Search

Purpose: To present a constrained optimal-control (OC) framework for designing large-flip-angle parallel-transmit (pTx) pulses satisfying hardware peak-power as well as regulatory local and global specific-absorption-rate (SAR) limits. The application is 2D and 3D spatial-selective 90° and 180° pulses., Theory and Methods: The OC gradient-ascent-pulse-engineering method with exact gradients and the limited-memory Broyden-Fletcher-Goldfarb-Shanno method is proposed. Local SAR is constrained by the virtual-observation-points method. Two numerical models facilitated the optimizations, a torso at 3 T and a head at 7 T, both in eight-channel pTx coils and acceleration-factors up to 4., Results: The proposed approach yielded excellent flip-angle distributions. Enforcing the local-SAR constraint, as opposed to peak power alone, reduced the local SAR 7 and 5-fold with the 2D torso excitation and inversion pulse, respectively. The root-mean-square errors of the magnetization profiles increased less than 5% with the acceleration factor of 4., Conclusion: A local and global SAR, and peak-power constrained OC large-flip-angle pTx pulse design was presented, and numerically validated for 2D and 3D spatial-selective 90° and 180° pulses at 3 T and 7 T. Magn Reson Med 77:374-384, 2017. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

The paper describes a family of novel recoupling pulse sequences, called three pulse recoupling. These pulse sequences can be employed for both homonuclear and heteronuclear recoupling experiments and are robust to dispersion in chemical shifts and rf-inhomogeneity. These recoupling pulse sequences can be used in design of two-dimensional solid state NMR experiments that use powdered dephased antiphase coherence (γ preparation) to encode chemical shifts in the indirect dimension. Both components of this chemical shift encoded gamma-prepared states can be refocused into inphase coherence by a recoupling element. This helps to achieve sensitivity enhancement in 2D NMR experiments by quadrature detection., (Copyright © 2015 Elsevier Inc. All rights reserved.)

