Branimir Vasilic

Effect of testosterone replacement on trabecular architecture in hypogonadal men.

We evaluated the effect of testosterone treatment on trabecular architecture by μMRI in 10 untreated severely hypogonadal men. After 2 years, μMRI parameters of trabecular connectivity improved significantly, suggesting the possibility that testosterone improves trabecular architecture.

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.

A novel local thresholding algorithm for trabecular bone volume fraction mapping in the limited spatial resolution regime of in vivo MRI

Recent advances in micro-magnetic resonance imaging have shown the possibility of in vivo assessment of trabecular bone architecture. However, the small feature size and relatively low signal-to-noise ratio (SNR) achievable in vivo cause the intensity histogram to be unimodal. The critical first step in the processing of these images is the extraction of bone volume fraction for each voxel. Here, we propose a local threshold algorithm (LTA) that determines the marrow intensity value in the neighborhood of each voxel based on nearest-neighbor statistics. Using the local marrow intensities we threshold the image and scale the intensities of voxels partially occupied by bone to produce a marrow volume fraction map of the trabecular bone region. We show that structural parameters derived with the LTA are highly correlated with those obtained with the previously published histogram deconvolution algorithm (HDA) and that the LTA is robust to image noise corruption. The LTA is found to correctly identify trabeculae with a significantly higher reliability than HDA. Finally, we demonstrate that the LTA is superior in preserving connectivity by showing for 75 in vivo images that the genus of the trabecular bone surface is always higher than when processed with the HDA.

In Vivo μMRI-Based Finite Element and Morphological Analyses of Tibial Trabecular Bone in Eugonadal and Hypogonadal Men Before and After Testosterone Treatment†‡

Osteoporosis is a major public health problem in men. Hypogonadal men have decreased BMD and deteriorated trabecular bone architecture compared with eugonadal men. Testosterone treatment improves their BMD and trabecular structure. We tested the hypothesis that testosterone replacement in hypogonadal men would also improve their bones mechanical properties. Ten untreated severely hypogonadal and 10 eugonadal men were selected. The hypogonadal men were treated with a testosterone gel for 24 mo to maintain their serum testosterone concentrations within the normal range. Each subject was assessed before and after 6, 12, and 24 mo of testosterone treatment by μMRI of the distal tibia. A subvolume of each μMR image was converted to a microfinite element (μFE) model, and six analyses were performed, representing three compression and three shear tests. The anisotropic stiffness tensor was calculated, from which the orthotropic elastic material constants were derived. Changes in microarchitecture were also quantified using newly developed individual trabeculae segmentation (ITS)‐based and standard morphological analyses. The accuracy of these techniques was examined with simulated μMR images. Significant differences in four estimated anisotropic elastic material constants and most morphological parameters were detected between the eugonadal and hypogonadal men. No significant change in estimated elastic moduli and morphological parameters was detected in the eugonadal group over 24 mo. After 24 mo of treatment, significant increases in estimated elastic moduli E22 (9.0%), E33 (5.1%), G23 (7.2%), and G12 (9.4%) of hypogonadal men were detected. These increases were accompanied by significant increases in trabecular plate thickness. These results suggest that 24 mo of testosterone treatment of hypogonadal men improves estimated elastic moduli of tibial trabecular bone by increased trabecular plate thickness.

Trabecular structure quantified with the MRI-based virtual bone biopsy in postmenopausal women contributes to vertebral deformity burden independent of areal vertebral BMD.

In postmenopausal women with a wide range of vertebral deformities, MRI‐based structural measures of topology and scale at the distal radius are shown to account for as much as 30% of vertebral deformity, independent of integral vertebral BMD.

Spatial autocorrelation and mean intercept length analysis of trabecular bone anisotropy applied to in vivo magnetic resonance imaging

Osteoporosis is characterized by bone loss and deterioration of the trabecular bone (TB) architecture that leads to impaired overall mechanical strength of the bone. Bone mineral density (BMD) measured by dual-energy x-ray absorptiometry is currently the standard clinical metric assessing bone integrity but it fails to capture the structural changes in the TB. Recent research suggests that structure contributes to bone strength in a manner complementary to BMD. Besides parameters of scale such as the mean TB thickness and mean bone volume fraction, parameters describing the anisotropy of the trabecular architecture play an important role in the characterization of TB since trabeculae are preferentially oriented along the direction of local loading. Therefore, the degree of structural anisotropy is of pivotal importance to the bones mechanical competence. The most common method for measuring structural anisotropy of TB is the mean-intercept length (MIL). In this work we present a method, based on the three-dimensional spatial autocorrelation function (ACF), for mapping of the full structural anisotropy ellipsoid of both TB thickness and spacing and we examine its performance as compared to that of MIL. Not only is the ACF method faster by several orders of magnitude, it is also considerably more robust to noise. Further, it is applicable at lower spatial resolution and is relatively insensitive to image shading. The chief reason for ACFs superior performance is that it does not require binarization, which is difficult to achieve in the limited spatial regime of in vivo magnetic resonance imaging. MIL and ACF have been applied to high-resolution magnetic resonances images of the tibia in a group of ten healthy postmenopausal women by comparing the structural anisotropy and principal direction of the computed fabric tensor for each method. While there is fair agreement between the two methods, ACF analysis yielded greater anisotropy than MIL for both TB thickness and spacing. There was good agreement between the two techniques as far as the eigenvectors of the fabric ellipsoids were concerned, which parallel the bones macroscopic axis.

