Quantitative Positron Emission Tomography Research Articles

Evaluation of PiB visual interpretation with CSF A\u03b2 and longitudinal SUVR in J-ADNI study

ObjectiveThe objectives of the present study were to investigate (1) whether trinary visual interpretation of amyloid positron emission tomography (PET) imaging (negative/equivocal/positive) reflects quantitative amyloid measurements and the time course of 11C-Pittsburgh compound B (PiB) amyloid accumulation, and (2) whether visually equivocal scans represent an early stage of the Alzheimer’s disease (AD) continuum in terms of an intermediate state of quantitative amyloid measurements and the changes in amyloid accumulation over time.MethodsFrom the National Bioscience Database Center Human Database of the Japanese Alzheimer’s Disease Neuroimaging Initiative, we selected 133 individuals for this study including 33 with Alzheimer’s disease dementia (ADD), 52 with late mild cognitive impairment (LMCI), and 48 cognitively normal (CN) subjects who underwent clinical assessment, PiB PET, and structural magnetic resonance imaging (MRI) with 2 or 3-years of follow-up. Sixty-eight of the 133 individuals underwent cerebrospinal fluid amyloid-β1-42 (CSF-Ab42) analysis at baseline. The standard uptake value ratio (SUVR) of PiB PET was calculated with a method using MRI at each visit. The cross-sectional values, longitudinal changes in SUVR, and baseline CSF-Ab42 were compared among groups, which were categorized based on trinary visual reads of amyloid PET (negative/equivocal/positive).ResultsFrom the trinary visual interpretation of the PiB PET images, 55 subjects were negative, 8 were equivocal, and 70 were positive. Negative interpretation was most frequent in the CN group (70.8/10.4/18.8%: negative/equivocal/positive), and positive was most frequent in the LMCI group (34.6/1.9/63.5%) and in the ADD group (9.1/6.1/84.8%). The baseline SUVRs were 1.08 ± 0.06 in the negative group, 1.23 ± 0.15 in the equivocal group, and 1.86 ± 0.31 in the positive group (F = 174.9, p < 0.001). The baseline CSF-Ab42 level was 463 ± 112 pg/mL in the negative group, 383 ± 125 pg/mL in the equivocal group, and 264 ± 69 pg/mL in the positive group (F = 37, p < 0.001). Over the 3-year follow-up, annual changes in SUVR were − 0.00 ± 0.02 in the negative group, 0.02 ± 0.02 in the equivocal group, and 0.04 ± 0.07 in the positive group (F = 8.4, p < 0.001).ConclusionsTrinary visual interpretation (negative/equivocal/positive) of amyloid PET imaging reflects quantitative amyloid measurements evaluated with PET and the CSF amyloid test as well as the amyloid accumulation over time evaluated with PET over 3 years. Subjects in the early stage of the AD continuum could be identified with an equivocal scan, because they showed intermediate quantitative amyloid PET, CSF measurements, and the amyloid accumulation over time.

Quantitative Analysis of [18F]FFMZ and [18F]FDG PET Studies in the Localization of Seizure Onset Zone in Drug-Resistant Temporal Lobe Epilepsy

Background: Positron emission tomography (PET) imaging in epilepsy is an in vivo technique that allows the localization of a possible seizure onset zone (SOZ) during the interictal period. Stereo-electro-encephalography (SEEG) is the gold standard to define the SOZ. The objective of this research was to evaluate the accuracy of PET imaging in localizing the site of SOZ compared with SEEG. Methods: Seven patients with refractory temporal lobe epilepsy (Ep) and 2 healthy controls (HC) underwent 2 PET scans, one with 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG) and another with 2’-[¹⁸F]fluoroflumazenil (FFMZ), acquired 1 day apart. FDG was acquired for 10 min (static scan) 1 h after administration. An FFMZ scan was acquired for 60 min from radiopharmaceutical administration in a dynamic mode. Each brain PET image was segmented using a standard template implemented in PMOD 3.8. The pons was used as the reference region for modeling of the nondisplaceable binding potential (BP_ND)for FFMZ, and to obtain uptake ratios for FDG. SEEG studies of patients were performed as a part of their surgical evaluation to define the SOZ. Results: Well-defined differences between HC and Ep were found with both radiopharmaceuticals, showing the utility to identify abnormal brain regions using quantitative PET imaging. Lateralization of the SOZ findings by PET (lower uptake/binding in a specific brain hemisphere) matched in 86% for FFMZ and 71% for FDG with SEEG data. Conclusion: Quantitative PET imaging is an excellent complementary tool that matches reasonably well with SEEG to define SOZ in presurgical evaluation.

