Systems and methods for detecting glucose metabolism in a patient

Abstract

The invention is entitled "System and method for detecting glucose metabolism in a patient." A method for detecting glucose metabolism in a patient is disclosed. The method includes generating a magnetic field that acts on the patient, and then acquiring magnetic resonance data of deuterated water in the patient, wherein deuterated glucose has been administered to the patient, wherein the deuterated water is produced during metabolism of the deuterated glucose by the patient, and wherein the magnetic resonance data is acquired at a resonance frequency of deuterium. The method further includes analyzing the magnetic resonance data acquired at the resonance frequency of non-spectrally resolved deuterium to generate a processed data set. The method further includes constructing an image based on the processed data set, wherein glucose metabolism in the patient is detected via the constructed image.

Description

Technical Field

[0001] This disclosure generally relates to systems and methods for detecting glucose uptake in a patient, and more specifically to the use of magnetic resonance imaging without requiring spectral resolution data to detect deuterated glucose and its uptake and metabolism. Background Technology

[0002] This disclosure generally relates to the use of magnetic resonance (MR) spectroscopy and magnetic resonance imaging (MRI) for detecting and measuring physiological processes in a patient.

[0003] Magnetic resonance spectroscopy and imaging techniques are generally known in the fields of medical diagnostics and medical imaging. Typically, MR techniques involve subjecting a patient to a uniform magnetic field within which the spins of magnetically responsive materials precess at specific frequencies depending on the strength of the magnetic field and the type of magnetically responsive material. The uniform magnetic field also causes the spin poles of the magnetically responsive materials within the patient to preferentially align in the direction of the magnetic field. A superconducting primary electromagnetic coil cooled by a cryostat filled with liquid helium can be used to generate this uniform magnetic field. Shimming coils can also be used to provide fine-tuning of the overall homogeneous, uniform magnetic field within the aperture of the MR scanner. Magnetic gradient coils can also be provided to spatially alter the magnetic field, such that different spatial positions of the magnetically responsive materials become associated with different precession or resonant frequencies. The magnetic field generated by the magnetic gradient coils can be pulsed, thus producing slight but predictable variations in the overall magnetic field within the aperture.

[0004] The patient is then subjected to intermittent pulses of one or more radio frequency (RF) pulses, which tilt the spins of the magnetically responsive material into a plane transverse to the uniform magnetic field. Once these excitation RF pulses are interrupted, the spins of the magnetically responsive material realign with the uniform magnetic field. Magnetic resonance data can be collected during this realignment process as the magnetically responsive material emits a resonant signal. Different nuclei of the magnetically responsive material can be identified as having different resonant frequencies upon returning to the realigned state. The same RF coil can both transmit RF pulses and receive magnetic resonance data generated by the spin-magnetically responsive material in response to the magnetic field and these RF pulses. In some cases, dedicated RF coils are used to transmit RF pulses, and separate RF coils are used in combination to detect resonant signals.

[0005] Exemplary magnetically responsive materials in a patient's body include hydrogen (H), deuterium (2H), or carbon-13 (13C) atoms, where the difference between protons and neutrons creates an electron cloud imbalance that causes the material to respond to a magnetic field. Different nuclear materials have different imbalances, resulting in different spin frequencies, which distinguish different substances from others. When the responsive material (whether it is hydrogen or carbon-13 atoms) is a molecular component, the electron cloud of the molecules affects the strength of the magnetic field experienced by the responsive material. This variation in the effective magnetic field strength results in a small change in the spin precession frequency. This change in precession frequency manifests as a chemical shift that allows different molecules containing the responsive material to be distinguished from each other. For example, hydrogen atoms in a water molecule and hydrogen atoms in a lipid molecule have different spin precession frequencies, resulting in different resonance frequencies under a uniform magnetic field, and this difference (chemical shift) allows for the identification and potential quantification of these two different molecules in vivo using magnetic resonance methods.

