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Objectives Acoustic noise in magnetic resonance imaging (MRI) negatively impacts patients. We assessed a silent gradient coil switched at 20 kHz combined with a T1-weighted magnetisation prepared rapid gradient-echo (MPRAGE) sequence at 7 T. Methods Five healthy subjects (21–29 years; three females) without previous 7-T MRI experience underwent both a quiet MPRAGE (Q-MPRAGE) and conventional MPRAGE (C-MPRAGE) sequence twice. Image quality was assessed quantitatively, and qualitatively by two neuroradiologists. Sound level was measured objectively and rated subjectively on a 0 to 10 scale by all subjects immediately following each sequence and after the whole examination (delayed). All subjects also reported comfort level, overall experience and willingness to undergo the sequence again. Results Compared to C-MPRAGE, Q-MPRAGE showed higher signal-to-noise ratio (10%; p = 0.012) and lower contrast-to-noise ratio (20%; p < 0.001) as well as acceptable to good image quality. Q-MPRAGE produced 27 dB lower sound level (76 versus 103 dB). Subjects reported lower sound level for Q-MPRAGE both immediate (4.4 ± 1.4 versus 6.4 ± 1.3; p = 0.007) and delayed (4.6 ± 1.4 versus 6.3 ± 1.3; p = 0.005), while they rated comfort level (7.4 ± 1.0 versus 6.1 ± 1.7; p = 0.016) and overall experience (7.6 ± 1.0 versus 6.0 ± 0.9; p = 0.005) higher. Willingness to undergo the sequence again was also higher, however not significantly (8.1 ± 1.0 versus 7.2 ± 1.3; p = 0.066). Conclusion Q-MPRAGE using a silent gradient coil reduced sound level by 27 dB compared to C-MPRAGE at 7 T while featuring acceptable-to-good image quality and a quieter and more pleasant subject experience.

Background: Patients with psychotic disorders often show prominent cognitive impairment. Glutamate seems to play a prominent role, but its role in deep gray matter (DGM) regions is unclear. Aims: To evaluate glutamate levels within deep gray matter structures in patients with a psychotic disorder in relation to cognitive functioning, using advanced spectroscopic acquisition, reconstruction, and post-processing techniques. Methods: A 7-Tesla magnetic resonance imaging scanner combined with a lipid suppression coil and subject-specific water suppression pulses was used to acquire high-resolution magnetic resonance spectroscopic imaging data. Tissue fraction correction and registration to a standard brain were performed for group comparison in specifically delineated DGM regions. The brief assessment of cognition in schizophrenia was used to evaluate cognitive status. Results: Average glutamate levels across DGM structures (i.e. caudate, pallidum, putamen, and thalamus) in mostly medicated patients with a psychotic disorder ( n = 16, age = 33, 4 females) were lower compared to healthy controls ( n = 23, age = 24, 7 females; p = 0.005, d = 1.06). Stratified analyses showed lower glutamate levels in the caudate ( p = 0.046, d = 0.76) and putamen p = 0.013, d = 0.94). These findings were largely explained by age differences between groups. DGM glutamate levels were positively correlated with psychomotor speed ( r(30) = 0.49, p = 0.028), but not with other cognitive domains. Conclusions: We find reduced glutamate levels across DGM structures including the caudate and putamen in patients with a psychotic disorder that are linked to psychomotor speed. Despite limitations concerning age differences, these results underscore the potential role of detailed in vivo glutamate assessments to understand cognitive deficits in psychotic disorders.

T2* mapping is promising for the evaluation of articular cartilage collagen. In this work, a groove model in a large animal is used as a model for posttraumatic arthritis. We hypothesized that T2* mapping could be employed to differentiate between healthy and (subtly) damaged cartilage. Eight carpal joints were obtained from four adult Shetland ponies that had been included in the groove study. In this model, grooves were surgically created on the proximal articular surface of the intermediate carpal bone (radiocarpal joint) and the radial facet of the third carpal bone (middle carpal joint) by either coarse disruption or sharp incision. After 9 months, T2* mapping of the entire carpal joint was carried out on a 7.0‐T whole‐body magnetic resonance imaging (MRI) scanner by means of a gradient echo multi‐echo sequence. Afterwards, assessment of collagen orientation was carried out based on Picrosirius Red‐stained histological sections, visualized by polarized light microscopy (PLM). The average T2* relaxation time in grooved samples was lower than in contralateral control sites. Opposite to the grooved areas, the “kissing sites” had a higher average T2* relaxation time than the grooved sites. PLM showed mild changes in orientation of the collagen fibers, particularly around blunt grooves. This work shows that T2* relaxation times are different in healthy cartilage vs (early) damaged cartilage, as induced by the equine groove model. Additionally, the average T2* relaxation times are different in kissing lesions vs the grooved sites., The median T2* relaxation time was lower in the sample group of grooved cartilage than in contralateral control sites. The sample group of kissing sites had a higher median T2* relaxation time as compared to the opposite, grooved sites. This work shows that T2* relaxation times are different in healthy cartilage vs (early) damaged cartilage, as induced by the equine groove model.

Introduction: Concurrent chemoradiotherapy remains the main treatment strategy for patients with stage IIIA non-small cell lung cancer (NSCLC); stage cT3N1 or cT4N0-1 may be eligible for surgery and potentially resectable stage IIIA (N2) NSCLC for neoadjuvant therapy followed by resection. We evaluated treatment patterns and outcomes of patients with stage IIIA NSCLC in The Netherlands. Material and Methods: Primary treatment data of patients with clinically staged IIIA NSCLC between 2010 and 2016 were extracted from The Netherlands Cancer Registry. Patient characteristics were tabulated and 5-year overall survival (OS) was calculated and reported. Results: In total, 9,591 patients were diagnosed with stage IIIA NSCLC. Of these patients, 41.3% were treated with chemoradiotherapy, 11.6% by upfront surgery and 428 patients (4.5%) received neoadjuvant treatment followed by resection. The 5-year OS was 26% after chemoradiotherapy, 40% after upfront surgery and 54% after neoadjuvant treatment followed by resection. Clinical over staging was seen in 42.3% of the patients that were operated without neoadjuvant therapy. Conclusion: In The Netherlands, between 2010 and 2016, 4.5% of patients with stage IIIA NSCLC were selected for treatment with neoadjuvant therapy followed by resection. The 5-year OS in these patients exceeded 50%. However, the outcome might be overestimated due to clinical over staging.

Objectives Patients with advanced stage non-small cell lung cancer (NSCLC) are generally considered incurable. The mainstay of treatment for these patients is systemic therapy. The addition of local treatment, including surgery, remains controversial. Oligoprogression is defined as advanced stage NSCLC with limited progression of disease after a period of prolonged disease stabilisation or after a partial or complete response on systemic therapy. In this retrospective study we evaluated outcome and survival of patients who underwent a resection for oligoprogression after systemic therapy for advanced stage NSCLC. Materials and Methods Patients with oligoprogression after systemic treatment for advanced NSCLC who were operated in the Antoni van Leeuwenhoek Hospital were included. Patient and treatment characteristics were collected in relation to progression free survival (PFS) and overall survival (OS). Results Between January 2015 and December 2019, 28 patients underwent surgery for an oligoprogressive lesion (primary tumor lung (n = 12), other metastatic site (n = 16)). Median age at time of resection was 60 years (39–86) and 57% were female. Postoperative complications were observed in 2 patients (7%). Progression of disease after resection of the oligoprogressive site was observed in 17 patients (61%). Median PFS was 7 months since date of resection (95% CI 6.0–25.0) and median OS was not reached. Seven patients (25%) died during follow-up. Age was predictive for OS and clinical T4 stage was predictive for PFS. M1 disease at initial presentation was predictive for better PFS compared to patients who were diagnosed with M0 disease initially. Patients who underwent resection because of oligoprogression of the primary lung tumour had a better PFS, when compared to oligoprogression of another metastastic site. Conclusion Surgical resection of an oligoprogressive lesion in patients with advanced NSCLC treated with systemic treatment is feasible and might be considered in order to achieve long term survival.

ObjectivesTo investigate the effectiveness of routine ultrasonography in the third trimester in reducing adverse perinatal outcomes in low risk pregnancies compared with usual care and the effect of this policy on maternal outcomes and obstetric interventions.DesignPragmatic, multicentre, stepped wedge cluster randomised trial.Setting60 midwifery practices in the Netherlands.Participants13 046 women aged 16 years or older with a low risk singleton pregnancy.Interventions60 midwifery practices offered usual care (serial fundal height measurements with clinically indicated ultrasonography). After 3, 7, and 10 months, a third of the practices were randomised to the intervention strategy. As well as receiving usual care, women in the intervention strategy were offered two routine biometry scans at 28-30 and 34-36 weeks’ gestation. The same multidisciplinary protocol for detecting and managing fetal growth restriction was used in both strategies.Main outcome measuresThe primary outcome measure was a composite of severe adverse perinatal outcomes: perinatal death, Apgar score ResultsBetween 1 February 2015 and 29 February 2016, 60 midwifery practices enrolled 13 520 women in mid-pregnancy (mean 22.8 (SD 2.4) weeks’ gestation). 13 046 women (intervention n=7067, usual care n=5979) with data based on the national Dutch perinatal registry or hospital records were included in the analyses. Small for gestational age at birth was significantly more often detected in the intervention group than in the usual care group (179 of 556 (32%) v 78 of 407 (19%), PConclusionIn low risk pregnancies, routine ultrasonography in the third trimester along with clinically indicated ultrasonography was associated with higher antenatal detection of small for gestational age fetuses but not with a reduced incidence of severe adverse perinatal outcomes compared with usual care alone. The findings do not support routine ultrasonography in the third trimester for low risk pregnancies.Trial registrationNetherlands Trial Register NTR4367.

