Dynamic Positron Emission Tomography Imaging Research Articles

Compartmental modeling for blood flow quantification from dynamic O-water PET images of humans: a systematic review.

Dynamic positron emission tomography (PET) can be used to non-invasively estimate the blood flow of different organs via compartmental modeling. Out of different PET tracers, water labeled with the radioactive O isotope of oxygen (half-life of 2.04min) is freely diffusable, and therefore, very well-suited for blood flow quantification. While the earlier O-water PET research has primarily focused on cerebral or myocardial blood flow quantification, the recent emergence of total-body PET scanners has enabled greater application possibilities for both PET imaging in general and also O-water PET based blood flow quantification in particular. However, to validate new methods, it is necessary to compare them to earlier research. To help in this process, we systematically review 53 articles quantifying blood flow via compartmental modeling. We introduce the articles organized within subcategories of cerebral, myocardial, renal, pulmonary, pancreatic, hepatic, muscle, and tumor blood flow and summarize their results so that they can easily be evaluated in terms of population characteristics of the patients such as age or sex ratio and their potential diagnoses. We compare how both the compartment model used and the potential corrections for arterial blood volume, non-perfusable tissue, spill-over from the heart cavities, and time delay caused while the tracer travels between different areas of interest are generally implemented in the articles. We also analyze the differences in the data pre-processing techniques. According to our results, the estimates of cerebral and tumor blood flow vary considerably more between the articles than those of myocardial blood flow. This might be caused by differences in the model approaches or the study populations. We also note that the choice of the unit for these estimates is quite inconsistent as certain researchers seem to prefer mL/min/g over mL/min/mL even if no weight or density parameter is present in the modeling. We encourage more research on sex- and age-based differences in blood flow estimates and organ-specific blood flow quantification studies for kidneys, lungs, liver, and other important organs besides brain and heart.

Convergence of Poisson point processes and of optimal transport regularization with application in variational analysis of PET reconstruction

Abstract Poisson distributed measurements in inverse problems often stem from Poisson point processes that are observed through discretized or finite-resolution detectors, one of the most prominent examples being positron emission tomography (PET). These inverse problems are typically reconstructed via Bayesian methods. A natural question then is whether and how the reconstruction converges as the signal-to-noise ratio tends to infinity and how this convergence interacts with other parameters such as the detector size. In this article we carry out a corresponding variational analysis for the exemplary Bayesian reconstruction functional from [1,2], which considers dynamic PET imaging (i.e. the object to be reconstructed changes over time) and uses an optimal transport regularization.

A deep learning method for total-body dynamic PET imaging with dual-time-window protocols.

Prolonged scanning durations are one of the primary barriers to the widespread clinical adoption of dynamic Positron Emission Tomography (PET). In this paper, we developed a deep learning algorithm that capable of predicting dynamic images from dual-time-window protocols, thereby shortening the scanning time. This study includes 70 patients (mean age ± standard deviation, 53.61 ± 13.53years; 32 males) diagnosed with pulmonary nodules or breast nodules between 2022 to 2024. Each patient underwent a 65-min dynamic total-body [18F]FDG PET/CT scan. Acquisitions using early-stop protocols and dual-time-window protocols were simulated to reduce the scanning time. To predict the missing frames, we developed a bidirectional sequence-to-sequence model with attention mechanism (Bi-AT-Seq2Seq); and then compared the model with unidirectional or non-attentional models in terms of Mean Absolute Error (MAE), Bias, Peak Signal-to-Noise Ratio (PSNR), and Structural Similarity (SSIM) of predicted frames. Furthermore, we reported the comparison of concordance correlation coefficient (CCC) of the kinetic parameters between the proposed method and traditional methods. The Bi-AT-Seq2Seq significantly outperform unidirectional or non-attentional models in terms of MAE, Bias, PSNR, and SSIM. Using a dual-time-window protocol, which includes a 10-min early scan followed by a 5-min late scan, improves the four metrics of predicted dynamic images by 37.31%, 36.24%, 7.10%, and 0.014% respectively, compared to the early-stop protocol with a 15-min acquisition. The CCCs of tumor' kinetic parameters estimated with recovered full time-activity-curves (TACs) is higher than those with abbreviated TACs. The proposed algorithm can accurately generate a complete dynamic acquisition (65min) from dual-time-window protocols (10 + 5min).

18F-FET PET/CT can aid in diagnosing patients with indeterminate MRI findings for brain tumors: a prospective study.

