Spherical Volume Of Interest Research Articles

Evaluation of blood supply and metabolism in tumor, axillary lymph node and normal breast tissue with F-18 FDG PET/CT in breast cancer: comparison with pathological prognostic factors

Background and purposePerfusion parameters obtained in F-18 FDG PET/CT performed for staging purposes in breast cancers may provide additional information about tumor biology as well as glucose metabolism. The aim of this study was to evaluate throughout F-18 FDG PET/CT the relationship between blood flow and glucose metabolism and histological parameters of the primary tumor, normal mammary gland, and axillary lymph nodes in breast cancer patients.Materials and methodsSixty six female patients (mean age 51 y ± 12,81) were prospectively included to this study. We performed dynamic blood flow (f) study that started with 296–444 MBq (8–12 mCi) F-18 FDG injection and lasted for 10 minutes, and glucose metabolism (m) imaging one hour later. On each frame, mean activity concentration (AC) values (Bq/mL) were recorded on a spherical volume of interest (VOI) having a volume of ~ 1 cm3 on the hottest voxel of primary tumor (T), across normal breast gland (NG) and ipsilaterally axillary lymph nodes (iLN). Correlations among PET parameters and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (c-erbB2) and Ki67 index were analyzed.ResultsT volume (TV) ranged from 1.1 to 85.28 cm3 [median (IR): 6.44 (11.78)]. There were positive correlations between c-erbB2 and TACf and between c-erbB2 and iLNACf (p = 0.045, r = + 0.248; p = 0.050, r = + 0.242). In the ER positive (ERP) patients, TV and TACm were significantly lower than those of ER negative (ERN) (respectively p = 0.044 and p = 0.041). In patients with two positive Ki-67 indices, iLN-SUVmax was significantly higher than one-positive patients (p = 0.020). There was a negative correlation between NGACm and histological grade of tumor (p = 0.005, r = − 0.365).ConclusionsBreast cancer shows differences in progression, metastasis and survival due to its diversity in terms of molecular, biological and angiogenesis. High glucose metabolism in breast cancers is associated with tumor aggressiveness. Being able to examine tumor tissue characteristics such as blood flow and glucose metabolism with a single diagnostic technique and to reveal its relationship with histological parameters can provide a reliable pretherapeutic evaluation in breast cancers.

Next-generation PET/CT imaging in meningioma—first clinical experiences using the novel SSTR-targeting peptide [18F]SiTATE

BackgroundSomatostatin-receptor (SSTR)-targeted PET/CT provides important clinical information in addition to standard imaging in meningioma patients. [18F]SiTATE is a novel, 18F-labeled SSTR-targeting peptide with superior imaging properties according to preliminary data. We provide the first [18F]SiTATE PET/CT data of a large cohort of meningioma patients.MethodsPatients with known or suspected meningioma undergoing [18F]SiTATE PET/CT were included. Uptake intensity (SUV) of meningiomas, non-meningioma lesions, and healthy organs were assessed using a 50% isocontour volume of interest (VOI) or a spherical VOI, respectively. Also, trans-osseous extension on PET/CT was assessed.ResultsA total of 107 patients with 117 [18F]SiTATE PET/CT scans were included. Overall, 231 meningioma lesions and 61 non-meningioma lesions (e.g., post-therapeutic changes) were analyzed. Physiological uptake was lowest in healthy brain tissue, followed by bone marrow, parotid, and pituitary (SUVmean 0.06 ± 0.04 vs. 1.4 ± 0.9 vs. 1.6 ± 1.0 vs. 9.8 ± 4.6; p < 0.001). Meningiomas showed significantly higher uptake than non-meningioma lesions (SUVmax 11.6 ± 10.6 vs. 4.0 ± 3.3, p < 0.001). Meningiomas showed significantly higher uptake than non-meningioma lesions (SUVmax 11.6±10.6 vs. 4.0±3.3, p<0.001). 93/231 (40.3%) meningiomas showed partial trans-osseous extension and 34/231 (14.7%) predominant intra-osseous extension. 59/231 (25.6%) meningioma lesions found on PET/CT had not been reported on previous standard imaging.ConclusionThis is the first PET/CT study using an 18F-labeled SSTR-ligand in meningioma patients: [18F]SiTATE provides extraordinary contrast in meningioma compared to healthy tissue and non-meningioma lesions, which leads to a high detection rate of so far unknown meningioma sites and osseous involvement. Having in mind the advantageous logistic features of 18F-labeled compared to 68Ga-labeled compounds (e.g., longer half-life and large-badge production), [18F]SiTATE has the potential to foster a widespread use of SSTR-targeted imaging in neuro-oncology.

Impact of Region-of-Interest Delineation on Stability and Reproducibility of Liver SNR Measurements in 68 Ga-PSMA PET/CT.

