Biomedical subjects

Felix W Wehrli

Publications and source records attributed to Felix W Wehrli.

14 recordsLinked to original sources

PubMed2003

An image-based finite difference model for simulating restricted diffusion.

Water diffusion in tissues is generally restricted and often anisotropic. Neural tissue is of particular interest, since it is well known that injury alters diffusion in a characteristic manner. Both Monte Carlo simulations and approximate analytical models have previously been reported in attempts to predict water diffusion behavior in the central nervous system. These methods have relied on axonal models, which assume simple geometries (e.g., ellipsoids, cylinders, and square prisms) and ignore the thickness of the myelin sheath. The current work describes a method for generating models using synthetic images. The computations are based on a 3D finite difference (FD) approximation of the diffusion equation. The method was validated with known analytic solutions for diffusion in a cylindrical pore and in a hexagonal array of cylinders. Therefore, it is envisioned that, by exploiting histologic images of neuronal tissues as input model, current method allows investigating the water diffusion behavior inside biological tissues and potentially assessing the status of neural injury and regeneration.

Axons↗

PubMed2003

Feasibility of probing boundary morphology of structured materials by 2D NMR q-space imaging.

It is well known that one-dimensional (1D) q-space imaging allows retrieval of structural information at cellular resolution. Here we demonstrate by simulation that boundary morphology of structured materials can be derived from 2D q-space mapping. Based on a finite-difference model for restricted diffusion, 2D q-space maps obtained from water diffusion inside apertures at various levels of asperity were simulated. The results indicate that the observed ring patterns (diffraction minima) reveal the boundary profiles of the apertures but become blurred in the case of significant variation in aperture size. For uniform size distribution of apertures, a quantitative measure of surface roughness can be established by means of spatial autocorrelation analysis. The results suggest that 2D q-space imaging may allow probing of the boundary morphology of structured materials and possibly biological cells.

Cells↗

PubMed2003

Topology-based orientation analysis of trabecular bone networks.

After bone mineral density, orientation is the major determinant of trabecular bone strength and is thus of significant interest in understanding the clinical implications of osteoporotic bone loss. The methods used to measure orientation and anisotropy of the trabecular bone have largely relied on deriving global measures along test lines, computing the best-fit ellipsoid, and decomposing to eigenvalue-eigenvector pairs that yield the mean orientation and anisotropy of the region. These techniques ignore the differences between measuring the orientation of trabecular plates versus rods, and do not provide insight into the relationship between local orientation and biomechanical stresses. Digital topological analysis allows a unique determination of each voxel's topological class as belonging to a plate, rod, or junction. The digital topology-based orientation analysis (DTA-O) method extracts the voxels belonging to plates and determines the local surface normal by fitting a plane through the local neighborhood BVF map. Modeling regional distributions of these vectors allows assessment of anisotropy measures, such as mean and variance of the orientation distribution. High-resolution microcomputed tomography, synthetic, and in vivo images were used for a validation of the new method and compare the results with the mean intercept length (MIL) technique. The results indicate that DTA-O is a better measure of trabecular orientation and anisotropy than MIL. Applying DTA-O to a recently completed study on the distal radius of 82 subjects [F.W. Wehrli et al., J. Bone Min. Res. 16, 1520 (2001)] shows that the mean orientation and anisotropy at the medial and lateral sides in the distal radius mataphyseal trabecular network are consistent with the mechanical stresses acting on the radius during common tasks.

Adult↗

PubMed2003

Deterioration of trabecular architecture in hypogonadal men.

Bone strength depends on trabecular architecture, characterized by interconnected plates and rods. In osteoporosis, the plates become fenestrated, resulting in more rods that deteriorate and become disconnected. In men, hypogonadism is a common cause of osteoporosis. To determine whether male hypogonadism affects trabecular architecture, we selected 10 men with severe, untreated hypogonadism, and for each hypogonadal man, we selected a eugonadal man matched for race and age. Trabecular architecture in the distal tibia was assessed by magnetic resonance microimaging. Two composite topological indices were determined: the ratio of surface voxels (representing plates) to curve voxels (representing rods), which is higher when architecture is more intact; and the erosion index, a ratio of parameters expected to increase upon architectural deterioration to those expected to decrease, which is higher when deterioration is greater. The surface/curve ratio was 36% lower (P = 0.004), and the erosion index was 36% higher (P = 0.003) in the hypogonadal men than in the eugonadal men. In contrast, bone mineral density of the spine and hip were not significantly different between the two groups. We conclude that male hypogonadism is associated with marked deterioration of trabecular architecture and to a greater degree than bone densitometry of the spine and hip suggests.

