Quantitative susceptibility mapping for detection of kidney stones, hemorrhage differentiation, and cyst classification in ADPKD.

BACKGROUND AND PURPOSE: The objective is to demonstrate feasibility of quantitative susceptibility mapping (QSM) in autosomal dominant polycystic kidney disease (ADPKD) patients and to compare imaging findings with traditional T1/T2w magnetic resonance imaging (MRI). METHODS: Thirty-three consecutive patients (11 male, 22 female) diagnosed with ADPKD were initially selected. QSM images were reconstructed from the multiecho gradient echo data and compared to co-registered T2w, T1w, and CT images. Complex cysts were identified and classified into distinct subclasses based on their imaging features. Prevalence of each subclass was estimated. RESULTS: QSM visualized two renal calcifications measuring 9 and 10 mm and three pelvic phleboliths measuring 2 mm but missed 24 calcifications measuring 1 mm or less and 1 larger calcification at the edge of the field of view. A total of 121 complex T1 hyperintense/T2 hypointense renal cysts were detected. 52 (43%) Cysts appeared hyperintense on QSM consistent with hemorrhage; 60 (49%) cysts were isointense with respect to simple cysts and normal kidney parenchyma, while the remaining 9 (7%) were hypointense. The presentation of the latter two complex cyst subtypes is likely indicative of proteinaceous composition without hemorrhage. CONCLUSION: Our results indicate that QSM of ADPKD kidneys is possible and uniquely suited to detect large renal calculi without ionizing radiation and able to identify properties of complex cysts unattainable with traditional approaches.

Maximum spherical mean value filtering for whole-brain QSM.

PURPOSE: To develop a tissue field-filtering algorithm, called maximum spherical mean value (mSMV), for reducing shadow artifacts in QSM of the brain without requiring brain-tissue erosion. THEORY AND METHODS: Residual background field is a major source of shadow artifacts in QSM. The mSMV algorithm filters large field-magnitude values near the border, where the maximum value of the harmonic background field is located. The effectiveness of mSMV for artifact removal was evaluated by comparing existing QSM algorithms in numerical brain simulation as well as using in vivo human data acquired from 11 healthy volunteers and 93 patients. RESULTS: Numerical simulation showed that mSMV reduces shadow artifacts and improves QSM accuracy. Better shadow reduction, as demonstrated by lower QSM variation in the gray matter and higher QSM image quality score, was also observed in healthy subjects and in patients with hemorrhages, stroke, and multiple sclerosis. CONCLUSION: The mSMV algorithm allows QSM maps that are substantially equivalent to those obtained using SMV-filtered dipole inversion without eroding the volume of interest.

Microstructure-Informed Myelin Mapping (MIMM) from Gradient Echo MRI using Stochastic Matching Pursuit.

Quantification of the myelin content of the white matter is important for studying demyelination in neurodegenerative diseases such as Multiple Sclerosis (MS), particularly for longitudinal monitoring. A novel noninvasive MRI method, called Microstructure-Informed Myelin Mapping (MIMM), is developed to quantify the myelin volume fraction (MVF) by utilizing a multi gradient echo sequence (mGRE) and a detailed biophysical model of tissue microstructure. Myelin is modeled as anisotropic negative susceptibility source based on the Hollow Cylindrical Fiber Model (HCFM), and iron as isotropic positive susceptibility source in the extracellular region. Voxels with a range of biophysical parameters are simulated to create a dictionary of MR echo time magnitude signals and total susceptibility values. MRI signals measured using a mGRE sequence are then matched voxel-by-voxel to the created dictionary to obtain the spatial distributions of myelin and iron. Three different MIMM versions are presented to deal with the fiber orientation dependent susceptibility effects of the myelin sheaths: a basic variation, which assumes fiber orientation is an unknown to fit, two orientation informed variations, which assume the fiber orientation distribution is available either from a separate diffusion tensor imaging (DTI) acquisition or from a DTI atlas based fiber orientation map. While all showed a significant linear correlation with the reference method based on T2-relaxometry (p < 0.0001), DTI orientation informed and atlas orientation informed variations reduced overestimation at white matter tracts compared to the basic variation. Finally, the implications and usefulness of attaining an additional iron susceptibility distribution map are discussed. Highlights: novel stochastic matching pursuit algorithm called microstructure-informed myelin mapping (MIMM) is developed to quantify Myelin Volume Fraction (MVF) using Magnetic Resonance Imaging (MRI) and microstructural modeling.utilizes a detailed biophysical model to capture the susceptibility effects on both magnitude and phase to quantify myelin and iron.matter fiber orientation effects are considered for the improved MVF quantification in the major fiber tracts.acquired myelin and iron maps may be utilized to monitor longitudinal disease progress.