This prospective study aimed to evaluate the diagnostic value of fluorine-18-labeled fluoroethyltyrosine (18F-FET) positron emission tomography (PET)/computed tomography (CT) in diagnosing brain tumors within an Asian patient population. Patients suspected of having primary or recurrent brain tumors were prospectively recruited. Each patient underwent 18F-FET and fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT on separate days within 1week. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy to compare the diagnostic performance of the two PET scans. The standardized uptake value (SUV) and tumor-to-background ratio (TBR) of the lesions were determined using static images. Additionally, time-activity curves (TACs) and time-to-peak (TTP) were generated from the dynamic PET images. From September 2019 to December 2023, 33 subjects were enrolled for reasons including suspected brain tumors (n = 20) or suspicious glioma recurrence (n = 8) on magnetic resonance imaging (MRI) and restaging for glioma (n = 5). Among the patients with suspected brain tumors or glioma recurrence on MRI, 25% had false-positive results. 18F-FET PET/CT accurately identified 86% of these false positives. The sensitivity, specificity, PPV, NPV, and accuracy of visual interpretation of 18F-FET PET/CT were 96.2%, 85.7%, 96.2%, 85.7%, and 93.9%, respectively. The corresponding 18F-FDG PET/CT values were 73.1%, 71.4%, 90.5%, 41.7%, and 72.7%. 18F-FET PET/CT demonstrated significantly higher sensitivity and accuracy than 18F-FDG PET (p = 0.031 and p = 0.030, respectively). Using TBRmean as an adjunct reference index enhanced the diagnostic accuracy of 18F-FET PET/CT, achieving a sensitivity and NPV of 100%. Wash-out TAC or TTP < 20min was associated with a PPV of 100% for brain tumors. 18F-FET PET/CT appears to be a valuable tool for assessing brain tumors with indeterminate MRI findings in this Asian cohort. 18F-FET PET/CT offers benefits over 18F-FDG PET in differentiating brain tumors from nontumor brain lesions, particularly when using semiquantitative analysis with TBR. This study was registered on CinicalTrial.gov (NCT06563024).

Cross-sectional and longitudinal relationships among blood-brain barrier disruption, Alzheimer's disease biomarkers, and cognition in cognitively normal older adults

Blood-brain barrier disruption (BBBd) occurs in aging, particularly in regions vulnerable to Alzheimer’s disease (AD) pathology. However, its relationship to pathological protein accumulation, neurodegeneration, and cognitive impairment in normal aging is unclear. We used dynamic contrast-enhanced MRI (DCE-MRI) and positron emission tomography (PET) imaging in cognitively normal older adults to explore how BBBd correlates with brain atrophy and cognitive function, and whether these relationships are influenced by Aβ or tau. We found that greater BBBd in the hippocampus (HC) and an averaged BBBd-susceptible ROI were linked to worse episodic memory, with interactions between BBBd and atrophy influencing this relationship, independent of Aβ and tau. However, there were no significant relationships between BBBd and non-memory cognitive performance. In participants with longitudinal AD biomarker and cognitive data acquired prior to DCE-MRI, faster longitudinal entorhinal cortex (EC) tau accumulation and episodic memory decline were associated with greater HC BBBd, independent of global Aβ changes and regional atrophy. These findings enhance our understanding of the complex relationships between AD biomarkers, cognitive decline, and BBBd.

Bidirectional dynamic frame prediction network for total-body [68Ga]Ga-PSMA-11 and [68Ga]Ga-FAPI-04 PET images

