Does consensus contour improve robustness and accuracy in 18F-FDG PET radiomic features?

PURPOSE: The purpose of our study is to validate the robustness and accuracy of consensus contour in 2-deoxy-2-[ 18 F]fluoro-D-glucose ( 18 F-FDG) PET radiomic features. METHODS: 225 nasopharyngeal carcinoma (NPC) and 13 extended cardio-torso (XCAT) simulated data were enrolled. All segmentation were performed with four segmentation methods under two different initial masks, respectively. Consensus contour (ConSeg) was then developed using the majority vote rule. 107 radiomic features were extracted by Pyradiomics based on segmentation and the intraclass correlation coefficient (ICC) was calculated for each feature between masks or among segmentation, respectively. In XCAT ICC between segmentation and simulated ground truth were also calculated to access the accuracy. RESULTS: ICC varied with the dataset, segmentation method, initial mask and feature type. ConSeg presented higher ICC for radiomic features in robustness tests and similar ICC in accuracy tests, compared with the average of four segmentation results. Higher ICC were also generally observed in irregular initial masks compared with rectangular masks in both robustness and accuracy tests. Furthermore, 19 features (17.76%) had ICC ≥ 0.75 in both robustness and accuracy tests for any of the segmentation methods or initial masks. The dataset was observed to have a large impact on the correlation relationships between radiomic features, but not the segmentation method or initial mask. CONCLUSIONS: The consensus contour combined with irregular initial mask could improve the robustness and accuracy in radiomic analysis to some extent. The correlation relationships between radiomic features and feature clusters largely depended on the dataset, but not segmentation method or initial mask.

Patient-specific radiation dose for Chinese pediatric patients undergoing whole-body PET/CT examinations.

Objective.To assess potential variations in the absorbed dose between Chinese and Caucasian children exposed to18F-FDG PET scan and to investigate the factors contributing to dose differences, this work employed patient-specific phantoms and our compartment model for calculating the patient-specific absorbed dose in Chinese children.Approach.Data of 29 Chinese pediatric patients undergoing whole-body18F-FDG PET/CT studies were retrospectively collected, including PET images for activity distributions and corresponding CT images for organ segmentation and phantom construction. A biokinetic compartment model was implemented to obtain cumulated activities. Absorbed radiation dose for both CT and PET component were calculated using Monte Carlo simulations. Regression models were fitted to time integrated activity coefficient (TIAC) and organ absorbed dose for each patient.Main results.TIACs of all the organs in our compartment model and the organ dose for 12 organs were correlated with patients' weight. Young children have significantly large uptake in brain compared to adults. The distinctions of anatomical and biological characteristics between Chinese and Caucasian children contribute to variations in the absorbed dose of18F-FDG PET scans. PET contributed more in organ dose than CT did in most organs, especially in brain and bladder. The average effective dose (± SD) was 4.5 mSv (± 1.12 mSv), 7.8 mSv (± 3.2 mSv) and 12.3 mSv (± 3.5 mSv) from CT, PET and their sum respectively. PET contributed 1.7 times higher than CT.Significance.To the best of our knowledge, this work represents the first attempt to estimate patient-specific radiation doses from PET/CT for Chinese pediatric patients. TIACs derived from our methodology in both age groups exhibited significant differences from the that reported in ICRP 128. Substantial differences in absorbed and effective doses were observed between Chinese and Caucasian children across all age groups. These disparities are attributed to markedly distinct anatomical and pharmacokinetic characteristics among adults and pediatric patients, and different racial groups. The application of data derived from adults to pediatric patients introduces considerable uncertainty. Our methodology offers a valuable approach not only for estimating pharmacokinetic characteristics and patient-specific radiation doses in pediatric patients undergoing18F-FDG studies but also for other cohorts with similar characteristics.

Estimation of kinetic parameters in dynamic FDG PET imaging based on shortened protocols: a virtual clinical study.

