Determining effects of external stimuli on the brain using PET

Abstract

A method of evaluating the effects of administering an external stimuli or treatment such as a psychoactive compound, a drug, or an environmental influence like temperature, noise, vibration, light and similar sensory-perceived influences, on a subject's brain using imaging techniques with position emission tomography (PET). The method measures cerebral metabolism before and after administering the external stimuli or treatment, and employs a behavioral clamp to control behavioral influences on the subject's brain after administration of the external stimuli or treatment.

Description

[0001] This application is a continuation-in-part of application Ser. No. 08 / 522,685 filed Sep. 1, 1995, now U.S. Pat. No. 5,827,499.BACKGROUND OF THE NVENTION[0002] The present invention relates to a method of evaluating the effects of external stimuli, such as pharmaceutical drugs and environmental influences like fragrances, temperature, noise, light, etc. on a subject's brain, and more particularly to a method of evaluating the effects of administering such stimuli on a subject's brain using imaging techniques with position emission tomography (PET).[0003] Position emission tomography (PET) is a radiotracer based method for producing images that qualitatively represent some biochemical property of the body (or portions of the body). In relation to this work, use of PET is confined to metabolic imaging of the brain. Although other methods are often used, the aspect of PET that is relevant to this particular work involves 2-fluoro-deoxyglucose (FDG) as the tracer in studies of cer...

AI Technical Summary

Problems solved by technology

The problem that we are interested in is to determine how certain external stimuli or treatments affect cerebral metabolism.

In actuality, there are a number of experimental difficulties that must be dealt with before this paradigm can be applied.

Even more critically, these factors may change in unknown ways in response to the external stimuli or treatment and hence the extent of their influence on observed metabolism becomes unpredictable.

It can, therefore, be difficult to determine which features of an image are due specifically to the experimental treatment and which are secondary, due to some other change that occurs because of the treatment.

Variation in the testing condition thus could make it difficult to isolate differences introduced by an external stimuli or treatment.

We, however, immediately recognized that this would create a problem.

Some of the drugs that we were planning to study (e.g., ethanol, diazepam) would likely incapacitate subjects to the point where they would not be able to perform the VMT adequately.

However, we were convinced that any dramatic change in behavior as a result of taking a drug would be impossible to interpret (as an extreme example, subjects who are sleeping after a drink of ethanol should not be compared to walking subjects--there would undoubtedly be differences, but these would not be due to the drug but the condition of the subjects).

Therefore, use of the VMT as part of our drug studies necessarily limits the dose of some drugs that can be studied.

However, it does nothing to control mood, another variable that could be different under reference versus external stimuli (e.g. drug treatment) conditions, but as with sleep in the behavioral domain, it would be incorrect to attribute metabolic changes to a drug.

Having deliberately chosen to deal with relatively small signals due to our external stimuli or treatment, we were next faced with the problem of detecting those signals.

In the case of repeated 0-15 scans we have even noticed significant changes in subject positions (up to 5 mm) Within the same session; this problem, of course, is exacerbated when metabolic studies occur in different sessions on different days.

2. The problem of different slices is even more serious when looking at different subjects since anatomical differences will prevent definition of identical ROIs.

At worst, it would only require the studying of a sufficiently large number of subjects to determine effects of any external stimuli (e.g. drug) treatment (this, of course, can be practically impossible, given the cost of PET studies).

Of course there are assumptions and limitations in this volumetric approach, but they are not necessarily worse than those of the slice-based approach.

Images