European Journal of Nuclear Medicine

, Volume 24, Issue 7, pp 754–761 | Cite as

Effects of aging on the cerebral distribution of technetium-99m hexamethylpropylene amine oxime in healthy humans

  • P. David Mozley
  • Ahmed M. Sadek
  • Abass Alavi
  • Ruben C. Gurt
  • Larry R. Muenz
  • Barry J. Bunow
  • Hee-Joung Kim
  • Mark H. Stecker
  • Paul Jolles
  • Andrew Newberg
Original Article


Some brain functions decline at a linear rate throughout adulthood. Others remain relatively stable until very late in the life cycle. This study characterized the effects of aging on the regional cerebral distribution of hexamethylpropylene amine oxime (HMPAO) in healthy human volunteers. The sample consisted of 26 men and 18 women with a mean age of 41.6±14.9 years (range: 19–73). Their past medical histories, physical examinations, and laboratory screening tests were normal. Single-photon emission tomography (SPET) scans of the brain were performed with a standardized acquisition and processing protocol on a triple-headed camera equipped with fan beam collimators. A 3-D restorative filter and a correction for uniform attenuation were applied before the images were reinterpolated in planes parallel to the line connecting the frontal and occipital poles. Mean counts per pixel were measured in multiple regions of interest (ROIs) within each hemisphere by custom fitting a set of templates to the images. The mean activity in each ROI was compared with the mean activity per pixel in the whole brain. Regression analyses were used to relate the activity ratios to age with both linear and nonlinear models. The relative concentration of radioactivity decreased significantly with age in most, but not all, gray matter structures. It increased in the white matter regions. The nonlinear model of aging fit the data significantly better than a straight line did. Most of the changes with age occurred during young adulthood. No further changes were detectable after the onset of middle age. The median breakpoint age at which the rate of change became negligible was 36.6 years. Aging significantly affects the relative uptake of HMPAO in healthy humans. It decreases in many gray matter regions and increases in most white matter regions. However, the changes do not appear to be linear. Most seem to occur during young adulthood before people reach their late thirties. The distribution then appears to remain relatively stable throughout middle age.

