Patent Application
20090264733
Images can be taken of the body, or certain portions or aspects thereof, using various medical imaging techniques, such as magnetic resonance imaging (MRI), computed tomography (CT), angiography, etc. There exists a need to improve certain aspects thereof.
In the drawings, which are not necessarily drawn to scale, like numerals may describe similar components in different views. Like numerals having different letter suffixes may represent different instances of similar components. The drawings illustrate generally, by way of example, but not by way of limitation, various embodiments discussed in the present document.
The present inventors have recognized, among other things, a system and method for magnetic resonance (MR) contrast using contrast agents having high transverse relaxation rates. In one example, an MR image (MRI) having positive contrast can be generated. In general, positive contrast appears as a bright region in an image and refers to shortened relaxation times on T1-weighted images. Negative contrast, on the other hand, reduces signal intensity and appears as a dark region in an image.
Part 1 includes a description of a magnetic resonance system. Part 2 includes a description of the SWIFT, UTE, and BLAST methodologies. Part 3 includes a description of methods for using a contrast agent.
Magnetic resonance system 100, in one example, depicts an imaging system 100 having magnet 105. In one example, system 100 includes an electron paramagnetic resonance system. Magnet 105 can provide a biasing magnetic field. Coil 115 and subject 110 are positioned within the field of magnet 105. Subject 110 can include a human body, an animal, a phantom, or other specimen. Coil 115, sometimes referred to as an antenna, can include a transmit coil, a receive coil, a separate transmit coil and receive coil, or a transceiver coil. Coil 115 is in communication with transmitter/receiver unit 120 and with processor 130. In various examples, coil 115 both transmits and receives radio frequency (RF) signals relative to subject 110. Transmitter/receiver unit 120 can include a transmit/receive switch, an analog-to-digital converter (ADC), a digital-to-analog converter (DAC), an amplifier, a filter, or other modules configured to excite coil 115 and to receive a signal from coil 115. Transmitter/receiver unit 120 is coupled to processor 330.
Processor 130 can include a digital signal processor, a microprocessor, a controller, or other module. Processor 130, in one example, is configured to generate an excitation signal (for example, a pulse sequence) for coil 115. Processor 130, in one example, is configured to perform a post-processing operation on the signal received from coil 115. Processor 130 is also coupled to storage 125, display 135 and output unit 140.
Storage 125 can include a memory for storing data. The data can include image data as well as results of processing performed by processor 130. In one example, storage 125 provides storage for executable instructions for use by processor 130. The instructions can be configured to generate and deliver a particular pulse sequence or to implement a particular algorithm.
Display 135 can include a screen, a monitor, or other device to render a visible image corresponding to subject 110. For example, display 135 can be configured to display a radial projection, a Cartesian coordinate projection, or other view corresponding to subject 110. Output unit 140 can include a printer, a storage device, a network interface or other device configured to receive processed data.
In nuclear magnetic resonance (NMR, also abbreviated as magnetic resonance, MR), RF excitation can be described as sequential, simultaneous, and random. Three different corresponding NMR techniques are used, including continuous wave (CW), pulsed, and stochastic.
Pulsed FT spectroscopy can be used with high resolution NMR. MRI has additional technical requirements over high resolution NMR. Because the objects of interest are much larger than a test tube, inevitably the static and RF fields used in MRI are more inhomogeneous than those used in high resolution NMR.
As in CW, the SWIFT method uses RF sweep excitation and uses a sweep rate that exceeds the sweep rate of the CW method by more than a few orders of magnitude. Unlike the CW method in which the signal is acquired in the frequency domain, in SWIFT, the signal is considered as a time function, as in the pulsed FT method. In addition, SWIFT uses the correlation method similar to stochastic NMR in order to extract proper spectral information from the spin system response.
The rapid-scan FT technique and SWIFT technique have some common properties but are different in point of view to system response on excitation. Rapid-scan FT considers the system response in frequency domain and SWIFT considers the system response in the time domain. As a result, the spectra obtained using SWIFT is insensitive to the linearity of the sweep rate. This permits use of a broad class of frequency modulated pulses having more uniform excitation profiles than the chirp excitation required in rapid-scan FT. SWIFT also provides virtually simultaneous excitation and acquisition of signal. Accordingly, SWIFT has a “zero echo time”, and so is well-suited for studying objects having very fast spin-spin (or transverse) relaxation (or very short T2). SWIFT allows analysis of R1 (T1) while substantially mitigating the effects of R2. SWIFT can be used for MRI of quadrupolar nuclei, such as sodium-23, potassium-39, and boron-11.
