Background and ObjectivesIt is important to identify at what age brain atrophy rates in genetic frontotemporal dementia (FTD) start to accelerate and deviate from normal aging effects to find the... Show moreBackground and ObjectivesIt is important to identify at what age brain atrophy rates in genetic frontotemporal dementia (FTD) start to accelerate and deviate from normal aging effects to find the optimal starting point for treatment. We investigated longitudinal brain atrophy rates in the presymptomatic stage of genetic FTD using normative brain volumetry software.MethodsPresymptomatic GRN, MAPT, and C9orf72 pathogenic variant carriers underwent longitudinal volumetric T1-weighted magnetic resonance imaging of the brain as part of a prospective cohort study. Images were automatically analyzed with Quantib (R) ND, which consisted of volume measurements (CSF and sum of gray and white matter) of lobes, cerebellum, and hippocampus. All volumes were compared with reference centile curves based on a large population-derived sample of nondemented individuals (n = 4,951). Mixed-effects models were fitted to analyze atrophy rates of the different gene groups as a function of age.ResultsThirty-four GRN, 8 MAPT, and 14 C9orf72 pathogenic variant carriers were included (mean age = 52.1, standard deviation = 7.2; 66% female). The mean follow-up duration of the study was 64 +/- 33 months (median = 52; range 13-108). GRN pathogenic variant carriers showed a faster decline than the reference centile curves for all brain areas, though relative volumes remained between the 5th and 75th percentiles between the ages of 45 and 70 years. In MAPT pathogenic variant carriers, frontal lobe volume was already at the 5th percentile at age 45 years and showed a further decline between the ages 50 and 60 years. Temporal lobe volume started in the 50th percentile at age 45 years but showed fastest decline over time compared with other brain structures. Frontal, temporal, parietal, and cerebellar volume already started below the 5th percentile compared with the reference centile curves at age 45 years for C9orf72 pathogenic variant carriers, but there was minimal decline over time until the age of 60 years.DiscussionWe provide evidence for longitudinal brain atrophy in the presymptomatic stage of genetic FTD. The affected brain areas and the age after which atrophy rates start to accelerate and diverge from normal aging slopes differed between gene groups. These results highlight the value of normative volumetry software for disease tracking and staging biomarkers in genetic FTD. These techniques could help in identifying the optimal time window for starting treatment and monitoring treatment response. Show less
Gao, S.; Klooster, R. van 't; Kitslaar, P.H.; Coolen, B.F.; Berg, A.M. van den; Smits, L.P.; ... ; Geest, R.J. van der 2017
Conclusions: Assessment of progression in hand OA defined by JSW measurements is possible, but performs less well than progression defined by JSN scoring. Therefore, the value of JSW measurements... Show moreConclusions: Assessment of progression in hand OA defined by JSW measurements is possible, but performs less well than progression defined by JSN scoring. Therefore, the value of JSW measurements in hand OA clinical trials remains questionable. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Show less
Damman, W.; Kortekaas, M.C.; Stoel, B.C.; Klooster, R. van 't; Rosendaal, F.R.; Kloppenburg, M. 2015
The main goal of this thesis was to develop methods for automated segmentation, registration and classification of the carotid artery vessel wall and plaque components using multi-sequence MR... Show moreThe main goal of this thesis was to develop methods for automated segmentation, registration and classification of the carotid artery vessel wall and plaque components using multi-sequence MR vessel wall images to assess atherosclerosis. First, a general introduction into atherosclerosis and different stages of the disease were described including the importance to differentiate between stable and vulnerable plaques. Several non-invasive imaging techniques were discussed and the advantages of multi-sequence MRI were highlighted. Different novel automated image segmentation and registration techniques for analysis of the MRI images have been developed. A 3D vessel model to automatically segment the vessel wall was presented. Automated image registration was applied to correct for patient movement during the acquisition of an MRI scan and between MRI scans. The last topic is the automatic classification of the different plaque components which can be present inside the vessel wall. All techniques were developed and validated using relevant patient data and reference standards. The work presented is an important contribution to the automated analysis of multi-sequence MR vessel wall imaging of the carotid artery. These techniques can speed up the current manual analysis and are potentially more accurate and more reproducible. Show less
