Biomedical subjects

A M Blamire

Publications and source records attributed to A M Blamire.

At least 37 records · Page 2Linked to original sources

PubMed2000

Spin echo entrapped perfusion image (SEEPAGE). A nonsubtraction method for direct imaging of perfusion.

Arterial spin-labeled perfusion imaging is increasingly being applied to the study of the brain and other organs. To date, perfusion information has invariably been obtained by subtraction of images with and without spin-labeling of inflowing water. Due to the relatively small amount of blood which enters tissue over a typical inflow period (1-1.5 sec), subtraction errors due to image instability or, in certain circumstances, magnetization transfer effects, can lead to very significant amounts of artifactual image intensity. These problems are avoided in the nonsubtraction method described here. Initially, spins in the imaging slice are selectively saturated, leaving other spins unaffected. A subsequent spin-echo train traps these magnetizations irrespective of flow. Finally, an imaging module generates intensity only from those spins which have entered the imaging slice during the inflow period. A slight modification of the sequence facilitates validation by detecting any contaminating signal in a control image.

Artifacts↗

PubMed2000

The effect of bulk susceptibility on murine snapshot imaging at 7.0 T: a comparison of snapshot imaging techniques.

The sensitivity of several single-shot imaging techniques to local field gradients (LFGs) generated by discontinuities in bulk magnetic susceptibility (BMS) were compared in mouse brain at 7.0 T. At high field, differences in BMS can cause substantial signal attenuation and image distortion. Because susceptibility effects scale with B(o), mouse brain single-shot imaging at high field is particularly susceptible to the effects of LFGs. The spin-echo techniques GRASE and RARE were found to have a decreased sensitivity to LFGs compared to echo-planar imaging (EPI). Images obtained using EPI and SE-EPI exhibit severe signal attenuation in regions of high LFGs such as near air-tissue interfaces and at the brain edges. In applications such as functional MRI and diffusion MRI, GRASE and RARE are likely to provide more comprehensive whole brain coverage in mouse brain at high field than EPI techniques, which are likely to image regions of the brain with strong LFGs with low signal to noise, reducing the probability of detecting significant physiologically based changes.

Animals↗

PubMed2000

Diffusion weighted imaging and magnetic resonance spectroscopy in a low flow ischaemia model due to endothelin induced vasospasm.

The aim of this MR study was to determine if vasospasm induced by application of endothelin-1 (ET-1) in the rat brain would model the abnormalities attributed to vasospasm described in patients with subarachnoid haemorrhage (SAH) with reversible neurological deficits. Following application of ET-1 in concentrations of 10(-4) M or 10(-6) M to the middle cerebral artery, there was an immediate drop in pH, an increase in the inorganic phosphate (P(i)) to phosphocreatine (PCr) ratio and elevated lactate. There was gradual recovery to control in the 10(-6) M group, but in the 10(-4) M group there was a loss of approximately 10% in the absolute signal intensities of PCr and adenosine triphosphate (ATP). In a second similarly treated group of animals, the area of the hemisphere with a low apparent diffusion coefficient (ADC) was 27 +/- 6% at 30 min and remained at about 20-21% at 90 min and beyond. Together these data suggest that the regions with persistently low ADC were metabolically compromised, with incomplete recovery of PCr and ATP, and represent irreversibly damaged tissue. This raises the possibility that MR spectroscopy and imaging could be a sensitive indicator of tissue viability. This is a potentially useful model of low flow as seen in clinical vasospasm following SAH.

Adenosine Triphosphate↗

PubMed2000

Correlating magnetic resonance imaging markers of axonal injury and demyelination in motor impairment secondary to stroke and multiple sclerosis.

