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The Canadian Journal of Cardiology May 2024In this article some of the recent advances in the use of noninvasive imaging applied to patients with hypertrophic cardiomyopathy (HCM) are discussed. Echocardiography... (Review)
Review
In this article some of the recent advances in the use of noninvasive imaging applied to patients with hypertrophic cardiomyopathy (HCM) are discussed. Echocardiography and cardiac computed tomography are briefly discussed with respect to their power to detect apical aneurysmal disease. Echocardiographic phenotype-genotype correlations and the use of echocardiography to characterize myocardial work are reviewed. Positron emission tomography is reviewed in the context of ischemia imaging and also in the context of the use of a new tracer that might allow for recognition of early activation of the fibrosis pathway. Next, the technical capabilities of cardiovascular magnetic resonance to measure myocardial perfusion, oxygenation, and disarray are discussed as they apply to HCM. The application of radiomics to improve prediction of sudden cardiac death is touched upon. Finally, a deep learning approach to the recognition of HCM vs phenocopies is presented as a potential future diagnostic aid in the not-too-distant future.
Topics: Humans; Cardiomyopathy, Hypertrophic; Echocardiography; Magnetic Resonance Imaging, Cine; Positron-Emission Tomography
PubMed: 38467329
DOI: 10.1016/j.cjca.2024.02.030 -
Clinical and Experimental Rheumatology Jul 2023Polymyalgia rheumatica (PMR) is an inflammatory disease with a diagnosis that is sometimes difficult to establish. Fluorine-18 fluorodeoxyglucose positron emission... (Observational Study)
Observational Study
OBJECTIVES
Polymyalgia rheumatica (PMR) is an inflammatory disease with a diagnosis that is sometimes difficult to establish. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) might be helpful. We analysed the usefulness of 18F-FDG PET/CT for the diagnosis of PMR.
METHODS
This was an observational retrospective study of individuals with PMR who underwent 18F-FDG PET/CT and a control group. We assessed clinical and 18F-FDG PET/CT characteristics. Sixteen sites were studied. The number of sites with significant FDG uptake, the mean maximum standardised uptake value (SUVmax) and the highest SUVmax value were assessed for each patient.
RESULTS
Data for 123 patients with PMR (37 with corticosteroids [CSTs] use) were analysed; 85 had new-onset PMR. As compared with the 75 controls, patients with new-onset PMR had higher mean ± SD number of sites with significant FDG uptake (11.3 ± 3.3 vs. 0.9 ± 1.1, p<0.001) and higher SUVmax scores (p<0.001). A cut-off of 5 hypermetabolic sites provided sensitivity of 96.5% and specificity 100%. For the total SUVmax score, a cut-off of 3 had the best sensitivity (92.6%) and specificity (86.1%). As compared with PMR patients using CSTs, those who were CST-naive had significantly higher CRP level (p<0.001), number of sites with significant FDG uptake (p<0.001) and SUVmax scores (p<0.01). In contrast, large-vessel vasculitis was more frequent in patients receiving CSTs than CST-naive patients (27% vs. 8%, p<0.01).
CONCLUSIONS
The number of hypermetabolic sites or SUVmax quantification might be useful for PMR diagnosis, and CSTs might affect the results of 18F-FDG PET/CT.
Topics: Humans; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Polymyalgia Rheumatica; Retrospective Studies; Radiopharmaceuticals; Giant Cell Arteritis; Positron-Emission Tomography
PubMed: 36533978
DOI: 10.55563/clinexprheumatol/kqyki5 -
International Journal of Molecular... Jul 2023Sigma (σ) receptors are a class of unique proteins with two subtypes: the sigma-1 (σ) receptor which is situated at the mitochondria-associated endoplasmic reticulum... (Review)
Review
Sigma (σ) receptors are a class of unique proteins with two subtypes: the sigma-1 (σ) receptor which is situated at the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), and the sigma-2 (σ) receptor, located in the ER-resident membrane. Increasing evidence indicates the involvement of both σ and σ receptors in the pathogenesis of Alzheimer's disease (AD), and thus these receptors represent two potentially effective biomarkers for emerging AD therapies. The availability of optimal radioligands for positron emission tomography (PET) neuroimaging of the σ and σ receptors in humans will provide tools to monitor AD progression and treatment outcomes. In this review, we first summarize the significance of both receptors in the pathophysiology of AD and highlight AD therapeutic strategies related to the σ and σ receptors. We then survey the potential PET radioligands, with an emphasis on the requirements of optimal radioligands for imaging the σ or σ receptors in humans. Finally, we discuss current challenges in the development of PET radioligands for the σ or σ receptors, and the opportunities for neuroimaging to elucidate the σ and σ receptors as novel biomarkers for early AD diagnosis, and for monitoring of disease progression and AD drug efficacy.
