R. Adam Horch

Characterization of 1H NMR Signal in Human Cortical Bone for Magnetic Resonance Imaging

Recent advancements in MRI have enabled clinical imaging of human cortical bone, providing a potentially powerful new means for assessing bone health with molecular‐scale sensitivities unavailable to conventional X‐ray‐based diagnostics. In human cortical bone, MRI is sensitive to populations of protons (1H) partitioned among water and protein sources, which may be differentiated according to intrinsic NMR properties such as chemical shift and transverse and longitudinal relaxation rates. Herein, these NMR properties were assessed in human cortical bone donors from a broad age range, and four distinct 1H populations were consistently identified and attributed to five microanatomical sources. These findings show that modern human cortical bone MRI contrast will be dominated by collagen‐bound water, which can also be exploited to study human cortical bone collagen via magnetization transfer. Magn Reson Med, 2010.

Non-invasive Predictors of Human Cortical Bone Mechanical Properties: T2-Discriminated 1H NMR Compared with High Resolution X-ray

Recent advancements in magnetic resonance imaging (MRI) have enabled clinical imaging of human cortical bone, providing a potentially powerful new means for assessing bone health with molecular-scale sensitivities unavailable to conventional X-ray-based diagnostics. To this end, 1H nuclear magnetic resonance (NMR) and high-resolution X-ray signals from human cortical bone samples were correlated with mechanical properties of bone. Results showed that 1H NMR signals were better predictors of yield stress, peak stress, and pre-yield toughness than were the X-ray derived signals. These 1H NMR signals can, in principle, be extracted from clinical MRI, thus offering the potential for improved clinical assessment of fracture risk.

Clinically compatible MRI strategies for discriminating bound and pore water in cortical bone

Advances in modern magnetic resonance imaging (MRI) pulse sequences have enabled clinically practical cortical bone imaging. Human cortical bone is known to contain a distribution of T1 and T2 components attributed to bound and pore water, although clinical imaging approaches have yet to discriminate bound from pore water based on their relaxation properties. Herein, two clinically compatible MRI strategies are proposed for selectively imaging either bound or pore water by utilizing differences in their T1s and T2s. The strategies are validated in a population of ex vivo human cortical bones, and estimates obtained for bound and pore water are compared to bone mechanical properties. Results show that the two MRI strategies provide good estimates of bound and pore water that correlate to bone mechanical properties. As such, the strategies for bound and pore water discrimination shown herein should provide diagnostically useful tools for assessing bone fracture risk, once applied to clinical MRI. Magn Reson Med, 2012.

Origins of the ultrashort‐T21H NMR signals in myelinated nerve: A direct measure of myelin content?

Recently developed MRI techniques have enabled clinical imaging of short‐lived 1H NMR signals with T2 < 1 ms. Using these techniques, novel signal enhancement has been observed in myelinated tissues, although the source of this enhancement has not been identified. Herein, we report studies of the nature and origins of ultrashort T2 (uT2) signals (50 μs < T2 < 1 ms) from amphibian and mammalian myelinated nerves. NMR measurements and comparisons with myelin phantoms and expected myelin components indicate that these uT2 signals arise predominantly from methylene 1H on/in the myelin membranes, which suggests that direct measurement of uT2 signals can be used as a new means for quantitative myelin mapping. Magn Reson Med, 2011.

Validation of quantitative bound- and pore-water imaging in cortical bone.

To implement and validate a previously proposed ultra‐short echo time method for measuring collagen‐bound‐ and pore‐water concentrations in bone based on their T2 differences.

RF coil considerations for short‐T2 MRI

With continuing hardware and pulse sequence advancements, modern MRI is gaining sensitivity to signals from short‐T2 1H species under practical experimental conditions. However, conventional MRI coils are typically not designed for this type of application, as they often contain proton‐rich construction materials that may contribute confounding 1H background signal during short‐T2 measurements. An example of this is shown herein. Separately, a loop‐gap style coil was used to compare different coil construction materials and configurations with respect to observed 1H background signal sizes in a small animal imaging system. Background signal sources were spatially identified and quantified in a number of different coil configurations. It was found that the type and placement of structural coil materials around the loop‐gap resonator, as well as the coils shielding configuration, are critical determinants of the coils background signal size. Although this study employed a loop‐gap resonator design, these findings are directly relevant to standard volume coils commonly used for MRI. Magn Reson Med, 2010.

