PET Acquisition Research Articles

Ultrashort Oncologic Whole-Body [18F]FDG Patlak Imaging Using LAFOV PET.

Methods to shorten [18F]FDG Patlak PET imaging procedures ranging from 65-90 to 20-30 min after injection, using a population-averaged input function (PIF) scaled to patient-specific image-derived input function (IDIF) values, were recently evaluated. The aim of the present study was to explore the feasibility of ultrashort 10-min [18F]FDG Patlak imaging at 55-65 min after injection using a PIF combined with direct Patlak reconstructions to provide reliable quantitative accuracy of lung tumor uptake, compared with a full-duration 65-min acquisition using an IDIF. Methods: Patients underwent a 65-min dynamic PET acquisition on a long-axial-field-of-view (LAFOV) Biograph Vision Quadra PET/CT scanner. Subsequently, direct Patlak reconstructions and image-based (with reconstructed dynamic images) Patlak analyses were performed using both the IDIF (time to relative kinetic equilibrium between blood and tissue concentration (t*) = 30 min) and a scaled PIF at 30-60 min after injection. Next, direct Patlak reconstructions were performed on the system console using only the last 10 min of the acquisition, that is, from 55 to 65 min after injection, and a scaled PIF using maximum crystal ring difference settings of both 85 and 322. Tumor lesion and healthy-tissue uptake was quantified and compared between the differently obtained parametric images to assess quantitative accuracy. Results: Good agreement was obtained between direct- and image-based Patlak analyses using the IDIF (t* = 30 min) and scaled PIF at 30-60 min after injection, performed using the different approaches, with no more than 8.8% deviation in tumor influx rate value (Ki ) (mean difference ranging from -0.0022 to 0.0018 mL/[min × g]). When direct Patlak reconstruction was performed on the system console, excellent agreement was found between the use of a scaled PIF at 30-60 min after injection versus 55-65 min after injection, with 2.4% deviation in tumor Ki (median difference, -0.0018 mL/[min × g]; range, -0.0047 to 0.0036 mL/[min × g]). For different maximum crystal ring difference settings using the scan time interval of 55-65 min after injection, only a 0.5% difference (median difference, 0.0000 mL/[min × g]; range, -0.0004 to 0.0013 mL/[min × g]) in tumor Ki was found. Conclusion: Ultrashort whole-body [18F]FDG Patlak imaging is feasible on an LAFOV Biograph Vision Quadra PET/CT system without loss of quantitative accuracy to assess lung tumor uptake compared with a full-duration 65-min acquisition. The ultrashort 10-min direct Patlak reconstruction with PIF allows for its implementation in clinical practice.

Whole-body PET image denoising for reduced acquisition time.

A reduced acquisition time positively impacts the patient's comfort and the PET scanner's throughput. AI methods may allow for reducing PET acquisition time without sacrificing image quality. The study aims to compare various neural networks to find the best models for PET denoising. Our experiments consider 212 studies (56,908 images) for 7MBq/kg injected activity and evaluate the models using 2D (RMSE, SSIM) and 3D (SUVpeak and SUVmax error for the regions of interest) metrics. We tested 2D and 2.5D ResNet, Unet, SwinIR, 3D MedNeXt, and 3D UX-Net. We have also compared supervised methods with the unsupervised CycleGAN approach. The best model for PET denoising is 3D MedNeXt. It improved SSIM on 38.2% and RMSE on 28.1% in 30-s PET denoising and on 16.9% and 11.4% in 60-s PET denoising when compared to the original 90-s PET reducing at the same time SUVmax discrepancy dispersion.

Quantitative brain [18F]FDG PET beyond normal blood glucose levels

Introduction SUV measurements from static brain [18F]FDG PET acquisitions are a commonly used tool in preclinical research, providing a simple alternative for kinetic modelling, which requires complex and time-consuming dynamic acquisitions. However, SUV can be severely affected by the animal handling and preconditioning protocols, primarily by those that may induce changes in blood glucose levels (BGL). Here, we aimed at developing and investigating the feasibility of SUV-based approaches for a wide range of BGL far beyond normal values, and consequently, to develop and validate a new model to generate standardized and reproducible SUV measurements for any BGL.Material and methods We performed dynamic and static brain [18F]FDG PET acquisitions in 52 male Sprague-Dawley rats sorted into control (n = 10), non-fasting (n = 14), insulin-induced hypoglycemia (n = 12) and glucagon-induced hyperglycemia (n = 16) groups. Brain [18F]FDG PET images were cropped, aligned and co-registered to a standard template to calculate whole-brain and regional SUV. Cerebral Metabolic Rate of Glucose (CMRglc) was also estimated from 2-Tissue Compartment Model (2TCM) and Patlak plot for validation purposes.Results Our results showed that BGL=100±6 mg/dL can be considered a reproducible reference value for normoglycemia. Furthermore, we successfully established a 2nd-degree polynomial model (C1=0.66E-4, C2=-0.0408 and C3=7.298) relying exclusively on BGL measures at pre-[18F]FDG injection time, that characterizes more precisely the relationship between SUV and BGL for a wide range of BGL values (from 10 to 338 mg/dL). We confirmed the ability of this model to generate corrected SUV estimations that are highly correlated to CMRglc estimations (R2= 0.54 2TCM CMRgluc and R2= 0.49 Patlak CMRgluc). Besides, slight regional differences in SUV were found in animals from extreme BGL groups, showing that [18F]FDG uptake is mostly directed toward central regions of the brain when BGLs are significantly decreased.Conclusion Our study successfully established a non-linear model that relies exclusively on pre-scan BGL measurements to characterize the relationship between [18F]FDG SUV and BGL. The extensive validation confirmed its ability to generate SUV-based surrogates of CMRglu along a wide range of BGL and it holds the potential to be adopted as a standard protocol by the preclinical neuroimaging community using brain [18F]FDG PET imaging.