QSM Throughout the Body.

Magnetic materials in tissue, such as iron, calcium, or collagen, can be studied using quantitative susceptibility mapping (QSM). To date, QSM has been overwhelmingly applied in the brain, but is increasingly utilized outside the brain. QSM relies on the effect of tissue magnetic susceptibility sources on the MR signal phase obtained with gradient echo sequence. However, in the body, the chemical shift of fat present within the region of interest contributes to the MR signal phase as well. Therefore, correcting for the chemical shift effect by means of water-fat separation is essential for body QSM. By employing techniques to compensate for cardiac and respiratory motion artifacts, body QSM has been applied to study liver iron and fibrosis, heart chamber blood and placenta oxygenation, myocardial hemorrhage, atherosclerotic plaque, cartilage, bone, prostate, breast calcification, and kidney stone.

Magnetic Susceptibility Source Separation Solely from Gradient Echo Data: Histological Validation.

Quantitative susceptibility mapping (QSM) facilitates mapping of the bulk magnetic susceptibility of tissue from the phase of complex gradient echo (GRE) MRI data. QSM phase processing combined with an R2* model of magnitude of multiecho gradient echo data (R2*QSM) allows separation of dia- and para-magnetic components (e.g., myelin and iron) that contribute constructively to R2* value but destructively to the QSM value of a voxel. This R2*QSM technique is validated against quantitative histology­optical density of myelin basic protein and Perls' iron histological stains of rim and core of 10 ex vivo multiple sclerosis lesions, as well as neighboring normal appearing white matter. We found that R2*QSM source maps are in good qualitative agreement with histology, e.g., showing increased iron concentration at the edge of the rim+ lesions and myelin loss in the lesions' core. Furthermore, our results indicate statistically significant correlation between paramagnetic and diamagnetic tissue components estimated with R2*QSM and optical densities of Perls' and MPB stains. These findings provide direct support for the use of R2*QSM magnetic source separation based solely on GRE complex data to characterize MS lesion composition.

Susceptibility source separation from gradient echo data using magnitude decay modeling.

BACKGROUND AND PURPOSE: The objective is to demonstrate feasibility of separating magnetic sources in quantitative susceptibility mapping (QSM) by incorporating magnitude decay rates R 2 ∗ $R_2^{\rm{*}}$ in gradient echo (GRE) MRI. METHODS: Magnetic susceptibility source separation was developed using R 2 ∗ $R_2^{\rm{*}}$ and compared with a prior method using R 2 ' = R 2 ∗ - R 2 ${R^{\prime}_2} = R_2^* - {R_2}$ that required an additional sequence to measure the transverse relaxation rate R2 . Both susceptibility separation methods were compared in multiple sclerosis (MS) patients (n = 17). Susceptibility values of negative sources estimated with R 2 ∗ $R_2^{\rm{*}}$ -based source separation in a set of enhancing MS lesions (n = 44) were correlated against longitudinal myelin water fraction (MWF) changes. RESULTS: In in vivo data, linear regression of the estimated χ + ${\chi}^{+}$ and χ - ${\chi}^{-}$ susceptibility values between the R 2 ∗ $R_2^*$ - and the R 2 ' ${R^{\prime}_2}$ -based separation methods performed across 182 segmented lesions revealed correlation coefficient r = .96 and slope close .99. Correlation analysis in enhancing lesions revealed a significant positive association between the χ - ${\chi}^{-}$ increase at 1-year post-onset relative to 0 year and the MWF increase at 1 year relative to 0 year (ß = -0.144, 95% confidence interval: [-0.199, -0.1], p = .0008) and good agreement between R 2 ' ${R^{\prime}_2}$ and R 2 ∗ $R_2^*$ methods (r = .79, slope = .95). CONCLUSIONS: Separation of magnetic sources based solely on GRE complex data is feasible by combining magnitude decay rate modeling and phase-based QSM and χ - ${\chi}^{-}$ change may serve as a biomarker for myelin recovery or damage in acute MS lesions.