Purpose: DWI is a promising modality in breast MRI, but its clinical acceptance is slow. Analysis of DWI is hampered by geometric distortion artifacts, which are caused by off-resonant spins in combination with the low phase-encoding bandwidth of the EPI sequence used. Existing correction methods assume smooth off-resonance fields, which we show to be invalid in the human breast, where high discontinuities arise at tissue interfaces. Methods: We developed a distortion correction method that incorporates high-resolution off-resonance maps to better solve for severe distortions at tissue interfaces. The method was evaluated quantitatively both ex vivo in a porcine tissue phantom and in vivo in 5 healthy volunteers. The added value of high-resolution off-resonance maps was tested using a Wilcoxon signed rank test comparing the quantitative results obtained with a low-resolution off-resonance map with those obtained with a high-resolution map. Results: Distortion correction using low-resolution off-resonance maps corrected most of the distortions, as expected. Still, all quantitative comparison metrics showed increased conformity between the corrected EPI images and a high-bandwidth reference scan for both the ex vivo and in vivo experiments. All metrics showed a significant improvement when a high-resolution off-resonance map was used (P < 0.05), in particular at tissue boundaries. Conclusion: The use of off-resonance maps of a resolution higher than EPI scans significantly improves upon existing distortion correction techniques, specifically by superior correction at glandular tissue boundaries.

The goal of this study was to introduce and evaluate the performance of a lightweight, high‐performance, single‐axis (z‐axis) gradient insert design primarily intended for high‐resolution functional magnetic resonance imaging, and aimed at providing both ease of use and a boost in spatiotemporal resolution. The optimal winding positions of the coil were obtained using a genetic algorithm with a cost function that balanced gradient performance (minimum 0.30 mT/m/A) and field linearity (≥16 cm linear region). These parameters were verified using field distribution measurements by B0‐mapping. The correction of geometrical distortions was performed using theoretical field distribution of the coil. Simulations and measurements were performed to investigate the echo planar imaging echo‐spacing reduction due to the improved gradient performance. The resulting coil featured a 16‐cm linear region, a weight of 45 kg, an installation time of 15 min, and a maximum gradient strength and slew rate of 200 mT/m and 1300 T/m/s, respectively, when paired with a commercially available gradient amplifier (940 V/630 A). The field distribution measurements matched the theoretically expected field. By utilizing the theoretical field distribution, geometrical distortions were corrected to within 6% of the whole‐body gradient reference image in the target region. Compared with a whole‐body gradient set, a maximum reduction in echo‐spacing of a factor of 2.3 was found, translating to a 344 μs echo‐spacing, for a field of view of 192 mm, a receiver bandwidth of 920 kHz and a gradient amplitude of 112 mT/m. We present a lightweight, single‐axis gradient insert design that can provide high gradient performance and an increase in spatiotemporal resolution with correctable geometrical distortions while also offering a short installation time of less than 15 min and minimal system modifications., A single‐axis gradient insert, designed to be plug‐and‐play while providing a significant boost in gradient performance (gradient strength = 200 mT/m and slew rate = 1300 T/m/s), was presented. This coil was characterized in terms of linearity, image distortions and reduction in echo‐spacing for echo planar imaging. Distortions were found to be correctable and echo‐spacing could be reduced by a factor of 2.3 compared with a whole‐body gradient set (40 mT/m and 200 T/m/s).

Item does not contain fulltext IMPORTANCE: Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity. OBJECTIVE: To assess whether a dose reduction of preoperative radiotherapy for myxoid liposarcoma would result in comparable oncological outcome with less morbidity. DESIGN, SETTING, AND PARTICIPANTS: The Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas (DOREMY) trial is a prospective, single-group, phase 2 nonrandomized controlled trial being conducted in 9 tertiary sarcoma centers in Europe and the US. Participants include adults with nonmetastatic, biopsy-proven and translocation-confirmed myxoid liposarcoma of the extremity or trunk who were enrolled between November 24, 2010, and August 1, 2019. Data analyses, using both per-protocol and intention-to-treat approaches, were conducted from November 24, 2010, to January 31, 2020. INTERVENTIONS: The experimental preoperative radiotherapy regimen consisted of 36 Gy in once-daily 2-Gy fractions, with subsequent definitive surgical resection after an interval of 4 or more weeks. MAIN OUTCOMES AND MEASURES: As a short-term evaluable surrogate for local control, the primary end point was centrally reviewed pathologic treatment response. The experimental regimen was regarded as a success when 70% or more of the resection specimens showed extensive treatment response, defined as 50% or greater of the tumor volume containing treatment effects. Morbidity outcomes consisted of wound complications and late toxic effects. RESULTS: Among the 79 eligible patients, 44 (56%) were men and the median (interquartile range) age was 45 (39-56) years. Two patients did not undergo surgical resection because of intercurrent metastatic disease. Extensive pathological treatment response was observed in 70 of 77 patients (91%; posterior mean, 90.4%; 95% highest probability density interval, 83.8%-96.4%). The local control rate was 100%. The rate of wound complication requiring intervention was 17%, and the rate of grade 2 or higher toxic effects was 14%. CONCLUSIONS AND RELEVANCE: The findings of the DOREMY nonrandomized clinical trial suggest that deintensification of preoperative radiotherapy dose is effective and oncologically safe and is associated with less morbidity than historical controls, although differences in radiotherapy techniques and follow-up should be considered. A 36-Gy dose delivered in once-daily 2-Gy fractions is proposed as a dose-fractionation approach for myxoid liposarcoma, given that phase 3 trials are logistically impossible to execute in rare cancers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02106312.

To assess articular cartilage in vivo, a noninvasive measurement is proposed to evaluate damage of the cartilage. It is hypothesized that glycosaminoglycan chemical exchange saturation transfer (gagCEST) can be applied as a noninvasive imaging technique as it would relate to electromechanical indentation and GAG content as measured with biochemical assays. This pilot study applies gagCEST MRI in total knee arthroplasty (TKA) patients to assess substantially damaged articular cartilage. The outcome was verified against electromechanical indentation and biochemical assays to assess the potential of gagCEST MRI. Five TKA patients were scanned on a 7.0 T MRI with a gagCEST sequence. Articular resurfacing cuts after TKA were obtained for electromechanical and biochemical analyses. The gagCEST MRI measurements on the medial condyle showed a moderate correlation with the GAG content, although sensitivity on the lateral condyle was lacking. Additionally, a strong negative correlation of gagCEST MRI with the electromechanical measurements was observed in the regression analysis. Correlation of gagCEST MRI with electromechanical measurements was shown, but the correlation of gagCEST MRI with GAG content was not convincing. In conclusion, gagCEST could be a useful tool to assess the GAG content in articular cartilage noninvasively, although the mismatch in heterogeneity requires further investigation., This pilot study applies gagCEST MRI in vivo in five total knee arthroplasty patients to assess substantially damaged articular cartilage. GagCEST MRI measurements show a moderate correlation with GAG content on the medial condyle and a strong correlation with electromechanical measurements. In conclusion, gagCEST could be a useful tool to assess the GAG content in articular cartilage noninvasively, although the mismatch in heterogeneity requires further investigation.

Voltage-gated Ca2+ channels are critical for the development and mature function of the nervous system. Variants in the CACNA2D4 gene encoding the α2δ-4 auxiliary subunit of these channels are associated with neuropsychiatric and neurodevelopmental disorders. α2δ-4 is prominently expressed in the retina and is crucial for vision, but extra-retinal functions of α2δ-4 have not been investigated. Here, we sought to fill this gap by analyzing the behavioral phenotypes of α2δ-4 knockout (KO) mice. α2δ-4 KO mice (both males and females) exhibited significant impairments in prepulse inhibition that were unlikely to result from the modestly elevated auditory brainstem response thresholds. Whereas α2δ-4 KO mice of both sexes were hyperactive in various assays, only females showed impaired motor coordination in the rotarod assay. α2δ-4 KO mice exhibited anxiolytic and anti-depressive behaviors in the elevated plus maze and tail suspension tests, respectively. Our results reveal an unexpected role for α2δ-4 in sensorimotor gating and motor function and identify α2δ-4 KO mice as a novel model for studying the pathophysiology associated with CACNA2D4 variants.

