scholarly journals A non-invasive nanoparticles for multimodal imaging of ischemic myocardium in rats

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiajing Chen ◽  
Yanan Zhang ◽  
Hui Zhang ◽  
Liang Zhang ◽  
Lingjuan Liu ◽  
...  

Abstract Background Ischemic heart disease (IHD) is the leading cause of morbidity and mortality worldwide, and imposes a serious economic load. Thus, it is crucial to perform a timely and accurate diagnosis and monitoring in the early stage of myocardial ischemia. Currently, nanoparticles (NPs) have emerged as promising tools for multimodal imaging, because of their advantages of non-invasion, high-safety, and real-time dynamic imaging, providing valuable information for the diagnosis of heart diseases. Results In this study, we prepared a targeted nanoprobe (termed IMTP-Fe3O4-PFH NPs) with enhanced ultrasound (US), photoacoustic (PA), and magnetic resonance (MR) performance for direct and non-invasive visual imaging of ischemic myocardium in a rat model. This successfully designed nanoprobe had excellent properties such as nanoscale size, good stability, phase transformation by acoustic droplet vaporization (ADV), and favorable safety profile. Besides, it realized obvious targeting performance toward hypoxia-injured cells as well as model rat hearts. After injection of NPs through the tail vein of model rats, in vivo imaging results showed a significantly enhanced US/PA/MR signal, well indicating the remarkable feasibility of nanoprobe to distinguish the ischemic myocardium. Conclusions IMTP-Fe3O4-PFH NPs may be a promising nanoplatform for early detection of ischemic myocardium and targeted treatment under visualization for the future.

2020 ◽  
Author(s):  
Marco Grisi ◽  
Gaurasundar M. Conley ◽  
Kyle J. Rodriguez ◽  
Erika Riva ◽  
Lukas Egli ◽  
...  

AbstractPerforming chemical analysis at the nanoliter (nL) scale is of paramount importance for medicine, drug development, toxicology, and research. Despite the numerous methodologies available, a tool for obtaining chemical information non-invasively is still missing at this scale. Observer effects, sample destruction and complex preparatory procedures remain a necessary compromise1. Among non-invasive spectroscopic techniques, one able to provide holistic and highly resolved chemical information in-vivo is nuclear magnetic resonance (NMR)2,3. For its renowned informative power and ability to foster discoveries and life-saving applications4,5, efficient NMR at microscopic scales is highly sought after6–10, but so far technical limitations could not match the stringent necessities of microbiology, such as biocompatible handling, ease of use, and high throughput. Here we introduce a novel microsystem, which combines CMOS technology with 3D microfabrication, enabling nL NMR as a platform tool for non-invasive spectroscopy of organoids, 3D cell cultures, and early stage embryos. In this study we show its application to microlivers models simulating non-alcoholic fatty liver disease (NAFLD), demonstrating detection of lipid metabolism dynamics in a time frame of 14 days based on 117 measurements of single 3D human liver microtissues.


Sensors ◽  
2019 ◽  
Vol 19 (2) ◽  
pp. 238 ◽  
Author(s):  
Yubin Liu ◽  
Lei Fu ◽  
Mengze Xu ◽  
Jun Zheng ◽  
Zhen Yuan

In this study, dual-modal fluorescence and photoacoustic microscopy was performed for noninvasive and functional in vivo imaging of inflammation induced by green fluorescent protein (GFP) transfected bacteria in mice ear. Our imaging results demonstrated that the multimodal imaging technique is able to monitor the tissue immunovascular responses to infections with molecular specificity. Our study also indicated that the combination of photoacoustic and fluorescence microscopy imaging can simultaneously track the biochemical changes including the bacterial distribution and morphological change of blood vessels in the biological tissues with high resolution and enhanced sensitivity. Consequently, the developed method paves a new avenue for improving the understanding of the pathology mechanism of inflammation.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marco Grisi ◽  
Gaurasundar M. Conley ◽  
Kyle J. Rodriguez ◽  
Erika Riva ◽  
Lukas Egli ◽  
...  

