Left ventricular shape index and eccentricity index with ECG-gated Nitrogen-13 ammonia PET/CT in patients with myocardial infarction, ischemia, and normal perfusion.

BACKGROUND: LV geometry with shape index (SI) and eccentricity index (EI) measured by myocardial perfusion positron emission tomography/computed tomography (PET/CT) may allow the evaluation of left ventricular (LV) adverse remodeling. This first study aims to explore the relationship of SI and EI values acquired by Nitrogen-13 ammonia PET/CT in patients with normal perfusion, ischemia, and myocardial infarction. And evaluate the correlations between the variables of LV geometry, and with the variables of LV function. METHODS AND RESULTS: One hundred and forty patients who underwent an electrocardiogram (ECG)-gated PET/CT were selected and classified into 4 groups according to ischemia or infarction burden (normal perfusion, mild ischemia, moderate-severe ischemia, and infarction). The variables were automatically retrieved using dedicated software (QPS/QGS; Cedars-Sinai, Los Angeles, CA, USA). On multicomparison analysis (one-way ANOVA and Dunnett's Test), subjects in the infarction group had significant higher values of SI end-diastolic rest (P < 0.001), and stress (P = 0.003), SI end-systolic rest (P = 0.002) and stress (P < 0.001) as well as statistically significant lower values of EI rest (P < 0.001) and stress (P < 0.001) when compared with all other groups. Regarding Pearson correlation, in the infarcted group all the variables of SI and EI were significantly correlated (P < 0.001) with strong correlation coefficients (>0.60). SI end-systolic correlated significantly with the variables of LV function independently of the group of patients (P < 0.05). CONCLUSIONS: Shape and eccentricity indices differ in patients with myocardial infarction as compared to patients with ischemia or normal perfusion. This encourage further research in their potential for detecting LV adverse remodeling.

Can Internal Carotid Arteries Be Used for Noninvasive Quantification of Brain PET Studies?

Because of the limited axial field of view of conventional PET scanners, the internal carotid arteries are commonly used to obtain an image-derived input function (IDIF) in quantitative brain PET. However, time-activity curves extracted from the internal carotids are prone to partial-volume effects due to the limited PET resolution. This study aimed to assess the use of the internal carotids for quantifying brain glucose metabolism before and after partial-volume correction. Methods: Dynamic [18F]FDG images were acquired on a 106-cm-long PET scanner, and quantification was performed with a 2-tissue-compartment model and Patlak analysis using an IDIF extracted from the internal carotids. An IDIF extracted from the ascending aorta was used as ground truth. Results: The internal carotid IDIF underestimated the area under the curve by 37% compared with the ascending aorta IDIF, leading to Ki values approximately 17% higher. After partial-volume correction, the mean relative Ki differences calculated with the ascending aorta and internal carotid IDIFs dropped to 7.5% and 0.05%, when using a 2-tissue-compartment model and Patlak analysis, respectively. However, microparameters (K 1, k 2, k 3) derived from the corrected internal carotid curve differed significantly from those obtained using the ascending aorta. Conclusion: These results suggest that partial-volume-corrected internal carotids may be used to estimate Ki but not kinetic microparameters. Further validation in a larger patient cohort with more variable kinetics is needed for more definitive conclusions.

Does FDG-PET/CT for incidentally found pulmonary lesions lead to a cascade of more incidental findings?

OBJECTIVE: To determine the frequency, nature, and downstream healthcare costs of new incidental findings that are found on whole-body FDG-PET/CT in patients with a non-FDG-avid pulmonary lesion ≥10 mm that was incidentally found on previous imaging. MATERIALS AND METHODS: This retrospective study included a consecutive series of patients who underwent whole-body FDG-PET/CT because of an incidentally found pulmonary lesion ≥10 mm. RESULTS: Seventy patients were included, of whom 23 (32.9 %) had an incidentally found pulmonary lesion that proved to be non-FDG-avid. In 12 of these 23 cases (52.2 %) at least one new incidental finding was discovered on FDG-PET/CT. The total number of new incidental findings was 21, of which 7 turned out to be benign, 1 proved to be malignant (incurable metastasized cancer), and 13 whose nature remained unclear. One patient sustained permanent neurologic impairment of the left leg due to iatrogenic nerve damage during laparotomy for an incidental finding which turned out to be benign. The total costs of all additional investigations due to the detection of new incidental findings amounted to €9903.17, translating to an average of €141.47 per whole-body FDG-PET/CT scan performed for the evaluation of an incidentally found pulmonary lesion. CONCLUSION: In many patients in whom whole-body FDG-PET/CT was performed to evaluate an incidentally found pulmonary lesion that turned out to be non-FDG-avid and therefore very likely benign, FDG-PET/CT detected new incidental findings in our preliminary study. Whether the detection of these new incidental findings is cost-effective or not, requires further research with larger sample sizes.

