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D G MacManus

Publications and source records attributed to D G MacManus.

At least 37 records · Page 2Linked to original sources
PubMed1999

Hippocampal layers on high resolution magnetic resonance images: real or imaginary?

To evaluate whether the lines occasionally detected on clinical magnetic resonance (MR) images are genuine hippocampal layers, a formalin fixed hippocampal specimen was scanned using T2 weighted sequences at 7 Tesla (voxel dimensions 0.064 x 0.064 x 1 mm) and at 1.5 Tesla (voxel dimensions: 0.156 x 0.156 x 1 mm) and compared with the results of histological examination. In addition, a healthy volunteer was scanned with a T2 weighted sequence at 1.5 Tesla (voxel dimensions: 0.469 x 0.469 x 2 mm). On 7 Tesla images hippocampal layers and the granule cell layer of the dentate were visible. On 1.5 Tesla images of the specimen, the hippocampal layers were again identified, but the granule cell layer of the dentate was not detectable. On 1.5 Tesla images of the hippocampus in vivo, 3 layers could be distinguished in the hippocampus on some slices. These mainly represented the alveus, pyramidal cell layer and stratum radiatum. A dark line consisting of a few pixels possibly represented the dentate gyrus. Our results show that the lines occasionally detected on clinical MR images are likely to be real hippocampal layers. However, the resolution currently used in clinical imaging (typically 0.469 x 0.469 x 2 mm or lower) is not sufficient for the detection of all hippocampal layers. For the reliable detection of all hippocampal layers on MR images an increase by a factor of approximately 20 would be necessary.

Adult↗
PubMed1999

Quantitative MRI in patients with clinically isolated syndromes suggestive of demyelination.

OBJECTIVE: To assess the long-term predictive value of quantitative lesion load measurement on brain MRIs in patients after a 10-year follow-up who presented initially with a clinically isolated syndrome of the optic nerve, brainstem, or spinal cord. BACKGROUND: Quantitative MRI measurement is being used in treatment trials as a surrogate marker in MS, but there is a lack of long-term MRI follow-up data in assessing the natural course of the disease from the earliest stages. METHODS: Using a semiautomated threshold technique, the total lesion volume (TLV), the course of the disease, and disability were assessed in 58 patients at onset and after 5 and 10 years. RESULTS: The TLV at presentation correlated significantly (r = 0.81, p = 0.0001) with the TLV and also with the Expanded Disability Status Scale (EDSS) score (r = 0.45, p = 0.001) at 10-year follow-up. In contrast there was no correlation of the TLV at 5 years with subsequent change in EDSS score over the next 5 years (r = 0.18, p = 0.12). The change in TLV over the first 5 years in patients who developed clinically definite MS (CDMS) differed significantly according to the type of disease course (relapsing-remitting with disability, secondary progressive, or benign) manifesting at 10-year follow-up. CONCLUSION: Quantification of changes detected by T2-weighted brain MRI at the earliest clinical stages is strongly predictive of the subsequent development of CDMS as well as the clinical course and level of disability 10 years later.

Adolescent↗
PubMed1998

Optimisation of unenhanced MRI for detection of lesions in multiple sclerosis: a comparison of five pulse sequences with variable slice thickness.

We used five MRI sequences in six patients with multiple sclerosis (MS): conventional spin-echo (CSE) with 5-mm slices; 2D fast spin-echo (FSE) with 2-mm slices; multishot T2*-weighted echo-planar imaging (EPI) with 5-mm slices; fast fluid-attenuated inversion recovery (fFLAIR) with 2-mm slices; and 3D fast spin-echo with 1.5-mm-thick slices. A total of 225 lesions were detected on CSE, 274 on 2D FSE, 137 on EPI, 385 on fFLAIR and 320 on 3D FSE. The EPI sequence was clearly the least sensitive and susceptibility artefact was a problem, particularly in the brain stem and temporal lobes. Fast FLAIR displayed a much higher number of supratentorial lesions (380) than 3D FSE (297), 2D FSE (264) or CSE (211). However, in the posterior cranial fossa 3D FSE was the most sensitive sequence (23 lesions), followed by CSE (14) and 2D FSE (10), while fFLAIR (5) was extremely insensitive.

Adult↗
PubMed1998

The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up.