The primary pathological mechanisms in stroke and multiple sclerosis (MS) are very different but in both diseases, impairment may arise from a final common pathway of axonal damage. We aimed to examine the relationship between motor impairment, magnetisation transfer ratio (MTR) (an index of demyelination), and N-acetyl aspartate (NAA) loss (an index of axonal injury) localised to the descending motor pathways in stroke and MS. Twelve patients between 1 and 10 months after first ischaemic stroke causing a motor deficit and 12 patients with stable MS with asymmetric motor deficit were examined. T(2)-weighted imaging of the brain together with MTR and proton (voxel 1.5x2x2 cm(3)) MRS localised to the posterior limb of the internal capsule were performed and correlated to a composite motor deficit score. MTR and NAA in the internal capsule were reduced in both stroke and MS patients compared to controls. NAA loss correlated with motor deficit score in both stroke and MS (p<0.001 and p = 0.04, respectively). Correlations were seen between MTR and motor deficit (p<0.001) MTR and NAA loss (p <0.001) in stroke patients but not in MS patients. Axonal injury in the descending motor tracts would appear to be an important determinant of motor impairment in both stroke and MS. In stroke, MTR measures of demyelination are closely related to axonal damage and thus also correlate with motor deficit. However in MS, MTR measures of demyelination do not correlate with NAA loss or motor deficit suggesting that demyelination and gliosis may occur independently of axonal damage and are less closely linked with functional impairment.

Adult↗

PubMed2000

Early proton magnetic resonance spectroscopy in normal-appearing brain correlates with outcome in patients following traumatic brain injury.

The long-term clinical outcome following traumatic brain injury (TBI) can be difficult to predict. Proton magnetic resonance spectroscopy (MRS) has previously been used to demonstrate abnormalities in regions of white matter that appear normal on conventional imaging in patients following TBI. We report MRI and MRS studies of 26 patients performed at an early time point following injury (mean 12 days, n = 21) and at a later time point (mean 6.2 months, n = 15). The proton MRS was acquired from the posterior part of a normal-appearing frontal lobe containing predominantly white matter using stimulated echo acquisition mode to localize, with a relaxation time of 3000 ms and echo time of 30 ms. At both the early and late time points the N:-acetylaspartate/creatine ratio (NAA/Cr) was significantly reduced (P = 0.03, P = 0.005, respectively), the choline/creatine ratio (Cho/Cr) significantly increased (P = 0.001, P = 0.004, respectively) and the myo-inositol/creatine ratio (Ins/Cr) significantly increased (P = 0.03, P = 0.03, respectively) compared with controls. There was a small, but significant, further reduction (P = 0.02) in the NAA/Cr between the two studies in the 10 patients for whom data was available, at both time points. The NAA/Cr acquired at the early time point significantly correlated with the clinical outcome of the patients, assessed using either the Glasgow outcome scale (P = 0.005, n = 17) or the disability rating scale (P < 0.001, n = 17). We conclude that there is a sustained alteration in NAA and Cho. These findings provide possible evidence for cellular injury (NAA loss reflecting neuroaxonal cell damage and raised Cho and Ins reflecting glial proliferation) not visible by conventional imaging techniques. This may be relevant to understanding the extent of disability following TBI.

Adolescent↗

PubMed2000

Evidence for cellular damage in normal-appearing white matter correlates with injury severity in patients following traumatic brain injury: A magnetic resonance spectroscopy study.

Neuropsychological studies in patients who have suffered traumatic brain injury show that the eventual clinical outcome is frequently worse than might be predicted from using conventional (CT or T(1)/T(2)-weighted MRI) imaging. Furthermore, patients who have sustained an initial mild or moderate injury may show long-term disability. This implies that there may be abnormalities in areas of the brain that actually appear normal on conventional imaging. Proton magnetic resonance spectroscopy studies have shown that N-acetylaspartate and choline-containing compounds can provide measures of cellular injury. We report MRI and proton magnetic resonance spectroscopy studies of 19 head-injured patients performed once the patients were clinically stable (mean 11 days after injury, range 3-38 days). Proton magnetic resonance spectra were acquired from frontal white matter that on conventional MRI appeared normal. The brain N-acetylaspartate/creatine ratio was reduced [patients (mean +/- standard deviation), 1.28 +/- 0.25; controls, 1.47 +/- 0. 24; P = 0.04] and the choline/creatine ratio was increased (patients, 0.85 +/- 0.18; controls, 0.63 +/- 0.10; P < 0.001) compared with controls. When the severity of the injury was assessed using either the Glasgow coma scale or the length of post-traumatic amnesia, the increase in the choline/creatine ratio was significant even in the mildly injured group (P = 0.008 and P = 0.04, respectively). Furthermore, there was a significant correlation (P = 0.008) between the severity of head injury and the N-acetylaspartate/choline ratio. We conclude that there is an early reduction in N-acetylaspartate and an increase in choline compounds in normal-appearing white matter which correlate with head injury severity, and that this may provide a pathological basis for the long-term neurological disability that is seen in these patients.

