DANIELE DE PAULA FARIA
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject C-11-pib pet showed a distinct cerebrospinal fluid pattern in patients with progressive multiple sclerosis(2020) PITOMBEIRA, M.; DURAN, F.; CAMPANHOLO, K.; SOUZA, A.; APOSTOLOS-PEREIRA, S.; RIMKUS, C. Medeiros; MENDES, M. F.; BUSATTO FILHO, G.; CALLEGARO, D.; BUCHPIGUEL, C.; FARIA, D. De Paula- Evaluation of 10-minute post-injection 11C-PiB PET and its correlation with 18F-FDG PET in older adults who are cognitively healthy, mildly impaired, or with probable Alzheimer's disease(2022) CARNEIRO, Camila de Godoi; FARIA, Daniele de Paula; COUTINHO, Artur Martins; ONO, Carla Rachel; DURAN, Fabio Luis de Souza; COSTA, Naomi Antunes da; GARCEZ, Alexandre Teles; SILVEIRA, Paula Squarzoni da; FORLENZA, Orestes Vicente; BRUCKI, Sonia Maria Dozzi; NITRINI, Ricardo; FILHO, Geraldo Busatto; BUCHPIGUEL, Carlos AlbertoObjective: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F] fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease.Methods: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early -phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or-negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping.Results: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early -phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration.Conclusions: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.
- Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters (vol 45, pg 616, 2020)(2020) COUTINHO, Artur Martins; BUSATTO, Geraldo F.; PORTO, Fabio Henrique de Gobbi; FARIA, Daniele de Paula; ONO, Carla Rachel; GARCEZ, Alexandre Teles; SQUARZONI, Paula; DURAN, Fabio Luiz de Souza; OLIVEIRA, Maira Okada de; TRES, Eduardo Sturzeneker; BRUCKI, Sonia Maria Dozzi; FORLENZA, Orestes Vicente; NITRINI, Ricardo; BUCHPIGUEL, Carlos Alberto
- Innate immune cells and myelin profile in multiple sclerosis: a multi-tracer PET/MR study(2022) PITOMBEIRA, Milena Sales; KOOLE, Michel; CAMPANHOLO, Kenia R.; SOUZA, Aline M.; DURAN, Fabio L. S.; SOLLA, Davi J. Fontoura; MENDES, Maria F.; PEREIRA, Samira L. Apostolos; RIMKUS, Carolina M.; BUSATTO, Geraldo Filho; CALLEGARO, Dagoberto; BUCHPIGUEL, Carlos A.; FARIA, Daniele de PaulaPurpose Neuropathological studies have demonstrated distinct profiles of microglia activation and myelin injury among different multiple sclerosis (MS) phenotypes and disability stages. PET imaging using specific tracers may uncover the in vivo molecular pathology and broaden the understanding of the disease heterogeneity. Methods We used the 18-kDa translocator protein (TSPO) tracer (R)[C-11]PK11195 and [C-11]PIB PET images acquired in a hybrid PET/MR 3 T system to characterize, respectively, the profile of innate immune cells and myelin content in 47 patients with MS compared to 18 healthy controls (HC). For the volume of interest (VOI)-based analysis of the dynamic data, (R)[C-11]PK11195 distribution volume (VT) was determined for each subject using a metabolite-corrected arterial plasma input function while [C-11]PIB distribution volume ratio (DVR) was estimated using a reference region extracted by a supervised clustering algorithm. A voxel-based analysis was also performed using Statistical Parametric Mapping. Functional disability was evaluated by the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Symbol Digit Modality Test (SDMT). Results In the VOI-based analysis, [C-11]PIB DVR differed between patients and HC in the corpus callosum (P = 0.019) while no differences in (R)-[C-11]PK11195 V-T were observed in patients relative to HC. Furthermore, no correlations or associations were observed between both tracers within the VOI analyzed. In the voxel-based analysis, high (R)-[C-11]PK11195 uptake was observed diffusively in the white matter (WM) when comparing the progressive phenotype and HC, and lower [C-11]PIB uptake was observed in certain WM regions when comparing the relapsing-remitting phenotype and HC. None of the tracers were able to differentiate phenotypes at voxel or VOI level in our cohort. Linear regression models adjusted for age, sex, and phenotype demonstrated that higher EDSS was associated with an increased (R)-[C-11]PK11195 V-T and lower [C-11]PIB DVR in corpus callosum (P = 0.001; P = 0.023), caudate (P = 0.015; P = 0.008), and total T-2 lesion (P = 0.007; P = 0.012), while better cognitive scores in SDMT were associated with higher [C-11]PIB DVR in the corpus callosum (P = 0.001), and lower (R)-[C-11]PK11195 V-T (P = 0.013). Conclusions Widespread innate immune cells profile and marked loss of myelin in T-2 lesions and regions close to the ventricles may occur independently and are associated with disability, in both WM and GM structures.
