Patent Publication Number: US-2023137188-A1

Title: Hyperpolarisation device, system and process

Description:
TECHNICAL FIELD 
     The present invention relates to a device, process and system for hyperpolarizing  13 C isotope-based Magnetic resonance imaging contrast agents for subsequent magnetic resonance imaging (MRI) applications. 
     BACKGROUND OF THE INVENTION 
     Magnetic resonance imaging (MRI) has been widely used in the medical discipline for obtaining the three-dimensional structural information from a human body. 
     By obtaining a three-dimensional image, medical practitioners are able to see through the organs of a patient, and determine if there are any structural abnormalities within the body of the patient. 
     One such abnormality is the presence of tumour tissue. Traditional MRI techniques detect 1H nuclei inside human bodies, such that the water and fat distribution can be seen. Since no ionizing radiation is involved, it is considered to be a safer investigation method than X-ray imaging techniques. 
     However, detecting 1H nuclei alone cannot always distinguish normal tissue and cancerous tissue and as such the techniques can be considered to be less applicable than X-ray computed tomography (CT) and positron emission tomography (PET). 
     Therefore, in order to enhance the contrast between normal and cancerous tissue, contrast agents are needed to be introduced into the body. These MRI contrast agents typically contain gadolinium, which, however, has certain toxicity towards the kidneys and the nervous system of a patient. 
     Patients with renal diseases are considered susceptible to kidney failure after injection of gadolinium-based contrast agents into the body. Moreover, gadolinium can remain in human body for a prolonged period time after MRI scanning, which also increases the risk of patient safety related issues. 
     Apart from gadolinium-based contrast agents, there has been some research on  13 C nuclei based MRI imaging to distinguish normal and cancerous tissues. Carbon, as is known, is the building block of all organic compounds. 
     Since  13 C nuclei are stable, there is considered no harm in using  13 C for MRI imaging in living organisms. However, the natural abundance of  13 C nuclei in carbon is only 1.1%, which is much smaller than the natural abundance of 99.98% of 1H nuclei in hydrogen. Moreover,  13 C signal in MRI is much weaker than 1H. 
     These two factors together can be considered to make MRI by  13 C very difficult practically. Nevertheless, there have been technologies for enriching  13 C abundance in biomolecules. Therefore,  13 C enhanced compounds with high purities can be obtained commercially. 
     Regarding the low signal of  13 C in comparison to 1H, there are also techniques for enhancement in the art. At room temperature, the nuclear spin alignment of  13 C within a magnetic field is little under thermal equilibrium. 
     OBJECT OF THE INVENTION 
     It is an object of the present invention to provide a device, process and system for hyperpolarizing  13 C isotope-based Magnetic resonance imaging contrast agents for subsequent magnetic resonance imaging (MRI) applications, which overcomes or at least partly ameliorates at some deficiencies as associated with the prior art. 
     SUMMARY OF THE INVENTION 
     In a first aspect, the present invention provides a device for enhancing polarization of  13 C isotope-based magnetic resonance imaging contrast agents, said device comprising:
     one or more diamond material structure and one or more channels provided adjacent to the diamond material structure;   wherein said diamond material structure provides a source of negatively charged nitrogen vacancy (NV-) centres for polarization of a  13 C isotope-based magnetic resonance imaging contrast agent disposed in said one or more channels; and;   wherein said diamond material structure provides a light guide for light for excitation of nitrogen vacancy (NV-) centres for polarization of said  13 C isotope-based magnetic resonance imaging contrast agent.   

     The device may include a plurality of plurality of columns defining said channels therebetween, wherein said columns are formed from said diamond material structure; 
     The diamond material structure may be formed from synthetic diamond. 
     The diamond material structure may be formed from CVD (chemical vapor deposition crystal formation) diamond. 
     The diamond material structure may be formed from HPHT (high-pressure high-temperature) diamond. 
     The light may be applied by an optical laser. The light may be provided by a pulse laser. The light is provided by a continuous laser. The light may be monochromatic. 
     The  13 C isotope-based magnetic resonance imaging contrast agents may pyruvate. 
