Quantitative Positron Emission Tomography Analysis Research Articles

Radiomics for the detection of diffusely impaired myocardial perfusion: A proof-of-concept study using 13N-ammonia positron emission tomography

AimThe current proof-of-concept study investigates the value of radiomic features from normal 13N-ammonia positron emission tomography (PET) myocardial retention images to identify patients with reduced global myocardial flow reserve (MFR). MethodsData from 100 patients with normal retention 13N-ammonia PET scans were divided into two groups, according to global MFR (i.e., < 2 and ≥ 2), as derived from quantitative PET analysis. We extracted radiomic features from retention images at each of five different gray-level (GL) discretization (8, 16, 32, 64, and 128 bins). Outcome independent and dependent feature selection and subsequent univariate and multivariate analyses was performed to identify image features predicting reduced global MFR. ResultsA total of 475 radiomic features were extracted per patient. Outcome independent and dependent feature selection resulted in a remainder of 35 features. Discretization at 16 bins (GL16) yielded the highest number of significant predictors of reduced MFR and was chosen for the final analysis. GLRLM_GLNU was the most robust parameter and at a cut-off of 948 yielded an accuracy, sensitivity, specificity, negative and positive predictive value of 67%, 74%, 58%, 64%, and 69%, respectively, to detect diffusely impaired myocardial perfusion. ConclusionA single radiomic feature (GLRLM_GLNU) extracted from visually normal 13N-ammonia PET retention images independently predicts reduced global MFR with moderate accuracy. This concept could potentially be applied to other myocardial perfusion imaging modalities based purely on relative distribution patterns to allow for better detection of diffuse disease.

Bone Metastases Are Measurable: The Role of Whole-Body MRI and Positron Emission Tomography.

Metastatic tumor deposits in bone marrow elicit differential bone responses that vary with the type of malignancy. This results in either sclerotic, lytic, or mixed bone lesions, which can change in morphology due to treatment effects and/or secondary bone remodeling. Hence, morphological imaging is regarded unsuitable for response assessment of bone metastases and in the current Response Evaluation Criteria In Solid Tumors 1.1 (RECIST1.1) guideline bone metastases are deemed unmeasurable. Nevertheless, the advent of functional and molecular imaging modalities such as whole-body magnetic resonance imaging (WB-MRI) and positron emission tomography (PET) has improved the ability for follow-up of bone metastases, regardless of their morphology. Both these modalities not only have improved sensitivity for visual detection of bone lesions, but also allow for objective measurements of bone lesion characteristics. WB-MRI provides a global assessment of skeletal metastases and for a one-step “all-organ” approach of metastatic disease. Novel MRI techniques include diffusion-weighted imaging (DWI) targeting highly cellular lesions, dynamic contrast-enhanced MRI (DCE-MRI) for quantitative assessment of bone lesion vascularization, and multiparametric MRI (mpMRI) combining anatomical and functional sequences. Recommendations for a homogenization of MRI image acquisitions and generalizable response criteria have been developed. For PET, many metabolic and molecular radiotracers are available, some targeting tumor characteristics not confined to cancer type (e.g. 18F-FDG) while other targeted radiotracers target specific molecular characteristics, such as prostate specific membrane antigen (PSMA) ligands for prostate cancer. Supporting data on quantitative PET analysis regarding repeatability, reproducibility, and harmonization of PET/CT system performance is available. Bone metastases detected on PET and MRI can be quantitatively assessed using validated methodologies, both on a whole-body and individual lesion basis. Both have the advantage of covering not only bone lesions but visceral and nodal lesions as well. Hybrid imaging, combining PET with MRI, may provide complementary parameters on the morphologic, functional, metabolic and molecular level of bone metastases in one examination. For clinical implementation of measuring bone metastases in response assessment using WB-MRI and PET, current RECIST1.1 guidelines need to be adapted. This review summarizes available data and insights into imaging of bone metastases using MRI and PET.

Quantitative 18F-FDG PET analysis in survival rate prediction of patients with non-small cell lung cancer.

