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12 Contrast-Enhanced Ultrasound ofthePediatric Kidneys
121
vs. 79.4%) [21]. Recently, a cohort of studies has
published high sensitivity and NPV of
CEUS.Barr etal. published sensitivity and NPV
of 100% [22] while Li etal. reported a sensitivity
of 93.3% and NPV of 99.2% respectively [23].
Our department study results support these assertions as applied to the pediatric patient, with a
sensitivity of 95.5% and NPV of 98.0% [24].
A confounding factor in the interpretation of
CEUS studies has been the differentiation of malignancy from benign tumors and in turn from an
inammatory lesion. This is due to the vascularity
Table 12.1 Summarizes the most frequent CEUS indications in pediatric patients with renal disorders
Indications of pediatric renal CEUS
• Renal focal solid lesions, assessment of
vascularity
• Complex cystic renal lesions
• Complicated renal infection
• Renal transplant complication
• Renal trauma
• Renal artery stenosis
a
Renal artery stenosis: not commonly used but may have
future indications
a
and enhancement of granulation tissue within these
inammatory lesions which can mimic tumors.
Some studies have shown that approximately 30%
of renal cell carcinoma (RCC) mimic angiomyolipoma (AML) on US and that half of the RCC can
be hyperechoic [25] (Table12.1).
12.5 Renal Angiomyolipoma
Classically a renal AML shows in-lling of the
UCA starting from the periphery of an echogenic
lesion and slowly spreading to the center of the
lesion with iso or hypoenhancement. This is most
likely due to most of the blood vessels in AML
being malformed with a tortuous course and disorganized blood vessels. These anatomical features
associated with renal AML result in difcult inow
and slow outow of the UCA: the start of the inow
and outow of the UCA is later in the lesion than in
the renal cortex. A typical renal AML is where the
lesion is seen to be less enhancing than the adjacent
normal renal parenchyma in all phases (i.e., arterial,
early venous, and delayed phases (Fig.12.4).
Fig. 12.4 Renal angiomyolipoma (AML) shown on a
split-screen view with the CEUS (left) and the baseline
low mechanical index (MI) ultrasound image (right). An
8-year-old boy, with an incidental note of a left kidney
mass on bedside ultrasound. Non-contrast image shows a
large echogenic exophytic mass (arrowheads), which
shows post-contrast enhancement, which is less enhancing than the renal parenchyma (star) at all phases. No signicant washout is seen within the lesion (arrows)
122
J. Kapur and Z. Harkanyi
12.6 Renal Parenchyma Defects
Ultrasound contrast agents are truly intravascular
and do not “leak” into the surrounding tissue (no
“equilibrium” phase) and are not subjected to renal
ltration; they behave like “vascular tracers.” Using
CEUS to identify the vessels, rather than color
Doppler US, to track the course of the renal artery
has been shown to be more accurate and shortens
examination time, particularly with unfavorable
body habitus, and can be used in patients with renal
impairment [24, 26]. Contrast- enhanced ultrasound
is an excellent modality to assess the perfusion pattern of a kidney, due to the unique ability to image
microcirculation. After UCA injection, there is an
immediate and prompt enhancement of the kidney,
usually seen within 10s. The main renal artery, its
bifurcation, the arcuate and segmental arteries rapidly enhance with perfusion seen up to the periphery of the renal cortex (Fig.12.5).
This ability to image the microcirculation to
the peripheral renal cortex is useful in the
assessment of any patient with a renal transplant. A cortical infarct often appears as a
wedge-shaped defect in all phases of the contrast enhancement when compared to the rest
of the renal cortex. Ischemia can be reliably
differentiated from a true infarction, as in ischemia, some slow inowing UCA will be visible
[27]. Similarly, in trauma, lacerations and
hematomas are seen as non-enhancing areas
when compared to the surrounding enhancing
renal parenchyma. Active bleeding and pseudoaneurysm formation are also easily identied. Renal transplant complications, including
vascular compromise, vascular patency, cortical infarcts, and acute cortical necrosis
(Fig. 12.6), can be investigated with a CEUS
examination, with relative ease at the bedside,
and with a condent interpretation.
