Forensic Biology & Its biological significance.pdf
Pptx
1. Presented by:
Md. Amzad Hossain
M.Sc. Student
Student Id : 0417032702
Session : April 2017
Contrast agents which are used in
Magnetic Resonance Imaging(MRI)
Course Co-ordinator:
Dr. Ayesha Sharmin
Assistant Professor
Department of Chemistry
Bangladesh University of
Engineering &Technology
2. Outlines
• Some terminology
• Introduction
• Why we need contrast agents
• Features of contrast agents
• Classification
• Gadolinium Based MRI Contrast Agent
• Contrast Mechanisms
• Side effect
• Conclusion
3. • Contrast agent
-Increase the contrast of structures or fluids within the body
• MRI contrast agents
-Improve the visibility of internal body structures in magnetic
resonance imaging (MRI)
• T1 relaxation
-Net magnetization (M) grows/returns to its initial maximum
value (Mo) parallel to magnetic field (Bo).
• T2 relaxation
-Transverse components of magnetization (Mxy) decay or
dephase.
Terminology
4. Introduction
• Paul Lauterbur and his
associates were the first used in
the 1970s
• Became available for clinical
use globally in 1988
• He got Nobel prize in 2003.
5. Why we need Contrast Agents
• Sometimes distinction between region of interest and
environment is impossible:
Signals are cancelled by space averaging
Tissue properties too similar
7. Types
• Positive contrast agents
• cause a reduction in the T1 relaxation time
• increased signal intensity on T1weighted images
• containing active element Gadolinium,
Manganese, or Iron etc.
• Negative contrast agents
• Produce predominantly spin spin
relaxation effects
• Results in shorter T1 and T2 relaxation times
• superparamagnetic iron oxide(SPIO)
8. Gadolinium Based MRI Contrast Agent
• Chelates surround an ion an make a cage
around it
• A chelate of gadolinium occupies all
available space around the ion except water
molecule
• Water molecules exchange in and out of that
one spot.
10. Contrast Mechanisms .
Tm = residence lifetime
of inner-sphere water
molecules
TR = the rotational
correlation time
11. Side Effects
Some of the more common side effects
include
• injection site pain,
• nausea,
• vomiting,
• itching,
• rash,
• headache and
• parasthesia (abnormal skin sensation, such as
prickling, burning or tingling)
12. Conclusion
• Although Gadolinium may cause side effects in some
people but these are usually mild and short lasting.
• By tuning the ligands structure it can be avoid some
extent.
13.
14.
15. • Estimation shows that a decrease of 0.2 A of the distance rGdH between the
coordinated water and Gd leads to a 50% increase in inner-sphere relaxivity
because the relaxivity has a sixth-order dependence on the distance
• The tuning of the steric environment in the vicinity
of the Gd centre can increase the dissociative water exchange
rate as well as the increase relaxivity.
• When in that spot, the spins have an extremely short T1. This accelerates the
overall relaxation rate, shortening T1.
16.
17. Contrast Agent Nanoparticle
The “free” or unchelated Gd3+ ion is toxic in
most biological systems largely because the ion
has ionic radius close to that of Ca2+ but also a
higher positive charge. Consequently, proteins
cannot distinguish between a
Gd3+ versus Ca2+ion so any free
Gd3+ introduced into a biological system
quickly binds to Ca2+ ion channels and other
Ca2+ requiring proteins such as calmodulin,
calsequistrin, and calexitin.
18. • Schematic representation of a Gd3+-complex (GdDOTA) with
one coordinated water molecule (inner-spherewater, its
oxygen is colored black) in solution (bulk water, oxygens are
red). Second-sphere water molecules (water oxygens are
blue) are close to the carboxylate groups with their
hydrogens oriented towards the carboxylate oxygens. The
parameters that govern the relaxivity are also represented:
Gd-H distance, the mean lifetime (τm) of the water
molecule(s) in the inner sphere, the rotational correlation
time (τR) and the electronic spin relaxation times
(T1e and T2e). For clinical agents, approximately 60% of the
relaxivity originates from inner sphere relaxation and 40%
from outer sphere effects.
19. • Positive contrast agents cause a reduction in the T1 relaxation
time (increased signal intensity on T1 weighted images). They (appearing bright
on MRI) are typically small molecular weight compounds containing as their
active element Gadolinium, Manganese, or Iron. All of these elements have
unpaired electron spins in their outer shells and long relaxivities.
Some typical contrast agents as gadopentetate dimeglumine, gadoteridol,
and gadoterate meglumine are utilized for the central nervous system and the
complete body; mangafodipir trisodium is specially used for lesions of
the liver and gadodiamide for the central nervous
system.Negative contrast agents (appearing predominantly dark on MRI) are small
particulate aggregates often termed superparamagnetic iron oxide (SPIO). These
agents produce predominantly spin spin relaxation effects (local field
inhomogeneities), which results in shorter T1 and T2 relaxationtimes.
SPIO's and ultrasmall superparamagnetic iron oxides (USPIO) usually consist of a
crystalline iron oxide core containing thousands of iron atoms and a shell of
polymer, dextran, polyethyleneglycol, and produce very high T2 relaxivities. USPIOs
smaller than 300 nm cause a substantial T1 relaxation. T2 weighted effects are
predominant.
20. where RIS
1p and ROS 1p are the relaxation enhancement in the
presence of the paramagnetic complex at 1 mM
concentration, Robs 1
is the overall measured relaxivity and RW 1 is the relaxation
rate
of the solvent in the absence of the paramagnetic complex
where [M] is the molar concentration of paramagnetic ions,
q the hydration number per Gd center, τm the residence
lifetime of inner-sphere water molecules, 1/T1M the
longitudinal
proton relaxation rates, γI the nuclear gyromagnetic ratio
(γ(H) = 42.6 MHz/T), S is 7/2 for Gd ions, g the electron
gfactor, μB the Bohr magneton, rGdH the electron spin–
proton
distance, ωI and ωs are the nuclear and electron Larmor
frequencies, respectively, and A/ is the hyperfine or scalar
coupling
constant between the electron spins of the paramagnetic
center
and the proton spins of the coordinated water molecule. The
correlation times have a relationship, as stated in Eqs. (1.6)
and
(1.7), where τR is the rotational correlation time, and T1e is
the
longitudinal electron spin relaxation time of the metal ion
21. The T1-agent,
which is commonly the
gadolinium complex, reduces
the longitudinal relaxation
time and gives a positive
contrast
The origin of relaxation is
the
dipole-dipole interactions
between the proton nuclear
spins
and the fluctuating local
magnetic field that results
from the
paramagnetic metal center.