Multimodality Review of Amyloid-related Diseases of the Central Nervous System

Abstract

Amyloid-β (Aβ) is ubiquitous in the central nervous system (CNS), but pathologic accumulation of Aβ results in four distinct neurologic disorders that affect middle-aged and elderly adults, with diverse clinical presentations ranging from chronic debilitating dementia to acute life-threatening intracranial hemorrhage. The characteristic imaging patterns of Aβ-related CNS diseases reflect the pathophysiology of Aβ deposition in the CNS. Aβ is recognized as a key component in the neuronal damage that characterizes the pathophysiology of Alzheimer disease, the most common form of dementia. Targeted molecular imaging shows pathologic accumulation of Aβ and tau protein, and fluorine 18 fluorodeoxyglucose positron emission tomography and anatomic imaging allow differentiation of typical patterns of neuronal dysfunction and loss in patients with Alzheimer disease from those seen in patients with other types of dementia. Cerebral amyloid angiopathy (CAA) is an important cause of cognitive impairment and spontaneous intracerebral hemorrhage in the elderly. Hemorrhage and white matter injury seen at imaging reflect vascular damage caused by the accumulation of Aβ in vessel walls. The rare forms of inflammatory angiopathy attributed to Aβ, Aβ-related angiitis and CAA-related inflammation, cause debilitating neurologic symptoms that improve with corticosteroid therapy. Imaging shows marked subcortical and cortical inflammation due to perivascular inflammation, which is incited by vascular Aβ accumulation. In the rarest of the four disorders, cerebral amyloidoma, the macroscopic accumulation of Aβ mimics the imaging appearance of tumors. Knowledge of the imaging patterns and pathophysiology is essential for accurate diagnosis of Aβ-related diseases of the CNS. (©)RSNA, 2016.

Figure 1a.

Pathologic changes in a patient with AD. (a) Photomicrograph of frontal cortex specimen shows Aβ plaques (large arrows) typical of AD. Coexistent CAA characterized by a hyalinized vessel with intramural Aβ (small arrow) is commonly found with pathologic results typical of AD. (Hematoxylin-eosin [H-E] stain; original magnification, ×400.) (b) Photomicrograph of frontal cortex specimen stained with an antibody to Aβ shows dark brown stain corresponding to scattered round Aβ plaques (short arrows) and ringlike Aβ deposition (long arrow) in the vessel wall. Vascular intramural deposition of Aβ characteristic of CAA pathologic results may coexist with typical pathologic findings of AD. (10D5 immunohistochemical stain; original magnification, ×200.)

Figure 1b.

Pathologic changes in a patient with AD. (a) Photomicrograph of frontal cortex specimen shows Aβ plaques (large arrows) typical of AD. Coexistent CAA characterized by a hyalinized vessel with intramural Aβ (small arrow) is commonly found with pathologic results typical of AD. (Hematoxylin-eosin [H-E] stain; original magnification, ×400.) (b) Photomicrograph of frontal cortex specimen stained with an antibody to Aβ shows dark brown stain corresponding to scattered round Aβ plaques (short arrows) and ringlike Aβ deposition (long arrow) in the vessel wall. Vascular intramural deposition of Aβ characteristic of CAA pathologic results may coexist with typical pathologic findings of AD. (10D5 immunohistochemical stain; original magnification, ×200.)

Figure 2a.

Structural MR imaging through the temporal lobes in a 62-year-old man with AD. (a) Coronal T1-weighted image shows mild nonspecific cerebral atrophy and mild widening of the sylvian fissures (arrows). (b) Coronal T1-weighted image obtained 7 years later shows progression of the cerebral atrophy in a pattern typical of AD, particularly in the temporal lobes, with dilatation of the ventricular system, sylvian fissures (arrows), and sulci. The rate of cerebral volume loss in patients with AD is more rapid than that attributed to normal aging in the healthy population.

Figure 2b.

Structural MR imaging through the temporal lobes in a 62-year-old man with AD. (a) Coronal T1-weighted image shows mild nonspecific cerebral atrophy and mild widening of the sylvian fissures (arrows). (b) Coronal T1-weighted image obtained 7 years later shows progression of the cerebral atrophy in a pattern typical of AD, particularly in the temporal lobes, with dilatation of the ventricular system, sylvian fissures (arrows), and sulci. The rate of cerebral volume loss in patients with AD is more rapid than that attributed to normal aging in the healthy population.

