Abdominal aortic hemodynamics in young healthy adults at rest and during lower limb exercise: quantification using image-based computer modeling

Localization of atherosclerotic lesions in the abdominal aorta has been previously correlated to areas of adverse hemodynamic conditions, such as flow recirculation, low mean wall shear stress, and high temporal oscillations in shear. Along with its many systemic benefits, exercise is also proposed to have local benefits in the vasculature via the alteration of these regional flow patterns. In this work, subject-specific models of the human abdominal aorta were constructed from magnetic resonance angiograms of five young, healthy subjects, and computer simulations were performed under resting and exercise (50% increase in resting heart rate) pulsatile flow conditions. Velocity fields and spatial variations in mean wall shear stress (WSS) and oscillatory shear index (OSI) are presented. When averaged over all subjects, WSS increased from 4.8 +/- 0.6 to 31.6 +/- 5.7 dyn/cm2 and OSI decreased from 0.22 +/- 0.03 to 0.03 +/- 0.02 in the infrarenal aorta between rest and exercise. WSS significantly increased, whereas OSI decreased between rest and exercise at the supraceliac, infrarenal, and suprabifurcation levels, and significant differences in WSS were found between anterior and posterior sections. These results support the hypothesis that exercise provides localized benefits to the cardiovascular system through acute mechanical stimuli that trigger longer-term biological processes leading to protection against the development or progression of atherosclerosis.     

MRI/MRS assessment of in vivo murine cardiac metabolism, morphology, and function at physiological heart rates

Transgenic mice are increasingly used to probe genetic aspects of cardiovascular pathophysiology. However, the small size and rapid rates of murine hearts make noninvasive, physiological in vivo studies of cardiac bioenergetics and contractility difficult. The aim of this report was to develop an integrated, noninvasive means of studying in vivo murine cardiac metabolism, morphology, and function under physiological conditions by adapting and modifying noninvasive cardiac magnetic resonance imaging (MRI) with image-guided (31)P magnetic resonance spectroscopy techniques used in humans to mice. Using spatially localized, noninvasive (31)P nuclear magnetic resonance spectroscopy and MRI at 4.7 T, we observe mean murine in vivo myocardial phosphocreatine-to-ATP ratios of 2.0 +/- 0.2 and left ventricular ejection fractions of 65 +/- 7% at physiological heart rates ( approximately 600 beats/min). These values in the smallest species studied to date are similar to those reported in normal humans. Although these observations do not confirm a degree of metabolic scaling with body size proposed by prior predictions, they do suggest that mice can serve, at least at this level, as a model for human cardiovascular physiology. Thus it is now possible to noninvasively study in vivo myocardial bioenergetics, morphology, and contractile function in mice under physiological conditions.     

Inferior vena caval hemodynamics quantified in vivo at rest and during cycling exercise using magnetic resonance imaging

Compared with the abdominal aorta, the hemodynamic environment in the inferior vena cava (IVC) is not well described. With the use of cine phase-contrast magnetic resonance imaging (MRI) and a custom MRI-compatible cycle in an open magnet, we quantified mean blood flow rate, wall shear stress, and cross-sectional lumen area in 11 young normal subjects at the supraceliac and infrarenal levels of the aorta and IVC at rest and during dynamic cycling exercise. Similar to the aorta, the IVC experienced significant increases in blood flow and wall shear stress as a result of exercise, with greater increases in the infrarenal level compared with the supraceliac level. At the infrarenal level during resting conditions, the IVC experienced higher mean flow rate than the aorta (1.2 +/- 0.5 vs. 0.9 +/- 0.4 l/min, P < 0.01) and higher mean wall shear stress than the aorta (2.0 +/- 0.6 vs. 1.3 +/- 0.6 dyn/cm(2), P < 0.005). During exercise, wall shear stress remained higher in the IVC compared with the aorta, although not significantly. It was also observed that, whereas the aorta tapers inferiorly, the IVC tapers superiorly from the infrarenal to the supraceliac location. The hemodynamic and anatomic data of the IVC acquired in this study add to our understanding of the venous circulation and may be useful in a clinical setting.     