According to one example, a short T2 (or T2*) value is less than approximately 5 ms. As such, a T2 value of less than 5 ms may present difficulties for gradient-echo (GRE) magnetic resonance imaging. A particularly short T2 (or T2*) value is less than, for example, 1 ms. On the other hand, SWIFT can be used for MR imaging with a T2 (or T2*) value shorter than 5 ms or shorter than 1 ms. Stated differently, an R2 (or R2*) greater than 200 is considered large and a particularly large value would be greater than 1,000.
SWIFT can be modeled by the method presented in
SWIFT provides novel and beneficial properties for MRI, including the following:
(a) fast: SWIFT eliminates the delays associated with refocusing pulses or gradient inversion, and also time for an excitation pulse, which is integrated with the acquisition period. As in other fast imaging sequences, SWIFT is limited by existing imaging system hardware and chosen compromise between acquisition speed, spatial resolution and SNR.
(b) sensitive to short T2: SWIFT is sensitive to excited spins having T2>1/SW (SW=spectral width). To be specifically resolved, T2>N/SW must be satisfied, which is theoretically feasible even for solid objects by increasing SW.
(c) reduced motion artifacts: Because SWIFT has no “echo time” it is less sensitive to motion artifacts. It loses less signal due to either diffusion in the presence of a gradient or uncompensated motion than other fast sequences.
(d) reduced dynamic range requirement: Because the different frequencies are excited sequentially the resulting signal is distributed in time with decreased amplitude of the acquired signal. This allows more effective utilization of the dynamic range of the digitizer.
(e) quiet: SWIFT uses a small step when changing gradients between projections, and thus, fast gradient switching that creates loud noise can be avoided. SWIFT can also be operated in rapid updated mode to reach high temporal resolution in dynamic studies. This pseudo-temporal resolution is possible because projection reconstruction, unlike Fourier imaging, samples the center of k-space with every acquisition.
An ultrashort echo-time (UTE) pulse sequence can be used for imaging tissues or tissue components having a small value spin-spin (transverse) relaxation time T2. With UTE imaging, the radio frequency pulse duration is of the order T2 and the rotation of tissue magnetization into the transverse plane is incomplete. Typically, UTE entails rapid data acquisition and a TE can be approximately 0.08 ms. An example of a UTE pulse sequence includes a half excitation pulse and radial imaging from the center of k-space. Variations of UTE can be tailored to suppress fat or for imaging short or long T2 components.
A pulse sequence described as Back-projection Low Angle ShoT (BLAST) can be used for fast imaging of liquids and solids. BLAST is typically associated with imaging of animals and is based on low angle pulse excitation in combination with back-projection reconstruction. BLAST, like UTE and like SWIFT, is suitable for use in imaging tissue or components having short T2.
At 320, method 300 includes generating magnetic resonance data. The data can be generated using a pulse sequence or protocol having a short dead time. Examples of MR protocols can include SWIFT, UTE, and BLAST.
Consider an example of method 300 using an in-vivo wild type mouse brain.
As shown in the figure, at 310, the contrast agent can injected. In one example, the contrast agent includes an intravenously administered bolus of mono-crystalline ion oxide nano-particle solution, sometimes referred to as MION-47. MION-47 has both R1 and R2* relaxivity, but the R2* relaxivity typically dominates at high concentrations and/or high fields (e.g., the R1 and R2 values are approximately 29 and 60 mMsec-1 at 0.47 T, 39° C.).
At 320, a magnetic resonance (MR) technique is used to generate data for the subject. An example of an MR technique includes SWeep Imaging with Fourier Transform (SWIFT). High field and high concentration R1 induced positive T1 contrast can be generated using a MION-47 dose of 5 mg/kg and 20 mg/kg.
As noted elsewhere in this document, SWIFT is a novel radial imaging sequence utilizing gapped frequency-swept pulse excitation and nearly simultaneous signal acquisition in the dead time between the gaps. SWIFT utilizes the correlation method which removes phase differences due to the time of excitation and produces free induction decay (FID) data as if the spins were simultaneously excited by a short duration pulse. SWIFT has an intrinsically short dead-time, for example, ˜5-15 μs. SWIFT, as with UTE and BLAST, provides good sensitivity to very fast relaxing spins (short T2 or T2*).
