Synopsis

Whether Magnetization Transfer could affect Multiexponential T₂ (MET₂) Relaxometry remains poorly explored. Here, the effects of irradiation at different offset frequencies on the MET₂ components were evaluated as novel contrast mechanisms for white matter in the rat spinal cord at 16.4T. MET₂ coefficients were found to shift with off-resonance saturation, showing unique tract-specific signatures across the irradiation frequency. Offset-saturation-induced (osi-) MET₂ Relaxometry maps show strong contrasts between microstructurally-distinct rat spinal cord tracts. The potential of exploiting the osi-MET₂ shift phenomenon to increase white matter contrast is discussed.

Purpose

Methods

All experiments were preapproved by the Institution’s animal ethics committee. Long Evans rats (n=3) were perfused and the cervical SC extracted. Experiments were conducted on a 16.4T Bruker Aeon scanner equipped with a 10mm micro5 probe and gradients capable of producing up to 3000 mT/m in all directions.

To investigate multiexponential relaxation, a Multi-Slice-Multi-Echo (MSME) sequence was employed with: TR=16000 ms; TE=1.2:1.2:96.0 ms; resolution=(63x63x800) µm³; NA=2; BW=200 kHz. The MSME was preceded by a MT module consisting of a 2 sec RF pulse, with peak power of 5 µT⁷, and a gradient crusher prior to the MSME acquisition. MT offset frequencies were varied between {-50,50 kHz} in 1 kHz increments. The 102 experiments took ~43.5h in total. One SC was excluded due to acquisition artefacts.

Nine ROIs including WM, grey matter (GM) and seven tracts in WM⁵ were drawn on the raw data (Figure 1). Z-Spectra and MT asymmetry (MTA) plots (AVG±SEM among SCs) normalized to the reference scan⁸ were calculated per ROI, for each echo. Subsequently, the signal decay at each frequency was individually fitted to a two-compartment model. T_2A, f_A and T_2B maps were obtained by similar voxelwise fits. To investigate if MT irradiation induces changes in these coefficients, the extracted coefficients were plotted against the irradiation frequency. From these spectra, six peaks were selected, and their integral was taken per coefficient per voxel, resulting in parametric offset-saturation-induced-MET₂ coefficient maps.

Results

Figure 1 shows the MTA plots for different ROIs and TEs. While MT provides a substantial WM/GM contrast, only minor changes were found among the different tracts in WM. The nonexponential signal decay is illustrated in Figure 2 for different MT presaturation offsets. In the absence of the saturation pulse, the AVG±SEM of T_2A, f_A, and T_2B in the entire WM was T_2A=12.65±0.50 ms, f_A=0.48±0.01, T_2B=30.11±0.01 ms, respectively. Small, yet clearly visible changes in the WM signal decay were observed after irradiation. Similarly, different WM tracts appeared to differ in their decay profiles when analysed at specific frequencies (Figure 2).

Figure 3 plots the extracted coefficients against irradiation offset. A clear modulation in all parameters is observed, which we term “Offset-Saturation-Induced” (osi-) and prefix to the respective coefficient. Interestingly, osi-T_2A, osi-T_2B and osi-f_A shifts were all found to carry a specific signature for each WM tract. To test whether they could be used to enhance contrast, we plot the integrals of peak-specific osi-coefficient maps in Figure 4A (n.b., peak 6 reflects a “reference” image with no MT-contrast). The irradiation effects are evident in all parametric maps, which show that the complex evolution patterns shown in Figure 3 are spatially distinct. Figures 4C and 4D show the osi parameters in the two microstructurally most distinct tracts, the dCST and VST, demonstrating large differences in osi-coefficient spectra.

Discussion

This study investigated the variation of MET₂ parameters modulated by irradiation offset in rat WM at 16.4T. An osi-MET₂ shift signature, undescribed so far (to the best of our knowledge) was indeed observed. MT thus adds another dimension which could be used to filter specific T₂­ components. It should be noted that the mechanism for these spectral signatures is complex: for example, if the MT module was simply erasing (through presaturation) a specific component’s magnetization, a change in the estimated T₂s would not be expected – only changes in the extracted fractions. One potential mechanism for effective T₂ variations is perturbation of the rotational correlation time spectrum, J(ω), which may be modulated by irradiation. Dipolar coupling and exchange effects would also need to be considered.

Interestingly, osi-coefficient signatures varied widely among SC tracts, which differ mainly in microstructure and much less so in myelin content^9,10. Hence, osi-coefficient contrast may be sensitive to underlying microstructural features. Both histology and a careful theoretical treatment are required to elucidate the observed mechanism. Nevertheless, the present data, suggests that osi phenomena might be used fruitfully for characterization of WM.

Conclusion

Acknowledgements

References

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