Preclinical assessment of a new magnetic resonance-based technique for determining bone quality by characterization of trabecular microarchitecture (original) (raw)

Role of Magnetic Resonance for Assessing Structure and Function of Trabecular Bone

2002

The strength of trabecular bone and its resistance to fracture has traditionally been associated with apparent density. This paradigm assumes that neither the ultrastructural nor microstructural make-up of the bone is altered during aging and osteoporosis. There has been growing evidence against this view from both laboratory and clinical studies. Recent advances in noninvasive imaging technology, notably micro-magnetic resonance imaging (µ-MRI), offers an opportunity to test the hypothesis that architecture is an independent contributor to bone strength. Critical hurdles to overcome have their origin in the limited signal-to-noise ratio, which precludes imaging at a voxel size much smaller than trabecular thickness. The resulting partial volume blurring calls for more elaborate processing and analysis techniques. This article reviews new approaches conceived in the authors' laboratory toward acquisition, processing and structural analysis of trabecular bone images in the limited spatial resolution regime of in vivo µ-MRI. The method, termed 'virtual bone biopsy' (VBB), provides detailed insight into the three-dimensional trabecular network topology and scale at the distal radius or distal tibia serving as surrogate sites. The resulting VBB structural parameters are shown to be associated with the bone's biomechanical properties and fracture resistance and the technology has advanced to a stage permitting serial studies in laboratory animals and humans as a means to evaluate the effects of treatment. The method is currently confined to peripheral skeletal sites and its extension to typical fracture sites such as the proximal femur hinges on further advances in detection sensitivity.

Survey of MRI Usefulness for the Clinical Assessment of Bone Microstructure

International Journal of Molecular Sciences

Bone microarchitecture has been shown to provide useful information regarding the evaluation of skeleton quality with an added value to areal bone mineral density, which can be used for the diagnosis of several bone diseases. Bone mineral density estimated from dual-energy X-ray absorptiometry (DXA) has shown to be a limited tool to identify patients’ risk stratification and therapy delivery. Magnetic resonance imaging (MRI) has been proposed as another technique to assess bone quality and fracture risk by evaluating the bone structure and microarchitecture. To date, MRI is the only completely non-invasive and non-ionizing imaging modality that can assess both cortical and trabecular bone in vivo. In this review article, we reported a survey regarding the clinically relevant information MRI could provide for the assessment of the inner trabecular morphology of different bone segments. The last section will be devoted to the upcoming MRI applications (MR spectroscopy and chemical shi...

Quantification of Trabecular Bone Structure Using Magnetic Resonance Imaging at 3 Tesla—Calibration Studies Using Microcomputed Tomography as a Standard of Reference

Calcified Tissue International, 2005

The purpose of this study is to use high-resolution magnetic resonance (MR) imaging at 3 Tesla (3T) to quantify trabecular bone structure in vitro using femoral head specimens, and to correlate the calculated structure measures with those that were determined using microcomputed tomography (μCT), the standard of reference. Fifteen cylindrical cores were obtained from fresh femoral heads after total hip arthroplasty. MR images were obtained at 3T using a transmit-receive wrist coil. Highresolution coronal images were acquired using a modified three-dimensional (3D) fast-gradient echo sequence. From these data sets two-dimensional (2D) structural parameters analogous to bone histomorphometry were derived by using both mean intercept length (MIL) methods based on the plate model and the more recent model-assumption free 3D distance-transformation (DT) methods. The parameters measured by the 2D plate model-based MIL method and the DT method included apparent (App). BV/TV (bone volume/total volume), App. Tb.Th (trabecular thickness), App. Tb.Sp (trabecular separation), and App. Tb.N (trabecular number). Identical regions of interest were analyzed in the MR images and the μCT data sets, and similar structure measures were derived. The means and standard deviations of the parameters over all slices were calculated and MR-derived measures were correlated with those derived from the μCT data sets using linear regression analyses. Structure measures were overestimated with MRI, for example, the mean App. BV/TV was 0.45 for MRI and 0.20 for μCT, and the slope of the graph was 1.45. App. Tb.Th was overestimated by a factor of 1.9, whereas App. Tb.Sp was underestimated; Tb.N showed the smallest effect. Correlations between the individual parameters were excellent (App. BV/TV, r 2 = 0.82; App. Tb.Sp, r 2 = 0.84; App. Tb.N, r 2 = 0.81), except for App. Tb.Th (r 2 = 0.67). The results of this study show that trabecular bone structure measures may be obtained using 3T MR imaging. These measures, although higher than the standard of reference, show a highly significant correlation with true structure measures obtained by μCT.

