AN INTEGRATED LOW FIELD MRI/RF EPRI FOR CO-REGISTERING IMAGING OF IN VIVO PHYSIOLOGY AND ANATOMY IN LIVING OBJECTS

Abstract: A method and apparatus of co-registering images of paramagnetic spin probe distribution, obtained from Electron Paramagnetic resonance imaging (EPRI) with morphological images obtained from Magnetic Resonance Imaging (MRI) in an integrated EPRI/MRI scanner includes a combination of low-field MRI and an Electron Paramagnetic Resonance Imager (EPRI) which utilize the same magnet/gradient coil assembly. Since low-field MRI and EPRI share the same magnetic field for resonance conditions, the operating frequency of EPR will be approximately 650 times higher than the frequency where MRI is performed, which is the ratio of the magnetic moments of the electron vs. proton.

Description: AN INTEGRATED LOW FIELD MRI/RF EPRI FOR CO-REGISTERING IMAGING OF IN VIVO PHYSIOLOGY AND ANATOMY IN LIVING OBJECTS BACKGROUND OF THE INVENTION Obtaining physiological information in a non-invasive manner from living tissue will provide valuable information in the treatment of solid tumors by chemotherapeutic drugs and ionizing radiation. For example, obtaining physiological information such as pO2 in tumors and normal tissue will help the clinician individualize treatment regimens for the effective treatment by using the appropriate scheduling of chemo- or radiation therapies. In addition, non-invasive measurements of tissue pO2 in areas such as cardiac, liver, and kidney tissue will provide both diagnostic and therapeutic assistance in the care of patients. Several invasive means exist to obtain tissue pO2, some of which are in use clinically by probing sites accessible for invasive procedures such as the Clark electrode oxymetry and fine needle aspiration followed by ex-vivo analyses. However, tumors which are not accessible by these techniques are not being treated appropriately. While MRI methods are excellent for providing images with fine anatomic detail, obtaining physiological information co-registered with anatomy with clinically relevant resolution is often not possible. With the use of non-toxic paramagnetic spin probes that can be administered in vivo in saline solutions, Electron Paramagnetic Resonance Imaging (EPRI) has become a useful tool in performing spectroscopic imaging and in obtaining the spatial distribution of oxygen, or the lack of it, with high resolution With the inverse relationship between the sensitivity of EPR detection and tissue oxygenation, EPRI becomes a desirable non-invasive tool for oxygen imaging. While the major advantage of EPRI is the lack of background from voxels not containing the spin probe and thus providing a clear demarcation of the volume containing the spin probe, the disadvantage of EPRI is the lack of proper orientation of the physiological images with respect to anatomy. To overcome this disadvantage, fiducial markers are being used to define the organs being imaged. However, such procedures will be of limited use clinically. SUMMARY OF THE INVENTION According to one aspect of the invention, a low-field MRI module is integrated into an EPRI system to provide an MRI scout image to properly orient the EPRI physiological data with respect to anatomy. According to another aspect of the invention, a common magnet/gradient coil assembly is used for both MRI and EPRI scans. This allows interleaved MRI/EPRI data collection and avoids the need of disturbing the object between scans. Additionally, errors in co-registration of EPRI image to the morphology obtained from the MRI image are minimized. According to a still further aspect of the invention, an MRI probe and an EPRI probe include concentric coils defining a common volume of interest (VOI). According to further aspect of the invention, a common data processor is used to process image data to generate and co-register an EPRI image with MRI morphological information. According to a further aspect of the invention, the RF source for the low field MRI can be derived from the same source as that of the EPR. The low-field MRI comprises MRI transmit and receive circuitry integrated to a data acquisition system suitable for the acquisition speeds compatible with the proton spin-spin and spin-lattice relaxation times. According to another aspect of the invention, the MRI coil will be tuned to an appropriate low frequency for resonance in the range 250 kHz - 2.5 MHz which corresponds to a resonant magnetic field of 