This work describes a role for endothelial N-cadherin in the regulation of endothelial permeability in the brain and lung. N-cadherin adhesions formed between endothelial cells and pericytes increase the abundance of VE-cadherin at adherens junctions through the RhoGEF Trio-dependent activation of RhoA and Rac1., Vascular endothelial (VE)–cadherin forms homotypic adherens junctions (AJs) in the endothelium, whereas N-cadherin forms heterotypic adhesion between endothelial cells and surrounding vascular smooth muscle cells and pericytes. Here we addressed the question whether both cadherin adhesion complexes communicate through intracellular signaling and contribute to the integrity of the endothelial barrier. We demonstrated that deletion of N-cadherin (Cdh2) in either endothelial cells or pericytes increases junctional endothelial permeability in lung and brain secondary to reduced accumulation of VE-cadherin at AJs. N-cadherin functions by increasing the rate of VE-cadherin recruitment to AJs and induces the assembly of VE-cadherin junctions. We identified the dual Rac1/RhoA Rho guanine nucleotide exchange factor (GEF) Trio as a critical component of the N-cadherin adhesion complex, which activates both Rac1 and RhoA signaling pathways at AJs. Trio GEF1-mediated Rac1 activation induces the recruitment of VE-cadherin to AJs, whereas Trio GEF2-mediated RhoA activation increases intracellular tension and reinforces Rac1 activation to promote assembly of VE-cadherin junctions and thereby establish the characteristic restrictive endothelial barrier.

Phosphorus (31P) MRSI provides opportunities to monitor potential biomarkers. However, current applications of 31P MRS are generally restricted to relatively small volumes as small coils are used. Conventional surface coils require high energy adiabatic RF pulses to achieve flip angle homogeneity, leading to high specific absorption rates (SARs), and occupy space within the MRI bore. A birdcage coil behind the bore cover can potentially reduce the SAR constraints massively by use of conventional amplitude modulated pulses without sacrificing patient space. Here, we demonstrate that the integrated 31P birdcage coil setup with a high power RF amplifier at 7 T allows for low flip angle excitations with short repetition time (T R) for fast 3D chemical shift imaging (CSI) and 3D T 1‐weighted CSI as well as high flip angle multi‐refocusing pulses, enabling multi‐echo CSI that can measure metabolite T 2, over a large field of view in the body. B 1 + calibration showed a variation of only 30% in maximum B 1 in four volunteers. High signal‐to‐noise ratio (SNR) MRSI was obtained in the gluteal muscle using two fast in vivo 3D spectroscopic imaging protocols, with low and high flip angles, and with multi‐echo MRSI without exceeding SAR levels. In addition, full liver MRSI was achieved within SAR constraints. The integrated 31P body coil allowed for fast spectroscopic imaging and successful implementation of the multi‐echo method in the body at 7 T. Moreover, no additional enclosing hardware was needed for 31P excitation, paving the way to include larger subjects and more space for receiver arrays. The increase in possible number of RF excitations per scan time, due to the improved B 1 + homogeneity and low SAR, allows SNR to be exchanged for spatial resolution in CSI and/or T 1 weighting by simply manipulating T R and/or flip angle to detect and quantify ratios from different molecular species., An integrated custom‐built whole‐body birdcage coil enabled 31P MRSI in large volumes without sacrificing space. The B1+‐field uniformity, comparable to 3 T proton MR birdcage coils, allowed using conventional amplitude modulated pulses. This massively reduced SAR constrains compared to adiabatic pulses. The increase in RF pulses per unit of time enabled fast and multi‐echo MRSI in the body at 7 T. Local liver spectra were acquired. Presented setup creates opportunities for new body‐focused 31P/X‐nuclei MRS methodologies.

The brain can be considered a network, existing of multiple interconnected areas with various functions. MRI provides opportunities to map the large-scale network organization of the brain. We tap into the neurobiochemical dimension of these networks, as neuronal functioning and signal trafficking across distributed brain regions relies on the release and presence of neurotransmitters. Using high-field MR spectroscopic imaging at 7.0 T, we obtained a non-invasive snapshot of the spatial distribution of the neurotransmitters GABA and glutamate, and investigated interregional associations of these neurotransmitters. We demonstrate that interregional correlations of glutamate and GABA concentrations can be conceptualized as networks. Furthermore, patients with epilepsy display an increased number of glutamate and GABA connections and increased average strength of the GABA network. The increased glutamate and GABA connectivity in epilepsy might indicate a disrupted neurotransmitter balance. In addition to epilepsy, the ‘neurotransmitter networks’ concept might also provide new insights for other neurological diseases., Highlights • We introduce the concept of “neurotransmitter networks”. • Ultrahigh field spectroscopic images of the brain were obtained. • Interregional correlations of Glutamate and GABA are conceptualized as networks. • Increased glutamate and GABA connectivity are shown in patients with epilepsy. • Neurotransmitter networks might provide new insights for neurological diseases.

The dynamic behavior of the wrist joint is governed by nonlinear properties, yet applied mathematical models, used to describe the measured input-output (perturbation-response) relationship, are commonly linear. Consequently, the linearly estimated model parameters will depend on properties of the applied perturbation properties (such perturbation amplitude and velocity). We aimed to systematically address the effects of perturbation velocity on linearly estimated neuromechanical parameters. Using a single axis manipulator ramp and hold perturbations were applied to the wrist joint. Effects of perturbation velocity (0.5, 1 and 3 rad/s) were investigated at multiple background torque levels (0, 0.5 and 1 N·m). With increasing perturbation velocity, estimated joint stiffness remained constant, while damping and reflex gain decreased. This variation in model parameters is dependent on background torque levels, i.e. muscle contraction. These observations support the future development of nonlinear models that are capable of describing wrist joint behavior over a larger range of loading conditions, exceeding the restricted range of operation that is required for linearization.

Contains fulltext : 193431.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To analyze cost-effectiveness of Pain Exposure Physical Therapy compared to conventional treatment alongside a randomized controlled trial (NCT00817128) in patients with complex regional pain syndrome type 1, where no clinical difference was shown between the two groups in an intention-to-treat analysis. DESIGN: Randomized controlled trial with 9 months follow-up. SETTING: Patients were recruited from hospitals and general practitioners in the region around a university hospital. SUBJECTS: A total of 56 patients, 45 (80.4%) female, were randomized. About 4 patients in the intervention and 11 patients in the conventional group switched groups. The mean (SD) age was 44.3 (16.6) years, and in 37 (66.1%) patients, the upper extremity was affected. INTERVENTIONS: Patients received either Pain Exposure Physical Therapy (maximum of five sessions), or conventional treatment conforming with the Dutch multidisciplinary guideline. MAIN MEASURES: For the economic evaluation difference between the groups in health-related quality of life (quality-adjusted life years (QALYs)), and the clinical outcomes Impairment level Sum Score-Restricted Version and Pain Disability was determined based on the intention-to-treat analysis as well as differences in both healthcare-related costs and travel expenses. Cost-effectiveness planes were constructed using bootstrapping to compare effects and costs. RESULTS: No significant effects were found for QALYs (mean difference = -0.02; 95% confidence interval (CI) -0.10 to 0.04) and clinical outcomes. A cost minimization analysis showed a significant difference in costs between groups. The conventional treatment was 64% more expensive than the Pain Exposure Physical Therapy. CONCLUSION: This economic analysis shows that Pain Exposure Physical Therapy compared to conventional treatment is cost-effective.

Aims/hypothesis Detection and management of gestational diabetes mellitus (GDM) are crucial to reduce the risk of pregnancy-related complications for both mother and child. In 2013, the WHO adopted new diagnostic criteria for GDM to improve pregnancy outcomes. However, the evidence supporting these criteria is limited. Consequently, these new criteria have not yet been endorsed in the Netherlands. The aim of this study was to determine the impact of these criteria on the number of GDM diagnoses and pregnancy outcomes. Methods Data were available from 10,642 women who underwent a 75 g OGTT because of risk factors or signs suggestive of GDM. Women were treated if diagnosed with GDM according to the WHO 1999 criteria. Data on pregnancy outcomes were obtained from extensive chart reviews from 4,431 women and were compared between women with normal glucose tolerance (NGT) and women classified into the following groups: (1) GDM according to WHO 1999 criteria; (2) GDM according to WHO 2013 criteria; (3) GDM according to WHO 2013 fasting glucose threshold, but not WHO 1999 criteria; and (4) GDM according to WHO 1999 2 h plasma glucose threshold (2HG), but not WHO 2013 criteria. Results Applying the new WHO 2013 criteria would have increased the number of diagnoses by 45% (32% vs 22%) in this population of women at higher risk for GDM. In comparison with women with NGT, women classified as having GDM based only on the WHO 2013 threshold for fasting glucose, who were not treated for GDM, were more likely to have been obese (46.1% vs 28.1%, p