A definitive diagnosis of multiple sclerosis cannot be made at presentation on patients with a clinically isolated syndrome of the optic nerve, spinal cord or brainstem suggestive of demyelination, as dissemination in time is not established. To determine the long-term risk of abnormalities on brain MRI for the development of multiple sclerosis and disability we performed a 10-year follow-up on 81 such patients who had T2-weighted brain MRI at presentation. Initial brain MRI was abnormal in 54 (67%). Follow up of those patients with an abnormal MRI revealed progression to clinically definite multiple sclerosis in 45 out of 54 (83%), of whom 11 (20%) had relapsing/remitting disease (EDSS > 3), 13 (24%) secondary progressive and 21 (39%) benign (relapsing/remitting with EDSS < or = 3) disease. For those with a normal MRI progression to clinically definite multiple sclerosis occurred in only three out of 27 (11%), all benign. There was a significant relationship between the number of lesions at presentation and both EDSS (r = 0.45, P < 0.001) and the type of disease at follow-up (P < 0.0001). Brain MRI at presentation with a clinically isolated syndrome is predictive of the long-term risk of subsequent development of multiple sclerosis, the type of disease and extent of disability.

Adolescent↗
PubMed1998

Asymptomatic spinal cord lesions in clinically isolated optic nerve, brain stem, and spinal cord syndromes suggestive of demyelination.

OBJECTIVES: Conventional T2 weighted MRI studies have highlighted the fact that the presence of clinically silent brain lesions increases the risk of developing clinically definite multiple sclerosis after an isolated syndrome of the optic nerve, brain stem, or spinal cord. The objectives of the present study are: (1) to show whether or not these patients also have asymptomatic abnormalities of the spinal cord, and (2) to recruit a new cohort of such patients using high resolution MRI of both brain and spinal cord. METHODS: The brain was imaged in the axial plane with 3 mm thick contiguous slices using a proton density and T2 weighted fast spin echo (FSE) sequence; a T1 weighted sequence after the injection of gadolinium-DTPA; and a fast fluid attenuated inversion recovery (fFLAIR) sequence. The spinal cord was imaged in the sagittal plane with 3 mm thick slices using a T2 weighted FSE and a T1 weighted gadolinium enhanced sequence. RESULTS: Thirty three patients, mean age 31 (16-46) were recruited. There were 14 men and 19 women. Brain MRI was abnormal in 22 (67%); no patient was seen with abnormalities on only one or other sequence. Six patients (18%) displayed one or more gadolinium enhancing lesions on brain MRI. In the spinal cord, nine (27%) patients displayed one or more clinically silent lesions on FSE. Two patients showed one and two gadolinium enhancing lesions in the spinal cord respectively. CONCLUSION: This high incidence of spinal cord lesions emphasises that asymptomatic demyelinating lesions may also involve clinically eloquent pathways. Follow up studies are required to determine their prognostic importance.

Adolescent↗
PubMed1998

The effect of section thickness on MR lesion detection and quantification in multiple sclerosis.

BACKGROUND AND PURPOSE: The purpose of our study was to investigate the effect of section thickness on MR detection of brain lesion volume and measurement precision in patients with multiple sclerosis (MS). METHODS: Eight subjects with known MS were studied on a 1.5-T MR system. We used a 3D fast fluid-attenuated inversion-recovery sequence to obtain contiguous axial brain images at section thicknesses of 5 mm, 3 mm, and 1 mm. Two sets of images were acquired at each section thickness during two sessions, between which the patient was removed from the scanner. Lesion volumes were measured at each section thickness using a semiautomated local thresholding technique. RESULTS: We found that progressive reduction in section thickness led to detection of smaller lesions, resulting in a significant (8%) increase in lesion volume on MR images as section thickness was reduced from 5 mm to 3 mm. However, despite a further increase in lesion detection at a section thickness of 1 mm, this did not result in an increase in total lesion volume. This finding indicates that the relationship between section thickness and lesion volume on MR images is not linear. Scan-rescan reproducibility was improved by reducing section thickness, at the cost of increased analysis time. CONCLUSION: This study shows that acquisition of very thin sections increases the sensitivity and precision of MS lesion measurement. Serial studies assessing lesion changes over time are needed to define the impact of this increase on sample size requirements for MS treatment trials.

Adult↗
PubMed1997

Magnetisation transfer ratio measurement in the cervical spinal cord: a preliminary study in multiple sclerosis.

MRI readily detects the lesions of multiple sclerosis (MS) in the brain and spinal cord. Conventional MRI sequences do not, however, permit distinction between the various pathological characteristics (oedema, demyelination, axonal loss and gliosis) of lesions in MS. Magnetisation transfer (MT) imaging may be more specific in distinguishing the pathologies responsible for disability in MS, namely demyelination and axonal loss, and therefore may have a potential role in monitoring treatment. We have applied MT imaging to the cervical spinal cord to see if it is feasible to measure MT ratios (MTR) in this region where pathological changes may result in considerable disability. We studied 12 patients with MS and 12 age- and sex-matched normal controls using a sagittal T2-weighted fast spin-echo sequence with and without an MT pulse. The median value for cervical cord mean MTR measurement in normal controls was 19.30% units (interquartile range 19.05-19.55), whereas values were significantly lower in MS patients (median = 17.95% units, interquartile range 17.25-19.00, P = 0.0004). There was a low intrarater variability for repeated mean MTR measurements. We conclude that it is possible to measure MTR in the cervical spinal cord, that a significant reduction occurs in patients with MS, and that there may be a role for this measure in future MS treatment trials.

