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David B Hackney

Publications and source records attributed to David B Hackney.

17 recordsLinked to original sources
PubMed2006

Effects of cord motion on diffusion imaging of the spinal cord.

Measurement of diffusion and its dependence on direction has become an important tool for clinical and research studies of the brain. Diffusion imaging of the spinal cord may likewise prove useful as an indicator of tissue damage and axonal integrity; however, it is more challenging to perform diffusion imaging in the cord than in the brain. Here we report a study of the effects of motion on single-shot fast spin echo (FSE) diffusion tensor imaging (DTI) of the spinal cord. Diffusion imaging was performed at four different times in the cardiac cycle both without and with velocity compensation of the diffusion gradients. Uncompensated diffusion images demonstrated substantial signal loss artifacts in the cord that were strongly dependent on the delay after the pulse-oximeter trigger. Quantitative diffusion analysis was also strongly affected by this motion artifact. The use of flow-compensated gradients helped to restore normal signal in the cord, especially at particular trigger delays. Theoretical arguments suggest that improved spatial resolution may help eliminate this signal loss. Even with higher spatial resolution, motion-related signal attenuation may still occur in diffusion imaging of pathologies that alter the motion of the cord. However, this same cord motion may contain diagnostically valuable information when probed using appropriate diffusion imaging approaches.

Adult↗
PubMed2005

MRI diffusion coefficients in spinal cord correlate with axon morphometry.

Following spinal cord injury, diffusion MRI (DWI) has been shown to detect injury and functionally significant neuroprotection following treatment that otherwise would go undetected with conventional MRI. The underlying histologic correlates to directional apparent diffusion coefficients (ADC) obtained with DWI have not been determined, however, and we address this issue by directly correlating ADC values with corresponding axon morphometry in the normal rat cervical spinal cord. ADC values transverse (perpendicular) and longitudinal (parallel) to axons both correlate with axon counts, however each directional ADC reflects distinct histologic parameters. DWI may therefore be capable of providing specific histologic data regarding the integrity of white matter.

Animals↗
PubMed2005

High-resolution anatomic, diffusion tensor, and magnetization transfer magnetic resonance imaging of the optic chiasm at 3T.

PURPOSE: To evaluate techniques for anatomical and physiological imaging of the intracranial optic nerve (ON), optic chiasm (OC), and optic tract (OT) at 3T with the aim of visualizing axonal damage in multiple sclerosis (MS). MATERIALS AND METHODS: Imaging was performed on a 3T scanner employing a custom-designed head coil that consisted of a coil array with four coils (30 x 30 cm(2)). Oblique fast spin echo (FSE) images, magnetization transfer (MT)-enhanced 3D gradient-echo (GRE) time-of-flight (TOF) images, and line scan diffusion images (LSDI) were obtained. Full diffusion tensor (DT) analysis was performed, and apparent diffusion coefficient (ADC), fractional anisotropy (FA), and fiber direction maps were obtained. RESULTS: FSE anatomic images were obtained with an in-plane resolution of 0.39 x 0.52 mm(2). The in-plane resolution of the MT and LSDI images was 0.78 x 0.78 mm(2). The OC, intracranial ON, and OT can be seen on these images. The dominant fiber orientations in the OC, ON, and OT, as derived from the DT images, are displayed. CONCLUSION: This study shows that by using 3T and a custom-designed, four-channel head coil, it is possible to acquire high-resolution anatomical and physiological images of the OC, ON, and OT. The pilot results presented here pave the way for imaging the anterior visual pathway in patients with MS.

Adult↗
PubMed2005

Apparent diffusion coefficients in spinal cord transplants and surrounding white matter correlate with degree of axonal dieback after injury in rats.

BACKGROUND AND PURPOSE: Abnormal apparent diffusion coefficient (ADC) values in injured spinal cord white matter and fibroblast transplants have been shown to correspond with qualitative histologic findings of axonal loss or regeneration. We proposed that ADC values would correlate with quantitative axonal tracing in the transected rubrospinal tract (RST). METHODS: Eleven rats received right-sided lateral funiculus lesions at C3-4 (disrupting the RST) and transplantation of fibroblasts that were unmodified or modified to secrete brain-derived neurotrophic factor (BDNF). Behavioral tests measured hindlimb function at 1, 2, 4, 6, 8, 10, and 12 weeks after injury. At 12 weeks after injury, the antegrade axon tracer biotinylated dextran amine was stereotactically injected into the red nucleus to label the injured RST axons. Animals were sacrificed 2 weeks later. Diffusion-weighted MR imaging of the excised, fixed spinal cord specimens was then performed at 9.4 T. RESULTS: In white matter surrounding transplants, ADC values transverse to axons were elevated and ADC values longitudinal to axons were decreased. These ADC values were more abnormal closer to the transplant, and this correlated with decreases in numbers of labeled RST axons. ADC values in BDNF-expressing fibroblast transplants were significantly lower than those in unmodified fibroblast transplants, and these lower values correlated with decreased axonal dieback. Behaviorally, all animals showed partial recovery, but animals with BDNF-expressing fibroblast transplants had slightly improved hindlimb function compared to those with unmodified fibroblast transplants. CONCLUSION: ADC values may be able to evaluate graft function after spinal cord injury by demonstrating the degree of axonal dieback and preservation.

Animals↗
PubMed2005

Ex vivo evaluation of ADC values within spinal cord white matter tracts.