Objective This study aims to assess the impact of various regions of interest (ROIs) and volumes of interest (VOIs) delineations on the reproducibility of liver signal-to-noise-ratio (SNRliver) measurements, as well as to find the most reproducible way to estimate it in gallium-68 positron emission tomography ( 68 Ga-PET) imaging. We also investigated the SNRliver-weight relationship for these ROIs and VOIs delineations. Methods A cohort of 40 patients (40 males; mean weight: 76.5 kg [58-115 kg]) with prostate cancer were included. 68 Ga-PET/CT imaging (mean injected activity: 91.4 MBq [51.2 MBq to 134.1 MBq] was performed on a 5-ring bismuth germanium oxide-based Discovery IQ PET/CT using ordered subset expectation maximization image reconstruction algorithm. Afterward, circular ROIs and spherical VOIs with two different diameters of 30 and 40 mm were drawn on the right lobe of the livers. The performance of the various defined regions was evaluated by the average standardized uptake value (SUV mean ), standard deviation (SD) of the SUV (SUV SD ), SNR liver , and SD of the SNR liver metrics. Results There were no significant differences in SUV mean among the various ROIs and VOIs ( p > 0.05). On the other hand, the lower SUV SD was obtained by spherical VOI with diameter of 30 mm. The largest SNR liver was obtained by ROI (30 mm). The SD of SNR liver with ROI (30 mm) was also the largest, while the lowest SD of SNR liver was observed for VOI (40 mm). There is a higher correlation coefficient between the patient-dependent parameter of weight and the image quality parameter of SNRliver for both VOI (30 mm) and VOI (40 mm) compared to the ROIs. Conclusion Our results indicate that SNR liver measurements are affected by the size and shape of the respective ROIs and VOIs. The spherical VOI with a 40 mm diameter leads to more stable and reproducible SNR measurement in the liver.

Correction factors for commissioning and patient specific quality assurance of stereotactic fields in a Monte Carlo based treatment planning system

Validation of small field dosimetry is crucial for stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). Accurate and considered measurement of linear accelerator dose must be compared to precise and accurate calculation by the treatment planning system (TPS). Monte Carlo calculated distributions contain statistical noise, reducing the reliance that should be given to single voxel doses. The average dose to a small volume of interest (VOI) can minimise the influence of noise, but for small fields introduces significant volume averaging. Similar challenges present during measurement of composite dose from clinical plans when a small volume ionisation chamber is used. This study derived correction factors for VOI averaged TPS doses calculated for small fields, allowing correction to an isocentre dose following account for statistical noise. These factors were used to determine an optimal VOI to represent small volume ionisation chambers during patient specific quality assurance (PSQA). A retrospective comparison of 82 SRS and 28 SBRT PSQA measurements to TPS calculated doses from varying VOI was completed to evaluate the determined volumes. Small field commissioning correction factors of under 5% were obtained for field sizes of 8 mm and larger. Optimal spherical VOI with radius between 1.5 and 1.8 mm and 2.5 to 2.9 mm were determined for IBA CC01 and CC04 ionisation chambers respectively. Review of PSQA confirmed an optimal agreement between CC01 measured doses and a volume of 1.5 to 1.8 mm while CC04 measured doses showed no variation with VOI.

A first-in-human study of [68Ga]Ga-CDI: a positron emitting radiopharmaceutical for imaging tumour cell death

PurposeThis study assesses human biodistribution, radiation dosimetry, safety and tumour uptake of cell death indicator labelled with 68Ga ([68Ga]Ga-CDI), a novel radiopharmaceutical that can image multiple forms of cell death.MethodsFive participants with at least one extracranial site of solid malignancy > 2 cm and no active cancer treatment in the 8 weeks prior to the study were enrolled. Participants were administered 205 ± 4.1 MBq (range, 200–211 MBq) of [68Ga]Ga-CDI and 8 serial PET scans acquired: the first commencing immediately and the last 3 h later. Participants were monitored for clinical, laboratory and electrocardiographic side effects and adverse events. Urine and blood radioactivity was measured. Spherical volumes of interest were drawn over tumour, blood pool and organs to determine biodistribution and calculate dosimetry. In one participant, tumour specimens were analysed for cell death using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining.Results[68Ga]Ga-CDI is safe and well-tolerated with no side effects or adverse events. [68Ga]Ga-CDI is renally excreted, demonstrates low levels of physiologic uptake in the other organs and has excellent imaging characteristics. The mean effective dose was 2.17E − 02 ± 4.61E − 03 mSv/MBq. It images constitutive tumour cell death and correlates with tumour cell death on histology.Conclusion[68Ga]Ga-CDI is a novel cell death imaging radiopharmaceutical that is safe, has low radiation dosimetry and excellent biodistribution and imaging characteristics. It has potential advantages over previously investigated radiopharmaceuticals for imaging of cell death and has progressed to a proof-of-concept trial.Trial registrationACTRN12621000641897 (28/5/2021, retrospectively registered)

