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      1. Author :
        McCann CM, Waterman P, Figueiredo JL, Aikawa E, Weissleder R and Chen JW
      2. Title :
        Combined magnetic resonance and fluorescence imaging of the living mouse brain reveals glioma response to chemotherapy
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Neuroimage
      6. Products :

        FMT Imaging SystemsProSense

      7. Volume :
        45
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        Neuroscience
      11. Keywords :
        FMT; in vivo imaging; ProSense
      12. 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.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19154791
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4544
      1. Author :
        Galina Gabriely, Thomas Wurdinger, Santosh Kesari, Christine C. Esau, Julja Burchard, Peter S. Linsley and Anna M. Krichevsky
      2. Title :
        MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Molecular and Cellular Biology
      6. Products :

        MMPSense

      7. Volume :
        28
      8. Issue :
        17
      9. Page Numbers :
        N/A
      10. Research Area :
        Neuroscience
      11. Keywords :
        in vivo imaging; MMPSense; microRNA 21; glioma
      12. Abstract :
        Substantial data indicate that microRNA 21 (miR-21) is significantly elevated in glioblastoma (GBM) and in many other tumors of various origins. This microRNA has been implicated in various aspects of carcinogenesis, including cellular proliferation, apoptosis, and migration. We demonstrate that miR-21 regulates multiple genes associated with glioma cell apoptosis, migration, and invasiveness, including the RECK and TIMP3 genes, which are suppressors of malignancy and inhibitors of matrix metalloproteinases (MMPs). Specific inhibition of miR-21 with antisense oligonucleotides leads to elevated levels of RECK and TIMP3 and therefore reduces MMP activities in vitro and in a human model of gliomas in nude mice. Moreover, downregulation of miR-21 in glioma cells leads to decreases of their migratory and invasion abilities. Our data suggest that miR-21 contributes to glioma malignancy by downregulation of MMP inhibitors, which leads to activation of MMPs, thus promoting invasiveness of cancer cells. Our results also indicate that inhibition of a single oncomir, like miR-21, with specific antisense molecules can provide a novel therapeutic approach for “physiological” modulation of multiple proteins whose expression is deregulated in cancer.
      13. URL :
        http://mcb.asm.org/cgi/content/abstract/28/17/5369
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4546
      1. Author :
        Klohs J, Baeva N, Steinbrink J, Bourayou R, Boettcher C, Royl G, Megow D, Dirnagl U, Priller J and Wunder A
      2. Title :
        In vivo near-infrared fluorescence imaging of matrix metalloproteinase activity after cerebral ischemia
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Journal of Cerebral Blood Flow and Metabolism
      6. Products :

        MMPSense

      7. Volume :
        29
      8. Issue :
        7
      9. Page Numbers :
        N/A
      10. Research Area :
        Neuroscience
      11. Keywords :
        MMPSense; in vivo imaging; matrix metalloproteinases; stroke
      12. Abstract :
        Matrix metalloproteinases (MMPs) have been implicated in the pathophysiology of cerebral ischemia. In this study, we explored whether MMP activity can be visualized by noninvasive near-infrared fluorescence (NIRF) imaging using an MMP-activatable probe in a mouse model of stroke. C57Bl6 mice were subjected to transient middle cerebral artery occlusion (MCAO) or sham operation. Noninvasive NIRF imaging was performed 24 h after probe injection, and target-to-background ratios (TBRs) between the two hemispheres were determined. TBRs were significantly higher in MCAO mice injected with the MMP-activatable probe than in sham-operated mice and in MCAO mice that were injected with the nonactivatable probe as controls. Treatment with an MMP inhibitor resulted in significantly lower TBRs and lesion volumes compared to injection of vehicle. To test the contribution of MMP-9 to the fluorescence signal, MMP9-deficient (MMP9(-/-)) mice and wild-type controls were subjected to MCAO of different durations to attain comparable lesion volumes. TBRs were significantly lower in MMP9(-/-) mice, suggesting a substantial contribution of MMP-9 activity to the signal. Our study shows that MMP activity after cerebral ischemia can be imaged noninvasively with NIRF using an MMP-activatable probe, which might be a useful tool to study MMP activity in the pathophysiology of the disease.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19417756
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4547
      1. Author :
        Rahul A. Sheth, Marco Maricevich and Umar Mahmood
      2. Title :
        In vivo optical molecular imaging of matrix metalloproteinase activity in abdominal aortic aneurysms correlates with treatment effects on growth rate
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Atherosclerosis
      6. Products :

        MMPSense

      7. Volume :
        212
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        Molecular imaging; Abdominal aortic aneurysm; Optical imaging; Pre-clinical; Endovascular imaging; Matrix metalloproteinase; in vivo imaging; MMPSense
      12. Abstract :
        Objectives: We present a method to quantify the inflammatory processes that drive abdominal aortic aneurysm (AAA) development that may help predict the rate of growth and thus guide medical and surgical management. We use an in vivo optical molecular imaging approach to quantify protease activity within the walls of AAAs in a rodent model.

