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Chris A Clark

Publications and source records attributed to Chris A Clark.

8 recordsLinked to original sources
PubMed2006

Effect of ethylene glycol, urea, and N-methylated glycines on DNA thermal stability: the role of DNA base pair composition and hydration.

The accumulation of the cosolutes ethylene glycol, urea, glycine, sarcosine, and glycine betaine at the single-stranded DNA surface exposed upon melting the double helix has been quantified for DNA samples of different guanine-cytosine (GC) content using the local-bulk partitioning model [Record, M. T., Jr., Zhang, W., and Anderson, C. F. (1998) Adv. Protein Chem. 51, 281-353]. Urea and ethylene glycol are both locally accumulated at single-stranded DNA relative to bulk solution. Urea exhibits a stronger affinity for adenine (A) and thymine (T) bases, leading to a greater net dehydration of these bases upon DNA melting; ethylene glycol local accumulation is practically independent of base composition. However, glycine, sarcosine, and glycine betaine are not necessarily locally accumulated at single strands after melting relative to bulk solution, although they are locally accumulated relative to double-stranded DNA. The local accumulation of glycine, sarcosine, and glycine betaine at single strands relative to double-stranded DNA decreases with bulk cosolute molality and increases with GC content for all N-methylated glycines, demonstrating a stronger affinity for G and C bases. Glycine also shows a minimum in melting temperature T(m) at 1-2 m for DNA samples of 50% GC content or less. Increasing ionic strength attenuates the local accumulation of urea, glycine, sarcosine, and glycine betaine and removes the minimum in T(m) with glycine. This attenuation in local accumulation results in counterion release during the melting transition that is dependent on water activity and, hence, cosolute molality.

Animals↗
PubMed2006

White matter pathway asymmetry underlies functional lateralization.

Structural and functional asymmetry of the human brain has been well documented using techniques such as magnetic resonance imaging (MRI). However, asymmetry of underlying white matter connections is less well understood. We applied an MRI technique known as diffusion tensor tractography to reveal the morphology of the white matter in vivo by mapping directions of maximum water diffusion in brain tissue. White matter pathway asymmetry was investigated in a normalized image data set of 30 right-handed young healthy individuals. We identified, for the first time, a rightwardly asymmetric pathway connecting the posterior temporal lobe to the superior parietal lobule. This pathway may be related to auditory spatial attention and working memory for which there is evidence for a rightward laterality from functional imaging studies. Additional leftward asymmetries connecting the parietal and frontal lobes to the temporal lobe may be more closely related to laterality of language.

Adult↗
PubMed2006

Correlations between MRS and DTI in cerebral small vessel disease.

Cerebral small vessel disease results in lacunar infarcts and cognitive impairment. Diffusion tensor imaging (DTI) demonstrates a reduction in fractional anisotropy and increase in mean diffusivity, which correlates more strongly with cognition than conventional MRI. The underlying pathological basis for these DTI changes is not known. In this study magnetic resonance spectroscopy was used to determine the biochemical basis of these DTI alterations. Twenty-five patients with lacunar stroke and radiological leukoaraiosis were recruited. Chemical shift imaging (CSI) and DTI were performed on a 1.5 T MRI scanner. A region of interest was positioned in the white matter of the centrum semiovale. Multivoxel CSI data were processed and the metabolite ratios estimated. DTI parameters corresponding to the exact region of tissue excited by CSI were obtained. Mean spectroscopy data and DTI values for each subject were correlated. Univariate analysis revealed a positive correlation between N-acetyl aspartate-creatine (NAA/Cr) and fractional anisotropy (r = 0.52, p = 0.008), and a negative correlation with mean diffusivity (r = -0.51, p = 0.009). Results remained little changed after controlling for mean percentage lesion and mean percentage white matter per voxel (with fractional anisotropy r = 0.54, p = 0.008, and with mean diffusivity r = -0.52, p = 0.01). These findings are consistent with axonal loss or dysfunction, or both, accounting for at least part of the DTI abnormalities found in patients with small vessel disease. It provides evidence that DTI identifies axonal disruption in white matter tracts.

Aged↗
PubMed2004

Singularities in diffusion tensor fields and their relevance in white matter fiber tractography.

The technique of diffusion tensor tractography utilizes directions of maximum diffusion to reconstruct pathways of white matter structures in the brain. Critically, successful tracking of these white matter pathways depends on well-defined maximal diffusion directional information. By examination of diffusion tensor field properties in the human brain, we demonstrate that the geometry of tracked pathways is influenced by points in the field where the maximum diffusion direction is poorly defined. In common with tensor fields describing other mathematical and physical phenomena, such as 3D surface differential geometry and gravitational fields, we refer to these points as singularities. Here we describe an automated procedure for detecting singularities and demonstrate that these occur where there is (i) fiber crossing, (ii) pathways passing close to one another within a voxel (partial volume effect), and (iii) noise propagation into low anisotropy regions. In order to highlight the relevance of singularities in tracking white matter structures, we determined their effect on computation of the cortico-spinal pathway.

Algorithms↗
PubMed2003

White matter fiber tracking in patients with space-occupying lesions of the brain: a new technique for neurosurgical planning?

The technique of fiber tracking based on diffusion tensor imaging offers the unique possibility of localizing the white matter pathways of the brain in vivo. In patients with cerebral tumors or space-occupying lesions of the brain, these pathways are often damaged or significantly displaced. Knowledge of the exact location of the lesion with respect to clinically eloquent white matter pathways is of great value to the neurosurgeon in planning the appropriate surgical strategy. We present here preliminary findings using the fiber tracking technique in four patients with space-occupying lesions and discuss the potential and limitations of the technique for lesion localization and neurosurgical planning.

Adult↗
PubMed2002

In vivo mapping of the fast and slow diffusion tensors in human brain.

Recent studies have shown that the diffusional signal decay in human brain is non-monoexponential and may be described in terms of compartmentalized water fractions. Diffusion tensor imaging (DTI), which provides information about tissue structure and orientation, typically uses b values up to 1000 s x mm(-2) so that the signal is dominated by the fast diffusing fraction. In this study b factors up to 3500 s x mm(-2) are utilized, allowing the diffusion tensor properties of the more slowly diffusing fraction to be mapped for the first time. The mean diffusivity (MD) of the slow diffusion tensor was found to exhibit strong white/gray matter (WM/GM) contrast. Maps depicting the principal direction of the slow tensor indicated alignment with the fast tensor and the known orientation of the WM pathways.

Anisotropy↗
PubMedDate not supplied

Diffusion tensor imaging in spinal cord: methods and applications - a review.

The spinal cord is a clinically eloquent site within the central nervous system, containing important sensorimotor tracts confined within a small cross-sectional area. Damage to the spinal cord may be caused by a wide range of pathologies, and can result in profound functional disability. Characterization of the structural integrity of the spinal cord can be assessed using diffusion tensor imaging methods. Development and application of this technique may improve our understanding of the nature and evolution of structural damage in spinal cord disease. Possible developments include improved detection of ischaemic lesions, clarification of the relationship between clinical disability and structural damage to the cord and monitoring of anti-inflammatory or neuroprotective therapies. In this review current technical aspects, clinical applications and the suggested future development of spinal cord diffusion imaging are discussed.

Animals↗