Structural and functional quantitative susceptibility mapping from standard fMRI studies.

Standard functional MRI (fMRI), which includes resting-state or paradigm-driven designs, is widely used in studies of brain function, aging, and disease. These fMRI studies typically use two-dimensional gradient echo-planar imaging, which inherently contains phase data that enables quantitative susceptibility mapping (QSM). This work focuses on the dual value of QSM within fMRI studies, by providing both a localized analysis of functional changes in activated tissue, and iron-sensitive structural maps in deep grey matter (DGM). Using a visual paradigm fMRI study on healthy volunteers at clinical (1.5 T) and high field strength (4.7 T), we perform functional analysis of magnitude and QSM time series, and at the same time harness structural QSM of iron-rich DGM, including globus pallidus, putamen, caudate head, substantia nigra, and red nucleus. The effects of fMRI spatial resolution and time series variation on structural DGM QSM are investigated. Our results indicate that structural DGM QSM is feasible within existing fMRI studies, provided that the voxel dimensions are equal to or less than 3 mm, with higher resolutions preferred. The mean DGM QSM values were about 40 to 220 ppb, while the interquartile ranges of the DGM QSM time series varied from about 3 to 9 ppb, depending on structure and resolution. In contrast, the peak voxel functional QSM (fQSM) changes in activated visual cortex ranged from about -10 to -30 ppb, and functional clusters were consistently smaller on QSM than magnitude fMRI. Mean-level DGM QSM of the time series was successfully extracted in all cases, while fQSM results were more prone to residual background fields and showed less functional change compared with standard magnitude fMRI. Under the conditions prescribed, standard fMRI studies may be used for robust mean-level DGM QSM, enabling study of DGM iron accumulation, in addition to functional analysis. Copyright © 2016 John Wiley & Sons, Ltd.

Glutamate levels in the medial prefrontal cortex of healthy pregnant women compared to non-pregnant controls.

Very little is known about maternal cerebral changes during pregnancy. Since there is an increased risk for major depression during pregnancy and postpartum, it is important to understand the structural and neurochemical changes that occur in the brain during pregnancy. Using proton magnetic resonance spectroscopy (1H-MRS) (3 T field strength), glutamate (Glu) levels were measured in the medial prefrontal cortex (MPFC) of 21 healthy gravid subjects 2-3 weeks before their due date (6.74 ± 1.39), and in 14 non-pregnant healthy controls during their follicular phase (8.53 ± 1.55). Water quantified MPFC Glu levels were decreased in pregnant women (p < 0.01). We also observed a 13.9% decrease in percentage grey matter (%GM) (p < 0.01) in our MPFC voxel. As Glu is mostly found in GM, we repeated the statistical analysis after adjustment for %GM and found that the difference in Glu levels was no longer statistically significant when adjusted for %GM (p = 0.10). This investigation is the only systematic direct investigation of brain tissue composition and Glu levels in pregnant women. The main finding of this investigation is the decreased %GM in healthy pregnant women compared to non-pregnant women. These findings of decreased %GM in pregnancy may be responsible for the frequent complaints by pregnant women of cognitive difficulties also described as pregnesia.

Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Deep gray matter iron accumulation is increasingly recognized in association with multiple sclerosis and can be measured in vivo with MR imaging. The cognitive implications of this pathology are not well-understood, especially vis-à-vis deep gray matter atrophy. Our aim was to investigate the relationships between cognition and deep gray matter iron in MS by using 2 MR imaging-based iron-susceptibility measures. MATERIALS AND METHODS: Forty patients with multiple sclerosis (relapsing-remitting, n = 16; progressive, n = 24) and 27 healthy controls were imaged at 4.7T by using the transverse relaxation rate and quantitative susceptibility mapping. The transverse relaxation rate and quantitative susceptibility mapping values and volumes (atrophy) of the caudate, putamen, globus pallidus, and thalamus were determined by multiatlas segmentation. Cognition was assessed with the Brief Repeatable Battery of Neuropsychological Tests. Relationships between cognition and deep gray matter iron were examined by hierarchic regressions. RESULTS: Compared with controls, patients showed reduced memory (P < .001) and processing speed (P = .02) and smaller putamen (P < .001), globus pallidus (P = .002), and thalamic volumes (P < .001). Quantitative susceptibility mapping values were increased in patients compared with controls in the putamen (P = .003) and globus pallidus (P = .003). In patients only, thalamus (P < .001) and putamen (P = .04) volumes were related to cognitive performance. After we controlled for volume effects, quantitative susceptibility mapping values in the globus pallidus (P = .03; trend for transverse relaxation rate, P = .10) were still related to cognition. CONCLUSIONS: Quantitative susceptibility mapping was more sensitive compared with the transverse relaxation rate in detecting deep gray matter iron accumulation in the current multiple sclerosis cohort. Atrophy and iron accumulation in deep gray matter both have negative but separable relationships to cognition in multiple sclerosis.

