Dietary cholesterol increases ventricular volume and narrows cerebrovascular diameter in a rabbit model of Alzheimer's disease.

Using structural magnetic resonance imaging in a clinical scanner at 3.0T, we describe results showing that following 12weeks on a diet of 2% cholesterol, rabbits experience a significant increase in the volume of the third ventricle compared to rabbits on a diet of 0% cholesterol. Using time-of-flight magnetic resonance angiography, we find cholesterol-fed rabbits also experience a decrease in the diameter of a number of cerebral blood vessels including the basilar, posterior communicating, and internal carotid arteries. Taken together, these data confirm that, despite the inability of dietary cholesterol to cross the blood-brain barrier, it does significantly enlarge ventricular volume and decrease cerebrovascular diameter in the rabbit - effects that are also seen in patients with Alzheimer's disease.

Impact of telephone triage on medical service use: implications for rural and remote areas.

Lack of ready access to health services is a continuing problem for the one-quarter of northern Ontario residents who live in non-urban areas. Teletriage has been proposed to help reduce medically unnecessary visits and thus free-up available resources. A mail survey obtained information about patients' use of teletriage and other health care services, as well as socioeconomic and demographic characteristics. Survey data (n = 2389) were used to determine the impact of teletriage on health service use by asking about the patient's intended use of health care service (intent), the service advised by the nurse (advice), and the actual health service used by the patient (action). Responses were compared among geographic categories based on commuter flows to urban areas in northern Ontario. Survey responses suggest that teletriage may have decreased visits to emergency departments relative to patient intent, and this effect appears to be stronger in communities with weak or no commuter flows (intent = 54%, action = 41%) than in urban areas (intent = 39%, action = 33%). Visits to physicians' offices or clinics may have increased relative to patient intent, but only for non-urban areas (intent = 16%, action = 21% to 23%) with strong, moderate, weak, or no commuter flows. Very little difference was found among geographic categories for calls or visits to other health care providers (overall: intent = 17%, action = 11%) or for informal care (self-care and care for others) (overall: intent = 16%, action = 29%). Results should be interpreted carefully, as there was evidence of selection and social desirability bias.

MRI-assessed volume of cerebellum correlates with associative learning.

Richard F. Thompson's cerebellar model of classical eyeblink conditioning highlights Purkinje cells in cerebellar cortex and principal cells in the deep cerebellar nucleus as the integrating cells for acquisition of conditioned responses (CRs). CR acquisition is significantly slower in rabbits with lesions to cerebellar cortex and in Purkinje cell-deficient mice that lose all cerebellar cortical Purkinje cells. Purkinje cells are the largest neurons in the cerebellum and contribute significantly to cerebellar volume. Magnetic resonance imaging (MRI) was used to assess cerebellar volume in humans. Cerebellar volume was related to eyeblink conditioning (400-ms delay procedure) in 8 adults (21-35 years) and compared to 8 older adults (77-95 years) tested previously (Woodruff-Pak, Goldenberg, Downey-Lamb, Boyko, & Lemieux, 2000). In the young adult sample, there was a high correlation between percentage of CRs in a session and cerebellar volume (corrected for total intracranial volume [TIV], r =.58, p =.066). There were statistically significant age differences in cerebellar volume, t(14) = 8.96, p <.001, and percentage of CRs, t(14) = 3.85, p <.002, but no age difference in TIV. Combining the young and older adult sample, the correlation between percentage of CRs and cerebellar volume (corrected for TIV) was.832 (p <.001). Cerebellar volume showed age-related deficits likely due to Purkinje cell loss. Individual differences in classical eyeblink conditioning are associated with differences in cerebellar volume, supporting Thompson's model of a cerebellar cortical role in facilitating this form of associative learning.

A cellular automaton model of early tumor growth and invasion.