- Topography of C-11-Pittsburgh compound B uptake in Alzheimer's disease: a voxel-based investigation of cortical and white matter regions(2019) FARIA, Daniele de P.; DURAN, Fabio L.; SQUARZONI, Paula; COUTINHO, Artur M.; GARCEZ, Alexandre T.; SANTOS, Pedro P.; BRUCKI, Sonia M.; OLIVEIRA, Maira O. de; TRES, Eduardo S.; FORLENZA, Orestes V.; NITRINI, Ricardo; BUCHPIGUEL, Carlos A.; BUSATTO FILHO, GeraldoObjective: To compare results of positron emission tomography (PET) with carbon-11-labeled Pittsburgh compound B (C-11-PIB) obtained with cerebellar or global brain uptake for voxel intensity normalization, describe the cortical sites with highest tracer uptake in subjects with mild Alzheimer's disease (AD), and explore possible group differences in C-11-PIB binding to white matter. Methods: C-11-PIB PET scans were acquired from subjects with AD (n=17) and healthy elderly controls (n=19). Voxel-based analysis was performed with statistical parametric mapping (SPM). Results: Cerebellar normalization showed higher C-11-PIB uptake in the AD group relative to controls throughout the cerebral cortex, involving the lateral temporal, orbitofrontal, and superior parietal cortices. With global uptake normalization, greatest cortical binding was detected in the orbitofrontal cortex; decreased C-11-PIB uptake in white matter was found in the posterior hippocampal region, corpus callosum, pons, and internal capsule. Conclusion: The present case-control voxelwise C-11-PIB PET comparison highlighted the regional distribution of amyloid deposition in the cerebral cortex of mildly demented AD patients. Tracer uptake was highest in the orbitofrontal cortex. Decreased C-11-PIB uptake in white-matter regions in this patient population may be a marker of white-matter damage in AD.
- The Association Between Acquired Color Deficiency and PET Imaging of Neurodegeneration in Mild Cognitive Impairment and Alzheimer Disease(2022) VIDAL, Kallene Summer Moreira; DECLEVA, Diego; BARBONI, Mirella Telles Salgueiro; NAGY, Balazs Vince; MENEZES, Paulo Augusto Hidalgo de; AHER, Avinash; COUTINHO, Artur Martins; SQUARZONI, Paula; FARIA, Daniele de Paula; DURAN, Fabio Luis de Souza; BUCHPIGUEL, Carlos Alberto; KREMERS, Jan; FILHO, Geraldo Busatto; VENTURA, Dora FixPURPOSE. To evaluate color vision changes and retinal processing of chromatic and lumi-nance pathways in subjects with Alzheimer disease (AD) and mild cognitive impairment (MCI) compared with a matched control group and whether such changes are associated with impaired brain glucose metabolism and beta-amyloid deposition in the brain.METHODS. We evaluated 13 patients with AD (72.4 +/- 7.7 years), 23 patients with MCI (72.5 +/- 5.5 years), and 18 controls of comparable age (P = 0.44) using Cambridge color test and the heterochromatic flicker ERG (HF-ERG). The Cambridge color test was performed using the trivector protocol to estimate the protan, deutan and tritan color confusion axes. HF-ERG responses were measured at a frequency of 12 Hz, which ERGs reflect chromatic activity, and at 36 Hz, reflecting luminance pathway. A study subsample was performed using neuropsychological assessments and positron emission tomography.RESULTS. Patients with AD presented higher mean values indicating poorer color discrim-ination for protan (P = 0.04) and deutan (P = 0.001) axes compared with the controls. Along the tritan axis, both patients with AD and patients with MCI showed decreased color vision (P = 0.001 and P = 0.001) compared with controls. The analyses from the HF-ERG protocol revealed no differences between the groups (P = 0.31 and P = 0.41). Diffuse color vision loss was found in individuals with signs of neurodegeneration (protan P = 0.002, deutan P = 0.003 and tritan P = 0.01), but not in individuals with signs of beta-amyloid deposition only (protan P = 0.39, deutan P = 0.48, tritan P = 0.63), regardless of their clinical classification.CONCLUSIONS. Here, patients with AD and patients with MCI present acquired color vision deficiency that may be linked with impaired brain metabolism.
