Value of cerebral blood flow quantification in the diagnosis of dementia

BackgroundQuantifying hemispheric cerebral blood flow (CBF) may improve diagnostic accuracy when combined with perfusion SPECT. AimTo explore the impact of measuring mean CBF on the differential diagnosis of dementia under clinical conditions. MethodsCBF was calculated from anterior planar dynamic images acquired over 100 s after i.v. bolus injection of 550 MBq of 99mTc-HMPAO using Patlak linearization of normalized time–activity curves derived from right and left hemispheric, and aortic ROIs. Regional perfusion was evaluated from SPECT imaging carried out 20 min later. ANCOVA was applied to compare age-dependent differences of CBF; model differences at P<0.05 were considered significant. Study populations consisted of controls, 34 patients with no focal or vascular abnormality or mood disorder and with normal MR or CT brain images (F:M, 16:18; age±SD; 54.3±20.2 years); and patients with probable dementia comprised two subgroups. The first consisted of 33 patients with primary degenerative aetiology (PDD) (DAT or mixed-type microvascular and DAT, Lewy body and fronto-temporal atrophy), F/M; 17:16, age±SD; 68.4±8.8 years. The second subgroup consisted of 13 patients with dementia related to subcortical microvascular leuco-encephalopathy (vLEP), M/F 7:6, age±SD; 71.7±12.6 years. Classification was mainly based on clinical findings according to DMS-IV criteria, combined with follow-up or functional and anatomical imaging. ResultsComputation of CBF on 100 consecutive patients showed excellent inter-user reproducibility in trained hands (variation coefficient <5%). Mean CBF in controls showed an age dependent decrease, the first order linear regression was CBF(left)=58.9−0.2×age (r=−0.648, P<0.001) and CBF(right)=57.9−0.02×age (r=−0.645). In comparison to controls, a slightly more pronounced but statistically insignificant age-dependent decrease in mCBF was found in the vLEP group, CBF(left)=55.5−0.21×age (r=−0.56) and CBF(right)=64.2−0.32×age (r=−0.645). In the PDD group CBF, after adjusting for age, was significantly lower than control values (P<0.001); CBF(left)=37−0.025×age and CBF(right)=39−0.057×age. More importantly, better discrimination between PDD and controls in patients of younger age (45–65 years) was found. In older patients (65–85 years) overlap slightly increased. ROC analysis of the cohort of dement patients and controls older than 46 years revealed a 93–94% sensitivity and a specificity of 73% and 77% for the left and right hemispheres, respectively, at a CBF cut-off value of 39.5 ml · min−1 · 100 g−1. ConclusionRoutine quantification of mean CBF by HMPAO–RNA is a simple and reproducible method which can be easily added to the standard brain perfusion SPECT without additional cost or increasing patient's radiation burden. Combined with regional perfusion it provides an additional tool for the aetiological classification of dementia.

[1]  P F Sharp,et al.  Technetium-99m HM-PAO stereoisomers as potential agents for imaging regional cerebral blood flow: human volunteer studies. , 1986, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[2]  Gereon R. Fink,et al.  HMPAO SPET and FDG PET in Alzheimer's disease and vascular dementia: comparison of perfusion and metabolic pattern , 1994, European Journal of Nuclear Medicine.

[3]  P. Huttenlocher Synaptic density in human frontal cortex - developmental changes and effects of aging. , 1979, Brain research.

[4]  G. C. Román,et al.  Vascular dementia , 1993, Neurology.

[5]  Dastur Dk Cerebral Blood Flow and Metabolism in Normal Human Aging, Pathological Aging, and Senile Dementia: , 1985 .

[6]  J. Trojanowski,et al.  Frontotemporal dementia and tauopathy , 2001, Current neurology and neuroscience reports.

[7]  H. Matsuda,et al.  Age-Matched Normal Values and Topographic Maps for Regional Cerebral Blood Flow Measurements by Xe-133 Inhalation , 1984, Stroke.

[8]  Hiroshi Matsuda,et al.  Noninvasive measurements of regional cerebral blood flow using technetium-99m hexamethylprophylene amine oxime , 1993, European Journal of Nuclear Medicine.

[9]  J. Morrison,et al.  Life and death of neurons in the aging brain. , 1997, Science.

[10]  R. Frackowiak,et al.  Quantitative Measurement of Regional Cerebral Blood Flow and Oxygen Metabolism in Man Using 15O and Positron Emission Tomography: Theory, Procedure, and Normal Values , 1980, Journal of computer assisted tomography.

[11]  S. Kety Human cerebral blood flow and oxygen consumption as related to aging. , 1956, Research publications - Association for Research in Nervous and Mental Disease.