Adolescent↗

PubMed2000

Relating MRI changes to motor deficit after ischemic stroke by segmentation of functional motor pathways.

BACKGROUND AND PURPOSE: Infarct size on T2-weighted MRI correlates only modestly with outcome, particularly for small strokes. This may be largely because of differences in the locations of infarcts and consequently in the functional pathways that are damaged. To test this hypothesis quantitatively, we developed a "mask" of the corticospinal pathway to determine whether the extent of stroke intersection with the pathway would be more closely related to clinical motor deficit and axonal injury in the descending motor pathways than total stroke lesion volume. METHODS: Eighteen patients were studied > or =1 month after first ischemic stroke that caused a motor deficit by use of brain T2-weighted imaging, MR spectroscopic (MRS) measurements of the neuronal marker compound N-acetyl aspartate in the posterior limb of the internal capsule, and motor impairment and disability measures. A corticospinal mask based on neuroanatomic landmarks was generated from a subset of the MRI data. The maximum proportion of the cross-sectional area of this mask occupied by stroke was determined for each patient after all brain images were transformed into a common stereotaxic brain space. RESULTS: There was a significant linear relationship between the maximum proportional cross-sectional area of the corticospinal mask occupied by stroke and motor deficit (r(2)=0.82, P<0.001), whereas the relationship between the total stroke volume and motor deficit was better described by a cubic curve (r(2)=0.76, P<0.001). Inspection of the data plots showed that the total stroke volume discriminated poorly between smaller strokes with regard to the extent of associated motor deficit, whereas the maximum proportion of the mask cross-sectional area occupied by stroke appeared to be a more discriminatory marker of motor deficit and also N-acetyl aspartate reduction. CONCLUSIONS: Segmentation of functional motor pathways on MRI allows estimation of the extent of damage specifically to that pathway by the stroke lesion. The extent of stroke intersection with the motor pathways was more linearly related to the magnitude of motor deficit than total lesion volume and appeared to be a better discriminator between small strokes with regard to motor deficit. This emphasizes the importance of the anatomic relationship of the infarct to local structures in determining functional impairment. Prospective studies are necessary to assess whether this approach would allow improved early estimation of prognosis after stroke.

Adult↗

PubMed1999

Measurement of myocardial pH by saturation transfer in man.

Myocardial pH has been shown in animal models to be a sensitive indicator of ischemia. In vivo measurement in humans using 31p magnetic resonance spectroscopy is complicated by the overlap of blood 2,3-diphosphoglycerate peaks with the P(i) peak used for pH measurement. A "saturation transfer" method combined with spatial presaturation of skeletal muscle signal is presented which can obtain spectra from the heart free of contamination of 2,3-DPG signal in which intracellular P(i) resonance can be clearly observed. Application to a group of six normal subjects found that the chemical shift of the intracellular inorganic phosphate peak was 4.95+/-0.06 relative to the phosphocreatine peak. This is equivalent to a pH of 7.11+/-0.05.

Adenosine Triphosphate↗

PubMed1999

Axonal injury in the internal capsule correlates with motor impairment after stroke.

Background and Purpose--Magnetic resonance spectroscopy (MRS) in ischemic stroke has shown a correlation between N-acetylaspartate (NAA) loss from the infarcted region and disability. We tested the hypothesis that NAA loss in the descending motor pathways, measured at the level of the posterior limb of the internal capsule, would determine motor deficit after a cortical, subcortical, or striatocapsular stroke. Methods--Eighteen patients with first ischemic stroke causing a motor deficit were examined between 1 month and 5 years after stroke. T2-weighted imaging of the brain and localized proton (voxel, 1.5x2x2 cm3) MRS from the posterior limb of each internal capsule were performed and correlated to a motor deficit score. Results--Mean internal capsule NAA was significantly lower in the patient group as a whole compared with the control group (P<0.001). Reductions in internal capsule NAA on the side of the lesion were seen in cases of cortical stroke in which there was no extension of the stroke into the voxel as well as in cases of striatocapsular stroke involving the voxel region. There was a strong relationship between reduction in capsule NAA and contralateral motor deficit (log curve, r2=0.9, P<0.001). Conclusions--Axonal injury in the descending motor pathways at the level of the internal capsule correlated with motor deficit in patients after stroke. This was the case for strokes directly involving the internal capsule and for strokes in the motor cortex and subcortex in which there was presumed anterograde axonal injury.

