Medical Imaging Contrast Agents: A Clinical Manual

Preface
Contents
1: Contrast Agents in Radiology: An Overview
	References
2: Chemistry, Physicochemical Properties and Pharmacokinetics of Iodinated Contrast Agents
	2.1	 Introduction
	2.2	 Physicochemical Properties
	2.3	 History
		2.3.1	 Physicochemistry
	2.4	 Characteristics of Ionic CAs
	2.5	 Viscosity
	2.6	 Osmolality
	2.7	 Chemical Composition of Ionic CA
		2.7.1	 Ionic CAs
		2.7.2	 Non-ionic CAs
			2.7.2.1	 Low-Osmolar Non-ionic CAs
			2.7.2.2	 Iso-osmolar Non-ionic CAs
	2.8	 Atropisomerism
	2.9	 Pharmacokinetics
	2.10	 Absorption
	2.11	 Distribution
		2.11.1	 Plasma Protein Binding
	2.12	 Metabolism
	2.13	 Elimination
	2.14	 Conclusion
	References
3: Nephrotoxicity of Iodinated Contrast Agents
	3.1	 Introduction
	3.2	 Terminology
	3.3	 Incidence
	3.4	 Diagnosis and Biomarkers
	3.5	 Risk Factors
		3.5.1	 Patient-Related Risk Factors
		3.5.2	 Procedure-Related Risk Factors
		3.5.3	 Risk Scoring Systems
	3.6	 Pathogenesis
	3.7	 Prevention
		3.7.1	 Avoiding the Use of ICM or Limiting the ICM Volume
		3.7.2	 Choosing Alternative Imaging Modalities
		3.7.3	 Stopping Nephrotoxic Drugs
		3.7.4	 Hydration
		3.7.5	 Pharmacological Premedication
	3.8	 Treatment
		3.8.1	 Medical Treatment
		3.8.2	 Intrarenal Drug Infusion
		3.8.3	 Remote Ischemic Conditioning
		3.8.4	 Forced Diuresis
		3.8.5	 Automated Contrast Injection Systems
		3.8.6	 Device-Based Approach
		3.8.7	 Renal Cooling
	3.9	 Metformin
	References
4: Adverse Reactions to Iodinated Contrast Agents
	4.1	 Introduction
	4.2	 General Adverse Reactions
		4.2.1	 Acute Adverse Reactions
			4.2.1.1	 Allergy-Like Reactions
			4.2.1.2	 Chemotoxic Reactions
				Risk Factors
					Allergies
					Beta-Blockers
					Age and Gender
					Sickle Cell Trait/Disease
					Pheochromocytoma
					Myasthenia Gravis
					Hyperthyroidism
				Premedication
					Premedication in Patients Undergoing Chronic Corticosteroid Therapy
					Benefits of Premedication
					Risks of Premedication
					Breakthrough Contrast Reactions
				Treatment
		4.2.2	 Late Adverse Reactions
			4.2.2.1	 Risk Factors
				Prophylaxis and Treatment
	4.3	 Organ-Specific Adverse Effects
		4.3.1	 Salivary Gland Adverse Effects
		4.3.2	 Central Nervous System Adverse Effects
		4.3.3	 Gastrointestinal Tract Adverse Effects
		4.3.4	 Hepatic Adverse Effects
		4.3.5	 Pancreatic Adverse Effects
		4.3.6	 Musculoskeletal Adverse Effects
		4.3.7	 Pulmonary Adverse Effects
		4.3.8	 Cardiovascular Adverse Effects
	4.4	 Adverse Reactions After ICA Administration by Other Routes
	4.5	 Adverse Reactions After ICA Administration in Pregnant or Potentially Pregnant Women
	4.6	 Adverse Reactions After ICA Administration in Breastfeeding Women
	4.7	 Adverse Reactions After ICA Administration in Oncologic Patients
	4.8	 Safe Injection of ICAs
		4.8.1	 Warming ICAs
		4.8.2	 Fasting Before Examination
	4.9	 Extravasation of ICAs
	4.10	 Conclusion
	References
5: Dose Reduction Strategies for Iodinated Contrast Agents: Low-Tube Voltage and Iterative Reconstruction
	5.1	 Introduction
	5.2	 Dose Reduction of Contrast Agents in Low-Tube-Voltage CT
		5.2.1	 Coronary CT Angiography
		5.2.2	 Pulmonary CT Angiography
		5.2.3	 Other Vascular Structures
		5.2.4	 Hepatic Dynamic CT
