Direct Characterization of Arterial Input Functions by Fluorescence Imaging of Exposed Carotid Artery to Facilitate Kinetic Analysis

Abstract

Purpose

With the goal of facilitating tracer kinetic analysis in small-animal planar fluorescence imaging, an experimental method for characterizing tracer arterial input functions is presented. The proposed method involves exposing the common carotid arteries by surgical dissection, which can then be imaged directly during tracer injection and clearance.

Procedures

Arterial concentration curves of IRDye-700DX-carboxylate, IRDye-800CW-EGF, and IRDye-800CW conjugated to anti-EGFR Affibody are recovered from athymic female mice (n = 12) by directly imaging exposed vessels. Images were acquired with two imaging protocols: a slow-kinetics approach (temporal resolution = 45 s) to recover the arterial curves from two tracers simultaneously, and a fast-kinetics approach (temporal resolution = 500 ms) to characterize the first-pass peak of a single tracer. Arterial input functions obtained by the carotid imaging technique, as well as plasma curves measured by blood sampling were fit with a biexponential pharmacokinetic model.

Results

Pharmacological fast- and slow-phase rate constants recovered with the proposed method were 0.37 ± 0.26 and 0.007 ± 0.001 min⁻¹, respectively, for the IRDye700DX-C. For the IRDye800CW-EGF, the rate constants were 0.11 ± 0.13 and 0.003 ± 0.002 min⁻¹. These rate constants did not differ significantly from those calculated previously by blood sampling, as determined by an F test; however, the between-subject variability was four times lower for arterial curves recovered using the proposed technique, compared with blood sampling.

Conclusions

The proposed technique enables the direct characterization of arterial input functions for kinetic analysis. As this method requires no additional instrumentation, it is immediately deployable in commercially available planar fluorescence imaging systems.