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Physiologic characterization of inflammatory arthritis in a rabbit model with BOLD and DCE MRI at 1.5 Tesla

  • Musculoskeletal
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Abstract

Objective

Our aim was to test the feasibility of blood oxygen level dependent magnetic resonance imaging (BOLD MRI) and dynamic contrast-enhanced (DCE) MRI to monitor periarticular hypoxic/inflammatory changes over time in a juvenile rabbit model of arthritis.

Methods

We examined arthritic and contralateral nonarthritic knees of 21 juvenile rabbits at baseline and days 1,14, and 28 after induction of arthritis by unilateral intra-articular injection of carrageenin with BOLD and DCE MRI at 1.5 Tesla (T). Nine noninjected rabbits served as controls. Associations between BOLD and DCE-MRI and corresponding intra-articular oxygen pressure (PO2) and blood flow [blood perfusion units (BPU)] (polarographic probes, reference standards) or clinical–histological data were measured by correlation coefficients.

Results

Percentage BOLD MRI change obtained in contralateral knees correlated moderately with BPU on day 0 (r = −0.51, p = 0.02) and excellently on day 28 (r = −0.84, p = 0.03). A moderate correlation was observed between peak enhancement DCE MRI (day 1) and BPU measurements in arthritic knees (r = 0.49, p = 0.04). In acute arthritis, BOLD and DCE MRI highly correlated (r = 0.89, p = 0.04; r = 1.0, p < 0.0001) with histological scores in arthritic knees.

Conclusion

The proposed techniques are feasible to perform at 1.5 T, and they hold potential as surrogate measures to monitor hypoxic and inflammatory changes over time in arthritis at higher-strength MRI fields.

Key points

• BOLD and DCE MRI detect interval perisynovial changes in a rabbit knee

• BOLD and DCE MRI act as surrogate markers of physiologic changes in arthritis

• BOLD MRI signal represents oxygen extraction compared with intra-articular PO 2

• DCE MRI measurements estimate physiologic periarticular vascular properties

• In rabbit knees with acute arthritis, BOLD/DCE MRI highly correlated with histological scores

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Abbreviations

BOLD:

Blood-oxygen-level-dependent

T:

Tesla

TE:

Echo time

TR:

Repetition time

NEX:

Number of averages

ROI:

Regions of interest

Diff_on_off t score:

Difference of on-and-off signal intensities

PT %:

Percentage of activated voxels

pos_neg:

Positive negative

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Acknowledgments

The scientific guarantor of this publication is Andrea S. Doria. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. This study has received funding by Radiological Society of North America – Seed Grant. One of the authors, Rahim Moineddin, has significant statistical expertise. Institutional Review Board approval was obtained.

Written informed consent was waived by the Institutional Review Board. Approval from the institutional animal care committee was obtained. Some study subjects or cohorts have been previously reported in Pediatric Radiology [45]. In the current study, arthritic and corresponding contralateral knee joints in 21 rabbits and 18 nonarthritic (control) knee joints in 30 untreated rabbits were imaged using BOLD MRI at 1.5 T at baseline and on days 1, 14, and 28 after arthritis induction. We tested: (1) the association between BOLD MRI measurements and intra-articular PO2 and blood flow measurements in knees of rabbits with inflammatory arthritis (criterion validity, objective #1), and (2) the association between BOLD MRI measurements, clinical (joint diameters), and histologic constructs (convergent validity, objective #2).

In the study titled “Systematic protocol for assessment of the validity of BOLD MRI in a rabbit model of inflammatory arthritis at 1.5 Tesla” recently accepted for publication in Pediatric Radiology, data from 21 arthritic and 21 contralateral knees, which served as internal controls, were analyzed. In addition, nine noninjected rabbits, comprising 18 noninjected knees, were used as external controls. In this study we optimized BOLD MRI reading parameters in an inflammatory arthritis rabbit model, including the most diagnostically accurate BOLD signal threshold (0.01 vs 0.2) method of measuring the BOLD signal (i.e., percentage of activated voxels vs difference between on and off signal intensities), and type of activations (positive, negative, and positive_negative). As previously mentioned, this study was necessary for reduction of parameters for interpretation of BOLD MRI and to support the methodology of the validation study.

Methodology: experimental, performed at one institution.

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Authors and Affiliations

  1. Department of Diagnostic Imaging, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada, M5G1X8

    Otilia C. Nasui, Michael W. Chan, George Nathanael, Hai-Ling Cheng, Andrea Kassner, Tammy Rayner, Ruth Weiss, Garry Detzler, Anguo Zhong & Andrea S. Doria

  2. Department of Neonatology, The Hospital for Sick Children, Toronto, ON, Canada

    Jaques Belik

  3. Department of Medical Imaging, University of Toronto, Toronto, ON, Canada

    Adrian Crawley, Hai-Ling Cheng, Andrea Kassner & Andrea S. Doria

  4. Department of Medical Imaging, Toronto Western Hospital, Toronto, ON, Canada

    Adrian Crawley

  5. Department of Public Health, Family and Community Medicine, Toronto, ON, Canada

    Rahim Moineddin

  6. Department of Pathology, Mount Sinai Hospital, Toronto, ON, Canada

    Roland Jong & Marianne Rogers

  7. Department of Diagnostic Imaging, Children’s Hospital of Eastern Ontario (CHEO), Ottawa, ON, Canada

    Elka Miller

Authors
  1. Otilia C. Nasui
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  2. Michael W. Chan
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  3. George Nathanael
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  4. Adrian Crawley
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  5. Elka Miller
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  6. Jaques Belik
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  7. Hai-Ling Cheng
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  8. Andrea Kassner
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  9. Tammy Rayner
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  10. Ruth Weiss
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  11. Garry Detzler
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  12. Anguo Zhong
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  13. Rahim Moineddin
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  14. Roland Jong
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  15. Marianne Rogers
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  16. Andrea S. Doria
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Correspondence to Andrea S. Doria.

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Nasui, O.C., Chan, M.W., Nathanael, G. et al. Physiologic characterization of inflammatory arthritis in a rabbit model with BOLD and DCE MRI at 1.5 Tesla. Eur Radiol 24, 2766–2778 (2014). https://doi.org/10.1007/s00330-014-3331-6

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  • DOI: https://doi.org/10.1007/s00330-014-3331-6

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