I Watt

Leiden University Medical Centre, Leyden, South Holland, Netherlands

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Publications (135)610.94 Total impact

  • Osteoarthritis and Cartilage 09/2008; 16. · 4.26 Impact Factor
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    ABSTRACT: Our objective was to test the hypothesis that focal diurnal changes occur in the femoral articular cartilage of the knee in asymptomatic young adults. Six volunteers each were scanned early in the morning, and at the end of a working day spent mainly standing. This protocol was repeated on three successive weeks. Femoral cartilage segmentations were obtained using a region-growing algorithm. These segmentations then were regridded onto a 500-pixel template, and differences in the resulting thickness maps were assessed. Analysis of variance showed no significant diurnal variation in mean thickness. There were, however, statistically-significant diurnal changes in the thickness maps. Cartilage thickness decreased during the day in three specific locations which suffer the greatest biomechanical force.
    09/2006: pages 328-337;
  • International Journal of Osteoarchaeology 05/2005; 4(2):165 - 167. · 0.95 Impact Factor
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    ABSTRACT: In human skeletons from archaeological sites, osteoarthritis is by far the most common disease found, but no case of erosive osteoarthritis has been described and we present here what we believe to be the first such case.
    International Journal of Osteoarchaeology 05/2005; 1(2):151 - 153. · 0.95 Impact Factor
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    ABSTRACT: MRI is a valuable imaging modality for assessment of the articular cartilage in rheumatoid arthritis (RA) and is potentially of use in monitoring disease progression and response to therapy. In this study, we investigated the sources of error in volume measurements obtained by segmentation of MR images of knee cartilage in patients with RA and followed cartilage volume in a group of RA patients for 12 months. 23 RA patient volunteers were recruited for knee imaging. Six subjects were imaged at baseline only, six were imaged at baseline and again within an hour in the same imaging session, six subjects were imaged at baseline and 7 days, and 17 subjects were imaged at baseline, 4+/-2 months and 12 months. Imaging was performed at 1.0 T using a three-dimensional spoiled gradient-echo sequence with fat-suppression. Manual image segmentation was performed once or twice on the lateral tibial, medial tibial, patellar and femoral compartment by either one or two segmenters. Coefficients of variation (CoV) for repeated volume measurement of total cartilage were 2.2% (same segmenter, same scan), 5.2% (different segmenter, same scan), 4.9% (same segmenter, different scan, same session), and 4.4% (same segmenter, different scan, different session). Over the 12 month duration of the study there was no significant change in total cartilage volume, nor were there significant changes in volume in any individual compartment. This measurement technique is reproducible, but any net change in cartilage volume over 1 year is very small.
    British Journal of Radiology 02/2005; 78(925):39-45. · 1.53 Impact Factor
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    ABSTRACT: Plain X-ray is an imprecise tool for monitoring the subchondral bony changes associated with the development of knee osteoarthritis (OA). Our objective was to develop and validate a technique for assessing tibial subchondral bone density (BMD) in knee OA using dual energy X-ray absorptiometry (DXA). Patients with OA of at least one knee underwent DXA scanning of both knees. Regions of interest (ROI) were placed in the lateral and medial compartments of tibial subchondral bone. Weight-bearing plain X-rays and Te (99m) scintiscans of both knees were obtained and scored. One hundred and twelve patients (223 knees) underwent DXA and radiography. Intra-observer CV% was 2.4% and 1.0% for the medial and lateral ROI respectively. Definite OA (Kellgren and Lawrence Grade 2, 3 or 4) was correlated with age-related preservation of subchondral BMD compared to radiographically normal knees. Raised BMD was also associated with subchondral sclerosis, and positive scintigraphy. DXA may provide a safe, rapid and reliable means of assessing knee OA. Cross-sectional age-related subchondral tibial BMD loss is attenuated by knee OA.
