Cardiac CT in Pediatric Patients

Marilyn J. Siegel, M.D.Mallinckrodt Institute of Radiology

Washington University School of MedicineSt. Louis, MO. USA

FDA Questions: Contrast-enhanced Pediatric Cardiac CT

• Indications for CT

• Impact of CT on diagnosis & treatment

• Contrast-specific questions:

– Methods of determining dosing

– Limitations of contrast-enhanced CT

– Methods of safety monitoring

• Efficacy data (adults & children)

• Direction of future drug development or utilization for contrast agents in children

Cardiac CT: Basic Facts

• Need multidetector CT

• Faster imaging times

– fewer motion artifacts

• Higher spatial resolution

– 0.5 to 1.25 mm

– superb 3D images

• Better contrast enhancement

• THE USE OF CT IS INCREASING

Frequency of Contrast Usage

• Contrast mandatory

–100% of cases

• Inherent problems in children

–Small patient size

– Lack of perivisceral fat

• Poor differentiation of soft tissue structures on non-enhanced CT scans

• Solution: IV contrast

FDA Questions: Contrast-enhanced Pediatric Cardiac CT

• Indications for CT

• Impact of CT on diagnosis & treatment

• Contrast-specific questions:

– Methods of determining dosing

– Limitations of contrast-enhanced CT

– Methods of safety monitoring

• Efficacy data (adults & children)

• Direction of future drug development or utilization for contrast agents in children

Indications: Pediatric Cardiac CT

• Detection of disease or pathology –i.e., diagnosis

• Improve clinical decision making–Need for other diagnostic testing–Use of specific intervention

• No role in defining normal anatomy• No role in assessing function• Not a screening tool

Specific Disease States or Pathology

• Extracardiac great vessel anomalies

• Intracardiac shunt lesions

• Post-operative anatomy

• In children, CT is performed most often for congenital diseases

Pediatric Heart Diseases

• Common extracardiac lesions– Aortic arch anomalies

– Aortic coarctation

– Interrupted arch

– Patent ductus arteriosus

– Pulmonary artery sling

Arch Anomalies

Neonate Adolescent

Right arch Double Arch

Pulmonary Sling:Left pulmonary artery arises from right pulmonary artery

Case from J. Schoepf

Neonate

Aortic Coarctation

10-day old girl with CHF; 8 cc contrast,

3D CTCT

Patent Ductus Arteriosus

CT MR

Other Indications for Pediatric Cardiac CT

• Diagnosis of cardiac shunts

–atrial septal defects

–ventricular septal defects

• Evaluate post-operative anatomy

–usually complex cyanotic heart disease

Shunt Lesion: Septal Defects

Post ASD repairASD/VSD

ASD

Post-operative Evaluation:

Graft right atrium to pulmonary artery

Grafts subclavian arteries to pulmonary arteries

FDA Questions: Contrast-enhanced Pediatric Cardiac CT

• Indications for CT

• Impact of CT on diagnosis & treatment

• Contrast-specific questions:

– Methods of determining dosing

– Limitations of contrast-enhanced CT

– Methods of safety monitoring

• Efficacy data (adults & children)

• Direction of future drug development or utilization for contrast agents in children

Impact on Management

• Predict whether patient should undergo further invasive diagnostic testing (angiography)

• Clarify equivocal angiographic findings

• Predict whether patient needs surgery

Therapeutic Intervention:Indications for Re-operation

Leaking Baffle

CT prompted angiography

Pseudoaneurysm

Prompted surgery

FDA Questions: Contrast-enhanced Pediatric Cardiac CT

• Indications for CT

• Impact of CT on diagnosis & treatment

• Contrast-specific questions:

– Methods of determining dosing

– Limitations of contrast-enhanced CT

– Methods of safety monitoring

• Efficacy data (adults & children)

• Direction of future drug development or utilization for contrast agents in children