     In a second aspect, the present invention provides a system for enhancing polarization of  13 C isotope-based magnetic resonance imaging contrast agents, said system comprising:
     a device according to the first aspect   a light source for optical pumping and providing excitation to the electron spins of the nitrogen vacancy (NV-) centres;   a radio frequency transmitter for providing a radio frequency signal;   a microwave transmitter for providing a microwave field, such that the NV centres are polarized and such that the electron spins of the NV centres are transferred to  13 C atoms upon the Rabi frequency of the NV centres matching the Larmor frequency of  13 C.   a tuneable electromagnet for providing a magnetic field, such that the nitrogen vacancy (NV-) centres electron spin active states of the nitrogen vacancy (NV-) centres are sufficiently separated, in order to provide unified electron spins states within the diamond under the presence of a microwave field.   

     The radio frequency signal may be a static radio frequency wave. The radio frequency signal is a pulsed signal. The microwave may be a continuous wave. The microwave may be a pulsed signal. 
     The electromagnet may be a tuneable magnet. 
     In a third aspect, the present invention provides a process for enhancing polarization of  13 C isotope-based magnetic resonance imaging contrast agents for subsequent MRI imaging, said process including the steps of:
     (i) providing a device according to the first aspect;   (ii) introducing a  13 C isotope-based magnetic resonance imaging contrast agent with the channels of said device;   (iii) polarizing said  13 C isotope-based magnetic resonance imaging contrast agent.   

     In a fourth aspect, the present invention provides a system for cleaning and disinfecting the device for enhancing polarization of  13 C isotope-based magnetic resonance imaging contrast agents of the first aspect, said system comprising:
     (i) a disinfection chamber, for cleaning and disinfecting said one or more devices simultaneously;   (ii) a disposal chamber, wherein any waste retained on said one or more devices are disposed from the system, and   (iii) a drying chamber for drying the cleaned one or more said devices.   

     The disinfection chamber may include an ultraviolet light source for disinfection of said one or more devices. The ultraviolet light source may be in the wavelength of 200 nm to 400 nm. The ultraviolet light source may be provided by LED or laser. 
     The disinfection chamber may have a reservoir for storing organic liquid, and any kinds of water, which allows said one or more devices to be cleaned therein. 
     The drying chamber may utilise furnace or electromagnetic wave as heat source for the drying purpose. The drying chamber may include an ultraviolet light source for disinfection of said one or more devices. The ultraviolet light source may be in the wavelength of 200 nm to 400 nm. The ultraviolet light source is provided by LED or laser. 
     In a fifth aspect, the present invention provides a process for enhancing the hyperpolarizing effect of the  13 C -isotope based contrast agent provided by the device of the first aspect, said process including the steps of:
     (i) treating said diamond material structure such that the diamond material is plamonic-based or photonic-based;   (ii) illuminating a light source to said diamond material structure for optical pumping and providing excitation to the electron spins of the nitrogen vacancy (NV-) centres, and as such to provide surface plasmons on the surface of said diamond material structure; and   (iii) providing electromagnetic perturbation to said device.   

     The diamond material may be treated by forming a metallic coating on the surface of the diamond material structure. The diamond material may be treated by coupling the diamond material with metallic micro or nanostructures. The diamond material may be treated by forming a dieletric coating on the surface of the diamond material structure. The diamond material may be is treated by coupling the diamond material structure with dieletric micro or nanostructures. 
     The electromagnetic perturbation may be provided by any one of microwave source, radio frequency wave source, or the like. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In order that a more precise understanding of the above-recited invention can be obtained, a more particular description of the invention briefly described above will be rendered by reference to specific embodiments thereof that are illustrated in the appended drawings. The drawings presented herein may not be drawn to scale and any reference to dimensions in the drawings or the following description is specific to the embodiments disclosed. 
         FIG.  1   a    (i) -  FIG.  1   a    (iv) show schematic exemplary examples of a device according to the present invention; 
         FIG.  1   b    shows a schematic representation of a system in accordance with the present invention; 
         FIG.  2    shows a schematic representation of an embodiment of a hyperpolarization device according to the present invention; 
         FIG.  3    shows a schematic representation of an embodiment of a hyperpolarization casing according to the present invention; 
         FIG.  4    shows a schematic representation of the formation of surface plasmons on the surface of the plasmonic-based or photonic based diamond; 
         FIG.  5   a    shows an energy diagram of a nitrogen vacancy of a diamond upon excitation by focused light, without the presence of surface plasmons on the diamond surface; 
         FIG.  5   b    shows an energy diagram of a nitrogen vacancy of a diamond upon excitation by focused light, with the presence of surface plasmons on the diamond surface; and 
         FIG.  6    shows a schematic representation of an embodiment of the disinfection system of one or more hyperpolarisation devices according to the present invention. 