PurposeTotal-body dynamic positron emission tomography (PET) imaging with total-body coverage and ultrahigh sensitivity has played an important role in accurate tracer kinetic analyses in physiology, biochemistry, and pharmacology. However, dynamic PET scans typically entail prolonged durations (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\ge\\:$$\\end{document}60 minutes), potentially causing patient discomfort and resulting in artifacts in the final images. Therefore, we propose a dynamic frame prediction method for total-body PET imaging via deep learning technology to reduce the required scanning time.MethodsOn the basis of total-body dynamic PET data acquired from 13 subjects who received [68Ga]Ga-FAPI-04 (68Ga-FAPI) and 24 subjects who received [68Ga]Ga-PSMA-11 (68Ga-PSMA), we propose a bidirectional dynamic frame prediction network that uses the initial and final 10 min of PET imaging data (frames 1–6 and frames 25–30, respectively) as inputs. The peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) were employed as evaluation metrics for an image quality assessment. Moreover, we calculated parametric images (68Ga-FAPI: \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{K}_{1}$$\\end{document}, 68Ga-PSMA: \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{K}_{i}$$\\end{document}) based on the supplemented sequence data to observe the quantitative accuracy of our approach. Regions of interest (ROIs) and statistical analyses were utilized to evaluate the performance of the model.ResultsBoth the visual and quantitative results illustrate the effectiveness of our approach. The generated dynamic PET images yielded PSNRs of 36.056 ± 0.709 dB for the 68Ga-PSMA group and 33.779 ± 0.760 dB for the 68Ga-FAPI group. Additionally, the SSIM reached 0.935 ± 0.006 for the 68Ga-FAPI group and 0.922 ± 0.009 for the 68Ga-PSMA group. By conducting a quantitative analysis on the parametric images, we obtained PSNRs of 36.155 ± 4.813 dB (68Ga-PSMA, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{K}_{1}$$\\end{document}) and 43.150 ± 4.102 dB (68Ga-FAPI, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{K}_{i}$$\\end{document}). The obtained SSIM values were 0.932 ± 0.041 (68Ga-PSMA) and 0.980 ± 0.011 (68Ga-FAPI). The ROI analysis conducted on our generated dynamic PET sequences also revealed that our method can accurately predict temporal voxel intensity changes, maintaining overall visual consistency with the ground truth.ConclusionIn this work, we propose a bidirectional dynamic frame prediction network for total-body 68Ga-PSMA and 68Ga-FAPI PET imaging with a reduced scan duration. Visual and quantitative analyses demonstrated that our approach performed well when it was used to predict one-hour dynamic PET images. https://github.com/OPMZZZ/BDF-NET.

Effects of List-Mode-Based Intraframe Motion Correction in Dynamic Brain PET Imaging.

Motion is unavoidable in dynamic [18F]-MK6240 Positron Emission Tomography (PET) imaging, especially in Alzheimer's disease (AD) research requiring long scan duration. To understand how motion correction affects quantitative analysis, we investigated two approaches: II-MC, which corrects for both inter-frame and intra-frame motion, and IO-MC, which only corrects for inter-frame motion. These methods were applied to 83 scans from 34 subjects, and we calculated distribution volume ratios (DVR) using the multilinear reference tissue model with two parameters (MRTM2) in tau-rich brain regions. Most of the studies yielded similar DVR results for both II-MC and IO-MC. However, in one scan of an AD subject, the inferior temporal region showed 14% higher DVR with II-MC compared to IO-MC. This difference was reasonable given the AD diagnosis, although similar results were not observed in other regions. Although discrepancies between IO-MC and II-MC results were rare, they underscore the importance of incorporating intra-frame motion correction for more accurate and dependable PET quantitation, particularly in the context of dynamic imaging. These findings suggest that while the overall impact of intra-frame motion correction may be subtle, it can improve the reliability of longitudinal PET data, ultimately enhancing our understanding of tau protein distribution in AD pathology.

18F-Florbetaben PET/CT for the Diagnosis and Subtyping of Cardiac Amyloidosis: A Case Series and Review of the Literature.

Cardiac amyloidosis (CA) is a type of systemic amyloidosis. Amyloid-targeting positron emission tomography (PET) has shown potential as an imaging method for CA. However, the optimal imaging protocol and role of 18F-florbetaben (FBB) PET in the diagnosis and subtyping of CA have yet to be determined. Patients with suspected CA who had positive or equivocal results of technetium-99m pyrophosphate (PYP) scintigraphy were enrolled for dynamic and late FBB PET imaging. In addition to visual assessment, a kinetic modeling-based approach including target-to-background ratio (TBR) and myocardial retention fraction (RF) of serial images reconstructed from a 20-min dynamic acquisition, and a late image at 110 min post-injection were performed. We compared FBB PET measures of four typical patients with light chain amyloidosis (AL), wild-type transthyretin amyloidosis (ATTRwt), variant transthyretin amyloidosis (ATTRv), and heart failure, respectively. We also reviewed the literature on the clinical use of amyloid PET in CA. Myocardial tracer retention was only found in the AL patient on the late images. TBR and RF were highest in the AL patient followed by the ATTRwt patient, and lowest in the ATTRv and non-CA patients. FBB PET has potential in the detection and non-invasive subtyping of CA, especially in subjects with equivocal PYP findings or monoclonal gammopathy.

Kappa opioid receptor availability predicts severity of anhedonia in schizophrenia.