Background and Aims Volumetric laser endomicroscopy (VLE) is an advanced imaging system that provides a near-microscopic resolution scan of the esophageal wall layers up to 3-mm deep. VLE has the potential to improve detection of early neoplasia in Barrett's esophagus (BE). However, interpretation of VLE images is complex because of the large amount of data that need to be interpreted in real time. The aim of this study was to investigate the feasibility of a computer algorithm to identify early BE neoplasia on ex vivo VLE images. Methods We used 60 VLE images from a database of high-quality ex vivo VLE-histology correlations, obtained from BE patients ± neoplasia (30 nondysplastic BE [NDBE] and 30 high-grade dysplasia/early adenocarcinoma images). VLE features from a recently developed clinical VLE prediction score for BE neoplasia served as input for the algorithm: (1) higher VLE surface than subsurface signal and (2) lack of layering. With this input, novel clinically inspired algorithm features were developed, based on signal intensity statistics and grayscale correlations. For comparison, generic image analysis methods were examined for their performance to detect neoplasia. For classification of the images in the NDBE or neoplastic group, several machine learning methods were evaluated. Leave-1-out cross-validation was used for algorithm validation. Results Three novel clinically inspired algorithm features were developed. The feature "layering and signal decay statistics" showed the optimal performance compared with the other clinically features ("layering" and "signal intensity distribution") and generic image analyses methods, with an area under the receiver operating characteristic curve (AUC) of .95. Corresponding sensitivity and specificity were 90% and 93%, respectively. In addition, the algorithm showed a better performance than the clinical VLE prediction score (AUC .81). Conclusions This is the first study in which a computer algorithm for BE neoplasia was developed based on VLE images with direct histologic correlates. The algorithm showed good performance to detect BE neoplasia in ex vivo VLE images compared with the performance of a recently developed clinical VLE prediction score. This study suggests that an automatic detection algorithm has the potential to assist endoscopists in detecting early neoplasia on VLE. Future studies on in vivo VLE scans are needed to further validate the algorithm.

Introduction Single‐voxel 1H MRS in body applications often suffers from respiratory and other motion induced phase and frequency shifts, which lead to incoherent averaging and hence to suboptimal results. Methods Here we show the application of metabolite cycling (MC) for liver STEAM‐localized 1H MRS on a 7 T parallel transmit system, using eight transmit‐receive fractionated dipole antennas with 16 additional, integrated receive loops. MC‐STEAM measurements were made in six healthy, lean subjects and compared with STEAM measurements using VAPOR water suppression. Measurements were performed during free breathing and during synchronized breathing, for which the subjects did breathe in between the MRS acquisitions. Both intra‐session repeatability and inter‐session reproducibility of liver lipid quantification with MC‐STEAM and VAPOR‐STEAM were determined. Results The preserved water signal in MC‐STEAM allowed for robust phase and frequency correction of individual acquisitions before averaging, which resulted in in vivo liver spectra that were of equal quality when measurements were made with free breathing or synchronized breathing. Intra‐session repeatability and inter‐session reproducibility of liver lipid quantification were better for MC‐STEAM than for VAPOR‐STEAM. This may also be explained by the more robust phase and frequency correction of the individual MC‐STEAM acquisitions as compared with the VAPOR‐STEAM acquisitions, for which the low‐signal‐to‐noise ratio lipid signals had to be used for the corrections. Conclusion Non‐water‐suppressed MC‐STEAM on a 7 T system with parallel transmit is a promising approach for 1H MRS applications in the body that are affected by motion, such as in the liver, and yields better repeatability and reproducibility compared with water‐suppressed measurements., Non‐water‐suppressed, metabolite‐cycled STEAM on a 7 T system with parallel transmit was shown to be a promising approach for 1H MRS applications in the body that are affected by motion, such as in the liver. Robust phase and frequency correction of individual acquisitions before averaging, enabled by the preserved water signal in the metabolite‐cycled spectra, yielded better repeatability and reproducibility compared with water‐suppressed measurements.

Purpose: Metabolic MRI is a noninvasive technique that can give new insights into understanding cancer metabolism and finding biomarkers to evaluate or monitor treatment plans. Using this technique, a previous study has shown an increase in pH during neoadjuvant chemotherapy (NAC) treatment, while recent observation in a different study showed a reduced amide proton transfer (APT) signal during NAC treatment (negative relation). These findings are counterintuitive, given the known intrinsic positive relation of APT signal to pH. Methods: In this study we combined APT MRI and 31P-MRSI measurements to unravel the relation between the APT signal and pH in breast cancer. Twenty-two breast cancer patients were scanned with a 7 T MRI before and after the first cycle of NAC treatment. pH was determined by the chemical shift of inorganic phosphate (Pi). Results: While APT signals have a positive relation to pH and amide content, we observed a direct negative linear correlation between APT signals and pH in breast tumors in vivo. Conclusions: As differentiation of cancer stages was confirmed by observation of a linear correlation between cell proliferation marker PE/Pi (phosphoethanolamine over inorganic phosphate) and pH in the tumor, our data demonstrates that the concentration of mobile proteins likely supersedes the contribution of the exchange rate to the APT signal.

Background The quality of carotid wall MRI can benefit substantially from a dedicated RF coil that is tailored towards the human neck geometry and optimized for image signal-to-noise ratio (SNR), parallel imaging performance and RF penetration depth and coverage. In last decades, several of such dedicated carotid coils were introduced. However, a comparison of the more successful designs is still lacking. Objective To perform a head-to-head comparison over four dedicated MR carotid surface coils with 4, 6, 8 and 30 coil elements, respectively. Material and methods Ten volunteers were scanned on a 3T scanner. For each subject, multiple black-blood carotid vessel wall images were measured using the four coils with different parallel imaging settings. The performance of the coils was evaluated and compared in terms of image coverage, penetration depth and noise correlations between elements. Vessel wall of a common carotid section was delineated manually. Subsequently, images were assessed based on vessel wall morphology and image quality parameters. The morphological parameters consisted of the vessel wall area, thickness, and normalized wall index (wall area/total vessel area). Image quality parameters consisted of vessel wall SNR, wall-lumen contrast-to-noise ratio (CNR), the vessel g-factor, and CNR index ((wall–lumen signal) / (wall+lumen signal)). Repeated measures analysis of variance (rmANOVA) was applied for each parameter for the averaged 10 slices for all volunteers to assess effect of coil and SENSE factor. If the rmANOVA was significant, post-hoc comparisons were conducted. Results No significant coil effect were found for vessel wall morphological parameters. SENSE acceleration affected some morphological parameters for 6- and 8-channel coils, but had no effect on the 30-channel coil. The 30-channel coil achieved high acceleration factors (10x) with significantly lower vessel g-factor values (ps 0.01), but lower vessel wall SNR and CNR values (ps 0.01). Conclusion All four coils were capable of high-quality carotid MRI. The 30-channel coil is recommended when rapid image acquisition acceleration is required for 3D measurements, whereas 6- and 8-channel coils demonstrated the highest SNR performance.

The purpose of this work was to investigate whether noninvasive early detection (after the first cycle) of response to neoadjuvant chemotherapy (NAC) in breast cancer patients was possible. 31 P-MRSI at 7 T was used to determine different phosphor metabolites ratios and correlate this to pathological response. 31 P-MRSI was performed in 12 breast cancer patients treated with NAC. 31 P spectra were fitted and aligned to the frequency of phosphoethanolamine (PE). Metabolic signal ratios for phosphomonoesters/phosphodiesters (PME/PDE), phosphocholine/glycerophosphatidylcholine (PC/GPtC), phosphoethanolamine/glycerophosphoethanolamine (PE/GPE) and phosphomonoesters/in-organic phosphate (PME/Pi) were determined from spectral fitting of the individual spectra and the summed spectra before and after the first cycle of NAC. Metabolic ratios were subsequently related to pathological response. Additionally, the correlation between the measured metabolic ratios and Ki-67 levels was determined using linear regression. Four patients had a pathological complete response after treatment, five patients a partial pathological response, and three patients did not respond to NAC. In the summed spectrum after the first cycle of NAC, PME/Pi and PME/PDE decreased by 18 and 13%, respectively. A subtle difference among the different response groups was observed in PME/PDE, where the nonresponders showed an increase and the partial and complete responders a decrease (P = 0.32). No significant changes in metabolic ratios were found. However, a significant association between PE/Pi and the Ki-67 index was found (P = 0.03). We demonstrated that it is possible to detect subtle changes in 31 P metabolites with a 7 T MR system after the first cycle of NAC treatment in breast cancer patients. Nonresponders showed different changes in metabolic ratios compared with partial and complete responders, in particular for PME/PDE; however, more patients need to be included to investigate its clinical value.

