Cortical Bone Water Research Articles

Frequency shifts of free water signals from compact bone: Simulations and measurements using a UTE-FID sequence.

Free water in cortical bone is either contained in nearly cylindrical structures (mainly Haversian canals oriented parallel to the bone axis) or in more spherically shaped pores (lacunae). Those cavities have been reported to crucially influence bone quality and mechanical stability. Susceptibility differences between bone and water can lead to water frequency shifts dependent on the geometric characteristics. The purpose of this study is to calculate and measure the frequency distribution of the water signal in MRI in dependence of the microscopic bone geometry. Finite element modeling and analytical approaches were performed to characterize the free water components of bone. The previously introduced UTE-FID technique providing spatially resolved FID-spectra was used to measure the frequency distribution pixel-wise for different orientations of the bone axis. The frequency difference between free water in spherical pores and in canals parallel to B0 amounts up to approximately 100 Hz at 3T. Simulated resonance frequencies showed good agreement with the findings in UTE-FID spectra. The intensity ratio of the two signal components (parallel canals and spherical pores) was found to vary between periosteal and endosteal regions. Spatially resolved UTE-FID examinations allow the determination of the frequency distribution of signals from free water in cortical bone. This frequency distribution indicates the composition of the signal contributions from nearly spherical cavities and cylindrical canals which allows for further characterization of bone structure and status.

T1 relaxation of bound and pore water in cortical bone.

MRI measures of bound and/or pore water concentration in cortical bone offer potential diagnostics of bone fracture risk. The transverse relaxation characteristics of both bound and pore water are relatively well understood and have been used to design clinical MRI pulse sequences to image each water pool quantitatively. However, these methods are also sensitive to longitudinal relaxation characteristics, which have been less well studied. Here, spectroscopic relaxometry measurements of 31 human cortical bone specimens provided a more detailed picture of of both bound and pore water. The results included mean, standard deviation, and range of spectra from both bound and pore water, as well as novel presentations of the 2D distribution of pore water. Importantly, for each sample the pore water spectrum was found to span more than one order of magnitude and varied substantially across the 31 sample studies. Because many existing methods assume pore water to be mono-exponential and constant across individuals, the results were used to compute the potential effect neglecting this intra- and intersample variation on accurate MRI measurement of both bound and pore water concentrations. The greatest effect was found for adiabatic inversion recovery (AIR) based measurements of bound water concentration, which showed an average of 8.8% and as much as 37% error when using a common mono-exponential assumption of pore water . Despite these errors, the simulated AIR measurements were still moderately well correlated with the bound water concentrations derived from the spectroscopic data.

Characterization of Baboon Cortical Bone Microstructural Changes by Low Field NMR and Correlation of Bone Mechanical Properties

A NMR spin-spin (T2) relaxation technique has been described for determining the porosity, mobile and the bound water distribution in baboon cortical bone and correlate to their mechanical properties. The technique of low-field proton NMR involves spin-spin relaxation and free induction decay (FID) measurements, and the computational inversion methods for decay data analysis. The advantages of using NMR T2 relaxation techniques for bone water distribution are illustrated. The CPMG T2 relaxation data can be inverted to T2 relaxation distribution and this distribution then can be transformed to a pore size distribution with the longer relaxation times corresponding to larger pores. The FID T2 relaxation data can be inverted to T2 relaxation distribution and this distribution then can be transformed to bound and mobile water distribution with the longest relaxation time corresponding to mobile water and the middle relaxation time corresponding to bound water. The technique is applied to quantify apparent changes in porosity, bound and mobile water in cortical bone. Overall bone porosity is determined using the calibrated NMR fluid volume from the proton relaxation data divided by overall bone volume. The NMR porosity, bound and mobile water components are determined from cortical bone specimens obtained from baboon donors of different ages, and the results are correlated to bone mechanical properties.

Near infrared spectroscopic assessment of loosely and tightly bound cortical bone water.