	5.3	 Effect of Decreased Flow Rate on Contrast Enhancement
		5.3.1	 Basics of Contrast Agent Injection Protocol
		5.3.2	 Effect of Decreased Flow Rate on Contrast Enhancement
		5.3.3	 Other Techniques for Improving Contrast Enhancement in Low-Voltage CT
	5.4	 Iterative Reconstruction in Low-Tube-Voltage CT
		5.4.1	 From Filtered Back Projection to Deep Learning Reconstruction
		5.4.2	 Index for Image Quality Assessment in Low-Tube-Voltage CT
	References
6: Gastrointestinal Iodinated Contrast Agents
	6.1	 Introduction
	6.2	 Positive Oral Contrast Agents
		6.2.1	 Barium Sulfate
			6.2.1.1	 Physical Properties of Barium Sulfate
			6.2.1.2	 Additives
			6.2.1.3	 Advantages of Barium over Iodinated Contrast Agents
			6.2.1.4	 Imaging of GIT Using Barium Enema
			6.2.1.5	 Side Effects
		6.2.2	 Water-Soluble Iodinated Contrast Agents
			6.2.2.1	 Computed Tomographic Colonography
			6.2.2.2	 Side Effects
			6.2.2.3	 Advantages of ICAs over Barium
			6.2.2.4	 Advantages of LOCM over HOCM
		6.2.3	 Suspicion of Perforation
	6.3	 Neutral Contrast Agents
	References
7: Chemistry, Physicochemical Properties and Pharmacokinetics of Gadolinium-Based Contrast Agents
	7.1	 Physiochemical Properties
		7.1.1	 Stability
		7.1.2	 Transmetallation
		7.1.3	 Relaxivity
		7.1.4	 Osmolality
		7.1.5	 Viscosity
	7.2	 Pharmacokinetics
	References
8: Magnetic Resonance Imaging (MRI) and Contrast-Enhancing Agents
	8.1	 Magnetic Resonance Imaging (MRI)
		8.1.1	 Gadolinium
		8.1.2	 Iron Oxide Nanoparticles
		8.1.3	 Manganese Chelates
		8.1.4	 CEST and PARACEST
	References
9: Gadolinium-Based Contrast Agent Toxicity and Accumulation
	9.1	 Introduction
	9.2	 Features of GBCAs
	9.3	 Adverse Reactions to GBCAs
		9.3.1	 Acute Adverse Reactions
		9.3.2	 Late Adverse Reactions
		9.3.3	 Very Late Adverse Reactions
	9.4	 Gadolinium Accumulation in the Human Body
		9.4.1	 Gadolinium Accumulation in the Brain
		9.4.2	 Gadolinium Washout from the Brain
		9.4.3	 Mechanism of Gadolinium Accumulation in the Brain: The Glymphatic System
		9.4.4	 Accumulation in Other Parts of the Human Body
		9.4.5	 Effects on the Human Body
	9.5	 GBCAs for Pregnant or Lactating Women
		9.5.1	 Safety During Pregnancy
		9.5.2	 Safety During Lactation
	9.6	 GBCAs for Children
	9.7	 Conclusion
	References
10: Basic Properties of Ultrasound Contrast Agents
	10.1	 Introduction
	10.2	 Short History of UCA
	10.3	 Ultrasound Contrast Agents (UCAs) [31, 34]
	10.4	 UCA Imaging
		10.4.1	 Contrast-Specific Imaging
		10.4.2	 Stimulated Acoustic Emission
		10.4.3	 Artefacts
		10.4.4	 Heterogeneous Long Liver Enhancement [46]
	10.5	 Examination Technique
		10.5.1	 CEUS Phases
			10.5.1.1	 Enhancement (Degree and Timing)
			10.5.1.2	 “Wash-In” and “Wash-Out”
	10.6	 Indications for UCA
		10.6.1	 CEUS-Guided Interventions
		10.6.2	 Paediatric Patients and Newborns
		10.6.3	 Extravascular (Intracavitary)
	10.7	 Quantification
	10.8	 UCA Safety
	10.9	 Conclusions
	References
11: Contrast Agents in Pregnancy and Breastfeeding
	11.1	 Introduction
	11.2	 Iodinated Contrast Agents
		11.2.1	 Types and FDA Categories
		11.2.2	 Transplacental Transfer and Biodistribution Within Fetus
		11.2.3	 Potential Harmful Effects
			11.2.3.1	 Mutagenicity and Teratogenicity
			11.2.3.2	 Effects on Fetal-Neonatal Thyroid Function
