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1.
Q J Nucl Med Mol Imaging ; 64(4): 414-421, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31089074

RESUMO

BACKGROUND: Three different amyloid tracers labeled with 18-flourine have been introduced into clinical use. The leaflets of tracers indicate different visual criteria for PET reporting. In clinical practice, it is not yet ascertained whether these criteria are equivalent in terms of diagnostic accuracy or if anyone is better than another. We aimed to evaluate the inter and intra-rater variability of visual assessment of 18F-Florbetapir PET/CT images among six independent readers with different clinical experience. METHODS: We analyzed 252 PET/CT scans, visually assessed by each reader three times, applying independently the three different reading criteria proposed. Each reader evaluated the regional uptake specifying for each cortical region a numeric value of grading of positivity in order to assign a final score. At the end of each reading a level of confidence was determined by assigning a score from 0 (negative) to 4 (positive). After first reading, those cases in which the evaluations by two experienced readers did not match (discordant cases) were independently reevaluated merging all the three different visual interpretation criteria. RESULTS: Good agreement was observed for visual interpretation among the six readers' confidence-level using independently the three visual reading criteria: ICC=0.83 (0.80-0.86) for 18F-florbetapir, ICC=0.84 (0.81-0.87) for 18F-florbetaben, and ICC=0.86 (0.83-0.88) for 18F-flutemetamol reading. A good inter-rater agreement was observed for final-score too: ICC=0.74 (0.70-0.78) for 18F-florbetapir; ICC=0.82 (0.79-0.85) for 18F-florbetaben; ICC=0.84 (0.81-0.87) for 18F-flutemetamol. Intra-rater agreement was good for final-score (from 0.76 to 0.90; P<0.001) and confidence-level (Spearman's rho from 0.89 to 1.00; P<0.001). Disagreement between the two experienced readers was observed in 22 of 252 cases (9%). The agreement converged over a second round of independent reading in 12 of 22 cases (54%), by merging all the criteria. CONCLUSIONS: All the criteria proposed are useful to determine the grading of positivity or negativity of amyloid deposition and their merging improves the diagnostic confidence and provides a better agreement.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Amiloide/metabolismo , Radioisótopos de Flúor/química , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/radioterapia , Compostos de Anilina/química , Benzotiazóis/química , Encéfalo , Etilenoglicóis/química , Radioisótopos de Flúor/farmacologia , Humanos , Interpretação de Imagem Assistida por Computador , Pessoa de Meia-Idade , Estilbenos/química
2.
Q J Nucl Med Mol Imaging ; 63(1): 83-92, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29697220

RESUMO

In May 2017 some representatives of the Italian nuclear medicine and neurological communities spontaneously met to discuss the issues emerged during the first two years of routine application of amyloid PET with fluorinated radiopharmaceuticals in the real world. The limitations of a binary classification of scans, the possibility to obtain early images as a surrogate marker of regional cerebral bloos flow, the need for (semi-)quantification and, thus, the opportunity of ranking brain amyloidosis, the correlation with Aß42 levels in the cerebrospinal fluid, the occurrence and biological meaning of uncertain/boderline scans, the issue of incidental amyloidosis, the technical pittfalls leading to false negative/positive results, the position of the tool in the diagnostic flow-chart in the national reality, are the main topics that have been discussed. Also, a card to justify the examination to be filled by the dementia specialist and a card for the nuclear medicine physician to report the exam in detail have been approved and are available in the web, which should facilitate the creation of a national register, as previewed by the 2015 intersocietal recommendation on the use of amyloid PET in Italy. The content of this discussion could stimulate both public institutions and companies to support further research on these topics.


Assuntos
Amiloide/metabolismo , Idioma , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Humanos , Processamento de Imagem Assistida por Computador , Itália , Traçadores Radioativos
3.
Neurobiol Aging ; 61: 93-101, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29059596

RESUMO

The aim of the study was to investigate the association between postoperative delirium (POD) and in vivo markers of Alzheimer's disease pathology in nondemented hip fracture surgery patients. POD was assessed with the Confusion Assessment Method. Amyloid load was quantified on 18F-Flutemetamol positron emission tomography images as standardized uptake value ratio. Secondary outcome measures were gray matter volumes, white matter integrity, and functional connectivity at rest. All the patients with POD (POD+, N = 5) were amyloid negative (standardized uptake value ratio <0.59), whereas 6 out of 11 patients without POD (POD-) showed brain amyloid positivity. POD+ compared to POD- displayed: lower gray matter volumes in the amygdala (p = 0.003), in the middle temporal gyrus and in the anterior cingulate cortex (p < 0.001), increased diffusivity in the genu of the corpus callosum and in the anterior corona radiata (p < 0.05), and higher functional connectivity within the default mode network (p < 0.001). POD patients showed altered gray and white matter integrity in the fronto-limbic regions in absence of brain amyloidosis. Based on this preliminary investigation, delirium pathophysiology might be independent of Alzheimer's disease. Future studies on larger samples are needed to confirm this hypothesis.


