Benjamin Pulli MD, Presenter: Nothing to Disclose

Gregory R. Wojtkiewicz MSC, Abstract Co-Author: Nothing to Disclose

Lionel Antoine Bure MD, Abstract Co-Author: Nothing to Disclose

Muhammad Ali MBBS, Abstract Co-Author: Nothing to Disclose

Stefan Schob, Abstract Co-Author: Nothing to Disclose

Li-Chun Hsieh MD, Abstract Co-Author: Nothing to Disclose

Dan Li, Abstract Co-Author: Nothing to Disclose

Hyun Ju Kim PhD, Abstract Co-Author: Nothing to Disclose

John Chen MD, PhD, Abstract Co-Author: Research Grant, Pfizer Inc

Clinical diagnosis of multiple sclerosis (MS) is challenging. We hypothesized that MPO-Gd, a molecular MRI probe specifically for myeloperoxidase can detect subclinical and chronic disease better than DTPA-Gd in a mouse model of MS.

Twenty-four female SJL mice were induced with experimental autoimmune encephalomyelitis, a mouse model of MS. To determine the earliest time point for disease detection, mice underwent MRI at 4.7T with a T1 sequence with MPO-Gd (n=8) or DTPA-Gd (n=6) on days 6, 8, and 10 post induction (p.i.). To investigate detection of chronic disease, mice underwent MRI at 4.7T with a T1 sequence with MPO-Gd (n=6) or DTPA-Gd (n=4) at the interval between acute disease and relapse (day 21) and at the relapse (days 24-30). Lesion number and volumes were quantified on post-contrast T1 images. Immunohistochemistry and flow cytometry for brain leukocytes and MPO were also performed.

MPO-Gd enhanced MRI detected disease earlier (8.0±1.1 vs. 9.7±0.8 days p.i.,) than DTPA-Gd, at a stage where there were fewer (1.25±0.46 vs. 3.6±2.7) and smaller (0.0045±0.003 vs. 0.0385±0.030 cm3) lesions with a smaller total affected volume (0.005±0.0028 vs. 0.145±0.210 cm3, all p<0.05). No difference was seen in disease onset or severity between the two groups (p>0.1). Flow cytometry demonstrated a significant increase in MPO-positive macrophages on day 8 (4992±1694 vs. 144±39 cells/brain, p<0.05), but not on day 6 (253±102 vs. 144±39 cells/brain, p>0.05) p.i., coinciding with the time of first detection with MPO-Gd. In chronic disease, more lesions and a greater total lesion volume were seen at the interval (5.5±0.84 vs. 1.25±0.96 lesions, and 0.047±0.02 vs. 0.010±0.006 cm3) and relapse (9.0±4.1 vs. 2.7±2.1 lesions, and 0.219±0.186 vs. 0.013±0.011 cm3, all p<0.05) with MPO-Gd.

MPO-Gd enhanced MRI can detect smaller inflammatory lesions earlier than DTPA-Gd, at the first time point when inflammatory cells accumulate in the brain. Furthermore, MPO-Gd demonstrated subclinical disease activity between the acute stage and the first relapse better than DTPA-Gd, and also detects significantly more lesions at the first relapse. 

Upon translation, earlier and more sensitive detection of subclinical disease could improve diagnosis in MS patients, and could be used as a better imaging biomarker.

Pulli, B, Wojtkiewicz, G, Bure, L, Ali, M, Schob, S, Hsieh, L, Li, D, Kim, H, Chen, J, Molecular MRI Targeting Myeloperoxidase Improves Detection of Subclinical and Chronic Disease in Murine Multiple Sclerosis Compared to Conventional Gadolinium-enhanced MRI.  Radiological Society of North America 2012 Scientific Assembly and Annual Meeting, November 25 - November 30, 2012 ,Chicago IL. http://archive.rsna.org/2012/12043647.html