    Skeletal Radiology 11/2004; 33(10):588-95. · 1.74 Impact Factor
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    D R Jeffrey, I Watt
    British Journal of Radiology 12/2003; 76(911):777-87. · 1.53 Impact Factor
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    ABSTRACT: Magnetic resonance imaging (MRI) has the potential to provide accurate quantification of structural changes in joint disease, with sensitivity to change, as it can provide direct visualization of the cartilage and bone. In this study, we investigated whether knee cartilage volume, as assessed by MRI, is sensitive to change over time in patients with osteoarthritis (OA). Sixteen patient volunteers (10 male, six female) with established OA of the knee were entered into the study and demographic data recorded. At baseline, 12 months and 37+/-2 months, patients underwent simple measures of disease severity, as well as extended weight-bearing AP knee X-rays. In addition the patient's index knee was imaged using MR at 1.0 T using a 3-D spoiled gradient-echo sequence with fat-suppression, repetition time 50 ms, echo time 11 ms, flip-angle 40 degrees, sagittal slice thickness 1.56 mm and in-plane pixel resolution 0.55 mm. Manual image segmentation was performed on all knee cartilage compartments and the respective cartilage volumes determined. Eleven of the original patients recruited completed the 3-year study. Radiographic features indicated that the majority had a spectrum of well-established OA at entry. The average decrease in medial tibiofemoral joint space width was 0.21+/-0.37 mm (mean+/-S.D.). Comparison of MR images at baseline and 37+/-2 months indicated little evidence of cartilage lesion shape or size change in any of the compartments. There was no significant MRI volume change in any of the knee cartilage compartments over the course of 1 year. The change in total knee cartilage volume, as measured by MRI, was a loss of only 1.6%, or 0.36+/-1.3 ml (mean+/-S.D.), over the 3 years. The failure to identify loss of cartilage volume over 3 years in this cohort of patients with established knee OA using MRI challenges the face validity of this endpoint to assess structural changes in OA.
    Osteoarthritis and Cartilage 01/2003; 10(12):929-37. · 4.66 Impact Factor
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    ABSTRACT: The aim of this investigation was to study the prevalence and distribution of Paget's disease in an archeological population. Paget's disease, first described over 100 years ago, is a well-recognized chronic disorder involving abnormal bone turnover with established radiological features. Prevalence within modern populations varies both within individual countries and between them. Paleopathological examples are uncommon and sporadically reported both from Europe and the Americas and from many periods of history. A large skeletal assemblage (2,770 individuals) from Barton on Humber, UK, provided an opportunity to examine the prevalence of Paget's disease in one area of the northern England over the period 900-1,850 AD. All bones were examined visually for evidence of Paget's disease of the bone (PDB) and all abnormal bones were examined further by plain radiography. Fifteen cases of probable Paget's disease were found. The overall prevalence was 2.1% in those aged >40 years. The prevalence before 1500 AD was 1.7% and post-1500 AD was 3.1%. The distribution of disease mirrored modern disease, with the lumbar spine, pelvis, and proximal femur being the commonest sites. The prevalence of Paget's disease in the United Kingdom over the last 1,000 years has been assessed. Although there is a trend of increasing prevalence, this did not reach statistical significance. This is likely caused by the small sample size, but this is by far the greatest number of cases of PDB described in a single skeletal assemblage to date. The distribution of lesions within the skeleton is unchanged.