This study investigated the estimation of kinetic parameters and production of related parametric Ki images in FDG PET imaging using the proposed shortened protocol (three 3-min/bed routine static images) by means of the simulated annealing (SA) algorithm. Six realistic heterogeneous tumors and various levels of [18F] FDG uptake were simulated by the XCAT phantom. An irreversible two-tissue compartment model (2TCM) using population-based input function was employed. By keeping two routine clinical scans fixed (60-min and 90-min post injection), the effect of the early scan time on optimizing the estimation of the pharmacokinetic parameters was investigated. The SA optimization algorithm was applied to estimate micro- and macro-parameters (K1, k2, k3, Ki). The minimum bias for most parameters was observed at a scan time of 20-min, which was < 10%. A highly significant correlation (> 0.9) as well as limited bias (< 10%) were observed between kinetic parameters generated from two methods [two-tissue compartment full dynamic scan (2TCM-full) and two-tissue compartment by SA algorithm (2TCM-SA)]. The analysis showed a strong correlation (> 0.8) between (2TCM-SA) Ki and SUV images. In addition, the tumor-to-background ratio (TBR) metric in the parametric (2TCM-SA) Ki images was significantly higher than SUV, although the SUV images provide better Contrast-to-noise ratio relative to parametric (2TCM-SA) Ki images. The proposed shortened protocol by the SA algorithm can estimate the kinetic parameters in FDG PET scan with high accuracy and robustness. It was also concluded that the parametric Ki images obtained from the 2TCM-SA as a complementary image of the SUV possess more quantification information than SUV images and can be used by the nuclear medicine specialist. This method has the potential to be an alternative to a full dynamic PET scan.

Does consensus contours improve robustness and accuracy on [Formula: see text]F-FDG PET imaging tumor delineation?

PURPOSE: The aim of this study is to explore the robustness and accuracy of consensus contours with 225 nasopharyngeal carcinoma (NPC) clinical cases and 13 extended cardio-torso simulated lung tumors (XCAT) based on 2-deoxy-2-[[Formula: see text]F]fluoro-D-glucose ([Formula: see text]F-FDG) PET imaging. METHODS: Primary tumor segmentation was performed with two different initial masks on 225 NPC [Formula: see text]F-FDG PET datasets and 13 XCAT simulations using methods of automatic segmentation with active contour, affinity propagation (AP), contrast-oriented thresholding (ST), and 41% maximum tumor value (41MAX), respectively. Consensus contours (ConSeg) were subsequently generated based on the majority vote rule. The metabolically active tumor volume (MATV), relative volume error (RE), Dice similarity coefficient (DSC) and their respective test-retest (TRT) metrics between different masks were adopted to analyze the results quantitatively. The nonparametric Friedman and post hoc Wilcoxon tests with Bonferroni adjustment for multiple comparisons were performed with [Formula: see text] 0.05 considered to be significant. RESULTS: AP presented the highest variability for MATV in different masks, and ConSeg presented much better TRT performances in MATV compared with AP, and slightly poorer TRT in MATV compared with ST or 41MAXin most cases. Similar trends were also found in RE and DSC with the simulated data. The average of four segmentation results (AveSeg) showed better or comparable results in accuracy for most cases with respect to ConSeg. AP, AveSeg and ConSeg presented better RE and DSC in irregular masks as compared with rectangle masks. Additionally, all methods underestimated the tumour boundaries in relation to the ground truth for XCAT including respiratory motion. CONCLUSIONS: The consensus method could be a robust approach to alleviate segmentation variabilities, but did not seem to improve the accuracy of segmentation results on average. Irregular initial masks might be at least in some cases attributable to mitigate the segmentation variability as well.

The valuable role of dynamic 18F FDG PET/CT-derived kinetic parameter Ki in patients with nasopharyngeal carcinoma prior to radiotherapy: A prospective study.