Helical flows and asymmetry of blood jet in dilated ascending aorta with normally functioning bicuspid valve

Bicuspid aortic valve (BAV) is associated with aortic dilatation and aneurysm. Several studies evidenced an eccentric systolic flow in ascending aorta associated with increased wall shear stresses (WSS) and the occurrence of an helical systolic flow. This study seeks to elucidate the connections between jet asymmetry and helical flow in patients with normally functioning BAV and dilated ascending aorta. We performed a computational parametric study by varying, for a patient-specific geometry, the valve area and the flow rate entering the aorta and drawing also a tricuspid valve (TAV). We considered also phase-contrast magnetic resonance imaging of four BAV and TAV patients. Measurement of normalized flow asymmetry index, systolic WSS and of a new index (positive helix fraction, PHF) quantifying the presence of a single a single helical flow were performed. In our computation, BAV cases featured higher values of all indices with respect to TAV in both numerical and imaged-based results. Moreover, all indices increased with decreasing valve area and/or with increasing flow rate. This allowed to separate the BAV and TAV cases with respect to the jet asymmetry, WSS localization and helical flow. Interestingly, these results were obtained without modeling the leaflets.     

MRI and CFD studies of pulsatile flow in healthy and stenosed carotid bifurcation models

Pulsatile flow was studied in physiologically realistic models of a normal and a moderately stenosed (30% diameter reduction) human carotid bifurcation. Time-resolved velocity measurements were made using magnetic resonance imaging, from which wall shear stress (WSS) vectors were calculated. Velocity measurements in the inflow and outflow regions were also used as boundary conditions for a computational fluid dynamics (CFD) model. Experimental flow patterns and derived WSS vectors were compared qualitatively with the corresponding CFD predictions. In the stenosed phantom, flow in the bulb region of the "internal carotid artery" was concentrated along the outer wall, with a region of low and recirculating flow near the inner wall. In the normal phantom, the converse was found, with a low flow region near the outer wall of the bulb. Time-averaged WSS and oscillatory shear index were also markedly different for the two phantoms.     

Towards the improved quantification of in vivo abnormal wall shear stresses in BAV-affected patients from 4D-flow imaging: Benchmarking and application to real data

Bicuspid aortic valve (BAV), i.e. the fusion of two aortic valve cusps, is the most frequent congenital cardiac malformation. Its progression is often characterized by accelerated leaflet calcification and aortic wall dilation. These processes are likely enhanced by altered biomechanical stimuli, including fluid-dynamic wall shear stresses (WSS) acting on both the aortic wall and the aortic valve. Several studies have proposed the exploitation of 4D-flow magnetic resonance imaging sequences to characterize abnormal in vivo WSS in BAV-affected patients, to support prognosis and timing of intervention. However, current methods fail to quantify WSS peak values.On this basis, we developed two new methods for the improved quantification of in vivo WSS acting on the aortic wall based on 4D-flow data.We tested both methods separately and in combination on synthetic datasets obtained by two computational fluid-dynamics (CFD) models of the aorta with healthy and bicuspid aortic valve. Tests highlighted the need for data spatial resolution at least comparable to current clinical guidelines, the low sensitivity of the methods to data noise, and their capability, when used jointly, to compute more realistic peak WSS values as compared to state-of-the-art methods.The integrated application of the two methods on the real 4D-flow data from a preliminary cohort of three healthy volunteers and three BAV-affected patients confirmed these indications. In particular, quantified WSS peak values were one order of magnitude higher than those reported in previous 4D-flow studies, and much closer to those computed by highly time- and space-resolved CFD simulations.     

Doppler echocardiographic reference values for healthy rhesus monkeys under ketamine hydrochloride sedation

Cardiac ultrasound is a noninvasive technique that is commonly used to serially evaluate cardiac structure and function. Recent advances in Doppler-Echocardiography enable the ultrasonographer to perform a sophisticated noninvasive assessment of cardiovascular physiology. The Rhesus monkey is a frequently used non-human primate animal model of human cardiovascular disease because this species closely models human anatomy and physiology. However, while this species is frequently used in cardiovascular research, standardized echocardiographic values generated from large numbers of normal Rhesus are not available. In the present study, we performed cardiac ultrasound imaging on 28 healthy Rhesus monkeys to obtain normal reference values of cardiovascular structure and function in this species. Nomograms were generated from these data by plotting parameters of cardiovascular geometry and function with body weight. These normal reference data were compared to previously reported values obtained from prior studies that used noninvasive, invasive, and morphometric techniques. Cardiac ultrasound is a noninvasive technique that is commonly used to serially evaluate cardiac structure and function. Recent advances in Doppler-Echocardiography enable the ultrasonographer to perform a sophisticated noninvasive assessment of cardiovascular physiology. The Rhesus monkey is a frequently used non-human primate animal model of human cardiovascular disease because this species closely models human anatomy and physiology. However, while this species is frequently used in cardiovascular research, standardized echocardiographic values generated from large numbers of normal Rhesus are not available. In the present study, we performed cardiac ultrasound imaging on 28 healthy Rhesus monkeys to obtain normal reference values of cardiovascular structure and function in this species. Nomograms were generated from these data by plotting parameters of cardiovascular geometry and function with body weight. These normal reference data were compared to previously reported values obtained from prior studies that used noninvasive, invasive, and morphometric techniques.     

