Analysis Of Positron Emission Tomography Images Research Articles

Characterizing the binding of TC-5619 and encenicline on the alpha7 nicotinic acetylcholine receptor using PET imaging in the pig.

The alpha7 nicotinic acetylcholine receptor (α7-nAChR) has has long been considered a promising therapeutic target for addressing cognitive impairments associated with a spectrum of neurological and psychiatric disorders, including Alzheimer's disease and schizophrenia. However, despite this potential, clinical trials employing α7-nAChR (partial) agonists such as TC-5619 and encenicline (EVP-6124) have fallen short in demonstrating sufficient efficacy. We here investigate the target engagement of TC-5619 and encenicline in the pig brain by use of the α7-nAChR radioligand 11C-NS14492 to characterize binding both with in vitro autoradiography and in vivo occupancy using positron emission tomography (PET). In vitro autoradiography demonstrates significant concentration-dependent binding of 11C-NS14492, and both TC-5619 and encenicline can block this binding. Of particular significance, our in vivo investigations demonstrate that TC-5619 achieves substantial α7-nAChR occupancy, effectively blocking approximately 40% of α7-nAChR binding, whereas encenicline exhibits more limited α7-nAChR occupancy. This study underscores the importance of preclinical PET imaging and target engagement analysis in informing clinical trial strategies, including dosing decisions.

Integrating Artificial Intelligence and PET Imaging for Drug Discovery: A Paradigm Shift in Immunotherapy.

The integration of artificial intelligence (AI) and positron emission tomography (PET) imaging has the potential to become a powerful tool in drug discovery. This review aims to provide an overview of the current state of research and highlight the potential for this alliance to advance pharmaceutical innovation by accelerating the development and deployment of novel therapeutics. We previously performed a scoping review of three databases (Embase, MEDLINE, and CENTRAL), identifying 87 studies published between 2018 and 2022 relevant to medical imaging (e.g., CT, PET, MRI), immunotherapy, artificial intelligence, and radiomics. Herein, we reexamine the previously identified studies, performing a subgroup analysis on articles specifically utilizing AI and PET imaging for drug discovery purposes in immunotherapy-treated oncology patients. Of the 87 original studies identified, 15 met our updated search criteria. In these studies, radiomics features were primarily extracted from PET/CT images in combination (n = 9, 60.0%) rather than PET imaging alone (n = 6, 40.0%), and patient cohorts were mostly recruited retrospectively and from single institutions (n = 10, 66.7%). AI models were used primarily for prognostication (n = 6, 40.0%) or for assisting in tumor phenotyping (n = 4, 26.7%). About half of the studies stress-tested their models using validation sets (n = 4, 26.7%) or both validation sets and test sets (n = 4, 26.7%), while the remaining six studies (40.0%) either performed no validation at all or used less stringent methods such as cross-validation on the training set. Overall, the integration of AI and PET imaging represents a paradigm shift in drug discovery, offering new avenues for more efficient development of therapeutics. By leveraging AI algorithms and PET imaging analysis, researchers could gain deeper insights into disease mechanisms, identify new drug targets, or optimize treatment regimens. However, further research is needed to validate these findings and address challenges such as data standardization and algorithm robustness.

A Comparison of Arterial Input Function Interpolation Methods for Patlak Plot Analysis of 68Ga-PSMA-11 PET Prostate Cancer Studies.

Positron emission tomography (PET) imaging enables quantitative assessment of tissue physiology. Dynamic pharmacokinetic analysis of PET images requires accurate estimation of the radiotracer plasma input function to derive meaningful parameter estimates, and small discrepancies in parameter estimation can mimic subtle physiologic tissue variation. This study evaluates the impact of input function interpolation method on the accuracy of Patlak kinetic parameter estimation through simulations modeling the pharmacokinetic properties of [68Ga]-PSMA-11. This study evaluated both trained and untrained methods. Although the mean kinetic parameter accuracy was similar across all interpolation models, the trained node weighting interpolation model estimated accurate kinetic parameters with reduced overall variability relative to standard linear interpolation. Trained node weighting interpolation reduced kinetic parameter estimation variance by a magnitude approximating the underlying physiologic differences between normal and diseased prostatic tissue. Overall, this analysis suggests that trained node weighting improves the reliability of Patlak kinetic parameter estimation for [68Ga]-PSMA-11 PET.

