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.

Figure 1: Schematic of the magnetization transfer (MT) experiment
saturation

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 2).

Figure 2: Magnetization transfer, measured as Ms/Mo, is linear with GAG concentration and exponential with collagen concentration for solutions and suspensions of GAG and collagen.
macromolecule

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 effect.

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 affec 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.

Figure 3: 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 molecular structure.
normalized

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. 2002;48:1081-4
  • Gray ML, Burstein D, Lesperance LM, Gehrke L. Magnetization transfer in cartilage and its constituent macromolecules. Magn Reson Med 1995; 34:319-325.

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.