Objectives The objective of this study is to evaluate whether there are differences in the long-term prognosis across various phenotypes of early arthritis (EA).Methods Three EA cohorts (Reade,... Show moreObjectives The objective of this study is to evaluate whether there are differences in the long-term prognosis across various phenotypes of early arthritis (EA).Methods Three EA cohorts (Reade, Etude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) and Early Arthritis Clinic (EAC)) were analysed. Clinical data were collected up to 24 years. Hands and feet radiographs were scored according to the Sharp van der Heijde (SvdH) method. Latent class analysis was applied to determine the EA phenotypes at baseline. Each class received a label reflecting its most prominent features. Prognostic outcomes included Health Assessment Questionnaire (HAQ), Short Form 36 (SF36) and SvdH score. The association between class membership and outcomes over time was tested in multivariable models.Results In total, 390 (Reade), 798 (ESPOIR) and 3991 (EAC) patients were analysed separately. Two classes with symmetrical polyarthritis emerged; one of these labelled as autoimmune inflammatory polyarthritis (AIPA), had high likelihood of acute phase reactants (APR) elevation and autoantibody positivity, while the other (mild-inflammatory polyarthritis; MIPA) had not. A third class had oligoarthritis of upper limbs (OAUL) and could be subdivided into autoimmune OAUL and mild-inflammatory OAUL. A fifth class had oligoarthritis of lower limbs. The SvdH scores were worse in patients with APR/autoantibodies (AIPA) than in those without (MIPA). No clinically meaningful differences across classes in HAQ or SF36 over time were found.Conclusion Radiographic progression over time primarily occurs in EA patients with APR/autoantibodies. The absence of these markers, however, does not necessarily translate into better long-term function and quality of life. Clinicians should not only aim at preventing joint damage, but look beyond structural progression in order to further improve the lives of people with EA. Show less
Congenital cytomegalovirus (cCMV) infection can cause fluctuating hearing loss and vestibulopathy. The pathogenesis is unknown. This report describes a 13-year old boy with cCMV and severe hearing... Show moreCongenital cytomegalovirus (cCMV) infection can cause fluctuating hearing loss and vestibulopathy. The pathogenesis is unknown. This report describes a 13-year old boy with cCMV and severe hearing loss in the right ear since age 3, presenting with fluctuating hearing loss in the left ear and vestibular symptoms. 3D fluid attenuated inversion recovery (FLAIR) MRI showed endolymphatic hydrops in the acutely affected ear. This is the first description of a child with cCMV subjected to this imaging technique, raising the question whether endolymphatic hydrops could play a role in the development of late-onset symptoms and demonstrating the possibilities of this MRI sequence. Show less
Objectives To update the EULAR recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV).Methods A systematic literature review update was performed to retrieve new... Show moreObjectives To update the EULAR recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV).Methods A systematic literature review update was performed to retrieve new evidence on ultrasound, MRI, CT and [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) for diagnosis, monitoring and outcome prediction in LVV. The task force consisted of 24 physicians, health professionals and patients from 14 countries. The recommendations were updated based on evidence and expert opinion, iterating until voting indicated consensus. The level of agreement was determined by anonymous votes.Results Three overarching principles and eight recommendations were agreed. Compared to the 2018 version, ultrasound is now recommended as first-line imaging test in all patients with suspected giant cell arteritis, and axillary arteries should be included in the standard examination. As an alternative to ultrasound, cranial and extracranial arteries can be examined by FDG-PET or MRI. For Takayasu arteritis, MRI is the preferred imaging modality; FDG-PET, CT or ultrasound are alternatives. Although imaging is not routinely recommended for follow-up, ultrasound, FDG-PET or MRI may be used for assessing vessel abnormalities in LVV patients with suspected relapse, particularly when laboratory markers of inflammation are unreliable. MR-angiography, CT-angiography or ultrasound may be used for long-term monitoring of structural damage, particularly at sites of preceding vascular inflammation.Conclusions The 2023 EULAR recommendations provide up-to-date guidance for the role of imaging in the diagnosis and assessment of patients with LVV. Show less