Water is an important component of bone and plays a key role in its mechanical and structural integrity. Water molecules in bone are present in different locations, including loosely or tightly bound to the matrix and/or mineral (biological apatite) phases. Identification of water location and interactions with matrix components impact bone function but have been challenging to assess. Here, we used near infrared (NIR) spectroscopy to identify loosely and tightly bound water present in cortical bone. In hydrated samples, NIR spectra have two primary water absorption bands at frequencies of ∼5200 and 7000 cm-1. Using lyophilization and hydrogen-deuterium exchange assays, we showed that these absorption bands are primarily associated with loosely bound bone water. Using further demineralization assays, thermal denaturation, and comparison to standards, we found that these absorption bands have underlying components associated with water molecules tightly bound to bone. In dehydrated samples, the peak at ∼5200 cm-1 was assigned to a combination of water tightly bound to collagen and to mineral, whereas the peak at 7000 cm-1 was exclusively associated with tightly bound mineral water. We also found significant positive correlations between the NIR mineral absorption bands and the mineral content as determined by an established mid infrared spectroscopic parameter, phosphate/amide I. Moreover, the NIR water data showed correlation trends with tissue mineral density (TMD) in cortical bone tissues. These observations reveal the ability of NIR spectroscopy to non-destructively identify loosely and tightly bound water in bone, which could have further applications in biomineralization and biomedical studies.

Environmentally-Controlled Near Infrared Spectroscopic Imaging of Bone Water

We have designed an environmentally-controlled chamber for near infrared spectroscopic imaging (NIRSI) to monitor changes in cortical bone water content, an emerging biomarker related to bone quality assessment. The chamber is required to ensure repeatable spectroscopic measurements of tissues without the influence of atmospheric moisture. A calibration curve to predict gravimetric water content from human cadaveric cortical bone was created using NIRSI data obtained at six different lyophilization time points. Partial least squares (PLS) models successfully predicted bone water content that ranged from 0–10% (R = 0.96, p < 0.05, root mean square error of prediction (RMSEP) = 7.39%), as well as in the physiologic range of 4–10% of wet tissue weight (R = 0.87, p < 0.05, RMSEP = 14.5%). Similar results were obtained with univariate and bivariate regression models for prediction of water in the 0–10% range. Further, we identified two new NIR bone absorbances, at 6560 cm−1 and 6688 cm−1, associated with water and collagen respectively. Such data will be useful in pre-clinical studies that investigate changes in bone quality with disease, aging and with therapeutic use.

Detection of Lumbar Spine Osseous Metastases Using Dual-Energy CT: Phantom Results and Preliminary Clinical Validation.

The purpose of this study was to evaluate the sensitivity, tumor conspicuity, and image quality of different material decomposition images of phantoms and patients with nearly isodense bone metastases using rapid-kilovoltage-switching dual-energy CT (DECT). Fifty-one semianthropomorphic lumbar spine phantoms embedded with 75 simulated tumors were scanned without and with outer torso-attenuating encasement under the same scan settings. Two radiologists independently reviewed the 70-keV virtual monochromatic and material decomposition images (hydroxyapatite-water, water-hydroxyapatite, cortical bone-water, water-cortical bone). The sensitivity of tumor detection, tumor conspicuity (on a 3-point scale), and image quality (on a 3-point scale) were recorded by two independent readers. McNemar and Wilcoxon signed rank tests were used to compare results between the image reconstructions. Six clinical abdominopelvic DECT scans (three men, three women; mean age, 52 years) with nine nearly isodense lumbar spine tumors missed in the clinical report but confirmed on other scans were also evaluated. The hydroxyapatite-water material decomposition algorithm showed improved sensitivity for isodense lesion detection (without torso phantom encasement, 94% vs 82%, p = 0.031; with torso phantom encasement, 38% vs 18%, p = 0.013), and higher tumor conspicuity scores (p < 0.0001) compared with 70-keV virtual monoenergetic images. Artifacts were more prevalent with all material decomposition images than with 70-keV virtual monoenergetic images. Similar results were seen in the patient study. Dual-energy CT with hydroxyapatite-water material decomposition may improve the detection of bone marrow metastases, especially for subtle isodense tumors. Further study in prospective clinical scans is warranted.

