Updated imaging markers in cerebral amyloid angiopathy: What radiologists need to know

Abstract

Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease pathologically characterized by the progressive accumulation of amyloid-beta (Aβ) peptide in cerebrovascular walls, affecting both cortical and leptomeningeal vessels. Amyloid deposition results in fragile vessels, which may lead to lobar intracerebral hemorrhage (ICH) and cognitive impairment. To evaluate the probability and severity of CAA, the imaging markers depicted on CT and MRI techniques are crucial, as brain pathological examination is highly invasive. Although the Boston criteria have established diagnostic value and have been updated to version 2.0, due to an aging population, the patients with CAA should also be assessed for their risk of future ICH or cognitive impairment. Furthermore, an increased awareness of CAA is essential when introducing anticoagulants for infarct in elderly patients or anti-amyloid antibodies for Alzheimer's disease, as these may worsen CAA-related hemorrhagic lesions. However, the radiological literature on CAA has not been comprehensively updated. Here, we review the imaging markers of CAA and clinical significance. We also discuss the clinical and imaging characteristics of CAA-related inflammation, amyloid-related imaging abnormalities, and iatrogenic-CAA.

Keywords: Alzheimer’s disease; Cerebral amyloid angiopathy; MRI; Small vessel disease.

Fig. 1

Representative imaging markers in cerebral amyloid angiopathy. Abbreviations: CMB cerebral microbleed, CMI cortical microinfarct, cSAH convexity subarachnoid hemorrhage, cSS cortical superficial siderosis, ICH intracerebral hemorrhage, PVS-CSO perivascular space in the centrum semiovale, WMH-MP white matter hyperintensities in a multispot pattern

Fig. 2

CAA diagnostic chart based on the Boston criteria version 2.0. Note: Cerebellar hemorrhagic lesions are not counted. Abbreviations: CAA cerebral amyloid angiopathy, cSAH convexity subarachnoid hemorrhage, cSS cortical superficial siderosis, CMB cerebral microbleed, ICH intracerebral hemorrhage, PVS-CSO perivascular space in the centrum semiovale, TFNE transient focal neurological episode, WMH-MP white matter hyperintensities in a multispot pattern. Figure quoted from Ref. [16] and modified

Fig. 3

A 60-year-old male with probable CAA with supporting pathology. CT shows left temporo-occipital hemorrhage with finger-like projection (arrows), extending both of the lateral ventricles (arrowheads)

Fig. 4

A 75-year-old male with probable CAA. Mini-Mental State Examination (MMSE) score is 20 out of 30. Susceptibility-weighted image (SWI) (a) shows multiple strictly lobar cerebral microbleeds (CMB) (arrows) in bilateral hemispheres with a posterior dominant distribution. Three-dimensional (3D) fluid-attenuated inversion recovery (FLAIR) (b) shows lacune (small arrow) in the left frontal lobe

Fig.5

A 79-year-old male with probable CAA. MMSE score is 18. SWI (a) shows cSS (arrows) with track-like appearance (circles), and also lobar CMBs (arrowheads) in bilateral occipital lobes. One year later, CT (b) shows a hemorrhage with finger-like projections (small arrows) in the left parietal lobe

Fig. 6

A 71-year-old female with probable CAA and mild cognitive impairment. She presents with headache and dementia with an MMSE score of 24. SWI (a) detects cSS in the sulci of the right frontal lobe (arrows) and lobar CMBs in the adjacent cortex (arrowheads). cSS is more clearly depicted on double-inversion recovery (DIR) (c) (arrows) than 3D-FLAIR (b) (arrows)

Fig. 7

An 84 year-old female with probable CAA. She complained of recurrent episodes of numbness in her right upper extremity, which were considered to represent TFNE. CT (a) detects convexity subarachnoid hemorrhage (cSAH) in the central sulcus (arrow). Diffusion-weighted image (DWI) (b) shows a small DWI lesion (arrow) in the left frontal lobe. On SWI (c), disseminated cSS (arrows) and multiple CMBs (arrowheads) in bilateral hemispheres

Fig. 8

A 69-year-old female with probable CAA. MMSE score is 21. T2*-weighted image (a) and T2-weighted image (b) show hypointensity in the left parietal gyrus, indicating an intragyral hemorrhage (arrow). In addition, enlarged PVS (arrowheads) are observed around the intragyral hemorrhage on T2-weighted image (b). CMBs in bilateral parietal lobes are also depicted (small arrow) on T2*-weighted image

Fig. 9

A 71-year-old male with probable CAA. MMSE score is 22. T2-weighted image shows severe PVS-CSO (arrows) in bilateral hemispheres. A hypointensity was observed in the right central sulcus, indicating cSS (arrowheads)

Fig.10

An 89-year-old male with probable CAA. MMSE score is 24. 3D FLAIR shows subcortical hyperintense areas in a multispot pattern (arrows)

Fig.11

A 74-year-old male with probable CAA. MMSE score is 27. 3D-DIR shows cortical hyperintensities in the left parietal lobe, suggesting a cortical microinfarct (arrows)

Fig. 12

A 63-year-old female with probable CAA. MMSE score is 21. SWI (a, b) shows hypointensities along the cerebellar fissures, indicating superficial siderosis (arrows), and numerous CMBs in bilateral cerebral and cerebellar hemispheres (arrowheads)

Fig. 13

A 69-year-old female with CAA-related inflammation. She presents with general weakness and dementia with a 21 MMSE score even after a ventriculoperitoneal shunt operation for Idiopathic normal pressure hydrocephalus. At the onset of the symptom, 2D FLAIR (a) shows hyperintensity in the right parietal to occipital lobe white matter (arrow). Thirteen weeks after the steroid therapy, the hyperintensity lesion on 2D FLAIR (b) is resolved. T2*-weighted image (c) shows multiple CMBs (arrowheads) in the right hemisphere

Fig. 14

A 72-year-old female with amyloid-related imaging abnormalities-effusion (ARIA-E), eight weeks after receiving lecanemab for the treatment of mild cognitive impairment. There are no symptoms associated with ARIA-E. Non-contrast-3D FLAIR (a, b) shows hyperintensities in the sulci of the left posterior lobe (arrows) without new hemorrhagic lesions. Contrast-enhanced 3D FLAIR (c, d) shows enhancement in the sulci of the left posterior lobe (circles)

Fig. 15

A 47-year-old female with iatrogenic CAA. MMSE score is 14. She had a history of cerebellar tumor resection when she was 5 years old. SWI (a) shows lobar CMBs (arrowheads) and cSS (circles). Contrast-enhanced 3D FLAIR (b) shows leptomeningeal enhancement in the left parieto-occipital lobe (arrows)