The kappa opioid receptor (KOR) and its endogenous agonist dynorphin have been implicated in multiple psychiatric conditions including psychotic disorders. We tested the hypotheses that kappa expression is elevated and associated with psychotic symptoms in schizophrenia. We measured kappa expression in unmedicated patients with schizophrenia (7 female, 6 male) and matched controls (7 female, 6 male) with positron emission tomography (PET). We also acquired a measurement of cumulative dopamine activity over the life span in the same subjects using neuromelanin sensitive MRI. We hypothesized that neuromelanin accumulation would be higher in patients than controls and that in patients there would be a positive association between KOR availability and neuromelanin accumulation. Fourteen patients and thirteen controls were enrolled. Whole brain dynamic PET imaging data using the KOR selective tracer [18F]LY245998 were acquired. Distribution volume (VT) was measured with region of interest analysis in 14 brain regions. Neuromelanin accumulation in midbrain dopaminergic nuclei was assessed in the same subjects. Positive and negative symptoms were measured by a clinical psychologist. We did not observe group level differences in KOR expression, neuromelanin accumulation or relationships of these to positive symptoms. Unexpectedly, we did observe strong positive associations between KOR expression and symptoms of anhedonia in the patients (Pearson r > 0.7, uncorrected p < 0.01 in 8 cortical brain regions). We also observed moderate associations between KOR expression and neuromelanin levels in patients. In conclusion, we did not observe a relationship between kappa and symptoms of psychosis but the observed relationship to the negative symptom of anhedonia is in line with recent work testing kappa antagonism as a therapy for anhedonia in depression.

Data driven surrogate signal extraction for dynamic PET using selective PCA: time windows versus the combination of components

Objective. Respiratory motion correction is beneficial in positron emission tomography (PET), as it can reduce artefacts caused by motion and improve quantitative accuracy. Methods of motion correction are commonly based on a respiratory trace obtained through an external device (like the real time position management system) or a data driven method, such as those based on dimensionality reduction techniques (for instance principal component analysis (PCA)). PCA itself being a linear transformation to the axis of greatest variation. Data driven methods have the advantage of being non-invasive, and can be performed post-acquisition. However, their main downside being that they are adversely affected by the tracer kinetics of the dynamic PET acquisition. Therefore, they are mostly limited to static PET acquisitions. This work seeks to extend on existing PCA-based data-driven motion correction methods, to allow for their applicability to dynamic PET imaging. Approach. The methods explored in this work include; a moving window approach (similar to the Kinetic Respiratory Gating method from Schleyer et al (2014)), extrapolation of the principal component from later time points to earlier time points, and a method to score, select, and combine multiple respiratory components. The resulting respiratory traces were evaluated on 22 data sets from a dynamic [18F]-FDG study on patients with idiopathic pulmonary fibrosis. This was achieved by calculating their correlation with a surrogate signal acquired using a real time position management system. Main results. The results indicate that all methods produce better surrogate signals than when applying conventional PCA to dynamic data (for instance, a higher correlation with a gold standard respiratory trace). Extrapolating a late time point principal component produced more promising results than using a moving window. Scoring, selecting, and combining components held benefits over all other methods. Significance. This work allows for the extraction of a surrogate signal from dynamic PET data earlier in the acquisition and with a greater accuracy than previous work. This potentially allows for numerous other methods (for instance, respiratory motion correction) to be applied to this data (when they otherwise could not be previously used).

Quantitative Dynamic Contrast-Enhanced Magnetic Resonance Imaging and Positron Emission Tomography (PET) for Distinguishing Metastatic Lymph Nodes from Nonmetastatic Among Patients with Rectal Cancer: A Systematic Review and Meta-Analysis

Abstract Objective The objective of this research was to assess the proficiency of quantitative dynamic contrast-enhanced magnetic resonance imaging (QDCE-MRI) and positron emission tomography (PET) imaging in distinguishing between metastatic and nonmetastatic lymph nodes in cases of rectal carcinoma. Method This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. Two independent reviewers systematically searched databases including PubMed, Embase, Web of Science, and the Cochrane Library. The research took place in July 2022, with no restriction on the initial date of publication. For the analysis, we utilized Stata software (version 16.0), Review Manager (version 5.3), and the Open Meta-Analyst computational tool. Results A total of 19 studies consisting of 1,451 patients were included in the current meta-analysis. The differences between metastatic and nonmetastatic lymph node parameters were significant by using short axis and Ktrans (6.9 ± 4 vs. 5.4 ± 0.5, 0.22 ± 0.1 vs. 0.14 ± 0.1, respectively). Contrast-enhanced MRI (CE-MRI) showed 73% sensitivity, 71% specificity, and 79% accuracy in detecting metastatic lymph nodes among rectal cancer patients based on six included studies (n = 530). The overall sensitivity, specificity, and accuracy of QDCE-MRI using Ktrans was calculated to be 80, 79, and 80%, respectively. Furthermore, PET-computed tomography (CT) showed a sensitivity of 80%, specificity of 91%, and accuracy of 86% in distinguishing metastatic lymph nodes. Quality utility analysis showed that using CE-MRI, QDCE-MRI, and PET-CT would increase the posttest probability to 69, 73, and 85%, respectively. Conclusion QDCE-MRI demonstrates a commendable sensitivity and specificity, but slightly overshadowed by the higher specificity of PET-CT at 91%, despite comparable sensitivities. However, the heterogeneity in PET-CT sensitivity across studies and its high specificity indicate variability that can influence clinical decision-making. Thus, combining these imaging techniques and perhaps newer methods like PET/MRI could enhance diagnostic accuracy, reduce variability, and improve patient management strategies in rectal cancer.

