Kassa Darge, MD, PhDProfessor of Radiology and Surgery

Perelman School of MedicineUniversity of Pennsylvania

Radiologist-in-Chief & William L. Van Alen Endowed Chair

Department of RadiologyChildren‘s Hospital of Philadelphia (CHOP)

Philadelphia, USA

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CONTRAST US RESEARCH GRANTS ▪National Institutes of Health [NIH]

▪Radiological Society of North America [RSNA]▪Society of Pediatric Radiology [SPR]

▪The Thrasher Foundation▪The Helfer Society

▪ Institute for Translational Medicine and Therapeutics [ITMAT] Grant▪Master of Science in Translational Resarch [MTR] Grant

▪The Foerder Grant▪Philips Heathcare

▪Siemens Healthineers▪Lantheus Medical Imaging

▪Bracco Diagnostics Inc.▪Bracco Suisse S.A, Geneva, Switzerland

CENTER FOR PEDIATRIC CONTRAST ULTRASOUND [CPCU]

Department of RadiologyChildren’s Hospital of Philadelphia

partly supported byBracco Diagnostics Inc., Monroe Township, NJ, USA

Pediatric

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Susan Back, MD | Sudha Anupindi, MD

Misun Hwang, MD | Ryne Didier, MD

Aikaterini Ntoulia, MD, PhD | Anush Sridharan, PhD

Laura Poznick, AAS, RDMS | Trudy Morgan, BS, RDMS

All CHOP sonographers

CHOP referring physicians

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Objective

•Describe the utility of contrast enhanced ultrasound [CEUS] for genitourinary applications in pediatrics

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS for GU imaging

•No nephrotoxicity•Multiple injections in one examination•Complete contrast elimination in 20 minutes

•No radiation

•Safe

•Reduce need for sedation

•Problem solving tool

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

US contrast agents

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

US contrast agents

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

US contrast agents

•500-600 million microbubbles/ml suspension

•Microbubbles resonate during US •Enhance sound reflection

•US software background subtraction

•Microbubbles remain intravascular•Depicts blood flow

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Administration routes of US contrast agents

•Intravenous•Intravesical•Intracavitary

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Safety of US contrast agents: INTRAVENOUS

2012 Dec;42(12):1471-80

Safety of US contrast agents: INTRAVENOUS

Number of PATIENTS 1707

Number of INJECTIONS 1891

Number of ADVERSE EVENTS 11

Percentage of adverse events/injections 0.58%

TYPES OF ADVERSE EVENTS

Serious: 1- anaphylactic reaction 1

Minor: 10- taste alteration 3

- urticaria 2

- nausea 2

- tachycardia 1

- hyperventilation 1

- hypertension 1

- single wheal 1

SonoVue® [Lumason ®]

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Safety of US contrast agents: INTRAVESICAL

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

▪ 26 Dysuria

▪ 15 Transient macrohematuria

▪ 3 Abdominal discomfort/pain

▪ 2 Anxiety/crying

▪ 2 Urinary retention

▪ 1 Frequency

▪ 1 Blood/mucous discharge

▪ 1 Perineal irritation

▪ 1 Urethral pain

▪ 1 Urinary tract infection

▪ 1 Vomiting

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Safety of US contrast agents

•High safety profile

•IV: transient minor adverse events

•IV: anaphylactic reaction very rare

•Code cart near US

•Intravesical adverse events: bladder catheter

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Current pediatric GU applications of CEUS

•Kidney

•Testes

•Voding urosonography and Urethrography

•Retrograde sonourethrography

•Genitography

•Interventions

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney

NORMAL KIDNEY

•Arterial phase 20 to 40 seconds Cortex then medulla

•Homogeneous 45 to 120 seconds

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: INFECTION

•Pyelonephritis: Hypoechoic•Abscess: Anechoic

•Infection: Bulge •Infarction: No bulge Fontanilla et al 2012 Abdom Imaging 37:639-646

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: INFECTION

▪ 11-year-old boy▪ Outside CT▪ Pyelonephritis

Left Kidney

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: INFECTION

Power Doppler

▪ 2 days after the CT

Left Kidney

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: INFECTION

Left Kidney

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: INFECTION

▪ 2-week follow-up6 months later

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: MASS

Solid or cystic

•CEUS more sensitive than CT - Shows blood flow in

hypovascular lesions- Shows blood flow in

septations and solid components

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: MASS

•1018 lesions•306 definite dx •139 malignant

•712 followed up to 10 years

Right KidneyD e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: MASS [cystic]

▪ 16-year-old boy▪ back pain▪ urinary incontinence

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: MASS [cystic]

Right KidneySurgery → cystic nephroma

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: MASS [solid]

▪ 7-year-old boy▪ History bladder

exstrophy▪ Incidental finding

Left Kidney

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: MASS [solid]

Left Kidney

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: MASS [solid]

Left Kidney

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: MASS [solid]

Surgery →renal cell carcinoma

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: MASS [pseudo]

▪ 17-year-old female▪ Recurrent pyelonephritis▪ Renal mass?

