Phase Variations in fMRI Time Series Analysis: Friend or Foe?

Functional MRI studies (fMRI) are based on the blood-oxygenation-level-dependent effect (BOLD) that arises in brain areas where neuronal activity takes place (Ogawa et al., 1990, 1993). BOLD induces changes in the local magnetic susceptibility and these can be measured by Gradient Echo (GE) Echo-Planar-Imaging (EPI). The fMRI signal thus observed consists of a complex value, which can be subdivided into a magnitude and a phase value, but in most fMRI studies the phase signal is discarded and only the magnitude changes are used to detect the activated brain areas

Magnetic properties of iron-filled hydrogel clusters: a model system for quantitative susceptibility mapping with MRI

Quantitative approaches in clinical Magnetic Resonance Imaging (MRI) benefit from the availability of adequate phantoms. Ideally, the phantom material should reflect the complexity of signals encountered in vivo. In the present study we validate and characterize clusters consisting of sodium-polyacrylate embedded in an alginate matrix that are unloaded or loaded with iron for Quantitative Susceptibility Mapping (QSM), yielding a non-uniform iron distribution and tissue-mimicking MRI properties. Vibrating sample magnetometry (VSM) was used to characterize the phantom material and verify the accuracy of previous MRI-based observations of the QSM based molar susceptibility (χM). MRI at 14.1 T with high resolution acquisitions was used to determine the size of hydrogel clusters and to further investigate the suitability of the phantom material as a model system for QSM at high field. VSM demonstrated that the iron-solution used for manufacturing the phantoms consisted of ferric iron. The χM of clusters with a constant iron-to-polyacrylate-ratio (8.3 μg/mg) observed with VSM was 50.7 ± 8.0 ppb mM−1 but showed a tendency towards saturation at total iron concentrations >1 mM. On unwrapped and background corrected phase-images obtained with gradient-echo MRI and an isotropic voxel size of 37 μm at 14.1T, the iron-free clusters had a roundish shape and blurry border with an equivalent sphere diameter of 276 ± 230 µm and a QSM of 7 ± 7 ppb. Iron-loading led to strong phase wrapping, necessitating the use of short echo times, or short inter-echo delays below 10 ms at 14.1 T. The equivalent sphere diameter of the iron-loaded clusters was estimated to 400–500 µm as verified using different MRI modalities (spin-echo, inversion recovery, and gradient echo MRI). With a constant iron-to-polyacrylate ratio, the cluster density was 10 mm−3 mM−1 iron. In agreement with previous observations, χM of samples with a constant amount of polyacrylate was 50.6 ± 11.4 ppb mM−1 at 3 T while samples containing clusters with a constant iron-to polyacrylate-ratio yielded χM = 56.1 ± 6.3 ppb mM−1 at 3T and 55.6 ± 0.7 ppb mM−1 at 14.1 T. In conclusion we found that the molar susceptibility of the proposed model system corresponds to that predicted for ferritin in vivo loaded with 3000 iron atoms. The reproducibility was within 12% across MR scanners, batches, and phantom types and compared well with results obtained with vibrating sample magnetometry

Prediction of motion induced magnetic fields for human brain MRI at 3T

Objective Maps of B0 field inhomogeneities are often used to improve MRI image quality, even in a retrospective fashion. These field inhomogeneities depend on the exact head position within the static field but acquiring field maps (FM) at every position is time consuming. Here we explore different ways to obtain B0 predictions at different head positions. Methods FM were predicted from iterative simulations with four field factors: 1) sample induced B0 field, 2) system's spherical harmonic shim field, 3) perturbing field originating outside the field of view, 4) sequence phase errors. The simulation was improved by including local susceptibility sources estimated from UTE scans and position-specific masks. The estimation performance of the simulated FMs and a transformed FM, obtained from the measured reference FM, were compared with the actual FM at different head positions. Results The transformed FM provided inconsistent results for large head movements (>5 degree rotation), while the simulation strategy had a superior prediction accuracy for all positions. The simulated FM was used to optimize B0 shims with up to 22.2% improvement with respect to the transformed FM approach. Conclusion The proposed simulation strategy is able to predict movement induced B0 field inhomogeneities yielding more precise estimates of the ground truth field homogeneity than the transformed FM