There is an increasing need for development of advanced radio-frequency (RF) pulse techniques in modern magnetic resonance imaging (MRI) systems driven by recent advancements in ultra-high magnetic field systems, new parallel transmit/receive coil designs, and accessible powerful computational facilities. 2D spatially selective RF pulses are an example of advanced pulses that have many applications of clinical relevance, e.g., reduced field of view imaging, and MR spectroscopy. The 2D spatially selective RF pulses are mostly generated and optimised with numerical methods that can handle vast controls and multiple constraints. With this study we aim at demonstrating that numerical, optimal control (OC) algorithms are efficient for the design of 2D spatially selective MRI experiments, when robustness towards e.g. field inhomogeneity is in focus. We have chosen three popular OC algorithms; two which are gradient-based, concurrent methods using first- and second-order derivatives, respectively; and a third that belongs to the sequential, monotonically convergent family. We used two experimental models: a water phantom, and an in vivo human head. Taking into consideration the challenging experimental setup, our analysis suggests the use of the sequential, monotonic approach and the second-order gradient-based approach as computational speed, experimental robustness, and image quality is key. All algorithms used in this work were implemented in the MATLAB environment and are freely available to the MRI community., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the ability of nm-scaled iron oxide particles conjugated with Azure A, a classic histological dye, to accumulate in areas of angiogenesis in a recently developed murine angiogenesis model., Materials and Methods: We characterised the Azure A particles with regard to their hydrodynamic size, zeta potential, and blood circulation half-life. The particles were then investigated by Magnetic Resonance Imaging (MRI) in a recently developed murine angiogenesis model along with reference particles (Ferumoxtran-10) and saline injections., Results: The Azure A particles had a mean hydrodynamic diameter of 51.8 ± 43.2 nm, a zeta potential of -17.2 ± 2.8 mV, and a blood circulation half-life of 127.8 ± 74.7 min. Comparison of MR images taken pre- and 24-h post-injection revealed a significant increase in R2(*) relaxation rates for both Azure A and Ferumoxtran-10 particles. No significant difference was found for the saline injections. The relative increase was calculated for the three groups, and showed a significant difference between the saline group and the Azure A group, and between the saline group and the Ferumoxtran-10 group. However, no significant difference was found between the two particle groups., Conclusion: Ultrahigh-field MRI revealed localisation of both types of iron oxide particles to areas of neovasculature. However, the Azure A particles did not show any enhanced accumulation relative to Ferumoxtran-10, suggesting the accumulation in both cases to be passive., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Currently, radiation treatments are being optimised based on in vivo imaging of radioresistant, hypoxic tumour areas. This study aimed at detecting nicotinamide's reduction of acute hypoxia in a mouse tumour model by two clinically relevant magnetic resonance imaging (MRI) methods at ultra-high magnetic field strength., Material and Methods: The C3H mammary carcinoma was grown to 200 mm(3) in the right rear foot of CDF1 mice. The mice were anaesthetised with ketamine and xylazine prior to imaging. A treatment group received nicotinamide intraperitoneally (i.p.) at the dose 1000 mg/kg, and a control group received saline. MRI was performed at 16.4 T with a spatial resolution of 0.156 × 0.156 × 0.5 mm(3). The imaging protocol included BOLD imaging and two DCE-MRI scans. Initial area under the curve (IAUC) and the parameters from the extended Toft's model were estimated from the DCE-MRI data. Tumour median values of 1) T2* mean, 2) T2* standard deviation, 3) DCE-MRI parameters, and 4) DCE-MRI parameter differences between scans were compared between the treatment groups using Student's t-test (significance level p < 0.05)., Results: Parametric maps showed intra- and inter-tumour heterogeneity. Blood volume was significantly larger in the nicotinamide-treated group, and also the blood volume difference between the two DCE-MRI scans was significantly larger in the treatment group., Conclusion: Higher blood volume and blood volume variation was observed by DCE-MRI in the treatment group. Other DCE-MRI parameters showed no significant differences, and the higher blood volume was not detected by BOLD MRI. The higher blood volume variation seen with DCE-MRI may be influenced by the drug effect reducing over time, and furthermore the anaesthesia may play an important role.

Aimed at (13)C metabolic magnetic resonance imaging (MRI) and spectroscopy (MRS) applications, we demonstrate that dynamic nuclear polarization (DNP) may be combined with optimal control 2D spatial selection to simultaneously obtain high sensitivity and well-defined spatial restriction. This is achieved through the development of spatial-selective single-shot spiral-readout MRI and MRS experiments combined with dynamic nuclear polarization hyperpolarized [1-(13)C]pyruvate on a 4.7 T pre-clinical MR scanner. The method stands out from related techniques by facilitating anatomic shaped region-of-interest (ROI) single metabolite signals available for higher image resolution or single-peak spectra. The 2D spatial-selective rf pulses were designed using a novel Krotov-based optimal control approach capable of iteratively fast providing successful pulse sequences in the absence of qualified initial guesses. The technique may be important for early detection of abnormal metabolism, monitoring disease progression, and drug research., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The use of increasingly strong magnetic fields in magnetic resonance imaging (MRI) improves sensitivity, susceptibility contrast, and spatial or spectral resolution for functional and localized spectroscopic imaging applications. However, along with these benefits come the challenges of increasing static field (B(0)) and rf field (B(1)) inhomogeneities induced by radial field susceptibility differences and poorer dielectric properties of objects in the scanner. Increasing fields also impose the need for rf irradiation at higher frequencies which may lead to elevated patient energy absorption, eventually posing a safety risk. These reasons have motivated the use of multidimensional rf pulses and parallel rf transmission, and their combination with tailoring of rf pulses for fast and low-power rf performance. For the latter application, analytical and approximate solutions are well-established in linear regimes, however, with increasing nonlinearities and constraints on the rf pulses, numerical iterative methods become attractive. Among such procedures, optimal control methods have recently demonstrated great potential. Here, we present a Krotov-based optimal control approach which as compared to earlier approaches provides very fast, monotonic convergence even without educated initial guesses. This is essential for in vivo MRI applications. The method is compared to a second-order gradient ascent method relying on the Broyden-Fletcher-Goldfarb-Shanno (BFGS) quasi-Newton method, and a hybrid scheme Krotov-BFGS is also introduced in this study. These optimal control approaches are demonstrated by the design of a 2D spatial selective rf pulse exciting the letters "JCP" in a water phantom.

