Contrast Media in CT Diagnostics

Contrast media in CT diagnostics E-Learning Contrast media in CT diagnostics Dr. med. Marco Wiesmüller PD Dr. med. habil. Matthias May Unrestricted Welcome - Contrast media in CT diagnostics [audf_001.mp3] Welcome to this e-learning workshop about contrast media in CT diagnostics. Outline & educational objectives Definition of “contrast media” (CM) Overview of CM used in radiology Classification of CM used for CT Negative CM Positive CM Special focus on iodine containing CM Adverse drug reactions CM application techniques Examples of routinely used CT protocols (Institute of Radiology, University Hospital Erlangen) Outline & educational objectives [audf_002.mp3] In this online training, the following items will be explained to you: Definition of ”contrast medium/media“ (referred to as “CM“ in the written text). Overview of different types of contrast media used in radiology Classification of contrast media used for computed tomography Negative contrast media Positive contrast media Special focus on iodine containing contrast media Adverse drug reactions to iodine containing contrast media Contrast media application techniques Examples of routinely used CT protocols at the Institute of Radiology, University Hospital Erlangen Definition of “contrast media” Contrast media (CM) enhance the presentation and perceptibility of human tissue and assist in the delineation of pathologies in medical diagnostics Ideal CM have no influence on physiological functions and show no toxicity or adverse drug reactions Definition of “contrast media” [audf_003.mp3] We begin by giving a definition of “contrast media“ and answering the question: "What do contrast media do in general?”   Contrast media enhance the presentation and perceptibility of human tissue and help the physician to delineate certain pathologies in medical diagnostics based on CT or MRI techniques.   An ideal contrast medium has no influence on physiological functions and shows no toxicity or adverse drug reactions after administration into the human body. Definition of “contrast media” by law CM are defined as medical drugs by law in Germany (§ 2 Abs. 1 Nr. 2, Arzneimittelgesetz (AMG)) CM are defined as medical products by European Directive (93/42/EWG, 1993) Definition of “contrast media” by law [audf_004.mp3] The definition of “contrast media“ by law is an important issue for physicians and the pharmaceutical industry, respectively.   Contrast media are defined as medical drugs by law in Germany; for other countries this may differ.   Furthermore, contrast media are defined as medical products by the indicated European Directive. Intravenous injection of iodine containing CM was first performed in 1923 in combination with radiographs Early application required general anesthesia due to severe pain Aromatic benzene ring (six carbon atoms) was introduced as iodine carrier in 1933, and is still in use today More than 40 years of research until painless and compatible iodine containing CM were introduced Brief history of iodine containing CM used in Radiology Benzene ring with three iodine atoms (I) R: side chains (different in each product; influence the chemical properties, e.g. solubility in water) R R R U. Nyman, Torsten Almen: The father of Non-ionic Iodine Contrast Media, Acta Radiol. 2016 Brief history of iodine containing CM used in Radiology [audf_005.mp3] Please let me introduce you to a brief history of iodine containing contrast media used in radiology.   Iodine containing contrast media have been used for almost 100 years but, in the early days of radiology, it was not entirely a success story to tell. Intravenous injection of early contrast media required general anesthesia due to severe pain during injection. In addition, patients suffered from a high rate of adverse drug reactions – even death – during the examination. The first pictures with injected contrast media were generated in combination with radiograph examinations.   Shortly after gaining some basic knowledge about the first iodine contrast media substances, research efforts into finding new contrast media substances were made, resulting in significant improvements.   In the 1930s, a groundbreaking new formula for iodine containing contrast media was developed. The new formula is shown in the drawing. A structure called an aromatic benzene ring with six carbon atoms was introduced as iodine carrier and this basic principle is still in use today for modern iodine containing contrast media.   It took another 40 years until this basic structure was perfected to avoid major adverse drug reactions and contrast media substances became fully compatible with daily use in radiology. Pharmacological properties, such as the solubility in water, can be manipulated with various side chains, which differ in each commercially available product. Sample image of an early radiograph study of the urinary tract D:\Bilder\ivu_2_be.jpg : Urinary tract at the height of the kidneys Sample image urinary tract [audf_006.mp3] This is a sample image of an early radiograph study using iodine containing contrast media. Contrast medium was injected intravenously and after a certain time, usually 30 minutes after injection, the urinary tract can be seen as white areas on each side of the radiograph. Two red asterisks mark the beginning of the urinary tract at the height of the kidneys.   These early examinations were performed to detect pathologies in the kidney and urinary tract system, for example kidney stones, which lead to the obstruction of one or sometimes even both urinary tracts. Stones may be seen as dark dots in the urinary tract because they do not contain contrast media. In this example, no stone could be found. Overview of CM used in Radiology Radiography and CT Iodine Barium Air, CO2 Water Magnetic Resonance Imaging (MRI) Gadolinium Iron Ultrasound (US) Microbubbles Overview of CM used in Radiology [audf_007.mp3] On this page, you can see an overview of typical contrast media used in radiology today.   The usage of different contrast media types can be arranged according to different imaging modalities. The first modality includes radiography and computed tomography, which use iodine and barium containing contrast media as well as air, CO2, and water. Gadolinium and iron containing contrast media are the two most popular used contrast media types for magnetic resonance imaging. For ultrasound examinations, microbubbles dissolved in water can be injected to gather different tissue signals during examination. General considerations – Why contrast media? High contrast examinations Usually native (= without CM) Examples: lung, skeleton Low contrast examinations Usually need CM to improve tissue contrast Examples: soft tissue structures (especially abdominal organs) General considerations – Why contrast media? [audf_008.mp3] Again, some general considerations about the usage of contrast media, especially for computed tomography.   Before a CT examination, the radiologist is confronted with two possible situations: First, the radiologist expects human tissue with very different CT densities. These tissues lead to a high contrast between each other and can be visualized very easily. This situation is typically found in examinations of the lungs or the skeleton, which do not need contrast media. The examination is called “native“ when no contrast medium is administered.   Second, tissues with similar density properties are expected and thus lead to a poor contrast between each other. Therefore, a contrast medium can alter the density properties of certain tissues to improve their contrast. Soft tissue structures, such as the liver, the kidney, or the spleen, highly benefit from the administration of contrast media to enhance radiological images. Sample image of a radiograph study to illustrate high contrast properties of the lung tissue : Right and left lung with typical “dark” appearance due to lesser X-ray absorption Sample image of lung tissue [audf_009.mp3] This is a sample image of a radiograph study to illustrate high contrast properties of the lung tissue. The red asterisks mark the relatively transparent lung tissue in contrast to the lesser transparency of vascular structures, the heart, and ribs. The high contrast between lung tissue and other tissues is due to the much lesser X-ray absorption of lung tissue leading to high contrast, even without contrast media. Sample images of a CT study to illustrate contrast properties of arterial vessels after intravenous administration of CM No CM Iodine containing CM (arterial vessel contrast) Sample images of arterial vessels [audf_010.mp3] These are sample images of a CT study illustrating contrast properties of different soft tissue structures in the abdomen.   In the left image, no contrast medium is used, and all soft tissue structures look more or less the same with low accuracy of discrimination.   In the right image, iodine containing contrast medium was injected intravenously and the CT examination was started at a time point when arterial vessels contain the major part of the contrast medium. As a result, you can clearly see the arterial vessels as white structures next to the organs. Furthermore, you can also see some changes in the abdominal organs themselves, representing the start of the perfusion of each organ with contrast medium. Sample images of a CT study to illustrate contrast properties of abdominal organs after intravenous administration of CM No CM Iodine containing CM (organ contrast) Sample images of abdominal organs [audf_011.mp3] On the left, you can see the same sample image as on the page before to illustrate the difference again when looking at the right image.   The right image illustrates a later time point when the major amount of injected contrast medium has reached the soft tissue organs and the veins. How to administer CM into human bodies? Through a cannula into arterial or venous vessel system Suitable CM are water-soluble iodine containing substances Enhances soft tissue organs and vessel system Image contrast depends on the delay of the examination after injection Early CT Series show arterial vessel contrast Later CT Series show soft tissue contrast (e.g. liver, kidney) Very Late CT Series show excretion through urinary tract How to administer CM into human bodies? [audf_012.mp3] Let me explain some of the basic principles of contrast media administration into human bodies to you.   Most contrast media are injected through a small-caliber cannula into the arterial or the venous vessel system. A typically used medical cannula is shown in the image.   