1. A Consensus Meeting for The Definitions of Subcortical lesions, Lacunes, Microbleeds, and Subcortical White Matter Change Jei Kim, MD

2. M/71, 2011. 1. 28

3. M/71, 2011. 1. 28

4. M/71, 2011. 1. 28

5. Subcortical lesions 1. Perivascular spaces (etatcrible) 2. Lacunes 3. Subcortical white matter changes 4. Microbleeds

6. Perivascular spaces (etatcrible)

7. 1. Perivascular spaces (etatcrible) 1) Histopathologic definition (ref. 1) : the dilatation of perivascular spaces around cerebral arterioles in the brain of elderly patients (Virchow-Robin space) 2) MRI definition (ref. 1) : the punctiform dilatations of the perivascular spaces often seen by brain MRI in the white matter and in the basal ganglia

8. 1. Perivascular spaces (etatcrible) 2) MRI definition : the punctiform dilatations of the perivascular spaces often seen by brain MRI in the white matter and in the basal ganglia : On T2WI – high intensity, same as the intensity of CSF : On FLAIR – dark (low), same as the intensity of CSF : On T1WI – dark (low), same as the intensity of CSF http://www.radiologyassistant.nl/en/4556dea65db62

9. M/80, 2011. 10. 13

10. Lacunes

11. 2. Lacunes 1) Histopathologic definition : a small, cystic cavity of the brain substance that usually results from an ischemic infarction in the territory of a penetrating arteriole (ref. 1)

12. 2. Lacunes 2) Vascular pathology of lacunes (ref. 13)

13. 2. Lacunes 3) Perforating arteries (1) Anterior perforating arteries (2) Posterior perforating arteries (3) Arterial supply of the brainstem

14. (1) Anterior perforating arteries

15. (1) Anterior perforating arteries A. Perforating branches arising from ACA and the recurrent artery of Heubner

16. (1) Anterior perforating arteries B. Perforating branches arising from MCA a. Perforating branches arising from MCA

17. (1) Anterior perforating arteries B. Perforating branches arising from MCA b. Percentage of perforating arteries arising from MCA trunk and its branches

18. (1) Anterior perforating arteries B. Perforating branches arising from MCA c. Origin of perforating arteries arising from MCA trunk and its branches

19. (1) Anterior perforating arteries B. Perforating branches arising from MCA d. Number of perforating arteries arising from different distances from the origin of MCA

20. (1) Anterior perforating arteries B. Perforating branches arising from MCA e. Branching characteristics of 508 perforating arteries arising from common stems of MCA

21. (2) Posterior perforating arteries

22. (3) Arterial supply of the brainstem A. Perforating arteries of the midbrain

23. (3) Arterial supply of the brainstem B. Perforating arteries of the pons

24. (3) Arterial supply of the brainstem C. Perforating arteries of the midbrain

25. Schematic diagram of origin of deep perforating branches from a parent artery

26. 2. Lacunes 4) Pathogenic implications of microcirculation (1) Perforating arteries 1) Stenosis or complete occlusion by atherosclerosis 2) Stenosis or occlusion of ostium of a branch point 3) Atherosclerotic narrowing of a parent artery 4) Proximal thrombus or embolus in atherosclerotic artery (2) Cortical branches

27. 4) Pathogenic implications of microcirculation (1) Perforating arteries A. Stenosis or complete occlusion by atherosclerosis

28. 4) Pathogenic implications of microcirculation (1) Perforating arteries B. Stenosis or occlusion of ostium of a branch point

29. 4) Pathogenic implications of microcirculation (1) Perforating arteries C. Atherosclerotic narrowing of a parent artery

30. 4) Pathogenic implications of microcirculation (1) Perforating arteries D. Proximal thrombus or embolus in atherosclerotic artery

31. 4) Pathogenic implications of microcirculation (2) Cortical branches

32. 2. Lacunes 5) MRI definition (ref. 2) : small hyperintense lesions on T2WI (ref. 2) : corresponding distinctive low intensity area on T1WI : Maximum size of lacune (ref. 4) - with a diameter of 5-10 mm : On CT (ref. 4) - areas of more or less complete focal tissue destruction - clearly defined borders with marked central hypodensity on CT : On MRI (ref. 4) - low intensity on T1WI, proton-density and FLAIR scans - high intensity on T2WI -> isointense to CSF

33. 2. Lacunes 5) MRI definition (ref. 17)

34. 2. Lacunes 1) Histopathologic definition : a small, cystic cavity of the brain substance that usually results from an ischemic infarction in the territory of a penetrating arteriole (ref. 1) : defined as cavitatedmicroinfarcts or encephalomalacic lesions, 2 mm or smaller in greatest dimension, not identifiable with certainty on gross inspection of the brain or non-cavitatedmicroinfarcts, focal gliotic areas without a cystic cavity (ref. 3)