Aimed at selective detection of (23)Na with specific quadrupolar couplings for in vitro NMR and MRI, we present a series of quadrupolar binomial pulse sequences offering high specificity with respect to the quadrupolar couplings of the excited species. It is demonstrated that pulse sequences with an increasing number of elements, e.g., 11, 121, 1331, 14641, and 15101051, with the units representing flip angles smaller than the 90 degrees pulses typically encountered in binomial spin-1/2 solvent suppression experiments, and different phase combinations may provide a high degree of flexibility with respect to quadrupolar coupling selectivity and robustness towards rf inhomogeneity. This may facilitate efficient separation of, for example, intra and extracellular (23)Na in tissues with efficient control of the excitation (or suppression) of central as well as satellite transitions through on- and off-resonance irradiation. The pulse sequences are described in terms of their analogy to binomial liquid-state NMR solvent suppression experiments and demonstrated numerically and experimentally through NMR and MRI experiments on a 7 T horizontal small-bore animal magnet system., ((c) 2010 Elsevier Inc. All rights reserved.)

The past decade has demonstrated increasing interests in using optimal control based methods within coherent quantum controllable systems. The versatility of such methods has been demonstrated with particular elegance within nuclear magnetic resonance (NMR) where natural separation between coherent and dissipative spin dynamics processes has enabled coherent quantum control over long periods of time to shape the experiment to almost ideal adoption to the spin system and external manipulations. This has led to new design principles as well as powerful new experimental methods within magnetic resonance imaging, liquid-state and solid-state NMR spectroscopy. For this development to continue and expand, it is crucially important to constantly improve the underlying numerical algorithms to provide numerical solutions which are optimally compatible with implementation on current instrumentation and at same time are numerically stable and offer fast monotonic convergence toward the target. Addressing such aims, we here present a smoothing monotonically convergent algorithm for pulse sequence design in magnetic resonance which with improved optimization stability lead to smooth pulse sequence easier to implement experimentally and potentially understand within the analytical framework of modern NMR spectroscopy. [ABSTRACT FROM AUTHOR]

In this work, a theranostic nanoparticle was developed for multimodal imaging and siRNA delivery. The core of the nanoparticles (NP) was formed by encapsulation of superparamagnetic iron oxides and indocyanine green in a PLGA matrix to serve as a multimodal probe for near-infrared (NIFR) and magnetic resonance (MR) imaging. The surface of the particle was coated with polyethylenimine (PEI) for siRNA delivery. Macrophages efficiently took up the nanoparticles and emitted strong NIFR and MR contrast. When transfected with siRNA targeting the pro-inflammatory enzyme cyclooxygenase-2 (COX-2), significant down-regulation of COX-2 was achieved in activated macrophages. Furthermore, after injection into a unilateral ureteral obstruction (UUO)-induced kidney injury model, NIFR and MRI imaging revealed accumulation of nanoparticles in the injury kidney. In addition, in vivo silencing of COX-2 was achieved by NP/PEI/siCOX-2, which further attenuated kidney injury. Our theranostic platform represents a promising approach for simultaneous diagnosis and treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Combining imaging and drug delivery of “theranostic” nanoparticles has enabled concurrent diagnosis and therapy of diseases. Here, we describe a novel theranostic system that combines two imaging tracers, perfluorooctyl bromide (PFOB) for 19 F magnetic resonance imaging (MRI) and indocyanine green (ICG) for near infrared (NIR) imaging, with the chemotherapeutic agent doxorubicin (Dox) into poly (lactic-co-glycolic acid)- poly (ethylene-glycol)-folate (PLGA-PEG-folate) nanoparticles. Cell culture studies using flow cytometry, confocal laser scanning microscope imaging, and 19 F MRI showed enhanced uptake of nanoparticles via folate receptors expressed on human nasopharyngeal epidermal carcinoma (KB) cells. In vivo , higher MRI and fluorescence signals were obtained from tumors with 19 F MRI and NIR, respectively, using folate-receptor-targeted nanoparticles compared with non-targeted equivalents. An in vitro cytotoxicity assay showed that folate-targeted nanoparticles were able to kill cancer cells more efficiently than non-folate conjugated particles. Our results suggest a potential use of PLGA-PEG-folate PFOB/ICG/Dox nanoparticles as a targeted chemotherapy agent traceable by either 19 F MRI or NIR imaging. [ABSTRACT FROM AUTHOR]

