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Automatic image analysis for decision support in rheumatoid arthritis and osteoporosis
Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Institute of Technology.ORCID iD: 0000-0002-3486-796X
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Low-energy trauma and fragility fractures represent a major public health problem. The societal cost of the fragility fractures that occurred in Sweden 2010 has been estimated at €4 billion.

In rheumatoid arthritis (RA), patient outcomes have improved greatly in recent years. However, the therapeutic decision making is still hampered by a lack of effective validated biomarkers. The cost of RA in Sweden 2010 has been estimated at €600 million, of which biologic drugs was €180 million.

Digital X-ray radiogrammetry (DXR) is a method to measure bone mineral density (BMD) in the metacarpals of the hand. It can be applied opportunistically in several workflows where a person is already at an X-ray machine, including fracture repositioning follow up, mammography screening and hand imaging in RA. This thesis explored DXR-BMD as a marker to identify individuals who would benefit from anti-osteoporotic treatment, change rate of DXR-BMD as a biomarker in RA and under what conditions historical X-ray images can be used to estimate DXR-BMD. An automated method for measurement of joint space width in metacarpophalangeal and interphalangeal joints was also developed and evaluated as a biomarker in RA.

Low DXR-BMD was predictive for hip fractures and predicted fragility fractures to a comparable degree as other BMD measurement sites. Rapid decrease of DXR-BMD was a strong and independent predictor for progression of radiographic damage in RA when manual radiographic progression scores were not available. Change of metacarpal joint space width was a statistically significant but weak predictor of joint space narrowing score progression. Guidelines and considerations for use of historical X-ray radiographs for DXR-BMD measurements in clinical trials have been developed and published.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. , 57 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1433
Keyword [en]
Osteoporosis, rheumatoid arthritis, digital X-ray radiogrammetry, joint space width, bone densitometry
National Category
Medical Image Processing
Identifiers
URN: urn:nbn:se:liu:diva-113680DOI: 10.3384/diss.diva-113680ISBN: 978-91-7519-170-6 (print)OAI: oai:DiVA.org:liu-113680DiVA: diva2:783988
Public defence
2015-03-13, Wrannesalen, CMIV, Campus US, Linköpings universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2015-01-28 Created: 2015-01-28 Last updated: 2015-03-26Bibliographically approved
List of papers
1. Does digital X-ray radiogrammetry have a role in identifying patients at increased risk for joint destruction in early rheumatoid arthritis?
Open this publication in new window or tab >>Does digital X-ray radiogrammetry have a role in identifying patients at increased risk for joint destruction in early rheumatoid arthritis?
2012 (English)In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 14, no 5, R219- p.Article in journal (Refereed) Published
Abstract [en]

Introduction

The aim of this study was to investigate the role of hand bone mineral density (BMD) loss analyzed with digital X-ray radiogrammetry (DXR) in early rheumatoid arthritis (RA) as a predictor for progression of joint damage.

Methods

In 379 patients with early RA, baseline and one-year hand BMD was measured with DXR and the hand bone loss (HBL) was analyzed using the smallest detectable change (HBLsdc) and tertiles (HBLtertiles). Joint damage in hands and feet were scored according to the Sharp van der Heijde (SHS) method at baseline and at one, two, five and eight years. At the same time-points Disease Activity Score (DAS28) was calculated and functional disability assessed. Rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (anti-CCP) were analyzed at baseline.

Results

Sixty-six percent of the patients had hand BMD loss in the first year of RA determined by HBLsdc and 65% by HBLtertiles. Radiographic progression after two, five and eight years was associated with hand bone loss defined by HBLsdc. By HBLtertiles there were significant associations at all time-points except at eight years. The change in DXR at one year (ChDXR1yr) correlated significantly and inversely with the change in SHS (ChSHS) at two, five and eight years. Multivariate analysis showed that only change in SHS during the first year and the presence of anti-CCP were independent predictors of long-term progressive joint damage. If radiographic scores were not included, DXR-BMD loss was an independent predictor. Patients with great bone loss by HBLtertiles had significantly more often high disease activity after two years. However, neither bone loss by HBLsdc or HBLtertiles nor by ChDXR1yr was an independent predictor of remission after two, five and eight years.