Fast volumetric imaging of bound and pore water in cortical bone using three-dimensional ultrashort-TE (UTE) and inversion recovery UTE sequences.

We report the three-dimensional ultrashort-TE (3D UTE) and adiabatic inversion recovery UTE (IR-UTE) sequences employing a radial trajectory with conical view ordering for bi-component T2 * analysis of bound water (T2 *(BW) ) and pore water (T2 *(PW) ) in cortical bone. An interleaved dual-echo 3D UTE acquisition scheme was developed for fast bi-component analysis of bound and pore water in cortical bone. A 3D IR-UTE acquisition scheme employing multiple spokes per IR was developed for bound water imaging. Two-dimensional UTE (2D UTE) and IR-UTE sequences were employed for comparison. The sequences were applied to bovine bone samples (n = 6) and volunteers (n = 6) using a 3-T scanner. Bi-component fitting of 3D UTE images of bovine samples showed a mean T2 *(BW) of 0.26 ± 0.04 ms and T2 *(PW) of 4.16 ± 0.35 ms, with fractions of 21.5 ± 3.6% and 78.5 ± 3.6%, respectively. The 3D IR-UTE signal showed a single-component decay with a mean T2 *(BW) of 0.29 ± 0.05 ms, suggesting selective imaging of bound water. Similar results were achieved with the 2D UTE and IR-UTE sequences. Bi-component fitting of 3D UTE images of the tibial midshafts of healthy volunteers showed a mean T2 *(BW) of 0.32 ± 0.08 ms and T2 *(PW) of 5.78 ± 1.24 ms, with fractions of 34.2 ± 7.4% and 65.8 ± 7.4%, respectively. Single-component fitting of 3D IR-UTE images showed a mean T2 *(BW) of 0.35 ± 0.09 ms. The 3D UTE and 3D IR-UTE techniques allow fast volumetric mapping of bound and pore water in cortical bone. Copyright © 2016 John Wiley & Sons, Ltd.

Cortical Bone Water Concentration: Dependence of MR Imaging Measures on Age and Pore Volume Fraction