Head-to-head comparison of 18F-sodium fluoride coronary PET imaging between a silicon photomultiplier with digital photon counting and conventional scanners

BackgroundWe compared silicone photomultipliers with digital photon counting (SiPM) and photomultiplier tubes (PMT) PET in imaging coronary plaque activity with 18F-sodium fluoride (18F-NaF) and evaluated comprehensively SiPM PET reconstruction settings. MethodsIn 25 cardiovascular disease patients (mean age 67±12 years), we conducted 18F-NaF PET on a SiPM (Biograph Vision) and conventional PET (Discovery 710) on the same day as part of a prospective clinical trial (NCT03689946). Following administration of 250 MBq of 18F-NaF, patients underwent a contrast-enhanced CT angiography and a 30-min PET acquisition in list mode on each PET consecutively. Image noise was defined as mean standard deviation of blood pool activity within the left atria. Target-to-background ratio (TBR) and signal-to-noise ratio (SNR) were measured within the whole-vessel tubular 3-dimensional volumes of interest on the cardiac motion and attenuation corrected 18F-NaF PET images using dedicated software. ResultsThere were significant differences in image noise and background activity between the two PETs (Image noise (%), PMT: 7.6±3.7 vs. SiPM: 4.0±2.3, p<0.001; background activity, PMT: 1.4±0.4 vs. SiPM: 1.0±0.3, p<0.001). Similarly, the SNR and TBR were significantly higher in vessels scanned with the SiPM PET (SNR, PMT: 16.3±11.5 vs. SiPM: 32.7±29.8, p<0.001; TBR, PMT: 0.8±0.4 vs. SiPM: 1.1±0.6, p<0.001). SiPM PET image reconstruction with a 256 matrix, 1.4 mm pixel, and 2 mm Gaussian filter provided best tradeoff in terms of maximal SNR, TBR and clinically practical file size. ConclusionsIn 18F-NaF coronary PET imaging, the SiPM PET showed superior image contrast and less image noise compared to PMT PET.

Determination of the optimal imaging protocol for [18F]PSMA-PET-CT for the detection of bone metastases in prostate cancer patients.

Prostate-specific membrane antigen-positron emission tomography (PSMA-PET) is a widely used diagnostic tool in patients with prostate cancer (PC).However, due to the limited availability of PET scanners and relevant acquisition costs, it is important to consider the indications and acquisition time.The aim of this investigation was to determine whether a PET scan from the skull base to the proximal thigh is sufficient to detect the presence of bone metastases. A retrospective analysis was conducted on 1050 consecutive [18F]PSMA-1007-PET-CT scans from the head to the proximal lower leg.The PET scans were categorised according to the presence and amount of bone metastases: (1) 1-5, (2) 6-19 and (3) ≥20. Additionally, the PET scans were evaluated for the presence of bone metastases below the proximal thigh as well as bone metastases above the skull base.Imaging results were compared to patients PSA values. Of the 391 patients with bone metastases, 146 (37.3%) exhibited metastases located below the proximal thigh and 104 (26.6%) above the skull base.The majority of bone metastases located below the proximal thigh (145, 99.3%) and above the skull base (94, 90.4%) were identified in patients with more than five bone metastases. No solitary distal metastasis was detected.The PSA value correlated significantly with number of bone metastases (e. g., 1-5 vs. ≥20 bone metastases, P < 0.001) and was significantly higher in patients with distal bone metastases (P < 0.001).ROC analysis showed that a PSA value of 11.15 ng/mL is the optimal cut-off for detecting bone metastases located below the proximal thigh, with an AUC of 0.919 (95% CI: 0.892-0.945, sensitivity 87%, specificity 86%).Similarly, the PSA value of 12.86 ng/mL is the optimal cut-off for detecting bone metastases above the skull base with an AUC of 0.904 (95% CI: 0.874-0.935, sensitivity 87%, specificity 83%). CONCLUSION: PSMA-PET acquisition protocols from the skull base to the proximal femur may be sufficient to accurately detect bone metastatic disease in PC. PSA values can provide decision support for individual PET acquisition protocols.