The differentiation grade of cervical cancer is histologically assessed by examining biopsies or surgical specimens. MRS is a highly sensitive technique that images tissue metabolism and can be used to increase the specificity of tissue characterization in a non-invasive manner. We aim to explore the feasibility of using in vivo 1 H-MRS at 7 T in women with cervical cancer to study tissue fatty acid composition. 10 women with histologically proven Stage IB1-IIB cervical cancer were scanned with a whole-body 7 T MR system with a multi-transmit system and an internal receive only monopole antenna. A STEAM sequence was used to obtain 1 H-MRS data. Fatty acid resonances were fitted with Lorentzian curves and the 2.1 ppm/1.3 ppm ratios were calculated. 1 H-MRS data showed fatty acid signals resonating at 2.1 ppm, 1.9 ppm, 1.5 ppm, 1.3 ppm and 0.9 ppm. Mean 2.1/1.3 ppm ratios were 0.019 ± 0.01, 0.021 ± 0.006, 0.12 ± 0.089 and 0.39 ± 0.27 for normal, Grade I, Grade II and Grade III groups respectively. Poorly differentiated tumor tissue (Grade III) showed elevated fatty acid ratios when compared with the well differentiated tumor (Grade I) or normal tissue. 1 H-MRS in cervical cancer at 7 T is feasible and individual fatty acid signals were detected. In addition, poorly differentiated tumors show more fatty acid unsaturation. The 2.1 ppm/1.3 ppm ratio has potential for tumor characterization in a non-invasive manner for uterine cervical cancer.

Contains fulltext : 175631.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Many pregnant women are concerned about the pain they will experience in labor and how to deal with this. This study's objective was to explore women's postpartum perception and view of how they dealt with labor pain. METHODS: Semistructured postpartum interviews were analyzed using the constant comparison method. Using purposive sampling, we selected 17 women from five midwifery practices across the Netherlands, from August 2009 to September 2010. RESULTS: Women reported that control over decision making during labor (about dealing with pain) helped them to deal with labor pain, as did continuous midwife support at home and in hospital, and effective childbirth preparation. Some of these women implicitly or explicitly indicated that midwives should know which method of pain management they need during labor and arrange this in good time. DISCUSSION: It may be difficult for midwives to discriminate between women who need continuous support through labor without pain medication and those who genuinely desire pain medication at a certain point in labor, and who will be dissatisfied postpartum if this need is unrecognized and unfulfilled.

Objectives Preterm birth is the leading pregnancy outcome associated with perinatal morbidity and mortality and remains difficult to prevent. There is evidence that some modifiable maternal health characteristics may influence the risk of preterm birth. Our aim was to investigate the relationships of self-reported maternal health behaviour and psychological characteristics in nulliparous women with spontaneous preterm birth in prenatal primary care. Methods The data of our prospective study was obtained from the nationwide DELIVER multicentre cohort study (September 2009–March 2011), which was designed to examine perinatal primary care in the Netherlands. In our study, consisting of 2768 nulliparous women, we estimated the relationships of various self-reported health behaviours (smoking, alcohol consumption, folic acid supplementation, daily fruit, daily fresh vegetables, daily hot meal and daily breakfast consumption) and psychological characteristics (anxious/depressed mood and health control beliefs) with spontaneous preterm birth as a dichotomous outcome. Due to the clustering of clients within midwife practices, Generalized Estimating Equations was used for these analyses. Results Low health control beliefs was the sole characteristic significantly associated with spontaneous preterm birth (odds ratio 2.26; 95 % confidence interval 1.51, 3.39) after being adjusted for socio-demographics, anthropometrics and the remaining health behaviour and psychological characteristics. The other characteristics were not significantly associated with spontaneous preterm birth. Conclusions for Practice Maternal low health control beliefs need to be explored further as a possible marker for women at risk for preterm birth, and as a potentially modifiable characteristic to be used in interventions which are designed to reduce the risk of spontaneous preterm birth.

Sexual ornamentation needs to be conspicuous to be effective in attracting potential mates and defending territories and indeed, a multitude of ways exists to achieve this. Two principal mechanisms for increasing conspicuousness are to increase the ornament's colour or brightness contrast against the background and to increase the size of the ornament. We assessed the relationship between the colour and size of the dewlap, a large extendible throat-fan, across a range of species of gliding lizards (Agamidae; genus Draco) from Malaysia and the Philippines. We found a negative relationship across species between colour contrast against the background and dewlap size in males, but not in females, suggesting that males of different species use increasing colour contrast and dewlap size as alternative strategies for effective communication. Male dewlap size also increases with increasing sexual size dimorphism, and dewlap colour and brightness contrast increase with increasing sexual dichromatism in colour and brightness, respectively, suggesting that sexual selection may act on both dewlap size and colour. We further found evidence that relative predation intensity, as measured from predator attacks on models placed in the field, may play a role in the choice of strategy (high chromatic contrast or large dewlap area) a species employs. More broadly, these results highlight that each component in a signal (such as colour or size) may be influenced by different selection pressures and that by assessing components individually, we can gain a greater understanding of the evolution of signal diversity.

In this study we evaluated the value of pre-operative glucose corrected maximum standard uptake value (GC-SUVmax) as prognostic factor in patients with early stage non-small cell lung cancer (NSCLC) after complete surgical resection. This study was designed as a retrospectively evaluated single center study with prospective data registry. Inclusion criteria were: histologically proven stage I NSCLC, 18F-FDG-PET/CT scan prior to surgery, complete resection (R0) and follow up in our outpatient department. Exclusion criteria were: history of malignancy other than NSCLC, diabetes and (neo) adjuvant therapy. Follow up period was 5 years. Between 2006 and 2008 a total of 33 patients (16 males, 17 females) met the inclusion criteria. SUVmax and GC-SUVmax were strongly correlated (Spearman’s ρ = 0.97). Five-year overall survival (OS) rate was 70 % (95 % CI = 56–87 %). Patients who died within 5 years of follow up had significantly higher pre-operative GC-SUVmax (median = 10.6, IQR = 8.3–14.4) than patients who were alive at 5-year follow up (median = 6.4, IQR = 3.0–9.8), p = 0.04. SUVmax showed similar differences: 10.4 (8–12.9) vs. 6.6 (3.0–8.8), p = 0.047. The area under the receiver-operating characteristic (ROC) curve at 5 years was 0.70 (95 % CI = 0.50–0.90) for GC-SUVmax and 0.71 (95 % CI = 0.51–0.91) for SUVmax (p = 0.75). Pre-operative FDG tumor uptake in patients with NSCLC is predictive for survival after complete surgical resection. GC-SUVmax, as an additional value to SUVmax, may better approach competitive inhibition of FDG and glucose in tumors, however, in this study this potential advantage, if any, was very small.

Item does not contain fulltext BACKGROUND: Self-management support is an important component of the clinical management of many chronic conditions. The validated Self-Management Screening questionnaire (SeMaS) assesses individual characteristics that influence a patient's ability to self-manage. AIM: To assess the effect of providing personalised self-management support in clinical practice on patients' activation and health-related behaviours. DESIGN AND SETTING: A cluster randomised controlled trial was conducted in 15 primary care group practices in the south of the Netherlands. METHOD: After attending a dedicated self-management support training session, practice nurses in the intervention arm discussed the results of SeMaS with the patient at baseline, and tailored the self-management support. Participants completed a 13-item Patient Activation Measure (PAM-13) and validated lifestyle questionnaires at baseline and after 6 months. Data, including individual care plans, referrals to self-management interventions, self-monitoring, and healthcare use, were extracted from patients' medical records. Multilevel multiple regression was used to assess the effect on outcomes. RESULTS: The PAM-13 score did not differ significantly between the control (n = 348) and intervention (n = 296) arms at 6 months. In the intervention arm, 29.4% of the patients performed self-monitoring, versus 15.2% in the control arm (effect size r = 0.9, P = 0.01). In the per protocol analysis (control n = 348; intervention n = 136), the effect of the intervention was significant on the number of individual care plans (effect size r = 1.3, P = 0.04) and on self-monitoring (effect size r = 1.0, P = 0.01). CONCLUSION: This study showed that discussing SeMaS and offering tailored support did not affect patient activation or lifestyle, but did stimulate patients to self-monitor and use individual care plans.

