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Autoimmunity Reviews Feb 2024Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition characterized by an elusive etiology and pathophysiology. This study aims to... (Meta-Analysis)
Meta-Analysis
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition characterized by an elusive etiology and pathophysiology. This study aims to evaluate the pathological role of neuroinflammation in ME/CFS by conducting an exhaustive analysis of 65 observational studies. Four neuroimaging techniques, including magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), electroencephalography (EEG), and positron emission tomography (PET), were employed to comparatively assess brain regional structure, metabolite profiles, electrical activity, and glial activity in 1529 ME/CFS patients (277 males, 1252 females) and 1715 controls (469 males, 1246 females). Clinical characteristics, including sex, age, and fatigue severity, were consistent with established epidemiological patterns. Regional alterations were most frequently identified in the cerebral cortex, with a notable focus on the frontal cortex. However, our meta-analysis data revealed a significant hypoactivity in the insular and thalamic regions, contrary to observed frequencies. These abnormalities, occurring in pivotal network hubs bridging reason and emotion, disrupt connections with the limbic system, contributing to the hallmark symptoms of ME/CFS. Furthermore, we discuss the regions where neuroinflammatory features are frequently observed and address critical neuroimaging limitations, including issues related to inter-rater reliability. This systematic review serves as a valuable guide for defining regions of interest (ROI) in future neuroimaging investigations of ME/CFS.
Topics: Female; Humans; Male; Brain; Electroencephalography; Fatigue Syndrome, Chronic; Magnetic Resonance Imaging; Neuroimaging; Neuroinflammatory Diseases; Positron-Emission Tomography
PubMed: 38016575
DOI: 10.1016/j.autrev.2023.103484 -
Translational Psychiatry Mar 2016The D2 dopamine receptor mediates neuropsychiatric symptoms and is a target of pharmacotherapy. Inter-individual variation of D2 receptor density is thought to influence... (Meta-Analysis)
Meta-Analysis Review
The D2 dopamine receptor mediates neuropsychiatric symptoms and is a target of pharmacotherapy. Inter-individual variation of D2 receptor density is thought to influence disease risk and pharmacological response. Numerous molecular imaging studies have tested whether common genetic variants influence D2 receptor binding potential (BP) in humans, but demonstration of robust effects has been limited by small sample sizes. We performed a systematic search of published human in vivo molecular imaging studies to estimate effect sizes of common genetic variants on striatal D2 receptor BP. We identified 21 studies examining 19 variants in 11 genes. The most commonly studied variant was a single-nucleotide polymorphism in ANKK1 (rs1800497, Glu713Lys, also called 'Taq1A'). Fixed- and random-effects meta-analyses of this variant (5 studies, 194 subjects total) revealed that striatal BP was significantly and robustly lower among carriers of the minor allele (Lys713) relative to major allele homozygotes. The weighted standardized mean difference was -0.57 under the fixed-effect model (95% confidence interval=(-0.87, -0.27), P=0.0002). The normal relationship between rs1800497 and BP was not apparent among subjects with neuropsychiatric diseases. Significant associations with baseline striatal D2 receptor BP have been reported for four DRD2 variants (rs1079597, rs1076560, rs6277 and rs1799732) and a PER2 repeat polymorphism, but none have yet been tested in more than two independent samples. Our findings resolve apparent discrepancies in the literature and establish that rs1800497 robustly influences striatal D2 receptor availability. This genetic variant is likely to contribute to important individual differences in human striatal function, neuropsychiatric disease risk and pharmacological response.
Topics: Brain; Genetic Variation; Humans; Molecular Imaging; Positron-Emission Tomography; Receptors, Dopamine D2; Tomography, Emission-Computed, Single-Photon
PubMed: 26926883
DOI: 10.1038/tp.2016.22 -
JACC. Cardiovascular Imaging Feb 2015Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular... (Review)
Review
Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular dysfunction (CMD) is present in 50% to 65% of these patients. The optimal treatment of this cohort is undefined. We performed a systematic review to evaluate treatment strategies for objectively-defined CMD in the absence of CAD. We included studies assessing therapy in human subjects with angina and coronary flow reserve or myocardial perfusion reserve <2.5 by positron emission tomography, cardiac magnetic resonance imaging, dilution methods, or intracoronary Doppler in the absence of coronary artery stenosis ≥50% or structural heart disease. Only 8 papers met the strict inclusion criteria. The papers were heterogeneous, using different treatments, endpoints, and definitions of CMD. The small sample sizes severely limit the power of these studies, with an average of 11 patients per analysis. Studies evaluating sildenafil, quinapril, estrogen, and transcutaneous electrical nerve stimulation application demonstrated benefits in their respective endpoints. No benefit was found with L-arginine, doxazosin, pravastatin, and diltiazem. Our systematic review highlights that there is little data to support therapies for CMD. We assess the data meeting rigorous inclusion criteria and review the related but excluded published data. We additionally describe the next steps needed to address this research gap, including a standardized definition of CMD, routine assessment of CMD in studies of chest pain without obstructive CAD, and specific therapy assessment in the population with confirmed CMD.
