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4 Contrast-Enhanced US, andUltrasound Elastography inChildhood
Fig. 4.5 VUR into caudal system of duplex kidney: ce-VUS in a girl after recurrent febrile UTIs
and sonographically known duplex kidney. ce-VUS depicts dilating VUR into massively distorted
and dilated pelvi-calyceal system (asterix) of the lower moiety (VUR V°) (a). Note torturous
course of dilated ureter (arrow) (b)
65
Additionally, by using the drip infusion as manometer—information can be
obtained on bladder function disturbance (such as intermittent infusion stops caused
by uncoordinated or premature detrusor contraction or sphincter detrusor dyscoordination) enhanced by features not visible by VCUG such as bladder wall thickening or trabeculation.
ce-VUS also reliable in duplex kidneys (Fig.4.5).
Always assess urethra (e.g., on a dedicated lling cycle), best by perineal
approach if feasible (see Fig.4.3c).
Restrictions of US Technique
• Limited depiction of mid-ureter portions (careful and graded compression sometimes helps to remove bowel gas, as well as access from ank).
• Restricted access to distal ureter at poor bladder lling.
• More difcult, sometimes cumbersome accessibility of urethra.
• Less-comprehensive overview of entire anatomy (one may try to use panoramic
imaging to show VUR from bladder up to kidney, e.g. using a coronal/lateral
view with a large curvilinear transducer)-feasible particularly in neonates or
infants with gross and bilateral VUR.
• Limited visualisation of diverticula (particularly those only posing intermittently
and thus only briey visible, e.g. during voiding).
• VUR I° may be missed in case of retrovesical shadowing or emptied bladder—
probably less important, as low-grade VUR usually does not indicate treatment,
and (due to longer observation period and different behaviour of UCA) ce-VUS
tends to rate VUR slightly higher than radiographic VCUG.
66
M. Riccabona and H. J. Mentzel
4.1.4 Other Intracavitary Use ofce-US: Sono-Genitography,
Sonographic Pyelography andMany Potential Others
UCA can be instilled into any other hollow organs or other cavities for improved
assessment particularly of size, form, stulae, connection to other compartments,
detailed anatomy, drainage, etc., as performed with uoroscopy.
UCA can be instilled after vaginal catheterisation for sono-genitography in geni-
tal malformations; after nephrostomy into the urinary tract; into the gall bladder and
biliary tract; in the stomach or jejunum orally, via a feeding tube or after PEG/PEJ;
for abscess drainage or cyst puncture; for agent instillation (into any structure—
cysts, vessels, etc.); into pleural or peritoneal space; or while shunting cerebral ventricles (even intraoperatively) in complicated anatomy (see Fig.4.1). UCA can also
be given orally/rectally for assessment of bowel course (e.g., query malrotation),
shape and possible stulae or connections (e.g., anorectal malformation spectrum,
urogenital sinus, etc.).
UCA concentration for intraluminal ce-US depends on application (e.g., higher
dose in communicating systems and high frequency transducers) and should not be
too high to avoid shadowing of deeper areas. “Eminence” based recommendations
derived on experience suggest similar dose as for ce-VUS: 0.1–0.5% up to 5% concentration—no dose ndings studies exist for childhood.
Note All these applications are off-label.
4.1.5 Intravenous ce-US (CEUS)
With increasing US potential both on grey scale and with aCDS, ce-(Doppler)US is
rarer necessary for depiction and display of anatomic structures; sometimes intravenous (IV) application of UCA (usually named CEUS) can be helpful in obese children or difcult scanning conditions (e.g., depiction of vascular malformations by
transcranial US, depiction of cerebral vessels/assessment of severe cerebral perfusion decit, deeply positioned vessels and visualisation of perfusion in vessels at
poor scanning conditions at very low ow status/bad insonation angle).
CEUS is particularly helpful in conditions where basic US intrinsically is poor to
depict potential changes (e.g., depicting parenchymal organ lesions in early posttraumatic setting—even using aCDS). CEUS signicantly improves lesion detection, not only for traumatic conditions but also in other circumstances (e.g., oncology
patients with suspected liver metastasis).
Dynamic CEUS (store cine loops for detailed analysis) improves detection and
characterisation of focal lesions in parenchymal organs, particularly in liver (documentation as image series possible—Figs. 4.6 and 4.7), but there are also other useful indications, e.g., complicated renal cysts.
Diagnostic criteria same as in adults, established primarily for liver—short over-
view given in Table4.2.
