Jeremy F. Magland

In vivo magnetic resonance detects rapid remodeling changes in the topology of the trabecular bone network after menopause and the protective effect of estradiol.

Introduction: Estrogen depletion after menopause is accompanied by bone loss and architectural deterioration of trabecular bone. The hypothesis underlying this work is that the μMRI‐based virtual bone biopsy can capture the temporal changes of scale and topology of the trabecular network and that estrogen supplementation preserves the integrity of the trabecular network.

Accuracy of High-Resolution In Vivo Micro Magnetic Resonance Imaging for Measurements of Microstructural and Mechanical Properties of Human Distal Tibial Bone

Micro magnetic resonance imaging (µMRI) is an in vivo imaging method that permits 3D quantification of cortical and trabecular bone microstructure. µMR images can also be used for building microstructural finite element (µFE) models to assess bone stiffness, which highly correlates with bones resistance to fractures. In order for µMRI‐based microstructural and µFE analyses to become standard clinical tools for assessing bone quality, validation with a current gold standard, namely, high‐resolution micro computed tomography (µCT), is required. Microstructural measurements of 25 human cadaveric distal tibias were performed for the registered µMR and µCT images, respectively. Next, whole bone stiffness, trabecular bone stiffness, and elastic moduli of cubic subvolumes of trabecular bone in both µMR and µCT images were determined by voxel‐based µFE analysis. The bone volume fraction (BV/TV), trabecular number (Tb.N*), trabecular spacing (Tb.Sp*), cortical thickness (Ct.Th), and structure model index (SMI) based on µMRI showed strong correlations with µCT measurements (r2 = 0.67 to 0.97), and bone surface‐to‐volume ratio (BS/BV), connectivity density (Conn.D), and degree of anisotropy (DA) had significant but moderate correlations (r2 = 0.33 to 0.51). Each of these measurements also contributed to one or many of the µFE‐predicted mechanical properties. However, model‐independent trabecular thickness (Tb.Th*) based on µMRI had no correlation with the µCT measurement and did not contribute to any mechanical measurement. Furthermore, the whole bone and trabecular bone stiffness based on µMRI were highly correlated with those of µCT images (r2 = 0.86 and 0.96), suggesting that µMRI‐based µFE analyses can directly and accurately quantify whole bone mechanical competence. In contrast, the elastic moduli of the µMRI trabecular bone subvolume had significant but only moderate correlations with their gold standards (r2 = 0.40 to 0.58). We conclude that most microstructural and mechanical properties of the distal tibia can be derived efficiently from µMR images and can provide additional information regarding bone quality.

Rapid magnetic resonance measurement of global cerebral metabolic rate of oxygen consumption in humans during rest and hypercapnia

The effect of hypercapnia on cerebral metabolic rate of oxygen consumption (CMRO2) has been a subject of intensive investigation and debate. Most applications of hypercapnia are based on the assumption that a mild increase in partial pressure of carbon dioxide has negligible effect on cerebral metabolism. In this study, we sought to further investigate the vascular and metabolic effects of hypercapnia by simultaneously measuring global venous oxygen saturation (SvO2) and total cerebral blood flow (tCBF), with a temporal resolution of 30 seconds using magnetic resonance susceptometry and phase-contrast techniques in 10 healthy awake adults. While significant increases in SvO2 and tCBF were observed during hypercapnia (P < 0.005), no change in CMRO2 was noted (P > 0.05). Additionally, fractional changes in tCBF and end-tidal carbon dioxide (R2 = 0.72, P < 0.005), as well as baseline SvO2 and tCBF (R2 = 0.72, P < 0.005), were found to be correlated. The data also suggested a correlation between cerebral vascular reactivity (CVR) and baseline tCBF (R2 = 0.44, P = 0.052). A CVR value of 6.1% ± 1.6%/mm Hg was determined using a linear-fit model. Additionally, an average undershoot of 6.7% ± 4% and 17.1% ± 7% was observed in SvO2 and tCBF upon recovery from hypercapnia in six subjects.

