Project description:Background To develop an accurate and robust 3-dimensional (3D) phase-unwrapping method that works effectively in the presence of severe noise, disconnected regions, rapid phase changes, and open-ended lines for quantitative susceptibility mapping (QSM). Methods We developed a 3D phase-unwrapping method based on voxel clustering and local polynomial modeling named CLOSE3D, which firstly explores the 26-neighborhood to calculate local variation of the phasor and the phase, and then according to the local variation of the phasor, clusters the phase data into easy-to-unwrap blocks and difficult-to-unwrap residual voxels. Next, CLOSE3D sequentially performs intrablock, interblock, and residual-voxel unwrapping by using the region-growing local polynomial modeling method. CLOSED3D was evaluated in simulation and using in vivo brain QSM data, and was compared with classical region-growing and region-expanding labeling for unwrapping estimates methods. Results The simulation experiments showed that CLOSE3D achieved accurate phase-unwrapping results with a mean error ratio <0.39%, even in the presence of serious noise, disconnected regions, and rapid phase changes. The error ratios of region-growing (P=0.000 and P=0.000) and region-expanding labeling for unwrapping estimates (P=0.007, P=0.014) methods were both significantly higher than that of CLOSE3D, when the noise level was ≥60%. The results of the in vivo brain QSM experiments showed that CLOSE3D unwrapped the phase data and accurately reconstructed quantitative susceptibility data, even with serious noise, rapid-varying phase, or an open-ended cutline. Conclusions CLOSE3D achieves phase unwrapping with high accuracy and robustness, which will help phase-related 3D magnetic resonance imaging (MRI) applications such as QSM and susceptibility weighted imaging.
Project description:The magnetic susceptibility of tissue within and around an image voxel affects the magnetic field and thus the local frequency in that voxel. Recently, it has been shown that spatial maps of frequency can be used to quantify local susceptibility if the contributions of surrounding tissue can be deconvolved. Currently, such quantitative susceptibility mapping (QSM) methods employ gradient recalled echo (GRE) imaging to measure spatial differences in the signal phase evolution as a function of echo time, from which frequencies can be deduced. Analysis of these phase images, however, is complicated by phase wraps, despite the availability and usage of various phase unwrapping algorithms. In addition, lengthy high-resolution GRE scanning often heats the magnet bore, causing the magnetic field to drift over several Hertz, which is on the order of the frequency differences between tissues. Here, we explore the feasibility of applying the WAter Saturation Shift Referencing (WASSR) method for 3D whole brain susceptibility imaging. WASSR uses direct saturation of water protons as a function of frequency irradiation offset to generate frequency maps without phase wraps, which can be combined with any image or spectroscopy acquisition. By utilizing a series of fast short-echo-time direct saturation images with multiple radiofrequency offsets, a frequency correction for field drift can be applied based on the individual image phases. Regions of interest were delineated with an automated atlas-based method, and the average magnetic susceptibilities calculated from frequency maps obtained from WASSR correlated well with those from the phase-based multi-echo GRE approach at 3T.
Project description:Quantitative susceptibility mapping (QSM) is a recently developed MRI technique that provides a quantitative measure of tissue magnetic susceptibility. To compute tissue magnetic susceptibilities based on gradient echoes, QSM requires reliable unwrapping of the measured phase images and removal of contributions caused by background susceptibilities. Typically, the two steps are performed separately. Here, we present a method that simultaneously performs phase unwrapping and HARmonic (background) PhasE REmovaL using the LAplacian operator (HARPERELLA). Both numerical simulations and in vivo human brain images show that HARPERELLA effectively removes both phase wraps and background phase, whilst preserving all low spatial frequency components originating from brain tissues. When compared with other QSM phase preprocessing techniques, such as path-based phase unwrapping followed by background phase removal, HARPERELLA preserves the tissue phase signal in gray matter, white matter and cerebrospinal fluid with excellent robustness, providing a convenient and accurate solution for QSM. The proposed algorithm is provided, together with QSM and susceptibility tensor imaging (STI) tools, in a shared software package named 'STI Suite'.