In vivo characterization of tau accumulation in patients with frontotemporal dementia: A PET study with 18F‐florzolotau

AbstractBackgroundFrontotemporal dementia (FTD) is a group of neurodegenerative disorders with diverse clinical and neuropathological features. However, in vivo neuropathological assessments of FTD at an individual level have not hitherto been successful. Here, we aimed to classify patients with FTD based on topologies of tau protein aggregates captured by positron emission tomography (PET) with 18F‐florzolotau, which allows high‐contrast imaging of diverse tau fibrils in Alzheimer’s disease (AD) and non‐AD tauopathies.MethodTwenty‐six patients with FTD, consisting of 15 patients with behavioral variant FTD (bvFTD) and 11 patients with other FTD phenotypes, and 20 age‐ and gender‐matched healthy controls were studied. They underwent PET imaging of amyloid and tau depositions with 11C‐PiB and 18F‐florzolotau, respectively.ResultBy combining visual and semiquantitative analyses of PET images, the bvFTD patients were classified into the following subgroups: 1) predominant tau accumulations in frontotemporal and frontolimbic cortices resembling three‐repeat tauopathies (n = 3); 2) predominant tau accumulations in subcortical structures accompanied by various degrees of neocortical accumulations resembling four‐repeat tauopathies (n = 4); 3) amyloid and tau accumulations consistent with AD (n = 4); and 4) no overt amyloid and tau pathologies (n = 4). Despite these distinctions, clinical symptoms and localization of brain atrophy were not significantly different among the identified bvFTD subgroups. Patients with other FTD phenotypes were also classified into similar subgroups.ConclusionTo conclude, PET with 18F‐florzolotau potentially enables the characterization of each individual with FTD on a biological basis, thereby possibly contributing to diagnostic and therapeutic approaches to this illness.

PET4 Response As an Independent Predictor of Long-Term Outcomes in ECHELON2 (A+CHP Vs. CHOP) in CD30+PTCL

Background: Peripheral T-cell lymphomas (PTCLs) are uncommon, heterogeneous, and often aggressive subtypes of lymphoma characterized by a high risk of progression even after combination chemotherapy. The phase III, ECHELON-2 trial showed that the combination of brentuximab vedotin with chemotherapy (A+CHP) in patients (pts) with CD30-positive PTCLs improved progression-free survival (PFS) and overall survival (OS) compared to CHOP. In PTCL, positron emission tomography (PET) is a valuable way to assess disease burden and stage at the time of diagnosis and evaluate treatment response. Prior retrospective studies have shown that interim and end of treatment PET may predict outcomes; however, there are no prospective studies confirming their predictive value. In the ECHELON-2 study, PET4 outcomes were prospectively collected, and the objective of this exploratory analysis is to investigate the potential for interim PET scans to predict treatment response and long-term outcomes. Objective: To evaluate the role of interim 18F-FDG PET imaging (PET4) in predicting end of treatment (EOT) response, progression free survival (PFS), and overall survival (OS) in pts (pts) with CD30+PTCL treated with A+CHP or CHOP in the ECHELON-2 trial. Methods: The ECHELON-2 trial included prospective 18F-FDG PET scans and assessment of treatment response including long-term PFS per investigator and OS. PET4 status was based on Deauville score by Independent Review Facility (IRF) assessment using scans at the cycle 4 response assessment. Deauville scores 1-3 are considered negative (PET4neg) and 4-5 positive (PET4pos). EOT response is the best response after completion of study treatment and prior to long term follow up per Cheson 2007 by IRF assessment. Kaplan-Meier methods were used to estimate PFS and OS; p-values are based on stratified log-rank tests. All analyses are exploratory, and p-values are descriptive. Results: In this study, 452 pts were included, with 226 randomized to the A+CHP treatment arm and 226 to the CHOP treatment arm; median follow up was 66.8 months (range 0-90). Of randomized pts, 32 pts in the A+CHP arm and 41 pts in the CHOP arm were not evaluable for PET4. The overall results showed that the PET4neg evaluable subgroup had a higher proportion of pts achieving complete responses (CR) than PET4pos (80% vs. 9%) at EOT (Table 1). In pts assessed for PET4, pts who were PET4neg had improved PFS and OS in both the A+CHP and CHOP treatment arms (Figure 1). For A+CHP pts, those who achieved PET4neg had an improved PFS [HR 0.36, CI-95 (0.19-0.66), p=0.0006] and OS [HR 0.38, CI-95 (0.18-0.78), p=0.0060] compared to those who were PET4pos. Similarly, pts in the CHOP arm who achieved PET4neg had an improved PFS [HR 0.26, CI-95 (0.17-0.41), p<0.0001] and OS [HR 0.24, CI-95 (0.14-0.41), p< 0.0001] compared to those who were PET4pos. Among pts with anaplastic large cell lymphoma (sALCL) (n=316), 19 pts in the A+CHP arm and 32 in the CHOP arm were not evaluable for PET4. The results in this subgroup show that 128/143 (90%) A+CHP pts who had PET4 assessments achieved PET4neg. These pts experienced improved PFS [HR 0.28, CI-95 (0.14-0.60), p=0.0004] and OS [HR 0.38, CI-95 (0.16-0.94), p 0.0292] compared to PET4pos pts. For CHOP pts who had PET4 assessments 98/122 (80%), achieved PET4neg; these pts experienced improved PFS [HR 0.31, CI-95 (0.12-0.55), p<0.0001] and improved OS [HR 0.25, CI-95 (0.12-0.25), p= 0.0002] compared to PET4pos pts. Conclusion: In an exploratory analysis of interim PET imaging as part of the ECHELON-2 study, PET4neg by Deauville was associated with improved PFS and OS in both the A+CHP and CHOP arms. Our findings support the use of PET4 response in PTCL as a predictor of outcomes in both the A+CHP and CHOP pts. These findings emphasize the potential of PET scans to enhance risk stratification, individualize therapy decisions, and improve pt outcomes in the management of PTCLs. Further analysis will be presented at the meeting.