Figure 3.

Axial gray-scale (top row) and color-scale (middle row) FDG PET images in a healthy control subject (Normal) and a patient with AD (AD pattern) and statistical thresholding overlays on a three-dimensional surface display in a patient with AD (bottom row) show the characteristic pattern of hypometabolism in the temporal and parietal lobes compared to normal brain. The AD pattern includes hypometabolism in the parietal and temporal cortices (arrowheads). The statistical thresholding images emphasize that the most severely affected areas of synaptic dysfunction and neuronal loss leading to hypometabolism seen on FDG PET images are in the precuneus and cingulate gyrus (black arrows) and temporal lobes (white arrows).

Figure 4a.

Aβ deposition at ¹⁸F-florbetapir brain PET in two patients. (a) Image in a 67-year-old cognitively healthy control subject shows uptake of florbetapir in the white matter (arrow), with relative lack of uptake in the cortex (arrowhead). The distinction between uptake in the gray and white matter is maintained. The findings were interpreted as normal physiologic accumulation of Aβ. MR images (not shown) demonstrated normal brain volume. (b) Image in a 68-year-old man with AD shows similar levels of activity in the white matter (arrow) and gray matter (arrowhead), with loss of the distinction between uptake in the gray and white matter. The findings indicate elevated fibrillary amyloid in the gray matter, and the study was interpreted as showing pathologic accumulation of Aβ.

Figure 4b.

Aβ deposition at ¹⁸F-florbetapir brain PET in two patients. (a) Image in a 67-year-old cognitively healthy control subject shows uptake of florbetapir in the white matter (arrow), with relative lack of uptake in the cortex (arrowhead). The distinction between uptake in the gray and white matter is maintained. The findings were interpreted as normal physiologic accumulation of Aβ. MR images (not shown) demonstrated normal brain volume. (b) Image in a 68-year-old man with AD shows similar levels of activity in the white matter (arrow) and gray matter (arrowhead), with loss of the distinction between uptake in the gray and white matter. The findings indicate elevated fibrillary amyloid in the gray matter, and the study was interpreted as showing pathologic accumulation of Aβ.

Figure 5a.

Tau protein accumulation in a 76-year-old woman with a clinical diagnosis of AD that was supported by CSF biomarker assay and amyloid PET findings compatible with AD. Coronal (a) and sagittal (b) ¹⁸F-T807 (AV-1451) PET images show increased radiotracer uptake in the left temporal and parietal lobes (arrows) and, to a lesser extent, in the right temporal and parietal lobes (arrowhead in a). The findings indicate an abnormal accumulation of tau protein in a pattern typical of AD.

Figure 5b.

Tau protein accumulation in a 76-year-old woman with a clinical diagnosis of AD that was supported by CSF biomarker assay and amyloid PET findings compatible with AD. Coronal (a) and sagittal (b) ¹⁸F-T807 (AV-1451) PET images show increased radiotracer uptake in the left temporal and parietal lobes (arrows) and, to a lesser extent, in the right temporal and parietal lobes (arrowhead in a). The findings indicate an abnormal accumulation of tau protein in a pattern typical of AD.

Figure 6a.

Pathologic changes of CAA. (a) Photomicrograph of parietal cortex specimen shows amyloid (dark pink; arrows) deposited in the vessel walls. * = vessel lumina. (H-E stain; original magnification, ×400.) (b) Photomicrograph of parietal cortex specimen stained with an antibody to Aβ (brown stain) shows amyloid deposition in multiple vessel walls (arrows). (10D5 immunohistochemical stain; original magnification, ×200.) (c) Photomicrograph of parietal cortex specimen shows typical fluorescence (green) associated with adherence of fluorescent stain to Aβ. The ring pattern of fluorescence corresponds to Aβ in the vessel walls. (Thioflavin S fluorescent stain; original magnification, ×400.) (Case courtesy of Kyle Hurth, MD, Department of Pathology, Washington University School of Medicine, St Louis, Mo).

Figure 6b.

Pathologic changes of CAA. (a) Photomicrograph of parietal cortex specimen shows amyloid (dark pink; arrows) deposited in the vessel walls. * = vessel lumina. (H-E stain; original magnification, ×400.) (b) Photomicrograph of parietal cortex specimen stained with an antibody to Aβ (brown stain) shows amyloid deposition in multiple vessel walls (arrows). (10D5 immunohistochemical stain; original magnification, ×200.) (c) Photomicrograph of parietal cortex specimen shows typical fluorescence (green) associated with adherence of fluorescent stain to Aβ. The ring pattern of fluorescence corresponds to Aβ in the vessel walls. (Thioflavin S fluorescent stain; original magnification, ×400.) (Case courtesy of Kyle Hurth, MD, Department of Pathology, Washington University School of Medicine, St Louis, Mo).

