Optimized T 1-MPRAGE Sequence for Better Visualization of Spinal CordMultiple Sclerosis Lesions at 3 T

BACKGROUND AND PURPOSE: Spinal cord lesions are highly prevalent in MS, and their visualization can help both in diagnosis and patient follow-up. However, the sensitivity of MR imaging to spinal cord lesions remains poor, primarily because of suboptimal contrast between lesions and a normal-appearing cord. Here, we propose an optimized 3DMPRAGE sequence for improveddetection ofMS lesions in the spinal cord at 3T. MATERIALS ANDMETHODS: Images were acquired by use of T2 FSE, STIR, T1-gradient recalled-echo (for T1 mapping), and T1-MPRAGE in the sagittal plane, and T2*-weighted scans in the axial plane, on 40 patients with MS and 7 healthy volunteers. Two observers qualitatively evaluated the images for lesion conspicuity. Lesions seen between the C1 and C4 segments in 10 randomly selected patients with MS were further evaluated quantitatively for contrast-to-noise ratio between the lesion and normal-appearing cord, and for lesion burden. RESULTS: Spinal cord lesions were more conspicuous on the optimized T1-MPRAGE sequence than on any other sequence tested. Detailed analysis revealed that lesionswere almost 3 timesmore conspicuous (P .01), and the total lesion volumewas 2 times greater (P .05, n 10), in the T1-MPRAGE sequence compared with the standard STIR sequence. Correlation of clinical disability (Expanded Disability Status Score) with lesion load from each sequence also demonstrated the importance of the improved lesion conspicuity with T1-MPRAGE. CONCLUSIONS: The optimized T1-MPRAGE sequence described here improves the reliability of lesion visualization and estimation of lesion burden, especially when used in conjunction with other well-established clinical sequences. ABBREVIATIONS: CNR contrast-to-noise ratio; EDSS Expanded Disability Status Score; GRAPPA generalized autocalibrating partially parallel acquisition; MERGE multi-echo recombined gradient-echo; NAC normal-appearing cord; PSIR phase-sensitive inversion recovery; GRE gradient recalled-echo MS is a disease of the central nervous system, and spinal cord lesions are widely prevalent in patients with MS. It is thought that, in the proper context, the presence of cord lesions is highly specific for the diagnosis of MS, and several studies have shown spinal cord abnormalities in 75%–90% of patients clinically diagnosed with MS. Visualization of spinal cord lesions allows approximately 18% more patients to meet the McDonald dissemination in space criteria for the diagnosis of MS. Cord lesions are also believed to occur in isolation, further highlighting the importance of visualizing lesions in the spinal cord for the diagnosis of MS. MR imaging of the spinal cord is challenging not only because of the small size of structures but also because of artifacts from respiration, cardiac, and CSF pulsation, and cord movement during the cardiac cycle. Although advances in MR imaging hardware and pulse sequences have mitigated some of these challenges, sensitivity to visualization of cord lesion remains poor. Several studies have proposed specialized and optimized sequences for improving lesion visualization in the spinal cord, especially the cervical cord, including double-echo spin-echo, STIR, phase-sensitive inversion recovery (PSIR), and multi-echo recombined gradient-echo (MERGE on GE scanners, also called Multi-Echo Data Image Combination or MEDIC on Siemens Received December 28, 2012; accepted after revision February 18, 2013. From the National Institute of Neurological Disorders and Stroke (G.N., M.A., D.S.R.), National Institutes of Health, Bethesda, Maryland; Neuroimaging Research Unit (M.A.) and Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; and Department of Radiology and Neurology (D.S.R.), Johns Hopkins University, Baltimore, Maryland. Support: Intramural Research Program of NINDS. Paper previously presented at: Annual Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), May 30–June 2, 2012; San Diego, California. Please address correspondence to Govind Nair, Translational Neuroradiology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health; Bldg 10, Rm 5C103; 10 Center Dr, MSC 1400; Bethesda, MD 20892; e-mail: reichds@ninds.nih.gov Indicates open access to non-subscribers at www.ajnr.org http://dx.doi.org/10.3174/ajnr.A3637 AJNR Am J Neuroradiol ●:● ● 2013 www.ajnr.org 1 Published June 13, 2013 as 10.3174/ajnr.A3637 Copyright 2013 by American Society of Neuroradiology. scanners and multi-echo Fast Field Gradient Echo or mFFE on Philips scanners). Of these, the proton density and T2 (double-echo) spin-echo or FSE and STIR sequences have been accepted as a clinical standard for spinal cord imaging in MS, primarily because of the ease of implementation on a wide range of scanners. However, lesions are demonstrably more conspicuous in sequences such as PSIR and MERGE. Furthermore, despite