BACKGROUND AND PURPOSE: Dynamic positron emission tomography/computed tomography (PET/CT) served the potential role of characterizing malignant foci. The main objective of this prospective study was to explore the advantage of dynamic PET/CT imaging in characterizing nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Patients with probable head and neck disease underwent a local dynamic PET/CT scan followed by a whole-body static scan. Patlak analysis was used to generate parametric influx rate constant (Ki) images from 48 frames obtained from a dynamic PET/CT scan. By delineating the volumes-of-interest (VOIs) of: primary tumor (PT), lymph node (LN), and normal nasopharyngeal tissues (N), we acquired the corresponding Ki mean and SUVmean of each site respectively to perform the quantitative statistical analysis. RESULTS: Qualified images of 71 patients with newly diagnosed NPC and 8 without nasopharyngeal malignant lesions were finally included. We found the correlations between Ki mean-PT and critical clinical features, including clinical stage (r = 0.368), T category (r = 0.643) and EBV-DNA copy status (r = 0.351), and Ki mean-PT differed within the group. SUVmean-PT showed correlations with clinical stage (r = 0.280) and T category (r = 0.472), but could hardly differ systematically within group of clinical features except T category. Ki mean-LN offered the positive correlations with N category (r = 0.294), M category (r = 0.238) and EBV-DNA copy status (r = 0.446), and differed within the group. In addition, Ki mean represented a sensitivity of 94.4 % and a specificity of 100 %, in distinguishing NPC from the non-NPC, when the cut-off was defined as 0.0106. When the cut-off of SUV being defined as 2.03, the sensitivity and specificity were both 100 %. CONCLUSION: Our research confirmed Ki compared favorably to SUV in characterizing NPC and found that Ki can serve as an effective imaging marker of NPC.

Impact of Tissue Classification in MRI-Guided Attenuation Correction on Whole-Body Patlak PET/MRI.

PURPOSE: The aim of this work is to investigate the impact of tissue classification in magnetic resonance imaging (MRI)-guided positron emission tomography (PET) attenuation correction (AC) for whole-body (WB) Patlak net uptake rate constant (Ki) imaging in PET/MRI studies. PROCEDURES: WB dynamic PET/CT data were acquired for 14 patients. The CT images were utilized to generate attenuation maps (µ-mapCTAC) of continuous attenuation coefficient values (Acoeff). The µ-mapCTAC were then segmented into four tissue classes (µ-map4-classes), namely background (air), lung, fat, and soft tissue, where a predefined Acoeff was assigned to each class. To assess the impact of bone for AC, the bones in the µ-mapCTAC were then assigned a predefined soft tissue Acoeff (0.1 cm-1) to produce an AC µ-map without bones (µ-mapno-bones). Thereafter, both WB static SUV and dynamic PET images were reconstructed using µ-mapCTAC, µ-map4-classes, and µ-mapno-bones (PETCTAC, PET4-classes, and PETno-bones), respectively. WB indirect and direct parametric Ki images were generated using Patlak graphical analysis. Malignant lesions were delineated on PET images with an automatic segmentation method that uses an active contour model (MASAC). Then, the quantitative metrics of the metabolically active tumor volume (MATV), target-to-background (TBR), contrast-to-noise ratio (CNR), peak region-of-interest (ROIpeak), maximum region-of-interest (ROImax), mean region-of-interest (ROImean), and metabolic volume product (MVP) were analyzed. The Wilcoxon test was conducted to assess the difference between PET4-classes and PETno-bones against PETCTAC for all images. The same test was also adopted to compare the differences between SUV, indirect Ki, and direct Ki images for each evaluated AC method. RESULTS: No significant differences in MATV, TBR, and CNR were observed between PET4-classes and PETCTAC for either SUV or Ki images. PET4-classes significantly overestimated ROIpeak, ROImax, ROImean, as well as MVP scores compared with PETCTAC in both SUV and Ki images. SUV images exhibited the highest median relative errors for PET4-classes with respect to PETCTAC (RE4-classes): 6.91 %, 6.55 %, 5.90 %, and 6.56 % for ROIpeak, ROImax, ROImean, and MVP, respectively. On the contrary, Ki images showed slightly reduced RE4-classes (indirect 5.52 %, 5.95 %, 4.43 %, and 5.70 %, direct 6.61 %, 6.33 %, 5.53 %, and 4.96 %) for ROIpeak, ROImax, ROImean, and MVP, respectively. A higher TBR was observed on indirect and direct Ki images relative to SUV, while direct Ki images demonstrated the highest CNR. CONCLUSIONS: Four-tissue class AC may impact SUV and Ki parameter estimation but only to a limited extent, thereby suggesting that WB Patlak Ki imaging for dynamic WB PET/MRI studies is feasible. Patlak Ki imaging can enhance TBR, thereby facilitating lesion segmentation and quantification. However, patient-specific Acoeff for each tissue class should be used when possible to address the high inter-patient variability of Acoeff distributions.

