Skip to main content

Advertisement

SpringerLink
Log in

Quantification of Skeletal Blood Flow and Fluoride Metabolism in Rats using PET in a Pre-Clinical Stress Fracture Model

  • Research Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

Blood flow is an important factor in bone production and repair, but its role in osteogenesis induced by mechanical loading is unknown. Here, we present techniques for evaluating blood flow and fluoride metabolism in a pre-clinical stress fracture model of osteogenesis in rats.

Procedures

Bone formation was induced by forelimb compression in adult rats. 15O water and 18F fluoride PET imaging were used to evaluate blood flow and fluoride kinetics 7 days after loading. 15O water was modeled using a one-compartment, two-parameter model, while a two-compartment, three-parameter model was used to model 18F fluoride. Input functions were created from the heart, and a stochastic search algorithm was implemented to provide initial parameter values in conjunction with a Levenberg–Marquardt optimization algorithm.

Results

Loaded limbs are shown to have a 26% increase in blood flow rate, 113% increase in fluoride flow rate, 133% increase in fluoride flux, and 13% increase in fluoride incorporation into bone as compared to non-loaded limbs (p < 0.05 for all results).

Conclusions

The results shown here are consistent with previous studies, confirming this technique is suitable for evaluating the vascular response and mineral kinetics of osteogenic mechanical loading.

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

Similar content being viewed by others

References

  1. Glowacki J (1998) Angiogenesis in fracture repair. Clin Orthop Relat Res Oct 355S:S82–S89

    Article  Google Scholar 

  2. Pliefke J, Rademacher G, Zach A et al (2009) Postoperative monitoring of free vascularized bone grafts in reconstruction of bone defects. Microsurgery 29(5):401–407

    Article  PubMed  Google Scholar 

  3. Banic A, Hertel R (1993) Double vascularized fibulas for reconstruction of large tibial defects. J Reconstr Microsurg 9(6):421–428

    Article  PubMed  CAS  Google Scholar 

  4. Pechak DG, Kujawa MJ, Caplan AI (1986) Morphological and histochemical events during first bone formation in embryonic chick limbs. Bone 7(6):441–458

    Article  PubMed  CAS  Google Scholar 

  5. Wohl GR, Towler DA, Silva MJ (2009) Stress fracture healing: fatigue loading of the rat ulna induces upregulation in expression of osteogenic and angiogenic genes that mimic the intramembranous portion of fracture repair. Bone 44(2):320–330

    Article  PubMed  CAS  Google Scholar 

  6. Hsieh YF, Silva MJ (2002) In vivo fatigue loading of the rat ulna induces both bone formation and resorption and leads to time-related changes in bone mechanical properties and density. J Orthop Res 20(4):764–771

    Article  PubMed  Google Scholar 

  7. De Souza RL, Matsuura M, Eckstein F et al (2005) Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element. Bone 37(6):810–818

    Article  PubMed  Google Scholar 

  8. Dyke JP, Aaron RK (2010) Noninvasive methods of measuring bone blood perfusion. Ann N Y Acad Sci 1192:95–102

    Article  PubMed  CAS  Google Scholar 

  9. McCarthy I (2006) The physiology of bone blood flow: a review. J Bone Joint Surg Am 88(S3):4–9

    Article  PubMed  Google Scholar 

  10. Kubo S, Yamamoto K, Magata Y et al (1991) Assessment of pancreatic blood flow with positron emission tomography and oxygen-15 water. Ann Nucl Med 5(4):133–138

    Article  PubMed  CAS  Google Scholar 

  11. de Langen AJ, Lubberink M, Boellaard R et al (2008) Reproducibility of tumor perfusion measurements using 15O-labeled water and PET. J Nucl Med 49(11):1763–1768

    Article  PubMed  Google Scholar 

  12. Rimoldi O, Schafers KP, Boellaard R et al (2006) Quantification of subendocardial and subepicardial blood flow using 15O-labeled water and PET: experimental validation. J Nucl Med 47(1):163–172

    PubMed  Google Scholar 

  13. Raichle ME, Martin WR, Herscovitch P, Mintun MA, Markham J (1983) Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation. J Nucl Med 24(9):790–798

    PubMed  CAS  Google Scholar 

  14. Doot RK, Muzi M, Peterson LM et al (2010) Kinetic analysis of 18F-fluoride PET images of breast cancer bone metastases. J Nucl Med 51(4):521–527

    Article  PubMed  CAS  Google Scholar 

  15. Temmerman OP, Raijmakers PG, Heyligers IC et al (2008) Bone metabolism after total hip revision surgery with impacted grafting: evaluation using H 152 O and [18F]fluoride PET; a pilot study. Mol Imaging Biol 10(5):288–293