Regional neuroinflammation induced by peripheral infection contributes to fatigue-like symptoms: a [18F]DPA-714 positron emission tomography study in rats.

A series of symptoms, including fever, widespread pain, fatigue, and even ageusia, have frequently been reported in the context of various infections, such as COVID-19. Although the pathogenic mechanisms underlying an infection causing fever and pain have been well established, the mechanisms of fatigue induced by infection in specific brain regions remain unclear. To elucidate whether and how the peripheral infection cause fatigue via regional neuroinflammation, we performed a brain-wide investigation of neuroinflammation in a peripheral pseudoinfection rat model using [18F]DPA-714 positron emission tomography (PET) imaging analysis, in which the polyriboinosinic: polyribocytidylic acid (poly I:C) was intraperitoneally injected. Transient fever lasting for several hours and subsequent suppression of spontaneous activity lasting a few days were induced by poly I:C treatment. Significant increase in plasma interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α were observed at 2 and 4 h following poly I:C treatment. PET imaging analysis revealed that the brain uptake of [18F]DPA-714 was significantly increased in several brain regions one day after poly I:C treatment, such as the dorsal raphe (DR), parvicellular part of red nucleus (RPC), A5 and A7 noradrenergic nucleus, compared with the control group. The accumulation of [18F]DPA-714 in the DR, RPC and A5 was positively correlated with subsequent fatigue-like behavior, and that in the A7 tended to positively correlate with fever. These findings suggest that peripheral infection may trigger regional neuroinflammation, which may cause specific symptoms such as fatigue. A similar mechanism might be involved in COVID-19.

Development of novel peptide-based radiotracers for detecting PD-L1 expression and guiding cancer immunotherapy.

Due to tumor heterogeneity, immunohistochemistry (IHC) showed poor accuracy in detecting the expression of programmed cell death ligand-1 (PD-L1) in patients. Positron emission tomography (PET) imaging is considered as a non-invasive technique to detect PD-L1 expression at the molecular level visually, real-timely and quantitatively. This study aimed to develop novel peptide-based radiotracers [68Ga]/[18F]AlF-NOTA-IMB for accurately detecting the PD-L1 expression and guiding the cancer immunotherapy. NOTA-IMB was prepared by connecting 2,2'-(7-(2-((2,5-dioxopyrrolidin-1-yl)oxy)- 2-oxoethyl)-1,4,7-triazonane-1,4-diyl) diacetic acid (NOTA-NHS) with PD-L1-targeted peptide IMB, and further radiolabeled with 68Ga or 18F-AlF. In vitro binding assay was conducted to confirm the ability of [68Ga]/[18F]AlF-NOTA-IMB to detect the expression of PD-L1. In vivo PET imaging of [68Ga]NOTA-IMB and [18F]AlF-NOTA-IMB in different tumor-bearing mice was performed, and dynamic changes of PD-L1 expression level induced by immunotherapy were monitored. Radioautography, western blotting, immunofluorescence staining and biodistribution analysis were carried out to further evaluate the specificity of radiotracers and efficacy of PD-L1 antibody immunotherapy. [68Ga]NOTA-IMB and [18F]AlF-NOTA-IMB were both successfully prepared with high radiochemical yield (> 95% and > 60%, n = 5) and radiochemical purity (> 95% and > 98%, n = 5). Both tracers showed high affinity to human and murine PD-L1 with the dissociation constant (Kd) of 1.00 ± 0.16/1.09 ± 0.21nM (A375-hPD-L1, n = 3) and 1.56 ± 0.58/1.21 ± 0.39nM (MC38, n = 3), respectively. In vitro cell uptake assay revealed that both tracers can specifically bind to PD-L1 positive cancer cells A375-hPD-L1 and MC38 (5.45 ± 0.33/3.65 ± 0.15%AD and 5.87 ± 0.27/2.78 ± 0.08%AD at 120min, n = 3). In vivo PET imaging and biodistribution analysis showed that the tracer [68Ga]NOTA-IMB and [18F]AlF-NOTA-IMB had high accumulation in A375-hPD-L1 and MC38 tumors, but low uptake in A375 tumor. Treatment of Atezolizumab induced dynamic changes of PD-L1 expression in MC38 tumor-bearing mice, and the tumor uptake of [68Ga]NOTA-IMB decreased from 3.30 ± 0.29%ID/mL to 1.58 ± 0.29%ID/mL (n = 3, P = 0.026) after five treatments. Similarly, the tumor uptake of [18F]AlF-NOTA-IMB decreased from 3.27 ± 0.63%ID/mL to 0.89 ± 0.18%ID/mL (n = 3, P = 0.0004) after five treatments. However, no significant difference was observed in the tumor uptake before and after PBS treatment. Biodistribution, radioautography, western blotting and immunofluorescence staining analysis further demonstrated that the expression level of PD-L1 in tumor-bearing mice treated with Atezolizumab significantly reduced about 3 times and correlated well with the PET imaging results. [68Ga]NOTA-IMB and [18F]AlF-NOTA-IMB were successfully prepared for PET imaging the PD-L1 expression noninvasively and quantitatively. Dynamic changes of PD-L1 expression caused by immunotherapy can be sensitively detected by both tracers. Hence, the peptide-based radiotracers [68Ga]NOTA-IMB and [18F]AlF-NOTA-IMB can be applied for accurately detecting the PD-L1 expression in different tumors and monitoring the efficacy of immunotherapy.

