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Biomedical subjects

M R Symms

Publications and source records attributed to M R Symms.

At least 19 recordsLinked to original sources

Magnetization transfer imaging in focal epilepsy.

OBJECTIVES: To test the hypothesis that magnetization transfer imaging (MTI), analyzed on a voxel-by-voxel basis, would identify areas of abnormal magnetization transfer ratio (MTR) in patients with focal epilepsy. METHODS: The authors used MTI maps and statistical parametric mapping (SPM) to objectively compare the cerebral structures of 15 patients with malformations of cortical development (MCD), 10 with partial seizures and acquired lesions, and 42 with partial seizures and normal conventional MRI with those of 30 control subjects. RESULTS: Significant reductions of MTR were identified in all 10 patients with acquired nonprogressive cerebral lesions and partial seizures. In all, the areas of decreased MTR concurred with abnormalities identified on visual inspection of conventional MRI. In 13 of the 15 patients with MCD, SPM detected regions of significantly reduced MTR, all of which corresponded to abnormalities identified on visual inspection of conventional MRI. In addition, in both groups, there were areas that were normal on conventional imaging that demonstrated abnormal MTR. There was a significant reduction of MTR in 15 of the 42 patients with cryptogenic focal epilepsy. In all of these, the areas of reduced MTR concurred with epileptiform EEG abnormality and clinical seizure semiology. CONCLUSIONS: Magnetization transfer imaging analyzed using statistical parametric mapping was sensitive in identifying malformations of cortical development and acquired cerebral lesions. Abnormalities of magnetization transfer ratio in individual MRI-negative patients suggest that minor structural disorganization exists in occult epileptogenic cerebral lesions.

Adolescent↗

Investigating regional white matter in schizophrenia using diffusion tensor imaging.

Diffusion tensor imaging (DTI) was used to investigate regional white matter in vivo in patients with schizophrenia. DTI is capable of providing information about the organization of white matter tracts and has only recently been used to study schizophrenia. In this study, a voxel based analysis of DTI maps in 14 patients and 19 controls did not reveal any areas of significant differences in DTI measures in white matter. The findings suggest that the structural integrity of white matter in these patients was not disrupted. These results are discussed in relation to previous studies reporting positive findings. It is concluded that further studies using DTI in larger samples, improved and standardised methods of data acquisition and analysis are needed.

Adult↗

A fast FLAIR dual-echo technique for hippocampal T2 relaxometry: first experiences in patients with temporal lobe epilepsy.

To evaluate the use of cerebrospinal fluid (CSF) signal nulling in MR T2 measurements of the hippocampus in normal control subjects and patients with temporal lobe epilepsy (TLE), dual-echo acquisitions covering the whole brain were used. T2 relaxation times were estimated in 12 standard Eurospin II MR test objects and in the hippocampi of 10 control subjects, using T2 maps constructed from conventional spin-echo (CSE), fast spin-echo (FSE), and fast FLAIR (FF) dual-echo sequences on a 1.5-T MR scanner. Hippocampal T2 values (HCT2) were measured on contiguous coronal 5-mm slices throughout the antero-posterior extent of each hippocampus in the 10 controls and 12 TLE patients, using both CSE and FF. Scan-rescan reproducibility in Eurospin II standard MR test objects was high for all sequences. There was a good correlation between T2 values from CSE, FF, and FSE sequences in test objects and in control hippocampi. In controls, the coefficient of variation of mean HCT2 values differed between slice positions, but was lowest for FF, followed by CSE data. The intrarater coefficient of reliability between repeated measurements in control subjects was lowest for FF HCT2, at 2.3%. The interrater coefficient of reliability for CSE HCT2 measurements in controls (4.8%) was slightly lower than the interrater coefficient for FF HCT2 (5.4%). HCT2 measurement with both CSE and FF identified abnormal values in the same 10 hippocampi of 12 patients. Hippocampal dual-echo T2 relaxometry using CSF nulling is reliable in control subjects, and identifies the abnormal hippocampi in patients with TLE. The increases in hippocampal T2 signal demonstrated using FF HCT2 measurements are unlikely to be partial volume effects from CSF.