    Journal of Bone and Mineral Research 07/2002; 17(6):1127-34. · 6.59 Impact Factor
  • Iain Watt, Mark Cobby
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    ABSTRACT: The radiologic findings of a placebo-controlled, dose-ranging, multicenter, multinational trial have been reported previously. Radiographs were evaluated using the Larsen scoring method and Erosion Joint Count. After completion of the study, a subset of the films was read again using a modified Sharp score. This article will focus on the methodologies, scoring indices, and outcomes of the Larsen and Erosion Joint Count evaluations. Modified Sharp scores are presented in a separate article. A 6-month, phase II, randomized, double-blind, placebo-controlled trial was conducted involving 472 patients with active rheumatoid arthritis. Patients from 41 centers in 11 countries were randomly selected to receive 30 mg/d, 75 mg/d, or 150 mg/d of recombinant human interleukin-1 receptor antagonist (IL-1ra) subcutaneously daily or placebo. Radiographic criteria were circulated to all centers, and the same 2 radiologists used the Larsen score and the Erosion Joint Count to score what was essentially a homogeneous film collection. At the completion of the study, a subset of radiographs also was read using the Genant-modified Sharp score. Patients in any of the treatment arms had the option of continuing in an extension trial for an additional 6 months, and those in the placebo arm had the option of being randomly placed into one of the treatment arms. The Larsen and Erosion Joint Count data from these patients confirm that at 24 weeks, patients receiving placebo worsened by an average of 6.49 Larsen units, whereas those receiving 30, 75, or 150 mg/d of IL-1ra worsened by 3.53, 4.19, and 3.90 Larsen units, respectively. Overall, patients receiving therapy worsened by an average of 3.86 units, achieving statistical significance versus placebo (P = .034). These data are not significantly different from those of the main trial. Mean values were ANOVA-adjusted for country and treatment-group interactions. Similarly, the Erosion Joint Count in placebo patients worsened by an average of 2.64, whereas those receiving 30, 75, or 150 mg/d of IL-1ra worsened by 1.46, 1.05, and 1.70, respectively. The overall therapy and 75 mg/d arm achieved significance versus placebo (P = .002 and P < or = .001, respectively). Preliminary data from the extension study indicate continuing benefit. Treatment with IL-1ra reduced the rate of joint deterioration and development of new bone erosions.
    Seminars in Arthritis and Rheumatism 04/2001; 30(5 Suppl 2):21-5. · 3.63 Impact Factor
  • J Kirwan, M Byron, I Watt
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    ABSTRACT: To test the hypotheses that the progression of joint space narrowing behaves differently from the progression of erosions and that clinically and radiologically assessed soft tissue swelling relates more to diffuse cartilage loss than to erosive damage. Radiographs and clinical data were obtained from 28 patients in a prospective, multicentre, randomized, placebo-controlled trial of prednisolone 7.5 mg daily over 2 yr. Radiographic scoring included the Larsen score, joint space narrowing and soft tissue swelling. Clinical joint inflammation in the hands was assessed every 3 months and cumulative synovitis score over the period of study was then calculated for each joint. The placebo-treated patients and the prednisolone-treated patients were analysed separately. The Larsen scores were compared after log transformation [transformed score=log(10) (original score+1)]. Changes in Larsen scores and joint space narrowing scores were compared with the cumulative presence of clinical synovitis and radiological soft tissue swelling using the correlation coefficient. There was a difference in the rate of progression in the Larsen score between placebo- and prednisolone-treated patients, but there was no significant difference in the rate of joint space loss. In placebo-treated patients, measures of synovitis correlated more strongly with progression of joint space narrowing than with changes in the Larsen score. In prednisolone-treated patients there was no correlation between clinical synovitis and change in Larsen score (r=0.029) and only a slight and non-significant correlation with joint space narrowing (r=0.127). Radiographic evidence of soft tissue swelling remained correlated with joint space narrowing (r=0.279, P:<0.001) but was not correlated with change in Larsen score (r=-0.113, P:<0.001 for difference between correlations). The correlation between Larsen score progression and joint space narrowing seen in the non-treated patients was completely abolished in the glucocorticoid-treated group (r=-0.003). The progression of joint space narrowing behaves differently from the progression of erosions. Prednisolone slows (or even stops) the progression of erosions (as assessed by the Larsen score) while making no difference to the progression of cartilage loss (as assessed by joint space narrowing). The results also suggest that synovitis, whether measured clinically or radiologically, is more closely related to diffuse cartilage loss than to erosion progression. Any link between synovitis and erosions is abolished by glucocorticoid therapy while the link between synovitis and cartilage loss is not, pointing to at least two different mechanisms for these observed radiological features.
