Journal Article

in vivo imaging; ProSense; GI imaging

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Journal Article

FMT; in vivo imaging; ProSense

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.

Journal Article

MMPSense; in vivo imaging; matrix metalloproteinases; stroke

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.

Journal Article

Molecular imaging; Abdominal aortic aneurysm; Optical imaging; Pre-clinical; Endovascular imaging; Matrix metalloproteinase; in vivo imaging; MMPSense

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.

Journal Article

Inflammation; Calcification; Atherosclerosis; Molecular imaging; in vivo imaging; ProSense; OsteoSense

Optical molecular imaging represents an emerging method that can detect pathobiological processes in vivo at the cellular and molecular levels, offering a dynamic link between imaging and biology. This review discusses the impact of molecular imaging methods in atherosclerosis research and preventive medicine and focuses on the inflammation-dependent mechanisms of arterial calcification.