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S. Vyas and A. Rao
Fig. 3.1 Ultrasound-guided
biopsy: (a) in-plane and (b)
out-of-plane approach
a
• USG allows simultaneous visualization of structures surrounding the target area like nerves, vessels, and hollow
viscus to prevent inadvertent injury to the surrounding
structures.
• Use of ultrasound reduces the number of unsuccessful
attempts and thus obviates the need for multiple needle
passes.
• USG reduces procedure time compared to blind procedures, causing a reduction in pain and stress experienced
by patients.
Advances in ultrasonography technology—a comprehen-
sive review of details of the advances in ultrasonography is
beyond the scope of the chapter; however, a few relevant
advances are discussed briey here.
• Needle tip visualization—various technological advances
help in better needle tip placement, for example:
– Mechanical needle guides help keep the needle path in
the desired direction. Moreover, the use of 3D/4D
ultrasonography and electronic beam steering helps in
correct needle placement.
– Electromagnet-specialized sensors attached to the
probe and the needle help in the estimation of needle position with the help of an external magnetic
eld.
– Optical tracking is done by using recorded images of
the needle and probe, which helps in deciphering the
relative position of both.
– Image fusion—Fusion of pre-procedural imaging with
real-time USG images creates a roadmap for needle
advancement and thus helps in exact placement.
b
– Image-based needle tracking can also be achieved by
means of advanced image processing algorithms [4]..
– ARFI is helpful in the detection of out-of-plane
approach of a needle based on the mechanical response
of various tissues to USG beam.
– Robotic assistance for needle placement is also used in
the experimental stage.
• Spatial compound imaging—this utilizes multiple angulated ultrasound beams combined to form a compound
image, which is helpful in the reduction of artifacts like
posterior acoustic shadowing, refractile shadowing, and
anisotropy. It helps in improved delineation of tissue
planes, vessels, nerves, and needle tip, in addition to providing a larger trapezoidal eld of image.
• Doppler mode including power Doppler—doppler mode
helps in the visualization of vascular structures and helps
in the assessment of ow-related parameters. Power
Doppler is even more sensitive in demonstrating low
amplitude vascularity, however, with loss of directional
ow information.
• Ultrasound elastography—this is a relatively recent
advance that measures tissue stiffness. Elastography has
proven helpful in differentiating benign and malignant
masses, especially in the breast, liver, and thyroid, diagnosing degeneration of tendinous/ligamentous structures,
and also has found application in treatment response
assessment.
• Computer-aided detection (CAD)—CAD utilizes various
computational algorithms to enhance image interpretations, especially in training radiologists. CAD based on
TIRADS and BIRADS has shown promise in lesion identication and diagnosis [5, 6].
3 Image Guidance inInterventional Radiology
15
3.2.2 Indications ofUSG-Guided
Interventions
1. Biopsy and ne needle aspiration [7].
2. Placement of drains.
3. Nerve blocks.
4. Ultrasound-guided central and peripheral venous access:
ultrasound is useful not only in deciding on the site of
venous access but also the suitability of vein, progression
of catheter or guidewire, needle tip visualization, and
assessment of complications like pneumothorax, hematoma, vascular thrombosis, and catheter malposition.
5. Transvaginal procedures—aspiration of adnexal cyst,
collection, egg retrieval [8].
6. Intra articular and synovial injections.
7. Breast marker/wire localizer placement.
8. USG-guided ablative procedures [9].
3.2.3 Limitations
1. Limited visualization of deeper structures as the resolu-
tion of ultrasonography is inversely proportional to the
depth of area of interest.
2. Image degradation and beam attenuation in obese
subjects.
3. The presence of air in the tissues causes artifacts like
reverberation artifacts and dirty shadowing.
4. Limited visualization due to small acoustic window in
intercostal spaces and other structures.
3.3 Fluoroscopy
throgram (RGU), micturating cystourethrogram (MCU), tracheoesophageal stula (TEF), intestinal malrotation, and
arthrography.