Topics: Humans; Receptors, sigma; Alzheimer Disease; Positron-Emission Tomography; Neuroimaging; Ligands
PubMed: 37569401
DOI: 10.3390/ijms241512025 -
Japanese Journal of Radiology Aug 2023Positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) has been commonly used in many oncological areas. High-resolution PET permits a three-dimensional... (Review)
Review
Positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) has been commonly used in many oncological areas. High-resolution PET permits a three-dimensional analysis of FDG distributions on various lesions in vivo, which can be applied for tissue characterization, risk analysis, and treatment monitoring after chemoradiotherapy and immunotherapy. Metabolic changes can be assessed using the tumor absolute FDG uptake as standardized uptake value (SUV) and metabolic tumor volume (MTV). In addition, tumor heterogeneity assessment can potentially estimate tumor aggressiveness and resistance to chemoradiotherapy. Attempts have been made to quantify intratumoral heterogeneity using radiomics. Recent reports have indicated the clinical feasibility of a dynamic FDG PET-computed tomography (CT) in pilot cohort studies of oncological cases. Dynamic imaging permits the assessment of temporal changes in FDG uptake after administration, which is particularly useful for differentiating pathological from physiological uptakes with high diagnostic accuracy. In addition, several new parameters have been introduced for the in vivo quantitative analysis of FDG metabolic processes. Thus, a four-dimensional FDG PET-CT is available for precise tissue characterization of various lesions. This review introduces various new techniques for the quantitative analysis of FDG distribution and glucose metabolism using a four-dimensional FDG analysis with PET-CT. This elegant study reveals the important role of tissue characterization and treatment strategies in oncology.
Topics: Humans; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Pilot Projects; Positron-Emission Tomography; Neoplasms; Medical Oncology; Radiopharmaceuticals
PubMed: 36947283
DOI: 10.1007/s11604-023-01411-4 -
Arteriosclerosis, Thrombosis, and... Jul 2023Assessments of coronary disease activity with F-sodium fluoride positron emission tomography and radiomics-based precision coronary plaque phenotyping derived from...
BACKGROUND
Assessments of coronary disease activity with F-sodium fluoride positron emission tomography and radiomics-based precision coronary plaque phenotyping derived from coronary computed tomography angiography may enhance risk stratification in patients with coronary artery disease. We sought to investigate whether the prognostic information provided by these 2 approaches is complementary in the prediction of myocardial infarction.
METHODS
Patients with known coronary artery disease underwent coronary F-sodium fluoride positron emission tomography and coronary computed tomography angiography on a hybrid positron emission tomography/computed tomography scanner. Coronary F-NaF uptake was determined by the coronary microcalcification activity. We performed quantitative plaque analysis of coronary computed tomography angiography datasets and extracted 1103 radiomic features for each plaque. Using weighted correlation network analysis, we derived latent morphological features of coronary lesions which were aggregated to patient-level radiomics nomograms to predict myocardial infarction.
RESULTS
Among 260 patients with established coronary artery disease (age, 65±9 years; 83% men), 179 (69%) participants showed increased coronary F-NaF activity (coronary microcalcification activity>0). Over 53 (40-59) months of follow-up, 18 patients had a myocardial infarction. Using weighted correlation network analysis, we derived 15 distinct eigen radiomic features representing latent morphological coronary plaque patterns in an unsupervised fashion. Following adjustments for calcified, noncalcified, and low-density noncalcified plaque volumes and F-NaF coronary microcalcification activity, 4 radiomic features remained independent predictors of myocardial infarction (hazard ratio, 1.46 [95% CI, 1.03-2.08]; =0.03; hazard ratio, 1.62 [95% CI, 1.04-2.54]; =0.02; hazard ratio, 1.49 [95% CI, 1.07-2.06]; =0.01; and hazard ratio, 1.50 (95% CI, 1.05-2.13); =0.02).
CONCLUSIONS
In patients with established coronary artery disease, latent coronary plaque morphological features, quantitative plaque volumes, and disease activity on F-sodium fluoride positron emission tomography are additive predictors of myocardial infarction.