Topics: Coronary Angiography; Coronary Circulation; Diagnosis, Differential; Humans; Magnetic Resonance Imaging, Cine; Microcirculation; Microvascular Angina; Myocardial Revascularization; Positron-Emission Tomography; Practice Guidelines as Topic; Regional Blood Flow
PubMed: 25677893
DOI: 10.1016/j.jcmg.2014.12.008 -
BMC Cardiovascular Disorders Dec 2018Cardiac Amyloidosis (CA) pertains to the cardiac involvement of a group of diseases, in which misfolded proteins deposit in tissues and cause progressive organ damage....
BACKGROUND
Cardiac Amyloidosis (CA) pertains to the cardiac involvement of a group of diseases, in which misfolded proteins deposit in tissues and cause progressive organ damage. The vast majority of CA cases are caused by light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). The increased awareness of these diseases has led to an increment of newly diagnosed cases each year.
METHODS
We performed multiple searches on MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. Several search terms were used, such as "cardiac amyloidosis", "diagnostic modalities cardiac amyloidosis" and "staging cardiac amyloidosis". Emphasis was given on original articles describing novel diagnostic and staging approaches to the disease.
RESULTS
Imaging techniques are indispensable to diagnosing CA. Novel ultrasonographic techniques boast high sensitivity and specificity for the disease. Nuclear imaging has repeatedly proved its worth in the diagnostic procedure, with efforts now focusing on standardization and quantification of amyloid load. Because the latter would be invaluable for any staging system, those spearheading research in magnetic resonance imaging of the disease are also trying to come up with accurate tools to quantify amyloid burden. Staging tools are currently being developed and validated for ATTR CA, in the spirit of the acclaimed Mayo Staging System for AL.
CONCLUSION
Cardiac involvement confers significant morbidity and mortality in all types of amyloidosis. Great effort is made to reduce the time to diagnosis, as treatment in the initial stages of the disease is tied to better prognosis. The results of these efforts are highly sensitive and specific diagnostic modalities that are also reasonably cost effective.
Topics: Amyloid Neuropathies, Familial; Biomarkers; Cardiomyopathies; Echocardiography; Humans; Immunoglobulin Light-chain Amyloidosis; Magnetic Resonance Imaging; Predictive Value of Tests; Prognosis; Reproducibility of Results; Severity of Illness Index; Tomography, Emission-Computed
PubMed: 30509186
DOI: 10.1186/s12872-018-0952-8 -
European Journal of Nuclear Medicine... Oct 2023Aim of this study was to define the prognostic value of stress myocardial perfusion imaging by cadmium zinc telluride (CZT) single-photon emission computed tomography... (Meta-Analysis)
Meta-Analysis
Prognostic value of myocardial perfusion imaging by cadmium zinc telluride single-photon emission computed tomography in patients with suspected or known coronary artery disease: a systematic review and meta-analysis.
BACKGROUND
Aim of this study was to define the prognostic value of stress myocardial perfusion imaging by cadmium zinc telluride (CZT) single-photon emission computed tomography (SPECT) for prediction of adverse cardiovascular events in patients with known or suspected coronary artery disease (CAD).
