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Original Contribution |

Multiple Sclerosis Lesions and Irreversible Brain Tissue Damage:  A Comparative Ultrahigh-Field Strength Magnetic Resonance Imaging Study

Tim Sinnecker; Paul Mittelstaedt; Jan Dörr, MD; Caspar F. Pfueller, MD; Lutz Harms, MD; Thoralf Niendorf, PhD; Friedemann Paul, MD; Jens Wuerfel, MD
Arch Neurol. 2012;69(6):739-745. doi:10.1001/archneurol.2011.2450.
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Background  In current clinical practice, T2-weighted magnetic resonance imaging (MRI) is commonly applied to quantify the accumulated multiple sclerosis (MS) lesion load, whereas T1-weighted sequences are used to differentiate edema, blood-brain barrier breakdown by contrast enhancement, and irreversible brain tissue damage (commonly called “black holes” owing to the loss of signal intensity in T1-weighted sequences). Black holes are histopathologically associated with axonal loss and severe tissue destruction. In addition, double inversion recovery techniques were developed to improve the sensitivity to cortical lesions.

Objective  To demonstrate the potential of ultrahigh-field 3-dimensional T1-weighted imaging using magnetization-prepared rapid acquisition and multiple gradient-echoes (MPRAGE) to detect and characterize white and gray matter pathology in MS.

Design  Comparative study.

Setting  The patients with MS were recruited from the outpatient clinics of the NeuroCure Clinical Research Center and underwent 7-T brain MRI at the Berlin Ultrahigh Field Facility, both of which are in Berlin, Germany.

Patients  Twenty patients with relapsing-remitting MS and 14 healthy controls underwent 7-T brain MRI, using a 24-channel receive head coil, and a subgroup of 18 patients with relapsing-remitting MS also underwent 1.5-T brain MRI. The imaging protocol included 2-dimensional T2-weighted fast low-angle shot (FLASH) and turbo inversion recovery magnitude (TIRM) sequences. For 3-dimensional T1-weighted imaging, the MPRAGE sequence was used. Each sequence was initially examined independently in separate analyses by an investigator blinded to all other data. In a second study, all detected lesions were retrospectively analyzed in a side-by-side comparison of all sequences.

Results  By use of 7-T T2-weighted FLASH imaging, 604 cerebral lesions were detected in the patients with relapsing-remitting MS (mean, 30.2 lesions per patient [range, 2-107 lesions per patient]), but none were detected in healthy controls. Cortical pathology was visible in 10 patients (6 cortical lesions and 37 leukocortical lesions). Within the 7-T acquisitions, each lesion detected at T2-weighted sequences and/or double inversion recovery sequences was also clearly delineated on corresponding MPRAGE sequences in side-by-side analysis. However, at 1.5 T, the MPRAGE images depicted only 452 of 561 lesions visualized in T2-weighted sequences and/or double inversion recovery sequences. In contrast, when analyzing each sequence separately, we found that the 7-T MPRAGE depicted more lesions than the 7-T FLASH (728 lesions vs 584 lesions), and almost twice as many as the 1.5-T MPRAGE (399 lesions). The 7-T MPRAGE also improved the detection of cortical and leukocortical lesions (15 lesions vs 58 lesions).

Conclusions  At ultrahigh-field strength, T1-weighted MPRAGE is highly sensitive in detecting MS plaques within the white and the gray brain parenchyma. Our results indicate structural damage beyond demyelination in every lesion depicted, which is in accordance with postmortem histopathological studies. The 7-T MPRAGE clearly delineated every cortical lesion that was visualized by any other MRI sequence at 1.5 or 7 T.

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Figures

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Figure 1. Characteristics of 7-T magnetic resonance imaging. At 7 T, each neuroinflammatory lesion is clearly marked with great distinction in the T1-weighted magnetization-prepared rapid acquisition and multiple gradient echo (T1 MPRAGE) image (A). At the same field strength, the T2-weighted fast low-angle shot (T2 FLASH) image reveals a perivascular location (black arrow) for the majority of lesions (B). Some of the lesions that express a hypointense rim are believed to be chronic plaques (white arrows).

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Figure 2. Three exemplary lesions in cortical gray matter, subcortical matter, and white matter. The 7-T T1-weighted magnetization-prepared rapid acquisition and multiple gradient echo (7-T T1 MPRAGE) images (A, E, and K) delineate each lesion (white arrows) as a distinct hypointensity. The 1.5-T MPRAGE sequence reveals only a subset of lesions (white arrows) detected on T2-weighted images (1.5-T T1 MPRAGE [B, G, and L]). The 7-T T2-weighted fast low-angle shot images (7-T T2 FLASH [C, H, and M]) reveal the perivascular setting (black arrows) of white matter multiple sclerosis (MS) plaques (white arrows). The asterisk indicates a hypointense rim characteristic for a proportion of MS plaques. The 1.5-T T2-weighted turbo spin-echo images (1.5-T T2 TSE) reveal MS lesions (white arrows [D, I, and N]). The 1.5-T double inversion recovery (DIR) images reveal MS lesions (white arrows [E, J, and O]).

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Figure 3. Example of lesions involving cortex and subcortical white matter. The total lesion area appears much greater on the 7-T magnetization-prepared rapid acquisition and multiple gradient echo (7-T MPRAGE) image (A; white circle) than it does on the 1.5-T MPRAGE image (B; white circle), and is much easier to distinguish compared with the 1.5-T T2-weighted turbo spin-echo (1.5-T T2 TSE) image (C; white circle). Accordingly, this lesion was discovered by and hence included in the 1.5-T MPRAGE lesion count.

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