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Biomedical subjects

C A Clark

Publications and source records attributed to C A Clark.

At least 19 recordsLinked to original sources
PubMed2006

Effects of breakfast meal composition on second meal metabolic responses in adults with Type 2 diabetes mellitus.

OBJECTIVE: We tested the relative importance of a low-glycemic response versus a high glycemic response breakfast meal on postprandial serum glucose, insulin and free fatty acid (FFA) responses after consumption of a standardized mid-day meal in adult individuals with Type 2 diabetes mellitus (DM). DESIGN: Following an overnight fast of 8-10 h, a randomized crossover intervention using control and test meals was conducted over a 3-week-period. A fasting baseline measurement and postprandial measurements at various time intervals after the breakfast and mid-day meal were taken. SUBJECTS: Forty-five Type 2 DM subjects completed the requirements and were included in the study results. INTERVENTIONS: Two different breakfast meals were administered during the intervention: (A) a high glycemic load breakfast meal consisting of farina (kJ 1833; carbohydrate (CHO) 78 g and psylium soluble fiber 0 g), (B) a low-glycemic load breakfast meal consisting of a fiber-loop cereal (kJ 1515; CHO 62 g and psyllium soluble fiber 6.6 g). A standardized lunch was provided approximately 4 h after breakfast. Blood plasma concentrations and area under the curve (AUC) values for glucose, insulin and FFA were measured in response to the breakfast and mid-day lunch. Statistical analyses were performed using SAS software (8.02). Comparisons between diets were based on adjusted Bonferroni t-tests. RESULTS: In post-breakfast analyses, Breakfast B had significantly lower area under the curve (AUC) values for plasma glucose and insulin compared to Breakfast A (P<0.05) (95% confidence level). The AUC values for FFA were higher for Breakfast B than for Breakfast A (P<0.05) (95% confidence level). Post-lunch analyses indicated similar glucose responses for the two breakfast types. Insulin AUC values for Breakfasts B were significantly lower than Breakfast A (P<0.05) (95% confidence level). The AUC values for FFA were unaffected by breakfast type. CONCLUSIONS: These data indicate that ingesting a low-glycemic load meal containing psyllium soluble fiber at breakfast significantly improves the breakfast postprandial glycemic, insulinemic and FFA responses in adults with Type 2 DM. These data revealed no residual postprandial effect of the psyllium soluble fiber breakfast meal beyond the second meal consumed. Thus, there was no evidence of an improvement postprandially in the glycemic, insulinemic and FFA responses after the consumption of the lunch meal.

Adult↗
PubMed2006

White matter damage on diffusion tensor imaging correlates with age-related cognitive decline.

BACKGROUND: Damage to white matter tracts, resulting in "cerebral disconnection," may underlie age-related cognitive decline. METHODS: Using diffusion tensor MRI (DTI) to investigate white matter damage, and magnetic resonance spectroscopy (MRS) to look at its underlying pathologic basis, the authors investigated the relationship between white matter structure and cognition in 106 healthy middle-aged and elderly adults. Fractional anisotropy (FA) and mean diffusivity (MD) values, whole brain white matter histograms, and regions of interest placed in the white matter of the centrum semiovale were analyzed. Correlations with executive function, working memory, and information-processing speed were performed. RESULTS: There was a progressive reduction in FA and increase in diffusivity with age in both region of interest (r = 0.551, p < 0.001), and whole brain histograms (r = 0.625, p < 0.001). DTI values correlated with performance in all three cognitive domains. After controlling for age, DTI parameters correlated with working memory but not with the other two cognitive domains. MRS studies found a correlation of N-acetyl aspartate, a neuronal marker, with DTI parameters (r = 0.253, p < 0.05). CONCLUSION: The results are consistent with white matter damage due to axonal loss, causing age- related cognitive decline. Working memory may be particularly dependent on complex networks dependent on white matter connections.

Aged↗
PubMed2005

Damage within a network of white matter regions underlies executive dysfunction in CADASIL.

OBJECTIVE: To identify the important sites of white matter disruption that underpin executive dysfunction in CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a genetic model of pure subcortical vascular disease. METHODS: The anatomic pattern of correlation between tissue integrity and executive function was explored with diffusion tensor imaging (DTI), which provides quantitative measures of tissue integrity. Eighteen nondemented patients with CADASIL underwent DTI and cognitive assessment. DTI was normalized to a standard template and correlations assessed at every voxel across the brain with Statistical Parametric Mapping with cluster-level correction for multiple comparisons. RESULTS: For executive tasks, correlations were found in a number of discrete regions in the white matter of the frontal lobes. A distinct, nonoverlapping pattern of correlation was seen for verbal memory. Significant independent correlations remained in some regions after co-varying for age and IQ. CONCLUSIONS: Different cognitive functions correlate with structural integrity at different sites in the white and subcortical gray matter. The distribution of regions correlating specifically with executive function provides clues to the organization of the relevant cognitive networks and their important white matter projections. The cingulum bundle is one candidate tract that may carry anteroposterior connections important for executive processes.

