Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
2000-03-31
2002-03-12
Lateef, Marvin M. (Department: 3737)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
C324S309000
Reexamination Certificate
active
06356781
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to physiology, diagnostics, and neuroscience in general, and, more particularly, to functional magnetic resonance imaging, which is commonly known as “fMRI.”
BACKGROUND OF THE INVENTION
The human brain comprises billions of neurons that interact in a manner that diagnosticians have long sought to fully understand. One fact that is known about the operation of the brain is that the brain responds to a stimulus with a cascade of neuronal events. For the purposes of this specification, a “stimulus” is defined as an agent, action, or condition, either internal or external, that elicits, inhibits, accelerates, or decelerates a physiological or psychological activity or response. A stimulus includes,.but is not limited to visual, audible, tactile, olfactory, sapid, electrical, and chemical input. For example, the brain can receive a stimulus through one of the sense organs or not, as in, for example, the case of neuro-pharmacological agents.
FIG. 1
depicts a diagram of a stimulus that triggers a cascade of neuronal events, as is well-known in the prior art. As shown in
FIG. 1
, each neuronal event is represented by a circle, and each neuronal event is triggered by either: (i) the stimulus, (ii) another neuronal event, or (iii) the confluence of two or more neuronal events. Some neuronal events trigger other neuronal events and some do not. Although the cascade depicted in FIG. I comprises several dozen neuronal events, a typical cascade in the human brain in response to a typical stimulus comprises hundreds or thousands of neuronal events or more.
The topology of a cascade is causal, and, therefore, if the same stimulus is administered to one person under identical circumstances but at different times, the same cascade will occur. Furthermore, because the operation of the brain is considered to be at least partially the result of genetic factors—in contrast to wholly the result of environmental factors—it is hypothesized that if the same stimulus is administered to different people under similar circumstances, a similar cascade will be generated in both people. If true, this hypothesis is useful because it suggests that a variation in a person's observed cascade from the predicted cascade is an indication of a pathological condition in that person.
To determine whether a person's cascade is nominal or not, a diagnostician must be able to: (1) detect and identify each neuronal event that makes up a cascade, (2) detect the sequence (or relative timing) in which the neuronal events that make up the cascade occur, and (3) distinguish the neuronal events that make up the cascade from other contemporaneous neuronal events that are not part of the cascade.
Two well-known techniques for detecting neuronal events are electroencephalography (commonly known as “EEG”) and magnetic encephalography (commonly known as “MEG”). Although these techniques are advantageous for detecting the existence and relative timing of temporally-disparate neuronal events, they are not well-suited for distinguishing between contemporaneous neuronal events.
As is well-known in the prior art, contemporaneous neuronal events can be distinguished from each other based on where in the brain they occur. For example, each neuronal event occurs not throughout the entire brain or at different places in the brain at different times but always at a specific spatially-defined region of the brain. In other words, each neuronal event always occurs in the same region of the brain each time it occurs and nowhere else. This fact is useful because it means that contemporaneous neuronal events can be distinguished based on where they occur (ie., on their spatial disparity).
Another well-known technique for studying brain activity is known as functional magnetic resonance imaging. The principal advantage of functional magnetic resonance imaging over electroencephalography and magnetic encephalography is that it is accurate at detecting whether a neuronal event has occurred at a specific region of the brain or not, and, therefore, it is well-suited to distinguishing between contemporaneous neuronal events.
On the other hand, functional magnetic resonance imaging is disadvantageous in comparison to electroencephalography and magnetic encephalography in several ways. First, it is laborious and slow to use functional magnetic resonance imaging to detect all of the neuronal events that make up a cascade. Second, functional magnetic resonance imaging is not well-suited for detecting the relative timing of neuronal events, which is necessary to ensure that the neuronal events in the cascade occur in the proper sequence. And third, functional magnetic resonance imaging does not directly detect a neuronal event, but only infers its occurrence by detecting some of its physiological effects. For example, a neuronal event at a region of the brain causes hemodynamic and metabolic effects at that region, and it is these hemodynamic and metabolic changes that the magnetic resonance imaging detects. For the purposes of this specification, the term “physiological effect” is defined as a function of a living organism or any of its parts, and explicitly includes: hemodynamic effects or metabolic effects or both. Although neuronal events are well defined temporally, their associated hemodynamic and metabolic effects are not well-defined temporally, and, therefore, it is difficult to precisely detect when a neuronal event occurs by observing either its hemodynamic or metabolic effects.
FIG. 2
depicts a time line that shows the temporal relationship of a stimulus to one of the many neuronal events triggered (either directly or indirectly) by that stimulus and to the hemodynamic and metabolic effects caused by that neuronal event. As shown in
FIG. 2
, a stimulus occurs at time t=t
S
, which triggers a neuronal event at time t =t
E
, which in turn causes an apparent physiological effect some time later. Although the neuronal event is temporally well defined and might last only a few milliseconds, the physiological effect is not temporally well defined and typically occurs many seconds after the neuronal event. Therefore, it is difficult to detect when a neuronal event occurs with high temporal accuracy by observing its physiological effects.
Another well-known technique for studying brain activity is positron emission tomography (commonly known as “PET”) where a patient is injected with a O
15
water injection and neuronal events are detected by observing changes in regional cerebral blood flow (commonly known as “rCBF”). In this sense, positron emission tomography is similar to magnetic resonance imaging, but positron emission tomography does not enable diagnosticians to observe neuronal events in real time.
Therefore, the need exists for a technique that is capable of detecting the occurrence of neuronal events with high temporal accuracy and of distinguishing between contemporaneous neuronal events.
SUMMARY OF THE INVENTION
The present invention is a technique for studying brain activity that avoids some of the costs and disadvantages associated with techniques in the prior art. In particular, the illustrative embodiment of the present invention is a technique that is capable of detecting the occurrence of neuronal events in a brain with high temporal accuracy and of distinguishing between contemporaneous neuronal events. Furthermore, some embodiments of the present invention are advantageous in that they are noninvasive and enable the observation of neuronal events in real time. For these reasons, some embodiments of the present invention might be useful in medicine and neuroscientific research.
In accordance with the illustrative embodiment of the present invention, the brain activity of a subject is tested by observing whether one or more predicted neuronal events (that are part of a cascade of neuronal events triggered by a known stimulus under controlled conditions) do occur when and as expected. In other words, a known stimulus is administered to a subject under contro
Lee Tso Ming
Ogawa Seija
Stepnoski Raymond Aaron
Breyer Wayne S.
DeMont Jason Paul
DeMont & Breyer LLC
Lateef Marvin M.
Lucent Technologies - Inc.
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