P2702Assessment of endothelial shear stress and functional significance of coronary lesions by computed tomography coronary angiography (CTCA) and computational fluid dynamics: a comparison with PET

Abstract Background The feasibility of assessing endothelial shear stress (ESS) in coronary lesions by non-invasive imaging and its potential role in different clinical settings has been recently explored. However, the relationship of ESS with functional indices derived by computed tomography coronary angiography (CTCA) and its value in predicting perfusion changes by quantitative positron emission tomography (PET) downstream stenotic vessels has not been assessed. Purpose To investigate the feasibility of calculating local ESS, its relationship with stenosis severity as well as with virtual functional assessment index (vFAI), and the comparative performance of the two parameters for predicting impaired coronary vasodilating capability in terms both of stress myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients submitted to CTCA. Methods Thirty-two patients (23 male-9 female, mean age 65.6±7.2 years) with intermediate pre-test likelihood of coronary artery disease (CAD), who were enrolled in the EVINCI and SMARTool projects, and had undergone CTCA with vFAI and PET myocardial perfusion imaging with 15 O-water or 13 N-ammonia were included in the study. PET was considered positive when &gt;1 contiguous segments showed both stress MBF ≤2.3 mL/g/min and MFR ≤2.5 for 15 O-water or ≤1.79 mL/g/min and ≤2.0, for 13 N-ammonia respectively. A vFAI threshold of 0.85 was used as predictor of impaired vasodilating capability. ESS computation was based on a mean aortic pressure of 100 mmHg for the inlet and a mean blood flow at rest of 0.00105 kg/s for the outlet. ESS was calculated (Pa) in the full length of the stenosis and the mean value was obtained. Results Hybrid imaging analysis was performed in CTCA and PET datasets. 51 coronary segments were assessed. There were 27 lesions with stenosis 31–50% and 24 lesions with stenosis 51–70%. ESS was higher in the latter (20.4, IQ: 11.4–32.1 vs. 10.4, IQ: 5.5–15.7, p=0.04). Similarly, ESS was higher in stenoses with impaired vasodilating capacity compared to those without, although this difference did not reach statistical significance (22.8, IQ: 13.2–35.1 vs. 10.6, IQ: 5.7–22.1, p=0.10). The ROC curve analysis for prediction of both abnormal stress MBF and MFR followed the same pattern (AUC=0.668, 95% confidence interval (CI): 0.490–0.810, p=0.11).On the other hand, there was a moderate negative correlation (r=−0.41, p=0.004) between ESS and vFAI and the former was lower in stenoses with vFAI &gt;0.85 compared to those below this threshold (7.35, IQ: 3.2–13.9 vs. 19.1, IQ: 14.1–32.8, p=0.012). vFAI was a good predictor of coronary flow capacity (AUC=0.737, CI: 0.58–0.85, p=0.02). Conclusion Calculation of ESS is feasible in CTCA datasets. ESS was related with stenosis severity and there was a trend to be higher in lesions with impaired coronary vasodilating capability. ESS is modestly related with vFAI and may also be an additional predictor of impaired regional myocardial flow obtained by PET imaging. Acknowledgement/Funding This study has received funding from the EU H2020 research and innovation programme under grant agreement No 689068 and from p-Med GR 5002802

Imaging for diagnosis, staging and response assessment of Hodgkin lymphoma and non-Hodgkin lymphoma.