		11.2.4	 Excretion of Iodinated Contrast Agents into Breast Milk
		11.2.5	 Current Recommendations for the Use of Iodinated Contrast Agents in Pregnancy
		11.2.6	 Current Recommendations for the Use of Iodinated Contrast Agents in Breastfeeding
	11.3	 Gadolinium-Based Contrast Agents (GBCAs)
		11.3.1	 Types and FDA Categories
		11.3.2	 Transplacental Transfer and Biodistribution Within Fetus
		11.3.3	 Potential Harmful Effects
			11.3.3.1	 Mutagenicity and Teratogenicity
		11.3.4	 Excretion of Gadolinium-Based Contrast Agents into Milk
		11.3.5	 Current Recommendations for the Use of Gadolinium-Based Contrast Agents in Pregnancy
		11.3.6	 Current Recommendations for the Use of Gadolinium-Based Contrast Agents in Breastfeeding
	11.4	 Ultrasound Contrast Agents (USCAs)
	11.5	 Gastrointestinal Contrast Agents
	11.6	 Management of Adverse Reactions Following Contrast Agent Use During Pregnancy
		11.6.1	 Premedication in Patients with Prior Allergic-Like Reactions to Iodinated or Gadolinium-Based Contrast Agents
		11.6.2	 Treatment
	11.7	 Periprocedural Counseling
	References
12: Contrast-Enhanced CT Scanning of the Liver and Pancreas
	12.1	 Introduction
	12.2	 Contrast-Enhanced CT of the Liver
		12.2.1	 Why Dynamic CT?
		12.2.2	 Recommended Protocol
			12.2.2.1	 NE-CT
			12.2.2.2	 AP (Late AP Is Strongly Preferred)
			12.2.2.3	 PVP
			12.2.2.4	 DP
		12.2.3	 Recommended Injection Method of CM
			12.2.3.1	 Iodine Dose
			12.2.3.2	 Iodine Concentration
			12.2.3.3	 Injection Duration
			12.2.3.4	 Saline Flush
		12.2.4	 Scan Timing of CT
	12.3	 Contrast-Enhanced CT of the Pancreas
		12.3.1	 Why Dynamic CT?
		12.3.2	 Recommended Protocol
			12.3.2.1	 NE-CT
			12.3.2.2	 Late AP or Pancreatic Parenchymal Phase (PPP) (Almost the Same)
			12.3.2.3	 PVP
			12.3.2.4	 DP
		12.3.3	 Recommended Injection Method of CM
		12.3.4	 Assessment of Tumor Spread
	12.4	 Conclusion
	References
13: Contrast-Enhanced Magnetic Resonance Imaging of the Liver and Pancreas
	13.1	 Liver
		13.1.1	 Selection of Contrast Material for Contrast-Enhanced Magnetic Resonance Imaging (CE-MRI) of the Liver
		13.1.2	 Acquisition of CE-MRI with ECCM or Gd-EOB-DTPA
		13.1.3	 EOB-MRI
			13.1.3.1	 Principle of Hepatic Uptake of Gd-EOB-DTPA in EOB-MRI
			13.1.3.2	 Characteristics of Hemodynamics and Image Contrast in EOB-MRI
			13.1.3.3	 Clinical Application of EOB-MRI
				Conventional (Hypervascular) Hepatocellular Carcinoma (c-HCC)
				Early (Hypovascular) Hepatocellular Carcinoma (e-HCC)
					Clinical Background and Diagnostic Significance in the Detection and Differentiation of e-HCC and Dysplastic Nodules
					Comparison of Detection and Differentiation of e-HCC Among EOB-MRI and Other Imaging Modalities
					Current Consensus for the Diagnosis of e-HCC with EOB-MRI
				Hepatic Metastasis
				Hemangioma
				Pseudolesion (Arterioportal Shunt; AP Shunt)
	13.2	 Pancreas
		13.2.1	 CE-MRI of the Pancreas
		13.2.2	 Application of EOB-MRI to Assess Pancreatic Lesions (Especially Invasive Ductal Adenocarcinoma)
		13.2.3	 Acquisition of Magnetic Resonance Cholangiopancreatography (MRCP) with Hepatocyte-Specific Contrast Material
	References
14: CT and MR Enterography and Enteroclysis
	14.1	 Small Bowel Imaging Methods
	14.2	 CT Enterography and Enteroclysis
		14.2.1	 CT Enterography (CTE)