3.3.2 Interventional Fluoroscopy
1. Intussusception reduction
2. Hysterosalpingography
3.3.2.1 Digital Subtraction Angiography
Digital subtraction angiography (DSA) is a type of uoroscopy procedure that involves subtraction of bone and other
radiopaque structures like soft tissue from a uoroscopy
image so as to improve visualization of contrast-opacied
vascular structures. It is an extremely valuable tool for interventional radiology as many diagnostic and therapeutic procedures are performed using DSA. The process involves
obtaining a pre-contrast injection image (mask image), following which intraluminal contrast is injected and successive images obtained. The post-contrast image is subtracted
from the mask image to reveal an image that shows contrastopacied structures to greater advantage [1, 10].
3.3.3 Advantages ofDSA Include
1. Less invasive than open/surgical procedures.
2. Able to access difcult to reach, small vascular structures
precisely with microcatheters.
3. Real-time manipulation can be performed.
4. Cost effective as it requires shorter hospital stays compared to open surgical procedures.
Fluoroscopy has been a valuable tool in interventional radiology; however, due to radiation exposure not only to the
patient but also to the operator as well, its widespread use has
been discontinued. The advent of multiple advancements in
cross-sectional imaging like CT, MRI, and USG has led to
limited current use of uoroscopy for diagnostic and interventional radiology. It, however, continues to show advantages over invasive surgical procedures [10]. Insufcient
training for residents and fewer staff with adequate expertise
also contribute to its declining use.
3.3.1 Indications
Diagnostic uoroscopy procedures form the current mainstay of procedures performed nowadays, notable among
them being esophageal abnormalities (like achalasia, esophageal pseudo diverticulosis, and benign and malignant strictures), postoperative setting (demonstration of leak),
myelography, hysterosalpingography (HSG), retrograde ure-
3.3.4 Indications ofDSA
1. Drainage procedures
2. Diagnosis and treatment of obstructive and nonobstructive vascular diseases
3. Functional assessment of vascular structures
4. Angioplasty and venoplasty
5. Vascular stenting
6. Placement of vascular lters
7. Evaluation of graft anatomy and patency
8. Treatment of vascular leaks and injuries
9. Retrieval of catheters and guidewires
3.3.5 Limitations ofDSA
1. Ionizing radiation
2. Limited spatial resolution
3. Small eld of work
16
S. Vyas and A. Rao
Various complications that can be seen in DSA procedures are vessel thrombosis, bleeding, pseudoaneurysm formation, arteriovenous stulation, vascular dissection,
embolism and breakage of hardware, and adverse contrast
reaction.
3.4 Computed Tomography
CT is widely used for a variety of interventional procedures
like biopsy, drainage procedures, and ablations at many centers. Two approaches may be used in CT guidance: the stepand-shoot approach and the CT uoroscopy approach. While
the former allows control of radiation exposure and 3D capability, it does not allow real-time visualization of the needle
tip and lesion, which may be inuenced by patient compliance and motion. The CT uoroscopy, on the other hand,
allows real-time visualization at the expense of increased
radiation exposure for both the patient and the operator [11,
12]. Advances like robotic guidance and augmented reality
guidance are under investigation to further ne tune the procedures [2, 13–15]. Respiratory motion, cardiac pulsations,
and patient movement make CT-guided intervention procedures challenging as in other guiding modalities.
3.4.1 Advantages ofCT-Guided Interventions
1. CT can visualise areas adjacent to bony structures and air
containing areas which are not accessible to USG beam.
2. CT allows access to deep-seated posterior areas in abdo-
men and pelvis.
3. High spatial and contrast resolution of CT allows accu-
rate demarcation of target area.
4. Precise localization of lesion and near real-time visual-
ization as repeated scans are undertaken with progressive
needle advancement.
5. 3D capability of CT allows accurate spatial correlation
for needle advancement.
6. Use of intravenous contrast agents allows the use of
enhancement characteristics of target lesion as well as
delineate vascular and non-enhancing necrotic foci.
