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42
1 Theory and Basics
a
Fig. 1.22 Elastography. (a) Gray 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, indicating potential
regional pathology
b
1.9.7 US with Contrast Enhancement (Echo-Enhanced US –
ee-US, Contrast-Enhanced US – ce-US/CEUS)
by Ultrasound Contrast Media (US-CM)
1.9.7.1 Basics
US-CM are materials that can be applied either intravenously or into cavities
that enhance (purely intravascular/intraluminal) reflection, improve visualisation/depiction of certain areas/structures. When observing these changes over
time, similar perfusion and enhancement patterns can be observed as in contrast-enhanced CT or MRI – improves not only lesion detection but also differentiation; enables improved functional imaging.
Many different US-CM: all based on some micro gas bubbles attached to carrier
molecule, stabilised by external capsule. Stabilising shell – usually palmitic acid.
Carrier molecule – e.g. galactose (Levovist, Bayer-Schering), proteins (Optison and
Avonex, Mallinckrodt), lipids (SonoVue, Bracco).
Modern US-CM relatively stable within blood, small enough to pass capillaries;
actually about size of an erythrocyte. New agents with improved stability, and
increased signal signature are being developed.
The only (older) US-CM still used in cardiology is Echovist (Bayer-Schering)
based on larger carrier molecule which cannot pass pulmonary capillary bed –
destroyed during lung passage. This enables a specific application: trying to indirectly assess patients for left to right shunt (e.g. septal defects with consequent risk of
paradoxical embolism), as US-CM only seen in systemic circulation if shunt exists.
Potential risks of US-CM: based on their relatively high osmolarity as well as on
chemical entity with specific reactions:
• Levovist is contraindicated in galactosemia.
• Proteins and lipids can cause allergic reactions.
• High osmolarity can cause systemic and local vascular reactions.
• Encapsulating substances usually do not cause significant problems.
1.9 Modern and Future US Methods and Techniques
Fig. 1.23 Malposition of drain after PCN – intracavitary ce-US. Double/split image display of
kidney after instillation of diluted US-CM (1 %) into a nephrostomy drain for assessment of drain
function and position: echogenic CM not only seen in central collecting system on the left hand
contrast-weighted image, but also scattered around kidney indicating either rupture/injury to collecting system or malposition of some drain side holes causing pararenal CM extravasation
43
In general US-CM have negligible side effects, particularly when compared with
CM commonly used for other imaging modalities such as CT, MR and catheter
angiography.
NOTE: US-CM particles are cavitation seeds! Thus risk of cavitation and cavitationinduced side effects increases – should be specifically considered when applying
these agents to risky areas (e.g. neonatal brain, bowel wall and testis). Intrinsically,
low MI techniques using very low sound pressure are preferable, not only for reducing cavitation risks but also as they spare US-CM/enable longer observation period
at lower US-CM dose.
1.9.7.2 Applications
Many different applications are established till now – though most mainly applied
to adults (due to restricted availability/lack of approval for paediatric use). Main
basic approaches:
• Lesion detection. Here US technique is optimised towards visualising structures
rather than contrast dynamics/enhancement patterns.
• Improved visualisation of either vascular structures or other hollow organs that
can be filled with US-CM (Fig. 1.23).
• Functional viewing focuses on perfusion/enhancement patterns: tries to evaluate
contrast behaviour within targeted structure over time analysing inflow, uptake
and washout similar to CM enhancement with other imaging techniques. In gen-
eral the same rules apply as for ce-CT or -MRI. Observing different arterial,
parenchymal and venous phase-enhancement patterns improves not only lesion
detection but also lesion characterisation. For this technique proper US-CM
application and potentially intermittent complete CM destruction within targeted
44
1 Theory and Basics
area (achievable, e.g. by single strong signal burst) allowing for reperfusion
assessment are necessary. Note that US-CM remains purely intravascular, except
for liver sinosoids or damaged vascular wall.
• Sometimes US-CM is used to enable sonographic depiction of structures impos-
sible to visualise on baseline US, as insufficient penetration or increased scattering
impairs proper gray scale or CDS analysis. For example transcranial Doppler
sonography may be cumbersome in older patients/adults; with US-CM vessels
more easily depicted, duplex gate placed properly, angle correction performed cor-
rectly – thus assessment is significantly improved. Same applies to visualisation of
vascular structures in deep body compartments or in difficult scanning conditions
particularly in adults, obese patients, with vessels at poor insonation angle, and
thus also helpfull in post transplant assessment.
• Further details described in respective chapters with individual applications.
