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Magnetic resonance imaging reveals therapeutic effects of interferon-beta on cytokine-induced reactivation of rat model of multiple sclerosis.

ABSTRACT: Interferon-? (IFN-?) drugs are considered to derive their beneficial effects on multiple sclerosis (MS) progression via their antiinflammatory properties, but the precise mechanism of action remains unclear. Here, we sought to discover how IFN-? impacts on inflammation-associated aggravation of MS-like lesions in rat. Animals with dormant focal experimental allergic encephalomyelitis (EAE) lesions were challenged intravenously with a replication-deficient adenovirus vector carrying interleukin (IL)-1? cDNA (AdIL-1?). Aggravation of inflammation and demyelination within the focal EAE lesion was observed after AdIL-1? injection with associated changes in tissue structure detected by diffusion and magnetization transfer imaging. Postgadolinium-DTPA T1-weighted images revealed contrast enhancement in the ipsilateral meninges, indicating breakdown of the blood-cerebrospinal fluid barrier, and increased left/right regional cerebral blood volume ratio was also observed after AdIL-1? injection. To determine the role of IFN-? on reactivation of the EAE lesion, rats were treated with therapeutic doses of IFN-? and focal EAE lesions showed significantly reduced reactivation in response to systemic AdIL-1? injection. In conclusion, these findings indicate a central role for peripheral IL-1? expression in the mechanism of MS lesion reactivation and that the therapeutic effects of IFN-? may, at least in part, reflect suppression of the effects of peripheral inflammation on MS lesion pathogenesis.

SUBMITTER: Serres S

PROVIDER: S-EPMC3652701 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Magnetic resonance imaging reveals therapeutic effects of interferon-beta on cytokine-induced reactivation of rat model of multiple sclerosis.

Serres Sébastien S Bristow Claire C de Pablos Rocío M RM Merkler Doron D Soto Manuel Sarmiento MS Sibson Nicola R NR Anthony Daniel C DC

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20130220 5

Interferon-β (IFN-β) drugs are considered to derive their beneficial effects on multiple sclerosis (MS) progression via their antiinflammatory properties, but the precise mechanism of action remains unclear. Here, we sought to discover how IFN-β impacts on inflammation-associated aggravation of MS-like lesions in rat. Animals with dormant focal experimental allergic encephalomyelitis (EAE) lesions were challenged intravenously with a replication-deficient adenovirus vector carrying interleukin ( ...[more]

PMID: 23423190

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Project description:Magnetic resonance imaging (MRI) is a fundamental tool in the diagnosis and management of neurological diseases such as multiple sclerosis (MS). New portable, low-field strength, MRI scanners could potentially lower financial and technical barriers to neuroimaging and reach underserved or disabled populations, but the sensitivity of these devices for MS lesions is unknown. We sought to determine if white matter lesions can be detected on a portable 64mT scanner, compare automated lesion segmentations and total lesion volume between paired 3T and 64mT scans, identify features that contribute to lesion detection accuracy, and explore super-resolution imaging at low-field. In this prospective, cross-sectional study, same-day brain MRI (FLAIR, T1w, and T2w) scans were collected from 36 adults (32 women; mean age, 50 ± 14 years) with known or suspected MS using Siemens 3T (FLAIR: 1 mm isotropic, T1w: 1 mm isotropic, and T2w: 0.34-0.5 × 0.34-0.5 × 3-5 mm) and Hyperfine 64mT (FLAIR: 1.6 × 1.6 × 5 mm, T1w: 1.5 × 1.5 × 5 mm, and T2w: 1.5 × 1.5 × 5 mm) scanners at two centers. Images were reviewed by neuroradiologists. MS lesions were measured manually and segmented using an automated algorithm. Statistical analyses assessed accuracy and variability of segmentations across scanners and systematic scanner biases in automated volumetric measurements. Lesions were identified on 64mT scans in 94% (31/33) of patients with confirmed MS. The average smallest lesions manually detected were 5.7 ± 1.3 mm in maximum diameter at 64mT vs 2.1 ± 0.6 mm at 3T, approaching the spatial resolution of the respective scanner sequences (3T: 1 mm, 64mT: 5 mm slice thickness). Automated lesion volume estimates were highly correlated between 3T and 64mT scans (r = 0.89, p < 0.001). Bland-Altman analysis identified bias in 64mT segmentations (mean = 1.6 ml, standard error = 5.2 ml, limits of agreement = -19.0-15.9 ml), which over-estimated low lesion volume and under-estimated high volume (r = 0.74, p < 0.001). Visual inspection revealed over-segmentation was driven venous hyperintensities on 64mT T2-FLAIR. Lesion size drove segmentation accuracy, with 93% of lesions > 1.0 ml and all lesions > 1.5 ml being detected. Using multi-acquisition volume averaging, we were able to generate 1.6 mm isotropic images on the 64mT device. Overall, our results demonstrate that in established MS, a portable 64mT MRI scanner can identify white matter lesions, and that automated estimates of total lesion volume correlate with measurements from 3T scans.

Dataset Information

Magnetic resonance imaging reveals therapeutic effects of interferon-beta on cytokine-induced reactivation of rat model of multiple sclerosis.

Publications

Magnetic resonance imaging reveals therapeutic effects of interferon-beta on cytokine-induced reactivation of rat model of multiple sclerosis.

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