Peter Countryman

Comparison of Digitized Images with Original Radiography for Semiquantitative Assessment of Osteoporotic Fractures

Abstract: We validated a vertebral fracture assessment (VFA) workstation developed by our group for semiquantitative assessment of vertebral fractures in large-scale, multicenter osteoporosis drug trials. Baseline and follow-up spine radiographs (lateral views) of 50 patients who participated in a clinical trial were digitized and were archived on CD-ROM. Both original radiographs and the digitized images were independently assessed by three experienced radiologists. Prevalent fracture scores of vertebrae were rated in increments of 1 on a 4-point scale. Incident fractures were defined as any worsening of grade on follow-up films. Generally good to excellent agreement among the three readers was found between the two methods, with kappa scores (κ) from 0.91 to 0.96 for prevalence of fractures, and from 0.80 to 0.90 for incidence of fractures. Reproducibility (intra-reader variability) of each method was comparable. For assessing prevalent fracture, κ was from 0.87 to 0.96 using radiographs, and from 0.87 to 0.94 using VFA images. For incident fractures, the κ was from 0.78 to 0.89 using radiographs, and from 0.82 to 0.88 using VFA images. Level-specific agreement between the two approaches was consistent. Overall, there is no difference between readings of digital images and readings of conventional radiographs. The quality of the new VFA for visualization of vertebral fracture is excellent.

Monitoring cartilage loss in the hands and wrists in rheumatoid arthritis with magnetic resonance imaging in a multi-center clinical trial: IMPRESS (NCT00425932)

IntroductionMagnetic resonance imaging (MRI) is increasingly being used in clinical trials of rheumatoid arthritis (RA) because of its superiority over x-ray radiography (XR) in detecting and monitoring change in bone erosion, osteitis and synovitis. However, in contrast to XR, the MRI scoring method that was used in most clinical trials did not include cartilage loss. This limitation has been an obstacle to accepting MRI as a potential alternative to XR in clinical trials. Cross-sectional studies have shown MRI to be sensitive for cartilage loss in the hands and wrist; although, longitudinal sensitivity to change has not yet been confirmed. In this study we examined the ability of MRI to monitor change in cartilage loss in patients with RA in a multi-site clinical trial setting.MethodsThirty-one active RA patients from a clinical trial (IMPRESS) who were randomized equally into treatment with either rituximab + methotrexate or placebo + methotrexate had MRI of the dominant hand/wrist at baseline, 12 weeks and 24 weeks at 3 clinical sites in the US. Twenty-seven of these patients also had XR of both hands/wrists and both feet at baseline and 24 weeks. One radiologist scored all XR images using the van der Heijde-modified Sharp method blinded to visit order. The same radiologist scored MR images for cartilage loss using a previously validated 9-point scale, and bone erosion using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA MRI Score (RAMRIS) blinded to visit order and XR scores. Data from the two treatment arms were pooled for this analysis.ResultsMean MRI cartilage score increased at 12 and 24 weeks, and reached statistical significance at 24 weeks. XR total Sharp score, XR erosion score and XR joint-space narrowing (JSN) score all increased at 24 weeks, but only XR total Sharp score increased significantly.ConclusionsTo our knowledge, this is the first publication of a study demonstrating MRIs ability to monitor cartilage loss in a multi-site clinical trial. Combined with MRIs established performance in monitoring bone erosions in RA, these findings suggest that MRI may offer a superior alternative to XR in multi-site clinical trials of RA.

Automated algorithm for the identification of joint space and phalanx margin locations on digitized hand radiographs

Rheumatoid arthritis (RA) of the hand can be characterized and assessed by the narrowing of the joint spaces which are ordinarily scored semiquantitatively by a radiologist using radiographs of the hand. Software which delineates and measures the joint spaces would be a useful tool for assessment. The first part of such an algorithm has been developed which determines the locations of the distal interphalangeal (DIP), proximal interphalangeal (PIP), and metacarpophalangeal (MCP) joint spaces for fingers 2–5 (index, middle, ring, and little) on digitized hand radiographs. In addition, points on the medial and lateral margins of each phalanx are identified which can be used as starting points for edge detection algorithms to provide segmentation of the phalanges. The algorithm is a C-language program running on a UNIX computer, uses a multiresolution approach operating, and requires approximately 10 CPU seconds per image. It was tested on a set of 54 radiographs taken from a multicenter rheumatoid arthritis study where a study protocol was followed. In addition, radiographs of individuals wearing rings and where nonanatomical structures contacted the anatomy proximal to the midpoint of the distal phalanx and distal to the MCP joint were eliminated from the data set. In order to make a quantitative assessment, regions of interest drawn by a trained radiologist were used as a gold standard. The algorithm had a success rate of 100% for the identification of each digit and over 99% for the identification of joint space locations and phalanx margins. Quantitative tests indicated excellent algorithm robustness. We have developed fully automated software which accurately identifies anatomical landmarks on digital images of the hand.

Magnetic resonance imaging in rheumatoid arthritis clinical trials: emerging patterns based on recent experience.

