Automated liver lesion detection in 68Ga DOTATATE PET/CT using a deep fully convolutional neural network.
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ABSTRACT: Background
Gastroenteropancreatic neuroendocrine tumors most commonly metastasize to the liver; however, high normal background 68Ga-DOTATATE activity and high image noise make metastatic lesions difficult to detect. The purpose of this study is to develop a rapid, automated and highly specific method to identify 68Ga-DOTATATE PET/CT hepatic lesions using a 2D U-Net convolutional neural network.Methods
A retrospective study of 68Ga-DOTATATE PET/CT patient studies (n = 125; 57 with 68Ga-DOTATATE hepatic lesions and 68 without) was evaluated. The dataset was randomly divided into 75 studies for the training set (36 abnormal, 39 normal), 25 for the validation set (11 abnormal, 14 normal) and 25 for the testing set (11 abnormal, 14 normal). Hepatic lesions were physician annotated using a modified PERCIST threshold, and boundary definition by gradient edge detection. The 2D U-Net was trained independently five times for 100,000 iterations using a linear combination of binary cross-entropy and dice losses with a stochastic gradient descent algorithm. Performance metrics included: positive predictive value (PPV), sensitivity, F1 score and area under the precision-recall curve (PR-AUC). Five different pixel area thresholds were used to filter noisy predictions.Results
A total of 233 lesions were annotated with each abnormal study containing a mean of 4 ± 2.75 lesions. A pixel filter of 20 produced the highest mean PPV 0.94 ± 0.01. A pixel filter of 5 produced the highest mean sensitivity 0.74 ± 0.02. The highest mean F1 score 0.79 ± 0.01 was produced with a 20 pixel filter. The highest mean PR-AUC 0.73 ± 0.03 was produced with a 15 pixel filter.Conclusion
Deep neural networks can automatically detect hepatic lesions in 68Ga-DOTATATE PET. Ongoing improvements in data annotation methods, increasing sample sizes and training methods are anticipated to further improve detection performance.
SUBMITTER: Wehrend J
PROVIDER: S-EPMC8487415 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundFluorine-18-labeled SSAs have the potential to become the next-generation tracer in SSTR-imaging in neuroendocrine tumor (NET) patients given their logistical advantages over the current gold standard gallium-68-labeled SSAs. In particular, [18F]AlF-OC has already shown excellent clinical performance. We demonstrated in our previous report from our prospective multicenter trial that [18F]AlF-OC PET/CT outperforms [68Ga]Ga-DOTA-SSA, but histological confirmation was lacking due to ethical and practical reasons. In this second arm, we therefore aimed to provide evidence that the vast majority of [18F]AlF-OC PET lesions are in fact true NET lesions by analyzing their MR characteristics on simultaneously acquired MRI. We had a special interest in lesions solely detected by [18F]AlF-OC ("incremental lesions").MethodsTen patients with a histologically confirmed neuroendocrine tumor (NET) and a standard-of-care [68Ga]Ga-DOTATATE PET/CT, performed within 3 months, were prospectively included. Patients underwent a whole-body PET/MRI (TOF, 3 T, GE Signa), 2 hours after IV injection of 4 MBq/kg [18F]AlF-OC. Positive PET lesions were evaluated for a corresponding lesion on MRI. The diagnostic performance of both PET tracers was evaluated by determining the detection ratio (DR) for each scan and the differential detection ratio (DDR) per patient.ResultsIn total, 195 unique lesions were detected: 167 with [68Ga]Ga-DOTATATE and 193 with [18F]AlF-OC. The DR for [18F]AlF-OC was 99.1% versus 91.4% for [68Ga]Ga-DOTATATE, significant for non-inferiority testing (p = 0.0001). Out of these 193 [18F]AlF-OC lesions, 96.2% were confirmed by MRI to be NET lesions. Thirty-three incremental lesions were identified by [18F]AlF-OC, of which 91% were confirmed by MRI and considered true positives.ConclusionThe DR of [18F]AlF-OC was numerically higher and non-inferior to the DR of [68Ga]Ga-DOTATATE. [18F]AlF-OC lesions and especially incremental lesions were confirmed as true positives by MRI in more than 90% of lesions. Taken together, these data further validate [18F]AlF-OC as a new alternative for SSTR PET in clinical practice. Trial registration ClinicalTrials.gov: NCT04552847. Registered 17 September 2020, https://beta.Clinicaltrialsgov/study/NCT04552847.
