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Diffusible iodine-based contrast-enhanced computed tomography (diceCT): an emerging tool for rapid, high-resolution, 3-D imaging of metazoan soft tissues.

ABSTRACT: Morphologists have historically had to rely on destructive procedures to visualize the three-dimensional (3-D) anatomy of animals. More recently, however, non-destructive techniques have come to the forefront. These include X-ray computed tomography (CT), which has been used most commonly to examine the mineralized, hard-tissue anatomy of living and fossil metazoans. One relatively new and potentially transformative aspect of current CT-based research is the use of chemical agents to render visible, and differentiate between, soft-tissue structures in X-ray images. Specifically, iodine has emerged as one of the most widely used of these contrast agents among animal morphologists due to its ease of handling, cost effectiveness, and differential affinities for major types of soft tissues. The rapid adoption of iodine-based contrast agents has resulted in a proliferation of distinct specimen preparations and scanning parameter choices, as well as an increasing variety of imaging hardware and software preferences. Here we provide a critical review of the recent contributions to iodine-based, contrast-enhanced CT research to enable researchers just beginning to employ contrast enhancement to make sense of this complex new landscape of methodologies. We provide a detailed summary of recent case studies, assess factors that govern success at each step of the specimen storage, preparation, and imaging processes, and make recommendations for standardizing both techniques and reporting practices. Finally, we discuss potential cutting-edge applications of diffusible iodine-based contrast-enhanced computed tomography (diceCT) and the issues that must still be overcome to facilitate the broader adoption of diceCT going forward.

SUBMITTER: Gignac PM

PROVIDER: S-EPMC5341577 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Diffusible iodine-based contrast-enhanced computed tomography (diceCT): an emerging tool for rapid, high-resolution, 3-D imaging of metazoan soft tissues.

Gignac Paul M PM Kley Nathan J NJ Clarke Julia A JA Colbert Matthew W MW Morhardt Ashley C AC Cerio Donald D Cost Ian N IN Cox Philip G PG Daza Juan D JD Early Catherine M CM Echols M Scott MS Henkelman R Mark RM Herdina A Nele AN Holliday Casey M CM Li Zhiheng Z Mahlow Kristin K Merchant Samer S Müller Johannes J Orsbon Courtney P CP Paluh Daniel J DJ Thies Monte L ML Tsai Henry P HP Witmer Lawrence M LM

Journal of anatomy 20160311 6

Morphologists have historically had to rely on destructive procedures to visualize the three-dimensional (3-D) anatomy of animals. More recently, however, non-destructive techniques have come to the forefront. These include X-ray computed tomography (CT), which has been used most commonly to examine the mineralized, hard-tissue anatomy of living and fossil metazoans. One relatively new and potentially transformative aspect of current CT-based research is the use of chemical agents to render visi ...[more]

PMID: 26970556

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Project description:ObjectivesCompanion dogs with naturally occurring cancer serve as an important large animal model in translational research because they share strong similarities with human cancers. In this study, we investigated a long circulating liposomal-iodine contrast agent (Liposomal-I) for computed tomography (CT) imaging of solid tumors in companion dogs with naturally occurring cancer.Materials and methodsThe institutional animal ethics committees approved the study and written informed consent was obtained from all owners. Thirteen dogs (mean age 10.1 years) with a variety of masses including primary and metastatic liver tumors, sarcomas, mammary carcinoma and lung tumors, were enrolled in the study. CT imaging was performed pre-contrast and at 15 minutes and 24 hours after intravenous administration of Liposomal-I (275 mg/kg iodine dose). Conventional contrast-enhanced CT imaging was performed in a subset of dogs, 90 minutes prior to administration of Liposomal-I. Histologic or cytologic diagnosis was obtained for each dog prior to admission into the study.ResultsLiposomal-I resulted in significant (p < 0.05) enhancement and uniform opacification of the vascular compartment. Non-renal, reticulo-endothelial systemic clearance of the contrast agent was demonstrated. Liposomal-I enabled visualization of primary and metastatic liver tumors. Sub-cm sized liver lesions grossly appeared as hypo-enhanced compared to the surrounding normal parenchyma with improved lesion conspicuity in the post-24 hour scan. Large liver tumors (> 1 cm) demonstrated a heterogeneous pattern of intra-tumoral signal with visibly higher signal enhancement at the post-24 hour time point. Extra-hepatic, extra-splenic tumors, including histiocytic sarcoma, anaplastic sarcoma, mammary carcinoma and lung tumors, were visualized with a heterogeneous enhancement pattern in the post-24 hour scan.ConclusionsThe long circulating liposomal-iodine contrast agent enabled prolonged visualization of small and large tumors in companion dogs with naturally occurring cancer. The study warrants future work to assess the sensitivity and specificity of the Liposomal-I agent in various types of naturally occurring canine tumors.

