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F W Wehrli

Publications and source records attributed to F W Wehrli.

At least 37 records · Page 2Linked to original sources

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↗

New architectural parameters derived from micro-MRI for the prediction of trabecular bone strength.

This article reviews recent progress in magnetic resonance microimaging of cancellous bone in vitro and in vivo from the perspective of the authors' laboratory. It is shown that in particular in vivo the key technical prerequisites to satisfy are: (i) achieving sufficient signal-to-noise ratio (SNR) to allow for adequate spatial resolution; (ii) the image processing algorithms have to be robust enough to provide accurate structural information in the limited spatial resolution regime, i.e., in the presence of inevitable partial volume blurring and noise. The practical lower limit of voxel size in vivo was found to be about 6 x 10(-3) mm3 in the radius, and about 10(-4) mm3 for small specimens in vitro with state-of-the-art equipment and scan times of 10 and 30 minutes, resp., and SNR approximately 10. Finally, data are presented highlighting the potential of these methods for predicting the bone's elastic modulus in vitro and fracture risk in vivo.

Algorithms↗

In vivo MR microscopy of the human skin.

The requirements for imaging the skin are dictated by the organ's layered structure, which extends only a few millimeters from the surface and thus demands extremely high resolution in this direction. While less critical, resolution in the remaining two dimensions determines whether the skin's accessory structures can be resolved. The problem is compounded by short transverse relaxation times, in particular of the dermis, the structure of most clinical interest. In this work images of the normal human skin were obtained in vivo at voxel sizes as small as 19 x 78 x 800 microm3, by means of customized 3D gradient and partial flip-angle spin-echo pulse sequences and very small transmit/receive coils on a 1.5T clinical imager equipped with high-power whole-body gradients. Structures resolved include hair follicles and the sublayers of the dermis. The very short time constant for the major component (91%) for transverse relaxation in the dermis (T2* approximately 10 ms) suggests the potential of substantial gains in achievable signal-to-noise ratio by shortening the echo time.

Adipose Tissue↗

Magnetic susceptibility measurement of insoluble solids by NMR: magnetic susceptibility of bone.

Measurements of the volume magnetic susceptibility of solids using the classical Gouy balance approach are hampered by variations in apparent density of the packed powder. In this paper a quantitative NMR measurement of the volume magnetic susceptibility of powdered solids is described and the volume susceptibility of bone is reported. The technique is based on the measurement of changes in incremental linewidth (1/pi T2') induced in a marker fluid whose susceptibility can be predictably modified by changing the composition, such as by addition of a soluble diamagnetic compound. The spectroscopic linewidth of the marker fluid is determined by the susceptibility difference between the fluid and the suspended solid. Changes in the linewidth are accompanied by bulk magnetic susceptibility induced frequency shifts in the fluid resonance. Correlating the two dependencies allows measurement of the absolute volume susceptibility of the solid. The susceptibility of bovine rib bone was found to be -0.9 +/- 0.02 x -10(-6) (CGS) confirming previous estimates which suggested bone to be more diamagnetic than the marrow constituents. Knowledge of the susceptibility of bone is relevant in view of the growing interest in MRI osteodensitometric techniques.

Animals↗

A single-scan imaging technique for measurement of the relative concentrations of fat and water protons and their transverse relaxation times.

A two-component chemical-shift-imaging technique is described from which fat and water images can be obtained in a single scan and in the presence of an inhomogeneous field. In addition, the method provides transverse relaxation rates R2 and R2' separately for each of the spectral components. The method is a combination and extension of the GESFIDE [gradient echo sampling of FID and echo, J. Ma and F. W. Wehrli, J. Magn. Reson. B 111, 61 (1996)] and the multipoint Dixon techniques. It is based on sampling the descending and ascending portions of a Hahn spin echo with a train of gradient echoes which are spaced at one-half of the chemical-shift modulation period. Processing of the complex echo data, involving an automated phase unwrapping algorithm, affords relative amplitudes and transverse relaxation rates of the two spectral components. An additional benefit of the method is its superior signal-to-noise ratio resulting from echo summation. Applications targeted and illustrated involve MRI osteodensitometry of trabecular bone in the presence of varying fractions of hematopoietic and fatty bone marrow.