Mechanistic insight into the physiological relevance of helical blood flow in the human aorta: an in vivo study

The hemodynamics within the aorta of five healthy humans were investigated to gain insight into the complex helical flow patterns that arise from the existence of asymmetries in the aortic region. The adopted approach is aimed at (1) overcoming the relative paucity of quantitative data regarding helical blood flow dynamics in the human aorta and (2) identifying common characteristics in physiological aortic flow topology, in terms of its helical content. Four-dimensional phase-contrast magnetic resonance imaging (4D PC MRI) was combined with algorithms for the calculation of advanced fluid dynamics in this study. These algorithms allowed us to obtain a 4D representation of intra-aortic flow fields and to quantify the aortic helical flow. For our purposes, helicity was used as a measure of the alignment of the velocity and the vorticity. There were two key findings of our study: (1) intra-individual analysis revealed a statistically significant difference in the helical content at different phases of systole and (2) group analysis suggested that aortic helical blood flow dynamics is an emerging behavior that is common to normal individuals. Our results also suggest that helical flow might be caused by natural optimization of fluid transport processes in the cardiovascular system, aimed at obtaining efficient perfusion. The approach here applied to assess in vivo helical blood flow could be the starting point to elucidate the role played by helicity in the generation and decay of rotating flows in the thoracic aorta.     

An innovative numerical approach to resolve the pulse wave velocity in a healthy thoracic aorta model

Aortic dissection and atherosclerosis are highly fatal diseases. The development of both diseases is closely associated with highly complex haemodynamics. Thus, in predicting the onset of cardiac disease, it is desirable to obtain a detailed understanding of the flowfield characteristics in the human cardiovascular circulatory system. Accordingly, in this study, a numerical model of a normal human thoracic aorta is constructed using the geometry information obtained from a phase-contrast magnetic resonance imaging (PC-MRI) technique. The interaction between the blood flow and the vessel wall dynamics is then investigated using a coupled fluid–structure interaction (FSI) analysis. The simulations focus specifically on the flowfield characteristics and pulse wave velocity (PWV) of the blood flow. Instead of using a conventional PC-MRI method to measure PWV, we present an innovative application of using the FSI approach to numerically resolve PWV for the assessment of wall compliance in a thoracic aorta model. The estimated PWV for a normal thoracic aorta agrees well with the results obtained via PC-MRI measurement. In addition, simulations which consider the FSI effect yield a lower predicted value of the wall shear stress at certain locations in the cardiac cycle than models which assume a rigid vessel wall. Consequently, the model provides a suitable basis for the future development of more sophisticated methods capable of performing the computer-aided analysis of aortic blood flows.     

Numerical investigation of mass transport through patient-specific deformed aortae

Blood flow in human arteries has been investigated using computational fluid dynamics tools. This paper considers flow modeling through three aorta models reconstructed from cross-sectional magnetic resonance scans of female patients. One has the normal control configuration, the second has elongation of the transverse aorta, and the third has tortuosity of the aorta with stenosis. The objective of this study is to determine the impact of aortic abnormal geometries on the wall shear stress (WSS), luminal surface low-density lipoproteins (LDLs) concentration, and oxygen flux along the arterial wall. The results show that the curvature of the aortic arch and the stenosis have significant effects on the blood flow, and in turn, the mass transport. The location of hypoxia areas can be predicted well by ignoring the effect of hemoglobin on the oxygen transport. However, this simplification indeed alters the absolute value of Sherwood number on the wall.     