     
    
    
     DETAILED DESCRIPTION OF THE DRAWINGS 
     The present inventors have identified shortcomings of the problems with the prior art, and have provided a system which is more consistent and reliable, and overcomes the problems of the prior art. 
     Present Invention 
     The present invention relates to hyperpolarization of enhancing the  13 C isotope-based Magnetic resonance imaging (MRI) contrast agents. The present inventors have provided a process, device and system to increase the efficiency of optical hyperpolarization  13 C isotope-based Magnetic resonance imaging contrast agents. 
     The present inventors have developed a process, device and system for enhancing the  13 C isotope-based Magnetic resonance imaging (MRI) contrast agents using optically pumping, which can be performed at room temperature. 
     Invention Background Theory 
     It is known that cancer cells exhibit a unique metabolic fingerprint that provides a means to differentiate them from benign tissues. In order to investigate the cancer cells, Magnetic resonance imaging is one of the tools. 
     In particular,  13 C Magnetic resonance imaging (MRI) is attractive for metabolic imaging because carbon serves as backbone of nearly all organic molecules, thus allowing the investigation in the area of cancer metabolism. 
     However, in practice, the signal from a  13 C labelled tracer has been considered too weak for in vivo imaging due to the very low natural abundance of the  13 C isotope. 
     In order to improve the MRI signal of  13 C nuclei, detection probes can be synthetically enriched to increase the concentration of the  13 C label in a molecule. MRI signal can be further enhanced dramatically by the process of hyperpolarization. 
     In order to enhance the  13 C signal, the ratio of aligned nuclear spin under magnetic field is needed to be greatly increased beyond thermal equilibrium. This phenomenon is called hyperpolarization within the art. 
     Dynamic nuclear polarization (DNP) is a method which can hyperpolarize  13 C so that  13 C signal can be enhanced by 10,000-fold compared to thermal equilibrium in room temperature. This makes use of compounds with radicals to provide lone pair electrons, whose aligned spins can polarize the nuclear spins of  13 C. By adding radicals into  13 C compounds at around 1 K in a magnetic field of 4.6 T to 5 T for 30 min to 90 min, the  13 C nuclear spin can be hyperpolarized. 
     As the radicals used in DNP have certain toxicity to human cells and the DNP process has to be done in cryo-environment, there have been proposed other methods developing for the hyperpolarization of  13 C. 
     The principle of hyperpolarization is the high spin polarization of a paramagnetic radical can be transferred to the  13 C nucleus on another molecule under resonant microwave irradiation. 
     However, conventional methods generally involve the conditions of low temperature (~&lt;=K) and high magnetic field (&gt;=3 T) to first generate the electron polarization. It is reported the hyperpolarization signal of  13 C nuclei can be increased with a factor of  720  against the thermal signal at 7 T and retained for multiple-minute long period via optical hyperpolarization. 
     Diamonds contain Nitrogen Vacancy (NV) centres with one negative charge captured from the surroundings. The diamond NV- centres are paramagnetic with spin S = 1 with a large zero field splitting, with D = 2.87 GHz, wherein D is the energy difference between electron spin state of zero-field splitting of NV center, the energy range is in microwave band. 
     Laser light can be used for optical pumping, providing excitation, to the electron spins of NV centres. The electron spins of the NC centres can then be transferred to  13 C atoms when the Rabi frequency of the NV centres match the Larmor frequency of 13 C. 
     Present Invention Details 
     In accordance with the present invention, a process, device and system has been proposed and developed to enhance the efficiency of optical pumping for hyperpolarizing  13 C isotope-based Magnetic resonance imaging contrast agents for subsequent magnetic resonance imaging (MRI) applications. 
     The present invention achieves such enhanced efficiency of optical pumping for hyperpolarizing  13 C isotope-based Magnetic resonance imaging contrast agents for subsequent magnetic resonance imaging (MRI) applications. 
     The manner in which the present inventors have overcome the deficiencies of the prior art and provided a solution which can enhance the efficiency of optical pumping, is by providing a hyperpolarization device which include a plurality of channels in which  13 C isotope-based Magnetic resonance imaging contrast agents, either as a solution or in particulate form, may be introduced therein. 
