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Noninvasive measurements of regional cerebral blood flow using technetium-99m hexamethylprophylene amine oxime

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Abstract

The previously reported method for quantitative measurements of whole-brain or hemispheric-brain perfusion using technetium-99m hexamethylpropylene amine oxime (HMPAO) radionuclide angiography is now further developed so that regional cerebral blood flow (rCBF) can be measured. Lassen's correction algorithm is used for the linearization of a curve-linear relationship between the radioactivity in the brain and blood flow as seen with single-photon emission tomography (SPET) images. In this algorithm, the cerebral hemisphere was chosen as the reference region and the correction factor α was adapted to rCBF in the reference region. This new method of measuring CBF from SPET has been validated in 33 normal subjects and 22 patients with cerebrovascular disease. Regional CBF values in 20 brain regions of the normal subjects were in good agreement with reported values measured by other methods. Regional CBF in the frontal cortex was greater than that in the temporal, parietal or occipital cortex for the entire age range. This hyperfrontal perfusion tended to be less pronounced with advancing age. Seventeen patients with unilateral brain infarction showed significantly lower rCBF than normal subjects. The infarct core showed a low rCBF value of 11.1 ml/ 100 g/min on average. An increase in rCBF after acetazolamide administration was observed and mesured with this method in five patients with unilateral occlusive vascular pathology. These results suggest that this non-invasive method (without any blood sampling) permits the routine measurement of rCBF from HMPAO SPET tomograms of blood flow.

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References

  1. Matsuda H, Tsuji S, Shuke N, Sumiya H, Tonami N, Hisada K. A quantitative approach to technetium-99m hexamethylpropylene amine oxime. Eur J Nucl Med 1992; 19:195–200.

    Google Scholar 

  2. 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.

    Google Scholar 

  3. Ichihara T. Development of a high-resolution SPET system. Toshiba Med Rev 1990; 33:29–35.

    Google Scholar 

  4. Lassen NA, Andersen AR, Freiberg L, Paulson OB. The retention of [99m-Tc]-d,l-HMPAO in the human brain after intracarotid bolus injection: a kinetic analysis. J Cereb Blood Flow Metab 1988; 8 Suppl 1: S13-S22.

    Google Scholar 

  5. Andersen AR, Freiberg H, Knudsen KBM, Barry DI, Paulson OB, Schmidt JF, Lassen NA, Neirinckx RD. Extraction of [99m-Tc]-d,l-HM-PAO across the blood-brain barrier. J Cereb Blood Flow Metabol 1988; 8 Suppl 1:S44-S51.

    Google Scholar 

  6. 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.

    Google Scholar 

  7. Lassen NA, Andersen AR, Neirinckx RD, Ell PJ, Costa DC. Validation of Ceretec. In: Ell PJ, Costa DC, Cullum ID, Jarritt PH, Lui D, eds. The clinical application of rCBF imaging by SPECT. Little Chalfont, England: Amersham International; 1987:14–18.

    Google Scholar 

  8. Langen K-J, Herzog H, Kuwert T, Roosen N, Rota E, Kiwit JCW, Bock WJ, Feinendegen LE. Tomographic studies of rCBF with [99mTc]-HM-PAO SPECT in patients with brain tumors: comparison with C15O2 continuous inhalation technique and PET. J Cereb Blood Flow Metab 1988; 8 Suppl 1:S90-S94.

    Google Scholar 

  9. Yonekura Y, Nishizawa S, Mukai T, Fujita T, Fukuyama H, Ishikawa M, Kikuchi H, Konishi J, Andersen AR, Lassen NA. SPECT with [99m-Tc]-d,l-hexamethyl-propylene amine oxime (HM-PAO) compared with regional cerebral blood flow measured by PET: effects of linearization. J Cereb Blood Flow Metab 1988; 8 Suppl 1:S82-S89.

    Google Scholar 

  10. Gemmel HG, Evans NTS, Besson JAO, Roeda D, Davidson J, Dodd MG, Sharp PF, Smith FW, Crawford JR, Newton RH, Kulkarni V, Mallard JR. Regional cerebral blood flow imaging: a quantitative comparison of technetium-99m-HMPAO SPECT with C15O2 PET. J Nucl Med 1990; 31:1595–1600.

    Google Scholar 

  11. Andersen AR, Freiberg HH, Schmidt JF, Hasselbalch SG. Quantitative measurements of cerebral blood flow using [99mTc]-d,l-HM-PAO compared to xenon-133. J Cereb Blood Flow Metabol 1988; 8 Suppl 1: S69-S81.

