The molecular cage holds the xenon, while the target unit (orange) allows it to selectively bind to the desired target molecule.  (Source: Berkeley Lab and UC Berkeley)

When the molecule finds its target, the cryptophan cage starts to convert polarized xenon gas to non-polarized xenon. The proess is temperature dependent, which can improve the accuracy of the detection.  (Source: Berkeley Lab and UC Berkeley)

The team that developed the new technology includes team leader Leif Schröder (left) with Monica Smith, who holds a probe housing a phantom target, and Tyler Meldrum, holding a model of a biosensor's cryptophane cage  (Source: Berkeley Lab and UC Berkeley)
Peeking inside the human body just got a little bit easier

Some very complex, but very important research breakthroughs have recently taken place at the labs of Alexander Pines and David Wemmer at Berkeley Lab and UC Berkeley.  The new breakthroughs revolve around the process of magnetic resonance imaging (MRI).  MRIs are valuable diagnostic tools, helping to reveal detailed information on neurological, musculoskeletal, cardiovascular, and oncological structure and health.  This in turn allows doctors to diagnose tumors and various other maladies.

The main problem with MRIs is that they’re slow, force the patient to lie still, and lack resolution.  The alternative is to take a biopsy of the possibly affected tissue, but many chemical tests must be done to analyze it.  Now a new method in essence lets a highly accurate MRI, thousands of times more precise to be conducted on biopsies, allowing individual molecules to be identified, and largely eliminating the need for multiple tests.

Tradition MRI devices rely on Nuclear Magnetic Resonance (NMR) imaging; a process by which RF radiation is sent, setting molecules spinning due to their odd number of protons.  Depending on the nearby structures, their spin will be altered.  RF radiation is subsequently emitted from the spinning molecule, revealing if it spins "up" or "down".  By measuring the number spinning up versus down, the nearby structures attached can be determined.  In MRIs the spin of the molecules is traditionally enhanced used a magnetic field.

Typically, MRIs measure spin from hydrogen atoms, an abundant element in the human body, which is largely composed of hydrocarbons.  Traditional biopsy methods typically rely on chemical indicators, which change color when they detect a specific target molecule.

The new method combines NMR/MRI technology with biopsy analysis.  The key is to use xenon gas molecules and a special organic molecular cage which holds them.   The molecule is composed of a cage which holds xenon molecules, an intermediate organic section, and a ligand (part of the molecule which bonds to other stuff) at its end.  The ligand ensures that the molecule only bonds to a specific target.

The molecules are injected along with polarized xenon gas into the sample.  When the cage molecules find the target of their ligand, they bond to it.  The cage then begins to depolarize xenon.  This depolarized xenon is then picked up by MRI devices.  This specialized type of Magnetic Resonance Imaging is dubbed Hyper-CEST for hyperpolarized xenon chemical-exchange saturation transfer.

The rate can also be temperature controlled, to improve the process.  Also using multiple cage designs can improve results.  The end result is a much higher accuracy version of MRI/biopsy processes.  Team member Tyler Meldrum, of the Materials Sciences Division describes these benefits stating, "Slight differences in cage composition, involving only a carbon atom or two, affect the frequency of the signal from the xenon and produce distinct peaks in the NMR spectrum.  If we design different cages for different xenon frequencies, we can put them all in at once and, by selectively tuning the rf pulses, see peaks at the frequencies corresponding to each kind of cage.

While this technology will likely take a while to get to market, it will likely provide a valuable diagnostic tool.  The researchers have solved half the problem -- the detection molecule -- now the real challenge that remains is cataloguing ligands that can bind selectively to the plethora of molecules produced when stuff goes right or wrong in the human body. 

This new diagnostic tool, while very promising, like many new promising drug delivery techniques, relies on the development of target molecules which can detect cancer cells or other items of interest.  The problem won't be solved overnight, but by slow and steady research.  This is why projects like Folding At Home remain so valuable to the medical community.

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