Figure 6c.

Pathologic changes of CAA. (a) Photomicrograph of parietal cortex specimen shows amyloid (dark pink; arrows) deposited in the vessel walls. * = vessel lumina. (H-E stain; original magnification, ×400.) (b) Photomicrograph of parietal cortex specimen stained with an antibody to Aβ (brown stain) shows amyloid deposition in multiple vessel walls (arrows). (10D5 immunohistochemical stain; original magnification, ×200.) (c) Photomicrograph of parietal cortex specimen shows typical fluorescence (green) associated with adherence of fluorescent stain to Aβ. The ring pattern of fluorescence corresponds to Aβ in the vessel walls. (Thioflavin S fluorescent stain; original magnification, ×400.) (Case courtesy of Kyle Hurth, MD, Department of Pathology, Washington University School of Medicine, St Louis, Mo).

Figure 7a.

CAA in a 64-year-old woman with spontaneous intracranial hemorrhage secondary to CAA. (a) Axial CT image of the brain shows a right frontal intraparenchymal hematoma with a peripheral lobar distribution typical of CAA. (b) Axial CT image shows subarachnoid blood, another common pattern of intracranial hemorrhage seen in patients with CAA. The finding typically is seen in combination with an adjacent intraparenchymal hemorrhage or in isolation because of rupture of a superficial cortical or leptomeningeal vessel.

Figure 7b.

CAA in a 64-year-old woman with spontaneous intracranial hemorrhage secondary to CAA. (a) Axial CT image of the brain shows a right frontal intraparenchymal hematoma with a peripheral lobar distribution typical of CAA. (b) Axial CT image shows subarachnoid blood, another common pattern of intracranial hemorrhage seen in patients with CAA. The finding typically is seen in combination with an adjacent intraparenchymal hemorrhage or in isolation because of rupture of a superficial cortical or leptomeningeal vessel.

Figure 8a.

CAA in a 62-year-old woman who underwent evaluation for rapidly progressive dementia attributed to biopsy-proven CAA. (a) Axial gradient-echo MR image shows numerous peripheral cortical and subcortical microhemorrhages (arrows) typical of CAA. (b) Axial susceptibility-weighted MR image shows many more microhemorrhages (arrow) than were seen on the gradient-echo image because of the inherent improved sensitivity of susceptibility-weighted imaging for microhemorrhage (52). (c) Axial FLAIR MR image obtained 1 year later shows a central distribution of white matter damage due to chronic ischemia.

Figure 8b.

CAA in a 62-year-old woman who underwent evaluation for rapidly progressive dementia attributed to biopsy-proven CAA. (a) Axial gradient-echo MR image shows numerous peripheral cortical and subcortical microhemorrhages (arrows) typical of CAA. (b) Axial susceptibility-weighted MR image shows many more microhemorrhages (arrow) than were seen on the gradient-echo image because of the inherent improved sensitivity of susceptibility-weighted imaging for microhemorrhage (52). (c) Axial FLAIR MR image obtained 1 year later shows a central distribution of white matter damage due to chronic ischemia.

Figure 8c.

CAA in a 62-year-old woman who underwent evaluation for rapidly progressive dementia attributed to biopsy-proven CAA. (a) Axial gradient-echo MR image shows numerous peripheral cortical and subcortical microhemorrhages (arrows) typical of CAA. (b) Axial susceptibility-weighted MR image shows many more microhemorrhages (arrow) than were seen on the gradient-echo image because of the inherent improved sensitivity of susceptibility-weighted imaging for microhemorrhage (52). (c) Axial FLAIR MR image obtained 1 year later shows a central distribution of white matter damage due to chronic ischemia.

Figure 9a.

