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CT Contrast Agents (Module 3)

CT Contrast Agents (Module 3). Recent Examples of Iodinated Contrast Agents.

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CT Contrast Agents (Module 3)

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  1. CT Contrast Agents (Module 3)

  2. Recent Examples of Iodinated Contrast Agents  Molecular structure (a) and scanning electron micrograph image (b) of 6-ethoxy-6-oxohexyl 3,5-diacetamido-2,4,6-triiodobenzoate (N1177) particles. (c) In vivo CT imaging of atherosclerosis. Intense red spots representing high CT number were detected in atherosclerotic plaques after administration of N1177 (left), but not in atherosclerotic plaques after administration of a conventional contrast agent (middle), nor in the aortic wall of a normal rabbit after injection of N1177 (right). (d) 3D reconstructed CT images of the thoracic cavities of a rat directly (left) and 2 h (right) after insufflation of N1177 dry powder.  Advanced MaterialsVolume 25, Issue 19, pages 2641-2660, 4 APR 2013 DOI: 10.1002/adma.201300081http://onlinelibrary.wiley.com/doi/10.1002/adma.201300081/full#fig6

  3. Recent Examples of Iodinated Contrast Agents Structures of iodinated metal organic frameworks (MOF) containing 2,3,5,6-tetraiodo-1,4-benzenedicarboxylic acid (I4-BDC-H2) as iodinated ligands. a) [Cu(I4-BDC)(dmf)2], b) [Cu(I4-BDC)(def)2(H2O)], c) [Cu(I4- BDC)(H2O)2]·2H2O, d) [Zn(I4-BDC)(dmf)2.5], and e) [Zn(I4- BDC)(EtOH)2]·2EtOH.  MOF was completely degraded in phosphate buffered saline (PBS) at 37 °C within 46 h, representing its biodegradable nature. Advanced MaterialsVolume 25, Issue 19, pages 2641-2660, 4 APR 2013 DOI: 10.1002/adma.201300081http://onlinelibrary.wiley.com/doi/10.1002/adma.201300081/full#fig12

  4. Metals for CT Contrast Agents Prerequisite features: High payload (>500k metal atoms/NP) High atomic number (Z) Metal with well-positioned K-edge energy Biocompatible surface Defined in vivo characteristics Bio-elimination Stability (shelf life/in-vivo) Coating Homing agent High Z metal Au Gd Yb Bi Z: 79 K-edge: 80.7 keV Pros/Cons + Well studied metal - Cost ($55/g.) - High k-edge Z: 83 K-edge: 90.8 keV Pros/Cons - Not water soluble - High k-edge Z: 70 K-edge: 61.3 keV Pros/Cons + Well placed K-edge + Cost efficient (~$10/g.) Z: 64 K-edge: 50.2 keV Pros/Cons + Well placed K-edge + Cost efficient + (In clinical practice) - Known Safety issues Schirra, Pan et al J. Mater. Chem., 2012, 22, 23071-23077 Pan, Schirra et al ACS Nano. 2012, 6(4):3364-70. Pan et. al. AngewChem Intl Ed. 2010, Ed. 9635-39

  5. K-edge energies and X-ray mass attenuation coefficients for heavy elements used in CT imaging

  6. Stable Xenon-enhanced Contrast CT Uses the inert gas xenon to measure cerebral blood flow (CBF) in various brain regions This technique uses stable non-radioactive 131Xe (At.#54; At. Wt. 131.293) An alternative to SPECT Patient inhales a mixture of xenon and oxygen over the period of a few minutes, allows measurement of their increased in density caused by the gas in brain tissue

  7. Advantages • Can be incorporated into all existing CT technologies . • Can be used to determine local cerebral blood flow in an area as small as 1 x 1 x 5 mm3 area • Can be repeated within 20 mins, allowing the assessment of hemodynamic states including (in certain well-defined settings) • Helps to evaluate acute stroke, occlusive vascular disease, carotid occlusion testing, vasospasm, arteriovenous malformations, and head trauma management

  8. Data are acquired during inhalation of a gas mixture containing 28% 131Xe and oxygen • A radio opaque, highly lipid soluble, diffusible indicator capable of crossing the blood brain barrier. • It provides a measure of tissue perfusion with quantification based on a modification of the Fick principle. where CO = Cardiac Output, Ca = Oxygen concentration of arterial blood and Cv = Oxygen concentration of mixed venous blood. and hence calculate cardiac output. Note that (Ca – Cv) is also known as the arteriovenous oxygen difference. VO2, oxygen consumption in ml of pure gaseous oxygen per minute. Ca, the oxygen concentration of blood taken from the pulmonary vein (representing oxygenated blood) Cv, the oxygen concentration of blood from an intravenous cannula (representing deoxygenated blood)

  9. Xenon-enhanced CT for Head Injury

  10. Disadvantages Not FDA approved yet. Approved in the Europe CT based perfusion imaging is considered investigational for all indications including the diagnosis and management of acute cerebral ischemia (stroke). Quantitative CBF studies can be difficult to perform in patients with associated pulmonary pathology since the technique is based on the assumption that the end-tidal xenon concentration is identical to the arterial concentration.

