The assessment of fetal brain growth in diabetic pregnancy using in utero magnetic resonance imaging.

AIM: To assess fetal brain growth over the third trimester in pregnant women with diabetes using in utero magnetic resonance imaging (iuMRI) to determine if greater brain growth occurs in type 1 (T1DM) when compared to gestational (GDM) diabetes mellitus. MATERIALS AND METHODS: Each consented participant was scanned at three fixed times during the third trimester using iuMRI. One hundred and fifty-seven patients were approached, 48 participants were recruited, and 36 complete data sets were analysed. Three-dimensional (3D) iuMRI volume data sets were manually segmented using software to construct models of the fetal brain from which brain volumes could be calculated. Inter-rater analysis was performed, and volume differences and growth rates were compared between T1DM and GDM. RESULTS: Recruitment proved difficult with low uptake and high attrition rates (77.1%). Inter-rater analysis revealed excellent correlation (intraclass correlation coefficient=0.93, p<0.001) and agreement with no significant difference between operators (p=0.194). There was no evidence of increased brain volume in the T1DM group. Growth rates between visit 1 and 3 for T1DM and GDM were not significantly different (p=0.095). CONCLUSION: T1DM brain volumes were not significantly larger than GDM volumes and there was no significant divergence of brain growth over the third trimester. Constructing volume models from 3D iuMRI acquisitions is a novel technique that can be used to assess fetal brain growth. No specialist software or knowledge is required. Larger studies attempting to recruit pregnant women in the later stages of pregnancy should employ multicentre recruitment to overcome recruitment difficulties and high attrition rates.

Surface reconstructions of foetal brain abnormalities using ultrafast steady state 3D acquisitions.

MRI of the foetal brain in utero is performed in routine clinical practice using sequences that produce two-dimensional (2D) images. Recent developments in image post-processing have allowed the construction of three-dimensional (3D) volume data sets from 2D images acquired in different anatomical planes, but these have limitations due to the unpredictable nature of foetal movement. These limitations have been overcome by development of several different advanced computer techniques, which require specialist knowledge, software, and processing methods, which are rarely available in routine clinical settings. Our aim was to develop a technique that can be used in routine clinical situations without the need for custom-developed or expensive software by utilizing MRI sequences that can produce a 3D data set in "ultrafast" timescales. The 3D dataset, combined with versatile image post-processing and visualization techniques, has resulted in the production of high-resolution images of foetal brain surfaces in utero. The aim of this paper is to demonstrate our methods and early results by way of a pictorial review illustrating a range of developmental brain disease in utero.

The Profiles and Correlates of Psychopathology in Adolescents and Adults with Williams, Fragile X and Prader-Willi Syndromes.

Psychopathology is prevalent in Williams (WS), fragile X (FXS) and Prader-Willi (PWS) syndromes. However, little is known about the potential correlates of psychopathology in these groups. A questionnaire study was completed by 111 caregivers of individuals with WS (n = 35); FXS (n = 50) and PWS (n = 26). Mean age was 26 years (range 12-57 years); 74 (67%) were male. Multiple regression analyses indicated that higher rates of health problems and sensory impairments predicted higher psychopathology in WS (p < .0001). In PWS, poorer adaptive ability predicted higher overall psychiatric disturbance (p = .001), generalised anxiety (p = .006) and hyperactivity (p = .003). There were no significant predictors in FXS. This study highlights dissociations in the potential risk markers of psychopathology between genetic syndromes. Implications for intervention are discussed.

Development and initial testing of normal reference MR images for the brain at ages 65-70 and 75-80 years.

Interpretation of brain images from older patients requires knowledge of changes that occur with healthy ageing. We constructed and tested a reference template for older subjects. We used MR images from normal subjects aged 65-70 and 75-80 to generate average age-specific images. We ranked the T2-weighted images by worsening brain tissue loss to create a diagram of key centiles. Two neuroradiologists tested the template during routine reporting; eight radiologists read 99 MR examinations without and then with the template. Fifty-four subjects (65-70 years) and 25 subjects (75-80 years) formed the reference images. For the two neuroradiologists, the reference template reduced the abnormal scan reporting from 28/42 without to 3/42 with the template. Of 99 MR examinations assessed by eight radiologists, 39/58 scans (67%) reported as moderate or severe atrophy without the template were reported as normal with the template (p = 0.00011). Reference templates of the brain at older ages can "calibrate" radiology reporting. They could also be useful for research into ageing and related conditions. Larger numbers of examinations from more diverse populations and at different ages are required to increase the versatility of these templates.