All contrast media used for injection must be water-soluble because human blood contains a high amount of water and can be regarded as some sort of aqueous solution. As you have seen on the prior sample images, contrast media can be used to enhance vessels and soft tissue organs.   The image contrast largely depends on the timing of the CT examination. Early CT Series will show arterial vessel contrast as arterial vessels will be the first to see the injected contrast medium. Later CT Series show soft tissue contrast as the arterial vessels transport the contrast medium to the soft tissue organs. Very late CT Series show the excretion of the contrast medium through the urinary tract. How to administer CM into human bodies? Some CM are suitable for enteral application Oral route (by drinking) Rectal application Gaseous CM are suitable for insufflation into enteral structures How to administer CM into human bodies? 2 [audf_013.mp3] Some contrast media are also suitable for drinking. In some cases, rectal application through a small pipe may be beneficial for the examination. Gaseous contrast media are also suitable for enteral structures and can be insufflated into human bodies if needed. Classification of CM used for Computed Tomography (CT) wasser- unlöslich Contrast Media positive negative Iodine Barium water- soluble water- insoluble Air, CO2 Mannitol Classification of CM used for Computed Tomography (CT) [audf_014.mp3] On this page, you see an overview of different contrast media used for computed tomography. This overview also provides a general classification system for contrast media used in CT diagnostics.   Contrast media for CT can be divided into two main groups: positive and negative contrast media. Negative contrast media are represented by air, CO2, and a substance called mannitol. Positive contrast media with their representatives iodine and barium can further be divided into water-soluble and water-insoluble. Barium containing contrast media are always water-insoluble, whereas iodine containing contrast media can be both. Negative CM Negative CM result in hyper-transparencies Increased permeability of X-ray photons  X-ray density drops Tissues with negative CM appear “darker” on CT images Negative CM [audf_015.mp3] Some basic features about negative contrast media. Negative contrast media result in hyper-transparencies due to increased X-ray permeability. All tissues containing negative contrast media appear darker on CT images. Air Air represents a major inherent negative CM in humans Responsible for classic appearance of chest CT images May indicate pathologies by its presence in atypic locations Air between lung tissue and chest wall (“pneumothorax”) Air outside of small and large bowel (“perforation”) Serious injuries sometimes contain air filled-spaces (“traumatic”) Air [audf_016.mp3] Air is a basic negative contrast medium inherent in every human body. As we have seen for radiographs, the high contrast appearance of lung tissue compared to other tissue is responsible for the image properties of a chest CT.   Additionally, the presence of air may indicate pathologies in the chest and abdominal region. For example, air between lung tissue and the chest wall is pathological and is called pneumothorax. Air outside the bowel is called perforation and indicates a certain damage of the bowel wall. Some serious injuries can lead to air-filled soft tissue areas, whereas air can also be displaced from the inside to the outside of the body. Air – Sample images of normal chest CT (soft tissue and lung window) Sample image of normal chest CT [audf_017.mp3] These are example images of a normal chest CT examination. As is common for chest CT, images are presented in a soft tissue window on the left side and in a lung tissue window on the right side, respectively. In both presentations, air-filled lung tissue has a darker appearance than surrounding tissue due to its higher X-ray permeability. Air – Sample image of abnormal air between lung tissue and chest wall (“pneumothorax”) : Abnormal air Sample image of abnormal air [audf_018.mp3] This sample image shows a patient with pathological air between lung tissue and the chest wall on the left side of the patient. Please note that all radiological images are presented mirror-inverted. Therefore, the right image side represents the left patient side. The red asterisk marks the pathological air accumulation, called a pneumothorax. Air – Sample image of abnormal air-filled spaces in the chest wall, caused by fractures of the ribs : Abnormal air inside chest wall and adjacent rib fracture Sample image of abnormal air-filled spaces [audf_019.mp3] Another sample image illustrates abnormal air-filled spaces in the chest wall next to the ribs on the right side. The patient suffered severe injuries with multiple rib fractures on the right side. These rib fractures injured the lung tissue and, thus, pathological air from the inside is accumulated in the nearby chest wall marked by the red asterisk. CO2 CO2 administration into vessels is uncommon for CT diagnostics CO2 is routinely used for insufflation of the large bowel for expansion An expanded large bowel is a necessary precondition for specific CT diagnostics of the large intestine (“Virtual Coloscopy CT”) CO2 disappears via naturalis or is absorbed through the intestinal wall and is exhaled Indications: Screening for Colorectal Cancer CO2 [audf_020.mp3] Another negative contrast medium is CO2 which can be delivered into the vessel system, but this is uncommon for CT diagnostics.   Alternatively, CO2 can be administered into the large bowel for expansion. An expanded bowel is necessary when looking for specific pathologies of the bowel structures, such as tumors.   CO2 is nontoxic when insufflated into enteral structures as it disappears following the natural path or can be exhaled after absorption through the intestinal wall.   One specific indication for CO2 in CT diagnostics is the screening for cancer in the large bowel. CO2 – Sample images of Virtual Coloscopy Gas-filled large bowel with 3D reconstructions; CO2 is invisible CO2 - Sample images of Virtual Coloscopy [audf_021.mp3] Here are some sample images of a CT examination with insufflated CO2 in the large bowel. The bowel is expanded for accurate diagnosis. Dedicated postprocessing algorithms allow to virtually render the large bowel from the inside in a 3D data set and enable almost the same impression as a conventional coloscopy. Mannitol Mannitol = sugar alcohol (fine-grained powder) Commonly used for bowel contrast (“Enterography”) Mannitol and water are mixed prior to application (mixing ratio: 45 g mannitol dissolved in 1.5 L water) Enables excellent bowel wall visibility and expands intestinal structures Indications: Suspected small or large bowel tumors or infections Mannitol [audf_022.mp3] The substance mannitol is commonly used in CT diagnostics. Mannitol is a sugar-based alcohol that is routinely used for negative bowel contrast. Mannitol and water are mixed prior to the CT examination and can be administered orally and rectally. Mannitol enables excellent bowel wall visibility and expands enteral structures. The two main indications for mannitol are suspected bowel tumors or infections. Mannitol – Sample images of expanded large bowel structures filled with mannitol-water mixture in the lesser pelvis CT Abdomen coronare Rekon RektumCA.jpg CT Abdomen axiale Rekon RektumCA.jpg CT Abdomen sagittale Rekon RektumCA.jpg : Negative contrast inside the bowel Mannitol - Sample images [audf_023.mp3] These sample images illustrate the expanded large bowel in the lesser pelvis after the administration of a mannitol-water mixture. The bowel wall is visible after the administration of an intravenous iodine containing contrast agent prior to the CT examination. Positive CM Positive CM increase absorption of X-ray photons Usually substances with a high atomic number (z) Iodine (z = 53) Barium (z = 56) Tissues or objects containing positive CM appear “brighter” or even “white” on CT images Help to generate contrast between different types of biological tissues Positive CM [audf_024.mp3] Contrary to negative contrast media, positive contrast media increase the absorption of X-ray photons.   Substances containing elements with a high atomic number feature a high absorption rate of X-ray photons.   On CT images, all tissues containing positive contrast media will appear brighter or even white.   Positive contrast media are the main substance group used for distinguishing between different types of biological tissues, e.g. healthy organ tissue and cancer tissue. X-ray attenuation of biologic tissues and iodine Difference in mass attenuation coefficient creates contrast between different materials Contrast between materials depends on X-ray energy level G.M. Currie, Pharmacology, Part 5: CT and MRI Contrast Media, J Nucl Med Technol 2019 X-ray attenuation of biologic tissues and iodine [audf_025.mp3] As positive contrast media are very important for CT diagnostics, we will go a little bit further into detail what is happening physically during a CT examination.   To understand why contrast is observed within CT images after the administration of contrast media, we need to consider two facts: First, the difference in a value called mass attenuation coefficient is responsible for the discrimination between different materials. You can see this effect on the Y-axis. For example, the mass attenuation coefficient for iodine differs from the mass attenuation coefficient of soft tissue and therefore creates a contrast between those two materials.   Second, the difference between mass attenuation coefficients depends on the X-ray energy level as you can see on the X-axis. Thus, contrast properties of the same materials differ when the X-ray energy varies. As a general rule, a high X-ray energy results in a poorer contrast, because the difference between the mass attenuation coefficients diminishes at higher energy levels. Positive CM Positive CM increase X-ray burden! Usage must be reasonable! The diagram illustrates increased DNA damage to cells in the presence of CM after irradiation, compared to cells without CM Grudzenski, Contrast Medium-Enhanced Radiation Damage Caused by CT Examinations, Radiology 2009 Positive CM [audf_026.mp3] We have talked about the basic principle of positive contrast media, the absorption of X-ray photons. This fact leads to one major drawback of this substance group. The X-ray absorption also leads to a significantly higher radiation burden for the patient. Therefore, the usage of any positive contrast media must be reasonable.   