scholarly journals Radiosafe micro-computed tomography for longitudinal evaluation of murine disease models

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Nathalie Berghen ◽  
Kaat Dekoster ◽  
Eyra Marien ◽  
Jérémie Dabin ◽  
Amy Hillen ◽  
...  
Keyword(s):  
Computed Tomography ◽  
High Resolution ◽  
Blood Cell ◽  
Lung Disease ◽  
Blood Platelets ◽  
Whole Body ◽  
Disease Models ◽  
Micro Computed Tomography ◽  
Cell Counts

AbstractImplementation of in vivo high-resolution micro-computed tomography (µCT), a powerful tool for longitudinal analysis of murine lung disease models, is hampered by the lack of data on cumulative low-dose radiation effects on the investigated disease models. We aimed to measure radiation doses and effects of repeated µCT scans, to establish cumulative radiation levels and scan protocols without relevant toxicity. Lung metastasis, inflammation and fibrosis models and healthy mice were weekly scanned over one-month with µCT using high-resolution respiratory-gated 4D and expiration-weighted 3D protocols, comparing 5-times weekly scanned animals with controls. Radiation dose was measured by ionization chamber, optical fiberradioluminescence probe and thermoluminescent detectors in a mouse phantom. Dose effects were evaluated by in vivo µCT and bioluminescence imaging read-outs, gold standard endpoint evaluation and blood cell counts. Weekly exposure to 4D µCT, dose of 540–699 mGy/scan, did not alter lung metastatic load nor affected healthy mice. We found a disease-independent decrease in circulating blood platelets and lymphocytes after repeated 4D µCT. This effect was eliminated by optimizing a 3D protocol, reducing dose to 180–233 mGy/scan while maintaining equally high-quality images. We established µCT safety limits and protocols for weekly repeated whole-body acquisitions with proven safety for the overall health status, lung, disease process and host responses under investigation, including the radiosensitive blood cell compartment.

scholarly journals Radiosafe micro-computed tomography for longitudinal evaluation of murine disease models

2019 ◽  
Author(s):  
Nathalie Berghen ◽  
Kaat Dekoster ◽  
Eyra Marien ◽  
Jérémie Dabin ◽  
Amy Hillen ◽  
...  
Keyword(s):  
Computed Tomography ◽  
High Resolution ◽  
Blood Cell ◽  
Lung Disease ◽  
Blood Platelets ◽  
Whole Body ◽  
Disease Models ◽  
Micro Computed Tomography ◽  
Cell Counts

AbstractImplementation of in vivo high-resolution micro-computed tomography (μCT), a powerful tool for longitudinal analysis of murine lung disease models, is hampered by the lack of data on cumulative low-dose radiation effects on the investigated disease models. We aimed to measure radiation doses and effects of repeated μCT scans, to establish cumulative radiation levels and scan protocols without relevant toxicity.Lung metastasis, inflammation and fibrosis models and healthy mice were weekly scanned over one-month with μCT using high-resolution respiratory-gated 4D and expiration-weighted 3D protocols, comparing 5-times weekly scanned animals with controls. Radiation dose was measured by ionization chamber, optical fiberradioluminescence probe and thermoluminescent detectors in a mouse phantom. Dose effects were evaluated by in vivo μCT and bioluminescence imaging read-outs, gold standard endpoint evaluation and blood cell counts.Weekly exposure to 4D μCT, dose of 540-699 mGy/scan, did not alter lung metastatic load nor affected healthy mice. We found a disease-independent decrease in circulating blood platelets and lymphocytes after repeated 4D μCT. This effect was eliminated by optimizing a 3D protocol, reducing dose to 180-233 mGy/scan while maintaining equally high-quality images.We established μCT safety limits and protocols for weekly repeated whole-body acquisitions with proven safety for the overall health status, lung, disease process and host responses under investigation, including the radiosensitive blood cell compartment.

scholarly journals Quantitative in vivo micro-computed tomography for assessment of age-dependent changes in murine whole-body composition

Bone Reports ◽  
2016 ◽  
Vol 5 ◽  
pp. 70-80 ◽  
Author(s):  
Kim L. Beaucage ◽  
Steven I. Pollmann ◽  
Stephen M. Sims ◽  
S. Jeffrey Dixon ◽  
David W. Holdsworth
Keyword(s):  
Computed Tomography ◽  
Body Composition ◽  
Whole Body ◽  
Micro Computed Tomography ◽  
Age Dependent

scholarly journals Mild Whole-Body Hyperthermia-Induced Interstitial Fluid Pressure Reduction and Enhanced Nanoparticle Delivery to PC3 Tumors: In Vivo Studies and Micro-Computed Tomography Analyses