Performing [18F]MFBG Long-Axial-Field-of-View PET/CT Without Sedation or General Anesthesia for Imaging of Children with Neuroblastoma.

Meta-[123I]iodobenzylguanidine ([123I]MIBG) scintigraphy with SPECT/CT is the standard of care for diagnosing and monitoring neuroblastoma. Replacing [123I]MIBG with the new PET tracer meta-[18F]fluorobenzylguanidine ([18F]MFBG) and further improving sensitivity and reducing noise in a new long-axial-field-of-view (LAFOV) PET/CT scanner enable increased image quality and a faster acquisition time, allowing examinations to be performed without sedation or general anesthesia (GA). Focusing on feasibility, we present our first experience with [18F]MFBG LAFOV PET/CT and compare it with [123I]MIBG scintigraphy plus SPECT/CT for imaging in neuroblastoma in children. Methods: A pilot of our prospective, single-center study recruited children with neuroblastoma who were referred for [123I]MIBG scintigraphy with SPECT/CT. Within 1 wk of [123I]MIBG scintigraphy and SPECT/low-dose CT, [18F]MFBG LAFOV PET/ultra-low-dose CT was performed 1 h after injection (1.5-3 MBq/kg) without sedation or GA, in contrast to the 24-h postinjection interval needed for scanning with [123I]MIBG, the 2- to 2.5-h acquisition time, and the GA often needed in children less than 6 y old. Based on the spirocyclic iodonium-ylide precursor, [18F]MFBG was produced in a fully automated good manufacturing practice-compliant procedure. We present the feasibility of the study. Results: In the first paired scans of the first 10 children included (5 at diagnosis, 2 during treatment, 2 during surveillance, and 1 at relapse), [18F]MFBG PET/CT scan showed a higher number of radiotracer-avid lesions in 80% of the cases and an equal number of lesions in 20% of the cases. The SIOPEN score was higher in 50% of the cases, and the Curie score was higher in 70% of the cases. In particular, intraspinal, retroperitoneal lymph node, and bone marrow involvement was diagnosed with much higher precision. None of the children (median age, 1.6 y; range, 0.1-7.9 y) had sedation or GA during the PET procedure, whereas 80% had GA during [123I]MIBG scintigraphy with SPECT/CT. A PET acquisition time of only 2 min without motion artifacts was the data requirement of the 10-min acquisition time for reconstruction to provide a clinically useful image. Conclusion: This pilot study demonstrates the feasibility of performing [18F]MFBG LAFOV PET/CT for imaging of neuroblastoma. Further, an increased number of radiotracer-avid lesions, an increased SIOPEN score, and an increased Curie score were seen on [18F]MFBG LAFOV PET/CT compared with [123I]MIBG scintigraphy with SPECT/CT, and GA and sedation was avoided in all patients. Thus, with a 1-d protocol, a significantly shorter scan time, a higher sensitivity, and the avoidance of GA and sedation, [18F]MFBG LAFOV PET/CT shows promise for future staging and response assessment and may also have a clinical impact on therapeutic decision-making for children with neuroblastoma.

Clinical evaluation of deep learning-enhanced lymphoma pet imaging with accelerated acquisition.

This study aims to evaluate the clinical performance of a deep learning (DL)-enhanced two-fold accelerated PET imaging method in patients with lymphoma. A total of 123 cases devoid of lymphoma underwent whole-body 18F-FDG-PET/CT scans to facilitate the development of an advanced SAU2Net model, which combines the advantages of U2Net and attention mechanism. This model integrated inputs from simulated 1/2-dose (0.07 mCi/kg) PET acquisition across multiple slices to generate an estimated standard dose (0.14 mCi/kg) PET scan. Additional 39 cases with confirmed lymphoma pathology were utilized to evaluate the model's clinical performance. Assessment criteria encompassed peak-signal-to-noise ratio (PSNR), structural similarity index (SSIM), a 5-point Likert scale rated by two experienced physicians, SUV features, image noise in the liver, and contrast-to-noise ratio (CNR). Diagnostic outcomes, including lesion numbers and Deauville score, were also compared. Images enhanced by the proposed DL method exhibited superior image quality (P<0.001) in comparison to low-dose acquisition. Moreover, they illustrated equivalent image quality in terms of subjective image analysis and lesion maximum standardized uptake value (SUVmax) as compared to the standard acquisition method. A linear regression model with y=1.017x + 0.110 ( ) can be established between the enhanced scans and the standard acquisition for lesion SUVmax. With enhancement, increasedsignal-to-noise ratio (SNR), CNR, and reduced image noise were observed, surpassing those of the standard acquisition. DL-enhanced PET images got diagnostic results essentially equavalent to standard PET images according totwo experienced readers. The proposed DL method could facilitate a 50% reduction in PET imaging duration for lymphoma patients, while concurrently preserving image quality and diagnostic accuracy.