Conclusions

This study confirms previous reports of an association of decrease in DXR-BMD during the first disease year with progression of radiographic joint damage over an extended period of time. This association was independent in a regression model only when radiological findings were excluded suggesting a possible predictive role of DXR-BMD in clinical practice when radiographic evaluation is not available. However, further studies are required before this can be established.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-90097 (URN)10.1186/ar4058 (DOI)000315488700031 ()
Available from: 2013-03-19 Created: 2013-03-19 Last updated: 2017-12-06
2. Potential sources of quantification error when retrospectively assessing metacarpal bone loss from historical radiographs by using digital X-ray radiogrammetry: an experimental study
Open this publication in new window or tab >>Potential sources of quantification error when retrospectively assessing metacarpal bone loss from historical radiographs by using digital X-ray radiogrammetry: an experimental study
2014 (English)In: Journal of clinical densitometry, ISSN 1094-6950, E-ISSN 1559-0747, Vol. 17, no 1, 104-108 p.Article in journal (Refereed) Published
Abstract [en]

During the past 15 yr, digital X-ray radiogrammetry (DXR) has been used to measure metacarpal bone mineral density (BMD). BMD is often measured in existing cohorts where X-ray images were not acquired in accordance with the DXR imaging protocol (DIP). The purpose of the present study was to analyze how deviations from DIP in historical radiographs may affect the reproducibility of DXR-BMD measurements. Cadaver hand phantoms were used to conduct repeat measurements of deviations from DIP with respect to voltage, exposure, lateral displacement, supination, combination of lateral displacement and supination or rotation, extension of the wrist, and edge enhancement. Direct digital radiography (Aristos; Siemens Healthcare, Erlangen, Germany) was used for image acquisition and dxr-online (Sectra, Linkoping, Sweden) for DXR-BMD measurements. The influence of the tested deviations from DIP ranged from 0 to 32.5 mg/cm(2) (0-6.8%). On repetition with the same specimen, none of the deviations resulted in a within-specimen reproducibility error greater than 2 mg/cm(2) (0.4%, equivalent to a T-score of 0.042). Among the tested deviations, all except tube voltage had a magnitude greater than the normal measurement noise for the technique and must therefore be considered when planning a study based on historical images.

Place, publisher, year, edition, pages
Elsevier, 2014
Keyword
Bone mineral density; digital X-ray radiogrammetry; osteoporosis; rheumatoid arthritis
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-105587 (URN)10.1016/j.jocd.2013.04.002 (DOI)000331598300018 ()23664111 (PubMedID)
Available from: 2014-03-28 Created: 2014-03-27 Last updated: 2017-12-05Bibliographically approved
3. Digital X-ray radiogrammetry of hand or wrist radiographs can predict hip fracture risk-a study in 5,420 women and 2,837 men
Open this publication in new window or tab >>Digital X-ray radiogrammetry of hand or wrist radiographs can predict hip fracture risk-a study in 5,420 women and 2,837 men
Show others...
2013 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 23, no 5, 1383-1391 p.Article in journal (Refereed) Published
Abstract [en]

