阅读说明：本技术 一种用于植入体辅助显影的聚合物及其方法 (Polymer for implant auxiliary development and method thereof ) 是由 陈洪波 于 2021-09-22 设计创作，主要内容包括：本发明公开了一种用于植入体辅助显影的聚合物及其方法,涉及医疗材料技术领域。聚合物包含如下单元：黏附单元、亲水单元以及造影单元。包括以下步骤：S1、原料的备用；S2、甲基丙烯酰氧基碘海醇的制备；S3、搅拌溶解处理；S4、引发剂的添加；S5、离心和沉淀处理；S6、聚合反应；S7、降温浓缩和包装。该用于植入体辅助显影的聚合物及其方法,本发明所属造影聚合物具有黏附单元、亲水单元和造影单元,其中黏附单元具有邻苯二酚结构,其能够与材料表面形成化学键,从而达到优异的黏附效果,能够黏附在造影效果不好的材料制备的产品上,亲水单元能够调整材料的亲疏水性,使造影聚合物具有一定生物亲和性。(The invention discloses a polymer for implant auxiliary development and a method thereof, relating to the technical field of medical materials. The polymer comprises the following units: adhesion unit, hydrophilic unit and contrast unit. The method comprises the following steps: s1, preparing raw materials for later use; s2, preparing methacryloxy iohexol; s3, stirring and dissolving; s4, adding an initiator; s5, centrifuging and precipitating; s6, carrying out polymerization reaction; s7, cooling, concentrating and packaging. The invention relates to a polymer for auxiliary development of an implant and a method thereof, wherein the contrast polymer comprises an adhesion unit, a hydrophilic unit and a contrast unit, wherein the adhesion unit has a catechol structure and can form a chemical bond with the surface of a material, so that an excellent adhesion effect is achieved, the polymer can be adhered to a product prepared from a material with a poor contrast effect, and the hydrophilic unit can adjust the hydrophilicity and hydrophobicity of the material, so that the contrast polymer has certain biological affinity.)

1. A polymer for use in implant-assisted visualization, the polymer comprising the following units: adhesion unit, hydrophilic unit and contrast unit.

2. The polymer for use in assisted visualization of implants according to claim 1, characterized in that the adhesion unit comprises a polymerizable monomer of catechol structure, in particular methacryloyloxyethoxy-3, 4-catechol.

3. The polymer for use in implant-assisted visualization according to claim 1, wherein the hydrophilic unit is at least one of an unsaturated fatty acid, an unsaturated fatty acid ester, or an unsaturated fatty amide, in particular methacrylic acid and hydroxyethyl methacrylate.

4. The polymer for use in implant-assisted visualization of claim 1, wherein the visualization unit is an acrylate derivative or a maleic anhydride derivative containing a contrast agent.

5. A method of polymers for implant assisted visualization according to claims 1 to 4, characterized by the steps of:

s1, preparing raw materials: weighing 5-8 parts by weight of methacryloyloxyethoxy-3, 4-catechol, 2-6 parts by weight of methacrylic acid, 1.5-7 parts by weight of hydroxyethyl methacrylate, 8-10 parts by weight of iohexol, 1-3 parts by weight of methacryloyl chloride, 1-5 parts by weight of triethylamine, 2-4 parts by weight of ethanol, 3-5 parts by weight of hydrogen peroxide and 2-4 parts by weight of ascorbic acid in sequence by weight for later use;

s2, preparation of methacryloyloxyiohexol: dissolving 1-3 parts by weight of iohexol in diethyl ether, keeping the temperature to 0 ℃ under the condition of ice-water bath, dropwise adding 1.2 parts by weight of methacryloyl chloride, dropwise adding 0.3 part by weight of triethylamine, reacting for 30min, carrying out decompression rotary evaporation to remove the diethyl ether and the triethylamine, collecting a solid product, washing for 3 times by using ethanol, and carrying out decompression distillation to obtain a methacryloyloxyiohexol product;

s3, stirring and dissolving treatment: adding 10 parts of deionized water into a four-neck flask provided with a stirring device, a condensation pipe and a thermometer, sequentially adding the methacryloxyethoxy-3, 4-catechol weighed in the step S1, methacrylic acid, hydroxyethyl methacrylate and the methacryloxyiohexol prepared in the step S2 into the four-neck flask, and stirring and dissolving to obtain a required mixture;

