynamics of the NCM were used as a motion surrogate for a linear correspondence motion model. The model performance was tested on five healthy volunteers with a liver as the target. The motion fields were calculated from the cineMR frames with an optical flow registration tool. RESULTS: The model estimated the liver motion with an average residual error of 2.3 mm (13% of the motion amplitude). The model formation takes 3 min and the model latency was 0.5 s in the current implementation. The limiting factor for the latency is the current update time of the NCM (0.48 s), which in principle can be reduced to 0.004 s with an alternative way to determine the NCM. CONCLUSIONS: The 2D respiratory motion of the liver can be effectively estimated with the linear motion model that uses the temporal behavior of the NCM as motion surrogate. Magn Reson Med 79:1730-1735, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

First patients treated with a 1.5 T MRI-Linac: clinical proof of concept of a high-precision, high-field MRI guided radiotherapy treatment.

The integration of 1.5 T MRI functionality with a radiotherapy linear accelerator (linac) has been pursued since 1999 by the UMC Utrecht in close collaboration with Elekta and Philips. The idea behind this integrated device is to offer unrivalled, online and real-time, soft-tissue visualization of the tumour and the surroundings for more precise radiation delivery. The proof of concept of this device was given in 2009 by demonstrating simultaneous irradiation and MR imaging on phantoms, since then the device has been further developed and commercialized by Elekta. The aim of this work is to demonstrate the clinical feasibility of online, high-precision, high-field MRI guidance of radiotherapy using the first clinical prototype MRI-Linac. Four patients with lumbar spine bone metastases were treated with a 3 or 5 beam step-and-shoot IMRT plan. The IMRT plan was created while the patient was on the treatment table and based on the online 1.5 T MR images; pre-treatment CT was deformably registered to the online MRI to obtain Hounsfield values. Bone metastases were chosen as the first site as these tumors can be clearly visualized on MRI and the surrounding spine bone can be detected on the integrated portal imager. This way the portal images served as an independent verification of the MRI based guidance to quantify the geometric precision of radiation delivery. Dosimetric accuracy was assessed post-treatment from phantom measurements with an ionization chamber and film. Absolute doses were found to be highly accurate, with deviations ranging from 0.0% to 1.7% in the isocenter. The geometrical, MRI based targeting as confirmed using portal images was better than 0.5 mm, ranging from 0.2 mm to 0.4 mm. In conclusion, high precision, high-field, 1.5 T MRI guided radiotherapy is clinically feasible.

Mid-term and long-term safety and efficacy of bioresorbable vascular scaffolds versus metallic everolimus-eluting stents in coronary artery disease: A weighted meta-analysis of seven randomised controlled trials including 5577 patients.

AIMS: Mid- and long-term safety and efficacy of the Absorb bioresorbable vascular scaffold (BVS) have been studied in randomised trials; however, most were not individually powered for clinical endpoints. We performed a weighted meta-analysis comparing mid- and long-term outcomes in patients treated with the BVS compared with the Xience metallic stent. METHODS AND RESULTS: Randomised trials comparing the BVS and Xience were identified by searching MEDLINE, EMBASE and conference abstracts. Seven trials were included (BVS n = 3258, Xience n = 2319) with follow-up between 1-3 years. The primary outcome of target lesion failure occurred more frequently in BVS compared with Xience [OR 1.34; 95% CI 1.11-1.62, p = 0.003]. Overall definite or probable device thrombosis occurred more frequently with the BVS [OR 2.86; 95% CI 1.88-4.36, p < 0.001] and this extended beyond 1 year of follow-up [OR 4.13; 95% CI 1.99-8.57, p < 0.001]. Clinically indicated or ischaemia driven target lesion revascularisation [OR 1.43; 95% CI 1.11-1.83, p = 0.005] and myocardial infarction (all MI) [OR 1.64; 95% CI 1.20-2.23, p = 0.002] were more frequently seen in the BVS compared with Xience. Rates of target vessel failure [OR 1.15; 95% CI 0.91-1.46, p = 0.25] and cardiac death [OR 0.91; 95% CI 0.57-1.46, p = 0.71] were not significantly different between BVS and Xience. CONCLUSION: This meta-analysis shows a higher rate of target lesion failure and an almost threefold higher rate of device thrombosis in BVS compared with Xience, which extends beyond the first year. Device thrombosis did not lead to an overall increased (cardiac) mortality.

