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F W Wehrli

Publications and source records attributed to F W Wehrli.

At least 19 recordsLinked to original sources

A noncontact, nondestructive method for quantifying intratissue deformations and strains.

The function of soft connective tissues is frequently characterized by quantifying tissue strain (e.g., during joint motion). Conventional techniques for quantifying tendon and ligament strain typically provide surface measures, using markers, stain lines or instrumentation that may influence the tissue. An alternative approach is to quantify intratendinous strain by applying texture correlation analysis to magnetic resonance (MR) images. This paper reports the accuracy and reproducibility of this approach by (1) assessing the reproducibility of MR images, (2) assessing texture correlation accuracy using simulated displacements, and (3) comparing texture correlation measures of displacement and strain from MR images to conventional techniques.

Cadaver↗

Water magnetic relaxation dispersion in biological systems: the contribution of proton exchange and implications for the noninvasive detection of cartilage degradation.

Magnetic relaxation has been used extensively to study and characterize biological tissues. In particular, spin-lattice relaxation in the rotating frame (T(1rho)) of water in protein solutions has been demonstrated to be sensitive to macromolecular weight and composition. However, the nature of the contribution from low frequency processes to water relaxation remains unclear. We have examined this problem by studying the water T(1rho) dispersion in peptide solutions ((14)N- and (15)N-labeled), glycosaminoglycan solutions, and samples of bovine articular cartilage before and after proteoglycan degradation. We find in model systems and tissue that hydrogen exchange from NH and OH groups to water dominates the low frequency water T(1rho) dispersion, in the context of the model used to interpret the relaxation data. Further, low frequency dispersion changes are correlated with loss of proteoglycan from the extra-cellular matrix of articular cartilage. This finding has significance for the noninvasive detection of matrix degradation.

Amino Acid Sequence↗

Trabecular bone volume fraction mapping by low-resolution MRI.

Trabecular bone volume fraction (TBVF) is highly associated with the mechanical competence of trabecular bone. TBVF is ordinarily measured by histomorphometry from bone biopsies or, noninvasively, by means of high-resolution microcomputed tomography and, more recently, by micro-MRI. The latter methods require spatial resolution sufficient to resolve trabeculae, along with segmentation techniques that allow unambiguous assignment of the signal to bone or bone marrow. In this article it is shown that TBVF can be measured under low-resolution conditions by exploiting the attenuation of the MR signal resulting from fractional occupancy of the imaging voxel by bone and bone marrow, provided that a reference signal is available from a marrow volume devoid of trabeculation. The method requires accurate measurement of apparent proton density, which entails correction for various sources of error. Key among these are the spatial nonuniformity in the RF field amplitude and effects of the slice profile, which are determined by B(1) field mapping and numerical integration of the Bloch equations, respectively. By contrast, errors from variations in bone marrow composition (hematopoietic vs. fatty) between trabecular and reference site are predicted to be small and usually negligible. The method was evaluated in phantoms and in vivo in the distal radius and found to be accurate to 1% in marrow volume fraction. Finally, in a group of 12 patients of varying skeletal status, TBVF in the calcaneus was found to strongly correlate with integral bone mineral density of the lumbar vertebrae (r(2) = 0.83, p < 0.0001). The method may fail in large imaging objects such as the human trunk at high magnetic field where standing wave and RF penetration effects cause intensity variations that cannot be corrected. Magn Reson Med 46:103-113, 2001.

Animals↗

Digital topological analysis of in vivo magnetic resonance microimages of trabecular bone reveals structural implications of osteoporosis.