Exact parameter identification in PET pharmacokinetic modeling using the irreversible two tissue compartment model * *This work was partly funded by the NIH Grants P41-EB017183 and R01-EB031199-02.

Objective. In quantitative dynamic positron emission tomography (PET), time series of images, reflecting the tissue response to the arterial tracer supply, are reconstructed. This response is described by kinetic parameters, which are commonly determined on basis of the tracer concentration in tissue and the arterial input function. In clinical routine the latter is estimated by arterial blood sampling and analysis, which is a challenging process and thus, attempted to be derived directly from reconstructed PET images. However, a mathematical analysis about the necessity of measurements of the common arterial whole blood activity concentration, and the concentration of free non-metabolized tracer in the arterial plasma, for a successful kinetic parameter identification does not exist. Here we aim to address this problem mathematically. Approach. We consider the identification problem in simultaneous pharmacokinetic modeling of multiple regions of interests of dynamic PET data using the irreversible two-tissue compartment model analytically. In addition to this consideration, the situation of noisy measurements is addressed using Tikhonov regularization. Furthermore, numerical simulations with a regularization approach are carried out to illustrate the analytical results in a synthetic application example.Main results. We provide mathematical proofs showing that, under reasonable assumptions, all metabolic tissue parameters can be uniquely identified without requiring additional blood samples to measure the arterial input function. A connection to noisy measurement data is made via a consistency result, showing that exact reconstruction of the ground-truth tissue parameters is stably maintained in the vanishing noise limit. Furthermore, our numerical experiments suggest that an approximate reconstruction of kinetic parameters according to our analytic results is also possible in practice for moderate noise levels. Significance. The analytical result, which holds in the idealized, noiseless scenario, suggests that for irreversible tracers, fully quantitative dynamic PET imaging is in principle possible without costly arterial blood sampling and metabolite analysis.

Effects of deep brain stimulation on dopamine D2 receptor binding in patients with treatment-refractory depression

BackgroundDepression is a chronic psychiatric disorder related to diminished dopaminergic neurotransmission. Deep brain stimulation (DBS) has shown effectiveness in treating patients with treatment-refractory depression (TRD). This study aimed to evaluate the effect of DBS on dopamine D2 receptor binding in patients with TRD. MethodsSix patients with TRD were treated with bed nucleus of the stria terminalis (BNST)-nucleus accumbens (NAc) DBS were recruited. Ultra-high sensitivity [11C]raclopride dynamic total-body positron emission tomography (PET) imaging was used to assess the brain D2 receptor binding. Each patient underwent a [11C]raclopride PET scan for 60-min under DBS OFF and DBS ON, respectively. A simplified reference tissue model was used to generate parametric images of binding potential (BPND) with the cerebellum as reference tissue. ResultsDepression and anxiety symptoms improved after 3–6 months of DBS treatment. Compared with two-day-nonstimulated conditions, one-day BNST-NAc DBS decreased [11C]raclopride BPND in the amygdala (15.9 %, p < 0.01), caudate nucleus (15.4 %, p < 0.0001) and substantia nigra (10.8 %, p < 0.01). LimitationsThis study was limited to the small sample size and lack of a healthy control group. ConclusionsChronic BNST-NAc DBS improved depression and anxiety symptoms, and short-term stimulation decreased D2 receptor binding in the amygdala, caudate nucleus, and substantia nigra. The findings suggest that DBS relieves depression and anxiety symptoms possibly by regulating the dopaminergic system.