     Advantageously, in order achieve the objectives of the invention, the material surrounding or adjacent the channels, is formed from diamond, preferably a synthetic diamond, which is also known as laboratory-grown diamond, or laboratory-created diamond. 
     Such diamonds are produced by a controlled process, as contrasted with natural diamonds which are created by geological processes, or imitation diamond made of non-diamond material that appears similar to diamond. 
     Synthetic diamonds are also widely known as HPHT (high-pressure high-temperature) diamond or CVD diamond (chemical vapor deposition crystal formation), as being formed from such methods. 
     As required for the hyperpolarization of  13 C isotope-based Magnetic resonance imaging (MRI) contrast agents, as the hyperpolarization device of the present invention includes a diamond material structure that is formed from diamond material, this diamond material of the diamond material structure provides the source of negatively charged nitrogen vacancy (NV-) for hyperpolarization of the  13 C isotope-based Magnetic resonance imaging (MRI) contrast agents, for use in subsequent MRI imaging of a patient. 
     As such, the hyperpolarization device provides for enhanced hyperpolarization of the  13 C isotope-based Magnetic resonance imaging (MRI) contrast agents, as it acts as:
     (i) the diamond material structure acts as a light guide for light as is required for hyperpolarization, and further into adjacent MRI contrast agents, thus providing greater penetration and increased hyperpolarization of MRI contrast agents, and   (ii) the diamond material structure provides the source of negatively charged nitrogen vacancy (NV-) as is required for hyperpolarization of the MRI contrast agents in accordance with the present invention.   

     Referring now to  FIG.  1   a    (i) -  FIG.  1   a     a ( iv ), there are shown schematic exemplary examples of a device  100   a ( i ),  100   a ( ii ),  100   a ( iii ) and  100   a ( iv ) for enhancing polarization of  13 C isotope-based magnetic resonance imaging contrast agents, according to the present invention. 
     The device  100   a ( i ),  100   a ( ii ),  100   a ( iii ) and  100   a ( iv ) includes one or more diamond material structure  120   a ( i ),  120   a ( ii ),  120   a ( iii ) and  120   a ( iv ) and one or more channels  105   a ( i ),  105   a ( ii ),  105   a ( iii ) and  105   a ( iv ) provided adjacent to the diamond material structure  120   a ( i ),  120   a ( ii ),  120   a ( iii ) and  120   a ( iv ). 
     The diamond material structure  120   a ( i ),  120   a ( ii ),  120   a ( iii ) and  120   a ( iv ) provides a source of negatively charged nitrogen vacancy (NV-) centres for polarization of a  13 C isotope-based magnetic resonance imaging contrast agent disposed in said one or more channels; and; 
     Further, the diamond material structure  120   a ( i ),  120   a ( ii ),  120   a ( iii ) and  120   a ( iv ) provides a light guide for light for excitation of nitrogen vacancy (NV-) centres for polarization of said 13C isotope-based magnetic resonance imaging contrast agent. 
     As will be seen in  FIG.  1   a    (i) and  FIG.  1   a    (ii), the diamond material structure  120   a ( i ),  120   a ( ii ), is unitary in structure, with channels  105   a ( i ),  105   a ( ii ) extending therethrough. As will be understood, there may be a plurality of channels or a single channel, in accordance with the present invention. 
     Now as will be seen in  FIG.  1   a    (iii) and  FIG.  1   a    (iv), the diamond material structure  120   a ( iii ),  120   a ( iv ) is not a unitary structure and is provided by separate components  121   a ( iii ), 121   a ( iv ). 
     It will be understood that not all of the separate components  121   a ( iii ), 121   a ( iv ) necessarily formed from a diamond material, however as long as sufficient diamond material is provided adjacent to a channel, the hyperpolarization process according to the present invention may be effected. 
     As will be understood, the channels  105   a ( iii ) and  105   a ( iv ) in the devices  100   a ( iii ) and  100   a ( iv ) a formed when the separate components  121   a ( iii ), 121   a ( iv ). are joined together. 
     As will also be understood, the channels  105   a ( i ),  105   a ( ii ),  105   a ( iii ) and  105   a ( iv ) suitably sized so as to provide for the hyperpolarization process as will be described further in detail in particular, in reference to  FIG.  2    as follows. 
