Nitrogen-13 ammonia cardiac positron emission tomography in mice: effects of clonidine-induced changes in cardiac work on myocardial perfusion

  • Masayuki Inubushi
  • Maria C. Jordan
  • Kenneth P. Roos
  • Robert S. Ross
  • Arion F. Chatziioannou
  • David B. Stout
  • Magnus Dahlbom
  • Heinrich R. Schelbert
Molecular Imaging

Abstract

We explored the feasibility of imaging myocardial perfusion and of demonstrating the flow changes in response to reduction of cardiac work non-invasively in anesthetized mice using high spatial resolution, dedicated small-animal positron emission tomography (microPET). In 31 C57BL/6 mice anesthetized with pentobarbital or isoflurane, 13N-ammonia was injected intravenously and images were recorded with microPET from 4 to 20 min. Fifteen mice (group 1) were studied consecutively at baseline (BL) and after reduction of heart rate (HR) with intraperitoneal injection of clonidine (CLN) to investigate effects of CLN-induced reduction of cardiac work on myocardial 13N-ammonia uptake. Eight mice (group 2) were imaged repeatedly at BL and eight mice (group 3) twice after CLN to examine reproducibility. Total myocardial 13N-ammonia accumulation was determined from the transaxial images and normalized for injected dose (%ID). HR was 412±97 beats/min at BL and 212±44 beats/min after CLN (P<0.0001). In group 1, the %ID significantly decreased from 1.50%±0.27% at BL to 1.29%±0.28% after CLN (P<0.0001). In groups 2 and 3, reproducibility of %ID was good (y=0.96x+0.105, SEE=0.212%, r2=0.749, P<0.0001). In conclusion, 13N-ammonia microPET imaging demonstrated non-invasively a reduction of myocardial perfusion induced by clonidine in mice. We believe this study is of importance as the first report on myocardial perfusion imaging and flow validation in in vivo mouse hearts with a left ventricular size of only 5 mm using 13N-ammonia and PET. MicroPET will aid in elucidating cardiac pathophysiology in transgenic mice and monitoring effects of gene therapies on myocardial perfusion.