6 - 20 mT. According to another aspect of the invention, the EPR resonant frequency will be derived from the same frequency source as that for MRI with the appropriate transmit circuitry integrated. The EPRI coil will be tuned to the resonant frequency of an optimal value in the range of 50 MHz - 400 MHz with a corresponding magnetic field of 5 - 20 mT. According to another aspect of the invention, the EPRI receive circuitry will be integrated with a high-speed data acquisition system compatible with the fast spin- spin and spin-lattice relaxation times. According to another aspect of the invention, the spatial encoding in MRI and EPRI is provided by the same set of a three axes gradient system with a gradient value in the range of 4.0 - 20.0 mT/meter. In MRI the gradient values can be programmed according to standard MRI slice selection methods or according to volume excitation methods. According to a further aspect of the invention, the image reconstruction is accomplished by standard Fourier imaging methods in MRI. In EPRI, the gradients are programmed for projection imaging with static gradients and the gradient orientation changed electrically. Back projection imaging is used to reconstruct the images of the spin probe distribution in EPRI. Co-registration of the EPRI with the anatomical image of the MRI will thus provide an overlay of physiological properties spatially encoded and appropriately co-registered with the anatomy. According to another aspect of the invention, a sequence of such EPRI images after infusion of the spin probe thus provide non-invasively important physiological information such as oxygen imaging and pharmacokinetic imaging of the clearance of redox-sensitive spin probes that reflect tissue redox status. Other features and advantages of the invention will be apparent in view of the following detailed description and preferred embodiments. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a schematic diagram of the protocol of a preferred embodiment of the invention; Fig. 2 A is a block diagram of a preferred embodiment of the invention; Fig. 2B is a flowchart of the steps performed during the operation of a preferred embodiment; Figs. 3A and B are timing diagrams of EPRI and MRI pulse sequences; and Fig. 4A-C are images depicting the process of co-registering EPRI with MRI anatomy. DESCRIPTION OF THE SPECIFIC EMBODIMENTS In the preferred embodiment, a low field MRI module is integrated into an EPRI system. The low field MRI maps the constituent protons in the object and provides a morphological image based on proton density with the appropriate RF circuitry operating at the low frequency. After the MRI scout image is obtained, the paramagnetic spin probe is administered to the object (human, animal or inanimate object) and the EPR Image is collected at the higher frequency. The EPR image corresponds to the spatial distribution of the spin probe. There will be no image intensity from regions where the spin probe does not accumulate. The EPR Images contain spectral information regarding the local physiological conditions such as oxygen status. This data, when overlaid with the morphology image obtained from MRI, co-registers the morphology with physiology. The use of the same magnet/gradient assembly for the scan and an interleaved MRI/EPRI data collection avoids disturbing the object between scans and minimizes errors in co-registration. Figure 1 shows a schematic overview of the experimental protocol 100 to co-register the morphological image from MRI (NMR) with the EPR images. The left side of the overview is the NMR chain 200 which is a component of the MRI scanner and the right side is the constituent of the EPR spectrometer 300 which provides the EPR data. In the middle of the overview are the elements common to MRI and EPRI. The NMR chain 200 includes an NMR Pulse Modulator and Amplifier 210 having an output coupled to the input of an NMR T/R (transmit/receive) Gate 212, a Pulsed Field Gradient Control 214, and an NMR Receiver, Amp. & ADC/Summer 216. The EPR spectrometer side 300 includes an EPR Pulse Modulator & Amp. 310 having an output coupled to the input of an EPR T/R Gate 312, an EPR Field Gradient Control 314, and an EPR Receiver, Amp. & ADC/Summer 316. The common elements are the NMR/EPR RF source, 410, Programmable Timing Unit 412, Power Amp. 414, NMR EPR Resonators, Magnet & Gradient Coil Assembly 416, and a Work Station for Automation and Image Processing 