Pathologic changes in patients with Aβ-related angiitis. (a) Photomicrograph of the superficial frontal cortex and leptomeningeal vessels shows granulomatous vasculitis. Note the luminal occlusion or near occlusion by intimal hyperplasia (arrowhead), intramural inflammation characterized by lymphocytes (arrows), and hemorrhage (*). (H-E stain; original magnification, ×200.) (b) Photomicrograph of the leptomeningeal vessels stained with an antibody to Aβ shows amyloid deposition in multiple vessels (brown stain; arrows), findings consistent with Aβ-related angiitis. (Aβ immunohistochemical stain; original magnification, ×200.) (c) Photomicrograph of the superficial frontal cortex and leptomeningeal vessels, with granulomatous vasculitis stained with an antibody (brown stain; arrows), highlights macrophages indicative of granulomatous inflammatory changes in and around the vessels. (CD163 immunohistochemical stain, original magnification, ×200). (d) Photomicrograph of the leptomeningeal vessels, with granulomatous vasculitis stained with an antibody to smooth muscle actin (brown stain), shows multiple foci of disruption (arrows = margins of disruption) and loss of the muscular layer. (Immunohistochemical stain; original magnification, ×400.)

Figure 9b.

Pathologic changes in patients with Aβ-related angiitis. (a) Photomicrograph of the superficial frontal cortex and leptomeningeal vessels shows granulomatous vasculitis. Note the luminal occlusion or near occlusion by intimal hyperplasia (arrowhead), intramural inflammation characterized by lymphocytes (arrows), and hemorrhage (*). (H-E stain; original magnification, ×200.) (b) Photomicrograph of the leptomeningeal vessels stained with an antibody to Aβ shows amyloid deposition in multiple vessels (brown stain; arrows), findings consistent with Aβ-related angiitis. (Aβ immunohistochemical stain; original magnification, ×200.) (c) Photomicrograph of the superficial frontal cortex and leptomeningeal vessels, with granulomatous vasculitis stained with an antibody (brown stain; arrows), highlights macrophages indicative of granulomatous inflammatory changes in and around the vessels. (CD163 immunohistochemical stain, original magnification, ×200). (d) Photomicrograph of the leptomeningeal vessels, with granulomatous vasculitis stained with an antibody to smooth muscle actin (brown stain), shows multiple foci of disruption (arrows = margins of disruption) and loss of the muscular layer. (Immunohistochemical stain; original magnification, ×400.)

Figure 9c.

Pathologic changes in patients with Aβ-related angiitis. (a) Photomicrograph of the superficial frontal cortex and leptomeningeal vessels shows granulomatous vasculitis. Note the luminal occlusion or near occlusion by intimal hyperplasia (arrowhead), intramural inflammation characterized by lymphocytes (arrows), and hemorrhage (*). (H-E stain; original magnification, ×200.) (b) Photomicrograph of the leptomeningeal vessels stained with an antibody to Aβ shows amyloid deposition in multiple vessels (brown stain; arrows), findings consistent with Aβ-related angiitis. (Aβ immunohistochemical stain; original magnification, ×200.) (c) Photomicrograph of the superficial frontal cortex and leptomeningeal vessels, with granulomatous vasculitis stained with an antibody (brown stain; arrows), highlights macrophages indicative of granulomatous inflammatory changes in and around the vessels. (CD163 immunohistochemical stain, original magnification, ×200). (d) Photomicrograph of the leptomeningeal vessels, with granulomatous vasculitis stained with an antibody to smooth muscle actin (brown stain), shows multiple foci of disruption (arrows = margins of disruption) and loss of the muscular layer. (Immunohistochemical stain; original magnification, ×400.)

Figure 9d.

Pathologic changes in patients with Aβ-related angiitis. (a) Photomicrograph of the superficial frontal cortex and leptomeningeal vessels shows granulomatous vasculitis. Note the luminal occlusion or near occlusion by intimal hyperplasia (arrowhead), intramural inflammation characterized by lymphocytes (arrows), and hemorrhage (*). (H-E stain; original magnification, ×200.) (b) Photomicrograph of the leptomeningeal vessels stained with an antibody to Aβ shows amyloid deposition in multiple vessels (brown stain; arrows), findings consistent with Aβ-related angiitis. (Aβ immunohistochemical stain; original magnification, ×200.) (c) Photomicrograph of the superficial frontal cortex and leptomeningeal vessels, with granulomatous vasculitis stained with an antibody (brown stain; arrows), highlights macrophages indicative of granulomatous inflammatory changes in and around the vessels. (CD163 immunohistochemical stain, original magnification, ×200). (d) Photomicrograph of the leptomeningeal vessels, with granulomatous vasculitis stained with an antibody to smooth muscle actin (brown stain), shows multiple foci of disruption (arrows = margins of disruption) and loss of the muscular layer. (Immunohistochemical stain; original magnification, ×400.)

