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Combined magnetic resonance and fluorescence imaging of the living mouse brain reveals glioma response to chemotherapy.

ABSTRACT: Fluorescent molecular tomographic (FMT) imaging can noninvasively monitor molecular function in living animals using specific fluorescent probes. However, macroscopic imaging methods such as FMT generally exhibit low anatomical details. To overcome this, we report a quantitative technique to image both structure and function by combining FMT and magnetic resonance (MR) imaging. We show that FMT-MR imaging can produce three-dimensional, multimodal images of living mouse brains allowing for serial monitoring of tumor morphology and protease activity. Combined FMT-MR tumor imaging provides a unique in vivo diagnostic parameter, protease activity concentration (PAC), which reflects histological changes in tumors and is significantly altered by systemic chemotherapy. Alterations in this diagnostic parameter are detectable early after chemotherapy and correlate with subsequent tumor growth, predicting tumor response to chemotherapy. Our results reveal that combined FMT-MR imaging of fluorescent molecular probes could be valuable for brain tumor drug development and other neurological and somatic imaging applications.

SUBMITTER: McCann CM

PROVIDER: S-EPMC2707831 | biostudies-other | 2009 Apr

REPOSITORIES: biostudies-other

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Combined magnetic resonance and fluorescence imaging of the living mouse brain reveals glioma response to chemotherapy.

McCann Corey M CM Waterman Peter P Figueiredo Jose-Luiz JL Aikawa Elena E Weissleder Ralph R Chen John W JW

NeuroImage 20081225 2

Fluorescent molecular tomographic (FMT) imaging can noninvasively monitor molecular function in living animals using specific fluorescent probes. However, macroscopic imaging methods such as FMT generally exhibit low anatomical details. To overcome this, we report a quantitative technique to image both structure and function by combining FMT and magnetic resonance (MR) imaging. We show that FMT-MR imaging can produce three-dimensional, multimodal images of living mouse brains allowing for serial ...[more]

PMID: 19154791

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Project description:Background:Glioma represents the most common malignant brain tumor. Outcomes of surgical resection are often unsatisfactory due to low sensitivity or resolution of imaging methods. Moreover, the use of traditional chemotherapeutics, such as doxorubicin (DOX), is limited due to their low blood-brain barrier (BBB) permeability. Recently, the development of nanotechnology could overcome these obstacles. Materials and methods:Hydrophobic superparamagnetic iron oxide nanoparticles (SPIO NPs) were prepared with the use of thermal decomposition method. They were coated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG 2000) and DOX using a thin-film hydration method followed by loading of indocyanine green (ICG) into the phospholipid layers. Details regarding the characteristics of NPs were determined. The in vitro biocompatibility and antitumor efficacy were established with the use of MTT assay. In vivo fluorescence and magnetic resonance (MR) imaging were used to evaluate BBB penetration and accumulation of NPs at the tumor site. Antitumor efficacy was evaluated using measures of tumor size, median survival times, body weights, and H&E staining. Results:The multifunctional NPs generated had an average diameter of 22.9 nm, a zeta potential of -38.19 mV, and were capable of providing a sustained release of DOX. In vitro experiments demonstrated that the SPIO@DSPE-PEG/DOX/ICG NPs effectively enhanced cellular uptake of DOX as compared with that of free DOX. In vivo fluorescence and MR imaging revealed that the NPs not only effectively crossed the BBB but selectively accumulated at the tumor site. Meanwhile, among all groups studied, C6 glioma-bearing rats treated with the NPs exhibited the maximal degree of therapeutic efficacy, including smallest tumor volume, lowest body weight loss, and longest survival times, with no obvious side effects. Conclusion:These results suggest that the SPIO@DSPE-PEG/DOX/ICG NPs can not only function as a nanoprobe for MR and fluorescence bimodal imaging, but also as a vehicle to deliver chemotherapeutic drugs to the tumor site, to achieve the theranostic treatment of glioma.

Project description:IntroductionIn addition to being a risk factor for breast cancer, breast density has been hypothesized to be a surrogate biomarker for predicting response to endocrine-based chemotherapies. The purpose of this study was to evaluate whether a noninvasive bedside scanner based on diffuse optical spectroscopic imaging (DOSI) provides quantitative metrics to measure and track changes in breast tissue composition and density. To access a broad range of densities in a limited patient population, we performed optical measurements on the contralateral normal breast of patients before and during neoadjuvant chemotherapy (NAC). In this work, DOSI parameters, including tissue hemoglobin, water, and lipid concentrations, were obtained and correlated with magnetic resonance imaging (MRI)-measured fibroglandular tissue density. We evaluated how DOSI could be used to assess breast density while gaining new insight into the impact of chemotherapy on breast tissue.MethodsThis was a retrospective study of 28 volunteers undergoing NAC treatment for breast cancer. Both 3.0-T MRI and broadband DOSI (650 to 1,000 nm) were obtained from the contralateral normal breast before and during NAC. Longitudinal DOSI measurements were used to calculate breast tissue concentrations of oxygenated and deoxygenated hemoglobin, water, and lipid. These values were compared with MRI-measured fibroglandular density before and during therapy.ResultsWater (r = 0.843; P < 0.001), deoxyhemoglobin (r = 0.785; P = 0.003), and lipid (r = -0.707; P = 0.010) concentration measured with DOSI correlated strongly with MRI-measured density before therapy. Mean DOSI parameters differed significantly between pre- and postmenopausal subjects at baseline (water, P < 0.001; deoxyhemoglobin, P = 0.024; lipid, P = 0.006). During NAC treatment measured at about 90 days, significant reductions were observed in oxyhemoglobin for pre- (-20.0%; 95% confidence interval (CI), -32.7 to -7.4) and postmenopausal subjects (-20.1%; 95% CI, -31.4 to -8.8), and water concentration for premenopausal subjects (-11.9%; 95% CI, -17.1 to -6.7) compared with baseline. Lipid increased slightly in premenopausal subjects (3.8%; 95% CI, 1.1 to 6.5), and water increased slightly in postmenopausal subjects (4.4%; 95% CI, 0.1 to 8.6). Percentage change in water at the end of therapy compared with baseline correlated strongly with percentage change in MRI-measured density (r = 0.864; P = 0.012).ConclusionsDOSI functional measurements correlate with MRI fibroglandular density, both before therapy and during NAC. Although from a limited patient dataset, these results suggest that DOSI may provide new functional indices of density based on hemoglobin and water that could be used at the bedside to assess response to therapy and evaluate disease risk.

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Combined magnetic resonance and fluorescence imaging of the living mouse brain reveals glioma response to chemotherapy.

Publications

Combined magnetic resonance and fluorescence imaging of the living mouse brain reveals glioma response to chemotherapy.

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