HomeRadiologyVol. 280, No. 2 PreviousNext CommunicationsFree AccessErrataCortical Bone Water Concentration: Dependence of MR Imaging Measures on Age and Pore Volume FractionCheng Li, Alan C. Seifert, Hamidreza Saligheh Rad, Yusuf A. Bhagat, Chamith S. Rajapakse, Wenli Sun, Shing Chun Benny Lam, Felix W. WehrliCheng Li, Alan C. Seifert, Hamidreza Saligheh Rad, Yusuf A. Bhagat, Chamith S. Rajapakse, Wenli Sun, Shing Chun Benny Lam, Felix W. WehrliCheng LiAlan C. SeifertHamidreza Saligheh RadYusuf A. BhagatChamith S. RajapakseWenli SunShing Chun Benny LamFelix W. WehrliPublished Online:Jul 18 2016https://doi.org/10.1148/radiol.2016164023MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Originally published in:Radiology 2014;272(3):796–806 DOI: 10.1148/radiol.14132585Erratum in:Radiology 2016;280(2):653 DOI:10.1148/radiol.2016164023The current address footnote for Hamidreza Saligheh Rad, PhD, should read as follows: Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran.Article HistoryPublished online: July 18 2016Published in print: Aug 2016 FiguresReferencesRelatedDetailsCited ByIn vivo quantitative imaging biomarkers of bone quality and mineral density using multi-band-SWIFT magnetic resonance imagingRachel K.Surowiec, SundareshRam, DjaudatIdiyatullin, RobertGoulet, Stephen H.Schlecht, Craig J.Galban, Kenneth M.Kozloff2021 | Bone, Vol. 143Principles of Bone BiologyKlausEngelke, Harry K.Genant, JamesGriffith2020Magnetic Resonance Imaging of Hard Tissues and Hard Tissue Engineered Bio-substitutesSimoneMastrogiacomo, WeiqiangDou, John A.Jansen, X. FrankWalboomers2019 | Molecular Imaging and Biology, Vol. 21, No. 6Applications of PET-MRI in musculoskeletal diseaseFeliksKogan, Stephen M.Broski, DaehyunYoon, Garry E.Gold2018 | Journal of Magnetic Resonance Imaging, Vol. 48, No. 1Accompanying This ArticleCortical Bone Water Concentration: Dependence of MR Imaging Measures on Age and Pore Volume FractionMay 2 2014RadiologyRecommended Articles Quantification of Human Cortical Bone Bound and Free Water in Vivo with Ultrashort Echo Time MR Imaging: A Model-based ApproachRadiology2017Volume: 283Issue: 3pp. 862-872Influence of Parathyroidectomy on Bone Calcium Concentration: Evaluation with Spectral CT in Patients with Secondary Hyperparathyroidism Undergoing Hemodialysis—A Prospective Feasibility StudyRadiology2017Volume: 284Issue: 1pp. 143-152Acute and Stress-related Injuries of Bone and Cartilage: Pertinent Anatomy, Basic Biomechanics, and Imaging PerspectiveRadiology2016Volume: 280Issue: 1pp. 21-38Elemental Imaging of Long-term Gadolinium Retention in Rodent FemurRadiology2022Volume: 306Issue: 2Contribution of Bone Calcium to Bone Mineral DensityRadiology2018Volume: 286Issue: 2pp. 727-728See More RSNA Education Exhibits New Approach to Osteoporosis: Bone Microstructure Revealed by Ultra-High Resolution CTDigital Posters2018Imaging Features of Chronic Kidney Disease Mineral and Bone Disorders (CKD-MBD)Digital Posters2019Ultrashort Echo Time (UTE) Imaging: Review of Technique and Musculoskeletal Applications with Examples of Utility in the KneeDigital Posters2019 RSNA Case Collection Skeletal Fluorosis RSNA Case Collection2022Osteoid osteoma of the femurRSNA Case Collection2022Osteomyelitis with sequestrumRSNA Case Collection2021 Vol. 280, No. 2 Metrics Altmetric Score PDF download

SU‐F‐J‐165: Spectral Characterization of Tissues in High Spectral and Spatial Resolution MR Images in Vitro: Implications for Classification‐Based Synthetic CT Algorithm

Purpose:To investigate features of spectral parameters of tissue for use in a synthetic CT algorithm.Methods:A phantom of fresh beef leg embedded in 1% agarose gel was imaged at 1.5T on a Siemens Aero using HiSS MRI with 1.0mm resolution and 11.1Hz spectral resolution. Post‐processing was performed off‐line and included labeling of fat and water peaks, and fitting the spectra. All spectra were normalized by the noise within each voxel; thus all parameters are reported in units of signal‐to‐noise (SNR). Images of the peak height (PH) and peak integral (PI) of both the water and fat resonances were analyzed. Several regions‐of‐interest (ROIs) were identified: bone marrow, cortical bone, adipose tissue, muscle, agar gel, and air. Distributions and scatterplots were generated. Water PH in cortical bone was compared to air using a t‐test. Composition of the various ROIs was also reported.Results:Bone marrow was 97% fat (mean PH=4.5SNR). Adipose tissue was mostly mixed fat/water voxels (66%); mean fat and water PH were 4.1 and 7.8 SNR, respectively. Cortical bone was 70% water (PH=2.3SNR). Muscle was 85% water (PH=4.2SNR, with fat PH=1.6SNR). For the air ROI, mean fat and water PH were 1.1SNR and 1.1SNR, respectively. The scatterplot of PH (water vs. fat) showed fair separation of bone marrow and adipose tissue. Water vs. fat PI scatterplot showed good separation of muscle and cortical bone. Cortical bone water PH was significantly different than air (p&lt;0.05). A scatterplot of the water PH vs. pixel value of a summation of the first three echoes showed a different distribution with slightly better separation of air and bone.Conclusion:This study shows promising results for utilizing HiSS imaging in a classification‐based syn‐CT algorithm. Reducing early echo times would improve SNR of bone and will be investigated along with further optimization.

