Use Of FDG-PET Research Articles

Évaluation de la réponse thérapeutique par TEP-FDG des cancers solides (critères PERCIST 1.0)

18F-Fluoro-Deoxyglucose (FDG) Positron Emission Tomography (PET) is an imaging technique used to study glucose metabolism in cells. It is particularly useful in oncology, especially for initial diagnosis and the detection of recurrence. Thanks to its functional approach to tissues, its use has evolved towards the evaluation of anticancer treatments, both in a personalized approach to patients and as part of clinical trials of new biotherapies. This technique provides additional information compared to conventional imaging, which is not always able to assess tumor viability of potentially necrotic or fibrotic residual masses after treatment. However, the use of FDG-PET requires a rigorous methodology, both for the performance of the studies and for their interpretation. Based on a large body of literature, interpretation criteria for solid tumors have been published and updated. PERCIST 1.0 (Positron Emission Tomography Response Criteria In Solid Tumors), proposed by an American task force in 2009, aims to clarify and standardize practice. These criteria will evolve according to the specificities of new biotherapies such as immunotherapy.

Long COVID and its association with neurodegenerative diseases: pathogenesis, neuroimaging, and treatment.

Corona Virus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has presented unprecedented challenges to the world. Changes after acute COVID-19 have had a significant impact on patients with neurodegenerative diseases. This study aims to explore the mechanism of neurodegenerative diseases by examining the main pathways of central nervous system infection of SARS-CoV-2. Research has indicated that chronic inflammation and abnormal immune response are the primary factors leading to neuronal damage and long-term consequences of COVID-19. In some COVID-19 patients, the concurrent inflammatory response leads to increased release of pro-inflammatory cytokines, which may significantly impact the prognosis. Molecular imaging can accurately assess the severity of neurodegenerative diseases in patients with COVID-19 after the acute phase. Furthermore, the use of FDG-PET is advocated to quantify the relationship between neuroinflammation and psychiatric and cognitive symptoms in patients who have recovered from COVID-19. Future development should focus on aggressive post-infection control of inflammation and the development of targeted therapies that target ACE2 receptors, ERK1/2, and Ca2+.

Baseline Characteristics and Use of Pretherapeutic 18 F-Fluorodeoxyglucose-PET for Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal malignancy. Surgical resection is the only curative modality combined with neoadjuvant chemotherapy to improve survival. Given the limitations of traditional responses such as cross-sectional imaging (CT/MRI) or tumor markers, carbohydrate antigen 19-9 (CA19-9), the 2023 National Comprehensive Cancer Network guidelines included 18 F-fluorodeoxyglucose (FDG)-PET as an adjunct to assess response to neoadjuvant chemotherapy. There are common misconceptions on the metabolic activity (tumor avidity) in PDAC so we aimed to describe the baseline characteristics and use of FDG-PET in a cohort of treatment-naive patients with PDAC. A single-center retrospective study was conducted capturing all biopsy-proven, treatment-naive patients with PDAC who underwent either baseline FDG-PET/CT or FDG-PET/MRI imaging between 2008 and 2023. Baseline FDG-PET characteristics were collected, including primary tumors' maximum standardized uptake value defined as metabolic activity (FDG uptake) of tumor compared with surrounding pancreatic parenchymal background, and the identification of extrapancreatic metastatic disease. We identified 1,095 treatment-naive patients with PDAC who underwent baseline FDG-PET imaging at diagnosis. CA19-9 was elevated in 76% of patients. Overall, 96.3% (1,054) of patients had FDG-avid tumors with a median maximum standardized uptake value of 6.4. FDG-PET also identified suspicious extrapancreatic metastatic lesions in 50% of patients, with a higher proportion (p < 0.001) in PET/MRI (59.9%) vs PET/CT (44.3%). After controlling for CA19-9 elevation, PET/MRI was superior in detection of extrapancreatic lesions compared with PET/CT. FDG-PET has significant use in PDAC as a baseline imaging modality earlier neoadjuvant therapy given the majority of tumors are FDG-avid. FDG-PET can identify additional extrapancreatic suspicious lesions allowing for optimal initial staging, with PET/MRI having increased sensitivity over PET/CT.

Adrenal findings in FDG-PET: analysis of a cohort of 1021 patients from a cancer center.

