PXMOD Model Reference > Reference Models for Receptor and other Tracers > MP4A (Nagatsuka RLS Ref): Multi-linear Reference Tissue Model for [11C]-MP4A (RLS)

The MP4A (Nagatsuka RLS Ref) model has been developed for the non-invasive quantification method (RLS) of the acetylcholinesterase (AChE) activity in the human brain from measurements with the 11C-MP4A acetylcholine analog [1]. In contrast to reference methods for receptor tracers which use a reference devoid of specific binding, the present method uses a reference with very high AChE activity which immediately traps the tracer so there is no washout. CT(t) is the TAC from a cortical target region, and CT'(t) the TAC from the reference region (striatum or cerebellum). k3 represents the rate of tracer hydrolysis by AChE.

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By applying the method of Blomqvist, the following multi-linear equation is derived

It can be fitted to CT(t) using multi-linear regression, yielding three regression coefficients from which three parameters of interest can be calculated:

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Acquisition and Data Requirements

Image Data

A dynamic PET data set with [11C]-MP4A.

Target tissue

TAC from a cortical target region.

Reference tissue

A suitable reference region must be selected as TAC 2. The findings in different publications indicate that cerebellum yields more stable results than striatum, most likely due to the higher impact of motion on the signal from the small striatum than the large cerebellum.

Note: specification of an appropriate reference TAC is crucial for the result!

Model Preprocessing

PXMOD MP4A Ref Model Pre-Processing

Percent masked pixels

Exclude the specified percentage of pixels based on histogram analysis of integrated signal energy. Not applied in the presence of a defined mask.

The result of a model fit during Model Preprocessing is shown in the Model Results panel for inspection.

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Model Configuration

PXMOD MP4A Parameters

k3	The main parameter, the rate of tracer hydrolysis by AChE.
k2	The rate of washout from brain to blood.
R1	First coefficient of multilinear regression (Nagatsuka Eq. 3), representing the relative delivery K1/K1'.
P2	Second coefficient of multilinear regression (Nagatsuka Eq. 3), representing Rl*k3
P3	Third coefficient of multilinear regression (Nagatsuka Eq. 3), representing -(k2+k3)

Reference

1.Nagatsuka Si S, Fukushi K, Shinotoh H, Namba H, Iyo M, Tanaka N, Aotsuka A, Ota T, Tanada S, Irie T: Kinetic analysis of [(11)C]MP4A using a high-radioactivity brain region that represents an integrated input function for measurement of cerebral acetylcholinesterase activity without arterial blood sampling. J Cereb Blood Flow Metab 2001, 21(11):1354-1366. DOI