Osteoporosis is a disease characterized by bone volume loss and architectural deterioration. The majority of work aimed at evaluating the structural implications of the disease has been performed based on stereologic analysis of histomorphometric sections. Only recently noninvasive imaging methods have emerged that provide sufficient resolution to resolve individual trabeculae. In this article, we apply digital topological analysis (DTA) to magnetic resonance microimages (mu-MRI) of the radius obtained at 137 x 137 x 350 microm3 voxel size in a cohort of 79 women of widely varying bone mineral density (BMD) and vertebral deformity status. DTA is a new method that allows unambiguous determination of the three-dimensional (3D) topology of each voxel in a trabecular bone network. The analysis involves generation of a bone volume fraction map, which is subjected to subvoxel processing to alleviate partial volume blurring, followed by thresholding and skeletonization. The skeletonized images contain only surfaces, profiles, curves, and their mutual junctions as the remnants of trabecular plates and rods after skeletonization. DTA parameters were compared with integral BMD in the lumbar spine and femur as well as MR-derived bone volume fraction (BV/TV). Vertebral deformities were determined based on sagittal MRIs of the spine with a semiautomatic method and the number of deformities counted after threshold setting. DTA structural indices were found the strongest discriminators of subjects with deformities from those without deformities. Subjects with deformities (n = 29) had lower topological surface (SURF) density (p < 0.0005) and surface-to-curve ratio (SCR; a measure of the ratio of platelike to rodlike trabeculae; p < 0.0005) than those without. Profile interior (PI) density, a measure of intact trabecular rods, was also lower in the deformity group (p < 0.0001). These data provide the first in vivo evidence for the structural implications inherent in postmenopausal osteoporosis accompanying bone loss, that is, the conversion of trabecular plates to rods and disruption of rods due to repeated osteoclastic resorption.

Adult↗

In vivo MR micro imaging with conventional radiofrequency coils cooled to 77 degrees K.

Cryogenically cooled conventional surface coils are shown to provide significant signal-to-noise ratio (SNR) gains for MR micro imaging of tissue structure in vivo. Measurements are described which employ a simple, all-polyvinyl chloride (PVC) vacuum dewar capable of maintaining a bath of liquid nitrogen around the coil, within 5 mm of the tissue to be imaged. Images acquired in vivo at 64 MHz with a 2-cm diameter copper coil cooled to 77 K demonstrated a gain in SNR of approximately 2.7 +/- 0.3 relative to those obtained with the same coil at room temperature under otherwise identical conditions. This increase is consistent with the reduction in coil resistance and the minor contribution to overall resistance from the imaging object. The performance of the coil is illustrated with images from the human finger and rabbit eye and potential applications are discussed.

Animals↗

Postprocessing technique to correct for background gradients in image-based R*(2) measurements.

Background static magnetic field gradients are a source of signal loss in gradient-echo imaging, as they typically result from discontinuity in the magnetic susceptibility at air-tissue boundaries. Moreover, these induced gradients severely compromise the measurement of R*(2), the effective transverse relaxation rate, which is of interest in many biomedical applications of MRI. Since the slice thickness is usually larger than the in-plane pixel dimensions, gradients parallel to the slice-select direction are of particular concern. In this work, a post-processing technique is introduced which attempts to correct the signal on the assumption that the background gradients are approximately linear across the voxel and the signal decay in the absence of these gradients is exponential. In this case, the time-domain signal is weighted by a sinc function characterized by the amplitude G(b) of the background gradient, which is typically not known a priori. The algorithm searches for the estimate of G(b) which yields the optimum fit of the corrected experimental data to an exponential. It is shown to be effective as long as this gradient is below a critical threshold. Evaluation in a phantom and in the human brain at 1.5 and 4 T demonstrates that this method can restore R(2)* in spite of the apparent rate constant exceeding the true value by up to 100%. Contrary to prospective correction techniques, the approach presented in this study does not prolong scan time.

Adult↗

High-speed spectroscopic imaging for cancellous bone marrow R(2)* mapping and lipid quantification.