Simulations of morphotype-dependent hemodynamics in non-dilated bicuspid aortic valve aortas

Bicuspid aortic valves (BAVs) generate flow abnormalities that may promote aortopathy. While positive helix fraction (PHF) index, flow angle (θ), flow displacement (d) and wall shear stress (WSS) exhibit abnormalities in dilated BAV aortas, it is unclear whether those anomalies stem from the abnormal valve anatomy or the dilated aorta. Therefore, the objective of this study was to quantify the early impact of different BAV morphotypes on aorta hemodynamics prior to dilation. Fluid-structure interaction models were designed to quantify standard peak-systolic flow metrics and temporal WSS characteristics in a realistic non-dilated aorta connected to functional tricuspid aortic valve (TAV) and type-I BAVs. While BAVs generated increased helicity (PHF>0.68) in the middle ascending aorta (AA), larger systolic flow skewness (θ>11.2°) and displacement (d>6.8 mm) relative to the TAV (PHF=0.51; θ<5.5°; d<3.3 mm), no distinct pattern was observed between morphotypes. In contrast, WSS magnitude and directionality abnormalities were BAV morphotype- and site-dependent. Type-I BAVs subjected the AA convexity to peak-systolic WSS overloads (up to 1014% difference vs. TAV). While all BAVs increased WSS unidirectionality on the proximal AA relative to the TAV, the most significant abnormality was achieved by the BAV with left-right-coronary cusp fusion on the wall convexity (up to 0.26 decrease in oscillatory shear index vs. TAV). The results indicate the existence of strong hemodynamic abnormalities in non-dilated type-I BAV AAs, their colocalization with sites vulnerable to dilation and the superior specificity of WSS metrics over global hemodynamic metrics to the valve anatomy.     

Wall shear stress distribution in a model human aortic arch: assessment by an electrochemical technique

Wall shear stress (WSS) distribution in a human aortic arch model is studied using 130 cathode electrodes flush-mounted on the model walls. Flow visualizations are made in a transparent geometry model to identify the regions of fluid mechanical interests, e.g. regions of flow separation, eddy formation and flow stagnancy. The 130 electrodes are strategically positioned in the arch based on information obtained from the flow visualizations. The measured data indicate that the aortic arch may be categorized into eight regions: three along the inner wall of the arch (A,B,C); and five near the outer wall (D,E,F,G,H). (1) The regions of low WSS are distributed along the inner wall of the ascending aorta A; the inner wall of the descending aorta C; and the upstream inner wall of the innominate and the common carotid branchings F. (2) The high WSS regions are distributed along the outer wall of the arch E; and the inner wall in the arch opposite to the left subclavian branching B. (3) In certain regions, high and low WSS may be found next to each other (e.g. G and H) without a definable boundary in between; and (4) as the Reynolds number increases, the areas of low WSS decrease, while the high WSS areas increase with no obvious change in magnitude of the stress along the inner wall of the arch. At the branchings, the WSS distribution is not affected by the Reynolds number within the range of observations. The measured WSS distribution is compared with Rodkiewicz's map of early atherosclerotic lesions in the aortic arch of cholesterol fed rabbits.     

Noninvasive determination of spatial distribution and temporal gradient of wall shear stress at common carotid artery

Wall shear stress (WSS) has been proved to play a critical role in formation and development of atherosclerotic plaques. Our objective was to quantify local WSS in vivo in normal subjects, and to analyze spatial distribution patterns and determine the temporal gradient of WSS. Seventy-eight CCAs of 42 healthy volunteers at common carotid arteries (CCAs) were studied. Cine phase-contrast MR sequence was used to acquire the flow velocity information. Three-dimensional paraboloid modeling was applied to fit the velocity profiles and WSS values were calculated. Mean WSS value for CCAs was 0.783+/-0.209, with the range of WSS value from -0.541 to 3.464 N/m(2). The 95% confidence interval for mean WSS value in CCA was (0.736-0.830) N/m(2). Different WSS spatial distribution patterns were classified into three types according to the location of low WSS values during a cardiac cycle. Mean value of maximum temporal gradient of WSS was 14.12+/-5.46, with the range from 5.87 to 33.23 N/m(2)s(-1). Skewed velocity profiles were displayed in most CCAs, indicating the flow patterns in CCA were more complicated than commonly assumed. Obvious inter-subject variation were found in magnitude, spatial distribution and the temporal gradient of WSS in CCAs, and the blood flow patterns as well.     