    Rheumatology 03/2001; 40(3):297-301. · 4.44 Impact Factor
  • I Watt
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    ABSTRACT: The classical features of osteoarthritis (OA) include osteophytosis, joint space narrowing, subchondral cyst formation, sclerosis, deformity and low-grade synovitis. OA has been tacitly assumed to be a homogeneous disorder and dismissed as "degenerative". This short article will seek to challenge this traditional view and suggest that at least two major processes emerge from detailed radiological studies in patients with OA. One comprises osteophytosis associated with hyaline cartilage thinning and perhaps joint instability. This may represent a normal response to joint instability, and be seen as a healing mechanism. The other, when subchondral sclerosis and bone attrition predominate, may reflect joint failure.
    Der Radiologe 01/2001; 40(12):1134-40. · 0.41 Impact Factor
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    ABSTRACT: To evaluate radiographic progression and the relationship of radiologic scores obtained by the Genant and Larsen methods in a clinical trial of recombinant human interleukin-1 receptor antagonist (IL-1Ra). Patients with rheumatoid arthritis (RA) were randomized into 4 groups: placebo (n = 121) or IL-1Ra at a daily dosage of 30 mg (n = 119), 75 mg (n = 116), or 150 mg (n = 116). Hand radiographs obtained at baseline, 24 weeks, and 48 weeks were scored using both methods. At 24 weeks, by the Genant method, there was significant reduction in the score for progression of joint space narrowing (JSN) and the total score (a combination of erosion and JSN) in all treatment groups. Least-squares mean changes in the Genant erosion score from baseline to 24 weeks were significantly reduced after treatment with IL-1Ra at 30 mg/day and for all IL-1Ra treatment groups combined. The changes corresponded to a reduction of 38% in erosion, 58% in JSN, and 47% in total score. Patients treated with IL-1Ra at 75 mg/day had a significant reduction in the Larsen erosive joint count (LEJC), and all IL-1RA-treated groups combined showed a 45% reduction. Correlations (r) between the Genant total and Larsen scores were 0.84 at baseline, 0.83 at week 24, and 0.83 at week 48 (P < 0.0001); correlations between the Genant erosion score and the LEJC were 0.83 (P < 0.0001) at all visits; correlations between the Genant total and the Larsen scores were 0.32 and 0.49 (P < 0.0001) for progression from baseline to week 24 and from baseline to week 48, respectively; correlations between the Genant erosion score and the LEJC were 0.36 and 0.41 (P < 0.0001) for progression to weeks 24 and 48, respectively. IL-1Ra reduced radiologic progression of RA. Scores by the 2 methods correlated strongly for each individual time point, but much less strongly for assessments of disease progression.
    Arthritis & Rheumatology 06/2000; 43(5):1001-9. · 7.87 Impact Factor
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    ABSTRACT: Our objective was to test the hypothesis that diurnal changes occur in thickness or volume of the femoral articular cartilage of the knee in asymptomatic young adults. Fat-suppressed three-dimensional (3D) spoiled gradient-echo magnetic resonance imaging (MRI) was employed. Six volunteers each were scanned early in the morning and at the end of a working day spent mainly standing. This protocol was repeated on 3 successive weeks. Femoral cartilage volumes were obtained via semiautomatic segmentation that employed a seeding algorithm. These segmentations then were regridded onto a 500-pixel template, and differences in the resulting thickness maps were assessed. Analysis of variance showed no significant diurnal variation in overall volume or thickness. The reproducibility for volume (test-retest coefficient of variation) was 1.6%. There were, however, statistically-significant diurnal changes in the thickness maps. Cartilage thickness decreased by up to 0.6 mm during the day in each of the following three specific locations: the patellofemoral compartment, the lateral tibiofemoral compartment, and the medial tibiofemoral compartment. Elsewhere, cartilage thickness was unchanged or increased by up to 0.5 mm. We conclude that, in asymptomatic young adults, cartilage volume does not change during the day; however, the cartilage does become thinner in locations that encounter the greatest biomechanical force.