Characterization of the Blood Oxygen Level Dependent Hemodynamic Response Function in Human Subcortical Regions With High Spatiotemporal Resolution

Subcortical brain regions are absolutely essential for normal human function. These phylogenetically early brain regions play critical roles in human behaviors such as the orientation of attention, arousal, and the modulation of sensory signals to cerebral cortex. Despite the critical health importance of subcortical brain regions, there has been a dearth of research on their neurovascular responses. Blood oxygen level dependent (BOLD) functional MRI (fMRI) experiments can help fill this gap in our understanding. The BOLD hemodynamic response function (HRF) evoked by brief (\u3c4 \u3es) neural activation is crucial for the interpretation of fMRI results because linear analysis between neural activity and the BOLD response relies on the HRF. Moreover, the HRF is a consequence of underlying local blood flow and oxygen metabolism, so characterization of the HRF enables understanding of neurovascular and neurometabolic coupling. We measured the subcortical HRF at 9.4T and 3T with high spatiotemporal resolution using protocols that enabled reliable delineation of HRFs in individual subjects. These results were compared with the HRF in visual cortex. The HRF was faster in subcortical regions than cortical regions at both field strengths. There was no significant undershoot in subcortical areas while there was a significant post-stimulus undershoot that was tightly coupled with its peak amplitude in cortex. The different BOLD temporal dynamics indicate different vascular dynamics and neurometabolic responses between cortex and subcortical nuclei

Distribution of corpora amylacea in the human midbrain: using synchrotron radiation phase-contrast microtomography, high-field magnetic resonance imaging, and histology

Corpora amylacea (CA) are polyglucosan aggregated granules that accumulate in the human body throughout aging. In the cerebrum, CA have been found in proximity to ventricular walls, pial surfaces, and blood vessels. However, studies showing their three-dimensional spatial distribution are sparse. In this study, volumetric images of four human brain stems were obtained with MRI and phase-contrast X-ray microtomography, followed up by Periodic acid Schiff stain for validation. CA appeared as hyperintense spheroid structures with diameters up to 30μm. An automatic pipeline was developed to segment the CA, and the spatial distribution of over 200,000 individual corpora amylacea could be investigated. A threefold—or higher—density of CA was detected in the dorsomedial column of the periaqueductal gray (860–4,200 CA count/mm3) than in the superior colliculus (150–340 CA count/mm3). We estimated that about 2% of the CA were located in the immediate vicinity of the vessels or in the peri-vascular space. While CA in the ependymal lining of the cerebral aqueduct was rare, the sub-pial tissue of the anterior and posterior midbrain contained several CA. In the sample with the highest CA density, quantitative maps obtained with MRI revealed high R2∗ values and a diamagnetic shift in a region which spatially coincided with the CA dense region

Protocol for 3D virtual histology of unstained human brain tissue using synchrotron radiation phase-contrast microtomography

X-ray phase-contrast micro computed tomography using synchrotron radiation (SR PhC-μCT) offers unique 3D imaging capabilities for visualizing microstructure of the human brain. Its applicability for unstained soft tissue is an area of active research. Acquiring images from a tissue block without needing to section it into thin slices, as required in routine histology, allows for investigating the microstructure in its natural 3D space. This paper presents a detailed step-bystep guideline for imaging unstained human brain tissue at resolutions of a few micrometers with SR PhC-μCT implemented at SYRMEP, the hard X-ray imaging beamline of Elettra, the Italian synchrotron facility. We present examples of how blood vessels and neurons appear in the images acquired with isotropic 5 μm and 1 μm voxel sizes. Furthermore, the proposed protocol can be used to investigate important biological substrates such as neuromelanin or corpora amylacea. Their spatial distribution can be studied using specifically tailored segmentation tools that are validated by classical histology methods. In conclusion, SR PhC-μCT using the proposed protocols, including data acquisition and image processing, offers viable means of obtaining information about the anatomy of the human brain at the cellular level in 3D