Background: Medical guidelines increasingly use risk stratification and implicitly assume that individuals classified in the same risk category forma homogeneous group, while individuals with similar, or even identical, predicted risks can still be very different. We evaluate a strategy to identify homogeneous subgroups typically comprising predicted risk categories to allow further tailoring of treatment allocation and illustrate this strategy empirically for cardiac surgery patients with high postoperative mortality risk. Methods: Using a dataset of cardiac surgery patients (n=6517) we applied cluster analysis to identify homogenous subgroups of patients comprising the high postoperative mortality risk group ( EuroSCORE >= 15%). Cluster analyses were performed separately within younger (= 75 years) patients. Validity measures were calculated to evaluate quality and robustness of the identified subgroups. Results: Within younger patients two distinct and robust subgroups were identified, differing mainly in preoperative state and indication of recent myocardial infarction or unstable angina. In older patients, two distinct and robust subgroups were identified as well, differing mainly in preoperative state, presence of chronic pulmonary disease, previous cardiac surgery, neurological dysfunction disease and pulmonary hypertension. Conclusions: We illustrated a feasible method to identify homogeneous subgroups of individuals typically comprising risk categories. This allows a single treatment strategy - optimal only on average, across all individuals in a risk category - to be replaced by subgroup-specific treatment strategies, bringing us another step closer to individualized care. Discussions on allocation of cardiac surgery patients to different interventions may benefit from focusing on such specific subgroups. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

BACKGROUND AND PURPOSE: Cerebral MR imaging in infants is usually performed with a field strength of up to 3T. In adults, a growing number of studies have shown added diagnostic value of 7T MR imaging. 7T MR imaging might be of additional value in infants with unexplained seizures, for example. The aim of this study was to investigate the feasibility of 7T MR imaging in infants. We provide information about the safety preparations and show the first MR images of infants at 7T. MATERIALS AND METHODS: Specific absorption rate levels during 7T were simulated in Sim4life using infant and adult models. A newly developed acoustic hood was used to guarantee hearing protection. Acoustic noise damping of this hood was measured and compared with the 3T Nordell hood and no hood. In this prospective pilot study, clinically stable infants, between term-equivalent age and the corrected age of 3 months, underwent 7T MR imaging immediately after their standard 3T MR imaging. The 7T scan protocols were developed and optimized while scanning this cohort. RESULTS: Global and peak specific absorption rate levels in the infant model in the centered position and 50-mm feet direction did not exceed the levels in the adult model. Hearing protection was guaranteed with the new hood. Twelve infants were scanned. No MR imaging–related adverse events occurred. It was feasible to obtain good-quality imaging at 7T for MRA, MRV, SWI, single-shot T2WI, and MR spectroscopy. T1WI had lower quality at 7T. CONCLUSIONS: 7T MR imaging is feasible in infants, and good-quality scans could be obtained.

To explore the use of five meandering dipole antennas in a multi-transmit setup, combined with a high density receive array for breast imaging at 7 T for improved penetration depth and more homogeneous B1 field. Five meandering dipole antennas and 30 receiver loops were positioned on two cups around the breasts. Finite difference time domain simulations were performed to evaluate RF safety limits of the transmit setup. Scattering parameters of the transmit setup and coupling between the antennas and the detuned loops were measured. In vivo parallel imaging performance was investigated for various acceleration factors. After RF shimming, a B1 map, a T1-weighted image, and a T2-weighted image were acquired to assess B1 efficiency, uniformity in contrast weighting, and imaging performance in clinical applications. The maximum achievable local SAR10g value was 7.0 W/kg for 5 × 1 W accepted power. The dipoles were tuned and matched to a maximum reflection of −11.8 dB, and a maximum inter-element coupling of −14.2 dB. The maximum coupling between the antennas and the receive loops was −18.2 dB and the mean noise correlation for the 30 receive loops 7.83 ± 8.69%. In vivo measurements showed an increased field of view, which reached to the axilla, and a high transmit efficiency. This coil enabled the acquisition of T1-weighted images with a high spatial resolution of 0.7 mm3 isotropic and T2-weighted spin echo images with uniformly weighted contrast.

Summary Energy metabolism of the human visual cortex was investigated by performing 31P functional MRS. Introduction The human brain is known to be the main glucose demanding organ of the human body and neuronal activity can increase this energy demand. In this study we investigate whether alterations in pH during activation of the brain can be observed with MRS, focusing on the mitochondrial inorganic phosphate (Pi) pool as potential marker of energy demand. Methods Six participants were scanned with 16 consecutive 31P‐MRSI scans, which were divided in 4 blocks of 8:36 minutes of either rest or visual stimulation. Since the signals from the mitochondrial compartments of Pi are low, multiple approaches to achieve high SNR 31P measurements were combined. This included: a close fitting 31P RF coil, a 7 T‐field strength, Ernst angle acquisitions and a stimulus with a large visual angle allowing large spectroscopy volumes containing activated tissue. Results The targeted resonance downfield of the main Pi peak could be distinguished, indicating the high SNR of the 31P spectra. The peak downfield of the main Pi peak is believed to be connected to mitochondrial performance. In addition, a BOLD effect in the PCr signal was observed as a signal increase of 2–3% during visual stimulation as compared to rest. When averaging data over multiple volunteers, a small subtle shift of about 0.1 ppm of the downfield Pi peak towards the main Pi peak could be observed in the first 4 minutes of visual stimulation, but no longer in the 4 to 8 minute scan window. Indications of a subtle shift during visual stimulation were found, but this effect remains small and should be further validated. Conclusion Overall, the downfield peak of Pi could be observed, revealing opportunities and considerations to measure specific acidity (pH) effects in the human visual cortex., Energy metabolism of the human visual cortex was investigated by performing 31P functional MRS, focused on mitochondrial inorganic phosphate (Pimi/ex) as potential marker of energy demand. Since the concentration is low, multiple approaches to acquire high SNR 31P measurements were combined. Results show that the mitochondrial Pi resonance could be detected. During visual stimulation a small subtle shift was observed, especially in the first 4 minutes. Overall, this reveals opportunities and considerations to measure pH effects in the visual cortex.

Background The purpose of this work was to investigate noninvasive early detection of treatment response of breast cancer patients to neoadjuvant chemotherapy (NAC) using chemical exchange saturation transfer (CEST) measurements sensitive to amide proton transfer (APT) at 7 T. Methods CEST images were acquired in 10 tumors of nine breast cancer patients treated with NAC. APT signals in the tumor, before and after the first cycle of NAC, were quantified using a three-pool Lorentzian fit of the z-spectra in the region of interest. The changes in APT were subsequently related to pathological response after surgery defined by the Miller-Payne system. Results Significant differences (P 0.05, Kruskal-Wallis test). Conclusions This preliminary study shows the feasibility of using APT CEST magnetic resonance imaging as a noninvasive biomarker to assess the effect of NAC in an early stage of NAC treatment of breast cancer patients. Trial registration Registration number, NL49333.041.14/NTR4980. Registered on 16 October 2014.

Introduction Malignant pleural mesothelioma (MPM) has limited treatment options and a poor outcome. Programmed death 1/programmed death ligand 1 (PD-L1) checkpoint inhibitors have proven efficacious in several cancer types. Nivolumab is a fully humanized monoclonal antibody against programmed death 1 with a favorable toxicity profile. In MPM, the immune system is considered to play an important role. We therefore tested nivolumab in recurrent MPM. Methods In this single-center trial, patients with MPM received nivolumab 3 mg/kg intravenously every 2 weeks. Primary endpoint was the disease control rate at 12 weeks. Pre- and on-treatment biopsy specimens were obtained to analyze biomarkers for response. Results Of the 34 patients included, 8 patients (24%) had a partial response at 12 weeks and another 8 had stable disease resulting in a disease control rate at 12 weeks of 47%. One reached a partial response at 18 weeks. In 4 patients with stable disease, the tumor remained stable for more than 6 months. Treatment-related adverse events of any grade occurred in 26 patients (76%), most commonly fatigue (29%) and pruritus (15%). Grades 3 and 4 treatment-related adverse events were reported in 9 patients (26%), with pneumonitis, gastrointestinal disorders, and laboratory disorders mostly seen. One treatment-related death was due to pneumonitis and probably initiated by concurrent amiodarone therapy. PD-L1 was expressed on tumor cells in nine samples (27%), but did not correlate with outcome. Conclusions Single-agent nivolumab has meaningful clinical efficacy and a manageable safety profile in pre-treated patients with mesothelioma. PD-L1 expression does not predict for response in this population.

High field

We evaluated uptake and diagnostic outcomes of voluntary hepatitis B (HBV) and C virus (HCV) screening offered during routine tuberculosis entry screening to migrants in Gelderland and Amsterdam, the Netherlands, between 2013 and 2015. In Amsterdam, HIV screening was also offered. Overall, 54% (461/859) accepted screening. Prevalence of chronic HBV infection (HBsAg-positive) and HCV exposure (anti-HCV-positive) in Gelderland was 4.48% (9/201; 95% confidence interval (CI): 2.37–8.29) and 0.99% (2/203; 95% CI: 0.27–3.52), respectively, all infections were newly diagnosed. Prevalence of chronic HBV infection, HCV exposure and chronic HCV infection (HCV RNA-positive) in Amsterdam was 0.39% (1/256; 95% CI: 0.07–2.18), 1.17% (3/256; 95% CI: 0.40–3.39) and 0.39% (1/256; 95% CI: 0.07–2.18), respectively, with all chronic HBV/HCV infections previously diagnosed. No HIV infections were found. In univariate analyses, newly diagnosed chronic HBV infection was more likely in participants migrating for reasons other than work or study (4.35% vs 0.83%; odds ratio (OR) = 5.45; 95% CI: 1.12–26.60) and was less likely in participants in Amsterdam than Gelderland (0.00% vs 4.48%; OR = 0.04; 95% CI: 0.00–0.69). Regional differences in HBV prevalence might be explained by differences in the populations entering compulsory tuberculosis screening. Prescreening selection of migrants based on risk factors merits further exploration.