3.4.3 Limitations
1. Radiation exposure and need for repeated scanning as the
needle advances to reach the target.
2. Need for iodinated contrast injection if the lesion is better
visualized in a particular phase of enhancement and if
there is proximity to vascular structures, which may be
associated with adverse effects.
3. Repeated scanning increases radiation exposure to both
the subject and the operator.
3.5 Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) has numerous advantages over previously mentioned imaging modalities like
uoroscopy and CT, in addition to having the highest soft
tissue resolution. However, historically, MRI-based interventions have been limited, owing to the limited availability
of MRI conditional hardware as well as non-availability of
MRI scanners. The technical advancements from the earlier
biplanar low-eld interventional MR systems to the current
higher eld strength wide short bore magnets has revolutionized the interventional capabilities of MRI [16]. Moreover,
tailoring of various MRI sequences have improved the visualization of the needle track and the ablation zones. It should
be remembered that there is a tradeoff between the signal-tonoise ratio and acquisition speed, as needle placement
requires higher temporal resolution sequences like GRE or
SSFSE, which lead to increased susceptibility artifacts and
lower spatial resolution [17–19].
There are several factors that must be taken into account
pertaining to safety inside the interventional MRI suite:
1. Projectile effects of ferrous objects in strong magnetic
elds can pose a risk to the patient and healthcare personnel. Standard and strict safety protocols are needed to be
implemented in the interventional MRI suite.
2. Heating of metallic devices can be caused by the radiofrequency eld during MRI procedure.
3. Loud noise produced by rapid switching of magnetic
elds can cause hearing loss due to prolonged exposure.
3.4.2 Indications
1. Biopsy/FNA procedures of lung, liver, adrenal, and bone
2. Tubes and drainage procedures like abdominopelvic
drainages
3. Ablation—radiofrequency ablation, microwave ablation
of tumors, osteoid osteoma
3.5.1 Advantages ofMRI-Guided
Interventions
1. Soft-tissue contrast resolution is high with MRI, thus
exact and accurate localization and targeting of abnormality can be performed.
2. High sensitivity to liver, prostate, bone, and breast focal
lesions.
3. Multiplanar capability.
3 Image Guidance inInterventional Radiology
17
4. No risk of ionizing radiation.
5. Ability to fuse images with other modalities like ultrasound, CT, PET CT, etc.
3.5.2 Indications ofMRI-Guided
Interventions
1. Biopsy of lesions visualized only on MRI scan.
2. Cryoablation of malignant and non-malignant lesions
with superior visualization and monitoring of ice ball
during cryoablation and thermal ablation during RFA,
MWA, laser ablation, and MR-guided FUS.
3. Sclerotherapy of poorly visualized lesions on ultrasound
as MRI shows high T2 signal of these lesions.
3.5.3 Limitations
1. Longer scanning time is required with MRI.
2. Limited availability of MRI conditional and MRI compatible devices.
3. High cost of MRI.
3.6 Dose Reduction Techniques
andRecent Advances
The healthcare team in an IR suite is responsible for the radiation safety in the workplace by keeping radiation exposure
to staff and the patient to “as low as reasonably achievable”
(ALARA). The main objective is minimizing the unnecessary and unwarranted radiation exposure while maintaining
adequate image quality. It is vitally important to understand
the key principles of occupational and public radiation protection (justication, optimization of protection, and dose
limitation).
3.6.1 Dose Reduction inFluoroscopy
While the improvement in patient care with uoroscopy is
undoubted, the equipment is capable of producing large
amounts of radiation output, which can create serious consequences for the patient and operator [20, 21]. The main
source of exposure to the patient is the x-ray beam, whereas
for the operator it is the scatter radiation. Various techniques
that have been employed to ensure the same are enumerated
as follows [20–23]:
• Default setting: A default setting determines the rate of
radiation production prior to the procedure. Activation of
an appropriate default setting helps to maintain the image
quality while limiting the radiation dose. The operator can
manually change the settings based on the need.
