Susie Y. Huang

The Human Connectome Project and beyond: initial applications of 300 mT/m gradients.

The engineering of a 3 T human MRI scanner equipped with 300 mT/m gradients - the strongest gradients ever built for an in vivo human MRI scanner - was a major component of the NIH Blueprint Human Connectome Project (HCP). This effort was motivated by the HCPs goal of mapping, as completely as possible, the macroscopic structural connections of the in vivo healthy, adult human brain using diffusion tractography. Yet, the 300 mT/m gradient system is well suited to many additional types of diffusion measurements. Here, we present three initial applications of the 300 mT/m gradients that fall outside the immediate scope of the HCP. These include: 1) diffusion tractography to study the anatomy of consciousness and the mechanisms of brain recovery following traumatic coma; 2) q-space measurements of axon diameter distributions in the in vivo human brain and 3) postmortem diffusion tractography as an adjunct to standard histopathological analysis. We show that the improved sensitivity and diffusion-resolution provided by the gradients are rapidly enabling human applications of techniques that were previously possible only for in vitro and animal models on small-bore scanners, thereby creating novel opportunities to map the microstructure of the human brain in health and disease.

Clinical correlates of atypical femoral fracture.

BACKGROUND Reports of atypical femur fracture in bisphosphonate-exposed women have prompted interest in characterizing the clinical profiles of these patients. METHODS Among women age ≥60 years with hip or femur fracture during 2007-2008, we identified 79 with low-trauma subtrochanteric or femoral shaft fracture. Radiographic images were reviewed to assign fracture pattern and distinguish atypical femur fracture from non-atypical femur fracture. Differences in clinical characteristics and pharmacologic exposures were compared. RESULTS Among 79 women (38 subtrochanteric and 41 femoral shaft fracture), 38 had an atypical femur fracture. Compared to those with a non-atypical femur fracture, women with atypical femur fracture were significantly younger (74.0 vs 81.0 years), more likely to be Asian (50.0 vs 2.4%) and to have received bisphosphonate therapy (97.4 vs 41.5%). Similarly, the contralateral femur showed a stress or complete fracture in 39.5% of atypical femur fractures vs 2.4% non-atypical femur fracture, and focal cortical hypertrophy of the contralateral femur in an additional 21.1% of atypical cases. CONCLUSIONS Women suffering atypical femur fractures have a markedly different clinical profile from those sustaining typical fractures. Women with atypical femur fracture tend to be younger, Asian, and bisphosphonate-exposed. The high frequency of contralateral femur findings suggests a generalized process.

The impact of gradient strength on in vivo diffusion MRI estimates of axon diameter

Diffusion magnetic resonance imaging (MRI) methods for axon diameter mapping benefit from higher maximum gradient strengths than are currently available on commercial human scanners. Using a dedicated high-gradient 3T human MRI scanner with a maximum gradient strength of 300 mT/m, we systematically studied the effect of gradient strength on in vivo axon diameter and density estimates in the human corpus callosum. Pulsed gradient spin echo experiments were performed in a single scan session lasting approximately 2h on each of three human subjects. The data were then divided into subsets with maximum gradient strengths of 77, 145, 212, and 293 mT/m and diffusion times encompassing short (16 and 25 ms) and long (60 and 94 ms) diffusion time regimes. A three-compartment model of intra-axonal diffusion, extra-axonal diffusion, and free diffusion in cerebrospinal fluid was fitted to the data using a Markov chain Monte Carlo approach. For the acquisition parameters, model, and fitting routine used in our study, it was found that higher maximum gradient strengths decreased the mean axon diameter estimates by two to three fold and decreased the uncertainty in axon diameter estimates by more than half across the corpus callosum. The exclusive use of longer diffusion times resulted in axon diameter estimates that were up to two times larger than those obtained with shorter diffusion times. Axon diameter and density maps appeared less noisy and showed improved contrast between different regions of the corpus callosum with higher maximum gradient strength. Known differences in axon diameter and density between the genu, body, and splenium of the corpus callosum were preserved and became more reproducible at higher maximum gradient strengths. Our results suggest that an optimal q-space sampling scheme for estimating in vivo axon diameters should incorporate the highest possible gradient strength. The improvement in axon diameter and density estimates that we demonstrate from increasing maximum gradient strength will inform protocol development and encourage the adoption of higher maximum gradient strengths for use in commercial human scanners.

