Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
  • G01R33/48—NMR imaging systems
  • G01R33/4808—Multimodal MR, e.g. MR combined with positron emission tomography [PET], MR combined with ultrasound or MR combined with computed tomography [CT]
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/60—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using electron paramagnetic resonance

Definitions

• 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.
• 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.
• tissue pO2 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.
• tumors which are not accessible by these techniques are not being treated appropriately.
• 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.
• 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
• EPRI With the inverse relationship between the sensitivity of EPR detection and tissue oxygenation, EPRI becomes a desirable non-invasive tool for oxygen imaging.
• 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.
• fiducial markers are being used to define the organs being imaged. However, such procedures will be of limited use clinically.
• 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.
• 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.
• an MRI probe and an EPRI probe include concentric coils defining a common volume of interest (VOI).
• VOI volume of interest
• a common data processor is used to process image data to generate and co-register an EPRI image with MRI morphological information.
• 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.
• 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 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 EPRI receive circuitry will be integrated with a high-speed data acquisition system compatible with the fast spin- spin and spin-lattice relaxation times.
• 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.
• the gradient values can be programmed according to standard MRI slice selection methods or according to volume excitation methods.
• the image reconstruction is accomplished by standard Fourier imaging methods in MRI.
• 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.
• 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.
• 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
• 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.
• 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.
• 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.
• 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.
• FIG. 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.
• NMR low field MRI
• 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.
• MRI Magnetic resonance
• EPRI EPRI
• 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).
• the EPRI spin probe 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.
• the gradient values are programmed according to standard MRI slice selection methods.
• the image reconstruction is accomplished by standard Fourier imaging methods in MRI.
• 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.
• co-registration of the two images, Fig. 4C provides guidance to the EPR image from the MRI scan.

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• 2000
  • 2000-10-31 WO PCT/US2000/030069 patent/WO2001033244A1/en not_active Application Discontinuation
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