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Biomedical subjects

D J Werring

Publications and source records attributed to D J Werring.

At least 19 recordsLinked to original sources
PubMed2005

Cerebral microbleeds are common in ischemic stroke but rare in TIA.

BACKGROUND: In patients with stroke, gradient-echo MRI commonly detects microbleeds, indicating small artery disease with increased risk of macroscopic intracranial bleeding. Antithrombotic treatments are frequently prescribed after TIA and stroke, but there have been no previous studies of microbleeds in TIA. Because microbleeds may predict the hemorrhagic risk of antithrombotic treatments, we studied the prevalence of microbleeds, risk factors, and pathophysiologic mechanisms in patients with ischemic stroke and TIA. METHODS: One hundred twenty-nine consecutive patients with ischemic stroke or TIA were studied with MRI including T2, fluid-attenuated inversion recovery, and gradient-echo MRI sequences. Blinded observers counted microbleeds and graded white matter T2 hyperintensities throughout the brain. TIA patients with previous ischemic stroke were excluded. RESULTS: Sixty-seven percent of patients had ischemic stroke; 33% had TIA. Microbleeds were found in 23% of ischemic stroke patients but only 2% of TIA patients (p < 0.001). There were no significant differences in conventional risk factors or the severity of white matter disease on T2 MRI between stroke and TIA patients. Patients with microbleeds were more often hypertensive (81 vs 59%; p = 0.04) and had more severe MRI white matter disease on T2 MRI (p = 0.003). CONCLUSIONS: Microbleeds are common in ischemic stroke but rare in TIA, an observation not explained by differences in vascular risk factors or severity of white matter disease seen on T2 MRI. This finding has implications for the safety of antithrombotic therapy and clinical trial design in the two groups. Microbleeds may also be a new marker for severe microvascular pathology with increased risk of permanent cerebral infarction.

Aged↗
PubMed2004

Functional magnetic resonance imaging of the cerebral response to visual stimulation in medically unexplained visual loss.

BACKGROUND: Medically unexplained visual loss occurs in 1 to 5% of patients attending ophthalmology clinics and for many it runs a chronic course. A psychogenic aetiology is presumed in such cases, but little is known about the underlying neural mechanisms. Recent studies have established the value of functional magnetic resonance imaging (fMRI) in understanding the mechanisms of unexplained motor and sensory symptoms. The purpose of this study was to use a similar strategy (fMRI) to evaluate the cerebral responses to visual stimulation in a group of patients with medically unexplained visual loss, in an attempt to determine the underlying neural mechanisms. METHOD: Brain activation induced by periodic (monocular) 8 Hz visual stimulation was detected by fMRI in five patients with unexplained visual loss who fulfilled DSM-IV criteria for conversion disorder, and seven normal volunteers. Between-group differences in mean power of activation were estimated by fitting a one-way analysis of variance (ANOVA) model at each intracerebral voxel in standard space. RESULTS: Compared with controls, patients showed reduced activation in visual cortices, but increased activation in left inferior frontal cortex, left insula-claustrum, bilateral striatum and thalami, left limbic structures, and left posterior cingulate cortex. CONCLUSIONS: This preliminary study has identified novel neural correlates in patients with unexplained visual loss. The abnormal pattern of activation may reflect inhibition of primary visual cortex or a shift towards non-conscious (implicit) processing.

Adolescent↗
PubMed2003

Diffusion tensor imaging detects corticospinal tract involvement at multiple levels in amyotrophic lateral sclerosis.

