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      Usefulness of Brain Positron Emission Tomography with Different Tracers in the Evaluation of Patients with Idiopathic Normal Pressure Hydrocephalous


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          Idiopathic normal pressure hydrocephalus (iNPH) is the only form of dementia that can be cured by surgery. Its diagnosis relies on clinical and radiological criteria. Identifying patients who can benefit from surgery is challenging, as other neurological diseases can be concomitant or mimic iNPH. We performed a systematic review on the role of positron emission tomography (PET) in iNPH. We retrieved 35 papers evaluating four main functional aspects with different PET radiotracers: (1) PET with amyloid tracers, revealing Alzheimer’s disease (AD) pathology in 20–57% of suspected iNPH patients, could be useful in predictions of surgical outcome. (2) PET with radiolabeled water as perfusion tracer showed a global decreased cerebral blood flow (CBF) and regional reduction of CBF in basal ganglia in iNPH; preoperative perfusion parameters could predict surgical outcome. (3) PET with 2-Deoxy-2-[ 18F]fluoroglucose ([ 18F]FDG ) showed a global reduction of glucose metabolism without a specific cortical pattern and a hypometabolism in basal ganglia; [ 18F]FDG PET may identify a coexisting neurodegenerative disease, helping in patient selection for surgery; postsurgery increase in glucose metabolism was associated with clinical improvement. (4) Dopaminergic PET imaging showed a postsynaptic D2 receptor reduction and striatal upregulation of D2 receptor after treatment, associated with clinical improvement. Overall, PET imaging could be a useful tool in iNPH diagnoses and treatment response.

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          Amyloid PET imaging in Alzheimer's disease: a comparison of three radiotracers.

          The increasing use of amyloid PET in Alzheimer's disease research and clinical trials has motivated efforts to standardize methodology. We compared retention of the (11)C radiotracer Pittsburgh Compound B (PiB) and that of two (18)F amyloid radiotracers (florbetapir and flutemetamol) using two study populations. We also examined the feasibility of converting between tracer-specific measures, using PiB as the common link between the two (18)F tracers. One group of 40 subjects underwent PiB and flutemetamol imaging sessions and a separate group of 32 subjects underwent PiB and florbetapir imaging sessions. We compared cortical and white matter retention for each (18)F tracer relative to that of PiB, as well as retention in several reference regions and image analysis methods. Correlations between tracer pairs were used to convert tracer-specific threshold values for amyloid positivity between tracers. Cortical retention for each pair of tracers was strongly correlated regardless of reference region (PiB-flutemetamol, ρ = 0.84-0.99; PiB-florbetapir, ρ = 0.83-0.97) and analysis method (ρ = 0.90-0.99). Compared to PiB, flutemetamol had higher white matter retention, while florbetapir had lower cortical retention. Two previously established independent thresholds for amyloid positivity were highly consistent when values were converted between tracer pairs. Despite differing white and grey matter retention characteristics, cortical retention for each (18)F tracer was highly correlated with that of PiB, enabling conversion of thresholds across tracer measurement scales with a high level of internal consistency. Standardization of analysis methods and measurement scales may facilitate the comparison of amyloid PET data obtained using different tracers.
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            Practice guideline: Idiopathic normal pressure hydrocephalus: Response to shunting and predictors of response: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

            We evaluated evidence for utility of shunting in idiopathic normal pressure hydrocephalus (iNPH) and for predictors of shunting effectiveness.
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              Association between in vivo fluorine 18-labeled flutemetamol amyloid positron emission tomography imaging and in vivo cerebral cortical histopathology.

              To determine the correspondence of in vivo quantitative estimates of brain uptake of fluorine 18-labeled flutemetamol with immunohistochemical estimates of amyloid levels in patients who underwent previous biopsy. Cross-sectional study of ¹⁸F-flutemetamol positron emission tomography (PET) findings in patients with prior cortical biopsy specimen stained for the presence or absence of amyloid plaques. University hospital. Patients Seven patients who previously had a prior right frontal cortical biopsy at the site of ventriculoperitoneal placement for presumed normal pressure hydrocephalus were recruited. Inclusion criteria included an adequate biopsy specimen for detection and quantification of β-amyloid pathology and age older than 50 years. Intervention All patients underwent an ¹⁸F-flutemetamol PET scan. Quantitative measures of ¹⁸F-flutemetamol uptake (standardized uptake value ratio, a ratio of mean target cortex activity divided by that in a cerebellar reference region) were made at a location contralateral to the biopsy site and compared with estimates of amyloid load based on immunohistochemical and histological staining. There was complete agreement between visual reads of ¹⁸F-flutemetamol PET scans (3 blinded readers with majority rule) and histology. A regression model, including time from biopsy as a covariate, demonstrated a significant relationship (P = .01) between ¹⁸F-flutemetamol uptake and percentage of area of amyloid measured by a monoclonal antibody raised against amyloid (NAB228). Similar results were found with the amyloid-specific monoclonal antibody 4G8 and Thioflavin S. To our knowledge, these data are the first to demonstrate the concordance of ¹⁸F-flutemetamol PET imaging with histopathology, supporting its sensitivity to detect amyloid and potential use in the study and detection of Alzheimer disease.

                Author and article information

                Int J Mol Sci
                Int J Mol Sci
                International Journal of Molecular Sciences
                07 September 2020
                September 2020
                : 21
                : 18
                : 6523
                [1 ]Department of Neurosciences, Imaging and Clinical Sciences, “G. d’Annunzio” Chieti-Pescara University, 66100 Chieti, Italy; mvittoriamattoli@ 123456yahoo.it (M.V.M.); annunziato.mangiola@ 123456ausl.pe.it (A.M.)
                [2 ]Clinic of Nuclear Medicine, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland
                [3 ]Academic Education, Research and Innovation Area, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland
                [4 ]Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland
                [5 ]Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, UOC di Medicina Nucleare, 00168 Rome, Italy; marialucia.calcagni@ 123456unicatt.it
                [6 ]Istituto di Medicina Nucleare, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
                [7 ]Neurosurgery Unit, Santo Spirito Hospital, 65124 Pescara, Italy; trevisi.gianluca@ 123456gmail.com
                [8 ]Istituto di Neurochirurgia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; carmelo.anile@ 123456policlinicogemelli.it
                Author notes
                [* ]Correspondence: giorgio.treglia@ 123456eoc.ch ; Tel.: +41-91-811-8919
                Author information
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                : 25 July 2020
                : 02 September 2020

                Molecular biology
                hydrocephalous,ventriculo-peritoneal shunt,positron emission tomography,pet,biomarker,[18f]fdg,amyloid,perfusion,dopaminergic


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