Background. Currently, radiation treatments are being optimised based on in vivo imaging of radioresistant, hypoxic tumour areas. This study aimed at detecting nicotinamide's reduction of acute hypoxia in a mouse tumour model by two clinically relevant magnetic resonance imaging (MRI) methods at ultra-high magnetic field strength. Material and methods. The C3H mammary carcinoma was grown to 200 mm3 in the right rear foot of CDF1 mice. The mice were anaesthetised with ketamine and xylazine prior to imaging. A treatment group received nicotinamide intraperitoneally (i.p.) at the dose 1000 mg/kg, and a control group received saline. MRI was performed at 16.4 T with a spatial resolution of 0.156 × 0.156 × 0.5 mm3. The imaging protocol included BOLD imaging and two DCE-MRI scans. Initial area under the curve (IAUC) and the parameters from the extended Toft's model were estimated from the DCE-MRI data. Tumour median values of 1) T2* mean, 2) T2* standard deviation, 3) DCE-MRI parameters, and 4) DCE-MRI parameter differences between scans were compared between the treatment groups using Student's t-test (significance level p < 0.05). Results. Parametric maps showed intra- and inter-tumour heterogeneity. Blood volume was significantly larger in the nicotinamide-treated group, and also the blood volume difference between the two DCE-MRI scans was significantly larger in the treatment group. Conclusion. Higher blood volume and blood volume variation was observed by DCE-MRI in the treatment group. Other DCE-MRI parameters showed no significant differences, and the higher blood volume was not detected by BOLD MRI. The higher blood volume variation seen with DCE-MRI may be influenced by the drug effect reducing over time, and furthermore the anaesthesia may play an important role. [ABSTRACT FROM AUTHOR]

An improved variant of the popular double cross-polarization (DCP) experiment for heteronuclear dipolar recoupling in solid-state NMR spectroscopy under magic-angle-spinning is introduced. By simple phase and amplitude modulation of the rf irradiation at the Hartman-Hahn sideband conditions, the new pulse sequence, dubbed iDCP, enables broadband excitation with the high efficiency of γ-encoded coherence transfer. The efficiency and robustness of iDCP toward isotropic chemical shift variations and chemical shift anisotropies, in the order typically applying for the backbone atoms in uniformly 13C,15N-labeled proteins, is demonstrated numerically and experimentally by 15N to 13C coherence transfer for 15N-labeled N-Ac-l-valyl-l-leucine and 13C,15N-labeled-l-threonine. [Copyright &y& Elsevier]

