Yung-Ya Lin

Signal irreproducibility in high-field solution magnetic resonance experiments caused by spin turbulence

Turbulent spin dynamics arising from the joint action of radiation damping and the distant dipolar field are shown to generate irreproducible measurements in popular high-field, gradient-based magnetic resonance (MR) experiments, undermining the prevailing assumption of essentially predictable observables in MR. Sizeable fluctuations in echo amplitudes are reported and numerically simulated for pulsed gradient spin echo and stimulated echo diffusion measurements. The underlying microscopic dynamical instability is characterized by analysis of the finite-time Lyapunov exponents. Perturbations to the modulated magnetization are shown to render magic-angle gradients ineffective in suppressing signal fluctuations. Alternative approaches are suggested for cancelling out the feedback interactions leading to spin turbulence.

Improving MRI differentiation of gray and white matter in epileptogenic lesions based on nonlinear feedback

A new method for enhancing MRI contrast between gray matter (GM) and white matter (WM) in epilepsy surgery patients with symptomatic lesions is presented. This method uses the radiation damping feedback interaction in high‐field MRI to amplify contrast due to small differences in resonance frequency in GM and WM corresponding to variations in tissue susceptibility. High‐resolution radiation damping‐enhanced (RD) images of in vitro brain tissue from five patients were acquired at 14 T and compared with corresponding conventional T1‐, T  2* ‐, and proton density (PD)‐weighted images. The RD images yielded a six times better contrast‐to‐noise ratio (CNR = 44.8) on average than the best optimized T1‐weighted (CNR = 7.92), T  2* ‐weighted (CNR = 4.20), and PD‐weighted images (CNR = 2.52). Regional analysis of the signal as a function of evolution time and initial pulse flip angle, and comparison with numerical simulations confirmed that radiation damping was responsible for the observed signal growth. The time evolution of the signal in different tissue regions was also used to identify subtle changes in tissue composition that were not revealed in conventional MR images. RD contrast is compared with conventional MR methods for separating different tissue types, and its value and limitations are discussed. Magn Reson Med, 2006.

Unibody core-shell smart polymer as a theranostic nanoparticle for drug delivery and MR imaging.

Developing novel multifunctional nanoparticles (NPs) with robust preparation, low cost, high stability, and flexible functionalizability is highly desirable. This study provides an innovative platform, termed unibody core-shell (UCS), for this purpose. UCS is comprised of two covalent-bonded polymers differed only by the functional groups at the core and the shell. By conjugating Gd(3+) at the stable core and encapsulating doxorubicin (Dox) at the shell in a pH-sensitive manner, we developed a theranostic NPs (UCS-Gd-Dox) that achieved a selective drug release (75% difference between pH 7.4 and 5.5) and MR imaging (r1 = 0.9 and 14.5 mm(-1) s(-1) at pH 7.4 and 5.5, respectively). The anti-cancer effect of UCS-Gd-Dox is significantly better than free Dox in tumor-bearing mouse models, presumably due to enhanced permeability and retention effect and pH-triggered release. To the best of our knowledge, this is the simplest approach to obtain the theranostic NPs with Gd-conjugation and Dox doping.

Designing feedback-based contrast enhancement for in vivo imaging

AbstractObjective: Nonlinear feedback interactions induced by the spins themselves have recently been introduced as novel MRI contrast enhancement mechanisms sensitive to small differences in MR parameters. Developing feedback-based contrast enhancement into a useful tool for in vivo imaging requires improved techniques that are robust to inhomogeneity and sensitive to subtle anatomical/physiological variations. Materials and methods: Three different imaging methods combining the radiation damping feedback field with the distant dipolar field, applied radio-frequency (RF) fields, and local dipole fields, respectively, were designed and tested through numerical simulations on simple phantoms. These methods were demonstrated experimentally on live guppy fish, developing frog embryos, and blood in in vitro tissue samples by microimaging at 14.1 T. Results: The developed feedback-based methods yielded images that identified distinct morphological features with superior contrast compared with conventional MR images and those acquired under radiation damping only. Positive contrast due to evolution under radiation damping and local dipole fields was also observed in SPIOs and blood. Conclusion: Approaches to enhancing feedback-based contrast were successfully designed and demonstrated in vitro and in vivo. The newly devised methods were less sensitive to field inhomogeneity and prolonged evolution under the feedback fields, allowing for better visualization of contrast in vivo.

