Journal of Cerebral Blood Flow and Metabolism 11:50-521 © 191 The Intenational Society of Cerebral Blood Flow and Metabolism ublished by Raven Press, Ltd., New York 99 mTc-d,I-HMPAO and SPECT of the Brain in Normal Aging Gunhild Waldemar, Steen G. Hasselbalch, Allan R. Andersen, tFlorence Delecluse, Palle Petersen, * Anni Johnsen, and Olaf B. Paulson Departments of Neurology and *Radiology, Rigshospitalet, Copenhagen, Denmark; and tDepartment of Neurology, H6pital Erasme, Brussels, Belgium Sumary: Single photon emission computed tomography (SPECT) with 99mTc-d,l-hexamethylpropyleneamine ox ime (99mTc-d,I-HMPAO) was used to determine global and regional CBF in 53 healthy subjects aged 21-83 years. For the whole group, global CBF normalized to the cer ebellum was 86.4% ± 8.4 (SD). The contribution of age, sex, and atrophy to variations in global CBF was studied using stepwise mUltiple regression analysis. There was a signiicant negative correlation of global CBF with sub jective ratings of cortical atrophy, but not with ratings of ventricular size, Evans ratio, sex, or age. In a subgroup of 33 subjects, in whom volumetric measurements of atro phy were performed, cortical atrophy was the only sig niicant determinant for global CBF, accounting for 27% of its variance. Mean global CBF as measured with the Tomographic measurement of regional CBF (rCBF) in humans was made possible several years ago with the development of a brain-dedicated dy namic single photon emission computed tomogra phy (SPECT) system designed for inhalation or in jection of the diffusible tracer \33Xe (Stokely et ai., 1980). This technique offers easy, repetitive, and quantitative measurements with a spatial and tem poral resolution suicient for studying cerebrovas cular disease. The recent development of tracers that are re tained in the brain for several hours and, if ideal, "trapped" in proportion to regional blood low has Received July 13, 1990; revised September 17, 1990; accepted September 24, 1990. Address correspondence and reprint requests to Dr. G. Waldemar at Department of Neurology, 9, Blegdamsvej , DK- 2\00 Copenhagen, Denmark. Abbreviations used: AP, anterior-posterior ratio ; CM, can thomeatal ; CT, computed tomography ; HMPAO, hexamethyl propyleneamine oxime ; PET, positron emission tomography ; rCBF, regional CBF; ROI, region of interest; SAl, side-to-side asymmetry index; SPECT, single photo emission computed to mography. 508 J33Xe inhalation technique and SPECT was 54 ± 9 mlJl0 glmin and did not correlate signiicantly with age. There was a preferential decline of CBF in the frontal cortex with advancing age. The side-to-side asymmetry of sev eral regions of interest increased with age. A method was described for estimation of subcortical CBF, which de creased with advancing cortical atrophy. The relative area of the subcortical low-low region increased with age. These results are useful in distinguishing the effects of age and simple atrophy from disease efects, when the 99mTc-d,I-HMPAO method is used. Key Words: Brain atrophy-Emission tomography-99mTc-d,I-Hexameth ylpropyleneamine oxime-Normal aging-Regional ce rebral blood low-133Xe inhalation. provided the opportunity of high-resolution static imaging without some of the drawbacks inherent to the \33Xe technique, e.g., the artifacts associated with the lung curve and with airway trapping of \33Xe. In addition, these tracers do not require a dynamic brain-dedicated SPECT system, but can also be used with the more widespread conven tional rotating gamma cameras, although the reso lution obtained is highly dependent on the instru ment. Recently, d,l-hexamethylpropyleneamine ox ime (d,l-HMPAO) che lated with 99mTc was introduced as a radiopharmaceutical tracer for mea surement of rCBF in humans with SPECT (Nei rinckx et ai., 1987). This lipophilic compound readily crosses the blood-brain barrier and is rap idly converted in the brain tissue to a hydrophilic compound that is retained in the brain for several hours (Sharp et ai., 1986; Neirinckx et ai., 1987; Lassen et aI., 1988) . The validity of 99mTc_ d,l-HMPAO for measurements of rCBF has been conirmed in quantitative studies using the 133Xe inhalation method with SPECT (Andersen et aI.,