In this work an interleaved multiple-gradient-echo chemical shift imaging (IMGE-CSI) technique was designed, implemented and evaluated at 1.5 and 4T for high-resolution lipid quantification and R(2)* measurement in-vivo. The method is analogous to echo planar CSI but utilizes conventional gradient echoes, exploiting the principle of spectroscopic bandwidth extension by interleaving temporally offset gradient-echo trains. It is shown that IMGE-CSI is able to measure true fat volume fraction in oil/water mixtures with high accuracy, not possible with Dixon-type methods which approximate the spectrum as consisting of only two spectral components. Correlation of the CSI- derived volume fractions with volumetry afforded r(2) > 0.99 with a slope of 0.98. The method is shown to be able to quantify regional variations in bone marrow composition in vivo with a spatial resolution of 2.5 x 2.5 x 5 mm(3.) R(2)* was obtained by multi-line spectral curve fitting. For the measurement of R(2)* in cancellous bone marrow the method is shown to agree well with time-domain fitting techniques but is superior in instances where the marrow has both hematopoietic and fatty constituents. Finally, excellent inter-scan reproducibility (1% coefficient of variation for global means and medians) was achieved, yielding r(2) = 0.98 of the test-retest correlation for three scans in four test subjects. In conclusion, IMGE-CSI is found to enable highly accurate lipid quantification and measurement of cancellous bone marrow R(2)* at spatial resolutions and scan times typical of standard clinical protocols.

Bone Marrow↗

Relationship between cancellous bone induced magnetic field and ultrastructure in a rat ovariectomy model.

The site-dependent variations in trabecular bone morphology were studied in the rat tibia by magnitude and phase difference three-dimensional nuclear magnetic resonance microscopy and image processing, and the implications of ovariectomy were evaluated. Specimens excised from the proximal tibial metaphysis in ovariectomized (n = 7) and intact control (n = 4) rats were imaged at 9.4T with their anatomic axes parallel to the direction of the magnetic field. An echo-offset 3D rapid spin-echo excitation pulse sequence was used to generate phase difference maps, from which the standard deviation of the phase difference, sigma(delta psi), was calculated. In addition, a fictitious rate constant, R2', was calculated from the slope of the exponential portion of the Fourier transform of the phase difference histogram. Trabecular bone volume fraction was also determined in the same volume of interest. The results show strong correlations between bone volume fraction and both sigma(delta psi) and R2', suggesting that these parameters could be useful for nondestructive assessment of trabecular bone volume.

Animals↗

Topological analysis of trabecular bone MR images.

Recently, imaging techniques have become available which permit nondestructive analysis of the three-dimensional (3-D) architecture of trabecular bone (TB), which forms a network of interconnected plates and rods. Most osteoporotic fractures occur at locations rich in TB, which has spurred the search for architectural parameters as determinants of bone strength. In this paper, we present a new approach to quantitative characterization of the 3-D microarchitecture of TB, based on digital topology. The method classifies each voxel of the 3-D structure based on the connectivity information of neighboring voxels. Following conversion of the 3-D digital image to a skeletonized surface representation containing only one-dimensional (1-D) and two-dimensional (2-D) structures, each voxel is classified as a curve, surface, or junction. The method has been validated by means of synthesized images and has subsequently been applied to TB images from the human wrist. The topological parameters were found to predict Young's modulus (YM) for uniaxial loading, specifically, the surface-to-curve ratio was found to be the single strongest predictor of YM (r2 = 0.69). Finally, the method has been applied to TB images from a group of patients showing very large variations in topological parameters that parallel much smaller changes in bone volume fraction (BVF).

Aged↗

Cross-sectional study of osteopenia with quantitative MR imaging and bone densitometry.

PURPOSE: To evaluation the cancellous bone-induced intravoxel spin dephasing rate (R2') and its relationship to bone mineral density and marrow fat and to examine these parameters as predictors of vertebral fracture status. MATERIALS AND METHODS: R2' and R2, the rate constants for reversible and irreversible spin dephasing, and marrow fat fraction were measured in the lumbar vertebrae and proximal femur. One hundred thirty-nine subjects (mean age, 62.4 years +/- 11.4 [SD]; 33 men, 106 women) had spinal dual-energy x-ray absorptiometric bone mineral density (BMD) T scores ranging from +3 to -5. R2', BMD, and bone marrow composition as determinants of vertebral fracture status were examined. RESULTS: Strongest single predictors of fracture status for BMD and R2' were the Ward triangle (r(2) = 0.48) and trochanter (r(2) = 0.37), respectively. Combined, the two parameters and sites increased fracture prediction (r(2) = 0. 62), whereas the combination of multiple BMD sites did not. Multivariate regression involving marrow fat fraction further improved fracture status prediction. R2' was correlated with BMD at all sites, although slopes differed by a factor of up to 2.5, which reflected differences in trabecular orientation relative to the static field. R2, the true transverse relaxation rate, was negatively correlated with marrow fat fraction. A non-age-related increase in marrow fat fraction in osteoporosis parallels earlier findings in animal models. CONCLUSION: Cancellous bone marrow R2' measured in the proximal femur provides information, which, with BMD, improves prediction of vertebral fracture status.

