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Alzheimer's & Dementia : the Journal of... Nov 2023Deposition of amyloid and tau pathology can be quantified in vivo using positron emission tomography (PET). Accurate longitudinal measurements of accumulation from these... (Review)
Review
Deposition of amyloid and tau pathology can be quantified in vivo using positron emission tomography (PET). Accurate longitudinal measurements of accumulation from these images are critical for characterizing the start and spread of the disease. However, these measurements are challenging; precision and accuracy can be affected substantially by various sources of errors and variability. This review, supported by a systematic search of the literature, summarizes the current design and methodologies of longitudinal PET studies. Intrinsic, biological causes of variability of the Alzheimer's disease (AD) protein load over time are then detailed. Technical factors contributing to longitudinal PET measurement uncertainty are highlighted, followed by suggestions for mitigating these factors, including possible techniques that leverage shared information between serial scans. Controlling for intrinsic variability and reducing measurement uncertainty in longitudinal PET pipelines will provide more accurate and precise markers of disease evolution, improve clinical trial design, and aid therapy response monitoring.
Topics: Humans; Alzheimer Disease; tau Proteins; Amyloid beta-Peptides; Positron-Emission Tomography; Amyloidogenic Proteins; Cognitive Dysfunction; Brain
PubMed: 37303269
DOI: 10.1002/alz.13158 -
The Quarterly Journal of Nuclear... Jun 2023Primary hyperparathyroidism (pHPT) is a common endocrine disorder caused by an autonomous overproduction of parathyroid hormone (PTH) by a parathyroid gland. Over the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Primary hyperparathyroidism (pHPT) is a common endocrine disorder caused by an autonomous overproduction of parathyroid hormone (PTH) by a parathyroid gland. Over the last decade, F-choline (FCH) PET has emerged as a highly performant imaging technique for guiding parathyroidectomy. As cure is the goal of surgery, the main aims of this study were to summarize patient-based sensitivity, positive predictive value (PPV), and cure rate of FCH PET guided surgery in the surgical management of pHPT.
EVIDENCE ACQUISITION
We conducted a systematic review and metaanalysis according to the PRISMA Guidelines. A literature search was performed in the PubMed, Web of Science and Cochrane databases, last updated November 2022. Original articles on choline PET in patients with pHPT mentioning patient-based sensitivity, PPV and cure rate were retained. Quality of included studies was assessed using the QUADAS-2 Tool. Patient-based sensitivity, PPV and cure rate were pooled by using a random-effects model.
EVIDENCE SYNTHESIS
Twenty-three studies including 1716 patients were included for quantitative assessment. FCH PET showed a pooled patient-based sensitivity of 93.8% (95% CI: 89.8-96.3) and PPV of 97% (95% CI: 92.8-98.8) in patients with pHPT. Parathyroid surgery was performed in 1129 patients. The pooled cure rate of PET-guided surgery was 92.8% (95% CI: 87.4-96.0). Heterogeneity was shown to be moderate for all effect sizes.
CONCLUSIONS
FCH PET showed a high patient-based sensitivity, PPV and cure rate of PET guided surgery in patients with pHPT.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Glands; Choline; Positron-Emission Tomography; Positron Emission Tomography Computed Tomography
PubMed: 36756935
DOI: 10.23736/S1824-4785.23.03512-4 -
Hellenic Journal of Nuclear Medicine 2020A meta-analysis was performed to compare the diagnostic performance of gallium-68 (Ga) somatostatin receptor positron emission tomography (Ga-SSTR PET) and... (Meta-Analysis)
Meta-Analysis
Comparison of gallium-68 somatostatin receptor and F-fluorodeoxyglucose positron emission tomography in the diagnosis of neuroendocrine tumours: A systematic review and meta-analysis.
OBJECTIVE
A meta-analysis was performed to compare the diagnostic performance of gallium-68 (Ga) somatostatin receptor positron emission tomography (Ga-SSTR PET) and fluorine-18-fluorodeoxyglucose (F-FDG) PET in patients with neuroendocrine tumours (NET) and whether the two imaging modalities can be mutually substituted in clinical work.
METHODS
We performed electronic literature searches of the MEDLINE, PubMed, Embase and Cochrane Library databases for English-language articles from the earliest available date of indexing through 30 July 2019. We calculated the pooled sensitivity, specificity and diagnostic odds ratios (DOR) with 95% confidence intervals (95% CI) of Ga-SSTR PET and F-FDG PET in NET. We drew a summary receiver operator characteristic (SROC) curve and calculated the area under the curve (AUC) to measure the accuracy of Ga-SSTR PET and F-FDG PET in patients or lesions with NET.