s4, addition of an initiator: adding an initiator consisting of hydrogen peroxide and ascorbic acid into the solution stirred and dissolved in the step S3 in sequence, and keeping the temperature of the water bath at 30-40 ℃ to obtain a required mixed solution;

s5, centrifugation and sedimentation treatment: centrifuging, washing and precipitating the mixed solution prepared in the step S4, and standing the precipitated filtrate in an open container at room temperature;

s6, polymerization: carrying out polymerization reaction on the filtrate prepared in the step S5, wherein the polymerization time is 4.5-5h, and the filtrate is reserved after the polymerization is finished;

s7, cooling, concentrating and packaging: and (5) cooling the product polymerized in the step (S6), concentrating, and packaging to obtain the required product.

6. The method of claim 5, wherein the initiator in the step S4 is prepared from hydrogen peroxide and ascorbic acid in a weight ratio of 1: (0.5-2) in combination.

7. The method of claim 5, wherein ethanol is added to the mixture during the precipitation process in step S5.

8. The method of claim 5, wherein the centrifugation step S5 comprises centrifuging at 1700rpm at 1500-.

9. The method of claim 5, wherein the washing step S5 is washing with deionized water for 3-5 times; and (4) cooling the product polymerized in the step S7, and concentrating the product until the solid content is 50%.

Technical Field

The invention relates to the technical field of medical materials, in particular to a polymer for implant auxiliary development and a method thereof.

Background

Medical imaging is a technique and process for obtaining an image of internal tissues of a human body or a part of the human body in a non-invasive manner for medical or medical research purposes. Implants are widely used in medical field, especially for adjuvant therapy, and these implants are generally made of degradable polymer materials, have excellent biocompatibility, and can be decomposed with time in human body environment, and the occupied position is replaced by normal tissue, so as to cure diseases.

The prior art implant materials often show lighter color under X-ray, and in order to clearly distinguish the shape and position of the material, the X-ray dosage is generally increased, which is harmful to human body, therefore, we propose a polymer for implant auxiliary development and a method thereof to solve the above problems.

Disclosure of Invention

In view of the deficiencies of the prior art, the present invention provides a polymer for implant-assisted visualization and a method thereof, which solve the problems set forth in the background above.

In order to achieve the purpose, the invention provides the following technical scheme: a polymer for use in implant-assisted visualization, the polymer comprising the following units: adhesion unit, hydrophilic unit and contrast unit.

A method of using a polymer for implant-assisted visualization, comprising the steps of:

s1, preparing raw materials: weighing 5-8 parts by weight of methacryloyloxyethoxy-3, 4-catechol, 2-6 parts by weight of methacrylic acid, 1.5-7 parts by weight of hydroxyethyl methacrylate, 8-10 parts by weight of iohexol, 1-3 parts by weight of methacryloyl chloride, 1-5 parts by weight of triethylamine, 2-4 parts by weight of ethanol, 3-5 parts by weight of hydrogen peroxide and 2-4 parts by weight of ascorbic acid in sequence by weight for later use;

s2, preparation of methacryloyloxyiohexol: dissolving 1-3 parts by weight of iohexol in diethyl ether, keeping the temperature to 0 ℃ under the condition of ice-water bath, dropwise adding 1.2 parts by weight of methacryloyl chloride, dropwise adding 0.3 part by weight of triethylamine, reacting for 30min, carrying out decompression rotary evaporation to remove the diethyl ether and the triethylamine, collecting a solid product, washing for 3 times by using ethanol, and carrying out decompression distillation to obtain a methacryloyloxyiohexol product;

s3, stirring and dissolving treatment: adding 10 parts of deionized water into a four-neck flask provided with a stirring device, a condensation pipe and a thermometer, sequentially adding the methacryloxyethoxy-3, 4-catechol weighed in the step S1, methacrylic acid, hydroxyethyl methacrylate and the methacryloxyiohexol prepared in the step S2 into the four-neck flask, and stirring and dissolving to obtain a required mixture;

s4, addition of an initiator: adding an initiator consisting of hydrogen peroxide and ascorbic acid into the solution stirred and dissolved in the step S3 in sequence, and keeping the temperature of the water bath at 30-40 ℃ to obtain a required mixed solution;

s5, centrifugation and sedimentation treatment: centrifuging, washing and precipitating the mixed solution prepared in the step S4, and standing the precipitated filtrate in an open container at room temperature;

s6, polymerization: carrying out polymerization reaction on the filtrate prepared in the step S5, wherein the polymerization time is 4.5-5h, and the filtrate is reserved after the polymerization is finished;

s7, cooling, concentrating and packaging: and (5) cooling the product polymerized in the step (S6), concentrating, and packaging to obtain the required product.