Absorptiometry, Photon↗

PubMed2002

Magnetic resonance microimaging of intraaxonal water diffusion in live excised lamprey spinal cord.

Anisotropy of water diffusion in axon tracts, as determined by diffusion-weighted MRI, has been assumed to reflect the restriction of water diffusion across axon membranes. Reduction in this anisotropy has been interpreted as degeneration of axons. These interpretations are based primarily on a priori reasoning that has had little empirical validation. We used the experimental advantages of the sea lamprey spinal cord, which contains several very large axons, to determine whether intraaxonal diffusion is isotropic and whether anisotropy is attributable to restriction of water mobility by axon surface membranes. Through the application of magnetic resonance microimaging, we were able to measure the purely intraaxonal diffusion characteristics of the giant reticulospinal axons (20-40 microm in diameter). The intraaxonal apparent diffusion coefficients of water parallel (longitudinal ADC, l-ADC) and perpendicular (transverse ADC, t-ADC) to the long axis were 0.98 +/- 0.06 (10(-3) mm2 sec) and 0.97 +/- 0.11 (10(-3) mm2 sec), respectively. In white matter regions that included multiple axons, l-ADCs were almost identical regardless of axon density in the sampled axon tract. By comparison, t-ADCs were reduced and varied inversely with the number of axons (and thus axolemmas) in a fixed cross-sectional area. Thus, diffusion was found to be isotropic when measured entirely within a single axon and anisotropic when measured in regions that included multiple axons. These findings support the hypothesis that the cell membrane is the primary source of diffusion anisotropy in fiber tracts of the central nervous system.

Animals↗

PubMed2002

In vivo NMR microscopy allows short-term serial assessment of multiple skeletal implications of corticosteroid exposure.

Corticosteroids are in widespread clinical use but are known to have adverse skeletal side effects. Moreover, it is not known how soon these effects become apparent. Here, we describe a longitudinal approach to evaluate the short-term implications of excess corticosteroid exposure by quantitative in vivo magnetic resonance imaging and spectroscopy in conjunction with digital image processing and analysis in a rabbit model. Two-week treatment with dexamethasone induced a significant reduction in trabecular bone volume, which occurred at the expense of uniform trabecular thinning without affecting network architecture. Paralleling the loss in bone volume was conversion of hematopoietic to yellow marrow in the femoral metaphysis and atrophy of the femoral epiphyseal growth plate. This work demonstrates that detailed quantitative morphometric and physiological information can be obtained noninvasively at multiple skeletal locations. The method is likely to eventually replace invasive histomorphometry in that it obviates the need to sacrifice groups of animals at multiple time points. Finally, this work, which was performed on a clinical scanner, has implications for evaluating patients on high-dose steroid treatment.

Animals↗

PubMed2002

Visualization of individual axons in excised lamprey spinal cord by magnetic resonance microscopy.

The direct visualization of axons within their native tissue environment by magnetic resonance (MR) microscopy is presented for the first time in the excised larval sea lamprey spinal cord. A home-built transverse radio frequency coil of 1.5 mm diameter was used in conjunction with a commercial 400 MHz MR microscopy system, implementing both 2-D and 3-D imaging pulse sequences. Images having nominal voxel sizes of 9x9x500 and 9x9x125 microm(3), respectively, in the lamprey spinal cord were obtained, resolving individual Mauthner and Müller axons. Furthermore, architectural changes associated with axonal degeneration were visualized in the spinal cord of one animal, excised 8 weeks after hemisection of the cord. Although the lamprey previously has not been the subject of MR microscopy investigations, these results demonstrate the method's potential for imaging this axon system, which is an important model of spinal cord injury and regeneration.

Animals↗

PubMed2002

Biexponential diffusion attenuation in the rat spinal cord: computer simulations based on anatomic images of axonal architecture.

Water diffusion in neurological tissues is known to possess multicomponent diffusion behavior. The fractions of fast and slow apparent diffusion components have often been attributed to the volume fractions of extracellular space (ECS) and intracellular space (ICS) although diffusion fractions are at variance with the tissue compartment volume ratios. In this article this puzzle was examined with a finite difference diffusion simulation model on the basis of optical images from sectioned rat spinal cord. Here the results show that assignment of fractions obtained from biexponential fits of fast and slow diffusion attenuation to ECS and ICS volume ratios is not correct. Rather, the observed multicomponent diffusion behavior is caused by motional restriction and limited intercompartmental water exchange in that at long diffusion times diffusion attenuation is shown to become monoexponential. Although the measured apparent diffusion fractions also depend on T2 relaxation time of water protons in the various compartments, the sensitivity to T2 is small and thus T2 differences are unlikely to explain the mismatch between apparent diffusion fractions and cellular volume fractions.

