APPLICATION-SPECIFIC OPTIMIZATION OF QUANTITATIVE SUSCEPTIBILITY MAPPING FOR CLINICAL IMAGING

Magnetic resonance imaging (MRI) is a noninvasive clinical imaging modality with very rich contrasts based on the physical properties of the imaged tissues. MRI can be used for quantification of volumetric distributions of various biomolecules and chemical elements - such as triglycerides, calcium and iron - that regarded as participants in normal tissue biochemistry, and whose dysregulations are often manifested in pathologic processes. This dissertation reports optimization steps undertaken to overcome technical challenges in quantitative susceptibility mapping (QSM) in different parts of human body. Often in QSM it is assumed that susceptibility is the only contributor to the observed field inhomogeneity, which may be a valid assumption for neuroimaging applications. However, multiple molecules found in biological tissues (e.g., triglycerides of fat) have a resonance frequency different from that of water, and this resonance frequency offset is referred to as chemical shift. This chemical shift affects the phase of the MRI signal. Although ways to estimate field inhomogeneity in the presence of chemical shift have been proposed, they often rely on the a priori knowledge of the chemical spectrum. Unfortunately, variability of chemical spectra have been reported. In this dissertation, an automated joint estimation of the chemical shift and the susceptibility from an MRI dataset is reported, where the chemical shift is also treated as an unknown variable subject to optimization. QSM may become a useful diagnostic tool for noninvasive assessment of bone health without the use of ionizing radiation, however this application has been a challenging task challenging because QSM requires complete measurements of phase everywhere within the region of interest, and cortical bone typically has very low or no signal at conventional echo times in gradient echo (GRE) imaging. An additional problem arises from intermingling of fat and water protons in the bone marrow, necessitating the application of water–fat separation techniques for field mapping. In this dissertation, a novel signal model is proposed, feasibility of using QSM for measuring bone MRI signal is investigated, and the inherent technical issues involved in this application are highlighted. QSM has been widely applied in neuroimaging. In particular, due to its ability to accurately map iron deposits in deep brain nuclei, QSM promises precise targeting of the subthalamic nucleus (STN) in deep brain stimulation surgery (DBS). This dissertation reports results of comparison between QSM and standard-of-care T2w imaging of the STN, and their performance in high-resolution presugrical anatomic imaging

Dynamics of superconducting nanowires shunted with an external resistor

We present the first study of superconducting nanowires shunted with an external resistor, geared towards understanding and controlling coherence and dissipation in nanowires. The dynamics is probed by measuring the evolution of the V-I characteristics and the distributions of switching and retrapping currents upon varying the shunt resistor and temperature. Theoretical analysis of the experiments indicates that as the value of the shunt resistance is decreased, the dynamics turns more coherent presumably due to stabilization of phase-slip centers in the wire and furthermore the switching current approaches the Bardeen's prediction for equilibrium depairing current. By a detailed comparison between theory and experimental, we make headway into identifying regimes in which the quasi-one-dimensional wire can effectively be described by a zero-dimensional circuit model analogous to the RCSJ (resistively and capacitively shunted Josephson junction) model of Stewart and McCumber. Besides its fundamental significance, our study has implications for a range of promising technological applications.Comment: 15 pages, 14 figure

Maximum Spherical Mean Value (mSMV) Filtering for Whole Brain Quantitative Susceptibility Mapping

To develop a tissue field filtering algorithm, called maximum Spherical Mean Value (mSMV), for reducing shadow artifacts in quantitative susceptibility mapping (QSM) of the brain without requiring brain tissue erosion.Residual background field is a major source of shadow artifacts in QSM. The mSMV algorithm filters large field 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 with existing QSM algorithms in numerical brain simulation as well as using in vivo human data acquired from 11 healthy volunteers and 93 patients. 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. The mSMV algorithm allows QSM maps that are substantially equivalent to those obtained using SMV-filtered dipole inversion without eroding the volume of interest.Comment: 12 pages, 5 figure

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

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

PurposeTo 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.MethodsThree-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.ResultsCompared 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.ConclusionsThe 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

Quantitative Susceptibility Mapping (QSM) Algorithms: Mathematical Rationale and Computational Implementations