Separation of collagen-bound and porous bone water transverse relaxation in mice: proposal of a multi-step approach.

The separation and quantification of collagen-bound water (CBW) and pore water (PW) components of the cortical bone signal are important because of their different contribution to bone mechanical properties. Ultrashort TE (UTE) imaging can be used to exploit the transverse relaxation from CBW and PW, allowing their quantification. We tested, for the first time, the feasibility of UTE measurements in mice for the separation and quantification of the transverse relaxation of CBW and PW in vivo using three different approaches for T2 * determination. UTE sequences were acquired at 4.7 T in six mice with 10 different TEs (50-5000 μs). The transverse relaxation time T2 * of CBW (T2 *cbw ) and PW (T2 *pw ) and the CBW fraction (bwf) were computed using a mono-exponential (i), a standard bi-exponential (ii) and a new multi-step bi-exponential (iii) approach. Regions of interest were drawn at multiple levels of the femur and vertebral body cortical bone for each mouse. The sum of the normalized squared residuals (Res) and the homogeneity of variance were tested to compare the different methods. In the femur, approach (i) yielded mean T2 * ± standard deviation (SD) of 657 ± 234 μs. With approach (ii), T2 *cbw , T2 *pw and bwf were 464 ± 153 μs, 15 777 ± 10 864 μs and 57.6 ± 9.9%, respectively. For approach (iii), T2 *cbw , T2 *pw and bwf were 387 ± 108 μs, 7534 ± 2765 μs and 42.5 ± 6.2%, respectively. Similar values were obtained from vertebral bodies. Res with approach (ii) was lower than with the two other approaches (p <0.007), but T2 *pw and bwf variance was lower with approach (iii) than with approach (ii) (p <0.048). We demonstrated that the separation and quantification of cortical bone water components with UTE sequences is feasible in vivo in mouse models. The direct bi-exponential approach exhibited the best approximation to the measured signal curve with the lowest residuals; however, the newly proposed multi-step algorithm resulted in substantially lower variability of the computed parameters. Copyright © 2016 John Wiley & Sons, Ltd.

Evaluation of bound and pore water in cortical bone using ultrashort-TE MRI

Bone water exists in different states with the majority bound to the organic matrix and to mineral, and a smaller fraction in 'free' form in the pores of cortical bone. In this study, we aimed to develop and evaluate ultrashort-TE (UTE) MRI techniques for the assessment of T2*, T1 and concentration of collagen-bound and pore water in cortical bone using a 3-T clinical whole-body scanner. UTE MRI, together with an isotope study using tritiated and distilled water (THO-H2O) exchange, as well as gravimetric analysis, were performed on ten sectioned bovine bone samples. In addition, 32 human cortical bone samples were prepared for comparison between the pore water concentration measured with UTE MRI and the cortical porosity derived from micro-computed tomography (μCT). A short T2* of 0.27 ± 0.03 ms and T1 of 116 ± 6 ms were observed for collagen-bound water in bovine bone. A longer T2* of 1.84 ± 0.52 ms and T1 of 527 ± 28 ms were observed for pore water in bovine bone. UTE MRI measurements showed a pore water concentration of 4.7-5.3% by volume and collagen-bound water concentration of 15.7-17.9% in bovine bone. THO-H2O exchange studies showed a pore water concentration of 5.9 ± 0.6% and collagen-bound water concentration of 18.1 ± 2.1% in bovine bone. Gravimetric analysis showed a pore water concentration of 6.3 ± 0.8% and collagen-bound water concentration of 19.2 ± 3.6% in bovine bone. A mineral water concentration of 9.5 ± 0.6% was derived in bovine bone with the THO-H2O exchange study. UTE-measured pore water concentration is highly correlated (R(2) = 0.72, p < 0.0001) with μCT porosity in the human cortical bone study. Both bovine and human bone studies suggest that UTE sequences could reliably measure collagen-bound and pore water concentration in cortical bone using a clinical scanner.