Stal, R.; Ramiro, S.; Heijde, D. van der; Gaalen, F.A. van; Baraliakos, X.; Machado, P.M.; ... ; Sepriano, A. 2023
Objectives To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. Methods Patients with radiographic... Show moreObjectives To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. Methods Patients with radiographic axial spondyloarthritis (r-axSpA) from the SIAS (Sensitive Imaging in Ankylosing Spondylitis) cohort and ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial were assessed at T0, T1 (SIAS: 1 year; ASSERT: 24 weeks) and T2 (2 years). Syndesmophytes assessed in each vertebral corner by whole spine lowdose CT (SIAS) or spinal radiographs (ASSERT) at T0 and T2 were considered present if seen by two of two readers. Inflammation (T0) and fat deposition (T0 and T1) on MRI were present if seen by ≥2 of 3 readers (SIAS) or 2 of 2 readers (ASSERT). Vertebral corners showing fat deposition or a syndesmophyte at baseline were ignored. Mediation analysis was applied to determine what proportion of the total effect of inflammation on syndesmophyte formation could be explained via the path of intermediate fat deposition. Results Forty-nine SIAS patients (with 2667 vertebral corners) and 168 ASSERT patients (with 2918 vertebral corners) were analysed. The presence of inflammation at T0 increased the probability of a new syndesmophyte in the same vertebral corner at T2 by 9.3%. Of this total effect, 0.2% (2% (0.2 of 9.3) of the total effect) went via intermediate new fat deposition. In ASSERT, the total effect was 7.3%, of which 0.8% (10% of the total effect) went via new fat deposition. Conclusion In r-axSpA, vertebral corner inflammation may lead to syndesmophyte formation but in a minority of cases via visible fat deposition. Show less
Stal, R.; Ramiro, S.; Heijde, D. van der; Gaalen, F.A. van; Baraliakos, X.; Machado, P.M.; ... ; Sepriano, A. 2023
Objectives: To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. Methods: Patients with... Show moreObjectives: To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. Methods: Patients with radiographic axial spondyloarthritis (r-axSpA) from the SIAS (Sensitive Imaging in Ankylosing Spondylitis) cohort and ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial were assessed at T0, T1 (SIAS: 1 year; ASSERT: 24 weeks) and T2 (2 years). Syndesmophytes assessed in each vertebral corner by whole spine low-dose CT (SIAS) or spinal radiographs (ASSERT) at T0 and T2 were considered present if seen by two of two readers. Inflammation (T0) and fat deposition (T0 and T1) on MRI were present if seen by & GE;2 of 3 readers (SIAS) or 2 of 2 readers (ASSERT). Vertebral corners showing fat deposition or a syndesmophyte at baseline were ignored. Mediation analysis was applied to determine what proportion of the total effect of inflammation on syndesmophyte formation could be explained via the path of intermediate fat deposition. Results: Forty-nine SIAS patients (with 2667 vertebral corners) and 168 ASSERT patients (with 2918 vertebral corners) were analysed. The presence of inflammation at T0 increased the probability of a new syndesmophyte in the same vertebral corner at T2 by 9.3%. Of this total effect, 0.2% (2% (0.2 of 9.3) of the total effect) went via intermediate new fat deposition. In ASSERT, the total effect was 7.3%, of which 0.8% (10% of the total effect) went via new fat deposition. Conclusion: In r-axSpA, vertebral corner inflammation may lead to syndesmophyte formation but in a minority of cases via visible fat deposition. Show less
Stal, R.; Ramiro, S.; Heijde, D. van der; Gaalen, F.A. van; Baraliakos, X.; Machado, P.M.; ... ; Sepriano, A. 2023
Objectives To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition.Methods Patients with radiographic... Show moreObjectives To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition.Methods Patients with radiographic axial spondyloarthritis (r-axSpA) from the SIAS (Sensitive Imaging in Ankylosing Spondylitis) cohort and ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial were assessed at T0, T1 (SIAS: 1 year; ASSERT: 24 weeks) and T2 (2 years). Syndesmophytes assessed in each vertebral corner by whole spine low-dose CT (SIAS) or spinal radiographs (ASSERT) at T0 and T2 were considered present if seen by two of two readers. Inflammation (T0) and fat deposition (T0 and T1) on MRI were present if seen by ≥2 of 3 readers (SIAS) or 2 of 2 readers (ASSERT). Vertebral corners showing fat deposition or a syndesmophyte at baseline were ignored. Mediation analysis was applied to determine what proportion of the total effect of inflammation on syndesmophyte formation could be explained via the path of intermediate fat deposition.Results Forty-nine SIAS patients (with 2667 vertebral corners) and 168 ASSERT patients (with 2918 vertebral corners) were analysed. The presence of inflammation at T0 increased the probability of a new syndesmophyte in the same vertebral corner at T2 by 9.3%. Of this total effect, 0.2% (2% (0.2 of 9.3) of the total effect) went via intermediate new fat deposition. In ASSERT, the total effect was 7.3%, of which 0.8% (10% of the total effect) went via new fat deposition.Conclusion In r-axSpA, vertebral corner inflammation may lead to syndesmophyte formation but in a minority of cases via visible fat deposition. Show less
