University of Illinois at Urbana-Champaign and Northwestern University develope Nanometer NMR - MRI's Research Cousin used for imaging Viruses and Bacteria in the Nanometer Twilight Zone

“It's a low-temperature environment; we have to cool things down to cryogenic temperatures. And there is a way to prep biological materials to survive that, but it's by no means trivial and is something we'll have to think about moving forward. It's by no means guaranteed that the image will be at all relevant to what's going on inside someone's body.”

Lead Researcher Dr. Raffi Budakian for the physicists from the University of Illinois at Urbana-Champaign and Northwestern University who’ve developed Nanometer NMR

A team of physicists from the University of Illinois at Urbana-Champaign and Northwestern University under the guidance of Lead Researcher Dr. Raffi Budakian have finally achieved the Holy Grail of imaging Bacteria and Viruses for which many a Biochemistry Student may be excited.

They’ve developed a technique to image these nanoscopic creatures using Nanometer MRI (Magnetic Resonance Imaging) albeit it’s really aimed at NMR (Nuclear Magnetic Resonance) Spectroscopy, also called Photon NMR Spectroscopy for Research folks as its focuses on Hydrogen Nuclei used for imaging as stated in the article “Physicists inch toward Atomic-scale MRI”, published September 27, 2013 4:59 PM PDT by Elizabeth Armstrong Moore, CNET News.

This newly developed Technique allows the Physicist to see the 3D details of Viruses and Bacteria for the first time in higher resolution than is even possible with the more destructible ESTM (Electron Scanning Tunneling Microscope) Technique or even X-Ray Crystallography….. or even Medical X-Ray CAT (Computer Aided Axial Tomography) or Fluoroscopy Techniques.

The full publication of the Research can be read in “Nanoscale Fourier-Transform Magnetic Resonance Imaging”, Received 15 February 2013; revised 23 May 2013; published 26 September 2013, Phys. Rev. X 3, 031016 (2013). You can also download a copy of the Abstract for their Research here.

In the words of Lead Researcher Dr. Raffi Budakian quote: “Imagine a 3D image slice-by-slice of an influenza Virus and then looking at all the chemical components with nanometer-scale resolution. That's our dream. It provides a toolset for biology that doesn't yet exist”. Their eventual aim is to develop the System to the point that they can eventually resolve individual Atoms at 1 and 3 nanometers. This would be a boon to Research in the Field on Nanotechnology to develop Medicine at the Nanometer Level.

Examples that readily come to mind are the development of Ebola, H1N1 and HIV (Human Immuno-Deficiency Virus) Cure from Bee venom Melletin used to coat Liposomes as explained in my blog article entitled “Washington University School of Medicine Researchers use Liposomes and Melittin to kill HIV - Olympus has Fallen and given us a Panacea for every disease on planet Earth”.

Or even to be used in studying the Bacteriophages, Viruses that attack Bacteria as explained in my blog article entitled “Bacteriophage Therapy from former USSR State Georgia is a potential treatment against Super-bug Bacteria - Hansel and Gretel Witch Hunters Panacea to eradicate Bacterial infections”.

What is NMR and MRI – Separating the Sheep from the Goats

Note that NMR Spectroscopy is the name used mainly for Biochemistry Research Field whereas MRI is used in the Medical Field, both locally here in Jamaica and abroad. As I go along, I’ll use my little knowledge gleaned from working at AREL Jamaica (2013) to explain Practical MRI.

I will also combine it with my studies in Organic Chemistry from Professor Helen Jacobs in the Chemistry Department, Faculty of Pure and Applied Sciences (now the Faculty of Science and Technology) at the University of the West Indies while doing my Degree in Electronics and Chemistry. I’ll try as much as possible to make basic distinctions between NMR Spectroscopy and MRI used by Medical Doctors in Hospitals.

This will help in the understanding of this breakthrough and its enormous significance to the Biochemistry Research Community especially as it relates to imaging Viruses and Bacteria structures, both cryogenically frozen and eventually (and hopefully!) alive and wriggling sometime in the future!

