Alan C. Seifert

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

PURPOSE 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. MATERIALS AND METHODS 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. RESULTS 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). CONCLUSION 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.

Bone mineral (31)P and matrix-bound water densities measured by solid-state (31)P and (1)H MRI.

Bone is a composite material consisting of mineral and hydrated collagen fractions. MRI of bone is challenging because of extremely short transverse relaxation times, but solid‐state imaging sequences exist that can acquire the short‐lived signal from bone tissue. Previous work to quantify bone density via MRI used powerful experimental scanners. This work seeks to establish the feasibility of MRI‐based measurement on clinical scanners of bone mineral and collagen‐bound water densities, the latter as a surrogate of matrix density, and to examine the associations of these parameters with porosity and donors’ age.

Bi-component T2* analysis of bound and pore bone water fractions fails at high field strengths

Osteoporosis involves the degradation of the bones trabecular architecture, cortical thinning and enlargement of cortical pores. Increased cortical porosity is a major cause of the decreased strength of osteoporotic bone. The majority of cortical pores, however, are below the resolution limit of MRI. Recent work has shown that porosity can be evaluated by MRI‐based quantification of bone water. Bi‐exponential T2* fitting and adiabatic inversion preparation are the two most common methods purported to distinguish bound and pore water in order to quantify matrix density and porosity. To assess the viability of T2* bi‐component analysis as a method for the quantification of bound and pore water fractions, we applied this method to human cortical bone at 1.5, 3, 7 and 9.4 T, and validated the resulting pool fractions against micro‐computed tomography‐derived porosity and gravimetrically determined bone densities. We also investigated alternative methods: two‐dimensional T1–T2* bi‐component fitting by incorporation of saturation recovery, one‐ and two‐dimensional fitting of Carr–Purcell–Meiboom–Gill (CPMG) echo amplitudes, and deuterium inversion recovery. The short‐T2* pool fraction was moderately correlated with porosity (R2 = 0.70) and matrix density (R2 = 0.63) at 1.5 T, but the strengths of these associations were found to diminish rapidly as the field strength increased, falling below R2 = 0.5 at 3 T. The addition of the T1 dimension to bi‐component analysis only slightly improved the strengths of these correlations. T2*‐based bi‐component analysis should therefore be used with caution. The performance of deuterium inversion recovery at 9.4 T was also poor (R2 = 0.50 vs porosity and R2 = 0.46 vs matrix density). The CPMG‐derived short‐T2 fraction at 9.4 T, however, was highly correlated with porosity (R2 = 0.87) and matrix density (R2 = 0.88), confirming the utility of this method for independent validation of bone water pools. Copyright

31P NMR relaxation of cortical bone mineral at multiple magnetic field strengths and levels of demineralization

Recent work has shown that solid‐state 1H and 31P MRI can provide detailed insight into bone matrix and mineral properties, thereby potentially enabling differentiation of osteoporosis from osteomalacia. However, 31P MRI of bone mineral is hampered by unfavorable relaxation properties. Hence, accurate knowledge of these properties is critical to optimizing MRI of bone phosphorus. In this work, 31P MRI signal‐to‐noise ratio (SNR) was predicted on the basis of T1 and T2* (effective transverse relaxation time) measured in lamb bone at six field strengths (1.5–11.7 T) and subsequently verified by 3D ultra‐short echo‐time and zero echo‐time imaging. Further, T1 was measured in deuterium‐exchanged bone and partially demineralized bone. 31P T2* was found to decrease from 220.3 ± 4.3 µs to 98.0 ± 1.4 µs from 1.5 to 11.7 T, and T1 to increase from 12.8 ± 0.5 s to 97.3 ± 6.4 s. Deuteron substitution of exchangeable water showed that 76% of the 31P longitudinal relaxation rate is due to 1H–31P dipolar interactions. Lastly, hypomineralization was found to decrease T1, which may have implications for 31P MRI based mineralization density quantification. Despite the steep decrease in the T2*/T1 ratio, SNR should increase with field strength as B00.4 for sample‐dominated noise and as B01.1 for coil‐dominated noise. This was confirmed by imaging experiments. Copyright

Selective in vivo bone imaging with long-T2 suppressed PETRA MRI

To design and evaluate an optimized PETRA (point‐wise encoding time reduction with radial acquisition) sequence with long‐T2 suppression at 3 Tesla.

Correction of Excitation Profile in Zero Echo Time (ZTE) Imaging Using Quadratic Phase-Modulated RF Pulse Excitation and Iterative Reconstruction

Zero-echo Time (ZTE) imaging is a promising technique for magnetic resonance imaging (MRI) of short-T2 tissue nuclei in tissues. A problem inherent to the method currently hindering its translation to the clinic is the presence of a spatial encoding gradient during excitation, which causes the hard pulse to become spatially selective, resulting in blurring and shadow artifacts in the image. While shortening radio-frequency (RF) pulse duration alleviates this problem the resulting elevated RF peak power and specific absorption rate (SAR) in practice impede such a solution. In this work, an approach is described to correct the artifacts by applying quadratic phase-modulated RF excitation and iteratively solving an inverse problem formulated from the signal model of ZTE imaging. A simple pulse sequence is also developed to measure the excitation profile of the RF pulse. Results from simulations, phantom and in vivo studies, demonstrate the effectiveness of the method in correcting image artifacts caused by inhomogeneous excitation. The proposed method may contribute toward establishing ZTE MRI as a routine 3D pulse sequence for imaging protons and other nuclei with quasi solid-state behavior on clinical scanners.