Objective To demonstrate imaging performance for cardiac MR imaging at 7 T using a coil array of 8 transmit/receive dipole antennas and 16 receive loops. Materials and methods An 8-channel dipole array was extended by adding 16 receive-only loops. Average power constraints were determined by electromagnetic simulations. Cine imaging was performed on eight healthy subjects. Geometrical factor (g-factor) maps were calculated to assess acceleration performance. Signal-to-noise ratio (SNR)-scaled images were reconstructed for different combinations of receive channels, to demonstrate the SNR benefits of combining loops and dipoles. Results The overall image quality of the cardiac functional images was rated a 2.6 on a 4-point scale by two experienced radiologists. Imaging results at different acceleration factors demonstrate that acceleration factors up to 6 could be obtained while keeping the average g-factor below 1.27. SNR maps demonstrate that combining loops and dipoles provides a more than 50% enhancement of the SNR in the heart, compared to a situation where only loops or dipoles are used. Conclusion This work demonstrates the performance of a combined loop/dipole array for cardiac imaging at 7 T. With this array, acceleration factors of 6 are possible without increasing the average g-factor in the heart beyond 1.27. Combining loops and dipoles in receive mode enhances the SNR compared to receiving with loops or dipoles only. Electronic supplementary material The online version of this article (10.1007/s10334-017-0665-5) contains supplementary material, which is available to authorized users.

Background Inter-professional collaboration is considered essential in effective maternity care. National projects are being undertaken to enhance inter-professional relationships and improve communication between all maternity care providers in order to improve the quality of maternity care in the Netherlands. However, little is known about primary care midwives' satisfaction with collaboration with other maternity care providers, such as general practitioners, maternity care assistance organisations (MCAO), maternity care assistants (MCA), obstetricians, clinical midwives and paediatricians. More insight is needed into the professional working relations of primary care midwives in the Netherlands before major changes are made Objective To assess how satisfied primary care midwives are with collaboration with other maternity care providers and to assess the relationship between their ‘satisfaction with collaboration' and personal and work-related characteristics of the midwives, their attitudes towards their work and collaboration characteristics (accessibility). The aim of this study was to provide insight into the professional working relations of primary care midwives in the Netherlands. Methods Our descriptive cross-sectional study is part of the DELIVER study. Ninety nine midwives completed a written questionnaire in May 2010. A Friedman ANOVA test assessed differences in satisfaction with collaboration with six groups of maternity care providers. Bivariate analyses were carried out to assess the relationship between satisfaction with collaboration and personal and work-related characteristics of the midwives, their attitudes towards their work and collaboration characteristics. Results Satisfaction experienced by primary care midwives when collaborating with the different maternity care providers varies within and between primary and secondary/tertiary care. Interactions with non-physicians (clinical midwives and MCA(O)) are ranked consistently higher on satisfaction compared with interactions with physicians (GPs, obstetricians and paediatricians). Midwives with more work experience were more satisfied with their collaboration with GPs. Midwives from the southern region of the Netherlands were more satisfied with collaboration with GPs and obstetricians. Compared to the urban areas, in the rural or mixed areas the midwives were more satisfied regarding their collaboration with MCA(O)s and clinical midwives. Midwives from non-Dutch origin were less satisfied with the collaboration with paediatricians. No relations were found between the overall mean satisfaction of collaboration and work-related and personal characteristics and attitude towards work. Conclusions Inter-professionals relations in maternity care in the Netherlands can be enhanced, especially the primary care midwives' interactions with physicians and with maternity care providers in the northern and central part of the Netherlands, and in urban areas. Future exploratory or deductive research may provide additional insight in the collaborative practice in everyday work setting.

Our aim was to determine whether a fermented milk drink containing probiotics could improve the bowel habits of frail elderly individuals living in a nursing home. A total of 135 participants were enrolled in this pilot study. The bowel habits (stool quality and bowel movements) were recorded by nursing staff during a baseline period of 3 weeks. After this period participants received daily a fermented milk drink containing minimally 6.5×109 colony forming units of Lactobacillus casei Shirota (LcS) for 6 weeks. During this period, bowel habits were recorded and compared to baseline period. Forty-four participants (74-99 years old) were compliant and used for analysis. Consumption of fermented milk containing LcS significantly increased the percentage of ideal stool types per week (P

PURPOSE: (13)C magnetic resonance spectroscopy (MRS) in combination with infusion of (13)C-labeled substrates has led to unique insights into human brain metabolism and neurotransmitter cycling. However, the low sensitivity of direct (13)C MRS and high radiofrequency (RF) power requirements has limited (13)C MRS studies to predominantly data acquisition in large volumes of the occipital cortex. The purpose of this study is to develop an MRS technique for localized detection of (13)C-labeling of glutamate and glutamine in the human frontal lobe. METHODS: We used an indirect ((1)H-[(13)C]), proton-observed, carbon-edited MRS sequence (selPOCE) for detection of (13)C-labeled metabolites in relatively small volumes located in the frontal lobe at 4 Tesla. SelPOCE allows for selective and separate detection of glutamate and glutamine resonances, which significantly overlap at magnetic field strengths used for clinical MRI. RESULTS: Phantom data illustrate how selPOCE can be tuned to selectively detect (13)C labeling in different metabolites. 3D specific absorption rates (SAR) simulations of RF power deposition show that the selPOCE method operates comfortably within the global and local FDA SAR guidelines. In vivo selPOCE data are presented acquired from a 45 mL volume in the frontal lobe of healthy subjects. The in vivo data show the time-dependent (13)C-labeling of glutamate and glutamine during intravenous infusion of [1-(13)C]-glucose. Metrics describing spectral fitting quality of the glutamate and glutamine resonances are reported. CONCLUSION: SelPOCE allows the detection of (13)C-labeling in glutamate and glutamine from a relatively small volume in the human frontal lobe at low RF power requirements.

We assessed the very long-term follow-up of a large cohort of unselected patients treated with coronary rotational atherectomy (RA). All 143 patients who underwent RA at our institution from 2000 to 2013 and with complete baseline and follow-up information were analyzed in a retrospective manner. Major adverse cardiac events (MACE) were defined as the composite of target vessel revascularization (TVR), acute myocardial infarction, and all-cause mortality. The mean follow-up was 8.2 years. The 10-year cumulative incidence of MACE for all patients was 57.9% (standard error [SE]: 5.0%). When comparing patients who received a drug-eluting stent (DES; n = 68) versus patients who did not (balloon only, bare-metal stent, or none of the aforementioned; n = 75), the RA + DES demonstrated very long-term MACE of 49.2% (SE: 7.5%) versus 62.7% (SE: 6.1%), P = .160 with TVR as the most discriminating factor, 10.7% (SE: 4.0%) versus 29.2% (SE: 6.0%), P = .016. Our results point to RA having reasonable long-term clinical results, especially in combined treatment with DES. To date, our study has the longest follow-up after RA.

Dynamic contrast‐enhanced MRI is the workhorse of breast MRI, where the diagnosis of lesions is largely based on the enhancement curve shape. However, this curve shape is biased by RF transmit (B 1 +) field inhomogeneities. B 1 + field information is required in order to correct these. The use of a generic, coil‐specific B 1 + template is proposed and tested. Finite‐difference time‐domain simulations for B 1 + were performed for healthy female volunteers with a wide range of breast anatomies. A generic B 1 + template was constructed by averaging simulations based on four volunteers. Three‐dimensional B 1 + maps were acquired in 15 other volunteers. Root mean square error (RMSE) metrics were calculated between individual simulations and the template, and between individual measurements and the template. The agreement between the proposed template approach and a B 1 + mapping method was compared against the agreement between acquisition and reacquisition using the same mapping protocol. RMSE values (% of nominal flip angle) comparing individual simulations with the template were in the range 2.00‐4.01%, with mean 2.68%. RMSE values comparing individual measurements with the template were in the range8.1‐16%, with mean 11.7%. The agreement between the proposed template approach and a B 1 + mapping method was only slightly worse than the agreement between two consecutive acquisitions using the same mapping protocol in one volunteer: the range of agreement increased from ±16% of the nominal angle for repeated measurement to ±22% for the B 1 + template. With local RF transmit coils, intersubject differences in B 1 + fields of the breast are comparable to the accuracy of B 1 + mapping methods, even at 7 T. Consequently, a single generic B 1 + template suits subjects over a wide range of breast anatomies, eliminating the need for a time‐consuming B 1 + mapping protocol.

