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Biomedical subjects

J E Rimmington

Publications and source records attributed to J E Rimmington.

10 recordsLinked to original sources

Methodological issues in volumetric magnetic resonance imaging of the brain in the Edinburgh High Risk Project.

The Edinburgh High Risk Project is a longitudinal study of brain structure (and function) in subjects at high risk of developing schizophrenia in the next 5-10 years for genetic reasons. In this article we describe the methods of volumetric analysis of structural magnetic resonance images used in the study. We also consider potential sources of error in these methods: the validity of our image analysis techniques; inter- and intra-rater reliability; possible positional variation; and thresholding criteria used in separating brain from cerebro-spinal fluid (CSF). Investigation with a phantom test object (of similar imaging characteristics to the brain) provided evidence for the validity of our image acquisition and analysis techniques. Both inter- and intra-rater reliability were found to be good in whole brain measures but less so for smaller regions. There were no statistically significant differences in positioning across the three study groups (patients with schizophrenia, high risk subjects and normal volunteers). A new technique for thresholding MRI scans longitudinally is described (the 'rescale' method) and compared with our established method (thresholding by eye). Few differences between the two techniques were seen at 3- and 6-month follow-up. These findings demonstrate the validity and reliability of the structural MRI analysis techniques used in the Edinburgh High Risk Project, and highlight methodological issues of general concern in cross-sectional and longitudinal studies of brain structure in healthy control subjects and neuropsychiatric populations.

Adolescent↗

Magnetic resonance imaging of brain in people at high risk of developing schizophrenia.

BACKGROUND: Schizophrenia is a multifactorial disorder that is associated with disturbed cerebral development. Structural brain-imaging studies have consistently shown that the volumes of some parts of the brain, particularly the mesial temporal lobes, are smaller in patients with schizophrenia than in healthy people. Whether these abnormalities of brain structure predate the onset of symptoms is not known. METHODS: 100 people at high risk of developing schizophrenia (two or more first-degree or second-degree relatives affected), 20 patients in their first episode of schizophrenia, and 30 healthy controls underwent magnetic resonance imaging of the brain. The volumes of regions of interest were measured by standard techniques. FINDINGS: Mean whole-brain volume was 1356 cm3 (SD 178) in the first-episode group, 1347 cm3 (122) in the high-risk group, and 1334 cm3 (149) in the controls (p=0.8). The mean volume of the left amygdala-hippocampal complex (AHC) was lower in the first-episode group (4.3 cm3 [0.6]) than in the high-risk group (4.6 cm3 [0.6]), and in turn than in the controls (4.8 cm3 [0.7]); these differences were significant (p<0.05) both for absolute volumes and values adjusted for brain volume and other confounders. The right AHC showed a similar pattern (absolute volumes 4.5 cm3 [0.7], 4.8 cm3 [0.6], 4.9 cm3 [0.9], respectively). Both thalamic nuclei were significantly smaller in the high-risk group than in the control group. INTERPRETATION: People at high risk of developing schizophrenia for genetic reasons have several structural brain abnormalities that are similar to those in patients with the disorder. If at-risk individuals with particularly small AHC or thalami are most likely to develop schizophrenia, this feature might assist in early detection and treatment.

Adolescent↗

Temporal lobe abnormalities in dementia and depression: a study using high resolution single photon emission tomography and magnetic resonance imaging.

OBJECTIVES: Perfusion SPECT and MRI were used to test the hypothesis that late onset depression is associated with brain abnormalities. METHODS: Forty depressed patients (DSM-III-R major depressive episode, not demented at two year follow up) were recruited who were either drug free, or on a stable dose of antidepressants for at least three weeks, as well as 22 demented patients (DSM-IIIR and NINCDS/ADRDA criteria for probable Alzheimer's disease). Patients were imaged at rest with a high resolution single slice 12 detector head scanner (SME-Neuro 900) and the cerebral perfusion marker 99mTc-exametazime (HM-PAO). Temporal lobe templates were fitted with brains pitched by 20 degrees-30 degrees. A subgroup of 41 patients (22 depressed) were also scanned using a Siemens Magnetron 1.0 Tesla magnetic resonance imager, using a FLAIR imaging sequence for the assessment of white matter hyperintensities, and a Turbo FLASH sequence for the measurement of medial temporal lobe width. RESULTS: Demented patients showed reduced perfusion, particularly in the left temporoparietal cortex. In these regions of interest, patients with late onset depression tended to have perfusion values intermediate between patients with early onset depression and demented patients. Differences in changes in white matter between demented and early and late onset depressive patients did not reach conventional levels of significance. Temporal lobe width differed between demented and depressed patients, but not between early and late onset depressed patients. Perfusion and temporal lobe width were not associated, but reductions of perfusion were associated with periventricular white matter changes. Mini mental state examination scores were associated with temporal perfusion in demented patients and with changes in deep white matter in depressed patients. Finally, severity of depressive symptoms was associated with decreased perfusion in frontotemporal and basal ganglia regions of interest. CONCLUSION: A cumulative effect of duration of illness on regional cerebral perfusion could not be confirmed. Late onset depression may show more abnormalities of deep white matter and of left temporoparietal perfusion than early onset depression, but the underlying pathology remains to be established.

Aged↗

Magnetic resonance imaging and single photon emission tomography in treatment-responsive and treatment-resistant schizophrenia.