Contrast-Enhanced Voiding Urosonography (ce-VUS)
Also known as sonographic VCU(G)/-MCU/MUS (micturition urosonography):
• Allows reliable assessment for vesicoureteral reflux (VUR) by US.
• Importance of VUR/VUR detection is decreasing – still remains common/important
condition in infants, particularly those with congenital urinary tract malformations
and recurrent febrile urinary tract infection (UTI) with potential renal scarring.
• Conventionally VUR assessment is performed by radiographic voiding cystoure-
terography (VCUG) which carries significant radiation burden. Thus, increas-
ingly ce-VUS is promoted – presently recommended in Europe as primary
investigation in girls, in screening conditions and for follow-up investigations
(EFSUMB recommendation).
• Conventional fluoroscopic VCUG (still?) is considered and indicated for preop-
erative anatomic assessment and assessment of diverticulae/urethral pathology
(e.g. male urethra – posterior urethral valve) (Table 1.3).
Technique: (ESUR / ESPR recommendation – see Pediatr Radiol 2008 and update
2014)
• Initial thorough US of entire genitourinary tract.
• Bladder is catheterised and emptied; urine sample taken to assure absence of
infection.
• Thereafter bladder filled by normal saline drip infusion from plastic containers at
physiological filling pressure levels (30–50 cm above bladder level).
• During filling, repetitive intermittent administration of US-CM is performed at
25, 50, 100 % bladder filling – dose depends on US-CM used (5–10 % of actual
bladder volume using Levovist; 0.2–1 % of filling volume for SonoVue, 0.5 %
for Optison). Constant alternating US monitoring of bladder, retrovesical space
(distal ureters) and both kidneys is performed – to depict potential reflux of echo-
genic US-CM into ureters/renal collecting system.
• When bladder is filled: voiding is attempted in whichever position patient accepts.
• During first voiding, US of bladder, retrovesical space and kidneys is repeated –
with post-void assessment of residual urine (volume measurement!); check for
potentially refluxed material in renal collecting system (Fig. 1.24a). Drainage of
refluxed material into bladder should also be noted.
1.9 Modern and Future US Methods and Techniques
Table 1.3 ce-VUS/grading of VUR
Adapted from Darge et al. (2002) EJR
VUR grades defined as with conventional fluoroscopic voiding cysto-urethrography; additionally
(as US visualises also non-refluxing systems) “a” is added for non-dilated, “b” for dilated systems:
this gives a scale from VUR 0°a/b to VUR V° a/b
45
NOTE: During voiding (period with maximum pressures) thorough evaluation
also of medullary areas should be attempted to depict intrarenal reflux (in patients
who exhibit grade III reflux or higher).
• Particularly in neonates and infants, cyclic filling (three attempts) should be per-
formed with repetitive CM application in order to not only improve VUR detec-
tion but also to enable (trans)perineal urethra assessment during voiding on a
dedicated cycle (Fig. 1.24b).
• After investigation: images are thoroughly assessed; VUR grading is performed
according to proposed grading scale (adopted from established international
VCUG VUR classification) (Table 1.3).
NOTE: ce-VUS cannot only show/detect VUR, measure residual volume and
assess drainage dynamics of refluxed material; it also may depict intrarenal
reflux, assess renal parenchyma as well as potentially dilated non-refluxing sys-
tems and reveal information on urethra and – by using the drip infusion as
manometer – 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.
46
Fig. 1.24 ce-VUS: double/
split image display –
contrast-weighted image to
the left in (a, b) and right in
(c). (a) US-CM filled urinary
bladder with echogenic CM
in dilated right distal ureter
retrovesically (+ +).
(b) Echogenic US-CM in
renal collecting system
indicating dilating high-grade
VUR into clubbed calices.
(c) Perineal view during
voiding during ce-VUS:
contrast-filled normal
urethra, but reflux of
echogenic US-CM into
non-dilated vagina without
fistula (baby girl with labial
synechia)
1 Theory and Basics
a
b
c
Restrictions of US technique:
• Limited depiction of mid-ureter portions.
• Restricted access to distal ureter at poor bladder filling.
• More difficult, sometimes cumbersome accessibility of urethra.
• Less-comprehensive overview of entire anatomy.
• Limited visualisation of diverticula (particularly those only posing intermittently
and thus only briefly visible, e.g. during voiding).
• VUR I° may be missed – potentially less important, as low-grade VUR probably
does not indicate treatment, and (due to longer observation period and different
behaviour of US-CM) ce-VUS tends to rate VUR slightly higher than radio-
graphic VCUG.