[0006] An exemplary MR system or MR scanner known in the art is the GE Healthcare 3T GE MR750 scanner equipped with multi-core spectroscopy hardware. Additional information regarding MR systems, imaging, and spectroscopy can also be found in U.S. Patent Nos. 8,933,697, 9,283,317, 7,795,868, and 8,968,703, and U.S. Patent Application Publication No. 2019 / 0094316, the entire contents of which are incorporated herein by reference. Summary of the Invention

[0007] This summary is provided to introduce a series of concepts that will be further described in the detailed embodiments below. This summary is not intended to identify key or essential features of the claimed subject matter, nor is it intended to help limit the scope of the claimed subject matter.

[0008] One embodiment of this disclosure generally relates to a method for detecting glucose metabolism in a patient. The method includes generating a magnetic field acting on the patient, then acquiring magnetic resonance data of deuterated water within the patient, wherein deuterated glucose has been administered to the patient, wherein deuterated water is produced during the patient's metabolism of the deuterated glucose, and wherein the magnetic resonance data is acquired at the resonance frequency of deuterium. The method further includes analyzing the magnetic resonance data acquired at a non-spectrally resolved resonance frequency of deuterium to generate a processed dataset. The method also includes constructing an image based on the processed dataset, wherein the patient's glucose metabolism is detected via the constructed image.

[0009] Another implementation typically involves a magnetic resonance imaging (MRI) scanner configured to detect glucose metabolism in a patient. The MRI scanner includes a magnetic coil system configured to generate a magnetic field acting on the patient. An acquisition system is configured to acquire magnetic resonance data of deuterated water produced within the patient during the metabolism of deuterated glucose administered to the patient, in response to the magnetic field, and wherein the magnetic resonance data is acquired at the resonant frequency of deuterium. A data analysis system is configured to analyze the magnetic resonance data acquired at the non-spectrally resolved resonant frequency of deuterium to generate a processed dataset. An image construction system is configured to construct images based on the processed dataset. The patient's glucose metabolism is detected via the constructed images.

[0010] Another implementation generally involves a method for detecting glucose metabolism in a patient. This method includes preparing deuterated glucose by binding deuterium to the carbon atoms of its pyranose ring, and then administering the deuterated glucose to the patient. The method also includes generating a magnetic field acting on the patient and acquiring magnetic resonance data of deuterated water within the patient's body, wherein the deuterated water is produced during the patient's metabolism of deuterated glucose, and wherein the magnetic resonance data is acquired only at the resonance frequency of deuterium, and specifically at the chemical shift of the deuterated water. The method further includes analyzing the magnetic resonance data acquired at the non-spectrally resolved resonance frequency of deuterium to generate a processed dataset, and then constructing an image based on the processed dataset. The patient's glucose metabolism is detected via the constructed image.

[0011] In some implementations, magnetic resonance data is acquired via gradient echo imaging.

[0012] In some implementations, magnetic resonance data is collected in less than 10 minutes.

[0013] In some embodiments, the magnetic resonance data are delayed magnetic resonance data acquired after a delay following administration of deuterated glucose to the patient, and also include baseline magnetic resonance data of deuterated water in the patient's body acquired before the deuterated glucose is metabolized by the patient, wherein analyzing the magnetic resonance data includes subtracting the baseline magnetic resonance data from the delayed magnetic resonance data to generate a processed dataset. In another embodiment, the delay time is at least 10 minutes.

[0014] Some implementation schemes also include: analyzing magnetic resonance data by applying diffusion weighting.

[0015] In some implementations, magnetic resonance data are fully acquired after the patient is given deuterated glucose.

[0016] In some implementations, the generated image is based on a processed dataset without requiring spectral resolution of individual peaks in the deuterium spectrum.

[0017] In some implementations, images are generated without using data from ionizing radiation sources.

[0018] In some embodiments, the acquisition system is configured to acquire magnetic resonance (MRI) data via gradient echo imaging. In another embodiment, the acquisition system acquires MRI data for less than 10 minutes. In yet another embodiment, the MRI data is delayed MRI data acquired after a delay following administration of deuterated glucose to the patient, wherein the acquisition system is further configured to acquire baseline MRI data of naturally abundant deuterated water in the patient's body before the deuterated glucose is metabolized by the patient, and wherein the data analysis system is further configured to subtract the baseline MRI data from the delayed MRI data to generate a processed dataset. In yet another embodiment, the delay time is at least 10 minutes.

