Skip to main content

Advertisement

SpringerLink
Log in

Contrast-enhanced triggered harmonic sonography for assessment of periarticular hemodynamic changes in experimental arthritis

  • Original Article
  • Published:
Pediatric Radiology Aims and scope Submit manuscript

Abstract

Background

Objective quantification is critical for assessment of functional sonography in inflammatory arthritis. To create a microbubble contrast-enhanced image of vessels that lie below the resolution of a standard US system, a technique is required that detects preferentially the contrast agent echo, rejecting that from background tissue: harmonic imaging.

Objectives

To investigate the ability of contrast-enhanced triggered harmonic sonography (CETHS) to evaluate periarticular hemodynamic changes over the course of experimental arthritis and to discriminate presence and absence of arthritis based on measurement values obtained at specific time-points.

Materials and methods

Arthritis was induced in rabbits knees by intra-articular injection of serum bovine albumin, which acted as an antigen. A total of 11 rabbits (8 with unilateral arthritis and 3 control animals) were imaged at 0, 1, 7, 14, 21 and 28 days of antigen-induced arthritis and euthanized at 28 days. A continuous infusion protocol was performed (triggering times 30.0, 20.0, 10.0, 5.0, 2.0, 1.0, and 0.5 s). Hemodynamic indices of synovial microvasculature (vascular volume, mean velocity and flow rate) were obtained and compared with clinical, laboratory, and histological surrogate markers.

Results

Although interval CETHS changes were noted for flow rate (P=0.007) and vascular volume (P=0.003) ratios in albumin-injected knees, no significant differences in ratios were identified over time between albumin-injected and non-injected knees for flow rate (P=0.52), vascular volume (P=0.23) and mean velocity (P=0.19). Flow rate most accurately differentiated between presence and absence of arthritis according to clinical measurements in early (day 1) arthritis, and mean velocity in mid-term arthritis (day 14; both P=0.02).

Conclusion

Although the measurement properties of CETHS indices were poor in the evaluation of hemodynamic differences over time in albumin-injected knees compared with non-injected knees, they enabled discrimination between presence and absence of arthritis at specific time-points in different stages.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Edmonds SE, Blake DR, Morris CJ, et al (1993) An imaginative approach to synovitis – the role of hypoxic reperfusion damage in arthritis. J Rheumatol Suppl 37:26–31

    PubMed  CAS  Google Scholar 

  2. Burns PN, Wilson SR, Muradali D, et al (1996) Microbubble destruction is the origin of harmonic signals from FS069. Radiology 201:158

    Google Scholar 

  3. Burns PN, Powers JE, Fritzsch T (1992) Harmonic imaging: a new imaging and Doppler method for contrast enhanced ultrasound. Radiology 185:142

    Google Scholar 

  4. Wilson SR, Burns PN, Muradali D, et al (2000) Harmonic hepatic US with microbubble contrast agent: initial experience showing improved characterization of hemangioma, hepatocellular carcinoma, and metastasis. Radiology 215:153–161

    PubMed  CAS  Google Scholar 

  5. Burns PN, Wilson SR, Simpson DH (2000) Pulse inversion imaging of liver blood flow: improved method for characterizing focal masses with microbubble contrast. Invest Radiol 35:58–71

    Article  PubMed  CAS  Google Scholar 

  6. Harvey CJ, Blomley MJ, Eckersley RJ, et al (2000) Hepatic malignancies: improved detection with pulse-inversion US in late phase of enhancement with SH U 508A – early experience. Radiology 216:903–908

    PubMed  CAS  Google Scholar 

  7. Imrie RC (1976) Animal models of arthritis. Lab Anim Sci 26:345–351

    PubMed  CAS  Google Scholar 

  8. Padhani AR (2002) Dynamic contrast-enhanced MRI in clinical oncology: current status and future directions. J Magn Reson Imaging 16:407–422

    Article  PubMed  Google Scholar 

  9. Guyatt GH, Feeny DH, Patrick DL (1993) Measuring health-related quality of life. Ann Intern Med 118:622–629

    PubMed  CAS  Google Scholar 

  10. Cooke TDV (1988) Antigen-induced arthritis, polyarthritis, and tenosynovitis. In: Greenwald RA, Diamond HS (eds) CRC handbook of animal models for rheumatoid diseases. CRC Press, Boca Raton, pp 53–79

    Google Scholar 

  11. Demsar F, Van Dijke CF, Kirk BA, et al (1996) Mapping abnormal synovial vascular permeability in temporomandibular joint arthritis in the rabbit using MRI. Br J Rheumatol 35 [Suppl 3]:23–25

    PubMed  Google Scholar 

  12. Strouse PJ, Londy F, DiPietro MA, et al (1999) MRI evaluation of infectious and non-infectious synovitis: preliminary studies in a rabbit model. Pediatr Radiol 29:367–371

    Article  PubMed  CAS  Google Scholar 

  13. Strouse PJ, DiPietro MA, Teo EL, et al (1999) Power Doppler evaluation of joint effusions: investigation in a rabbit model. Pediatr Radiol 29:617–623

    Article  PubMed  CAS  Google Scholar 

  14. Ferrara KW, Merritt CR, Burns PN, et al (2000) Evaluation of tumor angiogenesis with US: imaging, Doppler, and contrast agents. Acad Radiol 7:824–839

