Patent Grant
RE48347
The present invention relates to a pulse sequence for use in operating a magnetic resonance imaging apparatus, and in particular for lengthening the usable echo-train duration and reducing the power deposition for spin-echo-train magnetic resonance imaging.
Over the past twenty years, nuclear magnetic resonance imaging (MRI) has developed into an important modality for both clinical and basic-science imaging applications. A large portion of MRI techniques are based on spin-echo (SE) acquisitions because they provide a wide range of useful image contrast properties that highlight pathological changes and are resistant to image artifacts from a variety of sources such as radio-frequency or static-field inhomogeneities.
Spin-echo-based methods can be subdivided into two categories, including those that generate one spin echo for each desired image contrast following each excitation radio-frequency (RF) pulse, and those that generate more than one spin echo for each desired image contrast following each excitation RF pulse. The first category includes, but is not limited thereto, the techniques commonly referred to as “conventional SE” imaging. The second category includes, but is not limited thereto, a method called “RARE” (See Hennig J., Nauerth A., Friedburg H., “RARE Imaging: A Fast Imaging Method for Clinical MR”, Magn. Reson. Med. 1986, 3:823-833; and Mulkern R. V., Wong S. T. S., Winalski C., Jolesz F. A., “Contrast Manipulation and Artifact Assessment of 2D and 3D RARE Sequences”, Magn. Reson. Imaging 1990, 8:557-566, of which are hereby incorporated by reference in their entirety) and its derivatives, commonly referred to as “turbo-SE” or “fast-SE” imaging (See Melki P. S., Jolesz F. A., Mulkern R. V., “Partial RF Echo Planar Imaging with the FALSE Method. I Experimental and Theoretical Assessment of Artifact”, Magn. Reson. Med. 1992, 26:328-341 and Jones K. M., Mulkern R. V., Schwartz R. B., Oshio K., Barnes P. D., Jolesz F. A., “Fast Spin-Echo MR Imaging of the Brain and Spine: Current Concepts”, AJR 1992, 158:1313-1320, of which are hereby incorporated by reference in their entirety). For the purposes of this disclosure, we are primarily interested in the generalized form of techniques in the second category; however the present invention is applicable to the first category as well. The term “generalized” refers to the form of the spatial-encoding gradients that are applied following any given refocusing RF pulse. For example, RARE imaging encodes one line of spatial-frequency space (k-space) data following each refocusing RF pulse using a constant, frequency-encoding magnetic field gradient. In contrast, “GRASE” imaging (See Feinberg D. A., Oshio K. “GRASE (Gradient- And Spin-Echo) MR Imaging: A New Fast Clinical Imaging Technique”, Radiology 1991, 181: 597-602; and Oshio K., Feinberg D. A. “GRASE (Gradient- And Spin-Echo) Imaging: A Novel Fast MRI Technique”, Magn. Reson. Med. 1991, 20:344-349, of which are hereby incorporated by reference in their entirety) encodes three or more lines of k-space data following each refocusing RF pulse using an oscillating, frequency-encoding gradient waveform. This oscillating gradient waveform collects one line of k-space data that includes the spin echo, and one or more additional lines of k-space data before the spin echo and after the spin echo. One skilled in the art would appreciate that there exist an infinite number of possibilities for spatially encoding the MR signal following each refocusing RF pulse. For the purpose of this disclosure, we define the term “spin-echo-train” imaging to encompass all of these possibilities, including, but not limited thereto, RARE, turbo-SE, fast-SE and GRASE imaging, because the present invention deals with, among other things, the RF-pulse history during the echo train, not the details of the spatial encoding.
In general, one of the major goals of technique development for MRI has been to increase the amount of k-space data sampled per unit time, under the constraints of obtaining the desired image contrast and maintaining image artifacts at a tolerable level. Increases in the data rate are typically traded for a decrease in the image acquisition time and/or an increase in the spatial resolution. In this respect, spin-echo-train methods have played an important role; fast-SE imaging is routinely and widely used in clinical MRI.
