• computed tomography
• contrast agent
• photon-counting micro-CT
• preclinical
• tumor imaging
• tumor xenografts

• Animals
• Mice
• Contrast Media
• Photons
• Humans
• X-Ray Microtomography/instrumentation
• Cell Line, Tumor
• Female
• Breast Neoplasms/diagnostic imaging
• Mice, Nude
• Ovarian Neoplasms/diagnostic imaging
• Ovarian Neoplasms/pathology
• Nanoparticles

• R01 CA233888 NCI NIH HHS
• R01 CA237267 NCI NIH HHS
• R01 CA250636 NCI NIH HHS
• R01 CA271371 NCI NIH HHS
• Division of Cancer Epidemiology and Genetics, National Cancer Institute

• Cisplatin
• Hepatic arterial infusion
• Immunodeficient rat
• Liver metastasis
• Pancreatic ductal adenocarcinoma
• Patient-derived tumor xenograft

• Animals
• Carcinoma, Pancreatic Ductal/pathology
• Carcinoma, Pancreatic Ductal/drug therapy
• Humans
• Rats
• Infusions, Intra-Arterial
• Hepatic Artery
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/diagnostic imaging
• Liver Neoplasms/drug therapy
• Liver Neoplasms/pathology
• Liver Neoplasms/secondary
• Liver Neoplasms/diagnostic imaging
• Xenograft Model Antitumor Assays
• Cisplatin/administration & dosage
• Cisplatin/pharmacology
• Male
• Disease Models, Animal
• Antineoplastic Agents/administration & dosage
• Antineoplastic Agents/pharmacology

• 18K15596 JPSS KAKENHI
• Osaka Community Foundation
• Kobayashi Foundation for Cancer Research
• Japan Research Foundation for Clinical Pharmacology
• NOVARTIS Foundation (Japan) for the Promotion of Science
• Takeda Science Foundation
• Mochida Memorial Foundation for Medical and Pharmaceutical Research
• OMU Pancreatic Cancer Foundation

• Matrix inversion
• Micro-CT
• Multi-energy CT
• Phantom
• Simulation

• Photon-counting micro-CT
• color visualization
• computed tomography
• contrast agent
• live animal
• preclinical
• tumor imaging
• tumor xenografts

• R01 CA237267 NCI NIH HHS
• R01 CA250636 NCI NIH HHS

• Animals
• Mice
• Carcinoma, Hepatocellular/pathology
• Non-alcoholic Fatty Liver Disease/pathology
• Liver Neoplasms/pathology
• Mice, Inbred C57BL
• Liver/metabolism
• Diet, High-Fat/adverse effects
• Oxygen/metabolism
• Disease Models, Animal

• Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
• Association de soutien à la Paralysie Supranucléaire ProgressiveFondation Francis & Marie-France Minkoff
• Fondation Centre de Recherches Médicales Carlos et Elsie de Reuter
• Fondation Gilles Mentha
• Swiss Society of Gastroenterology (SGG-SSG)
• the Swiss Society of Visceral Surgery (SGVC-SSCV)
• Fondation Leenaards

• Meibomian glands
• cryotherapy
• dogs
• laser therapy
• microCT
• partial tarsal plate excision

• Contrast Media
• Diethylnitrosamine
• Hepatocellular Carcinoma
• Rats
• X-Ray Computed Tomography