High field structural MRI reveals specific episodic memory correlates in the subfields of the hippocampus.

The involvement of the hippocampus (HC) in episodic memory is well accepted; however it is unclear how each subfield within the HC contributes to memory function. Recent magnetic resonance imaging (MRI) studies suggest differential involvement of hippocampal subfields and subregions in episodic memory. However, most structural MRI studies have examined the HC subfields within a single subregion of the HC and used specialised experimental memory paradigms. The purpose of the present study was to determine the association between volumes of HC subfields throughout the entire HC structure and performance on standard neuropsychological memory tests in a young, healthy population. We recruited 34 healthy participants under the age of 50. MRI data was acquired with a fast spin echo (FSE) sequence yielding a 0.52×0.68×1.0 mm(3) native resolution. The HC subfields - the cornu ammonis 1-3 (CA), dentate gyrus (DG), and subiculum (SUB) - were segmented manually within three hippocampal subregions using a previously defined protocol. Participants were administered the Wechsler Memory Scale, 4th edition (WMS-IV) to assess performance in episodic memory using verbal (Logical Memory, LM) and visual (Designs, DE; visual-spatial memory, DE-Spatial; visual-content memory, DE-Content) memory subtests. Working memory subtests (Spatial Addition, SA; and Symbol Span, SSP) were included as well. Working memory was not associated with any HC volumes. Volumes of the DG were correlated with verbal memory (LM) and visual-spatial memory (DE-Spatial). Posterior CA volumes correlated with both visual-spatial and visual-object memory (DE-Spatial, DE-Content). In general, anterior subregion volumes (HC head) correlated with verbal memory, while some anterior and many posterior HC subregion volumes (body and tail) correlated with visual memory scores (DE-Spatial, DE-Content). In addition, while verbal memory showed left-lateralized associations with HC volumes, visual memory was associated with HC volumes bilaterally. This the first study to examine the associations between hippocampal subfield volumes across the entire hippocampal formation with performance in a set of standard memory tasks.

Mesial prefrontal cortex degeneration in amyotrophic lateral sclerosis: a high-field proton MR spectroscopy study.

BACKGROUND AND PURPOSE: Frontotemporal lobar degeneration is responsible for the cognitive abnormalities seen in patients with ALS. We sought to evaluate the in vivo neurochemical changes associated with this pathology indicative of neuronal loss and gliosis. MATERIALS AND METHODS: Twenty-four patients with ALS (2 with ALS-FTD) and 15 healthy controls were studied. High-field proton MR spectroscopy of the mesial prefrontal cortex was used to determine concentrations of NAA and mIns, markers of neuronal integrity and gliosis, respectively. Metabolite concentrations were correlated with cognitive tests (verbal fluency, ACE). RESULTS: NAA/mIns was decreased 17% (P =.002). Abnormalities were present to a lesser degree in the individual metabolites NAA (decreased 9%; P =.08) and mIns (increased 11%; P =.06) than the ratio of the 2 metabolites. These measures did not correlate significantly with verbal fluency or the ACE. CONCLUSIONS: Prefrontal lobe degeneration exists in patients with ALS as indicated by an abnormal mesial prefrontal cortex neurochemical profile. Further study is necessary to determine the potential utility of the NAA/mIns ratio as a biomarker for frontal lobe degeneration in ALS.