Figure 10a.

Aβ-related angiitis in a 44-year-old woman with transient expressive aphasia. (a) FLAIR MR image shows tumorlike edema in the left parietal lobe cortex and white matter, typical findings in Aβ-related angiitis. (b) Axial contrast-enhanced T1-weighted MR image shows mild leptomeningeal enhancement adjacent to the region of edema (arrows). (c) Axial susceptibility-weighted MR image shows a cluster of punctate areas of microhemorrhage in the region of edema, with sparing of the remainder of the brain.

Figure 10b.

Aβ-related angiitis in a 44-year-old woman with transient expressive aphasia. (a) FLAIR MR image shows tumorlike edema in the left parietal lobe cortex and white matter, typical findings in Aβ-related angiitis. (b) Axial contrast-enhanced T1-weighted MR image shows mild leptomeningeal enhancement adjacent to the region of edema (arrows). (c) Axial susceptibility-weighted MR image shows a cluster of punctate areas of microhemorrhage in the region of edema, with sparing of the remainder of the brain.

Figure 10c.

Aβ-related angiitis in a 44-year-old woman with transient expressive aphasia. (a) FLAIR MR image shows tumorlike edema in the left parietal lobe cortex and white matter, typical findings in Aβ-related angiitis. (b) Axial contrast-enhanced T1-weighted MR image shows mild leptomeningeal enhancement adjacent to the region of edema (arrows). (c) Axial susceptibility-weighted MR image shows a cluster of punctate areas of microhemorrhage in the region of edema, with sparing of the remainder of the brain.

Figure 11a.

CAA-related inflammation in a 67-year-old woman with headaches, cognitive decline, and upper extremity weakness. (a) Axial FLAIR MR image shows large territories of edema in both frontal lobes that involve both the cortex and the white matter, causing midline shift toward the right. (b) Axial contrast-enhanced T1-weighted MR image shows leptomeningeal contrast enhancement in the region of the tumoral edema (arrow). Other regions of leptomeningeal enhancement are not shown. The presence and degree of leptomeningeal enhancement can be variable in inflammatory variants of CAA. Contrast enhancement is rare in typical patients with CAA and helps differentiate CAA-related inflammation from CAA. (c) Axial susceptibility-weighted MR image shows multiple areas of cortical and subcortical punctate microhemorrhage concentrated in the area of edema and also seen in areas unaffected by edema.

Figure 11b.

CAA-related inflammation in a 67-year-old woman with headaches, cognitive decline, and upper extremity weakness. (a) Axial FLAIR MR image shows large territories of edema in both frontal lobes that involve both the cortex and the white matter, causing midline shift toward the right. (b) Axial contrast-enhanced T1-weighted MR image shows leptomeningeal contrast enhancement in the region of the tumoral edema (arrow). Other regions of leptomeningeal enhancement are not shown. The presence and degree of leptomeningeal enhancement can be variable in inflammatory variants of CAA. Contrast enhancement is rare in typical patients with CAA and helps differentiate CAA-related inflammation from CAA. (c) Axial susceptibility-weighted MR image shows multiple areas of cortical and subcortical punctate microhemorrhage concentrated in the area of edema and also seen in areas unaffected by edema.

Figure 11c.

CAA-related inflammation in a 67-year-old woman with headaches, cognitive decline, and upper extremity weakness. (a) Axial FLAIR MR image shows large territories of edema in both frontal lobes that involve both the cortex and the white matter, causing midline shift toward the right. (b) Axial contrast-enhanced T1-weighted MR image shows leptomeningeal contrast enhancement in the region of the tumoral edema (arrow). Other regions of leptomeningeal enhancement are not shown. The presence and degree of leptomeningeal enhancement can be variable in inflammatory variants of CAA. Contrast enhancement is rare in typical patients with CAA and helps differentiate CAA-related inflammation from CAA. (c) Axial susceptibility-weighted MR image shows multiple areas of cortical and subcortical punctate microhemorrhage concentrated in the area of edema and also seen in areas unaffected by edema.

Figure 12a.