RESULTS
Thirty studies comprising 3401 patients and 5793 lesions with NET were included in this meta-analysis. The pooled sensitivity, sensitivity, DOR and AUC for Ga-SSTR PET or PET/computed tomography (CT) in the diagnosis of NET, based on lesion patient, were 0.92(0.89-0.95), 0.91(0.83-0.95),119(51-282) and 0.96(0.94-0.98), and based on lesion, were 0.95(0.86-0.98), 0.93(0.83-0.97), 229(43-1205) and 0.98(0.96-0.99), respectively. The pooled sensitivity, sensitivity, DOR and AUC for F-FDG PET or PET/CT in NET were 0.70(0.41-0.89), 0.97(0.70-1.00), 67(7-612) and 0.94(0.92-0.96), respectively, when analyzed on a per-patient basis.The pooled sensitivities of Ga-SSTR PET/CT were 0.923 (95% CI: 0.884-0.952), 0.902 (0.862-0.934) and 0.578 (0.482-0.669) in the G1(ki67,≤2%), G2(ki67,>3%,≤20% and G3(ki67,>20%) groups based on patients with NET, respectively. The pooled sensitivities of F-FDG PET/CT were 0.378 (0.319-0.440), 0.554 (0.492-0.615) and 0.712 (0.633-0.783) in the G1, G2 and G3 groups based on patients with NET, respectively.
CONCLUSION
The Ga-SSTR PET has highly sensitive and had a greater diagnostic value than F-FDG PET for patients with NET. Fluorine-18-FDG PET, however, had significant specificity than Ga-SSTR PET. The Ga-SSTR has high sensitivity in G1/G2 NET, while F-FDG has a low positive rate. In G3 NET, however, the opposite is true. Therefore, the Ga-SSTR PET and F-FDG PET modalities are complementary rather than substitutive in clinical practice.
Topics: Fluorodeoxyglucose F18; Gallium Radioisotopes; Humans; Neuroendocrine Tumors; Positron-Emission Tomography; Receptors, Somatostatin
PubMed: 32716410
DOI: 10.1967/s002449912108 -
Current Oncology (Toronto, Ont.) Aug 2019Paraneoplastic neurologic syndrome (pns) is a rare condition indirectly caused by an underlying malignancy. In many cases, the malignancy is occult at the time of the... (Meta-Analysis)
Meta-Analysis
F-Fluorodeoxyglucose positron-emission tomography for the investigation of malignancy in patients with suspected paraneoplastic neurologic syndromes and negative or indeterminate conventional imaging: a retrospective analysis of the Ontario PET Access Program, with systematic review and...
OBJECTIVE
Paraneoplastic neurologic syndrome (pns) is a rare condition indirectly caused by an underlying malignancy. In many cases, the malignancy is occult at the time of the pns diagnosis, and the optimal diagnostic modality to detect the underlying tumour is unclear. In the present study, we aimed to assess the utility of F-fluorodeoxyglucose positron-emission tomography (fdg-pet) or pet integrated with computed tomography (pet/ct) in the investigation of these patients.
METHODS
We retrospectively analyzed data from the PET Access Program (pap) database in the province of Ontario to identify patients who underwent fdg-pet/ct imaging as part of a workup for pns. In all patients, prior conventional imaging was negative or indeterminate. To determine the diagnostic accuracy of fdg-pet/ct, data about demographics, presenting symptoms, and biochemical and radiologic workup, including fdg-pet/ct imaging results, were compared with data collected by the Ontario Cancer Registry (ocr). A systematic review of the literature and meta-analysis using our study inclusion criteria were performed for studies of fdg-pet accuracy.
RESULTS
Of 29 patients identified in the pap database, 9 had fdg-pet/ct results suspicious for malignancy. When correlated with data from the ocr, 5 fdg-pet/ct results were informative, resulting in a detection rate of 17%. Local sensitivity and specificity were 0.83 and 0.83 respectively. Two studies meeting our criteria were identified in the literature. The pooled sensitivity and specificity from the literature and local data were 0.88 and 0.90 respectively.
CONCLUSIONS
When investigating for underlying malignancy in patients with suspected pns and negative conventional imaging, pet has high sensitivity and specificity.