4 Contrast-Enhanced US, andUltrasound Elastography inChildhood
Fig. 4.6 Abdominal intravenous CEUS: double/split image display—contrast-weighted image to
the left. Normal homogenous enhancement spleen after intravenous application of UCA ruling out
laceration
67
Fig. 4.7 Contrast-enhanced US (CEUS, intravenously applied) in giant neonatal haemangioma/
haemangioendothelioma. (a) Native grey scale image: echogenic partition with relatively sharp
borders and large vessels primarily in the right liver lobe indicating a huge liver mass in this neonate. (b–d) Serial images of neonatal liver CEUS performed for lesion characterisation—it shows
the typical enhancement pattern, form early arterial peripheral inow to late portal-venous phase
with increasing centripetal UCA lling (c), typically for haemangioma; (b) additionally, early lling of large draining vein (d) indicating high shunt volume. Double/split image display—contrastweighted image to the left in (b, c), only contrast-weighted image in (d)
68
M. Riccabona and H. J. Mentzel
Table 4.2 CEUS enhancement pattern in liver lesions additional new line for hepatocellular
carcinoma
Entity
Arterial phase Portal-venous phase
Late phase
(A) Non-cirrhotic liver
Adult haemangioma
Typical features Peripheral nodular Partial/complete Complete
Additional features Enhancement Centripetal ll in Nonenhancing
Small lesion: Complete
Rapid centripetal
enhancement
Infantile haemangioma (NICH/RICH)—Haemangioendothelioma: Features vary with size
Typical features Peripheral enhancement Partial Incomplete
enhancement
Additional features Early large draining vessel
shunt
Centripetal ll in Nonenhancing
regions
Small lesion: Complete
Rapid centripetal
enhancement
Focal nodular hyperplasia (FNH)
Typical features Hyperenhancing from centre Hyperenhancing Iso-/
hyperenhancing
Additional features Complete, early Unenhanced central
scar
Unenhanced
central scar
Spoke-wheel arteries
Feeding artery
Hepatocellular adenoma
Typical features Hyperenhancing, complete
Isoenhancing Isoenhancing
nonenhancing regions
Additional features Hyperenhancing Slightly
hypoenhancing
Nonenhancing
regions
Nonenhancing
regions
Other paediatric tumours: Features vary with size, but not specic for entity, includes
malignancy
Typical features Hyperenhancing, Isoenhancing Iso-/
hypoenhancing
Additional features Nonenhancing regions Hyperenhancing Slightly
hypoenhancing
Nonenhancing
regions
Nonenhancing
regions
Focal fatty inltration
Typical features Isoenhancing Isoenhancing Isoenhancing
Focal fatty sparing
Typical features Isoenhancing Isoenhancing Isoenhancing
Abscess
Typical features Peripheral enhancement
a
Hyper-/isoenhancing
rim
Hypoenhancing
rim
4 Contrast-Enhanced US, andUltrasound Elastography inChildhood
Table 4.2 (continued)
Entity
Additional features No central enhancement No central
Simple cyst
Typical features Nonenhancing Nonenhancing Nonenhancing
(B) Cirrhotic liver
Regenerative nodule (±dysplastic)
Typical features
(not diagnostic)
Additional features Hypoenhancing, particularly
Hepatocellular
carcinoma (HCC)
Typical features Hyperenhancing Washout=Hpo-/
Additional features Time and intensity depends
Adapted from: Claudon M etal. (2012) Guidelines and good clinical practice recommendations for
Contrast Enhanced Ultrasound (CEUS) in the Liver—Update 2012, Ultraschall Med. https://doi.
org/10.1055/s-0032-1325499)
a
Valid in immunocompetent patients—on imunosuppressed patients with less reaction and less
membrane formation this sign may be missing
b
Cirrhosis rare in infants and children. In cirrhotic liver, simple cysts, haemangioma, carcinoma
and abscesses may also be found—show same enhancement pattern as in non-cirrhotic liver. All
other entities rare in childhood cirrhotic livers. No specic enhancement patterns for hepatoblastoma or other paediatric liver tumours yet reported; however, possibly rhabdomyosarcoma tend to
show a more centripedal enhancement, other tumours enhance more centrifugally
Arterial phase Portal-venous phase
enhancement
Enhanced septa Hypoenhancing rim
Hyperenhanced segment Enhanced septa
Hyperenhanced
segment
b
Non-/Isoenhancing Isoenhancing Isoenhancing
when becoming dysplastic
nonenhancing
on size and differentiation of
HCC
Late phase
No central
enhancement
Hypo-/
nonenhancing
69
Tip Some basic general comments for UCA application:
• Always obtain informed consent and assure justied indication.
• Have resuscitation equipment (drugs, suction, oxygen, etc.) at hand (for possible
anaphylactic reaction, though extremely rare).
