Three dimensional measurement of minimum joint space width in the knee from stereo radiographs using statistical shape models.

OBJECTIVES: An important measure for the diagnosis and monitoring of knee osteoarthritis is the minimum joint space width (mJSW). This requires accurate alignment of the x-ray beam with the tibial plateau, which may not be accomplished in practice. We investigate the feasibility of a new mJSW measurement method from stereo radiographs using 3D statistical shape models (SSM) and evaluate its sensitivity to changes in the mJSW and its robustness to variations in patient positioning and bone geometry. MATERIALS AND METHODS: A validation study was performed using five cadaver specimens. The actual mJSW was varied and images were acquired with variation in the cadaver positioning. For comparison purposes, the mJSW was also assessed from plain radiographs. To study the influence of SSM model accuracy, the 3D mJSW measurement was repeated with models from the actual bones, obtained from CT scans. RESULTS: The SSM-based measurement method was more robust (consistent output for a wide range of input data/consistent output under varying measurement circumstances) than the conventional 2D method, showing that the 3D reconstruction indeed reduces the influence of patient positioning. However, the SSM-based method showed comparable sensitivity to changes in the mJSW with respect to the conventional method. The CT-based measurement was more accurate than the SSM-based measurement (smallest detectable differences 0.55 mm versus 0. 82 mm, respectively). CONCLUSION: The proposed measurement method is not a substitute for the conventional 2D measurement due to limitations in the SSM model accuracy. However, further improvement of the model accuracy and optimisation technique can be obtained. Combined with the promising options for applications using quantitative information on bone morphology, SSM based 3D reconstructions of natural knees are attractive for further development.Cite this article: E. A. van IJsseldijk, E. R. Valstar, B. C. Stoel, R. G. H. H. Nelissen, N. Baka, R. van't Klooster, B. L. Kaptein. Three dimensional measurement of minimum joint space width in the knee from stereo radiographs using statistical shape models. Bone Joint Res 2016;320-327. DOI: 10.1302/2046-3758.58.2000626.

Sensitivity-to-change and validity of semi-automatic joint space width measurements in hand osteoarthritis: a follow-up study.

OBJECTIVE: To assess sensitivity-to-change and validity of longitudinal quantitative semi-automatic joint space width (JSW) measurements and to compare this method with semi-quantitative joint space narrowing (JSN) scoring in hand osteoarthritis (OA) patients. DESIGN: Baseline and 2-year follow-up radiographs of 56 hand OA patients (mean age 62 years, 86% women) were used. JSN was scored 0-3 using the Osteoarthritis Research Society International atlas and JSW was quantified in millimetres (mm) in the second to fifth distal, proximal interphalangeal and metacarpal joints (DIPJs, PIPJs, MCPJs). Sensitivity-to-change was evaluated by calculating Standardized Response Means (SRMs). Change in JSW or JSN above the Smallest Detectable Difference (SDD) defined progression on joint level. To assess construct validity, progressed joints were compared by cross-tabulation and by associating baseline ultrasound variables with progression (using generalized estimating equations, adjusting for age and sex). RESULTS: The JSW method detected statistically significant mean changes over 2.6 years (-0.027 mm (95%CI -0.01; -0.04), -0.024 mm (-0.01; -0.03), -0.021 mm (-0.01; -0.03) for DIPJs, PIPJs, MCPJs, respectively). Sensitivity-to-change was low (SRMs: 0.174, 0.168, 0.211, respectively). 9.1% (121/1336) of joints progressed in JSW, but 3.6% (48/1336) widened. 83 (6.2%) joints progressed in JSW only, 36 (2.7%) in JSN only and 37 (2.8%) in both methods. Progression in JSW showed weaker associations with baseline inflammatory ultrasound features than progression in JSN. 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 in hand OA clinical trials remains questionable.

Automated registration of multispectral MR vessel wall images of the carotid artery.