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Project description:68Ga-DOTA-JR11 is a somatostatin receptor subtype 2-specific antagonist used for PET/CT imaging. The purpose of this study was to compare 68Ga-DOTA-JR11 and 68Ga-DOTATATE PET/CT in patients with metastatic, well-differentiated neuroendocrine tumors. Methods: Patients with histologically proven, metastatic or unresectable, well-differentiated neuroendocrine tumors were prospectively recruited to this study. Each patient received an intravenous injection of 68Ga-DOTATATE (155 ± 52 MBq) on the first day and 68Ga-DOTA-JR11 (148 ± 52 MBq) on the second day. Whole-body PET/CT scans were performed at 40-60 min after injection on the same scanner. Physiologic normal-organ uptake, lesion numbers, and lesion uptake were compared. Results: Thirty-one patients were prospectively enrolled in the study. The SUVmax of the spleen, renal cortex, adrenal glands, pituitary glands, stomach wall, normal liver parenchyma, small intestine, pancreas, and bone marrow was significantly lower on 68Ga-DOTA-JR11 than on 68Ga-DOTATATE PET/CT (P < 0.001). 68Ga-DOTA-JR11 detected significantly more liver lesions (552 vs. 365, P = 0.001) but fewer bone lesions (158 vs. 388, P = 0.016) than 68Ga-DOTATATE. The target-to-background ratio of liver lesions was significantly higher on 68Ga-DOTA-JR11 (7.7 ± 5.4 vs. 3.4 ± 2.0, P < 0.001). 68Ga-DOTA-JR11 and 68Ga-DOTATATE PET/CT showed comparable results for primary tumors and lymph node metastases on both patient-based and lesion-based comparisons. Conclusion: 68Ga-DOTA-JR11 performs better in detecting liver metastases, with a better tumor-to-background ratio, whereas 68Ga-DOTATATE may outperform 68Ga-DOTA-JR11 in the detection of bone metastases. However, the lower somatostatin receptor subtype 2 affinity of 68Ga-DOTA-JR11 than of 177Lu-DOTA-JR11 may limit its role as a diagnostic pair for the theranostic approach with 177Lu-DOTA-JR11.
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Project description:PurposeIn the characterization of severe lung diseases, early detection of specific inflammatory cells could help to monitor patients' response to therapy and increase chances of survival. Macrophages contribute to regulating the resolution and termination of inflammation and have increasingly been of interest for targeted therapies. [68Ga]Ga-DOTA-TATE is an established clinical radiopharmaceutical targeting somatostatin receptor subtype 2 (SSTR 2). Since activated macrophages (M1) overexpress SSTR 2, the aim of this study was to investigate the applicability of [68Ga]Ga-DOTA-TATE for positron emission tomography (PET) imaging of M1 macrophages in pulmonary inflammation.MethodsInflammation in the pig lungs was induced by warm saline lavage followed by injurious ventilation in farm pigs (n = 7). Healthy pigs (n = 3) were used as control. A 60-min dynamic PET scan over the lungs was performed after [68Ga]Ga-DOTA-TATE injection and [18F]FDG scan was executed afterward for comparison. The uptake of both tracers was assessed as mean standardized uptake values (SUVmean) 30-60-min post-injection. The PET scans were followed by computed tomography (CT) scans, and the Hounsfield units (HU) were quantified of the coronal segments. Basal and apical segments of the lungs were harvested for histology staining. A rat lung inflammation model was also studied for tracer specificity using lipopolysaccharides (LPS) by oropharyngeal aspiration. Organ biodistribution, ex vivo autoradiography (ARG) and histology samples were conducted on LPS treated, octreotide induced blocking and control healthy rats.ResultsThe accumulation of [68Ga]Ga-DOTA-TATE on pig lavage model was prominent in the more severely injured dorsal segments of the lungs (SUVmean = 0.91 ± 0.56), compared with control animals (SUVmean = 0.27 ± 0.16, p < 0.05). The tracer uptake corresponded to the damaged areas assessed by CT and histology and were in line with HU quantification. The [68Ga]Ga-DOTA-TATE uptake in LPS treated rat lungs could be blocked and was significantly higher compared with control group.ConclusionThe feasibility of the noninvasive assessment of tissue macrophages using [68Ga]Ga-DOTA-TATE/PET was demonstrated in both porcine and rat lung inflammation models. [68Ga]Ga-DOTA-TATE has a great potential to be used to study the role and presence of macrophages in humans in fight against severe lung diseases.
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Project description:BackgroundInflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG PET), [18F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover.ObjectivesThis study tested the efficacy of gallium-68-labeled DOTATATE (68Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation.MethodsWe confirmed 68Ga-DOTATATE binding in macrophages and excised carotid plaques. 68Ga-DOTATATE PET imaging was compared to [18F]FDG PET imaging in 42 patients with atherosclerosis.ResultsTarget SSTR2 gene expression occurred exclusively in "proinflammatory" M1 macrophages, specific 68Ga-DOTATATE ligand binding to SST2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo 68Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). 68Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBRmax) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003). 68Ga-DOTATATE mTBRmax predicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p < 0.0001), and correlated with Framingham risk score (r = 0.53; 95% CI: 0.32 to 0.69; p <0.0001) and [18F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [18F]FDG mTBRmax differentiated culprit from nonculprit carotid lesions (median difference: 0.12; IQR: 0.0 to 0.23; p = 0.008) and high-risk from lower-risk coronary arteries (ROC AUC: 0.76; 95% CI: 0.62 to 0.91; p = 0.002); however, myocardial [18F]FDG spillover rendered coronary [18F]FDG scans uninterpretable in 27 patients (64%). Coronary 68Ga-DOTATATE PET scans were readable in all patients.ConclusionsWe validated 68Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that 68Ga-DOTATATE offers superior coronary imaging, excellent macrophage specificity, and better power to discriminate high-risk versus low-risk coronary lesions than [18F]FDG. (Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [VISION]; NCT02021188).