     Further, as will be understood, the channels  105   a ( i ),  105   a ( ii ),  105   a ( iii ) and  105   a ( iv ) need not necessarily be circular, and may be of any geometry and the present embodiments impart no geometric or size constraint in respect of the channels.  105   a ( i ),  105   a ( ii ),  105   a ( iii ) and  105   a ( iv ). Furthermore, although the channels  105   a ( i ),  105   a ( ii ),  105   a ( iii ) and  105   a ( iv ) depicted in the exemplary embodiments extend fully through the diamond material structure  120   a ( i ),  120   a ( ii ),  120   a ( iii ) and  120   a ( iv ), this need not necessarily be the case in all implementations of the invention, and again, the present environments are exemplary only and do not provide any limitation on the structure of the device  100   a ( i ),  100   a ( ii ),  100   a ( iii ) and  100   a ( iv ). 
     Further and advantageously, in embodiments of the invention, the hyperpolarization device  100   a ( i ),  100   a ( ii ),  100   a ( iii ) and  100   a ( iv ) can be incorporated into a hyperpolarization system, with requisite microwave generator, a magnetic field generator, and a laser light source for delivery of light of a requisite predetermined wavelength. 
     Referring to  FIG.  1   b   , there is shown a schematic representation of a system  100   b  in accordance with the present invention which may implement the device of the present invention. 
     The present invention provides a system, device and process for enhancing  13 C isotope MRI imaging signal via optically hyperpolarization at room temperature. 
     The system  100   b  can be placed in a same room with MRI (Magnetic Resonance Imagining) machine or in a separated room. 
       FIG.  1   b    shows a schematic representation of the system  100   b  which includes a controller  110   b  for controlling the operation of an optical excitation and collection device  130   b , a microwave (MW) transmitter and receiver  120   b  for providing a microwave field, as well as radio frequency (RF) transmitter and receiver  140   b  for providing a radio frequency, and tuneable electromagnet  160   b  for providing tuneable magnetic field. 
     The device  150   b  can be exposed to microwave, radio frequency, magnetic field and a light source. 
     The presence of magnetic fields allows the degenerated electron spin states splitting to non-degenerated electron spin sublevels in the order of microwave energy scale. 
     Degenerated electron spin states can be split and separated by magnetic field, which is known as the Zeeman effect, the sublevels are separated by very small amount of energy in the microwave region. Upon the illumination of a light energy, the sample can be excited from ground electronic and spin states to excited electronic and spin states. The sample will then decay back to ground state by releasing energy in form of light or heat. 
     During the excitation and decay processes, the electron spin states of the sample could be switched between fluorescence-active and fluorescence-inactive electron spin states. Microwave will be absorbed by the sample when there is any allowed transition between any two fluorescence-active and fluorescence-inactive electron spin states. 
     As such, the magnetic field splits and separate the degenerated electron spin states of the sample due to Zeeman effect, and thus providing unified electron spins states within the sample under the presence of a microwave field. 
     Without the presence of a magnetic field, the electron spins of NV centres within the sample cannot be unified and thus would be cancelled out. 
     Any kind microwave transmitter  120   b  can be used, and as such to provide pulsed or continuous microwave. The pulsed or continuous microwave can be applied on the device  130   b  uniformly or nonuniformly. 
     Any kind radio frequency transmitter  120   b  can be used, and as such to provide pulsed or continuous radio frequency. The pulsed or continuous radio frequency can be applied on the device  130   b  uniformly or nonuniformly. 
     Any kind electromagnet  160   b  can be used, and as such to provide pulsed or continuous magnetic field on sample. The pulsed or continuous magnetic field can be applied on the sample uniformly or nonuniformly. 
     Light can be provided by a laser light source  130   b  for example. The light may be pulsed light or continuous light. Preferably monochromatic light is used. Although the light source is preferably a laser light source, other light sources may be utilized in alternate configurations and embodiments. A magnetic field and a microwave field are also applied to the hyperpolarization device and the  13 C isotope based contrast agent therein, such that the NV centers of the diamond material are polarized and the electron spins of the NV centres of the diamond material will then be transferred to  13 C atoms when the Rabi frequency of the NV centres match the Larmor frequency of  13 C.Referring to  FIG.  2   , there is shown a schematic representation of an embodiment of a hyperpolarization device  200  according to the present invention for enhancing polarization of 13C isotope-based magnetic resonance imaging contrast agents. 
