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Biomedical subjects

J C Ford

Publications and source records attributed to J C Ford.

At least 37 records · Page 2Linked to original sources

A method for in vivo high resolution MRI of rat spinal cord injury.

We have developed an implanted radiofrequency coil to obtain high resolution in vivo MR images at 1.9 Tesla of rat spinal cords that have been injured using a standardized weight drop technique. The signal-to-noise ratio and motion artifact suppression of these images is superior to that achieved in earlier attempts at this field strength using an external surface coil. The high quality and spatial resolution provided by this technique afford the possibility for longitudinal studies of experimental spinal cord injury before and after treatment, as well as detailed correlation of in vivo MRI contrast, histopathological findings, and functional deficit, in a controlled setting.

Animals↗

MRI characterization of diffusion coefficients in a rat spinal cord injury model.

Apparent diffusion coefficients (ADC) were measured in a rat spinal cord weight-drop injury model. After sacrifice, the spinal cords were fixed in situ and excised for MR imaging and ADC measurement. Diffusion is anisotropic in normal gray and white matter. There were significant decreases in ADCs measured along the longitudinal axis of the injured cord and increases in ADCs measured transverse to the cord. Injured segments demonstrated reductions in diffusion anisotropy in the white matter. Diffusion was completely isotropic at the epicenter of the weight-drop injury. Significant decreases in longitudinal ADC and increases in transverse ADC were observed in portions of the cord which appeared normal on conventional spin-echo and calculated T2 images. Thus ADC measurement may complement routine imaging for evaluation of spinal cord injury.

Animals↗

Experimental spinal cord injury: imaging the acute lesion.

In order to obtain high resolution images of fixed excised rat spinal cords we have developed a technique using a 6-mm bore, two-turn saddle coil, with a usable imaging length of approximately 4 cm. MR imaging is performed on a prototype 31-cm bore, 1.9-T system with a 1.5-mm section thickness and 7.6-mm field of view.

Animals↗

High-resolution variable flip angle 3D MR imaging of trabecular microstructure in vivo.

Two conceptually related variable-flip-angle 3D spin-echo pulse sequences were designed for imaging at voxel sizes of 2-5 x 10(-3) mm3 corresponding to pixel areas of less than 100 x 100 microns2 and section thicknesses on the order of 300-400 microns on a conventional 1.5 T MR imaging system equipped with 1 G/cm imaging field gradients, providing 12 sections in 10 min imaging time. The pulse sequences make use of the concept of restoring longitudinal magnetization inverted by the 180 degrees phase reversal pulse and are derivatives of pulse sequences previously dubbed "FATE" and "RASEE." It is shown that even in the small-voxel regime (< 10(-2) mm3 voxel size) and at echo times on the order of 10 ms, gradient echo images are sensitive to intrinsic fields causing artifactual boundary effects, including signal loss from intravoxel phase scrambling and spatial mismapping. At this resolution the variable flip-angle spin-echo pulse sequences are demonstrated to be better suited for imaging magnetically heterogeneous systems such as trabecular bone microstructure in vivo. These pulse sequences are found to be substantially less sensitive to distortions from magnetic dipole fields occurring at the boundaries of two phases of different magnetic permeability.

Bone and Bones↗

Magnetic field distribution in models of trabecular bone.

A magnetostatic model consisting of a tetragonal lattice of struts of diamagnetic material, mimicking vertebral trabecular bone, was developed. The model allows estimation of the magnetic field histogram within the lattice's unit cell as a function of geometric parameters. The field was computed analytically from the induced magnetic surface charge density on the faces of the struts. The contribution from the induced magnetic field to the effective transverse relaxation rate, R2', was obtained as the mean decay rate of the Fourier transformed histograms, for both fixed and randomly oriented lattices. The model predicts the field distribution to increase with both strut thickness and density, paralleling material density. Finally, significant changes in R2' are predicted at constant material density, in that the field distribution widens with simultaneously increasing strut number density and decreasing strut thickness.

Algorithms↗

Potential role of nuclear magnetic resonance for the evaluation of trabecular bone quality.

This paper discusses two novel applications of nuclear magnetic resonance (NMR) as an investigational tool for the assessment of cancellous bone microarchitecture. It further outlines extensions of the method for in vivo clinical evaluation of bone strength in patients with skeletal disorders such as osteoporosis. The first method relies on the hypothesis that the presence of two phases of different magnetic permeability, i.e., bone and bone marrow, causes a spatial nonuniformity of the magnetic field across the measurement volume. The resulting spread in resonance frequency shortens the decay time constant (T2*) of the time domain proton signal in bone marrow or its substitute (water). Increased trabecular spacing, such as it occurs in osteoporosis, reduces the spatial field inhomogeneity and thus prolongs T2*, which has been shown both in vitro and in vivo. Subjects with osteoporosis, characterized by either low bone mineral density and/or spine compression fractures, have T2* values that are significantly prolonged. The second method focuses on a direct measurement of micromorphometric parameters of cancellous bone, using the principles of proton NMR microscopy in conjunction with computer processing of the resulting digital images. Image contrast between the trabeculae and the intertrabecular space is based on the marrow protons providing a signal, as opposed to bone, which appears with background intensity. Once tissues have been classified (into bone and marrow), for example, by means of a histogram-based segmentation algorithm, bone area fraction, mean trabecular plate density (MTPD), and mean trabecular plate thickness (MTPT) can be computed without the need for further operator intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Trabecular structure: preliminary application of MR interferometry.

