Value of cerebral blood flow quantification in the diagnosis of dementia

Abstract

Quantifying hemispheric cerebral blood flow (CBF) may improve diagnostic accuracy when combined with perfusion SPECT. To explore the impact of measuring mean CBF on the differential diagnosis of dementia under clinical conditions. CBF was calculated from anterior planar dynamic images acquired over 100 s after i.v. bolus injection of 550 MBq of (99m)Tc-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. Computation 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 x age (r=-0.648, P<0.001) and CBF(right)=57.9-0.02 x 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 x age (r=-0.56) and CBF(right)=64.2-0.32 x 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 x age and CBF(right)=39-0.057 x 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). Routine 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.