Hybrid &amp;#181;CT-FMT imaging and image analysis

Gremse, Felix; Doleschel, Dennis; Zafarnia, Sara; Babler, Anne; Jahnen‐Dechent, Willi; Lammers, Twan; Lederle, Wiltrud; Kießling, Fabian

doi:10.3791/52770

Cited by 30 publications

(70 citation statements)

References 31 publications

(42 reference statements)

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“…A diffuse phantom containing a cylindrical inclusion (100 µl), available from the FMT manufacturer, was used as previously described 4,31. The phantom was filled with diluted reference dyes in known concentrations (VM670XL at 0.40 µM, VM750 at 0.41 µM, VM790 at 0.78 µM).…”

Section: Methodsmentioning

confidence: 99%

Noninvasive Assessment of Elimination and Retention using CT-FMT and Kinetic Whole-body Modeling

et al. 2017

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Fluorescence-mediated tomography (FMT) is a quantitative three-dimensional imaging technique for preclinical research applications. The combination with micro-computed tomography (µCT) enables improved reconstruction and analysis. The aim of this study is to assess the potential of µCT-FMT and kinetic modeling to determine elimination and retention of typical model drugs and drug delivery systems.We selected four fluorescent probes with different but well-known biodistribution and elimination routes: Indocyanine green (ICG), hydroxyapatite-binding OsteoSense (OS), biodegradable nanogels (NG) and microbubbles (MB). µCT-FMT scans were performed in twenty BALB/c nude mice (5 per group) at 0.25, 2, 4, 8, 24, 48 and 72 h after intravenous injection. Longitudinal organ curves were determined using interactive organ segmentation software and a pharmacokinetic whole-body model was implemented and applied to compute physiological parameters describing elimination and retention.ICG demonstrated high initial hepatic uptake which decreased rapidly while intestinal accumulation appeared for around 8 hours which is in line with the known direct uptake by hepatocytes followed by hepatobiliary elimination. Complete clearance from the body was observed at 48 h. NG showed similar but slower hepatobiliary elimination because these nanoparticles require degradation before elimination can take place. OS was strongly located in the bones in addition to high signal in the bladder at 0.25 h indicating fast renal excretion. MB showed longest retention in liver and spleen and low signal in the kidneys likely caused by renal elimination or retention of fragments. Furthermore, probe retention was found in liver (MB, NG and OS), spleen (MB) and kidneys (MB and NG) at 72 h which was confirmed by ex vivo data. The kinetic model enabled robust extraction of physiological parameters from the organ curves.In summary, µCT-FMT and kinetic modeling enable differentiation of hepatobiliary and renal elimination routes and allow for the noninvasive assessment of retention sites in relevant organs including liver, kidney, bone and spleen.

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Section: Methodsmentioning

confidence: 99%

Noninvasive Assessment of Elimination and Retention using CT-FMT and Kinetic Whole-body Modeling

et al. 2017

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“…Tumor vascularization was assessed with first-pass analysis of BR1 and postprocessing with MIOT (24). Functional US with the clinically approved, short-circulating BR1 microbubbles showed a tendency toward decreasing rBV values in treated and control tumors, with values being lower in B20-treated tumors (Fig 3).…”

Section: Assessment Of Tumor Vascularization (Rbv) With First-pass Anmentioning

confidence: 96%

“…One observer was blinded to the types of microbubbles and experimental groups and confirmed the results. Image analysis was done with preclinical software (Imalytics; Gremse-IT, Aachen, Germany) (24). A region of interest was defined over the whole tumor.…”

Section: Monitoring Treatment Effects Of Antiangiogenic Therapymentioning

confidence: 99%

Squamous Cell Carcinoma Xenografts: Use of VEGFR2-targeted Microbubbles for Combined Functional and Molecular US to Monitor Antiangiogenic Therapy Effects

