Fig 3 - uploaded by Andre Obenaus
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Representative micro-CT images from a mouse. A) A lateral view reveals the location of the TLDs in the brain (A), heart (B), liver (C), ventral abdominal skin (D) and stomach (E). B) A second lateral view reveals the location of the TLDs in the brain (A), dorsal thoracal skin (F), ventral abdominal skin (D) and cecum (G). C) A ventral view reveals the location of the TLDs in the right lung (H) and bladder (I). All scans were reconstructed with 512 × 512 × 512 voxels with 0.117 mm voxel dimensions.
Source publication
The use of non-invasive imaging modalities, including micro X-ray computed tomography (micro-CT), is starting to be used extensively to investigate normal and pathological states in a variety of animal models. This increased use of in vivo imaging requires a better understanding of the radiation dose delivered during routine imaging. Our laboratory...
Context in source publication
Citations
... %). Thus, the amount of x-ray dose required for XFCT is roughly similar to that required for earlier generations of microCT [2][3][4]. This means that, if CT and XFCT were performed sequentially (or separately), a combined CT + XFCT scan would double the x-ray dose, which may not be desirable for small animal imaging. ...
Objective:
To investigate the image quality and x-ray dose associated with a transmission computed tomography (CT) component implemented within the same platform of an experimental benchtop x-ray fluorescence CT (XFCT) system for multimodal preclinical imaging applications.
Methods:
Cone-beam CT scans were performed using an experimental benchtop CT + XFCT system and a cylindrically-shaped 3D-printed polymethyl methacrylate phantom (3 cm in diameter, 7 cm in height) loaded with various concentrations (0.05-1 wt. %) of gold nanoparticles (GNPs). Two commercial CT quality assurance phantoms containing 3D line-pair (LP) targets and contrast targets were also scanned. The x-ray beams of 40 and 62 kVp, both filtered by 0.08 mm Cu and 0.4 mm Al, were used with 17 ms of exposure time per projection at three current settings (2.5, 5, and 10 mA). The ordered-subset simultaneous algebraic reconstruction and total variation-minimization methods were used to reconstruct images. Sparse projection and short scan were considered to reduce the x-ray dose. The contrast-to-noise ratio (CNR) and modulation transfer function (MTF) were calculated.
Results:
The lowest detectable concentration of GNPs (CNR > 5) and the highest spatial resolution (per MTF50%) were 0.10 wt. % and 9.5 LP/CM, respectively, based on the images reconstructed from 360 projections of the 40 kVp beam (or x-ray dose of 3.44 cGy). The background noise for the image resulting in the lowest GNP detection limit was 25 Hounsfield units.
Conclusion:
The transmission CT component within the current experimental benchtop CT + XFCT system produced images deemed acceptable for multimodal (CT + XFCT) imaging purposes, with less than 4 cGy of x-ray dose.
... CT doses for scans for live mice typically range between 50 and 800 mGy using current scanning technologies (4-7) CT doses for studies of rodent bone metrics and other higher resolution protocols used in for ex vivo imaging are commonly >1 Gy (6,7). CT exposure and dose minimization have been a constant subject of research over the years (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). ...
Ionizing radiation constitutes a health risk to imaging scientists and study animals. Both PET and CT produce ionizing radiation. CT doses in pre-clinical in vivo imaging typically range from 50 to 1,000 mGy and biological effects in mice at this dose range have been previously described. [¹⁸F]FDG body doses in mice have been estimated to be in the range of 100 mGy for [¹⁸F]FDG. Yearly, the average whole body doses due to handling of activity by PET technologists are reported to be 3–8 mSv. A preclinical PET/CT system is presented with design features which make it suitable for small animal low-dose imaging. The CT subsystem uses a X-source power that is optimized for small animal imaging. The system design incorporates a spatial beam shaper coupled with a highly sensitive flat-panel detector and very fast acquisition (<10 s) which allows for whole body scans with doses as low as 3 mGy. The mouse total-body PET subsystem uses a detector architecture based on continuous crystals, coupled to SiPM arrays and a readout based in rows and columns. The PET field of view is 150 mm axial and 80 mm transaxial. The high solid-angle coverage of the sample and the use of continuous crystals achieve a sensitivity of 9% (NEMA) that can be leveraged for use of low tracer doses and/or performing rapid scans. The low-dose imaging capabilities of the total-body PET subsystem were tested with NEMA phantoms, in tumor models, a mouse bone metabolism scan and a rat heart dynamic scan. The CT imaging capabilities were tested in mice and in a low contrast phantom. The PET low-dose phantom and animal experiments provide evidence that image quality suitable for preclinical PET studies is achieved. Furthermore, CT image contrast using low dose scan settings was suitable as a reference for PET scans. Total-body mouse PET/CT studies could be completed with total doses of <10 mGy.