Do acute diffusion- and perfusion-weighted MRI lesions identify final infarct volume in ischemic stroke?

BACKGROUND AND PURPOSE: An acute mismatch on diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) may represent the "tissue-at-risk." It is unclear which "semiquantitative" perfusion parameter most closely identifies final infarct volume. METHODS: Acute stroke patients underwent DWI and PWI (dynamic-susceptibility contrast imaging) on admission (baseline), and T2-weighted imaging (T2WI) at 1 or 3 months after stroke. "Semiquantitative" mean transit time (MTTsq=first moment of concentration/time curve), cerebral blood volume (CBVsq=area under concentration/time curve), and cerebral blood flow (CBFsq=CBVsq/MTTsq) were calculated. DWI and PWI lesions were measured at baseline and final infarct volume on T2WI acquired > or =1 month after stroke. Baseline DWI, CBFsq, and MTTsq lesion volumes were compared with final T2WI lesion volume. RESULTS: Among 46 patients, baseline DWI and CBFsq lesions were not significantly different from final T2WI lesion volume, but baseline MTTsq lesions were significantly larger. The correlation with final T2WI lesion volume was strongest for DWI (Spearman rank correlation coefficient rho=0.68), intermediate for CBFsq (rho=0.55), and weakest for MTTsq (rho=0.49) baseline lesion volumes. Neither DWI/CBFsq nor DWI/MTTsq mismatch predicted lesion growth; lesion growth was equally common in those with and without mismatch. CONCLUSIONS: Of the 2 PWI parameters, CBFsq lesions most closely identifies, and MTTsq overestimates, final T2WI lesion volume. "DWI/PWI mismatch" does not identify lesion growth. Patients without "DWI/PWI mismatch" are equally likely to have lesion growth as those with mismatch and should not be excluded from acute stroke treatment.

Effects of dexamethasone on cerebral perfusion and water diffusion in patients with high-grade glioma.

BACKGROUND AND PURPOSE: The mechanisms by which the glucocorticoid dexamethasone produces its therapeutic action in patients with intracranial tumors still remain unclear. The purpose of this study was to investigate whether dexamethasone affects cerebral perfusion and water molecule diffusion by using quantitative dynamic susceptibility contrast perfusion MR imaging (DSC-MR imaging) and diffusion tensor MR imaging (DT-MR imaging). METHODS: Ten consecutive patients with glioblastoma multiforme underwent DSC-MR imaging and DT-MR imaging before and 48-72 hours after dexamethasone treatment (16 mg/day). Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and water mean diffusivity () were measured for enhancing tumor, nonenhancing peritumoral edematous brain, and normal-appearing contralateral white matter before and after steroid therapy. The percentage change in CBF, CBV, MTT, and for the 3 tissue types was calculated for each patient, a mean value obtained for the population, and the statistical significance determined by using a paired-samples Student t test. RESULTS: After dexamethasone treatment, there was no significant change in tumor CBF, CBV, or MTT. Edematous brain CBV and MTT were also unchanged. There was, however, an increase in edematous brain CBF (11.6%; P = .05). was reduced in both enhancing tumor (-5.8%; P = .001) and edematous brain (-6.0%; P < .001). There was no significant change in CBF, CBV, MTT, or for normal-appearing contralateral white matter after treatment. CONCLUSION: These data suggest that dexamethasone does not significantly affect tumor blood flow but may, by reducing peritumoral water content and local tissue pressure, subtly increase perfusion in the edematous brain.

The effects of sediment size fraction and associated algal biofilms on the kinetics of phosphorus release.