[0019] In some implementations, the data analysis system is configured to analyze the magnetic resonance data via diffusion weighting. In other implementations, the magnetic resonance data is acquired completely after administration of deuterated glucose to the patient.

[0020] In some implementations, the generated image is based on a processed dataset without requiring spectral resolution of individual peaks in the deuterium spectrum.

[0021] In some implementations, images are generated without using data from ionizing radiation sources.

[0022] In some implementations, the magnetic resonance data is collected in less than 10 minutes, and the process also includes using diffusion-weighted analysis of the magnetic resonance data collected for deuterated water before constructing the image, wherein the processed dataset from which the image is generated is generated without spectral resolution of individual peaks in the deuterium spectrum, and the image is generated without using data from an ionizing radiation source.

[0023] Various other features, objects, and advantages of this disclosure will become apparent from the following embodiments, taken in conjunction with the accompanying drawings. Attached Figure Description

[0024] This disclosure is described with reference to the following figures.

[0025] Figure 1 This is a schematic diagram of an exemplary magnetic resonance imaging (MRI) scanner and system configured according to this disclosure;

[0026] Figure 2 This is a graph illustrating magnetic resonance data acquired from an MRI, where the data is spectrally resolved to identify the amplitudes of metabolites at various chemical shifts known in the art.

[0027] Figure 3 This is an exemplary method for detecting glucose metabolism according to the present disclosure;

[0028] Figure 4 This is another exemplary method for detecting glucose metabolism according to the present disclosure;

[0029] Figure 5 This is a graph showing magnetic resonance data of deuterated water analyzed at the natural or resonant frequency of deuterium according to this disclosure, with no spectrally resolved signals from any deuterated metabolites; and

[0030] Figure 6 It can be combined with Figure 1 A schematic diagram of an exemplary control system within the system shown. Detailed Implementation

[0031] The detection of changes in carbon metabolism has been used in various imaging modalities to diagnose diseases. For example, fluorodeoxyglucose-positron emission tomography (FDG-PET) utilizes the fact that many types of cancer cells have increased glucose uptake relative to “normal” cells, thus providing a basis for diagnostic imaging of primary and metastatic tumors. However, the inventors have recognized that PET imaging as a whole is limited by analogs of biological substrates and cannot inform the patient about the actual metabolism of molecules. For example, the most commonly used PET reagent, fluorodeoxyglucose, or FDG, is an analog of glucose in which the hydroxyl group of glucose is replaced by fluorine-18. This modification results in FDG not being metabolized in the same way as unmodified glucose.

[0032] MR metabolic imaging with 13C-rich (also known as carbon-13) but endogenous substrates has also been used. Isotopic enrichment of molecules generally does not alter their chemical properties. Therefore, 13C-rich molecules (i.e., carbon-12 replaced by carbon-13C) can be metabolized by cells in the same manner as non-rich molecules. However, the low sensitivity of the 13C nucleus makes this technique impractical without means to significantly increase the nuclear polarization of the imaging substrate, such as the dissolution dynamic nuclear polarization (DNP) method. Unfortunately, the dissolution DNP methods known in the art require expensive and complex instrumentation. Furthermore, the dissolution DNP method is generally only applicable to small molecules with long longitudinal relaxation times (commonly referred to in the art as T1). Molecules such as glucose and fatty acids have 13C relaxation times (T1) that are too short for in vivo imaging of the substrate and its metabolites in the case of dissolution DNP.

[0033] The use of deuterium-rich (2H)-rich metabolic substrates to assess carbon metabolism has recently attracted interest in the MR metabolic imaging community. In vivo studies using deuterated glucose to investigate glucose consumption rates and TCA circulation flux have demonstrated in animal models (Lu, M. et al.; J. Cereb. Blood Flow Metab. 2017 37(11): 3518-3530). Deuterated glucose has also recently been demonstrated to map metabolism in the normal human brain and to study metabolic changes in brain tumors (DeFeyter, HM. et al.; Sci Adv. 2018 4(8): eaat 7314).