Absorptiometry, Photon↗

In vivo micro-imaging using alternating navigator echoes with applications to cancellous bone structural analysis.

In micro-magnetic resonance imaging of cancellous bone architecture, involuntary subject motion even on a sub-millimeter scale is detrimental and generally precludes accurate quantification of architectural parameters. In this work a navigator-assisted three-dimensional spin-echo technique is described and evaluated for imaging at 137 microm resolution in humans. The method is based on gradient navigator echoes following the spin-echo readout for sensing translational displacements alternately in x- and y-directions with a spatial resolution of 273 microm and a temporal resolution of 0.2 sec. The technique is shown to improve micro-images of the distal forearm significantly and to enhance accuracy and reproducibility of bone volume fraction, transverse contiguity, and tubularity, parameters introduced in prior work to characterize the trabecular network. It is further shown that a fourfold reduction in navigator sampling time, along with zero-filling, improves the accuracy of the navigator correction while reducing the minimum pulse repetition time or gradient heating. The data indicate that navigator-assisted micro-imaging is capable of effectively correcting sub-millimeter displacements in micro-imaging.

Adult↗

Experimental evaluation of a surface charge method for computing the induced magnetic field in trabecular bone.

The magnetic field induced in the pores of trabecular bone as a result of the susceptibility difference between bone and bone marrow was computed with the aid of magnetic surface charge models generated from images of trabecular bone specimens acquired at 78 and 63 microm resolution. The predicted field was compared with the values derived from 2D and 3D field maps obtained by echo-offset imaging techniques and excellent agreement was found between the two methods. Finally, from the slopes of regression between the experimental and computed fields, the absolute susceptibility of bone was nondestructively determined as -11.0 x 10(-6) (MKS), which is in close agreement with a reported value of -11.3 x 10(-6) obtained with powdered bone by means of a spectroscopic susceptibility matching technique (J. A. Hopkins and F. W. Wehrli, Magn. Reson. Med. 37, 494-500 (1997)).

Animals↗

Effect of prostaglandin and bisphosphonate on cancellous bone volume and structure in the ovariectomized rat studied by quantitative three-dimensional nuclear magnetic resonance microscopy.

The purpose of this work was to evaluate the potential of nuclear magnetic resonance microscopy (NMRM) in conjunction with a processing technique to monitor the effect of preventive agents in an ovariectomized (OVX) rat. Twenty-five female Sprague-Dawley rats were OVX at 6 months of age (except for the intact control group), allowed to lose bone for 60 days, and then treated for 60 days. During treatment, animals were administered vehicle, prostaglandin E2 (PGE2; 6 mg/kg), or alendronate (3 microg/kg) subcutaneously once a day. Subsequently, tibiae were harvested and the marrow removed. NMRM was carried out at 9.4 T, with the specimens immersed in 1.2 mM diethylenetriaminepentaacetic acid-gadolinium salt (Gd-DTPA) aqueous solution. A three-dimensional (3D) partial flip-angle pulse sequence was used, providing a 1283 array of (46 microm)3 isotropic voxels. Fifty of the 128 axial images in the 3D data set comprising approximately 2.4 mm volume distal to the growth plate were processed from each specimen using a probability-based method for determining bone volume fraction (BVF), tubularity, contiguity, as well as the mean trabecular plate thickness and separation. PGE2 and alendronate altered BVF consistently at all tibial regions. The effect of alendronate was to keep BVF about midway between intact and OVX, whereas PGE2 returned BVF to intact levels. The other parameters showed similar responses to treatment. The strongest discriminator was trabecular BVF, which could obviously differentiate the groups. The study establishes NMRM as a nondestructive histomorphometric method for the quantitative evaluation of drug response in a rat ovariectomy model.

