Increase in the iron content of the substantia nigra and red nucleus in multiple sclerosis and clinically isolated syndrome: a 7 Tesla MRI study.

PURPOSE: To study iron deposition in the substantia nigra (SN) and red nuclei (RN), in patients with clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS) and healthy controls (HC). MATERIALS AND METHODS: Iron deposition was assessed using susceptibility maps and T2*-w images acquired at high resolution MRI at 7 Tesla (T). Mean intensities were calculated within circular regions of interest in the SN (d/v, dorsal/ventral) and RN on high resolution T2*-w, quantitative susceptibility maps and their product for: RRMS, CIS and HC (N = 14, 21, 27, respectively). RESULTS: Magnetic susceptibility was significantly greater in SNd and RN in RRMS compared with HC (P = 0.04 [0.001, 0.48] and P = 0.01 [0.005, 0.05]), with intermediate values for the CIS group. 1/T2*-w did not show significant inter-group differences (for SNv, SNd, RN, respectively: P = 0.5 [-0.352, 0976], P = 0.35 [-0.208, 0.778], P = 0.16 [-0.114, 0.885] for RRMS versus HC) and the T2*-susceptibility product maps showed the difference only for RN (P = 0.01, [0.009, 0.062]). Changes were independent of EDSS and disease duration. CONCLUSION: MR changes consistent with iron accumulation occurring in the SN and RN of CIS patients can be identified using susceptibility mapping; this may provide an additional method of monitoring early MS development.

Direct visualization of the subthalamic nucleus and its iron distribution using high-resolution susceptibility mapping.

Histological studies have shown a relatively high iron concentration in the subthalamic nucleus (STN). T2- and T2*-weighted sequences have previously been used to visualize the STN in vivo. The phase information of gradient-echo images reflects the magnetic tissue properties more directly, e.g., iron is more paramagnetic than water. Unfortunately, phase images suffer from non-local effects and orientation dependency. The goal of this study is to delineate the STN more precisely using susceptibility maps, calculated from phase images, which directly index magnetic tissue properties while removing the non-local effects and orientation dependency. Use of 7T MRI enables high spatial resolution with good signal to noise ratio (SNR). Eight healthy subjects were scanned at 7T using a high-resolution 3D gradient-echo sequence. Susceptibility maps were calculated from phase data using a thresholding Fourier approach and a regularization approach using spatial priors. The susceptibility maps clearly distinguish the STN from the adjacent substantia nigra (SN). Their susceptibilities are quantitatively different (0.06 and 0.1 ppm for the STN and SN, respectively). These maps allowed the STN, SN, and the red nucleus to be manually segmented, thus providing 3D visualization of their boundaries. In sum, the STN can be more clearly distinguished from adjacent structures in susceptibility maps than in T2*-weighted images or phase images.

Whole-brain susceptibility mapping at high field: a comparison of multiple- and single-orientation methods.

Optimisation and comparison of the performance of three different methods for calculating three-dimensional susceptibility maps of the whole brain from gradient-echo (phase and modulus) image data acquired at 7 T is described. The methods studied are a multiple-orientation method in which image data acquired with the head at several different angles to the main field are combined and two methods which use data acquired at a single orientation: the first of these is based on exclusion of some k-space data from the calculation (through thresholding of the dipolar field kernel), while the second incorporates a regularisation method that is based on using information from the modulus images. The methods were initially optimised via analysis of data from a phantom containing different compartments of known susceptibility. As part of this work, a novel high-pass filtering methodology was introduced to remove background fields from field maps based on phase data. The optimised methods were successfully applied to high-resolution (0.7 mm isotropic) whole-brain modulus and phase data acquired in vivo from five healthy male subjects, 25-30 years of age. The multiple-orientation method yielded high quality susceptibility maps, out-performing the single-orientation methods. Venous blood vessels as well as the substantia nigra and globus pallidus brain regions showed particularly high positive susceptibility offsets relative to surrounding tissue, consistent with high deoxyhemoglobin and non-heme iron content, respectively. To compare the performance of the different methods, regions of interest were drawn in deep grey matter structures and in cortical grey and white matter. The threshold-based approach was fast and simple to use, but underestimated susceptibility differences and showed significant artefacts due to noise amplification in difficult regions of k-space. The regularised single-orientation method yielded contrast dependent on the choice of spatial priors, but demonstrated the potential to yield susceptibility maps of a similar quality to those calculated using data acquired at multiple orientations to the field.

Susceptibility mapping in the human brain using threshold-based k-space division.

A method for calculating quantitative three-dimensional susceptibility maps from field measurements acquired using gradient echo imaging at high field is presented. This method is based on division of the three-dimensional Fourier transforms of high-pass-filtered field maps by a simple function that is the Fourier transform of the convolution kernel linking field and susceptibility, and uses k-space masking to avoid noise enhancement in regions where this function is small. Simulations were used to show that the method can be applied to data acquired from objects that are oriented at one angle or multiple angles with respect to the applied field and that the use of multiple orientations improves the quality of the calculated susceptibility maps. As part of this work, we developed an improved approach for high-pass filtering of field maps, based on using an arrangement of dipoles to model the fields generated by external structures. This approach was tested on simulated field maps from the substantia nigra and red nuclei. Susceptibility mapping was successfully applied to experimental measurements on a structured phantom and then used to make measurements of the susceptibility of the red nuclei and substantia nigra in healthy subjects at 3 and 7 T.

Using magnetic field simulation to study susceptibility-related phase contrast in gradient echo MRI.

Using a Fourier-based method for rapidly calculating the spatially varying magnetic field perturbation generated by a general susceptibility distribution, chi(r)<<1, maps of the NMR frequency variation in a structured phantom, the human cortex and mid-brain structures have been simulated and compared with experimental data acquired at 7 T. The results from the phantom indicate that the Fourier method can generate an accurate estimate of the NMR frequency variation in a complex structure where the magnitude of susceptibility variation is similar to that in the human brain. Simulations based on a 1-mm-resolution model of the human head show that susceptibility variation can give rise to sharp boundaries between grey and white matter regions. The frequency difference in the simulated data was found to be significantly less than the volume susceptibility difference scaled by three. Simulations based on a simple model of the substantia nigra, red nuclei and surrounding white matter, made up of three homogeneous compartments, showed patterns of field perturbation that were very similar to those seen in experimental data. These results indicate that care must be exercised in interpreting phase or susceptibility weighted images, since the simulations show that features such as rings and graded phase variation can easily be generated by simple homogeneous structures. The results also indicate that even after spatial filtering, frequency variation can be projected outside of localised structures. k-space analysis provides some insight into the conditions needed to ensure that the measured frequency perturbation directly represents the anatomical features.