Activities of Daily Living↗

PubMed1999

Optimising imaging parameters for post mortem MR imaging of the human brain.

PURPOSE: MR imaging of post mortem brains has the potential to yield volumetric information and define the extent of structural changes prior to pathological examination. Although standard T2-weighted clinical imaging sequences have been used for the examination of formalin-fixed brains, these protocols may not yield optimum contrast. We examined the effect of varying durations of formalin fixation on the transverse relaxation time (T2) and the tissue spin density. MATERIAL AND METHODS: Three post mortem brains were examined weekly during formalin fixation from the unfixed state to 35 days fixation. Standard MR spin-echo imaging was used at 5 echo times (20-100 ms) to calculate transverse relaxation time (T2) and spin density. RESULTS: T2 decreased significantly (ANOVA, p<0.001) in both grey and white matter by 7 days fixation and there was a further (but non-significant) trend towards lower values between 7 and 35 days. Grey and white matter T2 times converged with fixation. Conversely, the grey to white matter spin density ratio increased from 1.19+/-0.01 to 1.54+/-0.06 over five weeks of fixation. CONCLUSION: Our results suggest that spin density-weighted imaging sequences would provide improved grey to white matter contrast over T2-weighted sequences.

Aged↗

PubMed1998

Metabolic abnormalities in developmental dyslexia detected by 1H magnetic resonance spectroscopy.

BACKGROUND: Neurological and physiological deficits have been reported in the brain in developmental dyslexia. The temporoparietal cortex has been directly implicated in dyslexic dysfunction, and substantial indirect evidence suggests that the cerebellum is also implicated. We wanted to find out whether the neurological and physiological deficits manifested as biochemical changes in the brain. METHODS: We obtained localised proton magnetic resonance spectra bilaterally from the temporo-parietal cortex and cerebellum of 14 well-defined dyslexic men and 15 control men of similar age. FINDINGS: We found biochemical differences between dyslexic men and controls in the left temporo-parietal lobe (ratio of choline-containing compounds [Cho] to N-acetylaspartate [NA] p< or =0.01) and right cerebellum (Cho/NA, p< or = 0.01; creatine [Cre] to NA p< or =0.05; (not significant). We found lateral biochemical differences in dyslexic men in both these brain regions (Cho/NA in temporo-parietal lobe, left vs right, p< or =0.01; Cre/NA in cerebellum, left vs right, p< or =0.001). We found no such lateral differences in controls. There was no significant relation between the degree of contralateral chemical difference and handedness in dyslexic or control men. INTERPRETATION: We suggest that the observed differences reflect changes in cell density in the temporo-parietal lobe in developmental dyslexia and that the altered cerebral structural symmetry in dyslexia is associated with abnormal development of cells or intracellular connections or both. The cerebellum is biochemically asymmetric in dyslexic men, indicating altered development of this organ. These differences provide direct evidence of the involvement of the cerebellum in dyslexic dysfunction.

Adult↗

PubMed1998

Role of ischaemia in the genesis of oedema surrounding meningiomas assessed using magnetic resonance imaging and spectroscopy.

Oedema surrounding meningiomas is well known, but its pathogenesis remains obscure. Perfusion and metabolism in this peritumoural parenchyma were studied preoperatively in eight patients using magnetic resonance imaging, dynamic perfusion scanning and proton spectroscopy. Relative cerebral blood volumes (CBV) and metabolite ratios were calculated for the tumour and peritumoural brain. All meningiomas showed gadolinium enhancement, high choline (Ch), low creatine (Cr) and low N-acetyl aspartate (NAA) [Ch: (Ch + Cr) 0.67, SD 0.13, NAA: (Ch + Cr) 0.18, SD 0.15]. Lactate was present in four tumours [lactate: (Ch + Cr) 0.32, SD 0.27]. Extremely low gadolinium passage and low CBV were seen in the 2 cm peritumoural region, with elevated lactate [lactate: (Ch + Cr) 0.26, SD 0.18]. Four centimetres from tumour margin the CBV was still reduced (65, SD 20% with less lactate [lactate: (Ch + Cr) 0.12, SD 0.01]. Relative CBV is reduced around meningiomas and is associated with lactate, suggesting that oligaemia and altered metabolism may be part of the pathology in peritumoural oedema. Such changes may be important in determining functional recovery after surgery.