The diagram shows a study where the authors investigated the DNA damage of human cells after irradiation. It is clearly shown that the presence of a positive contrast medium significantly increases the DNA damage to cells compared to cells irradiated without contrast medium. Application rate of iodine containing CM per year http://www.sonyuserforum.de/galerie/data/media/815/Fsser2.JPG University Hospital Erlangen 3,931.39 liters per year ca. 2400 kg iodine Worldwide 75 million intravenous CT contrast doses administered G.M. Currie, Pharmacology, Part 5: CT and MRI Contrast Media, J Nucl Med Technol 2019 Application rate of iodine containing CM per year [audf_027.mp3] Positive contrast media, especially iodine containing contrast media, are used worldwide with high application rates.   At the University Hospital Erlangen, approximately 4000 liters of iodine containing contrast media are administered per year, which equals approximately 2.5 tons of pure iodine.   Worldwide, over 75 million intravenous contrast doses are administered per year in CT diagnostics. Barium Barium is generally mixed with water to create a milky suspension Not water-soluble Limited to oral and/or rectal administration Not for intravenous usage No mucosal uptake in the intestine Very good mucosal adhesion Commonly used for radiographic studies of the esophagus and the intestine Possible to use in CT diagnostics for very intense intestinal contrast Barium [audf_028.mp3] Barium is one representative contrast medium substance used worldwide.   Barium is mixed with water to create a milky suspension as shown on the right side. Barium suspensions are not water-soluble and therefore not suitable for intravenous application. Barium is limited to enteral usage only. In the pre-CT era, barium was commonly used for radiography studies of the esophagus and the bowel.   A barium suspension can be used in CT diagnostics whenever a very high contrast of the small or large bowel is required. Barium Barium must not be used when a penetration of the intestine is suspected  Free barium in the abdominal cavity causes severe inflammation (“barium peritonitis”) No usage in case of intestinal obstruction (“ileus”)  Barium possibly worsens the obstruction due to thickening of intestinal content Barium must not be used when swallowing is disturbed (“aspiration”)  Barium causes severe inflammation within lung tissue K. R. Beckett, Safe Use of Contrast Media: What the Radiologist Needs to Know, Radiographics 2015 Barium [audf_029.mp3] Some safety aspects for barium suspensions must be considered before their administration.   Barium must not be used when a damage of the bowel wall is suspected, because free barium in the abdominal cavity can cause a severe inflammation that is called “barium peritonitis“.   Another potential pitfall is the usage of barium when an enteral obstruction is suspected, because barium may worsen the obstruction due to thickening of the intestinal content.   Barium must not be administered when swallowing is disturbed or suspected to be disturbed, because barium can cause a severe inflammation when it gets into the lung. Barium – Sample image of radiographic study of the large intestine Barium creates the white boundary of the large bowel (red arrow) by adhesion to the mucosa D:\Bilder\colon_2_be.jpg Sample image of the large intestine [audf_030.mp3] This is a sample image of a radiographic study of the large bowel after administration of barium. Barium creates a white boundary on the bowel walls by adhesion to the mucosa. The red arrow indicates the thin mucosal adhesion of barium. Barium – Sample image of barium-filled stomach : Barium-filled stomach nativ Sample image of barium-filled stomach [audf_031.mp3] Here is another sample image with barium. In this CT study, the stomach of a patient is filled with barium to gain a very intense positive contrast inside the stomach. The red asterisk marks the barium-filled stomach. Iodine containing CM Iodine containing CM are established in medicine since almost 100 years The workhorse in CT diagnostics Suitable for intravenous and enteral application Two main groups Ionic (electrically charged) Non-ionic (not electrically charged) Iodine containing CM [audf_032.mp3] The second main group representing positive contrast media are iodine containing contrast media.   Iodine containing contrast media are well established in radiology for almost 100 years and are the workhorse in CT diagnostics.   One great advantage is the dual usability for intravenous and enteral applications.   Iodine containing contrast media can be divided into two main groups: ionic substances (which are electrically charged) and non-ionic substances (which are not electrically charged). Iodine containing CM – General structural formula Currently available CM are either monomers (1 benzene ring) or dimers (2 benzene rings) G.M. Currie, Pharmacology, Part 5: CT and MRI Contrast Media, J Nucl Med Technol 2019 Iodine containing CM – General structural formula [audf_033.mp3] In this drawing, you can see the basic chemical structural formulas for ionic and non-ionic iodine containing contrast media. Note the same benzene ring with the six carbon atoms from the introduction. Contrast media substances can be either monomers with one benzene ring or dimers with two connected benzene rings. Iodine containing CM – A variety of different substances Several different iodine containing CM were developed and introduced in the last decades with different physico-chemical properties as shown in the table G.M. Currie, Pharmacology, Part 5: CT and MRI Contrast Media, J Nucl Med Technol 2019 Iodine containing CM – A variety of different substances [audf_034.mp3] There is a variety of different iodine containing contrast media substances on the market, each formula with different physico-chemical properties. Important properties are the iodine concentration, osmolality, and viscosity of a specific substance.   In this compilation you can see a selection of different iodine containing contrast media with different physico-chemical properties. Iodine containing CM – Basic kinetics 90% eliminated 24 h after intravenous administration Mostly eliminated via the kidneys CM could be extracted by dialysis in case of renal failure or insufficiency Iodine containing CM cannot cross the cell membranes or the blood-brain barrier CM firstly transits through the vessel system (“vascular compartment”) and secondly enters the space between vessels and cells (“interstitial compartment”) by free diffusion M. Bourin, An Overview of the Clinical Pharmacokinetics of X-Ray Contrast Media, Clin. Pharmacokinet. 1997 Iodine containing CM – Basic kinetics [audf_035.mp3] In this section, let me introduce some of the basic kinetic properties of iodine containing contrast media to you.   All iodine containing contrast media are mostly eliminated through the urinary tract. 90% of the contrast medium is eliminated via the kidneys. In case of renal failure or insufficiency, iodine containing contrast media can be extracted from the human body by dialysis.   Contrast media cannot cross the cell membranes or the blood-brain barrier. After intravenous administration, the contrast medium travels to the heart and subsequently transits through the arterial vessel system to reach the organ system. Contrast media accumulate in the space between vessels and cells by free diffusion for a certain time, while simultaneously undergoing renal elimination. Iodine containing CM – Basic kinetics Scheme of a 2-compartment model for intravenously administered CM k1-6: rate constants describing the exchange between different compartments Almost exclusive elimination by filtration in the kidneys G.M. Currie, Pharmacology, Part 5: CT and MRI Contrast Media, J Nucl Med Technol 2019 Iodine containing CM – Basic kinetics [audf_036.mp3] This drawing shows in more detail the basic kinetics of iodine containing contrast media when administered intravenously.   After delivery through a cannula into the human body, the contrast medium travels in the vascular compartment before reaching the extravascular compartment in healthy or pathological tissue. Immediately after reaching the extravascular space, the elimination process by renal filtration begins. Iodine containing CM – Basic properties Principle: Physico-chemical properties of CM can differ from substance to substance and are mostly responsible for their adverse side effects A high water-solubility is necessary to obtain highly concentrated solutions Viscosity determines fluidity through medical devices, e.g. cannulas for intravenous application High viscosity can enhance the vessel contrast, but can also hamper the vessel wall Osmotic pressure G.M. Currie, Pharmacology, Part 5: CT and MRI Contrast Media, J Nucl Med Technol 2019 Iodine containing CM – Basic properties [audf_037.mp3] Let me introduce some of the basic properties of iodine containing contrast media to you.   As we have already seen, the physico-chemical properties are very different among different substances and are mostly responsible for adverse side effects.   A high water solubility is necessary to obtain highly concentrated solutions for optimal CT contrast.   Viscosity determines fluidity, for example through cannulas. A high viscosity can on the one hand enhance the vessel contrast but can on the other hand lead to a severe damage of the vessel wall.   Osmotic pressure is a key property of contrast media and will be discussed in detail on the next couple of pages. Iodine containing CM – Osmotic pressure Osmotic pressure is specified by Osmolarity (dissolved particles per liter of water) Osmolality (dissolved particles per kg of water) CM are usually specified by osmolality Osmolality of human blood is approximately 290 mOsmol/kg water Most iodine containing CM have higher osmolality than human blood High osmolality is responsible for several side effects Iodine containing CM – Osmotic pressure [audf_038.mp3] Osmotic pressure can be specified by two different values. Osmolarity is defined by dissolved particles per liter of water and osmolality is defined by dissolved particles per kilogram of water. Contrast media are usually specified by osmolality.   It is important to understand that most iodine containing contrast media have a higher osmolality than human blood and that this high osmolality is responsible for several side effects. Iodine containing CM – Side effects caused by hyperosmolality Hyperosmolality may cause Damage of vessel walls (patient feels pain during injection) Reduced heart rate (“bradycardia”) Heat sensation in case of fast injection Dilatation of vessels (“vasodilatation”) Urge to urinate (“diuresis”) Increase of circulating blood volume (“hypervolemia”) Iodine containing CM – Side effects caused by hyperosmolality [audf_039.mp3] On this page, you will learn about important adverse effects caused by high osmolality of iodine containing contrast media.   