Variability and Repeatability of Quantitative Uptake Metrics in 18F-FDG PET/CT of Non-Small Cell Lung Cancer: Impact of Segmentation Method, Uptake Interval, and Reconstruction Protocol.

There is increased interest in various new quantitative uptake metrics beyond SUV in oncologic PET/CT studies. The purpose of this study was to investigate the variability and test-retest ratio (TRT) of metabolically active tumor volume (MATV) measurements and several other new quantitative metrics in non-small cell lung cancer using 18F-FDG PET/CT with different segmentation methods, user interactions, uptake intervals, and reconstruction protocols. Methods: Ten patients with advanced non-small cell lung cancer received 2 series of 2 whole-body 18F-FDG PET/CT scans at 60 min after injection and at 90 min after injection. PET data were reconstructed with 4 different protocols. Eight segmentation methods were applied to delineate lesions with and without a tumor mask. MATV, SUVmax, SUVmean, total lesion glycolysis, and intralesional heterogeneity features were derived. Variability and repeatability were evaluated using a generalized-estimating-equation statistical model with Bonferroni adjustment for multiple comparisons. The statistical model, including interaction between uptake interval and reconstruction protocol, was applied individually to the data obtained from each segmentation method. Results: Without masking, none of the segmentation methods could delineate all lesions correctly. MATV was affected by both uptake interval and reconstruction settings for most segmentation methods. Similar observations were obtained for the uptake metrics SUVmax, SUVmean, total lesion glycolysis, homogeneity, entropy, and zone percentage. No effect of uptake interval was observed on TRT metrics, whereas the reconstruction protocol affected the TRT of SUVmax Overall, segmentation methods showing poor quantitative performance in one condition showed better performance in other (combined) conditions. For some metrics, a clear statistical interaction was found between the segmentation method and both uptake interval and reconstruction protocol. Conclusion: All segmentation results need to be reviewed critically. MATV and other quantitative uptake metrics, as well as their TRT, depend on segmentation method, uptake interval, and reconstruction protocol. To obtain quantitative reliable metrics, with good TRT performance, the optimal segmentation method depends on local imaging procedure, the PET/CT system, or reconstruction protocol. Rigid harmonization of imaging procedure and PET/CT performance will be helpful in mitigating this variability.

Quantitative Analysis of Heterogeneous [18F]FDG Static (SUV) vs. Patlak (Ki) Whole-body PET Imaging Using Different Segmentation Methods: a Simulation Study.