Topics: Adult; Aged; Aged, 80 and over; Female; Fluorodeoxyglucose F18; Humans; Male; Middle Aged; Ontario; Paraneoplastic Syndromes, Nervous System; Retrospective Studies; Sensitivity and Specificity; Young Adult
PubMed: 31548813
DOI: 10.3747/co.26.4583 -
Seminars in Nuclear Medicine Sep 2023Prostate-specific membrane antigen (PSMA) is a highly expressed protein in prostate cancer (PCa) and has become an increasingly popular target for molecular imaging in... (Meta-Analysis)
Meta-Analysis Review
Histopathologically Validated Diagnostic Accuracy of PSMA-PET/CT in the Primary and Secondary Staging of Prostate Cancer and the Impact of PSMA-PET/CT on Clinical Management: A Systematic Review and Meta-analysis.
Prostate-specific membrane antigen (PSMA) is a highly expressed protein in prostate cancer (PCa) and has become an increasingly popular target for molecular imaging in recent years. PSMA based positron-emission-tomography/computed tomography (PET/CT) is a well characterised hybrid imaging modality that combines the high sensitivity of PET with the high spatial resolution of CT imaging. The combination of these two imaging modalities provides an accurate tool for detecting and managing PCa. Several diagnostic accuracy and clinical management studies investigating the role of PSMA PET/CT in PCa have been published recently. This study aimed to perform an updated systematic review and meta-analysis to evaluate the diagnostic performance of PSMA PET/CT in localised, lymph node metastatic (LNM) and recurrent PCa patients and assess its impact on the clinical management of primary and recurrent PCa. Using Medline, Embase, PubMed and Cochrane Library databases, studies reporting the diagnostic accuracy and clinical management of PSMA PET/CT were analysed based on the PRISMA guidelines. Statistical analyses were conducted using random-effects models, and meta-regression explored observed heterogeneity. Results indicate that the sensitivity and specificity of PSMA PET/CT for localised PCa were 71.0% (95% confidence interval (CI): 58.0, 81.0) and 92.0% (95% CI: 86.0, 96.0), respectively (N = 10; n = 404 patients). Sensitivity and specificity in LNM were 57.0% (95% CI: 49.0, 64.0) and 96.0% (95% CI: 95.0, 97.0) (N = 36; n = 3,659 patients). For patients with biochemical recurrence (BCR), sensitivity was 84.0% (95% CI: 74.0, 90.0), and specificity was 97.0% (95% CI: 88.0, 99.0) (N = 9; n = 818 patients). The pooled proportion of management changes in primary (N = 16; n = 1,099 patients) and recurrent (N = 40; n = 5,398 patients) PCa was 28.0% (95% CI: 23.0, 34.0) and 54.0% (95% CI: 50.0, 58.0), respectively. In conclusion, PSMA PET/CT shows moderate sensitivity and high specificity in localised and LNM disease, while the accuracy in BCR patients was high. PSMA PET/CT also had a large impact on the clinical management of PCa patients. This is the most extensive and first systematic review to include three subgroups of PCa with histologically verified diagnostic accuracy and clinical management change reported separately in primary and recurrent disease settings.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Lymphatic Metastasis; Sensitivity and Specificity; Gallium Radioisotopes; Neoplasm Staging
PubMed: 37005145
DOI: 10.1053/j.semnuclmed.2023.02.006 -
NeuroImage Oct 2022Deep brain stimulation (DBS) is an established treatment for several brain disorders, including Parkinson's disease, essential tremor, dystonia and epilepsy, and an... (Review)
Review
Deep brain stimulation (DBS) is an established treatment for several brain disorders, including Parkinson's disease, essential tremor, dystonia and epilepsy, and an emerging therapeutic tool in many other neurological and psychiatric disorders. The therapeutic efficacy of DBS is dependent on the stimulation target, but its mechanisms of action are still relatively poorly understood. Investigating these mechanisms is challenging, partly because the stimulation devices and electrodes have limited the use of functional MRI in these patients. Molecular brain imaging techniques, such as positron emission tomography (PET) and single photon emission tomography (SPET), offer a unique opportunity to characterize the whole brain effects of DBS. Here, we investigated the direct effects of DBS by systematically reviewing studies performing an `on' vs `off' contrast during PET or SPET imaging. We identified 62 studies (56 PET and 6 SPET studies; 531 subjects). Approximately half of the studies focused on cerebral blood flow or glucose metabolism in patients Parkinson's disease undergoing subthalamic DBS (25 studies, n = 289), therefore Activation Likelihood Estimation analysis was performed on these studies. Across disorders and stimulation targets, DBS was associated with a robust local increase in ligand uptake at the stimulation site and target-specific remote network effects. Subthalamic nucleus stimulation in Parkinson's disease showed a specific pattern of changes in the motor circuit, including increased ligand uptake in the basal ganglia, and decreased ligand uptake in the primary motor cortex, supplementary motor area and cerebellum. However, there was only a handful of studies investigating other brain disorder and stimulation site combinations (1-3 studies each), or specific neurotransmitter systems, preventing definitive conclusions of the detailed molecular effects of the stimulation in these cases.