Adult↗

Ultra-fast low-angle rapid acquisition and relaxation enhancement (UFLARE) in patients with epilepsy.

MRI is an important diagnostic tool in patients with epilepsy, but patient motion during long scans may result in image artefacts. We studied the utility of an ultra-fast MR sequence in patients with epilepsy. Ultra-fast low-angle rapid acquisition and relaxation enhancement (UFLARE) images were acquired for 100 consecutive patients and nine control subjects. Scans were compared with routine T2-weighted spin echo images for signal-to-noise ratio, contrast, and conspicuity, followed by a blind review of lesion detectability. UFLARE scans were also acquired for 15 patients who moved during conventional scans. All UFLARE scans had lower signal-to-noise ratios and lower contrast than the T2-weighted images. Compared with T1- and T2-weighted, PD and FLAIR images, 86% of hippocampal sclerosis (HS), 92% of large but only 24% of small white-matter lesions were detected on the blind review of the UFLARE images. Reduced motion artefacts were seen on the UFLARE images in all 15 patients who moved during the conventional scans, and in three patients UFLARE was the only sequence we were able to obtain. Despite the lower lesion detectability for smaller lesions, the use of an ultra-fast MRI sequence such as UFLARE may be very useful in patients who are not able to co-operate during conventional MRI examinations, if a general anaesthetic is to be avoided.

Adolescent↗

Diffusion tensor imaging in patients with epilepsy and malformations of cortical development.

Malformations of cortical development (MCD) are a common cause of epilepsy. Studies of structural MRIs and PET data in patients with MCD have found widespread changes outside the visually identified lesions. The aim of this study was to investigate diffusion changes interictally in patients with MCD and to test the hypothesis that MCD would be associated with widespread abnormalities of diffusion. We used diffusion tensor imaging (DTI) and statistical parametric mapping (SPM) to compare objectively tissue organization in 22 patients with partial seizures and MCD, with 30 control subjects. Whole-brain DTI was acquired using echo planar imaging. Rotationally invariant anisotropy and diffusivity maps were calculated and, after normalization to Talairach space, each patient was compared with the group of control subjects using SPM. Areas of reduced anisotropy were found in 17 patients and areas of increased diffusivity in 10. Two patients had areas of increased anisotropy. There were no patients with reduced diffusivity. Areas of increased diffusivity were in general more extensive than areas of reduced anisotropy. Changes in tissue beyond the MCD, that appeared normal on conventional MRI, were found in six patients for anisotropy and nine patients for diffusivity. Both measurements showed widespread changes in tissue beyond the MCD, i.e. adding information to conventional MRI. Increased or abnormally located grey matter or pathological white matter with abnormal myelination or ectopic neurones could cause reduced anisotropy. Increased diffusivity could be caused by a defect of neurogenesis or cell loss resulting in increased extracellular space. The widespread nature of abnormalities should be considered if surgical treatment is contemplated.

Adult↗

Diffusion tensor imaging of cryptogenic and acquired partial epilepsies.