Further optimizing the technical scheme, the adhesion unit comprises a polymerizable monomer with a catechol structure, and specifically is methacryloyloxyethoxy-3, 4-catechol.

Further optimizing the technical scheme, the hydrophilic unit is at least one of unsaturated fatty acid, unsaturated fatty acid ester or unsaturated fatty amide, and specifically is methacrylic acid and hydroxyethyl methacrylate.

Further optimizing the technical scheme, the contrast unit is an acrylate derivative or a maleic anhydride derivative containing a contrast agent.

Further optimizing the technical scheme, the initiator in the step S4 is prepared from hydrogen peroxide and ascorbic acid in a weight ratio of 1: (0.5-2) in combination.

Further optimizing the technical scheme, when the precipitation treatment is performed in the step S5, ethanol is added to the mixed solution.

Further optimizing the technical scheme, the centrifugation operation of the step S5 comprises the steps of firstly centrifuging for 5-6min at the rotation speed of 1500-.

Further optimizing the technical scheme, the washing precipitation in the step S5 is washed by deionized water, and the washing times are 3-5 times; and (4) cooling the product polymerized in the step S7, and concentrating the product until the solid content is 50%.

Compared with the prior art, the invention provides a polymer for the auxiliary development of an implant and a method thereof, and the polymer has the following beneficial effects:

1. the invention relates to a polymer for auxiliary development of an implant and a method thereof, wherein the contrast polymer comprises an adhesion unit, a hydrophilic unit and a contrast unit, wherein the adhesion unit has a catechol structure and can form a chemical bond with the surface of a material, so that an excellent adhesion effect is achieved, the polymer can be adhered to a product prepared from a material with a poor contrast effect, such as polylactic acid and polycaprolactone, the hydrophilic unit can adjust the hydrophilicity and hydrophobicity of the material, so that the contrast polymer has certain biological affinity, the contrast unit can improve the sensitivity under medical imaging technologies such as X-ray and the like, a clear image can be displayed under the condition of lower X-ray, and the polymer can assist medical diagnosis, judge the position of the implant and the degradation condition.

2. The preparation method provided by the invention has the advantages of simple steps, low material cost, rapid preparation, high utilization rate of the prepared polymer, excellent imaging effect, biological safety and easiness in metabolism, and further can be applied to magnetic resonance imaging.

Drawings

FIG. 1 is a flow chart of a polymer for implant-assisted visualization and a method thereof according to the present invention.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The first embodiment is as follows: referring to fig. 1, the present invention discloses a polymer for implant assisted visualization, which comprises the following units: the adhesion unit comprises a polymerizable monomer with a catechol structure, specifically methacryloyloxyethoxy-3, 4-catechol, the hydrophilic unit is at least one of unsaturated fatty acid, unsaturated fatty acid ester or unsaturated fatty amide, specifically methacrylic acid and hydroxyethyl methacrylate, and the contrast unit is an acrylate derivative containing a contrast agent.

A method of using a polymer for implant-assisted visualization, comprising the steps of:

s1, preparing raw materials: weighing 7 parts by weight of methacryloyloxyethoxy-3, 4-catechol, 4 parts by weight of methacrylic acid, 1.5 parts by weight of hydroxyethyl methacrylate, 9 parts by weight of iohexol, 1 part by weight of methacryloyl chloride, 5 parts by weight of triethylamine, 2 parts by weight of ethanol, 3 parts by weight of hydrogen peroxide and 2 parts by weight of ascorbic acid in sequence for later use;