The use of FDG-PET for cancer staging has led to the increasing incidence of adrenal lesions, which are usually a clinical challenge. We aimed to characterize the adrenal lesions found in FDG-PET of patients followed in a cancer center. Retrospective analysis was conducted of all FDG-PET studies performed in our center in the last 10years. Exams reporting adrenal lesions in the CT component and/or anomalous adrenal FDG uptake were selected. Cases were characterized by the clinical, laboratory, imaging, and pathological findings. We identified 27,427 FDG-PET studies. Of those, 7.6% reported adrenal findings. We included 1364 exams corresponding to 1021 patients. Only 15.6% of the patients were referred to the Endocrinology Department and 38% of the lesions were not studied. In 38.9% of the studied patients, malignant lesions were present, including metastases in 37.5%, carcinoma in 1.2%, and other malignant tumors in 0.4%. The median SUVmax of malignant lesions was significantly higher than the SUVmax of the benign findings (p < 0.05). We also observed a higher median SUVmax in adrenal metastases than in adenomas (p < 0.05). There was a tendency for higher SUVmax of adrenal carcinomas when compared with other malignant lesions (p = 0.066). The median SUVmax was not different between pheochromocytomas and other tumors (p > 0.05). Occult adrenal lesions discovered during FDG-PET/CT are common in the cancer context and are frequently benign. SUVmax may be a useful tool in the workup of adrenal lesions but with several important caveats.

Molecular imaging of sarcomas with FDG PET.

Sarcoma comprises a heterogenous entity of musculoskeletal malignancies arising from a mesenchymal origin. The diagnosis and management of pediatric sarcoma requires a multidisciplinary approach and the use of various imaging modalities including CT, MRI and FDG PET scans. FDG PET/CT (FDG PET), as a metabolic imaging, complements and provides superior diagnostic information as against other imaging modalities alone. Advantages of FDG PET in differentiating malignant sarcomatous lesions from benign lesions, and value in staging and restaging have been noted in several studies. The use of FDG PET in clinical management has increased over the years. The data on prognostication of outcomes or predicting responders to therapy with FDG PET in patients with sarcoma is somewhat limited. This review will focus on the pearls and pitfalls of FDG PET and role of FDG PET in initial extent of disease assessment, treatment response, and surveillance imaging pertaining to osteosarcoma, chondrosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. We also discuss the limitations and unmet needs of FDG PET in the management of patients with sarcoma.

Full automation of total metabolic tumor volume from FDG-PET/CT in DLBCL for baseline risk assessments

BackgroundCurrent radiological assessments of 18fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging data in diffuse large B-cell lymphoma (DLBCL) can be time consuming, do not yield real-time information regarding disease burden and organ involvement, and hinder the use of FDG-PET to potentially limit the reliance on invasive procedures (e.g. bone marrow biopsy) for risk assessment.MethodsOur aim is to enable real-time assessment of imaging-based risk factors at a large scale and we propose a fully automatic artificial intelligence (AI)-based tool to rapidly extract FDG-PET imaging metrics in DLBCL. On availability of a scan, in combination with clinical data, our approach generates clinically informative risk scores with minimal resource requirements. Overall, 1268 patients with previously untreated DLBCL from the phase III GOYA trial (NCT01287741) were included in the analysis (training: n = 846; hold-out: n = 422).ResultsOur AI-based model comprising imaging and clinical variables yielded a tangible prognostic improvement compared to clinical models without imaging metrics. We observed a risk increase for progression-free survival (PFS) with hazard ratios [HR] of 1.87 (95% CI: 1.31–2.67) vs 1.38 (95% CI: 0.98–1.96) (C-index: 0.59 vs 0.55), and a risk increase for overall survival (OS) (HR: 2.16 (95% CI: 1.37–3.40) vs 1.40 (95% CI: 0.90–2.17); C-index: 0.59 vs 0.55). The combined model defined a high-risk population with 35% and 42% increased odds of a 4-year PFS and OS event, respectively, versus the International Prognostic Index components alone. The method also identified a subpopulation with a 2-year Central Nervous System (CNS)-relapse probability of 17.1%.ConclusionOur tool enables an enhanced risk stratification compared with IPI, and the results indicate that imaging can be used to improve the prediction of central nervous system relapse in DLBCL. These findings support integration of clinically informative AI-generated imaging metrics into clinical workflows to improve identification of high-risk DLBCL patients.Trial RegistrationRegistered clinicaltrials.gov number: NCT01287741.Graphical