The Behavior of Water in Collagen and Hydroxyapatite Sites of Cortical Bone: Fracture, Mechanical Wear, and Load Bearing Studies.

The mechanical properties of cortical bone, which is largely comprised of collagen, hydroxyapatite, and water, are known to hinge on hydration. Recently, the characteristics of water in bone have drawn attention as potential markers of bone quality. We report on the dynamics, diffusion, population, and exchange of water in cortical bone by NMR relaxation and diffusion methodologies. Relaxation measurements over timescales ranging from 0.001 to 4.2 s reveal two distinguishable water environments. Systematic exposure to ethylenediaminetetraacetic acid or collagenase reveals one peak in our 2D relaxation map belonging to water present in the hydroxyapatite rich environment, and a second peak with shorter relaxation times arising from a collagen rich site. Diffusion-T2 measurements allowed for direct measurement of the diffusion coefficient of water in all observable reservoirs. Further, deuterium relaxation methods were applied to study cortical bone under an applied force, following mechanical wear or fracture. The tumbling correlation times of water reduce in all three cases, indicating that water dynamics may be used as a probe of bone quality. Lastly, changes in the relative populations and correlation times of water in bone under an applied force suggest that load bearing occurs largely in the collagen rich environment and is reversible.

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

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. 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. 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. 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.

Effects of inversion time on inversion recovery prepared ultrashort echo time (IR‐UTE) imaging of bound and pore water in cortical bone

Water is present in cortical bone in different binding states. In this study we aimed to investigate the effects of inversion time (TI) on the signal from bound and pore water in cortical bone using an adiabatic inversion recovery prepared ultrashort echo time (IR-UTE) sequence on a clinical 3 T scanner. In total ten bovine midshaft samples and four human tibial midshaft samples were harvested for this study. Each cortical sample was imaged with the UTE and IR-UTE sequences with a TR of 300 ms and a series of TI values ranging from 10 to 240 ms. Five healthy volunteers were also imaged with the same sequence. Single- and bi-component models were utilized to calculate the T2 * and relative fractions of short and long T2 * components. Bi-component behavior of the signal from cortical bone was seen with the IR-UTE sequence, except with a TI of around 80 ms, where the short T2 * component alone were seen and a mono-exponential decay pattern was observed. In vivo imaging with the IR-UTE sequence provided high contrast-to-noise images with direct visualization of bound water and reduced signal from long T2 muscle and fat. Our preliminary results demonstrate that selective nulling of the pore water component can be achieved with the IR-UTE sequence with an appropriate TI, allowing selective imaging of the bound water component in cortical bone in vivo using clinical MR scanners.

Cortical bone water changes in ovariectomized rats during the early postoperative period: Objective evaluation using sweep imaging with Fourier transform.