BACKGROUND: Histopathological studies of amyotrophic lateral sclerosis (ALS) are of end stage disease. Diffusion tensor imaging (DTI) provides the opportunity to investigate indirectly corticospinal tract pathology of ALS in vivo. METHODS: DTI was used to study the water diffusion characteristics of the corticospinal tracts in 21 patients with ALS and 14 normal controls. The authors measured the fractional anisotropy (FA) and mean diffusivity (MD) along the pyramidal tracts from the internal capsules down to the pyramids. A mixed model regression analysis was used to compare FA and MD between the ALS and control groups. RESULTS: FA showed a downward linear trend from the cerebral peduncles to the pyramids and was lower in the ALS group than controls at multiple levels of the corticospinal tract. At the internal capsules, FA was higher on the right. MD showed an upward trend, progressing caudally from the internal capsules to the pyramids. MD was higher at the level of the internal capsule in the ALS group, but caudally this difference was not maintained. No correlations were found between clinical markers of disability and water diffusion indices. CONCLUSIONS: These findings provide insights into the pathological processes of ALS. Differences in diffusion characteristics at different anatomical levels may relate to underlying tract architecture or the distribution of pathological damage in ALS. Further development may permit monitoring of progression and treatment of disease.

Adult↗
PubMed2002

Functional magnetic resonance imaging of the cortical response to photic stimulation in humans following optic neuritis recovery.

Recovery from optic neuritis has been shown to be associated with an abnormal functional MRI (fMRI) response following exposure of the eye to an epoch based (ON-OFF design) flickering photic stimulus. Visual cortex activation is reduced during photic stimulation, whilst extra-occipital areas are extensively activated with a peak blood oxygen level dependent response during the OFF phase of the stimulus paradigm. We performed a further fMRI experiment to determine whether the abnormal extra-occipital response is a phase-specific phenomenon or whether it results from a delayed haemodynamic response. A cohort of patients that recovered from optic neuritis was studied, this time using a longer photic stimulation epoch (40 s). The extra-occipital response again peaked during the baseline condition, indicating that the phenomenon is phase dependent. Our results also reinforce the important findings of extra-occipital activation following optic neuritis which may represent an adaptive reorganization of the cerebral response.

Adult↗
PubMed2001

Investigation of MS normal-appearing brain using diffusion tensor MRI with clinical correlations.

OBJECTIVE: To quantitatively investigate water diffusion changes in normal-appearing white matter (NAWM) and gray matter in patients with MS, and to evaluate whether these changes are correlated with clinical disability and disease duration. BACKGROUND: Diffusion tensor imaging provides quantitative information about the magnitude and directionality (anisotropy) of water diffusion in vivo and detects pathologic changes in MS brain tissue. METHODS: Diffusion tensor imaging was performed in 39 patients with MS and in 21 age-matched control subjects. Quantitative indices, including fractional anisotropy, volume ratio, and mean diffusivity, were obtained in 30 regions of interest located in normal-appearing basal ganglia, cerebellar gray matter, and supratentorial and infratentorial NAWM. RESULTS: Patients with MS showed significantly reduced anisotropy and a trend toward increased diffusivity in the infratentorial and supratentorial NAWM, and significantly increased anisotropy in the basal ganglia. In all patients with MS, both fractional anisotropy and mean diffusivity in the cerebral peduncles were inversely correlated with the Expanded Disability Status Scale and pyramidal functional scores. In patients with relapsing-remitting MS, there was a strong correlation between Expanded Disability Status Scale score and fractional anisotropy in both supratentorial and infratentorial NAWM. In primary and secondary progressive MS, disease duration correlated strongly with mean diffusivity in infratentorial NAWM and fractional anisotropy in the cerebral peduncles, respectively. CONCLUSION: The most striking finding of decreased fractional anisotropy in supratentorial and infratentorial NAWM and increased fractional anisotropy in basal ganglia may result from axonal degeneration due to fiber transection in remote focal lesions. Diffusion tensor imaging indices, in particular fractional anisotropy, appear sensitive to structural damage in NAWM that is associated with disability and progression in MS.

Adult↗
PubMed2001

Asymmetrical activation of human visual cortex demonstrated by functional MRI with monocular stimulation.