Adult↗
PubMed1997

Sensitivity of contrast enhanced MRI in multiple sclerosis. Effects of gadolinium dose, magnetization transfer contrast and delayed imaging.

Although clinical end points remain the definitive measure of therapeutic efficacy in multiple sclerosis, more sensitive markers of disease activity are required to screen potential disease-modifying agents. The use of gadolinium contrast-media in MRI studies increases both the reliability and sensitivity of detecting active lesions in multiple sclerosis. We studied three potential methods for further improving sensitivity; the use of 0.3 mmol/kg (triple dose) gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA), magnetization transfer (MT) contrast imaging and the introduction of a delay between contrast-medium injection and imaging. Fifty patients were studied (seven with benign, 14 with relapsing-remitting, 10 with secondary progressive, 16 with primary progressive and three with transitional multiple sclerosis). Imaging was performed on two occasions, 24-72 h apart, with triple- and single-dose Gd-DTPA. Pairs of contrast-enhanced T 1-weighted studies, with and without MT, were obtained at three different times, i.e. within early (0-20 min), short-delay (20-40 min) and long-delay (40-60 min) time-windows. Nineteen patients did not have the full complement of studies. Seven patients suffered minor self-limiting adverse events possibly related to triple-dose Gd-DTPA. Overall, triple-dose Gd-DTPA resulted in a 75% increase in the number of enhancing lesions detected compared with the single dose (P < 0.002). The use of MT or delay alone did not significantly increase the sensitivity of either single- or triple-dose studies. The combination of MT and short delay increased the number of enhancing lesions detected with single-dose Gd-DTPA by 47% (P < 0.05) and with triple-dose Gd-DTPA by 27% (P < 0.01). Detection was not significantly further improved by a long delay. The most sensitive modality was MT imaging with a long delay following triple-dose Gd-DTPA, resulting in the detection of 126% more enhancing lesions than in standard single-dose imaging (P < 0.05). This applies to all subgroups except for primary progressive multiple sclerosis, in which none of these methods alone or in combination improved the sensitivity. We conclude that for relapsing-remitting and secondary progressive multiple sclerosis, the combination of triple-dose Gd-DTPA and delayed MT imaging more than doubles the sensitivity to contrast-enhancing lesions.

Adult↗
PubMed1997

Magnetisation transfer ratio of normal brain white matter: a normative database spanning four decades of life.

OBJECTIVES: To establish a normative database for magnetisation transfer ratio (MTR) measurements in the white matter of healthy adult brains. Such MTR values were evaluated for regional variation and evidence of differences associated with aging, sex, and handedness. METHODS: Forty one healthy volunteers, ranging in age from 16 to 55 years, underwent axial brain magnetisation transfer (MT) imaging on a 1.5 Tesla magnetic resonance scanner. Calculated MT images allowed evaluation of MTR from specific regions within the corpus callosum, cerebral hemispheres, and pons. RESULTS: Highest values were noted in the corpus callosum. No significant sex differences were seen for any region studied. Small but significant age related reductions in MTR were noted in the corpus callosum and other cerebral white matter regions studied. Comparing MTR values between young (16-35 years) and older (36-55 years) age groups, this was most apparent in the corpus callosum (40.82% units in the young group v 40.28% units in the older group, P < 0.05) and frontal white matter (39.65% units in the young group v 39.18% units in the older group, P < 0.005). In addition, values for MTR were analysed for evidence of hemispheric asymmetry. MTR values were higher in the left hemisphere for all regions studied, reaching significance in the centrum semiovale (37.75% units v 37.57% units, P < 0.05) and parieto-occipital white matter (37.67% units v 37.43% units, P < 0.05). No relation between such interhemispheric MTR differences and handedness was noted. CONCLUSIONS: Magnetisation transfer imaging shows significant age related changes in normal brain white matter. In addition to regional variations in MTR in the normal brain, there seem to be small but significant variations in MTR between the cerebral hemispheres. It is important to consider such normal variations when evaluating MTR in pathological states.

Adolescent↗
PubMed1997

Trigeminal neuralgia in patients with multiple sclerosis: lesion localization with magnetic resonance imaging.

We performed conventional T2-weighted brain MRI examinations in six patients with multiple sclerosis (MS) and trigeminal neuralgia. In all patients brainstem lesions in positions expected to involve trigeminal fibers, particularly the entry zone of sensory fibers, were demonstrated. Compression of the trigeminal nerve by ectatic vessels, a recognized cause of idiopathic trigeminal neuralgia, was not observed. We conclude that in MS trigeminal neuralgia is usually caused by demyelinating lesions affecting pontine trigeminal pathways.