Project description:To apply quantitative susceptibility mapping (QSM) in the basal ganglia of patients with multiple sclerosis (MS) and relate the findings to R2* mapping with regard to the sensitivity for clinical and morphologic measures of disease severity.The local ethics committee approved this study, and all subjects gave written informed consent. Sixty-eight patients (26 with clinically isolated syndrome, 42 with relapsing-remitting MS) and 23 control subjects underwent 3-T magnetic resonance (MR) imaging. Susceptibility and R2* maps were reconstructed from the same three-dimensional multiecho spoiled gradient-echo sequence. Mean susceptibilities and R2* rates were measured in the basal ganglia and were compared between different phenotypes of the disease (clinically isolated syndrome, MS) and the control subjects by using analysis of variance, and regressing analysis was used to identify independent predictors.Compared with control subjects, patients with MS and clinically isolated syndrome had increased (more paramagnetic) magnetic susceptibilities in the basal ganglia. R2* mapping proved less sensitive than QSM regarding group differences. The strongest predictor of magnetic susceptibility was age. Susceptibilities were higher with increasing neurologic deficits (r = 0.34, P < .01) and lower with normalized volumes of gray matter (r = -0.35, P < .005) and the cortex (r = -0.35, P < .005).QSM provides superior sensitivity over R2* mapping in the detection of MS-related tissue changes in the basal ganglia. With QSM but not with R2* mapping, changes were already observed in patients with clinically isolated syndrome, which suggests that QSM can serve as a sensitive measure at the earliest stage of the disease.
Project description:In Parkinson's disease (PD), iron elevation in specific brain regions as well as selective loss of dopaminergic neurons is a major pathologic feature. A reliable quantitative measure of iron deposition is a potential biomarker for PD and may contribute to the investigation of iron-mediated PD. The primary purpose of this study is to assess iron variations in multiple deep grey matter nuclei in early PD with a novel MRI technique, quantitative susceptibility mapping (QSM). The inter-group differences of susceptibility and R2* value in deep grey matter nuclei, namely head of caudate nucleus (CN), putamen (PUT), global pallidus (GP), substantia nigra (SN), and red nucleus (RN), and the correlations between regional iron deposition and the clinical features were explored in forty-four early PD patients and 35 gender and age-matched healthy controls. Susceptibility values were found to be elevated within bilateral SN and RN contralateral to the most affected limb in early PD compared with healthy controls (HCs). The finding of increased susceptibility in bilateral SN is consistent with work on a subgroup of patients at the earliest clinical detectable state (Hoehn and Yahr [1967]: Neurology 17:427-442; Stage I). However, increased R2* values were only seen within SN contralateral to the most affected limb in the PD group when compared with controls. Furthermore, bilateral SN magnetic susceptibility positively correlated with disease duration and UPDRS-III scores in early PD. This finding supports the potential value of QSM as a non-invasive quantitative biomarker of early PD.
Project description:BackgroundAccurate measurement of the liver iron concentration (LIC) is needed to guide iron-chelating therapy for patients with transfusional iron overload. In this work, we investigate the feasibility of automated quantitative susceptibility mapping (QSM) to measure the LIC.PurposeTo develop a rapid, robust, and automated liver QSM for clinical practice.Study typeProspective.Population13 healthy subjects and 22 patients.Field strength/sequences1.5 T and 3 T/3D multiecho gradient-recalled echo (GRE) sequence.AssessmentData were acquired using a 3D GRE sequence with an out-of-phase echo spacing with respect to each other. All odd echoes that were in-phase (IP) were used to initialize the fat-water separation and field estimation (T2 *-IDEAL) before performing QSM. Liver QSM was generated through an automated pipeline without manual intervention. This IP echo-based initialization method was compared with an existing graph cuts initialization method (simultaneous phase unwrapping and removal of chemical shift, SPURS) in healthy subjects (n = 5). Reproducibility was assessed over four scanners at two field strengths from two manufacturers using healthy subjects (n = 8). Clinical feasibility was evaluated in patients (n = 22).Statistical testsIP and SPURS initialization methods in both healthy subjects and patients were compared using paired t-test and linear regression analysis to assess processing time and region of interest (ROI) measurements. Reproducibility of QSM, R2 *, and proton density fat fraction (PDFF) among the four different scanners was assessed using linear regression, Bland-Altman analysis, and the intraclass correlation coefficient (ICC).ResultsLiver QSM using the IP method was found to be ~5.5 times faster than SPURS (P < 0.05) in initializing T2 *-IDEAL with similar outputs. Liver QSM using the IP method were reproducibly generated in all four scanners (average coefficient of determination 0.95, average slope 0.90, average bias 0.002 ppm, 95% limits of agreement between -0.06 to 0.07 ppm, ICC 0.97).Data conclusionUse of IP echo-based initialization enables robust water/fat separation and field estimation for automated, rapid, and reproducible liver QSM for clinical applications.Level of evidence1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:725-732.