		14.2.2	 CT Enteroclysis (CTEc)
		14.2.3	 CT Enterography and CT Enteroclysis Imaging Protocol
		14.2.4	 Oral Contrast Agents: CT Enterography and Enteroclysis
			14.2.4.1	 Neutral Oral Contrast Agents
			14.2.4.2	 Positive Oral Contrast Agents
	14.3	 MR Enterography and Enteroclysis
		14.3.1	 MR Enterography
		14.3.2	 MR Enteroclysis (MREc)
		14.3.3	 MRI Protocol of MRE and MREc
			14.3.3.1	 MRI Sequences (Table 14.1)
				Optional Sequences
		14.3.4	 Oral Contrast Agents: MR Enterography and Enteroclysis
			14.3.4.1	 Negative Oral Contrast Agents
			14.3.4.2	 Positive Oral Contrast Agents
			14.3.4.3	 Biphasic Oral Contrast Agents
	14.4	 Imaging Findings of Small Bowel Diseases
		14.4.1	 Inflammatory Bowel Disease
			14.4.1.1	 The Role of MRE in the Diagnosis of Crohn’s Disease
		14.4.2	 Small Bowel Neoplasms
		14.4.3	 Coeliac Disease
		14.4.4	 Intestinal Malformations
		14.4.5	 Small Bowel Ischemia
	References
15: CT and MR Angiography in the Chest and Abdomen
	15.1	 Introduction
	15.2	 Computed Tomography Angiography (CTA)
	15.3	 Magnetic Resonance Angiography (MRA)
		15.3.1	 Pulmonary Arteries
		15.3.2	 Thoracic Veins
		15.3.3	 Aorta
		15.3.4	 Abdominopelvic Veins
		15.3.5	 Mesenteric Vessels
		15.3.6	 Renal Vessels
	References
16: Contrast-Enhanced CT and MR Scanning of the Brain
	16.1	 CA Enhancement Mechanisms and Accumulation in Brain
		16.1.1	 Extraaxial Enhancement
		16.1.2	 Pachymeningeal Enhancement
		16.1.3	 Leptomeningeal Enhancement
		16.1.4	 Intraaxial Enhancement
			16.1.4.1	 Gyral Enhancement
			16.1.4.2	 Nodular Cortical and Subcortical Enhancement
			16.1.4.3	 Deep and Periventricular Enhancement
		16.1.5	 Deep Ring Enhancing Lesions
		16.1.6	 Necrotic High-Grade Primary Neoplasms
		16.1.7	 Ventricular Neoplasms
		16.1.8	 Cyst with a Mural Nodule Primary Neoplasms
		16.1.9	 Demyelination
		16.1.10	 Deep Lesions: Periventricular Pattern
	References
17: Perfusion CT and MR Imaging of the Brain
	17.1	 Introduction
	17.2	 Methods
		17.2.1	 Perfusion Weighted MR Imaging (PW-MRI)
			17.2.1.1	 Dynamic Contrast Enhanced-T1 MR Imaging (DCE-MRI)
			17.2.1.2	 Dynamic Susceptibility Contrast Enhanced T2* Imaging (DSC-MRI)
			17.2.1.3	 Arterial Spin Labeling (ASL)
		17.2.2	 CT Perfusion (CTP) Imaging
	17.3	 Clinical Applications
		17.3.1	 Neuro-oncologic Imaging
			17.3.1.1	 Tumor Grading
			17.3.1.2	 Molecular/Genetic Characteristics
			17.3.1.3	 Differentiation of Solitary Brain Tumors
			17.3.1.4	 Differentiating Primary Gliomas from Tumefactive Demyelinating Lesions
			17.3.1.5	 Guiding Biopsy and Radiosurgery
			17.3.1.6	 Differentiation of Recurrent Tumor and Response to Treatment
				Pseudoprogression
				Pseudoresponse
				Radiation Necrosis
			17.3.1.7	 Tumor Surveillance
		17.3.2	 Stroke Management
			17.3.2.1	 CT Perfusion
			17.3.2.2	 MR Perfusion
		17.3.3	 Delayed Cerebral Ischemia (DCI) due to a Vasospasm
	17.4	 Conclusion
	References
18: CT and MR Angiography of the Brain and Carotid Arteries
	18.1	 CT Angiography of the Brain and Carotid Arteries
	18.2	 MR Angiography of the Brain and Carotid Arteries
	References
19: Peripheral Contrast-Enhanced CT and MR Angiography
	19.1	 Introduction
	19.2	 CT Angiography (Fig. 19.1)
		19.2.1	 General Features
		19.2.2	 Protocol