The aim of the present study was to investigate the prognostic value of quantitative [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) parameters for patients with non-small cell lung cancer (NSCLC). The present study conducted a retrospective review of the medical records of 203 patients with NSCLC, of which 193 patients underwent baseline 18F-FDG PET/CT prior to initial therapy. Multivariate analyses using Cox's proportional hazards regression were performed for the assessment of the association between initial PET/CT measurements and overall survival (OS). The multivariate models were adjusted for sex, age, smoking status, disease stage, standardized uptake value (SUV), standardized uptake value corrected for lean body mass (SUL), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and standard deviation of SUV (SD). Kaplan-Meier (K-M) estimator curves were constructed following the formation of three approximately equal-sized groups using tertiles for each PET/CT measurement (n=65, 64 and 64). OS curves were plotted using K-M estimator curves. Results demonstrated significant associations between OS and MTVPET volume computerized assisted reporting (PETVCAR), MTV2.5, MTV25%, MTV42% and TLGPETVCAR; however, no significant associations were identified between OS and MTV50%, MTV75%, TLG2.5, all SUV and SUL. Subgroup analyses according to pathology demonstrated that there were statistically significant associations between OS and stage (P<0.001), MTV50% (P=0.002) and MTV42% (P=0.004) in the adenocarcinoma group, and SULmean (P=0.010), MTV25% (P=0.005) and MTV42% (P=0.001) in the squamous cell carcinoma group; however, no significant differences were identified between any other group. Furthermore, there was a significant association between OS and MTV42% (P=0.02) and MTV50% (P=0.04) in the early-stage group; however, no significant differences were identified in the advanced-stage group. K-M estimator curve analyses demonstrated that the pathology (P=0.01), stage (P<0.001) and all PET metabolic parameters with the exception of SD were significantly associated with OS (P<0.05). No significant associations were demonstrated between SD and OS. In conclusion, 18F-FDG PET/CT MTVPETVCAR, MTV2.5, MTV25%, MTV42% and TLGPETVCAR exhibit prognostic values with regard to OS. Overall, selection of appropriate metabolic parameters may predict NSCLC prognosis.

Positron Emission Tomography of Copper Metabolism in the Atp7b −/− Knock-out Mouse Model of Wilson’s Disease

This study aims to determine feasibility and utility of copper-64(II) chloride (⁶⁴CuCl₂) as a tracer for positron emission tomography (PET) of copper metabolism imbalance in human Wilson's disease (WD). Atp7b⁻/⁻ mice, a mouse model of human WD, were injected with ⁶⁴CuCl₂ intravenously and subjected to PET scanning using a hybrid PET-CT (computerized tomography) scanner, with the wild-type C57BL mice as a normal control. Quantitative PET analysis was performed to determine biodistribution of ⁶⁴Cu radioactivity and radiation dosimetry estimates of ⁶⁴Cu were calculated for PET of copper metabolism in humans. Dynamic PET analysis revealed increased accumulation and markedly reduced clearance of ⁶⁴Cu from the liver of the Atp7b⁻/⁻ mice, compared to hepatic uptake and clearance of ⁶⁴Cu in the wild-type C57BL mice. Kinetics of copper clearance and retention was also altered for kidneys, heart, and lungs in the Atp7b/⁻ mice. Based on biodistribution of ⁶⁴Cu in wild-type C57BL mice, radiation dosimetry estimates of ⁶⁴Cu in normal human subjects were obtained, showing an effective dose (ED) of 32.2 μ (micro)Sv/MBq (weighted dose over 22 organs) and the small intestine as the critical organ for radiation dose (61 μGy/MBq for males and 69 μGy/MBq for females). Radiation dosimetry estimates for the patients with WD, based on biodistribution of ⁶⁴Cu in the Atp7b⁻/⁻ mice, showed a similar ED of 32.8 μ (micro)Sv/MBq (p = 0.53), with the liver as the critical organ for radiation dose (120 μSv/MBq for male and 161 μSv/MBq for female). Quantitative PET analysis demonstrates abnormal copper metabolism in the mouse model of WD with improved time-resolution. Human radiation dosimetry estimates obtained in this preclinical study encourage direct radiation dosimetry of ⁶⁴CuCl₂ in human subjects. The results suggest feasibility of utilizing ⁶⁴CuCl₂ as a tracer for noninvasive assessment of copper metabolism in WD with PET.