Objective. The current validated magnetic resonance imaging (MRI) scoring method for rheumatoid arthritis (RA) in clinical trials, RA MRI Score (RAMRIS), incorporates all metacarpophalangeal (MCP) and wrist joints except MCP-1. The experience with radiographic scoring, however, was that excluding certain bones in the wrist improved the discriminative power for changes over time. In this study, we pool MRI data from randomized controlled clinical trails (RCT) to determine which combination of MCP and wrist joints are most sensitive and discriminative for structural changes over time. Methods. MR images from 4 multicenter RCT, including 522 RA patients, were read by 2 radiologists, using the RAMRIS scoring system for erosion, osteitis, and synovitis. In one RCT, joint-space narrowing (JSN) was assessed cross-sectionally by one radiologist using a previously validated method. Baseline frequencies of erosion, JSN, osteitis, and synovitis of different bones and joints in the hand and wrist were compared. Intraclass correlation coefficients between readers were determined for each location. Finally, 7 different combinations of bone/joint locations were compared for their ability to discriminate subjects showing increases or decreases from baseline greater than or equal to smallest detectable changes (SDC) at Weeks 12 or 24. Results. Frequency of involvement and reliability for assessing change varied by location. As in earlier analyses, excluding certain wrist bones increased the percentage of subjects showing changes greater than or equal to SDC. Conclusion. These findings suggest that excluding wrist bones that do not frequently or reliably demonstrate structural changes improves the discriminative power of the RAMRIS scoring system.

Short-term changes on MRI predict long-term changes on radiography in rheumatoid arthritis: an analysis by an OMERACT Task Force of pooled data from four randomised controlled trials

Objective In rheumatoid arthritis (RA), MRI provides earlier detection of structural damage than radiography (X-ray) and more sensitive detection of intra-articular inflammation than clinical examination. This analysis was designed to evaluate the ability of early MRI findings to predict subsequent structural damage by X-ray. Methods Pooled data from four randomised controlled trials (RCTs) involving 1022 RA hands and wrists in early and established RA were analysed. X-rays were scored using van der Heijde-modified or Genant-modified Sharp methods. MRIs were scored using Outcome Measures in Rheumatology (OMERACT) RA MRI Score (RAMRIS). Data were analysed at the patient level using multivariable logistic regression and receiver operating characteristic curve analyses. Results Progression of MRI erosion scores at Weeks 12 and 24 predicted progression of X-ray erosions at Weeks 24 and 52, with areas under the curve (AUCs) of 0.64 and 0.74, respectively. 12-week and 24-week changes in MRI osteitis scores were similarly predictive of 24-week and 52-week X-ray erosion progressions; pooled AUCs were 0.78 and 0.77, respectively. MRI changes in synovitis at Weeks 12 and 24 also predicted progression of X-ray joint damage (erosion and joint-space narrowing) at Weeks 24 and 52 (AUCs=0.72 and 0.65, respectively). Conclusions Early changes in joint damage and inflammation detected with MRI predict changes in joint damage evident on subsequent X-rays. These findings support the use of MRI as a valid method for monitoring structural damage in short-duration RCTs.

Fully automated algorithm for the segmentation of the middle and proximal phalanges of digitized hand radiographs

Rheumatoid arthritis of the hand can be characterized and assessed by the narrowing of the phalangeal joint spaces. These are ordinarily scored semi-quantitatively by a radiologist using radiographs of the hand. Software which delineates and measures the joint spaces would be a useful tool for diagnosis. The first part of such an algorithm has been developed which segments and identifies eight individual bones on digitized hand radiographs: the middle and proximal phalanges of the 2nd to 5th digits. The software also determines the locations of the distal interphalangeal, proximal interphalangeal, and metacarpophalangeal joint spaces for each digit.

Classification of vertebral fractures: Landmark-based shape recognition by neural networks

In the mexican group osteopenia was found in 33% of lumbar spine determinations and 35% of femoral necks studied. Osteoporosis was found 18% and .p% respectively. Duration of breast feeding and years after menopause were negasve correlated with BMD at lumbar spine and years after menopause and age were negative correlated with BMD al femoral neck in both countries. Time of estrogen use was also negatively correlated with BMD at lumbar spine in the mexican gmt~p. Number of pregnancies and alcohol consumption were negatively correlated with BMD at lumbar spine and femoral neck in the venezuelan group. CONCLUSION. Our results define a risk profile and are useful in decision making at the clinical practice as well as to characterize preventive intervention in patients and populations.

AC-CUTE: An Open-Label Study to Evaluate Progression of Structural Joint Damage and Inflammation in Subjects with Moderate to Severe Rheumatoid Arthritis

Aim Examine the efficacy of once-weekly subcutaneous tocilizumab (SC-TCZ) on joint damage at 24 weeks based on radiography of the hands and feet and magnetic resonance imaging (MRI) of the hand in subjects with moderate to severe rheumatoid arthritis (RA). Methods In this Australian open-label, multicentre, prospective, single-arm study, subjects received 162 mg SC-TCZ weekly. Primary endpoint was change in radiographic Genant-modified Total Sharp Score (TSS) between baseline and Week 24. Secondary endpoints included change from baseline to Week 24 in RA MRI scoring (RAMRIS) of erosions, synovitis, and osteitis and Cartilage Loss Score (CARLOS) in the dominant hand and disease activity score 28 (DAS28). Results 52 subjects were enrolled (80% female, mean (SD) age 57  (12) years). Radiography showed mild but not significant progression of joint damage (mean (SD) change in TSS 0.46 (1.29)). Synovitis reduced significantly on MRI; however, osteitis, erosion, and cartilage loss did not change significantly. DAS28 improved significantly by Week 24; 78% of subjects achieved DAS28 remission. SC-TCZ was generally well tolerated. Conclusion Synovitis and DAS28 decreased significantly; however, no significant change in osteitis or joint damage was observed at Week 24. Trial registration This trial is registered with Clinicaltrials.gov registration number NCT01951170 (ML28703).