In one example, a wild type mouse (20 g) can be anesthetized with 2% Isoflurane, catheterized with pre-loaded line of 10:1 dilution of MION-47 and placed in a 9.4 T 31 cm bore animal magnet. The animal can be placed in a heated holder and quadrature surface coil with two ˜1 cm loops at a location about 2 mm from the top of the head. A syringe reservoir of 0.5 cc of the diluted MION-47 can terminate the I.V. line. A pre-injection series of SWIFT images can be acquired during an initial 20 minute segment, and then MION solution can be injected slowly by hand to 5 mg/kg dose (100 μL). After approximately 10 minutes, a post contrast series of SWIFT images can be taken over a duration lasting approximately 30 minutes, and then another 300 μL bolus of MION dilution can be injected for a total dose of 20 mg/kg. Post second bolus imaging was acquired during next 30 minutes.
One example of a method allows T1 weighted imaging in the presence of large R1 relaxation. In the following, S denotes the system, S0 denotes the thermal equilibrium magnetization signal, and R2** (sometimes referred to as R2† or R2 dagger) denotes inhomogeneity.
For example:
S=S
0(1−exp(−TR/T1))exp(−TE/T2*)
In SWIFT, the TE˜=0, so the contrast becomes:
S=S
SS(1−exp(−TR/T1))
A typical non-short T2 sensitive sequence has exp(−TE/T2*)=0 when R2*=1/T2* is large.
In the example described herein, a series of images summarize the results. In the image datasets, the bandwidth (for excitation of base-band and acquisition) is 62.5 kHz. Each 3D radial SWIFT dataset includes 32,000 unique FID views (spokes). Duty cycle used for excitation Hyperbolic Secant pulse was 25%. TR was 6.1 ms with 4.1 ms of acquisition time included. The diameter of field of view (FOV) was 3 cm. Total time for each image was 3.5 minutes including steady state scans. Processing of the SWIFT data was accomplished by correlation with the RF shape file, and data driven RF distortion correction. The radial reconstruction was accomplished by gridding with 1.25× over-sampled width 2.5 Kaiser-Bessel kernel and 1/r2 density weighting.
Positive T1 contrast with Fe nanoparticles in a wild type mouse brain, in-vivo, can be generated using the present subject matter.
In certain examples, this system or method can allow for positive contrast (bright, hyperintense, or enhancing) image features to be obtained from contrast agents that with existing MRI methods would yield negative contrast (dark, or hypointense) image features. A short T2 sensitive method such as SWIFT, Ultra-short Time of Echo (UTE), or Back-projection Low-Angle shot (BLAST) MRI can be performed before, during, or after injection of a bolus or infusion of contrast agent. The contrast agent can produce a significantly higher R2 (transverse relaxation rate constant) value than Gd based agents and still yield positive contrast (enhancement) in the tissues or organs of interest.
In an example, the contrast agents can include an iron (Fe) based contrast agent (e.g., a mono-crystalline ion oxide nano-particle solution such as MION-47), a manganese (Mn) based contrast agent, a dysprosium (Dy) based contrast agent, or other contrast agent. In certain examples, the contrast agent can include a small particle iron oxide (or superparamagnetic iron oxide) (SPIO) (e.g., Ferridex, or Ferrum oxide), ultra small particle iron oxide (or ultrasmall superparamagnetic iron oxide) (USPIO), labeled, unlabeled, or other contrast agents.
In certain examples, the contrast agents can include one or more contrast agent illustrated in Table 1, below.
In an example, the present subject matter can include magnetic resonance (MR) clinical dynamic contrast enhancement (DCE) imaging, Magnetic Resonance Angiography (MRA), or other T1 weighted contrast enhanced MRI.
The present system and method allows the use of high R2 agents, such as Fe based agents. An example of the present subject matter does not rely on a low R2 value contrast agent such as those based on Gadolinium (Gd).
Gd based contrast agents may have side effects in some patients, such as Nephrogenic Systemic Fibrosis (NSF). The method embodied in this document allows many types of contrast agents (including non-Gd based agents) to be used for positive contrast MRI procedures. Iron (Fe) nanoparticle based agents can be used to attach multiple ligands (functionalization) and have additional degrees of freedom (such as size and shape) to fine tune the contrast mechanism. An example of the present subject matter does not rely on off-resonance pre-pulsing, intermolecular multiple quantum coherence or other filtering methods that may degrade the signal intensity and do not directly detect the T1 weighted signal.
In one example, the MR scanner is configured to apply a longitudinal relaxation time (T1) sensitive magnetic resonance imaging (MRI) pulse waveform on at least a portion of a subject and acquire a positive contrast image from the at least a portion of the subject. In an example, the acquired positive contrast image results from interaction with a contrast agent having a high transverse relaxation rate (R2).