Challenges in Pharmacokinetic Modelling of [18F]fluoro-PEG-folate PET/CT Imaging in Epithelial Ovarian Cancer Patients

PurposeTo describe the pharmacokinetic properties of the [18F]fluoro-polyethylene glycol(PEG)-folate radiotracer in PET/CT imaging of patients with advanced stage epithelial ovarian cancer (EOC).ProceduresIn five patients with advanced EOC (FIGO stage IIIB/IIIC, Fédération Internationale de Gynécologie et d’Obstétrique), a 90-min dynamic PET acquisition of the pelvis was performed directly after i.v. administration of 185 MBq [18F]fluoro-PEG6-folate. Arterial blood samples collected at nineteen timepoints were used to determine the plasma input function. A static volume of interest (VOI) for included tumor lesions was drawn manually on the PET images. Modelling was performed using PMOD software. Three different models (a 1-tissue compartment model (1T2k) and two 2-tissue compartment models, irreversible (2T3k) and reversible (2T4k)) were compared in goodness of fit with the time activity curves by means of the Akaike information criterion.ResultsThe pharmacokinetic analysis in the pelvic area has proven to be much more challenging than expected. Only four out of 22 tumor lesions in five patients were considered suitable to perform modelling on. The remaining tumor lesions were inapt due to either low tracer uptake, small size, proximity to other [18F]fluoro-PEG6-folate -avid structures and/or displacement by abdominal organ motion in the dynamic scan. Data from the four analyzed tumor lesions suggest that the irreversible 2T3k may best describe the pharmacokinetics. All 22 lesions were immunohistochemically stained positive for the folate receptor alpha (FRα) after resection.ConclusionPerforming pharmacokinetic analysis in the abdominal pelvic region is very challenging. This brief article describes the challenges and pitfalls in pharmacokinetic analysis of a tracer with high physiological accumulation in the intestines, in case of lesions of limited size in the abdominal pelvic area.

The Role of Total-Body PET in Drug Development and Evaluation: Status and Outlook.

Total-body PET, an emerging technique, enables high-quality simultaneous total-body dynamic PET acquisition and accurate kinetic analysis. It has the potential to facilitate the study of multiple tracers while minimizing radiation dose and improving tracer-specific imaging. This advancement holds promise for enhancing the development and clinical evaluation of drugs, particularly radiopharmaceuticals. Multiple clinical trials are using a total-body PET scanner to explore existing and innovative radiopharmaceuticals. However, challenges persist, along with the opportunities, with regard to the use of total-body PET in drug development and evaluation. Specifically, considerations relate to the role of total-body PET in clinical pharmacologic evaluations and its integration into the theranostic paradigm. In this review, state-of-the-art total-body PET and its potential roles in pharmaceutical research are explored.

Optimization of [18F]-FDOPA Brain PET Acquisition Times for Assessment of Parkinsonism in the Clinical Setting.

Fluorine 18-fluoro-L-dopa ([18F]-FDOPA) was approved by the FDA in 2019 and reimbursed by the Centers for Medicare & Medicaid Services in 2022 for use with PET to visualize dopaminergic nerve terminals in the striatum for evaluation of parkinsonism. We sought to determine the optimal image acquisition time for [18F]-FDOPA PET by evaluating rater-estimated FDOPA positivity and image quality across 4 time points. Brain PET/CT was acquired 90 minutes following injection of 185 megabecquerel (5 mCi) of [18F]-FDOPA. PET was acquired in list mode for 20 minutes, and data were replayed to represent 15-, 10-, and 5-minute acquisitions. By means of MIMneuro, PET/MR imaging or PET/CT was independently graded for FDOPA positivity and image quality by 2 readers, blinded to the clinical report and diagnosis. Expert neuroradiologist clinical reads were used as the criterion standard. Twenty patients were included, average age 65.6 years, 55% women. Image-quality ratings decreased with shorter acquisition times for both readers (reader 1, ρ = 0.23, P = .044; reader 2, ρ = 0.24, P = .036), but there was no association between abnormality confidence scores and acquisition time (reader 1, ρ = -0.13, P = .250; reader 2, ρ = -0.19, P = .100). There was a high degree of consistency in intra- and interrater agreement and agreement with the expert reads when using acquisition times of ≥10 minutes (maximal confidence score consistency [ρ = 0.92] and interrater agreement [κ = 0.90] were observed at 15 minutes), while image quality was consistently rated as low and FDOPA positivity ratings were inconsistent when using a 5-minute acquisition time. Our study suggests that image-quality ratings were stable after 15 minutes and that between-subject abnormality detection rates were highly consistent between the 2 readers when acquired for at least 10 and up to 20 minutes but were inconsistent at 5 minutes. Shorter [18F]-FDOPA PET acquisition times may help maximize patient comfort while increasing throughput in the clinical setting.