Advances in PET Imaging of Large Vessel Vasculitis: An Update and Future Trends.

Systemic vasculitides are autoimmune diseases characterized by inflammation of blood vessels. They are categorized based on the size of the preferentially affected blood vessels: large-, medium-, and small-vessel vasculitides. The main forms of large-vessel vasculitis include giant cell arteritis (GCA) and Takayasu arteritis (TAK). Depending on the location of the affected vessels, various imaging modalities can be employed for diagnosis of large vessel vasculitis: ultrasonography (US), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT). These imaging tools offer complementary information about vascular changes occurring in vasculitis. Recent advances in PET imaging in large vessel vasculitis include the introduction of digital long axial field-of-view PET/CT, dedicated acquisition, quantitative methodologies, and the availability of novel radiopharmaceuticals. This review aims to provide an update on the current status of PET imaging in large vessel vasculitis and to share the latest developments on imaging vasculitides.

Automated multiclass segmentation, quantification, and visualization of the diseased aorta on hybrid PET/CT-SEQUOIA.

BACKGROUND: Cardiovascular disease is the most common cause of death worldwide, including infection and inflammation related conditions. Multiple studies have demonstrated potential advantages of hybrid positron emission tomography combined with computed tomography (PET/CT) as an adjunct to current clinical inflammatory and infectious biochemical markers. To quantitatively analyze vascular diseases at PET/CT, robust segmentation of the aorta is necessary. However, manual segmentation is extremely time-consuming and labor-intensive. PURPOSE: To investigate the feasibility and accuracy of an automated tool to segment and quantify multiple parts of the diseased aorta on unenhanced low-dose computed tomography (LDCT) as an anatomical reference for PET-assessed vascular disease. METHODS: A software pipeline was developed including automated segmentation using a 3D U-Net, calcium scoring, PET uptake quantification, background measurement, radiomics feature extraction, and 2D surface visualization of vessel wall calcium and tracer uptake distribution. To train the 3D U-Net, 352 non-contrast LDCTs from (2-[18 F]FDG and Na[18 F]F) PET/CTs performed in patients with various vascular pathologies with manual segmentation of the ascending aorta, aortic arch, descending aorta, and abdominal aorta were used. The last 22 consecutive scans were used as a hold-out internal test set. The remaining dataset was randomly split into training (n = 264; 80%) and validation (n = 66; 20%) sets. Further evaluation was performed on an external test set of 49 PET/CTs. The dice similarity coefficient (DSC) and Hausdorff distance (HD) were used to assess segmentation performance. Automatically obtained calcium scores and uptake values were compared with manual scoring obtained using clinical softwares (syngo.via and Affinity Viewer) in six patient images. intraclass correlation coefficients (ICC) were calculated to validate calcium and uptake values. RESULTS: Fully automated segmentation of the aorta using a 3D U-Net was feasible in LDCT obtained from PET/CT scans. The external test set yielded a DSC of 0.867 ± 0.030 and HD of 1.0 [0.6-1.4] mm, similar to an open-source model with a DSC of 0.864 ± 0.023 and HD of 1.4 [1.0-1.8] mm. Quantification of calcium and uptake values were in excellent agreement with clinical software (ICC: 1.00 [1.00-1.00] and 0.99 [0.93-1.00] for calcium and uptake values, respectively). CONCLUSIONS: We present an automated pipeline to segment the ascending aorta, aortic arch, descending aorta, and abdominal aorta on LDCT from PET/CT and to accurately provide uptake values, calcium scores, background measurement, radiomics features, and a 2D visualization. We call this algorithm SEQUOIA (SEgmentation, QUantification, and visualizatiOn of the dIseased Aorta) and is available at https://github.com/UMCG-CVI/SEQUOIA. This model could augment the utility of aortic evaluation at PET/CT studies tremendously, irrespective of the tracer, and potentially provide fast and reliable quantification of cardiovascular diseases in clinical practice, both for primary diagnosis and disease monitoring.

Ultra-low dose CT scanning for PET/CT.