Assuntos
Amiloide/metabolismo , Encéfalo/metabolismo , Delírio/diagnóstico , Delírio/etiologia , Complicações Pós-Operatórias/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer , Encéfalo/diagnóstico por imagem , Delírio/metabolismo , Feminino , Fraturas do Quadril/cirurgia , Humanos , Masculino , Projetos Piloto , Tomografia por Emissão de Pósitrons
4.
Neurobiol Aging ; 49: 60-68, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27776263

RESUMO

The pathway leading from amyloid-ß deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa (Escherichia/Shigella, Pseudomonas aeruginosa, Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, and Bacteroides fragilis) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, interleukin [IL]-1ß, IL-6, IL-18, IL-8, inflammasome complex (NLRP3), tumor necrosis factor-alpha [TNF-α]; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n = 40, Amy+) and with no brain amyloidosis (n = 33, Amy-) and also in a group of controls (n = 10, no brain amyloidosis and no cognitive impairment). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3, and IL-1ß) compared with both controls and with Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of E. rectale and higher abundance of Escherichia/Shigella compared with both healthy controls (fold change, FC = -9.6, p < 0.001 and FC = +12.8, p < 0.001, respectively) and to Amy- (FC = -7.7, p < 0.001 and FC = +7.4, p = 0.003). A positive correlation was observed between pro-inflammatory cytokines IL-1ß, NLRP3, and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho = 0.60, p < 0.001; rho = 0.57, p < 0.001; and rho = 0.30, p = 0.007, respectively) and a negative correlation with the anti-inflammatory E. rectale (rho = -0.48, p < 0.001; rho = -0.25, p = 0.024; rho = -0.49, p < 0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation.


Assuntos
Doença de Alzheimer/etiologia , Transtornos Cognitivos/etiologia , Microbioma Gastrointestinal/fisiologia , Inflamação/etiologia , Intestinos/microbiologia , Idoso , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Transtornos Cognitivos/metabolismo , Citocinas/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Placa Amiloide/etiologia , Placa Amiloide/metabolismo
5.
JAMA Neurol ; 73(12): 1417-1424, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27802513

RESUMO

IMPORTANCE: Cerebral amyloidosis is a key abnormality in Alzheimer disease (AD) and can be detected in vivo with positron emission tomography (PET) ligands. Although amyloid PET has clearly demonstrated analytical validity, its clinical utility is debated. OBJECTIVE: To evaluate the incremental diagnostic value of amyloid PET with florbetapir F 18 in addition to the routine clinical diagnostic assessment of patients evaluated for cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS: The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study is a multicenter study involving 18 AD evaluation units from eastern Lombardy, Northern Italy, 228 consecutive adults with cognitive impairment were evaluated for AD and other causes of cognitive decline, with a prescan diagnostic confidence of AD between 15% and 85%. Participants underwent routine clinical and instrumental diagnostic assessment. A prescan diagnosis was made, diagnostic confidence was estimated, and drug treatment was provided. At the time of this workup, an amyloid PET/computed tomographic scan was performed, and the result was communicated to physicians after workup completion. Physicians were asked to review the diagnosis, diagnostic confidence, and treatment after the scan. The study was conducted from August 5, 2013, to December 31, 2014. MAIN OUTCOMES AND MEASURES: Primary outcomes were prescan to postscan changes of diagnosis, diagnostic confidence, and treatment. RESULTS: Of the 228 participants, 107 (46%) were male; mean (SD) age was 70.5 (7) years. Diagnostic change occurred in 46 patients (79%) having both a previous diagnosis of AD and an amyloid-negative scan (P < .001) and in 16 (53%) of those with non-AD diagnoses and an amyloid-positive scan (P < .001). Diagnostic confidence in AD diagnosis increased by 15.2% in amyloid-positive (P < .001; effect size Cohen d = 1.04) and decreased by 29.9% in amyloid-negative (P < .001; d = -1.19) scans. Acetylcholinesterase inhibitors and memantine hydrochloride were introduced in 61 (65.6%) patients with positive scan results who had not previously received those drugs, and the use of the drugs was discontinued in 6 (33.3%) patients with negative scan results who were receiving those drugs (P < .001). CONCLUSIONS AND RELEVANCE: Amyloid PET in addition to routine assessment in patients with cognitive impairment has a significant effect on diagnosis, diagnostic confidence, and drug treatment. The effect on health outcomes, such as morbidity and mortality, remains to be assessed.


Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina , Disfunção Cognitiva/diagnóstico , Etilenoglicóis , Tomografia por Emissão de Pósitrons/normas , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Feminino , Humanos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Valor Preditivo dos Testes
6.
J Alzheimers Dis ; 54(4): 1437-1457, 2016 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-27662288

RESUMO

The assessment of in vivo18F images targeting amyloid deposition is currently carried on by visual rating with an optional quantification based on standardized uptake value ratio (SUVr) measurements. We target the difficulties of image reading and possible shortcomings of the SUVr methods by validating a new semi-quantitative approach named ELBA. ELBA involves a minimal image preprocessing and does not rely on small, specific regions of interest (ROIs). It evaluates the whole brain and delivers a geometrical/intensity score to be used for ranking and dichotomic assessment. The method was applied to adniimages 18F-florbetapir images from the ADNI database. Five expert readers provided visual assessment in blind and open sessions. The longitudinal trend and the comparison to SUVr measurements were also evaluated. ELBA performed with area under the roc curve (AUC) = 0.997 versus the visual assessment. The score was significantly correlated to the SUVr values (r = 0.86, p < 10-4). The longitudinal analysis estimated a test/retest error of ≃2.3%. Cohort and longitudinal analysis suggests that the ELBA method accurately ranks the brain amyloid burden. The expert readers confirmed its relevance in aiding the visual assessment in a significant number (85) of difficult cases. Despite the good performance, poor and uneven image quality constitutes the major limitation.


Assuntos
Amiloidose/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/normas , Idoso , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Reprodutibilidade dos Testes , Método Simples-Cego
9.
Clin Trials ; 11(3): 355-361, 2014 06.
Artigo em Inglês | MEDLINE | ID: mdl-24711610

RESUMO

Background It has been proposed that in clinical trials in which the therapeutic strategy is driven by functional imaging, central review of the images should be done in real time. Purpose We report our experience with a new tool for image exchange and review, called Web-Based Imaging Diagnosis by Expert Network (WIDEN), which we implemented for the HD0607 prospective multicenter Italian clinical trial in which Hodgkin lymphoma treatment was adapted based on results of an interim positron emission tomography (PET) scan performed after the first two cycles of chemotherapy. Methods We used WIDEN for general management of the clinical trial, site imaging qualification, image exchange, workflow control, blinded independent central review, inter-observer variability assessment, consensus creation, audit, and statistical analysis. Results As of February 2013, the interim PET was available for 512 patients; upon central review, 103 of the scans were judged to be positive and 409 to be negative. The median scan uploading and downloading times were 1 min, 25 s and 1 min, 55 s, respectively; the average and median times for diagnosis exchange were 47 h, 53 min and 37 h, 43 min, respectively. The binary concordance between pairs of reviewers (Cohen's kappa) ranged from 0.72 to 0.85. The 5-point scale concordance among all reviewers (Krippendorf's alpha) was 0.77. Conclusions WIDEN proved to be an effective tool for medical imaging exchange and online review. Data security, simplicity, feasibility, and prompt scan review were demonstrated. Central reviews were completed promptly.


Assuntos
Ensaios Clínicos como Assunto , Diagnóstico por Imagem/métodos , Gestão da Informação , Humanos
10.
Clin Nucl Med ; 39(4): 391-2, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24561684

RESUMO

68Ga-DOTATOC PET/CT has been widely validated in diagnosis and follow-up of carcinoid. A 47-year-old woman with ileal carcinoid underwent a 68Ga-DOTATOC PET/CT for restaging purposes. Images showed extensive liver involvement and also a widespread metastatic subcutaneous metastases in the right chest wall and in the right laterocervical region. The presence of multiple soft-tissue metastases, as described in our case and imaged with 68Ga-DOTATOC, represents a very rare clinical entity.