Longitudinal patterns of companion animals in families with children during the COVID-19 pandemic: Findings from the Adolescent Brain Cognitive Development (ABCD) Study®.

Pet acquisition purportedly increased during the COVID-19 pandemic with individuals acquiring pets during periods of social isolation. Families with children experienced unique challenges during the COVID-19 pandemic, balancing childcare, remote schooling, and other needs and therefore patterns of pet acquisition and loss may differ from the broader population. The goal of this study was to understand patterns of pet ownership within families with adolescents during the pandemic to help identify areas for improved support and programmatic recommendations. Using self-reported survey data from a sample of 7,590 American adolescents from the Adolescent Brain Cognitive Development (ABCD) Study® COVID Survey, we found no evidence for large-scale changes in pet acquisition or relinquishment during the first year of the pandemic for families with adolescents in the U.S. Future research should explore the effects of pet acquisition and pet loss on families with adolescents and what resources are needed to support pet ownership during stressors such as the COVID-19 pandemic.

State-of-the-Art Hybrid Imaging of Neuroendocrine Neoplasms.

Neuroendocrine neoplasms (NENs) may be challenging to diagnose due to their small size and diverse anatomical locations. Hybrid imaging techniques, specifically positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI), represent the current state-of-the-art for evaluating NENs. The preferred radiopharmaceuticals for NEN PET imaging are gallium-68 (68Ga) DOTA-peptides, which target somatostatin receptors (SSTR) overexpressed on NEN cells. Clinical applications of [68Ga]Ga-DOTA-peptides PET/CT include diagnosis, staging, prognosis assessment, treatment selection, and response evaluation. Fluorodeoxyglucose-18 (18F-FDG) PET/CT aids in detecting low-SSTR-expressing lesions and helps in patient stratification and treatment planning, particularly in grade 3 neuroendocrine tumors (NETs). New radiopharmaceuticals such as fluorine-labeled SSTR agonists and SSTR antagonists are emerging as alternatives to 68Ga-labeled peptides, offering improved detection rates and favorable biodistribution. The maturing of PET/MRI brings advantages to NEN imaging, including simultaneous acquisition of PET and MRI images, superior soft tissue contrast resolution, and motion correction capabilities. The PET/MRI with [68Ga]Ga-DOTA-peptides has demonstrated higher lesion detection rates and more accurate lesion classification compared to PET/CT. Overall, hybrid imaging offers valuable insights in the diagnosis, staging, and treatment planning of NENs. Further research is needed to refine response assessment criteria and standardize reporting guidelines.

[18F]2-fluoro-2-deoxy-sorbitol ([18F]FDS) PET imaging repurposed for quantitative estimation of blood-brain barrier permeability in a rat model of Alzheimer's disease

Numerous studies suggest that blood-brain barrier (BBB) dysfunction may contribute to the progression of Alzheimer's disease (AD). Clinically available neuroimaging methods are needed for quantitative "scoring" of BBB permeability in AD patients. [18F]2-fluoro-2-deoxy-sorbitol ([18F]FDS), which can be easily obtained from simple chemical reduction of commercial [18F]2-fluoro-2-deoxy-glucose ([18F]FDG), was investigated as a small-molecule marker of BBB permeability, in a pre-clinical model of AD using in vivo PET imaging. Chemical reduction of [18F]FDG to [18F]FDS was obtained with a 100% conversion yield. Dynamic PET acquisitions were performed in the APP/PS1 rat model of AD (TgF344-AD, n=3) compared with age-matched littermates (WT, n=4). The brain uptake of [18F]FDS was determined in selected brain regions, delineated from a coregistered rat brain template. The brain uptake of [18F]FDS in the brain regions of AD rats versus WT rats was compared using a 2-way ANOVA. The uptake of [18F]FDS was significantly higher in the whole brain of AD rats, as compared with WT rats (P<0.001), suggesting increased BBB permeability. Enhanced brain uptake of [18F]FDS in AD rats was significantly different across brain regions (P<0.001). Minimum difference was observed in the amygdala (+89.0±7.6%, P<0.001) and maximum difference was observed in the midbrain (+177.8±29.2%, P<0.001). [18F]FDS, initially proposed as radio-pharmaceutical to estimate renal filtration using PET imaging, can be repurposed for non-invasive and quantitative determination of BBB permeability in vivo. Making the best with the quantitative properties of PET imaging, it was possible to estimate the extent of enhanced BBB permeability in a rat model of AD.

