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Quantum hyperpolarization enhances MRI sensitivity to detect cancer and brain tumors

Quantum technology (QT) applies quantum mechanical properties such as quantum entanglement, quantum superposition, and No-cloning theorem to quantum systems such as atoms, ions, electrons, photons, or molecules. Quantum technologies are already revolutionizing life on Earth. But they also have the potential to change the way we operate in space.


Quantum Sensing exploits the high sensitivity of quantum systems to external disturbances to develop highly sensitive sensors.  Quantum sensors are measuring device that takes advantage of quantum correlations, such as states in a quantum superposition or entanglement, for better sensitivity and resolution than can be obtained by classical systems. These sensors offer a particularly high level of sensitivity based on certain delicate quantum phenomena, such as quantum decoherence and quantum entanglement.


They can measure Quantities such as time, magnetic and electrical fields, inertial forces, temperature, and many others. They employ quantum systems such as NV centers, atomic vapors, Rydberg atoms, and trapped ions.


The discrimination of chemical analytes with sub-micron scale spatial resolution is an important frontier in nuclear magnetic resonance (NMR) spectroscopy. Quantum sensing methods have attracted attention as a pathway to accomplish these goals.


Conventional nuclear magnetic resonance (NMR) experiments are limited by low sensitivity and weak signals.  Such sensors predominantly operate at low magnetic fields. Instead, however, for high-resolution spectroscopy, the high-field regime is naturally advantageous because it allows high absolute chemical shift discrimination


Quantum sensors have attracted broad interest in the quest towards sub-micron scale NMR spectroscopy.  These are typified by sensors constructed from the nitrogen-vacancy (NV) defect center in diamond electrons that can be optically initialized and interrogated and made to report on nuclear spins in their environment. However, NV sensors are still primarily restricted to bulk crystals and operation at low magnetic fields (B0 < 0.3 T)


NMR experiments rely on creating a difference in population of nuclear spin energy levels, such that the net magnetic field they produce may be detected. This polarization, as it is called, is most commonly induced thermally by applying strong magnetic fields to establish an energetic preference for spins aligned with or against the applied field. Current magnetic resonance technologies have pushed towards increasingly stronger fields in order to overcome inherently poor nuclear polarization at thermal equilibrium, which remains as a limitation to sensitivity and scope of the capabilities of magnetic resonance. Even the most sophisticated instruments can achieve polarizations no greater than 0.01%, and such gains in sensitivity are nearly negated by the cost and impracticality of the resulting instruments.


For this reason, Researchers have focused on developing practical methods of producing nonequilibrium polarization – or hyperpolarization – for signal enhancement in magnetic resonance methods. Hyperpolarization techniques such as dynamic nuclear polarization (DNP) enhance NMR signals by several orders of magnitude, with applications to ligand-binding, drug transport and metabolic tracing.


A number of elegant solutions have been presented for hyperpolarizing nuclei either completely or on the order of parts per hundred rather than parts per million. These solutions generally transfer polarization to a nuclear ensemble from systems that can be easily polarized, using the interactions that couple the two. Due to their ease of polarization by magnetic fields, optical illumination, or chemical reaction, current sources for polarization transfer are electrons in solid-state systems and organic radicals, gaseous alkali atoms, and parahydrogen.



Towards greater MRI sensitivity by harnessing quantum hyperpolarization

Researchers at the University of Melbourne have developed a technique which could increase the sensitivity of magnetic resonance imaging (MRI) for patient diagnosis. The new technique works by increasing the strength of the magnetic field produced by molecules, and hence increasing their signal when measured by MRI.

The team engineered specific defects in diamond crystals that exert a controlled quantum mechanical influence over the nuclear spins in nearby molecules, including potentially those used in metabolic imaging of brain tumours, making them ‘line up’ (polarise) in a specific  orientation. This hyperpolarised state of nuclear spins is highly ordered and increases the magnetic field that can be detected by techniques like MRI.