Rheumatoid arthritis (RA) is an autoimmune disease that causes pain and tissue destruction in people worldwide. An accurate diagnosis is paramount in order to develop an effective treatment plan. This study demonstrates that combining near infrared (NIR) imaging and 19F MRI with the injection of labelled nanoparticles provides high diagnostic specificity for RA. The nanoparticles were made from poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (NP) or PLGA-PEG-Folate (Folate-NP), loaded with perfluorooctyl bromide (PFOB) and indocyanine green (ICG) and evaluated in vitro and in a collagen-induced arthritic (CIA) mouse model. The different particles had a similar size and a spherical shape according to dynamic light scattering (DLS) and transmission electron microscopy (TEM). Based on flow cytometry and 19F MRI analysis, Folate-NP yielded a higher uptake than NP in activated macrophages in vitro. The potential RA-targeting ability of the particles was studied in CIA mice using NIR and 19F MRI analysis. Both NP and Folate-NP accumulated in the RA tissues, where they were visible in NIR and 19F MRI for up to 24 hours. The presence of folate as a targeting ligand significantly improved the NIR signal from inflamed tissue at the early time point (2 hours), but not at later time points. Overall, these results suggest that our nanoparticles can be applied for combined NIR and 19F MRI imaging for improved RA diagnosis. [ABSTRACT FROM AUTHOR]

Contrast agents have been widely used in medicine to enhance contrast in magnetic resonance imaging (MRI). Among them, super paramagnetic iron oxide nanoparticles (SPION) have been reported to have low risk in clinical use. In our study, F127-Folate coated SPION was fabricated in order to efficiently target tumors and provide imaging contrast in MRI. SPION alone have an average core size of 15 nm. After stabilizing with Pluronic F127, the nanoparticles reached a hydrodynamic size of 180 nm and dispersed well in various kinds of media. The F127-Folate coated SPION were shown to specifically target folate receptor expressing cancer cells by flow cytometry analysis, confocal laser scanning microscope, as well as in vitro MRI. Furthermore, in vivo MRI images have shown the enhanced negative contrast from the F127-Folate coated SPION in tumor-bearing mice. In conclusion, our F127-Folate coated SPION have shown great potential as a contrast agent in MRI, as well as in the combination with drug delivery for cancer therapy. [ABSTRACT FROM AUTHOR]

Noninvasive therapeutic cell tracking methods in living animals are important for understanding cell function and fate in connection with cell therapy. Here we report a new particle system based on chitosan-coated poly(lactic-co-glycolic acid) perfluorooctyl bromide (PLGA PFOB) nanoparticles designed for 19 F magnetic resonance imaging (MRI) cell tracking. Chitosan was adsorbed onto the PLGA PFOB nanoparticles through electric interactions, which led to an increase in the hydrodynamic size and a surface charge proportional to the coating weight ratio. Confocal laser scanning microscopy, flow cytometry analysis and 19 F-MRI showed that to achieve the highest labeling efficiency in vitro , the optimal weight ratio of chitosan to the PLGA PFOB nanoparticles was 1:10 for human mesenchymal stem cells (hMSCs) and 1:100 for Raw 264.7 macrophages. In vivo 19 F-MRI showed that 19 F labeled hMSCs remained at the injected site 24 h after injection. Thus, this study validates that chitosan-coated PLGA PFOB nanoparticles have the potential to track cell migration in vivo . [ABSTRACT FROM AUTHOR]

Knowledge of the actual content of nitrogen, phosphorus, and potassium (NPK) in animal slurry is highly important to optimize crop production and avoid environmental pollution when slurry is spread on agricultural fields. Here, we present a mobile, low-field nuclear magnetic resonance (NMR) sensor suitable for online monitoring of the NPK content in animal slurry as an alternative to crude estimates or tedious nonspecific, off-site laboratory analysis. The sensor is based on 14N, 17O, 31P, and 39K NMR in a digital NMR instrument equipped with a 1.5 T Halbach magnet for direct detection of ammonium N, total P, and K and indirect evaluation of the organic N content, covering all practical components of NPK in animal slurry. In correlation studies, the obtained NMR measurements show good agreement with reference measurements from commercial laboratories. [ABSTRACT FROM AUTHOR]