Topics: Male; Humans; Middle Aged; Aged; Female; Coronary Artery Disease; Computed Tomography Angiography; Sodium Fluoride; Fluorine Radioisotopes; Radiopharmaceuticals; Plaque, Atherosclerotic; Positron-Emission Tomography; Positron Emission Tomography Computed Tomography; Myocardial Infarction; Calcinosis; Coronary Angiography
PubMed: 37165878
DOI: 10.1161/ATVBAHA.123.319332 -
Frontiers in Endocrinology 2023The most frequent extrathyroidal Graves' disease manifestation is Graves' orbitopathy (GO). The treatment of GO is determined by its severity and activity. There is... (Review)
Review
The most frequent extrathyroidal Graves' disease manifestation is Graves' orbitopathy (GO). The treatment of GO is determined by its severity and activity. There is currently no reliable, impartial method for assessing it clinically or distinguishing fibrosis from active inflammatory disorders. Today, imaging methods including orbital ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) are frequently employed to show pathological abnormalities in the ocular adnexa of GO patients. In addition, a not widely accepted technique - 99mTc-DTPA SPECT - has some potential to evaluate retrobulbar inflammation in GO patients. However, FDG-PET/CT is possibly superior to other imaging modalities in detecting inflammation in GO and it may be useful in assessing disease activity in case of clinical or serological uncertainty. It might also act as an early indicator of GO development and its aggravation before irreversible tissue alterations take place and may be used in the differential diagnosis of inflammatory disorders of the orbit. However, before FDG-PET/CT could be applied in daily clinical practice, the methodology of GO activity assessment with defined cut-off values for radionuclide concentration - standardized units of value (SUV) have to be established and validated. In addition, the limitations of this technique have to be recognized.
Topics: Humans; Graves Ophthalmopathy; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Graves Disease; Inflammation
PubMed: 37600686
DOI: 10.3389/fendo.2023.1138569 -
Translational Psychiatry Feb 2024Various plasma biomarkers for amyloid-β (Aβ) have shown high predictability of amyloid PET positivity. However, the characteristics of discordance between amyloid PET...
Various plasma biomarkers for amyloid-β (Aβ) have shown high predictability of amyloid PET positivity. However, the characteristics of discordance between amyloid PET and plasma Aβ42/40 positivity are poorly understood. Thorough interpretation of discordant cases is vital as Aβ plasma biomarker is imminent to integrate into clinical guidelines. We aimed to determine the characteristics of discordant groups between amyloid PET and plasma Aβ42/40 positivity, and inter-assays variability depending on plasma assays. We compared tau burden measured by PET, brain volume assessed by MRI, cross-sectional cognitive function, longitudinal cognitive decline and polygenic risk score (PRS) between PET/plasma groups (PET-/plasma-, PET-/plasma+, PET+/plasma-, PET+/plasma+) using Alzheimer's Disease Neuroimaging Initiative database. Additionally, we investigated inter-assays variability between immunoprecipitation followed by mass spectrometry method developed at Washington University (IP-MS-WashU) and Elecsys immunoassay from Roche (IA-Elc). PET+/plasma+ was significantly associated with higher tau burden assessed by PET in entorhinal, Braak III/IV, and Braak V/VI regions, and with decreased volume of hippocampal and precuneus regions compared to PET-/plasma-. PET+/plasma+ showed poor performances in global cognition, memory, executive and daily-life function, and rapid cognitive decline. PET+/plasma+ was related to high PRS. The PET-/plasma+ showed intermediate changes between PET-/plasma- and PET+/plasma+ in terms of tau burden, hippocampal and precuneus volume, cross-sectional and longitudinal cognition, and PRS. PET+/plasma- represented heterogeneous characteristics with most prominent variability depending on plasma assays. Moreover, IP-MS-WashU showed more linear association between amyloid PET standardized uptake value ratio and plasma Aβ42/40 than IA-Elc. IA-Elc showed more plasma Aβ42/40 positivity in the amyloid PET-negative stage than IP-MS-WashU. Characteristics of PET-/plasma+ support plasma biomarkers as early biomarker of amyloidopathy prior to amyloid PET. Various plasma biomarker assays might be applied distinctively to detect different target subjects or disease stages.