Alendronate↗

Variable TE gradient and spin echo sequences for in vivo MR microscopy of short T2 species.

Collagen-rich tissues such as skin or fibrous cartilage have very short T2 and thus, in order to be visible, demand a commensurate reduction in echo time. Whereas short echo time for imaging of humans is straightforward at large fields of view with currently available whole body gradient hardware, the problem is more challenging in the microscopic resolution regime (<100 microm). In this work a simple approach consisting of shortening the echo time dynamically toward the lower spatial frequencies is described for three-dimensional partial flip-angle gradient and spin-echo sequences. Microimages obtained in vivo at 50 microm resolution on a 1.5 T whole body scanner are shown to afford a signal-to-noise gain of over 100% in the dermis of the human skin. A point-spread function analysis indicates that the variable echo time gradient-echo sequence produces a unique not previously reported off-resonance artifact in the phase-encoding direction. The artifact results from the phase modulation occurring during the variable echo time and can manifest as both blurring and intensity fluctuations, as well as shifts of boundaries in the phase-encoding direction. However, for the on-resonance condition, the images are free from these artifacts and exhibit significantly improved signal-to-noise ratio.

Artifacts↗

Measurement of R'2 in the presence of multiple spectral components using reference spectrum deconvolution.

A method is described for measuring R'2, the RF reversible contribution to the effective transverse relaxation rate in yellow trabecular marrow, as a means to evaluate trabecular bone structure and density. The method exploits the similarity in spectral composition of the marrow and fat in subcutaneous tissue. Under these conditions the gradient echo envelope of the marrow signal can be regarded as a convolution of a function describing the bone marrow intravoxel line broadening (R'2) with a function expressing chemical shift modulation, which is obtained from the echo envelope of the subcutaneous fat signal in a reference region. Simple division of each of a series of echoes by the reference signal is shown to afford a smooth decay which can be fitted to a model to extract R'2. The method has been evaluated in the upper femur of test subjects and a strong correlation of the thus derived R'2 values with those obtained by the GESFIDE technique is demonstrated. The close correspondence in spectral composition of proximal femur marrow and subcutaneous fat is further illustrated by means of localized spectroscopy. The major potential error source is global inhomogeneity in the reference region which can lead to an underestimation of the demodulation-derived R'2.

Absorptiometry, Photon↗

Cancellous bone volume and structure in the forearm: noninvasive assessment with MR microimaging and image processing.

PURPOSE: To develop and apply a method for the derivation of cancellous bone architectural parameters from in vivo magnetic resonance (MR) images of the distal radius and to evaluate these parameters as predictors of vertebral fracture status in osteopenia. MATERIALS AND METHODS: MR images (137 x 137 x 500-micron3 voxel size) were acquired with a three-dimensional partial flip-angle spin-echo pulse sequence in the distal radius of 36 women. Subjects were classified as healthy or with osteoporosis on the basis of vertebral deformity and bone mineral density (BMD). Images rated as of adequate quality in 20 subjects were processed with a method that is applicable in the limited spatial resolution regime. The method relies on histogram deconvolution to obviate binary segmentation. Cancellous bone structure was treated as a quasi-regular lattice and analyzed with spatial autocorrelation, yielding parameters that quantify intertrabecular spacing, contiguity, and a measure of longitudinal alignment called tubularity. RESULTS: Whereas neither BMD nor any of the structural parameters individually correlated significantly with vertebral deformity fraction, a simple function that involved tubularity and longitudinal spacing predicted deformity fraction well (r = .78, P < .005). CONCLUSION: Histomorphometric parameters characterizing cancellous bone in the distal radius can be derived from in vivo MR microimages and are predictive of vertebral deformity.

Absorptiometry, Photon↗