Non-invasive imaging compared with intra-arterial angiography in the diagnosis of symptomatic carotid stenosis: a meta-analysis.

BACKGROUND: Accurate carotid imaging is important for effective secondary stroke prevention. Non-invasive imaging, now widely available, is replacing intra-arterial angiography for carotid stenosis, but the accuracy remains uncertain despite an extensive literature. We systematically reviewed the accuracy of non-invasive imaging compared with intra-arterial angiography for diagnosing carotid stenosis in patients with carotid territory ischaemic symptoms. METHODS: We searched for articles published between 1980 and April 2004; included studies comparing non-invasive imaging with intra-arterial angiography that met Standards for Reporting of Diagnostic Accuracy (STARD) criteria; extracted data to calculate sensitivity and specificity of non-invasive imaging, to test for heterogeneity and to perform sensitivity analyses; and categorised percent stenosis by the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method. RESULTS: In 41 included studies (2541 patients, 4876 arteries), contrast-enhanced MR angiography was more sensitive (0.94, 95% CI 0.88-0.97) and specific (0.93, 95% CI 0.89-0.96) for 70-99% stenosis than Doppler ultrasound, MR angiography, and CT angiography (sensitivities 0.89, 0.88, 0.76; specificities 0.84, 0.84, 0.94, respectively). Data for 50-69% stenoses and combinations of non-invasive tests were sparse and unreliable. There was heterogeneity between studies and evidence of publication bias. INTERPRETATION: Non-invasive tests, used cautiously, could replace intra-arterial carotid angiography for 70-99% stenosis. However, more data are required to determine their accuracy, especially at 50-69% stenoses where the balance of risk and benefit for carotid endarterectomy is particularly narrow, and to explore and overcome heterogeneity. Methodology for evaluating imaging tests should be improved; blinded, prospective studies in clinically relevant patients are essential basic characteristics.

Structural MRI of the brain in presumed carriers of genes for schizophrenia, their affected and unaffected siblings.

BACKGROUND: Schizophrenia is a highly heritable disorder associated with structural brain abnormalities. The aim of this study was to establish if the gene(s) for schizophrenia are associated with specific abnormalities of brain structure. SUBJECTS: Six sibships from multiple affected families were recruited. Each sibship consisted of one patient with schizophrenia, one "obligate carrier" without the disorder but with an affected child, and one "non-affected non-carrier". Such sibships are very rare, but present a powerful opportunity to separate the associations of genotype and phenotype. Obligates presumably have the gene(s) but not the disorder, affected siblings have both, whereas non-affected non-carrier siblings have neither. METHOD: Brain MRI was conducted with a semiautomated region of interest analysis. The risk of false positive findings was reduced by collapsing brain regions and sides into five regions and comparing groups by repeated measures analysis of variance. RESULTS: In terms of whole brain volumes and volumes of cortical structures, obligates resembled their non-affected non-carrier siblings, both groups having significantly greater volumes than their schizophrenic siblings (p=0.01 and p=0.04). Obligates also had significantly smaller ventricles than their schizophrenic siblings (p=0.03). However, with respect to the amygdalohippocampal complex, the obligates' brains resembled those of their schizophrenic siblings, both groups showing a significant reduction in volume when compared with their non-affected non-carrier siblings (p=0.001). CONCLUSIONS: In the families studied, reductions in volumes of cortical structures and reductions in whole brain volume seem to be associated with the phenotype of schizophrenia. By contrast, reduced volume of the amygdalohippocampal complex seems to be associated with genetic risk for the disorder even in the absence of disease.

Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H MRS) in schizophrenic subjects and normal controls.

Several proton magnetic resonance spectroscopy (1H MRS) studies in schizophrenia have found reduced N-acetyl aspartate (NAA) concentrations in pre-frontal and temporal regions of the brain. Reductions in NAA may reflect abnormalities of neuronal structure (e.g. reduced neuronal density or viability) or abnormalities of neuronal function. Diffusion tensor imaging (DTI) measures diffusion anisotropy, an indicator of the structural integrity of a neuronal tract. Both techniques were used to examine the anatomical basis of pre-frontal dysfunction in schizophrenia. Ten patients with DSM-IV schizophrenia were compared with 10 healthy controls. 1H MRS and DTI were performed on a clinical MR system and analysed with a region of interest approach. NAA concentrations and diffusion anisotropy were measured in the same pre-frontal white matter region. Diffusion anisotropy was also measured in a control region (occipital white matter). 1H MRS revealed non-significant but consistently reduced NAA concentrations (by 10-15%) in the pre-frontal white matter in schizophrenic subjects. Diffusion anisotropy measures revealed no such differences between schizophrenics and controls. It is concluded that the abnormalities of 'connectivity' reported in brain-imaging studies of schizophrenia may not be attributable to structural abnormalities of white matter and that reduced NAA in the pre-frontal white matter may reflect abnormal function of structurally intact neurons.

Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia.

BACKGROUND: Structural magnetic resonance imaging (MRI) of the brain in patients with schizophrenia has consistently demonstrated several abnormalities. These are thought to be neurodevelopmental in origin, as they have also been described in first episode cases, although there may be a progressive component. It is not known at which point in development these abnormalities are evident, nor to what extent they are genetically or environmentally mediated. METHODS: One hundred forty-seven high-risk subjects (with at least two affected first or second degree relatives), 34 patients in their first episode, and 36 healthy control subjects received an MRI scan covering the whole brain. After inhomogeneity correction, regions of interest were traced by three group-blind raters with good inter-rater reliability. Regional brain volumes were related to measures of genetic liability to schizophrenia and to psychotic symptoms elicited at structured psychiatric interviews. RESULTS: High-risk subjects had statistically significantly reduced mean volumes of the left and right amygdalo-hippocampus and thalamus, as compared to healthy control subjects. They also had bilaterally larger amygdalo-hippocampi and bilaterally smaller lenticular nuclei than the schizophrenics. High-risk subjects with symptoms had smaller brains than those without. The volumes of the prefrontal lobes and the thalamus were the only consistent associates of genetic liability. CONCLUSIONS: Subjects at high risk of developing schizophrenia have abnormalities of brain structure similar to but not identical to those found in schizophrenia. Our results suggest that some structural abnormalities are genetic trait or vulnerability markers, others are environmentally mediated, and that the development of symptoms is associated with a third overlapping group of structural changes. Particular risk factors for schizophrenia may interact at discrete time points of neurodevelopment with different effects on specific brain regions and may represent relatively distinct disease processes.

A factor model of the functional psychoses and the relationship of factors to clinical variables and brain morphology.

BACKGROUND: Despite more than 100 years of study, there remains no definitive diagnostic validation of the functional psychoses. Factor analysis suggests the presence of three or more psychopathological syndromes in functional psychoses as a whole. The relationship between these factors and cerebral anatomy has been investigated in schizophrenia only. This study aimed to address the relationship of symptom factors to clinically important variables and cerebral anatomy in a sample of psychotic patients with a spread of diagnoses. METHODS: In a sample of patients with functional psychoses, symptom data was obtained on four consecutive admissions using the OPCRIT symptom checklist. OPCRIT data was used to generate operational diagnoses in accordance with pre-set criteria and a principle components analysis was performed on symptom data. Factor loadings were compared between each admission to examine factor stability over time. Factor scores at first admission were also correlated with clinical variables obtained from patients' case notes. From the sample of 204 patients, 64 subjects were recruited and underwent an MRI scan of the brain. Regional anatomical volumes were compared with diagnosis and factor loadings at first admission. RESULTS: A principal components analysis gave a four-factor solution of 'manic', 'depressive', 'disorganization' and 'reality distortion' factors at each admission. Factors showed a high degree of stability over the four admissions studied. The factors were significantly associated with several clinical variables. Three of the four factors were associated with a specific pattern of cerebral anatomy. CONCLUSIONS: This study suggests that factors may correspond to relatively specific disease processes underlying functional psychotic illness. We propose that the use of symptom factors may facilitate the investigation of the underlying mechanisms of psychotic illness.

Neuroanatomy of comorbid schizophrenia and learning disability: a controlled study.

BACKGROUND: Reasons for the higher frequency of schizophrenia in learning-disabled populations are uncertain. We investigated the neuroanatomical basis for this phenomenon by structural magnetic resonance imaging (MRI) in patients with learning disability and schizophrenia, learning-disabled patients, and patients with schizophrenia. METHODS: Age-matched and sex-matched patients with learning disability (20 cases), schizophrenia (25), and both disorders (23) underwent MRI scans of the brain. Whole brain areas and specific regions of interest were examined. 29 normal controls were also scanned. FINDINGS: The scans of the group with both disorders were closely similar to those of the schizophrenic group, in terms of both general structures and the structure of the amygdala-hippocampus. However, the amygdala-hippocampus was significantly smaller on both sides than that of normal controls (left 4.1 vs 4.5 cm3, p=0.011; right 4.2 vs 4.99 cm3, p<0.0001). The brains of learning-disabled patients were generally smaller than those of the other three groups, but the amygdalohippocampal complexes were larger. INTERPRETATION: In terms of brain structure, patients with comorbid learning disability and schizophrenia resemble patients with schizophrenia and not those with learning disability. We suggest that the higher frequency of schizophrenia in learning-disabled patients is due to a greater tendency of schizophrenic patients to develop cognitive deficits, and that within the learning-disabled population there may be individuals whose deficits result from undiagnosed schizophrenia.

