MR image-based measurement of rates of change in volumes of brain structures. Part 1: Method and validation

A detailed analysis procedure is described for evaluating rates of volumetric change in brain structures based on structural magnetic resonance (MR) images. In this procedure, a series of image processing tools have been employed to address the problems encountered in measuring rates of change based on structural MR images. These tools include an algorithm for intensity non-uniforniity correction, a robust algorithm for three-dimensional image registration with sub-voxel precision and an algorithm for brain tissue segmentation. However, a unique feature in the procedure is the use of a fractional volume model that has been developed to provide a quantitative measure for the partial volume effect. With this model, the fractional constituent tissue volumes are evaluated for voxels at the tissue boundary that manifest partial volume effect, thus allowing tissue boundaries be defined at a sub-voxel level and in an automated fashion. Validation studies are presented on key algorithms including segmentation and registration. An overall assessment of the method is provided through the evaluation of the rates of brain atrophy in a group of normal elderly subjects for which the rate of brain atrophy due to normal aging is predictably small. An application of the method is given in Part 11 where the rates of brain atrophy in various brain regions are studied in relation to normal aging and Alzheimer's disease. (C) 2002 Elsevier Science Inc. All rights reserved.

MR image-based measurement of rates of change in volumes of brain structures. Part II: Application to a study of Alzheimer's disease and normal aging

We present global and regional rates of brain atrophy measured on serially acquired T1-weighted brain MR images for a group of Alzheimer's disease (AD) patients and age-matched normal control (NC) subjects using the analysis procedure described in Part I. Three rates of brain atrophy: the rate of atrophy in the cerebrum, the rate of lateral ventricular enlargement and the rate of atrophy in the region of temporal lobes, were evaluated for 14 AD patients and 14 age-matched NC subjects. All three rates showed significant differences between the two groups, However, the greatest separation of the two groups was obtained when the regional rates were combined. This application has demonstrated that rates of brain atrophy, especially in specific regions of the brain, based on MR images can provide sensitive measures for evaluating the progression of AD. These measures will be useful for the evaluation of therapeutic effects of novel therapies for AD. (C) 2002 Elsevier Science Inc. All rights reserved.

Finite difference time domain (FDTD) method for modeling the effect of switched gradients on the human body in MRI

Numerical modeling of the eddy currents induced in the human body by the pulsed field gradients in MRI presents a difficult computational problem. It requires an efficient and accurate computational method for high spatial resolution analyses with a relatively low input frequency. In this article, a new technique is described which allows the finite difference time domain (FDTD) method to be efficiently applied over a very large frequency range, including low frequencies. This is not the case in conventional FDTD-based methods. A method of implementing streamline gradients in FDTD is presented, as well as comparative analyses which show that the correct source injection in the FDTD simulation plays a crucial rule in obtaining accurate solutions. In particular, making use of the derivative of the input source waveform is shown to provide distinct benefits in accuracy over direct source injection. In the method, no alterations to the properties of either the source or the transmission media are required. The method is essentially frequency independent and the source injection method has been verified against examples with analytical solutions. Results are presented showing the spatial distribution of gradient-induced electric fields and eddy currents in a complete body model.

Routine ultrasound screening in diabetic pregnancies

Objectives To assess the detection rate of congenital fetal malformations and specific problems related to routine ultrasound screening in women with pre-existing diabetes. Methods A retrospective study was carried out to assess the performance of routine ultrasound screening in women with pre-existing diabetes (Types 1 and 2) within a tertiary institution. The incidence, type and risk factors for congenital fetal malformations were determined. The detection rate of fetal anomalies for diabetic women was compared with that for the low-risk population. Factors affecting these detection rates were evaluated. Results During the study period, 12 169 low-risk pregnant women and 130 women with pre-existing diabetes had routine ultrasound screening performed within the institution. A total of 10 major anomalies (7.7%) and three minor anomalies (2.3%) were present in the fetuses of the diabetic women. Central nervous system and cardiovascular system anomalies accounted for 60% of the major anomalies. Peri-conceptional hemoglobin A 1 c of more than 9% was associated with a high prevalence of major anomalies (14311000). Women who had fetuses with major anomalies bad a significantly higher incidence of obesity (78% vs. 37%; P < 0.05). Ultrasound examination of these diabetic pregnancies showed high incidences of suboptimal image quality (37%), incomplete examinations, and repeat examinations (17%). Compared to the 'low-risk' non-diabetic population from the same institution, the relative risk for a major congenital anomaly among the diabetic women was 5.9-fold higher (95% confidence interval, 2.9-11.9). The detection rate for major fetal anomalies was significantly lower for diabetic women (30% vs. 73%; P < 0.01), and the mean body mass index for the diabetic group was significantly higher (29 vs. 23 kg/m(2); P < 0.001). Conclusion The incidence of congenital anomalies is higher in diabetic pregnancies. Unfortunately, the detection rate for fetal anomalies by antenatal ultrasound scan was significantly, worse than that for the low-risk population. This is likely to be related to the maternal body habitus and unsatisfactory examinations. Methods to overcome these difficulties are discussed.