Small animal micro computed tomography (μCT) is an important tool in cancer research and is used to quantify liver and lung tumors. A type of cancer that is intensively investigated with μCT is hepatocellular carcinoma (HCC). μCT scans acquire projections from different angles of the gantry which rotates X-ray source and detector around the animal. Motion of the animal causes inconsistencies between the projections which lead to artifacts in the resulting image. This is problematic in HCC research, where respiratory motion affects the image quality by causing hypodense intensity at the liver edge and smearing out small structures such as tumors. Dealing with respiratory motion is particularly difficult in a high throughput setting when multiple mice are scanned together and projection removal by retrospective respiratory gating may compromise image quality and dose efficiency. In mice, inhalation anesthesia leads to a regular respiration with short gasps and long phases of negligible motion. Using this effect and an iterative reconstruction which can cope with missing angles, we discard the relatively few projections in which the gasping motion occurs. Moreover, since gated acquisition, i.e., acquiring multiple projections from a single gantry angle is not a requirement, this method can be applied to existing scans. We applied our method in a high throughput setting in which four mice with HCC tumors were scanned simultaneously in a multi-mouse bed. To establish a ground truth, we manually selected projections with visible respiratory motion. Our automated intrinsic breathing projection selection achieved an accordance of 97% with manual selection. We reconstructed volumetric images and demonstrated that our intrinsic gating method significantly reduces the hypodense depiction at the cranial liver edge and improves the detectability of small tumors. Furthermore, we show that projection removal in a four mice scan discards only 7.5% more projections than in a single-mouse setting, i.e., four mouse scanning does not substantially compromise dose efficiency or image quality. To the best of our knowledge, no comparable method that combines multi-mouse scans for high throughput, intrinsic respiratory gating, and an available iterative reconstruction has been described for liver tumor imaging before.

• Deutsche Forschungsgemeinschaft
• European Regional Development Fund
• Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen

Fluorescence imaging is a noninvasive and dynamic real-time imaging technique; however, it exhibits poor spatial resolution in centimeter-deep tissues because biological tissues are highly scattering media for optical radiation. The recently developed ultrasound-controlled fluorescence (UCF) imaging is a novel imaging technique that can overcome this bottleneck. Previous studies suggest that the effective contrast agent and sensitive imaging system are the two pivotal factors for generating high-resolution UCF images ex vivo and/or in vivo. Here, this review highlights the recent advances (2015–2020) in the design and synthesis of contrast agents and the improvement of imaging systems to realize high-resolution UCF imaging of deep tissues. The imaging performances of various UCF systems, including the signal-to-noise ratio, imaging resolution, and imaging depth, are specifically discussed. In addition, the challenges and prospects are highlighted. With continuously increasing research interest in this field and emerging multidisciplinary applications, UCF imaging with higher spatial resolution and larger imaging depth may be developed shortly, which is expected to have a far-reaching impact on disease surveillance and/or therapy.

•

The unique UCF technique in high resolution imaging was described.

Vascular research is largely performed in rodents with the goal of developing treatments for human disease. Micro-computed tomography (micro-CT) provides non-destructive three-dimensional imaging that can be used to study the vasculature of rodents. However, to distinguish vasculature from other soft tissues, long-circulating contrast agents are required. In this study, we demonstrated that poly(ethylene glycol) (PEG)-coated gadolinium nanoparticles can be used as a vascular contrast agent in micro-CT. The coated particles could be lyophilized and then redispersed in an aqueous solution to achieve 100 mg/mL of gadolinium. After an intravenous injection of the contrast agent into mice, micro-CT scans showed blood pool contrast enhancements of at least 200 HU for 30 min. Imaging and quantitative analysis of gadolinium in tissues showed the presence of contrast agent in clearance organs including the liver and spleen and very low amounts in other organs. In vitro cell culture experiments, subcutaneous injections, and analysis of mouse body weight suggested that the agents exhibited low toxicity. Histological analysis of tissues 5 days after injection of the contrast agent showed cytotoxicity in the spleen, but no abnormalities were observed in the liver, lungs, kidneys, and bladder.