Other Intracavitary Use of ce-US: Sono-Genitography, Sonographic Pyelography, Etc.
US-CM can be instilled into any other hollow organs for improved assessment particularly of size, form, fistulae, connection to other compartments, detailed anatomy, etc. – as performed with fluoroscopy.
US-CM can be instilled after catheterisation of vagina for sono-genitography
in genital malformations, after nephrostomy, for abscess drainage, cyst puncture,
agent instillation (into any structure – cysts, vessels, etc.), when shunting
1.9 Modern and Future US Methods and Techniques
Fig. 1.25 Abdominal intravenous CEUS: double/split image display – contrast-weighted image
to the left. Normal homogenous enhancement spleen after intravenous application of US-CM
ruling out laceration
47
cerebral ventricles (even intraoperatively) in complicated anatomy (see
Fig. 1.23).
Intravenous ce-US (CEUS)
With increasing US potential both on gray scale and with aCDS, ce-(Doppler)US is
rarer necessary for depiction and display of anatomic structures; sometimes intravenous (IV) application of US-CM (usually named CEUS) can be helpful in obese
children or difficult scanning conditions (e.g. depiction of vascular malformations
by transcranial US, depiction of cerebral vessels/assessment of severe cerebral perfusion deficit and visualisation of perfusion in vessels at poor scanning conditions
at very low flow status/bad insonation angle).
CEUS is particularly helpful in conditions where basic US intrinsically is unable
to depict potential changes (e.g. depicting parenchymal organ lesions in early posttraumatic setting – even using aCDS). CEUS significantly 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. 1.25 and 1.26).
Diagnostic criteria same as in adults, established primarily for liver – short overview given in Table 1.4.
TIP: Some basic general comments for US-CM application:
• Always obtain informed consent and justified indication.
• Have resuscitation equipment (drugs, suction, oxygen, etc.) at hand (for possible
anaphylactic reaction, though extremely rare).
• Use large vascular access, no filters on IV line (may destroy bubbles).
48
a
1 Theory and Basics
b
c
Fig. 1.26 Contrast-enhanced US (CEUS, intravenously applied) in giant neonatal haemangioma/
haemangioendothelioma. (a) Native gray 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 inflow to late portal venous phase
with increasing centripetal CM filling (c), typically for haemangioma; (b) additionally, early filling
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)
d
• Decide on slow infusion versus bolus injection ahead of scan, have saline flush
ready to push CM into circulation (often very small amounts are applied in
small children, otherwise US-CM remains in IV line – not available for
imaging).
• Scan and document area of interest before US-CM application.
• Use low MI techniques whenever possible (<0.3, better <0.1).
• Continuously scan area of interest; whenever possible document US-CM arrival/
dynamics by video clip with time display, with thorough review after investigation.
• Always observe late phases/washout.
• Repeat only when initial US-CM has dissolved – or destroy remaining CM by
high-energy sound burst (can also be used for reperfusion assessment).
Future ce-US Potential
In future, US-CM may serve not only for detection and characterisation of lesions
but also as carrier of specific drugs that can be regionally deployed in affected areas
using US-CM 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 sound
impulse at targeted site.