BACKGROUND: The use of computed tomography (CT) for attenuation correction (AC) in whole-body PET/CT can result in a significant contribution to radiation exposure. This can become a limiting factor for reducing considerably the overall radiation exposure of the patient when using the new long axial field of view (LAFOV) PET scanners. However, recent CT technology have introduced features such as the tin (Sn) filter, which can substantially reduce the CT radiation dose. PURPOSE: The purpose of this study was to investigate the ultra-low dose CT for attenuation correction using the Sn filter together with other dose reduction options such as tube current (mAs) reduction. We explore the impact of dose reduction in the context of AC-CT and how it affects PET image quality. METHODS: The study evaluated a range of ultra-low dose CT protocols using five physical phantoms that represented a broad collection of tissue electron densities. A long axial field of view (LAFOV) PET/CT scanner was used to scan all phantoms, applying various CT dose reduction parameters such as reducing tube current (mAs), increasing the pitch value, and applying the Sn filter. The effective dose resulting from the CT scans was determined using the CTDIVol reported by the scanner. Several voxel-based and volumes of interest (VOI)-based comparisons were performed to compare the ultra-low dose CT images, the generated attenuation maps, and corresponding PET images against those images acquired with the standard low dose CT protocol. Finally, two patient datasets were acquired using one of the suggested ultra-low dose CT settings. RESULTS: By incorporating the Sn filter and adjusting mAs to the lowest available value, the radiation dose in CT images of PBU-60 phantom was significantly reduced; resulting in an effective dose of nearly 2% compared to the routine low dose CT protocols currently in clinical use. The assessment of PET images using VOI and voxel-based comparisons indicated relative differences (RD%) of under 6% for mean activity concentration (AC) in the torso phantom and patient dataset and under 8% for a source point in the CIRS phantom. The maximum RD% value of AC was 14% for the point source in the CIRS phantom. Increasing the tube current from 6 mAs to 30 mAs in patients with high BMI, or with arms down, can suppress the photon starvation artifact, whilst still preserving a dose reduction of 90%. CONCLUSIONS: Introducing a Sn filter in CT imaging lowers radiation dose by more than 90%. This reduction has minimal effect on PET image quantification at least for patients without Body Mass Index (BMI) higher than 30. Notably, this study results need validation using a larger clinical PET/CT dataset in the future, including patients with higher BMI.

Current and Future Use of Long Axial Field-of-View Positron Emission Tomography/Computed Tomography Scanners in Clinical Oncology.

The latest technical development in the field of positron emission tomography/computed tomography (PET/CT) imaging has been the extension of the PET axial field-of-view. As a result of the increased number of detectors, the long axial field-of-view (LAFOV) PET systems are not only characterized by a larger anatomical coverage but also by a substantially improved sensitivity, compared with conventional short axial field-of-view PET systems. In clinical practice, this innovation has led to the following optimization: (1) improved overall image quality, (2) decreased duration of PET examinations, (3) decreased amount of radioactivity administered to the patient, or (4) a combination of any of the above. In this review, novel applications of LAFOV PET in oncology are highlighted and future directions are discussed.

The clinical value of quantitative cardiovascular molecular imaging: a step towards precision medicine.

Cardiovascular diseases (CVD) are the leading cause of death worldwide and have an increasing impact on society. Precision medicine, in which optimal care is identified for an individual or a group of individuals rather than for the average population, might provide significant health benefits for this patient group and decrease CVD morbidity and mortality. Molecular imaging provides the opportunity to assess biological processes in individuals in addition to anatomical context provided by other imaging modalities and could prove to be essential in the implementation of precision medicine in CVD. New developments in single-photon emission computed tomography (SPECT) and positron emission tomography (PET) systems, combined with rapid innovations in promising and specific radiopharmaceuticals, provide an impressive improvement of diagnostic accuracy and therapy evaluation. This may result in improved health outcomes in CVD patients, thereby reducing societal impact. Furthermore, recent technical advances have led to new possibilities for accurate image quantification, dynamic imaging, and quantification of radiotracer kinetics. This potentially allows for better evaluation of disease activity over time and treatment response monitoring. However, the clinical implementation of these new methods has been slow. This review describes the recent advances in molecular imaging and the clinical value of quantitative PET and SPECT in various fields in cardiovascular molecular imaging, such as atherosclerosis, myocardial perfusion and ischemia, infiltrative cardiomyopathies, systemic vascular diseases, and infectious cardiovascular diseases. Moreover, the challenges that need to be overcome to achieve clinical translation are addressed, and future directions are provided.

Long Versus Short Axial Field of View Immuno-PET/CT: Semiquantitative Evaluation for 89Zr-Trastuzumab.