418. Figure 2 A shows the block diagram of the EPRI and MRI parts of the integrated scanner. Elements identical or corresponding to elements in Fig. 1 are given the same reference numbers. The top portion depicts the EPRI chain 300 which implements a standard EPRI protocol and the bottom part the low field MRI (NMR) chain 200 which implements a standard MRI protocol. As in the previous figure, the magnet/gradient coil assembly is the same and the two resonator coils for MRI 215 and EPRI 316 are schematically shown in the figure as separate. The magnet assembly 416 includes a primary magnet 416P for generating a static magnetic field and gradient coils 416G for generating gradient magnetic fields. The operation of the system depicted in Fig. 2 A will now be described with reference to the flow chart of Fig. 2B. The object is placed in NMR and EPR resonator coils 216 and 316 which can be concentric within the magnet/gradient assembly 416 which provide spatial images. The timing sequences can be obtained from the same Programmable Timing Unit 412 for both NMR (MRI) or EPRI. In Fig. 2A the timing sequences for both chains are generated by the computer 418. The MRI coil will be tuned to an appropriate low frequency for resonance in the range 250 kHz - 2.5 MHz which corresponds to a resonant magnetic field of 6 - 20 mT. The MRI coil will be concentric with the EPRI coil with the same volume of interest (VOI). After collecting the MRI scout image of the object to define its anatomy, the EPRI spin probe will be infused and the EPRI image will be collected using the appropriate circuitry. The EPR resonant frequency will be derived from the same frequency source as that for MRI with the appropriate transmit circuitry integrated. The EPRI coil will be tuned to the resonant frequency of an optimal value in the range of 50 MHz - 400 MHz with a corresponding magnetic field of 5 - 20 mT. The image data from both the scans can be processed and images generated from the same work station. The spatial encoding in MRI and EPRI is provided by the same set of a three axes gradient system with a gradient value in the range of 4.0 - 20.0 mT/meter. In MRI the gradient values are programmed according to standard MRI slice selection methods. The image reconstruction is accomplished by standard Fourier imaging methods in MRI. In EPRI, the gradients are programmed for projection imaging with static gradients and the gradient orientation changed electrically. Back projection imaging is used to reconstruct the images of the spin probe distribution in EPRI. Co-registration of the EPRI with the anatomical image of the MRI will thus provide an overlay of physiological properties spatially encoded and appropriately co-registered with the anatomy. More details of the operation of the particular EPRI system disclosed are set forth in the commonly assigned U.S. Patent No. 5,678,548 to Murugesan et al. Figs. 3 A and B are the timing diagram of the individual imaging protocols. Fig. 3B depicts the MRI timing diagram which collects the morphology image with the standard Gradient recalled image from the constituent protons in the object. Fig. 3 A is the timing diagram of the EPRI protocol which shows the EPR data collection sequence. The projection data for imaging in EPR experiments are collected under static gradients. Figs. 4A-C show the co-registration of morphology of the object based on the proton distribution. Fig. 4 A is a proton density map of the object. Fig. 4B is the spin probe distribution from EPR images, which show image intensity from the regions of detectable accumulation of the spin probe. The absence of background makes the interpretation of the image equivocal. However, co-registration of the two images, Fig. 4C, provides guidance to the EPR image from the MRI scan. The invention has now been described with reference to the preferred embodiments. Alternatives and substitutions will now be apparent to persons of skill in the art. In particular, the described implementations of the MRI and EPRI systems are not critical to practicing the invention. Different methodologies may be required depending on the types of tissues and properties to be measured. Additionally, since PET (proton emission tomography) has similar limitations in identifying anatomy, integration of low-field MRI in a PET scanner will overcome these limitations. Accordingly, it is not intended to limit the invention except as provided by the appended claims.

