NH 5 - Hyperpolarised MRI: imaging tissue metabolism in real time
on Mar 2nd
08:30 - 10:00
1. To understand the basic principles of hyperpolarisation (how is it achieved, how long does it last, and how does it compare to PET).
2. To present clinical and preclinical applications of hyperpolarisation.
3. To explore potential future applications of hyperpolarisation.
Conventional MRI can access only 10-4-10-5 of the potential nuclear magnetic polarisation. Hyperpolarisation can achieve greater than 10% polarisation, i.e. more than 10,000 increase in polarisation and MRI signal of atoms such as 13C, 15N, 3He and 129Xe. This hyperpolarisation is achieved by transfer of polarisation from: polarised laser light, polarised supercooled electrons or polarised parahydrogen. Its short in-vivo T1 is usually much less than a minute. Since the hyperpolarisation is achieved outside the body, it must be quickly injected or inhaled and rapidly imaged with sequences adapted to optimal utilisation of the non-renewable nuclear magnetisation. Despite the hyperpolarisation, the signal is still relatively low, and large, usually non-physiologic, doses are required for imaging. In SNR it cannot compete with PET which has picomolar sensitivity. However, PET is not spectroscopic, i.e. it is not sensitive to the chemical bonds of the reporter atom. PET also has a much lower temporal resolution and does not have available the rich family of MRI sequences that can probe diffusion, motion, etc. Therefore, the promise and uniqueness of hyperpolarised MRI is in metabolic and physiologic quantitation and imaging. In our New Horizon session, some of the leading experts in the field will present the current status and research on applications of hyperpolarised MRI. We will finish off with a panel discussion and speculation on the future of hyperpolarised MRI.
1. To explore the role of metabolism in cancer development.
2. To understand how these changes in metabolism can be exploited using hyperpolarised 13C-pyruvate.
3. To review the current evidence for hyperpolarised carbon-13 imaging in oncology.
4. To understand potential clinical applications for hyperpolarised carbon-13 imaging.
5. To consider the role of new hyperpolarised molecules in oncology.
There is increasing evidence to support a role for metabolism in tumour development, for example, deregulation of cellular energetics is now considered to be one of the key hallmarks of cancer. Changes in tumour metabolism over time are now known to be early biomarkers of successful response to chemotherapy and radiotherapy. There are a number of imaging methods that have been used to probe cancer metabolism: the most widely available is 18F-fluorodeoxyglucose (FDG), an analogue of glucose, used in PET. Hyperpolarised carbon-13 MRI (13C-MRI) is an emerging molecular imaging technique for studying cellular metabolism, particularly in the field of oncology. This method allows non-invasive measurements of tissue metabolism in real time. To date, the most promising probe used in conjunction with hyperpolarised MRI has been 13C-labelled pyruvate: pyruvate is metabolised into lactate in normal tissue in the absence of oxygen, but in tumours this occurs very rapidly even in the presence of oxygen. Results from many animal models have shown that there is a reduction in the metabolism of pyruvate following successful treatment with chemotherapy. Tumour lactate labelling has also been shown to correlate with the grade of some tumour types. There are now a small number of sites performing human hyperpolarised carbon-13 MRI imaging. This talk will discuss the progress that has been made in this field within the area of oncology and potential clinical applications.
1. To become familiar with the principles of hyperpolarised MRI.
2. To understand the key parameters required to integrate a hyperpolariser into a MRI facility.
3. To learn about the cardiac metabolic pathways that can be probed by hyperpolarised MR.
The tremendous polarization enhancement afforded by dissolution dynamic nuclear polarization (DNP) can be taken advantage of to perform molecular and metabolic imaging. Following the injection of molecules that are hyperpolarized via dissolution DNP, real-time measurements of their biodistribution and metabolic conversion can be recorded. This technology, therefore, provides a unique and invaluable tool for probing cellular metabolism in vivo in a noninvasive manner. It gives the opportunity to follow and evaluate disease progression and treatment response without requiring ex vivo destructive tissue assays. Five sites across the globe are currently performing human studies using hyperpolarized 13C-pyruvate and several other institutions are on the brink of being ready to inject their first patients. One of the most promising fields of application of this technology is cardiology. Cardiac dysfunction is often associated with a shift in substrate preference for ATP production and hyperpolarized 13C magnetic resonance has the unique ability to detect real-time metabolic changes in vivo due to its high sensitivity and specificity. Several proposed methods for assessing metabolic flux through different enzymatic pathways will be presented. It will be shown how hyperpolarized 13C magnetic resonance enables mechanistic studies of the changing myocardial energetics often associated with disease.
1. To learn about the promises and challenges to build a hyperpolarised gas enhanced lung imaging programme.
2. To compare hyperpolarised gas enhanced lung MRI with emerging multinuclear functional lung MRI techniques without the need for hyperpolarised gas.
In the last decade, functional imaging of the lungs using hyperpolarized noble gases has entered the clinical stage. Both helium (3He) and xenon (129Xe) gas have been thoroughly investigated for their ability to assess both the global and regional patterns of lung ventilation. With advances in polarizer technology and the current transition towards the widely available 129Xe gas, this method is ready for translation to the clinic. Also advantages and disadvantages of hyperpolarized gas functional lung imaging are highlighted and compared to MRI techniques for regional ventilation quantification without the need for hyperpolarization such as 19F MRI and Fourier decomposition ventilation MRI.
1. To get an overview of the many targets available for hyperpolarised molecular targets.
2. To understand the basic chemical properties of hyperpolarised MRI molecular imaging probes.
3. To understand the role of stable-isotopes in hyperpolarised MRI.
4. To understand the biochemical processes that can be imaged with hyperpolarised MRI.
The dissolution-dynamic nuclear polarization technology had revolutionized the way small molecules can be imaged and their chemical evolution monitored, in physiologically relevant doses, by magnetic resonance imaging and spectroscopy. In this presentation, we will review several molecules that have proven useful as such molecular imaging probes. The specific stable isotopes with which these molecules were labelled will be reviewed (13C, 15N, 2H). The basis for these labelling strategies will be explained, predominantly the effects on MR visibility and T1. Naturally abundant nuclei such as protons and yttrium that are useful for hyperpolarized MRI will also be introduced. The main biochemical pathways that can be followed with hyperpolarized MRI and spectroscopy of these molecular imaging probes will be reviewed in the context of the potential emerging applications for hyperpolarized MRI and spectroscopy.