• Pulsed uoroscopy: A series of short bursts of x-rays is
used instead of a continuous x-ray emission. An increased
pulse rate increases the temporal resolution concurrently
leading to a higher radiation exposure. Hence, the pulse
rate is determined by the operator based on need for temporal resolution. A 50% reduction in pulse rate results in
30% reduction in dose.
• Higher kVp: The amount of x-rays produced is dependent
on kVp and mA.It is directly related to kVp; however, the
relationship is not linear. Increasing the voltage by 15%
doubles the amount of x-rays; the general rule is to use the
highest kVp to achieve minimally acceptable image
quality.
• Tube current: The number of x-rays produced by the x-ray
tube is determined by the tube current. Increase in tube
current reduces noise, concurrently increasing the radiation dose. Since patient dose increases more rapidly than
noise decreases, it is not an ideal way to improve image
quality.
• Beam ltration: Higher energy x-rays reach the image
receptor contributing to image quality, whereas the lowenergy x-rays are primarily absorbed by the patient
leading to unwarranted radiation exposure. Beam ltration removes low-energy x-rays from the uoroscopic
beam (bremsstrahlung curve is shifted to right), reducing the radiation dose while maintaining the image
quality. Copper is a common lter used in uoroscopic
units, thickness of 0.1–0.9 mm in interventional
uoroscopy.
• Automated brightness control/Automated exposure rate
control (ABC/AEC): It is a feedback control loop that
allows automatic variation in tube current, tube voltage,
pulse width, and/or added ltration in response to tissue
thickness and attenuation.
• Last-image hold (LIH): The last image of the uoroscopic
sequence is retained on the monitor after the pedal is
released. This allows its careful inspection without further
irradiation.
• Fluoro save (FS) or uoro grab: The operator can select
and store the LIH or grab a uoroscopic image during live
uoroscopy. The FS spares the additional dose of digital
radiographic image which is approximately 10 times
higher.
• Last uoro loop replay: This allows the operator to save
the last uoroscopic sequence by pushing a button when
the uoroscopic pedal is released.
• Source to skin distance: It is the distance between focal
spot in x-ray tube and entrance plane of patient body.
Small increase in SSD causes a signicant reduction in
radiation dose, e.g., doubling SSD—decreases radiation
dose to 25%.
18
S. Vyas and A. Rao
• Source to image receptor distance: It represents distance
between focal spot and image receptor. A small decrease
in SID causes a signicant decrease in radiation output.
• Air gap: It corresponds to the distance between patient
and image receptor and directly proportional to the
amount of scatter radiation. Reducing the air gap,
decreasing the scatter radiation, and a resultant decreased
exposure to the operator.
• Collimation: It controls the cross-sectional area of the primary x-ray beam to which the patient is exposed. Avoid
unnecessary radiation exposure (especially radiosensitive
organs, such as breast, thyroid, eyes, and gonads).
• Image receptor: A larger image receptor absorbs more
x-rays that is transmitted from the patient, henceforth
reducing the scatter radiation and a consequent reduction
in operator exposure.
3.6.2 Special Considerations ofRadiation
Protection inPediatric Population
Children are more radiosensitive than adults for approximately 30% of cancers (thyroid and leukemia, etc.) [22–25].
They have a higher tendency to develop cancer also because
of higher life expectancy after a radiological procedure. The
general techniques for radiation safety are the same as
described above, except a few as mentioned below.
3.6.3 Remove Anti-scatter Grid
3.6.5 Checklist
A step-by-step checklist should be part of institutional protocol to ensure compliance of ALARA principle.
To Check Pre-procedure
1. Appropriate history of prior radiation exposure (diagnostic and therapeutic).
2. History of adverse reaction to previous radiation
exposure.
3. Adequately informed consent for the procedure, especially if it entails a large exposure. For cases in which
high radiation exposure is expected, a discussion of
adverse effects of radiation is a must. A detailed discussion is also warranted before imaging pregnant patients.
4. Radiologist and technical staff should explore alternate
imaging like ultrasound and MRI for the clinical indication. This is even more relevant when repeated imaging
follow up is required.