     The device  200  comprises a diamond material structure  220  and one or more channels  205  provided adjacent to said diamond material structure. The diamond material structure  220  provides a source of negatively charged nitrogen vacancy (NV-) centres for polarization of a 13C isotope-based magnetic resonance imaging contrast agent disposed in said one or more channels. Furthermore, the diamond material structure  220  provides a light guide for light for excitation of nitrogen vacancy (NV-) centres for polarization of said 13C isotope-based magnetic resonance imaging contrast agent. 
     As is shown, the device  200  includes multi-hole channels  205  single-end opened cylindrical negatively charged nitrogen vacancy (NV-) enriched diamond tubes  210 . 
     The hyperpolarization device  200  as shown in  FIG.  2   , in use, is placed in a resonator including an electron paramagnetic resonator (EPR) and a nuclear magnetic resonator (NMR) with an optical perturbation channel. 
     Referring now to  FIG.  3   , there is shown a schematic representation of an embodiment of a hyperpolarization casing  300  according to the present invention. 
     As is shown in  FIG.  3   , of the hyperpolarization casing  300  there is shown a diamagnetic outer cover, shell, or cage  310  of the instrument, which enables magnetic shielding from external magnetic source including the MRI machine. 
     In accordance with the present invention, the electron paramagnetic resonator (EPR) and a nuclear magnetic resonator (NMR) can be operated simultaneously or separately operated. 
     Both of the EPR system and NMR system can be operated in continuous wave (CW) mode and also in pulsed mode. 
     The CW mode of EPR means a static microwave and continuously tuneable static magnetic can be applied to the samples during operation. The pulsed mode of electron paramagnetic resonator (EPR) means a pulsed microwave and fixed static magnetic can be applied to the samples during operation. 
     Similarly, the CW mode of NMR means a static radio frequency (RF) wave and continuously tuneable static magnetic can be applied to the samples during operation, and the pulsed mode of electron paramagnetic resonator (EPR) means a pulsed RF wave and fixed static magnetic were applied to the samples during operation. 
     The optically perturbed channel is made of laser or LED with the wavelength in a range from 500 nm to 600 nm. The optically perturbed channel can be operated in CW mode or pulsed mode. 
     Referring specifically to  FIG.  2   , the embodiment of the hyperpolarization device  200  includes a diamond material structure  220  that is made of a multi-hole channels single-end opened cylindrical negatively charged nitrogen vacancy (NV-) enriched diamond tubes  210 , which can store required amounts of samples of a  13 C isotope-based Magnetic resonance imaging (MRI) contrast agents, for use in subsequent MRI imaging of a patient. 
     The device  200  has a transparent bottom, which enables the optical perturbation enters from the bottom side. 
     A diamagnetic metallic coating is made at the device’s  200  outer side surface, which will trap and scatter light between the inner space of the sample holder and the contained samples. Moreover, the device  200  is reusable after an independent and appropriate disinfection procedure. 
     A pump-injection channel is connected to the open-end of the device  200  during the operation in order to inject the hyperpolarized samples to the patient in a short period for the MRI imaging use in the patient. The samples used in the instrument are  13 C isotope-based contrast agents. The samples for use as a contrasting agent, can be  13 C enriched pyruvate, for example. 
     The hyperpolerisation device  200  can be made of synthetic diamonds, for example chemical vapor deposition (CVD) diamonds, CVD diamonds are synthesized by chemical vapor deposition, which allows carbon atoms in a gas to settle on a substrate in crystalline diamond form. 
     Using CVD, properties such as the shape of the synthetic diamond can be well controlled during its growth, such that a hyperpolarization device  200  in the shape of multi-hole channels single-end opened cylinders, which can be easily produced. 
     This is advantageous over the use of natural diamonds which requires accurate cutting from the raw diamond. 
     The hyperpolerisation device  200  also acts the source of NV- centers, which upon excitation, electron spins within the NV centres of the hyperpolerisation device  200 . The electron spins of the NC centres can then be transferred to  13 C atoms when the Rabi frequency of the NV centres match the Larmor frequency of  13 C. 
     Within the present embodiment, the diamond material structure  220  is depicted as being formed from a single piece of diamond material, with columns defining the channels therebetween. 