Fig. 12.5 Normal renal perfusion. Post-contrast US
shows diffuse prompt homogenous uniform enhancement
of the kidney (arrows), with no perfusion defects or areas
of ischemia/necrosis. This appearance allows for the
exclusion of the possibility of a renal thrombo-embolic
episode
12 Contrast-Enhanced Ultrasound ofthePediatric Kidneys
Fig. 12.6 Renal cortical necrosis. A patient with blunt
abdominal trauma resulting in occlusion to the main left
renal artery. Following the administration of an ultrasound
contrast agent, there is an absence of enhancement to the
renal cortex (arrows), consistent with subcapsular cortical
necrosis
123
12.7 Focal Pyelonephritis
andAbscess Formation
In the appropriate clinical context, CEUS can be
used as an accurate tool in the assessment of
renal infection and inammatory renal masses.
Focal nephronia can often present as a
well- dened mass and presents a clinical conundrum for the referring pediatricians and concern
for the parents; CEUS can improve the ability to
differentiate a true renal malignancy from an area
of benign change (Fig.12.7). Often the characteristics on CT and MR imaging can be non-specic. Any regional difference in parenchymal
enhancement is better detected than any global
impairment to perfusion, as the adjacent normal
parenchyma serves as an internal reference.
Fig. 12.7 Lobar nephronia shown on a split-screen view
with the CEUS (left) and the baseline low mechanical
index (MI) ultrasound image (right). This 16-year-old boy
was being treated for urinary tract infection. A focal lesion
is identied at the upper aspect of the right kidney arrow).
Post-contrast US of the heterogeneous lesion demon-
strates enhancement similar to the rest of the renal parenchyma, with areas of non-enhancement in the center of the
lesion (arrowheads). No contrast washout was noted.
These features are similar to CT imaging features of lobar
nephronia
124
J. Kapur and Z. Harkanyi
Children with pyelonephritis can develop renal
abscesses as a complication. As conventional US
is suboptimal at depicting, or condently identifying an early renal abscess, especially when presenting on US as an indeterminate solid lesion. A
CEUS examination is ideal to depict an abscess
and will demonstrate a heterogeneous lesion with
a central cavity, with a thick enhancing rim and
often with a surrounding non-vascularized perinephric uid collection. There is normally
peripheral enhancement of the lesion on the
CEUS examination, with the uid central area of
pus demonstrating no central enhancement.
There is no washout on delayed images
(Fig.12.8).
12.8 Pseudotumors
A pseudotumor represents a number of normal
renal anatomic variants that can be misinterpreted
as a tumor on imaging. The most frequently
encountered normal variants are: persistence of
fetal lobulation, hypertrophied column of Bertin,
and dromedary or splenic hump [28]. In conventional US and color Doppler US, pseudotumors
have dened features. The addition of CEUS
allows for the identication of a normal renal
perfusion pattern, readily distinguished. This represents a major criterion for the diagnosis of a
pseudotumor. There is limited evidence for this,
but condent identication of a pseudotumor
Fig. 12.8 Renal abscess shown on a split-screen view
with the CEUS (left) and the baseline low mechanical
index (MI) ultrasound image (right). A 10-year-old boy
being treated for recurrent urinary tract infections. A bedside ultrasound was performed to look for secondary renal
ndings, due to persistent high fever, and elevated
C-reactive protein markers. Non-contrast images show
heterogeneous hypoechoic lesion (arrows). Post CEUS,
there is a prompt enhancement of the periphery of the
lesions, with no central enhancement (arrowheads) and no
delayed washout. The enhancement timing is similar to
the rest of the renal parenchyma
12 Contrast-Enhanced Ultrasound ofthePediatric Kidneys
125
Fig. 12.9 Renal pseudotumor on a split-screen view with
the CEUS (left) and the baseline low mechanical index
(MI) ultrasound image (right). A 15-year-old girl, with
incidental ndings of a non-specic “mass” on her bedside ultrasound study. Non-contrast US shows an area of
apparent altered echogenicity in the interpolar region of
directly on US will avoid the need for further
imaging with CT or MR (Fig.12.9).
12.9 Malignant Renal Lesions
Renal lesions are common incidental ndings in
adult abdominal imaging, with cysts diagnosed in
up to 35% of individuals after the seventh decade.