Hyperosmolality may cause damage to vessel walls, which equals pain during the process of injection.   Further side effects are a reduced heart rate, heat sensation in case of fast injection, dilatation of vessels, an urge to urinate, and an increase of the circulating blood volume. Iodine containing CM – Classification defined by osmolality Ionic CM Non-ionic CM Very high osmolality Moderate to high osmolality No admission for intravenous and intraarterial usage since 2000 Standard application for intravenous and intraarterial injection during CT examinations Iodine containing CM – Classification defined by osmolality [audf_040.mp3] We have learned about the classification into ionic and non-ionic iodine containing contrast media. Now we can expand this classification with our knowledge about the osmolality.   Ionic contrast media usually have a very high osmolality and, due to their high rate of unwanted side effects, they do not have admission for intravenous and intraarterial use since the year 2000.   Non-ionic contrast media have a moderate to high osmolality and represent the standard for intravenous and intraarterial usage. Iodine containing CM – Advantages of non-ionic CM Major advantages of non-ionic CM Significantly fewer moderate and severe side effects than ionic CM (nausea, vomiting, allergic reactions, allergic shock) No electric charge when dissolved  No interference with the cell membranes Iodine containing CM – Advantages of non-ionic CM [audf_041.mp3] Let me show you some of the advantages of non-ionic contrast media substances compared to ionic contrast media substances.   Non-ionic contrast media have significantly fewer side effects like nausea, vomiting, allergic reactions, and allergic shock. Moreover, non-ionic contrast media show no interference with cell membranes because they have no electric charge when dissolved. Iodine containing CM – Peritrast Peritrast as an example for oral and rectal usage Very high osmolality (ionic, 1380 mOsmol/kg) 300 mg iodine per mL May cause diarrhea due to hyperosmolality Dilution with water is necessary for CT usage (pure Peritrast can cause artifacts) Mixing ratio: 15 mL Peritrast per liter water Iodine containing CM – Peritrast [audf_042.mp3] On the next couple of pages, we will talk about some typical iodine containing contrast media substances routinely used in CT diagnostics.   Peritrast is a contrast medium for oral and rectal usage due to its very high osmolality which makes it unsuitable for intravenous or intraarterial usage.   Peritrast contains 300 mg of iodine per milliliter. Due to its hyperosmolal character, Peritrast may cause diarrhea.   In CT diagnostics, Peritrast needs to be diluted to a certain level because pure Peritrast can cause artifacts. Peritrast – Sample images of small and large intestine filled with Peritrast Sample images of small and large intestine [audf_043.mp3] These are sample images of a patient after receiving a Peritrast-water mixture orally, resulting in a very high positive contrast in the intestine. Note the similarity to barium-filled enteral structures shown earlier. Iodine containing CM – Iomeron Iomeron as an example for intravenous and intraarterial usage Non-ionic (500 to 600 mOsmol/kg) Available iodine content: 300, 350, and 400 mg iodine per mL Suitable for all CT examinations Excellent tolerance and relatively low rate of adverse side effects Iodine containing CM – Iomeron [audf_044.mp3] Another popular iodine containing contrast medium is Iomeron.   It is suitable for intravenous and intraarterial usage due to its moderate osmolality based on its non-ionic structure.   Iomeron is available with different iodine content: 300, 350, and 400 mg of iodine per milliliter are typically used.   Iomeron has a relatively low rate of unwanted side effects and is therefore tolerated by many patients. Iomeron – Sample images of intravenous usage of Iomeron : Enhancement of the pulmonary arteries Sample images of intravenous usage of Iomeron [audf_045.mp3] These are sample images of a patient after receiving Iomeron intravenously for vessel contrast of the pulmonary arteries. The red asterisks are marking the pulmonary arteries within the chest. Iodine containing CM – Adverse drug reactions All iodine containing CM may cause adverse drug reactions Side effects range from mild to severe and fatal Risks for adverse drug reactions Ionic CM have higher probability than non-ionic CM Intravenous and intraarterial usage have higher probability than oral and rectal usage Patients with a history of allergic reactions and asthma have higher probability Iodine containing CM – Adverse drug reactions [audf_046.mp3] It is very important to understand that all iodine containing contrast media may cause adverse drug reactions, no matter if they are ionic or non-ionic.   Adverse side effects range from mild to severe and sometimes even fatal events. As described earlier in this workshop, ionic contrast media have a higher probability for adverse reactions than non-ionic substances. Additionally, intravenous and intraarterial usage have a higher probability for adverse effects than oral and rectal usage. Patients with a history of allergic reactions and asthma are at higher risk for adverse reactions. Iodine containing CM – Adverse reactions Adverse drug reactions General adverse reactions (non-kidney related) Kidney-related adverse reactions (“renal”) Other adverse reactions Iodine containing CM – Adverse reactions [audf_047.mp3] Adverse reactions for iodine containing contrast media can be divided into three main groups: General reactions that are non-kidney related, kidney-related reactions, and other adverse reactions. Iodine containing CM – Adverse reactions Medical guidelines for handling adverse drug reactions related to contrast media: ESUR Guidelines (European Society of Urogenital Radiology) Current version 10.0 http://www.esur-cm.org/images/Version10/V10logo.png http://www.esur.org/esur-guidelines/ Iodine containing CM – Adverse reactions [audf_048.mp3] Information about handling adverse reactions can be found in the current ESUR Guidelines version 10.0.   ESUR guidelines include information about iodine and gadolinium containing contrast media for usage in CT and MRI diagnostics. Iodine containing CM – General adverse reactions General adverse drug reactions are not related to the CM dose Classification by time of occurrence Acute (within the first minutes after injection) Sub-acute (within two days after application) Late (later than two days after application) ESUR v10.0 Iodine containing CM – General adverse reactions [audf_049.mp3] General adverse reactions are not related to the administered contrast media dose.   The classification of general adverse reactions can be further specified by the time of occurrence after injection. Acute adverse reactions start within the first minutes, sub-acute reactions within two days, and late adverse reactions will appear more than two days, possibly a few weeks later. Iodine containing CM – General adverse reactions Acute general adverse drug reactions Mild reactions: nausea, itching, vomiting, heat sensation, skin rash, sneezing Severe reactions: shortness of breath, low blood pressure, loss of consciousness, heart failure, coma ESUR v10.0 Iodine containing CM – General adverse reactions [audf_050.mp3] Acute general adverse reactions can also be classified by their severity.   They can range from mild reactions, e.g. nausea or itching, to severe reactions such as low blood pressure or even coma. In case of a severe reaction, immediate medical treatment is necessary. Iodine containing CM – General adverse reactions Sub-acute general adverse reactions Skin reactions: rash, swelling Headache Nausea, vomiting, diarrhea Pain in location where the CM was administered (e.g. forearm) Flu-like symptoms (shivering, tiredness) ESUR v10.0 Iodine containing CM – General adverse reactions [audf_051.mp3] Sub-acute general adverse reactions may include skin reactions, headache, nausea, vomiting, and diarrhea. Pain in the area of injection as well as general flu-like symptoms may also occur.   Iodine containing CM – General adverse reactions Late general adverse drug reactions Malfunction of thyroid gland (“thyroid toxicosis”) Patients at risk Hyperfunction of the thyroid gland Autoimmune toxic diffuse goiter (Grave‘s disease, hyperfunction) Goiter Prevention strategy: 1200 mg sodium perchlorate (Irenat) 2 hours prior to examination and for 14 days afterwards ESUR v10.0 Iodine containing CM – General adverse reactions [audf_052.mp3] As said before, late general adverse reactions occur after a minimum of two days, but usually occur after several days or weeks.   A typical late general reaction is the malfunction of the thyroid gland with an excess of thyroid hormones after the injection of iodine containing contrast media. Patients at risk must be identified prior to the injection. A hyperfunction of the thyroid gland and autoimmune toxic diffuse goiter (also known as Grave‘s disease) are the two most common high-risk conditions prior to a CT examination.   As a prevention strategy, sodium perchlorate should be given approximately two hours prior to the CT examination and for 14 days afterwards to prevent the iodine from the contrast media to be absorbed by the thyroid gland. Nevertheless, subsequent inspections of the thyroid gland function are necessary. Iodine containing CM – Strategies to avoid and manage general adverse reactions Consider necessity of CM Consider alternatives (MRI, ultrasound) in case of history of adverse reactions or in case of high risk profile Application of non-ionic CM instead of ionic CM A different CM product should be used for previous CM reactors Premedication Monitoring of each patient for at least 30 min. after CM application Emergency equipment must be available ESUR v10.0 Iodine containing CM – Strategies to avoid and manage general adverse reactions [audf_053.mp3] According to the ESUR guidelines, general strategies to avoid and manage general adverse reactions are explained in the following.   Always consider the necessity of a contrast medium. In this context, always remember that positive contrast media increase the radiation burden for the patient.   Consider also alternative diagnostic modalities, such as ultrasound or MRI, in case of a history of adverse reactions or in case of a high risk profile. Always prefer non-ionic iodine containing contrast media over ionic contrast media.   In case of prior adverse reactions, consider switching to another contrast medium product. In some cases, additional substances added to the contrast media may be responsible for an adverse reaction.   