2.3.2 Tracer Behavior

In general, there are several physiologic requirements for a cerebral perfusion tracer. The agent must be carried to the brain in arterial blood and transferred across the blood-brain barrier (BBB) by passive transport only. More specifically, the tracer should: be electrically neutral, have a molecular weight less than 500 daltons for passive diffusion, have a lipophilicity where , have high first pass uptake to allow near immediate imaging after injection, be retained for a sufficiently long time to allow imaging, and use Tc as a radionuclide because modern SPECT detectors are optimally efficient at the 140 keV photon emission energy of Tc [SP87]. These are all properties of the lipophilic amine, HMPAO, which, when labeled with Tc, produces a tracer whose uptake properties in the brain closely parallels cerebral blood flow. HMPAO was introduced in 1985 by the Amersham Corporation and it is marketed under the trade name Ceretec [PSS92]. It crosses the BBB and is retained optimally in the brain a few minutes after injection so that the images produced are effectively ``snapshots'' of cerebral perfusion patterns at about the time of injection. It has a retention of about 68 %after about 24 hours with 38 %ejection by micturition. A total activity of about 30 mCi is typically administered, 4 to 9 %of which [SP87][CE91] localizes in the brain for a resultant cerebral dose of about 8 rads (this is an estimate for a 70 kg human adult with micturition every 2 hours from data from Oak Ridge Associated Universities, Radiopharmaceutical Internal Dose Information Center). Although optimal retention is achieved within about 2 minutes after injection, HMPAO's tracer kinetics are such that there exists some preferential back diffusion in high flow areas (such as the cerebellum) within those first few minutes after injection. Tc-HMPAO's tracer kinetics have been modeled using 3 compartment [AFK+88][IKU+88][LAFP88] and 4 compartment models [MTF+92] in efforts to study this back diffusion which results in images which are not completely linear with blood flow (see figure 2.5). Lassen's linearization and normalization correction from the 3 compartment model is an elegant and simple algorithm which may be applied to reconstructed brain data to obtain images with voxel values that are linear with blood flow [LAR90].