Determination of regional flow by use of intravascular PET tracers: Microvascular theory and experimental validation for pig livers

Today, the standard approach for the kinetic analysis of dynamic PET studies is compartment models, in which the tracer and its metabolites are confined to a few well-mixed compartments. We examine whether the standard model is suitable for modern PET data or whether theories including more physiologic realism can advance the interpretation of dynamic PET data. A more detailed microvascular theory is developed for intravascular tracers in single-capillary and multiple-capillary systems. The microvascular models, which account for concentration gradients in capillaries, are validated and compared with the standard model in a pig liver study. Methods: Eight pigs underwent a 5-min dynamic PET study after O-15-carbon monoxide inhalation. Throughout each experiment, hepatic arterial blood and portal venous blood were sampled, and flow was measured with transit-time flow meters. The hepatic dual-inlet concentration was calculated as the flow-weighted inlet concentration. Dynamic PET data were analyzed with a traditional single-compartment model and 2 microvascular models. Results: Microvascular models provided a better fit of the tissue activity of an intravascular tracer than did the compartment model. In particular, the early dynamic phase after a tracer bolus injection was much improved. The regional hepatic blood flow estimates provided by the microvascular models (1.3 +/- 0.3 mL min(-1) mL(-1) for the single-capillary model and 1.14 +/- 0.14 min(-1) mL(-1) for the multiple-capillary model) (mean +/- SEM mL of blood min(-1) mL of liver tissue(-1)) were in agreement with the total blood flow measured by flow meters and normalized to liver weight (1.03 +/- 0.12 mL min(-1) mL(-1)). Conclusion: Compared with the standard compartment model, the 2 microvascular models provide a superior description of tissue activity after an intravascular tracer bolus injection. The microvascular models include only parameters with a clear-cut physiologic interpretation and are applicable to capillary beds in any organ. In this study, the microvascular models were validated for the liver and provided quantitative regional flow estimates in agreement with flow measurements.

Medical marijuana initiatives - Are they justified? How successful are they likely to be?

The principal constituent of cannabis, Delta(9)-tetrahydrocannabinol (THC), is moderately effective in treating nausea and vomiting, appetite loss, and acute and chronic pain. Oral THC (dronabinol) and the synthetic cannabinoid, nabilone, have been registered for medical use in the US and UK, but they have not been widely used because patients find it difficult to titrate doses of these drugs. Advocates for the medical use of cannabis argue that patients should be allowed to smoke cannabis to relieve these above-mentioned symptoms. Some US state governments have legislated to allow the medical prescription of cannabis, but the US federal government has tried to prevent patients from obtaining cannabis and threatened physicians who prescribe it with criminal prosecution or loss of their licence to practise. In the UK and Australia, committees of inquiry have recommended medical prescription (UK) and exemption from criminal prosecution (New South Wales, Australia), but governments have not accepted these recommendations. The Canadian government allows an exemption from criminal prosecution to patients with specified medical conditions. It has recently legislated to provide cannabis on medical prescription to registered patients, but this scheme so far has not been implemented. Some advocates argue that legalising cannabis is the only way to ensure that patients can use it for medical purposes. However, this would be contrary to international drug control treaties and is electorally unpopular. The best prospects for the medical use of cannabinoids lie in finding ways to deliver THC that do not involve smoking and in developing synthetic cannabinoids that produce therapeutic effects with a minimum of psychoactive effects. While awaiting these developments, patients with specified medical conditions could be given exemptions from criminal prosecution to grow cannabis for their own use, at their own risk.