Quantitative MRI for the assessment of bone structure and function

NMR in Biomedicine, 2006

Osteoporosis is the most common degenerative disease in the elderly. It is characterized by low bone mass and structural deterioration of bone tissue, leading to morbidity and increased fracture risk in the hip, spine and wrist-all sites of predominantly trabecular bone. Bone densitometry, currently the standard methodology for diagnosis and treatment monitoring, has significant limitations in that it cannot provide information on the structural manifestations of the disease. Recent advances in imaging, in particular MRI, can now provide detailed insight into the architectural consequences of disease progression and regression in response to treatment. The focus of this review is on the emerging methodology of quantitative MRI for the assessment of structure and function of trabecular bone. During the past 10 years, various approaches have been explored for obtaining image-based quantitative information on trabecular architecture. Indirect methods that do not require resolution on the scale of individual trabeculae and therefore can be practiced at any skeletal location, make use of the induced magnetic fields in the intertrabecular space. These fields, which have their origin in the greater diamagnetism of bone relative to surrounding marrow, can be measured in various ways, most typically in the form of R 0 2 , the recoverable component of the total transverse relaxation rate. Alternatively, the trabecular network can be quantified by high-resolution MRI (m-MRI), which requires resolution adequate to at least partially resolve individual trabeculae. Micro-MRI-based structure analysis is therefore technically demanding in terms of image acquisition and algorithms needed to extract the structural information under conditions of limited signal-to-noise ratio and resolution. Other requirements that must be met include motion correction and image registration, both critical for achieving the reproducibility needed in repeat studies. Key clinical applications targeted involve fracture risk prediction and evaluation of the effect of therapeutic intervention.

Assessment of trabecular bone structure comparing magnetic resonance imaging at 3 Tesla with high-resolution peripheral quantitative computed tomography ex vivo and in vivo

Osteoporosis International, 2008

Summary In vivo high-resolution peripheral quantitative micro-CT (HR-pQCT) is a new modality for imaging peripheral sites like the distal tibia and the distal radius, providing structural bone parameters. Comparing HR-pQCT with MRI, we found that both modalities are capable of offering meaningful information on trabecular structure. Background Magnetic resonance imaging (MRI) has emerged as the leading in vivo method for measuring trabecular bone micro-architecture and providing structural information. Recently, an in vivo HR-pQCT modality was introduced for imaging peripheral sites like the distal tibia and the distal radius, providing structural bone parameters. The goal of this work was to compare and evaluate the performances and in vivo capabilities of HR-pQCT in comparison with MRI at 3 Tesla. Methods To this end images of 8 human specimens (5 tibiae and 3 radii) and 11 participants (6 tibia and 5 radii) were acquired with both modalities. Additionally, the radius specimens were scanned with micro-CT (μCT), which was used as a standard of reference. Structural parameters calculated from MRI were compared with results from HR-pQCT images and additionally μCT for the radii specimens. Results High correlations (r > 0.7) were found for trabecular number and trabecular spacing between the two modalities in vivo and ex vivo. 2D and 3D analysis revealed high correlations (r > 0.8) in structural bone parameters for all measurements. Using micro-CT as standard of reference both results from QCT and MRI correlated well. Conclusion Both imaging modalities were found to perform equally well regarding trabecular bone measurements.

Accuracy of high-resolution in vivo micro magnetic resonance imaging for measurements of microstructural and mechanical properties of human distal tibial bone

Journal of Bone and Mineral Research, 2010

Micro magnetic resonance imaging (µMRI) is an in vivo imaging method which permits three dimensional (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 bone's resistance to fractures. In order for µMR image-based microstructural and µFE analyses to become standard clinical tools for assessing bone quality, validation with a current gold standard, namely the high-resolution micro computed tomography (µCT) is required. Microstructural measurements of 25 human cadaveric distal tibiae were performed for the registered µMR and µCT images, respectively. Next, whole bone stiffness, trabecular bone stiffness, and elastic moduli of cubic sub-volumes 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) of µMRI showed strong correlations with µCT measurements (r 2 =0.67~0.97), and bone surface to volume ratio (BS/BV), connectivity density (Conn.D), and degree of anisotropy (DA) had significant but moderate correlations (r 2 =0.33~0.51). Each of these measurements also contributed to one or many of the µFE-predicted mechanical properties. However, model-independent trabecular thickness (Tb.Th * ) of µMRI had no correlation with the µCT measurement and did not contribute to any mechanical measurement. Furthermore, the whole bone and trabecular bone stiffness of µMR images were highly correlated to those of µCT images (r 2 =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 sub-volume had significant but only moderate correlations with their gold standards (r 2 =0.40~0.58). We conclude that most microstructural and mechanical properties of the distal tibia can be efficiently derived from µMR images and can provide additional information regarding bone quality.

