Durgesh Kumar Dwivedi
Department of NMR & MRI
AIIMS, New Delhi, India
MTI Theory and Application
Contents
 Magnetization Transfer (MT)
 T1 and T2 Relaxation in tissue
The physical basis of magnetization transfer
Attempts for quantification using MTR
Theoretical approach of MTR & Pulse sequence
Clinical Applications
Conclusion
MTI Theory and Application
Fundamental

Larmor Equation: ω= γ Bo
MTI Theory and Application
T1 relaxation
A radio frequency (RF) pulse is applied
(an oscillating electromagnetic wave) to the
system at exactly the Larmor frequency of the
precessing spin (‘on-resonance’). For hydrogen
atoms this RF pulse has a frequency of 64 MHz
for a magnetic field of 1.5 T.
T1 is a characteristic of tissue and is defined as
the time that it takes for the longitudinal
magnetization to reach 63% of its final value
MTI Theory and Application
T2 relaxation
T2 is the transverse relaxation time (or
spin-spin relaxation time) and describes
the disappearance of transverse
magnetization
Definition of T2 rel.: T2 is a characteristic
of tissue and is defined as the time that
it takes the transverse magnetization to
decrease to 37% of its starting value.
Bloch Equations
The signal intensity (SI) in the case of a simple
tissue, only reflecting T1 and T2 relaxation.
N(1H) is the proton density (PD).
Discovered accidentally : MT
 Magnetization transfer (MT) was first discovered accidentally
by Wolff and Balaban (Wolff and Balaban 1989)
They were trying to perform a spin transfer experiment by
selective saturation of urea and were looking for a small signal
suppression in water
Instead they found a significant loss of image intensity
This generalized signal suppression, now known as MT
MTI Theory and Application
Physical Basis of Magnetization Transfer
Magnetization transfer (MT) imaging is an MRI
technique that generates contrast dependent on
the phenomenon of magnetization exchange
between ‘free water’ protons and protons that
are ‘restricted’ in macromolecules
MTI Theory and Application
MT- unique contrast
MTI Theory and Application
How MT works???
Proton MRI detects signal only from mobile protons which
have sufficiently long T2 relaxation times (~10 ms)
The T2 of the less mobile protons associated with
macromolecules and membranes in biological tissues are too
short (< 1 ms) to be detected directly in MRI
Figure shows: Magnetization transfer between
restricted protons (part of a macromolecule) and
free protons in the surface layer
Coupling between the macromolecular protons and
the mobile or ‘liquid’ protons allows the spin state of
the macromolecular protons to influence the spin
state of the liquid protons through exchange
MTI Theory and Application
processes
Concept of MT
When an RF pulse is applied far
enough off resonance, it will saturate
the restricted protons without
directly affecting the liquid protons
The macromolecular spins have a
much broader absorption lineshape
than the liquid spins
 Making macromolecular spins as
much as 106 times more sensitive to
an
appropriately
placed
offresonance irradiation.
Fig: Absorption lineshapes of the free
protons (liquid pool) and restricted
protons (macromolecular pool).
This preferential saturation of the
macromolecular
spins
can
be
transferred to the liquid spins,
depending on the rate of exchange
between the two spin populations,
and hence can be detected with MRI
Continuous wave vs Pulsed wave MT
 Continuous wave (CW) saturation transfer techniques were
the first used to demonstrate MT effects in tissue (Henkelman et
al. 1993)
 Pulsed wave (PW) saturation techniques achieve selective
saturation of the restricted proton resonance using either brief
off-resonance RF pulses (applied at a frequency that is off-set
from the free water resonance) or on-resonance (applied near
the ‘free’ water resonance). (Sled et al. 2000)
For practical imaging experiments, pulsed wave is preferred.
Due to specific absorption rate (SAR) and RF transmitters
MTI Theory and Application
Specific Absorption Rate (SAR)
 Measures of the rate at which energy is absorbed by the body
when exposed to a RF field. It is defined as the power absorbed
per mass of tissue
 The radio frequency energy from an imaging sequence can cause
heating of the tissues of the body
 The USFDA recommends that the exposure to RF energy be
limited. SAR is the limiting measure [(SAR) = Joules of RF/second/kg
of body weight = Watts/kg]
The SAR for the whole body must be less than 0.4 W/kg . It must
be less than 3.2 W/kg averaged over the head. All sequences are
made according to guidelines
MTI Theory and Application
Two pool model: Theoretical approach
Two-pool model of MT exchange. The shaded region in each pool represents
saturated spins. RA & RB represent longitudinal relaxation rates (R=1/T) in liquid
and macromolecule pools, respectively. R is MT exchange between the pools.