Clinical characteristics of patients with suspected cardiac chest pain and angiographically normal coronary arteries in a secondary care hospital.

BACKGROUND: An important number of patients with suspected cardiac chest pain have non-obstructive coronary artery disease. Our purpose was to describe the clinical characteristics of patients with normal or near-normal coronary arteries in routine cardiological practice in a secondary care hospital. METHODS: In 2013, consecutive patients referred for invasive coronary angiography with suspected cardiac chest pain were analysed at a single-centre (Westfriesgasthuis, Hoorn, the Netherlands). Coronary arteries were defined as normal or near-normal if they showed no stenosis or only slight wall irregularities on visual assessment. Patients with a final non-cardiac diagnosis for the chest pain were excluded. RESULTS: A total of 558 patients were included. Of these, 151 (27%) showed normal or near-normal coronary arteries on visual assessment. This group of patients were significantly more often female (p < 0.001), younger (p < 0.001) and non-diabetic (p = 0.002). Forty percent of hospitalised patients who had normal or near-normal coronary arteries at coronary angiography showed an elevated troponin. CONCLUSION: In routine cardiological practice, around 1 out of 4 patients with suspected cardiac chest pain undergoing invasive angiography had normal or near-normal coronary arteries. We suggest that premenopausal women with suspected cardiac chest pain could be considered for non-invasive coronary imaging as a first step in clinical practice.

4D MR imaging using robust internal respiratory signal.

The purpose of this study is to investigate the feasibility of using internal respiratory (IR) surrogates to sort four-dimensional (4D) magnetic resonance (MR) images. The 4D MR images were constructed by acquiring fast 2D cine MR images sequentially, with each slice scanned for more than one breathing cycle. The 4D volume was then sorted retrospectively using the IR signal. In this study, we propose to use multiple low-frequency components in the Fourier space as well as the anterior body boundary as potential IR surrogates. From these potential IR surrogates, we used a clustering algorithm to identify those that best represented the respiratory pattern to derive the IR signal. A study with healthy volunteers was performed to assess the feasibility of the proposed IR signal. We compared this proposed IR signal with the respiratory signal obtained using respiratory bellows. Overall, 99% of the IR signals matched the bellows signals. The average difference between the end inspiration times in the IR signal and bellows signal was 0.18 s in this cohort of matching signals. For the acquired images corresponding to the other 1% of non-matching signal pairs, the respiratory motion shown in the images was coherent with the respiratory phases determined by the IR signal, but not the bellows signal. This suggested that the IR signal determined by the proposed method could potentially correct the faulty bellows signal. The sorted 4D images showed minimal mismatched artefacts and potential clinical applicability. The proposed IR signal therefore provides a feasible alternative to effectively sort MR images in 4D.

Gelation upon long storage of milk drinks with carrageenan.

The carrageenan-induced stabilization and gelation of ultra-high-temperature-treated milk was studied during long storage. Severe heating (causing increased protein denaturation), lowering of the pH, or the use of kappa-carrageenan (instead of iota-carrageenan) led to excessive gelation. It is suggested that the balance between carrageenan-carrageenan interactions and carrageenan-protein interactions determines the gel strength. If the interactions between carrageenan and proteins are decreased, more carrageenan is available for carrageenan-carrageenan interactions, leading to a stronger gel. This is the case if kappa-carrageenan is used instead of iota-carrageenan because the former forms weaker interactions with proteins than the latter. Also, heating and pH influence the attachment of whey proteins to the casein micelle surface, hindering the attachment of carrageenan to the casein proteins. Upon storage, gel strength increased. Particle size and rheology measurements indicated that upon storage, tenuous carrageenan-protein aggregates are formed. The firming of the gel was probably related to slow structural arrangements of the gel and not related to slowly changing calcium equilibria or age gelation.

Hollow-Fiber flow field-flow fractionation of synthetic polymers in organic solvents.