1.9 Modern and Future US Methods and Techniques
Table 1.4 CEUS enhancement pattern in liver lesions
Entity Arterial phase Portal venous phase Late phase
(A) Non-cirrhotic liver
Adult haemangioma
Typical
features
Additional
features
Infantile haemangioma (NICH/RICH) – haemangioendothelioma: features vary with size
Typical
features
Additional
features
Focal nodular hyperplasia (FNH)
Typical
features
Additional
features
Hepatocellular adenoma
Typical
features
Additional
features
Other paediatric tumours: features vary with size, but not specific for entity
Typical
features
Additional
features
Focal fatty infiltration
Typical
features
Focal fatty
sparing
Typical
features
Abscess
Peripheral nodular Partial/complete Complete
Enhancement Centripetal fill in Nonenhancing
Small lesion: complete
Rapid centripetal
enhancement
Peripheral enhancement Partial Incomplete
Early large draining
vessel shunt
Small lesion: complete
Rapid centripetal
enhancement
Hyperenhancing from
centre
Complete, early Unenhanced central
Spoke-wheel arteries
Feeding artery
Hyperenhancing,
complete nonenhancing
regions
Hyperenhancing, Isoenhancing Iso-/hypoenhancing
Nonenhancing regions Hyperenhancing Slightly
Isoenhancing Isoenhancing Isoenhancing
Isoenhancing Isoenhancing Isoenhancing
Centripetal fill in Nonenhancing
Hyperenhancing Iso-/hyperenhancing
scar
Isoenhancing Isoenhancing
Hyperenhancing Slightly
Nonenhancing
regions
Nonenhancing
regions
enhancement
regions
Unenhanced central
scar
hypoenhancing
Nonenhancing
regions
hypoenhancing
Nonenhancing
regions
(continued)
49
50
Table 1.4 (continued)
Entity Arterial phase Portal venous phase Late phase
Typical
features
Additional
features
Simple cyst
Typical
features
(B) Cirrhotic liver
Regenerative nodule (±dysplastic)
Typical
features (not
diagnostic)
Additional
features
Adapted from: Claudon M et al (2012) Guidelines and good clinical practice recommendations for
Contrast Enhanced Ultrasound (CEUS) in the Liver – Update 2012, Ultraschall Med. doi
10.1055/s-0032-1325499)
a
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 cirrhotic livers
No specific enhancement patterns for hepatoblastome or other pediatric liver tumours yet reported;
however, possibly rhabdomyosarcoma tend to show a more centripedal enhancement, other
tumours enhance more centrifugally
Peripheral enhancement Hyper-/isoenhancing
rim
No central enhancement No central
enhancement
Enhanced septa Hypoenhancing rim
Hyperenhanced segment Enhanced septa
Hyperenhanced
segment
Nonenhancing Nonenhancing Nonenhancing
a
Isoenhancing Isoenhancing Isoenhancing
Hypoenhancing
1 Theory and Basics
Hypoenhancing rim
No central
enhancement
1.9.8 Three- and Four-Dimensional US (3D-/4DUS)
1.9.8.1 Physics and Techniques
Several different techniques used for acquiring 3DUS data:
• Originally series of 2D images combined with some position information for
reconstructing 3D data set. Position information either derived from some sort of
positioning device (optical-, acoustic-, electromagnetic sensors, mechanical
positioning devices, etc.) or from estimated transducer shift, using information
derived from extended view – like vector analysis-based calculation.
• Presently most commonly used: 3D transducers – scan heads that have integrated
motor which mechanically moves scan head through acquisition field thus defining each individual plane by motor sweep speed.
• Most modern techniques – matrix transducers that have 2D crystal matrix; allows
for simultaneous acquisition of real volume by electronic steering.
After data acquisition and reconstruction of 3D volume – data viewed in multiple
displays:
• Multi-axial sections.
• CT-like tomographic parallel sections.
1.9 Modern and Future US Methods and Techniques
Fig. 1.27 Neonatal brain
3DUS: improved DDx and
conspicuous viewing by
3DUS. Tomographic display:
CT-like demonstration after
axial reconstruction of an
intracranial (arachnoid) cyst
that obviously does not
connect to the only slightly
dilated supratentorial
ventricles
51
• Any kind of reconstruction as with CT and MRI.
• Various rendering algorithms are applicable – to visualise and extract volume
information difficult to display in 2D planes (e.g. tortuous structures, cavities
and surfaces).
Repeated update of such 3D acquisitions allows for film-like visualisation – hence
called 4DUS, with time being the fourth dimension. Particularly useful when analysing motion-depending phenomena of structures only properly depicted by 3DUS
either due to inaccessible plane for conventional 2DUS or surface information.
1.9.8.2 Typical Paediatric 3DUS Applications
Neonatal Neurosonography
Using open fontanel and dedicated 3DUS transducers, practically the entire neonatal brain is covered in one or two 3D volumes. Standard sections comparable to CT
and MRI reconstructed, particularly crucial (axial, coronal) planes (often not available on 2DUS) retrievable from data set, valuable not only for documentation but
also for:
• DDx – particularly with cystic structures and anatomic correlation (Fig. 1.27).
• Analysis of complex and tortuous structures or hydrocephalus (Fig. 1.28).
• Standardised assessment of extra-axial fluid space, cerebral ventricles, major cere-
bral vessels, etc. Furthermore – provided sufficient extra-axial fluid around brain –
brain surface viewing can be attempted opening up completely new field for
research/US diagnostic potential (migration/gyration disorders, etc.) (Fig. 1.29).
3DUS of the Kidney
Particularly useful in hydronephrotic kidneys. Using segmentation algorithms, real
renal parenchymal volume (after deduction of dilated collecting system) can be
calculated, split renal volume can be estimated – reliably offers essential information in patients with obstructive uropathy, particularly valuable during follow-up
(Fig. 1.30):