PURPOSE: Atherosclerosis is the primary cause of heart disease and stroke. The detailed assessment of atherosclerosis of the carotid artery requires high resolution imaging of the vessel wall using multiple MR sequences with different contrast weightings. These images allow manual or automated classification of plaque components inside the vessel wall. Automated classification requires all sequences to be in alignment, which is hampered by patient motion. In clinical practice, correction of this motion is performed manually. Previous studies applied automated image registration to correct for motion using only nondeformable transformation models and did not perform a detailed quantitative validation. The purpose of this study is to develop an automated accurate 3D registration method, and to extensively validate this method on a large set of patient data. In addition, the authors quantified patient motion during scanning to investigate the need for correction. METHODS: MR imaging studies (1.5T, dedicated carotid surface coil, Philips) from 55 TIA∕stroke patients with ipsilateral <70% carotid artery stenosis were randomly selected from a larger cohort. Five MR pulse sequences were acquired around the carotid bifurcation, each containing nine transverse slices: T1-weighted turbo field echo, time of flight, T2-weighted turbo spin-echo, and pre- and postcontrast T1-weighted turbo spin-echo images (T1W TSE). The images were manually segmented by delineating the lumen contour in each vessel wall sequence and were manually aligned by applying throughplane and inplane translations to the images. To find the optimal automatic image registration method, different masks, choice of the fixed image, different types of the mutual information image similarity metric, and transformation models including 3D deformable transformation models, were evaluated. Evaluation of the automatic registration results was performed by comparing the lumen segmentations of the fixed image and moving image after registration. RESULTS: The average required manual translation per image slice was 1.33 mm. Translations were larger as the patient was longer inside the scanner. Manual alignment took 187.5 s per patient resulting in a mean surface distance of 0.271 ± 0.127 mm. After minimal user interaction to generate the mask in the fixed image, the remaining sequences are automatically registered with a computation time of 52.0 s per patient. The optimal registration strategy used a circular mask with a diameter of 10 mm, a 3D B-spline transformation model with a control point spacing of 15 mm, mutual information as image similarity metric, and the precontrast T1W TSE as fixed image. A mean surface distance of 0.288 ± 0.128 mm was obtained with these settings, which is very close to the accuracy of the manual alignment procedure. The exact registration parameters and software were made publicly available. CONCLUSIONS: An automated registration method was developed and optimized, only needing two mouse clicks to mark the start and end point of the artery. Validation on a large group of patients showed that automated image registration has similar accuracy as the manual alignment procedure, substantially reducing the amount of user interactions needed, and is multiple times faster. In conclusion, the authors believe that the proposed automated method can replace the current manual procedure, thereby reducing the time to analyze the images.

Carotid wall volume quantification from magnetic resonance images using deformable model fitting and learning-based correction of systematic errors.

We present a method for carotid vessel wall volume quantification from magnetic resonance imaging (MRI). The method combines lumen and outer wall segmentation based on deformable model fitting with a learning-based segmentation correction step. After selecting two initialization points, the vessel wall volume in a region around the bifurcation is automatically determined. The method was trained on eight datasets (16 carotids) from a population-based study in the elderly for which one observer manually annotated both the lumen and outer wall. An evaluation was carried out on a separate set of 19 datasets (38 carotids) from the same study for which two observers made annotations. Wall volume and normalized wall index measurements resulting from the manual annotations were compared to the automatic measurements. Our experiments show that the automatic method performs comparably to the manual measurements. All image data and annotations used in this study together with the measurements are made available through the website http://ergocar.bigr.nl.

Automated versus manual in vivo segmentation of carotid plaque MRI.

BACKGROUND AND PURPOSE: Automatically identifying carotid plaque composition using MR imaging remains a challenging task in vivo. The purpose of our study was to compare the detection and quantification of carotid artery atherosclerotic plaque components based on in vivo MR imaging data using manual and automated segmentation. MATERIALS AND METHODS: Sixty patients from a multicenter study were split into a training group (20 patients) and a study group (40 patients). Each MR imaging study consisted of 4 high-resolution carotid wall sequences (T1, T2, PDw, TOF). Manual segmentation was performed by delineation of the vessel wall and different plaque components. Automated segmentation was performed in the study group by a supervised classifier trained on images from the training group of patients. RESULTS: For the detection of plaque components, the agreement between the visual and automated analysis was moderate for calcifications (κ = 0.59, CI 95% [0.36-0.82]) and good for hemorrhage (0.65 [0.42-0.88]) and lipids (0.65 [0.03-1.27]). For quantification of plaque volumes, the intraclass correlation was high for hemorrhage (0.80 [0.54-0.92]) and fibrous tissue (0.80 [0.65-0.89]), good for lipids (0.65 [0.43-0.80]), and poor for calcifications. CONCLUSIONS: In 40 patients with carotid stenosis, our results indicated that it was possible to automatically detect carotid plaque components with substantial or good agreement with visual identification, and that the volumes obtained manually and automatically were reasonably consistent for hemorrhage and lipids but not for calcium.