Adult↗
PubMed2003

Quantitative magnetic resonance imaging in neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric symptoms are common in systemic lupus erythematosus (SLE) but are poorly understood. Although there is a wide spectrum of clinical manifestations, brain histology often simply shows a bland vasculopathy. Magnetic resonance techniques such as magnetic resonance spectroscopy, magnetization transfer imaging and diffusion weighted imaging have been used to try to improve our understanding of the pathophysiological mechanisms involved in neuropsychiatric lupus (NPSLE). This article reviews the current literature on the use of these techniques and their possible future role as diagnostic tools in NPSLE.

Brain↗
PubMed2001

Diffusion tensor imaging: concepts and applications.

The success of diffusion magnetic resonance imaging (MRI) is deeply rooted in the powerful concept that during their random, diffusion-driven displacements molecules probe tissue structure at a microscopic scale well beyond the usual image resolution. As diffusion is truly a three-dimensional process, molecular mobility in tissues may be anisotropic, as in brain white matter. With diffusion tensor imaging (DTI), diffusion anisotropy effects can be fully extracted, characterized, and exploited, providing even more exquisite details on tissue microstructure. The most advanced application is certainly that of fiber tracking in the brain, which, in combination with functional MRI, might open a window on the important issue of connectivity. DTI has also been used to demonstrate subtle abnormalities in a variety of diseases (including stroke, multiple sclerosis, dyslexia, and schizophrenia) and is currently becoming part of many routine clinical protocols. The aim of this article is to review the concepts behind DTI and to present potential applications.

Brain Diseases↗
PubMed2001

Diffusion time dependence of the apparent diffusion tensor in healthy human brain and white matter disease.

The diffusion time dependence of the brain water diffusion tensor provides information regarding diffusion restriction and hindrance but has received little attention, primarily due to limitations in gradient amplitude available on clinical MRI systems, required to achieve short diffusion times. Using new, more powerful gradient hardware, the diffusion time dependence of tensor-derived metrics were studied in human brain in the range 8-80 ms, which encompasses the shortest diffusion times studied to date. There was no evidence for a change in mean diffusivity, fractional anisotropy, or in the eigenvalues with diffusion time in healthy human brain. The findings are consistent with a model of unrestricted, but hindered water diffusion with semipermeable membranes, likely originating from the extracellular space in which the average extracellular separation is less than 7 microns. Similar findings in two multiple sclerosis plaques indicated that the size of the water diffusion space in the lesion did not exceed this dimension.

Anisotropy↗
PubMed2001

Towards inference of human brain connectivity from MR diffusion tensor data.

This paper describes a method to infer the connectivity induced by white matter fibers in the living human brain. This method stems from magnetic resonance tensor imaging (DTI), a technique which gives access to fiber orientations. Given typical DTI spatial resolution, connectivity is addressed at the level of fascicles made up by a bunch of parallel fibers. We propose first an algorithm dedicated to fascicle tracking in a direction map inferred from diffusion data. This algorithm takes into account fan-shaped fascicle forks usual in actual white matter organization. Then, we propose a method of inferring a regularized direction map from diffusion data in order to improve the robustness of the tracking. The regularization stems from an analogy between white matter organization and spaghetti plates. Finally, we propose a study of the tracking behavior according to the weight given to the regularization and some examples of the tracking results with in vivo human brain data.

Axons↗
PubMed2001

Pigmented striae of the anterior lens capsule and age-associated pigment dispersion of variable degree in a group of older African-Americans: an age, race, and gender matched study.