Hodgkin lymphoma and non-Hodgkin lymphoma are common malignancies in children and are now highly treatable. Imaging plays a major role in diagnosis, staging and response using conventional CT and MRI and metabolic imaging with positron emission tomography (PET)/CT and PET/MRI. Cross-sectional imaging has replaced staging laparotomy and splenectomy by demonstrating abdominal nodal groups and organ involvement. [F-18]2-fluoro-2-deoxyglucose (FDG) PET provides information on bone marrow involvement, and MRI elucidates details of cortical bone and confirmation of bone marrow involvement. The staging system for Hodgkin lymphoma is the Ann Arbor system with Cotswald modifications and is based on imaging, whereas the non-Hodgkin staging system is the St. Jude Classification by Murphy or the more recent revised International Pediatric Non-Hodgkin Lymphoma Staging System (IPNHLSS). Because all pediatric lymphomas are metabolically FDG-avid and identify all nodal, solid organ, cortical bone and bone marrow disease, staging evaluations require FDG PET as PET/CT or PET/MRI in both Hodgkin and non-Hodgkin lymphoma. Both diseases have in common issues of airway compromise at presentation demonstrated by imaging. Differences exist in that Hodgkin lymphoma has several independent poor prognostic factors seen by imaging such as large mediastinal adenopathy, Stage IV disease, systemic symptoms, pleural effusion and pericardial effusion. Non-Hodgkin lymphoma includes more organ involvement such as renal, ovary, central nervous system and skin. Early or interim PET-negative scans are a reliable indicator of improved clinical outcome and optimize risk-adapted therapy and patient management; imaging may not, however, predict who will relapse. A recent multicenter trial has concluded that it is usually sufficient for pediatric lymphoma at staging and interim assessment to evaluate children with PET imaging from skull base to mid-thigh. Various systems of assessment of presence of disease or response are used, including the Deauville visual scale, where avidity is compared to liver; Lugano, which includes size change as part of response; or quantitative PET, which uses standardized uptake values to define more accurate response. Newer methods of immunotherapy can produce challenges in FDG PET evaluation because of inflammatory changes that may not represent disease.

Identification and Development of an Irreversible Monoacylglycerol Lipase (MAGL) Positron Emission Tomography (PET) Radioligand with High Specificity.

Monoacylglycerol lipase (MAGL), a serine hydrolase extensively expressed throughout the brain, serves as a key gatekeeper regulating the tone of endocannabinoid signaling. Preclinically, inhibition of MAGL is known to provide therapeutic benefits for a number of neurological disorders. The availability of a MAGL-specific positron emission tomography (PET) ligand would considerably facilitate the development and clinical characterization of MAGL inhibitors via noninvasive and quantitative PET imaging. Herein, we report the identification of the potent and selective irreversible MAGL inhibitor 7 (PF-06809247) as a suitable radioligand lead, which upon radiolabeling was found to exhibit a high level of MAGL specificity; this enabled cross-species measurement of MAGL brain expression (Bmax), assessment of in vivo binding in the rat, and nonhuman primate PET imaging.

Microliter-ordered automatic blood sampling system for fully quantitative analysis of small-animal PET.

The objective of the present study was to develop a fully automated blood sampling system for kinetic analysis in mice positron emission tomography (PET) studies. Quantitative PET imaging requires radioactivity concentrations in arterial plasma to estimate the behavior of an administered radiopharmaceutical in target organs. Conventional manual blood sampling has several drawbacks, such as the need for troubleshooting in regard to blood collection, necessary personnel, and the radiation exposure dose. We recently developed and verified the operability of a fully automated blood sampling system (automatic blood dispensing system-ABDS). Here, we report the results of fully quantitative measurements of the cerebral metabolic rate of glucose (CMRglc) in mice using the ABDS. Under 1% isoflurane anesthesia, a catheter was inserted into the femoral artery of nine wild-type male mice. Immediately after injection of 18F-fluorodeoxyglucose (FDG) (13.2 ± 3.93MBq in 0.1mL saline), arterial blood samples were drawn using the ABDS and then analyzed using CD-Well, a system we previously developed that can measure radioactivity concentration (Bq/μL) using a few microliters of blood in the plasma and whole blood separately. In total, 16 blood samplings were conducted in 60min as follows: 10s × 9; 70s × 2; 120s × 1; 250s × 1; 10min × 2; and 30min × 1. Dynamic PET scans were conducted concurrently using a small-animal PET/computed tomography (CT) (PET/CT) scanner. Full kinetics modeling using a two-tissue-three-compartment model was applied to calculate CMRglc. Blood volume was also estimated. No significant differences were observed between the manual and ABDS measurements. A proportional error was detected only for plasma. The mean ± standard deviation CMRglc value in the mice was 5.43 ± 1.98mg/100g/min (30.2 ± 11 μmol/min/100g), consistent with a previous report. The automated microliter-ordered blood sampling system developed in the present study appears to be useful for absolute quantification of CMRglc in mice PET studies.

Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients.

Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results: 18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification.

Brain-Dedicated Emission Tomography Systems: A Perspective on Requirements for Clinical Research and Clinical Needs in Brain Imaging

Research applications of human brain positron emission tomography (PET) imaging have been in place for over 40 years. The unique combination of quantitative PET instrumentation and reconstruction, novel radiotracers, and kinetic modeling has led to the development and application of a huge number of imaging paradigms. These have been applied to the understanding of normal function and pathophysiology, the development of drugs for neuropsychiatric disorders, and the study of drug interactions with the brain. I have had been fortunate to be part of this great endeavor throughout my research career, using brain-dedicated PET scanners, such as the HRRT [item [1] in the Appendix]. Over time, these systems have offered important advantages over whole-body systems. However, due to the limited clinical market for brain PET imaging, scanner manufacturers have focused exclusively on large field-of-view systems for the past two decades [item [2] in the Appendix]. The goal of this perspective is to share a viewpoint on the utility of brain-dedicated PET systems for human research, particularly in the context of novel radiotracers with dynamic studies using kinetic modeling.

Penumbra detection in acute stroke with perfusion magnetic resonance imaging: Validation with 15 O-positron emission tomography.

ObjectiveAccurate identification of the ischemic penumbra, the therapeutic target in acute clinical stroke, is of critical importance to identify patients who might benefit from reperfusion therapies beyond the established time windows. Therefore, we aimed to validate magnetic resonance imaging (MRI) mismatch–based penumbra detection against full quantitative positron emission tomography (15O‐PET), the gold standard for penumbra detection in acute ischemic stroke.MethodsTen patients (group A) with acute and subacute ischemic stroke underwent perfusion‐weighted (PW)/diffusion‐weighted MRI and consecutive full quantitative 15O‐PET within 48 hours of stroke onset. Penumbra as defined by 15O‐PET cerebral blood flow (CBF), oxygen extraction fraction, and oxygen metabolism was used to validate a wide range of established PW measures (eg, time‐to‐maximum [Tmax]) to optimize penumbral tissue detection. Validation was carried out using a voxel‐based receiver‐operating‐characteristic curve analysis. The same validation based on penumbra as defined by quantitative 15O‐PET CBF was performed for comparative reasons in 23 patients measured within 48 hours of stroke onset (group B).ResultsThe PW map Tmax (area‐under‐the‐curve = 0.88) performed best in detecting penumbral tissue up to 48 hours after stroke onset. The optimal threshold to discriminate penumbra from oligemia was Tmax >5.6 seconds with a sensitivity and specificity of >80%.InterpretationThe performance of the best PW measure Tmax to detect the upper penumbral flow threshold in ischemic stroke is excellent. Tmax >5.6 seconds–based penumbra detection is reliable to guide treatment decisions up to 48 hours after stroke onset and might help to expand reperfusion treatment beyond the current time windows. ANN NEUROL 2019;85:875–886.

