Regional Multiparameter Estimation from Tomographic Diffusible Tracer Clearance Curves: Modification of the Double-Integral Method

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Abstract
Measurement of regional CBF in transverse section using inert, diffusible tracers can be carried out using a double-integral form of the Kety-Schmidt equation. An implementation of this form proposed by Kanno and Lassen (the K-L estimator) is utilized by the Tomomatic 64, a dynamic single-photon computed tomography system that records washin-washout data during and following inhalation of 133Xe gas. Advantages of the algorithm include noninvasive calibration of the input function and excellent depiction of ischemia; disadvantages are sensitivity to errors in input function delay (δ), the inability to estimate the partition coefficient (Λ) (hence, only the clearance index, k, is estimated), and a noise sensitivity proportional to k. A modification of the method is proposed that not only accounts for δ variations, but also provides an estimate of relative Λ (hence, the perfusion, f, is estimated). The proposed estimator is shown to be robust in the presence of noise with error variances equal to or better than those with the K-L estimator, yet estimates of both relative f and Λ are provided by the modification. New simulation results implicate the Compton scatter fraction as a major contributor in the overestimation of white matter perfusion values using both the K-L and proposed estimators, and illustrate the need for hardware and software scatter fraction reduction and control.

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