Aβ-related angiitis in a 70-year-old man with acute onset of headache. (a) Axial head CT image shows a subarachnoid hemorrhage in the left central sulcus (arrow). (b) Axial FLAIR MR image obtained the next day shows failure of suppression of CSF signal intensity in the left central sulcus (long arrow), corresponding to the subarachnoid hemorrhage seen at CT, and failure of suppression of signal intensity in other adjacent parietal and frontal sulci (short arrows) that did not clearly show subarachnoid blood at CT. (c) Axial contrast-enhanced T1-weighted MR image shows leptomeningeal enhancement along the central sulcus (arrows). The enhancement may have been due to leptomeningeal inflammation secondary to vasculitis or leptomeningeal irritation by subarachnoid blood products. (d) Axial susceptibility-weighted MR image shows gyriform low signal intensity corresponding to cortical surfaces in both cerebral hemispheres (arrows), including within sulci remote from the acute hemorrhage seen at CT and FLAIR imaging. This finding suggests superficial siderosis due to prior episodes of hemorrhage and is commonly described in patients with Aβ-related angiitis.

Figure 12b.

Aβ-related angiitis in a 70-year-old man with acute onset of headache. (a) Axial head CT image shows a subarachnoid hemorrhage in the left central sulcus (arrow). (b) Axial FLAIR MR image obtained the next day shows failure of suppression of CSF signal intensity in the left central sulcus (long arrow), corresponding to the subarachnoid hemorrhage seen at CT, and failure of suppression of signal intensity in other adjacent parietal and frontal sulci (short arrows) that did not clearly show subarachnoid blood at CT. (c) Axial contrast-enhanced T1-weighted MR image shows leptomeningeal enhancement along the central sulcus (arrows). The enhancement may have been due to leptomeningeal inflammation secondary to vasculitis or leptomeningeal irritation by subarachnoid blood products. (d) Axial susceptibility-weighted MR image shows gyriform low signal intensity corresponding to cortical surfaces in both cerebral hemispheres (arrows), including within sulci remote from the acute hemorrhage seen at CT and FLAIR imaging. This finding suggests superficial siderosis due to prior episodes of hemorrhage and is commonly described in patients with Aβ-related angiitis.

Figure 12c.

Aβ-related angiitis in a 70-year-old man with acute onset of headache. (a) Axial head CT image shows a subarachnoid hemorrhage in the left central sulcus (arrow). (b) Axial FLAIR MR image obtained the next day shows failure of suppression of CSF signal intensity in the left central sulcus (long arrow), corresponding to the subarachnoid hemorrhage seen at CT, and failure of suppression of signal intensity in other adjacent parietal and frontal sulci (short arrows) that did not clearly show subarachnoid blood at CT. (c) Axial contrast-enhanced T1-weighted MR image shows leptomeningeal enhancement along the central sulcus (arrows). The enhancement may have been due to leptomeningeal inflammation secondary to vasculitis or leptomeningeal irritation by subarachnoid blood products. (d) Axial susceptibility-weighted MR image shows gyriform low signal intensity corresponding to cortical surfaces in both cerebral hemispheres (arrows), including within sulci remote from the acute hemorrhage seen at CT and FLAIR imaging. This finding suggests superficial siderosis due to prior episodes of hemorrhage and is commonly described in patients with Aβ-related angiitis.

Figure 12d.

Aβ-related angiitis in a 70-year-old man with acute onset of headache. (a) Axial head CT image shows a subarachnoid hemorrhage in the left central sulcus (arrow). (b) Axial FLAIR MR image obtained the next day shows failure of suppression of CSF signal intensity in the left central sulcus (long arrow), corresponding to the subarachnoid hemorrhage seen at CT, and failure of suppression of signal intensity in other adjacent parietal and frontal sulci (short arrows) that did not clearly show subarachnoid blood at CT. (c) Axial contrast-enhanced T1-weighted MR image shows leptomeningeal enhancement along the central sulcus (arrows). The enhancement may have been due to leptomeningeal inflammation secondary to vasculitis or leptomeningeal irritation by subarachnoid blood products. (d) Axial susceptibility-weighted MR image shows gyriform low signal intensity corresponding to cortical surfaces in both cerebral hemispheres (arrows), including within sulci remote from the acute hemorrhage seen at CT and FLAIR imaging. This finding suggests superficial siderosis due to prior episodes of hemorrhage and is commonly described in patients with Aβ-related angiitis.

Figure 13a.