We have demonstrated asymmetric activation patterns in the visual cortices of normal humans who have undergone functional MRI with monocular photic stimulation. The contralateral hemisphere is activated more strongly and to a greater spatial extent than the ipsilateral hemisphere when either eye is stimulated. This asymmetry can be explained by nasotemporal asymmetries which have been described in anatomical studies of the visual system in primates and humans. In part, the representation of the monocular crescent of the temporal hemifield of either eye, which exists only in the crossed projection, may explain this. In addition, within the binocular field, there is a biased crossed projection of nasal retinal ganglion cells which drive the contralateral ocular dominance columns in V1. Finally, the blind spot representation in the ipsilateral visual cortex may also contribute to the observed asymmetries. Our study may in effect provide a functional correlate of the anatomical asymmetries that have been observed in humans and animals.

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

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

Nonlinear smoothing for reduction of systematic and random errors in diffusion tensor imaging.

Calculation and sorting of the eigenvectors of diffusion using diffusion tensor imaging has previously been shown to be sensitive to noise levels in the acquired data. This sensitivity manifests as random and systematic errors in the diffusion eigenvalues and derived parameters such as indices of anisotropy. An optimized application of nonlinear smoothing techniques to diffusion data prior to calculation of the diffusion tensor is shown to reduce both random and systematic errors, while causing little blurring of anatomical structures. Conversely, filtering applied to calculated images of fractional anisotropy is shown to fail in reducing systematic errors and in recovering anatomical detail. Using both real and simulated brain data sets, it is demonstrated that this approach has the potential to allow acquisition of data that would otherwise be too noisy to be of use.

Anisotropy↗
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

Recovery from optic neuritis is associated with a change in the distribution of cerebral response to visual stimulation: a functional magnetic resonance imaging study.

OBJECTIVES: Recovery to normal or near normal visual acuity is usual after acute demyelinating optic neuritis, despite the frequent persistence of conduction abnormalities as evidenced by the visual evoked potential (VEP). This raises the possibility that cortical adaptation to a persistently abnormal input contributes to the recovery process. The objective of this study was to investigate the pattern of cerebral response to a simple visual stimulus in recovered patients in comparison to normal subjects. METHODS: Functional magnetic resonance imaging (fMRI) was used to study the brain activation pattern induced by a periodic monocular 8Hz photic stimulus in seven patients who had recovered from a single episode of acute unilateral optic neuritis, and in seven normal controls. VEPs and structural optic nerve MRI were performed on patients. RESULTS: Stimulation of either eye in controls activated only the occipital visual cortex. However, in patients, stimulation of the recovered eye also induced extensive activation in other areas including the insula-claustrum, lateral temporal and posterior parietal cortices, and thalamus; stimulation of the clinically unaffected eye activated visual cortex and right insula-claustrum only. The volume of extraoccipital activation in patients was strongly correlated with VEP latency (r = 0.71, p = 0.005). CONCLUSIONS: The extraoccipital areas that were activated in patients all have extensive visual connections, and some have been proposed as sites of multimodal sensory integration. The results indicate a functional reorganisation of the cerebral response to simple visual stimuli after optic neuritis that may represent an adaptive response to a persistently abnormal input. Whether this is a necessary part of the recovery process remains to be determined.

Adult↗
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↗
PubMed1999

Diffusion tensor imaging of lesions and normal-appearing white matter in multiple sclerosis.

