1. Cardiac CT in Pediatric Patients Marilyn J. Siegel, M.D. Mallinckrodt Institute of Radiology Washington University School of Medicine St. Louis, MO. USA

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. Pediatric Heart Diseases Common extracardiac lesions –Aortic arch anomalies –Aortic coarctation –Interrupted arch –Patent ductus arteriosus –Pulmonary artery sling

9. Arch Anomalies Neonate Adolescent Right arch Double Arch

10. Pulmonary Sling: Left pulmonary artery arises from right pulmonary artery Case from J. Schoepf Neonate

11. Aortic Coarctation 10-day old girl with CHF; 8 cc contrast, 3D CT CT

12. Patent Ductus Arteriosus CT MR

13. 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

14. Shunt Lesion: Septal Defects Post ASD repair ASD/VSD ASD

15. Post-operative Evaluation: Graft right atrium to pulmonary artery Grafts subclavian arteries to pulmonary arteries

16. 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

17. Impact on Management Predict whether patient should undergo further invasive diagnostic testing (angiography) Clarify equivocal angiographic findings Predict whether patient needs surgery

18. Therapeutic Intervention: Indications for Re-operation Leaking Baffle CT prompted angiography Pseudoaneurysm Prompted surgery

19. 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

20. 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)

21. Contrast Injection Power Injection –Antecubital catheter –Flow rate: variable »22g1.5 -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

22. 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

23. Limitations of Contrast-Enhanced CT Contrast-related: –Extravasation at injection site –Adverse contrast reactions Device-related: –Radiation exposure

24. Contrast-Related Risks Extravasation at injection site –Power injector: 0.4% –Manual injection: 0.3% Kaste Pediatr Radiol 1995; 26:449

25. Incidence Contrast Reactions: Meta-analysis LOCM(NICM) –All1-3% –Minornear 1% –Major (severe).04%(1:10,000) –Late5-8% Mortality rate - LOCM since 1980 1:100,000

26. Adverse Contrast Reactions: Pediatric Population 321 children Questionnaire (73% return rate) Omnipaque 300/450 (Iohexol) Acute reactions1.9% –Minor (mild) –Older patients (> 24 kg) Late reactions6.2% –Mild or intermediate –Younger (< 24 kg) Mikkonen, Pediatr Radiol 1995; 25:350

27. 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

28. Radiation Exposure

29. Radiation Risks CT –10% of all radiological procedures –65% effective dose of all medical x-rays Chest X-ray0.10 mSv Pediatric chest CT 1-10 mSv Adult chest CT 7-15 mSv Cardiac Cath20-30 mSvCardiac Cath20-30 mSv –(3.5 min fluoro/75 sec cine)

30. 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.

31. 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

32. 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

33. Mitigating & Preventing Adverse Contrast Reactions Identify patients at risk: –Prior moderate contrast reaction –Medically treated asthma Premedication with corticosteroids

34. Safety Monitoring Radiation Dose Directly proportional to: –Tube current –Kilovoltage –Scan time –Slice thickness –Total number of slices

35. 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

36. 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

37. 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

38. 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

39. 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

40. 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

41. 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

42. Injection Rate vs. Arterial Enhancement  injection rate increases contrast enhancement Bae 2002

43.  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

44. Concentration vs. Enhancement Varying iodine concentrations Total iodine mass and flow rate constant (5mL/s)  iodine concentration =  contrast enhancement Bae 2002

45. 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

46. 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

47. CT: Future Clinical Utilization Ventricular function studies based on images in systole and diastole Pulmonary perfusion studies –Peak attenuation & time to peak attenuation measured

48. Pulmo CT: Color Coded Display Potential for studying perfusion abnormalities associated with heart/lung disease

49. Summary Role of CT will increase Challenges: –Optimize contrast enhancement –Lower radiation dose