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.

In vivo mapping of human spinal cord microstructure at 300 mT/m

The ability to characterize white matter microstructure non-invasively has important applications for the diagnosis and follow-up of several neurological diseases. There exists a family of diffusion MRI techniques, such as AxCaliber, that provide indices of axon microstructure, such as axon diameter and density. However, to obtain accurate measurements of axons with small diameters (<5μm), these techniques require strong gradients, i.e. an order of magnitude higher than the 40-80mT/m currently available in clinical systems. In this study we acquired AxCaliber diffusion data at a variety of different q-values and diffusion times in the spinal cord of five healthy subjects using a 300mT/m whole body gradient system. Acquisition and processing were optimized using state-of-the-art methods (e.g., 64-channel coil, template-based analysis). Results consistently show an average axon diameter of 4.5+/-1.1μm in the spinal cord white matter. Diameters ranged from 3.0μm (gracilis) to 5.9μm (spinocerebellar tracts). Values were similar across laterality (left-right), but statistically different across spinal cord pathways (p<10(-5)). The observed trends are similar to those observed in animal histology. This study shows, for the first time, in vivo mapping of axon diameter in the spinal cord at 300mT/m, thus creating opportunities for applications in spinal cord diseases.

Signal interferences from turbulent spin dynamics in solution nuclear magnetic resonance spectroscopy

Artifacts arising from aperiodic turbulent spin dynamics in gradient-based nuclear magnetic resonance (NMR) applications are comprehensively surveyed and numerically simulated by a nonlinear Bloch equation. The unexpected dynamics, triggered by the joint action of radiation damping and the distant dipolar field, markedly deteriorate the performance of certain pulse sequences incorporating weak pulsed-field gradients and long evolution times. The effects are demonstrated in three general classes of gradient NMR applications: solvent signal suppression, diffusion measurements, and coherence pathway selection. Gradient-modulated solvent transverse magnetization can be partially rephased in a series of self-refocusing gradient echoes that blank out solute resonances in the CHESS (chemical-shift-selective spectroscopy) and WATERGATE (gradient-tailored water suppression) solvent suppression schemes. In addition, the discovered dynamics contribute to erratic echo attenuation in pulsed gradient spin echo (PGSE) a...

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.

High-resolution in vivo diffusion imaging of the human brain with generalized slice dithered enhanced resolution: Simultaneous multislice (gSlider-SMS)

To develop an efficient acquisition for high‐resolution diffusion imaging and allow in vivo whole‐brain acquisitions at 600‐ to 700‐μm isotropic resolution.

Understanding third-order dipolar effects in solution nuclear magnetic resonance: Hahn echo decays and intermolecular triple-quantum coherences

Dipolar effects in solution nuclear magnetic resonance lead to additional peaks in two-dimensional experiments. These peaks, which have the experimental properties of intermolecular multiple-quantum coherences, have been used in a variety of applications. Most efforts have focused on intermolecular zero-quantum or double-quantum coherences, which originate in two-spin terms from the equilibrium density matrix. In this paper, we characterize the “third-order experiments” (Hahn echo decay and triple-quantum CRAZED, which both originate in the three-spin terms in the equilibrium density matrix) both theoretically and experimentally. For example, in the coupled-spin picture, Hahn echo decays in concentrated solutions arise initially from intermolecular, 3-spin, −1-quantum coherences, which are partially converted to 3-spin, +1-quantum coherences by the second pulse, and hence survive the 1:1 coherence transfer echo. Such terms require two dipolar couplings to become observable. We discuss the general properti...

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.