Variation of mechanical properties along the length of the aorta in C57bl/6 mice

The objective of the present study is to obtain a systematic set of data on the mechanical properties along the entire length of the mouse aorta. The ascending aorta of seven mice was cannulated near the aortic valve, and the aorta was preconditioned with several cyclic changes in pressure. The perfusion pressure was then increased in 30-mmHg increments from 0 to 150 mmHg. Cab-O-Sil, colloidal silica, was mixed into the perfusate to prevent flow through the microvessels and hence attain zero-flow distensions. Our results show that the residual circumferential strain leads to a uniformity of transmural strain of the aorta in the loaded state along the entire length of the aorta. This uniformity is attained in the range of 60-120 mmHg. At pressures <60 mmHg, the outer strain is greater than the inner strain, whereas at pressures >120 mmHg, the converse is true. Furthermore, we found that the circumferential and longitudinal stress-strain relationships are linear in the pressure range of 30-120 mmHg. Finally, the circumferential modulus is greatest (most rigid) near the diaphragm, and the majority of volume compliance (85%) is in the thoracic compared with the abdominal aorta. These findings are important for an understanding of the hemodynamics of the cardiovascular system of the normal mouse and will serve as a reference state for the study of various diseases in knock-in and knock-out models of this species.     

Noninvasive cardiovascular phenotyping in mice

With the growth of genetic engineering, mice have become common as models of human diseases, which in turn has stimulated the development of techniques to monitor and image the murine cardiovascular system. Invasive methods are often more quantitative, but noninvasive methods are preferred when measurements must be repeated serially on living animals during development or in response to pharmacological or surgical interventions. Because of the small size and high heart rates in mice, high spatial and temporal resolutions are required to preserve signal fidelity. Monitoring of body temperature and the electrocardiogram is essential when animals must be anesthetized for a measurement or other procedure. Several other groups have developed cardiovascular imaging modalities suitable for murine applications, and ultrasound is the most widely used. Our group has developed and applied high-resolution Doppler probes and signal processing for measuring blood velocity in the heart and peripheral vessels of anesthetized mice noninvasively. We can measure cardiac filling and ejection velocities as indices of systolic and diastolic ventricular function and for timing of cardiac events; velocity pulse arrival times for determining pulse-wave velocity and arterial stiffness; peripheral velocity waveforms as indices of arterial resistance, compliance, and wave reflections; stenotic velocities for estimation of pressure drop and detection of vorticity; and tail artery velocity for determining systolic and diastolic blood pressure using a pressure cuff. These noninvasive methods are convenient and easy to apply and have been used to detect and evaluate numerous cardiovascular phenotypes in mutant mice.     

Toward translating near-infrared spectroscopy oxygen saturation data for the non-invasive prediction of spatial and temporal hemodynamics during exercise

Image-based computational fluid dynamics (CFD) studies conducted at rest have shown that atherosclerotic plaque in the thoracic aorta (TA) correlates with adverse wall shear stress (WSS), but there is a paucity of such data under elevated flow conditions. We developed a pedaling exercise protocol to obtain phase contrast magnetic resonance imaging (PC-MRI) blood flow measurements in the TA and brachiocephalic arteries during three-tiered supine pedaling at 130, 150, and 170 % of resting heart rate (HR), and relate these measurements to non-invasive tissue oxygen saturation \((\hbox {StO}_{2})\) acquired by near-infrared spectroscopy (NIRS) while conducting the same protocol. Local quantification of WSS indices by CFD revealed low time-averaged WSS on the outer curvature of the ascending aorta and the inner curvature of the descending aorta (dAo) that progressively increased with exercise, but that remained low on the anterior surface of brachiocephalic arteries. High oscillatory WSS observed on the inner curvature of the aorta persisted during exercise as well. Results suggest locally continuous exposure to potentially deleterious indices of WSS despite benefits of exercise. Linear relationships between flow distributions and tissue oxygen extraction calculated from \(\hbox {StO}_{2}\) were found between the left common carotid versus cerebral tissue \((r^{2}=0.96)\) and the dAo versus leg tissue \((r^{2}=0.87)\). A resulting six-step procedure is presented to use NIRS data as a surrogate for exercise PC-MRI when setting boundary conditions for future CFD studies of the TA under simulated exercise conditions. Relationships and ensemble-averaged PC-MRI inflow waveforms are provided in an online repository for this purpose.     

Wall shear stress fixed points in cardiovascular fluid mechanics

Complex blood flow in large arteries creates rich wall shear stress (WSS) vectorial features. WSS acts as a link between blood flow dynamics and the biology of various cardiovascular diseases. WSS has been of great interest in a wide range of studies and has been the most popular measure to correlate blood flow to cardiovascular disease. Recent studies have emphasized different vectorial features of WSS. However, fixed points in the WSS vector field have not received much attention. A WSS fixed point is a point on the vessel wall where the WSS vector vanishes. In this article, WSS fixed points are classified and the aspects by which they could influence cardiovascular disease are reviewed. First, the connection between WSS fixed points and the flow topology away from the vessel wall is discussed. Second, the potential role of time-averaged WSS fixed points in biochemical mass transport is demonstrated using the recent concept of Lagrangian WSS structures. Finally, simple measures are proposed to quantify the exposure of the endothelial cells to WSS fixed points. Examples from various arterial flow applications are demonstrated.     

