PMC8294698_01
(A) Brain magnetic resonance imaging (MRI; 3T System, Skyra, Siemens, Germany) at the first admission. Susceptibility weighted images (SWI) showing a cortical hemorrhage (arrowhead) at the left parietal lobe cortex and cortical superficial siderosis (cSS) in the right parietal cortex (arrow). (B) In the same MRI, cSS was additionally observed in the left and right frontal cortices (arrows). (C) Brain computed tomography (CT) showing a second lobar hemorrhage at the right frontal subcortical area concurrent with left hemiparesis. (D) Brain CT showing a third lobar hemorrhage at the right parieto-occipital subcortical region. (E)
11C-PiB PET revealing widespread 11C-PiB retentions in the cerebral cortices (arrowheads) and precuneus (arrows). (F) Electrophoresis revealing a 2/2 pattern in the apolipoprotein E phenotype for this patient (PT). (G) Congophilic amyloid deposits shown in blood vessels of the resected brain tissue, as shown using polarizing microscopy (Scale bar: 20 mum). (H,I) Abeta-reactive structures in blood vessel walls identified by immunohistochemistry using anti-Abeta1-42 (H) and anti-Abeta1-40 (I) antibodies. Scale bars: 100 mum. (J) Laboratory serum results from the patient's first admission. (K) Serum lipoprotein electrophoresis reveals a broad-beta pattern (bar), where intermediate-density lipoprotein (fraction 3) and very-low-density lipoprotein (fraction 4) are aberrantly elevated.
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At the time of her first admission, cerebral magnetic resonance imaging (MRI) revealed a hemorrhage in the left parietal subcortical area (Figure 1A) and multiple regions of cSS (Figures 1A,B). This time she was admitted to the Geriatric Research Institute and Hospital for a left hemiparalysis with a lobar ICH at the right frontal lobe (Figure 1C). At age 77 years, she was admitted for a headache for the third time; this time she had left hemispatial neglect, caused by a lobar ICH in the right parieto-occipital lobes (Figure 1D). The apolipoprotein E (ApoE) was confirmed as a 2/2 protein by the western blot (Figure 1F). Congophilic amyloid deposits in blood vessels were confirmed on polarizing microscopy, undertaken using tissue resected during the second hospitalization (Figure 1G). Abeta-immunoreactive structures in blood vessels walls were revealed by an anti-Abeta1-42 antibody (Figure 1H) and an anti-Abeta1-40 antibody (Figure 1I) on immunohistochemical studies. The serum levels of apolipoprotein C-2 (ApoC-2), apolipoprotein E (ApoE), remnant-like lipoprotein (RLP), intermediate-density lipoprotein (IDL), and very-low-density lipoprotein (VLDL) were increased (Figure 1J). Furthermore, polyacrylamide gel (PAGE) electrophoresis of her serum revealed a broad-beta band which seemed to be mimicking type III dysliplidemia (Figure 1K) (BML Co.
18F-THK5351 imaging and MRI of the patient's brain. (A-F) Susceptibility-weighted MRI. (G-L)
18F-THK5351. (M-R)
18F-THK 5351 on transverse MRI (T1-weighted images). (S-X)
18F-THK 5351 on coronal MRI (T1-weighted images). 18F-THK5351 retentions areas were observed in the pyramidal tract at the pontine level, the cerebral peduncle of the midbrain, and the internal capsule, all at the right side (red circles: A-G-M-S, B-H-N-T, C-I-O-U, and D-J-P-V). The bilateral substantia nigra of the midbrain, the globus pallidum, the anterior caudate nuclei, amygdala, and the medial areas of thalamus (black circles: C-I-O-U and D-J-P-V) were considered the off-target retentions of 18F-THK5351 binding to MAO-B. They were also visible along the previous lobar hemorrhagic lesions in the right frontal lobe and the left parietal cortex, as well as an asymptomatic old cortical SAH lesion in the right parietal cortex (yellow circles: E-K-Q-W and F-L-R-X). Additional 18F-THK5351 retentions were observed in the bilateral medial temporal areas (blue circles: A-G-M-S and B-H-N-T), the left anterior frontal cortical areas (blue circles: B-H-N-T and C-I-O-U), the posterior areas in bilateral temporal cortices, and the bilateral fusiform, lingual, and parahippocampal gyruses (blue circles: C-I-O and D-J-P).
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18F-THK5351 retentions areas were observed at the right side of the pyramidal tract at the pontine level, the cerebral peduncle of the midbrain, and the internal capsule (red circles in Figure 2 A-G-M-S, B-H-N-T, C-I-O-U, and D-J-P-V).