It is the first time that this polarisation of molecular nuclei has been shown using such a diamond-based quantum probe. University of Melbourne School of Physics researcher Professor Lloyd Hollenberg led the research team, with the work published in Nature Communications.


Professor Hollenberg, who is CQC2T Deputy Director and Thomas Baker Chair at the University of Melbourne, said the best MRI scanners in the world are now reaching the maximum magnetic field that can be tolerated by the human body as the technology strives for greater sensitivity.


“The superconducting magnets that produce these fields are also the reason MRI scanners cost millions of dollars, as the magnets need to be kept at cryogenic temperatures,” Professor Hollenberg said. “Clearly a disruptive approach is needed, so we look to using quantum technology to produce a greater signal intensity of certain molecular targets at the atomic level.”


University of Melbourne PhD candidate David Broadway said the technique worked using a fridge magnet and a bit of atomic level quantum mechanics. “We can think of the atom’s nuclei like a compass needle that produces a magnetic field that depends on its orientation,” Mr Broadway said.

“When there are several compass needles pointing in different directions, the resulting field tends to average to zero, but when the compasses point all in the same direction the contributions to the field from each compass needle will add up to something measurable,” he said. “So having the nuclei all lined up makes the magnetic field stronger and therefore the MRI reading it can pick up more detail.

“Currently, MRI’s can get about one in a million nuclear spins to line up, whereas our method could achieve nearly 100 percent to line up within molecules, potentially enhancing the imaging sensitivity by orders of magnitude.”

The modified diamonds could be used to construct a “quantum hyperpolarisation” chip, over which a target molecular contrast agent could be flowed. The quantum mechanical interaction between target and quantum probes is harnessed to transfer the polarisation from the diamond to the agent, which could be injected into, or inhaled by, a patient prior to their MRI. The agent retains its polarisation long enough to, for example, travel to a tumour site, making it easier to image through MRI.

Postdoctoral researcher Dr Liam Hall said MRI-based precision medicine already employs this type of imaging, but the cost of the infrastructure required can rival that of the MRI scanners themselves.

“Additionally, we would only use light shone through diamonds in the quantum mechanical production of polarised contrast agents already approved for routine use. So nothing toxic would enter the body,” Dr Hall said.

“The technique came out of our work in developing quantum sensing technology, and the realisation that these diamond-based quantum probes can exert a powerful influence on surrounding nuclear spins when we optimise the conditions under which they directly “talk” to eachother,” said Dr Hall, who came up with the theoretical concept.

“In a sense, the quantum probe extracts random spin disorder from the (‘hot’) target molecule to produce an ordered (‘cold’) spin-aligned state. The potential for application in hyperpolarisation for MRI soon became clear.”

The power of the quantum technique is manifest from the experimental demonstration.

Professor Hollenberg said: “To put it in context, to achieve the same level of polarisation with a conventional approach, we’d need to increase the magnetic field by a factor of about 100,000 times, and you’re only going to find fields like that in a neutron star.”

Techniques for hyperpolarising nuclear spins could have a number of important applications in the physical and life sciences.

Hyperpolarised metabolites can be injected into patients and will travel to tumour sites and where they can be monitored in real-time using MRI as they’re metabolised; and hyperpolarised gases can be inhaled for MRI imaging of lungs and their function. Both of these techniques have central roles to play in the dawning era of personalised medicine.

Hyperpolarisation of target molecules also increases to signal to noise ratio of high-resolution Nuclear Magnetic resonance (NMR) spectroscopy, making it an important tool for studying complex biomolecular systems.

“Clearly the next step, which we are heavily focused on, is to repeat this process using macroscopically sized engineered arrays of these quantum probes in diamond to scale this technology up,” Professor Hollenberg said.