For instance, the echo trains used in clinical fast-SE imaging generally employ high flip angles (>100°) for the refocusing RF pulses, and their durations are typically less than the T2 relaxation times of interest for short effective echo times (e.g., T1 or proton-density weighting) or less than two to three times these T2 values for long effective echo times (e.g., T2 weighting or “FLAIR”; see Hajnal J. V., Bryant D. J., Kasuboski L., Pattany P. M., De Coene B., Lewis P. D., Pennock J. M., Oatridge A., Young I. R., Bydder G. M., “Use of Fluid Attenuated Inversion Recovery (FLAIR) Pulse Sequences in MRI of the Brain”, J. Comput. Assist. Tomogr. 1992, 16:841-844, of which is hereby incorporated by reference in its entirety). For example, considering brain imaging at 1.5 Tesla, these limits translate to echo-train durations of <100 ms and <300 ms for short and long effective echo times, respectively. When high flip angles are used for the refocusing RF pulses, echo-train durations that are longer than these limits can substantially degrade image contrast and introduce artifacts such as blurring (See Mulkern et al.; Melki et al.; Constable R. T., Gore J. C., “The Loss of Small Objects in Variable TE Imaging: Implications for FSE, RARE and EPI”, Magn. Reson. Med. 1992, 28:9-24; and Ortendahl D. A., Kaufman L., Kramer D. M., “Analysis of Hybrid Imaging Techniques”, Magn. Reson. Med. 1992, 26:155-173, of which are hereby incorporated by reference in their entirety).
Nonetheless, if it were possible to substantially lengthen echo-train durations beyond these limits, while achieving the desired image contrast and limiting artifacts, it would represent a useful and widely applicable advance.
Preliminary studies with the goal of lengthening the echo-train duration in spin-echo-train-based acquisitions have been performed by other researchers. Over a decade ago, Hennig (See Hennig J., “Multiecho Imaging Sequences with Low Refocusing Flip Angles”, J. Magn. Reson. 1988, 78:397-407, of which is hereby incorporated by reference in its entirety) proposed the use of constant, low-flip-angle refocusing RF pulses to introduce a T1 dependence to the evolution of the echo train and thereby lengthen its usable duration. More recently, this concept was extended by Alsop, who derived variable flip-angle series based on the “pseudosteady-state” condition of a constant signal level when T1 and T2 relaxation are neglected (See Alsop D. C., “The Sensitivity of Low Flip Angle RARE Imaging”, Magn. Reson. Med. 1997; 37:176-184, of which is hereby incorporated by reference in its entirety). Alsop also found that the echo-train performance was improved by using a signal evolution that decreased for the first few echoes and was then constant, instead of being constant for the complete echo train. Using these evolutions, artifact-free human brain images with T2-weighting were acquired by Alsop. An 80-echo train with a duration of 400 ms and asymptotic flip angles ranging from 17° to 90° were used.
Turning to the present invention, a method and related apparatus is provided for lengthening the usable echo-train duration for spin-echo-train imaging substantially beyond that achievable with the constant, low-flip-angle or pseudosteady-state approaches. The present invention method and apparatus explicitly consider the T1 and T2 relaxation times for the tissues of interest and thereby permit the desired image contrast to be incorporated into the tissue signal evolutions corresponding to the long echo train. Given the considerable role that spin-echo-train methods already play in MR imaging, the present invention methodology will be of significant importance.
This present invention comprises the methodology, related apparatus, and computer useable medium (readable media) for using a series of refocusing RF pulses with variable flip angles and, optionally, variable phase angles, in a spin-echo-train MRI pulse sequence wherein the flip-angle series is specifically designed to achieve a prescribed signal evolution during the echo train for selected T1 and T2 relaxation times. By employing such a series of refocusing RF pulses, the usable duration of the echo train can be extended substantially beyond that obtainable with conventional methods. This increase in the echo-train duration can be used to decrease the image acquisition time and/or increase the spatial resolution.
