“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.
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