s2, preparation of methacryloyloxyiohexol: dissolving 2 parts by weight of iohexol in diethyl ether, keeping the temperature to 0 ℃ under the condition of ice-water bath, dropwise adding 1.2 parts by weight of methacryloyl chloride, dropwise adding 0.3 part by weight of triethylamine, reacting for 30min, carrying out decompression rotary evaporation to remove the diethyl ether and the triethylamine, collecting a solid product, washing the solid product with ethanol for 3 times, and carrying out reduced pressure distillation to obtain a methacryloyloxyiohexol product;

s3, stirring and dissolving treatment: adding 10 parts of deionized water into a four-neck flask provided with a stirring device, a condensation pipe and a thermometer, sequentially adding the methacryloxyethoxy-3, 4-catechol weighed in the step S1, methacrylic acid, hydroxyethyl methacrylate and the methacryloxyiohexol prepared in the step S2 into the four-neck flask, and stirring and dissolving to obtain a required mixture;

s4, addition of an initiator: adding an initiator consisting of hydrogen peroxide and ascorbic acid into the solution stirred and dissolved in the step S3 in sequence, wherein the initiator consists of hydrogen peroxide and ascorbic acid in a weight ratio of 1: 0.5, keeping the temperature of water bath at 35 ℃ to obtain required mixed liquor;

s5, centrifugation and sedimentation treatment: centrifuging and washing the mixed solution prepared in the step S4, standing the precipitated filtrate in an open container at room temperature, adding ethanol into the mixed solution during precipitation treatment, centrifuging for 5min at 1500rpm to remove large-particle precipitates, centrifuging for 8min at 5000rpm, discarding the supernatant, taking the lower-layer precipitates, washing the precipitates with deionized water, and washing for 3 times;

s6, polymerization: carrying out polymerization reaction on the filtrate prepared in the step S5, wherein the polymerization time is 4.5h, and the filtrate is reserved after the polymerization is finished;

s7, cooling, concentrating and packaging: and (5) cooling and concentrating the product polymerized in the step (S6), cooling and concentrating the polymerized product until the solid content is 50%, and packaging after concentration to obtain the required product.

Example two: referring to fig. 1, the present invention discloses a polymer for implant assisted visualization, which comprises the following units: the adhesion unit comprises a polymerizable monomer with a catechol structure, specifically methacryloyloxyethoxy-3, 4-catechol, the hydrophilic unit is at least one of unsaturated fatty acid, unsaturated fatty acid ester or unsaturated fatty amide, specifically methacrylic acid and hydroxyethyl methacrylate, and the contrast unit is a maleic anhydride derivative containing a contrast agent.

A method of using a polymer for implant-assisted visualization, comprising the steps of:

s1, preparing raw materials: weighing 5 parts by weight of methacryloyloxyethoxy-3, 4-catechol, 2 parts by weight of methacrylic acid, 1.5 parts by weight of hydroxyethyl methacrylate, 8 parts by weight of iohexol, 1 part by weight of methacryloyl chloride, 3 parts by weight of triethylamine, 2 parts by weight of ethanol, 0.1 part by weight of hydrogen peroxide and 0.1 part by weight of ascorbic acid in sequence for later use;

s2, preparation of methacryloyloxyiohexol: dissolving 1 part by weight of iohexol in diethyl ether, keeping the temperature to 0 ℃ under the condition of ice-water bath, dropwise adding 1.2 parts by weight of methacryloyl chloride, dropwise adding 0.3 part by weight of triethylamine, reacting for 30min, carrying out decompression rotary evaporation to remove the diethyl ether and the triethylamine, collecting a solid product, washing the solid product with ethanol for 3 times, and carrying out reduced pressure distillation to obtain a methacryloyloxyiohexol product;

s3, stirring and dissolving treatment: adding 10 parts of deionized water into a four-neck flask provided with a stirring device, a condensation pipe and a thermometer, sequentially adding the methacryloxyethoxy-3, 4-catechol weighed in the step S1, methacrylic acid, hydroxyethyl methacrylate and the methacryloxyiohexol prepared in the step S2 into the four-neck flask, and stirring and dissolving to obtain a required mixture;

s4, addition of an initiator: adding an initiator consisting of hydrogen peroxide and ascorbic acid into the solution stirred and dissolved in the step S3 in sequence, wherein the initiator consists of hydrogen peroxide and ascorbic acid in a weight ratio of 0.1: 0.1, keeping the temperature of water bath at 30 ℃ to obtain required mixed liquor;

