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Biomedical subjects

A Coulthard

Publications and source records attributed to A Coulthard.

At least 19 recordsLinked to original sources
PubMed2004

Identification of a mutation in synapsin I, a synaptic vesicle protein, in a family with epilepsy.

A four generation family is described in which some men of normal intelligence have epilepsy and others have various combinations of epilepsy, learning difficulties, macrocephaly, and aggressive behaviour. As the phenotype in this family is distinct from other X linked recessive disorders linkage studies were carried out. Linkage analysis was done using X chromosome microsatellite polymorphisms to define the interval containing the causative gene. Genes from within the region were considered possible candidates and one of these, SYN1, was screened for mutations by direct DNA sequencing of amplified products. Microsatellite analysis showed that the region between MAOB (Xp11.3) and DXS1275 (Xq12) segregated with the disease. Two point linkage analysis demonstrated linkage with DXS1039, lod score 4.06 at theta = 0, and DXS991, 3.63 at theta = 0. Candidate gene analysis led to identification of a nonsense mutation in the gene encoding synapsin I that was present in all affected family members and female carriers and was not present in 287 control chromosomes. Synapsin I is a synaptic vesicle associated protein involved in the regulation of synaptogenesis and neurotransmitter release. The SYN1 nonsense mutation that was identified is the likely cause of the phenotype in this family.

Adolescent↗
PubMed2002

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS).

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS) is in progress. The study design, accrual to date, and related research projects are described. Revised accrual rates and expected recruitment are given. 15 cancers have been detected to date, from a total of 1236 screening measurements. This event rate and the tumour grades reported are compared with recent reports from other studies in women at high risk of breast cancer.

Adult↗
PubMed2001

International investigation of breast MRI: results of a multicentre study (11 sites) concerning diagnostic parameters for contrast-enhanced MRI based on 519 histopathologically correlated lesions.

A multicentre study was undertaken to provide fundamentals for improved standardization and optimized interpretation guidelines of dynamic contrast-enhanced MRI. Only patients scheduled for biopsy of a clinical or imaging abnormality were included. They underwent standardized dynamic MRI on Siemens 1.0 (163 valid lesions > or = 5 mm) or 1.5 T (395 valid lesions > or = 5 mm) using 3D fast low-angle shot (FLASH; 87 s) before and five times after standardized bolus of 0.2 mmol Gd-DTPA/kg. One-Tesla and 1.5 T data were analysed separately using a discriminant analysis. Only histologically correlated lesions entered the statistical evaluation. Histopathology and imaging were correlated in retrospect and in open. The best results were achieved by combining up to five wash-in or wash-out parameters. Different weighting of false-negative vs false-positive calls allowed formulation of a statistically based interpretation scheme yielding optimized rules for the highest possible sensitivity (specificity 30%), for moderate (50%) or high (64-71%) specificity. The sensitivities obtained at the above specificity levels were better at 1.0 T (98, 97, or 96%) than at 1.5 T (96, 93, 86%). Using a widely available standardized MR technique definition of statistically founded interpretation rules is possible. Choice of an optimum interpretation rule may vary with the clinical question. Prospective testing remains necessary. Differences of 1.0 and 1.5 T are not statistically significant but may be due to pulse sequences.

Adult↗
PubMed2001

Measuring extraocular muscle volume using dynamic contours.

The effect of medical treatment on extraocular muscle enlargement in thyroid associated ophthalmopathy (TAO) may be monitored by measuring the change in volume of the extraocular muscles on serial orbital MRI examinations. In theory, 3D image sets offer the opportunity to minimise errors due to poor repositioning and partial volume effects. This study describes an automated technique for estimating extraocular muscle volumes from 3D datasets. Operator input is minimal and the technique is robust. Verification of the technique on both simulated and real datasets is described. For simulated image sets, both automated segmentation and manual outlining produced estimates of volume which were on average 4% less than "true" volume. For real patient data, extraocular muscle volumes measured by the automated technique were 1.6% (SD 13%) less than volumes measured by manual outlining. Coefficient of variation for repeat outlining of the same image dataset for the automated technique was 1.0%, compared with 4% for manual outlining. The manual technique took an experienced operator approximately 20 min to perform, compared to 7 min for the automated technique. The automated method is therefore rapid, reproducible and at least as accurate as other available methods.

Algorithms↗
PubMed2001

Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease.