18F-fluoride as a prognostic indicator of bone regeneration

Positron emission tomography (PET) is a form of nuclear imaging, which quantitatively assesses the metabolic activity through the uptake of radioactive tracers. 18F-fluoride is a positron-emitting isotope with high affinity for bone. Despite its potential as a non-invasive measure of bone metabolism, quantitative 18F-fluoride PET has only been used sparsely in orthopaedic applications. It has been speculated that 18F-fluoride PET characterizes cellular activity of bone forming cells in the early stages of the regenerative process and therefore precedes the mineralization detected by conventional computed tomography (CT). Our aim was thus to combine in vivo PET and CT to map the spatiotemporal course of bone regeneration during fracture healing using an open femur fracture model in the rat and characterize regeneration in untreated and pharmacologically treated fractures using both imaging modalities. We hypothesized that PET 18F-fluoride tracer activity at an earlier time point is predictive of CT measured bone formation at a later time point. On the basis of the RMSE and R2 metrics of linear regression models it was conceivable for bone volumes to be predicted up to three weeks in advance in a rodent model (RMSE: 14 mm3–18 mm3, R2: 0.79–0.82). Moreover, the data suggested that 18F-fluoride positron-emitting activity had the potential to separate bone formation from resorption and thus could be of interest across a wide array of orthopaedic applications. Based on this data, we conclude that 18F-fluoride positron-emitting activity is strongly correlated to bone formation and could potentially predict the volume of bone regenerated at fracture sites. The volume of bone regenerated at a fracture site can be interpreted as a measure of the healing response and 18F-fluoride should be further investigated as a predictive diagnostic tool to identify if bone fractures will heal successfully or result in delayed healing or non-union. Statement of SignificanceWe aimed to combine in vivo PET and CT imaging to map the spatiotemporal course of bone regeneration during fracture healing using an open femur fracture model in the rat and characterize regeneration in untreated and pharmacologically treated fractures using both imaging modalities. We hypothesized that PET 18F-fluoride tracer activity at an earlier time point is predictive of CT measured bone formation at a later time point.Our data suggest that 18F-fluoride positron-emitting activity can separate bone formation from resorption and thus could be of interest across a wide array of orthopaedic applications including as a predictive diagnostic tool to identify if fractures will heal successfully or result in delayed healing or non-union.

Joint correction of attenuation and scatter in image space using deep convolutional neural networks for dedicated brain 18F-FDG PET

Dedicated brain positron emission tomography (PET) devices can provide higher-resolution images with much lower doses compared to conventional whole-body PET systems, which is important to support PET neuroimaging and particularly useful for the diagnosis of neurodegenerative diseases. However, when a dedicated brain PET scanner does not come with a combined CT or transmission source, there is no direct solution for accurate attenuation and scatter correction, both of which are critical for quantitative PET. To address this problem, we propose joint attenuation and scatter correction (ASC) in image space for non-corrected PET (PETNC) using deep convolutional neural networks (DCNNs). This approach is a one-step process, distinct from conventional methods that rely on generating attenuation maps first that are then applied to iterative scatter simulation in sinogram space. For training and validation, time-of-flight PET/MR scans and additional helical CTs were performed for 35 subjects (25/10 split for training and test dataset). A DCNN model was proposed and trained to convert PETNC to DCNN-based ASC PET (PETDCNN) directly in image space. For quantitative evaluation, uptake differences between PETDCNN and reference CT-based ASC PET (PETCT-ASC) were computed for 116 automated anatomical labels (AALs) across 10 test subjects (1160 regions in total). MR-based ASC PET (PETMR-ASC), a current clinical protocol in PET/MR imaging, was another reference for comparison. Statistical significance was assessed using a paired t test. The performance of PETDCNN was comparable to that of PETMR-ASC, in comparison to reference PETCT-ASC. The mean SUV differences (mean ± SD) from PETCT-ASC were 4.0% ± 15.4% (P < 0.001) and −4.2% ± 4.3% (P < 0.001) for PETDCNN and PETMR-ASC, respectively. The overall larger variation of PETDCNN (15.4%) was prone to the subject with the highest mean difference (48.5% ± 10.4%). The mean difference of PETDCNN excluding the subject was substantially improved to −0.8% ± 5.2% (P < 0.001), which was lower than that of PETMR-ASC (−5.07% ± 3.60%, P < 0.001). In conclusion, we demonstrated the feasibility of directly producing PET images corrected for attenuation and scatter using a DCNN (PETDCNN) from PETNC in image space without requiring conventional attenuation map generation and time-consuming scatter correction. Additionally, our DCNN-based method provides a possible alternative to MR-ASC for simultaneous PET/MRI.