Long-lasting treatment effect of rituximab in MuSK myasthenia.

OBJECTIVE: Rituximab has emerged as an efficacious option for drug-resistant myasthenia gravis (MG). However, reports published only describe the short-term follow-up of patients treated and little is known about their long-term clinical and immunologic evolution. Our objective was to report the clinical and immunologic long-term follow-up of 17 patients (6 MuSK+MG and 11 AChR+MG) and compare the response between AChR+MG and MuSK+MG patients. METHODS: Myasthenia Gravis Foundation America postintervention status and changes in treatment and antibody titers were periodically determined. Lymphocyte subpopulations, total immunoglobulin, immunoglobulin G (IgG) anti-MuSK subclasses, and anti-tetanus toxoid IgG before and after treatment were also studied. RESULTS: After a mean post-treatment period of 31 months, 10 of the AChR+MG patients improved but 6 of them needed reinfusions. In contrast, all MuSK+MG patients achieved a remission (4/6) or minimal manifestations (2/6) status and no reinfusions were needed. Consequently, in the MuSK+MG group, prednisone doses were significantly reduced and concomitant immunosuppressants could be withdrawn. Clinical improvement was associated with a significant decrease in the antibody titers only in the 6 MuSK+MG patients. At last follow-up MuSK antibodies were negative in 3 of these patients and showed a decrease of over 80% in the other 3. CONCLUSION: In view of the long-lasting benefit observed in MuSK+MG patients, we recommend to use rituximab as an early therapeutic option in this group of patients with MG if they do not respond to prednisone. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that IV rituximab improves the clinical and immunologic status of patients with MuSK+MG.

Automated image analysis of hand radiographs reveals widened joint spaces in patients with long-term control of acromegaly: relation to disease activity and symptoms.

OBJECTIVE: 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 (JSWs) of hand joints in patients with long-term control of acromegaly and to identify factors associated with JSW. METHODS: A cross-sectional study was carried out in 89 patients (age 58 ± 12 years, 49% women) with long-term controlled acromegaly and 471 controls without hand symptoms (age 46 ± 12 years, 42% women). Radiological JSWs of individual hand joints were measured by automated image analysis. RESULTS: Patients had wider mean joint spaces than controls: metacarpo-phalangeal (MCP) joints were ~24%, proximal interphalangeal joints ~21%, and distal interphalangeal joints were ~20% wider (patients vs controls; P < 0.001 for all joints). Mean JSW exceeded the 95th percentile of the values obtained in controls in 64% of patients. Higher IGF1 and GH concentrations at diagnosis were associated with larger JSWs (adjusted ß for pretreatment GH in tertiles: 0.09 (95% confidence interval (CI) 0.03-1.84) and for IGF1 in tertiles: 0.14 (95% CI 0.05-0.23) at the MCP joints in acromegalic patients. In male patients, but not in female patients, increased JSWs 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. JSWs 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.

Validity of joint space width measurements in hand osteoarthritis.

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 (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 (ß -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 ß -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.

Automatic quantification of osteoarthritis in hand radiographs: validation of a new method to measure joint space width.

