Advertisement

Diagnostic imaging techniques with special reference to PET

  • W.-D. Heiss
Conference paper
Part of the Key Topics in Brain Research book series (KEYTOPICS)

Summary

The late occurrence of gross morphologic changes in Alzheimer’s disease (AD) and the broad overlap of these alterations with those in normal age-matched controls preclude the use of CT and MRI for differential diagnosis of dementia syndromes. Because progressive cell loss and reduced cell and synaptic activity lead to a reduction in metabolism and blood flow, functional imaging techniques visualizing these variables can be helpful in detecting early alterations in AD. Positron emission tomography (PET) is currently the only technology affording three-dimensional measurement of the brain’s energy metabolism which is closely coupled to brain function. Studies of glucose metabolism by PET of (18F)-2-fluoro-2-deoxy-D-glucose are therefore widely applied to show the contribution of various brain structures in the performance of a variety of tasks or their participation in functional deficits associated with various diseases. Although glucose metabolism decreases slightly with age to a regionally different degree, most types of dementia show severe changes in glucose metabolism. Alzheimer’s disease (AD) is characterized by metabolic disturbances most prominent in the parietotemporal association cortex and later in the frontal lobe, whereas primary cortical areas, basal ganglia, thalamus, brainstem, and cerebellum are not affected. It is this typical pattern that distinguishes AD from other dementia syndromes. A ratio calculated from the metabolic rates of glucose of “affected” and “nonaffected” brain regions was able to separate patients with AD from age-matched controls and permitted the discrimination of patients with cognitive impairment of other origin in 85%. The discriminative power can be further improved by activation studies. A continuous visual recognition task increased the metabolic rate in normal subjects by 21% and in patients with AD by 6% on average, with significant regional differences. During activation the significant relation between severity of disease and temporoparietal metabolic rate became even stronger. In the assessment of effects of treatment on disturbed metabolism, PET studies demonstrated an equalization of metabolic heterogeneities in patients responding to a muscarinergic cholinergic agonist, whereas general increases in glucose utilization were observed with piracetam, pyritinol, and phosphatidylserine. The therapeutic relevance of such metabolic effects, however, must be proved in controlled clinical trials. Preliminary results in 4 groups of AD receiving either social support, or cognitive training alone, or cognitive training combined with medical treatment for 6 months suggest that neuropsychological performance and activated glucose metabolism can be improved by therapeutic interventions targeted to special symptoms.