In one aspect, the present invention features a method for generating a pulse sequence for operating a magnetic resonance imaging apparatus for imaging an object, the method comprising:
In a second aspect, the present invention features a magnetic resonance imaging apparatus for generating a pulse sequence for operating the apparatus for imaging an object, the apparatus comprising a main magnet system for generating a steady magnetic field; a gradient magnet system for generating temporary gradient magnetic fields; a radio-frequency transmitter system for generating radio-frequency pulses; a radio-frequency receiver system for receiving magnetic resonance signals; a reconstruction unit for reconstructing an image of the object from the received magnetic resonance signals; and a control unit for generating signals controlling the gradient magnet system, the radio-frequency transmitter system, the radio-frequency receiver system, and the reconstruction unit, wherein the control unit generates signals causing:
In a third aspect, the present invention features a computer readable media carrying encoded program instructions for causing a programmable magnetic resonance imaging apparatus to perform the method discussed above in the first aspect of the invention. Similarly, the invention features a computer program product comprising a computer useable medium having computer program logic for enabling at least one processor in a magnetic resonance imaging apparatus to generate a pulse sequence, the computer program logic comprising the method discussed above in the first aspect of the invention.
Because the flip angles for the refocusing RF pulses that are derived with this method are typically much less than 180° for a substantial portion of the total number of RF pulses, the power deposition is much less than that corresponding to 180° RF pulses, which are commonly used in conventional spin-echo-train pulse sequences. This feature is particularly important for high field MRI (>1.5 Tesla), wherein power deposition is a critical pulse-sequence design factor for human applications. The present invention permits long, closely-spaced echo trains to be used for high-field imaging that would not otherwise meet the safety guidelines established by the Food and Drug Administration for power deposition in human MRI.
Another potentially useful feature of the present invention is that, for specific forms of the encoding-gradient waveforms, signals from moving or flowing materials are strongly attenuated, even when the velocities are relatively low. A specific example of this behavior is the attenuation of the signal from cerebrospinal fluid (CSF) surrounding the cervical spinal cord due to its oscillatory motion, which can be used to generate CSF-suppressed T2-weighted MR images of the spinal cord without requiring inversion-nulling of the CSF signal. Studies have indicated that the full range of clinically-relevant cord lesions may not be adequately detected using inversion-nulling of the CSF signal (i.e., FLAIR) (See Hittmair K., Mallek R., Prayer D., Schindler E. G., Kollegger H., “Spinal Cord Lesions in Patients with Multiple Sclerosis: Comparison of MR Pulse Sequences”, AJNR 1996, 17:1555-1565; and Keiper M. D., Grossman R. I., Brunson J. C., Schnall M. D., “The Low Sensitivity of Fluid-Attenuated Inversion-Recovery MR in the Detection of Multiple Sclerosis of the Spinal Cord”, AJNR 1997, 18:1035-1039, of which are hereby incorporated by reference in their entirety).
These and other objects, along with advantages and features of the invention disclosed herein, will be made more apparent from the description, drawings and claims that follow.
The foregoing and other objects, features and advantages of the present invention, as well as the invention itself, will be more fully understood from the following description of preferred embodiments, when read together with the accompanying drawings, in which:
In the following, first presented is an exemplary embodiment of a MR apparatus for practicing the MR methods of the present invention for imaging an object, moving or stationary. Following are descriptions of preferred and alternative embodiments of the methods of the present invention, including their exemplary implementation as computer hardware, firmware, and/or software.
An Exemplary MR-Apparatus of the Present Invention
The MR apparatus also includes a gradient magnet system 3 for generating temporary magnetic fields Gx, Gy and Gz directed in the z-direction but having gradients in the x, y or z directions, respectively. With this magnetic gradient system, magnetic-field gradients can also be generated that do not have directions coinciding with the main directions of the above coordinate system, but that can be inclined thereto, as is known in the art. Accordingly, the present invention is not limited to directions fixed with respect to the MR apparatus. In this application, for ease of description, the directions x, y and z (and the gradients along these directions) are used for the read direction, the phase-encode direction and slice-selection direction (or second phase-encode direction for 3D imaging), respectively.