Experiments using flumes containing sediment of three different size fractions, from two sites on the River Tame, investigated the influences of sediment particle size, and an associated biofilm, on sediment-water exchanges in heterogeneous sediment deposits. This is the first study undertaken to understand the kinetics of the release of soluble reactive phosphorus from sediments of natural systems to identify which of the size compartments affected those fluxes most. Samples of fine material (<2 mm), gravel (2-20 mm), and stones (>20 mm) were collected over a period of several weeks and brought to a fluvarium where they were placed in artificial, controlled flow, and flume channels. Synthetic solutions of similar ionic strength to the river were prepared using calcium chloride. Temperature, pH, and dissolved oxygen of the solution overlying the sediment were monitored automatically whilst filtered samples were obtained at 2 h intervals over 48 h. The biomass, expressed as mg m(-2) chlorophyll a, of the algal component of the biofilm from the surface of the sediment was estimated using methanol extraction. Differences in the responses were observed between the sediment size fractions and the two sites, where contaminant concentrations varied. The equilibrium phosphate concentration and a phosphorus transfer index were used to establish that there was a net uptake of phosphorus by all three sediment size fractions, from both sites, at the time of sampling. The kinetic results showed very fast initial reactions of phosphorus release from the larger size fractions with a well-developed filamentous algal growth present implying a different mechanism than diffusion being involved. The stones and associated biofilms also released more phosphorus than the fine fraction, e.g. final release concentrations for the most contaminated site were: fines approximately 2.5 microM, gravel approximately 6.5 microM, and stones approximately 65.0 microM (expressed as soluble reactive phosphorus). Phosphorus fluxes, calculated assuming the concentration of phosphorus in the sediment was less than the equilibrium concentration, were a maximum at the most contaminated site, e.g. fines 6.4 nmol m(-2) s(-1), gravel 27 nmol m(-2) s(-1), and stones 109 nmol m(-2) s(-1) (normalised with respect to the river bed area). These results confirm that sediment having a biofilm and associated particulate material results in a greater flux than fine sediment, which does not support a filamentous biomass. Removal of the fine particulates trapped in the algal growth reduced soluble phosphorus release. These factors demonstrate that both gravel and stone substrates have an important control over the release of soluble reactive phosphorus.

Kinetics of phosphorus release from a natural mixed grain-size sediment with associated algal biofilms.

Experiments using flumes containing mixed grain-size sediment with an associated algal biofilm, from two sites on the R. Tame, investigated the sediment-water exchanges in heterogeneous sediment deposits. These results were considered in the light of findings of a companion study [Gainswin BE, et al. The effects of sediment size fraction and associated algal biofilms on the kinetics of phosphorus release. Sci Total Environ, this issue.] by considering this natural system in relation to the effects of the different sizes of material comprising the sediment. Sediment samples were collected in trays installed in the river over a period of one growth cycle (March 2001-April 2002) and placed in flume channels with controlled water flow. The temperature, pH, and dissolved oxygen of the solution overlying the sediment were monitored automatically whilst filtered samples were obtained at 2-0h intervals over 48 h. The biomass, expressed as chlorophyll a, of the algal component of the biofilm from the surface of the sediment was estimated using methanol extraction. The composition of the sediment, viz. size fractions, organic matter and porosity, were determined at the end of the experiments. The equilibrium phosphate concentration and a phosphorus transfer index were used to establish that a net uptake of phosphorus by some of the samples that occurred at the time of sampling. The results were modelled using a Diffusion Boundary Layer model and the maximum flux from the sediment (or limiting diffusion flux) compared for each of the samples. The limiting diffusion flux was highest at the most contaminated site--reaching approximately 180 nmol m(-2) s(-1) (normalised with respect to the river bed area). The limiting diffusion flux calculated for the composite samples was in agreement with the flux estimated from the contributions expected from the individual size fractions [Gainswin BE, et al. The effects of sediment size fraction and associated algal biofilms on the kinetics of phosphorus release. Sci Total Environ, this issue.]. The dominance of the flux contribution from the stones size fraction (>20 mm) confirms that sediment having a filamentous biofilm and associated particulate material results in a greater flux than a silt sediment without such a biomass.

Phenytoin and chlorpromazine in the treatment of spasticity.

The efficacy of phenytoin sodium and chlorpromazine hydrochloride in the reduction of spasticity was evaluated in both open and controlled studies. In each study, the majority of patients exhibited both objective and subjective signs of improvement. Reduction of motor tone in spastic muscles, as well as improvement in functiional status, was observed. Most patients experienced greater benefit from the combination of phenytoin and chlorpromazine than from either drug alone. The use of the drugs in combination permitted decreased chlorpromazine doses and reduced unwanted side effects such as lethargy and somnolence. These drugs may exert their action by suppressing fusimotor efferent as well as afferent discharged from muscle spindles. The results suggest that the fusimotor system is an important pharmacologic target in the treatment of spasticity.

Is diffusion imaging appearance an independent predictor of outcome after ischemic stroke?