In the pediatric population, a Wilms’ tumor is the
most prevalent renal malignancy. However, due
to the usually large size of a Wilms’ tumor at presentation, CT and MR imaging have normally
been performed, with the usefulness of using
CEUS not established. Although renal cell carcinoma (RCC) comprises only a small subset of
renal lesions in the child [15], these tumors are
often initially detected on imaging, preceding
any clinical signs. Over 50% of RCC are initially
the kidney (arrows), which was suspicious for a possible
renal tumor. Post-contrast US shows prompt and homogenous enhancement in this area (arrowheads), with similar
enhancement to rest of the kidney, with no abnormal
enhancement or washout, indicating the presence of normal renal tissue, likely a prominent column of Bertin
diagnosed in this manner on imaging and with
the insidious growth of an RCC, more than 60%
of patients do not show any classic symptoms of
hematuria, abdominal mass, or loin pain [29, 30].
Renal cell carcinomas are often identied by
their increased vasculature, an important nding
that is only seen with contrast-enhanced imaging
[9, 11, 31, 32]. Although CT and MR imaging
remains the modalities of choice, the limitations
imposed by renal impairment, contrast allergies,
radiation, and even technical and timing errors
are disadvantageous.
An RCC is characterized by numerous thinwalled blood vessels with increased blood ow
physiologically and intratumor necrosis with
hemorrhage and calcication common [33]. The
RCC enhances rapidly and intensely after UCA
administration due to this increased blood ow
(Figs.12.10 and 12.11). The UCA than washes
126
J. Kapur and Z. Harkanyi
Fig. 12.10 Renal cell carcinoma shown on a split-screen
view with the CEUS (left) and the baseline low mechanical index (MI) ultrasound image (right) in a 13-year-old
boy presented with hematuria for investigation. Following
UCA administration, the lesion showed homogenous cen-
Fig. 12.11 Renal cell carcinoma shown on a split-screen
view with the CEUS (left) and the baseline low mechanical index (MI) ultrasound image (right). A complex solid
tral enhancement (arrow) within the lesion, which
appeared less enhancing as compared to the rest of the
renal parenchyma, and showed washout in the delayed
images, suspicious for a malignant lesion
cystic encapsulated lesion at the lower pole of the left kidney (arrows) with immediate enhancement and areas of
washout after intravenous contrast injection (arrowheads)
12 Contrast-Enhanced Ultrasound ofthePediatric Kidneys
127
out rapidly in comparison to the adjacent liver/
spleen [10]. Almost all malignant renal lesions
show similar imaging characteristics on CEUS,
with immediate contrast enhancement and rapid
washout, appearing less enhancing than the adjacent renal parenchyma on delayed images [34].
Despite some conicting data on RCC vascularization patterns, published studies have generally been positive [35]. Of note, Barr et al.
evaluated the performance of CEUS in 1018
indeterminate renal lesions and showed high
sensitivity 100%; specicity 95.0%; PPV 94.7%;
and NPV of 100% [22]. The main advantage of
CEUS is the avoidance of any renal damage and
the issue with the increasing prevalence of acute
kidney injury limiting the use of contrastenhanced CT and MR [36]. Contrast-enhanced
ultrasound will play a larger role in evaluating
and differentiating benign from malignant renal
lesions in the future.
12.10 Summary
Contrast-enhanced ultrasound is useful in children, as this reduces the radiation burden of CT,
and this technique is likely to be benecial in
similar indications as in adults (such as differential of focal lesions in parenchymal organs,
organ perfusion) [2, 5, 37, 38]. Contrastenhanced ultrasound has proven to be an excellent tool in the assessment of renal perfusion,
renal infection (abscess), solid and cystic renal
masses (cysts, angiomyolipoma’s, neoplastic
lesions), and pseudo-tumors [27]. The main
benet of CEUS over other investigation modalities in assessing renal pathology in children is
that UCAs are not nephrotoxic and can be
employed safely in patients with impaired renal
function. Such an advantage, coupled with a
lack of ionizing radiation adds immense value
in the assessment of renal diseases. Possible
contraindication for the use of CEUS in the
pediatric age group would be a history of the
right to left shunts, severe cardiac rhythm disorders, and severe respiratory failure including
respiratory distress syndrome, in keeping with
the recommendations of the UCA manufacturer
[39].