A Surrogate Measure of Cortical Bone Matrix Density by Long T2‐Suppressed MRI

Magnetic resonance has the potential to image and quantify two pools of water within bone: free water within the Haversian pore system (transverse relaxation time, T2> 1 ms), and water hydrogen‐bonded to matrix collagen (T2 ∼ 300 to 400 μs). Although total bone water concentration quantified by MRI has been shown to scale with porosity, greater insight into bone matrix density and porosity may be gained by relaxation‐based separation of bound and pore water fractions. The objective of this study was to evaluate a recently developed surrogate measurement for matrix density, single adiabatic inversion recovery (SIR) zero echo‐time (ZTE) MRI, in human bone. Specimens of tibial cortical bone from 15 donors (aged 27 to 97 years; 8 female and 7 male) were examined at 9.4T field strength using two methods: (1) 1H ZTE MRI, to capture total 1H signal, and (2) 1H SIR‐ZTE MRI, to selectively image matrix‐associated 1H signal. Total water, bone matrix, and bone mineral densities were also quantified gravimetrically, and porosity was measured by micro‐CT. ZTE apparent total water 1H concentration was 32.7 ± 3.2 M (range 28.5 to 40.3 M), and was correlated positively with porosity (R2 = 0.80) and negatively with matrix and mineral densities (R2 =  0.90 and 0.82, respectively). SIR‐ZTE apparent bound water 1H concentration was 32.9 ± 3.9 M (range 24.4 to 39.8 M), and its correlations were opposite to those of apparent total water: negative with porosity (R2 = 0.73) and positive with matrix density (R2 = 0.74) and mineral density (R2 = 0.72). Porosity was strongly correlated with gravimetric matrix density (R2 = 0.91, negative) and total water density (R2 = 0.92, positive). The strong correlations of SIR‐ZTE‐derived apparent bound water 1H concentration with ground‐truth measurements suggest that this quantitative solid‐state MRI method provides a nondestructive surrogate measure of bone matrix density.

Correction: Feasibility of assessing bone matrix and mineral properties in vivo by combined solid-state 1H and 31P MRI

[This corrects the article DOI: 10.1371/journal.pone.0173995.].

Towards quantification of myelin by solid-state MRI of the lipid matrix protons

Purpose: Direct assessment of myelin has the potential to reveal central nervous system abnormalities and serve as a means to follow patients with demyelinating disorders during treatment. Here, we investigated the feasibility of direct imaging and quantification of the myelin proton pool, without the many possible confounds inherent to indirect methods, via long‐T2 suppressed 3D ultra‐short echo‐time (UTE) and zero echo‐time (ZTE) MRI in ovine spinal cord. Methods: ZTE and UTE experiments, with and without inversion‐recovery (IR) preparation, were conducted in ovine spinal cords before and after D2O exchange of tissue water, on a 9.4T vertical‐bore micro‐imaging system, along with some feasibility experiments on a 3T whole‐body scanner. Myelin density was quantified relative to reference samples containing various mass fractions of purified myelin lipid, extracted via the sucrose gradient extraction technique, and reconstituted by suspension in water, where they spontaneously self‐assemble into an ensemble of multi‐lamellar liposomes, analogous to native myelin. Results: MR signal amplitudes from reference samples at 9.4T were linearly correlated with myelin concentration (R2 = 0.98–0.99), enabling their use in quantification of myelin fraction in neural tissues. An adiabatic inversion‐recovery preparation was found to effectively suppress long‐T2 water signal in white matter, leaving short‐T2 myelin protons to be imaged. Estimated myelin lipid fractions in white matter were 19.9%–22.5% in the D2O‐exchanged spinal cord, and 18.1%–23.5% in the non‐exchanged spinal cord. Numerical simulations based on the myelin spectrum suggest that approximately 4.59% of the total myelin proton magnetization is observable by IR‐ZTE at 3T due to T2 decay and the inability to excite the shortest T2* components. Approximately 380 &mgr;m of point‐spread function blurring is predicted, and ZTE images of the spinal cord acquired at 3T were consistent with this estimate. Conclusion: In the present implementation, IR‐UTE at 9.4T produced similar estimates of myelin concentration in D2O‐exchanged and non‐exchanged spinal cord white matter. 3T data suggest that direct myelin imaging is feasible, but remaining challenging on clinical MR systems. Highlights9.4T spinal cord myelin density maps show expected contrast between GM and WM.IR‐preparation suppression pulses effectively suppress long‐T2 signal in white matter.Myelin densities measured in white matter are in the range of 18.1%–23.5%.Myelin density measurements are consistent in non‐exchanged and D2O‐exchanged cords.Feasibility of direct myelin imaging with ZTE was shown on a 3T clinical scanner.