35. M/80, 2011. 10. 13

36. 2. Lacunes 6) Grading of lacunes (ref. 2) Absent (2) Mild – 1-3 (3) Moderate – 4-10 (4) Severe - >10 7) Locations of lacunes (ref. 2) Cortico-subcortical (2) Basal ganglia (3) Thalamus (4) Brain stem (5) Cerebellum

37. Subcortical white matter change

38. 3. Subcortical white matter change 1) Definition of Binswanger’s disease (1894) : pronounced atrophy of the white matter, either confined to one or more gyri of the brain or in several sections of the hemisphere : in the most severe cases the entire white matter of a cerebral lobe appears to have completely wasted away : a severe atheromatosis of the arteries of the brain is always present in these cases : extensive atrophic degeneration or fatty degeneration of the small arterial and venous vessels : partial thickening of the inner and middle vascular membranes : the lumen is correspondingly narrowed

39. 3. Subcortical white matter change 2) Definition of leukoaraiosis (Hachinski et al., 1987) : loss of density of the periventricular white matter observed by CT of the brain : the white matter changes commonly observed in the elderly by MRI of the brain

40. 3. Subcortical white matter change 3) Mechanisms hypothesized to be involved in the pathogenesis of white matter change (ref. 14)

41. 3. Subcortical white matter change 4) Small vessel changes related to white matter changes (ref. 14)

42. 3. Subcortical white matter change 5) Evolution of white matter lesions (ref. 16)

43. 3. Subcortical white matter change 6) Definition of ‘Periventricular’ and ‘Deep white matter’ change (ref.5) (1) Periventricular - Start directly at the ventricular border

45. 3. Subcortical white matter change 6) Definition of ‘Periventricular’ and ‘Deep white matter’ change (ref.5) (3) Selective deep white matter lesion - usually characterized by a rim of normal-appearing tissue which separates them from the periventricular region

46. 3. Subcortical white matter change 6) Definition of ‘Periventricular’ and ‘Deep white matter’ change (ref.5) (4) Basal ganglia hypodensities on CT or hyperintensity on MRI (M/82)

47. 3. Subcortical white matter change 6) Definition of ‘Periventricular’ and ‘Deep white matter’ change (ref.24)

48. 3. Subcortical white matter change 6) Definition of ‘Periventricular’ and ‘Deep white matter’ change – (1) (ref.5) Periventricularhyperintensity 0 = absence 1 = “caps” or pencil-thin lining 2 = smooth “halo” 3 = irregular PVH extending into the deep white matter (2) Deep white matter hyperintense signal 0 = absence 1 = punctuate foci 2 = beginning confluence of foci 3 = large confluent areas

49. 3. Subcortical white matter change 7) Definition of ‘Periventricular’ and ‘Deep white matter’ –(3) (ref. 6) (1) White matter lesions 0 = no lesions (including symmetrical, well-defined caps or bands) 1 = Focal lesions 2 = Beginning confluence of lesions 3 = Diffuse involvement of the entire region, with or without involvement of U fibers (2) Basal ganglia lesions 0 = No lesions 1 = 1 focal lesion (≥ 5 mm) 2 = > 1 focal lesion 3 = Confluent lesions

50. 3. Subcortical white matter change 7) Definition of ‘Periventricular’ and ‘Deep white matter’ –(3) (ref. 6) 1. Score of 1

51. 3. Subcortical white matter change 7) Definition of ‘Periventricular’ and ‘Deep white matter’ –(3) (ref. 6) 2. Score of 2

52. 3. Subcortical white matter change 7) Definition of ‘Periventricular’ and ‘Deep white matter’ –(3) (ref. 6) 3. Score of 3

53. 3. Subcortical white matter change (1) White matter lesions 1 = Focal lesions

54. 3. Subcortical white matter change (1) White matter lesions 2 = Beginning confluence of lesions

55. 3. Subcortical white matter change (1) White matter lesions 3 = Diffuse involvement of the entire region, with or without involvement of U fibers (M/75)

56. 3. Subcortical white matter change (1) White matter lesions 3 = Diffuse involvement of the entire region, with or without involvement of U fibers (M/60)

57. 3. Subcortical white matter change (2) Basal ganglia lesions 1 = 1 focal lesion (≥ 5 mm)

58. 3. Subcortical white matter change (2) Basal ganglia lesions 2 = > 1 focal lesion

59. 3. Subcortical white matter change (2) Basal ganglia lesions 3 = Confluent lesions