    Magnetic Resonance in Medicine 02/2000; 43(1):126-32. · 3.40 Impact Factor
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    ABSTRACT: Our objective was to test the hypothesis that diurnal changes occur in thickness or volume of the femoral articular cartilage of the knee in asymptomatic young adults. Fat-suppressed three-dimensional (3D) spoiled gradient-echo magnetic resonance imaging (MRI) was employed. Six volunteers each were scanned early in the morning and at the end of a working day spent mainly standing. This protocol was repeated on 3 successive weeks. Femoral cartilage volumes were obtained via semiautomatic segmentation that employed a seeding algorithm. These segmentations then were regridded onto a 500-pixel template, and differences in the resulting thickness maps were assessed. Analysis of variance showed no significant diurnal variation in overall volume or thickness. The reproducibility for volume (test-retest coefficient of variation) was 1.6%. There were, however, statistically-significant diurnal changes in the thickness maps. Cartilage thickness decreased by up to 0.6 mm during the day in each of the following three specific locations: the patellofemoral compartment, the lateral tibiofemoral compartment, and the medial tibiofemoral compartment. Elsewhere, cartilage thickness was unchanged or increased by up to 0.5 mm. We conclude that, in asymptomatic young adults, cartilage volume does not change during the day; however, the cartilage does become thinner in locations that encounter the greatest biomechanical force. Magn Reson Med 43:126–132, 2000. © 2000 Wiley-Liss, Inc.
    Magnetic Resonance in Medicine 12/1999; 43(1):126 - 132. · 3.40 Impact Factor
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    ABSTRACT: To relate the vertical striations visualized in the deeper layers of articular cartilage by Magnetic Resonance Imaging (MRI) to histological features. Two knee joints recovered at post-mortem from males in their seventies with no history or visual evidence of joint disease were examined. MR images were obtained in a 4.7 T 400 mm-bore magnet, after which the knees were fixed, sectioned, and examined histologically. High resolution MR showed vertical high/low signal striations with a two to three-fold variation in signal intensity and a periodicity of 0.56 (+/-0.16 mm), most prominent in weight bearing areas. Histological sections revealed alternating light and dark staining areas with a periodicity of 1.01+/-0.54 mm in the lower zones of the cartilage, some, but not all of which clearly represented folding. Given that MR will only visualize vertical structures in cartilage aligned at 90 degrees, whereas histology will cut them at varying angles, it is likely that the vertical structures seen by each modality correspond, and that they represent structural heterogeneity in cartilage; perhaps the presence of plates of high collagen and proteoglycan content. The vertical striations seen routinely in the deep zones of hyaline articular cartilage on histological sections are not artefactual; they are likely to represent structural heterogeneity due to the presence of areas of high collagen and high proteoglycan content that exist in weight-bearing areas. This structural heterogeneity may be of great importance to the integrity and function of the cartilage.
    Osteoarthritis and Cartilage 10/1999; 7(5):480-5. · 4.66 Impact Factor
  • Medical Image Computing and Computer-Assisted Intervention - MICCAI'99, Second International Conference, Cambridge, UK, September 19-22, 1999, Proceedings; 01/1999
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    ABSTRACT: To evaluate the efficacy and safety of interleukin-1 receptor antagonist (IL-1Ra) in patients with rheumatoid arthritis (RA). Patients with active and severe RA (disease duration <8 years) were recruited into a 24-week, double-blind, randomized, placebo-controlled, multicenter study. Doses of nonsteroidal antiinflammatory drugs and/or oral corticosteroids (< or =10 mg prednisolone daily) remained constant throughout the study. Any disease-modifying antirheumatic drugs that were being administered were discontinued at least 6 weeks prior to enrollment. Patients were randomized to 1 of 4 treatment groups: placebo or a single, self-administered subcutaneous injection of IL-1Ra at a daily dose of 30 mg, 75 mg, or 150 mg. A total of 472 patients were recruited. At enrollment, the mean age, sex ratio, disease duration, and percentage of patients with rheumatoid factor and erosions were similar in the 4 treatment groups. The clinical parameters of disease activity were similar in each treatment group and were consistent with active and severe RA. At 24 weeks, of the patients who received 150 mg/day IL-1Ra, 43% met the American College of Rheumatology criteria for response (the primary efficacy measure), 44% met the Paulus criteria, and statistically significant improvements were seen in the number of swollen joints, number of tender joints, investigator's assessment of disease activity, patient's assessment of disease activity, pain score on a visual analog scale, duration of morning stiffness, Health Assessment Questionnaire score, C-reactive protein level, and erythrocyte sedimentation rate. In addition, the rate of radiologic progression in the patients receiving IL-1Ra was significantly less than in the placebo group at 24 weeks, as evidenced by the Larsen score and the erosive joint count. IL-1Ra was well tolerated and no serious adverse events were observed. An injection-site reaction was the most frequently observed adverse event, and this resulted in a 5% rate of withdrawal from the study among those receiving IL-1Ra at 150 mg/day. This study confirmed both the efficacy and the safety of IL-1Ra in a large cohort of patients with active and severe RA. IL-1Ra is the first biologic agent to demonstrate a beneficial effect on the rate of joint erosion.