We describe here a previously unknown, dominantly inherited, late-onset basal ganglia disease, variably presenting with extrapyramidal features similar to those of Huntington's disease (HD) or parkinsonism. We mapped the disorder, by linkage analysis, to 19q13.3, which contains the gene for ferritin light polypeptide (FTL). We found an adenine insertion at position 460-461 that is predicted to alter carboxy-terminal residues of the gene product. Brain histochemistry disclosed abnormal aggregates of ferritin and iron. Low serum ferritin levels also characterized patients. Ferritin, the main iron storage protein, is composed of 24 subunits of two types (heavy, H and light, L) which form a soluble, hollow sphere. Brain iron deposition increases normally with age, especially in the basal ganglia, and is a suspected causative factor in several neurodegenerative diseases in which it correlates with visible pathology, possibly by its involvement in toxic free-radical reactions. We found the same mutation in five apparently unrelated subjects with similar extrapyramidal symptoms. An abnormality in ferritin strongly indicates a primary function for iron in the pathogenesis of this new disease, for which we propose the name 'neuroferritinopathy'.

Adult↗
PubMed2001

Pictorial review: Trigeminal nerve: anatomy and pathology.

MRI is the imaging modality of choice when trigeminal nerve pathology is suspected. Most lesions are readily recognizable if appropriate imaging sequences are performed. Routine cranial MRI sequences augmented by a three-dimensional gradient echo sequence such as FISP (fast inflow with steady-state precession) are sufficient to demonstrate most pathological processes involving the trigeminal nerve and nucleus. Intravenous gadolinium-DTPA occasionally provides additional diagnostic information. MRI is particularly useful in planning the management of those conditions where surgical or medical intervention can result in improvement or resolution of symptoms. In this review, examples of a range of pathologies involving the trigeminal nerve and nucleus are presented.

Adult↗
PubMed2000

Magnetic resonance imaging screening in women at genetic risk of breast cancer: imaging and analysis protocol for the UK multicentre study. UK MRI Breast Screening Study Advisory Group.

The imaging and analysis protocol of the UK multicentre study of magnetic resonance imaging (MRI) as a method of screening for breast cancer in women at genetic risk is described. The study will compare the sensitivity and specificity of contrast-enhanced MRI with two-view x-ray mammography. Approximately 500 women below the age of 50 at high genetic risk of breast cancer will be recruited per year for three years, with annual MRI and x-ray mammography continuing for up to 5 years. A symptomatic cohort will be measured in the first year to ensure consistent reporting between centres. The MRI examination comprises a high-sensitivity three-dimensional contrast-enhanced assessment, followed by a high-specificity contrast-enhanced study in equivocal cases. Multiparametric analysis will encompass morphological assessment, the kinetics of contrast agent uptake and determination of quantitative pharmacokinetic parameters. Retrospective analysis will identify the most specific indicators of malignancy. Sensitivity and specificity, together with diagnostic performance, diagnostic impact and therapeutic impact will be assessed with reference to pathology, follow-up and changes in diagnostic certainty and therapeutic decisions. Mammography, lesion localisation, pathology and cytology will be performed in accordance with the UK NHS Breast Screening Programme quality assurance standards. Similar standards of quality assurance will be applied for MR measurements and evaluation.

Adult↗
PubMed2000

Rationale for a national multi-centre study of magnetic resonance imaging screening in women at genetic risk of breast cancer.

In 1994, the UK National Health Service identified as a research priority that magnetic resonance imaging (MRI) should be assessed as a screening tool for young, pre-menopausal women who are at a high genetic risk of developing breast cancer. In 1997 a national multicentre study was established to compare MRI with X-ray mammography as a method for screening for breast cancer in this group of women. This paper reviews the relevant literature and describes the rationale that led to the setting up of this study.

Journal Article↗
PubMed2000

Protocol for a national multi-centre study of magnetic resonance imaging screening in women at genetic risk of breast cancer.

The protocol of the national multicentre study of Magnetic Resonance Imaging (MRI) as a method of screening for breast cancer in women at genetic risk is described. The sensitivity and specificity of contrast-enhanced MRI will be compared with two-view X-ray mammography in a comparative trial. Approximately 500 women below the age of 50 at high genetic risk of breast cancer will be recruited per year for 3 years, with annual MRI and X-ray examination continuing for up to 5 years. A symptomatic cohort will be measured in the initial phase of the study to ensure consistent reporting between centres. The MRI examination will comprise an initial high-sensitivity screening measurement, followed by a high-specificity measurement in equivocal cases. Retrospective analysis will identify the most specific indicators of malignancy. Sensitivity and specificity, together with diagnostic performance, diagnostic impact and therapeutic impact will be assessed with reference to pathology, follow-up and changes in diagnostic certainty and therapeutic decisions. The psychological impact of screening in this high-risk group will be ascertained.