A comparison study of dynamic [18F]Alfatide II imaging and [11C]MET in orthotopic rat models of glioblastoma

PurposeTo investigate and compare the dynamic positron emission tomography (PET) imaging with [18F]Alfatide II Imaging and [11C]Methionine ([11C]MET) in orthotopic rat models of glioblastoma multiforme (GBM), and to assess the utility of [18F]Alfatide II in detecting and evaluating neoangiogenesis in GBM.Methods[18F]Alfatide II and [11C]MET were injected into the orthotopic GBM rat models (n = 20, C6 glioma cells), followed by dynamic PET/MR scans 21 days after surgery of tumor implantation. On the PET image with both radiotracers, the MRI-based volume-of-interest (VOI) was manually delineated encompassing glioblastoma. Time-activity curves were expressed as tumor-to-normal brain ratio (TNR) parameters and PET pharmacokinetic modeling (PKM) performed using 2-tissue-compartment models (2TCM). Immunofluorescent staining (IFS), western blotting and blocking experiment of tumor tissue were performed for the validation.ResultsCompared to 11C-MET, [18F]Alfatide II presented a persistent accumulation in the tumor, albeit with a slightly lower SUVmean of 0.79 ± 0.25, and a reduced uptake in the contralateral normal brain tissue, respectively. This resulted in a markedly higher tumor-to-normal brain ratio (TNR) of 18.22 ± 1.91. The time–activity curve (TACs) showed a significant increase in radioactive uptake in tumor tissue, followed by a plateau phase up to 60 min for [18F]Alfatide II (time to peak:255 s) and 40 min for [11C]MET (time to peak:135 s) post injection. PKM confirmed significantly higher K1 (0.23/0.07) and K3 (0.26/0.09) in the tumor region compared to the normal brain with [18F]Alfatide II. Compared to [11C]MET imaging, PKM confirmed both significantly higher K1/K2 (1.24 ± 0.79/1.05 ± 0.39) and K3/K4 (11.93 ± 4.28/3.89 ± 1.29) in the tumor region with [18F]Alfatide II. IFS confirmed significant expression of integrin and tumor vascularization in tumor region.Conclusion[18F]Alfatide II demonstrates potential in imaging tumor-associated neovascularization in the context of glioblastoma multiforme (GBM), suggesting its utility as a tool for further exploration in neovascular characterization.

Population-based deep image prior for dynamic PET denoising: A data-driven approach to improve parametric quantification

The high noise level of dynamic Positron Emission Tomography (PET) images degrades the quality of parametric images. In this study, we aim to improve the quality and quantitative accuracy of Ki images by utilizing deep learning techniques to reduce the noise in dynamic PET images. We propose a novel denoising technique, Population-based Deep Image Prior (PDIP), which integrates population-based prior information into the optimization process of Deep Image Prior (DIP). Specifically, the population-based prior image is generated from a supervised denoising model that is trained on a prompts-matched static PET dataset comprising 100 clinical studies. The 3D U-Net architecture is employed for both the supervised model and the following DIP optimization process. We evaluated the efficacy of PDIP for noise reduction in 25%-count and 100%-count dynamic PET images from 23 patients by comparing with two other baseline techniques: the Prompts-matched Supervised model (PS) and a conditional DIP (CDIP) model that employs the mean static PET image as the prior. Both the PS and CDIP models show effective noise reduction but result in smoothing and removal of small lesions. In addition, the utilization of a single static image as the prior in the CDIP model also introduces a similar tracer distribution to the denoised dynamic frames, leading to lower Ki in general as well as incorrect Ki in the descending aorta. By contrast, as the proposed PDIP model utilizes intrinsic image features from the dynamic dataset and a large clinical static dataset, it not only achieves comparable noise reduction as the supervised and CDIP models but also improves lesion Ki predictions.

Synthesis and Evaluation of [18F]AlF-NOTA-c-DVAP: A Novel PET Probe for Imaging GRP78 in Cancer.