PURPOSE: Whole-body (WB) dynamic positron emission tomography (PET) enables imaging of highly quantitative physiological uptake parameters beyond the standardized uptake value (SUV). We present a novel dynamic WB anthropomorphic PET simulation framework to assess the potential of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) net uptake rate constant (Ki) imaging in characterizing tumor heterogeneity. PROCEDURES: Validated heterogeneous [18F]FDG tumor kinetics were modeled within the XCAT phantom (ground truth). Thereafter, static (SUV) and dynamic PET data were simulated and reconstructed, followed by indirect WB Patlak Ki imaging. Subsequently, we compared the methods of affinity propagation (AP) and automatic segmentation with active contour (MASAC) to evaluate the impact of tumor delineation. Finally, we extracted the metabolically active tumor volume (MATV), Dice similarity coefficient (DSC), and the intratumoral heterogeneity metrics of the area under the cumulative intensity histogram curve (CIHAUC), homogeneity, entropy, dissimilarity, high-intensity emphasis (HIE), and zone percentage (ZP), along with the target-to-background (TBR) and contrast-to-noise ratios (CNR). RESULTS: Ki images presented higher TBR but lower CNR compared to SUV. In contrast to MASAC, AP segmentation resulted in smaller bias for MATV and DSC scores in Ki compared to SUV images. All metrics, except for ZP, were significantly different in AP segmentation between SUV and Ki images, with significant correlation observed for MATV, homogeneity, dissimilarity, and entropy. With MASAC segmentation, CIHAUC, homogeneity, and dissimilarity were significantly different between SUV and Ki images, with all metrics, except for HIE and ZP, being significantly correlated. In ground truth images, increased heterogeneity was observed with Ki compared to SUV, with a high correlation for all metrics. CONCLUSIONS: A novel simulation framework was developed for the assessment of the quantitative benefits of WB Patlak PET on realistic heterogeneous tumor models. Quantitative analysis showed that WB Ki imaging may provide enhanced TBR and facilitate lesion segmentation and quantification beyond the SUV capabilities.

Generic and robust method for automatic segmentation of PET images using an active contour model.

PURPOSE: Although positron emission tomography (PET) images have shown potential to improve the accuracy of targeting in radiation therapy planning and assessment of response to treatment, the boundaries of tumors are not easily distinguishable from surrounding normal tissue owing to the low spatial resolution and inherent noisy characteristics of PET images. The objective of this study is to develop a generic and robust method for automatic delineation of tumor volumes using an active contour model and to evaluate its performance using phantom and clinical studies. METHODS: MASAC, a method for automatic segmentation using an active contour model, incorporates the histogram fuzzy C-means clustering, and localized and textural information to constrain the active contour to detect boundaries in an accurate and robust manner. Moreover, the lattice Boltzmann method is used as an alternative approach for solving the level set equation to make it faster and suitable for parallel programming. Twenty simulated phantom studies and 16 clinical studies, including six cases of pharyngolaryngeal squamous cell carcinoma and ten cases of nonsmall cell lung cancer, were included to evaluate its performance. Besides, the proposed method was also compared with the contourlet-based active contour algorithm (CAC) and Schaefer's thresholding method (ST). The relative volume error (RE), Dice similarity coefficient (DSC), and classification error (CE) metrics were used to analyze the results quantitatively. RESULTS: For the simulated phantom studies (PSs), MASAC and CAC provide similar segmentations of the different lesions, while ST fails to achieve reliable results. For the clinical datasets (2 cases with connected high-uptake regions excluded) (CSs), CAC provides for the lowest mean RE (-8.38% ± 27.49%), while MASAC achieves the best mean DSC (0.71 ± 0.09) and mean CE (53.92% ± 12.65%), respectively. MASAC could reliably quantify different types of lesions assessed in this work with good accuracy, resulting in a mean RE of -13.35% ± 11.87% and -11.15% ± 23.66%, a mean DSC of 0.89 ± 0.05 and 0.71 ± 0.09, and a mean CE of 19.19% ± 7.89% and 53.92% ± 12.65%, for PSs and CSs, respectively. CONCLUSIONS: The authors' results demonstrate that the developed novel PET segmentation algorithm is applicable to various types of lesions in the authors' study and is capable of producing accurate and consistent target volume delineations, potentially resulting in reduced intraobserver and interobserver variabilities observed when using manual delineation and improved accuracy in treatment planning and outcome evaluation.