Animals↗

PubMed2002

Multislice double inversion pulse sequence for efficient black-blood MRI.

Over the last several years there has been a rapidly growing interest in high-resolution MRI of the vascular wall to assess the extent of atherosclerotic lesions. Vessels of particular clinical relevance are the carotid and coronary arteries. Currently, the preferred imaging sequence for these studies is a "black-blood" technique based on the double-inversion scheme to null the blood signal. A critical drawback of the black-blood technique, however, has been its single-slice nature, as there is only one point in time during the recovery of the blood magnetization from inversion at which the signal is completely nulled. Consequently, the total scan time can become prohibitively long, particularly when an imaging protocol includes several series of these datasets. In this work, a multiple-slice double-inversion technique is described that can reduce the scan time by a factor of two or more. It is demonstrated in vivo with examples from carotid and coronary arteries that one can acquire multiple slices with sufficient nulling of blood, following a single set of inversion pulses.

Adult↗

PubMed2002

Subvoxel processing: a method for reducing partial volume blurring with application to in vivo MR images of trabecular bone.

Partial volume blurring precludes accurate measurement of structural dimensions in the limited-resolution regime in which image voxel size is larger than the typical structural element to be resolved. Since acquiring images at increased resolution often exacts an unacceptable signal-to-noise ratio (SNR) penalty, methods to alleviate the adverse effects of partial volume blurring are instrumental for the accurate measurement of architectural parameters in applications such as predicting the mechanical competence of trabecular bone networks. In the current work, a novel post-processing method, referred to as "subvoxel processing," is described for increasing apparent image resolution. The method is applicable to volumes of interest containing material phases of two discrete signal intensities. The principal strategy consists of subdividing voxels and assigning voxel intensities to each subvoxel on the basis of local neighborhood criteria and strict mass conservation. In the current work, the method's accuracy has been evaluated using microcomputed tomography images (22 x 22 x 22 microm(3) voxel size) of human trabecular bone. The results demonstrate that subvoxel processing is significantly more accurate than trilinear interpolation in decreasing apparent voxel size, especially in the presence of noise. In addition, the method's effectiveness is illustrated with MR images of human trabecular bone acquired in vivo at 137 x 137 x 350 microm(3) voxel size. The subvoxel-processed images are shown to have architectural features characteristic of images acquired at higher spatial resolution.

Algorithms↗

PubMed2002

Diffusion of exchangeable water in cortical bone studied by nuclear magnetic resonance.

The rate-limiting step in the delivery of nutrients to osteocytes and the removal of cellular waste products is likely diffusion. The transport of osteoid water across the mineralized matrix of bone was studied by proton nuclear magnetic resonance spectroscopy and imaging by measuring the diffusion fluxes of tissue water in cortical bone specimens from the midshaft of rabbit tibiae immersed in deuterium oxide. From the diffusion coefficient (D(a) = (7.8 +/- 1.5) x 10(-7) cm(2)/s) measured at 40 degrees C (close to physiological temperature), it can be inferred that diffusive transport of small molecules from the bone vascular system to the osteocytes occurs within minutes. The activation energy for water diffusion, calculated from D(a) measured at four different temperatures, suggests that the interactions between water molecules and matrix pores present significant energy barriers to diffusion. The spatially resolved profile of D(a) perpendicular to the cortical surface of the tibia, obtained using a finite difference model, indicates that diffusion rates are higher close to the endosteal and periosteal surfaces, decreasing toward the center of the cortex. Finally, the data reveal a water component (approximately 30%) diffusing four orders of magnitude more slowly, which is ascribed to water tightly bound to the organic matrix and mineral phase.

Animals↗

PubMed2002

Intratendinous strain fields of the intact supraspinatus tendon: the effect of glenohumeral joint position and tendon region.