Topics: Brain; Deep Brain Stimulation; Humans; Ligands; Neuroimaging; Parkinson Disease
PubMed: 35842094
DOI: 10.1016/j.neuroimage.2022.119473 -
Seminars in Nuclear Medicine Sep 2023Fibroblast activation protein inhibitor (FAPI) is a promising tracer in oncologic positron emission tomography/computed tomography (PET/CT). Numerous studies have... (Review)
Review
Fibroblast activation protein inhibitor (FAPI) is a promising tracer in oncologic positron emission tomography/computed tomography (PET/CT). Numerous studies have demonstrated the superior sensitivity of FAPI PET/CT over fluorodeoxyglucose (FDG) PET/CT in several types of cancer. However, the cancer specificity of FAPI uptake remains understudied, and several cases of false-positive FAPI PET/CT findings have been reported. A systematic search of PubMed, Embase, and Web of Science was conducted for studies published prior to April 2022 reporting nonmalignant FAPI PET/CT findings. We included original peer-reviewed articles of studies in humans using FAPI tracers radiolabeled with Ga or F that were published in English. Papers without original data and studies with insufficient information were excluded. Nonmalignant findings were presented on a per-lesion basis and grouped according to the type of organ or tissue involved. The search identified a total of 1.178 papers, of which 108 studies were eligible. Eighty studies were case reports (74%), and the remaining 28 were cohort studies (26%). A total of 2.372 FAPI-avid nonmalignant findings were reported, with the most frequent being uptake in the arteries, e.g., related to plaques (n = 1178, 49%). FAPI uptake was also frequently related to degenerative and traumatic bone and joint lesions (n = 147, 6%) or arthritis (n = 92, 4%). For organs, diffuse or focal uptake was often seen in cases of inflammation, infection, fibrosis, and IgG4-related disease (n = 157, 7%). FAPI-avid inflammatory/reactive lymph nodes (n = 121, 5%) and tuberculosis lesions (n = 51, 2%) have been reported and could prove to be potential pitfalls in cancer staging. Periodontitis (n = 76, 3%), hemorrhoids (n = 47, 2%), and scarring/wound healing (n = 35, 2%) also presented as focal uptake on FAPI PET/CT. The present review provides an overview of the reported FAPI-avid nonmalignant PET/CT findings to date. A large number of benign clinical entities may show FAPI uptake and should be kept in mind when interpreting FAPI PET/CT findings in patients with cancer.