[0034] For reagent preparation, deuterium metabolism imaging (DMI) does not require expensive additional instruments such as cyclotrons or polarizers (many deuterium-rich molecules are available from specialized suppliers), and its safety at the doses used in these studies is well-established. However, like 13C MR without hyperpolarization, DMI has lower sensitivity due to the much lower gyromagnetic ratio of 2H compared to 1H, and the relatively low concentration of metabolites compared to endogenous water and lipid molecules. One advantage of DMI compared to 13C MR (without hyperpolarization) is the relatively short T1 of deuterium, allowing for more signal averaging within a given scan time. However, obtaining spatially resolved maps of metabolites generated from deuterated glucose in vivo (such as lactate and glutamate + glutamine) still requires scan times of approximately 10 minutes or longer. Therefore, methods to improve the sensitivity of DMI remain needed to make it more suitable for routine clinical imaging.

[0035] To date, DMI has been performed using MR spectroscopy acquisition following the administration of deuterated metabolite substrates. The spectroscopic modes allow for the independent resolution and quantification of resonances from deuterated water, injected 2H-rich glucose, and their metabolites (see [link to article]). Figure 2 Specifically, this spectral resolution is obtained by performing Fourier analysis on incoming magnetic resonance data acquired over a sufficiently long duration of free induction decay (FID). The result is peak spectra derived from deuterated molecules with different chemical shifts. However, the inventors have recognized that MR spectroscopic acquisition is time-consuming because a long acquisition window is required to capture a sufficiently long portion of the FID. Typically, the encoding gradient is not used during readout, so the total scan time can be excessively long for spatially resolved data.

[0036] Furthermore, significant overlap between peaks is often observed due to the small differences in chemical shifts between different deuterated substances and the broad line shape of these peaks contributed by the quadruple torque of the deuteron spin, making it difficult to distinguish and accurately quantify different deuteron resonances. Additionally, perhaps the biggest obstacle remains the low signal-to-noise ratio of the acquired magnetic resonance data, especially for low-concentration metabolites such as lactate.

[0037] Figure 1 An exemplary system 1 for acquiring magnetic resonance data according to this disclosure is shown, which can be used to detect glucose metabolism in a patient. System 1 includes a magnetic resonance (MR) scanner 10, such as the GE Healthcare 3T GE MR750. The MR scanner 10 receives a patient within a scanner aperture 12 in a manner known in the art. As discussed above in the Background section, the MR scanner 10 includes a magnetic coil system 20 comprising a primary electromagnetic coil 22, a magnetic gradient coil 24, and a radio frequency (RF) coil 26. The RF coil 26 also forms part of an acquisition system 30, thereby functioning in a manner currently known in the art. Thermal insulation material 14 surrounding the primary electromagnetic coil 22 and a cryostat layer filled with liquid helium 16 are also shown, as are also known in the art. A service connection 18 to the MR scanner 10 is also provided, for example, providing communication, power, and coolant channels to and from the MR scanner 10 in a manner known in the art.

[0038] The MR scanner 10 is configured to communicate with a console 40, currently shown as receiving communication from input devices 99 (e.g., keyboard, mouse, and other control devices), and also with an output device 101, shown here as a display 80 and an image archiving and communication system (PACS) 90. The console 40 shown here incorporates a data analysis system 50, an image construction system 60, and a controller 70; however, it should be understood that these systems and controllers may be provided separately and / or in different combinations.

[0039] In the example shown, the data analysis system 50 is configured to analyze magnetic resonance data received from the MR scanner 10, such as magnetic resonance data acquired at the resonant frequency of deuterium, and generate a processed dataset without requiring spectrally resolved magnetic resonance data. The image construction system 60 is then configured to receive the processed dataset from the data analysis system 50 and construct a 2D or 3D image based on the processed dataset. It will then be recognized that the patient's glucose metabolism can subsequently be detected via the constructed image, as discussed further below.

[0040] The console 40 is also shown as incorporating a controller 70, which is used to control the functions of the MR scanner 10 in a manner known in the art. Figure 6 An exemplary control system 100 is illustrated, which may be integrated within a console 40, or, if as a separate hardware device rather than a module within a common console 40, separately integrated into one or more of the data analysis system 50, image construction system 60, and / or controller 70 to perform their respective functions. In the case where the console 40 has the data analysis system 50, image construction system 60, and / or controller 70 as software-based modules, these separate modules may be stored within a memory system 120, and may be executed, for example, by a processing system 110. With the exemplary control system 100 provided herein, the console 40 may be of a type currently known in the art, including, for example, a console used in conjunction with the GE Healthcare 3T MR750MR scanner.

