The 2016 QSM Challenge: Lessons learned and considerations for a future challenge design.

PURPOSE: The 4th International Workshop on MRI Phase Contrast and QSM (2016, Graz, Austria) hosted the first QSM Challenge. A single-orientation gradient recalled echo acquisition was provided, along with COSMOS and the χ33 STI component as ground truths. The submitted solutions differed more than expected depending on the error metric used for optimization and were generally over-regularized. This raised (unanswered) questions about the ground truths and the metrics utilized. METHODS: We investigated the influence of background field remnants by applying additional filters. We also estimated the anisotropic contributions from the STI tensor to the apparent susceptibility to amend the χ33 ground truth and to investigate the impact on the reconstructions. Lastly, we used forward simulations from the COSMOS reconstruction to investigate the impact noise had on the metric scores. RESULTS: Reconstructions compared against the amended STI ground truth returned lower errors. We show that the background field remnants had a minor impact in the errors. In the absence of inconsistencies, all metrics converged to the same regularization weights, whereas structural similarity index metric was more insensitive to such inconsistencies. CONCLUSION: There was a mismatch between the provided data and the ground truths due to the presence of unaccounted anisotropic susceptibility contributions and noise. Given the lack of reliable ground truths when using in vivo acquisitions, simulations are suggested for future QSM Challenges.

Sympathetic activity contributes to the fMRI signal.

The interpretation of functional magnetic resonance imaging (fMRI) studies of brain activity is often hampered by the presence of brain-wide signal variations that may arise from a variety of neuronal and non-neuronal sources. Recent work suggests a contribution from the sympathetic vascular innervation, which may affect the fMRI signal through its putative and poorly understood role in cerebral blood flow (CBF) regulation. By analyzing fMRI and (electro-) physiological signals concurrently acquired during sleep, we found that widespread fMRI signal changes often co-occur with electroencephalography (EEG) K-complexes, signatures of sub-cortical arousal, and episodic drops in finger skin vascular tone; phenomena that have been associated with intermittent sympathetic activity. These findings support the notion that the extrinsic sympathetic innervation of the cerebral vasculature contributes to CBF regulation and the fMRI signal. Accounting for this mechanism could help separate systemic from local signal contributions and improve interpretation of fMRI studies.

Lesion magnetic susceptibility response to hyperoxic challenge: A biomarker for malignant brain tumor microenvironment?

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping has been previously used to differentiate lesions in patients with brain tumors. The aim of this work was to characterize the response of magnetic susceptibility differences in malignant brain tumors and surrounding edema to hyperoxic and hypercapnic respiratory challenges. METHODS: Images of malignant brain tumor patients (2 glioblastoma multiforme, 2 anaplastic astrocytoma, 1 brain metastasis) with clinical MRI exams (contrast-enhanced T1w) were acquired at 3T. 3D multi-gradient-echo data sets were acquired while the patients inhaled medical-air (21% O2), oxygen (100% O2), and carbogen (95% O2, 5% CO2). Susceptibility maps were generated from real and imaginary data. Regions of interest were analyzed with respect to respiration-gas-induced susceptibility changes. RESULTS: Contrast-enhancing tumor regions with high baseline magnetic susceptibility exhibited a marked susceptibility reduction under hyperoxic challenges, with a stronger effect (-0.040 to -0.100ppm) under hypercapnia compared to hyperoxia (-0.010 to -0.067ppm). In contrast, regions attributed to necrotic tissue and to edema showed smaller changes of opposite sign, i.e. paramagnetic shift. There was a correlation between malignant tumor tissue magnetic susceptibility at baseline under normoxia and the corresponding susceptibility reduction under hypercapnia and - to a lesser degree - under hyperoxia. CONCLUSION: In this small cohort of analysis, quantification of susceptibility changes in response to respiratory challenges allowed a complementary, functional differentiation of tumorous sub-regions. Those changes, together with the correlations observed between baseline susceptibility under normoxia and susceptibility reduction with challenges, could prove helpful for a non-invasive characterization of local tumor microenvironment.