Cerebral amyloidoma in a 71-year-old man with headache and blurred vision who underwent open surgical biopsy for an intracranial mass. (a) Low-power photomicrograph of the mass shows irregular lobules of acellular pale eosinophilic proteinaceous material (pink stain; arrows), findings suspicious for Aβ. (H-E stain; original magnification, ×100.) (b) Low-power photomicrograph of the same region confirms fluorescing Aβ (green stain; arrows) in cerebral amyloidoma. (Congo Red stain; original magnification, ×100.) (c) Axial nonenhanced head CT image shows a mass (arrows) in the left occipital lobe that is isointense relative to the gray matter, with surrounding edema (*), findings typically described in reported cases of amyloidoma (66,67). (d) Axial FLAIR MR image shows cerebral amyloidoma (arrow) that is hypointense relative to the white matter, with surrounding edema. (e) Axial contrast-enhanced T1-weighted MR image shows the typical solid enhancement of cerebral amyloidoma. The lesion is centered in the white matter, which is the most common location for cerebral amyloidomas. Note the radiating peripheral contrast enhancement (arrows) attributed to amyloid deposition along vessels surrounding the central mass (66,67). (f) Axial susceptibility-weighted MR image shows areas of microhemorrhage in cerebral amyloidoma. No additional areas of susceptibility effect were noted elsewhere in the brain. (Figs 13a and 13b courtesy of Robert Schmidt, MD, PhD, Department of Pathology, Washington University School of Medicine, St Louis, Mo.)

Figure 13b.

Cerebral amyloidoma in a 71-year-old man with headache and blurred vision who underwent open surgical biopsy for an intracranial mass. (a) Low-power photomicrograph of the mass shows irregular lobules of acellular pale eosinophilic proteinaceous material (pink stain; arrows), findings suspicious for Aβ. (H-E stain; original magnification, ×100.) (b) Low-power photomicrograph of the same region confirms fluorescing Aβ (green stain; arrows) in cerebral amyloidoma. (Congo Red stain; original magnification, ×100.) (c) Axial nonenhanced head CT image shows a mass (arrows) in the left occipital lobe that is isointense relative to the gray matter, with surrounding edema (*), findings typically described in reported cases of amyloidoma (66,67). (d) Axial FLAIR MR image shows cerebral amyloidoma (arrow) that is hypointense relative to the white matter, with surrounding edema. (e) Axial contrast-enhanced T1-weighted MR image shows the typical solid enhancement of cerebral amyloidoma. The lesion is centered in the white matter, which is the most common location for cerebral amyloidomas. Note the radiating peripheral contrast enhancement (arrows) attributed to amyloid deposition along vessels surrounding the central mass (66,67). (f) Axial susceptibility-weighted MR image shows areas of microhemorrhage in cerebral amyloidoma. No additional areas of susceptibility effect were noted elsewhere in the brain. (Figs 13a and 13b courtesy of Robert Schmidt, MD, PhD, Department of Pathology, Washington University School of Medicine, St Louis, Mo.)

Figure 13c.

Cerebral amyloidoma in a 71-year-old man with headache and blurred vision who underwent open surgical biopsy for an intracranial mass. (a) Low-power photomicrograph of the mass shows irregular lobules of acellular pale eosinophilic proteinaceous material (pink stain; arrows), findings suspicious for Aβ. (H-E stain; original magnification, ×100.) (b) Low-power photomicrograph of the same region confirms fluorescing Aβ (green stain; arrows) in cerebral amyloidoma. (Congo Red stain; original magnification, ×100.) (c) Axial nonenhanced head CT image shows a mass (arrows) in the left occipital lobe that is isointense relative to the gray matter, with surrounding edema (*), findings typically described in reported cases of amyloidoma (66,67). (d) Axial FLAIR MR image shows cerebral amyloidoma (arrow) that is hypointense relative to the white matter, with surrounding edema. (e) Axial contrast-enhanced T1-weighted MR image shows the typical solid enhancement of cerebral amyloidoma. The lesion is centered in the white matter, which is the most common location for cerebral amyloidomas. Note the radiating peripheral contrast enhancement (arrows) attributed to amyloid deposition along vessels surrounding the central mass (66,67). (f) Axial susceptibility-weighted MR image shows areas of microhemorrhage in cerebral amyloidoma. No additional areas of susceptibility effect were noted elsewhere in the brain. (Figs 13a and 13b courtesy of Robert Schmidt, MD, PhD, Department of Pathology, Washington University School of Medicine, St Louis, Mo.)

Figure 13d.