Also, while traditional commercial methods provide linear gradients in the x, y, or z directions it is also possible not to utilize all three of these linear gradients. For example, rather than using a linear z gradient, one skilled in the art can use a z-squared dependence or some other spatial dependence to provide desired results.
The magnet systems 2 and 3 enclose an examination zone(s) which is large enough to accommodate a part of an object 7 to be examined, for example a part of a human patient. A power supply means 4 feed the gradient magnet system 3.
The MR apparatus also includes an RF transmitter system including RF transmitter coil 5, which generates RF pulses in the examination zone and is connected via transmitter/receiver circuit 9 to a RF source and modulator 6. The RF transmitter coil 5 is arranged around the part of body 7 in the examination zone. The MR apparatus also comprises an RF receiver system including an RF receiver coil which is connected via transmitter/receiver circuit 9 to signal amplification and demodulation unit 10. The receiver coil and the RF transmitter coil 5 may be one and the same coil. The MR apparatus also includes an amplification and demodulation unit 10, which, after excitation of nuclear spins in a part of the body placed within the examination space by RF pulses, after encoding by the magnetic-field gradients and after reception of the resulting MR signals by the receiver coil, derives sampled phases and amplitudes from the received MR signals. An image reconstruction unit 12 processes the received MR imaging signals to, inter alia, reconstruct an image by methods well-known in the art, such as by Fourier transformation. It should be appreciated by one skilled in the art that various reconstruction methods may be employed besides the Fourier Transform (FT) depending on factors such as the type of signal being analyzed, the available processing capability, etc. For example, but not limited thereto, the present invention may employ Short-Time FT (STFT), Discrete Cosine Transforms (DCT), or wavelet transforms (WT). By means of an image processing unit 13, the reconstructed image is displayed, for example, on monitor 14. Further, the image reconstruction unit can optionally process MR navigator signals to determine the displacement of a portion of the patient.
The MR apparatus also includes a control unit 11 that generates signals for controlling the RF transmitter and receiver systems by means of a modulator 6, the gradient magnetic field system by means of the power supply means 4, an image reconstruction unit 12 and an image processing unit 13. In a preferred embodiment, the control unit 11 (and other control elements in the MR apparatus) are implemented with programmable elements, such as one or more programmable signal processors or microprocessors, communicating over busses with supporting RAM, ROM, EPROM, EEPROM, analog signal interfaces, control interfaces, interface to computer-readable media and so forth. These programmable elements are commanded by software or firmware modules loaded into RAM, EPROM, EEPROM or ROM, written according to well-known methods to perform the real-time processing required herein, and loaded from computer-readable media (or computer useable medium), such as magnetic disks or tapes, or optical disks, or network interconnections, removable storage drives, or so forth. The present invention may be implemented using hardware, software or a combination thereof and may be implemented in one or more computer systems or processing systems, such as personal digit assistants (PDAs), for various applications, e.g., remote care and portable care practices.
In a less preferred embodiment, the control unit that directs a MR apparatus for practicing the present invention can be implemented with dedicated electronic components in fixed circuit arrangements. In this case, these dedicated components are arranged to carry out the method described above. For example, the invention is implemented primarily in hardware using, for example, hardware components such as application specific integrated circuits(ASICs). Implementation of the hardware state machine to perform the functions described herein will be apparent to persons skilled in the relevant art(s).
In particular, the control unit commanded by its loaded software causes the generation of MR signals by controlling the application of MR pulse sequences, which comprise RF-pulses, time delays and temporary magnetic-field gradient pulses. These pulse sequences are generated according to the methods of the present invention as subsequently described, and generally include 2D and 3D imaging pulse sequences and optionally navigator pulse sequences for determining the displacement of the patient or material.