Spin amplification in solution magnetic resonance using radiation damping

The sensitive detection of dilute solute spins is critical to biomolecular NMR. In this work, a spin amplifier for detecting dilute solute magnetization is developed using the radiation damping interaction in solution magnetic resonance. The evolution of the solvent magnetization, initially placed along the unstable -z direction, is triggered by the radiation damping field generated by the dilute solute magnetization. As long as the radiation damping field generated by the solute is larger than the corresponding thermal noise field generated by the sample coil, the solute magnetization can effectively trigger the evolution of the water magnetization under radiation damping. The coupling between the solute and solvent magnetizations via the radiation damping field can be further improved through a novel bipolar gradient scheme, which allows solute spins with chemical shift differences much greater than the effective radiation damping field strength to affect the solvent magnetizations more efficiently. Experiments performed on an aqueous acetone solution indicate that solute concentrations on the order of 10(-5) that of the solvent concentration can be readily detected using this spin amplifier.

The transient dynamics leading to spin turbulence in high-field solution magnetic resonance: A numerical study

The dynamics under the joint action of radiation damping and the distant dipolar field in high-field solution magnetic resonance are investigated. Different dynamical regimes during the evolution are identified and their individual features are discussed. In the steady state, the dynamics can be associated with a strange attractor in phase space on which the motion is chaotic. The possibility of the observed chaotic motion being spatiotemporal is examined.

Sensitivity of feedback-enhanced MRI contrast to macroscopic and microscopic field variations

Nonlinear feedback interactions have been shown to amplify contrast due to small differences in resonance frequency arising from microscopic susceptibility variations. Determining whether the selectivity of feedback‐based contrast enhancement for small resonance frequency variations remains valid even in the presence of macroscopic field inhomogeneity is important for transitioning this new methodology into in vivo applications in imaging systems with lower field strengths and poorer homogeneity. This work shows that contrast enhancement under the radiation damping (RD) feedback field is sensitive to microscopic intravoxel frequency variations. Feedback‐enhanced contrast provides superior signal differentiation from voxels with distinct microscopic frequency distributions compared with T  2* ‐weighted imaging, while remaining robust to macroscopic field gradients, which frequently give rise to artifacts by other frequency‐sensitive methods. Applying multiple RF pulses during evolution under RD and actively adjusting the phase and amplitude of the feedback field are shown to further improve signal differentiation. Experimental results reveal that feedback‐enhanced contrast can generate positive contrast, reflecting microscopic field variations induced by strong local dipole fields, such as those created by blood vessels and superparamagnetic iron oxide nanoparticles. Extensions to in vivo imaging at lower field strengths are discussed in the context of amplifying the RD field via active electronic feedback. Magn Reson Med, 2009.

High-resolution nuclear magnetic resonance measurements in inhomogeneous magnetic fields: A fast two-dimensional J-resolved experiment

High spectral resolution in nuclear magnetic resonance (NMR) is a prerequisite for achieving accurate information relevant to molecular structures and composition assignments. The continuous development of superconducting magnets guarantees strong and homogeneous static magnetic fields for satisfactory spectral resolution. However, there exist circumstances, such as measurements on biological tissues and heterogeneous chemical samples, where the field homogeneity is degraded and spectral line broadening seems inevitable. Here we propose an NMR method, named intermolecular zero-quantum coherence J-resolved spectroscopy (iZQC-JRES), to face the challenge of field inhomogeneity and obtain desired high-resolution two-dimensional J-resolved spectra with fast acquisition. Theoretical analyses for this method are given according to the intermolecular multiple-quantum coherence treatment. Experiments on (a) a simple chemical solution and (b) an aqueous solution of mixed metabolites under externally deshimmed fields, and on (c) a table grape sample with intrinsic field inhomogeneity from magnetic susceptibility variations demonstrate the feasibility and applicability of the iZQC-JRES method. The application of this method to inhomogeneous chemical and biological samples, maybe in vivo samples, appears promising.

Spin chaos in magnetic resonance

The joint action of two readily observed effects in solution magnetic resonance-radiation damping and the dipolar field-are shown to generate spatiotemporal chaos in routine experiments. The extreme sensitivity of the chaotic spin dynamics to experimental conditions during the initial evolution period can be used to construct a spin amplifier to enhance sensitivity and contrast in magnetic resonance spectroscopy and imaging. Alternatively, amplification of intrinsic spin noise or tiny experimental perturbations such as temperature gradient fluctuations leads to signal interferences and highly irreproducible measurements. Controlling the underlying chaotic evolution provides the crucial link between amplifying weak signals and counteracting unwanted signal fluctuations.