WITHDRAWN: 3D-printed RF probeheads for low-cost, high-throughput NMR.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

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.

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

PURPOSE: 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. METHODS: Sat-UTE was compared with half-pulse and double-half pulse excited UTE within phantoms, as well as 3D-UTE within ex vivo femur and in vivo tibia. Numerical simulations were also used to quantify the effects of slice profile broadening and signal component amplitudes for quantitative UTE. RESULTS: Sat-UTE is robust to suppress out-of-slice signal, and produces short T2 signal decay curves comparable to 3D-UTE, but has a lower signal to noise ratio efficiency compared with other slice-selective methods. CONCLUSION: The proposed method is useful for fast, quantitative evaluation of short T2 signals, and is insensitive to gradient performance.

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

PURPOSE: 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. METHODS: Clinically compatible ultra-short echo time image sequences for quantitative T2 -based bound and pore-water imaging in bone were implemented and validated on a 3T human scanner and a 4.7T small bore system. Bound- and pore-water images were generating using T2 -selective adiabatic pulses. In both cases, the magnetization preparation was integrated into a three-dimensional ultra-short echo time acquisition, with 16 radial spokes acquired per preparation. Images were acquired from human cadaveric femoral mid-shafts from which isolated bone samples were subsequently extracted for nonimaging analysis using T2 spectroscopic measurements. RESULTS: A strong correlation was found between imaging-derived concentrations of bound and pore water and those determined from the isolated bone samples. CONCLUSIONS: These studies demonstrate the translation of the previously developed approaches for distinguishing bound and pore water from human cortical bone using practical human MRI constraints of gradient performance and radiofrequency power deposition.

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 T(1) and T(2) 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 T(1)s and T(2)s. 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.

Origins of the ultrashort-T2 1H NMR signals in myelinated nerve: a direct measure of myelin content?

Recently developed MRI techniques have enabled clinical imaging of short-lived (1)H NMR signals with T(2) < 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 T(2) (uT(2)) signals (50 µs < T(2) < 1 ms) from amphibian and mammalian myelinated nerves. NMR measurements and comparisons with myelin phantoms and expected myelin components indicate that these uT(2) signals arise predominantly from methylene (1)H on/in the myelin membranes, which suggests that direct measurement of uT(2) signals can be used as a new means for quantitative myelin mapping.

Non-invasive predictors of human cortical bone mechanical properties: T(2)-discriminated H 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, (1)H 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 (1)H NMR signals were better predictors of yield stress, peak stress, and pre-yield toughness than were the X-ray derived signals. These (1)H NMR signals can, in principle, be extracted from clinical MRI, thus offering the potential for improved clinical assessment of fracture risk.

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 ((1)H) 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 (1)H 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.

RF coil considerations for short-T2 MRI.

With continuing hardware and pulse sequence advancements, modern MRI is gaining sensitivity to signals from short-T(2) (1)H 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 (1)H background signal during short-T(2) 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 (1)H 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 coil's shielding configuration, are critical determinants of the coil's 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.

Aqueous urea as a model system for bi-exponential relaxation.

OBJECT: To evaluate the utility of aqueous urea, doped inner- and outer-sphere relaxation agents, as an adjustable two-component model system. MATERIALS AND METHODS: T2 was measured from 12 molal urea mixtures at pH 7.0 with varying amounts of the MnCl2 and FeO(1.44) (Feridex, Berlex Inc, Montville, NJ). RESULTS: Bi-exponential relaxation was observed, with rates that were bilinearly related to [MnCl2] and [FeO(1.44)]. FeO(1.44) had comparable relaxivities on both urea and water, while MnCl2 relaxivity was > 15x larger for water than for urea. CONCLUSION: Aqueous urea, doped with inner- and outer-sphere contrast agents, is a two-compartment model system, which can be exhibit a wide range of different T2s and signal fractions.

Nanoreinforcement of poly(propylene fumarate)-based networks with surface modified alumoxane nanoparticles for bone tissue engineering.

A novel composite material has been fabricated for bone tissue engineering scaffolds utilizing the biodegradable polymer poly(propylene fumarate)/poly(propylene fumarate)-diacrylate (PPF/PPF-DA) and surface-modified carboxylate alumoxane nanoparticles. Various surface-modified nanoparticles were added to the polymer including a surfactant alumoxane, an activated alumoxane, a mixed alumoxane containing both activated and surfactant groups, and a hybrid alumoxane containing both groups within the same substituent. These nanocomposites, as well as polymer resin and unmodified boehmite composites, underwent flexural and compressive mechanical testing and were examined using electron microscopy. Hybrid alumoxane nanoparticles dispersed in PPF/PPF-DA exhibited over a 3-fold increase in flexural modulus at 1 wt % loading compared to polymer resin alone. No significant loss of flexural or compressive strength was observed with increased loading of hybrid alumoxane nanoparticles. These dramatic improvements in flexural properties may be attributed to the fine dispersion of nanoparticles into the polymer and increased covalent interaction between polymer chains and surface modifications of nanoparticles.

In vitro cytotoxicity of injectable and biodegradable poly(propylene fumarate)-based networks: unreacted macromers, cross-linked networks, and degradation products.

This study evaluates the in vitro biocompatibility of an injectable and biodegradable polymeric network based on poly(propylene fumarate) (PPF) and the cross-linking agent PPF-diacrylate (PPF-DA). Using a methyl tetrazolium (MTT) assay, the effect of the concentrations of PPF and PPF-DA on the cytotoxicity of its unreacted macromers, cross-linked networks, and degradation products was examined. The influence of network structure properties on cell viability and attachment to the cross-linked material was also investigated. The unreacted macromers exhibited a time- and dose-dependent cytotoxic response that increased with more PPF-DA in the mixture. Conversely, the cross-linked networks formed with more PPF-DA did not demonstrate an adverse response because increases in conversion and cross-linking density prevented the extraction of toxic products. Fibroblast attachment was observed on the PPF/PPF-DA networks with the highest double bond conversions. The degradation products, obtained from the complete breakdown of the networks in basic conditions, displayed a dose-dependent cytotoxic response. These results show that there are concerns regarding the biocompatibility of injectable, biodegradable PPF/PPF-DA networks but also sheds light onto potential mechanisms to reduce the cytotoxic effects.

Effect of physiological temperature on the mechanical properties and network structure of biodegradable poly(propylene fumarate)-based networks.

Poly(propylene fumarate) (PPF)-based networks have exhibited increases in mechanical properties during their initial stages of degradation. This study was designed to investigate whether physiological temperatures are the source of this reinforcing behavior by influencing the formation of additional crosslinks within the network. Utilizing a model PPF network formed with the crosslinking agent poly(propylene fumarate)-diacrylate (PPF-DA), cylindrical specimens were stored in an inert environment and conditioned at -20 and 37 degrees C while their mechanical properties and network structure were monitored over a six week period. The PPF/PPF-DA specimens exposed to physiological temperatures showed an increase in compressive modulus from 1674 +/- 88 to 2059 +/- 75 MPa. The double bond conversion improved as well, from 64 +/- 1 to 70 +/- 1%, indicating that crosslinks were being formed in the network. The additional reactivity occurred exclusively with unreacted fumarate bonds. PPF/PPF-DA networks stored at -20 degrees C showed no changes in mechanical properties; however, they increased when subsequently conditioned at 37 degrees C. The results were used to explain that PPF-based networks undergo a biphasic degradation behavior due to the competing hydrolytic degradation and thermal induced crosslinking. In addition, heat treating the networks at higher temperatures can be utilized as a means to further reinforce PPF-based materials.