Furthermore, according to alternate embodiments of the present invention, the MR apparatus also optionally includes various other units (not illustrated) from which the state of motion of the part of the patient being imaged can be measured. These can include sensors directly indicating the instantaneous state of motion of the part of the patient being imaged, such as a chest belt for directly indicating chest displacement during respiration, or MR-active micro-coils whose position can be tracked, or optical means, or ultrasound means, or so forth. These units can also include sensors indirectly indicating the instantaneous state of motion of the part of the patient being imaged. For example, electrocardiogram and peripheral pulse sensors measure the temporal progress of the cardiac cycle, and permit inference of the actual state of motion of the heart from knowledge of cardiac displacements associated with each phase of the cardiac cycle. When these sensors are present to measure the state of motion, the control unit need not generate navigator pulse sequences.
Moreover, the control unit 11 may also include a communications interface 24. The communications interface 24 allows software and data to be transferred between and among, via communication path (i.e. channel) 28, the control unit 11, reconstruction unit 12, image processing unit 13, and monitor 14 and external devices. Examples of the communications interface 24 may include a modem, a network interface (such as an Ethernet card), a communications port, a PCMCIA slot and card, etc. Software and data transferred via communications interface 24 are in the form of signals which may be electronic, electromagnetic, optical or other signals capable of being received by communications interface 24. The signals are provided to communications interface 24 via the communications path (i.e., channel) 26. The channel 26 carries signals and may be implemented using wire or cable, fiber optics, a phone line, a cellular phone link, a RF link, IR link and other communications channels.
The preferred embodiments of the present invention may be implemented as software/firmware/hardware with various MR apparatuses, and methods, as one skilled in the art would appreciate. Other exemplary apparatuses and methods, but not limited thereto, are disclosed in the following U.S. patents, of which are hereby incorporated by reference in their entirety herein: U.S. Pat. No. 6,230,039 B1—Staber et. al.; U.S. Pat. No. 5,749,834—Hushek; and U.S. Pat. No. 5,656,776—Kanazawa.
The Methods of the Present Invention
Turning now to
Still referring to
For a spin-echo-train pulse sequence, an object of the present invention is to derive a series of refocusing RF pulses with variable flip angles, and, optionally, variable phase angles, that yields a specifically prescribed signal evolution during the echo train for selected T1 and T2 relaxation times. To achieve this, a mathematical model of the pulse sequence, incorporating the specific timing, gradient and RF parameters of choice, is used to calculate the signal evolution during the echo train. This model would typically be implemented in the form of a computer program that is based on the established mathematical equations that describe the behavior of the magnetization during a pulse sequence. See Haacke E. M., Brown R. W., Thompson M. R., Venkatesan R., “Magnetic Resonance Imaging: Physical Principles and Sequence Design”, John Wiley & Sons, New York, 1999, of which is hereby incorporated by reference in its entirety. Other exemplary spin-echo-train MR imaging methods are disclosed in the following U.S. patents, of which are hereby incorporated by reference in their entirety herein: U.S. Pat. No. 5,680,045—Feinberg; U.S. Pat. No. 5,612,619—Feinberg; U.S. Pat. No. 5,541,511—Henning; U.S. Pat. No. 5,315,249—Le Roux et al.; U.S. Pat. No. 5,270,654—Feinberg et al.; U.S. Pat. No. 4,901,020—Ladebeck et al. and U.S. Pat. No. 4,818,940—Henning et al.
Given such a computer-based calculation tool, the process for deriving this flip-angle series can be generally summarized in the following four steps (steps I-IV) briefly discussed below. Firstly, STEP I, the pulse sequence timing parameters (e.g., repetition time, echo spacing(s), other time delays), the pulse sequence magnetic-field gradient configuration, the desired shape of the prescribed signal evolution during the echo train, the T1 and T2 relaxation parameters and the proton density for the “target” tissue, and a target signal intensity are chosen. The signal evolution may assume any physically-realizable shape. Some examples, but not limited thereto, include: a constant; a linear decay; an exponential decay; a linear or exponential decay for the initial portion and a constant for the remainder; and a linear or exponential decay for the initial portion, a constant for the second portion and a linear or exponential decay for the remainder. The T1, T2 and proton density for the target tissue may equal those for a specific biological tissue (e.g., brain gray matter) or material, or they may be arbitrarily chosen. The target signal intensity is the desired signal intensity corresponding to a specific echo in the echo train (e.g., the first or the middle echo).
