The application of structural neuroimaging for MS patients has proven to be an invaluable tool for the diagnosis, clinical surveillance, management, and the assessment of therapeutic efficacy in pivotal MS clinical trials. The implementation of advanced radiological techniques is providing more insight into MS pathology compared to conventional imaging metrics by enhancing lesion morphology and spatial distribution.
Very high-field MR imaging of all CDMS patients at 7T was demonstrated to be safe, well tolerated, and provided high-resolution anatomical images allowing for the visualization and differentiation of structural abnormalities localized near or within the cortical layers. Clear involvement of the GM was observed in 1 patient at 7T, with improved morphological detail, appreciated qualitatively, in comparison to imaging at lower-field strengths. These data clearly support that MS pathology is not limited to the WM regions. GM involvement could be the result of retrograde (Wallerian) degeneration from lesions originating in the WM structures. Recent data, however, suggests a dissociation between cortical demyelination and WM pathology, suggesting that MS patients possess both gray and WM demyelinating pathology independently.20
To achieve ultra-high spatial resolution brain images in vivo, significant new technologies had to be developed and employed. New coils designed to be super-sensitive at the cortex were tested and the utility of the gain in SNR was investigated. Also, MR imaging sequences were optimized to produce images of the highest quality possible at this field strength. These developments allowed for high-quality images to be produced and emphasized the potential application to other patient populations.
Recent studies at 7T have demonstrated the utility of T2*-weighted imaging to the investigation of MS pathology, and have revealed new information on lesion location and relationships with brain vasculature.21,22
Also, new forms of lesion contrast have been achieved by looking at the signal phase information and its relationship to lesion characteristics.23
The image collection in this work was optimized for gray/white contrast, with the best SNR at the cortex, and although this imaging methodology was useful to produce ultra high-resolution images to identify lesions in the gray, subcortical, and WM, it is not without limitations. When using T2*-weighting, both cerebrospinal fluid and lesions appear bright, thus making lesion identification in and near the cortex challenging. Previous work with double-inversion recovery (DIR) at 3T has shown the ability of DIR to improve lesion identification in many regions of the brain.24
However, technical and safety limitations with the B1 field and production of 180° pulses on high-field systems make the implementation of this pulse sequence challenging at 7T.
Scanning at 7T provides several limitations from a clinical standpoint. With regard to patient safety and comfort, previous work has suggested that 7T is well tolerated by most subjects; however, the number of complaints was greater at 7T than at lower-field strengths.25
With this in mind, the imaging protocol used in this study was kept very short, ideally less than 35 minutes, to minimize possible discomfort, and the table was moved into the magnet bore very slowly to reduce the potential for sensation of vertigo. The short scan time limited the number of series that were done, as well as the coverage of each of the acquisitions. None of the T2*-weighted protocols resulted in full-brain coverage, but if the imaging session time allowed, full-brain coverage for the Axial-1, Axial-2, and Sagittal series could be achieved in approximately 16, 40, and 26 minutes, respectively. None of the patients enrolled in this study had to terminate the imaging session due to side effects, and only a small fraction reported disorientation when entering the magnet bore. Claustrophobia was no different than at lower-field strengths, and although patients commented on increased noise at 7T, it was not a limiting factor.
The coverage available using the optimized protocol is constrained not only by scan time, but also by the coils available for imaging at 7T. The 8-channel commercially available coil, as well as the coil developed in-house, have limited range in the S/I directions, and thus whole-brain coverage is difficult, if not impossible, to achieve. This limitation will be eliminated as more coils are specifically designed and tested for the 7T systems. Also, due to high coil sensitivity on the outer portion of the head, and the resulting brightness at the cortex, post-processing has to be carried out to get clinically useful images with uniform image intensity across the slice. Although this processing was done offline in this study, it can be completed in less than 1 second, and in the future could be included on the scanner if this were to be incorporated into regular clinical imaging.
The preliminary studies in MS patients indicated that very high-field MR imaging was well tolerated and provided ultra-high-resolution anatomical images allowing for the visualization of structural abnormalities associated with disease. These initial results show that scanning MS patients at 7T is not only feasible, but allows for the detection of lesions with adequate CNR at a higher spatial resolution than has been demonstrated at lower fields. MS lesions were clearly detected in both the white and cortical GM, with morphological details not fully appreciated at lower-field strengths. While still not applicable clinically in patient care, these advancements may allow for a more comprehensive understanding of multiple sclerosis, allowing for further investigation into the natural history and the in vivo delicate immune mediated systems responsible for the genesis of MS pathology in and around the cortical GM.