Radio frequency (RF) spectrally selective multiband pulses or tagging pulses, are applicable in a broad range of magnetic resonance methods. We demonstrate through simulations and experiments a new phase-modulation-only RF pulse for RF tagging based on the Frank poly-phase perfect sequence. In addition, we introduce an extended version with a WURST modulation (Frank-WURST). The new pulses exhibit interesting and flexible spin tagging properties and are easily implemented in existing MR sequences, where they can substitute slice-selective pulses with no additional alterations. [ABSTRACT FROM AUTHOR]

Highlights: [•] A modification of the basic Two-Pulse Phase-Modulation (TPPM) heteronuclear decoupling is proposed. [•] The design of the new scheme, rTPPM, is similar to that of the recently introduced rCW schemes. [•] The decoupling efficiency of the new sequence is tested with simulations and corroborated with experimental findings. [•] The robustness of the newly introduced scheme is compared to that of a few related decoupling methods. [ABSTRACT FROM AUTHOR]

Abstract: Aimed at 13C metabolic magnetic resonance imaging (MRI) and spectroscopy (MRS) applications, we demonstrate that dynamic nuclear polarization (DNP) may be combined with optimal control 2D spatial selection to simultaneously obtain high sensitivity and well-defined spatial restriction. This is achieved through the development of spatial-selective single-shot spiral-readout MRI and MRS experiments combined with dynamic nuclear polarization hyperpolarized [1-13C]pyruvate on a 4.7T pre-clinical MR scanner. The method stands out from related techniques by facilitating anatomic shaped region-of-interest (ROI) single metabolite signals available for higher image resolution or single-peak spectra. The 2D spatial-selective rf pulses were designed using a novel Krotov-based optimal control approach capable of iteratively fast providing successful pulse sequences in the absence of qualified initial guesses. The technique may be important for early detection of abnormal metabolism, monitoring disease progression, and drug research. [Copyright &y& Elsevier]

Abstract: Aimed at selective detection of 23Na with specific quadrupolar couplings for in vitro NMR and MRI, we present a series of quadrupolar binomial pulse sequences offering high specificity with respect to the quadrupolar couplings of the excited species. It is demonstrated that pulse sequences with an increasing number of elements, e.g., 11, 121, 1331, 14641, and 15101051, with the units representing flip angles smaller than the 90° pulses typically encountered in binomial spin-1/2 solvent suppression experiments, and different phase combinations may provide a high degree of flexibility with respect to quadrupolar coupling selectivity and robustness towards rf inhomogeneity. This may facilitate efficient separation of, for example, intra and extracellular 23Na in tissues with efficient control of the excitation (or suppression) of central as well as satellite transitions through on- and off-resonance irradiation. The pulse sequences are described in terms of their analogy to binomial liquid-state NMR solvent suppression experiments and demonstrated numerically and experimentally through NMR and MRI experiments on a 7T horizontal small-bore animal magnet system. [ABSTRACT FROM AUTHOR]

Abstract: We present the implementation of optimal control into the open source simulation package SIMPSON for development and optimization of nuclear magnetic resonance experiments for a wide range of applications, including liquid- and solid-state NMR, magnetic resonance imaging, quantum computation, and combinations between NMR and other spectroscopies. Optimal control enables efficient optimization of NMR experiments in terms of amplitudes, phases, offsets etc. for hundreds-to-thousands of pulses to fully exploit the experimentally available high degree of freedom in pulse sequences to combat variations/limitations in experimental or spin system parameters or design experiments with specific properties typically not covered as easily by standard design procedures. This facilitates straightforward optimization of experiments under consideration of rf and static field inhomogeneities, limitations in available or desired rf field strengths (e.g., for reduction of sample heating), spread in resonance offsets or coupling parameters, variations in spin systems etc. to meet the actual experimental conditions as close as possible. The paper provides a brief account on the relevant theory and in particular the computational interface relevant for optimization of state-to-state transfer (on the density operator level) and the effective Hamiltonian on the level of propagators along with several representative examples within liquid- and solid-state NMR spectroscopy. [Copyright &y& Elsevier]