Dynamic nuclear polarization: how a technique from particle physics is transforming medical imaging
An experimental technique that started life in nuclear and particle physics is now being used to measure chemical reactions inside the human body and to help diagnose cancer and heart disease in almost 50 clinical trials. Jack Miller charts the unexpected rise of dynamic nuclear polarization, which is vastly improving the quality of magnetic resonance imaging
Life, for physicists, is an odd thing, seeming to create order in a universe that mostly tends towards disorder. At a biochemical level, life is even stranger – controlled and thermodynamically powered by a myriad of different molecules that most of us have probably never heard of. In fact, there’s one molecule – pyruvic acid – that’s crucial in keeping us alive.
When burned, pyruvic acid releases carbon dioxide and water. If you’re exercising hard and your muscles are running low on oxygen, it’s converted anaerobically into lactic acid, which can give you a painful stitch. Later, your liver recycles the lactic acid back into sugars and the process starts anew.
But pyruvic acid – known chemically as 2-oxypropanoic acid (CH3CO-COOH) – is also a marker for what’s going on inside your body. Run up a flight of stairs, skip a meal or get anaesthetised, and the rate at which pyruvic acid is metabolized (and what it’s converted into) will change. The speed with which it’s made or consumed will also vary enormously if you’re unfortunate enough to have a heart attack or develop cancer.
As it turns out, we can track this molecule by exploiting the intrinsic angular momentum, or “spin”, of the nuclei in pyruvic acid. Spin is a fundamental physical property that comes in either integer or (in the case of protons and carbon-13 nuclei for example) half-integer multiples of ħ (Planck’s constant divided by 2π). Using an experimental technique known as “dissolution dynamic nuclear polarization” (d-DNP), it’s possible to create a version of the acid where many more of its carbon-13 nuclei exist in one spin state than another.
By injecting this “hyperpolarized” pyruvic acid into a biological system, we can improve the notoriously poor signal-to-noise ratio of magnetic-resonance imaging (MRI) by a staggering five orders of magnitude. MRI, which has been of huge benefit in medicine, uses a mix of strong magnetic fields and radio waves to yield detailed images of human anatomy and physiological process inside the body. Its downside is, though, that patients often have sit for over an hour in an MRI machine for clinicians to get images that have a good enough resolution for their needs.
With d-DNP, however, we can gain spectacular MRI images that reveal in detail what happens to pyruvic acid in biological systems. Over the last 20 years, the technique has been used to image bacteria, yeast and mammalian cells. It has looked at animals such as rats, mice, snakes, pigs, axolotls – and even dogs being treated for cancer. Most importantly, about 1000 people at 20 or so research labs around the world have been imaged using d-DNP with almost 50 clinical trials under way.
Ups and downs of magnetic resonance
Giving clinicians valuable images of the location of water and fat in the body, the beauty of MRI is that it’s non-invasive and won’t harm a patient – even if sitting inside the bore of a magnet is not particularly pleasant. But magnetic resonance can yield far more than just pretty pictures because the behaviour of a nucleus in an applied magnetic field depends on where the nucleus is in a molecule and its precise location in the human body. In fact, we can use radio waves to measure the quantity and location of those nuclei in biological systems, turning MRI into a spectroscopic technique.
MRI spectroscopy is able to reveal the precise distribution of molecules, such as lactic acid and adenosine triphosphate (ATP – the source of energy for use and storage at the cellular level) in almost any biological tissue. Unfortunately, these molecules are usually present at such low concentration that MRI images of them have a much lower resolution that equivalent images of water or fat. Worse, most MRI spectroscopy experiments require a patient to sit still for hours to get enough decent data, which is difficult especially if they’ve got an itchy nose or need the toilet.
In the late 1990s, however, Jan Henrik Ardenkjær-Larsen – a physicist at the Technical University of Denmark (TUD) in Copenhagen – realized that d-DNP could make MRI spectroscopy much more sensitive. Developed with his TUD colleague Klaes Golman and others, the technique of d-DNP involves some beautiful basic physics that emerged from nuclear and particle labs back in the 1950s (see box at the end of this article, “Stealing polarization from electrons”). At the heart of d-DNP is the concept of “nuclear polarization”, which comes from the energy levels of a nucleus with spin being split into two (or more) components when exposed to a magnetic field. The difference in energy, which is proportional to the strength of the field, provides useful information about the location of the nucleus.