OBJECTIVE: To quantify osteoarthritis (OA) by automatic measurement of the joint space width (JSW) in the finger joints in hand radiographs, and validate this against semi-quantitative scoring. METHODS: Forty subjects with primary OA at multiple sites were selected, 20 of which had no joint space narrowing (JSN) in the hand, and 20 had moderate to severe JSN. Conventional hand radiographs were acquired and the image set was split into a training and test set, for developing and evaluating the method, respectively. No methods to quantify the JSW automatically in OA exist; therefore a method was developed. First the semi-automatic image analysis program identifies the metacarpal and interphalangeal joints. Subsequently, the corresponding joint margins and measurement interval are determined. Finally the JSW is measured in millimetres as the average distance between the joint margins enclosed by the measurement interval. The success rates of different steps of the image analysis were evaluated and a comparison was made between the JSW and the semi-quantitative Osteoarthritis Research Society International score for JSN. RESULTS: The success rates for the identification of the joint locations and margins were 97.5% and 64.2%, respectively. The JSW decreased with increasing semi-quantitative scores, but increased as the joint was severely damaged. The agreement between the JSW and the semi-quantitative score was confirmed by a significant correlation (R2=0.54 and P<0.01) while assessing hand pairs instead of individual joints. CONCLUSION: The JSW measurement closely reflects semi-quantitative scoring of JSN. Therefore, this method is expected to offer a reproducible and accurate measurement of the JSW in OA.

Genotype-phenotype study in an FSHD family with a proximal deletion encompassing p13E-11 and D4Z4.

BACKGROUND: In the majority of facioscapulohumeral muscular dystrophy (FSHD) cases, the molecular basis of the disease is due to loss of subtelomeric D4Z4 repeat units at 4q35. Occasionally, an apparent absence of the contracted D4Z4 repeat is associated with FSHD. One explanation for this finding is a deletion in the region proximal to the D4Z4 repeat array that encompasses the p13E-11 (D4F104S1) probe-binding site used in the DNA diagnosis. The frequency of such proximally extended deletions is unknown, and to date, few patients have been described due to the difficulties in the molecular identification of such cases. METHODS: We describe a family (DUK 2531) in which a contracted D4Z4 allele and a large proximal deletion of approximately 75 kb are segregating to 11 individuals. This is the largest deletion identified to date. Family DUK 2531 was initially thought to have normal D4Z4 fragment size and therefore unlinked to the 4q35 region (FSHD1B). RESULTS: Further molecular analysis of DUK 2531 reveals the presence of 10 repeat units (33 kb). The extended deletion includes the probe p13E-11 and B31 binding sites, the inverted repeat D4S2463, and genes FRG2 and TUBB4Q. CONCLUSION: Despite the length of the proximal deletion in this family, the range and severity of the clinical manifestations are typical for the disorder. Because such deletions can lead to misinterpretation in the diagnostic setting, this suggests the need for additional diagnostic tests in facioscapulohumeral muscular dystrophy.

Phosphorylation of p42/44(MAPK) by various signal transduction pathways activates cytosolic phospholipase A(2) to variable degrees.

Arachidonic acid has been implicated to play a role in physiological and pathophysiological processes and is selectively released by the 85-kDa cytosolic phospholipase A(2) (cPLA(2)). The activity of cPLA(2) is regulated by calcium, translocating the enzyme to its substrate, and by phosphorylation by a mitogen-activated protein kinase (MAPK) family member and a MAPK-activated protein kinase. In this study, the signal transduction pathways in growth factor-induced phosphorylation of p42/44(MAPK) and cPLA(2) activation were investigated in Her14 fibroblasts. p42/44(MAPK) in response to epidermal growth factor was not only phosphorylated via the Raf-MEK pathway but mainly through protein kinase C (PKC) or a related or unrelated kinase in which the phosphorylated p42/44(MAPK) corresponded with cPLA(2) activity. Serum-induced phosphorylation of p42/44(MAPK) also corresponded with cPLA(2) activity but is predominantly mediated via Raf-MEK and partly through PKC or a related or unrelated kinase. In contrast, activation of PKC by phorbol ester did not result in increased cPLA(2) activity, while p42/44(MAPK) is phosphorylated, mainly via Raf-MEK and through MEK. Moreover, p42/44(MAPK) phosphorylation is present in quiescent and proliferating cells, and p42/44(MAPK) is entirely phosphorylated via Raf-MEK, but it only corresponds to cPLA(2) activity in the former cells. Collectively, these data show that p42/44(MAPK) in proliferating, quiescent, and stimulated cells is phosphorylated by various signal transduction pathways, suggesting the activation of different populations of p42/44(MAPK) and cPLA(2).