Adult↗

Probability-based structural parameters from three-dimensional nuclear magnetic resonance images as predictors of trabecular bone strength.

The mechanical competence of trabecular bone is a function of its apparent density and three-dimensional (3D) distribution. Three-dimensional structure is typically inferred from histomorphometry and stereology on a limited number of two-dimensional anatomic sections. In this work 3D nuclear magnetic resonance (NMR) images of anisotropic trabecular bone from the distal radius were analyzed in terms of a series of new structural parameters which are obtainable at relatively crude resolution, i.e., in the presence of substantial partial volume blurring. Unlike typical feature extraction techniques requiring image segmentation, the method relies on spatial autocorrelation analysis, which is based on the probability of finding bone at specified locations. The structural parameters were measured from high-resolution images (78x78x78 microm3 voxels) of 23 trabecular bone specimens from the distal radius. Maximum-likelihood bone volume fractions (BVF) were calculated for each voxel and a resolution achievable in vivo (156x156x391 microm3 voxels) was simulated by averaging BVF's from neighboring voxels. The parameters derived from the low-resolution images were found to account for 91% of the variation in Young's modulus. The results suggest that noninvasive assessment of the mechanical competence of trabecular bone in osteoporotic patients may be feasible.

Biomechanical Phenomena↗

Fast 3D large-angle spin-echo imaging (3D FLASE).

A rapid steady-state 3D spin-echo imaging pulse sequence, based on the principle of nutating the spins by an angle greater than 90 degrees, has been designed and implemented on a clinical 1.5-T whole-body MR scanner. The pulse sequence, denoted fast large-angle spin-echo (FLASE), has been optimized for high-resolution imaging of tissues with short T2 and T2*. Features of FLASE include a minimum-phase Shinnar-Le Roux excitation pulse and distribution of phase- and slice-encoding gradients before and after the 180 degrees refocusing pulse to minimize the critical time delay between inversion and restoration of the residual longitudinal magnetization and for minimizing echo time. A Bloch equation analysis, corroborated by experimental data, shows FLASE signal-to-noise to be superior to its closest analog, 3D rapid spin-echo excitation (RASEE) (Jara et al., Magn Reson Medicine 29, 528 (1993)), and 3D gradient-recalled acquisition in steady state (GRASS). It is demonstrated that with judicious RF phase-cycling and steady state operation, FLASE can produce high-quality microimages free of intravoxel phase dispersion from susceptibility-induced background gradients. The performance of the method is exemplified with ultra high-resolution images of trabecular bone in vitro and in vivo in the human calcaneus and wrist at voxel sizes as low as 98 x 98 x 200 microns3. Finally, the contrast behavior of refocused FLASE can be altered by disrupting the steady state analogous to gradient echo imaging.

Bone and Bones↗

Method for image-based measurement of the reversible and irreversible contribution to the transverse-relaxation rate.

A multislice NMR imaging pulse sequence capable of measuring both the reversible and irreversible contribution to the transverse-relaxation rate (R'2 and R2) in a single scan is described. The method, termed GESFIDE (gradient-echo sampling of FID and echo) is based on sampling the descending and ascending portions of a Hahn echo with a train of gradient echoes. R2 and R'2 are computed by exploiting the differential evolution of the transverse magnetization before and after the phase-reversal pulse. Salient features of the method are its insensitivity to RF pulse imperfections and its high precision and efficiency. Applications examined involve the characterization of magnetically inhomogeneous tissues and biomaterials such as trabecular bone marrow in the skeleton and brain iron.

Bone Marrow↗

Quantitative analysis of trabecular microstructure by 400 MHz nuclear magnetic resonance imaging.