• Use large vascular access, no lters on IV line (may destroy bubbles). If threeway valve used, always inject contrast slowly into straight line.
• Decide on slow infusion versus bolus injection ahead of scan, have saline ush
ready to push UCA into circulation (often only very small amounts applied in
small children, otherwise UCA remains in IV line—not available for imaging).
• Scan and document area of interest before UCA application.
• Use low MI techniques whenever possible (<0.3, better <0.1).
• Continuously scan area of interest; whenever possible document UCA arrival/
dynamics by video clip with time display, with thorough review after investigation—from those clips one may document/store just selected representative
images to PACS if not possible otherwise (Fig.4.8).
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M. Riccabona and H. J. Mentzel
a
d
Fig. 4.8 CEUS in liver mass. Incidental nding of echogenic liver mass in 8-week-old newborn—
CEUS (off-label use, 0.1mL SonoVue) performed trying to avoid contrast-enhanced MRI.Image
series: (a) unenhanced=hypoechoic lesion (+ …+). (b) After 16s (late arterial phase) dense bubble
wall, no central enhancement. (c) After 24s (late portal-venous phase) some bubbles appear more
centrally. (d) In parenchymal phase (after 45s) entire mass appears hyperechoic and stronger enhancing than surrounding liver parenchyma. (e) In delayed phase (after 65s) lesion still depcitable, only
slight washout with diminishing echogenicity observed; stays stable for rest of examination
(3–5min), i.e., no complete washout (not shown). Contrast dynamics consistent with a haemangioma
b
e
c
• Use higher UCA dose with higher frequencies and deep compartments.
• Always observe late phases/washout.
• Repeat only when initial UCA has dissolved—or destroy remaining UCA by
high-energy sound burst (can also be used for reperfusion assessment).
Tip Avoid any lters at injection side; use largest possible calibre of venous access.
Decide before whether you need bolus injection or slow infusion. Initially perform
dedicated US and assure proper US access. Store contrast dynamics as video clips
of targeted area for later analysis; clock should be included in clips for timing.
Remember too, that UCA are purely intravascular—enhancement pattern differs
from CT/MRI due to different contrast agent behaviour.
4.1.5.1 Potential Applications/Indications ofCEUS inNeonates,
Infants andChildren-Summary
Similar to adults various applications reported or suggested:
• Lesion detection in traumatic and non-traumatic scenarios in abdominal parenchymal organs (liver, spleen, pancreas, kidney) (Fig.4.9).
4 Contrast-Enhanced US, andUltrasound Elastography inChildhood
71
ba
Fig. 4.9 CEUS after trauma: 7-year-old boy after accident. (a) Unenhanced image shows some
irregular contours and hypoechoic focal parenchymal irregularities of lower spleen pole. (b) CEUS
(off-label use) delineates clearly the demarked spleen injury (laceration with subcapsular hematoma) without extravasation of echogenic bubbles—showing that there is no active bleeding and
no capsular damage
• Lesion characterisation in abdominal parenchymal organs (liver, spleen, pancreas, kidney) (Fig.4.10)
• Perfusion (and focal lesions) of transplanted organs.
• Other applications also described or being evaluated (lymph nodes, bowel wall,
testis, synovia, improved vessel decpition e.g. on TCI or deep coompartments ...).
4.1.5.2 Dose Recommendations
No ofcial dose nding studies, but based on experience and consensus (Table4.3).
Manufactures recommendation for use in the paediatric liver in USA (Lumason®/
Bracco, at present the only approved iv. Application in children): 0.03 ml/kg; but
company also states “… higher dose with higher frequencies and very young age…”.
Note
Except for paediatric liver applications in USA, all iv. applications in children
are off-label.
4.1.6 Future ce-US Potential
ce-US may serve for interventional US, e.g., to identify otherwise invisible target,
to prove proper placement in a cavity, to detect leakage or stulas.
In future, UCA may serve not only for detection and characterisation of lesions,
but also as carrier of specic drugs that can be regionally deployed in affected areas
using UCA as carrier and visualisation tool and also an ideal mean for focal drug
delivery, e.g. by destroying carrier molecule using a focused high-energy US
impulse at targeted site.
72
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cd
M. Riccabona and H. J. Mentzel
Fig. 4.10 CEUS for lesion characterisation: 10-year-old boy, abdominal pain—unenhanced US
reveals cyst-like hypoechoic lesion with some atypical shape in the right liver lobe (+ …. +) (a).