5. Use of appropriate radiation protection gear like apron,
glasses, thyroid shield by operators (lead aprons should
have 0.5mm Pb equivalent front and 0.25mm Pb equivalent on sides and back).
6. Mandatory use of personnel dosimeters (in radiation room,
staff should war the radiation dosimeters on collar outside
the lead apron and front of torso underneath apron).
7. Patient positioning should be such that hanging lead
shield/skirt/rolling shield can be used optimally.
8. Use of pediatric presets and setting of protocol based on
patient’s weight and size.
Radiographic equipment for pediatric population should
have provision to remove the grid easily. Patients with weight
of less than 18–20kg do not generate enough scatter radiation to cause signicant degradation of image quality. If grid
is not used in such patients, the small amount of scatter radiation generated will contribute to the required dose for optimum image production. This is especially true for
radiography involving high inherent contrast regions like
chest and barium/iodinated contrast studies [26, 27]. A tight
collimation is usually enough to keep the radiation dose low.
3.6.4 Pulsed Fluoroscopy
Appropriate pulse rate in a pediatric age group is as follows
[24, 25]:
Pediatric cardiac studies—30 pulse per second
Non-cardiac interventional studies—15 pulses per second
General uoroscopic study (GI or GU)—1–4 pulses per
second
To Check During the Procedure
1. X-ray beam collimation.
2. High source to object distance.
3. Image intensier to be as close to subject as possible.
This is not relevant while using the air-gap technique for
geometric magnication.
4. Low-pulse rate in uoroscopy.
5. Last-image hold whenever feasible.
6. Source-to-object distance is as large as possible.
7. Image intensier is as close as possible to the patient to
reduce radiation scatter, except when deliberately using
air-gap technique for geometric magnication.
8. During lateral view, keep arm out of the exposure.
9. Minimum staff in the exposure room.
10. In case substantial radiation dose levels (SRDL) are
exceeded, postponing of the study be considered depending on clinical scenario.
To Check Post-procedure
1. Check the record of patient dose metrics.
2. If dose exceeds thresholds, appropriate counseling of the
patient/attendant/guardian should be done.
3 Image Guidance inInterventional Radiology
19
3.7 Dose Reduction inCT
Radiation dose during a CT guided intervention is affected
by patient habitus, gantry rotation, pitch, slice thickness,
number of slices, area of imaging, tube voltage, and tube current. Various measures to reduce dosage can be done during
the pre-procedure scan, during the procedure, and at postprocedure scan times [20, 21, 23, 27].
• Pre-procedure scan—During the pre-procedure scan, the
length of the scan should include only the area of interest.
Moreover, the tube current can be reduced as diagnostic
quality imaging is not required, rather the scanning is
done to localize and mark the point of entry.
• During procedure—Once the area of interest is localized,
intermittent CT uoroscopy can be used with reduced
kVp and mAs setting. It should, however, be remembered
that a reduction in mAs may not be possible in obese subjects, especially in thickset body parts like lower abdomen and pelvis, where reduction in mAs might lead to
poor visualization of needle/guidewire due to increased
noise. In areas with inherent high contrast like thorax and
in thinset body parts, mAs reduction is extremely useful.
• Post-procedure scan—Post-procedure scan is advisable to
conrm placement of various tubes/catheters and to
screen for complications like bleeding and pneumothorax. Here also, the use of low mAs scanning is advisable
with the lowest scan length to reduce radiation exposure.
3.8 Special Considerations inPregnancy
Interventional radiologists play a key role in managing various complications of pregnancy during gestation and postpartum period. Various such complications include ectopic
pregnancy, symptomatic ovarian cysts, obstructive uropathy
in the antepartum and hemorrhage, post-cesarean section
abscess, and vesicouterine stula in the postpartum period.
Previously, surgery was considered the mainstay of management. However, surgery imposes a short-term risk of maternal/fetal morbidity and mortality or a long-term loss of
fertility. IR provides therapeutic options that obviates surgery, henceforth reduces maternal/fetal morbidity and preserves fertility [28, 29]. The maternal and fetal radiation
exposure during these procedures is also a matter of concern
due to possible long-term negative effects, making it imperative to restrict the radiation exposure to minimum
necessary.