[0041] Certain aspects of this disclosure are described or depicted as functional and / or logical block components or processing steps that can be performed by any number of hardware, software, and / or firmware components configured to perform specified functions. For example, some embodiments employ integrated circuit components (such as memory elements, digital signal processing elements, logic elements, lookup tables, etc.) configured to perform various functions under the control of one or more processors or other control devices. The connections between functional components and logical block components are merely exemplary and can be direct or indirect, and may follow alternative paths.

[0042] In some examples, control system 100 communicates with each of the console 40 and / or one or more components of system 1 via a communication link CL, which can be any wired or wireless link. Control module 100 is able to receive information and / or one or more operational characteristics of control system 1 and its various subsystems by sending and receiving control signals via the communication link CL. In one example, the communication link CL is a Controller Area Network (CAN) bus; however, other types of links may be used. It will be appreciated that the degree of connectivity and the communication link CL can actually be one or more shared connections or links between some or all of the components in system 1. Furthermore, the communication link CL lines are intended only to illustrate that various control elements can communicate with each other and do not represent actual wiring connections between the various elements, nor do they represent the only communication path between the elements. Additionally, system 1 can incorporate various types of communication devices and systems, and therefore the communication link CL shown can actually represent various different types of wireless data communication systems and / or wired data communication systems.

[0043] The control system 100 may be a computing system including a processing system 110, a memory system 120, and an input / output (I / O) system 130 for communicating with other devices, such as input devices 99 and output devices 101, any of which may or alternatively be stored in a cloud 102. The processing system 110 loads and executes an executable program 122 from the memory system 120, accesses data 124 stored in the memory system 120, and instructs the system 1 to operate as described in further detail below.

[0044] The processing system 110 may be implemented as a single microprocessor or other circuitry, or distributed across multiple processing devices or subsystems that cooperate to execute the executable program 122 from the memory system 120. Non-limiting examples of the processing system include general-purpose central processing units, dedicated processors, and logic devices.

[0045] The memory system 120 may include any storage medium capable of being read by the processing system 110 and capable of storing executable program 122 and / or data 124. The memory system 120 may be implemented as a single storage device or distributed across multiple storage devices or subsystems that cooperate to store computer-readable instructions, data structures, program modules, or other data. The memory system 120 may include volatile and / or non-volatile systems and may include removable and / or non-removable media for storing information, implemented in any method or technology. For example, the storage medium may include non-transitory and / or transient storage media, including random access memory, read-only memory, magnetic disk, optical disk, flash memory, virtual memory and non-virtual memory, magnetic storage devices, or any other medium that can be used to store information and accessed by an instruction execution system.

[0046] The inventors have developed a system and method disclosed herein for detecting glucose metabolism in patients, which differs from methods currently known in the art and does not require spectral resolution acquisition of magnetic resonance data. Specifically, the inventors have recognized that glucose consumption in tissues can be assessed using deuterium MR imaging without quantifying the amount of deuterium-rich metabolites (such as glutamate, glutamine, and lactate) produced during metabolic processes. Instead, the signal from water generated during glycolysis can be measured. If glucose is deuterated at a carbon in the pyranose ring (other than or replacing other common DMI sites), the water molecules generated from deuterated glucose will be deuterium-rich. In fact, for every glucose molecule consumed by cellular metabolism, two water molecules are generated as a product along with two pyruvate molecules.

[0047] Therefore, changes in deuterated water (HDO) signals can also be used to assess changes in glucose uptake and glycolysis flux during metabolic processes. The systems and methods disclosed in this invention require only deuterated water resonance imaging, rather than acquiring spectrally resolved 2H signals from all deuterated resonances to quantify deuterium-rich lactate and glutamate / glutamine. Magnetic resonance data is acquired solely from deuterated water resonances (see, for example...). Figure 5 The overall process of data acquisition and analysis is significantly simplified and made more efficient because spectral data is required.