The research described in this thesis implemented Magnetic Resonance Imaging (MRI) as a diagnostic imaging technique in uveal melanoma, by developing a dedicated eye MRI protocol and extensively... Show moreThe research described in this thesis implemented Magnetic Resonance Imaging (MRI) as a diagnostic imaging technique in uveal melanoma, by developing a dedicated eye MRI protocol and extensively evaluating the MR imaging characteristics of uveal melanoma. This improved the diagnosis and treatment of uveal melanoma, sometimes enabling an eye-preserving therapy instead of enucleation.Furthermore, the imaging characteristics of orbital inflammation were reviewed and a systematic approach for the radiological evaluation of these patients was proposed. It allows one to recognize an orbital solid enhancing lesion as inflammatory, and not to mistake it for infection or tumor, and it will help recognizing its underlying inflammatory disease. This enables the treating physician to establish an adequate treatment and at times a biopsy can be avoided. Finally, a dedicated eyelid MRI protocol was developed and it was assessed whether the different eyelid layers are possibly to identify on MRI (as well as on Computer Tomography), in order to improve the evaluation of the local extension of an eyelid tumor, important for the surgical planning and outcome. Show less
Khidir, S.J.H.; Dijk, B.T. van; Krijbolder, D.I.; Verstappen, M.; Mulligen, E. van; Helm-van Mil, A.H.M. van der 2023
Objectives: It is unknown whether rheumatoid arthritis (RA) starts in hands or feet. To investigate this, we performed functional, clinical and imaging studies during progression from clinically... Show moreObjectives: It is unknown whether rheumatoid arthritis (RA) starts in hands or feet. To investigate this, we performed functional, clinical and imaging studies during progression from clinically suspect arthralgia (CSA) to RA. Additionally, we studied whether functional disabilities of hands/feet at CSA onset contribute to predicting RA development. Methods: 600 patients with CSA were followed for clinical inflammatory arthritis (IA) during median follow-up of 25 months, during which 99 developed IA. Functional disabilities were measured at baseline/4/12/24 months with the Health Assessment Questionnaire Disability Index (HAQ); HAQ items assessing hand disabilities and foot disabilities were selected. The course of disabilities towards IA development (here considered as t=0) was depicted by increasing incidences and analysed using linear mixed models. To evaluate robustness of findings, tender hand/foot joints and subclinical joint inflammation (measured with CE-1.5TMRI) of hand/foot were additionally studied. Associations between disabilities at CSA presentation (here t=0) and future IA development were studied using Cox regression in the total CSA population.Results: During IA development, hand disabilities occurred earlier and more frequently than foot disabilities. Despite both hand disabilities and foot disabilities rose significantly towards IA development, hand disabilities were more severe during this course (mean difference over time: 0.41 units, 95% CI 0.28 to 0.55, p<0.001, on a range 0-3). Similar to functional disabilities, tender joints and subclinical joint inflammation occurred earlier in the hands than feet. In the total CSA population, a single HAQ question on difficulties with dressing (hand functioning) was independently predictive for IA development: HR=2.2, 95% CI 1.4 to 3.5, p=0.001.Conclusion: Evaluation of functional disabilities, supported by clinical and imaging findings, revealed that joint involvement starts predominantly in the hands during RA development. Additionally, a single question on dressing difficulties adds value to risk stratification in patients with CSA. Show less
Khidir, S.J.H.; Dijk, B.T. van; Krijbolder, D.I.; Verstappen, M.; Mulligen, E. van; Helm-van Mil, A.H.M. van der 2023