The purpose of this study was to quantify any differences between the SUVs of 89Zr immuno-PET scans obtained using a PET/CT system with a long axial field of view (LAFOV; Biograph Vision Quadra) compared to a PET/CT system with a short axial field of view (SAFOV; Biograph Vision) and to evaluate how LAFOV PET scan duration affects image noise and SUV metrics. Methods: Five metastatic breast cancer patients were scanned consecutively on SAFOV and LAFOV PET/CT scanners. Four additional patients were scanned using only LAFOV PET/CT. Scans on both systems lasted approximately 30 min and were acquired 4 d after injection of 37 MBq of 89Zr-trastuzumab. LAFOV list-mode data were reprocessed to obtain images acquired using shorter scan durations (15, 10, 7.5, 5, and 3 min). Volumes of interest were placed in healthy tissues, and tumors were segmented semiautomatically to compare coefficients of variation and to perform Bland-Altman analysis on SUV metrics (SUVmax, SUVpeak, and SUVmean). Results: Using 30-min images, 2 commonly used lesion SUV metrics were higher for SAFOV than for LAFOV PET (SUVmax, 16.2% ± 13.4%, and SUVpeak, 10.1% ± 7.2%), whereas the SUVmean of healthy tissues showed minimal differences (0.7% ± 5.8%). Coefficients of variation in the liver derived from 30-min SAFOV PET were between those of 3- and 5-min LAFOV PET. The smallest SUVmax and SUVpeak differences between SAFOV and LAFOV were found for 3-min LAFOV PET. Conclusion: LAFOV 89Zr immuno-PET showed a lower SUVmax and SUVpeak than SAFOV because of lower image noise. LAFOV PET scan duration may be reduced at the expense of increasing image noise and bias in SUV metrics. Nevertheless, SUVpeak showed only minimal bias when reducing scan duration from 30 to 10 min.

[15O]H2O PET: Potential or Essential for Molecular Imaging?

Imaging water pathways in the human body provides an excellent way of measuring accurately the blood flow directed to different organs. This makes it a powerful diagnostic tool for a wide range of diseases that are related to perfusion and oxygenation. Although water PET has a long history, its true potential has not made it into regular clinical practice. The article highlights the potential of water PET in molecular imaging and suggests its prospective role in becoming an essential tool for the 21st century precision medicine in different domains ranging from preclinical to clinical research and practice. The recent technical advances in high-sensitivity PET imaging can play a key accelerating role in empowering this technique, though there are still several challenges to overcome.

Image Reconstruction Analysis for Positron Emission Tomography With Heterostructured Scintillators.

The concept of structure engineering has been proposed for exploring the next generation of radiation detectors with improved performance. A TOF-PET geometry with heterostructured scintillators with a pixel size of 3.0 × 3.1 × 15 mm3 was simulated using Monte Carlo. The heterostructures consisted of alternating layers of BGO as a dense material with high stopping power and plastic (EJ232) as a fast light emitter. The detector time resolution was calculated as a function of the deposited and shared energy in both materials on an event-by-event basis. While sensitivity was reduced to 32% for 100-µm thick plastic layers and 52% for 50 µm, the coincidence time resolution (CTR) distribution improved to 204 ± 49 and 220 ± 41 ps, respectively, compared to 276 ps that we considered for bulk BGO. The complex distribution of timing resolutions was accounted for in the reconstruction. We divided the events into three groups based on their CTR and modeled them with different Gaussian TOF kernels. On an NEMA IQ phantom, the heterostructures had better contrast recovery in early iterations. On the other hand, BGO achieved a better contrast-to-noise ratio (CNR) after the 15th iteration due to the higher sensitivity. The developed simulation and reconstruction methods constitute new tools for evaluating different detector designs with complex time responses.

Exploring the Utility of Cardiovascular Magnetic Resonance Radiomic Feature Extraction for Evaluation of Cardiac Sarcoidosis.

