[Show abstract][Hide abstract] ABSTRACT: Purpose: The efficacy of pro-angiogenic therapy is difficult to evaluate with current diagnostic modalities. The objectives were to develop a non-invasive imaging strategy to define the temporal characteristics of angiogenesis and to evaluate the response to pro-angiogenic therapy in diabetic stroke mouse models.
Methods: A home-made ανβ3 integrin-targeted multi-modal nanoprobe was intravenously injected into mouse models at set time points after photothrombotic stroke. Magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging were carried out at 24 h post-injection. Bone marrow-derived endothelial progenitor cells (EPCs) were infused into the mouse models of ischemic stroke to stimulate angiogenesis.
Results: The peak signal intensity in the ischemic-angiogenic area of diabetic and wild-type mouse models was achieved on day 10, with significantly lower signal enhancement observed in the diabetic models. Although the signal intensity was significantly higher after EPC treatment in both models, the enhancement was less pronounced in the diabetic animals compared with the wild-type controls. Histological analysis revealed that the microvessel density and expression of β3 integrin were correlated with the signal intensity assessed with MRI and NIRF imaging.
Conclusions: The non-invasive imaging method could be used for early and accurate evaluation of the response to pro-angiogenic therapy in diabetic stroke models.
[Show abstract][Hide abstract] ABSTRACT: Bone-marrow derived endothelial progenitor cells (EPCs) play an important role in tumor neovasculature. Due to their tumor homing property, EPCs are regarded as promising targeted vectors for delivering therapeutic agents in cancer treatment. Consequently, non-invasive confirmation of targeted delivery via imaging is urgently needed. This study shows the development and application of a novel dual-modality probe for in vivo non-invasively tracking of the migration, homing and differentiation of EPCs.
The paramagnetic/near-infrared fluorescence probe Conjugate 1 labeled EPCs were systemically transplanted into mice bearing human breast MDA-MB-231 tumor xenografts. Magnetic resonance imaging (MRI) and near-infrared (NIR) fluorescence optical imaging were performed at different stages of tumor development. The homing of EPCs and the tumor neovascularization were further evaluated by immunofluorescence.
Conjugate 1 labeled EPCs can be monitored in vivo by MRI and NIR fluorescence optical imaging without altering tumor growth for up to three weeks after the systemic transplantation. Histopathological examination confirmed that EPCs were recruited into the tumor bed and then incorporated into new vessels two weeks after the transplantation. Tumor size and microvessel density was not influenced by EPCs transplantation in the first three weeks.
This preclinical study shows the feasibility of using a MRI and NIR fluorescence optical imaging detectable probe to non-invasively monitor transplanted EPCs and also provides strong evidence that EPCs are involved in the development of endothelial cells during the tumor neovascularization.
PLoS ONE 11/2012; 7(11):e50575. DOI:10.1371/journal.pone.0050575 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Brown adipose tissue (BAT) plays a key role in thermogenesis to protect the body from cold and obesity. White adipose tissue (WAT) stores excess energy in the form of triglycerides. To better understand the genetic effect on regulation of WAT and BAT, we investigated the fat fraction (FF) in two types of adipose tissues in ob/ob, human BSCL2/seipin gene knock-out (SKO), Fsp27 gene knock-out (Fsp27-/-), and wild type (WT) mice in vivo using chemical shift selective imaging and (1)H MR spectroscopy. We reported that the visceral fat volume in WAT was significantly larger in ob/ob mice, but visceral fat volumes were lower in SKO and Fsp27-/- mice compared to WT mice. BAT FF was significantly higher in ob/ob mice than WT group and similar to that of WAT. In contrast, WAT FFs in SKO and Fsp27-/- mice were lower and similar to that of BAT. The adipocyte size of WAT in ob/ob mice and the BAT adipocyte size in ob/ob, SKO, and Fsp27 mice were significantly larger compared to WT mice. However, the WAT adipocyte size was significantly smaller in SKO mice than WT mice. Positive correlations were observed between the adipocyte size and FFs of WAT and BAT. These results suggested that smaller adipocyte size correlates with lower FFs of WAT and BAT. In addition, the differences of FFs in WAT and BAT measured by MR methods in different mouse models were related to the different regulation effects of ob, seipin or Fsp27 gene on developing WAT and BAT.
[Show abstract][Hide abstract] ABSTRACT: We evaluated dual-echo Dixon in-phase and out-of-phase (IP-OP), chemical shift imaging (CSI), and (1)H MRS (hydrogen MR spectroscopy) in estimating fat content (FC) in phantoms and in livers of mice. Phantoms were made according to the volume percentage of fat ranging from 0% to 100%. The three MR methods were performed to measure FC in phantoms and in livers of obese leptin-deficient (ob/ob), human BSCL2/seipin gene knockout (SKO), and wild-type (WT) mice. The results were compared with known FC in phantoms and to a reference standard from mice by histological semiautomatic vacuole segmentation (HIS-S) procedure and liver lipid (LL) chemical analysis. In phantoms, CSI underestimated FC from 50% to 100%, to a lesser extent than IP-OP. In vivo, liver FC in ob/ob and SKO mice measured by the three MR methods were all significantly higher than that in WT mice. Liver FC measured by IP-OP were significantly lower than that measured by CSI and MRS, with no significant difference between CSI and MRS. CSI and MRS showed a linear correlation with LL analysis and with each other. IP-OP underestimated FC, whereas CSI and MRS were more accurate for quantifying FC in both phantoms and liver. CSI and MRS have the potential to replace HIS-S and LL analysis in longitudinal studies.
The Journal of Lipid Research 07/2011; 52(10):1847-55. DOI:10.1194/jlr.D016691 · 4.73 Impact Factor