BACKGROUND: Patients with schizophrenia differ from controls in several measures of brain structure and function, but it is uncertain how these relate to clinical features of the illness. We dichotomised patient groups by treatment response to test the hypothesis that treatment-resistant patients exhibit more marked biological abnormalities than treatment-responsive patients. METHOD: Twenty treatment-responsive and 20 treatment-resistant patients with schizophrenia, matched for sex, age, and illness duration, were compared by magnetic resonance imaging, single photon emission tomography, and detailed neuropsychological assessment. RESULTS: Brain-imaging variables were not statistically related to treatment response, although poorly responsive patients had lower volumes of most brain structures. Several highly significant differences emerged between patient groups on neuropsychological testing. Episodic memory functioning distinguished patient groups even after we controlled for global cognitive impairment. CONCLUSIONS: Cerebral structure and blood flow have a limited effect on treatment response in schizophrenia, but long-term episodic memory impairment is associated with, and may predict, poor prognosis.

Activities of Daily Living↗

Functional magnetic resonance imaging at 1 T: motor cortex, supplementary motor area and visual cortex activation.

Functional activation of the brain has been visualized using magnetic resonance imaging (MRI). Early studies used echo planar imaging and magnetic fields of 2 T and above. However, recent studies have successfully shown the activation of visual and motor areas of the brain using conventional clinical 1.5 T MRI systems. The purpose of the present study was to replicate these studies at a lower field strength. Eight motor and two visual activation studies were performed using a 1 T clinical scanner. Activation was seen in the contralateral motor cortex during motor stimulation in six of the eight volunteers. Activation was also documented within the contralateral supplementary motor area in four of the six volunteers with motor cortex activation. The supplementary motor area was located in the posteromedial aspect of the superior frontal gyrus. Both volunteers subjected to photic stimulation showed activation within the visual cortex. Results show that functional imaging can be successfully carried out with a 1 T clinical scanner. The size of the image intensity on activation change suggests that contrast may not be due solely to susceptibility changes.

Brain Mapping↗

Acoustic reflectometry for airway measurements in man: implementation and validation.

A practical implementation of acoustic reflectometry for determining airway areas in routine clinical use is described. Advances over previous systems include portability, free breathing during measurements, no need to equilibrate with helium/oxygen, and real-time display of airway areas. Validation of the reflectometer with an airway model gave accuracies and reproducibilities (coefficient of variation (CV)) in the range 5-10%. With human volunteers, the within-run CV was typically 10%, and the day-to-day CV was 20%. The effect of breathing pattern on airway areas is demonstrated. In ten normal volunteers, acoustic and magnetic resonance imaging (MRI) methods of assessing pharyngeal and glottal areas were compared. The results (mean +/- SD) for the oropharynx were 1.0 +/- 0.3 cm2 acoustically and 0.9 +/- 0.5 cm2 by MRI (p = 0.77). The corresponding figures for glottal areas were 1.3 +/- 0.3 cm2 and 1.1 +/- 0.4 cm2 (p = 0.09).

Humans↗

Effects of osmotic manipulation of intracellular hydration of HeLa S-3 cells on their proton NMR relaxation times.

Pellets of HeLa from suspension cultured cells in isotonic medium (300 mosmolar) were introduced into a Bruker CXP100 NMR spectrophotometer at 80 mHz within 5 min of the start of centrifugation. T1 and T2 times were measured within a total elapsed time of 20-25 min at 80 mHz and 37 degrees C, and averaged 1430 msec and 120 msec, respectively. Extrapolation to zero extracellular space gave a corrected T1 of 1370 msec. For cells collected after 10 min in hypotonic medium (down to 30 mosmolar) increased proton density correlated well with increased cell water content, but relaxation times did not rise in proportion to that predicted for the entry of "bulk" water (T1 of 4700 msec), except when swelling approached lysis point. Cells partially dehydrated by 10 min in hypertonic medium of up to 1500 mosmolar have also been analyzed, but once again the shortening of T1 was not proportional to the loss of "free" (bulk phase) water. At the upper limit of hypertonic treatment, lacunae or vacuoles of a watery nature separated within the cytomatrix, preventing maximum dehydration. The relationship of cell water to T1 is complex over the whole range of tonicity that HeLa S-3 cells tolerate. The data indicate, however, that hypotonically induced water probably has an average T1 time considerably lower than bulk phase water. In contrast, raising the total extracellular volume with medium had precisely the predicted effect on T1 time, further strengthening the case that water taken up by cell acquires a shorter T1 time. Cells adapting to hypotonic conditions oscillated in size and water content over 2-3 hr before returning to near their initial volume. Under these circumstances, T1 oscillated in the same way but with a reduced amplitude, consistent with the above findings.

Body Fluids↗

Effects of ethanol on the NMR characteristics of rat brain. Acute administration, dependency, and long-term effects.

In rats, neither acute administration of ethanol nor the establishment of ethanol dependence by chronic administration for 28 days produced significant 1H-NMR relaxation changes. However, chronic ethanol intake for six months produced a transient rise in T1, with no change in T2 or water content. The significance of these results for study in man is discussed and a hypothesis is proposed to explain discrepant differences between T1, T2 and water content. It is suggested that T1 change with long-term ethanol exposure is related to altered free/bound water state secondary to cell membrane changes.

Alcoholic Intoxication↗

Fetal imaging by nuclear magnetic resonance: a study in goats. Work in progress.

Nuclear magnetic resonance proton imaging was used to obtain images of goat fetuses in utero. The long T1 relaxation time of amniotic fluid makes it appear black on proton density images when examined using the Aberdeen imager, and so allows very good discrimination of the position and structure of the fetus. Some fetal internal tissues can be seen on T1 images. These findings suggest that NMR imaging has great potential in pregnancy studies.

Animals↗

Regional variation in rat brain proton relaxation times and water content.

Relaxation times (T1 and T2) and water content are measured in frontal cortex, amygdaloid cortex, hippocampus, mid-brain and cerebellum of rat brain. Differences are found in relaxation times, between areas containing a mixture of grey and white matter, and grey matter only. Differences were also found between certain grey matter areas. Relaxation times correlated with water content.

Amygdala↗