• Macrophage ablation
• clodronate
• molecular imaging
• reticuloendothelial system

Purpose: By taking advantage of 18F-FDG PET imaging and tissue nuclear magnetic resonance (NMR) metabolomics, we examined the dynamic metabolic alterations induced by liver irradiation in a mouse model for hepatocellular carcinoma (HCC). Methods: After orthotopic implantation with the mouse liver cancer BNL cells in the right hepatic lobe, animals were divided into two experimental groups. The first received irradiation (RT) at 15 Gy, while the second (no-RT) did not. Intergroup comparisons over time were performed, in terms of 18F-FDG PET findings, NMR metabolomics results, and the expression of genes involved in inflammation and glucose metabolism. Results: As of day one post-irradiation, mice in the RT group showed an increased 18F-FDG uptake in the right liver parenchyma compared with the no-RT group. However, the difference reached statistical significance only on the third post-irradiation day. NMR metabolomics revealed that glucose concentrations peaked on day one post-irradiation both, in the right and left lobes—the latter reflecting a bystander effect. Increased pyruvate and glutamate levels were also evident in the right liver on the third post-irradiation day. The expression levels of the glucose-6-phosphatase (G6PC) and fructose-1, 6-bisphosphatase 1 (FBP1) genes were down-regulated on the first and third post-irradiation days, respectively. Therefore, liver irradiation was associated with a metabolic shift from an impaired gluconeogenesis to an enhanced glycolysis from the first to the third post-irradiation day. Conclusion: Radiation-induced metabolic alterations in the liver parenchyma occur as early as the first post-irradiation day and show dynamic changes over time.

• 18F-FDG PET
• NMR
• glycolysis
• liver cancer
• radiation

• Animal models
• arthropathy
• haemophilia A
• hemarthrosis
• in vivo imaging
• micro‐CT

• Diseases screening
• Dynamic biosensor designs
• Healthcare industry
• Nano chipset sensor device
• Nanomaterials
• Virus detection

Computed tomography is a powerful medical imaging modality for longitudinal studies in cancer to follow neoplasia progression and evaluate anticancer therapies. Here, we report the generation of a photon-counting micro-computed tomography (PC-CT) method based on hybrid pixel detectors with enhanced sensitivity and precision of tumor imaging. We then applied PC-CT for longitudinal imaging in a clinically relevant liver cancer model, the Alb-R26^Met mice, and found a remarkable heterogeneity in the dynamics for tumors at the initiation phases. Instead, the growth curve of evolving tumors exhibited a comparable exponential growth, with a constant doubling time. Furthermore, longitudinal PC-CT imaging in mice treated with a combination of MEK and BCL-XL inhibitors revealed a drastic tumor regression accompanied by a striking remodeling of macrophages in the tumor microenvironment. Thus, PC-CT is a powerful system to detect cancer initiation and progression, and to monitor its evolution during treatment.

•

Development of photon-counting micro-computed tomography (PC-CT) with hybrid pixels

• Cancer
• Optical Imaging
• Optics

• Drug ratio
• Drug-mediated CT
• Dual prodrug polymer
• Light-activatable
• Synergistic chemotherapy

• Animals
• Antineoplastic Agents/chemistry
• Antineoplastic Agents/pharmacokinetics
• Antineoplastic Agents/pharmacology
• Cantharidin/chemistry
• Cantharidin/pharmacokinetics
• Cantharidin/pharmacology
• Contrast Media/chemistry
• Contrast Media/pharmacokinetics
• Contrast Media/pharmacology
• HeLa Cells
• Humans
• Light
• Mice
• Nanoparticles/chemistry
• Nanoparticles/therapeutic use
• Neoplasms, Experimental/diagnostic imaging
• Neoplasms, Experimental/drug therapy
• Prodrugs/chemistry
• Prodrugs/pharmacokinetics
• Prodrugs/pharmacology
• Tomography, X-Ray Computed
• Xenograft Model Antitumor Assays

• fluorescence imaging
• ultrasound
• imaging and sensing

• Animals
• Breast Neoplasms/metabolism
• Breast Neoplasms/pathology
• Contrast Media/administration & dosage
• Female
• Fluorescence
• Fluorescent Dyes/administration & dosage
• Heart/physiology
• Mice
• Mice, Inbred BALB C
• Optical Imaging/methods
• Spleen/metabolism
• Spleen/pathology
• Swine
• Tissue Distribution/physiology
• Ultrasonography/methods

• Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas)
• National Science Foundation (NSF)

The aim of this study was to evaluate the potential of microcomputed tomography (micro-CT) using the intravascular contrast agent ExiTron nano 12000 for aorta imaging and monitoring the dynamic changing process of the aorta in mouse models with aortic aneurysm and dissection.

