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Enabling Metabolic Imaging Using Hyperpolarized 13C Magnetic Resonance

使用超极化 13C 磁共振实现代谢成像

基本信息

批准号：
7612388
负责人：
Neal F Kalechofsky
金额：
$ 19.7万
依托单位：
MILLIKELVIN TECHNOLOGIES, LLC
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7612388
关键词：
Acetates Acetic Acids Acids Address American Businesses Capital Cardiac Cell Nucleus Citric Acid Cycle Clinical Data Development Diagnosis Disease Dose Environment Equilibrium Goals Heart Heart Diseases Hospitals Hour Image Knowledge Label Liquid substance Magnetic Resonance Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Manufactured Supplies Maps Measurable Measurement Measures Metabolic Metabolism Methods Modeling Myocardial Noise Nuclear Oxygen Consumption Patients Phase Physicians Poison Process Production Property Radioactivity Rattus Relaxation Research Research Personnel Risk Sampling Signal Transduction Site Sodium Acetate Sodium Hydroxide Solutions Suspension substance Suspensions System Techniques Technology Temperature Time Tissues Treatment Efficacy Yeasts base catalyst cold temperature commercial application cost cryostat effective therapy heart imaging heart metabolism improved in vivo interest magnetic field meetings novel outcome forecast public health relevance quantum research study scale up

项目摘要

DESCRIPTION (provided by applicant): The signal from 13C enriched molecules is much too low to permit them to be observed in vivo using MRI. To overcome this problem, researchers have turned to the use of hyperpolarized (HP) 13C molecules; hyperpolarization dramatically increases the signal from the 13C nuclei in the molecules and an increase in signal to noise ratio (SNR) by as much as 10,000 can be obtained in this manner. The increased SNR makes it possible to build images of metabolic processes in the heart which can be used to construct models as to the metabolic signature of various forms of heart disease. Present methods of hyperpolarization suffer from drawbacks that will severely impact clinical deployment of HP 13C molecules. For example, the only currently commercially available hyperpolarizer requires that the 13C molecule be mixed with toxic substances to hyperpolarize the 13C nuclei. In addition, present hyperpolarizers are not readily scalable to production levels needed for commercial supply. MKT has developed a method of hyperpolarization and associated business model that directly addresses these issues. Hyperpolarization of samples is carried out by allowing nuclei to relax in a very low temperature, very high field environment. The use of the "quantum" liquids 3He and 4He allow the relaxation process to be very rapid and carried out without the use of toxic materials. The HP samples are extracted from the cryostat without undue loss of polarization; this enables them to be transported over large distances thus removing the need for the polarizer to be in close proximity to the MRI machine. The process is scalable and applicable to a wide variety of samples including those of metabolic interest such as 13C enriched acetic acid. Our long term goal is to manufacture and supply HP materials to the clinical MRI marketplace. Our short term goal is to demonstrate that 13C enriched acetic acid can be hyperpolarized using our proprietary technique, extracted from the cryostat, transported to a nearby hospital, reacted with a sodium hydroxide base solution to form HP sodium acetate solution and then used to carry out a variety of hyperpolarized Magnetic Resonance Spectroscopy (MRS) experiments. We will demonstrate that the QRS technique produces SNR gains in excess of 5000 in HP acetic acid samples as compared to acetic acid samples in thermal equilibrium at room temperature (Aim I). We will demonstrate that HP 13C acetic acid may be transported for 2 hours (or more) without significant loss of polarization (Aim II). This will demonstrate that acetic acid may be hyperpolarized at one site and transported to another for use in different MRS applications. Next, we will demonstrate conversion of HP 13C acetic acid to an HP 13C acetate solution with SNR in excess of 1000 as compared to acetic acid samples in thermal equilibrium at room temperature (Aim III). The HP sodium acetate solution will then be used to follow metabolism in MRS experiments conducted in a respiring suspension of yeast and in isolated perfused rat hearts (Aim IV). PUBLIC HEALTH RELEVANCE: Over 700,000 Americans will die from heart disease this year. The ability to image metabolic processes of the heart has the potential to greatly improve both diagnosis and treatment of heart disease. The production of metabolic images of the heart requires the development of hyperpolarized 13C enriched molecules such as sodium acetate; Millikelvin Technologies has developed a method of manufacturing hyperpolarized sodium acetate that does not require the addition of poisonous materials, can be scaled up to meet widespread demand and will keep costs down by delivering the hyperpolarized sodium acetate as a consumable.

描述(申请人提供)：来自13C浓缩分子的信号太低，无法使用核磁共振在体内观察到它们。为了克服这个问题，研究人员转向使用超极化(HP)13C分子；超极化极大地增加了分子中13C核的信号，通过这种方式可以获得高达10,000的信噪比(SNR)。增加的信噪比使构建心脏代谢过程的图像成为可能，该图像可用于构建关于各种形式的心脏病的代谢特征的模型。目前的超极化方法存在缺陷，将严重影响Hp 13C分子的临床应用。例如，目前唯一商业化的超极化器需要13C分子与有毒物质混合才能使13C原子核超极化。此外，目前的超极化器不容易扩展到商业供应所需的生产水平。MKT开发了一种超极化方法和相关的商业模式，直接解决了这些问题。样品的超极化是通过允许原子核在非常低的温度、非常高的磁场环境中松弛来实现的。量子液体3He和4He的使用使松弛过程非常迅速，而且不使用有毒材料。HP样品是从低温恒温器中提取出来的，没有不必要的偏振损失；这使得它们能够远距离运输，从而消除了偏振器必须靠近核磁共振机器的需要。该过程是可扩展的，适用于各种样品，包括那些对代谢有兴趣的样品，如富含13C的醋酸。我们的长期目标是为临床MRI市场制造和供应惠普材料。我们的短期目标是证明使用我们的专利技术可以超极化13C浓缩酸，从低温恒温器中提取，运输到附近的医院，与氢氧化钠碱性溶液反应形成HP醋酸钠溶液，然后用于进行各种超极化磁共振波谱(MRS)实验。我们将演示QRS技术与室温热平衡的醋酸样品相比，在HP醋酸样品中产生超过5000的SNR增益(目标I)。我们将证明HP 13C醋酸可以运输2小时(或更长时间)而没有显著的极化损失(AIM II)。这将证明，醋酸可以在一个位置超极化，并被输送到另一个位置，用于不同的MRS应用。接下来，我们将演示将HP 13C醋酸转化为HP 13C醋酸酯溶液，与室温热平衡下的醋酸样品相比，信噪比超过1000(目标III)。然后，HP醋酸钠溶液将用于在酵母呼吸悬浮液中进行的MRS实验和在分离的灌流大鼠心脏中跟踪新陈代谢(目标IV)。与公共健康相关：今年将有超过70万美国人死于心脏病。对心脏代谢过程进行成像的能力有可能极大地改进心脏病的诊断和治疗。心脏代谢图像的产生需要开发超极化的13C浓缩分子，如醋酸钠；Millikelvin Technologies开发了一种制造超极化醋酸钠的方法，这种方法不需要添加有毒材料，可以扩大规模以满足广泛的需求，并将通过提供超极化醋酸钠作为消耗品来降低成本。