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

PURPOSE: To assess the potential of a real-time field-control (FC) system for mitigating effects of spatiotemporal field fluctuations in quantitative susceptibility mapping (QSM) at 7 T. METHODS: Magnitude, phase, and QSM images of phantoms and healthy volunteers were acquired under standard conditions and under induced field perturbation (FP) (phantoms: periodic water-bottle displacement; volunteers: deep breathing and forearm movement) with and without FC, which continuously detects and minimizes magnetic-field variations. RESULTS: Field control successfully eliminated FP-induced impairment of phantom image quality and deviations from a linear susceptibility increase for increasing gadolinium concentration in a Gd dilution series (y = 320x - 0.60, R2 = 0.93 for the scan with FP and FC versus y = 259x - 0.54, R2 = 0.78 for the scan with FP and no FC (slope literature value: 326 ppm L/mol)). Similarly, in volunteers, FC allowed a recovery of a FP-induced loss of identifiable brain structures and reduced the relative change of mean susceptibilities and standard deviations (93 ± 53% to 34 ± 46%) in all regions of interests with respect to the reference scan. CONCLUSIONS: Real-time FC improved the delineation of brain structures and the match of susceptibility values with reference values obtained without FP. Magn Reson Med 79:770-778, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

A comprehensive numerical analysis of background phase correction with V-SHARP.

Sophisticated harmonic artifact reduction for phase data (SHARP) is a method to remove background field contributions in MRI phase images, which is an essential processing step for quantitative susceptibility mapping (QSM). To perform SHARP, a spherical kernel radius and a regularization parameter need to be defined. In this study, we carried out an extensive analysis of the effect of these two parameters on the corrected phase images and on the reconstructed susceptibility maps. As a result of the dependence of the parameters on acquisition and processing characteristics, we propose a new SHARP scheme with generalized parameters. The new SHARP scheme uses a high-pass filtering approach to define the regularization parameter. We employed the variable-kernel SHARP (V-SHARP) approach, using different maximum radii (Rm ) between 1 and 15 mm and varying regularization parameters (f) in a numerical brain model. The local root-mean-square error (RMSE) between the ground-truth, background-corrected field map and the results from SHARP decreased towards the center of the brain. RMSE of susceptibility maps calculated with a spatial domain algorithm was smallest for Rm between 6 and 10 mm and f between 0 and 0.01 mm-1 , and for maps calculated with a Fourier domain algorithm for Rm between 10 and 15 mm and f between 0 and 0.0091 mm-1 . We demonstrated and confirmed the new parameter scheme in vivo. The novel regularization scheme allows the use of the same regularization parameter irrespective of other imaging parameters, such as image resolution. Copyright © 2016 John Wiley & Sons, Ltd.

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

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 fQSM-data 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.

Effect of respiratory hyperoxic challenge on magnetic susceptibility in human brain assessed by quantitative susceptibility mapping (QSM).

The purpose of this study was to measure the regional change of magnetic susceptibility in human brain upon inhalation of 100% oxygen by MRI quantitative susceptibility mapping (QSM). Fourteen healthy volunteers were scanned in a 3 T MR scanner with a 3D multi-gradient-echo sequence while breathing medical air (normoxia) and pure oxygen (hyperoxia). QSM images and R2* maps were calculated. Mean susceptibility differences versus white matter were measured in regions of interest covering veins, gray matter (GM), and cerebrospinal fluid (CSF) under both conditions. Hyperoxia resulted in a strong susceptibility decrease in large veins (-154.4 ± 65.9 ppb, p < 10(-6)), in a smaller reduction in GM (-1.3 ± 1 ppb, p < 0.001), and in a susceptibility increase in ventricular CSF (3.8 ± 1.8 ppb, p < 10(-5)). The susceptibility decrease in veins implied an increase of venous oxygen saturation (SvO2) by 10.1 ± 4.0%. Compared with QSM, R2* was more seriously affected by long-distance effects not related to local tissue oxygenation and increased in cerebral frontal regions (3 ± 2 s(-1), p < 0.0004) due to paramagnetic molecular oxygen in cavities. The results highlight the potential of QSM to yield region-specific quantitative oxygenation information, and, thus, for applications such as oxygen-therapy monitoring or identification of hypoxic tumor tissue during radiotherapy planning.