[12]  O. Paulson,et al.  99mTc-d,l-HMPAO and SPECT of the Brain in Normal Aging , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[13]  M. Tolnay,et al.  REVIEW: tau protein pathology in Alzheimer’s disease and related disorders , 1999, Neuropathology and applied neurobiology.

[14]  I. Odano,et al.  A comparative study of simple methods to measure regional cerebral blood flow using iodine-123-IMP SPECT. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[15]  S. Bentin,et al.  Reduction in Regional Cerebral Blood Flow During Normal Aging in Man , 1980, Stroke.

[16]  Carmen Martin-Ruiz,et al.  Nicotinic receptor abnormalities in Alzheimer’s disease , 2001, Biological Psychiatry.

[17]  D. Dastur Cerebral Blood Flow and Metabolism in Normal Human Aging, Pathological Aging, and Senile Dementia , 1985, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  R. DeTeresa,et al.  Neocortical cell counts in normal human adult aging , 1987, Annals of neurology.

[19]  H Toyama,et al.  Quantitative measurement of regional cerebral blood flow using N-isopropyl-(iodine-123)p-iodoamphetamine and single-photon emission computed tomography. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[20]  E M Stokely,et al.  Normal Distribution of Regional Cerebral Blood Flow Measured by Dynamic Single-Photon Emission Tomography , 1986, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[21]  F Shishido,et al.  Reduction in regional cerebral metabolic rate of oxygen during human aging. , 1986, Stroke.

[22]  Y Yonekura,et al.  A Multicenter Validation of Regional Cerebral Blood Flow Quantitation Using [123I]Iodoamphetamine and Single Photon Emission Computed Tomography , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[23]  K. Kosaka,et al.  Clinicopathological studies on diffuse Lewy body disease , 2000, Neuropathology : official journal of the Japanese Society of Neuropathology.

[24]  H. Eiberg,et al.  Linkage studies of cholestasis familiaris groenlandica/Byler-like disease with polymorphic protein and blood group markers. , 1993, Human heredity.

[25]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[26]  K. Van Laere,et al.  Non-invasive methods for absolute cerebral blood flow measurement using 99mTc-ECD: a study in healthy volunteers , 2001, European Journal of Nuclear Medicine.

[27]  M N Cantwell,et al.  Does cerebral blood flow decline in healthy aging? A PET study with partial-volume correction. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[28]  W. März,et al.  Apolipoprotein E isoforms and the development of low and high Braak stages of Alzheimer’s disease-related lesions , 1999, Acta Neuropathologica.

[29]  L. Jacobs,et al.  Subcortical Arteriosclerotic Encephalopathy (Binswanger's Disease): Computed Tomographic, Nuclear Magnetic Resonance, and Clinical Correlations , 1985 .

[30]  Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups. , 1994, Journal of neurology, neurosurgery, and psychiatry.

[31]  Hiroshi Matsuda,et al.  A quantitative approach to technetium-99m hexamethylpropylene amine oxime , 2004, European Journal of Nuclear Medicine.

[32]  J. Hatazawa,et al.  Quantitative mapping of regional cerebral blood flow using iodine-123-IMP and SPECT. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[33]  J. Seylaz,et al.  [Quantitative measurement of cerebral blood flow]. , 1976, Annales de medecine interne.

[34]  F. Sakai,et al.  Effects of advancing age on regional cerebral blood flow. Studies in normal subjects and subjects with risk factors for atherothrombotic stroke. , 1979, Archives of neurology.

[35]  Simplified quantification of regional cerebral blood flow with99mTc-ECD SPECT and continuous arterial blood sampling , 1996, Annals of nuclear medicine.

[36]  Richard S. J. Frackowiak,et al.  Cerebral blood flow, blood volume and oxygen utilization. Normal values and effect of age. , 1990, Brain : a journal of neurology.

[37]  D Comar,et al.  Regional Cerebral Blood Flow and Oxygen Consumption in Human Aging , 1984, Stroke.

[38]  K. Ogawa,et al.  A practical method for position-dependent Compton-scatter correction in single photon emission CT. , 1991, IEEE transactions on medical imaging.

[39]  H. Tachibana,et al.  Periventricular lucencies on computed tomography in multiple cerebral infarcts: correlation with cerebral blood flow measurements. , 1990, The International journal of neuroscience.

[40]  R. L. Rogers,et al.  Cerebral blood flow changes in benign aging and cerebrovascular disease , 1984, Neurology.

[41]  H. Matsuda,et al.  A quantitative approach to technetium-99m ethyl cysteinate dimer: a comparison with technetium-99m hexamethylpropylene amine oxime , 1995, European Journal of Nuclear Medicine.