Objectives Patients with stage IV non-small cell lung cancer (NSCLC) are considered incurable and are mainly treated with palliative intent. This patient group has a poor overall survival (OS) and progression free survival (PFS). The purpose of this study was to investigate PFS and OS of NSCLC patients diagnosed with synchronous oligometastatic disease who underwent radical treatment of both intrathoracic disease and metastases. Materials and methods Patients with NSCLC and oligometastatic disease at diagnosis, who were treated with radical intent between 2008 and 2016, were included in this observational study. Treatment consisted of systemic treatment and radical radiotherapy or resection of the intrathoracic disease. Treatment of the metastases consisted of radical or stereotactic radiotherapy, surgical resection or radiofrequency ablation. Results and conclusions Ninety-one patients (52% men, mean age 60 years) in good performance status were included. Thirty-eight patients (42%) died during follow-up (median follow-up 35 months). The cause of dead was lung cancer in all patients, except one. Sixty-three (69%) patients developed recurrent disease. Eleven recurrences (17%) occurred within the irradiated area. For the whole group, the median PFS was 14 months (range 2–89, 95%CI 12–16) and the median OS was 32 months (range 3–89, 95%CI 25–39). The 1- and 2-year OS rates were 85% and 58% and the 1- and 2-year PFS rates were 55% and 27%, respectively. Radical local treatment of a selected group of NSCLC patients with good performance status presenting with synchronous oligometastatic disease resulted in favorable long-term PFS and OS.

We studied the feasibility of high-resolution T2-weighted cervical cancer imaging on an ultra-high-field 7.0-T magnetic resonance imaging (MRI) system using an endorectal antenna of 4.7-mm thickness. A feasibility study on 20 stage IB1–IIB cervical cancer patients was conducted. All underwent pre-treatment 1.5-T MRI. At 7.0-T MRI, an external transmit/receive array with seven dipole antennae and a single endorectal monopole receive antenna were used. Discomfort levels were assessed. Following individualised phase-based B1 + shimming, T2-weighted turbo spin echo sequences were completed. Patients had stage IB1 (n = 9), IB2 (n = 4), IIA1 (n = 1) or IIB (n = 6) cervical cancer. Discomfort (ten-point scale) was minimal at placement and removal of the endorectal antenna with a median score of 1 (range, 0–5) and 0 (range, 0–2) respectively. Its use did not result in adverse events or pre-term session discontinuation. To demonstrate feasibility, T2-weighted acquisitions from 7.0-T MRI are presented in comparison to 1.5-T MRI. Artefacts on 7.0-T MRI were due to motion, locally destructive B1 interference, excessive B1 under the external antennae and SENSE reconstruction. High-resolution T2-weighted 7.0-T MRI of stage IB1–IIB cervical cancer is feasible. The addition of an endorectal antenna is well tolerated by patients. • High resolution T 2 -weighted 7.0-T MRI of the inner female pelvis is challenging • We demonstrate a feasible approach for T 2 -weighted 7.0-T MRI of cervical cancer • An endorectal monopole receive antenna is well tolerated by participants • The endorectal antenna did not lead to adverse events or session discontinuation

Aims Acute aortic dissection (AD) requires immediate treatment, but is a diagnostic challenge. We studied how often AD was missed initially, which patients were more likely to be missed and how this influenced patient management and outcomes. Methods A retrospective cohort study including 200 consecutive patients with AD as the final diagnosis, admitted to a tertiary hospital between 1998 and 2008. The first differential diagnosis was identified and patients with and without AD included were compared. Characteristics associated with a lower level of suspicion were identified using multivariable logistic regression, and Cox regression was used for survival analyses. Missing data were imputed. Results Mean age was 63 years, 39% were female and 76% had Stanford type A dissection. In 69% of patients, AD was included in the first differential diagnosis; this was less likely in women (adjusted relative risk [aRR]: 0.66, 95% CI: 0.44–0.99), in the absence of back pain (aRR: 0.51, 95% CI: 0.30–0.84), and in patients with extracardiac atherosclerosis (aRR: 0.64, 95% CI: 0.43–0.96). Absence of AD in the differential diagnosis was associated with the use of more imaging tests (1.8 vs. 2.3, p = 0.01) and increased time from admission to surgery (1.8 vs. 10.1 h, p < 0.01), but not with a difference in the adjusted long-term all-cause mortality (hazard ratio: 0.76, 95% CI: 0.46–1.27). Conclusion Acute aortic dissection was initially not suspected in almost one-third of patients, this was more likely in women, in the absence of back pain and in patients with extracardiac atherosclerosis. Although the number of imaging tests was higher and time to surgery longer, patient outcomes were similar in both groups. Electronic supplementary material The online version of this article (doi:10.1007/s12471-016-0921-8) contains supplementary material, which is available to authorized users.

Background The N -methyl-D-aspartate receptor hypofunction model of schizophrenia predicts dysfunction in both glutamatergic and gamma-aminobutyric acidergic (GABAergic) transmission. We addressed this hypothesis by measuring GABA, glutamate, glutamine, and the sum of glutamine plus glutamate concentrations in vivo in patients with schizophrenia using proton magnetic resonance spectroscopy at 7T, which allows separation of metabolites that would otherwise overlap at lower field strengths. In addition, we investigated whether altered levels of GABA, glutamate, glutamine, and the sum of glutamine plus glutamate reflect genetic vulnerability to schizophrenia by including healthy first-degree relatives. Methods Proton magnetic resonance spectroscopy at 7T was performed in 21 patients with chronic schizophrenia who were taking medication, 23 healthy first-degree relatives of patients with schizophrenia, and 24 healthy nonrelatives. Glutamate, glutamine, and GABA were measured cortically and subcortically in bilateral basal ganglia and occipital cortex. Results Patients with schizophrenia had reduced cortical GABA compared with healthy relatives and the combined sample of healthy relatives and healthy nonrelatives, suggesting that altered GABAergic systems in schizophrenia are associated with either disease state or medication effects. Reduced cortical glutamine relative to healthy control subjects was observed in patients with schizophrenia and the combined sample of healthy relatives and patients with schizophrenia, suggesting that altered glutamatergic metabolite levels are associated with illness liability. No group differences were found in the basal ganglia. Conclusions Taken together, these findings are consistent with alterations in GABAergic and glutamatergic systems in patients with schizophrenia and provide novel insights into these systems in healthy relatives.

Background Screening for, diagnosis and management of intrauterine growth restriction (IUGR) is often performed in multidisciplinary collaboration. However, variation in screening methods, diagnosis and management of IUGR may lead to confusion. In the Netherlands two monodisciplinary guidelines on IUGR do not fully align. To facilitate effective collaboration between different professionals in perinatal care, we undertook a Delphi study with uniform recommendations as our primary result, focusing on issues that are not aligned or for which specifications are lacking in the current guidelines. Methods We conducted a Delphi study in three rounds. A purposively sampled selection of 56 panellists participated: 27 representing midwife-led care and 29 obstetrician-led care. Consensus was defined as agreement between the professional groups on the same answer and among at least 70% of the panellists within groups. Results Per round 51 or 52 (91% - 93%) panellists responded. This has led to consensus on 27 issues, leading to four consensus based recommendations on screening for IUGR in midwife-led care and eight consensus based recommendations on diagnosis and eight on management in obstetrician-led care. The multidisciplinary project group decided on four additional recommendations as no consensus was reached by the panel. No recommendations could be made about induction of labour versus expectant monitoring, nor about the choice for a primary caesarean section. Conclusions We reached consensus on recommendations for care for IUGR within a multidisciplinary panel. These will be implemented in a study on the effectiveness and cost-effectiveness of routine third trimester ultrasound for monitoring fetal growth. Research is needed to evaluate the effects of implementation of these recommendations on perinatal outcomes.

Purpose To establish a preoperative decision model for accurate indication of systemic therapy in early-stage breast cancer using multiparametric MRI at 7-tesla field strength. Materials and methods Patients eligible for breast-conserving therapy were consecutively included. Patients underwent conventional diagnostic workup and one preoperative multiparametric 7-tesla breast MRI. The postoperative (gold standard) indication for systemic therapy was established from resected tumor and lymph-node tissue, based on 10-year risk-estimates of breast cancer mortality and relapse using Adjuvant! Online. Preoperative indication was estimated using similar guidelines, but from conventional diagnostic workup. Agreement was established between preoperative and postoperative indication, and MRI-characteristics used to improve agreement. MRI-characteristics included phospomonoester/phosphodiester (PME/PDE) ratio on 31-phosphorus spectroscopy (31P-MRS), apparent diffusion coefficients on diffusion-weighted imaging, and tumor size on dynamic contrast-enhanced (DCE)-MRI. A decision model was built to estimate the postoperative indication from preoperatively available data. Results We included 46 women (age: 43-74yrs) with 48 invasive carcinomas. Postoperatively, 20 patients (43%) had positive, and 26 patients (57%) negative indication for systemic therapy. Using conventional workup, positive preoperative indication agreed excellently with positive postoperative indication (N = 8/8; 100%). Negative preoperative indication was correct in only 26/38 (68%) patients. However, 31P-MRS score (p = 0.030) and tumor size (p = 0.002) were associated with the postoperative indication. The decision model shows that negative indication is correct in 21/22 (96%) patients when exempting tumors larger than 2.0cm on DCE-MRI or with PME>PDE ratios at 31P-MRS. Conclusions Preoperatively, positive indication for systemic therapy is highly accurate. Negative indication is highly accurate (96%) for tumors sized ≤2,0cm on DCE-MRI and with PME≤PDE ratios on 31P-MRS.