The Use of 18-fluorodeoxyglucose (FDG) Positron Emission Tomography in the Staging of Pancreatic Ductal Adenocarcinoma (PDAC)

Introduction: The use of FDG-PET in the staging of PDAC is subject to debate. We evaluated the utility of FDG-PET/CT in the detection of distant disease in PDAC patients. Methods: Between 2010 and 2019, we evaluated 699 patients with a diagnosis of PDAC in our multidisciplinary pancreas program; 63 (9%) patients had an FDG-PET/CT. Of these, 29 patients had their FDG-PET/CT and a standard staging CT performed within a 3-month period. Each study was scored by an experienced blinded radiologist along T-, N-, and M-staging criteria. The scores between FDG-PET/CT and CT were compared. Kappa statistics(K) were calculated to estimate inter-study variability. Results: Twenty-nine patients had an FDG-PET/CT and a CT within a median time of 25 days. The median age of diagnosis was 67+9 years old; 12 patients(41.4%) had biopsy-proven metastatic disease. Median CA 19-9 level was 615 U/L. Among modalities of treatment, 21 patients(72.4%) had neoadjuvant chemotherapy, 5 patients(17.2%) had surgical resection, 4 patients(13.8%) had radiation, and 4 patients(13.8%) had adjuvant chemotherapy. FDG avidity was seen in 82.8% of primary tumors with an average standardized uptake value of 9.85. One-year and five-year survival rate of this cohort is 72.4% and 3.4%, respectively. Inter-study variability demonstrated no agreement for T-staging(K= -0.06, p-value=0.49), minimal agreement for N-staging(K= 0.257; p-value = 0.05) and no agreement for M-staging(K= 0.076, p-value = 0.58) between FDG-PET/CT and CT scans. T-staging was the most discordant. FDG-PET/CT upstaged 5 patients(17.2%). Conclusion: There is a high degree of discordance between FDG-PET/CT and CT for staging PDAC, suggesting complementarity between modalities.

Management of Colorectal Cancer with Synchronous Liver Metastases: A Systematic Review of National and International Clinical Guidelines (CoSMIC-G)

Introduction: The World Health Organization’s (WHO) Health Research Advisory Committee recommends that evidence informs best practice. This study systematically reviews national guidelines for the management of patients with colorectal cancer with a specific focus on the advice for patients with synchronous liver-limited or liver-dominant metastases. Methods: This is a systematic review of clinical guidelines for the management of colorectal cancer with a specific focus on the advice for patients with synchronous liver metastases. The National Library of Medicine PubMed database was queried for metastatic colorectal cancer guidelines using the keywords “colorectal cancer”, “liver” and “guidelines”. Studies are included if they are national guidelines on the management of patients with colorectal cancer. The study period for inclusion is the ten year period from January 2011 to January 2021. The protocol was registered with PROSPERO (registration number CRD42021243744). Results: Searches returned 302 unique articles of which nineteen were colorectal cancer and/or metastatic colorectal cancer guidelines. For the purposes of this report, the 7 guidelines of the NCCN (USA), NICE (UK), France, Spain, Japan, China and Australia are included. Five (72%) recommend against routine use of FDG-PET for staging. All guidelines support neoadjuvant chemotherapy as the first treatment. Two (29%) support liver surgery as first step. Six support and 1 discourage synchronous surgery. Hepatic criteria for synchronous are defined in 2 (29%) and primary tumour criteria in 2 (29%). Conclusion: There is substantial variation between international guidelines on recommendations for the management of patients with colorectal cancer and synchronous liver metastases.

Challenges in Alzheimer's Disease Diagnostic Work-Up: Amyloid Biomarker Incongruences.