Project description:Various regularization methods have been proposed for single-orientation quantitative susceptibility mapping (QSM), which is an ill-posed magnetic field to susceptibility source inverse problem. Noise amplification, a major issue in inverse problems, manifests as streaking artifacts and quantification errors in QSM and has not been comparatively evaluated in these algorithms. In this paper, various QSM methods were systematically categorized for noise analysis. Six representative QSM methods were selected from four categories: two non-Bayesian methods with alteration or approximation of the dipole kernel to overcome the ill conditioning; four Bayesian methods using a general mathematical prior or a specific physical structure prior to select a unique solution, and using a data fidelity term with or without noise weighting. The effects of noise in these QSM methods were evaluated by reconstruction errors in simulation and image quality in 50 consecutive human subjects. Bayesian QSM methods with noise weighting consistently reduced root mean squared errors in numerical simulations and increased image quality scores in the human brain images, when compared to non-Bayesian methods and to corresponding Bayesian methods without noise weighting (p ≤ 0.001). In summary, noise effects in QSM can be reduced using Bayesian methods with proper noise weighting.
Project description:We propose local polynomial estimators for the conditional mean of a continuous response when only pooled response data are collected under different pooling designs. Asymptotic properties of these estimators are investigated and compared. Extensive simulation studies are carried out to compare finite sample performance of the proposed estimators under various model settings and pooling strategies. We apply the proposed local polynomial regression methods to two real-life applications to illustrate practical implementation and performance of the estimators for the mean function.
Project description:Mechanobiology requires precise quantitative information on processes taking place in specific 3D microenvironments. Connecting the abundance of microscopical, molecular, biochemical, and cell mechanical data with defined topologies has turned out to be extremely difficult. Establishing such structural and functional 3D maps needed for biophysical modeling is a particular challenge for the cytoskeleton, which consists of long and interwoven filamentous polymers coordinating subcellular processes and interactions of cells with their environment. To date, useful tools are available for the segmentation and modeling of actin filaments and microtubules but comprehensive tools for the mapping of intermediate filament organization are still lacking. In this work, we describe a workflow to model and examine the complete 3D arrangement of the keratin intermediate filament cytoskeleton in canine, murine, and human epithelial cells both, in vitro and in vivo. Numerical models are derived from confocal airyscan high-resolution 3D imaging of fluorescence-tagged keratin filaments. They are interrogated and annotated at different length scales using different modes of visualization including immersive virtual reality. In this way, information is provided on network organization at the subcellular level including mesh arrangement, density and isotropic configuration as well as details on filament morphology such as bundling, curvature, and orientation. We show that the comparison of these parameters helps to identify, in quantitative terms, similarities and differences of keratin network organization in epithelial cell types defining subcellular domains, notably basal, apical, lateral, and perinuclear systems. The described approach and the presented data are pivotal for generating mechanobiological models that can be experimentally tested.
Project description:PurposeTo develop an automated adaptive preconditioner for QSM reconstruction with improved susceptibility quantification accuracy and increased image quality.Theory and methodsThe total field was used to rapidly produce an approximate susceptibility map, which was then averaged and trended over R2∗ binning to generate a spatially varying distribution of preconditioning values. This automated adaptive preconditioner was used to reconstruct QSM via total field inversion and was compared with its empirical counterparts in a numerical simulation, a brain experiment with 5 healthy subjects and 5 patients with intracerebral hemorrhage, and a cardiac experiment with 3 healthy subjects.ResultsAmong evaluated preconditioners, the automated adaptive preconditioner achieved the fastest convergence in reducing the RMSE of the QSM in the simulation, suppressed hemorrhage-associated artifacts while preserving surrounding brain tissue contrasts, and provided cardiac chamber oxygenation values consistent with those reported in the literature.ConclusionAn automated adaptive preconditioner allows high-quality QSM from the total field in imaging various anatomies with dynamic susceptibility ranges.