Adult↗
PubMed1996

Spinal MRI in patients with suspected multiple sclerosis and negative brain MRI.

Although MRI detects the white matter lesions of multiple sclerosis within the brain with high sensitivity, a minority of patients have normal brain MRI. We describe 20 patients, selected from over 170 who had undergone brain imaging with minimal (n = 12) or no (n = 8) abnormalities (median number of lesions = I, range, 0-3) but in whom spinal MRI was abnormal. Twelve had clinically definite or laboratory supported definite multiple sclerosis according to the Poser criteria; one had clinically probable disease and seven, not fulfilling the Poser criteria, were classified as possible multiple sclerosis. All had presented with symptoms and signs referable to the spinal cord or optic nerves. Eleven had a primary progressive course, eight relapsing-remitting and only one secondary progressive. Moderate or severe disability was the rule in the primary progressive cases; all the relapsing-remitting patients had minimal disability. All had at least one lesion visible in the spinal cord (median 2; range 1-6). In patients in whom the diagnosis of multiple sclerosis is not supported by abnormalities on brain MRI, imaging of the spinal cord can be of considerable value.

Adult↗
PubMed1996

Brain and spinal cord MRI in motor neuron disease.

Motor neuron disease causes widespread degeneration of motor neurons within both the brain and spinal cord. Brain and spinal cord MRI were performed in 11 patients with motor neuron disease, and in 17 controls. Symmetric areas of high signal within the corticospinal tracts were found in nine patients on T2 weighted spin echo (SE) or fast spin echo (FSE) images of the brain and in eight on T2 or T2* weighed images of the spinal cord. High signal within the posterior limbs of the internal capsules was also found in four controls; this finding in isolation is therefore not pathological. No controls had abnormalities within the spinal cord. Low signal within the motor cortex was found in 10 patients, but was also seen in six controls. Thus MRI often displays characteristic abnormalities within the corticospinal tracts in patients with motor neuron disease, and should be considered in the investigation of suspected cases.

Adult↗
PubMed1996

Serial gadolinium-enhanced MRI of the brain and spinal cord in early relapsing-remitting multiple sclerosis.

Although serial MRI studies of the brain in relapsing-remitting MS have demonstrated frequent asymptomatic disease activity, less is known about the spinal cord. We carried out monthly gadolinium-enhanced brain and spinal cord MRI scans over 1 year in 10 patients with relapsing-remitting MS. Six of the patients had a total of 11 clinical relapses, eight of which involved the spinal cord. A total of 167 active (enhancing or new nonenhancing) lesions in the brain and 19 in the spinal cord were present. Only one active brain lesion was symptomatic compares with six spinal cord lesions. Overall, one-third of new spinal cord lesions were symptomatic, and three-quarters of clinical spinal cord relapses were associated with a new MRI lesion in a location appropriate to the symptoms. Activity in both the spinal cord and brain was more common around the time of relapse. There was a strong association between the spinal cord and brain MRI activity. We did not detect progressive spinal cord atrophy from measurements of a spinal cord cross-sectional area. We conclude that, in relapsing-remitting MS, imaging of the brain alone will detect 90% of active lesions; spinal cord MRI using current technology will therefore provide only modest gains in treatment trials in which lesion activity is the primary outcome measure. The lack of ++progressive spinal cord atrophy in these patients, suggesting that significant axonal loss has not occurred, is in keeping with their good recovery after relapse. That brain and spinal cord lesions occur concurrently implies a systemic trigger for disease activity.

Adult↗
PubMed1995

Magnetisation transfer ratios and transverse magnetisation decay curves in optic neuritis: correlation with clinical findings and electrophysiology.

Conventional MRI sequences do not permit the distinction between the different pathological characteristics (oedema, demyelination, gliosis, axonal loss) of the multiple sclerosis plaque. Magnetisation transfer imaging and transverse magnetisation decay curve (tMDC) analysis may be more specific. These techniques have been applied to the optic nerves in 20 patients with optic neuritis and the results correlated with clinical and visual evoked potential (VEP) findings. tMDC analysis failed to identify separate intracellular and extracellular water compartments within the optic nerve but gave a measure of transverse relaxation time (T2) without the confounding effects of CSF in the nerve sheath. Both T2 and magnetisation transfer ratio (MTR) were abnormal after an episode of optic neuritis. T2 did not correlate with visual function or with VEP latency or amplitude. There was a significant correlation between MTR reduction and prolongation of VEP latency: this increased latency may reflect an effect of myelin loss on MTR. Longer lesions were associated with worse visual outcome, implying that the overall extent of pathological involvement is likely to influence the degree of functional deficit.

Adult↗