sequence improvements, the correlation between lesion volume and clinical Expanded Disability Status Score (EDSS) remains low. One contributing factor could be that MR imaging sequences are insensitive to many lesions in the cord, and that radiologic calculation of lesion burden is inaccurate. An optimized sequence for detection of cord lesions may improve diagnostic efficiency and accuracy of CNS lesion load estimation. The MPRAGE sequence offers a unique opportunity, through optimization of T1-contrast and SNR. Here, we qualitatively evaluate a T1-weighted MPRAGE sequence for efficiency of visualizing lesions in the cervical and thoracic spinal cord and quantitatively compare its performance with other sequences including STIR, T2-weighted, T2*-weighted, and noninversionprepared T1-weighted gradient-echo sequences in the upper cervical spinal cord. MATERIALS AND METHODS Patients MR imaging of the cervical and thoracic spinal cord was performed on 40 patients and 7 healthy control participants. MR images from 10 patients with MS were randomly selected for a more detailed quantitative analysis of lesions in the upper cervical cord. Written, informed consent was obtained from all participants, and the Institutional Review Board at the National Institutes of Health approved all protocols. MR Imaging MR imaging was performed on a 3T Skyra system (Siemens, Erlangen, Germany) equipped with a 20-channel head-neck coil and a 16-channel spine-array coil. Standard clinical sequences and sequences optimized elsewhere that have been traditionally used to visualize spinal cord lesions such as T2-weighted FSE, STIR, T1-weighted gradient recalled-echo (GRE), and T2*-weighted GRE sequences were compared with the optimized T1-MPRAGE sequence in the cervical and thoracic regions separately. In the cervical spine, T2-weighted images were acquired in the sagittal plane by use of a 2D FSE sequence (T2-FSE) with TR, 3500 ms; TE, 102 ms; 0.7-mm nominal in-plane resolution; and 1-mm section thickness (no intersection gap), with a scan time of 3 minutes 40 seconds. STIR images were acquired in the sagittal plane with a 2D inversion-prepared FSE sequence with TR, 4000 ms; TE, 68 ms; TI, 210 ms; parallel imaging with generalized autocalibrating partially parallel acquisition (GRAPPA 2); 0.8-mm nominal in-plane resolution; 2-mm section thickness; a 10% gap between sections; and a scan time of 4 minutes 30 seconds. A 3D-MPRAGE sequence (T1-MPRAGE) was acquired in the sagittal plane with TR, 3000 ms; TE, 4.5 ms; TI, 750 ms; flip angle, 8°; parallel imaging (GRAPPA 2); 1-mm isotropic resolution; and a scan time of 7 minutes 30 seconds. T1 mapping was done by use of two 3D-gradient-echo sequences with TR, 7.8 ms; TE, 3 ms; 1-mm isotropic resolution; and flip angles of 3° and 16° (T1GRE), for a scan time of approximately 3 minutes per flip angle. Finally, T2*-weighted images were acquired in the axial plane with the 2D MEDIC sequence (T2*-GRE) with TR, 775 ms; TE, 11 ms; flip angle, 20°; parallel imaging (GRAPPA 2); nominal inplane resolution, 0.58 mm; section thickness, 5 mm (no intersection gap); and a scan time of 3 minutes 30 seconds. The protocols were very similar for imaging of the thoracic spine, except that the sequence was GRE, and field-of-view and acquisition matrix were modified to cover the entire thoracic spinal cord. The T1-GRE sequence was repeated postgadolinium (gadobutrol, 0.1 mmol/ kg) only if clinically indicated. Data Analysis By consensus, a neurologist (M.A., with 7 years of experience) and a neuroradiologist (D.S.R., with 10 years of experience) rated each lesion from the MS and healthy control groups in a blinded fashion. Images obtained from all of the sequences were assessed simultaneously, and lesions that were conspicuous in any of the pulse sequences were counted, and their vertebral levels noted for each patient. For detailed quantitative analysis, scans from 10 patients were randomly selected from the MS group. 3D scans were reformatted only in orthogonal (axial, coronal, and sagittal) planes in OsiriX (http://www.osirix-viewer.com/) for qualitative evaluation, and a lesion was labeled confirmed if it was present in more than 1 sequence or if it had a characteristic appearance on reformation. None of the quantitative analysis used curved or oblique reformatting. The conspicuity of each lesion in the various pulse sequences was scored as being absent or of poor, good, or excellent conspicuity (scores from 0 –3). Lesion detection efficiency for each sequence was calculated as an average percent of lesions detected with good or excellent conspicuity to the total number of lesions seen in each patient. T1 maps were calculated on a pixel-by-pixel basis in Matlab (MathWorks, Natick, Massachusetts) by use of the variable flip-angle GRE scans, described elsewhere. ROIs were drawn on visible lesions (L) and normal-appearing brain stem or cord (NAC) at the C1 level in