2020 ◽  
Vol 12 (6) ◽  
Author(s):  
Qimei Gu ◽  
Shuaishuai Liu ◽  
Arunendra Saha Ray ◽  
Stelios Florinas ◽  
Ronald James Christie ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Interstitial Fluid ◽  
Fluid Pressure ◽  
Whole Body ◽  
Control Group ◽  
Micro Computed Tomography ◽  
Nanoparticle Delivery ◽  
Whole Body Hyperthermia ◽  
Experimental Group

Abstract In this study, we performed in vivo experiments on mice to evaluate whether whole-body hyperthermia enhances nanoparticle delivery to PC3 (prostatic cancer) tumors. PC3 xenograft tumors in immunodeficient mice were used in this study. The mice in the experimental group were subjected to whole-body hyperthermia by maintaining their body temperatures at 39–40 °C for 1 h. Interstitial fluid pressures (IFPs) in tumors were measured before heating, immediately after, and at 2 and 24 h postheating in both the experimental group and in a control group (without heating). A total of 0.2 ml of a newly developed nanofluid containing gold nanoparticles (AuNPs) was delivered via the tail vein in both groups. The micro-computed tomography (microCT) scanned images of the resected tumors were analyzed to visualize the nanoparticle distribution in the tumors and to quantify the total amount of nanoparticles delivered to the tumors. Statistically significant IFP reductions of 45% right after heating, 47% 2 h after heating, and 52% 24 h after heating were observed in the experimental group. Analyses of microCT scans of the resected tumors illustrated that nanoparticles were more concentrated near the tumor periphery rather than at the tumor center. The 1-h whole-body hyperthermia treatment resulted in more nanoparticles present in the tumor central region than that in the control group. The mass index calculated from the microCT scans suggested overall 42% more nanoparticle delivery in the experimental group than that in the control group. We conclude that 1-h mild whole-body hyperthermia leads to sustained reduction in tumoral IFPs and significantly increases the total amount of targeted gold nanoparticle deposition in PC3 tumors. The present study suggests that mild whole-body hyperthermia is a promising approach for enhancing targeted drug delivery to tumors.

scholarly journals Mixing Matrix-corrected Whole-body Pharmacokinetic Modeling Using Longitudinal Micro-computed Tomography and Fluorescence-mediated Tomography

2021 ◽  
Author(s):  
Simin Zuo ◽  
Wa’el Al Rawashdeh ◽  
Stefanie Rosenhain ◽  
Zuzanna Magnuska ◽  
Yamoah Grace Gyamfuah ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Kinetic Model ◽  
Kinetic Parameters ◽  
Pharmacokinetic Modeling ◽  
Retention Rates ◽  
Whole Body ◽  
Labeled Compounds ◽  
Micro Computed Tomography ◽  
Mixing Matrix

Abstract Purpose Pharmacokinetic modeling can be applied to quantify the kinetics of fluorescently labeled compounds using longitudinal micro-computed tomography and fluorescence-mediated tomography (μCT-FMT). However, fluorescence blurring from neighboring organs or tissues and the vasculature within tissues impede the accuracy in the estimation of kinetic parameters. Contributions of elimination and retention activities of fluorescent probes inside the kidneys and liver can be hard to distinguish by a kinetic model. This study proposes a deconvolution approach using a mixing matrix to model fluorescence contributions to improve whole-body pharmacokinetic modeling. Procedures In the kinetic model, a mixing matrix was applied to unmix the fluorescence blurring from neighboring tissues and blood vessels and unmix the fluorescence contributions of elimination and retention in the kidney and liver compartments. Accordingly, the kinetic parameters of the hepatobiliary and renal elimination routes and five major retention sites (the kidneys, liver, bone, spleen, and lung) were investigated in simulations and in an in vivo study. In the latter, the pharmacokinetics of four fluorescently labeled compounds (indocyanine green (ICG), HITC-iodide-microbubbles (MB), Cy7-nanogels (NG), and OsteoSense 750 EX (OS)) were evaluated in BALB/c nude mice. Results In the simulations, the corrected modeling resulted in lower relative errors and stronger linear relationships (slopes close to 1) between the estimated and simulated parameters, compared to the uncorrected modeling. For the in vivo study, MB and NG showed significantly higher hepatic retention rates (P<0.05 and P<0.05, respectively), while OS had smaller renal and hepatic retention rates (P<0.01 and P<0.01, respectively). Additionally, the bone retention rate of OS was significantly higher (P<0.01). Conclusions The mixing matrix correction improves pharmacokinetic modeling and thus enables a more accurate assessment of the biodistribution of fluorescently labeled pharmaceuticals by μCT-FMT.

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