AbstractPerforming chemical analysis at the nanoliter (nL) scale is of paramount importance for medicine, drug development, toxicology, and research. Despite the numerous methodologies available, a tool for obtaining chemical information non-invasively is still missing at this scale. Observer effects, sample destruction and complex preparatory procedures remain a necessary compromise. Among non-invasive spectroscopic techniques, one able to provide holistic and highly resolved chemical information in-vivo is nuclear magnetic resonance (NMR). For its renowned informative power and ability to foster discoveries and life-saving applications, efficient NMR at microscopic scales is highly sought after, but so far technical limitations could not match the stringent necessities of microbiology, such as biocompatible handling, ease of use, and high throughput. Here we introduce a novel microsystem, which combines CMOS technology with 3D microfabrication, enabling nL NMR as a platform tool for non-invasive spectroscopy of organoids, 3D cell cultures, and early stage embryos. In this study we show its application to microlivers models simulating non-alcoholic fatty liver disease, demonstrating detection of lipid metabolism dynamics in a time frame of 14 days based on 117 measurements of single 3D human liver microtissues.


2020 ◽  
Vol 2020 ◽  
pp. 1-19 ◽  
Author(s):  
Yan-Jun Song ◽  
Chong-Bin Zhong ◽  
Wei Wu

Diabetic cardiomyopathy (DCM) is a common cardiovascular complication of diabetic mellitus that is characterized by diastolic disorder in the early stage and clinical heart failure in the later stage. Presently, DCM is considered one of the major causes of death in diabetic patients. Resveratrol (RSV), a naturally occurring stilbene, is widely reported as a cardioprotective substance in many heart diseases. Thus far, the specific roles of RSV in DCM prevention and treatment have attracted great attention. Here, we discuss the roles of RSV in DCM by focusing its downstream targets from both in vivo and in vitro studies. Among such targets, Sirtuins 1/3 and AMP-activated kinase have been identified as key mediators that induce cardioprotection during hyperglycemia. In addition, many other signaling molecules (e.g., forkhead box-O3a and extracellular regulated protein kinases) are also regulated in the presence of RSV and exert beneficial effects such as opposing oxidative stress, inflammation, and apoptosis in cardiomyocytes exposed to high-glucose conditions. The beneficial potential of an RSV/stem cell cotherapy is also reviewed as a promising therapeutic strategy for preventing the development of DCM.


2022 ◽  
Vol 23 (2) ◽  
pp. 899
Author(s):  
Tolulope Peter Saliu ◽  
Nao Yazawa ◽  
Kotaro Hashimoto ◽  
Kenshu Miyata ◽  
Ayane Kudo ◽  
...  

The early detection of diabetic nephropathy (DN) in mice is necessary for the development of drugs and functional foods. The purpose of this study was to identify genes that are significantly upregulated in the early stage of DN progression and develop a novel model to non-invasively monitor disease progression within living animals using in vivo imaging technology. Streptozotocin (STZ) treatment has been widely used as a DN model; however, it also exhibits direct cytotoxicity to the kidneys. As it is important to distinguish between DN-related and STZ-induced nephropathy, in this study, we compared renal responses induced by the diabetic milieu with two types of STZ models: multiple low-dose STZ injections with a high-fat diet and two moderate-dose STZ injections to induce DN. We found 221 genes whose expression was significantly altered during DN development in both models and identified serum amyloid A3 (Saa3) as a candidate gene. Next, we applied the Saa3 promoter-driven luciferase reporter (Saa3-promoter luc mice) to these two STZ models and performed in vivo bioluminescent imaging to monitor the progression of renal pathology. In this study, to further exclude the possibility that the in vivo bioluminescence signal is related to renal cytotoxicity by STZ treatment, we injected insulin into Saa3-promoter luc mice and showed that insulin treatment could downregulate renal inflammatory responses with a decreased signal intensity of in vivo bioluminescence imaging. These results strongly suggest that Saa3 promoter activity is a potent non-invasive indicator that can be used to monitor DN progression and explore therapeutic agents and functional foods.


PLoS ONE ◽  
2011 ◽  
Vol 6 (2) ◽  
pp. e17076 ◽  
Author(s):  
Sean E. Hofherr ◽  
Kristen E. Adams ◽  
Christopher Y. Chen ◽  
Shannon May ◽  
Eric A. Weaver ◽  
...  