“More probes equals more polarisation and more contrast agent molecules produced, but the probes start to upset each other quantum mechanically if they are packed in too closely, so we need to find the right balance,

“If we can tick that box, we can then think about polarising volumes of MRI contrast agents that are detectable by the MRI scanners found in research labs and hospitals.”


Revolutionizing Cancer Imaging with Quantum Technologies” project (QuE-MRI)

Detecting cancer cells in early stages, assessing them with greater precision and evaluating the effectiveness of treatments faster is facilitated by the visualization of metabolic processes in both diseased and healthy cells. This is known as metabolic imaging. To this end, diagnostically relevant molecules are injected into the body and their metabolism is monitored.

One approach is to use positron emission tomography (PET). However, this method requires radioactive substances and cannot distinguish between the initial and end products in metabolic processes. Magnetic resonance imaging (MRI), on the other hand, allows metabolic imaging of various metabolites without using radioactive substances. Albeit only if the MRI signal of the injected molecules is amplified sufficiently to make it detectable. Although initial patient studies show great potential of metabolic imaging with MRI, the signal amplification technologies deployed up to now are prohibitively expensive, insufficiently robust, or slow. This has prevented routine deployment of these technologies in clinical settings up to now.

The interdisciplinary research team of the “Revolutionizing Cancer Imaging with Quantum Technologies” project (QuE-MRI) is now developing a new solution: A so-called quantum hyperpolarizer uses quantum physical laws to amplify the signal of metabolic molecules in the MRI up to 100,000-fold.


Imaging with the laws of quantum mechanics

The technology of common MRI machines takes advantage of quantum mechanical properties of atomic nuclei associated with the so-called spin, or angular momentum. Each nuclear spin generates a magnetic moment, not unlike the dipole magnet of a compass needle.

The alignment of the nuclear spins determines the strength of the overall magnetic moment of the atomic nuclei. This in turn determines the signal strength, which is used for magnetic resonance imaging. When the directional distribution of the magnetic moments is random, they cancel each other out and the MRI machine detects no signal. The strongest signal is achieved when the magnetic moments of the nuclear spins point in the same direction, resulting in the maximum effective magnetization.

MRI uses very strong magnetic fields to make this possible. Nonetheless, the magnetic moments of the nuclear spins are nearly randomly distributed and thus have only low effective magnetization. The technique of hyperpolarization boosts the effective magnetization of the nuclear spins by factor of 10,000 to 100,000, thereby significantly increasing the sensitivity of MRI.

Hyperpolarization of diagnostically relevant metabolic molecules

However, in practice enticing the atomic nuclei of the metabolic molecules into a hyperpolarized state is difficult. The researchers therefore use an intermediate step based on a special magnetic state of hydrogen, called para-hydrogen. This can be produced at low temperatures using known methods with liquid nitrogen and stored in gas cylinders.

The properties of para-hydrogen also build on the laws of quantum mechanics. While para-hydrogen itself is magnetically shielded and not measurable using magnetic resonance methods, its spin configuration can hyperpolarize other atomic nuclei, increasing their visibility in MRI.

Using this approach, the researchers hyperpolarize molecules important for studying metabolic processes. Pyruvate, for example, a metabolic product that is processed into lactic acid by tumors, is particularly suitable for diagnostic purposes. The researchers dock para-hydrogen onto pyruvate in the hyperpolarizer and use its spin configuration to hyperpolarize a carbon atom of pyruvate in a magnetic field using radio waves. The signal from pyruvate is thereby enhanced in MRI, allowing the corresponding metabolic process to be visualized with temporal resolution.

Project partners have already developed functional prototypes of the hyperpolarizer. In the QuE-MRI project, researchers, physicians, industrial partners, and developers in the fields of medicine, physics, chemistry and engineering are now collaborating closely to optimize these prototypes so that the hyperpolarizer can be deployed clinically on a large scale. In addition, the project team plans to validate the non-invasive and non-radioactive technology in initial clinical trials for the diagnosis of cancer.


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