MOLECULAR

IMAGINING
.

GEMOMICS
CONTENTS
vIntroduction vOptical imaging
vDifference b/w MI vPositron
& Biomarker emission
vImaging tomography
modalities (PET)
vUltrasound vDissuasion
vMALDI imaging vQuestions
vMagnetic
resonance
imaging (MRI)
v
Introduction
 Molecular Imaging is a new discipline that
unites molecular biology and in vivo
imaging. It enables the visualization of the
cellular function and the follow-up of the
molecular process in living organisms.
vThe multiple and numerous potentialities of
thither multiple and numerous
potentialities of this field are applicable to
the diagnosis of diseases such as cancer,
and neurological and cardiovascular
diseases' field are applicable to the
diagnosis of diseases such as cancer, and
neurological and cardiovascular diseases.
DIFFERENCE B/W
 Biomarker  Molecular Imagining
 interact chemically with  primarily imaged
their surroundings and differences in qualities
in turn alter the image such as density or
according to molecular water content. This
changes occurring ability to image fine
within the area of molecular changes
interest. opens up an incredible
number of exciting
possibilities for
medical application,
including early
detection and
treatment of disease
and basic
pharmaceutical
development.
Imaging modalities

vUltrasound
vMALDI imaging
vMagnetic resonance imaging
(MRI)
vOptical imaging
vPositron emission tomography
(PET)
vSingle photon emission computed
tomography(SPET)

1-Ultrasound
 is cyclic sound pressure with a frequency greater
than the upper limit of human hearing.
 Principle: penetrate a medium and measure
the reflection signature or supply focused
energy. The reflection signature can reveal
details about the inner structure of the
medium.
 Medical sonography (ultrasonography):is an
ultrasound-based diagnostic medical imaging
technique used to visualize muscles, tendons,
and many internal organs, their size, structure
and any pathological lesions with real time
topographic images. It is also used to visualize
a fetus during routine and emergency prenatal
care.
Range OF Ultrasound
)

Imagining by Ultrasound

A fetus in its mother's womb, viewed in a

sonogram (brightness scan)
A fetus, aged 29 weeks, in a “3D
ultrasound
Work
 Ultrasound energy produces a mechanical pressure
wave through soft tissue. This pressure wave may
cause microscopic bubbles in living tissues, and
distortion of the cell membrane, influencing ion
fluxes and intracellular activity. When ultrasound
enters the body, it causes molecular friction and
heats the tissues slightly.
 This effect is very minor as normal tissue perfusion
dissipates heat. With high intensity, it can also cause
small pockets of gas in body fluids or tissues to
expand and contract/collapse in a phenomenon
called cavitations (this is not known to occur at
diagnostic power levels used by modern diagnostic
ultrasound units).
 The long-term effects of tissue heating and cavitations’
have shown decrease in size of red blood cells in
cattle when exposed to intensity higher than
diagnostic levels.
…….
 Ultrasound scanners have different
Doppler-techniques to visualize arteries
and veins. The most common is color
Doppler or power Doppler, but also
other techniques like b-flow are used to
show blood flow in an organ.
Advantages:

 as a "safe test" because it does not use

ionizing radiation, which imposes

hazards, such as cancer production and
chromosome breakage
Role in Genomics
 Ultrasound in the low MHz range in the form
of standing waves is an emerging tool for
contactless separation, concentration and
manipulation of micro particles and
biological cells, a method referred to as
acoustophoresis. The basis is the acoustic
radiation force, a non-linear effect which
causes particles to be attracted to either
the nodes or anti-nodes of the standing
wave depending on the acoustic contrast
factor, which is a function of the sound
velocities and densities of the particle and
of the medium in which the particle is
immersed.

2-MALDI imaging

 imaging is the use of matrix-assisted laser

desorption ionization as a mass
spectrometry imaging technique in which
the sample, often a thin tissue section, is
moved in two dimensions while the mass
spectrum is
recorded.
 take our polymer a solvent. Well
that all depends. The first
MALDI
experiment were done on proteins.
 Now proteins tend to be soluble in
 water, so water was the
…


primary solvent. It was common to use 70:30

mixture of water and acetonitrile (click on it to

see it in 3-D.

q The special ingredient is a compound like

trans-cinnamic acid or 2,5-
dihydroxybenzoic acid. It varies from
polymer to polymer, but the important
thing is that our special ingredient has to
absorb ultraviolet light. Usually we put
about 104 times more of our UV absorber
than polymer.