Objectives It is unknown whether rheumatoid arthritis (RA) starts in hands or feet. To investigate this, we performed functional, clinical and imaging studies during progression from clinically... Show moreObjectives It is unknown whether rheumatoid arthritis (RA) starts in hands or feet. To investigate this, we performed functional, clinical and imaging studies during progression from clinically suspect arthralgia (CSA) to RA. Additionally, we studied whether functional disabilities of hands/feet at CSA onset contribute to predicting RA development.Methods 600 patients with CSA were followed for clinical inflammatory arthritis (IA) during median follow-up of 25 months, during which 99 developed IA. Functional disabilities were measured at baseline/4/12/24 months with the Health Assessment Questionnaire Disability Index (HAQ); HAQ items assessing hand disabilities and foot disabilities were selected. The course of disabilities towards IA development (here considered as t=0) was depicted by increasing incidences and analysed using linear mixed models. To evaluate robustness of findings, tender hand/foot joints and subclinical joint inflammation (measured with CE-1.5TMRI) of hand/foot were additionally studied. Associations between disabilities at CSA presentation (here t=0) and future IA development were studied using Cox regression in the total CSA population.Results During IA development, hand disabilities occurred earlier and more frequently than foot disabilities. Despite both hand disabilities and foot disabilities rose significantly towards IA development, hand disabilities were more severe during this course (mean difference over time: 0.41 units, 95% CI 0.28 to 0.55, p<0.001, on a range 0–3). Similar to functional disabilities, tender joints and subclinical joint inflammation occurred earlier in the hands than feet. In the total CSA population, a single HAQ question on difficulties with dressing (hand functioning) was independently predictive for IA development: HR=2.2, 95% CI 1.4 to 3.5, p=0.001.Conclusion Evaluation of functional disabilities, supported by clinical and imaging findings, revealed that joint involvement starts predominantly in the hands during RA development. Additionally, a single question on dressing difficulties adds value to risk stratification in patients with CSA. Show less
In this thesis, multiple approaches have been investigated for the simultaneous acquisition of 4D angiography and perfusion images using arterial spin labeling (ASL) MRI. Time-encoded pseudo... Show moreIn this thesis, multiple approaches have been investigated for the simultaneous acquisition of 4D angiography and perfusion images using arterial spin labeling (ASL) MRI. Time-encoded pseudo-continuous (ASL) preparation was combined with multiple different readout modules, such as Look-Locker, Simultaneous multi-slice acquisition or a golden angle based non-Cartesian k-space trajectory to obtain high temporal resolution multi-time point data. These datasets were then used to improve the quantification of ASL signal and to obtain cerebral blood flow, arterial transit time and arterial blood volume maps. These quantitative maps hold the potential to provide important information in for example patients with stroke or Alzheimer’s disease. In addition, one of the assumptions within the two-component kinetic model to obtain these quantitative maps was investigated to study the separation of the macrovascular and perfusion component of the ASL signal. Show less
Background: Clinically suspect arthralgia (CSA) is characterised by arthralgia of small joints and considered a risk stage for development of rheumatoid arthritis (RA). However, it remains unknown... Show moreBackground: Clinically suspect arthralgia (CSA) is characterised by arthralgia of small joints and considered a risk stage for development of rheumatoid arthritis (RA). However, it remains unknown if the function of the hands is already affected and what mechanisms underlie impaired hand-function in CSA.Methods: We studied various measures of hand function in two CSA populations. CSA patients in the TREAT EARLIER-trial (n=236) were evaluated at baseline for: grip strength on a dynamometer (GS), patient-reported difficulties in the grip domain of the Health Assessment Questionnaire (HAQ) questionnaire and incomplete fist closure at physical examination. Findings were validated in an independent CSA cohort (n=600) where hand function was measured as: GS evaluated by squeezing the examiner's fingers, grip domain of the HAQ questionnaire and fist closure. Contrast-enhanced MRI of the hands measured synovitis, tenosynovitis and bone marrow oedema (summed as subclinical inflammation) in both cohorts. Results: GS (on a dynamometer) was reduced in 75% compared with reference values in healthy controls, 60% reported grip difficulties and 13% had incomplete fist closure. Reduced GS was associated with subclinical inflammation (-0.38 kg/point inflammation, 95% CI -0.68 to -0.08). Studying separate MRI features, GS reduction was independently associated with tenosynovitis, decreasing with -2.63 kg (95% CI -2.26 to -0.33)/point tenosynovitis (range observed tenosynovitis scores: 0-20). Similar relations with tenosynovitis were seen for patient-reported grip difficulties (OR 1.12/point, 95% CI 1.07 to 1.42) and incomplete fist closure (OR 1.36/point, 95% CI 1.03 to 1.79). In the validation cohort, 36% had decreased examiner-assessed GS, 51% reported grip difficulties and 14% incomplete fist closure: all were associated with tenosynovitis. Decreased dynamometer-measured GS was most sensitive for detecting tenosynovitis (75%), while incomplete fist closure was most specific (88%-90%). Conclusion: Hand function is already often affected before RA development. These limitations are related to subclinical inflammation and tenosynovitis in particular. Show less