Current optimal MRI identifies a relevant structural abnormality in up to 80% of patients with refractory partial seizures. Identification of a structural lesion is fundamental to pre-surgical evaluation. We used diffusion tensor imaging (DTI) and statistical parametric mapping (SPM) to examine objectively the diffusion properties, and hence structural organization, of cerebral tissue in 10 patients with partial seizures and acquired lesions and 30 patients with partial seizures and normal MRI. Fractional anisotropy and mean diffusivity maps were calculated and, using SPM, individual patients were compared with a group of 30 control subjects. Diffusion tensor imaging and voxel-by-voxel statistical comparisons identified significant increases in diffusivity and significant reductions of anisotropy in all patients with acquired non-progressive cerebral lesions and partial seizures. In all of these patients, the areas of increased diffusivity, and in nine patients the areas of decreased anisotropy, concurred with abnormalities identified on visual inspection of conventional MRI. In addition, there were 10 areas which were normal on conventional imaging which exhibited abnormal anisotropy or diffusivity. Individual analyses of the 30 patients with partial seizures and normal optimal MRI identified a significant increase in diffusivity in eight of the subjects. In six of these, the areas of increased diffusivity concurred with the localization of epileptiform EEG abnormality. Analysis of anisotropy in the MRI-negative patients revealed significant differences in two patients, one of which concurred with electroclinical seizure localization. Group analysis of nine patients with normal conventional MRI and electroclinical seizure onset localizing to the left temporal region revealed a significant increase in diffusivity and a significant reduction in anisotropy within the white matter of the left temporal lobe. DTI analysed using SPM was sensitive in patients with acquired cerebral damage. Significant differences in the diffusion indices in individual MRI negative patients and the group effect in patients with left temporal lobe epilepsy suggest that minor structural disorganization exists in occult epileptogenic cerebral lesions. These techniques are promising, non-invasive imaging methods for identifying the cause of partial seizures, and can contribute to pre-surgical evaluation.

Adult↗

Neuropathological abnormalities in schizophrenia: evidence from magnetization transfer imaging.

Post-mortem and structural brain imaging studies in schizophrenia have reported macroscopic changes such as global and regional cortical volume reductions, but it has been more difficult to characterize the histopathological changes that underlie these abnormalities. Magnetization transfer imaging (MTI), a novel MRI technique, more sensitive to subtle or early neuropathological changes than conventional MRI, provides a quantitative measure of macromolecular structural integrity represented by the magnetization transfer ratio (MTR). In this study, we used MTI to examine 25 patients with schizophrenia compared with 30 age-matched controls. A voxel-based analysis of the MTR maps revealed widespread MTR reductions in the cortex unrelated to volume reduction, predominantly in the frontal and temporal regions, in the schizophrenic patients when compared with controls. MTR reductions in bilateral parieto-occipital cortex and the genu of the corpus callosum were associated with the severity of negative symptoms in the schizophrenic patients. However, MTR changes were not related to other clinical variables of age, duration of illness and current dose of antipsychotic medication. This study demonstrates that MTR abnormalities in the cortex can be detected in chronic schizophrenia that may reflect subtle neuropathological changes involving neurones or neuronal processes. Longitudinal studies are needed to determine whether these abnormalities are related to disease progression or other disease manifestations such as cognitive changes.

Adult↗

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↗

Quantitative contrast-enhanced magnetic resonance imaging to evaluate blood-brain barrier integrity in multiple sclerosis: a preliminary study.

Gadolinium enhanced magnetic resonance imaging detects focal blood-brain barrier breakdown in new inflammatory multiple sclerosis lesions, but such lesions do not correlate with disease progression. To explore whether the latter might relate to subtle but widespread blood-brain barrier (BBB) breakdown with low grade inflammation mediating tissue damage, quantitative techniques were used to detect subtle gadolinium enhancement within otherwise normal-appearing white matter and within lesions not showing visible enhancement. T1-weighted imaging was performed prior to and at 5, 20 and 40 min following injection of 0.3 mmol/kg gadopentate dimeglumine in 33 patients with multiple sclerosis and five healthy control subjects. In healthy controls, a significant increase in white matter signal 5 min following contrast injection was observed (1.8%, P < 0.0005); the signal returned to baseline values by 20 min. In multiple sclerosis patients, a non-significant trend was noted for signal to remain elevated in normal-appearing white matter at the 20 and 40 min post-contrast time points; this was most apparent in primary progressive multiple sclerosis. Significant increases in signal intensity were noted at all time points post contrast in apparent non-enhancing lesions. The transient post contrast signal increase in controls is likely due to intravascular gadopentate dimeglumine. The persistent increases in signal intensity in non-enhancing lesions suggest more widespread abnormalities in BBB than is visually apparent, but substantiation of BBB leakage in normal appearing white matter will require further study using more sensitive methods.