- Cannabidiol Treatment Improves Glucose Metabolism and Memory in Streptozotocin-Induced Alzheimer's Disease Rat Model: A Proof-of-Concept Study(2022) FARIA, Daniele de Paula; SOUZA, Larissa Estessi de; DURAN, Fabio Luis de Souza; BUCHPIGUEL, Carlos Alberto; BRITTO, Luiz Roberto; CRIPPA, Jose Alexandre de Souza; FILHO, Geraldo Busatto; REAL, Caroline CristianoAn early and persistent sign of Alzheimer's disease (AD) is glucose hypometabolism, which can be evaluated by positron emission tomography (PET) with F-18-2-fluoro-2-deoxy-D-glucose ([F-18]FDG). Cannabidiol has demonstrated neuroprotective and anti-inflammatory properties but has not been evaluated by PET imaging in an AD model. Intracerebroventricular (icv) injection of streptozotocin (STZ) is a validated model for hypometabolism observed in AD. This proof-of-concept study evaluated the effect of cannabidiol treatment in the brain glucose metabolism of an icv-STZ AD model by PET imaging. Wistar male rats received 3 mg/kg of STZ and [F-18]FDG PET images were acquired before and 7 days after STZ injection. Animals were treated with intraperitoneal cannabidiol (20 mg/kg-STZ-cannabidiol) or saline (STZ-saline) for one week. Novel object recognition was performed to evaluate short-term and long-term memory. [F-18]FDG uptake in the whole brain was significantly lower in the STZ-saline group. Voxel-based analysis revealed a hypometabolism cluster close to the lateral ventricle, which was smaller in STZ-cannabidiol animals. The brain regions with more evident hypometabolism were the striatum, motor cortex, hippocampus, and thalamus, which was not observed in STZ-cannabidiol animals. In addition, STZ-cannabidiol animals revealed no changes in memory index. Thus, this study suggests that cannabidiol could be an early treatment for the neurodegenerative process observed in AD.