Micro–MR Imaging–based Computational Biomechanics Demonstrates Reduction in Cortical and Trabecular Bone Strength after Renal Transplantation

PURPOSE To examine the ability of three-dimensional micro-magnetic resonance (MR) imaging-based computational biomechanics to detect mechanical alterations in trabecular bone and cortical bone in the distal tibia of incident renal transplant recipients 6 months after renal transplantation and compare them with bone mineral density (BMD) outcomes. MATERIALS AND METHODS The study was approved by the institutional review board and complied with HIPAA guidelines. Written informed consent was obtained from all subjects. Micro-MR imaging of distal tibial metaphysis was performed within 2 weeks after renal transplantation (baseline) and 6 months later in 49 participants (24 female; median age, 44 years; range, 19-61 years) with a clinical 1.5-T whole-body imager using a modified three-dimensional fast large-angle spin-echo pulse sequence. Micro-finite-element models for cortical bone, trabecular bone, and whole-bone section were generated from each image by delineating the endosteal and periosteal boundaries. Mechanical parameters (stiffness and failure load) were estimated with simulated uniaxial compression tests on the micro-finite-element models. Structural parameters (trabecular bone volume fraction [BV/TV, bone volume to total volume ratio], trabecular thickness [TbTh], and cortical thickness [CtTh]) were computed from micro-MR images. Total hip and spine areal BMD were determined with dual-energy x-ray absorptiometry (DXA). Parameters obtained at the follow-up were compared with the baseline values by using parametric or nonparametric tests depending on the normality of data. RESULTS All mechanical parameters were significantly lower at 6 months compared with baseline. Decreases in cortical bone, trabecular bone, and whole-bone stiffness were 3.7% (P = .03), 4.9% (P = .03), and 4.3% (P = .003), respectively. Decreases in cortical bone, trabecular bone, and whole-bone failure strength were 7.6% (P = .0003), 6.0% (P = .004), and 5.6% (P = .0004), respectively. Conventional structural measures, BV/TV, TbTh, and CtTh, did not change significantly. Spine BMD decreased by 2.9% (P < .0001), while hip BMD did not change significantly at DXA. CONCLUSION MR imaging-based micro-finite-element analysis suggests that stiffness and failure strength of the distal tibia decrease over a 6-month interval after renal transplantation.

Retrospective correction for induced magnetic field inhomogeneity in measurements of large-vessel hemoglobin oxygen saturation by MR susceptometry.

MR susceptometry‐based blood oximetry relies on phase mapping to measure the difference in magnetic susceptibility between intravascular blood and surrounding tissue. The main source of error in MR susceptometry is the static field inhomogeneity caused by an interface between air and tissue or between adjacent tissue types. High‐pass filtering has previously been used in conjunction with shimming to reduce the effect of low spatial‐frequency modulations of the phase caused by large‐scale induced magnetic fields. We demonstrate that high‐pass filtering is not optimum for MR susceptometry because the results are sensitive to filter size. We propose an alternative method that acquires data without scanner‐implemented default shimming, and fits, after appropriate weighting and masking, the static field inhomogeneity to a second‐order polynomial. Compared to shimming the retrospective correction technique improved agreement between hemoglobin saturations measured in different segments of a vessel (femoral versus popliteal artery and vein) from three standard errors to less than one. Magn Reson Med, 2008.