METHODS AND RESULTS
Studies published until November 2022 were identified by database search. We included studies using stress myocardial perfusion imaging by CZT-SPECT to evaluate subjects with known or suspected CAD and providing primary data of adverse cardiovascular events. Total of 12 studies were finally included recruiting 36,415 patients. Pooled hazard ratio (HR) for the occurrence of adverse events was 2.17 (95% confidence interval, CI, 1.78-2.65) and heterogeneity was 66.1% (P = 0.001). Five studies reported data on adjusted HR for the occurrence of adverse events. Pooled HR was 1.69 (95% CI, 1.44-1.98) and heterogeneity was 44.9% (P = 0.123). Seven studies reported data on unadjusted HR for the occurrence of adverse events. Pooled HR was 2.72 (95% CI, 2.00-3.70). Nine studies reported data useful to calculate separately the incidence rate of adverse events in patients with abnormal and normal myocardial perfusion. Pooled incidence rate ratio was 2.38 (95% CI, 1.39-4.06) and heterogeneity was 84.6% (P < 0.001). The funnel plot showed no evidence of asymmetry (P = 0.517). At meta-regression analysis, we found an association between HR for adverse events and presence of angina symptoms and family history of CAD.
CONCLUSIONS
Stress myocardial perfusion imaging by CZT-SPECT is a valuable noninvasive prognostic indicator for adverse cardiovascular events in patients with known or suspected CAD.
Topics: Humans; Coronary Artery Disease; Cadmium; Myocardial Perfusion Imaging; Prognosis; Tomography, Emission-Computed
PubMed: 37480369
DOI: 10.1007/s00259-023-06344-8 -
Molecular Imaging and Biology Feb 2013This systematic review and meta-analysis aimed to quantify the diagnostic performance of pancreatic venous sampling (PVS), selective pancreatic arterial calcium... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This systematic review and meta-analysis aimed to quantify the diagnostic performance of pancreatic venous sampling (PVS), selective pancreatic arterial calcium stimulation with hepatic venous sampling (ASVS), and (18)F-DOPA positron emission tomography (PET) in diagnosing and localizing focal congenital hyperinsulinism (CHI).
PROCEDURES
This systematic review and meta-analysis was conducted according to the PRISMA statement. PubMed, EMBASE, SCOPUS and Web of Science electronic databases were systematically searched from their inception to November 1, 2011. Using predefined inclusion and exclusion criteria, two blinded reviewers selected articles. Critical appraisal ranked the retrieved articles according to relevance and validity by means of the QUADAS-2 criteria. Pooled data of homogeneous study results estimated the sensitivity, specificity, likelihood ratios and diagnostic odds ratio (DOR).
RESULTS
(18)F-DOPA PET was superior in distinguishing focal from diffuse CHI (summary DOR, 73.2) compared to PVS (summary DOR, 23.5) and ASVS (summary DOR, 4.3). Furthermore, it localized focal CHI in the pancreas more accurately than PVS and ASVS (pooled accuracy, 0.82 vs. 0.76, and 0.64, respectively). Important limitations comprised the inclusion of studies with small sample sizes, high probability of bias and heterogeneity among their results. Studies with small sample sizes and high probability of bias tended to overestimate the diagnostic accuracy.
CONCLUSIONS
This systematic review and meta-analysis found evidence for the superiority of (18)F-DOPA PET in diagnosing and localizing focal CHI in patients requiring surgery for this disease.
Topics: Congenital Hyperinsulinism; Dihydroxyphenylalanine; Fluorine Radioisotopes; Humans; Pancreas; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 22752652
DOI: 10.1007/s11307-012-0572-0 -
Health Technology Assessment... Jan 2011Breast cancer is the most common type of cancer in women. Evaluation of axillary lymph node metastases is important for breast cancer staging and treatment planning. (Review)
Review
Positron emission tomography (PET) and magnetic resonance imaging (MRI) for the assessment of axillary lymph node metastases in early breast cancer: systematic review and economic evaluation.
BACKGROUND
Breast cancer is the most common type of cancer in women. Evaluation of axillary lymph node metastases is important for breast cancer staging and treatment planning.
OBJECTIVES
To evaluate the diagnostic accuracy, cost-effectiveness and effect on patient outcomes of positron emission tomography (PET), with or without computed tomography (CT), and magnetic resonance imaging (MRI) in the evaluation of axillary lymph node metastases in patients with newly diagnosed early-stage breast cancer.
DATA SOURCES
A systematic review of literature and an economic evaluation were carried out. Key databases (including MEDLINE, EMBASE and nine others) plus research registers and conference proceedings were searched for relevant studies up to April 2009. A decision-analytical model was developed to determine cost-effectiveness in the UK.