A modified polyacrylonitrile (PAN) hollow-fiber membrane from a commercial source has been applied as the separation channel in flow field-flow fractionation (FFF). With the PAN membrane fiber, the application range of flow FFF could be extended to synthetic polymers that are soluble in a variety of organic solvents. The PAN membrane was shown to be resistant to hydrophobic solvents, such as dichloromethane (DCM), tetrahydrofuran (THF), ethyl acetate, and methyl ethyl ketone (MEK), as was illustrated by the successful fractionation of different polymer standards in these solvents. The system performance was assessed using polystyrene (PS) standards with ethyl acetate as the solvent. For a 100 kDa PS standard, the average recoverywas 57%, but for standards with a molar mass of 400 kDa and higher, 100% recovery was obtained. A linear relationship between peak area and injected mass was found. The run-to-run and fiber-to-fiber repeatability was determined using 100- and 400 kDa PS standards. The repeatability appeared to be satisfactory, with relative standard deviations < 2% for the retention times and < 5% for the recoveries of the standards. Plate numbers for the 400 kDa standard on different fibers were in the order of 110. From measurements on the fractionation of ferritin aggregates, it is concluded that the instrumental band-broadening is negligible. For an accurate determination of diffusion coefficients and molecular sizes based on retention times, calibration of the channel with standards appeared to be necessary. However, it was shown that the FFF system could be coupled to a multiangle light scattering (MALS) detector, thus providing an alternative on-line method for calibration. Expressions for the maximum obtainable plate number per unit of time have been derived for a hollow-fiber flow FFF system. It is shown that an increase in the system performance can be expected from a scaling down of the fiber diameter.

Influence of the carrier composition on thermal field-flow fractionation for the characterisation of sub-micron polystyrene latex particles.

A study on the influence of the carrier composition in a ThFFF system on the retention and thermal diffusion of sub-micron polystyrene latex particles has been carried out. Various factors that may influence retention were studied. These include: the type of electrolyte and surfactant, their respective concentrations, and the addition of an organic modifier. Particle retention is highly sensitive to small changes in the carrier composition. It is demonstrated that under the conditions applied, secondary effects, such as particle-wall and particle-particle interactions, are negligible. Addition of surfactants is required to minimise particle-wall interactions. Generally, retention increases at higher electrolyte concentration. Furthermore, the addition of acetonitrile (ACN) to an aqueous carrier leads also to an increased retention. The type of surfactant as well as its concentration is of influence on the retention time. The three surfactants that were studied, i.e., sodium dodecyl sulfate, Brij 35 and cetyltrimethylammonium bromide, showed significant differences in particle retention behaviour. The observed differences in retention in the carriers can be attributed to actual changes in thermal diffusion. D(T) appears to be mainly determined by the interaction between the particle's surface and the carrier liquid, and is therefore highly sensitive to changes in the chemical composition of the particle surface and the carrier. Strong differences in size selectivity were found for different carrier compositions. This allows a relatively easy optimisation of the separation. On the other hand, it complicates the size and composition analysis of particles.

Contrast sensitivity function in Graves' ophthalmopathy and dysthyroid optic neuropathy.

Contrast sensitivity function was measured by a computer automated method on 38 eyes with dysthyroid optic neuropathy and 34 eyes with Graves' ophthalmopathy only. The results were compared with 74 healthy control eyes. Disturbances of contrast sensitivity functions were found in both groups when compared with controls. The eyes affected with dysthyroid optic neuropathy showed pronounced loss of contrast sensitivity in the low frequency range, which facilitates differentiation between the two groups.

Detection and maturation of VEP albino asymmetry: an overview and a longitudinal study from birth to 54 weeks.

The genetic anomaly in albinism prevents adequate melanin metabolism within the fetal eye cup and stalk. This results in severe disruption of pre- and postnatal retinal development and the condition of abnormal temporal retinal projections. The obligate misrouting of retinal-geniculate-cortical projections in albinism can be detected in the topographical representation across the occiput of the visual evoked potential (VEP). Age-dependent misrouting detection methods are described which yield 100% detection rates with zero false positives across the life span. By combining appropriate state-defined neonatal recording procedures with the albino infant VEP test paradigm, the presence of aberrant optic pathway projections was observed in a 5-day-old full-term infant. Maximum asymmetry was observed within a long-latency window of the response which shifted during the postpartum period to shorter latencies. Longitudinal studies show two specific latency regions of significant VEP asymmetry. The first occurs within 40-70 ms after stimulus onset and remains constant across the age range. The second, more robust, cluster of asymmetry occurs within a longer latency window and shows an age-related shift towards shorter latencies. The decreasing latency of this asymmetry is concomitant with normal maturational changes of the evoked response. These results show that VEP misrouting can be extended to reliable albino diagnosis within the neonatal period and to the assessment of visual maturation.