PURPOSE: To investigate pigmented striae of the anterior lens capsule in African-Americans, a potential indicator of significant anterior segment pigment dispersion. METHODS: A group of 40 African-American subjects who exhibited pigmented lens striae (PLS) were identified from a non-referred, primary eye care population in Chicago, IL, USA. These subjects were then compared to an age, race, and gender matched control group relative to refractive error and the presence or absence of diabetes and hypertension. RESULTS: The PLS subjects (mean age = 65.4 +/- 8.8 years, range = 50-87 years) consisted of 36 females and 4 males. PLS were bilateral in 36 (85%) of the 40 subjects. Among the eyes with PLS, 21 (55%) of 38 right eyes and 22 (61%) of 36 left eyes also had significant corneal endothelial pigment dusting, commonly in the shape of a Krukenberg's spindle. Ten (25%) of the PLS subjects had either glaucoma or ocular hypertension (7 bilateral, 3 unilateral). The presence of trabecular meshwork pigment varied from minimal to heavy. The mean +/- SD (range) refractive error of the PLS right eyes was +1.61 +/- 1.43D (-1.50 to +5.00D) and +1.77 +/- 1.37D (-1.00 to +5.00D) for the left eyes. Based on these data, the PLS right eyes were +1.63D (Student's t, p = 0.0001; 95% CI = +0.82 to +2.44D) more hyperopic on average than the control right eyes, and the PLS left eyes were +1.77D (p = 0.0001; 95% CI = +0.92 to +2.63D) more hyperopic on average than the control left eyes. Trend analysis showed a gradually increasing likelihood of PLS with increasing magnitude of hyperopia in both eyes (Mantel-Haenszel chi-square, p = 0.001). Among PLS subjects, 24 (60%) of 40 were hypertensive and 9 (23%) of 40 were diabetic. However, these proportions were not significantly different (two-tailed Fisher's exact test; hypertension: p = 0.30; diabetes: p = 0.70) from the randomly selected controls. CONCLUSIONS: Among our African-American group, which consisted predominately of females >50 years of age, the likelihood of PLS increased with increasing hyperopic refractive error. This finding is consistent with the possibility that PLS may, in some circumstances, indicate a significant pigment dispersal process due to iris-lens rubbing that may be associated with crowding of anterior segment structures. Additional study is warranted to further assess the nature of PLS, their precise relationship with an age-related pigment dispersal process, and their true significance as a risk factor for development of glaucoma.

Adolescent↗
PubMed2001

Combined functional magnetic resonance imaging and diffusion tensor imaging demonstrate widespread modified organisation in malformation of cortical development.

A patient with a mild left hemiparesis and a malformation of cortical development in the right hemisphere was investigated with fMRI (functional magnetic resonance imaging) and DTI (diffusion tensor imaging). The motor cortex was studied using a finger tapping fMRI experiment. The fibre orientation was studied by displaying the principal eigenvector of the diffusion tensor in the spatially normalised brain of the patient and of control subjects. In addition, the anisotropy (directionality) of water diffusion of the patient was statistically compared with control subjects. The malformation was located in the right central region in the expected position of the motor cortex. fMRI showed activation anterior and posterior to the malformation. DTI disclosed that fibres with rostrocaudal orientation, presumably representing the pyramidal tract, were deviating from their normal orientation and passing around the malformation. There were widespread regions of reduced anisotropy affecting both hemispheres. In conclusion, fMRI and DTI provided concordant information showing widespread modified functional and structural organisation including regions which appeared normal on standard imaging.

Adult↗
PubMed2001

Water diffusion is elevated in widespread regions of normal-appearing white matter in multiple sclerosis and correlates with diffusion in focal lesions.

Pathological changes in the normal-appearing white matter in multiple sclerosis are well recognised, but their relationship to pathology in focal lesions is not well understood. Magnetic resonance diffusion imaging is sensitive to abnormalities in the integrity, size and geometry of water spaces in brain tissue. This study investigated the anatomical distribution of normal-appearing white matter diffusion abnormalities and their relationship to diffusion in focal lesions in multiple sclerosis (MS). The average apparent diffusion coefficient (ADCav) was measured by three-axis echoplanar diffusion imaging in normal-appearing white matter regions and lesions throughout the brain in 40 patients, and in white matter in 14 matched controls. The correlation between the ADCav in normal-appearing white matter and lesions was determined. In controls and patients, diffusion was highest in the corpus callosum. Patients had a higher mean ADCav than controls in widespread regions including the corpus callosum, cerebellar, temporal and occipital normal-appearing white matter. Mean normal-appearing white matter ADCav correlated strongly with mean lesion ADCav (r = 0.67, P < 0.001). This study demonstrates that water diffusion is elevated in widespread areas of normal-appearing white matter in MS, and is correlated with diffusion in lesions. These findings suggest that the pathogenetic mechanisms causing tissue damage in lesions and normal-appearing white matter are at least partly linked.

Adult↗
PubMed2000

Decreased hemispheric water mobility in hemiplegic migraine related to mutation of CACNA1A gene.

We report a reversible reduction of water diffusion in the brain during a prolonged attack of hemiplegic migraine. The patient had a sporadic mutation of the CACNA1A gene. The diffusion changes were observed in the contralateral hemisphere 3 and 5 weeks after the onset of hemiplegia. These results suggest the occurrence of hemispheric cytotoxic edema during severe attacks of hemiplegic aura. The mechanisms underlying such ultrastructural modifications are unknown but an abnormal release of excitatory amino acids can be hypothesized.

Adult↗
PubMed2000

Diffusion imaging of the spinal cord in vivo: estimation of the principal diffusivities and application to multiple sclerosis.