REVIEW METHODS
One reviewer assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers and screened them against inclusion criteria. Data from included studies were extracted by one reviewer using a standardised data extraction form and checked by a second reviewer. Discrepancies were resolved by discussion. Quality of included studies was assessed using the quality assessment of diagnostic accuracy studies (QUADAS) checklist, applied by one reviewer and checked by a second.
RESULTS
Forty-five citations relating to 35 studies were included in the clinical effectiveness review: 26 studies of PET and nine studies of MRI. Two studies were included in the cost-effectiveness review: one of PET and one of MRI. Of the seven studies evaluating PET/CT (n = 862), the mean sensitivity was 56% [95% confidence interval (CI) 44% to 67%] and mean specificity 96% (95% CI 90% to 99%). Of the 19 studies evaluating PET only (n = 1729), the mean sensitivity was 66% (95% CI 50% to 79%) and mean specificity 93% (95% CI 89% to 96%). PET performed less well for small metastases; the mean sensitivity was 11% (95% CI 5% to 22%) for micrometastases (≤ 2 mm; five studies; n = 63), and 57% (95% CI 47% to 66%) for macrometastases (> 2 mm; four studies; n = 111). The smallest metastatic nodes detected by PET measured 3 mm, while PET failed to detect some nodes measuring > 15 mm. Studies in which all patients were clinically node negative showed a trend towards lower sensitivity of PET compared with studies with a mixed population. Across five studies evaluating ultrasmall super-paramagnetic iron oxide (USPIO)-enhanced MRI (n = 93), the mean sensitivity was 98% (95% CI 61% to 100%) and mean specificity 96% (95% CI 72% to 100%). Across three studies of gadolinium-enhanced MRI (n = 187), the mean sensitivity was 88% (95% CI 78% to 94%) and mean specificity 73% (95% CI 63% to 81%). In the single study of in vivo proton magnetic resonance spectroscopy (n = 27), the sensitivity was 65% (95% CI 38% to 86%) and specificity 100% (95% CI 69% to 100%). USPIO-enhanced MRI showed a trend towards higher sensitivity and specificity than gadolinium-enhanced MRI. Results of the decision modelling suggest that the MRI replacement strategy is the most cost-effective strategy and dominates the baseline 4-node sampling (4-NS) and sentinel lymph node biopsy (SLNB) strategies in most sensitivity analyses undertaken. The PET replacement strategy is not as robust as the MRI replacement strategy, as its cost-effectiveness is significantly affected by the utility decrement for lymphoedema and the probability of relapse for false-negative (FN) patients.
LIMITATIONS
No included studies directly compared PET and MRI.
CONCLUSIONS
Studies demonstrated that PET and MRI have lower sensitivity and specificity than SLNB and 4-NS but are associated with fewer adverse events. Included studies indicated a significantly higher mean sensitivity for MRI than for PET, with USPIO-enhanced MRI providing the highest sensitivity. However, sensitivity and specificity of PET and MRI varied widely between studies, and MRI studies were relatively small and varied in their methods; therefore, results should be interpreted with caution. Decision modelling based on these results suggests that the most cost-effective strategy may be MRI rather than SLNB or 4-NS. This strategy reduces costs and increases quality-adjusted life-years (QALYs) because there are fewer adverse events for the majority of patients. However, this strategy leads to more FN cases at higher risk of cancer recurrence and more false- positive (FP) cases who would undergo unnecessary axillary lymph node dissection. Adding MRI prior to SLNB or 4-NS has little effect on QALYs, though this analysis is limited by lack of available data. Future research should include large, well-conducted studies of MRI, particularly using USPIO; data on the long-term impacts of lymphoedema on cost and patient utility; studies of the comparative effectiveness and cost-effectiveness of SLNB and 4-NS; and more robust UK cost data for 4-NS and SLNB as well as the cost of MRI and PET techniques.
FUNDING
This study was funded by the Health Technology Assessment programme of the National Institute of Health Research.
Topics: Axilla; Breast Neoplasms; Costs and Cost Analysis; Early Diagnosis; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Magnetic Resonance Imaging; Positron-Emission Tomography; United Kingdom
PubMed: 21276372
DOI: 10.3310/hta15040 -
Journal of the American College of... Apr 2011The purpose of this study was to critically appraise guidelines on imaging of asymptomatic coronary artery disease (CAD). (Review)
Review
OBJECTIVES
The purpose of this study was to critically appraise guidelines on imaging of asymptomatic coronary artery disease (CAD).