[0048] Since deuterium is naturally abundant at 0.015%, a background deuterated water signal will be present even without any applied deuterium-rich glucose. To obtain imaging contrast showing glucose metabolism, one method for monitoring the metabolic process is to perform a baseline scan before administering deuterated glucose. Once the deuterated glucose has been administered to the patient and sufficient time has passed for the metabolic process, subsequent delayed magnetic resonance acquisition data can be collected to detect deuterated water produced by glucose metabolism in the tissues. The baseline magnetic resonance acquisition data can then be subtracted from the delayed magnetic resonance acquisition data to remove the influence of naturally abundant deuterium and identify which tissues have metabolized glucose. This subtraction can be performed in ways known in the art, but deuterated water is used instead of spectrally resolved metabolites as described above.

[0049] Figure 3 The process is generally illustrated as an exemplary method 200. Method 200 begins with deuterated glucose in step 202, such that deuterium binds to the carbon of the pyranose ring of the glucose molecule. Step 204 then provides the acquisition of baseline magnetic resonance imaging (MRI) data of the patient prior to administration of the deuterated glucose using techniques known presently in the art. It will be appreciated that baseline MRI data can also be acquired after administration of the deuterated glucose, provided that the acquisition occurs only shortly after the administration. Since glucose uptake and metabolism typically take approximately several tens of minutes, in some embodiments, step 204 may be performed within 5 minutes of glucose administration (as a non-limiting example), for example, where the contribution of HDO generated by the administered glucose is minimal. The deuterated glucose is then administered to the patient in step 206, and as step 208, the process awaits a delay time after the administration of the deuterated glucose. After this delay time has elapsed, step 210 provides the acquisition of delayed MRI data of the patient after the delay time, which substantially repeats step 204, at which point the deuterated glucose has been at least partially metabolized by the patient. Step 210 can be repeated to provide dynamic information related to glucose metabolism.

[0050] Step 212 provides the analysis of non-spectrally resolved magnetic resonance data to generate a processed dataset. In method 200, this analysis includes subtracting the baseline magnetic resonance data collected in step 204 from the delayed magnetic resonance data in step 210, causing the naturally abundant deuterium in the patient's body to be eliminated, so that the only visible source of deuterium in the data is deuterium from the deuterated glucose administered to the patient in step 206. An image is then constructed based on the processed dataset from step 214, thereby allowing glucose metabolism to be detected in step 216 via the constructed image in a manner known in the art.

[0051] In short, significant time and cost savings can be achieved by eliminating the need for spectrally resolving all individual metabolites of deuterated glucose, as is currently done for DMI. Since spectral resolution across multiple metabolites is not required, the acquisition window for each FID can be much shorter, and less overall data needs to be sampled. Furthermore, spatial information can be encoded during readout using standard MRI methods, thus accelerating the scan. Perhaps most importantly, the fact that the signal from deuterated water is much stronger than that of the metabolites may eliminate the need for extensive signal averaging, which is currently performed in DMI using MR spectroscopy. This equates to shorter patient time in the scanner, for example, from 20 minutes or more to less than 10 minutes, or even 3 to 7 minutes, depending on factors such as the patient, the anatomy being imaged, etc.

[0052] Less processing is required, thus reducing the time to produce the final image. This, combined with reduced patient time in the scanner, improves patient throughput and efficiency using expensive and complex hardware. As mentioned above, this also leads to improved data quality, such as improved signal-to-noise ratio for analyzing magnetic resonance data collected only at the deuterated water resonance frequency relative to signals that are spectrally resolved for multiple metabolites.

[0053] While the baseline acquisition method using deuterated water represents an improvement over methods currently known in the art, the inventors have determined that further improvements can be achieved by detecting deuterated water for glucose uptake imaging. Specifically, baseline scanning requires more time to keep the patient in the MR scanner. Additionally, the baseline scan is temporally separate from the delayed acquisition following glucose administration. Therefore, the patient must remain in the scanner for the entire delayed period after glucose administration (typically 20 minutes or longer), increasing discomfort and system downtime, or be removed and returned to the scanner after another patient has been imaged. Similarly, subtracting two datasets can lead to motion errors due to patient movement or other issues during or between the two scans.