Key words

Aging Regional cerebral blood flow Single-photon emission tomography 


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  1. 1.
    Rapp PR, Amaral DG. Individual differences in the cognitive and neurobiological consequences of normal aging.Trends Neurosci 1992; 15: 340–345.PubMedGoogle Scholar
  2. 2.
    Lezak MD. Neuropsychological assessment, 2nd edn. New York: Oxford University Press, 1983.Google Scholar
  3. 3.
    Bak JS, Greene RL. Changes in neuropsychological functioning in an aging population.J Consult Clin Psychol 1980; 48: 395–399.PubMedGoogle Scholar
  4. 4.
    Harley JP, Leuthold CA, Matthews CG, Bergs LE.Wisconsin Neuropsychological Test Battery T-score norms for older Veterans Administration Medical Center patients. Madison, Wis.: CG Matthews, 1980.Google Scholar
  5. 5.
    Heaton RK, Grant I, Matthews CG. Differences in neuropsychological test performance associated with age, education, and sex. In: Grant I, Adams KM, eds.Neuropsychological assessment of neuropsychiatric disorders. New York: Oxford University Press; 1986: 100–120Google Scholar
  6. 6.
    Heaton RK, Grant I, Matthews CG.Comprehensive norms for an expanded Halstead-Reitan Battery. Odessa, Fl.: Psychological Assessment Resources, Inc.; 1991: 5–13.Google Scholar
  7. 7.
    Alavi A, Hirsch LJ. Studies of central nervous system disorders with single photon emission computed tomography and positron emission tomography: evolution over the past 2 decades.Semin Nucl Med 1991; 21: 58–81.PubMedGoogle Scholar
  8. 8.
    Ell PJ, Hocknell JML, Jarritt PH, Cullum I, Lui D, Campos-Costa D, Nowetnik DP, Pickett RD, Canning LR, Neirinckx RD. A 99m Tc-labelled radiotracer for the investigation of cerebral vascular disease.Nucl Med Commun 1985; 6: 437–441.PubMedGoogle Scholar
  9. 9.
    Sharp PF, Smith FW, Gemmel HG, et al. Technitium-99m HM-PAO stereoisomers as potential agents for imaging regional cerebral blood flow: human volunteer studies.J Nucl Med 1986; 27: 171–179.PubMedGoogle Scholar
  10. 10.
    Costa DC, Ell PJ, Cullum ID, Jarritt PH. The in vivo distribution of99Tcm-HMPAO in normal man.Nucl Med Commun 1986; 7: 647–658.PubMedGoogle Scholar
  11. 11.
    Podreka I, Suess E, Goldenberg G, Steiner M, Brucke T, Muller C, Lang W, Neirinckx RD, Deecke L. Initial experience with technetium-99m-HMPAO brain SPECT.J Nucl Med 1987; 28: 1657–1666.PubMedGoogle Scholar
  12. 12.
    Anderson AR. 99mTc-d,l-hexamethylene-proyleneamine oxime99mTc-HMPAO basic kinetic studies of a tracer of cerebral blood flow.Cerebrovasc Brain Metab Rev 1989; 1: 288–318.PubMedGoogle Scholar
  13. 13.
    Nickel O, Nagele-Wohrle B, Ulrich P, et al. RCBF quantification with99mTc-HMPAO-SPECT: theory and first results.Eur J Nucl Med 1989; 15: 1–8.PubMedGoogle Scholar
  14. 14.
    Di Rocco LRJ, Silva DA, Kuczynski BL, Narra RK, Ramalingam K, Jurrisson S, Nunn AD, Eckelman WC. The singlepass extraction and capillary permeability-surface area product of several putative cerebral blood flow imaging agents.J Nucl Med 1993; 34: 641–648.PubMedGoogle Scholar
  15. 15.
    Lassen NA, Andersen AR, Friberg L, Paulson OB. The retention of 99mTc-d,l-HM-PAO in the human brain after intracarotid bolus injection: a kinetic analysis.J Cereb Blood Flow Metab 1988; 8 Suppl 1: S13-S22.PubMedGoogle Scholar
  16. 16.
    Inugami A, Kanno I, Uemura K, Shishido F, Mrakami M, Tmura N, Fujita H, Higano S. Linearization correction of99mTc-d,l-hexamethylene-propylene oxime (HM-PAO) image in terms of regional CBF distribution: comparison to C15O2 inhalation steady-state method measured by positron emission tomography.J Cereb Bloow Flow Metab 1988; 8 Suppl 1: S52-S60.Google Scholar
  17. 17.
    Yonekura Y, Nishizawa S, Mukai T, Fujita T, Fukuyama H, Ishikawa M, Kikuchi H, Konishi J, Andersen AR, Lassen NA. SPECT with 99mTc-d,l-hexamethylene-propylene oxime (HM-PAO) compared with regional cerebral blood flow measured by PET: effects of linearization.J Cereb Blood Flow Metab 1988; 8 Suppl 1: S52-S60.PubMedGoogle Scholar
  18. 18.
    Tsuchida T, Yonekura Y, Nishizawa S, Sadato N, Tamaki N, Fujita T, Magata Y, Konishi J. Nonlinearity correction of brain perfusion SPECT based on permeability-surface area product model.J Nucl Med 1996; 37: 1237–1241.PubMedGoogle Scholar
  19. 19.
    Gemmell HG, Evans NTS, Besson JAO, et al. Regional cerebral blood flow imaging: a quantitative comparison of technetium-99m-HMPAO SPELT with C15O2 PET.J Nucl Med 1990; 31: 1595–1600.PubMedGoogle Scholar
  20. 20.