A- Liquid pool, B- semisolid pool; M is no. of spins
MTI Theory and Application
Understanding: Two pool model
 In tissues, the number of macromolecular spins is much
less than the liquid spins and the relative fraction is given by
M0B
 Number of spins in “A” compartment (M0A) is by
convention normalized to unity
 Unshaded portion: Longitudinal orientation
Shaded portion: Saturated spins
MTI Theory and Application
Two pool model contd…
 The effect of off-resonance irradiation on this system is
different for the two pools
During off-resonance irradiation:
Effe. saturation rate = [Prob. of absorption]at Δ * [Avg. RF power]at Δ
Δ = offset frequency
MTI Theory and Application
Two pool model contd…
In MT experiments, the intent is to manipulate the
liquid pool indirectly by saturating the macromolecular
pool
During off-resonance: liquid pool like rotating frame
of reference
Beff = B1 + Δ/γ; where Δ = ωrf – ωo (~2kHz)
MTI Theory and Application
MT Theory contd…
The most important process in MT is the exchange
between the macromolecular pool and the liquid pool
It is this exchange that transfers macromolecular
saturation to the liquid pool, resulting in decreased
longitudinal magnetization being available for imaging
This spin exchange can occur via dipolar coupling or via
direct chemical exchange
MTI Theory and Application
Pulse sequence
 The CW case gives a simplification of the Bloch
equations. The magnetization as a function of the
frequency offset is obtained
In case of PW: during one period (TR) a Gaussian RF pulse,
which is applied off-resonance, is followed by an excitation
pulse (figure below), after which the signal is read out
MTI Theory and Application
Quantitative Imaging: MT & MTR
 Two main advantages over conventional MR:
 Provides morphological and pathological
 It enables us to asses “invisible lesion” burden in so
called normal appearing white matter (NAWM)
 Quantitatively magnetization transfer ratio (MTR) is given
by
MTI Theory and Application
MTR Image Generation
Composition of an MTR image (FLASH3D) of an MS patient from a T1weighted image without (M0) and with MT pre-pulse (Ms).
MTI Theory and Application
Influence of different factors on MT
Lack of uniformity of the MTR ratios. It can be assumed that the
majority of variations in resulting MTR values is due to the degree of
MT saturation experienced within a particular tissue region
Certain features of the MR system that influence the degree of MT
saturation are fixed, e.g. strength of the B0 field, coil hardware,
prescan function; other features may be varied
With respect to the B0 field, the influence of field inhomogeneities
should be taken into account: shimming can decrease this problem
The parameters that determine the MTR values can be classified in
three groups: tissue properties, system parameters and data
processing
MTI Theory and Application
Influence of different factors on MT
Tissue properties: different tissues exhibit different degrees of
magnetization transfer
decreased MTR values may reflect demyelination or axonal loss;
For off-resonance saturation transfer techniques, unwanted direct
saturation effects play an important role, because off-resonance
pulses also saturate the free pool directly
System parameters: The amplitude, shape and duration of the MT
saturation pulse and the interpulse interval determine the degree of
saturation of both the free and restricted protons. Other factors: TR, TE,
excitation flip angle, etc
• MTR data processing: A shift of 1 mm or less due to patient motion may
be enough to render invalid the calculated MTR value. At tissue interfaces
(e.g. between grey and white matter, white matter and CSF, or lesion and
adjacent unaffected tissue),
MTI Theory and Application
Experimental demonstration
 Fig. shows the same MT for
4% agar at a single B1
amplitude frequency of 0.67
kHz.
 The shaded region shows
the amount of saturation
coming from saturated agar
spins exchanging with the
water spins
MTI Theory and Application
Where Ksat: rate constant;
T1SAT is the time constant
for the two pools to come
to
equilibrium
during
irradiation
Clinical application contd…
 Multiple sclerosis: Because of the demyelinating character of
MS, MT imaging, which is sensitive to the presence of restricted
protons, is a very useful method to monitor the destruction
Normalized MTR for the whole brain of a healthy individual (dotted line) and a
patient with MS (MS, solid line). The MS patient exhibits reduced peak MTR
value and a lager proportion of brain pixels with low MTR values reflecting
lesion In whole brain
MTI Theory and Application
Applications contd…
Magnetic resonance angiography
MR angio at 3T with MT suppression of brain tissue of
7-16% across image.
MTI Theory and Application
Applications contd…
 Optic neuritis
Magnetization transfer image of a patient with right optic neuritis
shows that the affected optic nerve has a dramatically lower MTR
(20.1%) compared with that of the contralateral nerve (47.7%). This
suggests structure loss of myelin as opposed to just edema.
MTI Theory and Application
Applications contd…
Breast Cancer
MTR:
Benign Lesions:
19.02±3.40
Malignant Lesions: 14.77±2.19 at 1.5T
BL (22.8 ± 4.2) and ML (19.9 ± 3.5) at 3T
There are molecules secreted only by
cancerous cells, Fibronectin, collagen
type IV, and laminin are among the
most frequent proteins related to
stromal and cancer growth
MTI Theory and Application
Applications contd…
 Prostate cancer
(A)T2-weighted image; (B) T2-weighted image showing the ROIs for the
calculation MTR; (C) image without MT pulse; and (D) image with MT
pulse.
Cancer: MTR value (8.29±3.49) and controls: MTR was 6.18±1.63
MTI Theory and Application
Conclusions & Future directions
 MT provides unique contrast
 MT has shown its value in MRA and white matter
disease and holds continuing promise for use in
imaging other tissues and diseases
Could improve image specificity (MTR)
 Attention: field inhomogeneities, pulse sequence
parameters, reproducibility etc.
MTI Theory and Application
Thank you 
MTI Theory and Application