X-Ray Phase-Contrast CT of a Pancreatic Ductal Adenocarcinoma Mouse Model

To explore the potential of grating-based x-ray phase-contrast computed tomography (CT) for preclinical research, a genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC) was investigated. One ex-vivo mouse specimen was scanned with different grating-based phase-contrast CT imaging setups covering two different settings: i) high-resolution synchrotron radiation (SR) imaging and ii) dose-reduced imaging using either synchrotron radiation or a conventional x-ray tube source. These experimental settings were chosen to assess the potential of phase-contrast imaging for two different types of application: i) high-performance imaging for virtual microscopy applications and ii) biomedical imaging with increased soft-tissue contrast for in-vivo applications. For validation and as a reference, histological slicing and magnetic resonance imaging (MRI) were performed on the same mouse specimen. For each x-ray imaging setup, attenuation and phase-contrast images were compared visually with regard to contrast in general, and specifically concerning the recognizability of lesions and cancerous tissue. To quantitatively assess contrast, the contrast-to-noise ratios (CNR) of selected regions of interest (ROI) in the attenuation images and the phase images were analyzed and compared. It was found that both for virtual microscopy and for in-vivo applications, there is great potential for phase-contrast imaging: in the SR-based benchmarking data, fine details about tissue composition are accessible in the phase images and the visibility of solid tumor tissue under dose-reduced conditions is markedly superior in the phase images. The present study hence demonstrates improved diagnostic value with phase-contrast CT in a mouse model of a complex endogenous cancer, promoting the use and further development of grating-based phase-contrast CT for biomedical imaging applications.     

Micro CT and Micro MR imaging of 3D architecture of animal skeleton

Quantitative assessment of three-dimensional (3D) trabecular structural characteristics may improve our ability to understand the pathophysiology of osteoporosis, to test the efficacy of pharmaceutical intervention, and to estimate bone biomechanical properties. Considerable progress has been made in advanced imaging techniques for noninvasive and/or nondestructive assessment of 3D trabecular structure and connectivity. Micro computed tomography (microCT) has been used to measure 3D trabecular bone structure in rats, both in vivo and in vitro. It can directly quantify 3D trabecular bone structure such as trabecular volume, trabecular thickness, number, separation, structure model index, degree of anisotropy, and connectivity, in a model-independent manner. We have used microCT to study ovariectomy (OVX) induced osteopenia in rats and its treatment with agents such as estrogen, and sodium fluoride. We have demonstrated that 3D microCT can quantify mouse trabecular and cortical bone structure with an isotropic resolution of 9 microm(3). It is also useful for studying osteoporosis in mice and in phenotypes of transgenic mice or gene knockout mice. MicroCT can be used to quantify osteogenesis in mouse Ilizarov leg lengthening procedures, to quantify osteoconduction in a rat cranial defect model, and to quantify cortical bone porosity. Recently, microCT using high intensity and tight collimation synchrotron radiation to achieve spatial resolution of 1-2 microm has provided the capability to assess additional features such as resorption cavities. Unlike microCT, micro magnetic resonance imaging (IMRI) is nonionizing. Recently, the ability of microMRI to assess osteoporosis in animal models has been explored. Using a small, high-efficiency coil in a high-field imager, microMRI can give resolutions sufficient to discriminate individual trabeculae. We have shown that, with appropriate settings, it is possible to image trabecular bone in rats in vivo and in vitro. In our study of OVX rats, analysis of microMR images can demonstrate differences in rat trabecular bone that are not detected by DXA measurements. In a rabbit OA model, with the OA induced by meniscectomy or anterior cruciate ligament transection, MRI shows decreased cartilage thickness, subchondral osteosclerosis and osteophytes, while radiographs can only show subchondral osteosclerosis and osteophytes could not be found. Advanced imaging methods are able to measure 3D trabecular structure and connectivity in arbitrary orientations in a highly automated, objective, non-user-specific manner, allowing greater numbers of samples for unbiased comparisons between controls and the disordered or treated. They can be utilized on a large sample leading to fewer sampling errors. They are non-destructive allowing multiple tests such as biomechanical testing and chemical analysis on the same sample; and non-invasive permitting longitudinal studies and reducing the number of animals needed.