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Project description:Purpose To evaluate dynamic gallium 68 (68Ga) tetraazacyclododecane tetraacetic acid octreotate (DOTATATE) brain PET/MRI as an adjunct modality in meningioma, enabling multiparametric standardized uptake value (SUV) and Patlak net binding rate constant (Ki) imaging, and to optimize static acquisition period. Materials and Methods In this prospective study (ClinicalTrials.gov no. NCT04081701, DOMINO-START), 68Ga-DOTATATE PET/MRI-derived time-activity curves (TACs) were measured in 84 volumes of interest in 19 participants (mean age, 63 years; range, 36-89 years; 13 women; 2019-2021) with meningiomas. Region- and voxel-specific Ki were determined using Patlak analysis with a validated population-based reference tissue TAC model built from an independent data set of nine participants. Mean and maximum absolute and relative-to-superior-sagittal-sinus SUVs were extracted from the entire 50 minutes (SUV50) and last 10 minutes (SUV10) of acquisition. SUV versus Ki Spearman correlation, SUV and Ki meningioma versus posttreatment-change Mann-Whitney U tests, and SUV50 versus SUV10 Wilcoxon matched-pairs signed rank tests were performed. Results Absolute and relative maximum SUV50 demonstrated a strong positive correlation with Patlak Ki in meningioma (r = 0.82, P < .001 and r = 0.85, P < .001, respectively) and posttreatment-change lesions (r = 0.88, P = .007 and r = 0.83, P = .02, respectively). Patlak Ki images yielded higher lesion contrast by mitigating nonspecific background signal. All SUV50 and SUV10 metrics differed between meningioma and posttreatment-change regions (P < .001). Within the meningioma group, SUV10 attained higher mean scores than SUV50 (P < .001). Conclusion Combined SUV and Patlak K i 68Ga-DOTATATE PET/MRI enabled multiparametric evaluation of meningioma, offering the potential to enhance lesion contrast with Ki imaging and optimize the SUV measurement postinjection window. Keywords: Molecular Imaging-Clinical Translation, Neuro-Oncology, PET/MRI, Dynamic, Patlak ClinicalTrials.gov registration no. NCT04081701 © RSNA, 2022.
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Project description:Background and purposeMeningiomas express the somatostatin receptor (SSTR), which normal bone and brain lack. PET imaging with SSTR ligands such as 68 Ga-DOTATATE have been recently shown to aid in the imaging and identification of menginiomas. We hypothesize that 68 Ga-DOTATATE PET/CT in conjunction with MRI aids in radiation (RT) target volume delineation and evaluating treatment response.Materials and methodsNineteen patients with meningiomas underwent 68 Ga-DOTATATE PET/CT and MRI for RT planning and/or post-treatment follow-up. Meningiomas were grade I (n = 9) or not biopsied (n = 8) and frequently involved base of skull (n = 10). Ten (53%) patients received post-operative RT and 9 (47%) received fractaionted RT. In the subgroup that underwent both pre- and post-RT 68 Ga-DOTATATE PET as well as MRI (n = 10), ROVER (ABX GmbH, Radeberg, Germany) adaptive thresholding software was utilized to measure total lesion activity (mean and max) before and after treatment. Tumor volume based on MRI was calculated before and after treatment. Total lesion activity and tumor volume changes were compared using Wilcoxon signed rank test.Results68 Ga-DOTATATE PET/CT identified intraosseous (n = 4, 22%), falcine (n = 5, 26%) and satellite lesions (n = 3, 19%) and clarified the diagnosis of meningioma, resulting in a change in management in three patients. Mean total lesion activity decreased 14.7% (median), from pre to post-RT 68 Ga-DOTATATE PET [range 97-8.5% (25-75%),S = - 26.5, p = 0.0039]. Max total lesion activity decreased 36% (median) over the same period [range 105-15% (25-75%), S = - 26.5 p = 0.0039]. In contrast, meningioma volumes based on MRI measurements did not significantly change per RECIST criteria and Wilcoxon signed rank test (S = - 3, p = 0.7422).Conclusion68 Ga-DOTATATE PET/CT helped confirm suspected diagnoses and delineate target volumes particularly when lesions involved osseous structures and the falx. Mean and max total tumor 68 Ga-DOTATATE activity on PET/CT decreased at three months following RT despite stable tumor volumes on MRI. Future studies are warranted to (1) assess the sensitivity and specificity of 68 Ga-DOTATATE PET/CT, (2) evaluate the impact of 68 Ga-DOTATATE PET/CT-based planning on treatment outcomes, and (3) assess the prognostic significance of these post-treatment imaging changes.
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