Skip to main content

Database of normal human cerebral blood flow measured by SPECT: I. Comparison between I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD as referred with O-15 labeled water PET and voxel-based morphometry

Abstract

Objectives

Three accumulative tracers, iodine-123-labeledN-isopropyl-p-iodoamphetamine (I-123-IMP), technetium-99m-labeled hexamethylpropyleneamineoxime (Tc-99m-HMPAO), and technetium-99m-labeled ethyl cysteinate dirtier (Tc-99m-ECD) are widely used to measure cerebral blood flow (CBF) in single-photon emission computed tomography (SPECT). In the present study, normal regional distribution of CBF measured with three different SPECT tracers was entered into a database and compared with regional distribution of CBF measured by positron emission tomography (PET) with H2 15O. The regional distribution of tissue fractions of gray matter determined by voxel-based morphometry was also compared with SPECT and PET CBF distributions.

Methods

SPECT studies with I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD were performed on 11, 20, and 17 healthy subjects, respectively. PET studies were performed on 11 healthy subjects. Magnetic resonance (MR) imaging studies for voxel-based morphometry were performed on 43 of the 48 subjects who underwent SPECT study. All SPECT, PET, and MR images were transformed into the standard brain format with the SPM2 system. The voxel values of each SPECT and PET image were globally normalized to 50 ml/100 ml/min. Gray matter, white matter, and cerebrospinal fluid images were segmented and extracted from all transformed MR images by applying voxel-based morphometry methods with the SPM2 system.

Results

Regional distribution of all three SPECT tracers differed from that of H2 15O in the pons, midbrain, thalamus, putamen, parahippocampal gyrus, posterior cingulate gyrus, temporal cortex, and occipital cortex. No significant correlations were observed between the tissue fraction of gray matter and CBF with any tracer.

Conclusion

Differences in regional distribution of SPECT tracers were considered to be caused mainly by differences in the mechanism of retention of tracers in the brain. Regional distribution of CBF was independent of regional distribution of gray matter fractions, and consequently the blood flow per gray matter volume differed for each brain region.

This is a preview of subscription content, access via your institution.

References

  1. Kanno I, Lassen NA. Two methods for calculating regional cerebral blood flow from emission computed tomography of inert gas concentrations.J Comput Assist Tomogr 1979; 3:71–76.

    PubMed  CAS  Article  Google Scholar 

  2. Herscovitch P, Markham J, Raichle ME. Brain blood flow measured with intravenous H2 15O. I. Theory and error analysis.J Nucl Med 1983; 24:782–789.

    PubMed  CAS  Google Scholar 

  3. Kanno I, Iida H, Miura S, Murakami M, Takahashi K,Sasaki H. et al. A system for cerebral blood flow measurement using an H2 15O autoradiographic method and positron emission tomography.J Cereb Blood Flow Metab 1987; 7:143–153.

    PubMed  CAS  Google Scholar 

  4. Winchell HS, Baldwin RM, Lin TH. Development of I-123- labeled amines for brain studies: localization of I-123 iodophenylalkyl amines in rat brain.J Nucl Med 1980; 21:940–946.

    PubMed  CAS  Google Scholar 

  5. Winchell HS, Horst WD, Braun L, Oldendorf WH, Hattner R, Parker H. N-isopropyl-[123I]p-iodoamphetamine: single-pass brain uptake and washout; binding to brain synapto-somes; and localization in dog and monkey brain.J Nucl Med 1980; 21:947–952.

    PubMed  CAS  Google Scholar 

  6. Sharp PF, Smith FW, Gemmell HG, Lyall D, Evans NT,Gvozdanovic D, et al. Technetium-99m HM-PAO stereoisomers as potential agents for imaging regional cerebral blood flow: human volunteer studies.J Nucl Med 1986; 27:171–177.

    PubMed  CAS  Google Scholar 

  7. Neirinckx RD, Canning LR, Piper IM, Nowotnik DP,Pickett RD, Holmes RA, et al. Technetium-99m d,l-HM- PAO: a new radiopharmaceutical for SPECT imaging of regional cerebral blood perfusion.J Nucl Med 1987; 28:191–202.

    PubMed  CAS  Google Scholar 

  8. Walovitch RC, Hill TC, Garrity ST, Cheesman EH, Burgess BA, O’Leary DH, et al. Characterization of technetium-99m-L,L.-ECD for brain perfusion imaging, part 1: pharmacology of technetium-99m ECD in nonhuman primates.J Nucl Med 1989; 30:1892–1901.

    PubMed  CAS  Google Scholar 

  9. Leveille J, Demonceau G, De Roo M, Rigo P, Taillefer R, Morgan RA, et al. Characterization of technetium-99m- l,l-ECD for brain perfusion imaging, Part 2: Biodistribution and brain imaging in humans.J Nucl Med 1989; 30:1902–1910.

    PubMed  CAS  Google Scholar 

  10. Ballinger JR, Reid RH, Gulenchyn KY. Technetium-99m HM-PAO stereoisomers: differences in interaction with glutathione.J Nucl Med 1988; 29:1998–2000.