…
…
Work
 vaporize the polymer it right between the
two electrodes. When our polymer forms
captions, we place the positive cathode
right behind the sample, and the negative
anode in front of the sample.
 , the positively charged polymers are going
in the direction of the anode, attracted to
its negative charge. If we play it right, we
can use this acceleration to shoot the
polymer molecules down to the detector at
the far end of the chamber.

..
 Most of the time, there is only one single
positive charge on each polymer
molecule. This means that the same
electrical force is applied on each
polymer molecule when it's being
accelerated in the electric field between
the two electrodes. But remember, the
polymer molecules have different
masses.
 Newton say about mass, force, and
acceleration F = ma , a=F/m
.
 For us this means that the big heavy
polymer molecules will take a lot longer to
get to the detector at the end of the
chamber. So the polymers will hit the
detector, the small ones first, then the big
ones. They hit completely in order by
mass. All the polymer molecules of the
same molecular weight will hit the detector
together. When they hit the detector, the
detector registers a peak.
 The size of the peak is proportional to the
number of molecules that hit at one time.
So when we're done we get a series of
peaks that looks like this:

 ,

That MALDI spectrum has always

reminded me of the giant
fin on the back of a
dimetredon, an extinct
reptile that lived millions
of years ago.
MALDI and SEC

 SEC measures hydrodynamic volume, not

molecular weight. We can then
approximate molecular weight, by
comparing the hydrodynamic volume of
the polymer we've tested to a standard,
usually polystyrene, for which we know the
exact relationship between hydrodynamic
volume and molecular weight.
 MALDI measures the mass more accurately,
because it doesn't compare the polymer
you're measuring to anything. It gives an
absolute measurement of mass. Given
time MALDI will probably replace SEC in
most laboratories.

Applications of MLIDI

 MALDI imaging mass spectrometry involves

the visualization of the spatial distribution
of proteins, peptides, drug candidate
compounds and their metabolites,
biomarkers or other chemicals within thin
slices of sample such as animal tissue or
plant. It is a promising tool for putative
biomarker characterization and drug
development.
 Recent work has also demonstrated the
capacity to create three-dimensional
molecular images using the MALDI imaging
technology and co-registration of these
image volumes to other imaging modalities
such as magnetic resonance imaging
(MRI).
 
3-Magnetic resonance imaging
(MRI)
 Magnetic Resonance Imaging (MRI), or
nuclear magnetic resonance imaging
(NMRI), is primarily a medical imaging
technique most commonly used in radiology to
visualize the internal structure and function of
the body.
 , it uses no ionizing radiation, but uses a
powerful magnetic field to align the nuclear
magnetization of (usually) hydrogen atoms in
water in the body. Radio frequency (RF) fields
are used to systematically alter the alignment
of this magnetization, causing the hydrogen
nuclei to produce a rotating magnetic field
detectable by the scanner. This signal can be
manipulated by additional magnetic fields to
build up enough information to construct an
image of the body.
,
 The body is largely composed of water
molecules which each contain two
hydrogen nuclei or protons. When a person
goes inside the powerful magnetic field of
the scanner, these protons align with the
direction of the field.
 The frequency of the emitted signal depends
on the strength of the magnetic field. The
position of protons in the body can be
determined by applying additional
magnetic fields during the scan which
allows an image of the body to be built up.
These are created by turning gradients
coils on and off which creates the knocking
sounds heard during an MR scan.

 .
The net magnetization vector has two components. The
longitudinal magnetization is due to a tiny excess of
protons in the lower energy state. This gives a
net polarization parallel to the external field.
Application of an RF pulse can destroy (with a so-
called 90° pulse) or even reverse (with a so-called 180°
pulse) this polarization v ector. The transverse
magnetization is due to coherences forming between the
two proton energy states following an RF pulse
typically of 90°. This gives a net polarization
perpendicular to the external field in the transverse
plane. The recovery of longitudinal magnetization is
called longitudinal or T1 relaxation and occurs
exponentially with a time constant T1. The loss of
phase coherence in the transverse plane is called
transverse or T2 relaxation. T1 is thus associated with
the enthalpy of the spin system (the number of nuclei
with parallel versus anti-parallel spin) while T2 is
associated with its entropy
 4-Single photon emission
computed tomography (SPECT)
 (SPET) is a nuclear medicine tomographic imaging technique
using gamma rays. It is very similar to conventional nuclear
medicine planar imaging using a gamma camera. However,
it is able to provide true 3D information. This information is
typically presented as cross-sectional slices through the
patient, but can be freely reformatted or manipulated as
required. In the same way that a plain X-ray is a 2-
dimensional (2-D) view of a 3-dimensional structure, the
image obtained by a gamma camera is a 2-D view of 3-D
distribution of radionuclide.SPECT imaging is performed by
using a gamma camera to acquire multiple 2-D images (also
called projections), from multiple angles. A computer is then
used to apply a topographic reconstruction algorithm to the
multiple projections, yielding a 3-D dataset. This dataset
may then be manipulated to show thin slices along any
chosen axis of the body, similar to those obtained from
other tomographic techniques, such as MRI, CT, and PET. 