[0054] The inventors have recognized that, instead of subtracting the baseline magnetic resonance dataset, the HDO signal generated by glucose metabolism can be separated from the HDO signal from background water by applying diffusion weighting during the scan. Specifically, at least initially, the water molecules generated by deuterated glucose metabolism will be intracellular. In contrast, most background water molecules (i.e., those containing naturally abundant deuterium) are extracellular. Intracellular water molecules have more limited diffusion than those extracellular, which are relatively more mobile. In this respect, the (deuterated) water newly generated from deuterated glucose is initially present in the cytosol compartment and is also more restricted in terms of mobility.

[0055] Therefore, a single diffusion-weighted scan using the HDO signal after administration of deuterated glucose is sufficient to produce the contrast required to detect increased glucose uptake and glycolysis in diseased tissues such as tumors.

[0056] Figure 4 An exemplary method 300 for detecting glucose metabolism using diffusion-weighted scanning technology is illustrated. Method 300 begins by administering deuterated glucose to a patient in step 302, followed by a delay time in step 304 after the administration of deuterated glucose. Step 306 provides the acquisition of delayed magnetic resonance (MRI) data of the patient after the delay time elapsed in step 304. This non-spectrally resolved MRI data is then analyzed in step 308 to generate a processed dataset. Figure 3 Similar to step 212 in method 200, the analysis of step 308 is performed on the dataset acquired using an MR imaging acquisition mode instead of an MR spectroscopy acquisition mode. Then, in step 310, an image is constructed based on the processed dataset from step 308, and glucose metabolism can then be detected again via the constructed image in step 312 in a manner known in the art.

[0057] It is also worth noting that when imaging HDO signals using non-spectrally resolved imaging methods, the non-resonance peaks from the applied deuterated glucose contribute to the total signal and can be a source of chemical shift artifacts. However, since many tumors are known to have increased glucose turnover, the increase in deuterated glucose signal can actually enhance the contrast between the tumor and the background signal from "normal" tissue. Furthermore, for deuterium imaging, the spatial resolution can be relatively coarse, and the frequency difference between HDO and deuterated glucose is quite small (approximately 20 Hz at 3T). Therefore, chemical shift artifacts are negligible in many cases.

[0058] Thus, the systems and methods disclosed in this invention provide substantial improvements over those systems and methods currently known in the art. As described above, these improvements include imaging glucose metabolism without the ionizing radiation associated with FDG-PET, and imaging more efficiently by directly imaging deuterated water molecules generated from glucose metabolism rather than by acquiring spectrally resolved deuterium spectra after administration of a dose of deuterated glucose. Furthermore, diffusion-weighted imaging of deuterated water enables imaging contrast without the time-consuming and erroneous baseline dataset subtraction.

[0059] The functional block diagrams, operation sequences, and flowcharts provided in the accompanying drawings illustrate exemplary architectures, environments, and methods for performing novel aspects of this disclosure. While the methods included herein may be in the form of functional diagrams, operation sequences, or flowcharts for the purpose of illustrative simplicity, and may be described as a series of actions, it should be understood and recognized that the methods are not limited to the order of actions, as some actions may occur in different orders and / or concurrently with other actions shown and described herein. For example, those skilled in the art will understand and recognize that the methods may alternatively be represented as a series of interrelated states or events, such as in a state diagram. Moreover, not all actions shown in the methods may be necessary for a novel implementation.

[0060] This written description uses examples to disclose the invention, including the best mode, and also enables those skilled in the art to perform and use the invention. Certain terms are used for the purposes of brevity, clarity, and ease of understanding. Unnecessary limitations should not be inferred from this description beyond the requirements of the prior art, as such terms are used for descriptive purposes only and are intended to be understood broadly. The patent scope of this invention is defined by the claims and may include other examples that would occur to those skilled in the art. These other examples are intended to be within the scope of the claims if they have features or structural elements that are not different from the literal language of the claims, or if they include equivalent features or structural elements that are not substantially different from the literal language of the claims.