A new approach to probe the structure of trabecular bone in the vertebral bodies in humans was evaluated, and preliminary data are presented. The proposed method is based on the hypothesis that the presence of two physical phases--bone and bone marrow--causes a magnetic field distribution across the imaging voxel. The resulting spread in resonance frequency produces line broadening, which is measured as the decay rate of the region of interest signal intensity that has the properties of an interferogram. The interferogram is the result of two principal chemically shifted components of bone marrow--fat and water--getting in and out of phase with one another while being attenuated by T2* processes from the magnetic field distribution within the measuring volume. The time constant for the decay (T2*) can then be obtained by means of curve-fitting techniques. T2* in healthy persons is found to increase slightly with age. However, patients with osteoporosis (low bone mineral density and/or spine compression fractures) have significantly prolonged T2* values, which are interpreted as arising from an increase in the intertrabecular space.

Adolescent↗

Reversed-phase liquid chromatography of site-specific mutagenized staphylococcal nuclease. Gradient retention and correlations with amino acid-based predictive scales.

Comparison of the gradient reversed-phase chromatographic retentions of twelve Staphylococcal nuclease mutants and the naturally occurring protein showed that the chain location and the chemical nature of the substituted amino acid(s) were equally significant in determining the retention. Correlations between the retention times of these nuclease mutants and of previously published data for interleukin 2 mutants and insulin variants with nineteen amino acid-based predictive scales revealed retention time to be significantly correlated to several scales. The use of mutagenized proteins allowed a more sensitive analysis of the individual amino acid contributions to retention than can be achieved by utilizing a more diverse set of proteins.

Amino Acids↗

A new polymorphic determinant on HLA-DQ molecules.

In man, the immune response genes are located within the HLA-D/DR region, and the gene products, the Ia antigens, are expressed on B lymphocytes, monocytes, and a percentage of null cells and activated T lymphocytes. We recently identified a human Ia antigen, K19, which appeared to be limited in its expression to B lymphocytes, and to be preferentially expressed on the more mature cells within this population. This work was facilitated by a monoclonal antibody. HK-19, which recognized a monomorphic determinant of this Ia molecule. We now report the characterization of a second monoclonal antibody, HK-13, which recognized the same molecule as HK-19, but only on cells from some individuals. The greater affinity of HK-13 allowed more complete characterization of the K19/K13 molecule. This characterization included cytofluorography, two-dimensional gel electrophoresis, tryptic peptide mapping, and partial N-terminal amino acid sequencing, and indicated that K19 and K13 were epitopes on HLA-DQ (DC) molecules. The pattern of reactivity of HK-13 on a panel of typing cells did not correlate with any of the known HLA-DQ polymorphic determinants. Thus, HK-13 is a new polymorphic determinant of the HLA-DQ series.

Amino Acid Sequence↗

Conformational effects in the reversed-phase liquid chromatography of ribonuclease A.

This paper examines the reversed-phase liquid chromatographic behavior of ribonuclease A (RNase) using an n-butyl chemically bonded phase and a gradient of 10 mM H3PO4 and l-propanol. At a column temperature of 25 degrees C, a broad band followed by an overlapped late-eluting sharp peak is observed. As the temperature is raised, the sharp peak grows at the expense of the broad band until at 37 degrees C, only a single narrow-eluting band is found. Using an absorbance ratio of A288/A254, it is demonstrated that the broad band represents a folded or native state of RNase and the late-eluting band a denatured state. Based on postcolumn absorbance ratio changes in the denatured state as a function of time and the known behavior of the protein, reversible refolding or renaturation is proposed to take place in solution. RNase is denatured upon adsorbing to the bonded phase, and upon migration down the column, reversible refolding takes place in the mobile phase. The relaxation time for native state formation is assumed to be comparable to the time spent by RNase in the mobile phase. As temperature is raised, both the native and denatured states exist at equilibrium in solution, thus slowing the refolding process, until at 37 degrees C only the denatured peak appears. Changes in peak shape with flow rate provide further evidence for this model. The use of HCl or H2SO4 instead of H3PO4 yields similar results except that the temperature at which only the denatured peak is observed follows the order of salt stabilization of the native state.

1-Propanol↗