Adult↗

PubMed1998

Discrepancies between cerebral perfusion and metabolism after subarachnoid haemorrhage: a magnetic resonance approach.

INTRODUCTION: There is a variable relation between angiographic vasospasm and delayed ischaemic neurological deficit (DIND). Magnetic resonance (MR) techniques have the potential to investigate the haemodynamic, metabolic, and structural changes occurring with these complications. These techniques have been applied to study DIND in patients recovering from subarachnoid haemorrhage. METHODS: Fifteen studies were performed on 11 patients, 10 with DIND. Vasospasm was diagnosed angiographically or with transcranial Doppler. The MR protocol consisted of T2 weighted imaging, contrast enhanced dynamic perfusion scanning, TI weighted imaging, and two dimensional localised proton spectroscopy. Relative cerebral blood volume maps were generated from perfusion scans. Metabolite ratios were calculated from proton spectra. RESULTS: All patients had cortical oedema on T2 weighted images, significantly more pronounced in patients of poor clinical grade (p<0.01). Spectra were normal in good grade patients. Lactate was increased and N-acetyl aspartate decreased in the poor grades, significantly worse in grade 4 compared with grade 3 patients (p<0.05). Spectral changes also correlated with the severity of oedema (p<0.05). Relative blood volumes were significantly higher in oedematous regions of poor compared with good grade patients (p<0.05). Lactate was seen in regions of the brain with increased relative blood volume. CONCLUSIONS: Despite the paramagnetic effects of haemorrhage, or of the coils and clips used to treat aneurysms, this study demonstrates that patients recovering from subarachnoid haemorrhage can undergo complex MR studies. Oedema, lactate, and increased relative blood volume correlate well with each other and with DIND and poor clinical grade.

Adult↗

PubMed1998

Brain biochemistry in Williams syndrome: evidence for a role of the cerebellum in cognition?

OBJECTIVE: To determine what biochemical changes may occur in the brain in Williams syndrome (WS) and whether these changes may be related to the cognitive deficits. BACKGROUND: WS is a rare, congenital disorder with a characteristic physical, linguistic, and behavioral phenotype with known cognitive deficits. METHODS: We obtained 31P magnetic resonance spectra (MRS) from a region consisting of mostly frontal and parietal lobe of 14 patients with WS (age, 8 to 37 years) and 48 similarly-aged controls. 1H MRS (27 cm3) localized to the left cerebellum obtained from the WS cohort were compared with those from 16 chronological age- and sex-matched normal controls. A battery of cognitive tests were administered to all subjects undergoing 1H MRS. RESULTS: WS brains exhibited significant biochemical abnormalities. All 31P MRS ratios containing the phosphomonoester (PME) peak were significantly altered in WS, suggesting that PME is significantly decreased. Ratios of choline-containing compounds and creatine-containing compounds to N-acetylaspartate (Cho/NA and Cre/NA) were significantly elevated in the cerebellum in WS cf. controls, whereas the ratio of Cho/Cre was not altered. This suggests a decrease in the neuronal marker N-acetylaspartate in the cerebellum. Significant correlations were found between the cerebellar ratios Cho/NA and Cre/NA and the ability of all subjects at various neuropsychological tests, including Verbal and Performance IQ, British Picture Vocabulary Scale, Ravens Progressive Matrices, and Inspection Time. CONCLUSIONS: The correlations can be interpreted in two ways: 1) Our sampling of cerebellar biochemistry reflects a measure of "global" cerebral biochemistry and is unrelated to cerebellar function, or 2) The relations indicate that cerebellar neuronal integrity is a requirement (on a developmental time scale or in real-time) for ability on a variety of cognitive tests.

Adenosine Triphosphate↗

PubMed1997

"Willed action": a functional MRI study of the human prefrontal cortex during a sensorimotor task.