2005 ◽  
Vol 4 (6) ◽  
pp. 593-602 ◽  
Author(s):  
Swadeshmukul Santra ◽  
Debamitra Dutta ◽  
Glenn A. Walter ◽  
Brij M. Moudgil

Optical imaging technique has strong potential for sensitive cancer diagnosis, particularly at the early stage of cancer development. This is a sensitive, non-invasive, non-ionizing (clinically safe) and relatively inexpensive technique. Cancer imaging with optical technique however greatly relies upon the use of sensitive and stable optical probes. Unlike the traditional organic fluorescent probes, fluorescent nanoparticle probes such as dye-doped nanoparticles and quantum dots (Qdots) are bright and photostable. Fluorescent nanoparticle probes are shown to be very effective for sensitive cancer imaging with greater success in the cellular level. However, cancer imaging in an in vivo setup has been recently realized. There are several challenges in developing fluorescent nanoparticle probes for in vivo cancer imaging applications. In this review, we will discuss various aspects of nanoparticle design, synthesis, surface functionalization for bioconjugation and cancer cell targeting. A brief overview of in vivo cancer imaging with Qdots will also be presented.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Gaurav Sharma ◽  
Alexander Funk ◽  
Xiaodong Wen ◽  
Crystal Harrison ◽  
Nesmine Maptue ◽  
...  

Introduction and Hypothesis: Conventional metabolic imaging methods such as PET, dobutamine stress echo or late gadolinium enhancement do not directly detect the functional state of the critical organelle in oxidative metabolism, the mitochondrion. Hyperpolarized (HP) 13 C-metabolic imaging has been used to assess mitochondrial function in preclinical models and is an exciting new imaging method for evaluating the ischemic myocardium noninvasively. This study aims to evaluate myocardial response to dobutamine stress in ischemic rat hearts using HP-[1- 13 C]pyruvate. Methods: Metabolism of HP[1- 13 C]pyruvate was investigated in male SD rats in four groups: 1. normal myocardium (NM), 2. ischemic myocardium (IM), 3. NM+dobutamine, 4. IM+dobutamine. The myocardial ischemic model was developed by partial occlusion of the coronary artery as described in earlier studies by others. For dobutamine stress HP-MRS, intra-peritoneal injection of 1.5 mg/kg of dobutamine was administered before positioning the animal in the MRI scanner. 13 C data were acquired 7 days after the surgery in a 4.7 T MRI scanner using a Varian 60 mm dual-tuned 1 H/ 13 C linear volume coil. Anatomical 1 H images were acquired for slice planning and positioning. 13 C intensity maps were generated and displayed as overlays on grayscale 1 H images. In separate experiments, in vivo HP- 13 C-MRS data acquisition was initiated immediately after the pyruvate injection. Results: The HP signals from [1- 13 C]lactate, [1- 13 C]alanine, and 13 C-bicarbonate were detected in real-time 13 C spectra from hearts following injection of HP[1- 13 C]pyruvate. In hearts with partial coronary ligation, the MRS data were acquired from a mixture of ischemic and nonischemic myocardium. A 27% decrease in bicarbonate production was observed in hearts with ischemic myocardium compared to control hearts. After stimulation of NM hearts with dobutamine, less bicarbonate was produced from HP-pyruvate likely due to an increased contribution of other endogenous substrates to acetyl-CoA. Production of bicarbonate was unchanged in IM hearts following adrenergic stimulation. Conclusions: Our results demonstrated that decreased oxidative metabolism of pyruvate as a result of myocardial ischemia and dobutamine stress.


Author(s):  
Jie Wang ◽  
Yuchao Zhang ◽  
Qi Shen ◽  
Jing Wu ◽  
Jian-Xin Li

Obesity is a chronic disease that increases the risk of type II diabetes, heart diseases and nonalcoholic fatty liver disease. Unfortunately, to date, only handful of drugs are approved for clinical use. This study aims at discovery of anti-obesity agents based on naturally sourced oleanolic acid (OA) derivatives. 3T3-L1 preadipocytes were differentiated into mature adipocytes for in vitro assays, and a high fat diet (HFD) induced obesity mice model was established for in vivo studies. The screening of the OA derivatives was performed with 3T3-L1 cell, and resulted in a discovery of a novel compound HA-20 with a potent inhibitory activity on 3T3-L1 adipogenesis. In vitro data demonstrated that HA-20 markedly suppressed the adipogenesis in 3T3-L1 at the early stage without cytotoxicity. In vivo research using HFD mice revealed that HA-20 lowered the body weight, and possessed a lipid-lowering effect. Transcriptome analysis discovered that the mainly adipogenesis/lipogenesis genes regulated by HA-20 were PPARγ, C/EBPα, Fas, ACC, and Fabp4/aP2. Mechanism study revealed that HA-20 played its bioactive roles at least via downregulating PPARγ-FABP4/aP2 pathway in 3T3-L1, which was further confirmed in HFD induced obesity mice. Our findings provided a new insight into fighting fat accumulation based on OA derivatives, and demonstrated that HA-20 may sever as a worthy leading compound for further development of anti-obesity agents.


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