Baetke¹,

Rix²,

Tranquart³

et al. 2016

Radiology

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Purpose-To assess the ability of vascular endothelial growth factor receptor type 2 (VEGFR2)-targeted and nontargeted ultrasonography (US) to depict antiangiogenic therapy effects and to investigate whether first-pass kinetics obtained with VEGFR2-targeted microbubbles provide independent data about tumor vascularization. Materials and Methods-Governmental approval was obtained for animal experiments.Vascularization in response to anti-vascular endothelial growth factor receptor or vehicle-control treatment (n=10/group) in HaCaT-ras A-5RT3 xenografts was longitudinally assessed in mice by means of first-pass kinetics of nontargeted microbubbles (BR1, BR38; Bracco, Geneva, Switzerland) and VEGFR2-targeted microbubbles (BR55; Bracco) before and 4, 7, and 14 days after therapy. VEGFR2 expression was determined 8 minutes after BR55 injection with destruction-replenishment analysis. US data were validated by immunohistochemistry. Significant differences were evaluated with the Mann-Whitney test.Results-First-pass analysis with BR1, BR38, and BR55 showed similar tendencies toward decreasing vascularization, with a stronger decrease in tumors treated with anti-VEGF antibody. Immunohistochemistry confirmed the lower microvessel density and VEGFR2-positive area fraction in tumors treated with anti-VEGF antibody. Europe PMC Funders GroupConclusion-Antiangiogenic therapy effects were detected earlier and more distinctly with VEGFR2-targeted US than with functional US. First-pass analyses with BR55, BR38, and BR1 revealed similar results, with a decrease in vascularization during therapy. Functional data showed that BR55 is not strongly affected by early binding of the microbubbles to VEGFR2. Thus, functional and molecular imaging of angiogenesis can be performed with BR55 within one examination.

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“…Several authors have pointed out how difficult the segmentation process can be Gremse et al, 2015;Kim et al, 2012), mainly due to poorly contrasted regions (in many F I G U R E 6 Segmentation process steps. Acheta domesticus female abdomen.…”

Section: Pro Ce Ss Ing Of X-r Ay C T Imag E Smentioning

confidence: 99%

“…As the tissue detection in the technique explored in this review relies on metal-based stains, X-ray CT can also be considered as a method to detect, monitor, and even infer physiological pathways of metallic pollution in small animals . Furthermore, combination with other techniques-for instance fluorescence microscopy-may allow to identify processes within the tissues for future studies on ecophysiology and ecotoxicology (e.g., angiogenesis, apoptosis, inflammation) (Gremse et al, 2015;Handschuh, Baeumler, Schwaha, & Ruthensteiner, 2013;Metscher, 2009a). Possible detrimental effects of radiation and stain ingestion on living organisms (especially invertebrates) remain to be elucidated.…”

Section: Per S Pec Tive S and Final Cons Ider Ationsmentioning

confidence: 99%

X‐ray computed tomography and its potential in ecological research: A review of studies and optimization of specimen preparation

Gutiérrez

Ott

Töpperwien

et al. 2018

Ecology and Evolution

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Imaging techniques are a cornerstone of contemporary biology. Over the last decades, advances in microscale imaging techniques have allowed fascinating new insights into cell and tissue morphology and internal anatomy of organisms across kingdoms. However, most studies so far provided snapshots of given reference taxa, describing organs and tissues under “idealized” conditions. Surprisingly, there is an almost complete lack of studies investigating how an organism′s internal morphology changes in response to environmental drivers. Consequently, ecology as a scientific discipline has so far almost neglected the possibilities arising from modern microscale imaging techniques. Here, we provide an overview of recent developments of X‐ray computed tomography as an affordable, simple method of high spatial resolution, allowing insights into three‐dimensional anatomy both in vivo and ex vivo. We review ecological studies using this technique to investigate the three‐dimensional internal structure of organisms. In addition, we provide practical comparisons between different preparation techniques for maximum contrast and tissue differentiation. In particular, we consider the novel modality of phase contrast by self‐interference of the X‐ray wave behind an object (i.e., phase contrast by free space propagation). Using the cricket Acheta domesticus (L.) as model organism, we found that the combination of FAE fixative and iodine staining provided the best results across different tissues. The drying technique also affected contrast and prevented artifacts in specific cases. Overall, we found that for the interests of ecological studies, X‐ray computed tomography is useful when the tissue or structure of interest has sufficient contrast that allows for an automatic or semiautomatic segmentation. In particular, we show that reconstruction schemes which exploit phase contrast can yield enhanced image quality. Combined with suitable specimen preparation and automated analysis, X‐ray CT can therefore become a promising quantitative 3D imaging technique to study organisms′ responses to environmental drivers, in both ecology and evolution.

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Hybrid µCT-FMT imaging and image analysis

Cited by 30 publications

References 31 publications

Noninvasive Assessment of Elimination and Retention using CT-FMT and Kinetic Whole-body Modeling

Noninvasive Assessment of Elimination and Retention using CT-FMT and Kinetic Whole-body Modeling

Squamous Cell Carcinoma Xenografts: Use of VEGFR2-targeted Microbubbles for Combined Functional and Molecular US to Monitor Antiangiogenic Therapy Effects

X‐ray computed tomography and its potential in ecological research: A review of studies and optimization of specimen preparation

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