  11. Barium Contrast Agents

  12. ExiTron12000 by MiltenyiBiotec is a barium-based nanoparticulate contrast agent. • It provides good contrast and remains in the vasculature for several hours. • A typical dose is 100 L injected iv and costs about $92. Volume-rendered CT angiography in mouse using ExiTronnano 12000. The inferior vena cava and the renal vascular tree are clearly visible.

  13. Mouse CT imaging with ExiTron nano12000 and LCT-200 (MiltenyiBioTech and Hitachi Aloka Medical, Ltd.) ①thoracic aorta, ②azygous vein, ③pulmonary arteriovenous, ④caudal vena cava, ⑤abdominal aorta, ⑥portal vein Abdomen and visualization of blood vessels Tomogram of heart Liver, spleen and kidney 3D tomogram of heart. G:3D tomogram of spleen. Whole body without sternum. Vascular system appears clear. without a liver. Notice visualization of caudal vena cava.

  14. Comparison Between Conventional and New Contrast Agents ExiTron

  15. Quickly phagocytosed by Kupffer cells and allows hepatic visualization for several weeks after injection. • Progression of mouse liver metastases over the period of 14 days monitored in micro-CT following a single administration of ExiTronnano 6000. • The individual lobes of the liver tissue appear clearly opacified.

  16. Mice were injected with ExiTron™ nano 12000 and whole body scans were performed for 60min post injection. (Prof. Dr. Marc Kachelrieß) Mice were injected with ExiTron™ nano 12000 and whole body scans were performed for 60min post injection.  Mouse vascular system: beating heart

  17. Volume rendered CT angiography of the mouse thorax for visualization of heart, thoracic bone, superior vena cava.

  18. Nanoparticle of Bismuth Experimental CT opacity of bismuth solutions as a function of concentration. The horizontal dashed lines indicate the opacities of air, water and 2.36 M (300 mg I ml-1) iodine contrast agent, for comparison. Inset: X-ray fluoroscopy of tubes containing PBS, 0.5 M Bi2S3 nanoparticle suspension (BPNPs) and 2.36 M iodine contrast agent (Iopromide).

  19. Lymph Node Imaging with Bi2S3 Nanoparticles CT imaging of a lymph node of a mouse with the BPNP imaging agent. a,b, Three-dimensional volume renderings of the CT data set, the length of the reconstruction is 3.8 cm. c, Coronal slice (length of the slice 2.3 cm). d, Transverse slice at the height indicated by the horizontal lines in b. The maximal diameter of the mouse 1.8 cm.

  20. a,b, Cell (U937 macrophages and HepG2 hepatocytes) viability as a function of bismuth concentration in the media as determined by the MTS assay for Bi3+ salt (filled circles) or BPNPs (open squares). Note the substantially lower toxicity of bismuth in BPNP form compared with ionic bismuth sulphosalicylate. c,d, Comparative ratios of efficacy and cellular toxicity. Lower numbers refer to better performance. Note that BPNPs outperform clinically used Iopromide in hepatocyte cultures. The error bars in a,b correspond to the standard deviation calculated from at least three repeats of each experiment. 

  21. Tantalum Oxide Nanoparticles Hydrolysis of Tantalum ethoxide, Ta(OEt)5 Ta Z: 73 K-edge: 90.8 keV Pros/Cons - Not water soluble - High k-edge In vitro and in vivo CT imaging studies. (A) In vitro phantom study comparing image contrast (HU) vs. X-ray energy (kVp) of tantalum (in the form of 2) and iodine (using iopromide) at equal molarity in water. (B) 3D-rendering of in vivo imaging exam before (top) and 10 s after (bottom) injection of 1 mL of 2 at 0.92 M Ta concentration. Chem. Commun., 2010, 46, 8956-8958

  22. PEG-Coated Tantalum Oxide Hydrogel Particles Images of synthesized PEG-TaOx nanoparticle with ~7nm (top) and ~19nm (bottom) diameters. Scale bars are 100nm In vivo imaging of the rat also showed significant vascular contrast enhancement immediately after tail veil injection Transducers 2013

  23. Tungsten Oxide Nanoparticles In vivo X-ray transverse CT images of tumor (a1 and a2) and 3-D renderings of in vivo CT images (b1 and b2) before (a1 and b1) and after (a2 and b2) intratumoral injection of PEGylated WO2.9 NRs (20 mg/kg). Scientific Reports 4, Article number: 3653 doi:10.1038/srep03653

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