A new approach for the quantitative analysis of trabecular microstructure, based on high-field proton nuclear magnetic resonance (NMR) imaging, is presented. NMR is ideal because it provides high contrast between the marrow proton signal and the bone, which appears with background intensity. Images from 1 cm3 defatted specimens of trabecular bone, suspended in water doped with 1 mM Gd(DTPA) to shorten T1 to about 300 ms, can be obtained at a resolution on the order of 30-50 microns and slice thickness of 150 microns, in 10 minutes at 400 MHz proton frequency. Digital image processing algorithms were designed and evaluated for the measurement of bone area fraction, perimeter length, mean trabecular thickness, and separation. Bone area fraction derived from the NMR images was found to be in excellent agreement with bone volume fraction measured independently (slope = 0.96, r2 = 0.924, p < 0.0001). Errors in the mean trabecular thickness and separation were < 6%. The effects of finite imaging slice thickness and signal-to-noise ratio (SNR) were also evaluated. The data suggest a resolution of 50 x 50 x 200 microns 3 and an SNR on the order of 10 to provide safe margins for precise and accurate structural analysis by means of the algorithms presented in this paper. The method allows simultaneous measurement at multiple locations within the specimen volume without the need for physical sectioning.

Algorithms↗

Three-dimensional nuclear magnetic resonance microimaging of trabecular bone.

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 from 9 x 9 x 4 mm3 volumes of defatted bone specimens in 15-20 minutes scan time at isotropic resolution corresponding to (78 microm)3 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 principle axes of the mean intercept length tensor.

Adult↗

Osteoporosis: clinical assessment with quantitative MR imaging in diagnosis.

PURPOSE: To determine if the magnetic resonance (MR) imaging effective transverse relaxation rate (R2*) of trabecular bone marrow is lowered in osteoporosis. MATERIALS AND METHODS: R2* was measured in 146 women. Control subjects (n = 77; mean age, 46.6 years) had high mean spinal bone mineral densities (BMDs) and no vertebral deformities. Patients with spinal osteoporosis (n = 59; mean age, 59.7 years) had at least one thoracic vertebral deformity and/or low BMDs. RESULTS: R2* was lower in patients for L-2 through L-5 (P < .001). Average R2* of L-3 through L-5 (R2*av) was the best discriminator (64.79 sec-1 +/- 1.18 [standard error] for control subjects vs 53.39 sec-1 +/- 1.24 for patients; P < .0001). R2*av decreased with age in control subjects. The difference in R2*av in a subset of 38 age-matched pairs of patients and control subjects was 8.25 sec-1 (P < .0001). Subjects with deformities had lower 52*av than did control subjects (52.3 sec-1 +/- 1.6 vs 62.5 sec-1 +/- 1.1, P < .0001). R2*av was correlated with mean BMD (r = .54, P < .0001). CONCLUSION: Patients with osteoporosis have lower R2*s in vertebral marrow.

Absorptiometry, Photon↗

A Bayesian approach to subvoxel tissue classification in NMR microscopic images of trabecular bone.

NMR microscopy is currently being used as an investigational tool for the evaluation of micromorphometric parameters of trabecular bone as a possible means to assess its strength. Since, typically, the image voxel size is not significantly smaller than individual trabecular elements, partial volume blurring can be a major complication for accurate tissue classification. In this paper, a Bayesian segmentation technique is reported that achieves improved subvoxel tissue classification. Each voxel is subdivided either into eight subvoxels twice the original resolution, or up to four subvoxels along the transaxial direction and the subvoxels optimally classified as volume blurring, the likelihood for the number of marrow subvoxels in each voxel can be computed on the basis of its measured signal. To resolve the ambiguity of the location of the marrow subvoxels, a Gibbs distribution is introduced to model the interaction between the subvoxels. Neighboring subvoxel pairs with the same tissue label are encouraged, and pairs with distinct labels are penalized. The segmentation is achieved by maximizing the a posteriori probability of the label image using the block ICM (iterative conditional mode) algorithm. The potential of the proposed technique is demonstrated in real and synthetic NMR microscopic images.

Algorithms↗