DeepPET: A deep encoder-decoder network for directly solving the PET image reconstruction inverse problem.

The purpose of this research was to implement a deep learning network to overcome two of the major bottlenecks in improved image reconstruction for clinical positron emission tomography (PET). These are the lack of an automated means for the optimization of advanced image reconstruction algorithms, and the computational expense associated with these state-of-the art methods. We thus present a novel end-to-end PET image reconstruction technique, called DeepPET, based on a deep convolutional encoder-decoder network, which takes PET sinogram data as input and directly and quickly outputs high quality, quantitative PET images. Using simulated data derived from a whole-body digital phantom, we randomly sampled the configurable parameters to generate realistic images, which were each augmented to a total of more than 291,000 reference images. Realistic PET acquisitions of these images were simulated, resulting in noisy sinogram data, used for training, validation, and testing the DeepPET network. We demonstrated that DeepPET generates higher quality images compared to conventional techniques, in terms of relative root mean squared error (11%/53% lower than ordered subset expectation maximization (OSEM)/filtered back-projection (FBP), structural similarity index (1%/11% higher than OSEM/FBP), and peak signal-to-noise ratio (1.1/3.8dB higher than OSEM/FBP). In addition, we show that DeepPET reconstructs images 108 and 3 times faster than OSEM and FBP, respectively. Finally, DeepPET was successfully applied to real clinical data. This study shows that an end-to-end encoder-decoder network can produce high quality PET images at a fraction of the time compared to conventional methods.

Molecular Imaging Visualizes Recruitment of Inflammatory Monocytes and Macrophages to the Injured Heart.

Paradigm shifting studies have revealed that the heart contains functionally diverse populations of macrophages derived from distinct embryonic and adult hematopoietic progenitors. Under steady-state conditions, the heart is largely populated by CCR2- (C-C chemokine receptor type 2) macrophages of embryonic descent. After tissue injury, a dramatic shift in macrophage composition occurs whereby CCR2+ monocytes are recruited to the heart and differentiate into inflammatory CCR2+ macrophages that contribute to heart failure progression. Currently, there are no techniques to noninvasively detect CCR2+ monocyte recruitment into the heart and thus identify patients who may be candidates for immunomodulatory therapy. To develop a noninvasive molecular imaging strategy with high sensitivity and specificity to visualize inflammatory monocyte and macrophage accumulation in the heart. We synthesized and tested the performance of a positron emission tomography radiotracer (68Ga-DOTA [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-ECL1i [extracellular loop 1 inverso]) that allosterically binds to CCR2. In naive mice, the radiotracer was quickly cleared from the blood and displayed minimal retention in major organs. In contrast, biodistribution and positron emission tomography demonstrated strong myocardial tracer uptake in 2 models of cardiac injury (diphtheria toxin induced cardiomyocyte ablation and reperfused myocardial infarction). 68Ga-DOTA-ECL1i signal localized to sites of tissue injury and was independent of blood pool activity as assessed by quantitative positron emission tomography and ex vivo autoradiography. 68Ga-DOTA-ECL1i uptake was associated with CCR2+ monocyte and CCR2+ macrophage infiltration into the heart and was abrogated in CCR2-/- mice, demonstrating target specificity. Autoradiography demonstrated that 68Ga-DOTA-ECL1i specifically binds human heart failure specimens and with signal intensity associated with CCR2+ macrophage abundance. These findings demonstrate the sensitivity and specificity of 68Ga-DOTA-ECL1i in the mouse heart and highlight the translational potential of this agent to noninvasively visualize CCR2+ monocyte recruitment and inflammatory macrophage accumulation in patients.