Claims

1. A method for detecting glucose uptake and metabolism in a patient, the method comprising: generating a magnetic field acting on the patient; acquiring non-spectrally resolved magnetic resonance data of deuterated water in the patient, wherein deuterated glucose has been administered to the patient, wherein the deuterated water is produced during the metabolism of the deuterated glucose by the patient, and wherein the magnetic resonance data is acquired at the resonance frequency of the deuterated water; analyzing the magnetic resonance data acquired at the resonance frequency of non-spectrally resolved deuterated water to generate a processed data set; and constructing an image based on the processed data set; wherein the metabolism of the glucose by the patient is detected via the constructed image.

2. The method of claim 1, wherein the magnetic resonance data is acquired via gradient echo imaging.

3. The method of claim 1, wherein the magnetic resonance data is collected in less than 10 minutes.

4. The method of claim 1, wherein the magnetic resonance data is delayed magnetic resonance data acquired at a delay time after administration of the deuterated glucose to the patient, the method further comprising acquiring baseline magnetic resonance data of deuterated water in the patient prior to metabolism of the deuterated glucose by the patient, and wherein analyzing the magnetic resonance data comprises subtracting the baseline magnetic resonance data from the delayed magnetic resonance data to generate the processed data set.

5. The method of claim 1, wherein analyzing the magnetic resonance data comprises applying diffusion weighting.

6. The method of claim 1, wherein the processed data set from which the image is generated does not require individual peaks in a spectrally resolved deuterium spectrum.

7. The method of claim 1, wherein the image is generated without using data from an ionizing radiation source.

8. A magnetic resonance imaging (MRI) scanner configured to detect glucose metabolism in a patient, the MRI scanner comprising: a magnetic coil system configured to generate a magnetic field acting on the patient; an acquisition system configured to acquire non-spectrally resolved magnetic resonance data of deuterated water in the patient in response to the magnetic field, wherein the deuterated water is produced during the metabolism of deuterated glucose administered to the patient, and wherein the magnetic resonance data is acquired at the resonance frequency of the deuterated water; a data analysis system configured to analyze the magnetic resonance data acquired at the resonance frequency of non-spectrally resolved deuterated water to generate a processed data set; and an image construction system configured to construct an image based on the processed data set; wherein glucose uptake and metabolism by the patient is detected via the constructed image.

9. The MRI scanner of claim 8, wherein the acquisition system is configured to acquire the magnetic resonance data via gradient echo imaging.

10. The MRI scanner of claim 8, wherein the acquisition system acquires the magnetic resonance data in less than 10 minutes.

11. The MRI scanner of claim 8, wherein the magnetic resonance data is delayed magnetic resonance data acquired at a delay time after administration of the deuterated glucose to the patient, wherein the acquisition system is further configured to acquire baseline magnetic resonance data of deuterated water in the patient prior to the deuterated glucose being metabolized by the patient, and wherein the data analysis system is further configured to subtract the baseline magnetic resonance data from the delayed magnetic resonance data to generate the processed data set.

12. The MRI scanner of claim 8, wherein data analysis system is configured to analyze the magnetic resonance data via diffusion weighting.

13. The MRI scanner of claim 8, wherein the processed data set from which the image is generated does not require spectral resolution of individual peaks in a deuterium spectrum.

14. A method for detecting glucose metabolism in a patient, the method comprising: deuterated glucose, such that deuterium is bound to a carbon on its pyranose ring, thereby producing deuterated glucose; administering the deuterated glucose to the patient; generating a magnetic field that acts on the patient; acquiring non-spectrally resolved magnetic resonance data of deuterated water in the patient, wherein the deuterated water is produced during the metabolism of the deuterated glucose by the patient, and wherein the magnetic resonance data is acquired only at the resonance frequency of the deuterated water; analyzing the magnetic resonance data acquired at the resonance frequency of non-spectrally resolved deuterated water to generate a processed data set; and constructing an image based on the processed data set; wherein the metabolism of the glucose by the patient is detected via the constructed image.

15. The method of claim 14, wherein the magnetic resonance data is collected in less than 10 minutes, the method further comprising analyzing the magnetic resonance data acquired for the deuterated water using diffusion weighting prior to constructing the image, wherein the processed data set from which the image is generated does not require spectral resolution of individual peaks in a deuterium spectrum, and wherein the image is generated without using data from an ionizing radiation source.

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