    Google Scholar 

  12. Inugami A, Kanno I, Uemura K, Shishido F, Murakami M, Tomura N, Fujita H, Higano S. Linearization correction of 99mTc-labeled hexamethyl-propylene amine oxime (HM-PAO) image in terms of regional CBF distribution: comparison to C15O2 inhalation steady-state method measured by positron emission tomography: J Cereb Blood Flow Metab 1988; 8 Suppl 1:S52-S60.

    Google Scholar 

  13. Andersen AR. [99mTc]-d,l-hexamethylene-propyleneamine oxime (99m-Tc-HMPAO); basic kinetic studies of a tracer of cerebral blood flow. Cerebrovasc Brain Metabol Rev 1989; 1:288–318.

    Google Scholar 

  14. Shirahata N, Henriksen L, Vorstrup S, Holm S, Lauritzen M, Paulson OB, Lassen NA. Regional cerebral blood flow assessed by 133Xe inhalation and emission tomography: normal values. J Comput Assist Tomogr 1985; 9:861–866.

    Google Scholar 

  15. Frackowiak RSJ, Lenzi G-L, Jones T, Heather JD. Quantitative measurement of regional cerebral blood flow and oxygen metabolism in man using 15O and positron emission tomography: theory, procedure, and normal values. J Comput Assist Tomogr 1980; 4:727–736.

    Google Scholar 

  16. Pantano P, Baron J-C, Lebrun-Grandie P, Duquesnoy N, Bousser M-G, Comar D. Regional cerebral blood flow and oxygen consumption in human aging. Stroke 1984; 15:635–641.

    Google Scholar 

  17. Yamaguchi T, Kanno I, Uemura K, Shishido F, Inugami A, Ogawa T, Murakami M, Suzuki K. Reduction in regional cerebral metabolic rate of oxygen during human aging. Stroke 1986; 17:1220–1228.

    Google Scholar 

  18. Leenders KL, Perani D, Lammertsma AA, Heather JD, Buckingham P, Healy MIR, Gibbs JM, Wise RJS, Hatazawa J, Herold S, Beaney RP, Brooks DJ, Spinks T, Rhodes C, Frackowiak RSJ, Jones T. Cerebral blood flow, blood volume and oxygen utilization. Brain 1990; 113:27–47.

    PubMed  Google Scholar 

  19. Lassen NA, Henriksen L, Paulson O. Regional cerebral blood flow in stroke by 133Xenon inhalation and emission tomography. Stroke 1981; 12:284–288.

    Google Scholar 

  20. Podreka I, Baumagartner C, Suess E, Müller C, Brücke T, Lang W, Holzner F, Steiner M, Deecke L. Quantification of regional cerebral blood flow with IMP-SPECT. Stroke 1989; 20:183–191.

    Google Scholar 

  21. Morawetz RB, DeGirolami U, Ojemann RG, Marcoux FW, Crowell RM. Cerebral blood flow determined by hydrogen clearance during middle cerebral artery occlusion in unanesthetized monkeys. Stroke 1978; 9:143–149.

    Google Scholar 

  22. Astrup J. Thresholds in cerebral ischemia — the ischemic penumbra. Stroke 1981; 12:723–725.

    Google Scholar 

  23. Heiss WD. Flow thresholds of functional and morphological damage of brain tissue. Stroke 1983; 14:329–331.

    Google Scholar 

  24. Baron J-C, Rougemont D, Bousser MG, Lebrun-Grandié P, Iba-Zizen MT, Chiras J. Local CBF, oxygen extraction fraction (OEF), and CMRO2; prognostic value in recent supratentorial infarction in humans. J Cereb Blood Flow Metab 1983; 3 Suppl 1:S1-S2.

    Google Scholar 

  25. Shishido F, Uemura K, Inugami A, Ogawa T, Yamaguchi T, Kanno I, Miura S, Iida H, Murakami M, Takahashi K, Sasaki H, Tagawa K, Yasui N. Cerebral circulation and metabolism in cerebral infarction of middle cerebral artery territory — a position CT study with HEADTOME III and 15O labeled gases. Jpn J Nucl Med (Kaku-Igaku) 1986; 23:123–133.

    Google Scholar 

  26. Baron JC, Bousser MG, Comar D, Castaigne P. Crossed cerebellar diaschisis in human supratentorial brain infarction. Trans Am Neurol Assoc 1980; 105:459–461.

    Google Scholar 

  27. Lagreźe HL, Levine RL, Pedula KL, Nickles RJ, Sunderland JS, Rowe BR. Contralateral flow reduction in unilateral stroke: evidence for transhemispheric diaschisis. Stroke 1987; 18:882–886.

