Magnetization transfer is a technique that takes advantage of the fact that
protons on water have a sharp NMR resonance signal (ie they resonate at a
narrow band of frequencies), while protons on the macromolecules have broad
resonances (ie they resonate with a broad band of frequencies). Therefore,
if one transmits a "saturation" pulse of radiofrequency at a frequency
which would just affect the macromolecular protons, the magnetization from
those protons will be eliminated. If then, one waits a given amount of time
during which the saturated protons transfer into free solution, and
measures the water signal, the signal will be decreased (see Figure 1).
The amount of decrease of the water signal in the presence of the
macromolecular saturation (Ms) relative to that in the absence of
saturation (Mo) is indicative of the amount of protons on macromolecules
and the transfer rate of those protons to free solution. Therefore the
experimental parameter of interest is Ms/Mo.
Schematic of the magnetization transfer (MT) experiment
In studies of suspensions of GAG and collagen, GAG was found to have a
small MT effect with a linear dependence of Ms/Mo on GAG concentration,
while collagen had a much stronger effect with Ms/Mo having an exponential
dependence on collagen concentration. The collagen curve matched that
obtained with trypsinized cartilage (i.e. GAG depleted cartilage) (Figure
Magnetization transfer, measured as Ms/Mo, is linear with GAG concentration
and exponential with collagen concentration for solutions and suspensions
of GAG and collagen.
Therefore, the MT effect is expected to be dominated by the collagen
component of cartilage. However, small changes in Ms/Mo could be due to
changes in either component, as GAG does contribute somewhat to the MT
The data above do not take into account molecular changes in collagen
structure, which also would be expected to alter the Ms/Mo measurement.
Effects of pathologic changes in Ms/Mo were measured by exposing bovine
cartilage to trypsin (expected to deplete the cartilage of GAG) and
interleukin-1 (expected to deplete GAG, but also affect the collagen
component). As can be seen in Figure 3, the two interventions had opposite
effects on Ms/Mo. Since GAG and hydration changed in the same direction for
the two interventions, the differential effect on Ms/Mo is presumably due
to collagen molecular changes.
Ms/Mo goes in opposite directions for the interventions of trypsin and IL-1
on cartilage; since GAG and hydration changed in the same direction, these
data imply that the two interventions have different effects on collagen
The results demonstrated that Ms/Mo in fact could not be used as a reliable
indicator of magnetization transfer in the presence of GdDPTA. However, a
full MT analysis demonstrated similar findings as those described in the
previous section, i.e. that the MT effect in cartilage changed in opposite
directions with trypsin and IL-1 degradation of the cartilage.
For more details, please refer to:
Henkelman RM, Stanisz GJ, Menezes N, Burstein D. Can MTR be used to
assess cartilage in the presence of Gd-DTPA2-? Magn Reson Med.
Gray ML, Burstein D, Lesperance LM, Gehrke L. Magnetization transfer in
cartilage and its constituent macromolecules. Magn Reson Med
Can MT be measured in the presence of Gd(DTPA) 2-?
Given the desire to equilibrate the cartilage in Gd(DTPA)2- for dGEMRIC
studies, we investigated the possibility of measuring MT in the presence of
the contrast agent. The contrast agent is expected to alter Ms/Mo due to
its affect on T1 (and hence the time available for exchange of the proton
magnetization; therefore, a full MT analysis was performed. The results
confirmed the effects observed in the previous study, that magnetization
transfer in trypsin and IL-1 degraded samples changed in the opposite
direction from control. However, the full MT analysis is prohibitive in
most biological and clinical applications.