Keywords

13N-ammonia Positron emission tomography Mice Heart Myocardial perfusion 

References

  1. 1.
    Chatziioannou AF, Cherry SR, Shao Y, Silverman RW, Meadors K, Farquhar TH, Pedarsani M, Phelps ME. Performance evaluation of microPET: a high-resolution lutetium oxyorthosilicate PET scanner for animal imaging. J Nucl Med 1999; 40:1164–1175.PubMedGoogle Scholar
  2. 2.
    Inubushi M, Wu JC, Gambhir SS, Sundaresan G, Satyamurthy N, Namavari M, Yee S, Barrio JR, Stout D, Chatziioannou AF, Wu L, Schelbert HR. Positron-emission tomography reporter gene expression imaging in rat myocardium. Circulation 2002; 107:326–332.CrossRefGoogle Scholar
  3. 3.
    Kudo T, Fukuchi K, Annala AJ, Chatziioannou AF, Allada V, Dahlbom M, Tai YC, Inubushi M, Huang SC, Cherry SR, Phelps ME, Schelbert HR. Non-invasive measurement of myocardial activity concentrations and perfusion defect sizes in rats with a new small animal positron emission tomograph. Circulation 2002; 106:118–123.CrossRefPubMedGoogle Scholar
  4. 4.
    Opie LH. The heart: physiology, from cell to circulation, 3rd edn. Philadelphia: Lippincott-Raven, 1998.Google Scholar
  5. 5.
    Chatziioannou A, Qi J, Moore A, Annala A, Nguyen K, Leahy R, Cherry SR. Comparison of 3-D maximum a posteriori and filtered backprojection algorithms for high-resolution animal imaging with microPET. IEEE Trans Med Imaging. 2000;19: 507–512.Google Scholar
  6. 6.
    Bergstrom M, Litton J, Eriksson L, Bohm C, Blomqvist G. Determination of object contour from projections for attenuation correction in cranial positron emission tomography. J Comput Assist Tomogr 1982; 6:365–372.PubMedGoogle Scholar
  7. 7.
    Tanaka N, Dalton N, Mao L, Rockman HA, Peterson KL, Gottshall KR, Hunter JJ, Chien KR, Ross J Jr. Transthoracic echocardiography in models of cardiac disease in the mouse. Circulation 1996; 94:1109–1117.PubMedGoogle Scholar
  8. 8.
    Bland J, Altman D. statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 1:307–310.PubMedGoogle Scholar
  9. 9.
    Krivokapich J, Smith GT, Huang SC, Hoffman EJ, Ratib O, Phelps ME, Schelbert HR.13N ammonia myocardial imaging at rest and with exercise in normal volunteers. Quantification of absolute myocardial perfusion with dynamic positron emission tomography [see comments]. Circulation 1989; 80:1328–1337.PubMedGoogle Scholar
  10. 10.
    Kuhle WG, Porenta G, Huang SC, Buxton D, Gambhir SS, Hansen H, Phelps ME, Schelbert HR. Quantification of regional myocardial blood flow using13N-ammonia and reoriented dynamic positron emission tomographic imaging. Circulation 1992; 86:1004–1017.PubMedGoogle Scholar
  11. 11.
    Hoffman EJ, Huang SC, Phelps ME. Quantitation in positron emission computed tomography: 1. Effect of object size. J Comput Assist Tomogr 1979; 3:299–308.PubMedGoogle Scholar
  12. 12.
    Shah A, Schelbert HR, Schwaiger M, Henze E, Hansen H, Selin C, Huang SC. Measurement of regional myocardial blood flow with N-13 ammonia and positron-emission tomography in intact dogs. J Am Coll Cardiol 1985; 5:92–100.Google Scholar
  13. 13.
    Nienaber CA, Ratib O, Gambhir SS, Krivokapich J, Huang SC, Phelps ME, Schelbert HR. A quantitative index of regional blood flow in canine myocardium derived noninvasively with N-13 ammonia and dynamic positron emission tomography. J Am Coll Cardiol 1991; 17:260–269.PubMedGoogle Scholar
  14. 14.
    Waller C, Kahler E, Hiller KH, Hu K, Nahrendorf M, Voll S, Haase A, Ertl G, Bauer WR. Myocardial perfusion and intracapillary blood volume in rats at rest and with coronary dilatation: MR imaging in vivo with use of a spin- labeling technique. Radiology 2000; 215:189–197.PubMedGoogle Scholar
  15. 15.
    Schelbert HR, Phelps ME, Hoffman EJ, Huang SC, Selin CE, Kuhl DE. Regional myocardial perfusion assessed with N-13 labeled ammonia and positron emission computerized axial tomography. Am J Cardiol 1979; 43:209–218.PubMedGoogle Scholar
  16. 16.
    Wu JC, Inubushi M, Sundaresan G, Schelbert HR, Gambhir SS. Positron emission tomography imaging of cardiac reporter gene expression in living rats. Circulation 2002; 106:180–183.CrossRefPubMedGoogle Scholar
  17. 17.
    Godecke A, Ziegler M, Ding Z, Schrader J. Endothelial dysfunction of coronary resistance vessels in apoE−/− mice involves NO but not prostacyclin-dependent mechanisms. Cardiovasc Res 2002; 53:253–262.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Masayuki Inubushi
    • 1
  • Maria C. Jordan
    • 2
  • Kenneth P. Roos
    • 2
  • Robert S. Ross
    • 2
  • Arion F. Chatziioannou
    • 3
  • David B. Stout
    • 3
  • Magnus Dahlbom
    • 1
  • Heinrich R. Schelbert
    • 1
  1. 1.Department of Molecular and Medical PharmacologyUniversity of California Los Angeles David Geffen School of MedicineLos AngelesUSA
  2. 2.Department of PhysiologyUniversity of California Los Angeles David Geffen School of MedicineLos AngelesUSA
  3. 3.The Crump Institute for Molecular ImagingUniversity of California Los Angeles David Geffen School of MedicineLos AngelesUSA

Personalised recommendations