Consider also a premedication strategy for high-risk patients. Each patient should be monitored at least for 30 minutes after the application of contrast media.   Emergency equipment must be ready at all times. Iodine containing CM – Premedication prior to CM Benefits and effectiveness of premedication prior to CM application are controversial Corresponding to ESUR guidelines 10.0: Premedication is not recommended because there is not good evidence for its effectiveness ESUR v10.0 Iodine containing CM – Premedication prior to CM [audf_054.mp3] Premedication prior to the application of contrast media seems to be an effective way of controlling adverse reactions, but the benefits and effectiveness of these drug-based pretreatments are subject of a controversial debate. For several years, patients at risk or with a history of adverse reactions received steroids and other anti-allergic medication prior to CT examination. However, in the latest ESUR guidelines premedication is not recommended because there are no data available for its effectiveness. Iodine containing CM – Kidney-related adverse drug reactions Kidney damage after CM application is a severe side effect which can lead to a total loss of kidney function Risk factors Low kidney function estimated filtration rate < 45 mL/min/1.73 m² for intraarterial injection before the kidney arteries estimated filtration rate < 30 mL/min/1.73 m² for intraarterial injection after the kidney arteries or intravenous injection Acute renal failure High osmolality of the CM Multiple CM injections within 48 to 72 hours ESUR v10.0 Iodine containing CM – Kidney-related adverse drug reactions [audf_055.mp3] Kidney-related adverse reactions are dreaded and can lead to severe consequences. The total loss of the kidney function is possible after a single dose of iodine containing contrast media.   Risk factors which should be assessed prior to the CT examination are a low kidney function, acute renal failure, high osmolality of a substance, and multiple contrast media injections within 3 days. Iodine containing CM – Kidney-related adverse drug reactions Strategies to avoid kidney damage after CM application Preventive hydration prior to the examination (3-4 hours before CM application; 1 mL sodium chloride infusion per kg body weight per hour) Hydration after CM application (4-6 hours after CM application) Oral hydration is not recommended as the sole method of prevention Surveillance of kidney function within 48 hours after CM application If the kidney function deteriorates, patient monitoring for at least 30 days is necessary Dialysis of CM is possible, but no evidence for protection of kidney function if performed after CM application ESUR v10.0 Iodine containing CM – Kidney-related adverse drug reactions [audf_056.mp3] What to do if a patient has a low kidney function but a CT examination is crucial for the following therapy or a CT with contrast medium is even vitally important?   A preventive intravenous hydration prior to the CT scan and afterwards is recommended for all patients with a reduced kidney function. Oral hydration is not recommended as the sole method of prevention. After the CT examination, surveillance of the kidney function is mandatory within 48 hours to a maximum of 30 days. Immediate dialysis is possible, but no evidence for its effectiveness exists in the literature. Iodine containing CM – Other adverse drug reactions Other adverse drug reactions Failed intravenous or intraarterial injection (“paravasation”) Interaction with other drugs Application during pregnancy Application during lactation ESUR v10.0 Iodine containing CM – Other adverse drug reactions [audf_057.mp3] Other adverse reactions may be a failed intravenous or intraarterial injection, which can cause a painful contrast medium depot within the skin tissue.   Interactions are known with other medical drugs.   The application during pregnancy and lactation period is a controversial issue. Failed intravenous injection – Sample image of Iomeron located within the soft tissues of the right elbow : Paravasation Sample image of elbow [audf_058.mp3] Sample images of a patient with a failed intravenous injection of iodine containing contrast medium. The contrast medium forms a depot located within the skin and soft tissue of the right elbow. Red asterisks mark the so-called paravasation of the contrast medium. Iodine containing CM – Other adverse drug reactions Interaction with other drugs For example: Metformin (antidiabetic drug), Cyclosporin (immunosuppression), Cisplatin (chemotherapy), and many others … Usage during pregnancy If essential for diagnosis, CM may be given Thyroid function of the newborn should be evaluated in the first week after birth Usage during lactation Breast feeding may be continued regularly ESUR v10.0 Iodine containing CM – Other adverse drug reactions [audf_059.mp3] Several drug interactions are well known, e.g. with metformin, a classic antidiabetic drug. Other interactions may happen during chemotherapy or immunosuppression.   Usage of iodine containing contrast media during pregnancy is not prohibited, but the application should be restricted to cases where its usage is essential for diagnosis. The thyroid function of the newborn should be evaluated after birth.   The usage of contrast media during the lactation period is unproblematic, breast feeding may be continued regularly. Some physicians advise to stop breast feeding for 48 hours. Role of modern CT diagnostics CT systems with improved spatial and temporal resolution allow highly sophisticated examinations, such as cardiac CT and CT angiography CT angiography can replace conventional catheter-based angiography in many situations Functional CT imaging, e.g. perfusion CT of the brain, has become a routine examination Modern CT techniques demand advanced scanning protocols with special focus on CM application techniques K.T. Bae, Intravenous Contrast Medium Administration and Scan Timing at CT, Radiology 2010 Role of modern CT diagnostics [audf_060.mp3] We have learned about the basic physico-chemical properties of iodine containing contrast media and possible side effects after administration. In the next part of this workshop, you will hear about the different application techniques of contrast media in CT diagnostics.   As an introduction, the role of modern CT is explained in a few comments. Continuous improvements of CT technology have led to scanning systems with enhanced spatial and temporal resolution. These modern scanning systems allow highly sophisticated examinations such as cardiac CT and CT angiography. For example, CT angiography has replaced conventional catheter-based angiography in many situations and delivers precise information about the vessel anatomy and its related pathologies. In some situations, the knowledge of functional properties of the human tissue is highly beneficial for further therapeutical strategies and decisions. For example, perfusion CT of the brain is a routine examination for stroke patients.   In summary, all these advanced modern CT techniques call for advanced scanning protocols with a special focus on contrast media application techniques. Diagnostic targets for CM application Vessel contrast (arteries and veins) Organ contrast (tumor detection, infection, …) Organ perfusion (e.g. brain tissue  stroke detection) Intestine (transport, tumor, …) Urinary tract (excretion, tumor, …) Diagnostic targets for CM application [audf_061.mp3] Prior to each CT examination, the radiologist has to determine the diagnostic targets.   The referring physician may have questions about the vessel contrast, the organ contrast, the organ perfusion, the intestinal system, or the urinary tract. Image contrast weight cardiac function stenosis aneurysm breathhold voltage delay duration collimation rotation time concentration flow temperature flux bolus length volume split bolus chaser direction arrival time Image contrast [audf_062.mp3] One important issue to understand is that CT diagnostics consists of diverse variables with patient-specific, CT-specific, and injector-specific values.   As a general rule, standardizing most of these variables can be regarded as a major goal in CT diagnostics. CT-specific and injector-specific variables are much easier to control and standardize than patient-specific variables.   In summary, due to all these different variables, a worldwide standard for every CT examination is impossible to define. CM application technique Basic variables for CM injection (intravenous & intraarterial) Concentration (mg iodine per mL) CM volume (mL) Flow rate (mL/s) Iodine flux (mg/s) Viscosity CM application technique [audf_063.mp3] Key variables for the injection of contrast media are concentration, injection volume, flow rate, iodine flux, and viscosity.   We will discuss those basic contrast media specific variables in detail on the next pages. Relationship between iodine flux and enhancement K.T. Bae, Intravenous Contrast Medium Administration and Scan Timing at CT, Radiology 2010 Contrast enhancement curves of the aorta in a 70 kg male: CM volume = 125 mL CM injection rate = 4 mL/s Higher concentrations increase the iodine flux and therefore the peak attenuation. Relationship between iodine flux and enhancement [audf_064.mp3] The relationship between iodine flux and enhancement is quite simple as more injected iodine per time will increase the attenuation of X-ray photons and enhance the contrast. Note that the enhancement is also a function of time. Relationship between injection duration and enhancement K.T. Bae, Intravenous Contrast Medium Administration and Scan Timing at CT, Radiology 2010 Contrast enhancement curves of the aorta in a 70 kg male: CM injection rate = 2 mL/s CM concentration = 350 mg(iodine)/mL Larger CM volumes at constant injection rates go along with increased and later peak attenuations. Relationship between injection duration and enhancement [audf_065.mp3] To understand the relationship between injection duration and enhancement, please note that the injection rate is constant in this example. A greater contrast medium volume takes more time to be injected. Consequently, the peak enhancement is reached later. Due to the greater contrast medium dose injected, the enhancement peak also increases. Relationship between injection rate and enhancement K.T. Bae, Intravenous Contrast Medium Administration and Scan Timing at CT, Radiology 2010 Contrast enhancement curves of the aorta in a 70 kg male: CM volume = 125 mL CM concentration = 350 mg(iodine)/mL Peak of contrast enhancement increases with rising injection rate, but the duration of high-magnitude contrast enhancement decreases (= smaller diagnostic window). Relationship between injection rate and enhancement [audf_066.mp3] The relationship between injection rate and enhancement is illustrated by two important facts. Peak enhancement increases with rising injection rate, but the duration of the high-magnitude contrast enhancement decreases. This leads to a smaller diagnostic window in examinations where a high contrast in a certain tissue is required. Relationship between iodine concentration, voltage, and enhancement K.T. Bae, Intravenous Contrast Medium Administration and Scan Timing at CT, Radiology 2010 For a given tube voltage, contrast enhancement is proportional to the iodine concentration. The use of lower tube voltage results in increased iodine contrast at a given concentration. Consequently, the required amount of injected CM may be reduced by using lower tube voltage settings, but at the expense of higher image noise if the tube current remains constant. Relationship between iodine concentration, voltage, and enhancement [audf_067.mp3] The relationship between iodine concentration, tube voltage, and enhancement is the basis for one of the latest CT scanning technologies concerning the reduction of the radiation burden, called automated tube voltage adaptation (CarekV).   