Experiments were performed on healthy mice and mice with aortic dissection. Mice that were developing aortic dissection and healthy mice underwent micro-CT imaging after injection of ExiTron nano 12000. Time-dependent signal enhancement (at 1, 2, 3, 6, and 12 hours after intravenous injection of the contrast agent, respectively) in the aorta of healthy mice was measured to confirm the optimal imaging time of aorta. Various contrast agent doses (70, 100, and 150 μl per 25 g mouse, respectively) were investigated to determine the optimal required dose for imaging of the aorta. The mice were scanned with micro-CT at 1, 14, and 28 days after onset of aneurysm and dissection to monitor the dynamic changing process of the aorta. Mouse aortas were stained with hematoxylin and eosin staining, and the diameter of the aorta was measured and compared with those obtained by micro-CT.

Time-dependent signal enhancement in the aorta shows that the contrast agent has a long blood half-life of 6 hours, with a peak enhancement at 2 hours after injection. Injection of 100 μl ExiTron nano 12000 per 25 g mouse allows for effective visualization of the aorta. Micro-CT combined with contrast agent can monitor the changing process of the aorta in the mouse model of aortic aneurysm and dissection dynamically. The values of the diameter of the aortas obtained from the in vivo micro-CT imaging were compared with those obtained from histology and showed a significant correlation (R² = 0.96).

These data demonstrate that in vivo micro-CT is an accurate and feasible technique to detect aortic aneurysm or dissection in a mouse model, and the micro-CT technique using the innovative contrast agent ExiTron nano 12000 allows for monitoring various processes dynamically such as aortic remodeling in longitudinal studies.

• ExiTron nano 12,000
• Kupffer cell
• Micro-computed tomography
• Nonclinical imaging

• cell sheet
• intrahepatic tumor-bearing mouse
• pharmaceuticals test
• transplantation
• tumor formation

• animal models
• arthropathy
• haemarthrosis
• haemophilia A
• in vivo imaging
• micro-CT

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.

• adjuvant immunotherapy
• bacterial ghosts
• colon cancer
• immunogenic cell death
• oxaliplatin
• peritoneal carcinomatosis

We herein developed a micro-CT method using the innovative contrast agent ExiTron™ MyoC 8000 to longitudinally monitor cardiac processes in vivo in small animals. Experiments were performed on healthy mice and mice with myocardial infarction inflicted by ligation of the left anterior descending artery. Time-dependent signal enhancement in different tissues of healthy mice was measured and various contrast agent doses were investigated so as to determine the minimum required dose for imaging of the myocardium. Due to its ability to be taken up by healthy myocardium but not by infarct tissue, ExiTron MyoC 8000 enables detection of myocardial infarction even at a very low dose. The signal enhancement in the myocardium of infarcted mice after contrast agent injection was exploited for quantification of infarct size. The values of infarct size obtained from the imaging method were compared with those obtained from histology and showed a significant correlation (R² = 0.98). Thus, the developed micro-CT method allows for monitoring of a variety of processes such as cardiac remodeling in longitudinal studies.

• Chronic stress
• Computed tomography
• Glucocorticoids
• House sparrow
• Hypothalamus-pituitary-adrenal axis
• In vivo imaging

• Animals
• Animals, Wild/physiology
• Body Composition/drug effects
• Body Composition/physiology
• Breeding
• Corticosterone/blood
• Fear/drug effects
• Fear/physiology
• Female
• Hypothalamo-Hypophyseal System/drug effects
• Hypothalamo-Hypophyseal System/physiology
• Male
• Mitotane/pharmacology
• Pituitary-Adrenal System/drug effects
• Pituitary-Adrenal System/physiology
• Social Environment
• Sparrows/physiology
• Stereotyped Behavior/drug effects
• Stereotyped Behavior/physiology
• Stress, Psychological/physiopathology