Assuntos
Tumor Carcinoide/patologia , Neoplasias do Íleo/patologia , Imagem Multimodal , Octreotida/análogos & derivados , Compostos Organometálicos , Tomografia por Emissão de Pósitrons , Pele , Tomografia Computadorizada por Raios X , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica
11.
Nucl Med Rev Cent East Eur ; 16(2): 82-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24068638

RESUMO

Bone scintigraphy is widely considered as an important technique able to investigate various pathological conditions of the skeletal system. Many unexpected extraosseous uptakes have been reported in literature. We present here three cases of unexpected 99mTc-oxidronate (HDP) myocardial extraosseous uptakes in patients undergoing bone scan for staging purposes. In particular, we present the first reported case ofa myocardial uptake in a patient with IgM-related amyloidosis. Subsequently, we perform a review of the existing literature about extraosseous uptakes.


Assuntos
Osso e Ossos/diagnóstico por imagem , Achados Incidentais , Miocárdio/metabolismo , Idoso , Transporte Biológico , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Cintilografia , Medronato de Tecnécio Tc 99m/análogos & derivados
14.
Nucl Med Mol Imaging ; 47(3): 205-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24900109

RESUMO

Sarcoidosis is a systemic chronic inflammatory disease of unknown aetiology, characterised by granulomatous lesions with heterogeneous clinical manifestations affecting multiple organs and tissues. Although the respiratory system is most commonly affected, the disease may also present with bone lesions. We report the case of a 31-year-old woman who presented with low back pain and no history of cancer and who was found to have suspicious lesions involving the entire spine on magnetic resonance imaging (MRI). The patient underwent 18F-fluorodeoxyglucose (FDG) PET/CT to search for a primary tumour and for staging purposes. 18F-FDG PET/CT revealed a pattern of hypermetabolic activity in widespread skeletal lesions and in a single left cervical lymph node. The primary tumour was not found, thus suggesting a haematologic disorder. Subsequent biopsies of a cervical lymph node and of bone tissue from L4 revealed active sarcoidosis with no evidence of cancer. This underlines the importance of considering all alternatives when hypermetabolic lesions are found on 18F-FDG PET/CT. Furthermore, 18F-FDG PET can be very useful to indicate accessible sites for guiding fine-needle aspiration cytology (FNAC).

15.
Tumori ; 94(5): 737-41, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19112950

RESUMO

Optimal treatment for HER2/neu-positive, node-positive early breast cancer should include the monoclonal antibody trastuzumab. This relatively new agent has shown very limited pulmonary toxicity. Our report describes a case of life-threatening interstitial pneumonitis associated with Guillain-Barré syndrome that occurred during the administration of adjuvant trastuzumab. The severity of the clinical presentation and the limited number of reports in the literature of acute trastuzumab-related lung injury make the description of this case of crucial interest.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Síndrome de Guillain-Barré/complicações , Doenças Pulmonares Intersticiais/etiologia , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Antineoplásicos/administração & dosagem , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Trastuzumab
16.
Eur J Gastroenterol Hepatol ; 19(8): 711-3, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17625442

RESUMO

Gastrointestinal stromal tumours are rare tumours of the gastrointestinal tract. We describe the case of a 57-year-old man with a locally advanced gastrointestinal stromal tumour of the rectum. We started Gleevec. The pathological examination documented a complete pathological response. An already described mutation in KIT exon 11 was observed in the gastrointestinal stromal tumour of the rectum. At the same time as the treatment of our patient, his brother received a neoadjuvant therapy for a locally advanced rectal adenocarcinoma. During the surgical procedure, a gastric lesion was excised and the pathological examination showed a low-grade gastrointestinal stromal tumour. We analysed DNA extracted from the tumoral mass and normal tissue of both patients. No mutations, either in KIT or in PDGFRA, were detected in the subserosal stomach gastrointestinal stromal tumour. After 18 months, both patients are free from recurrence. Our clinical case suggests that preoperative imatinib therapy may enable radical surgery in patients with an inoperable disease.


Assuntos
Antineoplásicos/uso terapêutico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Benzamidas , Quimioterapia Adjuvante , Saúde da Família , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/genética , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Tomografia por Emissão de Pósitrons , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/genética
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