Computational Study on Use of Single-Point Analysis Method for Quantitating Local Cerebral Blood Flow in Mice

Abstract

The benefits of a mouse model are efficiency and availability of transgenics/ knockouts. Quantitation of cerebral blood in small animals is difficult because the cannulation procedure may introduce errors. The [14C]-iodoantipyrine autoradiography (IAP) method requires both the tissue concentration and the time course of arterial concentration of the [14C] radioactive tracer. A single point-analysis technique was evaluated for measuring blood flow in mice (30 g +/- 0.3 g; n = 11) by using computational models of sensitivity analysis, which quantitates relationships between the predictions of a model and its parameters. Using [14C]-IAP in conjunction with mathematical algorithms and assumed arterial concentration-versus-time profiles, cortical blood flow was deduced from single-point measurements of the arterial tracer concentration. The data showed the arterial concentration profile that produced the most realistic blood flows (1.6 +/- 0.4; mean +/- SD, ml/g/min) was a profile with a ramp time of 30 sec followed by a constant value over the remaining time period of 30 sec. Sensitivity analysis showed that the total experimental time period was a more important parameter than the lag period and the ramp period. Thus, it appears that the accuracy of the assumption of linearly increasing arterial concentration depends on the experimental time period and the final arterial [14C]-iodoantipyrine concentration.

The effect of acetyl-L-carnitine and R-α-lipoic acid treatment in ApoE4 mouse as a model of human Alzheimer's disease

“…Age-dependent effects of ApoE4 on CBF were measured using [ 14 C] iodoantipyrene autoradiography in conjunction with a mathematical algorithm (42). Measurement of regional blood flow (rBF) was determined by a [ 14 C] - iodoantipyrene (IAP, New England Nuclear) autoradiography technique modified for mice and described earlier by us (42, 43).…”

“…Measurement of regional blood flow (rBF) was determined by a [ 14 C] - iodoantipyrene (IAP, New England Nuclear) autoradiography technique modified for mice and described earlier by us (42, 43). This method measures local CBF by combining an intraperitoneal tracer with a single blood sampling from the heart.…”

“…Brains were thin-sectioned at the levels of atlas plate 13, 30 and 69 (described in detail by Puchowicz, et al) and then placed on glass slides. The slides were placed on Amersham Hyperfilm β-Max autographic film along with calibrated standards (Amersham [ 14 C] Micro-scales, RPA 504 and RPA 511) and then exposed for 3 months (42). The films were digitized using a BIOQUANT image analysis system (R & M Biometrics, INC) and background corrected.…”