The prognostic power of [11C]methionine PET in IDH-wildtype diffuse gliomas with lower-grade histological features: venturing beyond WHO classification.

IDH-wildtype (IDH-wt) diffuse gliomas with histological features of lower-grade gliomas (LGGs) are rare and heterogeneous primary brain tumours. [11C]Methionine (MET) positron emission tomography (PET) is commonly used to evaluate glial neoplasms at diagnosis. The present study aimed to assess the prognostic value of MET PET in newly diagnosed, treatment naïve IDH-wt gliomas with histological features of LGGs. Patients with a histological diagnosis of IDH-wt LGG who underwent preoperative (< 100days) MET PET/CT and surgery were retrospectively included. Qualitative and semi-quantitative analyses of MET PET images were performed. Progression-free survival (PFS) and overall survival (OS) were analysed by Kaplan-Meier curves. Cox proportional-hazards regression was used to test the association of imaging and clinical data to PFS and OS. We included 48 patients (M:F = 25:23; median age 55). 39 lesions were positive and 9 negative at MET PET. Positive MET PET was significantly associated with shorter median PFS (15.7months vs. not reached, p = 0.0146) and OS time (32.6months vs. not reached, p = 0.0253). Incomplete surgical resection and higher TBRmean values were independent predictors of shorter PFS on multivariate analysis (p < 0.001 for both). Higher tumour grade and incomplete surgical resection were independent predictors of OS at multivariate analysis (p = 0.027 and p = 0.01, respectively). MET PET is useful for the prognostic stratification of patients with IDH-wt glial neoplasms with histological LGGs features. Considering their huge biological heterogeneity, the combination of MET PET and molecular analyses may help to improve the prognostic accuracy in these diffuse gliomas subset and influence therapeutic choices accordingly.

Validation of quantitative assessment of florbetaben PET scans as an adjunct to the visual assessment across 15 software methods.

Amyloid positron emission tomography (PET) with [18F]florbetaben (FBB) is an established tool for detecting Aβ deposition in the brain in vivo based on visual assessment of PET scans. Quantitative measures are commonly used in the research context and allow continuous measurement of amyloid burden. The aim of this study was to demonstrate the robustness of FBB PET quantification. This is a retrospective analysis of FBB PET images from 589 subjects. PET scans were quantified with 15 analytical methods using nine software packages (MIMneuro, Hermes BRASS, Neurocloud, Neurology Toolkit, statistical parametric mapping (SPM8), PMOD Neuro, CapAIBL, non-negative matrix factorization (NMF), AmyloidIQ) that used several metrics to estimate Aβ load (SUVR, centiloid, amyloid load, and amyloid index). Six analytical methods reported centiloid (MIMneuro, standard centiloid, Neurology Toolkit, SPM8 (PET only), CapAIBL, NMF). All results were quality controlled. The mean sensitivity, specificity, and accuracy were 96.1 ± 1.6%, 96.9 ± 1.0%, and 96.4 ± 1.1%, respectively, for all quantitative methods tested when compared to histopathology, where available. The mean percentage of agreement between binary quantitative assessment across all 15 methods and visual majority assessment was 92.4 ± 1.5%. Assessments of reliability, correlation analyses, and comparisons across software packages showed excellent performance and consistent results between analytical methods. This study demonstrated that quantitative methods using both CE marked software and other widely available processing tools provided comparable results to visual assessments of FBB PET scans. Software quantification methods, such as centiloid analysis, can complement visual assessment of FBB PET images and could be used in the future for identification of early amyloid deposition, monitoring disease progression and treatment effectiveness.

A Protocol for Simultaneous In Vivo Imaging of Cardiac and Neuroinflammation in Dystrophin-Deficient MDX Mice Using [18F]FEPPA PET.

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by dystrophin loss-notably within muscles and the central neurons system. DMD presents as cognitive weakness, progressive skeletal and cardiac muscle degeneration until pre-mature death from cardiac or respiratory failure. Innovative therapies have improved life expectancy; however, this is accompanied by increased late-onset heart failure and emergent cognitive degeneration. Thus, better assessment of dystrophic heart and brain pathophysiology is needed. Chronic inflammation is strongly associated with skeletal and cardiac muscle degeneration; however, neuroinflammation's role is largely unknown in DMD despite being prevalent in other neurodegenerative diseases. Here, we present an inflammatory marker translocator protein (TSPO) positron emission tomography (PET) protocol for in vivo concomitant assessment of immune cell response in hearts and brains of a dystrophin-deficient mouse model [mdx:utrn(+/-)]. Preliminary analysis of whole-body PET imaging using the TSPO radiotracer, [18F]FEPPA in four mdx:utrn(+/-) and six wildtype mice are presented with ex vivo TSPO-immunofluorescence tissue staining. The mdx:utrn(+/-) mice showed significant elevations in heart and brain [18F]FEPPA activity, which correlated with increased ex vivo fluorescence intensity, highlighting the potential of TSPO-PET to simultaneously assess presence of cardiac and neuroinflammation in dystrophic heart and brain, as well as in several organs within a DMD model.