Indications include
• USG-directed chemical injection in ectopic sac.
• Uterine artery embolization if adhesive placental disorders, atonic PPH.
• Glue obliteration of uterine AVM nidus as part of fertility
preserving procedure.
• Percutaneous nephrostomy in pregnancy-related obstructive uropathy.
• Percutaneous suprapubic cystostomy for bladder drainage
in traumatic vesicouterine stula.
3.9 Conclusion
Various radiological modalities are used to guide interventional procedures, each with their unique advantages and
limitations. The modality that best depicts and is best suitable for a specic clinical scenario is often decided based on
multidisciplinary discussion, local expertise, and availability of equipment, so as to provide optimum care to the
patients.
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Contrast andDrugs inInterventional
Radiology
SnehaGoswami, SmitaManchanda, AshuSeithBhalla,
andPriyankaNaranje
4
Key Messages
1. Iodinated contrast media (ICM) are crucial for radiological procedures, with risk mitigation strategies including
proper hydration and low or iso-osmolar agents.
2. Carbon dioxide (CO2) serves as a negative contrast
agent, offering an alternative in patients with iodinated
contrast contraindications, requiring proper administration technique.
3. Thrombolytics like alteplase and tenecteplase are effective for arterial ischemia and venous thrombosis but
have contraindications such as active bleeding.
4. Anticoagulants like unfractionated heparin and novel
oral anticoagulants prevent thrombus formation with
specic indications and monitoring needs.
5. Antiplatelet drugs such as aspirin and clopidogrel inhibit
platelet aggregation, requiring careful management
before high-risk procedures.
6. Reversible P2Y12 inhibitors like ticagrelor and cangrelor prevent platelet aggregation with specic dosing
regimens and routes of administration.
7. Glycoprotein IIb/IIIa inhibitors block platelet aggregation and are administered intravenously, with varying
durations of action.
8. Vasodilators like nitroglycerine and verapamil relieve
arterial spasm, each with specic indications and dosing
considerations.
9. Vasopressin induces vascular smooth muscle contraction and is primarily used for acute gastroenterological
bleeding, with tailored dosing protocols.
10. Thrombin accelerates clot formation and is used for
treating pseudoaneurysms, requiring careful patient
selection and monitoring.
4.1 Introduction
Over the past few years, there has been a tremendous increase
in indications for various vascular and non-vascular procedures performed in the interventional radiology suite with
advances in technology in imaging equipment, tools, and
pharmacologic agents. With the growing indications and several interventional radiological procedures performed, it has
become necessary for the radiologist to know about the uses,
side effects, and various interactions of these pharmaceutical
agents that can potentially lead to adverse consequences for
the patient. Therefore, radiologists and their staff need to be
aware of these risks to be able to prevent and manage them
as well. This chapter includes various commonly used contrast agents and drugs that are used during interventional
radiological procedures (Table4.1, Fig.4.1).
Table 4.1 Classes of pharmaceutical agents used commonly in interventional radiology
I.Contrast agents
• Iodinated contrast agents: Iopamidol, iomeprol, iopromide, and
iohexol
• Carbon dioxide (CO
II.Anticoagulation and antiplatelet medications
• Thrombolytics: Prourokinase, Rt-PA (recombinant tissue
plasminogen activator), streptokinase, urokinase
• Anticoagulants: Unfractionated heparin (UFH), low molecular-
weight heparins (LMWH)