    PubMed  CAS  Google Scholar 

  11. Walovitch RC, Cheesman EH, Maheu LJ, Hall KM. Studies of the retention mechanism of the brain perfusion imaging agent99mTc-bicisate (99mTc-ECD).J Cereb Blood Flow Metab 1994; 14 Suppl 1:S4–11.

    PubMed  CAS  Google Scholar 

  12. Koyama M, Kawashima R, Ito H, Ono S, Sato K, Goto R, et al. SPECT imaging of normal subjects with technetium-99m-HMPAO and technetium-99m-ECD.J Nucl Med 1997; 38:587–592.

    PubMed  CAS  Google Scholar 

  13. Inoue K, Nakagawa M, Goto R, Kinomura S, Sato T, Sato K, et al. Regional differences between99mTc-ECD and99mTc-HMPAO SPET in perfusion changes with age and gender in healthy adults.Eur J Nucl Med Mol Imaging 2003; 30:1489–1497.

    PubMed  Article  Google Scholar 

  14. Hoedt-Rasmussen K. Regional cerebral flow in man measured externally following intra-arterial administration of85Kr or133Xe dissolved in saline.Acta Neurol Scand Suppl 1965; 14:65–68.

    PubMed  CAS  Google Scholar 

  15. Ingvar DH, Cronqvist S, Ekberg R, Risberg J, Hoedt-Rasmussen K. Normal values of regional cerebral blood flow in man, including flow and weight estimates of gray and white matter. A preliminary summary.Acta Neurol Scand Suppl 1965; 14:72–78.

    PubMed  CAS  Google Scholar 

  16. Hoedt-Rasmussen K, Sveinsdottir E, Lassen NA. Regional cerebral blood flow in man determined by intra-arterial injection of radioactive inert gas.Circ Res 1966; 18:237–247.

    PubMed  CAS  Google Scholar 

  17. Iida H, Law I, Pakkenberg B, Krarup-Hansen A, Eberl S, Holm S, et al. Quantitation of regional cerebral blood flow corrected for partial volume effect using O-15 water and PET: I. Theory, error analysis, and stereologic comparison.J Cereb Blood Flow Metab 2000; 20:1237–1251.

    PubMed  Article  CAS  Google Scholar 

  18. Law I, Iida H, Holm S, Nour S, Rostrup E, Svarer C, et al. Quantitation of regional cerebral blood flow corrected for partial volume effect using O-15 water and PET: II. Normal values and gray matter blood flow response to visual activation.J Cereb Blood Flow Metab 2000; 20:1252–1263.

    PubMed  Article  CAS  Google Scholar 

  19. Ashburner J, Friston KJ. Voxel-based morphometry —the methods.Neuroimage 2000; 11:805–821.

    PubMed  Article  CAS  Google Scholar 

  20. Good CD, Johnsrude IS, Ashburner J, Henson RN, Friston KJ, Frackowiak RS. A voxel-based morphometric study of ageing in 465 normal adult human brains.Neuroimage 2001; 14:21–36.

    PubMed  Article  CAS  Google Scholar 

  21. Good CD, Johnsrude I, Ashburner J, Henson RN, Friston KJ, Frackowiak RS. Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains.Neuroimage 2001; 14:685–700.

    PubMed  Article  CAS  Google Scholar 

  22. Kimura K, Hashikawa K, Etani H, Uehara A, Kozuka T, Moriwaki H, et al. A new apparatus for brain imaging: four-head rotating gamma camera single-photon emission computed tomograph [see comments].J Nucl Med 1990; 31:603–609.

    PubMed  CAS  Google Scholar 

  23. Chang LT. A method for attenuation correction in radionu-clide computed tomography.IEEE Trans Nucl Sci 1978; 25:638–643.

    Article  Google Scholar 

  24. Chang LT. Attenuation correction and incomplete projection in single photon emission computed tomography.IEEE Trans Nucl Sci 1979; 26:2780–2789.

    Article  Google Scholar 

  25. Iida H, Miura S, Kanno I, Ogawa T, Uemura K. A new PET camera for noninvasive quantitation of physiological functional parametric images: Headtome-V-dual. In: Myers R, Cunningham V, Bailey D, Jones T, eds.Quantification of brain function using PET. San Diego; Academic Press, 1996: 57–61.

    Google Scholar 

  26. Iida H, Kanno I, Miura S, Murakami M, Takahashi K, Uemura K. Error analysis of a quantitative cerebral blood flow measurement using H2 15O autoradiography and positron emission tomography, with respect to the dispersion of the input function.J Cereb Blood Flow Metab 1986; 6:536- 545.

    PubMed  CAS  Google Scholar 

  27. Iida H, Higano S, Tomura N, Shishido F, Kanno I, Miura S, et al. Evaluation of regional differences of tracer appearance time in cerebral tissues using [l5O]water and dynamic positron emission tomography.J Cereb Blood Flow Metab 1988; 8:285–288.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  29. Friston KJ, Frith CD, Liddle PF, Dolan RJ, Lammertsma AA, Frackowiak RS. The relationship between global and local changes in PET scans.J Cereb Blood Flow Metab 1990; 10:458–466.