QQ-NET - using deep learning to solve quantitative susceptibility mapping and quantitative blood oxygen level dependent magnitude (QSM+qBOLD or QQ) based oxygen extraction fraction (OEF) mapping.

PURPOSE: To improve accuracy and speed of quantitative susceptibility mapping plus quantitative blood oxygen level-dependent magnitude (QSM+qBOLD or QQ) -based oxygen extraction fraction (OEF) mapping using a deep neural network (QQ-NET). METHODS: The 3D multi-echo gradient echo images were acquired in 34 ischemic stroke patients and 4 healthy subjects. Arterial spin labeling and diffusion weighted imaging (DWI) were also performed in the patients. NET was developed to solve the QQ model inversion problem based on Unet. QQ-based OEF maps were reconstructed with previously introduced temporal clustering, tissue composition, and total variation (CCTV) and NET. The results were compared in simulation, ischemic stroke patients, and healthy subjects using a two-sample Kolmogorov-Smirnov test. RESULTS: In the simulation, QQ-NET provided more accurate and precise OEF maps than QQ-CCTV with 150 times faster reconstruction speed. In the subacute stroke patients, OEF from QQ-NET had greater contrast-to-noise ratio (CNR) between DWI-defined lesions and their unaffected contralateral normal tissue than with QQ-CCTV: 1.9 ± 1.3 vs 6.6 ± 10.7 (p = 0.03). In healthy subjects, both QQ-CCTV and QQ-NET provided uniform OEF maps. CONCLUSION: QQ-NET improves the accuracy of QQ-based OEF with faster reconstruction.

Global cerebrospinal fluid as a zero-reference regularization for brain quantitative susceptibility mapping.

BACKGROUND AND PURPOSE: The objective ofthis study was to demonstrate a global cerebrospinal fluid (CSF) method for a consistent and automated zero referencing of brain quantitative susceptibility mapping (QSM). METHODS: Whole brain CSF mask was automatically segmented by thresholding the gradient echo transverse relaxation ( R2∗) map, and regularization was employed to enforce uniform susceptibility distribution within the CSF volume in the field-to-susceptibility inversion. This global CSF regularization method was compared with a prior ventricular CSF regularization. Both reconstruction methods were compared in a repeatability study of 12 healthy subjects using t-test on susceptibility measurements, and in patient studies of 17 multiple sclerosis (MS) and 10 Parkinson's disease (PD) patients using Wilcoxon rank-sum test on radiological scores. RESULTS: In scan-rescan experiments, global CSF regularization provided more consistent CSF volume as well as higher repeatability of QSM measurements than ventricular CSF regularization with a smaller bias: -2.7 parts per billion (ppb) versus -0.13 ppb (t-test p<0.05) and a narrower 95% limits of agreement: [-7.25, 6.99] ppb versus [-16.60, 11.19 ppb] (f-test p<0.05). In PD and MS patients, global CSF regularization reduced smoothly varying shadow artifacts and significantly improved the QSM quality score (p<0.001). CONCLUSIONS: The proposed whole brain CSF method for QSM zero referencing improves repeatability and image quality of brain QSM compared to the ventricular CSF method.

QSM in canine model of acute cerebral ischemia: A pilot study.

PURPOSE: In the present study, we investigated the potential of QSM to assess the physiological state of cortical tissue in the middle cerebral artery occlusion canine model of a cerebral ischemia. METHODS: Experiments were performed in 8 anesthetized canines. Gradient echo, perfusion, and DWI data of brains at normal and ischemic states were acquired. In the postprocessed susceptibility and quantitative cerebral blood flow maps, changes in values within the middle cerebral artery-fed cortical territories were quantified both on the ischemic and normal contralateral hemisphere side. RESULTS: QSM values in critically ischemic tissue were significantly different from contralateral values-namely, susceptibility increase was observed in the cases in which cerebral perfusion was maintained above the threshold of neuronal death. Furthermore, the data indicates presence of a significant correlation between the changes in susceptibility values, cerebral perfusion, and the infarct volume and pial collateral scores. Additionally, our data suggests that difference in cortical susceptibility is prospectively indicative of the infarct growth rate. CONCLUSION: In an experimental permanent middle cerebral artery occlusion model, QSM was shown to correlate with the functional parameters characterizing viability of ischemic tissue, thus warranting further research on its ability to provide complementary information during acute stroke MRI examinations in humans.