However, the use of CEUS as an imaging
modality does have some limitations: a relatively
short diagnostic window that might need two
UCA injections for the same kidney or one injection for each kidney. Simultaneous assessment of
more than one focal lesion may be difcult and
may require multiple injections during the examination. In general, US is relatively harder to perform and interpret in the obese child and bowel
gas can interfere with images. Patient compliance
is required as the lesion may not be visible in one
particular position or the patient may be required
to hold his or her breath, which is not always possible with the child. As the UCA is not excreted
by the kidney, it is not possible to assess the renal
excretory function and detailed anatomy of the
urinary collecting system. There is not universal
approval for the use of UCA in children, and
often these agents are used off-label, not an issue
in medical practice [40]. With the approval of the
use of an intravenous UCA in the United States,
it is expected that the applications will increase.
In conclusion, CEUS is an accurate, inexpensive, non-radiation modality, with an accurate
depiction of enhancement patterns of focal renal
lesions. It is safe to be used in children with renal
insufciency and renal failure and appears to
have minimal episodes of contrast allergy. Its
accuracy is at least similar, if not better than CT
or MR imaging in the assessment of focal renal
lesions and can be used as a modality of choice
for solitary focal renal lesions in presence of
renal insufciency. Its role in the pediatric age
group has been less dened and further studies
should be performed to validate its use as a safe
and viable alternative to CT and MR imaging for
renal diseases.
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Pediatric Contrast-Enhanced
Ultrasonography (CEUS)
oftheSpleen
DorisFranke andZoltanHarkanyi
13
13.1 Introduction
The spleen is rarely affected by primary diseases,
but secondary diffuse or focal alterations may be
seen in a broad variety of causes. For all imaging
modalities, including contrast-enhanced ultrasound (CEUS), characterization of focal or diffuse splenic lesions is more difcult than in the
liver. Blood pool agents however allow a better
description of the parenchymal perfusion and
vascularization pattern. Contrast-enhanced ultrasound of the spleen increases the detection rate of
splenic infarction, trauma, and splenuncula [1, 2]
and is an ideal indication for CEUS in children in
order to reduce the overall radiation burden [3].
13.2 Investigation Technique
The enhancement pattern of the ultrasound contrast agent (UCA) is described in the early arterial and later parenchymal phase as being hyper-,
D. Franke
Pediatric Ultrasonography, Department of Pediatric
Kidney, Liver and Metabolic Diseases, Children’s
Hospital, Hannover Medical School,
Hannover, Germany
e-mail: Franke.Doris@mh-hannover.de
Z. Harkanyi (*)
Department of Radiology, Heim Pal National
Pediatric Institute, Budapest, Hungary
e-mail: harkanyi@heimpalkorhaz.hu
iso, or hypo-enhancing in comparison to the surrounding splenic tissue and the enhancement of
the left kidney. The reasons for the comparably
long duration and higher intensity of UCA
enhancement of the spleen in relation to other
organs are not fully understood. Pooling of the
UCA in the sinusoids or splenic tropism [4, 5] is
likely caused and under discussion.
The arterial phase in the spleen lasts for 5–60s
and the parenchymal phase up to 5min (or even
longer) after UCA injection [4]. Depending on
the indication, the sonographic investigation
should be performed in an intermittent manner in
order to avoid bubble destruction. The dose
depends on the age and weight of the child, the
ultrasound device, the software and transducer
used, the depth of the lesion, and lesion vascularity. The UCA dosage is usually less than the dosage for the liver or kidney due to the intense and
long-lasting UCA enhancement in the spleen.
During scanning, UCA intensity, homogenicity, and focal lesions should be observed.
Limitations for CEUS are the same as for B-mode
US imaging: difcult viewing of the subdiaphragmatic and neighboring areas of the spleen
due to lung or colon gas overlay, great depth, or
small lesions (<1cm).
In the arterial phase, a typically inhomogeneous pattern of UCA enhancement can be
observed in many patients. This is termed the
“tiger or zebra pattern” and thought to be caused
by different UCA velocities in splenic capillaries,
© Springer Nature Switzerland AG 2021
P. S. Sidhu et al. (eds.), Contrast-Enhanced Ultrasound in Pediatric Imaging,
https://doi.org/10.1007/978-3-030-49691-3_13
131