BACKGROUND: The aim of this study is to explore the utility of cardiac magnetic resonance (CMR) imaging of radiomic features to distinguish active and inactive cardiac sarcoidosis (CS). METHODS: Subjects were classified into active cardiac sarcoidosis (CSactive) and inactive cardiac sarcoidosis (CSinactive) based on PET-CMR imaging. CSactive was classified as featuring patchy [18F]fluorodeoxyglucose ([18F]FDG) uptake on PET and presence of late gadolinium enhancement (LGE) on CMR, while CSinactive was classified as featuring no [18F]FDG uptake in the presence of LGE on CMR. Among those screened, thirty CSactive and thirty-one CSinactive patients met these criteria. A total of 94 radiomic features were subsequently extracted using PyRadiomics. The values of individual features were compared between CSactive and CSinactive using the Mann-Whitney U test. Subsequently, machine learning (ML) approaches were tested. ML was applied to two sub-sets of radiomic features (signatures A and B) that were selected by logistic regression and PCA, respectively. RESULTS: Univariate analysis of individual features showed no significant differences. Of all features, gray level co-occurrence matrix (GLCM) joint entropy had a good area under the curve (AUC) and accuracy with the smallest confidence interval, suggesting it may be a good target for further investigation. Some ML classifiers achieved reasonable discrimination between CSactive and CSinactive patients. With signature A, support vector machine and k-neighbors showed good performance with AUC (0.77 and 0.73) and accuracy (0.67 and 0.72), respectively. With signature B, decision tree demonstrated AUC and accuracy around 0.7; Conclusion: CMR radiomic analysis in CS provides promising results to distinguish patients with active and inactive disease.

Oral administration of PET tracers: Current status.

The oral route is the most widely used and preferable way of drug administration. Several pharmacokinetic processes play a role in the distribution of administered drugs. Therefore, accurate quantification of absorption, distribution, metabolism, excretion, and characterisation of drug kinetics after oral administration is extremely important for developing new human drugs. In vivo methods, such as gamma-scintigraphy, magnetic resonance imaging (MRI), and positron emission tomography (PET), have been used to analyse gastrointestinal tract (GIT) absorption behaviour. This scoping review provides an overview of PET studies that used oral tracer administration. A systematic literature search was performed using PubMed, EMBASE, Scopus, Science Direct, and Web of Science databases. Extensive variation between these studies was seen concerning acquisition protocols, quantification methods, and pharmacokinetic outcome parameters. Studies in humans indicate that it takes 10 to 30 min for the tracer to be in the intestine and about 100 min to reach its maximum concentration in the brain. In rodent studies, different pharmacokinetic parameters for the brain, blood, and GIT were estimated, showing the potential of PET to measure the absorption and distribution of drugs and pharmaceuticals non-invasively. Finally, regarding radiation protection, oral administration has a higher absorbed dose in GIT and, consequently, a higher effective dose. However, with the recent introduction of Long Axial Field of View (LAFOV) PET scanners, it is possible to reduce the administered dose, making oral administration feasible for routine clinical studies.

An Automated Method for Artifical Intelligence Assisted Diagnosis of Active Aortitis Using Radiomic Analysis of FDG PET-CT Images.

The aim of this study was to develop and validate an automated pipeline that could assist the diagnosis of active aortitis using radiomic imaging biomarkers derived from [18F]-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography (FDG PET-CT) images. The aorta was automatically segmented by convolutional neural network (CNN) on FDG PET-CT of aortitis and control patients. The FDG PET-CT dataset was split into training (43 aortitis:21 control), test (12 aortitis:5 control) and validation (24 aortitis:14 control) cohorts. Radiomic features (RF), including SUV metrics, were extracted from the segmented data and harmonized. Three radiomic fingerprints were constructed: A-RFs with high diagnostic utility removing highly correlated RFs; B used principal component analysis (PCA); C-Random Forest intrinsic feature selection. The diagnostic utility was evaluated with accuracy and area under the receiver operating characteristic curve (AUC). Several RFs and Fingerprints had high AUC values (AUC > 0.8), confirmed by balanced accuracy, across training, test and external validation datasets. Good diagnostic performance achieved across several multi-centre datasets suggests that a radiomic pipeline can be generalizable. These findings could be used to build an automated clinical decision tool to facilitate objective and standardized assessment regardless of observer experience.

Extending the clinical capabilities of short- and long-lived positron-emitting radionuclides through high sensitivity PET/CT.

This review describes the main benefits of using long axial field of view (LAFOV) PET in clinical applications. As LAFOV PET is the latest development in PET instrumentation, many studies are ongoing that explore the potentials of these systems, which are characterized by ultra-high sensitivity. This review not only provides an overview of the published clinical applications using LAFOV PET so far, but also provides insight in clinical applications that are currently under investigation. Apart from the straightforward reduction in acquisition times or administered amount of radiotracer, LAFOV PET also allows for other clinical applications that to date were mostly limited to research, e.g., dual tracer imaging, whole body dynamic PET imaging, omission of CT in serial PET acquisition for repeat imaging, and studying molecular interactions between organ systems. It is expected that this generation of PET systems will significantly advance the field of nuclear medicine and molecular imaging.