Common transcriptome, plasma molecules, and imaging signatures in the aging brain and a Mendelian neurovascular disease, cerebral cavernous malformation.

Brain senescence is associated with impaired endothelial barrier function, angiogenic and inflammatory activity, and propensity to brain hemorrhage. The same pathological changes occur in cerebral cavernous malformations (CCM), a genetic neurovascular anomaly. We hypothesized common transcriptomic and plasma cytokine signatures in the aging brain and CCM. We identified 320 genes [fold change ≥1.5; p < 0.05; false discovery rate (FDR) corrected] commonly dysregulated in the aging brain and CCM. Ontology and pathway analyses of the common differentially expressed genes were related to inflammation and extracellular matrix organization. Plasma levels of C-reactive protein and angiopoietin-2 were significantly greater in older compared to younger healthy non-CCM subjects and were also greater in CCM (Sporadic and Familial) subjects regardless of age (all: p < 0.05; FDR corrected). Plasma levels of vascular endothelial growth factor were significantly greater in older compared to younger subjects, in both healthy non-CCM and Sporadic-CCM groups (all: padj < 0.05). Plasma levels of vascular endothelial growth factor were also significantly greater in Familial-CCM cases with germ line mutations regardless of age (all: padj < 0.05) compared to both healthy non-CCM and Sporadic-CCM subjects. Brain white matter vascular permeability assessed by MRI followed the same pattern as vascular endothelial growth factor across all groups. In addition, quantitative susceptibility mapping of brain white matter, a measure of iron deposition, was increased in older compared to younger healthy non-CCM subjects. Genetic aberrations, plasma molecules, and imaging biomarkers in a well characterized Mendelian neurovascular disease may also be applicable in the aging brain. Graphical abstract.

Clinical Integration of Quantitative Susceptibility Mapping Magnetic Resonance Imaging into Neurosurgical Practice.

OBJECTIVE: To introduce quantitative susceptibility mapping (QSM), a novel magnetic resonance imaging sequence, to the field of neurosurgery. METHODS: QSM is introduced both in its historical context and by providing a brief overview of the physics behind the technique tailored to a neurosurgical audience. Its application to clinical neurosurgery is then highlighted using case examples. RESULTS: QSM offers a quantitative assessment of susceptibility (previously considered as an artifact) via a single, straightforward gradient echo acquisition. QSM differs from standard susceptibility weighted imaging in its ability to both quantify and precisely localize susceptibility effects. Clinical applications of QSM are wide reaching and include precise localization of the deep nuclei for deep brain stimulation electrode placement, differentiation between blood products and calcification within brain lesions, and enhanced sensitivity of cerebral micrometastasis identification. CONCLUSIONS: We present this diverse range of QSM's clinical applications to neurosurgical care via case examples. QSM can be obtained in all patients able to undergo magnetic resonance imaging and is easily integratable into busy neuroradiology programs because of its short acquisition time and straightforward, automated offline postprocessing workflow. Clinical integration of QSM may help clinicians better identify and characterize neurosurgical lesions, thereby improving patient care.

High-resolution QSM for functional and structural depiction of subthalamic nuclei in DBS presurgical mapping.

OBJECTIVE: Faithful depiction of the subthalamic nucleus (STN) is critical for planning deep brain stimulation (DBS) surgery in patients with Parkinson's disease (PD). Quantitative susceptibility mapping (QSM) has been shown to be superior to traditional T2-weighted spin echo imaging (T2w). The aim of the study was to describe submillimeter QSM for preoperative imaging of the STN in planning of DBS. METHODS: Seven healthy volunteers were included in this study. T2w and QSM were obtained for all healthy volunteers, and images of different resolutions were reconstructed. Image quality and visibility of STN anatomical features were analyzed by a radiologist using a 5-point scale, and contrast properties of the STN and surrounding tissue were calculated. Additionally, data from 10 retrospectively and randomly selected PD patients who underwent 3-T MRI for DBS were analyzed for STN size and susceptibility gradient measurements. RESULTS: Higher contrast-to-noise ratio (CNR) values were observed in both high-resolution and low-resolution QSM images. Inter-resolution comparison demonstrated improvement in CNR for QSM, but not for T2w images. QSM provided higher inter-quadrant contrast ratios (CR) within the STN, and depicted a gradient in the distribution of susceptibility sources not visible in T2w images. CONCLUSIONS: For 3-T MRI, submillimeter QSM provides accurate delineation of the functional and anatomical STN features for DBS targeting.