    PubMed  CAS  Google Scholar 

  30. Renkin EM. Transport of potassium-42 from blood to tissue in isolated mammalian skeletal muscles.Am J Physiol 1959; 197:1205–1210.

    PubMed  CAS  Google Scholar 

  31. Crone C. The permeability of capillaries in various organs as determined by use of the ‘indicator diffusion’ method.Acta Physiol Scand 1963; 58:292–305.

    PubMed  CAS  Google Scholar 

  32. Iida H, Akutsu T, Endo K, Fukuda H, Inoue T, Ito H, et al. A multicenter validation of regional cerebral blood flow quantitation using [l23I]iodoamphetamine and single photon emission computed tomography.J Cereb Blood Flow Metab 1996; 16:781–793.

    PubMed  Article  CAS  Google Scholar 

  33. Okazawa H, Yamauchi H, Sugimoto K, Toyoda H, Kishibe Y, Takahashi M. Effects of acetazolamide on cerebral blood flow, blood volume, and oxygen metabolism: a positron emission tomography study with healthy volunteers.J Cereb Blood Flow Metab 2001; 21:1472–1479.

    PubMed  Article  CAS  Google Scholar 

  34. Ito H, Kanno I, Iida H, Hatazawa J, Shimosegawa E, Tamura H, et al. Arterial fraction of cerebral blood volume in humans measured by positron emission tomography.Ann Nucl Med 2001; 15:111–116.

    PubMed  CAS  Article  Google Scholar 

  35. Iida H, Narita Y, Kado H, Kashikura A, Sugawara S, Shoji Y, et al. Effects of scatter and attenuation correction on quantitative assessment of regional cerebral blood flow with SPECT.J Nucl Med 1998; 39:181–189.

    PubMed  CAS  Google Scholar 

  36. Ito H, Iida H, Kinoshita T, Hatazawa J, Okudera T, Uemura K. Effects of scatter correction on regional distribution of cerebral blood flow using I-123-IMP and SPECT.Ann Nucl Med 1999; 13:331–336.

    PubMed  CAS  Article  Google Scholar 

  37. Kogure D, Matsuda H, Ohnishi T, Asada T, Uno M, Kunihiro T, et al. Longitudinal evaluation of early Alzheimer’s disease using brain perfusion SPECT.J Nucl Med 2000; 41:1155–1162.

    PubMed  CAS  Google Scholar 

  38. Rodriguez G, Vitali P, Calvini P, Bordoni C, Girtler N, Taddei G, et al. Hippocampal perfusion in mild Alzheimer’s disease.Psychiatry Res 2000; 100:65–74.

    PubMed  Article  CAS  Google Scholar 

  39. Callen DJ, Black SE, Caldwell CB. Limbic system perfusion in Alzheimer’s disease measured by MRI-coregistered HMPAO SPET.Eur J Nucl Med Mol Imaging 2002; 29:899–906.

    PubMed  Article  Google Scholar 

  40. Frisoni GB, Testa C, Zorzan A, Sabattoli F, Beltramello A, Soininen H, et al. Detection of grey matter loss in mild Alzheimer’s disease with voxel based morphometry.J Neurol Neurosurg Psychiatry 2002; 73:657–664.

    PubMed  Article  CAS  Google Scholar 

  41. Karas GB, Burton EJ, Rombouts SA, van Schijndel RA, O’Brien JT, Scheltens P, et al. A comprehensive study of gray matter loss in patients with Alzheimer’s disease using optimized voxel-based morphometry.Neuroimage 2003; 18:895–907.

    PubMed  Article  CAS  Google Scholar 

  42. Chetelat G, Desgranges B, De La Sayette V, Viader F, Eustache F, Baron JC. Mapping gray matter loss with voxel-based morphometry in mild cognitive impairment.Neuroreport 2002; 13:1939–1943.

    PubMed  Article  Google Scholar 

  43. Ishii K, Sasaki M, Yamaji S, Sakamoto S, Kitagaki H, Mori E. Paradoxical hippocampus perfusion in mild-to-moderate Alzheimer’s disease.J Nucl Med 1998; 39:293–298.

    PubMed  CAS  Google Scholar 

  44. Kitayama N, Matsuda H, Ohnishi T, Kogure D, Asada T, Uno M, et al. Measurements of both hippocampal blood flow and hippocampal gray matter volume in the same individuals with Alzheimer’s disease.Nucl Med Commun 2001; 22:473–477.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Kentaro Inoue.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Fro, H., Inoue, K., Goto, R. et al. Database of normal human cerebral blood flow measured by SPECT: I. Comparison between I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD as referred with O-15 labeled water PET and voxel-based morphometry. Ann Nucl Med 20, 131–138 (2006). https://doi.org/10.1007/BF02985625

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02985625

Key words

  • SPECT
  • CBF
  • I-123-IMP
  • Tc-99m-HMPAO
  • Tc-99m-ECD