Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
2001-03-30
2004-06-15
Robinson, Daniel (Department: 3742)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
C324S307000
Reexamination Certificate
active
06751495
ABSTRACT:
BACKGROUND
1. Field of Invention
The invention generally relates to methods for obtaining, processing and displaying parameters associated with in vivo tissue water diffusion as pathologically significant images using magnetic resonance imaging. More particularly, the invention relates to methods for obtaining and processing diffusion weighted output signals from a magnetic resonance imaging apparatus, and to the fast creation of high definition images of internal bodily tissue(s) utilizing the so processed magnetic resonance output signals.
2. Summary of the Prior Art
Tissue differentiation and localization always have been basic goals of magnetic resonance imaging. Indeed, the desire to distinguish between normal tissue and tumor tissue using magnetic resonance imaging techniques was recognized at least thirty years ago. At that time, it was realized that the spin-lattice, so-called “T1”, as well as the spin-spin, so-called “T2”, relaxation parameters are different between normal and cancerous tissues. Accordingly, by appropriately mapping the various T1 and/or T2 relaxation times determined from magnetic resonance signals of various voxels in an anatomical slice of interest as relative image amplitudes, it was possible to create images generally showing the demarcation of tumor tissue from adjacent normal tissue.
In the intervening time period, methods of obtaining T1- or T2-weighted images using magnetic resonance imaging techniques have improved. In addition, a large amount of experience has been gained in the in vivo application of these methods in conjunction with the use of various paramagnetic contrast agents. In fact, the latter methodology has evolved to the point that presently the use of contrast agent enhanced T1- and/or T2-weighted imaging for the purpose of demarcating tissue boundaries is considered to be basically conventional. Nevertheless, the determination of tumor margins using this “conventional” methodology still is not entirely successful.
More recently, diffusion-weighted magnetic resonance imaging has been proposed as a novel contrast mechanism for demarcating the boundaries of certain tumors. In this regard, so-called “apparent diffusion coefficient” (ADC) maps seem to provide useful information about the structural details of tumors. Hence, there are reports in the literature that suggest that peritumoral edema, solid enhancing, solid necrotic non-enhancing and cystic parts of tumors can be recognized on ADC maps.
Still further, so-called “diffusion tensor imaging” is believed to add information about the directional dependence of molecular diffusion that may prove to be helpful in the demarcation of tumor margins. Again, however, these methods, even when used in conjunction with contrast enhanced T1 and T2 relaxation-weighted imaging, are not totally successful.
To better understand the above concepts, and the acquisition and use of magnetic resonance measurements of in vivo diffusion as contemplated by the present invention, it will be instructive to first generally discuss some basics. First, the concepts of isotropic diffusion, the so-called “diffusion coefficient”, and the measurement of the “diffusion coefficient” with magnetic resonance will be presented in a generalized manner. Second, the concepts of the extension of the definition of diffusion to so-called “anisotropic” diffusion, and the characterization of diffusion with a diffusion tensor, rather than a single coefficient, will be presented. Third, the effects of blood perfusion in the micro-circulatory system as causing deviations in expected magnetic resonance signal behavior will be discussed. Finally, the phenomenon of a departure from the normally adopted magnetic resonance signal behavior when the diffusion encoding range is extended substantially beyond the parameters currently in clinical use will lead to a discussion of the present invention.
First, with regard to isotropic diffusion and its measurement using magnetic resonance, it will be recognized that in a pure liquid such as water at room temperature, the individual water molecules are in constant motion due to the phenomenon of thermal agitation. This phenomenon is commonly referred to as “Brownian motion”. The so-called “diffusion coefficient” (herein sometimes referred to as “D ”) is a measure of this molecular motion, and it can be determined with magnetic resonance techniques.
More particularly, a magnetic field gradient can be used to “tag”atomic level spins in a sample according to their location in space at the time of the application of a first magnetic gradient to the sample. A second gradient, applied at a later time, then serves to probe how far, on average, the individual spins have moved between the time of the first gradient application and the time of the second gradient application. In the ideal case, these magnetic field gradients are applied in brief, strong bursts separated by a common well-defined time period. In practice in clinical magnetic resonance systems, however, the gradients typically are applied for a moderate duration of several tens of milliseconds, and the leading edges of the respective bursts are separated by delays of a similar length of time.
Under these conditions, the diffusion encoding level, i.e., the so-called “b-factor”, is defined by the following relationship:
b=&ggr;
2
G
2
&dgr;
2
(&Dgr;−&dgr;/3)
where &ggr; is the gyromagnetic ratio (42.58 MHz/Tesla for protons), G is the gradient amplitude, &dgr; is the duration of each gradient lobe, and &Dgr; is the separation between lobes. Thus, with one gradient pulse placed prior to and the other following the 180° pulse of a spin echo sequence (90° RF-TE/2-180° RF-TE/2 - acquire), the signal S of the spin-echo measured at echo time TE for isotropic diffusion is given by the mono-exponential relationship:
S=S
0
exp (−
bD
).
In this relationship, S
0
depends upon machine constants, the spin-spin relaxation time T2, the spin-lattice relaxation time T1 in any experiment that repeats measurements every repetition time period TR, and the spin density &rgr;. Specifically, the diffusion coefficient D may be measured by making multiple measurements of S as a function of b, plotting the natural logarithm of S vs. b and then performing a linear regression analysis whose slope provides the experimental measurement of D. The value of b is most conveniently varied by keeping the time delay fixed and incrementing the amplitude G of the magnetic field gradient.
As will be seen from
FIG. 1
, the logarithmic decay of signal intensity from neat solutions of water, ethanol and isopropanol as a function of b derived using a single column sampling technique on a clinical scanner follows a straight-line. This is indicative of mono-exponential decay above the respective baseline noise levels for each of the solutions. The water signal decays the fastest, thereby indicating that it has the highest diffusion coefficient. However, the actual diffusion coefficients measured from the slopes of the decays shown above the base line noise values are in excellent agreement with the published literature for all three samples. Hence, for isotropic diffusion, it may be said that the logarithm of the intensity of the magnetic resonance signal varies linearly with b above a given noise threshold.
Second, the extension of the foregoing concepts to the measurement of tissue water diffusion within the context of magnetic resonance imaging led to certain adjustments in the above-stated theory. Thus, it was quickly realized that in certain organs like the brain, preferred directions of water diffusion exist. More particularly, diffusion along one direction, as selected by the direction of the magnetic field gradient vector could be different than the diffusion along another direction. In the brain, this lack of isotropy of the diffusion coefficient (the so-called “diffusion anisotropy”) was, and is, attributed to the presence of nerve fiber tracts along which water is more free to move than it is in directions perpendicular to these tracts.
Acc
Maier Stephan E.
Mulkern, Jr. Robert V.
Brigham & Womens' Hospital
Edwards & Angell LLP
Neuner George W.
Robinson Daniel
Tucker David A.
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