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.

Volumetric magnetic resonance imaging study of the brain in subjects with sex chromosome aneuploidies.

OBJECTIVES: Cognitive impairment has been reported in people with sex chromosome aneuploides (SCAs) and it has been proposed that the presence of an extra sex chromosome may have an adverse effect on neurodevelopment. This study examines the hypothesis with structural MRI of the brain. METHODS: Thirty two subjects with SCA (XXX (n=12), XYY (n=10), and XXY (n=10)) from a birth cohort study were matched groupwise for age, parental social class, and height with normal controls (13 female, 26 male). Brain MRI, measurements of IQ, and a structured psychiatric interview were performed. RESULTS: The XXX females and XXY males had significantly smaller whole brain volumes than controls of the same phenotypic sex (p=0.003 and p

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.

Brain abnormalities demonstrated by magnetic resonance imaging in adult IDDM patients with and without a history of recurrent severe hypoglycemia.

OBJECTIVE: Previous studies of a cohort of 100 patients with IDDM have shown that a history of recurrent severe hypoglycemia is associated with a modest impairment of cognitive function. The aim of the present study was to determine whether IDDM patients with and without a history of severe hypoglycemia have lesions in the brain that are identifiable by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) and to investigate the putative relationship of any structural brain abnormalities with cognitive function. RESEARCH DESIGN AND METHODS: MRI and MRS of the brain were performed in 22 patients from the original cohort. Eleven IDDM patients with no history of severe hypoglycemia (group A) were compared with 11 IDDM patients who had a history of five or more episodes of severe hypoglycemia (group B). RESULTS: Nine patients (41%) had abnormal scans. Two types of abnormalities were observed: high-intensity rounded lesions, > 3 mm in diameters, distributed in the periventricular white matter (leukoaraiosis) in four patients; and cortical atrophy in five patients. Five patients in group B had cortical atrophy, whereas no patient in group A demonstrated this feature (P < 0.05). MRS of the frontal and parietal lobes showed no differences in the N-acetyl aspartate/creatine or N-acetyl aspartate/choline ratios between groups A and B. Patients with cortical atrophy showed a nonsignificant trend toward reduced performance on Rapid Visual Information Processing. CONCLUSIONS: Brain abnormalities demonstrated by MRI are common in patients with IDDM of long duration and are suggestive of premature aging of the brain. IDDM per se may be an important pathogenic factor, but a significant association was observed between a history of recurrent severe hypoglycemia and cortical atrophy, which may be related to the modest impairment of cognitive function that has been reported previously.

Qualitative cerebral morphology in schizophrenia: a magnetic resonance imaging study and systematic literature review.

Patients with schizophrenia have larger lateral ventricles, less cerebral substance and smaller mesial temporal lobe structures than groups of normal controls, but it has proved difficult to link these volumetric abnormalities with clinical features of the illness. Such quantitative techniques may overlook qualitative abnormalities of importance. We therefore compared a neuroradiologists' clinical assessment of gross structural abnormalities, generalised 'atrophy' and high intensity signal (HIS) foci, as detected on the first and second echo of a long TR sequence, in 42 patients with schizophrenia (22 treatment responsive, 20 treatment resistant) and 50 normal controls. The schizophrenic group included two (5%) subjects with gross lesions, two (5%) with cerebellar atrophy, 21 (52%) with at least a mild degree of cerebral atrophy, and 15 (38%) with one or more HIS foci; the comparable figures in the controls being 2, 0, 2 and 14%, respectively. Controlling for age, patients with schizophrenia had a substantially elevated rate of cerebral atrophy (odds ratio (OR) = 11.7, p < 0.0001). Treatment-resistant schizophrenics showed a tendency (OR = 2.8, p = 0.06) to greater atrophy than those who were treatment responsive, whereas our previous volumetric study showed no such difference. In contrast, the presence of HIS foci was only related to age. The degree of atrophy was correlated with the number of HIS foci (r = 0.31, p = 0.014). Taken together with previous studies, these findings demonstrate the value of qualitative examination of MRI images in patients with schizophrenia.