Keywords

Positron Emission Tomography Positron Emission Tomography Study Cognitive Training Cereb Blood Flow Dementia Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alavi A, Fazekas F, Chawluk J, Zimmerman R (1987) Magnetic resonance imaging of the brain in normal aging and dementia. In: Meyer JS, Lechner H, Reivich M, Ott EO (eds) Cerebral vascular disease 6. Excerpta Medica, Amsterdam New York Oxford, pp 191–195.Google Scholar
  2. Benson DF, Kuhl DE, Hawkins RA, Phelps ME, Cummings JL, Tsai SY (1983) The fluorodeoxyglucose 18 F scan in Alzheimer’s disease and multiinfarct dementia. Arch Neurol 40:711–714.PubMedCrossRefGoogle Scholar
  3. Chase TN, Fedio P, Foster NL, Brooks R, Di Chiro G, Mansi L (1984) Wechsler adult intelligence scale performance. Cortical localization by fluorodeoxyglucose F-18 positron emission tomography. Arch Neurol 41:1244–1247.PubMedCrossRefGoogle Scholar
  4. DeKosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol 27:457–464.PubMedCrossRefGoogle Scholar
  5. DeLeon MJ, Ferris SH, George AE, Reisberg B, Christman DR, Kricheff II, Wolf AP (1983) Computed tomography and positron emission transaxial tomography evaluations of normal aging and Alzheimer’s disease. J Cereb Blood Flow Metab 3:391–394.CrossRefGoogle Scholar
  6. Duara R, Grady C, Haxby J, Sundaram M, Cutler NR, Heston L, Moore A, Schlageter N, Larson S, Rapoport SI (1986) Positron emission tomography in Alzheimer’s disease. Neurology 36:879–887.PubMedGoogle Scholar
  7. Evans AC, Beil C, Marrett S, Thompson GJ, Hakim A (1988) Anatomical-functional correlation using an adjustable MRI-based region of interest atlas with positron emission tomography. J Cereb Blood Flow Metab 8:513–530.PubMedCrossRefGoogle Scholar
  8. Ferris SH, Reisberg B, Crook T, Friedman E, Schneck K, Mir P, Sherman KA, Corwin J, Gershon S, Bartus RT (1982) Pharmacologic treatment of senile dementia: choline, L-dopa, piracetam, and choline plus piracetam. Aging 19:475–481.Google Scholar
  9. Foster NL, Chase TN, Fedio P, Patronas NJ, Brooks RA, DiChiro G (1983) Alzheimer’s disease: focal cortical changes shown by positron emission tomography. Neurology 33:961–965.PubMedGoogle Scholar
  10. Foster NL, Chase TN, Patronas NJ, Gillespie MM, Fedio P (1986) Cerebral mapping of apraxia in Alzheimer’s disease by positron emission tomography. Ann Neurol 19:139–143.PubMedCrossRefGoogle Scholar
  11. Frackowiak RSJ, Pozzilli C, Legg NJ, DuBoulay GH, Marshall J, Lenzi GL, Jones T (1981) Regional cerebral oxygen supply and utilization in dementia. A clinical and physiological study with oxygen-15 and positron tomography. Brain 104:753–788.PubMedCrossRefGoogle Scholar
  12. Friedland RP, Budinger TF, Ganz E, Yano Y, Mathis CA, Koss B, Ober BA, Huesman RH, Derenzo SE (1983) Regional cerebral metabolic alterations in dementia of the Alzheimer type: positron emission tomography with (18F)-fluorodeoxyglucose. J Comput Assist Tomogr 7:590–598.PubMedCrossRefGoogle Scholar
  13. Friston KJ, Frith CD, Liddle PF, Dolan RJ, Lammertsma AA, Frackowiak RSJ (1990) The relationship between global and local changes in PET scans. J Cereb Blood Flow Metab 10:458–466.PubMedCrossRefGoogle Scholar
  14. Gibbs JM, Frackowiak RSJ, Legg NJ (1986) Regional cerebral blood flow and oxygen metabolism in dementia due to vascular disease. Gerontology 32[Suppl 1]:84–88.PubMedCrossRefGoogle Scholar
  15. Hachinski VC, Iliff LD, Zilkha E, Duboulay GH, McAllister VL, Marshall J, Ross-Russell RW, Symon L (1975) Cerebral blood flow in dementia. Arch Neurol 32:632–637.PubMedCrossRefGoogle Scholar
  16. Haxby JV, Grady CL, Duara R, Schlageter N, Berg G, Rapoport SI (1986) Neocortical metabolic abnormalities precede nonmemory cognitive defects in early Alzheimer’s type dementia. Arch Neurol 43:882–885.PubMedCrossRefGoogle Scholar
  17. Hayden MR, Hewitt J, Stoessl AJ, Clark C, Ammann W, Martin WRW (1987) The combined use of positron emission tomography and DNA polymorphisms for preclinical detection of Huntington’s disease. Neurology 37:1441–1447.PubMedGoogle Scholar
  18. Heiss W-D, Hebold I, Klinkhammer P, Ziffling P, Szelies B, Pawlik G, Herholz K (1988) Effect of piracetam on cerebral glucose metabolism in Alzheimer’s disease as measured by PET. J Cereb Blood Flow Metab 8:613–617.PubMedCrossRefGoogle Scholar
  19. Heiss W-D, Herholz K, Böcher-Schwarz HG, Pawlik G, Wienhard K, Steinbrich W, Friedmann G (1986) PET, CT, and MR imaging in cerebrovascular disease. J Comput Assist Tomogr 10:903–911.PubMedCrossRefGoogle Scholar
  20. Heiss W-D, Herholz K, Pawlik G, Hebold I, Klinkhammer P, Szelies B (1989) Positron emission tomography findings in dementia disorders: contributions to differential diagnosis and objectivizing of therapeutic effects. Keio J Med 38:111–135.PubMedCrossRefGoogle Scholar
  21. Heiss W-D, Kessler J, Slansky I, Mielke R, Szelies B, Herholz K (1993) Longterm metabolic changes in Alzheimer’s disease under various therapeutic interventions. J Cereb Blood Flow Metab 13[Suppl 1]:S5.CrossRefGoogle Scholar
  22. Heiss W-D, Pawlik G, Herholz K, Göldner H, Wienhard K (1984) Regional kinetic constants and cerebral metabolic rate for glucose in normal human volunteers determined by dynamic positron emission tomography of (18F)-2-fluoro-2-deoxy-D-glucose. J Cereb Blood Flow Metab 4:212–223.PubMedCrossRefGoogle Scholar