To assess whether digital X-ray radiogrammetry (DXR) analysis of standard clinical hand or wrist radiographs obtained at emergency hospitals can predict hip fracture risk. less thanbrgreater than less thanbrgreater thanA total of 45,538 radiographs depicting the left hand were gathered from three emergency hospitals in Stockholm, Sweden. Radiographs with insufficiently included metacarpal bone, fractures in measurement regions, foreign material or unacceptable positioning were manually excluded. A total of 18,824 radiographs from 15,072 patients were analysed with DXR, yielding a calculated BMD equivalent (DXR-BMD). Patients were matched with the national death and inpatient registers. Inclusion criteria were age a parts per thousand yen 40 years, no prior hip fracture and observation time andgt; 7 days. Hip fractures were identified via ICD-10 codes. Age-adjusted hazard ratio per standard deviation (HR/SD) was calculated using Cox regression. less thanbrgreater than less thanbrgreater than8,257 patients (65.6 % female, 34.4 % male) met the inclusion criteria. One hundred twenty-two patients suffered a hip fracture after their radiograph. The fracture group had a significantly lower DXR-BMD than the non-fracture group when adjusted for age. The HR/SD for hip fracture was 2.52 and 2.08 in women and men respectively. The area under the curve was 0.89 in women and 0.84 in men. less thanbrgreater than less thanbrgreater thanDXR analysis of wrist and hand radiographs obtained at emergency hospitals predicts hip fracture risk in women and men. less thanbrgreater than less thanbrgreater thanKey Points less thanbrgreater than less thanbrgreater thanDigital X-ray radiogrammetry of emergency hand/wrist radiographs predicts hip fracture risk. less thanbrgreater than less thanbrgreater thanDigital X-ray radiogrammetry (DXR) predicts hip fracture risk in both women and men. less thanbrgreater than less thanbrgreater thanOsteoporosis can potentially be identified in patients with suspected wrist fractures. less thanbrgreater than less thanbrgreater thanDXR can potentially be used for selective osteoporosis screening.

Place, publisher, year, edition, pages
Springer Verlag (Germany), 2013
Keyword
Osteoporosis, Hip fracture, Digital X-ray radiogrammetry, Cohort, BMD
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-103399 (URN)10.1007/s00330-012-2706-9 (DOI)000317427500029 ()
Note

Funding Agencies|Stockholm County Council||Karolinska Institutet||

Available from: 2014-01-20 Created: 2014-01-20 Last updated: 2017-12-06Bibliographically approved
4. Feasibility, precision and validity of a novel fully automated quantitative method developed for measurement of digital joint space width in inflammatory arthritis
Open this publication in new window or tab >>Feasibility, precision and validity of a novel fully automated quantitative method developed for measurement of digital joint space width in inflammatory arthritis
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objectives

In rheumatoid arthritis (RA) radiographic joint damage is a key long-term outcome and is often evaluated in clinical trials through the van der Heijde modified Sharp method which includes the joint space narrowing (JSN) score. The aim of this study was to investigate the feasibility, the precision and the validity of a novel fully automated method for quantifying joint space width (JSW) in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints in order to develop a method for use in the clinic where manual scoring is usually not available.

Methods

Radiographs from the SWEFOT trial were examined and processed for automated quantification of 1 year change (1yCh) in average JSW in MCP joints 2, 3 and 4 and proximal PIP joints 2 and 3. The relationship between change in JSW and change in JSN was studied using linear regression.

Results

1yCh in MCP234 and PIP23 was successfully measured in 119/119 and 117/119 patients respectively. Reproducibility expressed as coefficient of variation was 1.4% for MCP234 JSW and 1.6% for PIP23 JSW. There was a significant relationship between 1yCh in MCP234 JSW and 1yCh in JSN (r= -0.19, p=0.036). In contrast, 1yCh in PIP23 JSW was not independently significantly associated with 1yCh in JSN.

Conclusion

Automated measurement of change in MCP234 JSW was technically feasible and it was related to the change in JSN. Adding PIP23 JSW did not strengthen the association to JSN. We are continuing to study the possible utility of JSW in clinical trials and clinical practice.

Keyword
Joint space width, rheumatoid arthritis, Computer-aided joint space analysis, Sharp van der Heijde score, Digital X-ray radiogrammetry
National Category
Medical Image Processing Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-114401 (URN)
Available from: 2015-02-20 Created: 2015-02-20 Last updated: 2015-02-20Bibliographically approved

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