1. IMAGING OF INCIDENTAL ADRENAL LESIONS: PRINCIPLES, TECHNIQUES AND ALGORITHMS Giles W.L. Boland Massachusetts General Hospital Harvard Medical School

2. Objectives Comprehensive overview of adrenal imaging Comprehensive overview of adrenal imaging Basic principles Basic principles Techniques (CT, MRI, PET/CT) Techniques (CT, MRI, PET/CT) Algorithms Algorithms

3. Why characterize lesions? Most adrenal lesions detected by CT Most adrenal lesions detected by CT 2-7% of CT’s depending on age 2-7% of CT’s depending on age Almost always benign in the non-oncology patient Almost always benign in the non-oncology patient Song et al. 973 patients without cancer - none had malignant masses (AJR 2008) Song et al. 973 patients without cancer - none had malignant masses (AJR 2008) Further characterization needed in a patient with cancer - up to 50% lesions metastatic Further characterization needed in a patient with cancer - up to 50% lesions metastatic

4. Which is metastatic?

5. LUNG CANCER No adrenal metastases No adrenal metastases Primary lesion can be surgically removed and curative therapy performed Primary lesion can be surgically removed and curative therapy performed

6. LUNG CANCER Adrenal metastasis Adrenal metastasis Lung lesion now inoperable and palliative therapy performed Lung lesion now inoperable and palliative therapy performed

7. Principles Why it’s important to characterize lesions Why it’s important to characterize lesions Macroscopic features Macroscopic features Serial Imaging Serial Imaging Lipid sensitive techniques (CT and MRI) Lipid sensitive techniques (CT and MRI) Physiologic techniques (CT washouts) Physiologic techniques (CT washouts) Functional techniques (PET and PET/CT) Functional techniques (PET and PET/CT)

8. Principles: lesion morphology Size lesions > 4 cm tend to be metastases or carcinoma

9. Lesion morphology Shape Shape irregular shape often malignant (but not always) irregular shape often malignant (but not always)

10. Lesion morphology Lesion heterogeneity inhomogeneous - often malignant homogeneous - indeterminate

11. Change in lesion size Use cheapest radiological test: Use cheapest radiological test: “the old film” - prior CT “the old film” - prior CT No change: adenoma No change: adenoma Increase in size: metastasis Increase in size: metastasis

12. 2001 1996

13. 2008 2009 Metastatic disease

14. Serial imaging - lymphoma 2005 2007 2008

15. 2007 2008 Serial imaging - hematoma

16. Morphologic features Usually not helpful Usually not helpful Better tests needed to avoid biopsy Better tests needed to avoid biopsy Needs high specificity Needs high specificity Sensitivity less important but adequate Sensitivity less important but adequate Ideally serial imaging not required Ideally serial imaging not required

17. LESION CHARACTERIZATION Test devised to confidently diagnose adenomas Test devised to confidently diagnose adenomas Reduces # of percutaneous biopsies Reduces # of percutaneous biopsies Curative therapy for primary tumor possible Curative therapy for primary tumor possible

18. TEST SPECIFICITY: ADENOMA SPECIFICITY needs to be close to 100% SPECIFICITY needs to be close to 100% Non-specific: curative surgery will be performed for primary malignant lesion when adrenal metastases is present Non-specific: curative surgery will be performed for primary malignant lesion when adrenal metastases is present

19. TEST SENSITIVITY: ADENOMA SENSITIVITY less crucial SENSITIVITY less crucial Lesion remains indeterminate and therefore biopsy/MRI performed and adenoma confirmed Lesion remains indeterminate and therefore biopsy/MRI performed and adenoma confirmed

20. Lipid sensitive techniques Based on lipid content of detected lesion Based on lipid content of detected lesion Abundant intracytoplasmic fat in adrenal cortex (both functioning and non- functioning adenomas) - cholesterol, fatty acids neutral fat Abundant intracytoplasmic fat in adrenal cortex (both functioning and non- functioning adenomas) - cholesterol, fatty acids neutral fat Metastases lipid poor Metastases lipid poor CT and MRI CT and MRI

21. Macroscopic fat - myelolipoma

22. Lipid sensitive techniques 70% adenomas lipid-rich 70% adenomas lipid-rich 30% lipid-poor lesions 30% lipid-poor lesions All metastases are lipid-poor All metastases are lipid-poor Lipid-poor adenomas and mets are therefore indeterminate Lipid-poor adenomas and mets are therefore indeterminate These lesions require further characterization (follow-up, washouts, PET, biopsy) These lesions require further characterization (follow-up, washouts, PET, biopsy)

23. Lipid sensitive CT Non-contrast CT Non-contrast CT Place ROI on lesion Place ROI on lesion Lee et al 1991 Lee et al 1991 38 adenomas:-2.2 HU 38 adenomas:-2.2 HU 28 metastases: 29 HU 28 metastases: 29 HU

25. HU Sensitivity Specificity 041 100 041 100 247 100 247 100 45599 45599 86598.5 86598.5 107198 12 73 97 18 86 88 Boland et al. AJR 1998

