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C A Clark

Publications and source records attributed to C A Clark.

At least 19 recordsLinked to original sources
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

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↗
PubMed2000

The pathogenesis of lesions and normal-appearing white matter changes in multiple sclerosis: a serial diffusion MRI study.

The idea that the initiating event in the formation of all new multiple sclerosis lesions is a focal blood-brain barrier (BBB) leakage associated with perivascular inflammation has been challenged recently by the observation of subtle abnormalities in some quantitative magnetic resonance (MR) parameters (including the magnetization transfer ratio) prior to lesion enhancement. MR diffusion imaging can non-invasively quantify the average apparent diffusion coefficient (ADC(av)), a measure of water molecule random motion that is sensitive to pathological change in multiple sclerosis lesions and to abnormalities in the normal-appearing white matter (NAWM). We therefore used MR diffusion imaging to investigate the dynamic evolution of water diffusion measurements in new enhancing multiple sclerosis lesions, in the NAWM from which they arise, and in anatomically matched contralateral NAWM regions from which no visible lesions develop. Gadolinium diethylenetriaminepentaacetic acid (Gd)-enhanced MRI and MR diffusion studies were performed monthly for 1 year in five multiple sclerosis patients with clinically and radiologically active disease. The ADC(av) was calculated at each time point of the study (before, during and after lesion appearance on Gd-enhanced scans) for each new enhancing lesion, and for regions matched for size and position in the contralateral NAWM. A steady and moderate increase in ADC(av) in prelesion NAWM was observed, which was followed by a rapid and marked increase at the time of Gd enhancement and a slower decay after the cessation of enhancement. In matched contralateral NAWM regions there was a significant but milder increase in ADC(av) at the time of the first noted lesion enhancement. These findings indicate that new focal lesions associated with frank BBB leakage are preceded by subtle, progressive alterations in tissue integrity beyond the resolution of conventional MRI. The increases in ADC(av) in anatomically matched contralateral regions after lesions have appeared supports the concept that structural damage in lesions causes damage or dysfunction in connected areas of NAWM.

Adult↗
PubMed2000

Neuropathological abnormalities of the corpus callosum in schizophrenia: a diffusion tensor imaging study.

OBJECTIVES: Diffusion tensor imaging (DTI), a technique capable of examining water diffusion in different tissues and the organisation of white matter tracts, was used to investigate the neuropathology of the corpus callosum in vivo in patients with schizophrenia. METHODS: Diffusion tensor imaging was performed in 20 schizophrenic patients and 25 healthy controls. Two complementary measures, mean diffusivity and fractional anisotropy, which are considered to be sensitive indices of axonal integrity, were obtained from regions of interest in the genu (anterior) and splenium (posterior) of the corpus callosum. RESULTS: Mean diffusivity was significantly increased and fractional anisotropy significantly reduced in the splenium but not the genu of the corpus callosum in the schizophrenic group compared with controls. There were no significant sex differences in the DTI measures for either the schizophrenic or control group. Clinical variables such as age, duration of illness, dose of antipsychotic medication, and schizophrenic symptoms did not predict the DTI changes in the schizophrenic patients. CONCLUSIONS: The presence of DTI changes in the splenium but not the genu of the corpus callosum suggests that there may be a focal disruption of commisural connectivity in schizophrenia. However, these findings do not exclude the possibility of abnormalities in other areas of the corpus callosum or other regions of white matter and further research using different methods of analysis may enable us to clarify this. Diffusion tensor imaging is a valuable tool in investigating the structure of white matter in schizophrenia.

Adult↗
PubMed2000

Diffusion tensor imaging demonstrates deviation of fibres in normal appearing white matter adjacent to a brain tumour.

The objective was to study fibre orientation in the cerebral white matter of a patient with a brain tumour using diffusion tensor imaging (DTI). A patient with a mild left hemiparesis and a tumour in the right frontal lobe and 20 healthy volunteers were scanned with a DTI sequence. The scans were spatially normalised and the fibre orientation in the patient compared with the fibre orientation in normal controls. DTI disclosed a change of the orientation of fibres in the patient compared with normal controls. In the normal appearing white matter adjacent to the tumour fibres deviated from the normal superior inferior orientation in the corona radiata by about 30 degrees. This finding was consistent with a displacement by distant mass effect rather than a destruction of fibres, in agreement with the neurological examination. In conclusion, DTI demonstrated a deviation of fibres in normal appearing white matter adjacent to a tumour. The technique will improve understanding of the effects of structural abnormalities on fibres. This will assist the interpretation of clinical findings and functional imaging studies and guide neurosurgical interventions.

Brain↗
PubMed2000

Diffusion tensor imaging can detect and quantify corticospinal tract degeneration after stroke.

Diffusion tensor imaging (DTI) fully characterises water molecule mobility in vivo, allowing an exploration of fibre tract integrity and orientation in the human brain. Using DTI this study demonstrates reduced fibre coherence (anisotropy) associated with cerebral infarction and in the corticospinal tract remote from the lesion, in five patients 2 to 6 months after ischaemic stroke. The study highlights the potential of DTI to detect and monitor the structural degeneration of fibre pathways, which may provide a better understanding of the pattern of clinical evolution after stroke.

Adult↗
PubMed2000

Cerebral hemodynamics in CADASIL before and after acetazolamide challenge assessed with MRI bolus tracking.

BACKGROUND: White matter lesions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are underlaid by severe ultrastructural changes of the arteriolar wall. Although chronic ischemia is presumed to cause the tissue lesions, the pattern of perfusion abnormalities and hemodynamic reserve in CADASIL, particularly within the white matter, remains unknown. METHODS: We used the MRI bolus tracking method in 15 symptomatic patients with CADASIL (5 with dementia) and 10 age-matched control subjects before and 20 minutes after the intravenous injection of acetazolamide (ACZ, 17 mg/kg). Cerebral blood flow (CBF), blood volume (CBV), and mean transit time (MTT) were calculated both in the cortex and in the white matter according to the singular value decomposition technique. Perfusion parameters were obtained in regions of hyperintensities and within the normal-appearing white matter as observed on T2-weighted images. Analysis was performed with both absolute and relative (region/whole brain) values. RESULTS: A significant reduction in absolute and relative CBF and CBV was found within areas of T2 hyperintensities in white matter in the absence of significant variations of MTT. This reduction was more severe in demented than in nondemented patients. No significant change in absolute CBF and CBV values was observed in the cortex of patients with CADASIL. A decrease in relative CBF and CBV values was detected in the occipital cortex. After ACZ administration, CBF and CBV increased significantly in both the cortex and white matter of affected subjects, but the increase in absolute CBF was lower within areas of increased signal on T2-weighted images in patients than in the white matter of control subjects. CONCLUSIONS: In CADASIL, both basal perfusion and hemodynamic reserve are decreased in areas of T2 hyperintensities in the white matter. This hypoperfusion appears to be related to the clinical severity. The significant effect of ACZ on CBF and CBV suggests that cerebral perfusion might be increased using pharmacological vasodilation in CADASIL.

Acetazolamide↗
PubMed2000

The threat is real.

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Biological Warfare↗