Secondly, STEP II, the flip angle βi (see
Thirdly, STEP III, the pulse number i is incremented and the second step is repeated until all flip angles for a given echo train are calculated. If, for any value of i, the desired signal intensity for the ith echo interval cannot be achieved, the target signal intensity is reduced and the calculation process is restarted.
Fourthly, STEP IV, if the pulse sequence under consideration requires more than one repetition of the echo train to acquire the desired k-space data, the second and third steps are repeated as necessary until a steady state of the magnetization is reached.
After a given series of variable flip angles are derived, the target signal intensity can be incremented until the maximum value for which the prescribed signal-evolution shape can be realized is reached, thus allowing determination of the maximum signal and/or contrast values that can be obtained for a specific pulse sequence configuration and signal evolution.
Next, exemplary hardware, firmware and software implementations of the methods of the present invention are discussed.
During step 300, flip angles and phases are calculated for refocusing RF pulses that are applied in subsequent data-acquisition steps so as to yield—for selected values of T1 and T2 relaxation times and proton density—a prescribed time course for the amplitudes and phases of the RF magnetic resonance signals that are generated by the refocusing RF pulses.
During step 400, data-acquisition is achieved based on an echo-train acquisition, comprising the following: i) an excitation RF pulse having a flip angle and phase; ii) at least two refocusing RF pulses, each having a flip angle and phase as determined by the calculation step; and iii) magnetic-field gradient pulses that encode spatial information into at least one of the RF magnetic resonance signals that follow at least one of the at least two refocusing RF pulses.
Also, in step 500, magnetization-recovery is provided whereby the magnetization-recovery comprises a time delay to allow magnetization to relax. Finally, as illustrated by step 550, the aforementioned method is repeated until a predetermined extent of spatial-frequency space has been sampled.
It is important to appreciate that the various steps discussed herein need not be performed in the illustrated order, and in fact it may be preferred to perform the steps, at least in part, simultaneously or omit some of the illustrated steps, at least in part.
Next, turning to
Turning to the exemplary contrast-preparation process as shown in
Turning to the exemplary data-acquisition process as shown in
Specific implementations of the present invention methodology are useful to illustrate its nature. These examples are non-limiting and are offered as exemplary only. For this purpose, set forth herein are experimental studies in which the present invention method was used to generate variable-flip-angle series for three-dimensional (3D) T2-weighted MR imaging of the human brain and cervical spine using a “turbo-SE” type (i.e., RARE-as set forth in Henning et al., Magn. Res. Med. 1986, 3:823-833) spin-echo-train pulse sequence, of which is hereby incorporated by reference in its entirety. Brain studies were performed at 1.5 Tesla and 3 Tesla; spine studies were performed at 1.5 Tesla. MR images were obtained using a 1.5-Tesla commercial whole-body imager (MAGNETOM SYMPHONY, Siemens Medical Systems, Iselin, N.J.) or a 3-Tesla commercial whole-body imager (MAGNETOM ALLEGRA, Siemens Medical Systems, Iselin, N.J.). The standard head RF coil supplied with the imager was used. Informed consent was obtained from all subjects prior to imaging.
Turning to
In summary, using the variable-flip-angle series of
Finally, referring to
Next, referring to
Referring to
An advantage of the present invention is that it provides a method, apparatus, and computer useable medium (readable media) to extend the usable duration of the echo train in magnetic resonance imaging pulse sequences such as RARE, turbo-spin-echo, fast-spin-echo or GRASE, substantially beyond that obtainable with conventional methods. This increase in the echo-train duration can be used to decrease the image acquisition time and/or increase the spatial resolution. The power deposition achieved with this technique is much less than that for conventional spin-echo-train pulse sequences, and thus the invention shall be especially useful, among other things, for human imaging applications at high magnetic field strengths.