Quantitative comparative analysis of amyloid PET images using three radiopharmaceuticals

ObjectiveAmyloid positron emission tomography (PET) with F-18 florbetaben (FBB), F-18 flutemetamol (FMM), and F-18 florapronol (FPN) is being used clinically for the evaluation of dementia. These radiopharmaceuticals are commonly used to evaluate the accumulation of beta-amyloid plaques in the brain, but there are structural differences between them. We investigated whether there are any differences in the imaging characteristics.MethodsA total of 605 subjects were enrolled retrospectively in this study, including healthy subjects (HS) and patients with mild cognitive impairment or Alzheimer’s disease. Participants underwent amyloid PET imaging using one of the three radiopharmaceuticals. The PET images were analyzed visually and semi-quantitatively using a standardized uptake value ratio (SUVR). In addition, we calculated and compared the cut-off SUVR of the representative regions for each radiopharmaceutical that can distinguish between positive and negative scans.ResultsIn the negative images of the HS group, the contrast between the white matter and the gray matter was high in the FMM PET images, while striatal uptake was relatively higher in the FPN PET images. The SUVR showed significant differences across the radiopharmaceuticals in all areas except the temporal lobe, but the range of differences was relatively small. Accuracy levels for the global cut-off SUVR to discriminate between positive and negative images were highest in FMM PET, with a value of 0.989. FBB PET also showed a high value of 0.978, while FPN PET showed a relatively low value of 0.901.ConclusionsNegative amyloid PET images using the three radiopharmaceuticals showed visually and quantitatively similar imaging characteristics except in the striatum. Binary classification using the cut-off of the global cortex showed high accuracy overall, although there were some differences between the three PET images.

Acute Left Atrial Myocarditis due to Close Contact With Inflammatory Nodes and Identified by Combined Cardiac Magnetic Resonance and 68Ga-Dotatoc Positron Emission Tomography Image Analysis.

HomeCirculation: Cardiovascular ImagingAhead of PrintAcute Left Atrial Myocarditis due to Close Contact With Inflammatory Nodes and Identified by Combined Cardiac Magnetic Resonance and 68Ga-Dotatoc Positron Emission Tomography Image Analysis No AccessCase ReportRequest AccessAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplementary MaterialsNo AccessCase ReportRequest AccessAcute Left Atrial Myocarditis due to Close Contact With Inflammatory Nodes and Identified by Combined Cardiac Magnetic Resonance and 68Ga-Dotatoc Positron Emission Tomography Image Analysis Caroline Boursier, MD, Orianne Weizman, MD, MPH, Elodie Chevalier, MD, Laetitia Imbert, PhD, Damien Mandry, MD, PhD, Jeanne Varlot, MD, Arnaud Hueber, MD and Pierre-Yves Marie, MD, PhD Caroline BoursierCaroline Boursier Department of Nuclear Medicine, Université de Lorraine, and Nancyclotep Imaging Platform, CHRU-Nancy, F-54000, Nancy, France. (C.B., E.C., L.I., P.-Y.M.) Search for more papers by this author , Orianne WeizmanOrianne Weizman https://orcid.org/0000-0002-1527-0332 Department of Cardiology, Claude Bernard Clinic Hospital, Metz, France (O.W., A.H.). Search for more papers by this author , Elodie ChevalierElodie Chevalier Department of Nuclear Medicine, Université de Lorraine, and Nancyclotep Imaging Platform, CHRU-Nancy, F-54000, Nancy, France. (C.B., E.C., L.I., P.-Y.M.) Search for more papers by this author , Laetitia ImbertLaetitia Imbert Department of Nuclear Medicine, Université de Lorraine, and Nancyclotep Imaging Platform, CHRU-Nancy, F-54000, Nancy, France. (C.B., E.C., L.I., P.-Y.M.) IADI, INSERM, UMR 1254, Université de Lorraine, Nancy, France (L.I., D.M.). Search for more papers by this author , Damien MandryDamien Mandry Department of Radiology, CHRU-Nancy, F-54000, Nancy, France. (D.M.) IADI, INSERM, UMR 1254, Université de Lorraine, Nancy, France (L.I., D.M.). Search for more papers by this author , Jeanne VarlotJeanne Varlot Department of Cardiology, CHRU-Nancy, F-54000, Nancy, France (J.V.). Université de Lorraine, INSERM, UMR 1116, 54000, Nancy, France (J.V., P.-Y.M.). Search for more papers by this author , Arnaud HueberArnaud Hueber Department of Cardiology, Claude Bernard Clinic Hospital, Metz, France (O.W., A.H.). Search for more papers by this author and Pierre-Yves MariePierre-Yves Marie Correspondence to: Pierre-Yves Marie, MD, PhD, Médecine Nucléaire, CHRU-Nancy, Hôpital de Brabois, Allée du Morvan, 54500 Vandoeuvre, France. Email E-mail Address: [email protected] https://orcid.org/0000-0001-7319-3737 Department of Nuclear Medicine, Université de Lorraine, and Nancyclotep Imaging Platform, CHRU-Nancy, F-54000, Nancy, France. (C.B., E.C., L.I., P.-Y.M.) Université de Lorraine, INSERM, UMR 1116, 54000, Nancy, France (J.V., P.-Y.M.). Search for more papers by this author Originally published30 Jan 2023https://doi.org/10.1161/CIRCIMAGING.122.014770Circulation: Cardiovascular Imaging. 2023;0:e014770FootnotesSupplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCIMAGING.122.014770.For Sources of Funding and Disclosures, see page XXX.Correspondence to: Pierre-Yves Marie, MD, PhD, Médecine Nucléaire, CHRU-Nancy, Hôpital de Brabois, Allée du Morvan, 54500 Vandoeuvre, France. Email p.[email protected]fr Previous Back to top Next FiguresReferencesRelatedDetails Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.122.014770PMID: 36715021 Originally publishedJanuary 30, 2023 Keywordsmagnetic resonance imaginglymph nodessomatostatin receptorsmyocarditispositron emission tomographyPDF download Advertisement SubjectsMagnetic Resonance Imaging (MRI)Nuclear Cardiology and PET