Cerebral amyloidoma in a 71-year-old man with headache and blurred vision who underwent open surgical biopsy for an intracranial mass. (a) Low-power photomicrograph of the mass shows irregular lobules of acellular pale eosinophilic proteinaceous material (pink stain; arrows), findings suspicious for Aβ. (H-E stain; original magnification, ×100.) (b) Low-power photomicrograph of the same region confirms fluorescing Aβ (green stain; arrows) in cerebral amyloidoma. (Congo Red stain; original magnification, ×100.) (c) Axial nonenhanced head CT image shows a mass (arrows) in the left occipital lobe that is isointense relative to the gray matter, with surrounding edema (*), findings typically described in reported cases of amyloidoma (66,67). (d) Axial FLAIR MR image shows cerebral amyloidoma (arrow) that is hypointense relative to the white matter, with surrounding edema. (e) Axial contrast-enhanced T1-weighted MR image shows the typical solid enhancement of cerebral amyloidoma. The lesion is centered in the white matter, which is the most common location for cerebral amyloidomas. Note the radiating peripheral contrast enhancement (arrows) attributed to amyloid deposition along vessels surrounding the central mass (66,67). (f) Axial susceptibility-weighted MR image shows areas of microhemorrhage in cerebral amyloidoma. No additional areas of susceptibility effect were noted elsewhere in the brain. (Figs 13a and 13b courtesy of Robert Schmidt, MD, PhD, Department of Pathology, Washington University School of Medicine, St Louis, Mo.)

Figure 13e.

Cerebral amyloidoma in a 71-year-old man with headache and blurred vision who underwent open surgical biopsy for an intracranial mass. (a) Low-power photomicrograph of the mass shows irregular lobules of acellular pale eosinophilic proteinaceous material (pink stain; arrows), findings suspicious for Aβ. (H-E stain; original magnification, ×100.) (b) Low-power photomicrograph of the same region confirms fluorescing Aβ (green stain; arrows) in cerebral amyloidoma. (Congo Red stain; original magnification, ×100.) (c) Axial nonenhanced head CT image shows a mass (arrows) in the left occipital lobe that is isointense relative to the gray matter, with surrounding edema (*), findings typically described in reported cases of amyloidoma (66,67). (d) Axial FLAIR MR image shows cerebral amyloidoma (arrow) that is hypointense relative to the white matter, with surrounding edema. (e) Axial contrast-enhanced T1-weighted MR image shows the typical solid enhancement of cerebral amyloidoma. The lesion is centered in the white matter, which is the most common location for cerebral amyloidomas. Note the radiating peripheral contrast enhancement (arrows) attributed to amyloid deposition along vessels surrounding the central mass (66,67). (f) Axial susceptibility-weighted MR image shows areas of microhemorrhage in cerebral amyloidoma. No additional areas of susceptibility effect were noted elsewhere in the brain. (Figs 13a and 13b courtesy of Robert Schmidt, MD, PhD, Department of Pathology, Washington University School of Medicine, St Louis, Mo.)

Figure 13f.

Cerebral amyloidoma in a 71-year-old man with headache and blurred vision who underwent open surgical biopsy for an intracranial mass. (a) Low-power photomicrograph of the mass shows irregular lobules of acellular pale eosinophilic proteinaceous material (pink stain; arrows), findings suspicious for Aβ. (H-E stain; original magnification, ×100.) (b) Low-power photomicrograph of the same region confirms fluorescing Aβ (green stain; arrows) in cerebral amyloidoma. (Congo Red stain; original magnification, ×100.) (c) Axial nonenhanced head CT image shows a mass (arrows) in the left occipital lobe that is isointense relative to the gray matter, with surrounding edema (*), findings typically described in reported cases of amyloidoma (66,67). (d) Axial FLAIR MR image shows cerebral amyloidoma (arrow) that is hypointense relative to the white matter, with surrounding edema. (e) Axial contrast-enhanced T1-weighted MR image shows the typical solid enhancement of cerebral amyloidoma. The lesion is centered in the white matter, which is the most common location for cerebral amyloidomas. Note the radiating peripheral contrast enhancement (arrows) attributed to amyloid deposition along vessels surrounding the central mass (66,67). (f) Axial susceptibility-weighted MR image shows areas of microhemorrhage in cerebral amyloidoma. No additional areas of susceptibility effect were noted elsewhere in the brain. (Figs 13a and 13b courtesy of Robert Schmidt, MD, PhD, Department of Pathology, Washington University School of Medicine, St Louis, Mo.)