Comparison of small animal CT contrast agents

Mannheim, Julia G.; Kuebler, Laura; Quintanilla-Martı́nez, Leticia; Kohlhofer, Ursula; Kneilling, Manfred; Pichler, Bernd J.

doi:10.1002/cmmi.1689

Cited by 36 publications

(33 citation statements)

References 32 publications

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“…Furthermore, some organs such as the spleen are difficult to segment due to low soft tissue contrast, which may result in quantification errors due to over- or under-segmentation. This can be improved for liver and spleen using µCT contrast agents with long-term accumulation which avoids repeated injections during longitudinal studies 35.…”

Section: Discussionmentioning

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: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…This non-toxic, commercially available, alkaline earth metal-based nanoparticulate contrast agent circulates in the blood stream and is taken up by the Kupffer cells. It significantly enhances the CT-contrast in spleen and liver 21,41 as clearly shown in Fig. 1.…”

Section: Methodsmentioning

confidence: 75%

“…Preclinical contrast agents often show a longer blood half-life time or a more specific uptake than their clinical counterparts. Examples of them are contrast-producing lipids, iodine-containing aqueous colloids, or alkaline earth metal-based nanoparticulate contrast agents 21,22 .…”

Section: Background and Summarymentioning

confidence: 99%

A preclinical micro-computed tomography database including 3D whole body organ segmentations

et al. 2018

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The gold-standard of preclinical micro-computed tomography (μCT) data processing is still manual delineation of complete organs or regions by specialists. However, this method is time-consuming, error-prone, has limited reproducibility, and therefore is not suitable for large-scale data analysis. Unfortunately, robust and accurate automated whole body segmentation algorithms are still missing. In this publication, we introduce a database containing 225 murine 3D whole body μCT scans along with manual organ segmentation of most important organs including heart, liver, lung, trachea, spleen, kidneys, stomach, intestine, bladder, thigh muscle, bone, as well as subcutaneous tumors. The database includes native and contrast-enhanced, regarding spleen and liver, μCT data. All scans along with organ segmentation are freely accessible at the online repository Figshare. We encourage researchers to reuse the provided data to evaluate and improve methods and algorithms for accurate automated organ segmentation which may reduce manual segmentation effort, increase reproducibility, and even reduce the number of required laboratory animals by reducing a source of variability and having access to a reliable reference group.

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“…Therefore, when arterial phase imaging is of interest – for example for the analysis of tumor-associated vasculature - the use of an infusion pump system is necessary 18 . Alternatively, modern nanoparticles or high molecular weight polymers might be used which stay in the circulation for several days 19 , 20 . Micro-CT provides an excellent resolution with pixel sizes of 9, 18 or 35 μm - thereby outperforming hrUS and MRI by far in this regard.…”

Section: Discussionmentioning

confidence: 99%

“…hrUS = high-resolution ultrasonography, μCT = contrast-enhanced in-vivo computed tomography, MRI = 9.4T magnetic resonance imaging, PET = positron emission tomography, BOLD = blood oxygen level dependent, ASL = arterial spin labeling, DCE = dynamic contrast-enhanced, DWI = diffusion-weighted imaging. hrUS μCT 9.4T MRI spatial resolution very high (33 μm) very high (18 μm) high (100 μm) soft tissue contrast good poor very good metastases screening liver bone, lung all organ systems options for functional imaging Doppler 35 , contrast agents 16 , 17 , 36 , photoacoustic imaging 37 contrast agents 20 , combination with PET 38 alternative protocols (BOLD, ASL, DCE, DWI) 23 – 30 , contrast agents 17 , 39 , combination with PET 38 examination time very short (5 minutes) short (12.5 minutes) long (37.9 minutes) radiation exposure none yes (radiation dose depending on protocol and number of scans) none costs (purchase) moderate moderate high …”

Section: Discussionmentioning

confidence: 99%

Experimental imaging in orthotopic renal cell carcinoma xenograft models: comparative evaluation of high-resolution 3D ultrasonography, in-vivo micro-CT and 9.4T MRI

Linxweiler

Körbel

Müller

et al. 2017

Sci Rep

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In this study, we aimed to comparatively evaluate high-resolution 3D ultrasonography (hrUS), in-vivo micro-CT (μCT) and 9.4T MRI for the monitoring of tumor growth in an orthotopic renal cell carcinoma (RCC) xenograft model since there is a lack of validated, non-invasive imaging tools for this purpose. 1 × 106 Caki-2 RCC cells were implanted under the renal capsule of 16 immunodeficient mice. Local and systemic tumor growth were monitored by regular hrUS, μCT and MRI examinations. Cells engrafted in all mice and gave rise to exponentially growing, solid tumors. All imaging techniques allowed to detect orthotopic tumors and to precisely calculate their volumes. While tumors appeared homogenously radiolucent in μCT, hrUS and MRI allowed for a better visualization of intratumoral structures and surrounding soft tissue. Examination time was the shortest for hrUS, followed by μCT and MRI. Tumor volumes determined by hrUS, μCT and MRI showed a very good correlation with each other and with caliper measurements at autopsy. 10 animals developed pulmonary metastases being well detectable by μCT and MRI. In conclusion, each technique has specific strengths and weaknesses, so the one(s) best suitable for a specific experiment may be chosen individually.

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Comparison of small animal CT contrast agents

Cited by 36 publications

References 32 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

A preclinical micro-computed tomography database including 3D whole body organ segmentations

Experimental imaging in orthotopic renal cell carcinoma xenograft models: comparative evaluation of high-resolution 3D ultrasonography, in-vivo micro-CT and 9.4T MRI

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