Feature article

How new methods of magnetizing cells makes MR imaging more convenient and affordable

What if cancer patients and oncologists could find out whether or not chemo or radiation therapy worked on the day of treatment instead of months later? Imagine patients even in remote locations of the world having access to affordable and convenient MRI scans with a hand-held mobile device. Or a physician who can personalize patient treatment in real-time by conducting MRI scans in the operating theater or during office visits that improve outcomes for critical conditions, such as concussions, tumor resection, aneurysms, and hemorrhagic stroke.

MRI is used to perform millions of scans per year to study the structure and function of biological systems for diagnosis and research. Visualizations produced can detect structures as small as half a millimeter.1 Today assessment of much smaller cellular components down to a single nanometer, or molecule, are being examined and it’s opening a whole new world of advancements in MR imaging.

Nano visualizations

Researchers in California wanted to know what happens in tissues at a resolution of a single micrometer, or about 500 times smaller than what has traditionally been possible with MRI visualizations.2,3,4 Up until now, scanner resolution has allowed physicians to see details of organs down to a half millimeter in size but not much smaller.2,3,4 Beyond that, they have to infer what is happening to cells in the tissue.2,3,4

Using a method called nitrogen-vacancy (NV) magnetometry and an NV magneto-microscope custom built to conduct their experiments, a team of scientists introduced a technique that correlates magnetic field patterns in tissue, which occur on micrometer scales, with the larger, millimeter-scale features of MRI images.2,3,4 They were able to increase the resolution of MRI images and allow structures as small as a few micrometers to be visualized enabling better diagnosis from MRI imaging.2,3,4

In one experiment, locations of inflamed tissues in a patient's body were identified based on MRI images of immune cells called macrophages labeled with magnetic iron particles.2,3,4 After the macrophage cells absorb and store the iron particles via endocytosis, they migrate toward and reveal the locations of tissue inflammation.2,3,4

A team of researchers in the U.S. and Canada have also introduced a new high-resolution MRI method that can produce scans with resolutions down to two nanometers, or the width of a DNA strand.1 They combined a special kind of magnetic field generator and specifically engineered laser pulses to detect and control the properties of atomic nuclei during imaging.1 A tool called a current-focusing field gradient source (CFFGS) was used to produce a strong magnetic field that changes quickly over short distances.1,5 Scientists are particularly optimistic about this technique because it addresses some of the limitations of other nano-MRI techniques.1,5

The impact of magnetizing and visualizing substances and structures at higher resolutions down to the nanometer or micrometer is advancing personalized medicine and treatment outcomes in a wide range of areas.

Buyers Guide_950x250.jpg

Magnetizing Molecules

A team of researchers in Denmark has developed a new method of using MRI imaging to detect cellular level metabolism that could help doctors determine if a patient’s chemo or radiotherapy treatment was effective on the same day instead of months later.6

Using a hyperpolarization device developed by the research team, the new method magnetizes a naturally occurring tracer such as glucose pyruvate that can be detected in MRI scans.6 When injected into a patient beforehand, it is absorbed by the body’s cells and boosts the MRI signal by a factor of up to 20,000.6

Cancer cells are known for their characteristically high metabolism that converts and breaks down sugar molecules into metabolites, including lactate, more quickly than non-cancerous cells.6 Cells that are highly active break down more glucose producing higher concentrations of lactate which increase the number of cells that are illuminated on the MRI scan.6 If the amount of metabolites decreases, it means that the cancer tumor activity is declining.6 Because the magnetic signal of lactate produces a strongly lit area in the MRI scan doctors can see in real-time how active cancer cells in a tumor are before and after administering treatment.6

Researchers report this method of determining the effectiveness of cancer therapy is gentler and less harmful than other diagnostic methods such as injection of radioactive trace elements or biopsy.6 It is currently being used by physicians to carry out clinical studies in patients and investigated for its usefulness in monitoring other diseases such as diabetes and cardiovascular diseases that also manifest as a result of metabolic changes in cells.6

One challenge with this hyperpolarization method has been the short shelf life of the tracer magnetism.6 It requires the polarizer device be placed close to the MRI scanner and the tracer be injected into the patient immediately after magnetization.6 Researchers are now developing a method based on new knowledge that the magnetism of electrons can be activated with UV light and deactivated with heat, essentially turning them on and off.6 Doctors would then be able to hyperpolarize the contrast medium long before use thereby overcoming the concern about short shelf life magnetism.6

In England, a team of researchers has developed a method for making molecules that occur naturally in the body, such as urea, pyruvate, and glucose, more magnetic and, consequently, more visible on MRI scans.7  By using the ‘invisible’ magnetism of parahydrogen, a magnetic form of hydrogen gas, and ammonia as the carrier, substances like urea are hyperpolarized without changing their composition into a toxic form.7

This alternative method of increasing the magnetism of nontoxic naturally occurring substances found in the body is considered a significant step toward enabling doctors to personalize life-saving medical treatments and allow real-time imaging to occur.7 In the operating theater, a surgeon’s goal is to remove all cancerous tissue and as little healthy tissue as possible during tumor resection.7 This low-cost, nontoxic new method of cell magnetization can provide the accuracy and depth of visualization needed during the procedure that has not previously been available.7