Chung, P.K.; Schornagel, F.; Oudesluys-Murphy, A.M.; Vries, L.S. de; Soede, W.; Zwet, E. van; Vossen, A. 2022
ObjectiveTo evaluate clinical, audiological and neuroimaging findings in a cohort of infants diagnosed with congenital cytomegalovirus (cCMV) infection after failure at newborn hearing screening.... Show moreObjectiveTo evaluate clinical, audiological and neuroimaging findings in a cohort of infants diagnosed with congenital cytomegalovirus (cCMV) infection after failure at newborn hearing screening. MethodsA prospective observational study in the Netherlands, using the existing newborn hearing screening infrastructure for well babies. Between July 2012 and November 2016, cytomegalovirus (CMV) PCR testing of neonatally obtained dried blood spots (DBS) was offered to all infants who failed newborn hearing screening. Clinical, neuroimaging and audiological data were collected. ResultsDBS of 1374 infants were successfully tested and 59 were positive for CMV (4.3%). Data of 54 infants were retrieved. Three were small for gestational age and six had microcephaly. Forty-eight (89%) had sensorineural hearing loss (SNHL), of whom half had unilateral SNHL. In both unilaterally and bilaterally affected children, the majority of the impaired ears had severe or profound hearing loss. Neuroimaging abnormalities were found in 40 of 48 (83%) children who had evaluable cranial ultrasound and/or cerebral MRI. The abnormalities were mild in 34, moderate in 3 and severe in 3 infants. The degree of SNHL and the severity of neuroimaging abnormalities were found to be correlated (p=0.002). ConclusionsThe yield of targeted cCMV screening following newborn hearing screening failure was eight times higher than the estimated national birth prevalence of cCMV. The majority of this cohort of infants with clinically unsuspected cCMV disease had confirmed SNHL, neuroimaging abnormalities and lower than average birth weights and head circumferences. Newborns who fail newborn hearing screening should be tested for CMV to ensure appropriate clinical, neurodevelopmental and audiological follow-up. Show less
Heijde, D. van der; Baraliakos, X.; Sieper, J.; Deodhar, A.; Inman, R.D.; Kameda, H.; ... ; Song, I.H. 2022
Objectives: To evaluate the efficacy and safety of upadacitinib, a Janus kinase inhibitor, in patients with active ankylosing spondylitis (AS) with an inadequate response (IR) to biological disease... Show moreObjectives: To evaluate the efficacy and safety of upadacitinib, a Janus kinase inhibitor, in patients with active ankylosing spondylitis (AS) with an inadequate response (IR) to biological disease-modifying antirheumatic drugs (bDMARDs). Methods: Adults with active AS who met modified New York criteria and had an IR to one or two bDMARDs (tumour necrosis factor or interleukin-17 inhibitors) were randomised 1:1 to oral upadacitinib 15 mg once daily or placebo. The primary endpoint was Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Sequentially tested secondary endpoints included Ankylosing Spondylitis Disease Activity score, Spondyloarthritis Research Consortium of Canada MRI spine inflammation score, total back pain, nocturnal back pain, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index and Maastricht Ankylosing Spondylitis Enthesitis Score. Results are reported from the 14-week double-blind treatment period. Results: A total of 420 patients with active AS were randomised (upadacitinib 15 mg, n=211; placebo, n=209). Significantly more patients achieved the primary endpoint of ASAS40 at week 14 with upadacitinib vs placebo (45% vs 18%; p<0.0001). Statistically significant improvements were observed with upadacitinib vs placebo for all multiplicity-controlled secondary endpoints (p<0.0001). Adverse events were reported for 41% of upadacitinib-treated and 37% of placebo-treated patients through week 14. No events of malignancy, major adverse cardiovascular events, venous thromboembolism or deaths were reported with upadacitinib. Conclusion: Upadacitinib 15 mg was significantly more effective than placebo over 14 weeks of treatment in bDMARD-IR patients with active AS. No new safety risks were identified with upadacitinib. Show less