     However, as should be appreciated and understood, the diamond material structure of the device may be comprised of more than one pieces of diamond material, and the device may also include other materials which may form part of a boundary of a channel. However, provided that the diamond material structure is arranged such that a channel is provided for the adjacent introduction of contrast agent, and the diamond material structure can act as a light guide for the hyperpolarisation as is herein described, such an embodiment will be understood to fall within the scope of the present invention, 
     As such, one or diamond material structures may be arranged to form a channel or part thereof adjacent the diamond material, or a channel may extend at least partly though a diamond material structure. 
     The present invention provides no structural limitations on the shape, geometry or size of the diamond material structure. 
     Examples of the Invention 
     The system and device can be placed in same room with MRI machine in a clinical environment, or in a separated room. 
     The system may contain a samples holder placed in a resonator composited of an electron paramagnetic resonator and a nuclear magnetic resonator with an optical perturbation channel. 
     The instrument can have a diamagnetic outer cover, shell, or cage of the instrument, which enables magnetic shielding from external magnetic source including the MRI. 
     The electron paramagnetic resonator and the nuclear magnetic resonator can be operated simultaneously, or separately. 
     Both of the electron paramagnetic resonator and the nuclear magnetic resonator can be operated in continuous wave (CW) mode and also in pulsed mode. 
     The CW mode of electron paramagnetic resonator means a static microwave and continuously tuneable static magnetic can be applied to the samples during operation. 
     The pulsed mode of electron paramagnetic resonator means a pulsed microwave and fixed static magnetic can be applied to the samples during operation. 
     The CW mode of nuclear magnetic resonator means a static radio frequency (RF) wave and continuously tuneable static magnetic were applied to the samples during operation. 
     The pulsed mode of electron paramagnetic resonator means a pulsed RF wave and fixed static magnetic can be applied to the samples during operation. 
     The optically perturbed channel may be provided by laser or LED, or any appropriate light source. 
     The wavelength of the optically perturbed channel is in the range from 500 nm to 600 nm. 
     The optically perturbed channel can be operated in CW mode and in pulsed mode. 
     The samples holder may be a multi-hole channels single-end opened cylindrical diamond tubes, which can store required number of samples. 
     The device may be made of negatively charged nitrogen vacancy (NV-) enriched diamond. 
     The device may have a diamagnetic metallic coating at its outer side surface. 
     The diamagnetic metallic surface coating provides trapping and scattering of light between the inner space of the device and the contained samples of agent. 
     The device enables the optical perturbation enters from the bottom side of the samples holder. 
     The device may be reusable after disinfection. 
     A pump-injection channel may be connected to the open-end of the sample holder during the operation in order to inject the patient in short period for the MRI imaging use. 
     The samples are preferably  13 C isotope-based contrast agents. 
     Enhancing the Hyperpolarizing Effect of the  13 C Isotope-Based Contrast Agent 
     In an embodiment of the present invention, the hyperpolarizing effect of the  13 C isotope-based contrast agent can be enhanced by manipulating the nitrogen vacancy electron spin within the diamond with a plasmon-assisted method. 
     As is known by people within the art, surface plasmons (SPs) are coherent delocalized electron oscillations that exist at the interface between any two materials where the real part of the dielectric function changes sign across the interface (e.g. a metal-dielectric interface, such as a metal sheet in air). 
     In accordance with the present invention, surface plasmons are provided onto the surface of the diamond material of the hyperpolarisation device by illuminating a highly concentrated light beam to the surface of the diamond material, which is treated to be plasmonic-based or photonic based. 
     As is shown in  FIG.  4   , upon the illumination of a highly focused laser  410  onto the surface of a plasmonic-based or photonic based diamond  420 , surface plasmons are formed  430  are formed on the surface of the diamond  420 . 
     The treatment to the diamond material which causes it to be plasmonic-based or photonic based may be achieved by providing metallic coatings to the diamond surface or coupling the diamonds with metallic micro/nanostructures. Alternatively, the treatment may also refer to the forming of a dielectric coating to the diamond surface or coupling the diamonds with dielectric micro/nanostructures. 
     With the surface plasmons  430  present on the surface of the plasmonic-based or photonic based diamond material  420 , the nitrogen vacancy electron spin of the diamond can be manipulated upon excitation by a light source, when subjected to an appropriate microwave field. 