With the possibility of performing regular and repeated highly sensitive scans due to reduced cost and nontoxic contrast mediums, researchers believe this could transform the ability to diagnose and treat a range of diseases, including cancer, diabetes, and dementia with more successful outcomes.7

While looking for a way to enhance the signal of an MRI tracer, a team of researchers in Iowa and Florida discovered a process that can increase the signal of the body’s most common substance: water.8 Strengthening the signal of water as a contrast medium makes it a much more appealing agent than a chemical contrast that can be costly and toxic to the human body.8

Water’s naturally occurring weak magnetic signal is enhanced by bubbling a magnetized form of hydrogen gas through water containing an intermetallic compound.8 When the aligned spin of the hydrogen gas and water meet at the surface of the compound, the interaction that occurs transfers the aligned spin of the magnetized hydrogen to water.8

Separating the intermetallic compound from the water becomes easy leaving pure water aligned in a way that produces a strong signal in MRI scans.8 The magnetic signal of the water is so strong after this process that it can be detected by a weak magnetic field such as might be possible with smaller, less expensive portable device that can be used with greater flexibility where larger machines are not available or possible.8 Researchers expect this new method could have a variety of applications ranging from low-field MRI to drug discovery.9

Contrast agents have a history of making it difficult to interpret MRI scans correctly because the medium can appear similar to human tissue, which gives off their own MRI signals.10 A common example occurs when a dark patch on a scan located near a tumor cannot be distinguished with certainty as a contrast agent bound to a tumor or an irrelevant signal from surrounding tissue.10

Researchers in California decided to develop MRI contrast agents that could be turned off, or erased, on command with ultrasound to make it easier to assess scans with greater certainty.10 Their erasable MRI agent is a nanoscale structure naturally produced by some microbes and known as a gas vesicle.10 These sac-like structures have hollow interior chambers that collapse when hit with ultrasound waves of a high enough pressure making it possible to turn the magnetic signal off and reveal their exact location in the scan.10

Each vesicle consists of a protein shell with a hollow interior chamber that bounces back sound waves in a distinctive manner.10 This not only makes them easy to identify from regular tissue but they also stand out in MRI scans because air in their hollow interiors reacts differently to magnetic fields causing a darkening on the MRI scan when compared to tissues around them.10

Earlier studies with gas vesicles demonstrated the ability to genetically modify them to target specific cells, such as cancer, or engineer them to function separately in order to visualize two types of tissue at once, such as tumor versus healthy.10 In a new study performed in mice, the researchers were able to use MRI to detect the hollow chambered sacs in certain tissues and organs, such as the brain and liver.10

Clinicians and researchers across specialties are truly excited about opening the door to modalities of magnetic resonance that, although they have been envisioning for them decades, could not be achieved until now with the technological advancements required to bring them to fruition.

 

 

REFERENCES:

  1. Huge Advancement in MRI Tech Captures Teeny Molecules With Incredible Resolution. Gizmodo. https://gizmodo.com/huge-advancement-in-mri-tech-captures-teeny-molecules-w-1823428939 Accessed 8/30/3018
  2. Taking MRI technology down to micrometer scales. Science X Phys.org. https://phys.org/news/2018-03-mri-technology-micrometer-scales.html Accessed 8/30/2018
  3. Mapping the microscale origins of magnetic resonance image contrast with subcellular diamond magnetometry. Nature. https://www.nature.com/articles/s41467-017-02471-7 Accessed 8/30/2018
  4. Taking MRI Technology Down to Micrometer Scales. CALTECH News. http://www.caltech.edu/news/taking-mri-technology-down-micrometer-scales-81663 Accessed 8/30/2018
  5. High-Resolution Nanoscale Solid-State Nuclear Magnetic Resonance Spectroscopy. American Physical Society Physical Review X Journal.  https://journals.aps.org/prx/abstract/10.1103/PhysRevX.8.011030 Accessed 8/30/2018
  6. Magnetic contrast agent behind clear MRI images. DTU Technical University of Denmark. http://www.dtu.dk/english/news/2018/06/dynamo-theme-3-magnetisk-kontraststof-bag-skarpe-mr-billeder?id=dad214b9-ded6-4514-aea6-a4e52d68ce2d Accessed 8/30/2018
  7. Next-generation medical scanning. ScienceDaily. https://www.sciencedaily.com/releases/2018/01/180105142456.htm Accessed 8/30/2018
  8. New discovery may change MRI technology. Iowa State University News. https://news.las.iastate.edu/2018/04/20/new-discovery-may-change-mri-technology/ Accessed 8/30/2018
  9. Surface-Mediated Hyperpolarization of Liquid Water from Parahydrogen. Journal of Chemistry by Cell Press. https://www.sciencedirect.com/science/article/pii/S2451929418301177 Accessed 8/30/2018
  10. Why we need erasable MRIs. ScienceDaily. https://www.sciencedaily.com/releases/2018/04/180425120143.htm Accessed 8/30/2018