    Arthritis & Rheumatology 12/1998; 41(12):2196-204. · 7.87 Impact Factor
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    ABSTRACT: To investigate the potential of quantitative magnetic resonance imaging (MRI) to differentiate between therapeutically induced changes in inflammation and synovial proliferation in rheumatoid arthritis (RA) of the knee. MRI of the knee was performed on patients with RA before and one week after injection with corticosteroid (triamcinolone acetonide, TA group, n = 9) and before, four, and 12 weeks after injection with yttrium-90 plus TA (TA+Y group, n = 7). MRI scans were analysed by subjective visual grading by a trained observer and by computer aided quantitation for three features: synovial fluid volume, synovial pannus volume, and synovial enhancement after intravenous contrast agent. All TA subjects improved clinically at one week but the effects of TA+Y were more variable. TA significantly reduced synovial enhancement and effusion volume, whereas TA+Y at 12 weeks tended to increase synovial enhancement and decrease pannus volume. Quantitative MRI values agreed well with subjective assessment of scans. Comparison of calculated change on MRI scan before and immediately after aspiration with actual volume aspirated showed high correlation (r = 0.96). Quantitative MRI correlates with subjective visual assessment and, at least for synovial fluid, is accurate. MRI can differentiate actions of two therapeutic modalities on various pathological processes and is sensitive enough to detect change after one week. With the additional advantage of lack of observer bias, it will probably become a useful tool in the development and assessment of existing and novel treatments.
    Annals of the Rheumatic Diseases 07/1997; 56(6):378-81. · 9.27 Impact Factor
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    ABSTRACT: Conventional radiograms have been used to quantitate the progression of rheumatoid arthritis, mainly through the assessment of bone erosions, but this approach has many limitations. It has been suggested that an advantage of contrast-enhanced Gd-DTPA MRI over radiography may be its prognostic value due to its ability to show the natural history of active destructive to inactive fibrous pannus. The aim of this study was to evaluate the possible prognostic value of MRI for future development of bone erosive changes in small hand joints in patients with RA. The results of the study confirm that in joints in which inflammatory active pannus is shown by contrast-enhanced MRI, progression of bone-destructive changes can be expected.
    British journal of rheumatology 01/1997; 35 Suppl 3:26-30.

Publication Stats

3k Citations
610.94 Total Impact Points

Institutions

  • 2005–2013
    • Leiden University Medical Centre
      • • Department of Radiology
      • • Department of Rheumatology
      Leyden, South Holland, Netherlands
  • 2001
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 1988–2001
    • University of Bristol
      • Medical School
      Bristol, England, United Kingdom
  • 1996
    • University of the West of England, Bristol
      Bristol, England, United Kingdom
  • 1993
    • Hospital Kuala Lumpur
      Kuala Lumpor, Kuala Lumpur, Malaysia