• S10 OD010322 NIH HHS

• Atherosclerosis
• Contrast media
• Image segmentation
• Micro-CT imaging
• Wall shear stress

• Animals
• Apolipoproteins E/genetics
• Blood Flow Velocity
• Carotid Arteries/diagnostic imaging
• Carotid Arteries/physiopathology
• Contrast Media/chemistry
• Coronary Vessels/pathology
• Endothelial Cells/cytology
• Endothelium, Vascular/physiopathology
• Female
• Image Processing, Computer-Assisted
• Imaging, Three-Dimensional
• Mice
• Mice, Inbred C57BL
• Shear Strength
• Stress, Mechanical
• X-Ray Microtomography/methods

There is an increasing need for small animal in vivo imaging in murine orthotopic glioma models. Because dedicated small animal scanners are not available ubiquitously, the applicability of a clinical CT scanner for visualization and measurement of intracerebrally growing glioma xenografts in living mice was validated.

2.5x10⁶ U87MG cells were orthotopically implanted in NOD/SCID/ᵞc^-/- mice (n = 9). Mice underwent contrast-enhanced (300 μl Iomeprol i.v.) imaging using a micro-CT (80 kV, 75 μAs, 360° rotation, 1,000 projections, scan time 33 s, resolution 40 x 40 x 53 μm) and a clinical CT scanner (4-row multislice detector; 120 kV, 150 mAs, slice thickness 0.5 mm, feed rotation 0.5 mm, resolution 98 x 98 x 500 μm). Mice were sacrificed and the brain was worked up histologically. In all modalities tumor volume was measured by two independent readers. Contrast-to-noise ratio (CNR) and Signal-to-noise ratio (SNR) were measured from reconstructed CT-scans (0.5 mm slice thickness; n = 18).

Tumor volumes (mean±SD mm³) were similar between both CT-modalities (micro-CT: 19.8±19.0, clinical CT: 19.8±18.8; Wilcoxon signed-rank test p = 0.813). Moreover, between reader analyses for each modality showed excellent agreement as demonstrated by correlation analysis (Spearman-Rho >0.9; p<0.01 for all correlations). Histologically measured tumor volumes (11.0±11.2) were significantly smaller due to shrinkage artifacts (p<0.05). CNR and SNR were 2.1±1.0 and 1.1±0.04 for micro-CT and 23.1±24.0 and 1.9±0.7 for the clinical CTscanner, respectively.

Clinical CT scanners may reliably be used for in vivo imaging and volumetric analysis of brain tumor growth in mice.

• Animals
• Brain/diagnostic imaging
• Brain/pathology
• Brain Neoplasms/diagnostic imaging
• Cell Line, Tumor
• Contrast Media/administration & dosage
• Female
• Glioblastoma/diagnostic imaging
• Humans
• Interleukin Receptor Common gamma Subunit/deficiency
• Interleukin Receptor Common gamma Subunit/genetics
• Iopamidol/administration & dosage
• Iopamidol/analogs & derivatives
• Male
• Mice, Inbred NOD
• Mice, Knockout
• Mice, SCID
• Reproducibility of Results
• Signal-To-Noise Ratio
• Transplantation, Heterologous
• X-Ray Microtomography/methods

• Genetically induced hepatocellular carcinoma
• Hepatocyte-specific Trim24-null mouse
• High-resolution micro-computed tomography (micro-CT-scan)
• Myo-inositol trispyrophosphate (ITPP)
• Transgenic mouse

• Animals
• Contrast Media/administration & dosage
• Contrast Media/chemistry
• Dog Diseases/diagnostic imaging
• Dogs
• Female
• Iodine/administration & dosage
• Iodine/chemistry
• Liposomes/chemistry
• Liver/diagnostic imaging
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/veterinary
• Lung/diagnostic imaging
• Lung Neoplasms/diagnostic imaging
• Lung Neoplasms/veterinary
• Mammary Glands, Animal/diagnostic imaging
• Mammary Neoplasms, Animal/diagnostic imaging
• Tomography, X-Ray Computed/methods