60. Microbleeds

61. 4. Microbleeds 1) Histopathologic and MRI definition : paramagnetic material which produces local susceptibility gradients and thereby causes a faster decay of transverse magnetization on gradient-echo acquisition (ref. 18) : remnants of even minor blood leakage through damaged vessel walls

62. 4. Microbleeds 1) Histopathologic definition : Postmortem gradient-echo-T2*-weighted MRI and histopathologic finding (ref. 19)

63. 4. Microbleeds 2) Severity of amyloidangiopathy (ref. 27) Figure 1. Grading of CAA severity in single brain samples (ref. 27) 0: No cerebral vessels showed immunopositivity for beta amyloid 1+: Amyloid is restricted to a rim around smooth muscle fibers in the media of occasional normal vessels 2+: The media is thicker than normal and circumferentially replaced by amyloid in a few vessels 3+: Widespread medial thickening and circumferential amyloid deposition with a small halo of immunoreactivity in the surrounding parenchyma : A focus of wall leakage as evidenced by fresh hemorrhage or hemosiderin-laden macrophages, or occlusion, or recanalization

64. 4. Microbleeds 3) MRI definition of microbleed (ref. 2, 19, 20, 21) (1) Homogeneous round signal loss lesion with a diameter of up to 5 mm (or <10 mm) on gradient echo image Distinct from a. Vascular flow voids on subarachnoid space b. Leptomeningealhemasiderosis c. Non-hemorrhagic subcortical mineralization

71. In CADASIL Pt.

73. 4. Microbleeds 4) Degree of severity of microbleeds (ref. 2) (1) Absent (2) Mild – total number of MBs, 1-5 (3) Moderate – total number of MBs, 6-15 (4) Severe – total number of MBs, >15

74. 4. Microbleeds 5) The locations of the microbleeds and lacunes (ref. 2) (1) Cortico-subcortical (2) Basal ganglia (3) Thalamus (4) Brain stem (5) Cerebellum

75. Evaluation of the vessel stenosis

76. Definition of coronary artery stenosis (ref. 8) 1) Significant stenosis - >50% 2) No significant stenosis - <50%

77. The degrees of stenoocclusive disease (ref. 7) 1) Normal – 0% - 29% diameter stenosis 2) Mildly stenotic – 30% - 49% 3) Moderately stenotic – 50% - 79% 4) Severely stenotic – 80%- 99% 5) Occluded

78. Regional location of stenosis (ref. 9) : Schematic representation of 11 arterial segments studied by transcranial Doppler and duplex ultrasound MCA – 1 and 2 ACA – 3 and 4 PCA – 5 and 6 Siphon ICA – 7 and 8 Extracranial ICA - 9 and 10 Vertebrobasilar artery – 11

80. Measuement of vessel stenosis (ref. 10) 2. Criteria for normal proximal artery (3) Third choice A. If the entire intracranial artery was diseased -> the most distal, parallel, non-tortous normal segment of the feeding artery B. If the entire middle cerebral artery was diseased -> measured at the most distal, parallel segement of the supraaclinoid carotid artery C. If the entire intracranial vertebral artery was diseased -> measured at the most distal, parallel, non-tortous normal segment of the extracranial vertebral artery

81. Measuement of vessel stenosis (ref. 10) 2. Criteria for normal proximal artery 2) For the ICA (1) First choice : The precavernous, cavernous, and postcavernous stenoses of ICA -> measured at the widest, non-tortous, normal portion of the petrous carotid artery that had parallel margins

82. Measuement of vessel stenosis (ref. 10) 2. Criteria for normal proximal artery 2) For the ICA (2) Second choice - If the entire petrous carotid was diseased -> the most distal, parallel part of the extracranial internal carotid artery was substituted - If tandem intracranial lesions were present -> percent stenosis of both sites was measured and the more severe stenosis was selected - When a “gap sign” was present -- the lumen of the vessel could not be visualized at the site of severe stenosis -- could not be measured -- defined as 99% luminal stenosis

83. Measuement of vessel stenosis (ref. 10) 1. Equation for measuring intracranial arterial stenosis

84. Measuement of vessel stenosis 2. Equation for measuring extracranial arterial stenosis 1) Severity of intracranial stenosis (ref. 11, 12) (1) Mild - <30% (2) Moderate – 30% - 69% (3) Severe – 70% - 99% - in case of segmental signal void -> the stenosis was graded as severe (>70%) (4) Occluded

85. Measuement of vessel stenosis 2. Equation for measuring extracranial arterial stenosis 2) Measurement of the carotid artery stenosis (ref. 12) (1) NASCET : (1-md/C)x100% (2) ECST : (1-md/B)x100% (3) CC : (1-md/A)x100%