Topics: Humans; Biological Transport; Fluorodeoxyglucose F18; Gallium Radioisotopes; Inflammation; Positron Emission Tomography Computed Tomography
PubMed: 36813670
DOI: 10.1053/j.semnuclmed.2023.02.001 -
Neuroscience and Biobehavioral Reviews Apr 2024Conflicting evidence exists on the relationship between diabetes mellitus (DM) and Alzheimer's disease (AD) biomarkers. Therefore, we conducted a random-effects... (Meta-Analysis)
Meta-Analysis
Conflicting evidence exists on the relationship between diabetes mellitus (DM) and Alzheimer's disease (AD) biomarkers. Therefore, we conducted a random-effects meta-analysis to evaluate the correlation of glucose metabolism measures (glycated hemoglobin, fasting blood glucose, insulin resistance indices) and DM status with AD biomarkers of amyloid-β and tau measured by positron emission tomography or cerebrospinal fluid. We selected 37 studies from PubMed and Embase, including 11,694 individuals. More impaired glucose metabolism and DM status were associated with higher tau biomarkers (r=0.11[0.03-0.18], p=0.008; I2=68%), but were not associated with amyloid-β biomarkers (r=-0.06[-0.13-0.01], p=0.08; I=81%). Meta-regression revealed that glucose metabolism and DM were specifically associated with tau biomarkers in population settings (p=0.001). Furthermore, more impaired glucose metabolism and DM status were associated with lower amyloid-β biomarkers in memory clinic settings (p=0.004), and in studies with a higher prevalence of dementia (p<0.001) or lower cognitive scores (p=0.04). These findings indicate that DM is associated with biomarkers of tau but not with amyloid-β. This knowledge is valuable for improving dementia and DM diagnostics and treatment.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Cognitive Dysfunction; Diabetes Mellitus; Glucose; Peptide Fragments; Positron-Emission Tomography; tau Proteins
PubMed: 38423195
DOI: 10.1016/j.neubiorev.2024.105604 -
Clinical Neuroradiology Dec 2021Alzheimer's disease (AD) is a heterogeneous progressive neurocognitive disorder. Although different neuroimaging modalities have been used for the identification of... (Review)
Review
Alzheimer's disease (AD) is a heterogeneous progressive neurocognitive disorder. Although different neuroimaging modalities have been used for the identification of early diagnostic and prognostic factors of AD, there is no consolidated view of the findings from the literature. Here, we aim to provide a comprehensive account of different neural correlates of cognitive dysfunction via magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), functional MRI (fMRI) (resting-state and task-related), positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) modalities across the cognitive groups i.e., normal cognition, mild cognitive impairment (MCI), and AD. A total of 46 meta-analyses met the inclusion criteria, including relevance to MCI, and/or AD along with neuroimaging modality used with quantitative and/or functional data. Volumetric MRI identified early anatomical changes involving transentorhinal cortex, Brodmann area 28, followed by the hippocampus, which differentiated early AD from healthy subjects. A consistent pattern of disruption in the bilateral precuneus along with the medial temporal lobe and limbic system was observed in fMRI, while DTI substantiated the observed atrophic alterations in the corpus callosum among MCI and AD cases. Default mode network hypoconnectivity in bilateral precuneus (PCu)/posterior cingulate cortices (PCC) and hypometabolism/hypoperfusion in inferior parietal lobules and left PCC/PCu was evident. Molecular imaging revealed variable metabolite concentrations in PCC. In conclusion, the use of different neuroimaging modalities together may lead to identification of an early diagnostic and/or prognostic biomarker for AD.
Topics: Alzheimer Disease; Cognitive Dysfunction; Diffusion Tensor Imaging; Humans; Magnetic Resonance Imaging; Neuroimaging
PubMed: 34297137
DOI: 10.1007/s00062-021-01057-7 -
Journal of Neurology May 2023To evaluate the difference of tau burden between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs) or other neurodegenerative diseases using... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To evaluate the difference of tau burden between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs) or other neurodegenerative diseases using tau-positron emission tomography (PET) imaging.
METHODS
A systematic search on PubMed, Embase, and Web of Science databases was performed for tau-PET studies in PSP patients, up to April 1, 2022. Standardized mean differences (SMDs) of tau tracer uptake were calculated using random-effects models. Subgroup analysis based on the type of tau tracers, meta-regression, and sensitivity analysis were conducted.
RESULTS
Twenty-seven studies comprising 553 PSP, 626 HCs, and 406 other neurodegenerative diseases were included. Compared with HCs, PSP patients showed elevated tau binding in basal ganglia, midbrain, dentate nucleus, cerebellar white matter, and frontal lobe with decreasing SMD (SMD: 0.390-1.698). Compared with Parkinson's disease patients, increased tau binding was identified in the midbrain, basal ganglia, dentate nucleus, and frontal and parietal lobe in PSP patients with decreasing SMD (SMD: 0.503-1.853). PSP patients showed higher tau binding in the subthalamic nucleus (SMD = 1.351) and globus pallidus (SMD = 1.000), and lower binding in the cortex and parahippocampal gyrus than Alzheimer's disease patients (SMD: - 2.976 to - 1.018). PSP patients showed higher midbrain tau binding than multiple system atrophy patients (SMD = 1.269).
CONCLUSION
Tau PET imaging indicates different topography of tau deposition between PSP patients and HCs or other neurodegenerative disorders. The affinity and selectivity of tracers for 4R-tau and the off-target binding of tracers should be considered when interpreting the results.
Topics: Humans; Supranuclear Palsy, Progressive; tau Proteins; Basal Ganglia; Parkinson Disease; Positron-Emission Tomography
PubMed: 36633672
DOI: 10.1007/s00415-022-11556-3