Advanced nasopharyngeal carcinoma radiotherapy with volumetric modulated arcs and the potential role of flattening filter-free beams.

PURPOSE: The purpose of this study is to investigate the dosimetric characteristics of volumetric modulated arc therapy (VMAT) with flattening filter-free (FFF) beams and assess the role of VMAT in the treatment of advanced nasopharyngeal carcinoma (NPC). METHODS: Ten cases of CT data were randomly selected from advanced NPC patients. Three treatment plans were optimized for each patient, RapidArc with FFF beams (RA-FFF), conventional beams (RA) and static gantry intensity-modulated radiation therapy (IMRT). The doses to the planning target volumes (PTVs), organs at risk (OARs), skin and normal tissue were compared. All the plans were delivered on a Varian TrueBeam linear accelerator and verified using the Delta4 phantom. Technical delivery parameters including the mean gamma score, treatment delivery time and monitor units (MUs) were also analyzed. RESULTS: All the techniques delivered adequate doses to the PTVs. RA-FFF gave the highest D(1%) (dose received by 1% of the volume), but the poorest conformity index (CI) and homogeneity index (HI) among the PTVs except for the planning target volume of involved regional lymph nodes (PTV66) CI, which showed no significant difference among three techniques. For the planning target volume of the primary nasopharyngeal tumor (PTV70), RA-FFF provided for higher mean dose than other techniques. For the planning target volume receiving 60 Gy (PTV60) and PTV66, RA delivered the lowest mean doses whereas IMRT delivered the highest mean doses. IMRT demonstrated the highest percentage of target coverage and D(99%) for PTV60. RA-FFF provided for the highest doses to the brain stem, skin and oral cavity. RA gave the highest D(1%) to the right optic nerve among three techniques while no significant differences were found between each other. IMRT delivered the highest mean doses to the parotid glands and larynx while RA delivered the lowest mean doses. Gamma analysis showed an excellent agreement for all the techniques at 3%/3 mm. Significant differences in the MUs were observed among the three techniques (p < 0.001). Delivery times for RA-FFF and RA were 152 ± 7s and 153 ± 7s, respectively, nearly 70% lower than the 493 ± 24s mean time for IMRT. CONCLUSIONS: All treatment plans met the planning objectives. The dose measurements also showed good agreement with computed doses. RapidArc technique can treat patients with advanced NPC effectively, with good target coverage and sparing of critical structures. RA has a greater dosimetric superiority than RA-FFF.

Volumetric modulation arc radiotherapy with flattening filter-free beams compared with conventional beams for nasopharyngeal carcinoma: a feasibility study.

There is increasing interest in the clinical use of flattening filter-free (FFF) beams. In this study, we aimed to investigate the dosimetric characteristics of volumetric modulated arc radiotherapy (VMAT) with FFF beams for nasopharyngeal carcinoma (NPC). Ten NPC patients were randomly selected to undergo a RapidArc plan with either FFF beams (RA-FFF) or conventional beams (RA-C). The doses to the planning target volumes (PTVs), organs at risk (OARs), and normal tissues were compared. The technical delivery parameters for RapidArc plans were also assessed to compare the characteristics of FFF and conventional beams. Both techniques delivered adequate doses to PTVs. For PTVs, RA-C delivered lower maximum and mean doses and improved conformity and homogeneity compared with RA-FFF. Both techniques provided similar maximum doses to the optic nerves and lenses. For the brain stem, spinal cord, larynx, parotid glands, oral cavity, and skin, RA-FFF showed significant dose increases compared to RA-C. The dose to normal tissue was lower in RA-FFF. The monitor units (MUs) were (536 ± 46) MU for RA-FFF and (501 ±25) MU for RA-C. The treatment duration did not significantly differ between plans. Although both treatment plans could meet clinical needs, RA-C is dosimetrically superior to RA-FFF for NPC radiotherapy.