Volumetric BOLD fMRI simulation: from neurovascular coupling to multivoxel imaging

Chen and Calhoun BMC Medical Imaging 2012, 12:8 http://www.biomedcentral.com/1471-2342/12/8 RESEARCH ARTICLE Open Access Volumetric BOLD fMRI simulation: from neurovascular coupling to multivoxel imaging Zikuan Chen1* and Vince Calhoun1,2 Abstract Background: The blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) modality has been numerically simulated by calculating single voxel signals. However, the observation on single voxel signals cannot provide information regarding the spatial distribution of the signals. Specifically, a single BOLD voxel signal simulation cannot answer the fundamental question: is the magnetic resonance (MR) image a replica of its underling magnetic susceptibility source? In this paper, we address this problem by proposing a multivoxel volumetric BOLD fMRI simulation model and a susceptibility expression formula for linear neurovascular coupling process, that allow us to examine the BOLD fMRI procedure from neurovascular coupling to MR image formation. Methods: Since MRI technology only senses the magnetism property, we represent a linear neurovascular-coupled BOLD state by a magnetic susceptibility expression formula, which accounts for the parameters of cortical vasculature, intravascular blood oxygenation level, and local neuroactivity. Upon the susceptibility expression of a BOLD state, we carry out volumetric BOLD fMRI simulation by calculating the fieldmap (established by susceptibility magnetization) and the complex multivoxel MR image (by intravoxel dephasing). Given the predefined susceptibility source and the calculated complex MR image, we compare the MR magnitude (phase, respectively) image with the predefined susceptibility source (the calculated fieldmap) by spatial correlation. Results: The spatial correlation between the MR magnitude image and the magnetic susceptibility source is about 0.90 for the settings of TE = 30 ms, B0 = 3 T, voxel size = 100 micron, vessel radius = 3 micron, and blood volume fraction = 2%. Using these parameters value, the spatial correlation between the MR phase image and the susceptibility-induced fieldmap is close to 1.00. Conclusion: Our simulation results show that the MR magnitude image is not an exact replica of the magnetic susceptibility source (spatial correlation ≈ 0.90), and that the MR phase image conforms closely with the susceptibility-induced fieldmap (spatial correlation ≈ 1.00). Keywords: Bold fMRI, Neurovascular coupling, Neuroactive blob (NAB), Blood magnetism, Intravoxel dephasing, Voxelization, Magnetic fieldmap, Spatial correlation Background Blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely accepted for brain functional mapping and neuroimaging [1-6]. The imaging principle of BOLD fMRI is that: a neuroactivity incurs cerebral vascular blood magnetism perturbation that can be detected by magnetic resonance imaging (MRI). In neurophysiology, the BOLD fMRI can be described by a neurovascular coupling * Correspondence: 1 The Mind Research Network and LBERI, Albuquerque 87106, NM, USA Full list of author information is available at the end of the article model as follows [7-11]: a neuronal activity incurs a vascular response in terms of changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO2). The neuroactivityinduced biomagnetic susceptibility perturbation can be detected by T2*-weighted MRI (T2*MRI) [12]. An overall BOLD fMRI model can be decomposed into a cascade of two modules [13]. One is a neurophysiology module that addresses the vascular response to a neuroactivity in context of neurovascular coupling [7-11]; The neurovascular coupling process produces an intravascular blood biomagnetism perturbation that is © 2012 Chen and Calhoun; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Chen and Calhoun BMC Medical Imaging 2012, 12:8 http://www.biomedcentral.com/1471-2342/12/8 detectable by T2*MRI [12]. Another is a MRI technology module dedicated to imaging the susceptibilityexpressed neurovascular coupling states. Despite its wide acceptance for neuroimaging and brain mapping, the BOLD fMRI mechanism is not fully understood [5,14,15]. Specifically, the complicated neurovascularcoupled BOLD process is not fully understood, and the imaging performance of T2*MRI detection on a BOLD state has never been quantitatively examined in a multivoxel simulation. In past decades, there have been many published reports on numerical simulations of BOLD mechanism [1,6,16-18]. To our knowledge, previous BOLD simulations were carried out for investigating single voxel signals and did not address multiple voxels. This may be partially due to the computational burden and the implementation difficulty in manipulating a large 3D image matrix (e.g. 2048 × 2048 × 2048 in our simulation). In practice, a BOLD fMRI experiment produces a 4D dataset that consists of a time series of 3D image matrices (typically in size of 64 × 64 × 32 voxels) captured by T2*MRI at a discrete time point (snapshot). A multivoxel image offers many spatial features, such as “contrast and texture”, “geometry: edge/shape/pattern”, “topography”, “topology”, and so on. Furthermore, given an input source and its corresponding output image, we can assess its overall imaging performance in terms of point spread function, spatial invariance/variance, and linearity/nonlinearity of a digital imaging system. Since T2*MRI is designed to sense an inhomogeneous fieldmap that is established via magnetization of an inhomogeneous susceptibility distribution, the underlying source of fMRI is the susceptibility-expressed distribution of a neurovascular coupling state. Therefore, for numerical BOLD fMRI simulation, we need numerically characterize the neurovascular coupling process in terms of biomagnetism susceptibility perturbation for the purpose of T2*MRI detectibility. Given a susceptibility map (representing a snapshot of dynamic BOLD susceptibility perturbation), we can carry out T2*MRI simulation in a way similar to BOLD voxel signal simulations [19-21]. Intuitively, a multivoxel BOLD fMRI simulation may be implemented by spatially arranging individual voxel signal values. In the implementation, nonetheless, we need account for the electromagnetic interaction among the voxels (due to the nonlocal effect of vascular blood magnetization [22]), especially for the magnetic influence from vasculatures in surrounding voxels that may influence the BOLD voxel signal by 10% [23]. In this paper, we propose a volumetric BOLD fMRI model that deals with a cortical field of view (FOV), as a whole matrix (without dividing into submatrices), in which the ma (...truncated)