Probing neuronal activation by functional quantitative susceptibility mapping under a visual paradigm: A group level comparison with BOLD fMRI and PET

Abstract

Dynamic changes of brain-tissue magnetic susceptibility provide the basis for functional MR imaging (fMRI) via T2*-weighted signal-intensity modulations. Promising initial work on a detection of neuronal activity via quantitative susceptibility mapping (fQSM) has been published but consistently reported on ill-understood positive and negative activation patterns (Balla et al., 2014;Chen and Calhoun, 2015a). We set out to (i) demonstrate that fQSM can exploit established fMRI data acquisition and processing methods and to (ii) better describe aspects of the apparent activation patterns using fMRI and PET as standards of reference. Under a standardized visual-stimulation paradigm PET and 3-T gradient-echo EPI-based fQSM, fMRI data from 9 healthy volunteers were acquired and analyzed by means of Independent Component Analysis (ICA) at subject level and, for the first time, at group level. Numbers of activated (z-score>2.0) voxels were counted and their mean z-scores calculated in volumes of interest (occipital lobe (Nocc_lobe), segmented occipital gray-matter (NGM_occ_lobe), large veins (Nveins)), and in occipital-lobe voxels commonly activated in fQSM and fMRI component maps. Common but not entirely congruent regions of apparent activation were found in the occipital lobe in z-score maps from all modalities, fQSM, fMRI and PET, with distinct BOLD-negatively correlated regions in fQSM data. At subject-level, Nocc_lobe, NGM_occ_lobe and their mean z-scores were significantly smaller in fQSM than in fMRI, but their ratio, NGM_occ_lobe/Nocc_lobe, was comparable. Nveins did not statistically differ and the ratio Nveins/NGM_occ_lobe as well as the mean z-scores were higher for fQSM than for fMRI. In veins and immediate vicinity, z-score maps derived from both phase and fQSMdata showed positive and negative lobes resembling dipole shapes in simulated field and phase maps with no correlate in fMRI or PET data. Our results show that standard fMRI tools can directly be used for fQSM processing, and suggest that fQSM may have the potential to detect gray-matter activation distant from large veins, to improve detection of veins with stimulus-induced venous oxygen saturation (SvO2) variations, and to better localize areas of activation. However, our results seem to clearly expose issues that phenomenologically resemble an incomplete dipolar inversion and that need to be subject to further investigation. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. fMRI. In veins and immediate vicinity, z-score maps derived from both phase and fQSM-data showed positive and negative lobes resembling dipole shapes in simula...

Methods for cleaning the BOLD fMRI signal

“…However, the phase signal contains biologically relevant information about the vasculature contained within voxels that exhibits susceptibility-related signal changes in response to neuronal activity (Hoogenraad et al, 2001). Hence, considering both magnitude and phase changes helps to enhance the mapping of the BOLD response in terms of sensitivity and spatial specificity in complex-based fMRI analysis (Arja et al, 2010; Calhoun et al, 2002; Kociuba and Rowe, 2016; Lee et al, 2009; Rowe and Logan, 2004; 2005; Tomasi and Caparelli, 2007; Yu et al, 2015), and enables functional quantitative susceptibility mapping (Balla et al, 2014; Bianciardi et al, 2014; Chen and Calhoun, 2016; Özbay et al, 2016). …”

Enhanced quantitative susceptibility mapping (QSM) using real‐time field control

“…An advantage of the field‐probe/real‐time correction setup in this comparison is that it typically requires only minor changes to the imaging pulse sequence , as it operates rather independently, except for the effect of the field gradients on the probe signals, which, without further precaution, precludes a sampling of probe signals while gradients are switched on. Apart from our 3D gradient‐echo QSM sequence, it has also been shown to, for example, improve gradient‐echo echo‐planar imaging–based functional MRI , which could also yield data for functional QSM , or allow physiology tracking . A navigator‐based approach, on the other hand, needs to be individually adjusted to every scanner pulse sequence, and the acquisition of additional data also potentially increases scan times.…”

Anatomical modeling of brain vasculature in two-photon microscopy by generalizable deep learning

“…In particular, measuring vascular dynamics has proved to be important for early diagnosis of critical cerebrovascular and neurological disorders, such as stroke and Alzheimer's disease [2]. Existing tools for the measurement of cerebral vascular dynamics rely on functional imaging techniques, for example functional magnetic resonance imaging (fMRI), positive emission tomography (PET), and optical imaging [1,3]. Importantly, mathematical models have been proposed for these neuroimaging methods, which provide valuable insight into the relation between the measured signals, and the underlying physiological parameters, such as cerebral blood flow, oxygen consumption, and rate of metabolism [4][5][6][7].…”