• biodistribution
• contrast agents
• pharmacokinetics
• side-effects
• small animal CT

Non-bone in vivo micro-CT imaging has many potential applications for preclinical evaluation. Specifically, the in vivo quantification of changes in the vascular network and organ morphology in small animals, associated with the emergence and progression of diseases like bone fracture, inflammation and cancer, would be critical to the development and evaluation of new therapies for the same. However, there are few published papers describing the in vivo vascular imaging in small animals, due to technical challenges, such as low image quality and low vessel contrast in surrounding tissues. These studies have primarily focused on lung, cardiovascular and brain imaging. In vivo vascular imaging of mouse hind limbs has not been reported. We have developed an in vivo CT imaging technique to visualize and quantify vasculature and organ structure in disease models, with the goal of improved quality images. With 1–2 minutes scanning by a high speed in vivo micro-CT scanner (Quantum CT), and injection of a highly efficient contrast agent (Exitron nano 12000), vasculature and organ structure were semi-automatically segmented and quantified via image analysis software (Analyze). Vessels of the head and hind limbs, and organs like the heart, liver, kidneys and spleen were visualized and segmented from density maps. In a mouse model of bone metastasis, neoangiogenesis was observed, and associated changes to vessel morphology were computed, along with associated enlargement of the spleen. The in vivo CT image quality, voxel size down to 20 μm, is sufficient to visualize and quantify mouse vascular morphology. With this technique, in vivo vascular monitoring becomes feasible for the preclinical evaluation of small animal disease models.

• Angiography/methods
• Animals
• Contrast Media/pharmacology
• Mice
• Neoplasms, Experimental/blood supply
• Neoplasms, Experimental/diagnostic imaging
• Neovascularization, Pathologic/diagnostic imaging
• Organ Specificity
• X-Ray Microtomography/methods

The use of Micro-Computed Tomography (MicroCT) for in vivo studies of small animals as models of human disease has risen tremendously due to the fact that MicroCT provides quantitative high-resolution three-dimensional (3D) anatomical data non-destructively and longitudinally. Most importantly, with the development of a novel preclinical iodinated contrast agent called eXIA160, functional and metabolic assessment of the heart became possible. However, prior to the advent of commercial MicroCT scanners equipped with X-ray flat-panel detector technology and easy-to-use cardio-respiratory gating, preclinical studies of cardiovascular disease (CVD) in small animals required a MicroCT technologist with advanced skills, and thus were impractical for widespread implementation. The goal of this work is to provide a practical guide to the use of the high-speed Quantum FX MicroCT system for comprehensive determination of myocardial global and regional function along with assessment of myocardial perfusion, metabolism and viability in healthy mice and in a cardiac ischemia mouse model induced by permanent occlusion of the left anterior descending coronary artery (LAD).

AIM: To explore the potential of contrast-enhanced computed tomography (CECT) using ExiTron nano6000 for assessment of liver lesions in mouse models.

METHODS: Three mouse models of liver lesions were used: bile duct ligation (BDL), lipopolysaccharide (LPS)/D-galactosamine (D-GalN), and alcohol. After injection with the contrast agent ExiTron nano6000, the mice were scanned with micro-CT. Liver lesions were evaluated using CECT images, hematoxylin and eosin staining, and serum aminotransferase levels. Macrophage distribution in the injury models was shown by immunohistochemical staining of CD68. The in vitro studies measured the densities of RAW264.7 under different conditions by CECT.

RESULTS: In the in vitro studies, CECT provided specific and strong contrast enhancement of liver in mice. CECT could present heterogeneous images and densities of injured livers induced by BDL, LPS/D-GalN, and alcohol. The liver histology and immunochemistry of CD68 demonstrated that both dilated biliary tracts and necrosis in the injured livers could lead to the heterogeneous distribution of macrophages. The in vitro study showed that the RAW264.7 cell masses had higher densities after LPS activation.