Rotator cuff tears are a common shoulder pathology and are hypothesized to relate to excessive tissue deformation. Few data exist, however, describing deformation of the rotator cuff as an intact, functional unit. Our purpose was to determine regional variations of intratendinous rotator cuff strain over a range of clinically relevant joint positions. A novel, MRI-based technique was utilized to quantify intratendinous strains in cadaveric shoulder specimens at 15 degrees, 30 degrees, 45 degrees, and 60 degrees of glenohumeral abduction in the scapular plane. The strain data were grouped into superior, middle, and inferior locations across the region where most rotator cuff tears occur clinically. A repeated measures ANOVA assessed the effects of joint position and tendon region on intratendinous strain. Few differences in intratendinous strain existed across tendon regions, but joint position had a pronounced effect. Specifically, intratendinous strain increased with increasing joint angle, and the 60 degrees strain was significantly greater than the 15 degrees strain across all tendon regions. These data suggest that joint position plays a larger role in rotator cuff mechanics than previously believed. Future studies will utilize this technique for quantifying intratendinous strain to assess the effects of partial-thickness rotator cuff tears.

Adult↗

PubMed2002

Role of magnetic resonance for assessing structure and function of trabecular bone.

The strength of trabecular bone and its resistance to fracture traditionally have 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. During the past decade there has been growing evidence from both laboratory and clinical studies against this view. Recent advances in noninvasive imaging technology, notably micro-magnetic resonance imaging (micro MRI) and computed tomography, offer an opportunity to test the hypothesis that architecture is an independent contributor to bone strength. MRI appears to be ideally suited for this task because bone marrow has uniform high signal intensity while bone appears with background intensity, thus yielding a binary system tomographic system. However, in vivo trabecular bone imaging is hampered by the limited signal-to-noise ratio that precludes voxel sizes much smaller than trabecular thickness, which would be required to yield a bimodal intensity histogram for segmentation of the image into bone and marrow. The resulting partial volume blurring leads to fuzzy boundaries. Successful structure analysis thus demands more elaborate processing strategies. 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 regimen of in vivo micro MRI. These methods are shown to provide detailed insight into the three-dimensional trabecular network topology and scale at the distal radius or distal tibia that typically serve as surrogate sites. The micro MRI-derived structural parameters are shown to be associated with the bone's biomechanical properties and fracture resistance. Further, 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 currently is confined to peripheral skeletal sites, and its extension to typical fracture sites such as the proximal femur hinges on further advances in detection sensitivity.

Animals↗

PubMed2002

Quantitative magnetic resonance imaging in the calcaneus and femur of women with varying degrees of osteopenia and vertebral deformity status.

Quantitative magnetic resonance imaging (QMRI) allows measurement of two parameters that are related to the integrity of the trabecular bone: R2*, the rate constant of the free induction signal, and trabecular bone volume fraction (BVF), the counterpart of apparent density. In this work, R2* and BVF were measured in 68 women (mean age, 58.2 +/- 9.5 years) of varying spinal bone mineral density (BMD) T scores (mean, -1.37 +/- 1.54) and vertebral fracture status on a commercial 1.5 T whole-body imager using customized image acquisition and processing techniques. Twenty-five of the patients had vertebral fractures, characterized by the total cumulative deformity burden exceeding 200%. R2* was measured in the calcaneus and proximal femur and BVF could be measured in the calcaneus only. On a pixel-by-pixel basis, calcaneal R2* and BVF within each subject were highly positively correlated (r2 = 0.61 +/- 0.11) but the correlation of region-of-interest (ROI) means for different calcaneal sites among patients was weaker (r2 = 0.34; p < 0.0001). The strongest discriminator of vertebral deformity was R2* of the calcaneus, which was lower in the fracture group, consistent with lower trabecular density. Among the calcaneal sites examined, the subtalar region, a location characterized by dense nearly horizontal trabeculae that transmit the stresses imparted by body weight from the tibia to the heel, best discriminated the two groups (p = 0.0001), with 77% diagnostic accuracy as determined from the area under the receiver operating characteristic (ROC) curve (compared with 66% for vertebral BMD). The cavum calcanei, an anterior site of low trabecular density, and the tuber calcanei (the location ordinarily used for ultrasound measurements) also had significantly reduced R2* in the fracture group (p < 0.005 and p = 0.01, respectively). The R2av*, computed as the average of all pixels in the calcaneus, was a strong discriminator as well (p < 0.005). On the other hand, calcaneal BVF was only marginally discriminating (p = 0.05). Among the BMD sites examined, the lumbar spine (average L1-L4) was significant (p = 0.005, 66% diagnostic accuracy), as was the femoral neck (p = 0.01). The data suggest the calcaneus to be suited as a surrogate site to assess vertebral osteoporosis and that R2* is sensitive to alterations in bone quality not captured by density.

Absorptiometry, Photon↗