InitialFollow-up

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: MASS [pseudo]

No renal massHypertrophied column of Bertin

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: TRAUMA

• Stable blunt abdominal trauma

• Limitation collecting system injury

CEUS = CT

CEUS > US

CEUS = CT

CEUS > USMissed 26/67

parenchymal

lesions

Prospective 18 children

Sensitivity

US 45%

CEUS 86%

CT 100%

Missed 2/21

parenchymal

lesions

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: TRAUMA

▪ 16-year-old boy▪ kneed in the abdomen [baseball]

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: TRAUMA

perinephric collection

▪ 2 days later Hb 11 g/dL → 8 g/dL

Right Kidney

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: TRAUMA

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: TRAUMA

active bleeding

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the kidney: TRAUMA

▪ 1 month follow-up

Right Kidney

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the testes

•CEUS as a problem solving tool

•Malignant pattern - early enhancement with washout

• Small tumors color Doppler may not show flow

• Improved diagnostic accuracy incidental testicular lesions

• Fracture lines and contour abnormalities better depicted

• Torsion - Doppler artifact or arterial pulsation from the contralateral testis Valentino et al. 2011 Eur Radiol 21:1831–1840 37

Huang et al. 2012 Br J Radiol 85:S41-53Lock et al. 2011 Urology 77:1049-1053

Isidori et al. 2014 Radiology 273:606-61

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the testes▪ 16-year-old boy▪ scrotal swelling 2 weeks after straddle injury

Right Testis

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the testes

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

CEUS of the testes Surgery →Testicular rupture & ovotestis

Right Testis

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

ceVUS: contrast enhanced Voiding Urosonography

• Compared with voiding cystourethrography [VCUG] and radionuclide cystography [RNC]

• ceVUS detects more vesicoureteral reflux

• ceVUS detects higher grades of reflux

VCUG: 71% Grade I > ceVUS: Grade II or higherDarge K 2008 Pediatr Radiol 38:54-63

> 10% more VUR

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

ceVUS: contrast enhanced Voiding Urosonography

Bladder Left Kidney

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

ceVUS: contrast enhanced Voiding Urosonography

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

ceVUS: contrast enhanced Voiding Urosonography

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

ceVUS: contrast enhanced Voiding Urosonography

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

ceVUS: contrast enhanced Voiding Urosonography

1 mo boy9 yo girl

Urethrosonography: Transperineal

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

ceVUS: contrast enhanced Voiding Urosonography

Urethrosonography: Suprapubic

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

ceVUS: contrast enhanced Voiding Urosonography

▪ Posterior urethral valve

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Contrast enhanced retrograde urethrography

• In place of fluoroscopic retrograde urethrography [RUG]

• Direct visualization of urethra

• Intraoperative performance

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Contrast enhanced retrograde urethrography

▪ 17-year-old boy▪ difficult voiding

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Contrast enhanced retrograde urethrography

▪ Intraoperative US

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Contrast enhanced retrograde urethrography

▪ Intraoperative US

Bulbar urethral stricture

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Contrast enhanced genitosonography

▪ In place of fluoroscopic fistulography▪ Direct visualization of different cavities▪ Easier examination field▪ Multiple fillings not a limitation

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Contrast enhanced genitosonography

V

B

U

▪ 5-month-old girl▪ Congenital adrenal

hyperplasia▪ Disorder of sexual

differentiation

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Contrast enhanced genitosonography

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Contrast enhanced genitosonography

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Contrast enhanced genitosonography

V

B

U

V

B

U

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Interventional GU contrast US

• In place of fluoroscopy

•Biopsy• Improve conspicuity of lesion• Target viable part of tumor and not necrosis

•Guide nephrostomy tube

•Determine connection of cysts

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Interventional GU contrast US

▪ 13-year-old girl, left upper pole renal cyst

Left Kidney

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

Interventional GU contrast US

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a

TAKE-HOME-POINTS

▪ Contrast US: high safety profile▪ GU contrast US:

IV, intravesical, interventional▪ Multiple advantages▪ Numerous indications▪ Expansion of indications in the future

D e p a r t m e nt o f R a d i o l o g y, C h i l d r e n ’s H o s p i ta l o f P h i l a d e l p h i a