s5, centrifugation and sedimentation treatment: centrifuging and washing the mixed solution prepared in the step S4, standing the precipitated filtrate in an open container at room temperature, adding ethanol into the mixed solution during precipitation treatment, centrifuging for 5min at a rotation speed of 1600rpm to remove large-particle precipitates, centrifuging for 8min at 5500rpm, discarding the supernatant, taking the lower-layer precipitates, washing the precipitates with deionized water, and washing for 4 times;

s6, polymerization: carrying out polymerization reaction on the filtrate prepared in the step S5, wherein the polymerization time is 4.5-5h, and the filtrate is reserved after the polymerization is finished;

s7, cooling, concentrating and packaging: and (5) cooling and concentrating the product polymerized in the step (S6), cooling and concentrating the polymerized product until the solid content is 50%, and packaging after concentration to obtain the required product.

Example three: referring to fig. 1, the present invention discloses a polymer for implant assisted visualization, which comprises the following units: the adhesion unit comprises a polymerizable monomer with a catechol structure, specifically methacryloyloxyethoxy-3, 4-catechol, the hydrophilic unit is at least one of unsaturated fatty acid, unsaturated fatty acid ester or unsaturated fatty amide, specifically methacrylic acid and hydroxyethyl methacrylate, and the contrast unit is an acrylate derivative containing a contrast agent.

A method of using a polymer for implant-assisted visualization, comprising the steps of:

s1, preparing raw materials: weighing 7 parts by weight of methacryloyloxyethoxy-3, 4-catechol, 4 parts by weight of methacrylic acid, 1.8 parts by weight of hydroxyethyl methacrylate, 8 parts by weight of iohexol, 1 part by weight of methacryloyl chloride, 3 parts by weight of triethylamine, 2 parts by weight of ethanol, 4 parts by weight of hydrogen peroxide and 2 parts by weight of ascorbic acid in sequence for later use;

s2, preparation of methacryloyloxyiohexol: dissolving 2 parts by weight of iohexol in diethyl ether, keeping the temperature to 0 ℃ under the condition of ice-water bath, dropwise adding 1.2 parts by weight of methacryloyl chloride, dropwise adding 0.3 part by weight of triethylamine, reacting for 30min, carrying out decompression rotary evaporation to remove the diethyl ether and the triethylamine, collecting a solid product, washing the solid product with ethanol for 3 times, and carrying out reduced pressure distillation to obtain a methacryloyloxyiohexol product;

s3, stirring and dissolving treatment: adding 10 parts of deionized water into a four-neck flask provided with a stirring device, a condensation pipe and a thermometer, sequentially adding the methacryloxyethoxy-3, 4-catechol weighed in the step S1, methacrylic acid, hydroxyethyl methacrylate and the methacryloxyiohexol prepared in the step S2 into the four-neck flask, and stirring and dissolving to obtain a required mixture;

s4, addition of an initiator: adding an initiator consisting of hydrogen peroxide and ascorbic acid into the solution stirred and dissolved in the step S3 in sequence, wherein the initiator consists of hydrogen peroxide and ascorbic acid in a weight ratio of 1: 0.5, keeping the temperature of water bath at 35 ℃ to obtain required mixed liquor;

s5, centrifugation and sedimentation treatment: centrifuging and washing the mixed solution prepared in the step S4, standing the precipitated filtrate in an open container at room temperature, adding ethanol into the mixed solution during precipitation treatment, centrifuging for 5min at a rotation speed of 1500rpm to remove large-particle precipitates, centrifuging for 8min at 5500rpm, discarding supernatant, taking lower-layer precipitates, washing the precipitates with deionized water, and washing for 5 times;

s6, polymerization: carrying out polymerization reaction on the filtrate prepared in the step S5, wherein the polymerization time is 4.5h, and the filtrate is reserved after the polymerization is finished;

s7, cooling, concentrating and packaging: and (5) cooling and concentrating the product polymerized in the step (S6), cooling and concentrating the polymerized product until the solid content is 50%, and packaging after concentration to obtain the required product.