Combined whole-body dynamic and static PET/CT with low-dose [18F]PSMA-1007 in prostate cancer patients

AimIn addition to significant improvements in sensitivity and image quality, the recent introduction of long axial field-of-view (LAFOV) PET/CT scanners has enabled dynamic whole-body imaging for the first time. We aim herein to determine an appropriate acquisition time range for static low-dose [18F]PSMA-1007 PET imaging and to investigate the whole-body pharmacokinetics of [18F]PSMA-1007 by dynamic PET with the LAFOV Biograph Vision Quadra PET/CT in a group of prostate cancer patients.MethodologyIn total, 38 prostate cancer patients were enrolled in the analysis for staging or re-staging purposes. Thirty-four patients underwent dynamic whole-body PET/CT (60 min) followed by static whole-body PET/CT and four patients underwent static whole-body PET/CT only. The activity applied was 2 MBq/kg [18F]PSMA-1007. The static PET images of 10-min duration (PET-10) were reconstructed and further split into 8-min (PET-8), 6-min (PET-6), 5-min (PET-5), 4-min (PET-4), and 2-min (PET-2) duration groups. Comparisons were made between the different reconstructed scan times in terms of lesion detection rate and image quality based on SUV calculations of tumor lesions and the spleen, which served as background. Analysis of the dynamic PET/CT data was based on a two-tissue compartment model using an image-derived input function obtained from the descending aorta.ResultsAnalysis of lesion detection rate showed no significant differences when reducing PET acquisitions from 10 up to 5 min. In particular, a total of 169 lesions were counted with PET-10, and the corresponding lesion detection rates (95% CI for the 90% quantile of the differences in tumor lesions) for shorter acquisitions were 100% (169/169) for PET-8 (95% CI: 0–0), 98.8% (167/169) for PET-6 (95% CI: 0–1), 95.9% (162/169) for PET-5 (95% CI: 0–3), 91.7% (155/169) for PET-4 (95% CI: 1–2), and 85.2% (144/169) for PET-2 (95% CI: 1–6). With the exception of PET-2, the differences observed between PET-10 and the other shorter acquisition protocols would have no impact on any patient in terms of clinical management. Objective evaluation of PET/CT image quality showed no significant decrease in tumor-to-background ratio (TBR) with shorter acquisition times, despite a gradual decrease in signal-to-noise ratio (SNR) in the spleen. Whole-body quantitative [18F]PSMA-1007 pharmacokinetic analysis acquired with full dynamic PET scanning was feasible in all patients. Two-tissue compartment modeling revealed significantly higher values for the parameter k3 in tumor lesions and parotid gland compared to liver and spleen, reflecting a higher specific tracer binding to the PSMA molecule and internalization rate in these tissues, a finding also supported by the respective time-activity curves. Furthermore, correlation analysis demonstrated a significantly strong positive correlation (r = 0.72) between SUV and k3 in tumor lesions.ConclusionsIn prostate cancer, low-dose (2 MBq/kg) [18F]PSMA-1007 LAFOV PET/CT can reduce static scan time by 50% without significantly compromising lesion detection rate and objective image quality. In addition, dynamic PET can elucidate molecular pathways related to the physiology of [18F]PSMA-1007 in both tumor lesions and normal organs at the whole-body level. These findings unfold many of the potentials of the new LAFOV PET/CT technology in the field of PSMA-based diagnosis and theranostics of prostate cancer.

68 Ga-Pentixafor PET/CT for in-vivo mapping of CXCR4 receptors as potential radiotheranostic targets in soft tissue and bone sarcoma: preliminary results.

To evaluate the diagnostic utility of 68 Ga-Pentixafor PET/CT for in vivo imaging of CXCR4 receptors in soft tissue/bone sarcoma. Ten (7M: 3F; mean age = 24.7 ± 14.2 years) consecutive patients with clinical and radiological evidence of bone/soft tissue sarcoma were recruited prospectively whole body 68 Ga-Pentixafor PET/CT imaging was performed at 60-min after tracer administration. After performing standard CT, PET acquisition from head to toe was done (3 min/bed position) in a caudocranial direction. PET/CT data was reconstructed and SUV max , SUV mean values, target-to-background ratio (TBR) and active tumor volume (cc) were computed for the tracer avid lesions. Histopathological and IHC analysis was performed on the surgically excised primary tumors. CXCR4 receptors' intensity was evaluated by visual scoring. The mean SUV max and SUV mean values in the primary tumors were 4.80 ± 1.0 (3.9-7.7) and 2.40 ± 0.60 (0.9-4.0). The mean TBR and tumor volume (cc) were 1.84 ± 1.3 and 312.2 ± 285. Diagnosis of osteosarcoma in 7, chondrosarcoma, leiomyosarcoma and synovial sarcoma in 1 patient each was confirmed on HP analysis. Distant metastatic lesions were seen in 3/10 patients. Nuclear CXCR4 receptors' positivity was seen in 5, cytoplasmic in 4 and both pattern seen in 1 patient. The mean CXCR4 receptors' intensity was found to be 7.6 ± 2. The highest SUV max value of 7.7 was observed in the patient having both cytoplasmic and nuclear CXCR4 expression. SUV max was found to be poorly correlated ( r = 0.441) with CXCR4 expression. 68 Ga-Pentixafor PET/CT detects CXCR4 receptors over-expressed in sarcoma, its radio-theranostics potential needs detailed evaluation.