    Article  PubMed  CAS  Google Scholar 

  15. Kaul S (1997) Myocardial contrast echocardiography: 15 years of research and development. Circulation 96:3745–3760

    PubMed  CAS  Google Scholar 

  16. Wei K, Jayaweera AR, Firoozan S, et al (1998) Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. Circulation 97:473–483

    PubMed  CAS  Google Scholar 

  17. Kane D, Roth J, Frosch M, et al (2003) Increased perivascular synovial membrane expression of myeloid-related proteins in psoriatic arthritis. Arthritis Rheum 48:1676–1685

    Article  PubMed  CAS  Google Scholar 

  18. Roth J, Teigelkamp S, Wilke M, et al (1992) Complex pattern of the myelo-monocytic differentiation antigens MRP8 and MRP14 during chronic airway inflammation. Immunobiology 186:304–314

    PubMed  CAS  Google Scholar 

  19. Koizumi F, Matsuno H, Wakaki K, et al (1999) Synovitis in rheumatoid arthritis: scoring of characteristic histopathological features. Pathol Int 49:298–304

    Article  PubMed  CAS  Google Scholar 

  20. Oehler S, Neureiter D, Meyer-Scholten C, et al (2002) Subtyping of osteoarthritic synoviopathy. Clin Exp Rheumatol 20:633–640

    PubMed  CAS  Google Scholar 

  21. Altman DG, Bland JM (1994) Diagnostic tests 3: receiver operator characteristic plots. BMJ 309:188

    PubMed  CAS  Google Scholar 

  22. DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44:837–845

    Article  PubMed  CAS  Google Scholar 

  23. Kono Y, Mattery RF, Summers H, et al (1999) Visualization of tumor vessels with ultrasound contrast and the potential for qualitative analysis of relative tumor blood flow and fractional blood volume. Proceedings of the Bioengineering Consortium Conference, National Institutes of Health, Bethesda

  24. Doria AS, Noseworthy M, Oakden W, et al (2006) Dynamic contrast-enhanced MRI quantification of synovium microcirculation in antigen-induced arthritis. AJR 186:1165–1171

    Article  PubMed  Google Scholar 

  25. Burns P, Wilson S (2003) Assessing antivascular therapy for hepatocellular carcinoma using US contrast agents: a baseline reproducibility study. Radiology Suppl, p 529

  26. Johnson RG, Herbert MA, Wright S, et al (1983) The response of articular cartilage to the in vivo replacement of synovial fluid with saline. Clin Orthop Relat Res 174:285–292

    PubMed  Google Scholar 

  27. Jain RK (1988) Determinants of tumor blood flow: a review. Cancer Res 48:2641–2658

    PubMed  CAS  Google Scholar 

  28. Simkin PA (1979) Synovial permeability in rheumatoid arthritis. Arthritis Rheum 22:689–696

    Article  PubMed  CAS  Google Scholar 

  29. Levick JR (1990) Hypoxia and acidosis in chronic inflammatory arthritis; relation to vascular supply and dynamic effusion pressure. J Rheumatol 17:579–582

    PubMed  CAS  Google Scholar 

  30. Adler DD, Carson PL, Rubin JM, et al (1990) Doppler ultrasound color flow imaging in the study of breast cancer: preliminary findings. Ultrasound Med Biol 16:553–559

    Article  PubMed  CAS  Google Scholar 

  31. Birdwell RL, Ikeda DM, Jeffrey SS, et al (1997) Preliminary experience with power Doppler imaging of solid breast masses. AJR 169:703–707

    PubMed  CAS  Google Scholar 

  32. Carson PL, Moskalik AP, Govil A, et al (1997) The 3D and 2D color flow display of breast masses. Ultrasound Med Biol 23:837–849

    Article  PubMed  CAS  Google Scholar 

  33. Lassau N, Paturel-Asselin C, Guinebretiere JM, et al (1999) New hemodynamic approach to angiogenesis: color and pulsed Doppler ultrasonography. Invest Radiol 34:194–198

    Article  PubMed  CAS  Google Scholar 

  34. Lovell DJ, Giannini EH, Reiff A, et al (2000) Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric rheumatology collaborative study group. N Engl J Med 342:763–769

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Marianne Rogers for preparation of histological slides of synovium, Niels Celeghin for analysis of data, and Sheri Holmberg and Jeff Powers, PhD, for help with standardization of technical parameters at the initial phase of the study.

Definity contrast agent was funded by Bristol-Myers Squibb Laboratory, Billerica, Mass.

Author information

Authors and Affiliations

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

    Andrea S. Doria, Arun Mohanta & Anguo Zhong

  2. Department of Research Imaging, Sunnybrook Women’s College Hospital, Toronto, Canada

    Raffi Karshafian & Peter Burns

  3. Department of Public Health, Family and Community Medicine, University of Toronto, Toronto, Canada

    Rahim Moineddin

  4. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada

    Maria Mendes, Kenneth Pritzker & Roland Jong

Authors
  1. Andrea S. Doria
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raffi Karshafian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rahim Moineddin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Arun Mohanta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anguo Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maria Mendes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kenneth Pritzker
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Roland Jong
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Peter Burns
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea S. Doria.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Doria, A.S., Karshafian, R., Moineddin, R. et al. Contrast-enhanced triggered harmonic sonography for assessment of periarticular hemodynamic changes in experimental arthritis. Pediatr Radiol 36, 1242–1251 (2006). https://doi.org/10.1007/s00247-006-0300-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00247-006-0300-5

Keywords

Search

Navigation