Non-invasive methods for absolute cerebral blood flow measurement using Tc-99m-ECD: a study in healthy volunteers

Radionuclide angiography with technetium-99m ethyl cysteinate dimer (ECD) a llows non-invasive estimation of absolute cerebral blood flow (CBF), either by graphical Patlak-Gjedde analysis (PGA) or by spectral analysis, (SA). O ther methods estimate CBF by means of single-point arterial or venous sampl ing. The aim of this study was to evaluate radionuclide scanning and single -point venous sampling as. potential clinical non- to minimally invasive me thods for CBF determination in a large set of carefully screened healthy vo lunteers over the adult age range. Eighty-three carefully screened healthy volunteers (20-81 years, 43 males, 40 females) underwent planar radionuclid e angiography with 925 MBq Tc-99m-ECD. After correction for camera dead-tim e loss, hemispheric CBF was calculated from brain perfusion indices (BPI): BPIG for PGA and BPIS for SA. Of the volunteers, 49 also underwent venous s ampling 6 min post injection, from which the lipophilic octanol. extraction fraction and hemispheric brain fractionation index (BFI) were determined. All datasets were correlated and evaluated as a function of age and gender. Intrasubject variability for the BPI measurements was assessed in 11 volun teers by repeat study within 2 weeks of the first acquisition. Graphical an d spectral analysis BPIs were strongly correlated (R=0.846, P <0.00001). Th is correlation coefficient increased to R=0.903 for the 74 Cases in which g raphical analysis was not hampered by temporal tracer retention in cervicob rachial venous valves. The BFI was weakly correlated to both BPI indices (B PIG: R=0.34, P=0.02; BPIS: R=0.31, P=0.04). The right hemisphere showed sig nificant asymmetry for BPIs (AI=2.7%+/-4.3%, P <0.001), in correspondence w ith previous Tc-99m-ECD data. BPIG, BPIs and BFI were all inversely related to age, with an increased gradient after the age of 55 years, while there was no significant gender difference. The ratio of BPIG to BIPS, which is a measure of the cerebral extraction fraction for Tc-99m-ECD, was not depend ent on age. Intersubject variability was 15.5% for both radionuclide scanni ng-based methods and 18.2% for venous sampling, and in all cases was indepe ndent of age. A much lower intrasubject variability was observed for BPIS ( 7.2%) than for BPIG (12.6%). This study provides reference values for norma l perfusion indices assessed by graphical and spectral analysis. The result s also indicate that spectral analysis allows the most reproducible estimat e of hemispheric perfusion by means of an operator-independent and objectiv e approach. Whereas accurate calibration of normal BPIs values to hemispher ic CBF with established methods needs to be performed, non-invasive calcula tion of regional absolute CBF using Tc-99m-ECD is possible by application o f a linearisation algorithm.