#ResearchAdvancements #InnovationInHealthcare #DrugDevelopment #PrecisionMedicine #FunctionalImaging#MetabolicMRI#MRIEnhancement #ParticlePhysicsInMedicine#MedicalImaging#DynamicNuclearPolarization
Life, for physicists, is an odd thing, seeming to create order in a universe that mostly tends towards disorder. At a biochemical level, life is even stranger – controlled and thermodynamically powered by a myriad of different molecules that most of us have probably never heard of. In fact, there’s one molecule – pyruvic acid – that’s crucial in keeping us alive.
When burned, pyruvic acid releases carbon dioxide and water. If you’re exercising hard and your muscles are running low on oxygen, it’s converted anaerobically into lactic acid, which can give you a painful stitch. Later, your liver recycles the lactic acid back into sugars and the process starts anew.
But pyruvic acid – known chemically as 2-oxypropanoic acid (CH3CO-COOH) – is also a marker for what’s going on inside your body. Run up a flight of stairs, skip a meal or get anaesthetised, and the rate at which pyruvic acid is metabolized (and what it’s converted into) will change. The speed with which it’s made or consumed will also vary enormously if you’re unfortunate enough to have a heart attack or develop cancer.
As it turns out, we can track this molecule by exploiting the intrinsic angular momentum, or “spin”, of the nuclei in pyruvic acid. Spin is a fundamental physical property that comes in either integer or (in the case of protons and carbon-13 nuclei for example) half-integer multiples of ħ (Planck’s constant divided by 2π). Using an experimental technique known as “dissolution dynamic nuclear polarization” (d-DNP), it’s possible to create a version of the acid where many more of its carbon-13 nuclei exist in one spin state than another.
By injecting this “hyperpolarized” pyruvic acid into a biological system, we can improve the notoriously poor signal-to-noise ratio of magnetic-resonance imaging (MRI) by a staggering five orders of magnitude. MRI, which has been of huge benefit in medicine, uses a mix of strong magnetic fields and radio waves to yield detailed images of human anatomy and physiological process inside the body. Its downside is, though, that patients often have sit for over an hour in an MRI machine for clinicians to get images that have a good enough resolution for their needs.
With d-DNP, however, we can gain spectacular MRI images that reveal in detail what happens to pyruvic acid in biological systems. Over the last 20 years, the technique has been used to image bacteria, yeast and mammalian cells. It has looked at animals such as rats, mice, snakes, pigs, axolotls – and even dogs being treated for cancer. Most importantly, about 1000 people at 20 or so research labs around the world have been imaged using d-DNP with almost 50 clinical trials under way.
Ups and downs of magnetic resonance
Giving clinicians valuable images of the location of water and fat in the body, the beauty of MRI is that it’s non-invasive and won’t harm a patient – even if sitting inside the bore of a magnet is not particularly pleasant. But magnetic resonance can yield far more than just pretty pictures because the behaviour of a nucleus in an applied magnetic field depends on where the nucleus is in a molecule and its precise location in the human body. In fact, we can use radio waves to measure the quantity and location of those nuclei in biological systems, turning MRI into a spectroscopic technique.
MRI spectroscopy is able to reveal the precise distribution of molecules, such as lactic acid and adenosine triphosphate (ATP – the source of energy for use and storage at the cellular level) in almost any biological tissue. Unfortunately, these molecules are usually present at such low concentration that MRI images of them have a much lower resolution that equivalent images of water or fat. Worse, most MRI spectroscopy experiments require a patient to sit still for hours to get enough decent data, which is difficult especially if they’ve got an itchy nose or need the toilet.
In the late 1990s, however, Jan Henrik Ardenkjær-Larsen – a physicist at the Technical University of Denmark (TUD) in Copenhagen – realized that d-DNP could make MRI spectroscopy much more sensitive. Developed with his TUD colleague Klaes Golman and others, the technique of d-DNP involves some beautiful basic physics that emerged from nuclear and particle labs back in the 1950s (see box at the end of this article, “Stealing polarization from electrons”). At the heart of d-DNP is the concept of “nuclear polarization”, which comes from the energy levels of a nucleus with spin being split into two (or more) components when exposed to a magnetic field. The difference in energy, which is proportional to the strength of the field, provides useful information about the location of the nucleus.
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