If the tube voltage is kept constant, the enhancement is proportional to the administered iodine concentration. In contrast to what one might expect, the use of lower tube voltages results in an increased iodine enhancement at a given iodine concentration. The use of lower tube voltage protocols can significantly reduce the radiation burden but may also increase image noise if the tube current remains constant. CM viscosity Viscosity increases with CM concentration Viscosity depends on temperature (high temperature  lower viscosity) CM should be warmed prior to injection (35° Celsius) Warm CM allow for higher peaks and steeper slopes of the attenuation K.T. Bae, Intravenous Contrast Medium Administration and Scan Timing at CT, Radiology 2010 CM viscosity [audf_068.mp3] The viscosity of contrast media is also an important variable. In general, the viscosity increases with the contrast media concentration and decreases with higher temperatures. Therefore, contrast media should be warmed prior to injection to avoid vessel damage. Warm contrast media allow for higher peaks and steeper slopes of the attenuation. CT parameters CT examination parameters are crucial for the acquisition of contrast-enhanced images Scan duration Scan direction CM bolus arrival time Scan delay K.T. Bae, Intravenous Contrast Medium Administration and Scan Timing at CT, Radiology 2010 CT parameters [audf_069.mp3] Besides injection parameters, technical CT parameters are also essential for the acquisition of any contrast-enhanced examination.   The four most important CT parameters are scan duration, scan direction, contrast bolus arrival time, and scan delay. These parameters will be explained in detail. CT examination duration Scan duration is an essential input parameter for calculation of the CM bolus design Long CT examinations require long CM injections as a basic principle Duration of a CT examination depends on collimation, rotation time, and pitch While many CT protocols are < 10 seconds, some examinations require a longer duration: CT angiography with large anatomic coverage to allow CM to transit into peripheral arteries Perfusion acquisitions with different phases of contrast enhancement K.T. Bae, Intravenous Contrast Medium Administration and Scan Timing at CT, Radiology 2010 CT examination duration [audf_070.mp3] By defining the CT scan duration time, the design of the contrast media bolus subsequently has to follow this calculation. In general, long CT examinations require long injection times of the contrast medium. While most CT examinations are below 10 seconds of duration, some examinations require a longer duration. Among the long-lasting procedures is CT angiography with a large volume coverage to allow the contrast medium to transit into peripheral body areas, especially when the heart function is reduced. Perfusion examinations with different phases of contrast enhancement also require a longer duration. CT scan direction Scan direction is typically chosen in the same direction as the CM propagation to “surf on the bolus”: Craniocaudal (from top to bottom) direction below the shoulders Caudocranial (from bottom to top) direction above the shoulders One exception is pulmonary CT angiography: Caudocranial direction to avoid streak artifacts from venous CM inflow in the upper veins and to avoid motion artifacts from the diaphragm (breathing in case of shortness of breath) K.T. Bae, Intravenous Contrast Medium Administration and Scan Timing at CT, Radiology 2010 CT scan direction [audf_071.mp3] As a general principle, the scan direction is chosen in the same direction as the contrast medium is propagated inside the human body, either craniocaudal below the shoulders or caudocranial above the shoulders.   One exception is pulmonary CT angiography where the scan direction is switched to caudocranial to avoid artifacts from venous inflow into the upper veins and to avoid motion artifacts from the diaphragm. Determination of CM arrival time CM bolus arrival time is heavily affected by the individual cardiovascular physiology (“CM transit time”) CM transit time can be measured prior to the CT examination by two different methods: “Test bolus” method “Bolus tracking” method Both methods measure the bolus arrival time by periodically repeated sequential single-slice acquisitions after CM injection A dedicated delay of the examination can be added after bolus arrival K.T. Bae, Intravenous Contrast Medium Administration and Scan Timing at CT, Radiology 2010 Determination of CM arrival time [audf_072.mp3] The precise determination of the arrival time of the contrast medium within the human body is crucial to perform a CT scan with the highest iodine contrast. If needed, the examination can also be started after setting an additional delay. The bolus arrival time is heavily affected by the individual cardiovascular function and is called contrast media transit time.   The individual contrast medium transit time can be measured prior to the CT examination by two different methods, the test bolus method and the bolus tracking method. Both methods measure the arrival time of the contrast medium bolus by repeated sequential single-slice acquisitions. Determination of CM arrival time “Test bolus” method Small volume (e.g. 10 mL) of CM injected intravenously Sequential single-slice position acquisitions to measure the bolus arrival in the target volume Peak attenuation in the vessel permits calculation of individual CT scan delay “Bolus tracking” method Definition of a target vessel in a single-slice acquisition Injection of the entire volume of CM Sequential single-slice position acquisitions until bolus arrival Automated or manual start of the CT scan after a defined attenuation threshold (e.g. 100 HU) is attained Determination of CM arrival time [audf_073.mp3] When using the test bolus method, a small volume of contrast medium, e.g. 10 milliliters, is injected intravenously. In a target volume, e.g. the aorta or another bigger arterial vessel, the arrival time is measured by using sequential single-slice acquisitions. After identification of the peak attenuation in the target volume, the individual arrival time permits the calculation of the individual CT scan delay.   The second method, the bolus tracking method, uses a similar approach, but after defining the target volume the entire contrast medium volume is injected at once. Similar to the test bolus method, a sequential single-slice acquisition is performed repeatedly until the injected contrast medium arrives and reaches a predefined threshold attenuation in the target volume. After reaching the threshold attenuation, the CT scan may commence immediately or after an additional delay time. Determination of scan delay and injection duration K.T. Bae, Intravenous Contrast Medium Administration and Scan Timing at CT, Radiology 2010 The bolus tracking method was used in this figure with a threshold of 50 HU in the aorta (= CM arrival time). Scan delay is the sum of CM arrival time plus an additional, target-region dependent delay. The additional delay considers CM injection duration and scan duration. The CT acquisition should be centered around the peak enhancement. Determination of scan delay and injection duration [audf_074.mp3] As shown in this figure, the bolus tracking method was used with an attenuation threshold of 50 Hounsfield Units in the target volume. The target volume was defined in the aorta. The scan delay is the sum of the contrast medium arrival time plus an additional delay depending on the examined target region. The additional delay considers the contrast medium injection duration and the scan duration.   The CT acquisition should be centered around the peak enhancement of the target region. Different body regions K.T. Bae, Intravenous Contrast Medium Administration and Scan Timing at CT, Radiology 2010 Time-enhancement plots for different target regions. Different scan delays are necessary to meet the peak enhancement of each organ. Different body regions [audf_075.mp3] One important fact to understand is that different body regions require different scan delays to meet the peak enhancement of each target organ after administration of a contrast medium. Sample image of a workflow to determine CM arrival time prior to CT scan with the bolus tracking method : Region of Interest (ROI) in a single-slice position in the aorta : Threshold Sample image of a workflow [audf_076.mp3] This is a sample image of a workflow to determine the contrast medium arrival time prior to the CT scan with the bolus tracking method. The red circle marks the target volume (also called “Region of Interest“) in the aorta, the green circle marks the predefined threshold of the target volume. Sample image of the bolus tracking workflow (1: Topogram) : The pre-monitoring slice is determined in the topogram Sample image of the bolus tracking workflow 1 [audf_077.mp3] The bolus tracking workflow begins with the topogram on which the pre-monitoring slice is determined. Sample image of the bolus tracking workflow (2: Pre-monitoring slice) The pre-monitoring slice is scanned once before CM injection to determine the ROI position for the threshold measurements Sample image of the bolus tracking workflow 2 [audf_078.mp3] The pre-monitoring slice is scanned once before the injection of the contrast medium to determine the correct position of the target volume for the threshold measurements. Sample image of the bolus tracking workflow (3: Monitoring slice) The monitoring slice is then scanned repeatedly until the enhancement within the defined ROI reaches the threshold : ROI Sample image of the bolus tracking workflow 3 [audf_079.mp3] After the injection of the contrast medium, the monitoring slice with the target volume is scanned repeatedly until the attenuation reaches the threshold value within the target volume. The red circle marks the target volume in the aorta. Patient-related factors The most important patient-related factor is body weight Larger patients have higher blood volumes; thus, injected CM is diluted to a higher degree, which may result in lower peak enhancement Age, sex, site of venous access, heart and renal functions, and many others are considered to be less influential K.T. Bae, Intravenous Contrast Medium Administration and Scan Timing at CT, Radiology 2010 Patient-related factors [audf_080.mp3] Last but not least, patient-related factors have to be considered before performing a CT scan with contrast medium injection. The most important factor is the body weight. Larger patients have larger blood volumes. Thus, the injected amount of contrast medium is diluted to a higher degree, which may result in a lower peak enhancement.   