... Eng. Express 4 (2018) 062001 L Ayala-Domínguez and M E Brandan made with thermo-luminescent dosimeters (TLDs) ex vivo, with TLD-100[69]. A novel TLD approach involves the calibration of TLD-100 response as a function of the effective beam energy determined by TLD-300[65,70]. ...
Angiogenesis is the formation of new blood vessels from the pre-existing vasculature, it is essential for tumor growth and development. Quantitative evaluation of vascular parameters that allow to identify angiogenesis in early stages of tumor development could have an impact on lesion detection, cancer treatment, and patient outcome. The aim of this study was to define the factors related to contrast medium administration and image acquisition that allow to quantify vascular parameters from contrast-enhanced micro-computed tomography (CE-microCT) images. Type of contrast-medium, dose and image acquisition time were determined for single-energy (SE) and dual-energy (DE) CE-microCT imaging protocols using a tumor angiogenesis murine model. Enhancement and relative blood volume (rBV) were quantified from SE and DE images in muscle, tumor core, tumor periphery and the whole tumor. The differences in enhancement between muscle and the tumor regions quantified in SE images were not statistically significant. A statistically significant difference was found for rBV between muscle and tumor periphery in SE images, but the differences with tumor core and the whole tumor were not significant. For the DE protocol, more animals need to be included in the study in order to evaluate the differences in enhancement and rBV. Validation studies are also required to evaluate the correlation between rBV and angiogenesis biomarkers. Despite these limitations, rBV quantified from CE-microCT images seems to be a promising vascular parameter that could help to describe the angiogenic status of a tumor during cancer progression.
... Radiation dose may cause damage to the animals and may also affect the natural development of a tumor model. Measures of the entrance dose in micro-CT studies with rodents have been made with thermo-luminescent dosimeters (TLDs) ex vivo, with TLD-100 [69]. A novel TLD approach involves the calibration of TLD-100 response as a function of the effective beam energy determined by TLD-300 [65,70]. ...
Tissue contrast is a major challenge in the application of computed tomography (CT) and micro-computed tomography (micro-CT) techniques for imaging cancer. Contrast medium is used in order to enhance contrast of certain organs of interest, as well as tumors. Several types of contrast media have been used to assess tumor vasculature, perfusion and angiogenesis in preclinical studies. In general, low molecular weight contrast media have been used to characterize the first pass vascular dynamics of tumors with fast CT systems, while blood pool agents have been preferred to explore the delayed vascular dynamics with micro-CT systems. Together, these approaches provide qualitative, semi-quantitative, and quantitative information of the vascular architecture and vascular functionality of tumors in the preclinical scenario. Herein, we present an overview of contrast media, imaging techniques, image analysis methods, and quantitative parameters that have been used to evaluate tumor angiogenesis in vivo in recent preclinical studies. Preclinical applications on lesion detection and characterization, evaluation of vascular parameters as prognostic and predictive biomarkers, and evaluation of treatment response are also reviewed. These applications have demonstrated the potential of contrast-enhanced x-ray imaging to provide, in a noninvasive manner, a landscape of the spatial and temporal heterogeneity of the angiogenic process underlying tumor development.
... Presumably, guinea pigs would be able to tolerate Ͼ10 sequential micro-CT exposures before reaching LD 50/30 radiation levels, owing to their larger size. In support of this probability, it has also been reported that the skin of mice and rats can absorb as much 0.045 and 0.028 Gy, respectively, during 1 micro-CT whole body scanning session but that the internal organs receive significantly lower doses, typically averaging Ͻ0.035 and Ͻ0.024 Gy in mice and rats, respectively (29). Thus, based on body mass and size scaling, with a typical young adult mouse weighing 20 -30 g, a typical young adult rat weighing 300 -500 g, and our studied young adult guinea pigs weighing 600 -900 g, it would be expected that the skin of guinea pigs would cumulatively absorb Ͻ0.028 Gy in 1 micro-CT exposure and their internal organs even less than that amount during 1 micro-CT imaging session. ...