The role of computed tomographic examination of the pelvis in the management of testicular germ cell tumours.

AIM: To clarify the role of pelvic CT in the imaging of patients with germ cell testicular tumours (GCTT). PATIENTS AND METHODS: A retrospective analysis was undertaken of all CT examinations performed on patients with GCTT at a regional oncological centre over a 3-year-period. Patient notes were reviewed and data on histology, tumour marker levels, therapy and clinical course obtained. The review interpretation was combined with the original radiological report and clinical data to arrive at a consensus result. RESULTS: Four hundred and forty-three examinations on 167 patients were included. One hundred and nineteen examinations (27%) demonstrated abdominal and/or pelvic lymph node enlargement. Nodal metastasis was entirely or predominantly ipsilateral in 73/77 examinations from left-sided primary tumours (95%) and 35/42 examinations from right-sided tumours (83%). Pelvic nodal enlargement was identified in 37 examinations from 16 patients. Thirteen of these sixteen patients possessed an identifiable risk factor for pelvic nodal metastasis; the remaining three had unequivocal nodal metastases in the abdomen. Combined abdominopelvic CT increased the effective dose equivalent (EDE) by 2.6 mSv (74%) compared with abdominal examination alone. Three hundred pelvic CT examinations were performed on 117 patients without risk factors for pelvic nodal metastasis. For this cohort the radiation burden from pelvic CT was 0.78 manSv, giving a risk of induction of a single fatal cancer of 3.9%. CONCLUSION: We advocate pelvic CT only at the time of staging, except in patients with a risk factor for pelvic nodal metastasis. Any unequivocal abdominal lymph node enlargement should be regarded as a risk factor. Implementation of this policy would safely reduce pelvic CT examinations in patients with testicular tumours by nearly 50%, with a consequent reduction in patient radiation exposures and a resource saving.

Measurement of CT lung density in patients with chronic asthma.

Evidence for the presence of emphysema in patients with asthma is controversial. We have previously shown that decreased lung density, measured by computed tomographic (CT) scanning, preoperatively, correlates with morphometric measurements of microscopic emphysema in subsequently resected lungs. The aim of this study was to compare CT lung density, in 17 patients with chronic asthma (forced expiratory volume in one second (FEV1) 1.98 (SD 0.77) L), 17 patients with chronic bronchitis and emphysema (FEV1 0.97 (0.56) L) and seven normal subjects (FEV1 3.5 (034) L). All subjects underwent CT scanning of the lungs and respiratory function testing within 2 days of each other. In five of the asthmatic patients a CT scan was performed on two occasions before and after treatment with nebulized bronchodilator. In a different group of five asthmatics these measurements were performed at the end of and 6 weeks after an exacerbation. The mean value of the lowest fifth percentile of the CT lung density in the patients with chronic obstructive pulmonary disease (COPD) was -942 (SD 36) Hounsfield units (HU), in the 17 asthmatic patients was -912 (34) HU, and in normal subjects was -880 (13). Despite a significant increase in peak expiratory flow rate from 266 (SD 102) to 406 (83) L x s(-1) (p<0.02) following nebulized beta2-agonist in five patients with chronic asthma, there was no significant change in CT lung density (p>0.05) Our study indicates that at least some patients with chronic, stable asthma develop a reduction in computed tomography lung density, similar to that in patients with emphysema.

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.

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.

Spinal tract pathology in AIDS: postmortem MRI correlation with neuropathology.

Vacuolar myelopathy (VM) and tract pallor are poorly understood spinal tract abnormalities in patients with the acquired immunodeficiency syndrome (AIDS). We studied the ability of magnetic resonance imaging (MRI) to detect these changes in spinal cord specimens postmortem and whether criteria could be formulated which would allow these conditions to be differentiated from other lesions of the spinal cord in AIDS, such as lymphoma, cytomegalovirus (CMV) and human immunodeficiency virus (HIV) myelitis. We imaged 38 postmortem specimens of spinal cord. The MRI studies were interpreted blind. The specimens included cases of VM myelin pallor, CMV myeloradiculitis, HIV myelitis, lymphoma as well as normal cords, both HIV+ve and HIV-ve. MRI showed abnormal signal, suggestive of tract pathology, in 10 of the 14 cases with histopathological evidence of tract changes. The findings in VM and tract pallor on proton-density and T2-weighted MRI were increased signal from the affected white-matter tracts, present on multiple contiguous slices and symmetrical in most cases. The pattern was sufficiently distinct to differentiate spinal tract pathology from other spinal cord lesions in AIDS.

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).