    Article  PubMed  Google Scholar 

  16. Grynpas MD (1990) Fluoride effects on bone crystals. J Bone Miner Res 5(S1):S169–S175

    Article  PubMed  CAS  Google Scholar 

  17. Hsu WK, Feeley BT, Krenek L et al (2007) The use of 18F-fluoride and 18F-FDG PET scans to assess fracture healing in a rat femur model. Eur J Nucl Med Mol Imaging 34(8):1291–1301

    Article  PubMed  CAS  Google Scholar 

  18. Silva MJ, Uthgenannt BA, Rutlin JR et al (2006) In vivo skeletal imaging of 18F-fluoride with positron emission tomography reveals damage- and time-dependent responses to fatigue loading in the rat ulna. Bone 39(2):229–236

    Article  PubMed  CAS  Google Scholar 

  19. Piert M, Machulla HJ, Jahn M et al (2002) Coupling of porcine bone blood flow and metabolism in high-turnover bone disease measured by [(15)O]H(2)O and [(18)F]fluoride ion positron emission tomography. Eur J Nucl Med Mol Imaging 29(7):907–914

    Article  PubMed  CAS  Google Scholar 

  20. Torrance AG, Mosley JR, Suswillo RF, Lanyon LE (1994) Noninvasive loading of the rat ulna in vivo induces a strain-related modeling response uncomplicated by trauma or periostal pressure. Calcif Tissue Int 54(3):241–247

    Article  PubMed  CAS  Google Scholar 

  21. Matsuzaki H, Wohl GR, Novack DV, Lynch JA, Silva MJ (2007) Damaging fatigue loading stimulates increases in periosteal vascularity at sites of bone formation in the rat ulna. Calcif Tissue Int 80(6):391–399

    Article  PubMed  CAS  Google Scholar 

  22. Kety SS (1960) Theory of blood–tissue exchange and its application to measurement of blood flow. Methods Med Res 8:223–227

    Google Scholar 

  23. Hawkins RA, Choi Y, Huang SC et al (1992) Evaluation of the skeletal kinetics of fluorine-18-fluoride ion with PET. J Nucl Med 33(5):633–642

    PubMed  CAS  Google Scholar 

  24. Bloomfield SA, Hogan HA, Delp MD (2002) Decreases in bone blood flow and bone material properties in aging Fischer-344 rats. Clin Orthop Relat Res Mar 396:248–257

    Article  Google Scholar 

  25. Brenner W, Vernon C, Muzi M et al (2004) Comparison of different quantitative approaches to 18F-fluoride PET scans. J Nucl Med 45(9):1493–1500

    PubMed  CAS  Google Scholar 

  26. Blau M, Ganatra R, Bender MA (1972) 18F-fluoride for bone imaging. Semin Nucl Med 2(1):31–37

    Article  PubMed  CAS  Google Scholar 

  27. Genant HK, Bautovich GJ, Singh M, Lathrop KA, Harper PV (1974) Bone-seeking radionuclides: an in vivo study of factors affecting skeletal uptake. Radiology 113(2):373–382

    PubMed  CAS  Google Scholar 

  28. Uthgenannt BA, Kramer MH, Hwu JA, Wopenka B, Silva MJ (2007) Skeletal self-repair: stress fracture healing by rapid formation and densification of woven bone. J Bone Miner Res 22(10):1548–1556

    Article  PubMed  Google Scholar 

  29. Hsu WK, Virk MS, Feeley BT et al (2008) Characterization of osteolytic, osteoblastic, and mixed lesions in a prostate cancer mouse model using 18F-FDG and 18F-fluoride PET/CT. J Nucl Med 49(3):414–421

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Funded by a grant from the National Institutes of Health (AR050211). The authors would like to acknowledge Nikki Fettig, Lori Strong, Dr. Richard Laforest, and JR Rutlin for their assistance in PET scanning. Mechanical loading performed in facilities supported by the Washington University Center for Musculoskeletal Research (P30AR057235).

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Washington University in St. Louis, 660 S. Euclid Ave., Campus Box 8233, St. Louis, MO, 63110, USA

    Ryan E. Tomlinson & Matthew J. Silva

  2. Department of Biomedical Engineering, Washington University in St. Louis, 1 Brookings Dr., Campus Box 1097, St. Louis, MO, 63130, USA

    Ryan E. Tomlinson & Matthew J. Silva

  3. Department of Radiology, Washington University in St. Louis, 510 S. Kingshighway Blvd., Campus Box 8225, St. Louis, MO, 63110, USA

    Kooresh I. Shoghi

Authors
  1. Ryan E. Tomlinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew J. Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kooresh I. Shoghi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kooresh I. Shoghi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tomlinson, R.E., Silva, M.J. & Shoghi, K.I. Quantification of Skeletal Blood Flow and Fluoride Metabolism in Rats using PET in a Pre-Clinical Stress Fracture Model. Mol Imaging Biol 14, 348–354 (2012). https://doi.org/10.1007/s11307-011-0505-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-011-0505-3

Key words

Search

Navigation