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Distinguishing inflammation from tumor and peritumoral edema by myeloperoxidase magnetic resonance imaging.

ABSTRACT: Inflammation occurs routinely when managing gliomas and is not easily distinguishable from tumor regrowth by current MRI methods. The lack of noninvasive technologies that monitor inflammation prevents us to understand whether it is beneficial or detrimental for the patient, and current therapies do not take this host response in consideration. We aim to establish whether a gadolinium (Gd)-based agent targeting the inflammatory enzyme myeloperoxidase (MPO) can selectively detect intra- and peritumoral inflammation as well as glioma response to treatment by MRI.We carried out serial Gd-bis-5-HT-DTPA (MPO-Gd) MRI before and after treating rodent gliomas with different doses of oncolytic virus (OV) and analyzed animal survival. The imaging results were compared with histopathologic and molecular analyses of the tumors for macrophage/microglia infiltration, virus persistence, and MPO levels.Elevated MPO activity was observed by MRI inside the tumor and in the peritumoral cerebrum at day 1 post-OV injection, which corresponded with activation/infiltration of myeloid cells inhibiting OV intratumoral persistence. MPO activity decreased, whereas tumor size increased, as the virus and the immune cells were cleared (days 1-7 post-OV injection). A 10-fold increase in viral dose temporally decreased tumor size, but augmented MPO activity, thus preventing extension of viral intratumoral persistence.MPO-Gd MRI can distinguish enhancement patterns that reflect treatment-induced spatiotemporal changes of intratumoral and intracerebral inflammation from those indicating tumor and peritumoral edema. This technology improves the posttreatment diagnosis of gliomas and will increase our understanding of the role of inflammation in cancer therapy.

SUBMITTER: Kleijn A

PROVIDER: S-EPMC3131449 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Distinguishing inflammation from tumor and peritumoral edema by myeloperoxidase magnetic resonance imaging.

Kleijn Anne A Chen John W JW Buhrman Jason S JS Wojtkiewicz Gregory R GR Iwamoto Yoshiko Y Lamfers Martine L ML Stemmer-Rachamimov Anat O AO Rabkin Samuel D SD Weissleder Ralph R Martuza Robert L RL Fulci Giulia G

Clinical cancer research : an official journal of the American Association for Cancer Research 20110510 13

<h4>Purpose</h4>Inflammation occurs routinely when managing gliomas and is not easily distinguishable from tumor regrowth by current MRI methods. The lack of noninvasive technologies that monitor inflammation prevents us to understand whether it is beneficial or detrimental for the patient, and current therapies do not take this host response in consideration. We aim to establish whether a gadolinium (Gd)-based agent targeting the inflammatory enzyme myeloperoxidase (MPO) can selectively detect ...[more]

PMID: 21558403

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Project description:BACKGROUND:Myocardial edema in acute myocardial infarction (AMI) is commonly imaged using dark-blood short tau inversion recovery turbo spin echo (STIR-TSE) cardiovascular magnetic resonance (CMR). The technique is sensitive to cardiac motion and coil sensitivity variation, leading to myocardial signal nonuniformity and impeding reliable depiction of edematous tissues. T2-prepared balanced steady state free precession (T2p-bSSFP) imaging has been proposed, but its contrast is low, and averaging is commonly needed. T2 mapping is useful but requires a long scan time and breathholding. We propose here a single-shot magnetization prepared sequence that increases the contrast between edema and normal myocardium and apply it to myocardial edema imaging. METHODS:A magnetization preparation module (T2STIR) is designed to exploit the simultaneous elevation of T1 and T2 in edema to improve the depiction of edematous myocardium. The module tips magnetization down to the -z axis after T2 preparation. Transverse magnetization is sampled at the fat null point using bSSFP readout and allows for single-shot myocardial edema imaging. The sequence (T2STIR-bSSFP) was studied for its contrast behavior using simulation and phantoms. It was then evaluated on 7 healthy subjects and 7 AMI patients by comparing it to T2p-bSSFP and T2 mapping using the contrast-to-noise ratio (CNR) and the contrast ratio as performance indices. RESULTS:In simulation and phantom studies, T2STIR-bSSFP had improved contrast between edema and normal myocardium compared with the other two edema imaging techniques. In patients, the CNR of T2STIR-bSSFP was higher than T2p-bSSFP (5.9?±?2.6 vs. 2.8?±?2.0, P?<?0.05) but had no significant difference compared with that of the T2 map (T2 map: 6.6?±?3.3 vs. 5.9?±?2.6, P?=?0.62). The contrast ratio of T2STIR-bSSFP (2.4?±?0.8) was higher than that of the T2 map (1.3?±?0.1, P?<?0.01) and T2p-bSSFP (1.4?±?0.5, P?<?0.05). CONCLUSION:T2STIR-bSSFP has improved contrast between edematous and normal myocardium compared with commonly used bSSFP-based edema imaging techniques. T2STIR-bSSFP also differentiates between fat that was robustly suppressed and fluids around the heart. The technique is useful for single-shot edema imaging in AMI patients.

Dataset Information

Distinguishing inflammation from tumor and peritumoral edema by myeloperoxidase magnetic resonance imaging.

Publications

Distinguishing inflammation from tumor and peritumoral edema by myeloperoxidase magnetic resonance imaging.

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