MRI and NMR – A Rose by any other Name is still a Rose

MRI also called NMR (Nuclear Magnetic Resonance) Spectroscopy uses Magnetic Field to force the Hydrogen Atoms in your body to align to the Magnetic Field passing through the subject perpendicular to the applied Magnetic Field in keeping with Fleming’s Left Hand Rule. Most NMR Spectroscopy, which are used for Research, usually have Magnetic Fields as high as 3 Tesla or higher. Please note that 1 tesla is equivalent to 10,000 (or 104) G (gauss). To produce a frequency of 1 GHz an NMR magnetic field would have to be set to 23.5 Teslas. Typically most NMR Spectroscopy Equipment used for research are usually 4 Tesla at most!

Hydrogen Atoms in the Magnetic Field are then exposed to Radio Waves over a range of frequencies and the Hydrogen Atoms absorb the Radio Waves, which are a part of the EM (Electro Magnetic) Spectrum and resonate back at a certain frequency. The resonance is really due to the Hydrogen Atoms being aligned vertically in the Magnetic Field according to Fleming’s Left Hand Rule and thus they can basically be said to be in the same Quantum Mechanical State.

At this point, they all are aligned so that they all produce Resonance based on the rotation or precession about their Vertical Axis. These Hydrogen Nuclei produce Radio Wave based on their bonding relationship with the compounds they are present in and how tightly or loosely held their single electron is in that Covalent, Metallic or Hydrogen Bond. This is a lot like the phenomenon that occurs when a motor vehicle with a loud music System passes your house and causes the Glass and other loose structures to resonate and reverberate with every high energy pulse of sound coming from that vehicle’s very loud Sound System.

Hence the name “Resonance” in the older, less aesthetic name. The Medical Field, however, interfaces with regular people, thus they choose to use the more aesthetically pleasing name MRI so as not to scare patients into thinking they are being irradiated. The Magnets used both in NMR Spectroscopy and MRI are giant Super-cooled superconducting Ceramic Electromagnets. These Electromagnets have a permanent electrical current circulating in them that is maintained by keeping the Magnet at close to 4 Degrees Celsius above absolute zero, the boiling point of Liquid Helium.

Based on the functional groups to which each of the Hydrogen Atoms are attached, they resonate at slightly different frequencies and thus one can actually determine the nature of the molecule just by looking at NMR Spectroscopy Readings. Detectors in the MRI/NMR Spectroscopy Chamber detect the Radio Waves and Computer Algorithms interprets the Radio Waves into images. Consequently when MRI and NMR Spectroscopy Rooms are being built, they have to be Magnetically shielded using a Copper Faraday Cage during initial construction.

Also, note here among Medical professionals, MRI resolution is rated in terms slices and slice thickness not the smallest object it can see. So for the Medical community, a MRI that is a 64 slice or higher is very good and anything above is even better for observing living, moving tissue in patients. In the Hospital setting, the patient is prepped by telling them to absolve from eating for 24 hour prior to the MRI to avoid creating excess Organic matter in the body that not part of the persons and any associate artifacts.

The focus of this article, however is Research NMR Spectroscopy used in the Biomedical and Biological Fields. As such I make the distinction and the videos and articles included here within should help to clear things up a bit.

Imaging the Nanoscopic- EMI Noise in MRI is music to NMR Research Ears

The problem with this imaging technique is that albeit it’s non-destructive to tissue, it requires the subject to sit perfectly still, as moving moves the physical 3D location of the Hydrogen Atoms, which are on a nanometer scale. Consequently the resolution of the MRI is usually only a few micrometers at the smallest due to artifacts created by movement of tissue.

Backscatter EMI (Electro Magnetic Interference) within the examination room as well as the resonant Radio Waves produced by other Atoms in the molecules of the subject creates artifacts or interference as Telecom Technicians and Engineers call Background Noise. These artifacts are usually removed by using software Algorithms in MRI.

But in NMR Spectroscopy they are processed as if the room is magnetically shield and all conditions are good for a scan of the subject, then it means all Radio Waves are coming from resonant Atoms of Hydrogen, Carbon and Nitrogen abundant in Organic matter and thus have to be processed for a clearer picture for the Researchers to utilize.

The Backscatter EMI produced by other Atoms of Carbon and Nitrogen, the next most common Atoms in living Organic tissue, however, cannot be avoided. So most Algorithms for Research NMR Spectroscopy are designed to detect them as well as Hydrogen Atoms. Thus note the following distinctions:

1.      Medical MRI is mainly designed to focus on imaging patients using the resonance from Hydrogen Atoms

2.      Biochemistry Research NMR Spectroscopy is designed to capture all that Resonance Data from other Atoms and analyzing it as well.