... Gafchromic films can be used to develop a depth profile if more detailed information is needed [14,23,61,80]. Others have implanted thermoluminescence dosimeters (TLDs) or nanoDots near specific organs within an animal to measure the doses at specific locations [14,29,42,76,77,[81][82][83][84][85][86][87]. The most complete map of dose in every tissue requires Monte-Carlo-based simulations, although the implementation complexity and variability in the results makes these techniques challenging to reproduce [10,29,35,36,76]. ...
Purpose
X-ray micro-computed tomography (μCT) is a widely used imaging modality in preclinical research with applications in many areas including orthopedics, pulmonology, oncology, cardiology, and infectious disease. X-rays are a form of ionizing radiation and, therefore, can potentially induce damage and cause detrimental effects. Previous reviews have touched on these effects but have not comprehensively covered the possible implications on study results. Furthermore, interpreting data across these studies is difficult because there is no widely accepted dose characterization methodology for preclinical μCT. The purpose of this paper is to ensure in vivo μCT studies can be properly designed and the data can be appropriately interpreted.
Procedures
Studies from the scientific literature that investigate the biological effects of radiation doses relevant to μCT were reviewed. The different dose measurement methodologies used in the peer-reviewed literature were also reviewed. The CT dose index 100 (CTDI100) was then measured on the Quantum GX μCT instrument. A low contrast phantom, a hydroxyapatite phantom, and a mouse were also imaged to provide examples of how the dose can affect image quality.
Results
Data in the scientific literature indicate that scenarios exist where radiation doses used in μCT imaging are high enough to potentially bias experimental results. The significance of this effect may relate to the study outcome and tissue being imaged. CTDI100 is a reasonable metric to use for dose characterization in μCT. Dose rates in the Quantum GX vary based on the amount of material in the beam path and are a function of X-ray tube voltage. The CTDI100 in air for a Quantum GX can be as low as 5.1 mGy for a 50 kVp scan and 9.9 mGy for a 90 kVp scan. This dose is low enough to visualize bone both in a mouse image and in a hydroxyapatite phantom, but applications requiring higher resolution in a mouse or less noise in a low-contrast phantom benefit from longer scan times with increased dose.
Conclusions
Dose management should be considered when designing μCT studies. Dose rates in the Quantum GX are compatible with longitudinal μCT imaging.
... Although available, X-ray CT and nuclear imaging were not incorporated into this study. This was principally due to the limited number of scanning time points that could be performed, but also to avoid the use of modalities that require ionising radiation, particularly as there is some evidence that repeated exposure may impact on tumour growth [47]. ...
Background:
Research using orthotopic and transgenic models of cancer requires imaging methods to non-invasively quantify tumour burden. As the choice of appropriate imaging modality is wide-ranging, this study aimed to compare low-field (1T) magnetic resonance imaging (MRI), a novel and relatively low-cost system, against established preclinical techniques: bioluminescence imaging (BLI), ultrasound imaging (US), and high-field (9.4T) MRI.
Methods:
A model of colorectal metastasis to the liver was established in eight mice, which were imaged with each modality over four weeks post-implantation. Tumour burden was assessed from manually segmented regions.
Results:
All four imaging systems provided sufficient contrast to detect tumours in all of the mice after two weeks. No significant difference was detected between tumour doubling times estimated by low-field MRI, ultrasound imaging or high-field MRI. A strong correlation was measured between high-field MRI estimates of tumour burden and all the other modalities (p < 0.001, Pearson).
Conclusion:
These results suggest that both low-field MRI and ultrasound imaging are accurate modalities for characterising the growth of preclinical tumour models.
... Transaxial (a) and (b), coronal (c) and sagittal (d) contrast-enhanced images of an anesthetized mouse were shown inFig. 2. The effective radiation dose was estimated to be about 150 mGy, about 2% of theLD50/30 for small rodent[48]. Usage of blood-pool contrast agent improved the contrast performance of soft tissues significantly. ...