		19.2.3	 Image Processing
		19.2.4	 Drawbacks of CT Angiography
			19.2.4.1	 Evaluation of Severe Calcified Lesion
			19.2.4.2	 Evaluation of Critical Limb Ischemia
			19.2.4.3	 Radiation Exposure
			19.2.4.4	 Toxicity of Contrast Agents: Contrast-Induced Nephropathy
	19.3	 MR Angiography (Fig. 19.3)
		19.3.1	 General Features
		19.3.2	 Protocol
		19.3.3	 Image Processing
		19.3.4	 Drawbacks of MR Angiography
			19.3.4.1	 Evaluation of Calcification
			19.3.4.2	 Toxicity of Contrast Agents: Nephrogenic Systemic Fibrosis
	19.4	 Conclusion
	References
20: Contrast Agent Use and Safety in Pediatric Patients
	20.1	 Introduction
	20.2	 Barium Sulfate
	20.3	 Iodinated Contrast Agents
	20.4	 Allergic-Like Reactions and Chemotoxicity with Iodine-Based Contrast Agents
	20.5	 Contrast-Induced Renal Toxicity
	20.6	 Contrast Agent Extravasation
	20.7	 Gadolinium-Containing Contrast Agents
	References
21: Contrast-Enhanced Breast MR Imagıng
	21.1	 Breast MR Imaging
		21.1.1	 Assessment of Morphology
		21.1.2	 Semiquantitative Kinetic Enhancement Features
		21.1.3	 Quantitative Kinetic Enhancement Features
		21.1.4	 Intravoxel Incoherent Motion DWI
		21.1.5	 Abbreviated MRI
	References
22: Musculoskeletal Imaging and Contrast Agents
	22.1	 Sonography of Musculoskeletal Imaging
	22.2	 Computed Tomography in Musculoskeletal Imaging
	22.3	 Magnetic Resonance Imaging in Musculoskeletal Imaging
		22.3.1	 MSK Infections
		22.3.2	 MSK Tumor Imaging
	References
23: Optimal Contrast-Enhanced Computed Tomography and Magnetic Resonance Cardiac Imaging
	23.1	 Contrast Optimization in Cardiac CT
		23.1.1	 Contrast Injection Protocols
			23.1.1.1	 Contrast Infusion Method
			23.1.1.2	 Timing Method: Test Bolus Versus Bolus Tracking
		23.1.2	 CT Scanning Factors
		23.1.3	 Optimal Contrast Enhancement for Specific Imaging Protocols
			23.1.3.1	 Pulmonary Vein Demonstration
			23.1.3.2	 Congenital Heart Diseases
			23.1.3.3	 Triple Rule-Out
			23.1.3.4	 Pre-procedural Transcatheter Aortic Valve Replacement Planning
	23.2	 Contrast Optimization in Cardiac MRI
		23.2.1	 Late Gadolinium Enhancement
		23.2.2	 Myocardial Perfusion Imaging
		23.2.3	 Extracellular Volume Mapping
		23.2.4	 Coronary MRI Angiography with Contrast Medium
		23.2.5	 Appropriate Use of Contrast-Enhanced Sequences in Specific Imaging Protocols
			23.2.5.1	 Myocardial Infarction and Ischemia
			23.2.5.2	 Nonischemic Cardiomyopathy
			23.2.5.3	 Cardiac Masses
	References
24: Contrast Agents in Vascular Interventional Radiology
	24.1	 Introduction
	24.2	 Iodine-Based Contrast Agents
		24.2.1	 Contrast Enhancement in DSA Images
		24.2.2	 Adverse Effects of Contrast Agents Regarding Their Properties
			24.2.2.1	 Patient Discomfort Associated with Intra-arterial Injections
			24.2.2.2	 Post-contrast Acute Kidney Injury in Vascular Interventional Radiology
	24.3	 CO2 as a Contrast Agent
		24.3.1	 History
		24.3.2	 Physical and Chemical Properties of CO2
			24.3.2.1	 High Solubility
			24.3.2.2	 Fluid Displacement
			24.3.2.3	 Low Viscosity
			24.3.2.4	 Buoyancy
			24.3.2.5	 Reflux
			24.3.2.6	 Compressibility
	24.4	 Delivery Systems
	24.5	 Injection of CO2: Tips and Tricks
	24.6	 Advantages and Indications
	24.7	 Disadvantages and Contraindications
	References
25: Quo Vadis: An Epilog
	References