Quantitative susceptibility mapping (QSM) is a novel technique which allows determining the bulk magnetic susceptibility distribution of tissue in vivo from gradient echo magnetic resonance phase ...images. It is commonly assumed that paramagnetic iron is the predominant source of susceptibility variations in gray matter as many studies have reported a reasonable correlation of magnetic susceptibility with brain iron concentrations in vivo. Instead of performing direct comparisons, however, all these studies used the putative iron concentrations reported in the hallmark study by Hallgren and Sourander (1958) for their analysis. Consequently, the extent to which QSM can serve to reliably assess brain iron levels is not yet fully clear. To provide such information we investigated the relation between bulk tissue magnetic susceptibility and brain iron concentration in unfixed (in situ) post mortem brains of 13 subjects using MRI and inductively coupled plasma mass spectrometry. A strong linear correlation between chemically determined iron concentration and bulk magnetic susceptibility was found in gray matter structures (r=0.84, p<0.001), whereas the correlation coefficient was much lower in white matter (r=0.27, p<0.001). The slope of the overall linear correlation was consistent with theoretical considerations of the magnetism of ferritin supporting that most of the iron in the brain is bound to ferritin proteins. In conclusion, iron is the dominant source of magnetic susceptibility in deep gray matter and can be assessed with QSM. In white matter regions the estimation of iron concentrations by QSM is less accurate and more complex because the counteracting contribution from diamagnetic myelinated neuronal fibers confounds the interpretation.
► Brain iron concentration correlates with bulk magnetic susceptibility. ► Iron is the dominant contributor to magnetic susceptibility in gray matter tissue. ► Iron and susceptibility are weaker correlated in WM, indicating effects of myelin.
This work's aim was to minimize the acquisition time of a radial 3D ultra-short echo-time (UTE) sequence and to provide fully automated, gradient delay compensated, and therefore artifact free, ...reconstruction. The radial 3D UTE sequence (echo time 60 μs) was implemented as single echo acquisition with center-out readouts and improved time efficient spoiling on a clinical 3T scanner without hardware modifications. To assess the sequence parameter dependent gradient delays each acquisition contained a quick calibration scan and utilized the phase of the readouts to detect the actual k-space center. This calibration scan does not require any user interaction. To evaluate the robustness of this automatic delay estimation phantom experiments were performed and 19 in vivo imaging data of the head, tibial cortical bone, feet and lung were acquired from 6 volunteers. As clinical application of this fast 3D UTE acquisition single breath-hold lung imaging is demonstrated. The proposed sequence allowed very short repetition times (TR~1ms), thus reducing total acquisition time. The proposed, fully automated k-phase based gradient delay calibration resulted in accurate delay estimations (difference to manually determined optimal delay -0.13 ± 0.45 μs) and allowed unsupervised reconstruction of high quality images for both phantom and in vivo data. The employed fast spoiling scheme efficiently suppressed artifacts caused by incorrectly refocused echoes. The sequence proved to be quite insensitive to motion, flow and susceptibility artifacts and provides oversampling protection against aliasing foldovers in all directions. Due to the short TR, acquisition times are attractive for a wide range of clinical applications. For short T2* mapping this sequence provides free choice of the second TE, usually within less scan time as a comparable dual echo UTE sequence.
Quantitative magnetic susceptibility mapping (QSM) has recently been introduced to provide a novel quantitative and local MRI contrast. However, the anatomical contrast represented by in vivo ...susceptibility maps has not yet been compared systematically and comprehensively with gradient (recalled) echo (GRE) magnitude, frequency, and R2⁎ images. Therefore, this study compares high-resolution quantitative susceptibility maps with conventional GRE imaging approaches (magnitude, frequency, R2⁎) in healthy individuals at 7T with respect to anatomic tissue contrast. Volumes-of-interest were analyzed in deep and cortical gray matter (GM) as well as in white matter (WM) on R2⁎ and susceptibility maps. High-resolution magnetic susceptibility maps of the human brain exhibited superb contrast that allowed the identification of substructures of the thalamus, midbrain and basal ganglia, as well as of the cerebral cortex. These were consistent with histology but not generally visible on magnitude, frequency or R2⁎-maps. Common target structures for deep brain stimulation, including substantia nigra pars reticulata, ventral intermediate nucleus, subthalamic nucleus, and the substructure of the internal globus pallidus, were clearly distinguishable from surrounding tissue on magnetic susceptibility maps. The laminar substructure of the cortical GM differed depending on the anatomical region, i.e., a cortical layer with increased magnetic susceptibility, corresponding to the Stria of Gennari, was found in the GM of the primary visual cortex, V1, whereas a layer with reduced magnetic susceptibility was observed in the GM of the temporal cortex. Both magnetic susceptibility and R2⁎ values differed substantially in cortical GM depending on the anatomic regions. Regression analysis between magnetic susceptibility and R2⁎ values of WM and GM structures suggested that variations in myelin content cause the overall contrast between gray and white matter on susceptibility maps and that both R2⁎ and susceptibility values provide linear measures for iron content in GM. In conclusion, quantitative magnetic susceptibility mapping provides a non-invasive and spatially specific contrast that opens the door to the assessment of diseases characterized by variation in iron and/or myelin concentrations. Its ability to reflect anatomy of deep GM structures with superb delineation may be useful for neurosurgical applications.