Journal Article↗
PubMed2000

The spectrum of hearing loss due to mitochondrial DNA defects.

Heteroplasmic mitochondrial DNA (mtDNA) defects are an important cause of neurological disease. Although hearing impairment is common in patients with mtDNA defects, the spectrum and pathophysiology of the hearing loss is not well characterized. We therefore studied the relationship between cochlear and brainstem auditory function in 23 patients harbouring a range of different mtDNA mutations. Based upon the pure tone audiogram, patients fell into three distinct groups: (i) normal hearing, (ii) mild to moderate predominantly high frequency hearing loss, and (iii) severe or profound hearing loss at all frequencies. Within this study group only certain genetic defects were associated with hearing loss, and for individuals harbouring the A3243G point mutation, the severity of the hearing loss correlated with the percentage level of mutated mtDNA (mutation load) in skeletal muscle. The 10 patients who had a moderate hearing loss or less had normal brainstem auditory evoked responses and MRI, but it was not possible to interpret the brainstem auditory evoked responses in 13 patients with severe hearing loss. Otoacoustic emissions were absent in patients with a moderate or more severe hearing loss. These findings are consistent with a predominantly cochlear origin for the hearing deficit, which is determined by the precise genetic defect and the percentage mutation load.

Adult↗
PubMed2000

Hereditary vascular dementia linked to notch 3 mutations. CADASIL in British families.

The most common form of familial vascular dementia is considered to be CADASIL or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, which is now also increasingly manifest in the United Kingdom. CADASIL has been previously dubbed as a familial form of Binswanger disease. However, unlike in Binswanger disease CADASIL does not involve hypertension or other risk factors associated with cardiovascular disease. CADASIL appears to be essentially a disorder of the arteries that is linked to single missense mutations in the NOTCH 3 gene locus on chromosome 19. The pathogenesis of the disorder or the genetic mechanism leading to brain infarcts and dementia is not known. The elucidation of the microvascular pathology evident in CADASIL may be an interesting way to delineate effects of defective genes on brain cells from systemic vascular influences.

Cardiovascular Diseases↗
PubMed2000

MRI screening for acoustic neuroma: a comparison of fast spin echo and contrast enhanced imaging in 1233 patients.

Gadolinium enhanced MRI is the gold standard investigation for the detection of acoustic neuroma. Non-contrast MRI sequences have been suggested as an alternative for screening examinations. In order to determine the utility of fast spin echo imaging, both gadolinium enhanced T1 weighted images and fast spin echo T2 weighted images were acquired in 1233 consecutive patients referred for exclusion of acoustic neuroma. Two radiologists independently recorded their findings. Fast spin echo T2 weighted images were evaluated with respect to the visibility of nerves within the internal auditory canals and allocated a confidence score for the presence or absence of acoustic neuroma. 33 acoustic neuromas were identified. Only 56% were confidently identified on fast spin echo T2 weighted images alone; gadolinium enhanced T1 weighted images were required to confirm the diagnosis in 44% of the cases, including 9 of the 10 intracanalicular tumours. However, when identification of two normal intracanalicular nerves is employed as the criterion of normality, the single fast spin echo T2 weighted sequence excluded acoustic neuroma in 59% of this screened population. It is concluded that an imaging strategy intended to identify small intracanalicular acoustic neuromas cannot rely on fast spin echo T2 weighted imaging alone. Gadolinium enhanced T1 weighted imaging could be restricted to patients where fast spin echo images do not exclude acoustic neuroma but this strategy requires continuous supervision by an experienced radiologist. In most practices the screening examination should continue to include a gadolinium enhanced sequence in order to optimize the detection of small acoustic neuromas.

Adolescent↗
PubMed2000

Distribution of cranial MRI abnormalities in patients with symptomatic and subclinical CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare, inherited cause of early stroke and dementia, with a poor prognosis. This study was performed to clarify lesion appearance and pattern of lesion distribution in CADASIL. 20 members of a single family were tested for the CADASIL gene mutation and studied with cranial MRI. Scans were evaluated for lesion load and pattern of lesion distribution. 19 patients had cranial MRI, of whom 11 had normal MRI scans, were clinically unaffected and tested negative for the CADASIL gene mutation. The remaining eight patients had abnormal cranial MRI scans: seven patients were positive for the CADASIL gene mutation and one (untested) patient was severely clinically affected. Three of the patients who tested positive for the CADASIL gene mutation were clinically unaffected at the time of imaging. All eight patients with abnormal cranial MRI had subcortical white matter abnormalities, mostly in frontal and temporal lobes. Lesions involving the corpus callosum were present on sagittal T2 weighted images in four of five clinically affected and one of three clinically unaffected patients. Lesions involving the deep grey nuclei and the brain stem were common. On T1 weighted images, lesions were either poorly defined (confluent white matter hypointensity) or well defined (cystic infarcts or enlarged perivascular spaces). Atrophy was infrequent. Familiarity with the range of cranial MRI appearances may aid diagnosis of CADASIL. Recognition of cranial imaging features in asymptomatic CADASIL patients could prompt earlier diagnosis.