M3S-Net: multi-modality multi-branch multi-self-attention network with structure-promoting loss for low-dose PET/CT enhancement.

Objective.PET (Positron Emission Tomography) inherently involves radiotracer injections and long scanning time, which raises concerns about the risk of radiation exposure and patient comfort. Reductions in radiotracer dosage and acquisition time can lower the potential risk and improve patient comfort, respectively, but both will also reduce photon counts and hence degrade the image quality. Therefore, it is of interest to improve the quality of low-dose PET images.Approach.A supervised multi-modality deep learning model, named M3S-Net, was proposed to generate standard-dose PET images (60 s per bed position) from low-dose ones (10 s per bed position) and the corresponding CT images. Specifically, we designed a multi-branch convolutional neural network with multi-self-attention mechanisms, which first extracted features from PET and CT images in two separate branches and then fused the features to generate the final generated PET images. Moreover, a novel multi-modality structure-promoting term was proposed in the loss function to learn the anatomical information contained in CT images.Main results.We conducted extensive numerical experiments on real clinical data collected from local hospitals. Compared with state-of-the-art methods, the proposed M3S-Net not only achieved higher objective metrics and better generated tumors, but also performed better in preserving edges and suppressing noise and artifacts.Significance.The experimental results of quantitative metrics and qualitative displays demonstrate that the proposed M3S-Net can generate high-quality PET images from low-dose ones, which are competable to standard-dose PET images. This is valuable in reducing PET acquisition time and has potential applications in dynamic PET imaging.

Quantitative Amyloid‐PET in Real‐World Practice: Lessons from the Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) study

AbstractBackgroundAmyloid‐PET quantification was developed in research settings using highly selected samples, harmonized acquisition protocols, and MRI‐based preprocessing. We aimed to analyze scans from IDEAS, a large‐scale, real‐world study of amyloid‐PET. Major challenges lie in scans being acquired on various PET/PET‐CT/PET‐MR scanners without standardization of acquisition or reconstruction protocols, and without MRI to preprocess data.Method18,295 Medicare beneficiaries with MCI or dementia underwent PET with [18F]florbetapir, [18F]florbetaben, or [18F]flutemetamol at 343 facilities. Sites shared 10,700 raw scans with their visual interpretation (positive or negative) by local radiologists/nuclear medicine physicians. Scans were processed using a PET‐only pipeline, which derives Centiloid based on a cortex‐to‐cerebellum tissue ratio in template space. Processed scans underwent standard visual quality control by 2 raters (Fig 1a‐b), and flagged scans were reviewed in a consensus meeting to discuss troubleshooting options. Injected dose and time between tracer injection and PET acquisition start were obtained from DICOM file header.Result9,963 scans (93%) were successfully pre‐processed with default parameters (Fig 1a) and 403 additional scans (4%) were included after manual intervention (Fig 1c). 339 scans (3%) were excluded because of technical artifacts or major bilateral lesions (Fig 1c). The final sample (n = 10,361) is described in Table 1, with example scans in Fig 1d. Centiloids showed the expected bimodal distribution (Fig 2a) and differentiated visually positive from negative scans (median = ‐2 versus 74 CL; area under the curve = 0.913, Fig 2b). PET acquisition generally followed tracer‐specific FDA recommendations for injected dose and acquisition time, but major variability was observed (Fig 2c). Centiloid values were independent from injected dose but were higher in patients scanned at later time windows for [18F]flutemetamol, resulting from known slow tracer kinetics (Fig 2c).ConclusionMRI‐free, amyloid‐PET quantification in a real‐world setting was feasible, with results conforming to expected distribution of Centiloid values and concordant with visual reads. However, greater standardization of PET acquisition than is currently required by FDA labels will be needed to reliably quantify amyloid PET in clinical practice (e.g., to monitor response to amyloid lowering therapy). The IDEAS dataset will be made available via the Global Alzheimer’s Association Interactive Network in 2023.

