Be careful not to hit the pit of the contrast agent!

If imaging is the magic weapon of neurological diagnosis, then the contrast agent can be regarded as the sunflower treasure that helps it unify the rivers and lakes
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The dynamic and static vessels are narrow and obstructed.
Wherever the contrast agent reaches, it can be traced, with bizarre appearances, mysterious inferences, and instantly surfaced
.

It can be said that the discovery and popularization of contrast agents is an important milestone in the history of disease diagnosis and treatment.
However, this technique sometimes makes a difference and even becomes an "uninvited guest", which instead becomes a hindrance to us
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This article mainly introduces the potential "side effects" of contrast agents in neurology, and promotes clinicians' recognition and treatment of related symptoms
.

Author: Tsai This article is published by Yimaitong authorized by the author, please do not reprint without authorization
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 First of all, we first reviewed a medical record and image of a ~46-year-old female who underwent a brain MRA examination for headache and revealed a middle cerebral artery aneurysm (15mm×12mm), and was admitted to the hospital to complete the dSA examination
.

Nervous system examination was negative on admission
.

He had high blood pressure, hypothyroidism and polycystic kidney disease in the past
.
He started hemodialysis 4 years ago due to chronic renal failure .

Hemodialysis was completed 1 day before dSA operation.
A saccular aneurysm of the middle cerebral artery was found during the operation.
The size was 16mm×13mm×9mm.
The whole process lasted 20 minutes.
A total of 80 non-ionic, hypotonic contrast agent "Iopamiro370" (Iopamidol )
.

This patient used iodine-containing contrast agent for the first time.
During the operation, when the contrast agent was injected into the left and right carotid arteries and right vertebral artery, there was no discomfort or side effect.
When injected into the left vertebral artery, the patient complained of blurred vision and progressed to complete blindness within a few minutes.
At that time, the pupils on both sides were equal in size and could reflect light.
The rest of the nervous system was normal
.

About 1 hour after the operation, the patient developed a generalized tonic-clonic seizure
.

An emergency head CT scan revealed bilateral symmetrical density increase in the parieto-occipital cortex, subarachnoid space, and thalamus (Figure 1A).
Consider the diagnosis of Contrast-in duce dencep halopathy (CIE) and promptly undergo hemodialysis
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In the following 24 hours, the patient remained unconscious, irritable, accompanied by severe headache and vomiting
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Brain MRI examination on the first day after surgery revealed bilateral symmetrical hyperintensity in the basal ganglia, parieto-occipital cortex, and corpus callosum T2 and FLAIR.
dWI and A dC images showed limited diffusion in the same area (Figure 1B)
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The patient underwent hemodialysis every day for the following 3 days and was treated with dexamethasone.
The symptoms gradually began to improve, and the neurological symptoms disappeared completely on the 5th day
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One month later, the follow-up brain MRI showed no residual lesions (Figure 1C)
.