Contrast Dosing

• Contrast volume is determined empirically based on patient weight

• Nonionic contrast medium

–280 to 320 mg I

• Dose

–2 mL/kg (max 4 mL/kg or 125 mL)

Contrast Injection

• Power Injection

–Antecubital catheter

–Flow rate: variable

»22g 1.5 -2.0 mL/sec

»20 g 2.0 -3.0 mL/sec

»24g or central line 1.0 mL/sec

• Hand Injection:

–Peripherally positioned catheter

FDA Questions: Contrast-enhanced Pediatric Cardiac CT

• Indications for CT

• Impact of CT on diagnosis & treatment

• Contrast-specific questions:

– Methods of determining dosing

– Limitations of contrast-enhanced CT

– Methods of safety monitoring

• Efficacy data (adults & children)

• Direction of future drug development or utilization for contrast agents in children

Limitations of Contrast-Enhanced CT

• Contrast-related:

–Extravasation at injection site

–Adverse contrast reactions

• Device-related:

–Radiation exposure

Contrast-Related Risks

• Extravasation at injection site

–Power injector: 0.4%

–Manual injection: 0.3%

Kaste Pediatr Radiol 1995; 26:449

Incidence Contrast Reactions:Meta-analysis

• LOCM(NICM)

– All 1-3%

– Minor near 1%

– Major (severe) .04% (1:10,000)

– Late 5-8%

• Mortality rate - LOCM since 1980 1:100,000

Adverse Contrast Reactions:Pediatric Population

• 321 children• Questionnaire (73% return rate)• Omnipaque 300/450 (Iohexol)• Acute reactions 1.9%

– Minor (mild) – Older patients (> 24 kg)

• Late reactions 6.2%– Mild or intermediate– Younger (< 24 kg)

Mikkonen, Pediatr Radiol 1995; 25:350

Adverse Contrast Reactions

• Nonionic n=168,363 (1986-1988)• Overall prevalence of ADRS: 3.13%

– Severe 0.04%, deaths 0.004%• 70% within 5 minutes, remainder later• Prevalence by age:

– < 10 yrs: 0.4%– 10-19 yrs: 2.52%– 20-49 yrs: 4.1-4.6%– > 50 yrs: 1.5-2.6%

Katayama H. Radiology 1990; 175:621

Radiation Exposure

Radiation Risks

• CT

– 10% of all radiological procedures

– 65% effective dose of all medical x-rays• Chest X-ray 0.10 mSv• Pediatric chest CT 1-10 mSv• Adult chest CT 7-15 mSv

• Cardiac CathCardiac Cath 20-30 20-30 mSv mSv

– (3.5 min fluoro/75 sec cine)(3.5 min fluoro/75 sec cine)

Relative Risks

• To individual:– Lifetime risk of cancer: 20-25% (1 in 4 or 5)

– Added risk: 0.05% (negligible, 1 in 2000)

• To population:– 600,000 pediatric CT’s in the US / year

– Without CT: 135,000 will die of cancer

– With CT: 135,300 will die of cancer

Courtesy Jim Brink, M.D.

FDA Questions: Contrast-enhanced Pediatric Cardiac CT

• Indications for CT

• Impact of CT on diagnosis & treatment

• Contrast-specific questions:

– Methods of determining dosing

– Limitations of contrast-enhanced CT

– Methods of safety monitoring

• Efficacy data (adults & children)

• Direction of future drug development or utilization for contrast agents in children

Safety Monitoring

• Dosing

– IV contrast drawn up by technologist

– Dose verified by radiologist prior to injection

– Contrast administered by radiologist

• Procedural

– Catheter site monitored for extravasation

Mitigating & Preventing Adverse Contrast Reactions

• Identify patients at risk:

–Prior moderate contrast reaction

–Medically treated asthma

• Premedication with corticosteroids

Safety MonitoringRadiation Dose

• Directly proportional to:

–Tube current

–Kilovoltage

–Scan time

–Slice thickness

–Total number of slices

Radiation Risks: Recommendations

• Optimize CT settings–Reduce tube current and voltage–Increase table speed (mm/sec)–Limit number of scans–Use automated dose reduction technology

• Eliminate inappropriate referrals for CT

FDA Questions: Contrast-enhanced Pediatric Cardiac CT

• Indications for CT

• Impact of CT on diagnosis & treatment

• Contrast-specific questions:

– Methods of determining dosing

– Limitations of contrast-enhanced CT

– Methods of safety monitoring

• Efficacy data (adults & children)

• Direction of future drug development or utilization for contrast agents in children

Efficacy Data

• In adults, large amount of data related to CT angiography of the coronary arteries and acute aortic events

• In children, overall paucity of data

– Minimal data on aortic imaging

• Several review articles on CT angiography of congenital heart disease

Coronary Artery Stenosis

• Several studies have shown that CT allows reliable detection of coronary artery disease

• 95% sensitivity, 86% specificity

»detecting > 50% stenosis

»vessels 2-4 mm in diameter

Nieman: Circulation 2002; 106:2051 Fayad: Circulation 2002; 106:2026

Pediatric Aortic Arch Anomalies

• 22 pediatric patients

• Confirmatory studies:

– Echocardiography (n=7)

– Angiography (n=7)

– Surgery (n=8)

• Accuracy CT: 96%

– Stenotic vessels: 2 to 5 mm in diameter

Lee E, Siegel MJ. AJR, In Press

FDA Questions: Contrast-enhanced Pediatric Cardiac CT

• Indications for CT

• Impact of CT on diagnosis & treatment

• Contrast-specific questions:

– Methods of determining dosing

– Limitations of contrast-enhanced CT

– Methods of safety monitoring

• Efficacy data (adults & children)

• Direction of future drug development or utilization for contrast agents in children

Future Directions in Contrast-Enhanced CT

• Goal: To get the highest contrast enhancement with the least amount of contrast agent

• 2 main factors affect contrast enhancement:

– Flow rate or injection duration

– Iodine concentration

Injection Rate vs. Arterial Enhancement

0

50

100

150

200

250

300

350

Con

tras

t E

nha

ncem

ent

(HU

)

0 25 50 75 100 125 150 175 200

Time (sec)

1 mL/s3 mL/s5 mL/s

injection rate increases contrast enhancement

Bae 2002

Injection rate

• Higher levels of enhancement may result in smaller volumes of contrast

• But in children there is a limit how fast we can inject, because small gauge catheters and catheters in hand and foot need slower injection rate

Concentration vs. Enhancement

0

50

100

150

200

250

300

350

0 10 20 30 40 50Time (sec)

Ao

rtic

CE

(H

U)

400 mgI/mL350 mgI/mL300 mgI/mL

Varying iodine concentrations

Total iodine mass and flow rate constant (5mL/s)

iodine concentration = contrast enhancement

Bae 2002

Concentration vs. Flow Rate

• Left ventricular density (200-300 HU)

– 300 mgI/mL at 3.5 mL/sec

– 400 mgI/mL at 2.5 mL/sec

• Injecting low-concentration contrast at high flow rate or higher-concentration at lower flow rate produces similar enhancement density

Becker Appl Radiol 2003; S50

Effect of Iodine Concentration

• Implication in children

• Use of higher concentration contrast material at may result in smaller contrast volumes

• Disadvantage Viscosity (not usable > 400 mgI/mL)

• Challenge for future research

CT: Future Clinical Utilization

• Ventricular function studies based on images in systole and diastole

• Pulmonary perfusion studies

– Peak attenuation & time to peak attenuation measured

Pulmo CT: Color Coded Display

Potential for studying perfusion abnormalities associated with heart/lung disease

Summary

• Role of CT will increase

• Challenges:

–Optimize contrast enhancement

–Lower radiation dose