OBJECTIVE: To determine whether diffusion tensor imaging (DTI) can detect structural changes in normal-appearing white matter, and to distinguish between plaques of different pathologic severity, in patients with MS. BACKGROUND: Conventional MRI detects lesions sensitively in MS but has limited pathologic specificity. The diffusion of water molecules in brain tissue, most fully expressed mathematically by a tensor quantity, reflects its intrinsic microstructure. It is now possible to estimate the diffusion tensor noninvasively in the human brain using MR DTI. This method is unique in providing precise and rotationally invariant measurements of the amount and directional bias (anisotropy) of diffusion in white matter tracts relating to tissue integrity and orientation. METHODS: DTI was performed in six patients with MS and in six age-matched control subjects. Diffusion was characterized in normal-appearing white matter in both groups, and in lesions of different pathologic subtypes (inflammatory, noninflammatory, T1 hypointense, and T1 isointense). RESULTS: DTI identified significantly altered water diffusion properties in the normal-appearing white matter of patients compared with control subjects (p < 0.001), and distinguished between lesion types. The highest diffusion was seen in destructive (T1 hypointense) lesions, whereas the greatest change in anisotropy was found in inflammatory (gadolinium-enhancing) lesions. CONCLUSIONS: DTI detects diffuse abnormalities in the normal-appearing white matter of MS patients, and the findings in lesions appear to relate to pathologic severity. Its use in serial studies and in larger clinical cohorts may increase our understanding of pathogenetic mechanisms of reversible and persistent disability.

Adult↗
PubMed1999

A direct demonstration of both structure and function in the visual system: combining diffusion tensor imaging with functional magnetic resonance imaging.

The relationships between functional activation patterns and the structural properties of brain pathways have not been widely studied. The recently developed magnetic resonance imaging technique of diffusion tensor imaging (DTI) allows a full characterization of water molecule mobility in three dimensions, providing new structural information that is not available from other in vivo imaging techniques. The directional bias of diffusion (anisotropy) may be derived from the diffusion tensor, and is related to fiber tract integrity and orientation. Since DTI and functional magnetic resonance imaging (fMRI) both require rapid (generally echoplanar) imaging it is possible to obtain geometrically matched images from the two modalities. fMRI and DTI were combined in a visual system study using photic stimulation to demonstrate the feasibility of combining the two methods and to investigate the structural properties of activated regions compared to the white matter tracts. Blood oxygenation level-dependent (BOLD) fMRI activation maps were directly overlayed upon fractional anisotropy (FA) maps, avoiding registration and spatial transformation by carefully matching acquisition parameters. Activated regions had lower FA than optic radiation white matter, supporting the hypothesis that most BOLD signal change occurs within the relatively isotropic cortical grey matter. The combination of these modalities in future studies may provide further insights into relationships between brain structure and function in both health and disease.

Adult↗
PubMed1999

Comparison of multiple sclerosis clinical subgroups using navigated spin echo diffusion-weighted imaging.

The apparent diffusion coefficient (ADC) of tissue provides an indication of the size, shape, and orientation of the water spaces in tissue. Thus, pathologic differences between lesions in multiple sclerosis (MS) patients with different clinical courses may be reflected by changes in ADC measurements in lesions and white matter. Twelve healthy subjects and 35 MS patients with a relapsing-remitting (n = 10), benign (n = 8), secondary progressive (n = 8) and primary progressive (n = 9) clinical course were studied. T2-weighted and post-gadolinium T1-weighted images were obtained using a 1.5 T Signa Echospeed magnetic resonance imaging (MRI) system. Diffusion-weighted imaging was implemented using a pulsed gradient spin echo (PGSE) sequence with diffusion gradients applied in turn along three orthogonal directions in order to obtain the average apparent diffusion coefficient (ADCav). Navigator echo correction and cardiac gating were used to reduce motion artifact. ADC maps were derived using a two point calculation based on the Stejskal-Tanner formula. Diffusion anisotropy was estimated using the van Gelderen formula to calculate an anisotropy index. MS lesions had a higher ADC and reduced anisotropy compared with normal appearing white matter. Highest ADC values were found in gadolinium enhancing lesions and non-enhancing hypointense lesions on T1-weighted imaging. MS white matter had a slightly higher ADC and lower anisotropy than white matter of healthy subjects. Lesion and white matter ADC values did not differ between patients with different clinical courses of MS. There was no correlation between lesion ADC and disability. Diffusion-weighted imaging with measurement of ADC using the PGSE method provides quantitative information on acute edematous MS lesions and chronic lesions associated with demyelination and axonal loss but does not distinguish between clinical subtypes of MS.

Brain↗