Imaging the norepinephrine transporter with positron emission tomography: initial human studies with (S,S)-[18F]FMeNER-D2

(S,S)-[(18)F]FMeNER-D(2) is a recently developed positron emission tomography (PET) ligand for in vivo quantification of norepinephrine transporter. A monkey occupancy study with the radioligand indicated that (S,S)-[(18)F]FMeNER-D(2) can be useful for quantitative PET analysis. In this preliminary study, regional distributions in the living human brain were evaluated. Brain PET measurements were performed for a total of 255 min after the injection of 188.3 +/- 5.7 MBq of (S,S)-[(18)F]FMeNER-D(2) in four healthy male subjects. Regions of interests were drawn on the thalamus and the caudate in the coregistered MRI/PET images. (S,S)-[(18)F]FMeNER-D(2) displayed good brain penetration and selective retention in regions rich in norepinephrine reuptake sites. The transient peak equilibrium was reached during the PET measurements. The ratios of radioactivity uptake in the thalamus to that in the caudate were 1.50 +/- 0.06 for the time period of 90-255 min. The present preliminary investigation indicates that (S,S)-[(18)F]FMeNER-D(2) has suitable characteristics for probing the norepinephrine reuptake system with PET in the human brain.

Improvement in preoperative staging of gastric adenocarcinoma with positron emission tomography

Positron emission tomography (PET) with 18- fluorodeoxyglucose (FDG) has been used to both detect and stage a variety of malignancies. The current study examined the value of PET for preoperative staging of gastric adenocarcinoma. Sixty-eight patients (49 males and 19 females) with gastric adenocarcinoma, who were referred for preoperative FDG-PET scans, were enrolled in this study. The patients underwent spiral-computed tomography (CT) within 1 week of referral. The final diagnosis in all patients was made by histologic and surgical findings. For quantitative PET analysis, the regional tumor FDG uptake was measured by the standardized uptake value (SUV). For the primary tumor of a gastric adenocarcinoma, PET demonstrated an increased uptake in 64 of 68 patients (sensitivity, 94%), with a mean SUV of 7.0 (range, 0.9-27.7). A comparison of FDG uptake and clinicopathologic features showed significant association between FDG uptake and macroscopic type, tumor size, lymph node metastasis, histologic type, and TNM stage. The PET scan had a similar accuracy with that of CT for diagnosing local and distant lymph node metastases as well as peritoneal status. In assessing local lymph node status, however, PET had a higher specificity than CT (92% vs. 62%, P = 0.000). Moreover, PET had additional diagnostic value in 10 (15%) of 68 patients by upstaging 4 (6%) and downstaging 6 (9%) patients. PET combined with CT was more accurate for preoperative staging than either modality alone (66% vs. 51%, 66% vs. 47%, respectively; P = 0.002). FDG-PET improves the preoperative TNM staging of gastric adenocarcinoma. Based on its superior specificity, FDG-PET can facilitate the selection of patients for a curative resection by confirming a nodal status identified by CT.

Quantitative PET analysis of regional cerebral blood flow and glucose and oxygen metabolism in response to fenfluramine in living porcine brain

The serotonin agonist fenfluramine has been used widely in humans for studying neuronal activation. We carried out the present study in order to determine whether anesthetized pigs could be used for studying effects of fenfluramine on cerebral functions using positron emission tomography (PET). We obtained quantitative measures of regional cerebral blood flow (rCBF) and of glucose and oxygen utilization (rCMR glc and rCMR O2) during intravenous administration of fenfluramine, using [ 15O]water, [ 18F]FDG and [ 15O]oxygen, respectively. Fenfluramine (25 mg/h i.v.) caused a significant rise in rCBF and, to a lesser extent, in rCMR O2, but it failed to affect rCMR glc. The findings indicate that quantitative estimation of rCBF by repeated injection of [ 15O]water was more sensitive than either rCMR O2 or rCMR glc for detecting effects of fenfluramine on serotonin neurotransmission in living porcine brain.

False Lateralization of Temporal Lobe Epilepsy with FDG Positron Emission Tomography

We report 2 patients in whom visual interpretation of interictal positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) suggested false lateralization of an epileptic focus. PET scans were interpreted as showing diffuse left temporal lobe hypometabolism in 1 patient and lateral temporal hypometabolism in the other. However, seizures began in the right mesial temporal lobe in both patients, and both responded favorably to right temporal lobectomy. In 1 patient, the intracranial EEG showed continuous asymptomatic subclinical seizure activity emanating from the right amygdala. These limbic discharges probably caused unrecognized right temporal lobe hypermetabolism. In the other case, quantitative analysis of metabolic rates showed conflicting mesial and lateral metabolic indexes. Frequent mesial interictal discharges might have increased lateral temporal metabolism. We conclude that asymptomatic epileptiform activity may alter temporal lobe metabolism and that quantitative PET analysis helps clarify contradictory visual PET interpretations.