• Antiplatelets: Aspirin, clopidogrel, dipyridamole, glycoprotein
IIb/IIIa inhibitors
III. Vasodilators: Nitroglycerin, verapamil
IV. Vasoconstrictors: Vasopressin, desmopressin
V. Prothrombotics: Thrombin
) as a negative contrast agent
2
S. Goswami · S. Manchanda (*) · A. S. Bhalla · P. Naranje
Department of Radiodiagnosis and Interventional Radiology,
All India Institute of Medical Sciences, Delhi, India
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2024
S. H. Chandrashekhara (ed.), Textbook of Interventional Radiology, https://doi.org/10.1007/978-981-97-9601-4_4
21
22
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bc
S. Goswami et al.
Fig. 4.1 (a) Iopromide
(Ultravist, conc. 370mg L/
mL); (b) Iohexol
(Omnipaque, 350mg L/mL);
(c) Iomeprol (Iomeron,
400mg L/mL); (d)
Thrombolytic: Streptokinase;
(e) Anticoagulant:
Unfractionated heparin; (f)
Vasoconstrictor: Vasopressin;
and (g) Vasodilator:
Nitroglycerin
a
de
4.2 Pharmaceutical Agents
4.2.1 Contrast Agents
For most radiological procedures, diagnostic or interventional,
contrast media have a crucial role in providing accurate diagnoses by improving contrast. An ideal contrast agent is water
soluble, chemically stable, biologically inert, and low in viscosity with osmolality same or lower than human serum, safe,
and cost-effective [1]. Contrast agents can be classied as
positive or negative; positive contrast agents are more radiopaque than the surrounding tissue, e.g., iodinated contrasts
and barium sulfate, while negative contrast agents are gases of
low density and appear radiolucent, e.g., carbon dioxide [2].
For safe administration and favorable outcomes, the areas
to be focused upon are screening, patient selection, premedication, and treatment of adverse events.
4.2.2 Iodinated Contrast Media (ICM)
Iodinated contrast agents are the most commonly used intravascular agents in interventional radiology. These are generally considered safe when appropriately administered,
however, life-threatening reactions are known to occur, and
risk in patients with impaired renal function is well established. Therefore, it is important to be aware of the various
contrast reactions as well as the current guidelines for the
prevention and management of these complications.
American College of Radiology manual lays down the
guidelines for contrast media administration and management of related complications [3].
4.2.2.1 Basic Chemistry ofICM
Benzene is the parent molecule of iodinated contrast media,
and the carbon atoms are numbered in a clockwise manner
from 1 to 6. By introducing iodine atoms at second, fourth,
and sixth locations, we get a tri-iodinated benzene ring that
is common among all ICM [4].
Iodine has a higher atomic number and weight (atomic
weight 127) and K shell electron binding energy (34keV)
which increases the likelihood of a photoelectric effect as it
is near the mean energy used in diagnostic X-rays, thereby
improving the image quality [5].
4.2.2.2 Types ofICM
Iodine-based contrast agents are divided according to osmolality (high, low, or iso-osmolar) compared with the human
serum, ionicity (ionic or non-ionic), and the number of benzene rings (monomer or dimer depending upon the number
of benzene rings in each molecule) [6]. The osmolality of
high-osmolar contrast media (HOCM) is approximately
1400 mOsm/kg H2O osmolality which is about 5–8 times
the osmolarity of the plasma [7].
4 Contrast andDrugs inInterventional Radiology
23
Low-osmolar contrast media (LOCM) were developed in
the 1970s and have largely supplanted HOCM in clinical
use. All are able to carry three iodine particles per one
osmotic particle (3:1 ratio) and most are non-ionic as they
have covalent bonding. They do not dissociate in the plasma
due to which lesser osmotically active particles are available,
and therefore, they are low in osmolality (600–900mOsm)
[7]. Ioxaglate (Hexabrix®, Covidien plc, Dublin, Ireland)
being an ionic dimer is an exception. It is an ionic LOCM
and carries six iodine particles per two osmotic particles and
dissociates in plasma, also resulting in a ratio of three iodine
particles to a single osmotic particle [8].
Iso-osmolar contrast media (IOCM) are the newest contrast agents. They are nonionic dimers allowing six iodine
particles to be attached to one osmotic particle (6:1 ratio).