Other factors (such as age, sex, site of venous access, heart function, renal function, and many others) are considered to be less influential. Patient-related factors K.T. Bae, Intravenous Contrast Medium Administration and Scan Timing at CT, Radiology 2010 Contrast enhancement curves in the liver at different body weights: CM volume = 125 mL CM injection rate = 4 mL/s Peak enhancement is inversely proportional to the body weight. Adjustment of the contrast agent dose to the body weight is recommended to attain comparable image contrast in a clinical collective. Patient-related factors [audf_081.mp3] This figure illustrates the inversely proportional relationship between body weight and peak enhancement. Higher body weight results in lower peak enhancement if the contrast medium volume and injection rate are kept constant. CM dose adaption to body weight and tube voltage Table with 4 columns and 12 rows Body weight 120 kV tube voltage 100 kV tube voltage 80 kV tube voltage 40 kg 57 mL 46 mL 34 mL 50 kg 71 mL 57 mL 43 mL 60 kg 86 mL 69 mL 51 mL 70 kg 100 mL 80 mL 60 mL 80 kg 114 mL 91 mL 69 mL 90 kg 129 mL 103 mL 77 mL 100 kg 143 mL 114 mL 86 mL 110 kg 157 mL 126 mL 94 mL 120 kg 172 mL 137 mL 103 mL 130 kg 186 mL 149 mL 111 mL 140 kg 200 mL 160 mL 120 mL Standard operating procedure (SOP) for CM dose (350 mg/mL) in abdominal CT, University Hospital Erlangen E. Perrin, Weight-adapted iodinated contrast media administration in abdomino-pelvic CT: Can image quality be maintained?, Radiography 2018 CM dose adaption to body weight and tube voltage [audf_082.mp3] For this reason, contrast media doses are usually adapted to the individual body weight and are also adapted to the tube voltage. We have already discussed that lower tube voltages can result in higher peak enhancement and, therefore, the amount of required contrast media can be lowered. Factors with influence on the CM dose calculation A variety of technical and patient-related factors affect the application of CM General CM and CT protocols cannot be provided due to the plurality of influencing factors: Factors with influence on the CM dose calculation [audf_083.mp3] In summary, a variety of technical and patient-related factors affect the application strategy of contrast media in CT diagnostics.   Due to the plurality of influencing factors it is not possible to provide general protocols or parameters for contrast media application or CT acquisition. Examples of different protocols CT of the pulmonary arteries CT of the coronary arteries CT of the lower extremities CT of the aorta CT of the carotid arteries CT of the abdomen CT of a brain perfusion Examples of different protocols [audf_084.mp3] In the last part of this e-learning workshop, some examples of routinely used CT protocols from the Institute of Radiology of the University Hospital Erlangen are presented. CT Angiography of the pulmonary arteries Indication: occlusion of the pulmonary arteries (“pulmonary embolism”) Positioning: supine position with elevated arms CM administration: 50 mL (350 mg/mL) + 60 mL saline solution (0.9% NaCl) Injection rate: 5 mL/s Timing: bolus tracking Pre-monitoring slice: mid-chest; ROI: pulmonary trunk Delay: 5 s after threshold (120 HU) SOP, Department of Radiology, University Hospital Erlangen, Suggested Reading: M. Righini, Diagnosis of Pulmonary Embolism, Rev Med Interne 2019, H. Robert-Ebadi, The Evolution of Imaging Techniques for the Diagnosis of Pulmonary Embolism, Rev Med Suisse 2016 CT Angiography of the pulmonary arteries [audf_085.mp3] If an occlusion of the pulmonary arteries is suspected, a CT angiography of the pulmonary arteries is a robust diagnostic tool.   The patient is positioned with elevated arms. 50 milliliters of an iodine containing contrast medium at a flow rate of 5 milliliters per second are administered. The contrast medium arrival time is measured with the bolus tracking method. The threshold is defined at 120 Hounsfield Units and a 5-second delay after reaching the threshold is added. Sample image for CT Angiography of the pulmonary arteries :Pulmonary arteries Lungenembolie beidseits MIP Sample image of the pulmonary arteries [audf_086.mp3] This sample image illustrates the high enhancement in the pulmonary arteries, marked by the red asterisk. CT Angiography of the coronary arteries Indication: assessment of the coronary arteries for stenosis Positioning: supine position with elevated arms CM administration: 60 mL CM (350 mg/mL) + 50 mL split bolus of 20% CM and 80% saline solution (0.9% NaCl) Injection rate: 5 mL/s Timing: test bolus Pre-monitoring slice: mid-chest; ROI: ascending aorta Delay: 2 s SOP, Department of Radiology, University Hospital Erlangen, Suggested Reading: A. Busse, Cardiac CT: Why, When, and How: Update 2019, Radiologe 2019, H. Machida, Current and Novel Imaging Techniques in Coronary CT, Radiographics 2015 CT Angiography of the coronary arteries [audf_087.mp3] Many patients suffer from vessel stenosis of the coronary arteries which supply the heart muscle. A severe stenosis can lead to cardiac infarction and death. A dedicated, non-invasive diagnostic method for assessment of the coronary arteries is CT angiography of the coronary arteries.   The patient is positioned in a supine position with elevated arms. The administration of contrast medium is performed using a split-bolus technique with two contrast medium administrations at an injection rate of 5 milliliters per second. The arrival time of the contrast medium bolus is defined by using the test bolus method with an additional delay of 2 seconds. Sample images for CT Angiography of the coronary arteries :Coronary arteries \\teamspace.healthcare.siemens.com@SSL\DavWWWRoot\content\80000005\CTMKALL\docs\ImagingCenter_Selection\goTop\goTop_43_Cardio\automatisch_curvRCA\Top_43_automatic_curvedRCA.bmp \\teamspace.healthcare.siemens.com@SSL\DavWWWRoot\content\80000005\CTMKALL\docs\ImagingCenter_Selection\goTop\goTop_43_Cardio\cVRT\Top43_cVRT.bmp \\teamspace.healthcare.siemens.com@SSL\DavWWWRoot\content\80000005\CTMKALL\docs\ImagingCenter_Selection\goTop\goTop_43_Cardio\automatisch_curvLAD\Top_43_automatic_curvedLAD.bmp \\teamspace.healthcare.siemens.com@SSL\DavWWWRoot\content\80000005\CTMKALL\docs\ImagingCenter_Selection\goTop\goTop_43_Cardio\automatisch_curvCX\Top_43_automatic_curvedCX.bmp \\teamspace.healthcare.siemens.com@SSL\DavWWWRoot\content\80000005\CTMKALL\docs\ImagingCenter_Selection\goTop\goTop_43_Cardio\autoVRT_coronaries\Top43_autoVRT_coronaries.6.bmp Sample images of the coronary arteries [audf_088.mp3] These sample images illustrate reconstructions of both coronary arteries, marked in the 3D reconstruction with red asterisks. CT Angiography of the lower extremities (“run off”) Indication: circulatory disorders, e.g. stenosis Positioning: supine position with elevated arms CM administration: 100 mL CM (350 mg/mL) + 50 mL saline solution (0.9% NaCl) Injection rate: 5 mL/s Timing: bolus tracking, low pitch (scan duration should be > 20 s) Pre-monitoring slice: upper abdomen; ROI: descending aorta below the kidneys Delay: 10 s after threshold SOP, Department of Radiology, University Hospital Erlangen, Suggested Reading: D. Fleischmann, CT Angiography of Peripheral Arterial Disease, J Vasc Interv Radiol 2006 CT Angiography of the lower extremities (“run off”) [audf_089.mp3] CT angiography of the lower extremities is a typical examination for patients suffering from circulatory disorders.   The patient is positioned in a supine position with elevated arms. 100 milliliters of a contrast medium are injected at a high injection rate of 5 milliliters per second. The arrival time is defined by the bolus tracking method. CT scanning is performed with a slower pitch to prevent the CT scan from overtaking the contrast medium while it is transiting through the vessel system. An additional delay of 10 seconds is applied after reaching the threshold. Sample images for CT Angiography of the pelvis and the lower extremities Sample images of the pelvis and the lower extremities [audf_090.mp3] Sample images of a patient with 3D reconstructed images of the arteries of the pelvis and the lower extremities on both sides. CT Angiography of the aorta Indication: any suspected pathology of the aorta, e.g. wall tear (“dissection”) Positioning: supine position with elevated arms CM administration: 100 mL CM (350 mg/mL) + 50 mL saline solution (0.9% NaCl) Injection rate: 5 mL/s Timing: bolus tracking Pre-monitoring slice: mid-chest; ROI: ascending aorta Delay: 5 s after threshold ECG-triggered acquisition of the heart + spiral acquisition of the entire aorta SOP, Department of Radiology, University Hospital Erlangen, Suggested Reading: N.J. Hansen, Computed Angiography of the Abdominal Aorta, Radiol Clin North Am 2016, J.H. Chung, CT angiography of thoracic aorta, Radiol Clin North Am 2010 CT Angiography of the aorta [audf_091.mp3] Any patient with suspected pathologies of the aorta will receive a CT angiography of the aorta to assess potential life-threatening disease as quickly as possible.   