Another advantage of the present invention is that it improves the imaging of various objects and zones, including the brain. The present invention is also applicable to other regions of the body such as the spinal cord or joints. In particular, the present invention enables high-resolution 3D imaging of the brain with clinically-reasonable acquisition times, which is useful for quantitative imaging of disseminated diseases such as multiple sclerosis. For these diseases, high-resolution 3D imaging provides a valuable tool for monitoring disease progression and response to therapy during treatment or drug trials. The present invention is also useful for non-human applications of magnetic resonance, such as imaging of materials (e.g., plants or food products) or animal models of disease at high field.
Further yet, an advantage of the present invention is that it provides a means to shorten image acquisition times and/or increase spatial resolution for widely-used spin-echo-train magnetic resonance imaging techniques. Such improvements will in turn make it feasible to obtain images with certain valuable combinations of resolution and image contrast which have not been practical heretofore. In addition, the present invention permits spin-echo-train methods to be used for high-field imaging that would not otherwise meet the safety guidelines established by the Food and Drug Administration for power deposition in human MRI.
Finally, another advantage of the present invention method and apparatus is that it explicitly considers the T1 and T2 relaxation times for the tissues of interest and thereby permits the desired image contrast to be incorporated into the tissue signal evolutions corresponding to the long echo train. Given the considerable role that spin-echo-train methods already play in MR imaging, the present invention methodology will be of significant importance.
All US patents and US patent applications cited herein are incorporated herein by reference in their entirety and for all purposes to the same extent as if each individual patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety for all purposes.
The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting of the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced herein.
Notice: More than one reissue application has been filed for the reissue of U.S. Pat. No. 7,164,268. The reissue applications are Ser. No. 16/195,079 (the present application), application Ser. No. 14/708,875 (now U.S. Pat. No. RE47,178), filed May 11, 2015, application Ser. No. 14/053,190 (now U.S. Pat. No. RE45,725), filed Oct. 14, 2013, and application Ser. No. 12/354,471 (now U.S. Pat. No. RE44,644), filed Jan. 15, 2009. The present application is a reissue continuation of application Ser. No. 14/708,875. This application is a national stagereissue continuation of U.S. patent application Ser. No. 14/708,875, filed on May 11, 2015, which is a reissue continuation of U.S. patent application Ser. No. 14/053,190, filed on Oct. 14, 2013 (now, U.S. Pat. No. RE45,725), which was a reissue continuation of U.S. patent application Ser. No. 12/354,472, filed on Jan. 15, 2009 (now, U.S. Pat. No. RE44,644), which was a reissue of U.S. Pat. No. 7,164,268, which issued from U.S. patent application Ser. No. 10/451,124, filed on Jun. 19, 2003 as a U.S. National Stage filing of International Application No. PCT/US01/50551, filed 21 Dec. 2001, which claims benefitpriority under 35 U.S.C. Section 119(e) from U.S. Provisional Patent Application Ser. No. 60/257,182, filed on Dec. 21, 2000, entitled “Spin-Echo-Train MR Imaging Using Prescribed Signal Evolutions,” the entire disclosuredisclosures of which is herebyare incorporated by reference herein. The present application is related to U.S. Pat. No. 5,245,282, filed on Jun. 28, 1991, entitled “Three-dimensional Magnetic Resonance Imaging,” the entire disclosure of which is hereby incorporated by reference herein.