A hybrid cellular automaton model is described and used to simulate early tumor growth and examine the roles of host tissue vascular density and tumor metabolism in the ability of a small number of monoclonal transformed cells to develop into an invasive tumor. The model incorporates normal cells, tumor cells, necrotic or empty space, and a random network of native microvessels as components of a cellular automaton state vector. Diffusion of glucose and H(+)ions (the latter largely resulting from the tumor's excessive reliance on anaerobic metabolism) to and from the microvessels, and their utilization or production by cells, is modeled through the solution of differential equations. In this way, the cells and microvessels affect the extracellular concentrations of glucose and H(+)which, in turn, affect the evolution of the automaton. Simulations of the model demonstrate that: (i) high tumor H(+)ion production is favorable for tumor growth and invasion; however for every H(+)ion production rate, there exists a range of optimal microvessel densities (leading to a local pH favorable to tumor but not to normal cells) for which growth and invasion is most effective, (ii) at vascular densities below this range, both tumor and normal cells die due to excessively low pH, (iii) for vascular densities above the optimal range the microvessel network is highly efficient at removing acid and therefore the tumor cells lose their advantage over normal cells gained by high local H(+)concentration. While significant spatial gradients of glucose formed, no regions of detrimentally poor glucose perfusion (for either cell type) were observed, regardless of microvessel density. Depending on metabolic phenotype, a variety of tumor morphologies similar to those clinically observed were realized in the simulations. Lastly, a sharp transition (analogous to that of the adenoma-carcinoma sequence) between states of initial tumor confinement and efficient invasiveness was observed when H(+)production reached a critical value.

Cerebellar volume in humans related to magnitude of classical conditioning.

Neural circuits in the cerebellum are essential for eyeblink classical conditioning, and hippocampal activation is also present during acquisition. Anatomical (volumetric) brain MRI, delay eyeblink conditioning and neuropsychological tests were administered to eight healthy older subjects. The correlation between cerebellar volume (corrected for total cerebral volume) and conditioned response percentage was 0.81 (p < 0.02), but neither hippocampal nor total cerebral volume correlated with conditioning or any neuropsychological test scores. There was no relationship between age and cerebellar volume, but the correlation between hippocampal volume and age was -0.80 (p < 0.02). These volumetric results add to the increasing evidence in humans demonstrating a relationship between the integrity of the cerebellum and eyeblink classical conditioning.

Nuclear oncology and the Imagene concept.

Over the past 2 decades we have witnessed an explosion of new radioisotopic tracers aimed at detecting, staging and eventually treating tumors. In fact, nuclear oncology has evolved into a field on its own. Aside from aspecific radioisotopic tracers such as thallium 201 or gallium 67, clinicians and oncologists can now use specific radiolabeled monoclonal antibodies and metabolic tracers. In the near future, molecular probes based on the sequencing of the human genome with an exquisite specificity should also become available. In this article, we shall review the most recent developments in this new field.

An infrared device for monitoring the respiration of small rodents during magnetic resonance imaging.

A device that uses infrared reflectometry for monitoring the respiratory waveform of small rodents during MRI was developed. This system uses a photoplethysmograph coupled to the animal by a light pipe to detect movements as small as 1.0 mm. This device can also be used for monitoring larger animals or for controlling respiratory-compensated or respiratory-triggered MRI.

Decomposition of inflow and blood oxygen level-dependent (BOLD) effects with dual-echo spiral gradient-recalled echo (GRE) fMRI.

Image contrast with gradient-recalled echo sequences (GRE) used for fMRI can have both blood oxygen level-dependent (BOLD) and inflow components, and the latter is often undesirable. A dual-echo technique can be used to differentiate these mechanisms, because modulation of signal from inflow is common to both echoes, whereas susceptibility and diffusion-related signal losses are larger in the second echo. An efficient dual-echo interleaved spiral sequence was developed for use with a conventional scanner. It uses a k-space trajectory that spirals out from the origin while the first echo is collected, then spirals back in while collecting the second echo. Decomposition of the data provides separate images of the inflow and T2-weighted components. Results demonstrate the decomposition with phantom experiments and with photic stimulation in normal volunteers.