Discordance among amyloid biomarkers is a challenge to overcome in order to increase diagnostic accuracy in dementia. 1) To verify that cerebrospinal fluid (CSF) Aβ42/Aβ40 ratio (AβR) better agrees with Amyloid PET (Amy-PET) results compared to CSF Aβ42; 2) to detect differences among concordant positive, concordant negative, and discordant cases, basing the concordance definition on the agreement between CSF AβR and Amy-PET results; 3) to define the suspected underlying pathology of discordant cases using in vivo biomarkers. We retrospectively enrolled 39 cognitively impaired participants in which neuropsychological tests, apolipoprotein E genotype determination, TC/MRI, FDG-PET, Amy-PET, and CSF analysis had been performed. In all cases, CSF analysis was repeated using the automated Lumipulse method. In discordant cases, FDG-PET scans were evaluated visually and using automated classifiers. CSF AβR better agreed with Amy-PET compared to CSF Aβ42 (Cohen's K 0.431 versus 0.05). Comparisons among groups did not show any difference in clinical characteristics except for age at symptoms onset that was higher in the 6 discordant cases with abnormal CSF AβR values and negative Amy-PET (CSF AβR+/AmyPET-). FDG-PET and all CSF markers (Aβ42, AβR, p-Tau, t-Tau) were suggestive of Alzheimer's disease (AD) in 5 of these 6 cases. 1) CSF AβR is the CSF amyloid marker that shows the better level of agreement with Amy-PET results; 2) The use of FDG-PET and CSF-Tau markers in CSFAβR+/Amy-PET-discordant cases can support AD diagnosis; 3) Disagreement between positive CSF AβR and negative Amy-PET in symptomatic aged AD patients could be due to the variability in plaques conformation and a negative Amy-PET scan cannot be always sufficient to rule out AD.

FDG PET Application for Management of Breast Cancer Patient: A Narrative Review

Background: The application of FDG PET/CT scan for assessment of patients with breast cancer is increasing. The cost effectiveness of the application could be different in a developing country with limited PET scanners and treatment prioritiesMethods: Open discussions of the PET reviewers from 2 out of 4 PET centers of Tehran, the capital city of Iran, were organized to provide insight into their opinions on the indications of FDG PET in breast cancer patients.&#x0D; Results: The sensitivity of FDG PET scan is high for detection of distant metastases; however, assessment of lymph node pathology and the local extension of the breast cancer are questionable. Considering the cost of the procedure itself and the downstream diagnostic procedures, its application and diagnostic accuracy are hindered for breast cancer screening, staging, and assessment of response to treatment and prognosis. The advantages and disadvantages of FDG PET CT and dedicated breast FDG PET scan have been briefed in different clinical scenarios with a focus on limitations faced by a developing country.Conclusion: We suggest reserving the use of FDG PET for selected cases of suspected but not proven recurrent disease and in patients with high risk of metastasis before high risk surgery.

Current role of 18F-FDG-PET in the differential diagnosis of the main forms of dementia

We aim to present and critically evaluate the use of FDG-PET in the differential diagnosis between dementing conditions including Alzheimer disease (AD), frontotemporal dementia (FTD) and its variants, vascular dementia (VaD) and pseudodepressive dementia. This review is based on the available consensus recommendations for the use of FDG-PET and current clinical diagnostic criteria. In addition, we updated these reviews with relevant publications in the field after conducting a literature search during the last 5 years through predefined keyword strings relating to the specific terms related to the diseases covered in this review and a common part (‘FDG-PET’). Neurodegenerative disease are complex groups of several forms of dementia and their clinical diagnostic criteria are progressively incorporating imaging biomarkers as a supporting tool. The role of FDG-PET is currently increasing as part of the clinical practice supporting the clinical diagnosis of AD (at both mild cognitive impairment—MCI—and early dementia stages), FTD and its variants, as well as VaD and pseudodepressive dementia. The pattern of AD is well defined and its negative predicted value may help the differential diagnosis when comorbidities like vascular disease or depression are present. However, the formal evidence supporting the use of FDG-PET is reasonable for MCI due to AD, and the differential diagnosis between FTD and AD, but lacking for the remaining clinical uses. Interestingly, the evidence provided during the last years reinforces these recommendations and gives additional clues about the usefulness of semiquantitative methods in addition to visual reading. The large experience accumulated using FDG-PET for the differential diagnosis of the main conditions with dementia has been translated into more formal evidence to support its clinical use. Although FDG-PET form currently part of the clinical practice in many countries, there is still a lack of studies using standardized analysis that confirm specific patterns at individual level.