To evaluate the cortical bone signal-to-noise ratio (SNR) in ovariectomized (OVX) rats during the early postoperative period as a method to measure bone quality using the sweep imaging with Fourier transform (SWIFT) technique. Twelve-week-old female Sprague-Dawley rats (n = 64) were divided into sham and OVX groups. Preoperative tetracycline was immediately administered subcutaneously to distinguish new cortical bone area, and tibial samples were collected at 2, 4, 8, and 12 weeks postoperatively. Magnetic resonance imaging (MRI) was performed using proton density-weighted imaging (PDWI) and SWIFT to obtain cross-sectional images of the tibial diaphysis. The cortical bone SNR was calculated. Bone histomorphometry was performed. Histomorphometry findings showed that the new bone area was significantly greater at 8 and 12 weeks postoperatively in the OVX group (P < 0.05) while the porosity area decreased gradually in both groups (P < 0.001). The difference of SNR receiving PDWI did not reach statistical significance (P = 0.057). The SWIFT technique showed that the SNR was significantly higher at 8 and 12 weeks postoperatively in the OVX group (P < 0.05) and was correlated with the new bone area (R(2) = 0.430). The SWIFT findings suggest that the SWIFT technique may depict early changes in cortical bone quality.

Cortical Bone Water Concentration: Dependence of MR Imaging Measures on Age and Pore Volume Fraction

To quantify bulk bone water to test the hypothesis that bone water concentration (BWC) is negatively correlated with bone mineral density (BMD) and is positively correlated with age, and to propose the suppression ratio (SR) (the ratio of signal amplitude without to that with long-T2 suppression) as a potentially stronger surrogate measure of porosity, which is evaluated ex vivo and in vivo. Human subject studies were conducted in compliance with institutional review board and HIPAA regulations. Healthy men and women (n = 72; age range, 20-80 years) were examined with a hybrid radial ultrashort echo time magnetic resonance (MR) imaging sequence at 3.0 T, and BWC was determined in the tibial midshaft. In a subset of 40 female subjects, the SR was measured with a similar sequence. Cortical volumetric BMD (vBMD) was measured by means of peripheral quantitative computed tomography (CT). The method was validated against micro-CT-derived porosity in 13 donor human cortical bone specimens. Associations among parameters were evaluated by using standard statistical tools. BWC was positively correlated with age (r = 0.52; 95% confidence interval [CI]: 0.22, 0.73; P = .002) and negatively correlated with vBMD at the same location (r = -0.57; 95% CI: -0.76, -0.29; P < .001). Data were suggestive of stronger associations with SR (r = 0.64, 95% CI: 0.39, 0.81, P < .001 for age; r = -0.67, 95% CI: -0.82, -0.43, P < .001 for vBMD; P < .001 for both), indicating that SR may be a more direct measure of porosity. This interpretation was supported by ex vivo measurements showing SR to be strongly positively correlated with micro-CT porosity (r = 0.88; 95% CI: 0.64, 0.96; P < .001) and with age (r = 0.87; 95% CI: 0.62, 0.96; P < .001). The MR imaging-derived SR may serve as a biomarker for cortical bone porosity that is potentially superior to BWC, but corroboration in larger cohorts is indicated.

The effect of excitation and preparation pulses on nonslice selective 2D UTE bicomponent analysis of bound and free water in cortical bone at 3T

The purpose of this study was to investigate the effect of excitation, fat saturation, long T2 saturation, and adiabatic inversion pulses on ultrashort echo time (UTE) imaging with bicomponent analysis of bound and free water in cortical bone for potential applications in osteoporosis. Six bovine cortical bones and six human tibial midshaft samples were harvested for this study. Each bone sample was imaged with eight sequences using 2D UTE imaging at 3T with half and hard excitation pulses, without and with fat saturation, long T2 saturation, and adiabatic inversion recovery (IR) preparation pulses. Single- and bicomponent signal models were utilized to calculate the T2(*)s and/or relative fractions of short and long T2(*)s. For all bone samples UTE T2(*) signal decay showed bicomponent behavior. A higher short T2(*) fraction was observed on UTE images with hard pulse excitation compared with half pulse excitation (75.6% vs 68.8% in bovine bone, 79.9% vs 73.2% in human bone). Fat saturation pulses slightly reduced the short T2(*) fraction relative to regular UTE sequences (5.0% and 2.0% reduction, respectively, with half and hard excitation pulses for bovine bone, 6.3% and 8.2% reduction, respectively, with half and hard excitation pulses for human bone). Long T2 saturation pulses significantly reduced the long T2(*) fraction relative to regular UTE sequence (18.9% and 17.2% reduction, respectively, with half and hard excitation pulses for bovine bone, 26.4% and 27.7% reduction, respectively, with half and hard excitation pulses for human bone). With IR-UTE preparation the long T2(*) components were significantly reduced relative to regular UTE sequence (75.3% and 66.4% reduction, respectively, with half and hard excitation pulses for bovine bone, 87.7% and 90.3% reduction, respectively, with half and hard excitation pulses for human bone). Bound and free water T2(*)s and relative fractions can be assessed using UTE bicomponent analysis. Long T2(*) components are affected more by long T2 saturation and IR pulses, and short T2(*) components are affected more by fat saturation pulses.