Functional MRI (fMRI) was used to examine human brain activity within the dorsolateral prefrontal cortex during a sensorimotor task that had been proposed to require selection between several responses, a cognitive concept termed "willed action" in a positron emission tomography (PET) study by Frith et al. [Frith, C. D., Friston, K., Liddle, P. F. & Frackowiak, R. S. J. (1991) Proc. R. Soc. London Ser. B 244, 241-246]. We repeated their sensorimotor task, in which the subject chooses to move either of two fingers after a stimulus, by fMRI experiments in a 2.1-T imaging spectrometer. Echo-planar images were acquired from four coronal slices in the prefrontal cortex from nine healthy subjects. Slices were 5 mm thick, centers separated by 7 mm, with nominal in-plane spatial resolution of 9.6 x 5.0 mm2 for mean data. Our mean results are in agreement with the PET results in that we saw similar bilateral activations. The present results are compared with our previously published fMRI study of a verbal fluency task, which had also been proposed by Frith et al. to elicit a "willed action" response. We find a clear separation of activation foci in the left dorsolateral prefrontal cortex for the sensorimotor (Brodmann area 46) and verbal fluency (Brodmann area 45) tasks. Hence, assigning a particular activated region to "willed action" is not supported by the fMRI data when examined closely because identical regions are not activated with different modalities. Similar modality linked activations can be observed in the original PET study but the greater resolution of the fMRI data makes the modality linkages more definite.

Female↗

PubMed1997

FMRI of the prefrontal cortex during overt verbal fluency.

Verbal fluency is known to be associated with activity in the left prefrontal cortex. Recent positron emission tomography (PET) results confirmed this finding. In the present study, high resolution functional magnetic resonance imaging (fMRI) was used to further localize activity in the prefrontal cortex related to verbal fluency. Activation was observed in three behavioral tasks: (1) Repeat-subjects repeated words, (2) Opposite-subjects produced the antonym of words, and (3) Generate-subjects generated words beginning with a given letter. When comparing Generate with both Repeat and Opposite, we observed small areas of activation in the left inferior frontal gyrus and anterior cingulate, similar to the centers of mass reported using PET. We also found additional activation around the superior frontal sulcus.

Adult↗

PubMed1997

Functional magnetic resonance imaging assessment of the human brain auditory cortex response to increasing word presentation rates.

In an investigation of the auditory cortex response to speech, six subjects were studied using echo-planar functional magnetic resonance imaging (fMRI) at 2.1T. The subjects were asked to listen to English nouns presented at various rates ranging from 0 words per minute (wpm) to 130 wpm while fMRI images encompassing their primary and posterior superior secondary auditory cortices were acquired. An asymmetric spin echo imaging sequence was used with an induced T2 weighting of 50 ms to allow for transverse relaxation effects. Images were acquired in two or four axial-oblique slices with a repetition time of 3.75 or 7.5 s, in plane resolution of 6 x 3 mm, and a slice thickness of 5 mm. Localized activation centered over grey matter was consistently observed in all subjects in the transverse temporal gyrus (TTG), the transverse temporal sulcus (TTS), and the posterior superior aspect of the superior temporal gyrus (STG). The total activate volume and the integrated signal response in bilateral primary and posterior superior secondary auditory cortices increased with increasing rate of word presentation, peaking at 90 wpm (with some intersubject variability) with a subsequent fall at 130 wpm. There were no significant differences in the rate dependence of the signal response in bilateral primary and bilateral posterior superior secondary auditory cortices (P < 0.05).

Adult↗

PubMed1996

Dynamic shim updating: a new approach towards optimized whole brain shimming.

The static magnetic field within two widely spaced axial slices of the human brain was mapped in five subjects following global shimming. This revealed a first order field shift in the anterior-posterior direction between the cerebellum and cerebrum, which has implications for functional and spectroscopic magnetic resonance imaging. A new method is described called dynamic shim updating (DSU) to compensate for these field differences whereby the shim correction fields are updated in real time during multislice data acquisition to match the current imaging or spectroscopy slice. A hardware unit is presented to demonstrate the method using the first order shim corrections, which can be updated virtually instantaneously between slice acquisitions to give optimal shimming of each slice. The efficiency of the approach is demonstrated using field mapping and high speed MR imaging (echo-planar imaging), which are sensitive to field inhomogeneity.

Brain↗