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BIONANOTECHNOLOGY

Open Elective

Dr. Kalyan Sundar Ghosh


Dept. of Chemistry
Magnetic resonance imaging (MRI)
To visualize internal structures of the body in detail. MRI makes use
of the property of Nuclear Magnetic Resonance (NMR) to image
nuclei of atoms inside the body

MRI machines make use of the fact that body tissue contains lots of
water, and hence protons from water will be aligned in a large
magnetic field.

When a person is inside the powerful magnetic field of the scanner,


the average magnetic moment of many protons becomes aligned with
the direction of the field.

A radio frequency will briefly be turned on and which one has just
the right frequency (known as the resonance frequency) will be
absorbed and flip the spin of the protons in the magnetic field.
After the electromagnetic field is turned off, the spins of the
protons return to thermodynamic equilibrium and the bulk
magnetization becomes re-aligned with the static magnetic field.

During this relaxation, a radio frequency signal (electromagnetic


radiation in the RF range) is generated, which can be measured with
receiver coils.

This rotating magnetic field will be detectable by the scannerand


this information is recorded to construct an image of the scanned
area of the body.

Magnetic field gradients cause nuclei at different locations to rotate


at different speeds. By using gradients in different directions 2D
images or 3D volumes can be obtained in any arbitrary orientation. 3d
image compiled from multiple 2d images
MRI contrast agents (CA)
MRI contrast agents alter the relaxation times of atoms within body
tissues where they are present
MRI contrast agents may be injected intravenously to improve the
visibility of internal body structures and to enhance the appearance
of blood vessels, tumors or inflammation.

Mechanism of magnetic CA:


Applied radiofrequency pulse causes some atoms (including those in
contrast agents) to spin and then relax after the pulse stops.
Shortening of relaxation time in presence of contrast agents, will
increase in rate of stimulated emission from high energy spin states
(spin anti-aligned with the main field) to low energy spin states (spin
aligned). Thermal vibration of the strongly magnetic metal ions in the
contrast agent will create oscillating electromagnetic fields at
frequencies corresponding to the energy difference between the
spin states and results in the requisite stimulation
Magnetic nanoparticles as contrast agent
Superparamagnetic iron oxide particles will shorten water relaxation
time
Two types of CA
(i) A core of superparamagnetic iron oxide with polymer coating (may
not be recognized specifically)
Example of Application: Polydisperse superparamagnetic iron oxide
can darken normal liver tissues over cancerous lesions, therefore
serving as contrast agent. At lower size of nanoparticles, the blood
half life can be extended and thus increase uptake.

Improvement of superparamagnetic iron oxide nanoparticles as CA


1st generation: polymer coated polydisperse (broad size range)
2nd generation: polymer coated monodisperse (narrow size range)
3rd generation: amine functionalized, crosslinked iron oxide
(can be used as magneto/optical nanoparticles, MR based biosensors,
Cell loading, Targeted MR CA)

(ii) Molecularly targeted nanoparticles, which are designed to bind a


specific target, typically by attaching a biomolecule
A: MRI Pre contrast, B: MRI Post contrast. Tumor darkens due to
uptake of magneto nanoparticles by microglia in tumor

Molecularly targeted nanoparticle based MRI


contrast agent
Attachment of Biomolecules (antibody or proteins) on the coating
polymer (eg. dextran) of the nanoparticles for specific targeting of
the cell based on the specificity of the biomolecules
Magnetic nanoparticles as biosensors
When multivalent magnetic nanoparticles bind to multivalent targets
in solution they form stable nanoassemblies and thus decrease spin-
spin relaxation time. Nanoassemblies can be disassembled and
returned to their original dispersed state by a number of methods
(heat, enzymatic cleavage etc.). Thus nanoparticles switch between a
dispersed and nanoassembled states and are termed as Magnetic
Relaxation Switches (MRSW).

They are unique biosensors, as they do not employ any biomolecule


immobilized on a solid phase and uses radiofrequency of water
protons. It can be used to detect a variety of different molecular
interactions in biological samples with minimal or no sample
preparation.

T2 is relaxation time

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