  23. Herholz K, Adams R, Kessler J, Szelies B, Grond M, Heiss W-D (1990) Criteria for the diagnosis of Alzheimer’s disease with positron emission tomography. Dementia 1:156–164.Google Scholar
  24. Kamo H, McGeer PL, Harrop R, McGeer EG, Calne DB, Martin WRW, Pate BD (1987) Positron emission tomography and histopathology in Pick’s disease. Neurology 37:439–445.PubMedGoogle Scholar
  25. Kessler J, Herholz K, Grond M, Heiss W-D (1991) Impaired metabolic activation in Alzheimer’s disease: a PET study during continous visual recognition. Neuropsychologia 29:229–243.PubMedCrossRefGoogle Scholar
  26. Klinkhammer P, Szelies B, Heiss W-D (1990) Effect of phosphatidylserine on cerebral glucose metabolism in Alzheimer’s disease. Dementia 1:197–201.Google Scholar
  27. Kuhl DE, Metter EJ, Benson DF, Ashford JW, Riege WH, Fujikawa DG, Markham CH, Mazziotta JC, et al (1985) Similarities of cerebral glucose metablism in Alzheimer’s and Parkinsonian dementia. J Cereb Blood Flow Metab 5[Supp 11]:S169–S170.Google Scholar
  28. Kuhl DE, Metter EJ, Riege WH, Hawkins RA, Mazziotta JC, Phelps DE, Kling AS (1983) Local cerebral glucose utilization in elderly patients with depression, multiple infarct dementia, and Alzheimer’s disease. J Cereb Blood Flow Metab 3[Suppl 1]:S494–495.Google Scholar
  29. Kuhl DE, Metter EJ, Riege WH, Markham CH (1984) Patterns of cerebral glucose utilization in Parkinson’s disease and Huntington’s disease. Ann Neurol 15[Suppl 1]:S119–S125.PubMedCrossRefGoogle Scholar
  30. Mazziotta JC, Phelps ME, Pahl JJ, Huang S-C, Baxter LR, Riege WH, et al (1987) Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington’s disease. N Engl J Med 316:357–362.PubMedCrossRefGoogle Scholar
  31. McKhann G, Drachman D, Folstein MF, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease. Neurology 34:939–944.PubMedGoogle Scholar
  32. Mielke R, Herholz K, Grond M, Kessler J, Heiss W-D (1991) Differences of regional cerebral glucose metabolism between presenile and senile dementia of Alzheimer type. Neurobiol Aging 13:93–98.CrossRefGoogle Scholar
  33. Nahmias C, Garnett ES, Firnau G, Lang A (1985) Striatal dopamine distribution in Parkinsonian patients during life. J Neurol Sci 69:223–230.PubMedCrossRefGoogle Scholar
  34. Pawlik G (1988) Positron emission tomography and multiregional statistical analysis of brain function: from exploratory methods for single cases to inferential tests for multiple group designs. In: Willems JL, van Bemmel JH, Michel J (eds) Progress in computer-assisted function analysis. Elsevier, North-Holland, pp 401–408.Google Scholar
  35. Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE (1979) Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)-2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol 6:371–388.PubMedCrossRefGoogle Scholar
  36. Pietrzyk U, Herholz K, Heiss W-D (1990) Three-dimensional alignment of functional and morphological tomograms. J Comput Assist Tomogr 14:51–59.PubMedCrossRefGoogle Scholar
  37. Reisberg B, Ferris SH, DeLeon MJ, Crook T (1982) The global deterioration scale for assessment of primary degenerative dementia. Am J Psychiatry 139:1136–1139.PubMedGoogle Scholar
  38. Reivich M, Kuhl D, Wolf A, Greenberg J, Phelps M, Ido T, Casella V, Fowler J, Hoffman E, Alavi A, Som P, Sokoloff L (1979) The (18F)fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man. Circ Res 44:127–137.PubMedGoogle Scholar
  39. Riege WH, Metter EJ, Kuhl DE, Lanto AB, Small GW, Fujikawa DG, Mazziotta JC, Dorsey DA, Maltese A (1987) Alzheimer’s disease: cerebral metabolic abnormalities coincide with early memory deficits. Soc Neurosci Abstr 13:1628.Google Scholar
  40. Smith RC, Vroulis G, Johnson R, Morgan R (1984) Pharmacologie treatment of Alzheimer’s type dementia: new approaches. Psychopharmacol Bull 20:542–545.PubMedGoogle Scholar
  41. Sokoloff L, Reivich M, Kennedy C, Des Rosiers M-H, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The (14C)deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897–916.PubMedCrossRefGoogle Scholar
  42. Szelies B, Herholz K, Pawlik G, Beil C, Wienhard K, Heiss W-D (1986) Zerebraler Glukosestoffwechsel bei präseniler Demenz vom Alzheimer-Typ — Verlaufskontrolle unter Therapie mit muskarinergem Cholinagonisten. Fortschr Neurol Psychiatr 54:364–373.PubMedCrossRefGoogle Scholar
  43. Szelies B, Karenberg A (1986) Störungen des Glukosestoffwechsels bei Pick’scher Erkrankung. Fortschr Neurol Psychiatr 54:393–397.PubMedCrossRefGoogle Scholar
  44. Wienhard K, Eriksson L, Grootoonk S, Casey M, Pietrzyk U, Heiss W-D (1992) Performance evaluation of the positron scanner ECAT EXACT. J Comput Assist Tomogr 16:804–813.PubMedCrossRefGoogle Scholar
  45. Wienhard K, Pawlik G, Herholz K, Wagner R, Heiss W-D (1985) Estimation of local cerebral utilization by positron emission tomography of (18F)-2-fluoro-2-deoxy-D-glucose: a critical appraisal of optimization procedures. J Cereb Blood Flow Metab 5:115–125.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1994

Authors and Affiliations

  • W.-D. Heiss
    • 1
  1. 1.Max-Planck-Institut für neurologische ForschungNeurologische UniversitätsklinkKölnFederal Republic of Germany

Personalised recommendations