In Situ and Real-Time Studies, via Synchrotron X-ray Scattering, of the Orientational Order of Cellulose Nanocrystals during Solution Shearing.

In this manuscript, we report on the ordering of the cellulose nanocrystals (CNCs) as they experience shear forces during the casting process. To achieve these measurements, in situ and in real time, we used synchrotron-based grazing incidence wide-angle X-ray scattering (GIWAX). We believe that the GIWAX technique, although not commonly used to probe these types of phenomena, can open new avenues to gain deeper insights into film formation processes and surface-driven phenomena. In particular, we investigated the influence of solution concentration, shear-cast velocity, and drying temperature on the ordering of cellulose nanocrystals (CNCs) using GIWAXS. The films were prepared from aqueous suspensions of cellulose nanocrystals at two concentration values (7 and 9 wt %). As the films were cast, the X-ray beam was focused on a fixed position and GIWAXS patterns were recorded at regular time intervals. Structural characterization of the dry films was carried out via polarized optical microscopy and scanning electron microscopy. In addition, a rheological study of the CNC suspensions was performed. Our results show that the morphology of the CNC films was significantly influenced by shear velocity, concentration of the precursor suspension, and evaporation temperature. In contrast, we observed that the orientation parameter of the films was not significantly affected. The scattering intensity of the peak (200) was analyzed as a function of time, following a sigmoidal profile, hence indicating short- and long-range interactions within the anisotropic domains as they reached their final orientation state. A model capable of describing the resulting film morphologies is also proposed. The results and analysis presented in this manuscript provide new insights into the controlled alignment of cellulose nanocrystals under shear. This controlled alignment has significant implications in the development of advanced coatings and films currently used in a myriad of applications, such as catalysis, optics, electronics, and biomedicine.

Bone quantitative susceptibility mapping using a chemical species-specific R2* signal model with ultrashort and conventional echo data.

PURPOSE: To develop quantitative susceptibility mapping (QSM) of bone using an ultrashort echo time (UTE) gradient echo (GRE) sequence for signal acquisition and a bone-specific effective transverse relaxation rate ( R2*) to model water-fat MR signals for field mapping. METHODS: Three-dimensional radial UTE data (echo times ≥ 40 µs) was acquired on a 3 Tesla scanner and fitted with a bone-specific signal model to map the chemical species and susceptibility field. Experiments were performed ex vivo on a porcine hoof and in vivo on healthy human subjects (n = 7). For water-fat separation, a bone-specific model assigning R2* decay mostly to water was compared with the standard models that assigned the same decay for both fat and water. In the ex vivo experiment, bone QSM was correlated with CT. RESULTS: Compared with standard models, the bone-specific R2* method significantly reduced errors in the fat fraction within the cortical bone in all tested data sets, leading to reduced artifacts in QSM. Good correlation was found between bone CT and QSM values in the porcine hoof (R2 = 0.77). Bone QSM was successfully generated in all subjects. CONCLUSIONS: The QSM of bone is feasible using UTE with a conventional echo time GRE acquisition and a bone-specific R2* signal model. Magn Reson Med 79:121-128, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Joint estimation of chemical shift and quantitative susceptibility mapping (chemical QSM).

PURPOSE: The purpose of this work is to address the unsolved problem of quantitative susceptibility mapping (QSM) of tissue with fat where both fat and susceptibility change the MR signal phase. THEORY AND METHODS: The chemical shift of fat was treated as an additional unknown and was estimated jointly with susceptibility to provide the best data fitting using an automated and iterative algorithm. A simplified susceptibility model was used to calculate an updated value of the chemical shift based on the local magnetic field in each iteration. Numerical simulation, phantom experiments and in vivo imaging were performed. Artifacts were assessed by measuring the susceptibility variance in uniform regions. Accuracy was assessed by comparison with ground truth in simulation, and using a susceptibility matching approach in phantom. RESULTS: Using the proposed method, artifacts on the QSM image were markedly suppressed in all tested datasets compared with results generated using fixed chemical shifts. Accuracy of the estimated susceptibility was also improved in numerical simulation and phantom experiments. CONCLUSION: A joint estimation of fat content and magnetic susceptibility using an iterative chemical shift update was shown to improve image quality and accuracy on QSM images.