GRP78, a member of the HSP70 superfamily, is an endoplasmic reticulum chaperone protein overexpressed in various cancers, making it a promising target for cancer imaging and therapy. Positron emission tomography (PET) imaging offers unique advantages in real time, noninvasive tumor imaging, rendering it a suitable tool for targeting GRP78 in tumor imaging to guide targeted therapy. Several studies have reported successful tumor imaging using PET probes targeting GRP78. However, existing PET probes face challenges such as low tumor uptake, inadequate in vivo distribution, and high abdominal background signal. Therefore, this study introduces a novel peptide PET probe, [18F]AlF-NOTA-c-DVAP, for targeted tumor imaging of GRP78. [18F]AlF-NOTA-c-DVAP was radiolabeled with fluoride-18 using the aluminum-[18F]fluoride ([18F]AlF) method. The study assessed the partition coefficients, stability in vitro, and metabolic stability of [18F]AlF-NOTA-c-DVAP. Micro-PET imaging, pharmacokinetic analysis, and biodistribution studies were carried out in tumor-bearing mice to evaluate the probe's performance. Docking studies and pharmacokinetic analyses of [18F]AlF-NOTA-c-DVAP were also performed. Immunohistochemical and immunofluorescence analyses were conducted to confirm GRP78 expression in tumor tissues. The probe's binding affinity to GRP78 was analyzed by molecular docking simulation. [18F]AlF-NOTA-c-DVAP was radiolabeled in just 25 min with a high yield of 51 ± 16%, a radiochemical purity of 99%, and molar activity within the range of 20-50 GBq/μmol. [18F]AlF-NOTA-c-DVAP demonstrated high stability in vitro and in vivo, with a logD value of -3.41 ± 0.03. Dynamic PET imaging of [18F]AlF-NOTA-c-DVAP in tumors showed rapid uptake and sustained retention, with minimal background uptake. Biodistribution studies revealed rapid blood clearance and excretion through the kidneys following a single-compartment reversible metabolic model. In PET imaging, the T/M ratios for A549 tumors (high GRP78 expression), MDA-MB-231 tumors (medium expression), and HepG2 tumors (low expression) at 60 min postintravenous injection were 10.48 ± 1.39, 6.25 ± 0.47, and 3.15 ± 1.15% ID/g, respectively, indicating a positive correlation with GRP78 expression. This study demonstrates the feasibility of using [18F]AlF-NOTA-c-DVAP as a PET tracer for imaging GRP78 in tumors. The probe shows promising results in terms of stability, specificity, and tumor targeting. Further research may explore the clinical utility and potential therapeutic applications of this PET tracer for cancer diagnosis.

Improvement in the estimation of perfusable tissue fraction and myocardial flow reserve in the ischemic myocardial lesions using ECG-gated dynamic myocardial PET with 15O-water.

Perfusable tissue fraction (PTF) and myocardial flow reserve (MFR) from 15O-water dynamic positron emission tomography (PET) are parameters of myocardial viability. However, myocardial motion causes errors in these values. We aimed to develop accurate estimation of PTF and MFR in ischemic lesions using an electro-cardiogram (ECG)-gated dynamic myocardial PET with 15O-water. Twenty-seven patients with ischemic heart disease were enrolled. All patients underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). List mode 3D PET data and ECG signals were acquired using Philips Gemini TF64 instrument. For each scan, 500MBq of 15O-water was infused slowly for 2min, and the dynamic data were scanned for 6min. Both non-gated dynamic images and ECG-gated diastolic dynamic images were reconstructed. On the myocardial PET images of each patient, the entire myocardial region of interest (ROI) was set and divided into 17 segments. Myocardial blood flow in the resting state (rest MBF), hyperemic state (stress MBF), PTF, and MFR in each segment were estimated from both non-gated and ECG-gated dynamic PET images. Coronary arteriograms were obtained for all patients. In total, 128 normal segments without stenosis and 50 ischemic segments with > 90% stenosis were evaluated. In the ischemic myocardial segments, the PTF with ECG-gated PET was estimated as significantly lower than that with non-gated PET (0.63 ± 0.09 vs. 0.72 ± 0.08 [mL/mL], p < 0.001). The ECG-gated PET estimated a significantly lower PTF in the ischemic segments than in the normal segments (0.63 ± 0.09 vs. 0.67 ± 0.07 [mL/mL], p < 0.01). In the normal segments, the ECG-gated PET detected no significant difference in MFR compared with those from the non-gated PET (2.15 ± 0.76 vs. 2.24 ± 0.79, p = 0.28). However, in the ischemic myocardial segments, the MFR with ECG-gated PET was estimated as significantly lower than that with the non-gated PET (1.23 ± 0.29 vs. 1.69 ± 0.71, p < 0.001). The ECG-gated PET presented a significantly higher inter-observer reproducibility of PTF and rest MBF than the non-gated PET (p < 0.01). Neither stress MBF nor MFR yielded significant differences in inter-observer reproducibility between the ECG-gated and non-gated PET. The ECG-gated dynamic 15O-water PET suppressed the myocardial motion effect and resulted in a lower PTF and MFR in ischemic myocardial lesions than the non-gated PET. The ECG-gated PET seemed to be better than the conventional non-gated dynamic PET for the detection of ischemic myocardial lesion.

Preliminary study on the dynamic positron emission tomography imaging with 11C-ER176 to delineate macrophage activation in diabetic gastroparesis.