    Anderson AR, Friberg HH, Schmidt JF, Hasselbalch SG. Quantitative measurements of cerebral blood flow using SPELT and [99mTc]-d,l-HMPAO compared to xenon-133.J Cereb Blood Flow Metab 1988; 8: S69-S81.PubMedGoogle Scholar
  21. 21.
    Nishizawa S, Yonekura Y, Fujita T, Senda M, Mukai T, Saji H, Shibata T, Yamamoto K, Tamaki N, Fukuyama H, Harada K, Ishikawa M, Torizuka K. Brain perfusion SPECT with technetium-99m HM-PAO: comparative study with I-123 IMP and CBF measured by PET.J Nucl Med 1987; 28: 569.Google Scholar
  22. 22.
    Buell U, Stirrer H, Braun H, et al. SPECT with99Tcm-HMPAO and99mTc-pertechnetate to assess regional cerebral blood flow (rCBF) and blood volume (rCBV). Preliminary re sults in cerebrovascular disease and interictal epilepsy.Nucl Med Commun 1987; 8: 519–524.PubMedGoogle Scholar
  23. 23.
    Langen K-J, Herzog H, Rota E, Roosen N Wieler H, Kiwit J, Kuwert T, Storch-Becker A, Feinendegen L. Tomographic studies of rCBF with99mTc-HM-PAO SPECT in comparison with PET in patients with primary brain tumors.Neurosurg Rev 1987; 10: 23–24.PubMedGoogle Scholar
  24. 24.
    Pupi A, Castagnoli A, De Cristofaro MT, Bacciottini L, Petti AR. Quantitative comparison between99mTc-HMPAO and99mTc-ECD: measurement of arterial input and brain retention.Eur J Nucl Med 1994; 21: 124–130.PubMedGoogle Scholar
  25. 25.
    Sperling B, Lassen NA. Hyperfixation of HMPAO in subacute ischemic stroke leading to spuriously high estimates of cerebral blood flow by SPECT.Stroke 1993; 24: 193–194.PubMedGoogle Scholar
  26. 26.
    Tsuchida T, Nishizawa S, Yonekura Y, et al. SPECT images of technetium-99m-ethyl cysteinate dimer in cerebrovascular diseases: comparison with other cerebral perfusion tracers and PET.J Nucl Med 1994; 35: 27–31.PubMedGoogle Scholar
  27. 27.
    Kuwabara Y, Ichiya Y, Sasake M, Akashi Y, Yoshida T, Fukumura T, Masuda K. Cerebellar vascular response to acetazolamide in crossed cerebellar diaschisis: a comparison of99mTc-HMPAO single-photon emission tomography with15O-H2O positron emission tomography.Eur J Nucl Med 1996; 23: 683–689.PubMedGoogle Scholar
  28. 28.
    Koyama M, Kawashima R, Ito H, Ono S, Sato K, Goto R, Kinomura S, Yoshioka S, Sato T, Fukuda H. SPECT imaging of normal subjects with technetium-99m-HMPAO and technetium-99m-ECD.J Nucl Med 1997; 587–592.Google Scholar
  29. 29.
    Heiss WD, Herholz K, Podreka I, Neubauer I, Pietrzyk U. Comparison of [99mTc]HMPAO SPECT with [18F]fluorometh-ane PET in cerebrovascular disease.J Cereb Blood Flow Metab 1990; 10: 687–697.PubMedGoogle Scholar
  30. 30.
    Papazyan J-P, Delavelle J, Burkhard P, Rossier P, Morel C, Maton B, Pizzolato GP, Rüfenacht DA, Slosman DO. Discrepancies between HMPAO and ECD SPECT imaging in brain tumors.J Nucl Med 1997; 38: 592–596.PubMedGoogle Scholar
  31. 31.
    Som P, Oster ZH, Yamamoto K, Meinken GE, Srivastava SC, Yonekura Y, Ebner SA, Atkins HL, Brill AB, Fawwaz RA, Alderson PO, Coffey J, Carlton E, Hubner KF. Some factors affecting the cerebral and extracerebral accumulation ofN-isopropyl-p-iodo-amphetamine (IMP).Int J Nucl Med Biol 1985; 12: 185–196.PubMedGoogle Scholar
  32. 32.
    Yonekur Y, Fujita T, Nishizawa S, Twasaki Y, Mukai T, Konishi J. Temporal changes in accumulation ofN-isopropyl-p-iodoamphetamine in human brain: relation to lung clearance.J Nucl Med 1989; 30: 1977–1981.PubMedGoogle Scholar
  33. 33.
    Waldemar G, Hasselbalch SG, Andersen AR, Delecluse F, Petersen P, Johnsen A, Paulson OB.99mTc-d,l-HMPAO and SPECT of the brain in normal aging.J Cereb Blood Flow Metab 1991; 11: 508–521.PubMedGoogle Scholar
  34. 34.
    Suess E, Malessa S, Ungersbock K, Kitz P, Podreka I, Heimberger K, Hornykiewicz O, Deecke L. Technetium-99m-d,l-hexamethylpropyleneamine oxime (HMPAO) uptake and glutathione content in brain tumors.J Nucl Med 1991; 32: 1675–1681.PubMedGoogle Scholar
  35. 35.
    Jacquier-Sarlin MR, Polla BS, Slosman DO. Oxido-reductive state: the major determinant for cellular retention of99mTc-HMPAO.J Nucl Med 1996; 37: 1413–1416.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • P. David Mozley
    • 1
  • Ahmed M. Sadek
    • 2
  • Abass Alavi
    • 1
  • Ruben C. Gurt
    • 1
  • Larry R. Muenz
    • 1
  • Barry J. Bunow
    • 1
    • 2
    • 3
    • 4
  • Hee-Joung Kim
    • 3
  • Mark H. Stecker
    • 1
  • Paul Jolles
    • 4
  • Andrew Newberg
    • 1
  1. 1.The University of PennsylvaniaPhiladelphiaUSA
  2. 2.The University of CairoEgypt
  3. 3.Yonsei UniversitySeoulSouth Korea
  4. 4.The Medical College of VirginiaRichmondUSA

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