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.

Enhancement or modulation of the vector competence of ochlerotatus vigilax (Diptera : Culicidae) for Ross River virus by temperature

Two different doses of Ross River virus (1111) were fed to Ochlerotatus vigilax (Skuse), the primary coastal vector in Australia; and blood engorged females were held at different temperatures up to 35 d. After ingesting 10(4.3) CCID50/Mosquito, mosquitoes reared at 18 and 25degreesC (and held at the same temperature) had higher body remnant and head and salivary gland titers than those held at 32degreesC, although infection rates were comparable. At 18, 25, and 32degreesC, respectively, virus was first detected in the salivary glands on days 3, 2, and 3. Based on a previously demonstrated 98.7% concordance between salivary gland infection and transmission, the extrinsic incubation periods were estimated as 5, 4, and 3 d, respectively, for these three temperatures. When Oc. vigilax reared at 18, 25, or 32degreesC were fed a lower dosage of 10(3.3) CCID50 RR/mosquito, and assayed after 7 d extrinsic incubation at these (or combinations of these) temperatures, infection rates and titers were similar. However, by 14 d, infection rates and titers of those reared and held at 18 and 32degreesC were significantly higher and lower, respectively. However, this process was reversible when the moderate 25degreesC was involved, and intermediate infection rates and titers resulted. These data indicate that for the strains of RR and Oc. vigilax used, rearing temperature is unimportant to vector competence in the field, and that ambient temperature variations will modulate or enhance detectable infection rates only after 7 d: extrinsic incubation. Because of the short duration of extrinsic incubation, however, this will do little to influence RR epidemiology, because by this time some Oc. vigilax could be seeking their third blood meal, the latter two being infectious.

James W. Gerard: His image of imperial Germany, 1913-1918

The subject of this study was a typical, if in some respects well qualified, U.S. ambassadorial appointee for his time, the early twentieth century: an attorney, judge, and politician who served competently in his one diplomatic assignment, in Berlin, before returning to private life.—Ed.

Antibody-dependent enhancement of Murray Valley encephalitis virus virulence in mice

Enhancement of flavivirus infection in vitro in the presence of subneutralizing concentrations of homologous or heterologous antiserum has been well described. However, the importance of this phenomenon in the enhancement of flavivirus infection in vivo has not been established. In order to study antibody- mediated enhancement of flavivirus infection in vivo, we investigated the effect of passive immunization of mice with Japanese encephalitis virus (JE) antiserum on the outcome of infection with Murray Valley encephalitis virus (MVE). We show that prior treatment of mice with subneutralizing concentrations of heterologous JE antiserum resulted in an increase in viraemia titres and in mortality following challenge with wild-type MVE. Our findings support the hypothesis that subneutralizing concentrations of antibody may enhance flavivirus infection and virulence in vivo. These findings are of potential importance for the design of JE vaccination programs in geographic areas in which MVE co-circulates. Should subneutralizing concentrations of antibody remain in the population following JE vaccination, it is possible that enhanced disease may be observed during MVE epidemics.