Work described herein was supported by Federal Grant Number NS-35142, awarded by the National Institutes of Health. The United States Government possesses certain rights in and to this invention.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/US01/50551 | 12/21/2001 | WO | 00 | 6/19/2003 |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO02/50574 | 6/27/2002 | WO | A |
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| 7425828 | Garwood et al. | Sep 2008 | B2 |
| 7847551 | Park | Dec 2010 | B2 |
| 8040135 | Cukur et al. | Oct 2011 | B1 |
| 8067936 | Garwood et al. | Nov 2011 | B2 |
| 8228060 | Busse | Jul 2012 | B2 |
| 8258786 | Hennel | Sep 2012 | B2 |
| RE44644 | Mugler, III | Dec 2013 | E |
| RE45725 | Mugler, III | Oct 2015 | E |
| RE47178 | Mugler, III | Dec 2018 | E |
| 20040051527 | Mugler III et al. | Mar 2004 | A1 |
| 20040090230 | Appel et al. | May 2004 | A1 |
| 20080319301 | Busse | Dec 2008 | A1 |
| 20100013479 | Park | Jan 2010 | A1 |
| 20110288402 | Pikkemaat et al. | Nov 2011 | A1 |
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| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. Q—Invalidity of the '644 Patent and 190 Application in view of Haacke 1999. |
| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. R—Invalidity of the '644 Patent and 190 Application in view of Mugler 3D TurboSE Imaging 1999 Disclosure. |
| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. S—Invalidity of the '644 Patent and 190 Application in view of Mugler, Optimized 3D Spin-Echo Imaging 2000. |
| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. T—Invalidity of the '644 Patent and 190 Application in view of the Mugler Advances in 3D MR Imaging 2000 Disclosure. |
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| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. V—Invalidity of the '644 Patent and 190 Application in view of Mugler 1992. |
| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. W—Invalidity of the '644 Patent and 190 Application in view of Mugler, Low-Flip Angle Refocusing RF Pulses 2001 and the Mugler Low-Flip Angle Refocusing RF Pulses 2001 Disclosure. |
| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. X—Invalidity of the '644 Patent and 190 Application in view of Hennig, Hyperechoes Basic Principles 2001. |
| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. Y—Invalidity of the '644 Patent and 190 Application in view of Hennig, Hyperechoes in RARE 2001. |
| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. Z—Invalidity of the '644 Patent and 190 Application in view of Disclosure to Siemens of Draft Mugler, Imaging Using Very Long SE Trains 2000 (UVAPFGE006011-12, marked Confidential (CEO). |
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| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. A—Invalidity of the '644 Patent and 190 Application in view of Mugler, Imaging Using Very Long Spin-Echo Trains 2000 and/or the Mugler Imaging Using Very Long Spin-Echo Trains 2000 Disclosure. |
| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. B—Invalidity of the '644 Patent and 190 Application in view of Mugler, 3D Spin-Echo-Train Imaging 1999 and/or the Mugler 3D Spin-Echo-Train Imaging 1999 Disclosure. |
| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. C—Invalidity of the '644 Patent and 190 Application in view of Mugler, Motion-Artifact-Free Imaging 2000 and the Mugler Motion-Artifact-Free Imaging 2000 Disclosure. |
| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. D—Invalidity of the '644 Patent and 190 Application in view of Schäffter 1994, the Schäffter 1994 Disclosure, and/or the Schäffter 1994 Research. |
| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. E—Invalidity of the '644 Patent and 190 Application in view of Schäffter 1994 Thesis Reference. |
| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. F.—Invalidity of the '644 Patent and 190 Application in view of Alsop, Low Flip Angle RARE Imaging 1997. |
| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. G—Invalidity of the '644 Patent and 190 Application in view of Le Roux 1993. |
| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. H—Invalidity of the '644 Patent and 190 Application in view of U.S. Pat. No. 5,345,176 to Le Roux et al./ U.S. Pat. No. 5,315,249 to Le Roux et al. |
| Invalidity Contention Documents served by Defendant in University of Virginia Patent Foundation v. General Electric Company (Case No. 3:14-CV-00051-NKM-JCH), Exh. I—Invalidity of the '644 Patent and '190 Application in view of Mugler 3D FLAIR Imaging 1999 and/or the Mugler 3D FLAIR Imaging 1999 Disclosure. |
| Number | Date | Country | |
|---|---|---|---|
| 60257182 | Dec 2000 | US |
| Number | Date | Country | |
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| Parent | 14708875 | May 2015 | US |
| Child | 10451124 | US | |
| Parent | 14053190 | Oct 2013 | US |
| Child | 14708875 | US | |
| Parent | 12354471 | Jan 2009 | US |
| Child | 14053190 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 10451124 | Dec 2001 | US |
| Child | 16195079 | US | |
| Parent | 10451124 | Dec 2001 | US |
| Child | 12354471 | US |