Claims: WHAT IS CLAIMED IS: 1. An integrated MRI/EPRI system comprising: a common primary magnet for generating a static magnetic field; common gradient coils, disposed about said primary magnet, for generating gradient magnetic fields and defining common gradient axes for MRI/EPRI; an EPRI RF probe, disposed within said primary magnet, defining a volume of interest (VOI); an MRI RF probe, disposed with said primary magnet, to define the same VOI; a common RF frequency source for providing RF energy to said EPRI and MRI RF probes; a common programmable timing unti to generate EPRI and MRI pulse sequences; an NMR chain, coupled to said MRI RF probe, said common RF frequency source, and said common programmable timing unti for implementing standard MRI protocols to obtain a scout image of a object placed in the VOI to provide background morphology for co-registering an EPRI image; and an EPRI chain, coupled to said EPRI RF probe, said common RF frequency source, and said common programmable timing unti for forming an EPRI image to be co-registered with the scout image. 2. The system of claim 1, further comprising: a common data acquisition and imaging unit, coupled to the NMR and EPRI chains, for generating and co-registering MRI and EPRI images. 3. The system of claim 1 , wherein said common primary magnet generates a static magnetic field having a value in the range of about 5 to 20 mT. 4. The system of claim 3, wherein: said common gradient coils provide a common set of axes and generate in magnetic field of amplitude in the range of 4.0 to 20.0 mT/meter. 5. The system of claim 1, wherein: said EPRI RF probe includes a coil tuned to resonate at frequencies in the range of about 250 kHz to 2.5 MHz and is concentric with the MRI RF probe, and said MRI RF probe includes a coil tuned to resonate at frequencies in the range of about 50 MHz to 100 MHz. 6. A method for co-registering MRI and EPRI images, said method comprising the steps of: providing a common primary magnet for generating a static magnetic field and common gradient coils, disposed about the primary magnet, for generating gradient magnetic fields; providing an MRI RF probe, disposed within the primary magnet, defining a volume of interest; providing an EPRI RF probe, disposed with said primary magnet, to define the same VOI; placing an object within said VOI; implementing a standard MRI protocol to generate MRI data for forming a scout image defining the morphology of the object; implementing a standard EPRI protocol to generate EPRI data for forming an EPRI image; and processing said EPRI and MRI data to generate and co-register the scout image and the EPRI image. 7. The method of claim 5, further comprising the step of: infusing a spin probe into the object prior to implementing the standard EPRI protocol. 8. The method of claim 5, further including the steps of: setting the static magnetic field to have a value in the range of about 6 to 20 mT when acquiring MRI imaging data; providing excitation pulses having frequencies in the range of 250 kHz to 2.5 MHz to said MRI RF probe when acquiring MRI imaging data; setting the static magnetic field to have a value in the range of about 6 to 20 mT when acquiring MRI imaging data; and providing excitation pulses having frequencies in the range of 50 MHz to 400 MHz to said MRI RF probe when acquiring MRI imaging data. 9. The method of claim 5, further including the step of: utilizing a common set of gradient axes, generated by said common gradient coils, to generate and co-register EPRI and MRI images to overlay physiological properties imaged by EPRI with anatomy imaged by MRI.

Inventors: CHERUKURI MURALI K, COOK JOHN A, DEVASAHAYAM NALLATHAMBY, MITCHELL JAMES B, SUBRAMANIAN SANKARAN, CHERUKURI, MURALI, K., COOK, JOHN, A., DEVASAHAYAM, NALLATHAMBY, MITCHELL, JAMES, B., SUBRAMANIAN, SANKARAN
Applicants: CHERUKURI MURALI K, COOK JOHN A, DEVASAHAYAM NALLATHAMBY, MITCHELL JAMES B, SUBRAMANIAN SANKARAN, US HEALTH, CHERUKURI, MURALI, K., COOK, JOHN, A., DEVASAHAYAM, NALLATHAMBY, MITCHELL, JAMES, B., SUBRAMANIAN, SANKARAN, THE GOVERNMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE DEPARTMENT OF HEALTH AND HUMANSERVICES
Application year: 2000
Main classification: G01R33
IPC codes: G01R33