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► Susceptibility maps display anatomic structures consistent with histology. ► Myelin causes susceptibility contrast between cortical gray and white matter. ► Magnetic susceptibility reveals variations across layers in cortical gray matter. ► Susceptibility and R2⁎ provide linear measures for iron content in gray matter.
To investigate the influence of anisotropic electrical conductivity in white matter on the forward and inverse solution in electroencephalography (EEG) and magnetoencephalography (MEG) numerical ...simulation studies were performed. A high-resolution (1 mm3 isotropic) finite element model of a human head was implemented to study the sensitivity of EEG and MEG source localization. In vivo information on the anisotropy was obtained from magnetic resonance diffusion tensor imaging and included into the model, whereas both a direct transformation and a direct transformation with volume normalization were used to obtain conductivity tensors. Additionally, fixed artificial anisotropy ratios were also used, while considering only the orientation information from DTI, to generate conductivity tensors. Analysis was performed using over 25,000 single dipolar sources covering the full neocortex. Major findings of the study include that EEG is more sensitive to anisotropic conductivities in white matter compared to MEG. Especially with the inverse analysis, we found that sources placed deep in sulci are located more laterally if anisotropic conductivity of white matter tissue is neglected. Overall, the single-source localization errors resulting from a neglect of anisotropy were found to be smaller compared to errors associated with other modeling errors, like misclassified tissue or the use of nonrealistic head models. In contrast to the small localization error we observed significant changes in magnitude and orientation. The latter is important since dipole orientation might be more important than absolute dipole localization in assigning, e.g., epileptic activity to the wall of the affected brain sulcal area. If high-resolution finite element models are used to perform source localization in EEG and MEG experiments and the quality of the measured data permits localization accuracy of 1 mm and below, the influence of anisotropic compartments has to be taken into account.
Quantitative susceptibility mapping (QSM) and effective transverse relaxation rate (R2*) mapping are both highly sensitive to variations in brain iron content. Clinical Magnetic Resonance Imaging ...(MRI) studies report changes of susceptibilities and relaxation rates in various neurological diseases which are often equated with changes in regional brain iron content. However, these mentioned metrics lack specificity for iron, since they are also influenced by the presence of myelin. In this study, we assessed the extent to which QSM and R2* reflect iron concentration as well as histological iron and myelin intensities. Six unfixed human post-mortem brains were imaged in situ with a 7 T MRI scanner. After formalin fixation, the brains were sliced axially and punched. 671 tissue punches were subjected to ferrozine iron quantification. Subsequently, brain slices were embedded in paraffin, and histological double-hemispheric axial brain slices were stained for Luxol fast blue (myelin) and diaminobenzidine (DAB)-enhanced Turnbull blue (iron). 3331 regions of interest (ROIs) were drawn on the histological stainings to assess myelin and iron intensities, which were compared with MRI data in corresponding ROIs. QSM more closely reflected quantitative ferrozine iron values (r = 0.755 vs. 0.738), whereas R2* correlated better with iron staining intensities (r = 0.619 vs. 0.445). Myelin intensities correlated negatively with QSM (r = −0.352), indicating a diamagnetic effect of myelin on susceptibility. Myelin intensities were higher in the thalamus than in the basal ganglia. A significant relationship was nonetheless observed between quantitative iron values and QSM, confirming the applicability of the latter in this brain region for iron quantification.
•Brain iron can be visualized using quantitative susceptibility (QSM) and R2* mapping.•Anatomical structures show different contributions of iron and myelin to QSM or R2*.•Iron and myelin have opposite effects on QSM throughout the human brain.•The relation between brain iron and myelin differs between anatomical structures.
The magnetic properties of tissues affect MR images and differences in magnetic susceptibility can be utilized to provide impressive image contrast. Specifically, phase images acquired with gradient ...echo MRI provide unique and superb contrast which reflects variations in the underlying tissue composition. There is great interest in extracting tissue susceptibility from image data since magnetic susceptibility is an intrinsic tissue property that reflects tissue composition much more closely than MRI phase. Still, this major tissue contrast mechanism is largely unexplored in magnetic resonance imaging because non-conventional reconstruction and dipole deconvolution are required to quantitatively map tissue susceptibility properly. This short review summarizes the current state of susceptibility contrast and susceptibility mapping and aims to identify future directions.
