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Biomedical subjects

David B Hackney

Publications and source records attributed to David B Hackney.

8 recordsLinked to original sources

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↗

Ex vivo MR determined apparent diffusion coefficients correlate with motor recovery mediated by intraspinal transplants of fibroblasts genetically modified to express BDNF.

The purpose of this study was to determine whether apparent diffusion coefficients (ADCs) in ex vivo spinal cord white matter, calculated from diffusion weighted MR (DWI) images, correlate with axonal growth and behavioral recovery following subtotal hemisection and transplantation of fibroblasts genetically modified to express brain derived neurotrophic factor (BDNF). These genetically modified fibroblasts have been shown to promote axonal growth, diminish retrograde degenerative changes in axotomized Red nucleus neurons, and are associated with behavioral recovery. Since changes in ADC appear to reflect damage to axons and myelin sheaths, which conventional MR techniques do not identify, partial repair mediated by BDNF-secreting fibroblasts should be detected with ADC measures. Accordingly, we transplanted unmodified fibroblasts (Fb-UM) or fibroblasts modified to secrete BDNF (Fb-BDNF) into cervical subtotal hemisection cavities in adult rats. Rats with Fb-BDNF transplants showed significantly greater behavioral recovery over 12 weeks, as measured by tests of forelimb exploration and open field locomotor activity. Lesion sizes and transplant survival did not differ between the two groups, but immunocytochemical examination showed substantial growth of axons into the Fb-BDNF grafts and little growth into the Fb-UM grafts. Fixed spinal cords were imaged in a 9.4-T magnet. ADCs perpendicular (tADC) and parallel (lADC) to the long axis of the cord were measured in the dorsal lateral white matter, rostral and caudal to the transplant. tADC values and anisotropy index (AI = tADC/lADC) were elevated in both transplant types, indicating white matter damage, but were closer to normal in rats with Fb-BDNF, consistent with known neuroprotection and axonal growth elicited by BDNF. Closer to normal tADC and AI values correlated with improved behavioral recovery. These findings suggest that high-resolution imaging with measurement of tADC and lADC can provide a measure of functionally significant repair that may otherwise go undetected with conventional MR techniques.

Animals↗

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↗

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↗

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↗

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↗

Diffusion-weighted imaging of the spinal cord.

Spinal cord DWI may be useful in providing information not available with conventional MR imaging. More work, however, is required to explain what the qualitative and quantitative results actually represent. Computer simulations and detailed radiologic-histologic correlations will therefore be necessary.

Animals↗

Estimation of tumor volume with fuzzy-connectedness segmentation of MR images.

BACKGROUND AND PURPOSE: Reproducible measurements of brain tumor volume are helpful in evaluating the response to therapy and the need for changing treatment plans. Our purpose was to adapt the fuzzy-connectedness segmentation technique to measure tumor volume. This technique requires only limited operator interaction. METHODS: Routine postoperative brain MR imaging was performed in 19 patients with primary malignant gliomas of the brain. Segmentation was performed on axial and coronal gadolinium-enhanced and axial fluid-attenuated inversion recovery (FLAIR) images by using a fuzzy-connectedness algorithm, and tumor volumes were generated. Operator interaction was limited to selecting representative seed points within the tumor and, if necessary, editing the segmented image to include or exclude improperly classified regions. RESULTS: Measurements of tumor volume were highly reproducible when they were obtained with no editing; intraobserver coefficients of variation were 0.15-0.37% and 0.29-0.38%, respectively, for enhanced images and FLAIR images. Editing consistently produced smaller volumes, at the cost of greater variability in volume measurements. Coefficients of variation for volumes with editing ranged from 0.2% to 1.3%. CONCLUSIONS: Fuzzy-connected segmentation permits rapid, reliable, consistent and highly reproducible measurement of tumor volume from MR images with limited operator interaction.

Adult↗