CEUS (1ml SonoVue—off-label) shows early arterial enhancement of cyst wall and enhancing
septum (b), the enhancement increasing in thickness and intensity over time (c, d). Final diagnosis
not yet established (e.g., cystic harmatoma). Same approch would apply also to cyst characterisation in other organs (e.g., for renal cysts)
Table 4.3 Empirical dose recommendations for CEUS with SonoVue
Neonates 0.1–0.15mL/kg
Infants/till 2years 0.08–0.1mL/kg
After 3years till puberty (14years) 0.05–0.08mL/kg
Young adolescents (14–18years)=as adults 2.4–4.8mL (0.02–0.05mL/kg)
Some use 0.1mL/year of life
Usually single dose, often even lower dose at ~50% sufcient,
Repetition possible when old bolus dissolved (within 15–20min)
UCA dose based on various experiences and recommendations, adapted from Riccabona M etal.
(2018). ESPR Abdominal (GU and GI) Imaging Task Force—Imaging Recommendations in
Paediatric Uroradiology, Part X: How to perform paediatric gastrointestinal ultrasonography, use
of Gadolinium as a MRI contrast agent in children, follow-up of paediatric testicular microlithiasis, and update in paediatric contrast-enhanced ultrasound. Pediat Radiol 48, 1528–1536;
Riccabona M. (2014) Contrast Media Use in Pediatrics: Safety Issues. Chapter 17, In: Thomson
HS, Webb AW (eds) Contrast Media: Safety issues and ESUR guidelines. 3rd ed., Springer: BerlinNew York, pp.245–251, and Riccabona M, Mentzel HJ (2018). Contrast media in childhood—
application and safety considerations. In Riccabona M. “Pediatric Urogenital Radiology.” 3rd ed.,
Springer, Heidelberg, pp.123–133
®
(Bracco/Italy)
4 Contrast-Enhanced US, andUltrasound Elastography inChildhood
73
4.2 Ultrasound-/Sonoelastography
New method—presently primarily used in adults for breast and liver applications,
but increasingly also other areas are being investigated, but paucity of studies
regarding US elastography in children.
Denition
Elasticity= property of material to oppose mechanical resistance to applied force
and, after discharge, to return to its original shape. Tissue elasticity varies with tissue composition and water content, age, trauma, inammation or tumour—with
some more inuencing factors.
• Based on analysis of non-linear sound effects, reecting tissue behaviour and
“stiffness”—different from conventional US which basically only relies on
intensity of reected echoes.
• Exploited non-linear sound effects in tissue: backscattering, changes in sound
velocity, generated shear waves.
• (Gentle) pressure applied after/during scanning of dened area (either manually
or by standardised sound pressure impulse from transducer); indirect compression by pulsation or respiration can be used also.
4.2.1 Methods
4.2.1.1 Strain Elastography
Strain elastography provides parametric maps to differentiate between stiff and
elastic tissues. Evaluation of deformation quotients
• Advantage: easy to perform.
• Disadvantage: subjective, little standardisation, only semiquantitative.
4.2.1.2 Transient Elastography (TE)
A single point method developed only for liver evaluation without b-mode control
(Echosens FibroScan)
• Advantage: easy to perform, no experience in US necessary.
• Disadvantage: no control for positioning, does not work in obesity and ascites.
4.2.1.3 Shear Wave Elastography (SWE)
Works in a region of interest (Acoustic Radiation Force Impulse Imaging=ARFI)
with push pulse (high MI) inducing tissue compression. After discharge shear waves
measurable (velocity 1–5m/s).
• Advantage: quantitative stiffness estimation (m/s, can be mathematically converted into kPa), image controlled.
• Disadvantage: limited penetration depth.
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M. Riccabona and H. J. Mentzel
Changes in lateral sound propagation/backscattering analysed to depict areas of
different response towards pressure: stiff areas show less change than compressible
areas, as number of reectors within given eld changes and thus echo signature
from certain areas changes variably, furthermore sound (shear wave) velocity
changes.
Information is superimposed on conventional grey scale image; generally colour
coding used to visualise areas with altered compressibility versus areas of high elasticity (Fig.4.11).
Can also be displayed in “stiffness” numbers (usually kPa) or shear wave veloc-
ity (m/s)—varies with equipment and individual transducer, no normal values yet
available for infants and children’s organs (Fig.4.12).
Fig. 4.11 Strain Elastography in a term neonate: swollen and enlarged kidney exhibits generally
increased stiffness compared to adjacent liver in a baby girl with renal vein thrombosis
ba
Fig. 4.12 Elastography. (a) Grey scale image of testis with microlithiasis, minor inhomogeneity
of central parenchyma depicted. (b) Colour-encoded “elastography” image depicts an obvious area
of altered tissue stiffness with different colours in different areas of scrotum/testis, indicating
potential regional pathology