BACKGROUND: MR diffusion-weighted imaging (DWI) in ischemic stroke can be quantified by calculating the apparent diffusion coefficient (ADC) or measuring lesion volume. OBJECTIVE: To clarify the association between DWI lesion parameters, clinical stroke severity at baseline, and the relationship with functional outcome. METHODS: Consecutive patients with stroke were categorized for stroke type (Oxford Community Stroke Project Classification [OCSP]) and severity (Canadian Neurologic Scale [CN Scale]) before DWI. The ratio of the trace of the apparent diffusion tensor in the ischemic lesion to the mirror image area in the contralateral hemisphere was calculated (r). The volume of the visible lesion on DWI was measured. Any visible lesion on T2-weighted imaging (T2WI) was noted. All assessments were blind to all other information. A blinded observer obtained a 6-month Rankin score. Univariate and multivariate analyses were performed to test for independent associations with outcome. RESULTS: In 108 patients, those with lower (i.e., more abnormal) r values had more severe strokes according to the CN Scale (p = 0.01) and the OCSP stroke type (p = 0.002), a large lesion on DWI (p = 0.05), a visible lesion on T2WI (p = 0.001), and poor 6-month functional outcome (p = 0.009). However, on logistic regression, neither r nor DWI lesion volume were independent predictors of 6-month outcome over and above age and stroke severity. CONCLUSION: The r is associated with functional outcome, but that is because it and DWI lesion volume are also associated with stroke severity. Although DWI lesion features are univariate surrogate outcome predictors, the authors were unable to show that they were independent outcome predictors in the current study. Differences between these and other results may be due to differences in study design, sample size, and case mix.

Multistage models of carcinogenesis.

The simple multistage model of carcinogenesis is outlined. It provides a satisfactory explanation of the power law for the age incidence of many forms of epithelial carcinoma, for the effects in human populations of changing exposures to supposed carcinogenic agents, and for many of the observed effects of applied carcinogens in animal experiments. In particular, the evidence on the effects of starting and stopping cigarette smoking suggests that both an early and a late stage may be affected. In the absence of direct evidence on the nature of the cellular changes there is some reluctance to accept a model with more than two stages, and several forms of two-stage models provide good general explanations of observed phenomena. Such a model has recently been applied to breast cancer; another approach to this disease, effectively involving transformations of the time scale, is discussed.

National Health Survey Systems in the European community.

This paper is based on the report of a conference held in October 1975 to discuss the possibilities for collaborative action between countries of the European Community in conducting various forms of health survey. Health interview surveys offer the principal opportunity for such action, and it may be possible to incorporate health questions into multi-purpose international surveys. Health examination surveys are less likely to be developed widely in the immediate future. Hospital in-patient discharge records are collected routinely in many countries, and further international cooperation seems feasible. These possibilities are now being kept under continuous review by a working party.

A study of the apparent diffusion coefficient of grey and white matter in human ischaemic stroke.

We examined whether there was any difference in the value, and temporal evolution, of the apparent diffusion tensor trace (ADC) in acute and subacute grey and white matter lesions. Thirty-seven patients underwent diffusion imaging once (up to 3 days), 15 patients were scanned twice (up to 7 days), and seven patients were scanned three times (up to 14 days) after stroke. Values of the ratio of ischaemic to contralateral ADC (ADCr) were reduced on average by 30% (p<0.001) in the whole hyperintense region up to 7 days post-ictus. No difference was seen between ADCr values of grey and white matter in individual subjects within the patient groups scanned up to 7 days. However, in the subgroup of patients scanned beyond 7 days, ADCr for grey matter rose significantly (p=0.02) from ADCr approximately 0.7 (< 7 days) to 0.95 (> or = 10 days). This increase did not occur in white matter whose ADCr remained fairly constant (ADCr approximately 0.7) over the time course of the study.

Hycanthone dose-response in treatment of schistosomiasis mansoni in St. Lucia.

Clinical trials of hycanthone (single intramuscular dose) were undertaken in schistosomiasis mansoni patients in St. Lucia at five dose levels: 3.0, 2.5, 2.0, 1.5, and 1.0 mg/kg body weight. The most common side effect, vomiting, decreased in frequency from 51% at the highest dose to 3% at the lowest; minor side effects showed a similar trend. Three fecal specimens were examined before and at 6 months after treatment by qualitative, quantitative, and hatching techniques. All dose levels caused reductions in egg excretion of 89 to 98%. Rates of cure (absence of eggs by all three methods) according to dose (descending), pretreatment egg output (0-19, 20-49, 50-399, 400+ eggs/ml feces), and age (0-7, 8-14, 15-29, 30+ years) were analyzed to estimate the effect of each variable if the others had been constant. For dose, the standardized percentage success rates were 53.9%, 62.0%, 51.2% 54.0%, and 27.4%; for egg output, 67.0%, 51.8%, 43.2%, and 21.7%; and for age, 25.2%, 34.5%, 59.3% and 57.4%. Logit regression analysis shows a significant difference in cure rate (a) between the lowest dose and all others, among which latter there was no difference, (b) between patients excreting 0 to 49 eggs/ml before treatment and those excreting 50+ eggs/ml, and (c) between the age groups 0 to 14 and 15+ years. All dose levels caused some regression in enlargement of liver or spleen. A dose of 1.5 to 2.0 mg/kg body weight is considered to be as effective as one of 3.0 mg/kg and more acceptable for a control program because of the marked reduction in side effects.