Figure 1 Changes in CT and MRI images of the head (A after the end of angiography; B on the second day after surgery; C at 1 month follow-up) The contrast agent encephalopathy (CIE) mentioned in the above medical records may also be heard slightly, but it is used as a contrast agent The rare adverse reaction of cerebrovascular disease, and its initial symptoms are difficult to distinguish from cerebrovascular disease, and it is often misdiagnosed or missed clinically.
This can be regarded as a small trap brought to us by the era of the prevalence of contrast agents
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From this, apart from CIE, what other "pits" related to contrast agents that we may step on in the course of clinical practice? Let's take an inventory one by one
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 From a neurological point of view, the contrast agents we most often come into contact with are iodine-containing contrast agents for CT enhancement, gadolinium contrast agents for MRI enhancement, ultrasound-related contrast agents, and nuclear medicine imaging-related contrast agents such as 18F Labeled 2-deoxyglucose (18FDG), etc.
(Figure 2).
This article mainly introduces neurological adverse reactions related to iodine contrast agents
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 The nature of iodine contrast agent In 1927, iodine-containing contrast agent was first used for carotid angiography
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With the advancement of technology, the composition of contrast agents has been improved.
Low toxicity, low osmotic pressure and non-ionic iodine contrast agents have been used in more and more clinical applications, but the side effects and adverse reactions that follow are also called influences.
The main obstacle to its application
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The efficacy and adverse effects of iodinated contrast agents are mainly determined by the following characteristics: ① Iodine concentration: the iodine content (mg) per unit volume (mL) of the contrast agent solution
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The iodine concentration range of iodine-containing CT contrast media is 11-46%.
The higher the iodine concentration, the higher the viscosity and the higher the radio-impermeability, but the higher the risk of adverse reactions
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At present, most CT contrast agents are non-ionic, with large differences in iodine content.
The dimer structure helps reduce adverse reactions and toxicity without affecting radiopacity
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The concentration of ordinary iodinated contrast agents is about 300 mg/mL (range 200-400 mg/mL), and different dosage forms of the same contrast agent can have different iodine concentrations (such as Omnipaque 240, Omnipaque 300, and Omnipaque 370; GE Healthcare)
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② Osmotic pressure: a measure of the number of active particles (mOsm/kg) when the agent is dissolved in 1 kg of water
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Tension is related to the influence of the osmotic pressure of the solution on surrounding cells
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The osmotic pressure of isotonic solution (general radiopharmaceutical) is equal to blood (290 mOsm/kg water), and has no effect on surrounding cells; the osmotic pressure of hypertonic solution is higher than that of blood, causing water to leak out of blood cells, CT's iodine contrast agent The osmotic pressure of blood is 7 times that of blood; the osmotic pressure of hypotonic solution is lower than that of blood, causing water to enter blood cells
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Iodinated contrast media are classified into high osmotic pressure contrast media (HOCM), low osmotic pressure contrast media (LOCM) or isotonic contrast media (IOCM), but both HOCM and LOCM are hypertonic, but the degree is different, there is no real low Iodinated contrast agent
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The traditional iodinated contrast agent is usually HOCM (1300-2140 mOsm/kg water), and the new contrast agent developed since the 1980s is usually LOCM (600-850 mOsm/kg water)
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Osmotic pressure can cause water to move from the interstitial space to the vascular compartment, leading to increased blood viscosity, endothelial damage, hypervolemia, vasodilation, neurotoxic edema, decreased myocardial contractility, and toxicity
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The osmotic pressure of IOCM iodinated contrast agent is equal to that of blood, opening up new horizons for iodine contrast agents
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The purpose of iodinated CT contrast agents is to obtain sufficient iodine concentration to obtain radioopacity, so the ratio of iodine atoms to particles in the solution is very important
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The ratio of HOCM is 0.
5; LOCM, 3.
0; IOCM, 6.
0
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③ Viscosity: depends on the flow friction, resistance or thickness of the contrast agent
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Iodinated contrast media is significantly more viscous than radiopharmaceuticals, which determines its requirements for intravenous injection, flow rate and required tubing specifications
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Viscosity is affected by temperature, molecular structure and composition
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The viscosity of the contrast agent can be reduced at body temperature (37°C) instead of room temperature (the viscosity at 20C is about twice that at 37C), which is advantageous for injection
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Compared with meglumine, sodium-containing solutions will reduce viscosity, but will increase endothelial irritation
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LOCM has a higher viscosity than HOCM, and the viscosity increases with increasing iodine content
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High-viscosity intravenous iodine contrast agent requires longer infusion time and may affect local circulation; while low-viscosity allows rapid bolus injection (conducive to rapid imaging)
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In addition, the increase in viscosity also increases the risk of nephrotoxicity
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④ Chemical structure (monomer, dimer, triiodide): A monomer is a simple molecule or basic unit that can be polymerized
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In the iodinated contrast agent, the monomer is a 2,4,6-triiodinated benzene ring; the dimer is the combination of two monomer units after polymerization to form a binary oligomer
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The monomer has a higher osmotic pressure than the dimer, and the dimer is usually LOCM or IOCM
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The covalently bonded iodine atom associated with CT contrast agents will attenuate in the X-ray wavelength range, and the attenuation characteristics can be enhanced by the triiodide structure, and the benzene ring structure can reduce toxicity
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Therefore, triiodide (a derivative of benzoic acid) contrast agent has become the main CT contrast agent for intravenous injection
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⑤ Ionic and non-ionic: The tendency of reagents to separate into charged substances (ions) when dissolved in a solution
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Ionic iodide CT contrast agents can be decomposed into ion pairs, while non-ionic types do not (most non-ionic contrast agents are LOCM)
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The fully saturated triiodide benzoic acid derivative monomer CT contrast agent decomposes into ions in the solution.
The anion contains iodine atoms, and the cation contains sodium or meglumine.
It is often hypertonic (osmotic pressure is 5 times that of blood).
Adverse reactions are frequent
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The dimer form (2 triiodinated benzoic acid ring) can contain high iodine concentration but low osmotic pressure
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The non-ionic monomer CT contrast agent has a longer side chain ratio, which increases the molecular weight and reduces the osmotic pressure, but does not change the iodine concentration
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Non-ionic dimer structure is generally isotonic; low osmotic pressure drugs are less toxic and have fewer adverse reactions
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The four main categories of iodinated CT contrast agents include ionic monomers, ionic dimers, non-ionic monomers, and non-ionic dimers
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Figure 2 The chemical structure of four iodinated CT contrast agents: ionic monomer, ionic dimer, non-ionic monomer and non-ionic dimer
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The carboxyl group (COOH) of ionic contrast agents ionizes with sodium or meglumine (COO-) to form anion and cation pairs; non-ionic contrast agents tend to have longer side chains (R)
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  Possible mechanisms Common adverse reactions of iodine contrast agents include specific reactions such as allergic reactions, general weakness, nausea and hypotension, and dose-related adverse reactions to specific organ systems, such as contrast-induced nephropathy
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However, the current research has found that the effect of iodine contrast agent on the nervous system is second only to the cardiovascular system, which requires clinical attention
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Nervous system adverse reactions caused by iodine contrast agents are often dose-dependent, and are more common after cerebral artery and aortic angiography
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The specific mechanism is still unclear, and may be related to the direct toxicity to the brain or spinal cord parenchyma and the induced hematological and vascular changes
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Animal studies have found that high-concentration contrast agents can cause red blood cells to accumulate and increase blood viscosity, thereby blocking cerebral blood vessels; but contrast agents have a relaxing effect on blood vessels, and cerebral blood flow increases after carotid angiography
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Certain hypertonic contrast agents will release water from brain capillary endothelial cells, thereby destroying the blood-brain barrier (BBB), causing the cells to shrink and separate tight junctions
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Due to the vasodilation effect of the contrast agent and the high pressure of the contrast agent injection, the tension in the lumen increases, which makes the mechanism of separation of tight junctions more complicated
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Areas not protected by BBB, such as the hypothalamus and the posterior area, are more likely to be exposed to higher toxic concentrations, and thus more vulnerable to injury, and the degree of damage is related to the duration of the injection
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It is worth noting that in disease states such as infection that increase the permeability of the BBB, the contrast agent is more likely to enter the brain and cause further damage
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 Nervous system adverse reactions related to iodine contrast agents are extensive and vary in severity, including nausea, vomiting, vasovagal reactions, headaches, seizures, cortical blindness, spinal cord ischemia, cortical edema, and localization.
Focal neurological deficits, etc.
(Table 1)
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Most of the adverse events occurred when the cumulative dose of contrast agent was greater than 100, and occasionally when the cumulative dose of contrast agent was less than 45
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Various contrast agents and their adverse reactions are shown in Table 2
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Table 1 Nervous system adverse reactions related to iodine contrast agents and possible mechanisms Table 2 Different types of iodine contrast agents and related nervous system adverse reactions Note: GCS, Glasgow Coma Scale.
Contrast agent encephalopathy (CIE) CIE is a rare group (0.
3-1 %) of the clinical syndromes of encephalopathy, epileptic seizures, motor and sensory disturbances, visual disturbances and focal neurological deficits, most of which are completely resolved within 48-72 hours
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Hypertension, diabetes, renal impairment, extensive use of iodine contrast agents, percutaneous coronary intervention or selective angiography of internal breast grafts, and previous adverse reactions to iodine contrast agents are common risk factors for the occurrence of CIE
.

