Dataset Information

¹⁸ F-fluoromisonidazole uptake in advanced stage non-small cell lung cancer: A voxel-by-voxel PET kinetics study.

ABSTRACT:

Purpose

The aim of this study was to determine the relative abilities of compartment models to describe time-courses of ¹⁸ F-fluoromisonidazole (FMISO) uptake in tumor voxels of patients with non-small cell lung cancer (NSCLC) imaged using dynamic positron emission tomography. Also to use fits of the best-performing model to investigate changes in fitted rate-constants with distance from the tumor edge.

Methods

Reversible and irreversible two- and three-tissue compartment models were fitted to 24 662 individual voxel time activity curves (TACs) obtained from tumors in nine patients, each imaged twice. Descriptions of the TACs provided by the models were compared using the Akaike and Bayesian information criteria (AIC and BIC). Two different models (two- and three-tissue) were fitted to 30 measured voxel TACs to provide ground-truth TACs for a statistical simulation study. Appropriately scaled noise was added to each of the resulting ground-truth TACs, generating 1000 simulated noisy TACs for each ground-truth TAC. The simulation study was carried out to provide estimates of the accuracy and precision with which parameter values are determined, the estimates being obtained for both assumptions about the ground-truth kinetics. A BIC clustering technique was used to group the fitted rate-constants, taking into consideration the underlying uncertainties on the fitted rate-constants. Voxels were also categorized according to their distance from the tumor edge.

Results

For uptake time-courses of individual voxels an irreversible two-tissue compartment model was found to be most precise. The simulation study indicated that this model had a one standard deviation precision of 39% for tumor fractional blood volumes and 37% for the FMISO binding rate-constant. Weighted means of fitted FMISO binding rate-constants of voxels in all tumors rose significantly with increasing distance from the tumor edge, whereas fitted fractional blood volumes fell significantly. When grouped using the BIC clustering, many centrally located voxels had high-fitted FMISO binding rate-constants and low rate-constants for tracer flow between the vasculature and tumor, both indicative of hypoxia. Nevertheless, many of these voxels had tumor-to-blood (TBR) values lower than the 1.4 level commonly expected for hypoxic tissues, possibly due to the low rate-constants for tracer flow between the vasculature and tumor cells in these voxels.

Conclusions

Time-courses of FMISO uptake in NSCLC tumor voxels are best analyzed using an irreversible two-tissue compartment model, fits of which provide more precise parameter values than those of a three-tissue model. Changes in fitted model parameter values indicate that levels of hypoxia rise with increasing distance from tumor edges. The average FMISO binding rate-constant is higher for voxels in tumor centers than in the next tumor layer out, but the average value of the more simplistic TBR metric is lower in tumor centers. For both metrics, higher values might be considered indicative of hypoxia, and the mismatch in this case is likely to be due to poor perfusion at the tumor center. Kinetics analysis of dynamic PET images may therefore provide more accurate measures of the hypoxic status of such regions than the simpler TBR metric, a hypothesis we are presently exploring in a study of tumor imaging versus histopathology.