This results in a contrast medium that is iso-osmolar
(300 mOsm) to plasma [8]. In patients with normal renal
function, LOCM is preferred over HOCM as these are better
tolerated and have fewer side effects. In high-risk patients,
IOCM is preferred over LOCM for IA administration as
despite a lack of any compelling evidence in the literature of
its safety over LOCM, however, IOCM has better tolerance.
LOCM and IOCM are used in angiography as they are
associated with the least amount of vasospasm and also the
least peripheral discomfort during peripheral angiograms [9].
Several studies demonstrated that iodixanol is associated with
less pain and heat discomfort [10]. Better tolerance potentially leads to fewer motion artifact and better image quality
during digital subtraction angiography (DSA) acquisition.
This eventually results in reduced contrast and radiation dose.
4.2.2.3 Post-contrast Acute Kidney Injury
andContrast-Associated Acute Kidney
Injury (CA-AKI)
Contrast-associated acute kidney injury (CA-AKI) describes
a sudden renal dysfunction occurring within 48h of administration of intravascular iodinated contrast media. It is to be
noted that this does not necessarily implicate contrast
medium as the cause of renal dysfunction [11–20].
Previously termed contrast-induced nephropathy,
contrast- induced acute kidney injury (CI-AKI) is dened as
a sudden deterioration in renal function caused by the intravascular administration of iodinated contrast medium; hence,
CI-AKI is a subgroup of CA-AKI.
While there are only a limited number of studies that have
a suitable control group, reported incidence in CA-AKI
includes a combination of both CA-AKI and CI-AKI.However,
the reader should note that these are not synonymous terms
[11–20].
Pathogenesis
The pathophysiology of CI-AKI remains elusive. Various contributing factors such as direct tubular toxicity and altered renal
hemodynamics (vasoconstriction) have been proposed [21–31].
Risk Factors
The most important risk factor is pre-existing severe renal
function impairment. Other risk factors include diabetes
mellitus, hypertension, cardiovascular disease, hyperuricemia, diuretics, old age, and administration of multiple doses
of contrast medium within 24h [3, 13, 32–35].
Various equations are available to provide a theoretical
threshold value for the maximal contrast dose that can be
administered; however, these equations have limitations that
should be considered. It is to be noted that multiple myeloma
is not considered a risk factor [36–38].
The risk of CI-AKI is much higher with cardiac angiography compared to intravenous administration of contrast
medium due to these reasons: intra-arterial and supra-renal
injection; more abrupt and concentrated contrast medium
dose to the kidneys; and catheter used for the injection can
disrupt atheroemboli [12, 15, 39].
Choice ofContrast
In patients having renal functional impairment, LOCM is
considered less nephrotoxic than HOCM and should be preferred [40]. There is no evidence to suggest a higher risk of
nephrotoxicity associated with HOCM in patients having
normal renal function.
There is also no evidence in the current literature to suggest that IOCM is better than LOCM in terms of risk of
developing nephrotoxicity [41–44].
Diagnosis
Diagnosis of CA-AKI is based upon the Kidney Disease
Improving Global Outcomes (KDIGO) criteria for AKI,
which is common for dening intrinsic acute kidney injury
regardless of etiology [45–47]. Therefore, it can be used to
dene the parameters of CA-AKI as well as CI-AKI.
According to KDIGO criteria, AKI is diagnosed if one of
the following occurs within 48h after a nephrotoxic event
(e.g., intravascular iodinated contrast medium exposure) [46]:
(i) An absolute rise in serum creatinine ≥0.3 mg/dL
(>26.4μmol/L)
(ii) ≥50% (≥1.5-fold above baseline) increase in the serum
creatinine or
(iii) Urine output reduced to ≤0.5mL/kg/h for at least 6h
It should be kept in mind that elevations in serum creatinine are neither sensitive nor specic for individual types of
AKI.
Risk Threshold
There is no denite and widely accepted threshold of serum
creatinine or eGFR beyond which intravascular ICM should
never be administered due to the risk of CI-AKI [3]. However,
most evidence-based threshold value is 30mL/min/1.73m
2
if a threshold value needs to be considered [13].