Quantifying cortical bone water in vivo by three-dimensional ultra-short echo-time MRI

Bone contains a significant fraction of water that is not detectable with ordinary Cartesian imaging sequences. The advent of ultra‐short echo‐time (UTE) methods has allowed the recovery of this submillisecond T2* water. In this work, we have developed a new three‐dimensional hybrid‐radial ultra‐short echo‐time (3D HRUTE) imaging technique based on slab selection by means of half‐sinc pulses, variable‐TE slice encoding and algorithms for quantification. The protocol consists of collecting two datasets differing in TR, from which T1 is extracted, which is needed for quantification. Unlike T2*, which has been found to vary within a narrow range and does not require individual correction, T1 is critically subject dependent (range, 100–350 ms). No soft‐tissue suppression was used to preserve the signal‐to‐noise ratio of the short‐T2 bone water protons or to minimize the loss of relatively mobile water in large pores. Critical for quantification is correction for spatial variations in reception field and selection of the endosteal boundary for inclusion of pixels in the bone water calculation, because of the ruffled boundary stemming from trabecularization of the endosteal surface. The reproducibility, evaluated in 10 subjects covering the age range 30–80 years, yielded an average coefficient of variation of 4.2% and an intraclass correlation coefficient of 0.95, suggesting that a treatment effect on the order of 5% could be detected in as few as 10 subjects. Lastly, experiments in specimens by means of graded deuterium exchange showed that approximately 90% of the detected signal arises from water protons, whose relaxation rates (1/T1 and 1/T2*) scale linearly with the isotopic volume fraction of light water after stepwise exchange with heavy water. The data thus show conclusively that the method quantifies water even though, in vivo, no distinction can be made between various fractions, such as collagen‐bound vs pore‐resident water. Copyright

Ultra-short echo-time MRI detects changes in bone mineralization and water content in OVX rat bone in response to alendronate treatment

In this work we hypothesize that bisphosphonate treatment following ovariectomy manifests in increased phosphorus and decreased water concentration, both quantifiable nondestructively with ultra-short echo-time (UTE) (31)P and (1)H-MRI techniques. We evaluated this hypothesis in ovariectomized (OVX) rats undergoing treatment with two regimens of alendronate. Sixty female four-month-old rats were divided into four groups of 15 animals each: ovariectomized (OVX), OVX treatment groups ALN1 and ALN2, receiving 5 microg/kg/day and 25 microg/kg/day of alendronate, and a sham-operated group (NO) serving as control. Treatment, starting 1 week post-surgery, lasted for 50 days at which time animals were sacrificed. Whole bones from the left and right femora were extracted from all the animals. (31)P and (1)H water concentration were measured by UTE MRI at 162 and 400 MHz in the femoral shaft and the results compared with other measures of mineral and matrix properties obtained by (31)P solution NMR, CT density, ash weight, and water measured by dehydration. Mechanical parameters (elastic modulus, EM, and ultimate strength, US) were obtained by three-point bending. The following quantities were lower in OVX relative to NO: phosphorus concentration measured by (31)P-MRI (-8%; 11.4+/-0.9 vs. 12.4+/-0.8%, p<0.005), (31)P-NMR (-4%; 12.8+/-0.4 vs. 13.3+/-0.8 %, p<0.05) and micro-CT density (-2.5%; 1316+/-34 vs. 1349+/-32 mg/cm(3), p=0.005). In contrast, water concentration by (1)H-MRI was elevated in OVX relative to NO (+6%; 15.5+/-1.7 vs. 14.6+/-1.4 %, p<0.05). Alendronate treatment increased phosphorus concentration and decreased water concentration in a dose-dependent manner, the higher dose yielding significant changes relative to values found in OVX animals: (31)P-MRI (+14%; p<0.0001), (31)P-NMR (+9%; p<0.0001), ash content (+1.5%; p<0.005), micro-CT mineralization density (+2.8%; p<0.05), and (1)H-MRI, (-19%, p<0.0001). The higher dose raised phosphorus concentration above and water concentration below NO levels: (31)P-MRI (+6%; p<0.05), (31)P-NMR (+5%; p=0.01), ash content (+1.5%; p=0.005), (1)H-MRI (-14%; p<0.0001), and drying water (-10%; p<0.0005). Finally, the group means of phosphorus concentration were positively correlated with EM and US (R(2)> or =0.98, p<0.001 to p<0.05) even though the pooled data from individual animals were not. The results highlight the implications of estrogen depletion and bisphosphonate treatment on mineral composition and mechanical properties and the potential of solid-state MR imaging to detect these changes in situ in an animal model of rat ovariectomy.