SUBMITTER: McGowan DR

PROVIDER: S-EPMC5600259 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Hypoxic tumors exhibit increased resistance to radiation, chemical, and immune therapies. 18F-fluoromisonidazole (18F-FMISO) PET is a noninvasive, quantitative imaging technique used to evaluate the magnitude and spatial distribution of tumor hypoxia. In this study, pharmacokinetic analysis (PKA) of 18F-FMISO dynamic PET extended to 3 h after injection is reported for the first time, to our knowledge, in stage III-IV non-small cell lung cancer (NSCLC) patients. Methods: Sixteen patients diagnosed with NSCLC underwent 2 PET/CT scans (1-3 d apart) before radiation therapy: a 3-min static 18 F-FDG and a dynamic 18F-FMISO scan lasting 168 ± 15 min. The latter data were acquired in 3 serial PET/CT dynamic imaging sessions, registered with each other and analyzed using pharmacokinetic modeling software. PKA was performed using a 2-tissue, 3-compartment irreversible model, and kinetic parameters were estimated for the volumes of interest determined using coregistered 18F-FDG images for both the volume of interest-averaged and the voxelwise time-activity curves for each patient's lesions, normal lung, and muscle. Results: We derived average values of 18F-FMISO kinetic parameters for NSCLC lesions as well as for normal lung and muscle. We also investigated the correlation between the trapping rate (k3) and delivery rate (K1), influx rate (Ki ) constants, and tissue-to-blood activity concentration ratios (TBRs) for all tissues. Lesions had trapping rates 1.6 times larger, on average, than those of normal lung and 4.4 times larger than those in muscle. Additionally, for almost all cases, k3 and Ki had a significant strong correlation for all tissue types. The TBR-k3 correlation was less straightforward, showing a moderate to strong correlation for only 41% of lesions. Finally, K1-k3 voxelwise correlations for tumors were varied, but negative for 76% of lesions, globally exhibiting a weak inverse relationship (average R = -0.23 ± 0.39). However, both normal tissue types exhibited significant positive correlations for more than 60% of patients, with 41% having moderate to strong correlations (R > 0.5). Conclusion: All lesions showed distinct 18F-FMISO uptake. Variable 18F-FMISO delivery was observed across lesions, as indicated by the variable values of the kinetic rate constant K1 Except for 3 cases, some degree of hypoxia was apparent in all lesions based on their nonzero k3 values.

Project description:BackgroundConventional PET/CT imaging reconstruction is typically performed using voxel size of 3.0-4.0 mm in three axes. It is hypothesized that a smaller voxel sizes could improve the accuracy of small lesion detection. This study aims to explore the advantages and conditions of small voxel imaging on clinical application.MethodsBoth NEMA IQ phantom and 30 patients with an injected dose of 3.7 MBq/kg were scanned using a total-body PET/CT (uEXPLORER). Images were reconstructed using matrices of 192 × 192, 512 × 512, and 1024 × 1024 with scanning duration of 3 min, 5 min, 8 min, and 10 min, respectively.ResultsIn the phantom study, the contrast recovery coefficient reached the maximum in matrix group of 512 × 512, and background variability increased as voxel size decreased. In the clinical study, SUVmax, SD, and TLR increased, while SNR decreased as the voxel size decreased. When the scanning duration increased, SNR increased, while SUVmax, SD, and TLR decreased. The SUVmean was more reluctant to the changes in imaging matrix and scanning duration. The mean subjective scores for all 512 × 512 groups and 1024 × 1024 groups (scanning duration ≥ 8 min) were over three points. One false-positive lesion was found in groups of 512 × 512 with scanning duration of 3 min, 1024 × 1024 with 3 min and 5 min, respectively. Meanwhile, the false-negative lesions found in group of 192 × 192 with duration of 3 min and 5 min, 512 × 512 with 3 min and 1024 × 1024 with 3 min and 5 min were 5, 4, 1, 4, and 1, respectively. The reconstruction time and storage space occupation were significantly increased as the imaging matrix increased.ConclusionsPET/CT imaging with smaller voxel can improve SUVmax and TLR of lesions, which is advantageous for the diagnosis of small or hypometabolic lesions if with sufficient counts. With an 18F-FDG injection dose of 3.7 MBq/kg, uEXPLORER PET/CT imaging using matrix of 512 × 512 with 5 min or 1024 × 1024 with 8 min can meet the image requirements for clinical use.