Assessment of cortical bone with clinical and ultrashort echo time sequences

We describe the use of ultrashort echo time (UTE) sequences and fast spin echo sequences to assess cortical bone using a clinical 3T scanner. Regular two- and three-dimensional UTE sequences were used to image both bound and free water in cortical bone. Adiabatic inversion recovery prepared UTE sequences were used to image water bound to the organic matrix. Two-dimensional fast spin echo sequences were used to image free water. Regular UTE sequences were used together with bicomponent analysis to measure T*2s and relative fractions of bound and free water components in cortical bone. Inversion recovery prepared UTE sequences were used to measure the T*2 of bound water. Saturation recovery UTE sequences were used to measure the T1 of bone water. Eight cadaveric human cortical bone samples and a lower leg specimen were studied. Preliminary results show two distinct components in UTE detected signal decay, a single component in inversion recovery prepared UTE detected signal decay, and a single component in saturation recovery UTE detected signal recovery. Regular UTE sequences appear to depict both bound and free water in cortical bone. Inversion recovery prepared UTE sequences appear to depict water bound to the organic matrix. Two-dimensional fast spin echo sequences appear to depict bone structure corresponding to free water in large pores.

Deuterium nuclear magnetic resonance unambiguously quantifies pore and collagen-bound water in cortical bone

Bone water (BW) plays a pivotal role in nutrient transport and conferring bone with its viscoelastic mechanical properties. BW is partitioned between the pore spaces of the Haversian and lacuno-canalicular system, and water predominantly bound to the matrix proteins (essentially collagen). The general model of BW is that the former predominantly experiences fast isotropic molecular reorientation, whereas water in the bone matrix undergoes slower anisotropic rotational diffusion. Here, we provide direct evidence for the correctness of this model and show that unambiguous quantification in situ of these two functionally and dynamically different BW fractions is possible. The approach chosen relies on nuclear magnetic resonance (NMR) of deuterium ((2) H) that unambiguously separates and quantifies the two fractions on the basis of their distinguishing microdynamic properties. Twenty-four specimens of the human tibial cortex from 6 donors (3 male, 3 female, ages 27-83 years) were cored and (2) H spectra recorded at 62 MHz (9.4 Tesla) on a Bruker Instruments DMX 400 spectrometer after exchange of native BW with (2) H(2) O. Spectra consisted of a doublet signal resulting from quadrupole interaction of water bound to collagen. Doublet splittings were found to depend on the orientation of the osteonal axis with respect to the magnetic field direction (8.2 and 4.3 kHz for parallel and perpendicular orientation, respectively). In contrast, the isotropically reorienting pore-resident water yielded a single resonance line superimposed on the doublet. Nulling of the singlet resonance allowed separation of the two fractions. The results indicate that in human cortical bone 60% to 80% of detectable BW is collagen-bound. Porosity determined as the difference between total BW and collagen bound water fraction was found to strongly parallel micro-computed tomography (µCT)-based measurements (R(2) = 0.91). Our method provides means for direct validation of emerging relaxation-based measurements of cortical bone porosity by proton MRI.

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.