The dual-modality systems combined fluorescence molecular tomography (FMT) and micro-computed tomography (micro-CT) can provide molecular and anatomical information of small animals simultaneously. Except for anatomic localization, micro-CT should also offer boundary of different organs as reconstruction priors for FMT, which is more challenging than acquisition of structural information. In this paper, we propose a framework to extract structural priors of a living mouse with micro-CT. The iodinated lipid emulsion contrast agent was adopted to enhance the contrast of the soft tissues of the mouse. Then organs in thorax and abdomen were segmented with different approaches depending on the characteristics of the organs. Bone, lung, heart, liver, spleen, and muscles were separately segmented. And the results were compared with that manually segmented. The Tanimoto coefficient and the relative volume difference of segmented slices were measured to be 91.28 ± 5.78 and 0.27 ± 3.15, respectively. In our simulation study of FMT reconstruction, the errors of measured position and concentration of the fluorophore with priors declined by 89.7% and 79.6% in thorax, as well as 80.8% and 78.3% in abdomen, respectively, compared with the results without priors. The proposed scheme will make FMT reconstruction much more reliable and practical in small animal study.
... An examination of previous dose assessments performed on the similar microCAT imaging platform (Siemens Medical Solutions USA, Inc.) indicates that the delivered dose is very similar but tends to be lower on the newer Inveon platform. Measurements on the Inveon platform had a maximum dose value of 17.3 cGy for the skin where previous dose assessments have shown the microCAT line of scanners to have maximums on the order of 19–22 cGy [11,13]. Other work using the microCAT platform referenced in this paper had significant variation in values for dose ranging from 2.8–9.0 cGy, however, the experimental conditions were different, either in the beam settings or in the type of instrumentation used to measure the dose. ...
Dose continues to be an area of concern in preclinical imaging studies, especially for those imaging disease progression in longitudinal studies. To our knowledge, this work is the first to characterize and assess dose from the Inveon CT imaging platform using nanoDot dosimeters. This work is also the first to characterize a new low-dose configuration available for this platform.
nanoDot dosimeters from Landauer, Inc. were surgically implanted into 15 wild type mice. Two nanoDots were placed in each animal: one just under the skin behind the spine and the other located centrally within the abdomen. A manufacturer-recommended CT protocol was created with 1 projection per degree of rotation acquired over 360 degrees. For best comparison of the low dose and standard configurations, noise characteristics of the reconstructed images were used to match the acquisition protocol parameters. Results for all dose measurements showed the average dose delivered to the abdomen to be 13.8 cGy±0.74 and 0.97 cGy±0.05 for standard and low dose configurations respectively. Skin measurements of dose averaged 15.99 cGy±0.72 and 1.18 cGy±0.06. For both groups, the standard deviation to mean was less than 5.6%. The maximum dose received for the abdomen was 15.12 cGy and 0.97 cGy while the maximum dose for the skin was 17.3 cGy and 1.32 cGy. Control dosimeters were used for each group to validate that no unwanted additional radiation was present to bias the results.
This study shows that the Inveon CT platform is suitable for imaging mice both for single and longitudinal studies. Use of low-dose detector hardware results in significant reductions in dose to subjects with a >12x (90%) reduction in delivered dose. Installation of this hardware on another in vivo microCT platform resulted in dose reductions of over 9x (89%).
... Specifically, the use of 11-pixel CdTe detectors would reduce the total x-ray dose by a factor of 11, resulting in the total x-ray dose required for XFCT imaging using the current methodology to be roughly 20 cGy. This is clearly much less than the general LD 50 (50% Lethal Dose) for mice of about 7 Gy (Hall and Giaccia, 2006), and possibly less than typical ranges of x-ray doses delivered during micro-CT scanning of small animals (Boone et al., 2004;Obenaus and Smith, 2004). ...
This report presents the first experimental demonstration, to our knowledge, of benchtop polychromatic cone-beam x-ray fluorescence computed tomography (XFCT) for a simultaneous determination of the spatial distribution and amount of gold nanoparticles (GNPs) within small-animal-sized objects. The current benchtop experimental setup successfully produced XFCT images accurately showing the regions containing small amount of GNPs (on the order of 0.1 mg) within a 3 cm diameter plastic phantom. In particular, the performance of the current XFCT setup was improved remarkably (e.g., at least a factor of 3 reduction in XFCT scan time) using a tin-filtered polychromatic beam in comparison with a lead-filtered beam. The results of this study strongly suggest that the current benchtop XFCT configuration can be made practical with a few modifications such as the deployment of array detectors, while meeting realistic constraints on x-ray dose, scan time and image resolution for routine pre-clinical in vivo imaging with GNPs.