Meta-Analysis of the Diagnostic Accuracy of Primary Bone and Soft Tissue Sarcomas by 18F-FDG-PET

Objectives: The goal of this meta-analysis was to assess the use of FDG-PET in the diagnosis of primary bone and soft tissue sarcomas. Subjects and Methods: Several databases, including PubMed, Embase, Cochrane Library, and Web of Science, were searched. In addition to sensitivity and specificity, the diagnostic accuracy region for detecting and grading sarcomas were pooled using bivariate and hierarchical summary receiver-operating characteristic (HSROC) models. Subgroup analysis included pooling soft tissue and bone sarcomas separately, and sensitivity analysis included high-quality studies. The quality of eligible studies was assessed using QUADAS-2. Results: Of the 1,258 papers screened, 21 studies satisfied the inclusion criteria. The pooled sensitivity and specificity of FDG-PET combined with CT for the detection of sarcomas were 89.2 and 76.3%, respectively. These diagnostic accuracy measures were higher when combined with CT than those of PDG-PET alone. Diagnostic accuracy for bone and soft tissue lesions were comparable but slightly better for soft tissue tumors. Pooling only the high-quality studies with low risk of bias yielded a sensitivity of 88.5% and specificity reduced to 65.6%. There was no evidence for publication bias, but significant heterogeneity among the studies was apparent. This study also showed that FDG-PET can efficiently differentiate between benign and malignant tumors, with a mean standard uptake value of maximally 2.52 units in benign and 6.81 units in malignant tumors (89.2% sensitivity and 75.1% specificity). Conclusion: Our findings indicate FDG-PET can efficiently differentiate between benign and malignant bone and soft tissue tumors. We also found that FDG-PET improves accuracy in diagnosing soft tissue sarcomas when combined with CT.

Clinical relevance of fluorodeoxyglucose positron emission tomography/computed tomography and magnifying endoscopy with narrow band imaging in decision-making regarding the treatment strategy for esophageal squamous cell carcinoma.

BACKGROUNDRecent advances in endoscopic technology, especially magnifying endoscopy with narrow band imaging (ME-NBI) enable us to detect superficial esophageal squamous cell carcinoma (ESCC), but determining the appropriate method of resection, endoscopic resection (ER) vs surgical resection, is often challenging. Recently, several studies have reported that 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a useful indicator for decision-making regarding treatment for superficial ESCC. Although, there are not enough reports on association between FDG-PET uptake and clinicopathological characteristics of superficial ESCC. And, there are not enough reports on evaluating the usefulness of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC. This study evaluated clinical relevance of FDG-PET and ME-NBI in decision-making regarding the treatment strategy for ESCC.AIMTo investigate the association between FDG uptake and the clinicopathological characteristics of superficial ESCC and its usefulness of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC.METHODSA database of all patients with superficial ESCC who had undergone both ME-NBI and FDG-PET for pre-treatment staging at Aichi Cancer Center Hospital between January 2008 and November 2018 was retrospectively analyzed. FDG uptake was defined positive or negative whether the primary lesion was visualized or could be distinguished from the background, or not. The invasion depth of ESCC was classified according to the Japan Esophageal Society. Primary endpoint is to evaluate the association between FDG uptake and clinicopathological characteristics of superficial ESCC. Secondary endpoint is to investigate the efficacy of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC.RESULTSA total of 82 lesions in 82 patients were included. FDG-PET showed positive uptake in 29 (35.4%) lesions. Univariate analysis showed that uptake of FDG-PET had significant correlations with circumferential extension (P = 0.014), pathological depth of tumor invasion (P < 0.001), infiltrative growth pattern (P < 0.001), histological grade (P = 0.002), vascular invasion (P = 0.001), and lymphatic invasion (P < 0.001). On multivariate analysis, only depth of tumor invasion was independently correlated with FDG-PET/computed tomography visibility (P = 0.018). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of Type B2 in ME-NBI for the invasion depth of T1a muscularis mucosae and T1b upper submucosal layer were 68.4%/79.4%/50.0%/89.3%/76.8%, respectively, and those of Type B3 for the depth of T1b middle and deeper submucosal layers (SM2 and SM3) were 46.7%/100%/100%/89.3%/90.2%, respectively. On the other hand, those of FDG-PET for SM2 and SM3 were 93.3%/77.6%/48.2%/98.1%/80.5%, respectively, whereas, if the combination of positive FDG uptake and type B2 and B3 was defined as an indicator for radical esophagectomy or definitive chemoradiotherapy, the sensitivity, specificity, PPV, NPV, and accuracy were 78.3%/91.5%/78.3%/91.5%/87.8%, respectively.CONCLUSIONFDG uptake was correlated with the invasion depth of superficial ESCC. Combined use of FDG-PET and ME-NBI, especially with the microvascular findings of Type B2 and B3, is useful to determine whether ER is indicated for the lesion.

