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Generalized autocalibrating partially parallel acquisition (GRAPPA) has been a widely used parallel MRI technique. However, noise deteriorates the reconstructed image when reduction factor increases or even at low reduction factor for some noisy datasets. Noise, initially generated from scanner, propagates noise-related errors during fitting and interpolation procedures of GRAPPA to distort the final reconstructed image quality. The basic idea we proposed to improve GRAPPA is to remove noise from a system identification perspective. In this paper, we first analyze the GRAPPA noise problem from a noisy input-output system perspective; then, a new framework based on errors-in-variables (EIV) model is developed for analyzing noise generation mechanism in GRAPPA and designing a concrete method—instrument variables (IV) GRAPPA to remove noise. The proposed EIV framework provides possibilities that noiseless GRAPPA reconstruction could be achieved by existing methods that solve EIV problem other than IV method. Experimental results show that the proposed reconstruction algorithm can better remove the noise compared to the conventional GRAPPA, as validated with both of phantom and in vivo brain data. [ABSTRACT FROM AUTHOR]