Pulse sequences such as GESFIDE^[1] and GESSE^[2] enable the simultaneous measurement of irreversible transverse relaxation rates, typically characterized by $$$R_2=1/T_2$$$, and reversible transverse relaxation rates, typically characterized by $$$R_2^{'}=1/T_2^{'}$$$. Both of these rates have been proposed as correlates of brain iron concentration^[3]. Our goal was to use GESSE to measure these rates in the basal ganglia—subcortical structures which accumulate iron at different rates over the lifespan^[4]—at 7T, where standard methods for mapping $$$R_2$$$ (e.g., CPMG) are hindered by high SAR and B₁ inhomogeneity.

Eleven volunteers (6F/5M, ages: 23-81 years), having given informed consent, were scanned on a Siemens 7T whole-body scanner (Siemens Healthcare, Erlangen, Germany) using a custom-built 32-channel head receive coil and birdcage transmit coil. On each volunteer, 2D multi-slice GESSE data were acquired in ~4 minutes with the following parameters: TR=2 s, 15 unipolar gradient-echoes with the 8^th gradient-echo coinciding with the spin-echo at TE=24 ms (BW=2441 Hz/px), 19 axial slices with 2/1 mm slice thickness/gap and 2×2 mm² in-plane resolution (matrix=128×96). On two subjects (S01 and S02), additional GESSE datasets were acquired with the spin-echo at TE=40 ms (BW=543 Hz/px) and at TE=60 ms (BW=313 Hz/px), and on one subject (S02), these scans were repeated on a Siemens 3T Trio scanner, also with a 32-channel receive coil.

Fits of Lorentzian and Gaussian models to per-voxel GESSE time-domain signals were performed^[5], leading to the characterization of reversible transverse relaxation rates by $$$R_2^{'}$$$ and $$$\sigma$$$, respectively, with irreversible transverse relaxation rates characterized by $$$R_2$$$. Regions of interest (ROIs) for globus pallidus (GP; green) and putamen (PUT; red) were drawn on the spin-echo images, and the mean value of the relaxation rates within each ROI was computed.

As reported previously^[5], the Gaussian model was found to fit GESSE time-domain signals as well as or better than the Lorentzian model (see Fig. 1); reversible transverse relaxation rates are therefore characterized herein by $$$\sigma$$$ rather than $$$R_2^{'}$$$. Figs. 2 and 3 show $$$R_2$$$ and $$$\sigma$$$ maps, respectively, of the same subject at 7T and 3T, for various choices of spin-echo time (TE). Note that much higher relaxation rates are observed at 7T than 3T, especially in GP; consequently these maps are compromised at 7T when using the longer TEs of 40 or 60 ms, since much of the signal in GP has decayed away at these times. However, with TE=24 ms at 7T, the $$$R_2$$$ values in GP stand out—a result that was seen consistently across subjects (Fig. 4). Fig. 5 shows plots of subject age versus $$$R_2$$$ and $$$\sigma$$$ in GP and putamen, along with curves of the form $$$y = a(1-e^{-bx})+c$$$ taken from the landmark Hallgren and Sourander^[4] postmortem study of age ($$$x$$$) versus iron concentration ($$$y$$$) in various structures in the brain. We used their values of $$$a$$$, $$$b$$$ and $$$c$$$ for GP and putamen, but applied a vertical scaling factor to each curve to account for the difference between their measures of iron concentration (units of mg of iron per 100 g fresh weight) and our measures of relaxation rates (units of s^-1). Both the $$$R_2$$$ and $$$\sigma$$$ plots are consistent with Hallgren and Sourander’s finding that iron in GP accumulates rapidly at an early age and then levels off, whereas iron in putamen accumulates more gradually with age.

To the best of our knowledge, only one other study has investigated the use of GESFIDE/GESSE at 7T—a study that focused on transverse relaxation rates in cortical gray matter and white matter^[6]. Our focus, in contrast, was on basal ganglia structures, which have much higher iron content and therefore require a very different consideration of acquisition parameters such as echo times in order to capture the more rapidly decaying signal.

The relative merits of reversible versus irreversible transverse relaxation rates as indicators of iron content have been vigorously debated^[3,7,8]; however, with GESFIDE/GESSE, choosing between the two is unnecessary—maps of both rates, in perfect register, are readily available with a single acquisition. Furthermore, since irreversible relaxation is sensitive to field perturbations smaller than the diffusion length whereas reversible relaxation reflects inhomogeneities at a larger scale, the agreement we see between both rates and Hallgren and Sourander’s data (Fig. 5) suggests that iron deposition in these structures is likely to lead to field variations at multiple spatial scales. Comparing irreversible and reversible relaxation rates may therefore reveal information about the microscopic and mesoscopic distribution and concentration of iron in tissue.