Example four: referring to fig. 1, the present invention discloses a polymer for implant assisted visualization, which comprises the following units: the adhesion unit comprises a polymerizable monomer with a catechol structure, specifically methacryloyloxyethoxy-3, 4-catechol, the hydrophilic unit is at least one of unsaturated fatty acid, unsaturated fatty acid ester or unsaturated fatty amide, specifically methacrylic acid and hydroxyethyl methacrylate, and the contrast unit is an acrylate derivative containing a contrast agent.

A method of using a polymer for implant-assisted visualization, comprising the steps of:

s1, preparing raw materials: weighing 5 parts by weight of methacryloyloxyethoxy-3, 4-catechol, 4 parts by weight of methacrylic acid, 3 parts by weight of hydroxyethyl methacrylate, 8 parts by weight of iohexol, 3 parts by weight of methacryloyl chloride, 3 parts by weight of triethylamine, 2 parts by weight of ethanol, 3 parts by weight of hydrogen peroxide and 2 parts by weight of ascorbic acid in sequence for later use;

s2, preparation of methacryloyloxyiohexol: dissolving 2 parts by weight of iohexol in diethyl ether, keeping the temperature to 0 ℃ under the condition of ice-water bath, dropwise adding 1.2 parts by weight of methacryloyl chloride, dropwise adding 0.3 part by weight of triethylamine, reacting for 30min, carrying out decompression rotary evaporation to remove the diethyl ether and the triethylamine, collecting a solid product, washing the solid product with ethanol for 3 times, and carrying out reduced pressure distillation to obtain a methacryloyloxyiohexol product;

s3, stirring and dissolving treatment: adding 10 parts of deionized water into a four-neck flask provided with a stirring device, a condensation pipe and a thermometer, sequentially adding the methacryloxyethoxy-3, 4-catechol weighed in the step S1, methacrylic acid, hydroxyethyl methacrylate and the methacryloxyiohexol prepared in the step S2 into the four-neck flask, and stirring and dissolving to obtain a required mixture;

s4, addition of an initiator: adding an initiator consisting of hydrogen peroxide and ascorbic acid into the solution stirred and dissolved in the step S3 in sequence, wherein the initiator consists of hydrogen peroxide and ascorbic acid in a weight ratio of 1: 0.8, keeping the temperature of water bath at 35 ℃ to obtain required mixed liquor;

s5, centrifugation and sedimentation treatment: centrifuging and washing the mixed solution prepared in the step S4, standing the precipitated filtrate in an open container at room temperature, adding ethanol into the mixed solution during precipitation treatment, centrifuging for 5min at 1500rpm to remove large-particle precipitates, centrifuging for 9min at 5000rpm, discarding the supernatant, taking the lower-layer precipitates, washing the precipitates with deionized water, and washing for 5 times;

s6, polymerization: carrying out polymerization reaction on the filtrate prepared in the step S5, wherein the polymerization time is 4.5-5h, and the filtrate is reserved after the polymerization is finished;

s7, cooling, concentrating and packaging: and (5) cooling and concentrating the product polymerized in the step (S6), cooling and concentrating the polymerized product until the solid content is 50%, and packaging after concentration to obtain the required product.

And (4) judging the standard: through comparison of the four embodiments, the best effect is the second embodiment, and therefore, the second embodiment is selected as the best embodiment, and the specific change of the amount also belongs to the protection scope of the technical scheme.

The invention has the beneficial effects that: the invention relates to a polymer for auxiliary development of an implant and a method thereof, wherein the contrast polymer comprises an adhesion unit, a hydrophilic unit and a contrast unit, wherein the adhesion unit has a catechol structure and can form a chemical bond with the surface of a material, so that an excellent adhesion effect is achieved, the polymer can be adhered to a product prepared from a material with a poor contrast effect, such as polylactic acid and polycaprolactone, the hydrophilic unit can adjust the hydrophilicity and hydrophobicity of the material, so that the contrast polymer has certain biological affinity, the contrast unit can improve the sensitivity under medical imaging technologies such as X-ray and the like, a clear image can be displayed under the condition of lower X-ray, and the polymer assists medical diagnosis, judges the position of the implant and the degradation condition; the preparation method provided by the invention has the advantages of simple steps, low material cost, rapid preparation, high utilization rate of the prepared polymer, excellent imaging effect, biological safety and easiness in metabolism, and further can be applied to magnetic resonance imaging.

Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.