Impact of different image reconstructions on PET quantification in non-small cell lung cancer: a comparison of adenocarcinoma and squamous cell carcinoma

Positron emission tomography (PET) using 18F-fludeoxyglucose (18F-FDG) is an established imaging modality for tumor staging in patients with non-small cell lung cancer (NSCLC). There is a growing interest in using 18F-FDG PET for therapy response assessment in NSCLC which relies on quantitative PET parameters such as standardized uptake values (SUV). Different reconstruction algorithms in PET may affect SUV. We sought to determine the variation of SUV in patients with NSCLC when using ordered subset expectation maximization (OSEM) and block sequential regularized expectation maximization (BSREM) in latest-generation digital PET/CT, including a subanalysis for adenocarcinoma and squamous cell carcinoma. A total of 58 patients (34 = adenocarcinoma, 24 = squamous cell carcinoma) who underwent a clinically indicated 18F-FDG PET/CT for staging were reviewed. PET images were reconstructed with OSEM and BSREM reconstruction with noise penalty strength β-levels of 350, 450, 600, 800 and 1200. Lung tumors maximum standardized uptake value (SUVmax) were compared. Lung tumors SUVmax were significantly lower in adenocarcinomas compared to squamous cell carcinomas in all reconstructions evaluated (all p < 0.01). Comparing BSREM to OSEM, absolute SUVmax differences were highest in lower β-levels of BSREM with + 2.9 ± 1.6 in adenocarcinoma and + 4.0 ± 2.9 in squamous cell carcinoma (difference between histology; p-values > 0.05). There was a statistically significant difference of the relative increase of SUVmax in adenocarcinoma (mean + 34.8%) and squamous cell carcinoma (mean 23.4%), when using BSREM350 instead of OSEMTOF (p < 0.05). In NSCLC the relative change of SUV when using BSREM instead of OSEM is significantly higher in adenocarcinoma as compared to squamous cell carcinoma. The impact of BSREM on SUV may vary in different histological subtypes of NSCLC. This highlights the importance for careful standardization of β-value used for serial 18F-FDG PET scans when following-up NSCLC patients.

Links Between Metabolic and Structural Changes in the Brain of Cognitively Normal Older Adults: A 4-Year Longitudinal Follow-Up.

We aimed to longitudinally assess the relationship between changing brain energy metabolism (glucose and acetoacetate) and cognition during healthy aging. Participants aged 71 ± 5 year underwent cognitive evaluation and quantitative positron emission tomography (PET) and magnetic resonance imaging (MRI) scans at baseline (N = 25) and two (N = 25) and four (N = 16) years later. During the follow-up, the rate constant for brain extraction of glucose (Kglc) declined by 6%–12% mainly in the temporo-parietal lobes and cingulate gyri (p ≤ 0.05), whereas brain acetoacetate extraction (Kacac) and utilization remained unchanged in all brain regions (p ≥ 0.06). Over the 4 years, cognitive results remained within the normal age range but an age-related decline was observed in processing speed. Kglc in the caudate was directly related to performance on several cognitive tests (r = +0.41 to +0.43, all p ≤ 0.04). Peripheral insulin resistance assessed by the homeostasis model assessment of insulin resistance (HOMA-IR) was significantly inversely related to Kglc in the thalamus (r = −0.44, p = 0.04) and in the caudate (r = −0.43, p = 0.05), and also inversely related to executive function, attention and processing speed (r = −0.45 to −0.53, all p ≤ 0.03). We confirm in a longitudinal setting that the age-related decline in Kglc is directly associated with declining performance on some tests of cognition but does not significantly affect Kacac.

PET Counting Response Variability Depending on Tumor Location, Activity, and Patient Obesity: A Feasibility Study of Solitary Pulmonary Nodule Using Monte Carlo.