Topics: Humans; Cross-Sectional Studies; tau Proteins; Amyloid beta-Peptides; Alzheimer Disease; Positron-Emission Tomography; Cognitive Dysfunction; Biomarkers
PubMed: 38341444
DOI: 10.1038/s41398-024-02766-6 -
Molecular Pharmaceutics Jul 2023Cysteine cathepsin B (CTS-B) is a crucial enzyme that is overexpressed in numerous malignancies and contributes to the invasion and metastasis of cancer. Therefore, this...
Cysteine cathepsin B (CTS-B) is a crucial enzyme that is overexpressed in numerous malignancies and contributes to the invasion and metastasis of cancer. Therefore, this study sets out to develop and evaluate an activity-based multimodality theranostic agent targeting CTS-B for cancer imaging and therapy. A CTS-B activity-based probe, BMX2, was synthesized and labeled efficiently with Ga and Y to produce Ga-BMX2 for multimodality imaging and Y-BMX2 for radiation therapy. The affinity and specificity of BMX2 binding with the CTS-B enzyme were determined by fluorescent western blots using recombined active human CTS-B enzyme (rh-CTS-B) and four cancer cell lines including HeLa, HepG2, MCF7, and U87MG, with CA074 as the CTS-B inhibitor for control. Confocal laser scanning microscope imaging and cell uptake measurement were also performed. Then, in vivo PET imaging and fluorescence imaging were acquired on HeLa xenografts. Finally, the therapeutic effect of Y-BMX2 was tested. BMX2 could be specifically activated by rh-CTS-B and stably bound to the enzyme. The binding of BMX2 with CTS-B is time-dependent and enzyme concentration-dependent. Although CTS-B expression varied between cell lines, all showed significant uptake of BMX2 and Ga-BMX2. In vivo optical and PET imaging showed a high tumor uptake of BMX2 and Ga-BMX2 and accumulation for more than 24 h. Y-BMX2 could significantly inhibit HeLa tumor growth. The development of Ga/Y-BMX2, a radioactive and fluorescent dual modality theranostic agent, demonstrated an effective theranostic approach for PET diagnostic imaging, fluorescence imaging, and radionuclide therapy of cancers, which may have a potential for clinical translation for cancer theranostics in the future.
Topics: Humans; Cysteine; Gallium Radioisotopes; Precision Medicine; Fluorescent Dyes; Cathepsin B; Positron-Emission Tomography; Neoplasms; Cell Line, Tumor
PubMed: 37289648
DOI: 10.1021/acs.molpharmaceut.3c00148 -
The British Journal of Radiology Dec 2023Cardiovascular diseases (CVD) are the leading cause of death worldwide and have an increasing impact on society. Precision medicine, in which optimal care is identified... (Review)
Review
Cardiovascular diseases (CVD) are the leading cause of death worldwide and have an increasing impact on society. Precision medicine, in which optimal care is identified for an individual or a group of individuals rather than for the average population, might provide significant health benefits for this patient group and decrease CVD morbidity and mortality. Molecular imaging provides the opportunity to assess biological processes in individuals in addition to anatomical context provided by other imaging modalities and could prove to be essential in the implementation of precision medicine in CVD. New developments in single-photon emission computed tomography (SPECT) and positron emission tomography (PET) systems, combined with rapid innovations in promising and specific radiopharmaceuticals, provide an impressive improvement of diagnostic accuracy and therapy evaluation. This may result in improved health outcomes in CVD patients, thereby reducing societal impact. Furthermore, recent technical advances have led to new possibilities for accurate image quantification, dynamic imaging, and quantification of radiotracer kinetics. This potentially allows for better evaluation of disease activity over time and treatment response monitoring. However, the clinical implementation of these new methods has been slow. This review describes the recent advances in molecular imaging and the clinical value of quantitative PET and SPECT in various fields in cardiovascular molecular imaging, such as atherosclerosis, myocardial perfusion and ischemia, infiltrative cardiomyopathies, systemic vascular diseases, and infectious cardiovascular diseases. Moreover, the challenges that need to be overcome to achieve clinical translation are addressed, and future directions are provided.
Topics: Humans; Cardiovascular Diseases; Precision Medicine; Heart; Tomography, Emission-Computed, Single-Photon; Radiopharmaceuticals; Positron-Emission Tomography
PubMed: 37786997
DOI: 10.1259/bjr.20230704 -
Journal of the American Heart... Dec 2023
Topics: Humans; Acetazolamide; Tomography, X-Ray Computed; Positron-Emission Tomography; Cerebrovascular Disorders; Hemodynamics
PubMed: 38084748
DOI: 10.1161/JAHA.123.032657