Validation and Optimization of Proximal Femurs Microstructure Analysis Using High Field and Ultra-High Field MRI

Diagnostics

Trabecular bone could be assessed non-invasively using MRI. However, MRI does not yet provide resolutions lower than trabecular thickness and a comparative analysis between different MRI sequences at different field strengths and X-ray microtomography (μCT) is still missing. In this study, we compared bone microstructure parameters and bone mineral density (BMD) computed using various MRI approaches, i.e., turbo spin echo (TSE) and gradient recalled echo (GRE) images used at different magnetic fields, i.e., 7T and 3T. The corresponding parameters computed from μCT images and BMD derived from dual-energy X-ray absorptiometry (DXA) were used as the ground truth. The correlation between morphological parameters, BMD and fracture load assessed by mechanical compression tests was evaluated. Histomorphometric parameters showed a good agreement between 7T TSE and μCT, with 8% error for trabecular thickness with no significative statistical difference and a good intraclass correlation coeff...

Three-dimensional nuclear magnetic resonance microimaging of trabecular bone

Journal of Bone and Mineral Research, 2009

The conventional approach to measuring structural parameters in trabecular bone rests on stereology from optical images, derived from sections of embedded bone. In order to provide data that are statistically representative of a sufficiently large volume, multiple sections need to be analyzed in each of the three orthogonal planes. In this work, an alternative technique is presented which is based on three-dimensional (3D) volumetric proton nuclear magnetic resonance (NMR) microimaging. The method presented provides images from 9 x 9 X 4 mm3 volumes of defatted bone specimens in 15-20 minutes scan time at isotropic resolution corresponding to (78 pm)j voxel size. Surface-rendered images of bovine and human trabecular bone are shown and an algorithm was developed and implemented for determining the orientation and magnitude of the principal axes of the mean intercept length

MRI Techniques for the Examination of Trabecular Bone Structure

Current Medical Imaging Reviews, 2005

It is well known that bone mineral density measurement is a widely available means of identifying individuals with osteoporosis. However, bone strength depends not only on the amount of material but also on properties related to bone quality. Significant progress has been made in the development of magnetic resonance imaging (MRI) techniques for assessing bone status during the past years. This review discusses the technical principles, clinical applications, recent advances, limitations, and future trends of MRI techniques available for the diagnosis of osteoporosis. Using MRI, bone status can be evaluated either by T2* measurements, which are sensitive to field inhomogeneities caused by susceptibility differences at the marrowbone interfaces, or by high-resolution imaging. In T2* relaxometry, the decrease in marrow T2* measurements and its decay characteristics provide useful information about the structure and quality of the trabecular bone. T2* measurements have been performed at several locations of the axial and peripheral skeleton such as spine, proximal femur and calcaneus. It has also been shown that osteoporotic and normal subjects may be distinguished using T2* decay characteristics. In addition to T2* relaxometry, high-resolution MR imaging may be used to quantify trabecular bone architecture. Gradient echo and spin echo sequences have been used to obtain images in vitro and in vivo mainly at peripheral sites of the skeleton. Several image-processing methods have been applied to measure bone structure. Technological advances in MRI scanners offer exciting new possibilities in bone analysis and may contribute to our understanding of osteoporosis.

Ex vivo assessment of trabecular bone structure from three-dimensional projection reconstruction mr micro-images

IEEE Transactions on Biomedical Engineering, 2003

Magnetic resonance (MR) imaging has recently been proposed for assessing osteoporosis and predicting fracture risks. However, accurate acquisition techniques and image analysis protocols for the determination of the trabecular bone structure are yet to be defined. The aim of this study was to assess the potential of projection reconstruction (PR) MR microscopy in the analysis of the three-dimensional (3-D) architecture of trabecular bone and in the prediction of its biomechanical properties. High-resolution 3-D PR images (41 x 41 x 82 microm3 voxels) of 15 porcine trabecular bone explants were analyzed to determine the trabecular bone volume fraction (Vv), the mean trabecular thickness (Tb.Th), and the mean trabecular separation (Tb.Sp) using the method of directed secants. These parameters were then compared with those derived from 3-D conventional spin-echo microimages. In both cases, segmentation of the high-resolution images into bone and bone marrow was obtained using a spatial adaptive threshold. The contemporary inclusion of Vv, Tb.Th and 1/Tb.Sp in a multiple regression analysis significantly improved the prediction of Young's modulus (YM). The parameters derived from the PR spin-echo images were found to be stronger predictors of YM (R2 = 0.94, p = 0.004) than those derived from conventional spin-echo images (R2 = 0.79, p = 0.051). Our study indicates that projection reconstruction MR microscopy appears to be more accurate than the conventional Fourier transform method in the quantification of trabecular bone structure and in the prediction of its bioimechanical properties. The proposed PR approach should be readily adaptable to the in vivo MRI studies of osteoporosis.