BACKGROUND AND PURPOSE: Our purpose was to evaluate the effect of fixative on apparent diffusion coefficient (ADC) values and anisotropy within spinal cord white matter. As glutaraldehyde (GL) better preserves axonal ultrastructure as compared with paraformaldehyde (PF), we hypothesize that spinal cord white matter fixed with GL will have increased anisotropic water diffusion as compared with specimens fixed with PF. METHODS: Eleven rats were perfusion-fixed with either 4% PF or a combination of 2.5% GL and 4% PF. Diffusion-weighted imaging of the ex vivo spinal cord was performed using a 9.4T magnet with b values up to 3100 s/mm(2). In-plane resolution was 39 mum x 39 mum, and section thickness was 500 mum. RESULTS: Overall, animals fixed with a combination of GL and PF (GL-PF) showed a greater increase in longitudinal ADC (lADC) as compared to those fixed with PF only, without differences in transverse ADC (tADC). As a consequence of the increased lADC, overall anisotropic diffusion increased in those animals fixed with GL-PF, as measured with an anisotropy index (AI = tADC/lADC). Evaluation of specific tracts demonstrated that lADC for animals fixed with GL-PF were significantly elevated in the rubrospinal, vestibulospinal, and reticulospinal tracts as compared with animals fixed with PF only. CONCLUSION: Using a fixative of GL-PL results in increased anisotropy (decreased AI values) in spinal cord white matter tracts, as compared with PF fixation only, largely owing to increases in the lADC values. This finding may be due to better fixation of intra-axonal cytoskeletal proteins that results when GL is combined with PF and sheds further light on underlying sources of anisotropic water diffusion in CNS white matter.

Animals↗
PubMed2004

Assessment of axonal fiber tract architecture in excised rat spinal cord by localized NMR q-space imaging: simulations and experimental studies.

NMR q-space imaging is a method designed to obtain information from porous materials where diffusion-diffraction phenomena were observed from which pore size was derived. Recently, the technique has been applied to the study of biological structures as well. Although diffusive diffraction has so far not been observed in multicellular systems, displacement profiles have been used with some success as a means to estimate structure size. However, there have been no quantitative correlations of the retrieved structure sizes with histology. Clearly, the complexity of tissue architecture poses significant challenges to the interpretation of q-space data. In this work, simulations were first performed on a two-compartment model to demonstrate the effects of interference of the diffraction patterns arising from intra and extra-axonal compartments and finite boundary permeability on q-space data. Second, q-space echo attenuation was simulated on the basis of histologic images of various rat spinal cord fiber tracts and the information obtained from the displacement profiles were compared with structural parameters computed from the histologic images. The results show that calculated mean displacements and kurtosis parallel mean axon size and axonal density. Finally, spatially localized q-space measurements were carried out at the locations where simulations had previously been performed, resulting in displacement data that support those obtained by simulation. The data suggest the NMR q-space approach has potential for nondestructive analysis of the axonal architecture in the mammalian spinal cord.

Animals↗
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

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↗
PubMed2003

Diffusion-weighted MRI and the evaluation of spinal cord axonal integrity following injury and treatment.

Diffusion-based magnetic resonance imaging (MRI) (DWI) has been shown experimentally to detect both injury and functionally significant neuroprotection of injured spinal cord white matter that would otherwise go undetected with conventional MRI techniques. The diffusion of water in the central nervous system (CNS) is thought to be affected by both its location (intracellular or extracellular), and by diffusion barriers formed by cell membranes and myelin sheaths. There is, however, controversy concerning how to obtain, interpret, and present DWI data. Computer simulations and MR microscopy have been helpful in resolving some of these issues, as well as determining exact histologic correlates to DWI findings.

Animals↗
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↗
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

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

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↗
PubMed2002

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↗
PubMedDate not supplied

Magnetization transfer micro-MR imaging of live excised lamprey spinal cord: characterization and immunohistochemical correlation.

BACKGROUND AND PURPOSE: Membrane constituents may play a key role in the magnetization transfer (MT) effect. In lamprey spinal cord, axonal diameters range from <1 microm in the dorsal region to 20-40 microm in the ventral region. There is a corresponding range of axonal, and hence cell membrane, density. These characteristics permit determination of the effect of cell membrane density on MT. The purpose of this study was to characterize regional MT effects in lamprey spinal cord. METHODS: Excised spinal cords from eight sea lampreys were measured with a 9.4-T MR imaging system. MT saturation was applied for spin-echo sequences. The MT ratio (MTR) was calculated in each location (dorsal, lateral, and ventral columns). Spinal cords from five other lampreys were prepared with an antibody to lamprey glial keratin (LCM 29). The percentage of area staining with LCM29 was calculated for each location. RESULTS: Mean MTR (+/- SD) for the dorsal, lateral, and ventral columns were 62.4 +/- 4.2, 59.2 +/- 2.7, and 56.9 +/- 3.0, respectively; all differences were significant (P < .05). Mean LCM29-positive areas for the dorsal, lateral, and ventral columns were 85.1%, 69.7%, and 50.9%, respectively. MTR and percentage LCM29-positive area were significantly correlated (r(2) = 0.98). CONCLUSION: Regional differences in MT effect exist in the lamprey spinal cord. MTR is well correlated with percentage LCM29-positive area. These results support the hypothesis that membrane constituents are at least partly responsible for regional variations in MT effect.

Animals↗