Adult↗
PubMed2000

Quality assurance for MRI: practical experience.

The aim of this study is to propose guidelines for quality assurance (QA) in MRI, based on a comprehensive assessment of QA parameters undertaken on a busy clinical MRI scanner over the course of 1 year. QA phantoms supplied by the scanner manufacturer were used together with the Eurospin MRI phantom set. Signal-to-noise ratio (SNR) and image uniformity were measured daily from spin echo images acquired using a quadrature send-receive head coil and from a gradient echo sequence using the Helmholtz body coil. The voltage of the transmit radiofrequency (RF) amplifier was noted. Monthly measurements of slice thickness, geometric distortion, slice position, image resolution and image ghosting were acquired using the head coil. In addition, SNR was measured monthly on a selection of commonly used coils. Apart from some drift of the RF amplifier voltage, all measurements were within acceptable limits and were stable over the course of 1 year. Satisfactory measurements of SNR were possible using the simple phantom supplied with the scanner. The SNR, geometric distortion and RF amplifier voltage are simple to determine and can be measured in less than 15 min by the scanner operator, using the scanner software. Weekly recording of these parameters is recommended for busy clinical MRI scanners, as this should allow deviations from acceptable limits to be identified early. Such in-house checks can usefully be compared with the less frequent estimations performed by the service engineer. Comprehensive QA routines are discussed for systems used for quantitative measurements.

Electricity↗
PubMed2000

Pitfalls of breast MRI.

This article reviews some of the common pitfalls associated with breast MRI. Pitfalls can be broadly considered as "technical" (relating to patient factors or machine factors, which can influence image interpretation) or "non-technical" (relating to misinterpretation of imaging findings in the absence of technical problems). Awareness of potential pitfalls is important if MRI is to maximize its potential in breast imaging.

Artifacts↗
PubMed2000

Evaluation of a technique for estimation of extraocular muscle volume using 2D MRI.

Measurements of extraocular muscle volume may be useful as an outcome indicator in the assessment of treatment options in thyroid-associated ophthalmopathy. In this study, a technique for estimating extraocular muscle volume from two-dimensional T1 weighted MR images acquired in the coronal plane is described. For each image slice, the cross-sectional area of individual extraocular muscles was estimated using a combination of semi-automated outlining based on a local thresholding technique and manual outlining where thresholding was not possible. The technique was assessed using three sets of images: a computer-generated virtual image set with "extraocular muscles" of known volumes; a set of images from 19 biochemically and clinically euthyroid patients; and images from 7 patients with thyroid-associated ophthalmopathy. From the computer-generated images, the accuracy was determined as 7.6%. Intraobserver agreement was investigated using repeated MRI scans on a single subject and repeat outlining of muscles on five sets of images from different subjects. The mean difference between repeat measurements was 2% (SD 5.9%). We conclude that two-dimensional MR images can be used to determine changes in muscle volume of greater than 12% during treatment of thyroid-associated ophthalmopathy.

Adult↗
PubMed1999

MRI in routine breast cancer follow-up: correlation with clinical outcome.

AIM: Magnetic resonance imaging (MRI) of the breast has been shown to be useful as an additional imaging test in patients suspected of having recurrent disease, when clinical examination or mammography are equivocal. This study examines the utility of MRI as a routine test in the follow-up of treated breast cancer patients without equivocal clinical or imaging findings. MATERIALS AND METHODS: Contrast-enhanced breast MRI was performed as part of routine breast cancer follow-up in 26 patients with equivocal clinical or mammographic findings and 33 control patients in whom clinical and imaging findings were consistent with post-treatment changes only. Clinical outcome was assessed at 3 years post MRI. RESULTS: Four patients with equivocal clinical or mammographic findings had abnormal MRI: all MRI abnormalities were subsequently shown to represent benign disease. None of the equivocal group developed local recurrence, although two of 26 developed distant metastases. One of the control group had unsuspected distant metastases detected by MRI: the other 32 patients had no significant abnormality on MRI. Three patients subsequently developed local tumour recurrence. CONCLUSION: A single normal breast MRI examination during follow-up is a poor predictor of subsequent local recurrence.

Adult↗