Computational biomechanics of the distal tibia from high-resolution MR and micro-CT images

The mechanical properties of bone estimated by micro-finite element (microFE) analysis on the basis of in vivo micro-MR images (microMRIs) of the distal extremities provide a new tool for direct assessment of the mechanical consequences of intervention. However, the accuracy of the method has not previously been investigated. Here, we compared microFE-derived mechanical parameters obtained from microMRIs at 160 microm isotropic voxel size now achievable in vivo with those derived from 25 microm isotropic (reference) microCT images of 30 cadaveric tibiae from 15 donors (4 females and 11 males, aged 55-84 years). Elastic and shear moduli estimated from 5mm(3) subvolumes of trabecular bone (TB) derived from microMRIs were significantly correlated with those derived from volume-matched reference microCT images (R(2)=0.60-0.67). Axial stiffness of whole-bone sections (including both cortical and trabecular compartments) derived from microMR-based models were highly correlated (R(2)=0.85) with those from high-resolution reference images. Further, microFE models generated from microCT images after downsampling to lower resolutions relevant to in vivo microMRI (100-160 microm) showed mechanical parameters to be strongly correlated (R(2)>0.93) with those derived at reference resolution (25 microm). Incorporation of grayscale image information into the microMR-based microFE model yielded slopes closer to unity than binarized models (1.07+/-0.15 vs. 0.71+/-0.11) when correlated with reference subregional elastic and shear moduli. This work suggests that elastic properties of distal tibia can be reliably estimated by microFE analysis from microMRIs obtainable at in vivo resolution.

Accuracy and precision of MR blood oximetry based on the long paramagnetic cylinder approximation of large vessels

An accurate noninvasive method to measure the hemoglobin oxygen saturation (%HbO2) of deep‐lying vessels without catheterization would have many clinical applications. Quantitative MRI may be the only imaging modality that can address this difficult and important problem. MR susceptometry–based oximetry for measuring blood oxygen saturation in large vessels models the vessel as a long paramagnetic cylinder immersed in an external field. The intravascular magnetic susceptibility relative to surrounding muscle tissue is a function of oxygenated hemoglobin (HbO2) and can be quantified with a field‐mapping pulse sequence. In this work, the methods accuracy and precision was investigated theoretically on the basis of an analytical expression for the arbitrarily oriented cylinder, as well as experimentally in phantoms and in vivo in the femoral artery and vein at 3T field strength. Errors resulting from vessel tilt, noncircularity of vessel cross‐section, and induced magnetic field gradients were evaluated and methods for correction were designed and implemented. Hemoglobin saturation was measured at successive vessel segments, differing in geometry, such as eccentricity and vessel tilt, but constant blood oxygen saturation levels, as a means to evaluate measurement consistency. The average standard error and coefficient of variation of measurements in phantoms were <2% with tilt correction alone, in agreement with theory, suggesting that high accuracy and reproducibility can be achieved while ignoring noncircularity for tilt angles up to about 30°. In vivo, repeated measurements of %HbO2 in the femoral vessels yielded a coefficient of variation of less than 5%. In conclusion, the data suggest that %HbO2 can be measured reproducibly in vivo in large vessels of the peripheral circulation on the basis of the paramagnetic cylinder approximation of the incremental field. Magn Reson Med, 2009.

Implications of pulse sequence in structural imaging of trabecular bone

To investigate the SNR and image properties of 3D steady‐state free precession (SSFP), fast large‐angle spin echo (FLASE), gradient‐recalled acquisition in steady state (GRASS), and spoiled GRASS (SPGR) for structural imaging of trabecular bone (TB).