Offset-Saturation-Induced (osi-) Variations in Multiexponential T2 at 16.4T: A New Dimension for Probing White Matter Contrast
Teresa Serradas Duarte1 and Noam Shemesh1

1Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Lisbon, Portugal


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.


Out of the many contrasts available in MRI, Magnetization Transfer (MT) and Multiexponential T2 (MET2) Relaxometry have histologically correlated sensitivity to white matter (WM)1–3. Several studies comparing MET2 and MT were conducted4–6; however, whether magnetization transfer could actively affect MET2-derived relaxation rates has not been demonstrated insofar. This study investigates how spectrally-resolved off-resonance irradiation modulates MET2 components, and its potential to contrast different WM tracts of the rat spinal cord (SC) at 16.4T.


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. T2A, fA and T2B 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.


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 T2A, fA, and T2B in the entire WM was T2A=12.65±0.50 ms, fA=0.48±0.01, T2B=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-T2A, osi-T2B and osi-fA 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.


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 content9,10. 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.


MET2 coefficients were found to shift with off-resonance saturation, showing unique, spatially distinct, tract-specific signatures across the irradiation frequency. This phenomenon adds a new dimension for tissue characterization.


This study was supported through funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Starting Grant, agreement No. 679058). The authors would like to acknowledge Dr. Daniel Nunes for providing tissue.


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Figure 1 - A) Left: WM/GM ROIs overlaid on the magnitude image. Middle: Corresponding MTA plots. Arrows highlight peaks selected for comparing MET2 decays on Figure 2. Right: MTA plot of WM is compared for different TEs. Negligible changes were reported. B) Left: WM tract ROIs (as in5). Middle: Corresponding MTA plots. Right: To facilitate comparison, dCST and VST (the two microstructurally most distinct tracts) are plotted. Their normalized z-spectra are shown in the inset. While MTA provides distinct WM/GM contrast, no evident changes are observed across different WM tracts.

Figure 2 - A) Logarithm of normalized signal decay over TE in WM for different MT presaturation offsets (frequencies marked in Figure 1) and in the absence of saturation. The inset shows the same decays over the entire time range and without log. B) Logarithm of normalized signal decay of the WM tracts with offset saturation at -13 kHz (inset with full range, without log). C) Parametric maps from two-compartment fitting in the absence of saturation (left) and with presaturation at -13 kHz (right). Visible differences between decays of different offset frequencies and different WM tracts were evidenced.

Figure 3 - Unnormalized offset-saturation-induced shift plots of A) T2A, B) T2B and C) fA (n.b., fB=1-fA) of three WM tract ROIs on the left (FC, ReST and STT5) and the remaining ROIs on the right (dCST, FC, FG, VST5). N.b., the y-axis scale is not the same in the left and right. MET2 coefficients were found to shift with off-resonance saturation, showing unique tract-specific signatures across the irradiation frequency.

Figure 4 - A) Integrals of peak-specific osi-T2A, osi-T2B, osi-fA and osi-fB maps of one exemplary rat spinal cord. Osi-T2B (the longer T2 component) provides the highest contrast across WM tracts. Visible changes are observed for different peak maps. B) Difference maps between peak 6 (without MT-contrast, as shown in D) and peak 3 (local/global minimum, as shown in C). The irradiation effects are evident in all peak-specific maps. The selection of specific peaks was grounded from C) osi-MET2 shift plots and D) z-spectrum of dCST and VST tracts. Results suggest a potential to highlight targeted tracts.

Proc. Intl. Soc. Mag. Reson. Med. 25 (2017)