Magnetic resonance (MR) diffusion imaging is a useful technique with which to increase our understanding of pathologic damage to the central nervous system. To fully quantitate diffusion and anisotropy in the spinal cord, as in other tissues, it is necessary to determine the diffusion tensor. If spinal cord diffusion is assumed to be cylindrically symmetric and the orientation of the cord in the gradient frame is known, then it is shown that full quantification is possible from only three images, two of which are diffusion-weighted. Mean diffusivity and volume ratio were determined in the normal cord of four healthy volunteers and in seven cord lesions of three patients with clinically definite multiple sclerosis (MS) who had locomotor disability suggesting the presence of spinal pathology. MS cord lesions exhibited increased mean diffusivity reflecting structural damage to the cord white matter. Quantification of diffusion and anisotropy using spinal cord diffusion imaging provides new structural information in relation to spinal cord pathology in vivo.

Adult↗
PubMed2000

Test liquids for quantitative MRI measurements of self-diffusion coefficient in vivo.

A range of liquids suitable as quality control test objects for measuring the accuracy of clinical MRI diffusion sequences (both apparent diffusion coefficient and tensor) has been identified and characterized. The self-diffusion coefficients for 15 liquids (3 cyclic alkanes: cyclohexane to cyclooctane, 9 n-alkanes: n-octane to n-hexadecane, and 3 n-alcohols: ethanol to 1-propanol were measured at 15-30 degrees C using an NMR spectrometer. Values at 22 degrees C range from 0.36 to 2.2 10(-9) m(2)s(-1). Typical 95% confidence limits are +/-2%. Temperature coefficients are 1.7-3.2% degrees C. T1 and T2 values at 1.5 T and proton density are given. n-tridecane has a diffusion coefficient close to that of normal white matter. The longer n-alkanes may be useful T2 standards. Measurements from a spin-echo MRI sequence agreed to within 2%.

Alcohols↗
PubMed2000

Water diffusion compartmentation and anisotropy at high b values in the human brain.

Biexponential diffusion decay is demonstrated in the human brain in vivo using b factors up to 4000 sec mm(-2). Fitting of the signal decay data yields values for the slow and fast diffusion components and volume fractions in agreement with previous studies in rat and human brain. In addition, differences in the fitted parameters are demonstrated in the white and gray matter and diffusion anisotropy is demonstrated in both the slow and fast diffusing components. Apparent anisotropy in the component fractions is discussed in terms of directionally dependent exchange rates between the compartments. The lack of a relationship between the estimated contribution to the signal of the fast and slow components and echo time appears to rule out T(2) differences in the observed water compartments. Values obtained for the fast diffusion coefficient, including differences between white and gray matter and the degree of anisotropy are compatible with the predictions of extracellular diffusion of water based on tortuosity models and the diffusion of tetramethylammonium ions in rat brain.

Anisotropy↗
PubMed2000

Improved reduction of motion artifacts in diffusion imaging using navigator echoes and velocity compensation.

Navigator echoes provide a means with which to remove motion artifacts from diffusion-weighted images obtained using any multishot imaging technique. However, residual motion artifact is often present in the corrected images rendering the technique unreliable. It is shown that velocity-compensated diffusion sensitization when used in tandem with a navigator echo further reduces the degree of residual motion artifacts present in the corrected images and improves the reliability and clinical utility of the technique. This is demonstrated by applying a method for quantification of motion artifact to brain images of healthy volunteers scanned using both conventional (Stejskal-Tanner) and velocity-compensated gradient sensitization. Other factors affecting the efficacy of the navigator echo technique, such as brain pulsatile motion, gradient b factor, and navigator echo signal-to-noise ratio, are also discussed.

Artifacts↗
PubMed2000

Regularization of diffusion-based direction maps for the tracking of brain white matter fascicles.

Magnetic resonance diffusion tensor imaging (DTI) provides information about fiber local directions in brain white matter. This paper addresses inference of the connectivity induced by fascicles made up of numerous fibers from such diffusion data. The usual fascicle tracking idea, which consists of following locally the direction of highest diffusion, is prone to erroneous forks because of problems induced by fiber crossing. In this paper, this difficulty is partly overcomed by the use of a priori knowledge of the low curvature of most of the fascicles. This knowledge is embedded in a model of the bending energy of a spaghetti plate representation of the white matter used to compute a regularized fascicle direction map. A new tracking algorithm is then proposed to highlight putative fascicle trajectories from this direction map. This algorithm takes into account potential fan shaped junctions between fascicles. A study of the tracking behavior according to the influence given to the a priori knowledge is proposed and concrete tracking results obtained with in vivo human brain data are illustrated. These results include putative trajectories of some pyramidal, commissural, and various association fibers.

Algorithms↗