The imaging manifestations of CIE include local cortical enhancement, increased subarachnoid density, brain edema, etc.
, but other neurological diseases such as thromboembolism after angiography, subarachnoid hemorrhage, and reperfusion syndrome need to be differentiated
.

CT appearance (measured by Hounsfield Unit (HU)) helps to distinguish between blood and contrast agent.
Compared with blood (40-60 HU), the attenuation value of contrast agent (100-300 HU) is higher; CIE patients on MRI It shows high signal on spin-spin relaxation time, FLAIR and DWI imaging, and there is no change in ADC (diagnosing cerebral infarction), but it may overlap with reversible posterior leukoencephalopathy syndrome (PRES)
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PRES is a reversible clinical radiology subcortical vasogenic edema.
Patients present with acute neurological symptoms (such as seizures, encephalopathy, visual impairment, and focal neurological deficits).
The frequency of occurrence is uncontrolled hypertension and chronic Higher in patients with kidney disease
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In addition, the cerebrospinal fluid examination can help rule out subarachnoid hemorrhage through the absence of yellowing or red blood cells
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The high concentration of iodine contrast agent in both cerebrospinal fluid and serum supports the extravasation of the contrast agent instead of bleeding
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Most CIE patients have a good prognosis and can be quickly relieved by supportive treatment such as intravenous infusion and close observation
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Anticonvulsants may be effective against seizures, and mannitol can be used to reduce brain pressure
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If necessary, steroid hormones such as dexamethasone can be used to reduce inflammation
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Routine mental state testing and visual field examination after DSA are helpful for early diagnosis
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Neurotoxic reactions often occur within a few minutes or hours after angiography, and resolve on their own within 72 hours
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Occasionally, serious complications, such as fatal brain edema due to neurotoxicity of the contrast agent in the early stage of angiography, and low osmotic pressure contrast agent can induce permanent neurological dysfunction and fatal brain edema
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 Summary With the continuous development of diagnostic imaging technology, CT imaging technology has become an important diagnostic tool
.

With the continuous increase in applications, its adverse reactions have been gradually revealed.
The adverse reactions related to the nervous system may be more common than the nephropathy induced by contrast agents
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Therefore, for high-risk groups, such as hypertension, diabetes, and renal insufficiency, it needs to be used with caution.
At the same time, additional attention is needed for neurological complications with a higher incidence, such as changes in mental status and cortical blindness
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