Double-injection method for sequentially measuring cerebral blood flow with N-isopropyl-(I-123)p-iodoamphetamine

We investigated the accuracy of a double-injection method for sequentially measuring cerebral blood flow (CBF) with N-isopropyl-(I-123)p-iodoamphetami ne (IMP) in simulation studies based on patient data and in clinical studie s. The unidirectional clearance of IMP from the blood to the brain (K-1; ne arly equal to CBF) in the first and second sessions was calculated by means of a microsphere model. The K-1 values in the first session (K-1(l)) were calculated from C-b(5)/Int_C-a(I), where C-b(5) and Int_C-a(I) are values f or brain radioactivity 5 min after the first injection and for arterial blo od radioactivity obtained by 5-min continuous sampling. The K-1 values in t he second session (K-1(II)) were calculated by means of the following four methods. Method 1: [C-b(t(z) + 5) - C-b(t(z))]/[Int_C-a(II) - C-a(t(z)) x 5 ], where C-b(t(z) + 5) and C-b(t(z)) are the brain radioactivity levels 5 m in after the second injection and at the time the second session was starte d (t(z)), respectively. Int_C-a(II) and C-a(t(z)) are the arterial blood ra dioactivity levels obtained by 5-min continuous sampling after the second i njection and at t(z), respectively. Method 2: [C-b(t(z) + 5) - C-b(t(z))]/[ Int_C-a(I) x R], where R is the injection dose ratio. Method 3: [C-b(t(z) 5) - C-b(t(z)) x exp(- K-1(I) x 5/lambda)]/Int_C-a(II), where lambda is th e population averaged partition coefficient. Method 4: same as Method 3 exc ept that K-1(I) was replaced by K-1(II) obtained by means of Method 2. Theo retically, Method 4 appeared to be the best of the four methods. The change in K-1 during the second session obtained by Method 1 or 2 largely depende d on R and t(z), whereas Method 3 or 4 yielded a more reliable estimate tha n Method 1 or 2, without largely depending on R and t(z). Since Method 2 wa s somewhat superior to other methods in terms of noninvasiveness and simpli city, it also had the potential for routine clinical use. The reproducibili ty of two sequential measurements of K-1 was investigated with clinical dat a obtained without any intervention. The response of CBF to acetazolamide c hallenge was also assessed by the above four methods. The knowledge gained by this study may assist in selecting a method for sequentially measuring C BF with a double injection of IMP.