Baraliakos, X.; Ostergaard, M.; Lambert, R.G.W.; Eshed, I.; Machado, P.M.; Pedersen, S.J.; ... ; Maksymowych, W. 2022
Objectives: Spinal MRI is used to visualise lesions associated with axial spondyloarthritis (axSpA). The ASAS MRI working group (WG) updated and validated the definitions for inflammatory and... Show moreObjectives: Spinal MRI is used to visualise lesions associated with axial spondyloarthritis (axSpA). The ASAS MRI working group (WG) updated and validated the definitions for inflammatory and structural spinal lesions in the context of axSpA. Methods: After review of the existing literature on all possible types of spinal MRI pathologies in axSpA, the group (12 rheumatologists and two radiologists) consented on the required revisions of lesion definitions compared with the existing nomenclature of 2012. In a second step, using 62 MRI scans from the ASAS classification cohort, the proposed definitions were validated in a multireader campaign by global (absent/present) and detailed (inflammation and structural) lesion assessment at the vertebral corner (VC), vertebral endplate, facet joints, transverse processes, lateral and posterior elements. Intraclass correlation coefficient (ICC) was used for analysis. Results: Revisions were made for both inflammatory (bone marrow oedema, BMO) and structural (fat, erosion, bone spur and ankylosis) lesions, including localisation (central vs lateral), extension (VC vs vertebral endplate) and extent (minimum number of slices needed), while new definitions were suggested for the type of lesion based on lesion maturity (VC monomorphic vs dimorphic). The most reliably assessed lesions were VC fat lesion and VC monomorphic BMO (ICC (mean of all 36 reader pairs/overall 9 readers): 0.91/0.92; 0.70/0.67, respectively. Conclusions: The lesion definitions for spinal MRI lesions compatible with SpA were updated by consensus and validated by a group of experienced readers. The lesions with the highest frequency and best reliability were fat and monomorphic inflammatory lesions at the VC. Show less
Background Aortic stiffness, assessed through pulse wave velocity (PWV), is an independent predictor for cardiovascular disease risk. However, the scarce availability of normal and reference values... Show moreBackground Aortic stiffness, assessed through pulse wave velocity (PWV), is an independent predictor for cardiovascular disease risk. However, the scarce availability of normal and reference values for cardiovascular magnetic resonance imaging (CMR) based PWV is limiting clinical implementation. The aim of this study was to determine normal and reference values for CMR assessed PWV in the general population. Methods From the 2,484 participants of the Netherlands Epidemiology of Obesity (NEO) study that have available CMR-PWV data, 1,394 participants free from cardiovasculard disease, smokers or treatment for diabetes, hypertension or dyslipidaemia were selected (45-65 years, 51% female). Participants were divided into sex, age and blood pressure (BP) subgroups. Normal values were specified for participants with a BP < 130/80 mmHg and reference values for elevated BP subgroups (>= 130/80 and < 140/90 mmHg; and >= 140/90 mmHg). Differences between groups were tested with independent samples t-test or ANOVA. Due to an oversampling of obese individuals in this study, PWV values are based on a weighted analysis making them representative of the general population. Results Normal mean PWV was 6.0 m/s [95% CI 5.8-6.1]. PWV increased with advancing age and BP categories (both p < 0.001). There was no difference between sex in normal PWV, however in the BP > 140/90 mmHg women had a higher PWV (p = 0.005). The interpercentile ranges were smaller for participants < 55 years old compared to participants >= 55 years, indicating an increasing variability of PWV with age. PWV upper limits were particularly elevated in participants >= 55 years old in the high blood pressure subgroups. Conclusion This study provides normal and reference values for CMR-assessed PWV per sex, age and blood pressure category in the general population. Show less