Project description:BackgroundThe low level of circulating tumor DNA (ctDNA) in the blood is a well-known challenge for the application of liquid biopsies in early-stage non-small cell lung cancer (NSCLC) management. Studies of metastatic NSCLC indicate that ctDNA levels are associated with tumor metabolic activity as measured by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT). This study investigated this association in NSCLC patients considered for potentially curative treatment and explored whether the two methods provide independent prognostic information.MethodPatients with stage I-III NSCLC who had routinely undergone an 18F-FDG PET/CT scan and exploratory ctDNA analyses were included. Tumor glucose uptake was measured by maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) from the 18F-FDG PET/CT scans. ctDNA detectability and quantity, using variant allele frequency, were estimated by tumor-informed ctDNA analyses.ResultsIn total, 63 patients (median age 70 years, 60% women, and 90% adenocarcinoma) were included. The tumor glucose uptake (SUVmax, MTV, and TLG) was significantly higher in patients with detectable ctDNA (n = 19, p < 0.001). The ctDNA quantity correlated with MTV (Spearman's ρ = 0.53, p = 0.021) and TLG (Spearman's ρ = 0.56, p = 0.013) but not with SUVmax (Spearman's ρ = 0.034, p = 0.15). ctDNA detection was associated with shorter OS independent of MTV (HR: 2.70, 95% CI: 1.07-6.82, p = 0.035) and TLG (HR: 2.63, 95% CI: 1.06-6.51, p = 0.036). Patients with high tumor glucose uptake and detectable ctDNA had shorter overall survival and progression-free survival than those without detectable ctDNA, though these associations were not statistically significant (p > 0.05).ConclusionThere was a positive correlation between plasma ctDNA quantity and MTV and TLG in early-stage NSCLC patients. Despite the correlation, the results indicated that ctDNA detection was a negative prognostic factor independent of MTV and TLG.

Project description:BackgroundGlioma grading with dynamic 18F-FET PET (0-40 min p.i.) is typically performed by analysing the mean time-activity curve of the entire tumour or a suspicious area within a heterogeneous tumour. This work aimed to ensure a reader-independent glioma characterisation and identification of aggressive sub-volumes by performing a voxel-based analysis with diagnostically relevant kinetic and static 18F-FET PET parameters. One hundred sixty-two patients with a newly diagnosed glioma classified according to histologic and molecular genetic properties were evaluated. The biological tumour volume (BTV) was segmented in static 20-40 min p.i. 18F-FET PET images using the established threshold of 1.6?×?background activity. For each enclosed voxel, the time-to-peak (TTP), the late slope (Slope15-40), and the tumour-to-background ratios (TBR5-15, TBR20-40) obtained from 5 to 15 min p.i. and 20 to 40 min p.i. images were determined. The percentage portion of these values within the BTV was evaluated with percentage volume fractions (PVFs) and cumulated percentage volume histograms (PVHs). The ability to differentiate histologic and molecular genetic classes was assessed and compared to volume-of-interest (VOI)-based parameters.ResultsAggressive WHO grades III and IV and IDH-wildtype gliomas were dominated by a high proportion of voxels with an early peak, negative slope, and high TBR, whereby the PVHs with TTP <?20 min p.i., Slope15-40 <?0 SUV/h, and TBR5-15 and TBR20-40 >?2 yielded the most significant differences between glioma grades. We found significant differences of the parameters between WHO grades and IDH mutation status, where the effect size was predominantly higher for voxel-based PVHs compared to the corresponding VOI-based parameters. A low overlap of BTV sub-volumes defined by TTP <?20 min p.i. and negative Slope15-40 with TBR5-15?>?2- and TBR20-40?>?2-defined hotspots was observed.ConclusionsThe presented approach applying voxel-wise analysis of dynamic 18F-FET PET enables an enhanced characterisation of gliomas and might potentially provide a fast identification of aggressive sub-volumes within the BTV. Parametric 3D 18F-FET PET information as investigated in this study has the potential to guide individual therapy instrumentation and may be included in future biopsy studies.

Dataset Information

¹⁸ F-fluoromisonidazole uptake in advanced stage non-small cell lung cancer: A voxel-by-voxel PET kinetics study.

Purpose

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

18 F-fluoromisonidazole uptake in advanced stage non-small cell lung cancer: A voxel-by-voxel PET kinetics study.

Purpose

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

¹⁸ F-fluoromisonidazole uptake in advanced stage non-small cell lung cancer: A voxel-by-voxel PET kinetics study.