Probabilistic deconvolution of PET images using informed priors

PurposeWe present a probabilistic approach to medical image analysis that requires, and makes use of, explicit prior information provided by a medical expert. Depending on the choice of prior model the method can be used for image enhancement, analysis, and segmentation.MethodsThe methodology is based on a probabilistic approach to medical image analysis, that allows integration of 1) arbitrarily complex prior information (for which realizations can be generated), 2) information about a convolution operator of the imaging system, and 3) information about the noise in the reconstructed image into a posterior probability density. The method was demonstrated on positron emission tomography (PET) images obtained from a phantom and a patient with lung cancer. The likelihood model (multivariate log-normal) and the convolution operator were derived from phantom data. Two examples of prior information were used to show the potential of the method. The extended Metropolis-Hastings algorithm, a Markov chain Monte Carlo method, was used to generate realizations of the posterior distribution of the tracer activity concentration.ResultsA set of realizations from the posterior was used as the base of a quantitative PET image analysis. The mean and variance of activity concentrations were computed, as well as the probability of high tracer uptake and statistics on the size and activity concentration of high uptake regions. For both phantom and in vivo images, the estimated images of mean activity concentrations appeared to have reduced noise levels, and a sharper outline of high activity regions, as compared to the original PET. The estimated variance of activity concentrations was high at the edges of high activity regions.ConclusionsThe methodology provides a probabilistic approach for medical image analysis that explicitly takes into account medical expert knowledge as prior information. The presented first results indicate the potential of the method to improve the detection of small lesions. The methodology allows for a probabilistic measure of the size and activity level of high uptake regions, with possible long-term perspectives for early detection of cancer, as well as treatment, planning, and follow-up.

PET imaging studies to investigate functional expression of mGluR2 using [11C]mG2P001

Metabotropic glutamate receptor 2 (mGluR2) has been extensively studied for the treatment of various neurological and psychiatric disorders. Understanding of the mGluR2 function is pivotal in supporting the drug discovery targeting mGluR2. Herein, the positive allosteric modulation of mGluR2 was investigated via the in vivo positron emission tomography (PET) imaging using 2-((4-(2-[11C]methoxy-4-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)-1-methyl-1H-imidazo[4,5-b]pyridine ([11C]mG2P001). Distinct from the orthosteric compounds, pretreatment with the unlabeled mG2P001, a potent mGluR2 positive allosteric modulator (PAM), resulted in a significant increase instead of decrease of the [11C]mG2P001 accumulation in rat brain detected by PET imaging. Subsequent in vitro studies with [3H]mG2P001 revealed the cooperative binding mechanism of mG2P001 with glutamate and its pharmacological effect that contributed to the enhanced binding of [3H]mG2P001 in transfected CHO cells expressing mGluR2. The in vivo PET imaging and quantitative analysis of [11C]mG2P001 in non-human primates (NHPs) further validated the characteristics of [11C]mG2P001 as an imaging ligand for mGluR2. Self-blocking studies in primates enhanced accumulation of [11C]mG2P001. Altogether, these studies show that [11C]mG2P001 is a sensitive biomarker for mGluR2 expression and the binding is affected by the tissue glutamate concentration.