    Google Scholar 

  28. Pappata S, Dinh ST, Baron JC, Cambon H, Syrota A. Remote metabolic effects of cerebrovascular lesions: magnetic resonance and positron tomography imaging. Neuroradiology 1987; 29:1–6.

    Google Scholar 

  29. Choksey MS, Costa DC, Iannotti F, Ell PJ, Crockard HA. 99mTc-HMPAO SPET and cerebral blood flow: a study of CO2 reactivity. Nucl Med Commun 1989; 10:609–618.

    Google Scholar 

  30. Vorstrup S, Boyson G, Brun B, Engell HC. Evaluation of the regional cerebral vasodilatory capacity before carotid endarterectomy by acetazolamide test. Neurol Res 1987; 9:10–18.

    Google Scholar 

  31. Kreisig T, Schmiedek P, Leinsinger G, Einäupt K, Moser E. 133Xe-DSPECT: normal values of cerebral blood flow at rest and of reserve capacity. Nucl Med 1987; 26:192–197.

    Google Scholar 

  32. Bonte FJ, Devous MD, Reisch JS, Ajmani AK, Weiner MF, Hom J, Tintner R. The effect of acetazolamide on regional cerebral blood flow in patients with Alzheimer's disease or stroke as measured by single-photon emission computed tomography. Invest Radiol 1989; 24:99–103.

    Google Scholar 

  33. Kety SS. Human cerebral blood flow and oxygen consumption as related to aging. J Clin Invest 1956; 8:478–486.

    Google Scholar 

  34. Dastur DK. Cerebral blood flow and metabolism in normal human aging, pathological aging, and senile dementia. J Cereb Blood Flow Metab 1985; 5:1–9.

    Google Scholar 

  35. Naritomi H, Meyer JS, Sakai F, Yamaguchi F, Shaw T. Effects of advancing age on regional cerebral blood flow. Studies in normal subjects and subjects with risk factors for atherothrombotic stroke. Arch Neurol 1979; 36:410–416.

    Google Scholar 

  36. Melamed E, Lavy S, Bentin S, Cooper G, Rinot Y. Reduction in regional cerebral blood flow during normal aging in man. Stroke 1980; 11:31–35.

    Google Scholar 

  37. Matsuda H, Maeda T, Yamada M, Luo X-G, Tonami N, Hisada K. Age-matched normal values and topographic maps for regional cerebral blood flow measurements by Xe-133 inhalation. Stroke 1984; 15:336–342.

    Google Scholar 

  38. Shaw TG, Mortel KF, Meyer JS, Rogers RL, Hardenberg J, Cutaia MM. Cerebral blood flow changes in benign aging and cerebrovascular disease. Neurology 1984; 34:855–862.

    Google Scholar 

  39. Gur RC, Gur RE, Obrist WD, Skolnick BE, Reivich M. Age and regional cerebral blood flow at rest and during cognitive activity. Arch Gen Psychiatry 1987; 44:617–621.

    Google Scholar 

  40. Ingvar DH. “Hyperfrontal” distribution of the cerebral grey matter flow in resting wakefulness; on the functional anatomy of the conscious state. Acta Neurol Seand 1979; 60:12–25.

    Google Scholar 

  41. Syed GMS, Eagger S, Toone BK, Levy R, Barrett JJ. Quantification of regional cerebral blood flow (rCBF) using 99mTc-HMPAO and SPECT; choice of the reference region. Nucl Med Commun 1992; 13:811–816.

    Google Scholar 

  42. Cameron OG, Modell JG, Hichwa RD, Agranoff BW, Koeppe, RA. Changes in sensory-cognitive input: effects on cerebral blood flow. J Cereb Blood Flow Metab 1990; 10:38–42.

    Google Scholar 

  43. Woods SW, Hegeman IM, Zubal IG, Krystal JH, Koster K, Smith EO, Heninger GR, Hoffer PB. Visual stimulation increases technetium-99m-HMPAO distribution in human visual cortex. J Nucl Med 1991; 32:210–215.

    Google Scholar 

  44. Matsuda H, Oba H, Seki H, Higashi S, Sumiya H, Tsuji S, Terada H, Imai K, Shiba K, Mori H, Hisada K. Determination of flow and rate constants in a kinetic model of [99mTc]-hexamethyl-propylene amine oxime in the human brain. J Cereb Blood Flow Metab 1988; 8 Suppl 1:S61-S68.

    Google Scholar 

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Matsuda, H., Tsuji, S., Shuke, N. et al. Noninvasive measurements of regional cerebral blood flow using technetium-99m hexamethylprophylene amine oxime. Eur J Nucl Med 20, 391–401 (1993). https://doi.org/10.1007/BF00208997

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  • DOI: https://doi.org/10.1007/BF00208997

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