Functional quantitative susceptibility mapping (fQSM)

Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is a powerful technique, typically based on the statistical analysis of the magnitude component of the complex time-series. Here, we additionally interrogated the phase data of the fMRI time-series and used quantitative susceptibility mapping (QSM) in order to investigate the potential of functional QSM (fQSM) relative to standard magnitude BOLD fMRI. High spatial resolution data (1 mm isotropic) were acquired every 3 seconds using zoomed multi-slice gradient-echo EPI collected at 7 T in single orientation (SO) and multiple orientation (MO) experiments, the latter involving 4 repetitions with the subject's head rotated relative to B0. Statistical parametric maps (SPM) were reconstructed for magnitude, phase and QSM time-series and each was subjected to detailed analysis. Several fQSM pipelines were evaluated and compared based on the relative number of voxels that were coincidentally found to be significant in QSM and magnitude SPMs (common voxels). We found that sensitivity and spatial reliability of fQSM relative to the magnitude data depended strongly on the arbitrary significance threshold defining “activated” voxels in SPMs, and on the efficiency of spatio-temporal filtering of the phase time-series. Sensitivity and spatial reliability depended slightly on whether MO or SO fQSM was performed and on the QSM calculation approach used for SO data. Our results present the potential of fQSM as a quantitative method of mapping BOLD changes. We also critically discuss the technical challenges and issues linked to this intriguing new technique

The three-prong method: a novel assessment of residual stress in laser powder bed fusion

<p><b>Boxplots of quantitative parameters</b> included <b>a)</b> ratio of N-acetylaspartate and N-acetylaspartylglutamate (NAA) to creatine and phosphocreatine (Cr) both for chemical shift imaging (CSI) and single voxel (SV) measurements, <b>b)</b> ratio of choline containing compounds (Cho) to Cr both for CSI and SV, <b>c)</b> myelin water fraction (MWF), <b>d)</b> magnetization transfer ratio (MTR), <b>e)</b> quantitative susceptibility mapping (QSM), and <b>f)</b> R2*. Parameters were measured in frontal white matter (WM) and two parameters within the cortico-spinal tract (CST): at the level of the posterior limb of internal capsule (PLIC) and at the level of the centrum semiovale (CS), see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0167274#pone.0167274.g001" target="_blank">Fig 1</a>.</p

Myogenin Regulates Exercise Capacity and Skeletal Muscle Metabolism in the Adult Mouse

Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear. We sought to determine myogenin's function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we performed indirect calorimetry, monitored blood glucose and lactate levels, and performed histochemical analyses on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low- and high-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle

The PanCareSurFup consortium:research and guidelines to improve lives for survivors of childhood cancer

Background: Second malignant neoplasms and cardiotoxicity are among the most serious and frequent adverse health outcomes experienced by childhood and adolescent cancer survivors (CCSs) and contribute significantly to their increased risk of premature mortality. Owing to differences in health-care systems, language and culture across the continent, Europe has had limited success in establishing multi-country collaborations needed to assemble the numbers of survivors required to clarify the health issues arising after successful cancer treatment. PanCareSurFup (PCSF) is the first pan-European project to evaluate some of the serious long-term health risks faced by survivors. This article sets out the overall rationale, methods and preliminary results of PCSF. Methods: The PCSF consortium pooled data from 13 cancer registries and hospitals in 12 European countries to evaluate subsequent primary malignancies, cardiac disease and late mortality in survivors diagnosed between ages 0 and 20 years. In addition, PCSF integrated radiation dosimetry to sites of second malignancies and to the heart, developed evidence-based guidelines for long-term care and for transition services, and disseminated results to survivors and the public. Results: We identified 115,596 individuals diagnosed with cancer, of whom 83,333 were 5-year survivors and diagnosed from 1940 to 2011. This single data set forms the basis for cohort analyses of subsequent malignancies, cardiac disease and late mortality and case–control studies of subsequent malignancies and cardiac disease in 5-year survivors. Conclusions: PCSF delivered specific estimates of risk and comprehensive guidelines to help survivors and care-givers. The expected benefit is to provide every European CCS with improved access to care and better long-term health