18F-FDG in the differential diagnosis of neurodegenerative dementias

The diagnostic workflow of patients with cognitive decline needs an extensive clinical evaluation. The use of FDG-PET can be helpful because the finding of a rather specific pattern of hypometabolism could point to specific neurodegenerative disorders. In patients with memory impairment and visuo-spatial deficits, FDG-PET may reveal a pattern of temporo-parietal hypometabolism that is associated with Alzheimer’s disease or a more extended area of hypometabolism that spreads to the occipital cortex, as in posterior cortical atrophy indicating signs of neurodegeneration in the associative visual cortex. In the spectrum of fronto-temporal lobe degeneration, FDG-PET is used to support the diagnosis by excluding AD and to identify areas of hypometabolism that are associated with the behavioural variant of FTD or with progressive primary aphasia. When cognitive impairment develops along with parkinsonism, FDG-PET can be used to differentiate among the different forms of disorders, such as dementia with Lewy bodies, progressive supranuclear palsy and cortico-basal degeneration, occurring with different specific pattern of altered metabolism. In this pictorial essay, we present a series of clinical cases in which the use of FDG-PET contributed to the final diagnosis.

P1.17-12 Osteogenic and Brain Metastases After Resection of NSCLC: Implications for the Use of FDG-PET and Brain MRI in Postoperative Surveillance

P1.17-12 Osteogenic and Brain Metastases After Resection of NSCLC: Implications for the Use of FDG-PET and Brain MRI in Postoperative Surveillance

I122] Quantitative molecular imaging: Can we trust the SUV?

Metabolic activity can be measured using FDG PET/CT. Quantification of FDG PET/CT studies is often based on so-called standardised uptake values (SUV). SUVs or other metabolic parameters, such as metabolic volume and total lesion glycolysis can be used for metabolic phenotyping of the tumor. These quantitative metrics are affected by various sources of bias [1] . Factor influencing tracer uptake can be described as technical, imaging physics related or biological uncertainties. Effects of the above mentioned factors on SUV should be mitigated and/or harmonized as much as possible [2] . Harmonization of PET/CT examinations aims at making SUV reads as exchangeable (comparable) and reproducible as possible by harmonizing imaging procedures, image quality and quantitation and harmonizing data analysis methods and interpretation. The main challenge of harmonisation arises from differences in PET/CT imaging procedures and in technology across multiple sites and users. To this end the European Association of Nuclear Medicine published FDG PET/CT imaging guidelines [2] and started a multicentre accreditation program. Moreover, continuous monitoring of the FDG PET/CT data quality is warranted [3] . In this lecture the principles of metabolic imaging with PET, the mechanism of FDG uptake, various factors affecting FDG PET/CT tracer uptake and its quantification by SUV will be discussed. Moreover, the need for validation of simplified uptake metrics, such as SUV, against full kinetic analysis and use of FDG PET as quantitative metabolic imaging biomarker will be addressed. Finally, it will be shown that by standardisation of imaging procedures and by ongoing quality control of the PET/CT systems, FDG uptake can be reliably quantified.

Diagnostic utility of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) in asymptomatic subjects at increased risk for Alzheimer's disease.

To assess the clinical utility of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) for detection of early signs of neurodegeneration in conditions of increased risk for Alzheimer's disease (AD) as defined by: subjective cognitive decline (SCD), evidence of cerebral amyloid-pathology, apolipoprotein E (APOE) ε4-positive genotype, or autosomal dominant forms of AD (ADAD) in asymptomatic stages. A comprehensive literature search was conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted using the Delphi method on three different diagnostic scenarios. The level of empirical study evidence for the use of FDG-PET to detect meaningful early signs of neurodegeneration was considered to be poor for ADAD and lacking for SCD and asymptomatic persons at risk, based on APOE ε4-positive genotype or cerebral amyloid pathology. Consequently, and consistent with current diagnostic criteria, panelists decided not to recommend routine clinical use of FDG-PET in these situations and to currently mainly reserve it for research purposes. Currently, there is limited evidence on which to base recommendations regarding the clinical routine use of FDG-PET to detect diagnostically meaningful early signs of neurodegeneration in asymptomatic subjects with ADAD, with APOE ε4-positive genotype, or with cerebral amyloid pathology, and in subjects with SCD. Future prospective studies are warranted and in part already ongoing, aiming to assess the added value of FDG-PET in this context beyond research applications.

