Neuro-degenerative diseases · 2013
Prospective flutemetamol positron emission tomography and histopathology in normal pressure hydrocephalus.
Клиническое исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Rinne Juha O, Frantzen Janek, Leinonen Ville, Lonnrot Kimmo, Laakso Aki, Virtanen Kirsi A, Solin Olof, Kotkansalo Anna, Koivisto Anne, Sajanti Juha, Karppinen Atte, Lehto Hanna, Rummukainen Jaana, Buckley Chris, Smith Adrian, Jones Paul A, Sherwin Paul, Farrar Gill, McLain Richard, Kailajarvi Marita, Grachev Igor D
Аннотация
UNLABELLED: BACKGOUND/OBJECTIVE: To determine the level of association between uptake of the amyloid positron emission tomography (PET) imaging agent [(18)F]flutemetamol and the level of amyloid-β measured by immunohistochemical and histochemical staining in a frontal cortical region biopsy site.
METHODS: Seventeen patients with probable normal pressure hydrocephalus (NPH) underwent prospective [(18)F]flutemetamol PET and subsequent frontal cortical brain biopsy during ventriculoperitoneal shunting. Tissue amyloid-β was evaluated using the monoclonal antibody 4G8, thioflavin S and Bielschowsky silver stain.
RESULTS: Four of the 17 patients (23.5%) had amyloid-β pathology based on the overall pathology read and also showed increased [(18)F]flutemetamol uptake. [(18)F]Flutemetamol standardized uptake values from the biopsy site were significantly associated with biopsy specimen amyloid-β levels (Pearson's r = 0.67; p = 0.006). There was also good correlation between the biopsy specimen amyloid-β level and uptake of [(18)F]flutemetamol in the region contralateral to the biopsy site (r = 0.67; p = 0.006), as well as with composite cortical [(18)F]flutemetamol uptake (r = 0.65; p = 0.008). The blinded visual read showed a high level of agreement between all readers (κ = 0.88). Two of 3 readers were in full agreement on all images; 1 reader disagreed on 1 of the 17 NPH cases. Blinded visual assessments of PET images by 1 reader were associated with 100% sensitivity to the overall pathology read, and assessments by the 2 others were associated with 75% sensitivity (overall sensitivity by majority read was 75%); specificity of all readers was 100%.
CONCLUSIONS: [(18)F]Flutemetamol detects brain amyloid-β in vivo and shows promise as a valuable tool to study and possibly facilitate diagnosis of Alzheimer's disease both in patients with suspected NPH and among the wider population.
METHODS: Seventeen patients with probable normal pressure hydrocephalus (NPH) underwent prospective [(18)F]flutemetamol PET and subsequent frontal cortical brain biopsy during ventriculoperitoneal shunting. Tissue amyloid-β was evaluated using the monoclonal antibody 4G8, thioflavin S and Bielschowsky silver stain.
RESULTS: Four of the 17 patients (23.5%) had amyloid-β pathology based on the overall pathology read and also showed increased [(18)F]flutemetamol uptake. [(18)F]Flutemetamol standardized uptake values from the biopsy site were significantly associated with biopsy specimen amyloid-β levels (Pearson's r = 0.67; p = 0.006). There was also good correlation between the biopsy specimen amyloid-β level and uptake of [(18)F]flutemetamol in the region contralateral to the biopsy site (r = 0.67; p = 0.006), as well as with composite cortical [(18)F]flutemetamol uptake (r = 0.65; p = 0.008). The blinded visual read showed a high level of agreement between all readers (κ = 0.88). Two of 3 readers were in full agreement on all images; 1 reader disagreed on 1 of the 17 NPH cases. Blinded visual assessments of PET images by 1 reader were associated with 100% sensitivity to the overall pathology read, and assessments by the 2 others were associated with 75% sensitivity (overall sensitivity by majority read was 75%); specificity of all readers was 100%.
CONCLUSIONS: [(18)F]Flutemetamol detects brain amyloid-β in vivo and shows promise as a valuable tool to study and possibly facilitate diagnosis of Alzheimer's disease both in patients with suspected NPH and among the wider population.