In Vivo Quantitative MR Imaging of Bound and Pore Water in Cortical Bone

PURPOSE To translate and evaluate an in vivo magnetic resonance (MR) imaging protocol for quantitative mapping of collagen-bound and pore water concentrations in cortical bone that involves relaxation-selective ultrashort echo time (UTE) methods. MATERIALS AND METHODS All HIPAA-compliant studies were performed with institutional review board approval and written informed consent. UTE imaging sequences were implemented on a clinical 3.0-T MR imaging unit and were used for in vivo imaging of bound and pore water in cortical bone. Images of the lower leg and wrist were acquired in five volunteers each (lower leg: two men and three women aged 24, 24, 49, 30, and 26 years; wrist: two men and three women aged 31, 23, 25, 24, and 26 years) to generate bound and pore water concentration maps of the tibia and radius. Each volunteer was imaged three times, and the standard error of the measurements at the region-of-interest (ROI) level was computed as the standard deviation across studies, pooled across volunteers and ROIs. RESULTS Quantitative bound and pore water maps in the tibia and radius, acquired in 8-14 minutes, had per-voxel signal-to-noise ratios of 18 (bound water) and 14 (pore water) and inter-study standard errors of approximately 2 mol (1)H per liter of bone at the ROI level. CONCLUSION The results of this study demonstrate the feasibility of quantitatively mapping bound and pore water in vivo in human cortical bone with practical human MR imaging constraints.

Partial removal of pore and loosely bound water by low-energy drying decreases cortical bone toughness in young and old donors.

With an ability to quantify matrix-bound and pore water in bone, (1)H nuclear magnetic resonance (NMR) relaxometry can potentially be implemented in clinical imaging to assess the fracture resistance of bone in a way that is independent of current X-ray techniques, which assess bone mineral density as a correlate of bone strength. Working towards that goal, we quantified the effect of partial dehydration in air on the mechanical and NMR properties of human cortical bone in order to understand whether NMR is sensitive to water-bone interactions at low energy and whether such interactions contribute to the age-related difference in the toughness of bone. Cadaveric femurs were collected from male and female donors falling into two age groups: 21-60 years of age (young) and 74-99 years of age (old). After extracting two samples from the medial cortex of the mid-shaft, tensile tests were conducted on Wet specimens and paired, Partially Dry (PtlD) specimens (prepared by low-energy drying in air to remove ∼3% of original mass before testing). Prior analysis by micro-computed tomography found that there were no differences in intra-cortical porosity between the Wet and PtlD specimens nor did an age-related difference in porosity exist. PtlD specimens from young and old donors had significantly less toughness than Wet specimens, primarily due to a dehydration-related decrease in post-yield strain. The low-energy drying protocol did not affect the modulus and yield strength of bone. Subsequent dehydration of the PtlD specimens in a vacuum oven at 62°C and then 103°C, with quantification of water loss at each temperature, revealed an age-related shift from more loosely bound water to more tightly bound water. NMR detected a change in both bound and pore water pools with low-energy air-drying, and both pools were effectively removed when bone was oven-dried at 62°C, irrespective of donor age. Although not strictly significant due to variability in the drying and testing conditions, the absolute difference in toughness between Wet and PtlD tended to be greater for the younger donors that had higher bone toughness and more bound water for the wet condition than did the older donors. With sensitivity to low-energy bone-water interactions, NMR, which underpins magnetic resonance imaging, has potential to assess fracture resistance of bone as it relates to bone toughness.

Simple and robust saturation-based slice selection for ultrashort echo time MRI.

To present a new method for localizing signal within a two‐dimensional (2D) slice suitable for ultrashort echo time (UTE) imaging, called saturation‐based UTE (sat‐UTE). The new method digitally subtracts two acquisitions that are nonselectively excited with and without selective saturation of the slice of interest.

WITHDRAWN: 3D-printed RF probeheads for low-cost, high-throughput NMR

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