Objective: This study evaluated the correlation between intratumoural stmma proportion, expressed as tumour-stroma ratio (TSR), and apparent diffusion coefficient (ADC) values in patients with... Show moreObjective: This study evaluated the correlation between intratumoural stmma proportion, expressed as tumour-stroma ratio (TSR), and apparent diffusion coefficient (ADC) values in patients with rectal cancer.Methods: This multicentre retrospective study included all consecutive patients with rectal cancer, diagnostically confirmed by biopsy and MRI. The training cohort (LUMC, Netherlands) included 33 patients and the validation cohort (VHIO, Spain) 69 patients. Two observers measured the mean and minimum ADCs based on single-slice and whole-volume segmentations. The TSR was determined on diagnostic haematoxylin & eosin stained slides of rectal tumour biopsies. The correlation between TSR and ADC was assessed by Spearman correlation (r(s)).Results: The ADC values between stroma-low and stroma-high tumours were not significantly different. Intraclass correlation (ICC) demonstrated a good level of agreement for the ADC measurements, ranging from 0.84-0.86 for single slice and 0.86-0.90 for the whole-volume protocol. No correlation was observed between the TSR and ADC values, with ADC(mean), r(s) = -0.162 (p= 0.38) and ADC(m)(in), r(s) = 0.041 (p= 0.82) for the single-slice and r(s) = -0.108 (p= 0.55) and r(s) = 0.019 (p= 0.92) for the whole-volume measurements in the training cohort, respectively. Results from the validation cohort were consistent; ADC(mean )r(s) = -0.022 (p= 0.86) and ADC(min), r(s) = 0.049 (p= 0.69) for the single-slice and r(s) = -0.064 (p= 0.59) and r(s) = -0.063 (p= 0.61) for the whole-volume measurements.Conclusions: Reproducibility of ADC values is good. Despite positive reports on the correlation between TSR and ADC values in other tumours, this could not be confirmed for rectal cancer. Show less
This thesis focused on investigating the early identification of Rheumatoid Arthritis (RA), assessing the burden of disease, and enhancing understanding of disease mechanisms in the earliest... Show moreThis thesis focused on investigating the early identification of Rheumatoid Arthritis (RA), assessing the burden of disease, and enhancing understanding of disease mechanisms in the earliest disease phases. Many of the studies in this thesis focused on data from the Leiden Clinically Suspect Arthralgia (CSA) cohort. The CSA cohort is an inception cohort at the rheumatology outpatient clinic of the Leiden University Medical Centre, in Leiden, the Netherlands. CSA patients had recent-onset (We showed that although early identification is increasingly improving, there remains a large proportion of patients that cannot be accurately identified despite a suspect pattern of signs and symptoms, as well as information on autoantibodies. Furthermore, the burden of disease is already substantial during the symptomatic pre-arthritis phase of CSA. Future studies will have to provide evidence for the effectiveness of preventing persistent RA and functional disability with prescribing Disease-modifying antirheumatic drugs (DMARD) treatment in the phase of CSA. Show less
This thesis investigates the relations between metabolism and anatomy through the use of Magnetic Resonance Imaging (MRI). Two model systems are studied: Botryococcus braunii, a green oleaginous... Show moreThis thesis investigates the relations between metabolism and anatomy through the use of Magnetic Resonance Imaging (MRI). Two model systems are studied: Botryococcus braunii, a green oleaginous algae and Medicago truncatula, a small leguminous plant in symbiosis with Sinorhizobium meliloti bacteria. In order to map the variation of metabolic profiles across tissues, MRI is used extensively, including Chemical Shift Imaging, Magnetic Resonance Spectroscopy and Diffusion-Weigthed Imaging. Home-built microcoils for ultra-high magnetic field strength are developed for studying the model organisms. Show less
This thesis about deep vein thrombosis consists of two parts. The studies described in the first part of this thesis aimed to improve the diagnostic management of deep vein thrombosis (DVT) in... Show moreThis thesis about deep vein thrombosis consists of two parts. The studies described in the first part of this thesis aimed to improve the diagnostic management of deep vein thrombosis (DVT) in general, and in diagnostic challenging circumstances specifically. First, a new diagnostic safety threshold for all future diagnostic studies in deep vein thrombosis was established, adjusted to the disease prevalence in the study population. Thereafter a new simpler clinical decision rule, as first step in the diagnostic management of DVT was designed, selecting 4 items of the Wells rule. In the following chapter’s, studies using the MRI technique: Magnetic Resonance Direct Thrombus Imaging (MRDTI) were described. This is a non-contrast enhanced MRI technique by which a thrombus can be visualized directly. This technique was applied to diagnose DVT in challenging circumstances: ipsilateral recurrent DVT, DVT in pregnant woman and upper extremity DVT. The second part of this thesis describes studies that aimed to improve the prognosis of DVT by evaluation of the persistence to prescribed therapy and predictors of the development of post thrombotic syndrome (PTS). Show less