Fast Low‐Angle Dual Spin‐Echo (FLADE): A new robust pulse sequence for structural imaging of trabecular bone

Mechanical strength and fracture resistance of trabecular bone (TB) are largely determined by the structural arrangement of individual trabeculae. Fast 3D spin‐echo approaches are preferable to gradient echoes in that they are less sensitive to local induced gradients at the bone/marrow interface caused by magnetic susceptibility difference between the two tissues. FLASE is a 3D pulse sequence that serves this purpose. Here, we present a new pulse sequence dubbed FLADE (fast low‐angle dual spin‐echo) that overcomes some of the limitations inherent to FLASE, such as sensitivity to artifactual stimulated echoes. The double‐echo sequence features a flip angle <90 degrees allowing for TR ≪ T1. The second phase‐reversal pulse has the dual function of creating a second echo and restoring inverted longitudinal magnetization. The prolonged TR, made possible by sampling only half of kz‐space, is used to collect navigator echoes in adjacent slabs for sensing subpixel translational displacements. FLADE is shown to provide SNR comparable to FLASE while having narrower point‐spread function and being more robust to imperfections in the nonselective 180 degree pulses. Structural parameters derived from the in vivo images with the two pulse sequences are highly correlated, therefore suggesting that clinical data obtained with either pulse sequence can be merged. Magn Reson Med, 2006.

Classification of trabeculae into three-dimensional rodlike and platelike structures via local inertial anisotropy

Trabecular bone microarchitecture is a significant determinant of the bones mechanical properties and is thus of major clinical relevance in predicting fracture risk. The three-dimensional nature of trabecular bone is characterized by parameters describing scale, topology, and orientation of structural elements. However, none of the current methods calculates all three types of parameters simultaneously and in three dimensions. Here the authors present a method that produces a continuous classification of voxels as belonging to platelike or rodlike structures that determines their orientation and estimates their thickness. The method, dubbed local inertial anisotropy (LIA), treats the image as a distribution of mass density and the orientation of trabeculae is determined from a locally calculated tensor of inertia at each voxel. The orientation entropies of rods and plates are introduced, which can provide new information about microarchitecture not captured by existing parameters. The robustness of the method to noise corruption, resolution reduction, and image rotation is demonstrated. Further, the method is compared with established three-dimensional parameters including the structure-model index and topological surface-to-curve ratio. Finally, the method is applied to data acquired in a previous translational pilot study showing that the trabecular bone of untreated hypogonadal men is less platelike than that of their eugonadal peers.

Coherence-induced artifacts in large-flip-angle steady-state spin-echo imaging.

High‐resolution imaging of trabecular bone aimed at analyzing the bones microarchitecture is preferably performed with spin‐echo‐type pulse sequences. Unlike gradient echoes, spin‐echoes are immune to artifactual broadening of trabeculae caused by local static field gradients near the bone–bone marrow interface and signal loss from chemical shift dephasing at k‐space center. However, the previously practiced 3D fast large‐angle spin‐echo (FLASE) pulse sequence was found to be prone to a low‐frequency modulation artifact in both the readout and slice direction. The artifact is caused by deviations in the effective flip angle of the nonselective 180° pulse, which converts a fraction of the phase‐encoded transverse magnetization to longitudinal magnetization. The latter recurs as transverse magnetization in the subsequent pulse sequence cycle forming a spurious stimulated echo. The objective of this work was to perform a k‐space analysis of this steady‐state artifact and propose two modifications of the original 3D FLASE that effectively remove it. The results of the simulations were in exact agreement with the experiments and the proposed remedy was found to eliminate the artifact. Magn Reson Med 52:346–353, 2004.

Study of trabecular bone microstructure using spatial autocorrelation analysis

The spatial autocorrelation analysis method represents a powerful, new approach to quantitative characterization of structurally quasi-periodic anisotropic materials such as trabecular bone (TB). The method is applicable to grayscale images and thus does not require any preprocessing, such as segmentation which is difficult to achieve in the limited resolution regime of in vivo imaging. The 3D autocorrelation function (ACF) can be efficiently calculated using the Fourier transform. The resulting trabecular thickness and spacing measurements are robust to the presence of noise and produce values within the expected range as determined by other methods from μCT and μMRI datasets. TB features found from the ACF are shown to correlate well with those determined by the Fuzzy Distance transform (FDT) in the transverse plane, i.e. the plane orthogonal to bone’s major axis. The method is further shown to be applicable to in-vivo μMRI data. Using the ACF, we examine data acquired in a previous study aimed at evaluating the structural implications of male hypogonadism characterized by testosterone deficiency and reduced bone mass. Specifically, we consider the hypothesis that eugonadal and hypogonadal men differ in the anisotropy of their trabecular networks. The analysis indicates a significant difference in trabecular bone thickness and longitudinal spacing between the control group and the testosterone deficient group. We conclude that spatial autocorrelation analysis is able to characterize the 3D structure and anisotropy of trabecular bone and provides new insight into the structural changes associated with osteoporotic trabecular bone loss.