Processing speed dysfunction is associated with functional corticostriatal circuit alterations in childhood epilepsy with centrotemporal spikes: a PET and fMRI study

PurposeEpilepsy with centrotemporal spikes (ECTS) is the most common epilepsy syndrome in children and usually presents with cognitive dysfunctions. However, little is known about the processing speed dysfunction and the associated neuroimaging mechanism in ECTS. This study aims to investigate the brain functional abnormality of processing speed dysfunction in ECTS patients by using the 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI).MethodsThis prospective study recruited twenty-eight ECTS patients who underwent the 18F-FDG PET, rs-fMRI, and neuropsychological examinations. Twenty children with extracranial tumors were included as PET controls, and 20 healthy children were recruited as MRI controls. The PET image analysis investigated glucose metabolism by determining standardized uptake value ratio (SUVR). The MRI image analysis explored abnormal functional connectivity (FC) within the cortical–striatal circuit through network-based statistical (NBS) analysis. Correlation analysis was performed to explore the relationship between SUVR, FC, and processing speed index (PSI).ResultsCompared with healthy controls, ECTS patients showed normal intelligence quotient but significantly decreased PSI (P = 0.04). PET analysis showed significantly decreased SUVRs within bilateral caudate, putamen, pallidum, left NAc, right rostral middle frontal gyrus, and frontal pole of ECTS patients (P < 0.05). Rs-fMRI analysis showed absolute values of 20 FCs were significantly decreased in ECTS patients compared with MRI controls, which connected 16 distinct ROIs. The average SUVR of right caudate and the average of 20 FCs were positively correlated with PSI in ECTS patients (P = 0.034 and P = 0.005, respectively).ConclusionThis study indicated that ECTS patients presented significantly reduced PSI, which is closely associated with decreased SUVR and FC of cortical–striatal circuit. Caudate played an important role in processing speed dysfunction.Clinical trial registrationNCT04954729; registered on July 8, 2021, public site, https://clinicaltrials.gov/ct2/show/NCT04954729

A Prospective Investigation of Tumor Hypoxia Imaging with 68Ga-Nitroimidazole PET/CT in Patients with Carcinoma of the Cervix Uteri and Comparison with 18F-FDG PET/CT: Correlation with Immunohistochemistry.

Hypoxia in cervical cancer has been associated with a poor prognosis. Over the years 68Ga labelled nitroimidazoles have been studied and have shown improved kinetics. We present our initial experience of hypoxia Positron Emission Tomography (PET) imaging in cervical cancer with 68Ga-Nitroimidazole derivative and the correlation with 18F-FDG PET/CT and immunohistochemistry. Twenty women with cervical cancer underwent both 18F-FDG and 68Ga-Nitroimidazole PET/CT imaging. Dual-point imaging was performed for 68Ga-Nitroimidazole PET. Immunohistochemical analysis was performed with hypoxia inducible factor-1α (HIF-1α). We documented SUVmax, SUVmean of the primary lesions as well as tumor to muscle ratio (TMR), tumor to blood (TBR), metabolic tumor volume (MTV) and hypoxic tumor volume (HTV). There was no significant difference in the uptake of 68Ga-Nitroimidazole between early and delayed imaging. Twelve patients had uptake on 68Ga-Nitroimidazole PET. Ten patients demonstrated varying intensities of HIF-1α expression and six of these also had uptake on 68Ga-Nitroimidazole PET. We found a strong negative correlation between HTV and immunohistochemical staining (r = −0.660; p = 0.019). There was no correlation between uptake on PET imaging and immunohistochemical analysis with HIF-1α. Two-thirds of the patients demonstrated hypoxia on 68Ga-Nitroimidazole PET imaging.

Short-Term Efficacy of Transcranial Focused Ultrasound to the Hippocampus in Alzheimer's Disease: A Preliminary Study.

Preclinical studies have suggested that low-intensity transcranial focused ultrasound (tFUS) may have therapeutic potential for Alzheimer’s disease (AD) by opening the blood–brain barrier (BBB), reducing amyloid pathology, and improving cognition. This study investigated the effects of tFUS on BBB opening, regional cerebral metabolic rate of glucose (rCMRglu), and cognitive function in AD patients. Eight patients with AD received image-guided tFUS to the right hippocampus immediately after intravenous injection of microbubble ultrasound contrast agents. Patients completed magnetic resonance imaging (MRI), 18F-fluoro-2-deoxyglucose positron emission tomography (PET), and cognitive assessments before and after the sonication. No evidence of transient BBB opening was found on T1 dynamic contrast-enhanced MRI. However, immediate recall (p = 0.03) and recognition memory (p = 0.02) were significantly improved on the verbal learning test. PET image analysis demonstrated increased rCMRglu in the right hippocampus (p = 0.001). In addition, increases of hippocampal rCMRglu were correlated with improvement in recognition memory (Spearman’s ρ = 0.77, p = 0.02). No adverse event was observed. Our results suggest that tFUS to the hippocampus of AD patients may improve rCMRglu of the target area and memory in the short term, even without BBB opening. Further larger sham-controlled trials with loger follow-up are warranted to evaluate the efficacy and safety of tFUS in patients with AD.