Project description:ObjectivesNon-contrast computed tomography (NCCT) markers are robust predictors of parenchymal hematoma expansion in intracerebral hemorrhage (ICH). We investigated whether NCCT features can also identify ICH patients at risk of intraventricular hemorrhage (IVH) growth.MethodsPatients with acute spontaneous ICH admitted at four tertiary centers in Germany and Italy were retrospectively included from January 2017 to June 2020. NCCT markers were rated by two investigators for heterogeneous density, hypodensity, black hole sign, swirl sign, blend sign, fluid level, island sign, satellite sign, and irregular shape. ICH and IVH volumes were semi-manually segmented. IVH growth was defined as IVH expansion > 1 mL (eIVH) or any delayed IVH (dIVH) on follow-up imaging. Predictors of eIVH and dIVH were explored with multivariable logistic regression. Hypothesized moderators and mediators were independently assessed in PROCESS macro models.ResultsA total of 731 patients were included, of whom 185 (25.31%) suffered from IVH growth, 130 (17.78%) had eIVH, and 55 (7.52%) had dIVH. Irregular shape was significantly associated with IVH growth (OR 1.68; 95%CI [1.16-2.44]; p = 0.006). In the subgroup analysis stratified by the IVH growth type, hypodensities were significantly associated with eIVH (OR 2.06; 95%CI [1.48-2.64]; p = 0.015), whereas irregular shape (OR 2.72; 95%CI [1.91-3.53]; p = 0.016) in dIVH. The association between NCCT markers and IVH growth was not mediated by parenchymal hematoma expansion.ConclusionsNCCT features identified ICH patients at a high risk of IVH growth. Our findings suggest the possibility to stratify the risk of IVH growth with baseline NCCT and might inform ongoing and future studies.Clinical relevance statementNon-contrast CT features identified ICH patients at a high risk of intraventricular hemorrhage growth with subtype-specific differences. Our findings may assist in the risk stratification of intraventricular hemorrhage growth with baseline CT and might inform ongoing and future clinical studies.Key points• NCCT features identified ICH patients at a high risk of IVH growth with subtype-specific differences. • The effect of NCCT features was not moderated by time and location or indirectly mediated by hematoma expansion. • Our findings may assist in the risk stratification of IVH growth with baseline NCCT and might inform ongoing and future studies.

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Project description:Phase-contrast computed tomography (PCCT) is an X-ray-based imaging method measuring differences in the refractive index during tissue passage. While conventional X-ray techniques rely on the absorption of radiation due to differing tissue-specific attenuation coefficients, PCCT enables the determination of the electron density (ED). By the analysis of respective phantoms and ex vivo specimens, we identified the components responsible for different electron densities in murine adipose tissue depots to be cellular fat and mitochondrial content, two parameters typically different between white adipose tissue (WAT) and brown adipose tissue (BAT). Brown adipocytes provide mammals with a means of non-shivering thermogenesis to defend normothermia in a cold environment. Brown adipocytes are found in dedicated BAT depots and interspersed within white fat depots, a cell type referred to as brite (brown in white) adipocyte. Localization and quantification of brown and brite adipocytes in situ allows an estimate of depot thermogenic capacity and potential contribution to maximal metabolic rate in the cold. We utilized PCCT to infer the composition of white, brite, and brown adipose tissue from ED of individual depots. As proof of principle, we imaged mice 10, 20, and 30 days of age. During this period, several WAT depots are known to undergo transient browning. Based on ED, classical WAT and BAT could be clearly distinguished. Retroperitoneal and inguinal WAT depots increased transiently in ED during the known remodeling from white to brite/brown and back to white. We systematically analyzed 18 anatomically defined adipose tissue locations and identified changes in fat content and mitochondrial density that imply an orchestrated pattern of simultaneous browning and whitening on the organismic level. Taken together, PCCT provides a three-dimensional imaging technique to visualize ED of tissues in situ. Within the adipose organ, ED provides a measure of mitochondrial density and fat content. Depending on experimental setting, these constitute surrogate markers of cellular distribution of white, brite, and brown adipocytes and thereby an estimate of thermogenic capacity.

Dataset Information

Diffusible iodine-based contrast-enhanced computed tomography (diceCT): an emerging tool for rapid, high-resolution, 3-D imaging of metazoan soft tissues.

Publications

Diffusible iodine-based contrast-enhanced computed tomography (diceCT): an emerging tool for rapid, high-resolution, 3-D imaging of metazoan soft tissues.

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