.
 A Lung SPECT / CT Fusion
image
SPECT is similar to PET in its use of

radioactive tracer material and

detection of gamma rays. In
contrast with PET, however, the
tracer used in SPECT emits
gamma radiation that is measured
directly, whereas PET tracer emits
positrons which annihilate with
electrons up to a few millimeters
away, causing two gamma
photons to be emitted in opposite
directions.
5-Optical imaging

 Chemical imaging or molecular imaging involves

inference from the deflection of light emitted from
(e.g. laser, infrared) source to structure, texture,
anatomic and chemical properties of material (e.g.
crystal, cell tissue). Optical imaging systems may be
divided into diffusive and ballistic imaging systems.
 . Detectors composed of optical fiber bundles are
located a few centimeters away from the light
source. These detectors sense how the path of light
is altered, either through absorption or scattering, as
it traverses brain tissue.
 First, it can be used to measure the absorption of light,
which is related to concentration of chemicals
Second, it can measure the scattering of light, which
is related to physiological characteristics

 6-Positron emission tomography
(PET)
 (PET) is a nuclear medicine
imaging technique which
produces a three-
dimensional image or
picture of functional
processes in the body. The
system detects pairs of
gamma rays emitted
indirectly by a positron-
emitting radionuclide
(tracer), which is introduced
into the body on a
biologically active molecule.
Images of tracer
concentration in 3-
dimensional space within
the body are then
 .
The most significant fraction
of
electron-positron decays result
In two 511 keV gamma photons
being emitted at almost 180
degrees
to each other; hence it is
possible to localize their
source along a straight
line of coincidence (also called
normally the line of response
or LOR).
Dissuasion

 More commonly, a technique much like the

reconstruction (CT) and (SPECT) data is used,
although the data set collected in PET is much poorer
than CT, so reconstruction techniques are more
difficult.
 Combination of PET with CT and MRI

PETscans are increasingly read alongside CT (MRI)

scans, the combination (co-registration") giving both

anatomic and metabolic information (i.e., what the
structure is, and what it is doing biochemically).
Because PET imaging is most useful in combination
with anatomical imaging, such as CT, modern PET
scanners are now available with integrated high-end
multi-detector-row CT scanners. Because the two scans
can be performed in immediate sequence during the
same session, with the patient not changing position
between the two types of scans, the two sets of images
are more-precisely registered
.

 PET-MRI: At the Jülich Institute of

Neurosciences and Biophysics, the world
largest PET/MRI device will begin operation
in April 2009: a 9.4-tesla magnetic
resonance tomography (MRT) combined
with a positron emission tomography
(PET). Presently, only the head and brain
can be imaged at these high magnetic field
strengths.
 Limitations to the widespread use of PET
arise from the high costs of cyclotrons
needed to produce the short-lived
radionuclide's for PET scanning and the
need for specially adapted on-site chemical
synthesis apparatus to produce the
radiopharmaceuticals.
.
 Image reconstruction
Coincidence events can be grouped into projections images,

called sonograms. The sonograms are sorted by the angle of

each view and tilt, the latter in 3D case images. The
sonogram images are analogous to the projections captured
by computed tomography (CT) scanners, and can be
reconstructed in a similar way. However, the statistics of the
data is much worse than those obtained through
transmission tomography. A normal PET data set has millions
of counts for the whole acquisition, while the CT can reach a
few billion counts. As such, PET data suffer from scatter and
random events much more dramatically than CT data does.
 In practice, considerable pre-processing of the data is
required - correction for random coincidences, estimation
and subtraction of scattered photons, detector dead-time
correction (after the detection of a photon, the detector
must "cool down" again) and detector-sensitivity
correction (for both inherent detector sensitivity and
changes in sensitivity due to angle of incidence).

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QUSTIONS
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THANK YOU