Association between blood pressure and Alzheimer’s disease biomarkers in cognitively unimpaired adults

AbstractBackgroundHigh blood pressure is an established risk factor for dementia. However, the underlying mechanisms are not completely understood. We aimed to evaluate the association between blood pressure and Alzheimer’s disease (AD) biomarkers in cognitively unimpaired adults from the ALFA+ study.MethodWe analyzed data from 301 participants with available cross‐sectional blood pressure measures (acquired by trained staff with an oscillometric device after 5 minutes of rest) and cerebrospinal fluid (CSF) AD core biomarkers data (CSF p‐tau and t‐tau were measured with Elecsys® immunoassays and CSF Aβ42 and Aβ40 with the Roche NeuroToolKit, a panel of robust prototype assays, both from Roche Diagnostics International Ltd), and a subset of 278 participants with amyloid PET data, of whom 110 had a second follow‐up PET acquisition (3.4 years after in average). We used separate linear regression models to analyze the association of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP = SBP‐DBP) with CSF and PET biomarkers at a cross‐sectional level, and their association with the annualized rate of change in amyloid PET [(follow‐up centiloids – baseline centiloids) / years between PET scan acquisition]. We adjusted all models by age, sex, APOE status, waist‐to‐hip ratio, dyslipidemia, diabetes, tobacco and alcohol consumption, physical activity, and antihypertensive treatment.ResultHigher baseline SBP (but not DBP or PP) was significantly associated with increased amyloid PET uptake over time (p = 0.043). In cross‐sectional analyses, DBP was negatively associated with Aβ42 (p = 0.013), Aβ40 (p = 0.026), and t‐tau (p = 0.045), and marginally associated with p‐tau (p = 0.069), but not with the Aβ42/40 ratio nor baseline amyloid PET uptake. Associations with Aβ42 and t‐tau were no longer significant after further adjustment by CSF Aβ40 levels. SBP and PP were not associated with CSF biomarkers or baseline amyloid PET uptake.ConclusionHigher SBP is associated with longitudinal brain amyloid accumulation, which reinforces the importance of blood pressure control in AD prevention. DBP is also associated at a cross‐sectional level with AD biomarker concentration in CSF, but the attenuation of this association after adjusting by Aβ40 suggests a non‐specific.

Practical Considerations for Total-Body PET Acquisition and Imaging.

The world's first total-body PET/CT system has been in routine clinical and research use at UC Davis since 2019. The uEXPLORER total-body PET scanner has been designed with an axial field-of-view long enough to completely encompass most human subjects (194cm or 76 inches long), allowing for a 15-68-fold gain in the PET signal collection efficiency over conventional PET scanners. A high-sensitivity PET scanner that can image the entire subject with a single bed position comes with new benefits and challenges to consider for efficient and practical use. In this chapter, we discuss the common clinical and research imaging protocols implemented at our institution, along with the appropriate technical and practical considerations of total-body PET imaging.

NIMG-20. ASSESSMENT OF RESPONSE TO REGORAFENIB IN RECURRENT GLIOMA PATIENTS USING FET PET AND MRI INCLUDING ADC VALUES

Abstract INTRODUCTION Currently, data on O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET and MRI parameters for the evaluation of response to regorafenib in glioma patients remain scarce. METHODS Twenty patients (age range, 30-72 years) with recurrent CNS WHO grade 3 or 4 gliomas (glioblastoma, 85%) were treated according to the REGOMA trial. FET PET and MRI were performed at baseline and follow-up after the second cycle. Static FET PET parameters comprised tumor-to-brain ratios (TBR) and metabolic tumor volumes (MTV). Parameters derived from dynamic FET PET acquisition were time-to-peak and slope. MRI response assessment was based on RANO criteria. Additionally, various apparent diffusion coefficients (ADC) parameters were obtained from diffusion-weighted MRI. Thresholds derived from FET PET and ADC parameters were defined using ROC analyses to predict an overall survival (OS) of ≥6 months. The predictive values of FET PET parameters, ADC values, and RANO criteria were subsequently evaluated using univariate and multivariate survival estimates. RESULTS Patients received a median of three regorafenib cycles (range, 2-10 cycles). After treatment initiation, the median follow-up was 8.6 months (range, 3.2-27.3 months). After two cycles of regorafenib, a reduction of mean TBR values by ≥10% predicted significantly longer OS (9.9 vs. 5.3 months; P=0.023). Additionally, absolute mean TBR values ≤2.0 at follow-up were prognostic and associated with a significantly longer OS (10.6 vs. 4.5 months; P=0.007). In contrast, MTV, dynamic PET parameters, RANO criteria, and ADC values were not predictive for response or were prognostic (all P &amp;gt;0.05). Multivariate survival analyses revealed that relative mean TBR changes were most potent in predicting response to regorafenib (P=0.038; HR, 0.246) and absolute mean TBR values for prognostication (P&amp;lt; 0.001; HR, 0.005). CONCLUSION In contrast to MRI metrics, FET PET parameters are clinically valuable for identifying responders to regorafenib early after treatment initiation and helpful for prognostication.