CONCLUSION: Micro-CT with the contrast agent ExiTron nano6000 is feasible for detecting various liver lesions by emphasizing the heterogeneous textures and densities of CECT images.

• Micro-computed tomography
• ExiTron Nano6000
• Liver injury

• Animals
• Antigens, CD/metabolism
• Antigens, Differentiation, Myelomonocytic/metabolism
• Bile Ducts/surgery
• Chemical and Drug Induced Liver Injury/blood
• Chemical and Drug Induced Liver Injury/diagnostic imaging
• Chemical and Drug Induced Liver Injury/etiology
• Cholestasis/blood
• Cholestasis/diagnostic imaging
• Cholestasis/etiology
• Contrast Media
• Disease Models, Animal
• Ethanol
• Immunohistochemistry
• Ligation
• Lipopolysaccharides
• Liver/diagnostic imaging
• Liver/metabolism
• Liver Diseases, Alcoholic/blood
• Liver Diseases, Alcoholic/diagnostic imaging
• Liver Diseases, Alcoholic/etiology
• Macrophages/diagnostic imaging
• Macrophages/metabolism
• Male
• Mice
• Mice, Inbred C57BL
• Nanoparticles
• Predictive Value of Tests
• RAW 264.7 Cells
• Severity of Illness Index
• Time Factors
• X-Ray Microtomography

Although radiotherapy is a key component of cancer treatment, its implementation into pre-clinical in vivo models with relatively small target volumes is frequently omitted either due to technical complexity or expected side effects hampering long-term observational studies. We here demonstrate how an affordable industrial micro-CT can be converted into a small animal IGRT device at very low costs. We also demonstrate the proof of principle for the case of partial brain irradiation of mice carrying orthotopic glioblastoma implants.

A commercially available micro-CT originally designed for non-destructive material analysis was used. It consists of a CNC manipulator, a transmission X-ray tube (10–160 kV) and a flat-panel detector, which was used together with custom-made steel collimators (1–5 mm aperture size). For radiation field characterization, an ionization chamber, water-equivalent slab phantoms and radiochromic films were used. A treatment planning tool was implemented using a C++ application. For proof of principle, NOD/SCID/γc^−/− mice were orthotopically implanted with U87MG high-grade glioma cells and irradiated using the novel setup.

The overall symmetry of the radiation field at 150 kV was 1.04±0.02%. The flatness was 4.99±0.63% and the penumbra widths were between 0.14 mm and 0.51 mm. The full width at half maximum (FWHM) ranged from 1.97 to 9.99 mm depending on the collimator aperture size. The dose depth curve along the central axis followed a typical shape of keV photons. Dose rates measured were 10.7 mGy/s in 1 mm and 7.6 mGy/s in 5 mm depth (5 mm collimator aperture size). Treatment of mice with a single dose of 10 Gy was tolerated well and resulted in central tumor necrosis consistent with therapeutic efficacy.

A conventional industrial micro-CT can be easily modified to allow effective small animal IGRT even of critical target volumes such as the brain.

• Animals
• Brain Neoplasms/pathology
• Brain Neoplasms/radiotherapy
• Mice
• Radiotherapy, Image-Guided/methods
• Reproducibility of Results
• X-Ray Microtomography/methods

• Micro-CT
• contrast agents
• contrast enhancement
• hepatocellular carcinoma
• mouse model

• Animals
• Carcinoma, Hepatocellular/chemistry
• Carcinoma, Hepatocellular/diagnostic imaging
• Carcinoma, Hepatocellular/metabolism
• Computer Simulation
• Contrast Media/pharmacokinetics
• Image Interpretation, Computer-Assisted/methods
• Iodine/pharmacokinetics
• Liver Neoplasms/chemistry
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/metabolism
• Metabolic Clearance Rate
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Models, Biological
• Nanoparticles/chemistry
• Reference Values
• Reproducibility of Results
• Sensitivity and Specificity
• Tomography, X-Ray Computed/methods

• X-ray computed tomography
• contrast agent
• gold nanorod
• spleen