26. Region of interest 38 HU 46 HU 6 HU

27. MRI Chemical Shift Imaging Chemical Shift Imaging Fat protons precess < water Fat protons precess < water Equal proportion within voxel = zero signal Equal proportion within voxel = zero signal Detects same tissue as CT (i.e. fat) Detects same tissue as CT (i.e. fat) In theory offers no advantages In theory offers no advantages Longer test Longer test Less availability Less availability

28. Lipid-Rich Adenoma In-phaseOut-of-phase

29. Lipid-poor metastasis Out-of-phase In-phase

30. Chemical shift – voxel water/fat ratio CTIn-phaseOut-of-phase

31. Contrast-enhanced CT Adrenals enhance Adrenals enhance Metastases tend to enhance to a higher HU than adenomas Metastases tend to enhance to a higher HU than adenomas HU measurements meaningless on dynamic study HU measurements meaningless on dynamic study Too much cross-over of HU values between benign and malignant lesions Too much cross-over of HU values between benign and malignant lesions

33. Perfusion Imaging: CT Washouts Adenomas washout faster than metastases Adenomas washout faster than metastases Even lipid poor adenomas washout faster Even lipid poor adenomas washout faster Delayed CT Delayed CT Ratio of enhanced to delayed HU Ratio of enhanced to delayed HU Disrupt busy CT schedule Disrupt busy CT schedule Better for patient in one sitting Better for patient in one sitting

34. Korobkin AJR 1998 Relative % washout Relative % washout Absolute % washout Absolute % washout Rule of thumb Rule of thumb Adenomas washout > 40% (> 60% absolute) Adenomas washout > 40% (> 60% absolute) Non-adenomas 60% absolute) Non-adenomas 60% absolute)

35. Washout Absolute: Enhanced - Delayed x 100% Absolute: Enhanced - Delayed x 100% Enhanced - Unenhanced Enhanced - Unenhanced Relative: Enhanced - Delayed x 100% Relative: Enhanced - Delayed x 100% Enhanced Enhanced

38. Lipid Poor Adenomas: Caoili et al. Radiology 2002 127 adenomas: 39 non-adenomas 127 adenomas: 39 non-adenomas 22 lipid poor 22 lipid poor Adrenal protocol Adrenal protocol Characterize 19/22 masses as benign Characterize 19/22 masses as benign 124/127 adenomas characterized by CT 124/127 adenomas characterized by CT Other masses had additional features to suggest adenoma Other masses had additional features to suggest adenoma

39. Blake et al. Radiology 2005 MDCT MDCT 122 masses 122 masses 10 minute delay 10 minute delay RPW threshold 38% RPW threshold 38% 100/98% sensitivity/specificity 100/98% sensitivity/specificity All malignant lesions RPW < 40% All malignant lesions RPW < 40%

40. Metabolic Imaging PET PET Metabolically hyperactive cells trap FDG Metabolically hyperactive cells trap FDG Used since early 1990’s Used since early 1990’s Now in favor due to PET/CT Now in favor due to PET/CT How useful? How useful?

41. Metastasis

43. Visual, SUV and SUR RSNA 2008 (Jagtiani et al) RSNA 2008 (Jagtiani et al) Meta-analysis 15 reports Meta-analysis 15 reports 878 adrenal lesions (457 benign and 421 malignant lesions) in 763 patients 878 adrenal lesions (457 benign and 421 malignant lesions) in 763 patients 10 PET stand-alone, 5 PET/CT scanners 10 PET stand-alone, 5 PET/CT scanners Visual as effective as SUR/SUV Visual as effective as SUR/SUV

44. Uptake < liver = benign

45. Uptake = liver = benign

46. Uptake slightly > liver = indeterminate

47. Uptake >> liver = malignant

48. Adrenal algorithm Non contrast CT: < 10 HUSTOP Non contrast CT: < 10 HUSTOP > 10 HUWashouts > 10 HUWashouts Washouts: Absolute:> 60% Adenoma Washouts: Absolute:> 60% Adenoma < 60% Mets Relative:> 40% Adenoma Relative:> 40% Adenoma < 40%Mets < 40%Mets 10 versus 15 minutes delays? 10 versus 15 minutes delays?

49. Best Test PET/CT PET/CT Combines functional PET with anatomy Combines functional PET with anatomy Even better with washouts Even better with washouts Multiple reports Multiple reports > 95% accuracy > 95% accuracy

50. Which test? No test has a monopoly No test has a monopoly Non-contrast CT effective for adenoma Non-contrast CT effective for adenoma CT washouts with CT protocol CT washouts with CT protocol Can stop there Can stop there Will be some indeterminate lesions Will be some indeterminate lesions Suspicious lesions Suspicious lesions PET/CT increasingly common PET/CT increasingly common Few lesions will need biopsy Few lesions will need biopsy

51. THANK YOU! Radiology 2008;249:756-77 Incidental Adrenal Lesions: Principles, Techniques, and Algorithms for Imaging Characterization