Diagnostic utility of FDG-PET in the differential diagnosis between different forms of primary progressive aphasia

PurposeA joint effort of the European Association of Nuclear Medicine (EANM) and the European Academy of Neurology (EAN) aims at clinical guidance for the use of FDG-PET in neurodegenerative diseases. This paper addresses the diagnostic utility of FDG-PET over clinical/neuropsychological assessment in the differentiation of the three forms of primary progressive aphasia (PPA).MethodsSeven panelists were appointed by the EANM and EAN and a literature search was performed by using harmonized PICO (Population, Intervention, Comparison, Outcome) question keywords. The studies were screened for eligibility, and data extracted to assess their methodological quality. Critical outcomes were accuracy indices in differentiating different PPA clinical forms. Subsequently Delphi rounds were held with the extracted data and quality assessment to reach a consensus based on both literature and expert opinion.ResultsCritical outcomes for this PICO were available in four of the examined papers. The level of formal evidence supporting clinical utility of FDG-PET in differentiating among PPA variants was considered as poor. However, the consensual recommendation was defined on Delphi round I, with six out of seven panelists supporting clinical use.ConclusionsQuantitative evidence demonstrating utility or lack thereof is still missing. Panelists decided consistently to provide interim support for clinical use based on the fact that a typical atrophy or metabolic pattern is needed for PPA according to the diagnostic criteria, and the synaptic failure detected by FDG-PET is an earlier phenomenon than atrophy. Also, a normal FDG-PET points to a non-neurodegenerative cause.

Clinical utility of FDG-PET for the differential diagnosis among the main forms of dementia.

To assess the clinical utility of FDG-PET as a diagnostic aid for differentiating Alzheimer's disease (AD; both typical and atypical forms), dementia with Lewy bodies (DLB), frontotemporal lobar degeneration (FTLD), vascular dementia (VaD) and non-degenerative pseudodementia. A comprehensive literature search was conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted on six different diagnostic scenarios using the Delphi method. The level of empirical study evidence for the use of FDG-PET was considered good for the discrimination of DLB and AD; fair for discriminating FTLD from AD; poor for atypical AD; and lacking for discriminating DLB from FTLD, AD from VaD, and for pseudodementia. Delphi voting led to consensus in all scenarios within two iterations. Panellists supported the use of FDG-PET for all PICOs-including those where study evidence was poor or lacking-based on its negative predictive value and on the assistance it provides when typical patterns of hypometabolism for a given diagnosis are observed. Although there is an overall lack of evidence on which to base strong recommendations, it was generally concluded that FDG-PET has a diagnostic role in all scenarios. Prospective studies targeting diagnostically uncertain patients for assessing the added value of FDG-PET would be highly desirable.

Clinical utility of FDG-PET in amyotrophic lateral sclerosis and Huntington's disease.

To evaluate the incremental value of FDG-PET over clinical tests in: (i) diagnosis of amyotrophic lateral sclerosis (ALS); (ii) picking early signs of neurodegeneration in patients with a genetic risk of Huntington's disease (HD); and detecting metabolic changes related to cognitive impairment in (iii) ALS and (iv) HD patients. Four comprehensive literature searches were conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted using the Delphi method on these four diagnostic scenarios. The availability of evidence was good for FDG-PET utility to support the diagnosis of ALS, poor for identifying presymptomatic subjects carrying HD mutation who will convert to HD, and lacking for identifying cognitive-related metabolic changes in both ALS and HD. After the Delphi consensual procedure, the panel did not support the clinical use of FDG-PET for any of the four scenarios. Relative to other neurodegenerative diseases, the clinical use of FDG-PET in ALS and HD is still in its infancy. Once validated by disease-control studies, FDG-PET might represent a potentially useful biomarker for ALS diagnosis. FDG-PET is presently not justified as a routine investigation to predict conversion to HD, nor to detect evidence of brain dysfunction justifying cognitive decline in ALS and HD.