- [C-11]PIB PET imaging can detect white and grey matter demyelination in a non-human primate model of progressive multiple sclerosis(2019) CARVALHO, Robert H. F.; REAL, Caroline C.; CININI, Simone; GARCEZ, Alexandre T.; DURAN, Fabio L. S.; MARQUES, Fabio L. N.; MELLO, Luiz Eugenio; BUSATTO FILHO, Geraldo; VRIES, Erik F. J. de; BRITTO, Luiz R. G. de; BUCHPIGUEL, Carlos A.; FARIA, Daniele de PaulaBackground: Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system. Its diagnosis is clinical, often confirmed by magnetic resonance imaging. This image modality, however, is not ideal for discrimination of demyelination in grey and white matter regions from inflammatory lesions. Positron Emission Tomography (PET), using specific radiopharmaceuticals, can be a tool to differentiate between these processes. The radiopharmaceutical [C-11]PIB is widely used for detection of beta-amyloid plaques, but has also been suggested for the analysis of myelin content due to its consistent uptake in white matter. The aim of this study was to evaluate [C-11]PIB PET imaging as a tool for detecting demyelinated regions in white and grey matter of non-human primate model of progressive MS. Methods: Experimental autoimmune encephalomyelitis (EAE) was induced in marmosets by injection of re-combinant human myelin oligodendrocyte glycoprotein (rhMOG) emulsified in either Incomplete Freund's Adjuvant (IFA) or Complete Freund's Adjuvant (CFA). [C-11]PIB PET images were acquired prior to immunization (baseline) and after symptoms were present (end of experiment). Brain tissue was isolated for histochemical analysis. Results: All rhMOG/IFA-treated and rhMOG/CFA-treated animals showed clinical signs of EAE. The rhMOG/CFA group presented a significant [C-11]PIB uptake reduction only in the left motor cortex (9%, P = 0.011). For the rhMOG/IFA group, significant decrease in [C-11]PIB uptake was observed in the whole brain (15%, P = 0.015), in the right hemisphere of body of corpus callosum (34%, P = 0.02), splenium of corpus callosum (38%, P = 0.004), hippocampus (19%, P = 0.036), optic tract (13%, P = 0.025), thalamus (14%, P = 0.041), Globus pallidus (23%, P = 0.017), head of caudate nucleus (25%, P = 0.045), tail of caudate nucleus (29%, P = 0.003), putamen (28%, P = 0.047) and left hemisphere of body of corpus callosum (14%, P = 0.037) and head of caudate nucleus (23%, P = 0.023). [C-11]PIB uptake significantly correlated with luxol fast blue histology (myelin marker), both in the rhMOG/IFA (r(2) = 0.32, P < 0.0001) and the rhMOG/CFA group (r(2) = 0.46, P < 0.0001). Conclusion: [C-11]PIB PET imaging is an efficient tool for detecting demyelination in grey and white matter, in a non-human primate model of progressive MS.
conferenceObject Is the early phase (CPIB)-C-11 PET imaging similar to (18)FFDG PET imaging in normal elderly and Alzheimer's disease(2018) CARNEIRO, Camila; COUTINHO, Artur; DURAN, Fabio; ONO, Carla; GARCEZ, Alexandre; PICOLO, Douglas; BUSATTO, Geraldo; FARIA, Daniele; BUCHPIGUEL, Carlos- Deficits in short-term memory binding are detectable in individuals with brain amyloid deposition in the absence of overt neurodegeneration in the Alzheimer's disease continuum(2021) CECCHINI, Mario Amore; YASSUDA, Monica Sanches; SQUARZONI, Paula; COUTINHO, Artur Martins; FARIA, Daniele de Paula; DURAN, Fabio Luiz de Souza; COSTA, Naomi Antunes da; PORTO, Fabio Henrique de Gobbi; NITRINI, Ricardo; FORLENZA, Orestes Vicente; BRUCKI, Sonia Maria Dozzi; BUCHPIGUEL, Carlos Alberto; PARRA, Mario A.; BUSATTO, Geraldo F.The short-term memory binding (STMB) test involves the ability to hold in memory the integration between surface features, such as shapes and colours. The STMB test has been used to detect Alzheimer's disease (AD) at different stages, from preclinical to dementia, showing promising results. The objective of the present study was to verify whether the STMB test could differentiate patients with distinct biomarker profiles in the AD continuum. The sample comprised 18 cognitively unimpaired (CU) participants, 30 mild cognitive impairment (MCI) and 23 AD patients. All participants underwent positron emission tomography (PET) with Pittsburgh compound B labelled with carbon-11 ([C-11]PIB) assessing amyloid beta (A beta) aggregation (A) and 18fluorine-fluorodeoxyglucose ([F-18]FDG)-PET assessing neurodegeneration (N) (A -N-[n = 35]); A+N-[n = 11]; A+ N+ [n = 19]). Participants who were negative and positive for amyloid deposition were compared in the absence (A-N vs. A+N-) of neurodegeneration. When compared with the RAVLT and SKT memory tests, the STMB was the only cognitive task that differentiated these groups, predicting the group outcome in logistic regression analyses. The STMB test showed to be sensitive to the signs of AD pathology and may represent a cognitive marker within the AD continuum.