In other examples, one or more other system or method described herein can be implemented using an MR scanner, or one or more other component, such as a processor or other controller, a memory device, a display, or other device configured to assist in acquiring a positive contrast image from at least a portion of a subject.
In certain examples, the system or method described herein can be implemented using a set of instructions in a computer-readable medium or machine readable medium.
In certain examples, the contrast agent can have both R1 and R2 (and R2*) relaxivity, but can be quantified predominantly by R1 relaxivity. Further, the contrast agent can be injected into the vasculature, can be injected into a tissue, can be expressed as part of a reporter gene system, or can be intrinsic to a tissue (e.g., including Iron containing plaques). In other examples, one or more cell can be labeled with the contrast agent or be injected.
Further, any bodily tissue can be imaged using the system or method disclosed herein, generally including the vasculature (e.g., using angiography, in any part of the body), or including, but not limited to, the brain, the heart, the extremities, the liver, the kidney, the spleen, etc. In certain examples, the liver, the spleen, or other high natural Fe content tissue can be analyzed.
In an example, cancer in any part of the body can be analyzed suing the system or method disclosed herein, including the brain, breast, lung, liver, bone, etc. In certain examples, this can be accomplished utilizing pre-contrast and post-contrast subtraction, or dynamic (pre-contrast and multiple post-contrast time course images), or perfusion imaging using pre and one or more post-contrast timed doses.
The above detailed description includes references to the accompanying drawings, which form a part of the detailed description. The drawings show, by way of illustration, specific embodiments in which the invention can be practiced. These embodiments are also referred to herein as “examples.” All publications, patents, and patent documents referred to in this document are incorporated by reference herein in their entirety, as though individually incorporated by reference. In the event of inconsistent usages between this document and those documents so incorporated by reference, the usage in the incorporated reference(s) should be considered supplementary to that of this document; for irreconcilable inconsistencies, the usage in this document controls.
In this document, the terms “a” or “an” are used, as is common in patent documents, to include one or more than one, independent of any other instances or usages of “at least one” or “one or more.” In this document, the term “or” is used to refer to a nonexclusive or, such that “A or B” includes “A but not B,” “B but not A,” and “A and B,” unless otherwise indicated. In the appended claims, the terms “including” and “in which” are used as the plain-English equivalents of the respective terms “comprising” and “wherein.” Also, in the following claims, the terms “including” and “comprising” are open-ended, that is, a system, device, article, or process that includes elements in addition to those listed after such a term in a claim are still deemed to fall within the scope of that claim. Moreover, in the following claims, the terms “first,” “second,” and “third,” etc. are used merely as labels, and are not intended to impose numerical requirements on their objects.
Method examples described herein can be computer-implemented at least in part. Some examples can include a computer-readable medium or machine-readable medium encoded with instructions operable to configure an electronic device to perform methods as described in the above examples. An implementation of such methods can include code, such as microcode, assembly language code, a higher-level language code, or the like. Such code can include computer readable instructions for performing various methods. The code can form portions of computer program products. Further, the code can be tangibly stored on one or more volatile or non-volatile computer-readable media during execution or at other times. These computer-readable media can include, but are not limited to, hard disks, removable magnetic disks, removable optical disks (e.g., compact disks and digital video disks), magnetic cassettes, memory cards or sticks, random access memories (RAM's), read only memories (ROM's), and the like.
The above description is intended to be illustrative, and not restrictive. For example, the above-described examples (or one or more aspects thereof) can be used in combination with each other. Other embodiments can be used, such as by one of ordinary skill in the art upon reviewing the above description. The Abstract is provided to comply with 37 C.F.R. §1.72(b), to allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. Also, in the above Detailed Description, various features can be grouped together to streamline the disclosure. This should not be interpreted as intending that an unclaimed disclosed feature is essential to any claim. Rather, inventive subject matter can lie in less than all features of a particular disclosed embodiment. Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separate embodiment. The scope of the invention should be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.
This patent application claims the benefit of priority, under 35 U.S.C. Section 119(e), to Curtis A. Corum et al, U.S. Provisional Patent Application Ser. No. 61/045,927, entitled “POSITIVE CONTRAST MRI USING HIGH TRANSVERSE RELAXATION RATE CONTRAST AGENT,” filed on Apr. 17, 2008 (Attorney Docket No. 00600.721PRV), which is incorporated herein by reference.
This invention was made with government support under award number BTRR P 41 RR008079 from the National Institutes of Health (NIH). The government has certain rights in this invention.
| Number | Date | Country | |
|---|---|---|---|
| 61045927 | Apr 2008 | US |