Animal models and human data have suggested macrophage-driven immune dysregulation in diabetic gastroparesis (DG). Translocator protein (TSPO) upregulation has been suggested to indicate activated state of macrophages and ER176 is a high affinity third generation TSPO-specific radioligand. The aim of this study was to determine feasibility of dynamic 11C-ER 176 PET to identify macrophage activation in DG. Twelve patients, all females, were recruited (4 DG, 4 diabetics, and 4 healthy volunteers) for 11C-ER 176 PET/CT scanning. The standardized uptake value (SUVmax) in the gastric fundus, body, pylorus, and descending part of the duodenum were compared between three groups using Kruskal-Wallis test to perform the comparisons, and a p-value of 0.05 was considered statistically significant. Age was comparable among the three groups with a median of 53 years. The uptake was higher in pylorus in diabetics compared to DG and healthy (SUVmax healthy 4.6 ± 0.2, diabetics 8.4 ± 4.1, DG 5.5 ± 1.0, p = 0.04). The uptake was similar in gastric fundus (9.0 ± 1.6, 13.1 ± 8.3, 7.8 ± 1.9 respectively, p = 0.3), body (7.7 ± 1.9, 13 ± 9.2, 7.8 ± 1.9 respectively, p = 0.8), and duodenum (6.2 ± 2.1, 9.5 ± 6.8, 7.0 ± 1.8 respectively, p = 0.6). No correlation was observed between SUVmax uptake and either HbA1C or fasting blood glucose. Female diabetic gastroparesis patients did not demonstrate increased TSPO ligand 11C-ER 176 uptake in the stomach. Possible explanations include lack of specificity of ligand for specific macrophage phenotypes in DG, sex effect, or small sample size. Further studies investigating non-invasive ways of analyzing immune dysregulation in neurogastrointestinal disorders are warranted.

In vivo real-time positron emission particle tracking (PEPT) and single particle PET

Positron emission particle tracking (PEPT) enables 3D localization and tracking of single positron-emitting radiolabelled particles with high spatiotemporal resolution. The translation of PEPT to the biomedical imaging field has been limited due to the lack of methods to radiolabel biocompatible particles with sufficient specific activity and protocols to isolate a single particle in the sub-micrometre size range, below the threshold for capillary embolization. Here we report two key developments: the synthesis and 68Ga-radiolabelling of homogeneous silica particles of 950 nm diameter with unprecedented specific activities (2.1 ± 1.4 kBq per particle), and the isolation and manipulation of a single particle. We have combined these developments to perform in vivo PEPT and dynamic positron emission tomography (PET) imaging of a single radiolabelled sub-micrometre size particle using a pre-clinical positron emission tomography/computed tomography scanner. This work opens possibilities for quantitative assessment of haemodynamics in vivo in real time, at the whole-body level using minimal amounts of injected radioactive dose and material.

Distribution of insulin in primate brain following nose-to-brain transport.

Nose-to-brain (N2B) insulin delivery has potential for Alzheimer's disease (AD) therapy. However, clinical implementation has been challenging without methods to follow N2B delivery non-invasively. Positron emission tomography (PET) was applied to measure F-18-labeled insulin ([18F]FB-insulin) from intranasal dosing to brain uptake in non-human primates following N2B delivery. [18F]FB-insulin was prepared by reacting A1,B29-di(tert-butyloxycarbonyl)insulin with [18F]-N-succinimidyl-4-fluorobenzoate. Three methods of N2B delivery for [18F]FB-insulin were compared - delivery as aerosol via tubing (rhesus macaque, n = 2), as aerosol via preplaced catheter (rhesus macaque, n = 3), and as solution via preplaced catheter (cynomolgus macaque, n = 3). Following dosing, dynamic PET imaging (120 min) quantified delivery efficiency to the nasal cavity and whole brain. Area under the time-activity curve was calculated for 46 regions of the cynomolgus macaque brain to determine regional [18F]FB-insulin levels. Liquid instillation of [18F]FB-insulin by catheter outperformed aerosol methods for delivery to the subject (39.89% injected dose vs 10.03% for aerosol via tubing, 0.17% for aerosol by catheter) and subsequently to brain (0.34% injected dose vs 0.00020% for aerosol via tubing, 0.05% for aerosol by catheter). [18F]FB-insulin was rapidly transferred across the cribriform plate to limbic and frontotemporal areas responsible for emotional and memory processing. [18F]FB-insulin half-life was longer in olfactory nerve projection sites with high insulin receptor density compared to the whole brain. The catheter-based liquid delivery approach combined with PET imaging successfully tracked the fate of N2B [18F]FB-insulin and is thought to be broadly applicable for assessments of other therapeutic agents. This method can be rapidly applied in humans to advance clinical evaluation of N2B insulin as an AD therapeutic. [18F]FB-insulin passage across the cribriform plate was detected by PET.Intranasal [18F]FB-insulin reached the brain within 13 min.[18F]FB-insulin activity was highest in emotional and memory processing regions.Aerosol delivery was less efficient than liquid instillation by preplaced catheter.Insulin delivery to the cribriform plate was critical for arrival in the brain.