Also Medical MRI maxes out at about 128 slices at increasingly smaller thickness expressed in centimeters and millimeters.  The slice number being expressed is in increasing powers of 2, a convention adopted in the MRI Design industry due to the binary nature of the Data Processing involved. Research NMR Spectroscopy goes even higher, upwards of 1028 slices and higher and has slice thickness as small as 1 micro meter is size.

Thus for processing Resonance Radio Signals from the subject, Research NMR Spectroscopy has to process all signal Data and rapidly as well, requiring special new techniques as well as more powerful Computers bordering on Super Computers to sift through all that Data. This is where the true distinction between Medical MRI and Research NMR Spectroscopy really begin: processing all signal Data for all Atoms that precess around their axis and resonate, producing Radio Waves instead of filtering it out as in the Case of Medical MRI means that the resolution is much higher.

Imaging the Nanoscopic - Bacteria and Viruses, Freeze in Suspended Animation

What the physicists from the University of Illinois at Urbana-Champaign and Northwestern University have basically done it to stop the Bacteria and Viruses from Vibrating, an improvement on the Research originally done back in 2009 as published in the article “New views at the nanoscale: MIT researchers are building a microscope that uses MRI technology to image viruses and other tiny biological structures”, published April 27, 2010

Anne Trafton, MIT News Office, MIT News, which couldn’t see beyond a few cubic micrometers.

To advance this technique, they cryogenically freeze the Bacteria or Viruses in a specially designed culture whose component are known and for which Computer Algorithms can be used to remove the artifacts created by the Atoms in the liquid culture medium. Thus they froze the Bacteria and Viruses in place, a process similar to Crystallizing a sample in X-Ray Crystallography in order to see it more clearly as when a sample is in Crystal form. This as it has a fixed rigid structure that X-Ray Diffraction or ESTM (Electron Scanning Tunneling Microscope) can examine more closely.

This is also done rapidly preferably in a non-aqueous i.e. no Water, Organic tissue culture medium that’s designed to immobilize the Bacteria or Viruses but not kill them or destroy them, making it possible to study their physical structure. This is somewhat similar to preserving organic material from Living Creatures by placing them in formaldehyde to preserve them for dissection and examination autopsy.

All of this preparation of the samples to be effectively placed in Suspended Animation via Cryogenic Freezing is done in a vacuum free from EMI, both Radio Waves and Visible light and shielded magnetically in order to prevent the formation of ice Crystals oriented to the Magnetic Field of the Earth.

In addition, when it comes time to scan the now cryogenically frozen samples that are now in Suspended Animation, the NMR Spectroscopy are designed as follows:

1.      Super-cooled Superconducting Ceramic Magnets with Magnetic Flux of 3 Tesla or Higher

2.       Improved MRI Algorithm to speed up the processing of Data from the subject as stated in the article New algorithm speeds up MRI scans, published November 1, 2011 10:56 AM PDT by Elizabeth Armstrong Moore, CNET News

3.      Designed to run on Linux OS use faster Computer Processors, most likely Liquid Cooled and configured as Mini Super Computers or Workstations.

4.      Massive SSD (Solid State Drives) Hard-drives storage capabilities

5.      Large amounts of super fast DDR4 memory

6.      Fiber Optic connectivity both within the Computer between the Motherboard and connected Storage and Memory

7.      Fiber Optic connectivity for communications between the MRI Room and the Workstation.

8.      Slice values of 1028 and higher

9.      Slice thickness as little as nanometer across, making them well suited to imaging Bacteria and Viruses

Using a standard 3 Tesla or higher NMR Spectroscopy Equiptment, the procedure produces the mountains of Data which is processed in real time thanks to these adjustments. The Cryogenically frozen samples that are now in Suspended Animation are then scanned within the Magnetically shielded Room designed for this massive behemoth of a Magnet. The images produced encompass not just Data from Hydrogen Atoms but also Carbon and Nitrogen Atoms as well as other Atoms in the Database.

This allows the Physicist to not only see the 3D details of Viruses and Bacteria for the first time in higher resolution than is even possible with the more destructible ESTM (Electron Scanning Tunneling Microscope) Technique but to also get an idea of the chemical composition of the structures within these living organisms.