International audienceQuantitative susceptibility mapping (QSM) solves the magnetic field-to-magnetization (tissue susceptibility) inverse problem under conditions of noisy and incomplete field data acquired using magnetic resonance imaging. Therefore, sophisticated algorithms are necessary to treat the ill-posed nature of the problem and are reviewed here. The forward problem is typically presented as an integral form, where the field is the convolution of the dipole kernel and tissue susceptibility distribution. This integral form can be equivalently written as a partial differential equation (PDE). Algorithmic challenges are to reduce streaking and shadow artifacts characterized by the fundamental solution of the PDE. Bayesian maximum a posteriori estimation can be employed to solve the inverse problem, where morphological and relevant biomedical knowledge (specific to the imaging situation) are used as priors. As the cost functions in Bayesian QSM framework are typically convex, solutions can be robustly computed using a gradient-based optimization algorithm. Moreover, one can not only accelerate Bayesian QSM, but also increase its effectiveness at reducing shadows using prior knowledge based preconditioners. Improving the efficiency of QSM is under active development, and a rigorous analysis of preconditioning needs to be carried out for further investigation.Quantitative susceptibility mapping (QSM) solves the magnetic field-to-magnetization (tissue susceptibility) inverse problem under conditions of noisy and incomplete field data acquired using magnetic resonance imaging. Therefore, sophisticated algorithms are necessary to treat the ill-posed nature of the problem and are reviewed here. The forward problem is typically presented as an integral form, where the field is the convolution of the dipole kernel and tissue susceptibility distribution. This integral form can be equivalently written as a partial differential equation (PDE). Algorithmic challenges are to reduce streaking and shadow artifacts characterized by the fundamental solution of the PDE. Bayesian maximum a posteriori estimation can be employed to solve the inverse problem, where morphological and relevant biomedical knowledge (specific to the imaging situation) are used as priors. As the cost functions in Bayesian QSM framework are typically convex, solutions can be robustly computed using a gradient-based optimization algorithm. Moreover, one can not only accelerate Bayesian QSM, but also increase its effectiveness at reducing shadows using prior knowledge based preconditioners. Improving the efficiency of QSM is under active development, and a rigorous analysis of preconditioning needs to be carried out for further investigation

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

International audienc

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

Dimethyl fumarate reduces inflammation in chronic active multiple sclerosis lesions

BACKGROUND AND OBJECTIVES: To determine the effects of dimethyl fumarate (DMF) and glatiramer acetate on iron content in chronic active lesions in patients with multiple sclerosis (MS) and in human microglia in vitro. METHODS: This was a retrospective observational study of 34 patients with relapsing-remitting MS and clinically isolated syndrome treated with DMF or glatiramer acetate. Patients had lesions with hyperintense rims on quantitative susceptibility mapping, were treated with DMF or glatiramer acetate (GA), and had a minimum of 2 on-treatment scans. Changes in susceptibility in rim lesions were compared among treatment groups in a linear mixed effects model. In a separate in vitro study, induced pluripotent stem cell-derived human microglia were treated with DMF or GA, and treatment-induced changes in iron content and activation state of microglia were compared. RESULTS: Rim lesions in patients treated with DMF had on average a 2.77-unit reduction in susceptibility per year over rim lesions in patients treated with GA (bootstrapped 95% CI -5.87 to -0.01), holding all other variables constant. Moreover, DMF but not GA reduced inflammatory activation and concomitantly iron content in human microglia in vitro. DISCUSSION: Together, our data indicate that DMF-induced reduction of susceptibility in MS lesions is associated with a decreased activation state in microglial cells. We have demonstrated that a specific disease modifying therapy, DMF, decreases glial activity in chronic active lesions. Susceptibility changes in rim lesions provide an in vivo biomarker for the effect of DMF on microglial activity. CLASSIFICATION OF EVIDENCE: This study provided Class III evidence that DMF is superior to GA in the presence of iron as a marker of inflammation as measured by MRI quantitative susceptibility mapping.Published versionStudy Funding: This study was supported by NINDS/NIH RO1 NS102267, an investigator-initiated Clinical Trial/US-BGT-13-10516 (Biogen), BI-2007-36725 (NMSS), and by grant number UL1 TR 002384 from the National Center for Advancing Translational Sciences (NCATS) of the NIH. The Article Processing Charge was funded by the authors