We aim to investigate the counting response variations of positron emission tomography (PET) scanners with different detector configurations in the presence of solitary pulmonary nodule (SPN). Using experimentally validated Monte Carlo simulations, the counting performance of four different scanner models with varying tumor activity, location, and patient obesity is represented using a noise equivalent count rate (NECR). NECR is a well-established quantitative metric which has positive correlation with clinically perceived image quality. The combined effect of tumor displacement and increased activity shows a linear ascending trend for NECR with slope ranges of (12.5-18.2)*10-3 (kBq/cm3)-1 for three-ring (3R) scanners and (15.3-21.5)*10-3 (kBq/cm3)-1 for four-ring (4R). The trend for the combined effect of tumor displacement and patient obesity is exponential decay with 3R configurations weakly dependent on the patient obesity if the tumor is located at the center of the field of view with exponent's range of (6.6-33.8)*10-2cm-1. The dependence is stronger for 4R scanners (9.6-38.5)*10-2cm-1. The analysis indicates that quantitative PET data from the same SPN patient possibly examined in different time points (e.g., during staging or for the evaluation of treatment response) are affected by the different detector configurations and need to be normalized with patient weight, activity, and tumor location to reduce unwanted bias of the diagnosis. This paper provides also with a proof of concept for the ability of properly tuned simulations to provide additional insights into the counting response variability especially in tumor types where often borderline decisions have to be made regarding their characterization.

The relationship between quantitative positron emission tomography parameters, the invasive lung adenocarcinoma grading system of International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society, and survival

BACKGROUND: The impact of newly defined subtypes and grades of adenocarcinoma on the survival and their reflection on imaging methods and nuclear medicine practices are popular research topics. AIMS: The aim of the study is to investigate quantitative positron emission tomography (PET) parameters and the adenocarcinoma grading system of the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society in terms of survival and potential prognosis prediction value in operated lung adenocarcinoma patients. STUDY DESIGN: One hundred and seventy-nine patients who were surgically treated for adenocarcinoma of the lung were included in the study. 2-deoxy-2-(18F) fluoro-D-glucose (FDG) PET/computerized tomography (CT) was applied for initial staging. MATERIALS AND METHODS: For quantitative evaluation, maximum standardized uptake values (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors were calculated. RESULTS: There was a statistically significant relation between grade and radiological appearance, but tumor grade and SUVmax, TLG, and MTV parameters showed no significant correlation. Pathological tumor size and PET/CT had strong correlation (P CONCLUSION: Metabolic parameters are still superior to new adenocarcinoma grading system in terms of survival. Measurement of tumor size on PET/CT is an important predictive value about pathological T-stage.

Microvascular Dysfunction in Hypertrophic Cardiomyopathy

In hypertrophic cardiomyopathy (HCM), the presence of vessel abnormalities with microvascular dysfunction is a well-known feature. The aim of this review is to present the evidences that support this notion and to describe the physiopathologic and clinical consequences of microvascular dysfunction. After having demonstrated the presence and significance of microvascular dysfunction in HCM, the myocardial blood flow (MBF) measurement by positron emission tomography (PET) is ready to develop into a clinical tool for disease evaluation, in particular for patient prognostication. Alternative methods are becoming available, but they are not yet equally reliable. By means of MBF measurement using quantitative PET, the importance of microvascular dysfunction in HCM has been clearly demonstrated, explaining the chest pain and the ischemic abnormalities frequently registered in this disease. The physiopathologic implications of microvascular dysfunction have been established, and an increasing number of reports indicate that the assessment of microvascular dysfunction is as well important for patient characterization and prognostication. Most recently, perfusion measurements using magnetic resonance imaging have been used, but their role is still under debate.

Информативность количественных показателей миокардиального кровотока и коронарного резерва по данным позитронно-эмиссионной томографии с 13N-аммонием, совмещенной с компьютерной томографией, в оценке функциональной значимости стенозов коронарных артерий

Информативность количественных показателей миокардиального кровотока и коронарного резерва по данным позитронно-эмиссионной томографии с 13N-аммонием, совмещенной с компьютерной томографией, в оценке функциональной значимости стенозов коронарных артерий

Comparison of maximal hyperemic myocardial blood flow response between regadenoson and adenosine: A quantitative positron emission tomography 13n-ammonia study

Comparison of maximal hyperemic myocardial blood flow response between regadenoson and adenosine: A quantitative positron emission tomography 13n-ammonia study