Electricity: measuring and testing – Particle precession resonance – Using a nuclear resonance spectrometer system
Reexamination Certificate
2001-03-20
2003-03-04
Lefkowitz, Edward (Department: 2862)
Electricity: measuring and testing
Particle precession resonance
Using a nuclear resonance spectrometer system
C324S309000
Reexamination Certificate
active
06528997
ABSTRACT:
FIELD OF THE INVENTION
The present invention is directed to magnetic resonance (MR) imaging and more particularly to such imaging using intermolecular double-quantum coherence (DQC) for soft tissue contrast in human subjects.
DESCRIPTION OF RELATED ART
Intermolecular multiple quantum coherence (iMQC) among water spins is a physical phenomenon that possesses many interesting characteristics. The iMQC originates from dipolar interactions among spatially separated water nuclear spins, and the signal intensity from iMQC depends on, among other things, a correlation distance for the dipolar interactions which can be selected with experimental parameters. The potential use of this signal source to form MR images with novel contrast is tremendous, but very little work has been done in the past, due to a lack of sound understanding of factors affecting the formation, signal-to-noise ratio, and contrast of the images.
One particular form of iMQC is DQC, or double quantum coherence. DQC was mentioned briefly in W. S. Warren et al, “Generation of impossible cross-peaks between bulk water and biomolecules in solution NMR,”
Science
1993; 262:2005-2009. However, that article is primarily concerned with ZQC (zero-quantum coherence) and teaches that the correlation gradient eliminates all but the ZQCs.
Multiple spin echoes (MSEs) and intermolecular multiple-quantum coherences (MQCs) in highly polarized systems have generated tremendous interest but also controversy in the NMR community over the past few years. These phenomena have been described using either classical theory for the demagnetizing field or quantum-mechanical density matrix treatments. To date, both treatments have led to fully quantitative predictions of the signals for simple sequences, such as correlated 2D spectroscopy (COSY) or COSY Revamped by Asymmetric Z gradient Echo Detection (CRAZED) experiments. Warren et al have determined the connection between the demagnetizing field and intermolecular dipolar coupling. The residual dipolar couplings between distant spins are responsible for the dipolar demagnetizing field and give rise to the intermolecular MQCs. From the classical viewpoint, these phenomena are due to the demagnetizing field produced by the spatial modulation of the nuclear magnetization arising in the sample following the second pulse in the CRAZED sequence. Though there are still some theoretical issues which remain to be addressed, intermolecular dipolar interaction effects have lost much of their mystical character and are becoming useful tools in NMR. Recently there has been great interest in the potential of the MQC or MSE contrast mechanisms for MRI because these contrast mechanisms may provide improved detection of tumors and eliminate the need for contrast agent injection.
Warren and co-workers first proposed intermolecular zero-quantum coherence (ZQC) imaging which is insensitive to the magnetic field inhomogeneity and has a relatively higher signal-to-noise ratio (SNR) than other MQCs. They have obtained ZQC images with varying contrast which reveal structural features not seen in, conventional MR images. However, DQC imaging utilizing the prototype sequence 90°-t
1
-{gradient}-90°-{double-area gradient}-t
2
, was believed to be unable to result in meaningful signals from the DQCs with a long detection time t
2
and a short evolution t
1
, which are the preferred conditions for imaging. Navon and co-workers used
1
H double-quantum filtered (DQF) MRI to detect molecules associated with ordered structures, thus identifying a new type of contrast. That method, however, only detects signals from semi-solid constituents and is specific for imaging of connective tissues such as cartilage and tendons. Based on classical demagnetization field theory, van Zijl and co-workers attempted to form an image from the second spin echo, but found that the image had a very low SNR and no detectable contrast even at the high field strength of 4.7 T. Recently, Bifone and co-workers showed that MSE spectroscopic signals in a localized volume can be observed in vivo with a 1.5 T clinical MR scanner. However, the sensitivity of the detected signal was too low for MR Imaging. However, the experimental parameters for the acquisition of the signal from the DQCs were not optimized in these previous reports.
SUMMARY OF THE INVENTION
It is a primary object of the invention to develop an MRI imaging method based on MQC, and in particular on DQC. It is a further object of the invention to develop such an imaging method for soft tissue imaging in humans.
To achieve the above and other objects, the present invention is directed to a method of forming MR images using a source of signals that have previously been considered as either non-existent or too difficult to be detected. Theoretical analysis and computer numerical simulations have been used to characterize the behavior of spins undergoing multiple-quantum coherences (MQCs) and to design an optimal imaging acquisition scheme. The present invention permits double-quantum coherence (DQC) MR images in human brains. The invention also permits human brain multiple-quantum coherence images to be taken using a 1.5T NMR scanner. A theoretical analysis has been carried out, demonstrating how the signals from MQC should change as function of magnetic field strength, and has permitted the determination of the relative sensitivity of MQCs of different transition orders.
A combination of quantum and classical formalisms was used to describe the behavior of the evolution of nuclear spins, including the effects of relaxation and long-range dipolar interactions. Theoretical analysis was used to aid in the design of a DQC imaging sequence with conventional or echo planar imaging acquisitions on a 1.5T clinical scanner.
In spite of the relatively low sensitivity, DQC images of human brains have been obtained for the first time with acceptable signal-to-noise ratio on a whole-body 1.5 T scanner. The theoretical analysis suggests that signals from the intermolecular DQCs have sensitivity better than those from the zero-quantum coherence (ZQCs) for human brain imaging. Signals from non-DQCs were filtered out by selective magnetic field gradients, and signals from ZQCs were further suppressed through application of a two-step cycling of the gradients. Other experimental adjustments such as an adaptive receiver gain, longer TR, and increased acquisition windows were used to maximize the available signal. Images in phantoms and human brains demonstrate that the imaging sequence has excellent selection for the signal from DQCs. These images demonstrate contrast of various brain tissues different from conventional images. It reflects susceptibility variations over adjustable sub-voxel distances. When the pulse sequence was implemented with EPI acquisition, whole brain DQC images of reasonable signal-to-noise ratios can be obtained in less than a minute.
Acquisition of the human brain images based on DQCs in water was successfully achieved for the first time on a 1.5T clinical scanner. The DQC signal provides new contrast for the detection of varying microstructure in soft tissues, which may potentially improve detection of tumors, and supply a new imaging tool for human brain functional studies.
The theoretical analysis shows that the present methods using DQC provide higher sensitivity than what was presented previously by Warren et al using ZQC. This higher sensitivity persists at all imaging field strengths. Experiments confirm the conclusions.
A new methodology is provided for using the DQC to study tumor oxygenation, human brain functional activation, and molecular diffusion imaging.
Pulse sequences, acquisition schemes, and gradient waveforms allow most efficient acquisitions of iMQC signals, and specific quantitation of different parameters.
The present technique will have large impacts on the research and clinical applications in which MRI is used.
Specifically, there are several technical developments which distinguish the present invention over the work of Warren et al:
Chen Zhong
Kwok Wingchi E.
Zhong Jianhui
Blank Rome LLP
Fetzner Tiffany A.
Lefkowitz Edward
University of Rochester
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