     Referring now to  FIGS.  5   a  and  5   b    which show the possible energy diagram of electron spin of the diamond material with or without the presence of surface plasmons on the surface of the plasmonic-based or photonic based diamond. 
       FIG.  5   a    shows an energy diagram of NV electron spin of diamond without surface plasmons. A microwave field  540   a  is provided to pump the nitrogen vacancy centers of the diamond to an electron spin active state. Upon excitation by a focused ion beam  510   a , the excited nitrogen vacancy (NV-) centre will either return to the ground energy state by fluorescence decay  520   a , or by emitting photons as indicated by arrows  530   a . 
     In conventional hyperpolarisation methods where plasmons are not involved, the return of an excited nitrogen vacancy (NV-) centre to its ground energy level is usually predominant by the photons emission pathway  530   a  which has a lower electron spin active rate than that as provided by the fluorescence decay  520   a . Thus, the overall hyperpolarisation rate of  13 C isotope-based contrast agent will be hindered. 
     In contrast, with the presence of the surface plasmons, as is shown in the energy diagram of  FIG.  5   b   , it has a higher opportunity for an excited nitrogen vacancy (NV-) centre to return to its ground energy level by fluorescence decay  520   b  rather than by the emission of photons  530   b , upon the excitation by a focused light beam  510   b  and the presence of a microwave field  540   b  to pump the nitrogen vacancy center of the diamond to an electron spin active state. 
     Such a plasmonic-assisted method manipulates the nitrogen vacancy electron spin to predominantly undergo fluorescence decay which has a higher electron spin active rate, and thus leading to a more effective hyperpolarizing of  13 C -samples. 
     Disinfection System of the Hyperpolarisation Devices 
     The hyperpolarisation devices of the present invention can be reused for multiple times upon appropriate cleaning and disinfection with the utilisation of a disinfection system as shown in  FIG.  6   . 
       FIG.  6    shows a disinfection system  600  for cleaning and disinfecting one or more hyperpolarisation device simultaneously. After providing activation to the  13 C isotope-based MRI contrast agent, the hyperpolarisation devices are sent to the disinfection system  600  for thorough cleaning, which can then be reused after the disinfection process. 
     As is shown in  FIG.  6   , the disinfection system  400  includes three chambers, these being: (i) a disinfection chamber  610 , (ii) a disposal chamber  630 , and (iii) a drying chamber  650 . 
     The disinfection chamber  610  provides the major cleaning and disinfection function to the one or more used hyperpolarisation devices  615 . There is arranged a reservoir  612  which contains fluid  613  such as cleaning agent, organic fluid and water, the one or more used hyperpolarisation devices  615  are to be placed therein for thorough cleaning. 
     There is also arranged an ultraviolet light source  611  for emitting ultraviolet light to the used hyperpolarisation devices  615  and thereby disinfecting them. In an embodiment, the ultraviolet source can be provided by LED or laser, and the emitted ultraviolet light is in the wavelength ranging from 200 nm to 400 nm. 
     After cleaning and disinfection, the one or more hyperpolarisation devices  615  are then sent to the disposal chamber  630  wherein the disposal chamber  630  allows the disposal of any waste, including wastewater and retained cleansing agent, from the body of the hyperpolarisation devices  635 . The waste is guided away from the disposal chamber  633  as is shown by the arrow  633 . 
     In the last step of the disinfection process, the one or more hyperpolarisation devices  635  are sent to the drying chamber  650  wherein there is installed a drying unit  653  for drying the cleaned hyperpolarisation devices  655  and remove any liquid which are still retained thereon. The drying chamber  650  also includes an ultraviolet light source  651  which, same as that in the disinfection chamber, is used to further disinfect the hyperpolarisation devices  655  by irradiating ultraviolet light thereon. 
     In an embodiment, the ultraviolet light source may be a LED or a laser, and the wavelength of the ultraviolet light emitted ranges from 200 nm to 400 nm. 
     The drying chamber  650  provides sufficient room for multiple hyperpolarisation devices  655  to be dried simultaneously after the cleaning process, and therefore the cleaning and drying process can be carried out effectively and efficiently. 
     The present invention provides advantages, including enhanced hyperpolarisation time so as to be suitable for use in a contrasting agent in a clinical environment for MRI investigation, no additional elements need to be introduced in the contrasting agent, and direct delivery of the contrasting agent to a patient.