BACKGROUND
Various imaging tests exist to detect CAD in asymptomatic persons. Because randomized controlled trials are lacking, guidelines that address the use of CAD imaging tests may disagree.
METHODS
Guidelines in English published between January 1, 2003, and February 26, 2010, were retrieved using MEDLINE, Cumulative Index to Nursing and Allied Health Literature, the National Guideline Clearinghouse, the National Library for Health, the Canadian Medication Association Infobase, and the Guidelines International Network International Guideline Library. Guidelines developed by national and international medical societies from Western countries, containing recommendations on imaging of asymptomatic CAD were included. Rigor of development was scored by 2 independent reviewers using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. One reviewer performed full extraction of recommendations, which was checked by a second reviewer.
RESULTS
Of 2,415 titles identified, 14 guidelines met our inclusion criteria. Eleven of 14 guidelines reported relationship with industry. The AGREE scores varied across guidelines from 21% to 93%. Two guidelines considered cost effectiveness. Eight guidelines recommended against or found insufficient evidence for testing of asymptomatic CAD. The other 6 guidelines recommended imaging patients at intermediate or high CAD risk based on the Framingham risk score, and 5 considered computed tomography calcium scoring useful for this purpose.
CONCLUSIONS
Guidelines on risk assessment by imaging of asymptomatic CAD contain conflicting recommendations. More research, including randomized controlled trials, evaluating the impact of imaging on clinical outcomes and costs is needed.
Topics: Asymptomatic Diseases; Coronary Angiography; Coronary Artery Disease; Echocardiography, Stress; Exercise Test; Humans; Magnetic Resonance Angiography; Myocardial Perfusion Imaging; Practice Guidelines as Topic; Tomography, X-Ray Computed
PubMed: 21474039
DOI: 10.1016/j.jacc.2010.10.055 -
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 -
The British Journal of Radiology Jul 2022The present systematic review and meta-analysis compared the diagnostic performance of F-18 fludeoxyglucose positron emission tomography (F-FDG PET) and conventional... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The present systematic review and meta-analysis compared the diagnostic performance of F-18 fludeoxyglucose positron emission tomography (F-FDG PET) and conventional imaging, including MRI, echocardiography, and CT, in characterising cardiac masses.
METHODS
A literature search of the PubMed, Cochrane, and EMBASE databases for studies comparing the diagnostic accuracies of F-FDG PET and conventional imaging in characterising cardiac masses, from inception of indexing to 31 July 2020, was performed. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess study quality. Sensitivity and specificity across the studies were determined, positive and negative likelihood ratios (LR+ and LR-, respectively) were calculated, and summary receiver operating characteristic curves were constructed.
RESULTS
Of six included studies ( = 212 patients), F-FDG PET demonstrated a pooled sensitivity of 0.89 (95% confidence interval [CI] 0.81-0.94) and a pooled specificity of 0.89 (95% CI 0.80-0.94). LR syntheses yielded an overall LR+ of 7.9 (95% CI 4.3-14.6) and LR- of 0.12 (95% CI 0.07-0.22). The calculated pooled diagnostic odds ratio (DOR) was 64 (95% CI 23-181). For conventional imaging, the pooled sensitivity was 0.70 (95% CI 0.57-0.81) and the pooled specificity was 0.96 (95% CI 0.88-0.98). LR syntheses yielded an overall LR+ of 16.1 (95% CI 5.8-44.5) and LR- of 0.31 (95% CI 0.21-0.46). The evaluated pooled DOR was 52 (95% CI 17-155).
CONCLUSION
F-FDG PET and conventional imaging demonstrated comparable diagnostic accuracies for the characterisation of cardiac masses. Further large multicentre studies are, however, required to corroborate the diagnostic performances of F-FDG PET and conventional imaging for the characterisation of cardiac masses.
ADVANCES IN KNOWLEDGE
No previous studies have comprehensively analysed the diagnostic performance of F-FDG PET/CT compared with conventional imaging techniques including echocardiography, CT, and MRI. According to the current study, F-FDG PET/CT yielded a pooled DOR of 64, whereas other conventional imaging techniques demonstrated a DOR of 52. As such, F-FDG PET/CT demonstrated sensitivity and specificity, with a high pooled DOR comparable with other conventional imaging modalities.
Topics: Diagnostic Tests, Routine; Fluorodeoxyglucose F18; Humans; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity
PubMed: 35612548
DOI: 10.1259/bjr.20210263