Electricity: measuring and testing – Particle precession resonance – Using a nuclear resonance spectrometer system
Reexamination Certificate
1998-03-09
2001-01-30
Oda, Christine K. (Department: 2862)
Electricity: measuring and testing
Particle precession resonance
Using a nuclear resonance spectrometer system
C324S309000
Reexamination Certificate
active
06181134
ABSTRACT:
BACKGROUND OF THE INVENTION
Neurodegenerative disorders include Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, and multiple sclerosis. Selective neuronal loss or necrosis is also associated with disorders such as schizophrenia, ischemia, cancer, and stroke. Reduced levels of NAA are also associated with mesial temporal lobe epilepsy.
A dicarboxylic acid found almost exclusively in neurons, N-acetylaspartic acid (NAA) is endogenously localized in the cytoplasm. Formed in the presence of acetyl CoA and a membrane-bound enzyme from brain or spinal cord, NAA is the amino acid or amino acid derivative found in highest concentration in the brain, except for glutamic acid. NAA appears to be metabolically inert in adults and may function as an anion or to effect behavioral changes. The level of NAA correlates with neuronal health. Mapping levels and distribution of NAA in a brain is a noninvasive measure of neuronal density, which is useful in the study, staging, and diagnosis of disorders relating to neuronal injury, loss, or degeneration.
Conventional magnetic resonance spectroscopic imaging (MRSI), or chemical shift imaging (CSI), has been used to map NAA. See, for example, Brown et al.,
Proc. Natl. Acad. Sci. (USA)
79:3523-3526 (1982), and Maudsley et al.,
J. Magn. Reson.
51:147-152 (1983). Spatial and spectral information can be acquired simultaneously by using a time-varying, periodic magnetic field gradient wave form during the data acquisition (Echo Planar-CSI or EPCSI). Mansfield,
Magn. Reson. Med.
1:370-386 (1984). Other approaches include acquiring data from different slices in the brain, and using multiple echoes. Duyn et al.,
Radiology
188:277-282 (1993) and Spielman et al.,
J. Magn. Reson. Imaging
2:253-262, (1992).
These methods provide an NAA map of 16×16 or 32×32 pixels, the latter requiring about 17 minutes by conventional CSI/MRSI techniques. A 256×64 image would take a minimum of 4.5 hours. EP-CSI can acquire a 32×32×16 matrix in a 17 minute scan with degraded spectral resolution. EP-CSI requires post-processing algorithms even more complicated than conventional CSI/MRSI. The acquired data is manipulated and reconstructed with the aid of custom software and a skilled operator.
SUMMARY OF THE INVENTION
The invention features a method for imaging the distribution of a marker compound in a sample, such as living tissue, using magnetic resonance imagining. The method includes i) exciting the tissue to generate magnetic resonance signals, including signals corresponding to the marker compound and ii) suppressing non-marker compound magnetic resonance signals using band selective inversion with gradient dephasing and chemical shift selective pre-excitation. The method can further include iii) encoding the remaining marker compound signal using conventional readout and phase encoding gradients. Examples of marker compounds include n-acetyl aspartic acid, citrate, choline, phosphocreatine, and lactate in mammalian tissue.
One aspect of the invention is a method for imaging the distribution of n-acetylaspartic acid (NAA) in mammalian neuronal tissue. This method includes the steps of (a) exciting the neuronal tissue to generate magnetic resonance signals, including signals corresponding to NAA; and (b) suppressing non-NAA magnetic resonance signals by a combination of band selective inversion with gradient dephasing, and chemical shift selective pre-excitation and dephasing. The suppressing step (b) can suppress magnetic resonances down field from 2.5 ppm. The chemical shift selective pre-excitation can includes an excitation bandwidth of about 1.8 ppm to 2.5 ppm, where the bandwidth includes the water resonance. The band selective inversion can include an excitation bandwidth of about 1.8 ppm to 2.5 ppm. The dephasing can produce a suppression band which includes the water resonance at about 4.7 ppm, the choline resonance at about 3.2 ppm, and the phosphocreatine resonance at about 3.0 ppm.
Embodiments of the invention can further include after the suppressing step (b), the step (c) of encoding the NAA signal with conventional readout and phase encode gradients. This step is an encoding step, in other words, a data acquisition step. One aspect of the invention further includes, after the encoding step (c), the step (d) of reconstructing the image using two-dimensional Fourier transformation to obtain a NAA weighted image. The encoding step (c) has, for example a minimum imaging time of 96 seconds for a spatial encoding matrix of at least 256×64; or a minimum imaging time of between 30 and 260 seconds for a spatial encoding matrix of 256×256. The exciting step (a) can include slice selective spin-echo excitation. An example of slice selective spin-echo excitation includes volume selective double spin-echo excitation (which in turn can include orthogonal slice selection pulses in a double spin echo configuration (
90°-180°-180
° or, alternatively, a STEAM localization configuration (
90°-90°-90
°).
The above methods can be used, for example, to measure citrate in prostate tissue; lactate, choline, or phosphocreatine in any tissue; or n-acetyl aspartic acid, choline, or phosphocreatine in neuronal tissue.
Other features and advantages of the invention will be apparent from the disclosure, figures, and claims below.
REFERENCES:
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Spielman et al., Lipid-suppressed single- and multisection proton spectro
Clark & Elbing LLP
Fetzner Tiffany A.
Oda Christine K.
The McLean Hospital Corporation
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