The patient is positioned in a supine position with elevated arms. A 100-milliliter contrast medium bolus with an injection rate of 5 milliliters per second is injected. The contrast medium arrival time is defined by the bolus tracking method. A delay of 5 seconds is added after reaching the threshold. To avoid any motion artifacts by the heart, the acquisition is performed with electrocardiogram gating. Sample images for CT Angiography of the thoracic aorta : Aorta Sample images of the thoracic aorta [audf_092.mp3] These sample images illustrate a satisfying examination result with almost no motion artifacts of the aorta. The red asterisk marks the aorta with high vessel enhancement. Sample images for CT Angiography of the entire aorta ANONYMOUS RA2 Sample images of the entire aorta [audf_093.mp3] These sample images illustrate a CT angiography study of the whole aorta with different reconstruction techniques. CT Angiography of the carotid arteries Indication: any suspected pathology of carotid arteries, e.g. stenosis Positioning: supine position with lowered arms CM administration: 50 mL CM (350 mg/mL) + 30 mL saline solution (0.9% NaCl) Injection rate: 4 mL/s Timing: bolus tracking Pre-monitoring slice: mid-neck; ROI: carotid artery Delay: 2 s after threshold SOP, Department of Radiology, University Hospital Erlangen, Suggested Reading: A. Eller, Carotid CTA at the Lowest Tube Voltage (70kV) in Comparison With Automated Tube Voltage Adaption, Am J Neuroradiology 2019 CT Angiography of the carotid arteries [audf_094.mp3] Any stenosis of the carotid arteries can lead to severe damage of brain tissue. Therefore, a dedicated CT angiography of the carotid vessels is strongly indicated.   Patients are positioned in a supine position with lowered arms. A 50-milliliter contrast medium bolus is injected with an injection rate of 4 milliliters per second. The contrast medium arrival time is defined with the bolus tracking method. An additional delay of 2 seconds is added after reaching the threshold. Sample images for CT Angiography of the carotid arteries :Carotid artery CT Angio parasagittal Schlaganfall 3.png CTA_Carotis1 Sample images of the carotid arteries [audf_095.mp3] These sample images illustrate the carotid arteries of a patient. The red asterisk marks one carotid artery. CT abdomen Indication: any suspected pathology of the abdominal organs, e.g. tumor or infection Positioning: supine position with elevated arms CM administration: body weight and tube voltage adapted CM + 40 mL / 30 mL saline solution (0.9% NaCl), optional oral (1.5 liters) and rectal (1 liter) CM administration (Diatrizoate) Injection rate: 3 mL/s Delay timing: bolus tracking Pre-monitoring slice: at the height of upper abdomen; ROI: aorta Scan start delay: 45 s after threshold (100 HU) SOP, Department of Radiology, University Hospital Erlangen CT abdomen [audf_096.mp3] A CT of the abdomen is performed when a severe pathology is suspected, e.g. a tumor or an infection.   The patient is positioned in a supine position with elevated arms. The contrast medium administration is performed according to the individual body weight and adapted to the desired tube voltage. The application of oral and rectal contrast medium is optional and may help to identify pathologies within the intestine. The injection rate is set to 3 milliliters per second. The contrast medium arrival time is defined by the bolus tracking method with a delay of 45 seconds after reaching the threshold. Sample images for abdominal CT PortalV_mixed Arterial Arterial contrast enhancement Organ contrast enhancement Sample images for abdominal CT [audf_097.mp3] These are two sample images of an abdominal CT study with arterial vessel contrast on the left side and organ contrast on the right side. CT Brain Perfusion Indication: stroke Positioning: supine position with lowered arms CM administration: 35 mL CM (350 mg/mL) + 60 mL saline solution (0.9% NaCl) Injection rate: 5 mL/s Scan start delay: 2 s SOP, Department of Radiology, University Hospital Erlangen, Suggested Reading: P. Krishnan, CT-based Techniques for Brain Perfusion, Top Magn Reson Imaging 2017, A. M. Allmendinger, Imaging of Stroke: Part 1, Perfusion CT – Overview of Imaging Technique, Interpretation Pearls, and Common Pitfalls, Am J Roentgenol 2012 CT Brain Perfusion [audf_098.mp3] Patients with a suspected stroke may benefit from a perfusion CT examination of the brain. Perfusion of the brain can help to identify a stroke earlier than a conventional CT scan and can help to detect viable brain tissue.   Patients are positioned in a supine position with lowered arms. 35 milliliters of contrast medium are administered with an injection rate of 5 milliliters per second. The scan start delay is set to 2 seconds. No contrast medium arrival time method is applied. Sample images for Brain Perfusion CT without CM (no detection of the stroke area in the early phase) Malperfusion on the right side (warm colors) represents the stroke area CT nativ Schlaganfall .png CT PWI (TTP) Schlaganfall.png Sample images for Brain Perfusion [audf_099.mp3] These sample images illustrate a brain perfusion study on the right with an early stroke on the right patient side. The stroke area is colored in red, healthy brain tissue is colored in green. In contrast, a CT study without contrast medium on the left shows no stroke detection. Future concepts - Dynamic examination Future concepts - Dynamic examination [audf_100.mp3] On the last page of this workshop, you can see a future CT concept with a dynamic examination protocol of the pelvis and parts of the lower extremities after the administration of iodine containing contrast medium. Disclaimer The herein illustrated statements made by Siemens’ customers and physicians are based on their own and discrete opinion. The speaker is responsible for obtaining permission to use any previously published figures or tables. The speaker is also responsible for obtaining permission to reproduce any photograph showing recognizable persons. The statements by Siemens’ customers described herein are based on results that were achieved in the customer's unique setting. Since there is no "typical" setting and many variables exist there can be no guarantee that other customers will achieve the same results. Some products/features (here mentioned) are not necessarily commercially available in all countries. Due to regulatory reasons their availability cannot be guaranteed. Please contact your local Siemens organization for further details. Disclaimer Disclaimer Please note that the learning material is for training purposes only! For the proper use of the software or hardware, please always use the Operator Manual or Instructions for Use (hereinafter collectively “Operator Manual”) issued by Siemens Healthineers. 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Copyright © Siemens Healthcare GmbH, 2020 Disclaimer Question Bank 1 Contrast Media in CT Diagnostics 1 Contrast media in CT diagnostics 1.1 Welcome - Contrast media in CT diagnostics 1.2 Outline & educational objectives 1.3 Definition of “contrast media” 1.4 Definition of “contrast media” by law 1.5 Brief history of iodine containing CM used in Radiology 1.6 Sample image urinary tract 1.7 Overview of CM used in Radiology 1.8 General considerations – Why contrast media? 1.9 Sample image of lung tissue 1.10 Sample images of arterial vessels 1.11 Sample images of abdominal organs 1.12 How to administer CM into human bodies? 1.13 How to administer CM into human bodies? 2 Classification of CM 1.14 Classification of CM used for Computed Tomography (CT) 1.15 Negative CM 1.16 Air 1.17 Sample image of normal chest CT 1.18 Sample image of abnormal air 1.19 Sample image of abnormal air-filled spaces 1.20 CO2 1.21 CO2 - Sample images of Virtual Coloscopy 1.22 Mannitol 1.23 Mannitol - Sample images 1.24 Positive CM 1.25 X-ray attenuation of biologic tissues and iodine 1.26 Positive CM 1.27 Application rate of iodine containing CM per year 1.28 Barium 1.29 Barium 1.30 Sample image of the large intestine 1.31 Sample image of barium-filled stomach 1.32 Iodine containing CM 1.33 Iodine containing CM – General structural formula 1.34 Iodine containing CM – A variety of different substances 1.35 Iodine containing CM – Basic kinetics 1.36 Iodine containing CM – Basic kinetics 1.37 Iodine containing CM – Basic properties 1.38 Iodine containing CM – Osmotic pressure 1.39 Iodine containing CM – Side effects caused by hyperosmolality 1.40 Iodine containing CM – Classification defined by osmolality 1.41 Iodine containing CM – Advantages of non-ionic CM 1.42 Iodine containing CM – Peritrast 1.43 Sample images of small and large intestine 1.44 Iodine containing CM – Iomeron 1.45 Sample images of intravenous usage of Iomeron 1.46 Iodine containing CM – Adverse drug reactions 1.47 Iodine containing CM – Adverse reactions 1.48 Iodine containing CM – Adverse reactions 1.49 Iodine containing CM – General adverse reactions 1.50 Iodine containing CM – General adverse reactions 1.51 Iodine containing CM – General adverse reactions 1.52 Iodine containing CM – General adverse reactions 1.53 Iodine containing CM – Strategies to avoid and manage general adverse reactions 1.54 Iodine containing CM – Premedication prior to CM 1.55 Iodine containing CM – Kidney-related adverse drug reactions 1.56 Iodine containing CM – Kidney-related adverse drug reactions 1.57 Iodine containing CM – Other adverse drug reactions 1.58 Sample image of elbow 1.59 Iodine containing CM – Other adverse drug reactions 1.60 Role of modern CT diagnostics 1.61 Diagnostic targets for CM application 1.62 Image contrast 1.63 CM application technique 1.64 Relationship between iodine flux and enhancement 1.65 Relationship between injection duration and enhancement 1.66 Relationship between injection rate and enhancement 1.67 Relationship between iodine concentration, voltage, and enhancement 1.68 CM viscosity 1.69 CT parameters 1.70 CT examination duration 1.71 CT scan direction 1.72 Determination of CM arrival time 1.73 Determination of CM arrival time 1.74 Determination of scan delay and injection duration 1.75 Different body regions 1.76 Sample image of a workflow 1.77 Sample image of the bolus tracking workflow 1 1.78 Sample image of the bolus tracking workflow 2 1.79 Sample image of the bolus tracking workflow 3 1.80 Patient-related factors 1.81 Patient-related factors 1.82 CM dose adaption to body weight and tube voltage 1.83 Factors with influence on the CM dose calculation 1.84 Examples of different protocols 1.85 CT Angiography of the pulmonary arteries 1.86 Sample image of the pulmonary arteries 1.87 CT Angiography of the coronary arteries 1.88 Sample images of the coronary arteries 1.89 CT Angiography of the lower extremities (“run off”) 1.90 Sample images of the pelvis and the lower extremities 1.91 CT Angiography of the aorta 1.92 Sample images of the thoracic aorta 1.93 Sample images of the entire aorta 1.94 CT Angiography of the carotid arteries 1.95 Sample images of the carotid arteries 1.96 CT abdomen 1.97 Sample images for abdominal CT 1.98 CT Brain Perfusion 1.99 Sample images for Brain Perfusion 1.100 Future concepts - Dynamic examination 1.101 Disclaimer