From positron emission tomography to cell analysis of the 18-kDa Translocator Protein in mild traumatic brain injury

Traumatic brain injury (TBI) leads to a deleterious neuroinflammation, originating from microglial activation. Monitoring microglial activation is an indispensable step to develop therapeutic strategies for TBI. In this study, we evaluated the use of the 18-kDa translocator protein (TSPO) in positron emission tomography (PET) and cellular analysis to monitor microglial activation in a mild TBI mouse model. TBI was induced on male Swiss mice. PET imaging analysis with [18F]FEPPA, a TSPO radiotracer, was performed at 1, 3 and 7 days post-TBI and flow cytometry analysis on brain at 1 and 3 days post-TBI. PET analysis showed no difference in TSPO expression between non-operated, sham-operated and TBI mice. Flow cytometry analysis demonstrated an increase in TSPO expression in ipsilateral brain 3 days post-TBI, especially in microglia, macrophages, lymphocytes and neutrophils. Moreover, microglia represent only 58.3% of TSPO+ cells in the brain. Our results raise the question of the use of TSPO radiotracer to monitor microglial activation after TBI. More broadly, flow cytometry results point the lack of specificity of TSPO for microglia and imply that microglia contribute to the overall increase in TSPO in the brain after TBI, but is not its only contributor.

Texture analysis of 18F-FDG PET images for the detection of cervical lymph node metastases in patients with oral squamous cell carcinoma

ObjectivesThis study aimed to determine whether texture analysis of positron emission tomography (PET) images from patients with oral squamous cell carcinoma (OSCC) can accurately diagnose cervical lymph node (LN) metastases. MethodsWe conducted a retrospective chart review of 166 patients with newly pathologically diagnosed OSCC. The patient inclusion criteria were LNs exhibiting high 18F-fluorodeoxyglucose uptake [maximum standardised uptake value (SUVmax) ≥2.5] and/or LNs diagnosed as metastatic cervical LNs by a board-certified nuclear medicine physician, irrespective of the SUVmax value. The patient exclusion criteria were LNs with a metabolic tumour volume (MTV) of ≤1.0 cm3. The primary predictor variables were 31 textural indices, SUVmax and MTV. The diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analysis. ResultsAnalyses of 91 cervical LNs (48 positives, 43 negatives) indicated that long-run emphasis (LRE) could demonstrate the highest area under the ROC curve (AUC) of 0.809. Comparison of the AUCs between SUVmax and LRE indicated that the AUC of LRE was marginally higher than that of SUVmax (p = 0.067). Furthermore, the diagnostic performance of the combination of SUVmax and LRE was more accurate than that of SUVmax alone (p = 0.04). ConclusionsThe combination of SUVmax and LRE may improve the diagnostic accuracy of determining cervical LN metastases.

Dynamic 18F-FDopa PET Imaging for Newly Diagnosed Gliomas: Is a Semiquantitative Model Sufficient?

PurposeDynamic amino acid positron emission tomography (PET) has become essential in neuro-oncology, most notably for its prognostic value in the noninvasive prediction of isocitrate dehydrogenase (IDH) mutations in newly diagnosed gliomas. The 6-[18F]fluoro-l-DOPA (18F-FDOPA) kinetic model has an underlying complexity, while previous studies have predominantly used a semiquantitative dynamic analysis. Our study addresses whether a semiquantitative analysis can capture all the relevant information contained in time–activity curves for predicting the presence of IDH mutations compared to the more sophisticated graphical and compartmental models.MethodsThirty-seven tumour time–activity curves from 18F-FDOPA PET dynamic acquisitions of newly diagnosed gliomas (median age = 58.3 years, range = 20.3–79.9 years, 16 women, 16 IDH-wild type) were analyzed with a semiquantitative model based on classical parameters, with (SQ) or without (Ref SQ) a reference region, or on parameters of a fit function (SQ Fit), a graphical Logan model with input function (Logan) or reference region (Ref Logan), and a two-tissue compartmental model previously reported for 18F-FDOPA PET imaging of gliomas (2TCM). The overall predictive performance of each model was assessed with an area under the curve (AUC) comparison using multivariate analysis of all the parameters included in the model. Moreover, each extracted parameter was assessed in a univariate analysis by a receiver operating characteristic curve analysis.ResultsThe SQ model with an AUC of 0.733 for predicting IDH mutations showed comparable performance to the other models with AUCs of 0.752, 0.814, 0.693, 0.786, and 0.863, respectively corresponding to SQ Fit, Ref SQ, Logan, Ref Logan, and 2TCM (p ≥ 0.10 for the pairwise comparisons with other models). In the univariate analysis, the SQ time-to-peak parameter had the best diagnostic performance (75.7% accuracy) compared to all other individual parameters considered.ConclusionsThe SQ model circumvents the complexities of the 18F-FDOPA kinetic model and yields similar performance in predicting IDH mutations when compared to the other models, most notably the compartmental model. Our study provides supportive evidence for the routine clinical application of the SQ model for the dynamic analysis of 18F-FDOPA PET images in newly diagnosed gliomas.