Ultrasonic absorption in polymer gel dosimeters

Ultrasonic absorption in polymer gel dosimeters was investigated. An ultrasonic interferometer was used to study the frequency (f) dependence of the absorption coefficient (alpha) in a polyacrylamide gel dosimeter (PAG) in the frequency range 5-20 MHz. The frequency dependence of ultrasonic absorption deviated from that of an ideal viscous fluid. The presence of relaxation mechanisms was evidenced by the frequency dependence of alpha/f(2) and the dispersion in ultrasonic velocity. It was concluded that absorption in polymer gel dosimeters is due to a number of relaxation processes which may include polymer-solvent interactions as well as relaxation due to motion of polymer side groups. The dependence of ultrasonic absorption on absorbed dose and formulation was also investigated in polymer gel dosimeters as a function of pH and chemical composition. Changes in dosimeter pH and chemical composition resulted in a variation in ultrasonic dose response curves. The observed dependence on pH was considered to be due to pH induced modifications in the radiation yield while changes in chemical composition resulted in differences in polymerisation kinetics. (C) 2003 Elsevier B.V. All rights reserved.

Influence of magnetically-induced E-fields on cardiac electric activity during MRI: A modeling study

In modern magnetic resonance imaging (MRI), patients are exposed to strong, time-varying gradient magnetic fields that may be able to induce electric fields (E-fields)/currents in tissues approaching the level of physiological significance. In this work we present theoretical investigations into induced E-fields in the thorax, and evaluate their potential influence on cardiac electric activity under the assumption that the sites of maximum E-field correspond to the myocardial stimulation threshold (an abnormal circumstance). Whole-body cylindrical and planar gradient coils were included in the model. The calculations of the induced fields are based on an efficient, quasi-static, finite-difference scheme and an anatomically realistic, whole-body model. The potential for cardiac stimulation was evaluated using an electrical model of the heart. Twelve-lead electrocardiogram (ECG) signals were simulated and inspected for arrhythmias caused by the applied fields for both healthy and diseased hearts. The simulations show that the shape of the thorax and the conductive paths significantly influence induced E-fields. In healthy patients, these fields are not sufficient to elicit serious arrhythmias with the use of contemporary gradient sets. However, raising the strength and number of repeated switching episodes of gradients, as is certainly possible in local chest gradient sets, could expose patients to increased risk. For patients with cardiac disease, the risk factors are elevated. By the use of this model, the sensitivity of cardiac pathologies, such as abnormal conductive pathways, to the induced fields generated by an MRI sequence can be investigated. (C) 2003 Wiley-Liss, Inc.

Effect of functional gain on satisfaction with medical rehabilitation after stroke

Objective: To examine the association between gain in motor and cognitive functional status with patient satisfaction 3-6 mo after rehabilitation discharge. Design: Patient satisfaction and changes in functional status were examined in 18,375 patients with stroke who received inpatient medical rehabilitation. Information was obtained from 144 hospitals and rehabilitation facilities contributing records to the Uniform Data System for Medical Rehabilitation and the National Follow-up Services. Results: Data analysis revealed significant (P < 0.05) differences in satisfaction responses based on whether information was collected from patient self-report or from a family member proxy, and the two subsets were analyzed separately. Logistic regression revealed the following significant predictors of satisfaction for data collected from stroke patients: cognitive and motor gain, rehospitalization, who the patient was living with at follow-up, age, and follow-up therapy. In the patient-reported data subset, compared with patients who showed improved cognitive or motor functional status, those with no change, respectively, had a 31% and 33% reduced risk of dissatisfaction. In addition, rehospitalized patients had a higher risk of dissatisfaction. For the proxy reported data subset, significant influences on satisfaction were health maintenance, rehospitalization, stroke type, ethnicity, cognitive FIM(TM) gain, length of stay, and follow-up therapy. Conclusions: Ratings of satisfaction with rehabilitation services were affected by change in functional status and whether the information was collected from patient rating or proxy response.

Graduate entry to medical studies: thoughts from 'down under' (editorial)

This invited editorial, reflecting on expectations of changing to graduate entry, eg enhanced maturity in the student cohort with greater self-sufficiency and taking of responsibility for learning in the context of adoption of a problem-based learning model, examines experiences of early post-change years and raises questions for contemplation by medical schools considering graduate entry.