Adult↗

Spatio-temporal imaging of focal interictal epileptiform activity using EEG-triggered functional MRI.

EEG-triggered, blood oxygen level-dependent functional MRI (BOLD-fMRI) was used in 24 patients with localization-related epilepsy and frequent interictal epileptiform discharges (spikes) to identify those brain areas involved in generating the spikes, and to study the evolution of the BOLD signal change over time. The location of the fMRI activation was compared with the scalp EEG spike focus and the structural MR abnormality. Twelve patients (50%) had an fMRI activation concordant with the EEG focus and structural brain abnormalities where present (n = 7). In 2 other patients, the fMRI activation was non-concordant with electroclinical findings. The remaining 10 patients (41.7%) showed no significant fMRI activation. These patients had significantly lower mean spike amplitudes compared to those with positive fMRI results (p = 0.03). The time course of the BOLD response was studied in 3 patients and this revealed a maximum signal change 1.5 to 7.5 sec after the spike. In conclusion, EEG-triggered fMRI can directly identify the generators of interictal epileptiform activity, with high spatial resolution, in selected patients with frequent spikes. The superior spatial resolution obtainable through EEG-triggered fMRI may provide an additional non-invasive tool in the presurgical evaluation of patients with intractable focal seizures.

Action Potentials↗

EEG recording during fMRI experiments: image quality.

Electroencephalographic (EEG) monitoring during functional magnetic resonance imaging (fMRI) experiments is increasingly applied for studying physiological and pathological brain function. However, the quality of the fMRI data can be significantly compromised by the EEG recording due to the magnetic susceptibility of the EEG electrode assemblies and electromagnetic noise emitted by the EEG recording equipment. We therefore investigated the effect of individual components of the EEG recording equipment on the quality of echo planar images. The artifact associated with each component was measured and compared to the minimum scalp-cortex distance measured in normal controls. The image noise originating from the EEG recording equipment was identified as coherent noise and could be eliminated by appropriate shielding of the EEG equipment. It was concluded that concurrent EEG and fMRI could be performed without compromising the image quality significantly if suitable equipment is used. The methods described and the results of this study should be useful to other researchers as a framework for testing of their own equipment and for the selection of appropriate equipment for EEG recording inside a MR scanner.

Adolescent↗

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↗

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↗

The relationship between the apparent diffusion coefficient measured by magnetic resonance imaging, anoxic depolarization, and glutamate efflux during experimental cerebral ischemia.

A reduction in the apparent diffusion coefficient (ADC) of water measured by magnetic resonance imaging (MRI) has been shown to occur early after cerebrovascular occlusion. This change may be a useful indicator of brain tissue adversely affected by inadequate blood supply. The objective of this study was to test the hypothesis that loss of membrane ion homeostasis and depolarization can occur simultaneously with the drop in ADC. Also investigated was whether elevation of extracellular glutamate ([GLU]e) would occur before ADC changes. High-speed MRI of the trace of the diffusion tensor (15-second time resolution) was combined with simultaneous recording of the extracellular direct current (DC) potential and on-line [GLU]e from the striatum of the anesthetized rat. After a control period, data were acquired during remote middle cerebral artery occlusion for 60 minutes, followed by 30 minutes of reperfusion, and cardiac arrest-induced global ischemia. After either focal or global ischemia, the ADC was reduced by 10 to 25% before anoxic depolarization occurred. After either insult, the time for half the maximum change in ADC was significantly shorter than the corresponding DC potential parameter (P < 0.05). The [GLU]e remained at low levels during the entire period of varying ADC and DC potential and did not peak until much later after either ischemic insult. This study demonstrates that ADC changes can occur before membrane depolarization and that high [GLU]e has no involvement in the early rapid ADC decrease.

Animals↗

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↗