Klooster, R. van 't; Patterson, A.J.; Young, V.E.; Gillard, J.H.; Reiber, J.H.C.; Geest, R.J. van der 2013
Objective: Arthropathy is an invalidating complication of acromegaly. Although acromegalic arthropathy shares features with primary osteoarthritis, joint spaces are widened rather than narrowed in... Show moreObjective: Arthropathy is an invalidating complication of acromegaly. Although acromegalic arthropathy shares features with primary osteoarthritis, joint spaces are widened rather than narrowed in patients with long term cure of acromegaly. The late effects of acromegaly on hand joints have not been characterized. Therefore the objective of the current study was to assess joint space widths of hand joints in patients with long-term control of acromegaly and to identify factors associated with joint space width.Design: Cross-sectional studyMethods: Cross-sectional study in 89 patients(age 58±12yr, 49% women) with long-term controlled acromegaly and 471 controls without hand symptoms(age 46±12yr, 42% women). Radiological joint space widths of individual hand joints were measured by automated image analysis.Results: Patients had wider mean joint spaces than controls: MCP-joints were ~24%, PIP-joints ~21%, and DIP-joints ~20% wider (patients vs controls; p<0.001 for all joints). Mean joint space width exceeded the 95th percentile of the values obtained in controls in 64% of patients. Higher IGF-1 and GH concentrations at diagnosis were associated with larger joint space widths (adjusted ß for pretreatment GH in tertiles:0.09(95%CI 0.03-1.84) and for IGF-1 in tertiles 0.14(95%CI 0.05-0.23) at the MCP-joints in acromegalic patients. In male, but not in female, patients increased joint space widths were associated with more self-reported pain(p=0.02).Conclusions: Using a new semi-automated image analysis of hand radiographs, acromegalic patients with long-term disease control appeared to have increased joint spaces of all hand joints. Joint space widths were positively related to disease activity at diagnosis, but not to duration of follow-up, suggesting irreversible cartilage hypertrophy. Irreversible cartilage hypertrophy may partly explain persisting hand complaints, despite long-term disease control. Show less
OBJECTIVE To investigate the validity of joint space width (JSW) measurements in millimeters (mm) in hand osteoarthritis (OA) patients by comparison to controls, grading of joint space narrowing ... Show moreOBJECTIVE To investigate the validity of joint space width (JSW) measurements in millimeters (mm) in hand osteoarthritis (OA) patients by comparison to controls, grading of joint space narrowing (JSN), and clinical features. METHODS Hand radiographs of 235 hand OA patients (mean age 65 years, 83% women) and 471 controls were used. JSW was measured with semi-automated image analysis software in the distal, proximal interphalangeal and metacarpal joints (DIPJs, PIPJs and MCPJs). JSN (grade 0-3) was assessed using the osteoarthritis research society international (OARSI) atlas. Associations between the two methods and clinical determinants (presence of pain, nodes and/or erosions, decreased mobility) were assessed using Generalized Estimating Equations with adjustments for age, sex, body mass index (BMI) and mean width of proximal phalanx. RESULTS JSW was measured in 5631 joints with a mean JSW of 0.98 mm (standard deviation (SD) 0.21), being the smallest for DIPJs (0.70 (SD 0.25)) and largest for MCPJs (1.40 (SD 0.25)). The JSN=0 group had a mean JSW of 1.28 mm (SD 0.34), the JSN=3 group 0.17 mm (SD 0.23). Controls had larger JSW than hand OA patients (P-value<0.001). In hand OA, females had smaller JSW than men (β -0.08, (95% confidence interval (95% CI) -0.15 to -0.01)) and lower JSW was associated with the presence of pain, nodes, erosions and decreased mobility (adjusted β -0.21 (95% CI -0.27, -0.16), -0.37 (-0.40, -0.34), -0.61 (-0.68, -0.54) and -0.46 (-0.68, -0.24) respectively). These associations were similar for JSN in grades. CONCLUSION In hand OA the quantitative JSW measurement is a valid method to measure joint space and shows a good relation with clinical features. Show less
