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.

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.

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 comparison of cobalt (57Co) bleomycin scanning and contrast-enhanced CT scanning for assessment of the mediastinum in lung cancer.

Sixty patients with histologically proven lung cancer who had been accepted for mediastinoscopy or thoracotomy were prospectively entered into a study to evaluate computed tomographic (CT) scanning, 57Co-bleomycin scanning, and barium swallow in preoperative assessment of mediastinal lymph node metastasis. Fifty-six patients had thoracotomy at which all accessible lymph nodes were sampled. Twenty-four patients were found to have mediastinal tumor on histologic analysis of the resected mediastinal lymph nodes. Neither 57Co-bleomycin scanning nor barium swallow were clinically useful, with sensitivities of 21 percent and 11 percent respectively, whereas CT scanning was helpful. However, there was no clear cutoff point of node size to optimize sensitivity and specificity for CT scanning. When nodes greater than or equal to 15 mm were taken to indicate likely malignancy, the sensitivity was 58 percent and the specificity was 87 percent and when greater than or equal to 10 mm was used the sensitivity was 80 percent but the specificity was only 55 percent. There was no clear relationship between the size of the largest resected lymph node in each patient and the presence of malignant lymph nodes. Only 42 percent of patients with resected nodes greater than or equal to 2 cm had histologic evidence of metastases. We conclude that CT scanning should be used to indicate the presence and site of mediastinal lymph nodes, which, when visualized, should always be sampled and histologically examined prior to resection of primary tumor.

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 relationship of cerebral atrophy and T1 in alcoholics: an MRI study.

There was a significant correlation between two measures of cerebral atrophy (the ventricle to brain ratio and the relative cerebral volume) and T1 in 19 detoxified alcoholics. This provides further evidence that T1 is a marker of structural damage in alcoholics although the partial volume effect of CSF may contribute to this finding. This has implications for studies comparing alcoholics to normal controls and suggests that better ways of excluding CSF need to be found.

Brain hydration during alcohol withdrawal in alcoholics measured by magnetic resonance imaging.

Twenty-seven patients had a first Magnetic Resonance Imaging (MRI) scan 1-3 days after stopping drinking and a second approximately 2 weeks later with no change in whole brain T1 or T1 in selected brain areas. Six patients whose first scan was over 36 h after the last drink underwent an increase in whole brain T1 in the interval to the second scan. The later the first scan was performed the greater was the increase in T1. These results are compatible with a very early fall in brain water immediately on cessation of drinking (perhaps due to a rebound increase of vasopressin activity) with a return to 'baseline' after two weeks. A third scan after discharge from hospital in 23 individuals who had abstained from alcohol or drank very little did not reveal any further significant change in brain T1.

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.

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.

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.

The role of abdominal computed tomography in lymphoma following treatment.

Two hundred and six patients with biopsy-proven lymphoma, 74 with Hodgkin's disease and 132 with non-Hodgkin's lymphoma had abdominal computed tomography for assessment of remission status (108 patients) or for investigation of relapse (98 patients). In 43 patients with diffuse large cell lymphomas scanned at a time of apparent complete remission CT was abnormal in 21. Sixteen of these patients have relapsed and died. Only one patient has relapsed in the group who have normal CT scans. This difference was significant (p=0.00001). This difference was not seen in nodular lymphomas. There were very few patients with Hodgkin's disease in whom the CT scan was abnormal and there is a suggestion that many abnormalities following treatment may represent inactive Hodgkin's disease or fibrosis only. CT played a major role in diagnosing the full extent of relapse in both non-Hodgkin's lymphoma and Hodgkin's disease. Over 50% of the abnormal sites detected by CT would not have been shown by any other non-invasive investigation. Five patients with treated Hodgkin's disease who had "B" symptoms only suggesting relapse were all shown by CT to have extensive intra-abdominal disease.

The installation of a commercial resistive NMR imager.

It has been demonstrated that a relatively low-cost resistive NMR imager can be installed in a normal hospital environment without many major or expensive modifications. The magnet can be adjusted to give adequate uniformity and there is sufficient RF shielding to give good quality clinical images (Fig. 3). The fringe field of the magnet of this system, which operates at the lowest field strength of any commercial NMR imager, does not present a problem to imaging unit staff (NRPB, 1984). The long term reliability and detailed specifications with regard to image quality have yet to be determined. These will be determined whilst the imager is being used for clinical studies as part of the national clinical evaluation of NMR imaging supported by the Medical Research Council.

Correlation of human NMR T1 values measured in vivo and brain water content.

A relationship has been demonstrated between nuclear magnetic resonance (NMR) longitudinal relaxation times (T1 values) obtained in vivo in both normal and oedematous (peritumoral) brain tissue, and measurements of brain water obtained by gravimetric analysis of operative samples. Significant correlations were found in seven patients in both cortex (r = 0.97, P less than 0.001) and white matter (r = 0.92, P less than 0.001). These findings suggest that NMR may prove a useful technique for monitoring brain oedema.

99Tcm-MAG3: in vitro stability and in vivo behaviour at different times after preparation.

A kit for preparing technetium-99m mercaptoacetyltriglycine (99Tcm-MAG3), a new radiopharmaceutical for gamma camera renography, is available commercially. A drawback to the use of this kit is the recommended 1h expiry for 99Tcm-MAG3. This short expiry is a consequence of the possible growth of an impurity which undergoes hepatobiliary excretion and might interfere with renal imaging. Radiochemical purity of 99Tcm-MAG3 was measured by high performance liquid chromatography at 0, 1 and 6 h after preparation and was found to be consistently greater than 95. 99Tcm-MAG3 was shown to contain five impurities, one of which increased from 0.5% to 1% over 6 h. Dilution of 99Tcm-MAG3 eliminated this effect. A two-part clinical study was undertaken. For Part I, 99Tcm-MAG3 was prepared at 400 MBq/4 ml. For Part II, 99Tcm-MAG3 was prepared at 1 GBq/4 ml then subdivided and diluted to give single doses of 175 MBq/2.5 ml. In both parts, 10 patients were injected within 1 h after preparation and 10 were injected 5-6 h after preparation. From gamma camera images of the abdomen acquired 30 min after injection, the % injected 99Tcm in gall bladder and liver were calculated. In both parts, the % injected 99Tcm in gall-bladders and livers of the 1 h group were compared with those in the 5-6 h group and not found significantly different (p greater than 0.05). In conclusion, 99Tcm-MAG3 prepared according to the methods described, can be used up to 6 h after preparation.

Prediction of fracture healing in the tibia by quantitative radionuclide imaging.

The uptake of 99mTc-MDP was studied in 73 patients after a tibial fracture. The image obtained five minutes after injection during a period between one and four weeks after fracture was found to be related to the incidence of non-union after six months. A ratio of 1.3 between the uptake at the fracture site and at normal bone adjacent to it predicted non-union in an individual patient with a sensitivity of about 70% and a specificity of 90%.

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).

Triple phase bone scanning of an intraosseous ganglion: case report and discussion.

The appearance of an intraosseous ganglion on a static bone scan has been described. This report describes the appearance on triple phase bone scanning, and discusses the implications for differential diagnosis of similar benign-looking subarticular cystic lesions of bone.