        Methods: AAAs were generated in mice by topical application of calcium chloride, followed by the administration of the MMP inhibitor doxycycline for 3 months. After this time period, an enzyme-activatable optical molecular imaging agent sensitive to MMP activity was administered, and MMP proteolytic activity was measured in vivo. Histology and in situ zymography were performed for validation. AAAs were also generated in rats, and MMP activity within the walls of the AAAs was also quantified endovascularly.

        Results: A dose-dependent response of AAA growth rate to doxycycline administration was demonstrated, with high doses of the drug resulting in nearly complete suppression of aneurysm formation. There was a direct relationship between the rate of aneurysmal growth and measured MMP activity, with a linear best-fit well approximating the relationship. We additionally performed endovascular imaging of AAAs in rats and demonstrated a similar suppression of intramural MMP activity following doxycycline administration.

        Conclusions: We present an in vivo evaluation of MMP activity within the walls of AAAs in rodents and show a direct, linear relationship between proteolytic activity and aneurysmal growth. We also illustrate that this functional imaging method can be performed endovascularly, demonstrating potential pre-clinical and clinical applications.
      13. URL :
        http://www.atherosclerosis-journal.com/article/S0021-9150(10)00390-4/abstract
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4550
      1. Author :
        N/A
      2. Title :
        Spectroscopy to improve identification of vulnerable plaques in cardiovascular disease
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        International Journal of Cardiovascular Imaging
      6. Products :

        MMPSense

      7. Volume :
        26
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        Cardiovascular disease; Atherosclerosis; Vulnerable plaque; Spectroscopy; Intravascular; in vivo imaging; MMPSense
      12. Abstract :
        Many apparent healthy persons die from cardiovascular disease, despite major advances in prevention and treatment of cardiovascular disease. Traditional cardiovascular risk factors are able to predict cardiovascular events in the long run, but fail to assess current disease activity or nearby cardiovascular events. There is a clear relation between the occurrence of cardiovascular events and the presence of so-called vulnerable plaques. These vulnerable plaques are characterized by active inflammation, a thin cap and a large lipid pool. Spectroscopy is an optical imaging technique which depicts the interaction between light and tissues, and thereby shows the biochemical composition of tissues. In recent years, impressive advances have been made in spectroscopy technology and intravascular spectroscopy is able to assess the composition of plaques of interest and thereby to identify and actually quantify plaque vulnerability. This review summarizes the current evidence for spectroscopy as a measure of plaque vulnerability and discusses the potential role of intravascular spectroscopic imaging techniques.
      13. URL :
        http://www.springerlink.com/content/kx38073782g98666/
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4552
      1. Author :
        Luis Rodriguez-Menocal1, Yuntao Wei1, Si M. Pham, Melissa St-Pierre, Sen Li, Keith Webster, Pascal Goldschmidt-Clermont and Roberto I. Vazquez-Padron
      2. Title :
        A novel mouse model of in-stent restenosis
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Atherosclerosis
      6. Products :

        FMT Imaging SystemsMMPSense FAST

      7. Volume :
        209
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        In-stent restenosis; Mouse; Stent; Animal model; in vivo imaging; MMPSense FAST; FMT
      12. Abstract :
        Background and aims: In-stent restenosis (ISR) is the major complication that occurs after percutaneous coronary interventions to facilitate coronary revascularization. Herein we described a simple and cost-effective model, which reproduces important features of ISR in the mouse.

        Methods and results: Microvascular bare metal stents were successfully implanted in the abdominal aorta of atherosclerotic ApoE-null mice. Patency of implanted stents was interrogated using ultrasound biomicroscopy. Aortas were harvested at different time points after implantation and processed for histopathological analysis. Thrombus formation was histologically detected after 1 day. Leukocyte adherence and infiltration were evident after 7 days and decreased thereafter. Neointimal formation, neointimal thickness and luminal stenosis simultaneously increased up to 28 days after stent implantation. Using multichannel fluorescence molecular tomography (FMT) for spatiotemporal resolution of MMP activities, we observed that MMP activity in the stented aorta of Apo-E null mice was 2-fold higher than that of wild-type mice. Finally, we compared neointimal formation in response to stenting in two genetically different mouse strains. In-stent neointimas in FVB/NJ mice were 2-fold thicker than in C57BL/6J mice (p=0.002).

        Conclusion: We have developed a model that can take advantage of the multiple genetic resources available for the mouse to study the mechanisms of in-stent restenosis.
      13. URL :
        http://www.atherosclerosis-journal.com/article/S0021-9150(09)00825-9/abstract
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4555
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