Therapeutic trial of intracisternal human tetanus immunoglobulin in clinical tetanus.

A trial has been conducted of the efficacy of human tetanus immunoglobulin (250 I U) administered intrathecally (intracisternally) in addition to standard treatment (equine antitoxin intravenously, penicillin, anticonvulsants). The trial was analysed sequentially and was stopped for 120 patients when there was no longer any chance of achieving a statistically significant difference in favour of intrathecal administration. The sequential plan was modified during the trial. A prognostic correlation was found between onset of the first symptom and admission to hospital.

Accuracy of a miniature intracranial pressure monitor, its function during magnetic resonance scanning, and assessment of image artifact generation.

OBJECTIVE: We examined the accuracy and repeatability of an intracranial pressure (ICP) monitor (Codman MicroSensor; Johnson & Johnson Professional, Inc., Raynham, MA) in a nonmagnetic environment and during magnetic resonance imaging (MRI). The resulting image artifact generation was calculated. ICP monitoring is essential in management of severe head injury, but few ICP monitoring devices are compatible with use in an MRI scanner. The use of MRI to assess head injury is increasing, and developing safe methods of continuously monitoring ICP may improve patient care. METHODS: A water manometer was used as the standard for comparison. We assessed pressure readings from the ICP monitor in a nonmagnetic environment using a standard and a long connector cable between the pressure transducer and display unit. This long cable permitted testing during MRI sequences because the display unit could be distanced from the magnet. Accuracy was determined during T2-weighted imaging, proton spectroscopy, and diffusion-weighted imaging, and artifact generation was assessed. RESULTS: We found a high degree of accuracy for repeated measurements over a clinical pressure range using both standard and long connector cables outside the MRI room. During MRI scanning, the ICP monitor was accurate during T2 and proton spectroscopy sequences. Accuracy during diffusion-weighted imaging, however, was clinically unacceptable. This ICP monitor creates a reduction in signal-to-noise ratio in the received signal during T2-weighted imaging and proton spectroscopic imaging, with the obtained images still radiologically interpretable. CONCLUSION: The Codman ICP monitor is sufficiently accurate and free of artifact generation to be used during most clinical MRI applications. This could enhance patient monitoring and safety.

On the use of water phantom images to calibrate and correct eddy current induced artefacts in MR diffusion tensor imaging.

The accurate determination of absolute measures of diffusion anisotropy in vivo using single-shot, echo-planar imaging techniques requires the acquisition of a set of high signal-to-noise ratio, diffusion-weighted images that are free from eddy current induced image distortions. Such geometric distortions can be characterized and corrected in brain imaging data using magnification (M), translation (T), and shear (S) distortion parameters derived from separate water phantom calibration experiments. Here we examine the practicalities of using separate phantom calibration data to correct high b-value diffusion tensor imaging data by investigating the stability of these distortion parameters, and hence the eddy currents, with time. It is found that M, T, and S vary only slowly with time (i.e., on the order of weeks), so that calibration scans need not be performed after every patient examination. This not only minimises the scan time required to collect the calibration data, but also the computational time needed to characterize these eddy current induced distortions. Examples of how measurements of diffusion anisotropy are improved using this post-processing scheme are also presented.

A theoretical study of the effect of experimental noise on the measurement of anisotropy in diffusion imaging.

Diffusion tensor imaging (DTI) is a modality known to be highly sensitive to the detrimental effects of experimental noise. Here, using Monte Carlo simulations, we compare and contrast how noise complicates the measurement of diffusion anisotropy in diffusion tensor and conventional diffusion-weighted imaging (DWI). As the signal-to-noise ratio (SNR) decreases below a value of approximately 20, the eigenvalues (lambda(i)) of the diffusion tensor D are found to diverge rapidly from their true values, with the result that the measured anisotropy can be significantly in error and isotropic structures falsely assigned a high level of anisotropy. The effect of noise on the rotationally variant indices, calculated from a conventional diffusion-weighted imaging experiment, is found to be much less insidious, because the apparent diffusion coefficients (ADCs) diverge only slowly as the signal-to-noise decreases. Thus, although rotationally variant indices almost always underestimate the true diffusion anisotropy, they show only a small susceptibility to experimental noise and hence, are preferred to their rotationally invariant counterparts when the signal-to-noise ratio is small.