Interventional studies suggest that changes in physical fitness affect brain function and structure. We studied the influence of high intensity physical exercise on hippocampal volume and metabolism ...in 17 young healthy male adults during a 6-week exercise program compared with matched controls. We further aimed to relate these changes to hypothesized changes in exercised-induced brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). We show profound improvement of physical fitness in most subjects and a positive correlation between the degree of fitness improvement and increased BDNF levels. We unexpectedly observed an average volume decrease of about 2%, which was restricted to right hippocampal subfields CA2/3, subiculum, and dentate gyrus and which correlated with fitness improvement and increased BDNF levels negatively. This result indicates that mainly those subjects who did not benefit from the exercise program show decreased hippocampal volume, reduced BDNF levels, and increased TNF-α concentrations. While spectroscopy results do not indicate any neuronal loss (unchanged N-acetylaspartate levels) decreased glutamate-glutamine levels were observed in the right anterior hippocampus in the exercise group only. Responder characteristics need to be studied in more detail. Our results point to an important role of the inflammatory response after exercise on changes in hippocampal structure.
Purpose:
Identification of calcifications and hemorrhages is essential for the etiological diagnosis of cerebral lesions. The purpose of this work was to develop a robust method for characterization ...of para- and diamagnetic intracerebral lesions based on clinical gradient-echo magnetic resonance phase data acquired at 1.5 Tesla.
Methods:
The magnetic susceptibility distribution of biological tissue produces a distinct magnetic field pattern, which is directly reflected in gradient-echo magnetic resonance phase images. Compared to brain parenchyma, iron-laden tissues are more paramagnetic, whereas mineralized tissues usually possess more diamagnetic susceptibilities. Magnetic resonance phase data were inverted to the underlying susceptibility distribution utilizing additional geometrical information about the lesions, which was obtained from the gradient-echo magnitude signal void corresponding to the lesions. Clinical magnetic resonance exams of three patients with multiple brain lesions (total
n
=
70
) were processed and evaluated. For one patient, the results were validated by an additionally available computed tomography scan. Numerical simulations were conducted to evaluate the robustness of the method.
Results:
The obtained susceptibility maps showed impressive delineation of lesions, vessels, and potentially iron-laden tissue. Compensation of the nonlocal field perturbations was clearly discernable on the susceptibility maps. In all cases, discrimination of para- from diamagnetic lesions was achieved and the results were confirmed by the additional computed tomography. The numerical simulations demonstrated that robust determination of the total magnetic moment of lesions is possible. Thus, the proposed method is able to yield quantitative values for the minimum magnetic susceptibility of lesions.
Conclusions:
A method has been developed for noninvasive, semiautomatic characterization of brain lesions based on magnetic resonance imaging data. Initial clinical results demonstrated that the proposed technique can be applied to diagnosis of lesions with calcifications or hemorrhages. If confirmed by larger studies, it bears the potential to obviate the need for confirmation with computed tomography.
The peripheral autonomic nervous system (ANS) adjusts the heart rate (HR) to intrinsic and extrinsic demands. It is controlled by a group of functionally connected brain regions assembling the ...so-called central autonomic network (CAN). More specifically, forebrain cortical regions, limbic and brainstem structures within the CAN have been identified as important components of circuits involved in HR regulation. The present study aimed to investigate whether functional connectivity (FC) between these regions varies in subjects with different heart rates. Thus, 84 healthy subjects were separated according to their HR in slow, medium and fast. We observed a direct association between HR and FC in CAN regions, where stronger FC was related to slower HR. This relationship, however, is non-linear, follows an exponential course and is not restricted to CAN areas only. The network-based analysis (NBS) using time series from 262 independent anatomical ROIs revealed significantly increased functional connectivity in subjects with slow HR compared to subjects with fast HR mainly in regions being part of the salience network, but also of the default-mode network. We additionally simulated the effect of aliasing on the functional connectivity using several TRs and heart rates to exclude the possibility that FC differences might be due to different aliasing effects in the data. The result of the simulation indicated that aliasing cannot explain our findings.
Thus, present results imply a functionally meaningful coupling between FC and HR that need to be accounted for in future studies. Moreover, given the established link between HR and emotional, cognitive and social processes, present findings may also be considered to explain individual differences in brain activation or connectivity when using corresponding paradigms in the MR scanner to investigate such processes.
•Intrinsic functional connectivity of regions involved in autonomic control depends on the subject's heart rate.•Slow heart rate is associated with stronger functional connectivity.•The coupling between heart rate and functional connectivity follows an exponential course.
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