Comparison of PET/CT SUV metrics across different clinical software platforms

ObjectiveTo assess the agreement of SUV metrics across the different clinical PET reading software platforms available at our institution. MethodsPET/CT images were reviewed on four different FDA-approved software platforms: syngoMMWP VE36A and syngo.via VB30A (Siemens), Intellispace Portal 9.0 (Philips), and Encore 6.7 (MIM Software). A total of thirty SUV measurements were derived from ten 18F-FDG PET/CT oncology studies. A volume of interest (VOI) was drawn around the primary tumor to determine lesion SUVmax and a 3 cm diameter spherical VOI was placed in the right lobe of the liver to determine liver SUVmean and liver SUVmax. ResultsFor lesion SUVmax, statistically significant differences were found for syngoMMWP VE36A vs syngo.via VB30A (p = 0.002), syngoMMWP VE36A vs Intellispace Portal 9.0 (p = 0.002), and syngoMMWP VE36A vs Encore 6.7 (p = 0.001), respectively. For liver SUVmax, a statistically significant difference was found for syngoMMWP VE36A vs syngo.via VB30A (p = 0.033) only, whereas for liver SUVmean, no statistically significant differences were determined. A small systematic bias was found between syngoMMWP VE36A and all other platforms for lesion SUVmax. ConclusionSignificant differences and systematic biases were observed when measuring lesion SUVmax using different reader software systems. Although these differences may not be clinically significant, this bias could confound outcomes for quantitative, precision-research protocols. Hence, it is important for nuclear medicine departments to take SUV metric agreement into consideration, especially when transitioning to a new clinical platform.

A deep learning masked segmentation alternative to manual segmentation in biparametric MRI prostate cancer radiomics

ObjectivesTo determine the value of a deep learning masked (DLM) auto-fixed volume of interest (VOI) segmentation method as an alternative to manual segmentation for radiomics-based diagnosis of clinically significant (CS) prostate cancer (PCa) on biparametric magnetic resonance imaging (bpMRI).Materials and methodsThis study included a retrospective multi-center dataset of 524 PCa lesions (of which 204 are CS PCa) on bpMRI. All lesions were both semi-automatically segmented with a DLM auto-fixed VOI method (averaging < 10 s per lesion) and manually segmented by an expert uroradiologist (averaging 5 min per lesion). The DLM auto-fixed VOI method uses a spherical VOI (with its center at the location of the lowest apparent diffusion coefficient of the prostate lesion as indicated with a single mouse click) from which non-prostate voxels are removed using a deep learning–based prostate segmentation algorithm. Thirteen different DLM auto-fixed VOI diameters (ranging from 6 to 30 mm) were explored. Extracted radiomics data were split into training and test sets (4:1 ratio). Performance was assessed with receiver operating characteristic (ROC) analysis.ResultsIn the test set, the area under the ROC curve (AUCs) of the DLM auto-fixed VOI method with a VOI diameter of 18 mm (0.76 [95% CI: 0.66–0.85]) was significantly higher (p = 0.0198) than that of the manual segmentation method (0.62 [95% CI: 0.52–0.73]).ConclusionsA DLM auto-fixed VOI segmentation can provide a potentially more accurate radiomics diagnosis of CS PCa than expert manual segmentation while also reducing expert time investment by more than 97%.Key Points• Compared to traditional expert-based segmentation, a deep learning mask (DLM) auto-fixed VOI placement is more accurate at detecting CS PCa.• Compared to traditional expert-based segmentation, a DLM auto-fixed VOI placement is faster and can result in a 97% time reduction.• Applying deep learning to an auto-fixed VOI radiomics approach can be valuable.

Reproducibility of Standardized Uptake Values Including Volume Metrics Between TOF-PET-MR and TOF-PET-CT.

PurposeTo investigate the reproducibility of tracer uptake measurements, including volume metrics, such as metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG) obtained by TOF-PET-CT and TOF-PET-MR.Materials and MethodsEighty consecutive patients with different oncologic diagnoses underwent TOF-PET-CT (Discovery 690; GE Healthcare) and TOF-PET-MR (SIGNA PET-MR; GE Healthcare) on the same day with single dose−18F-FDG injection. The scan order, PET-CT following or followed by PET-MR, was randomly assigned. A spherical volume of interest (VOI) of 30 mm was placed on the liver in accordance with the PERCIST criteria. For liver, the maximum and mean standard uptake value for body weight (SUV) and lean body mass (SUL) were obtained. For tumor delineation, VOI with a threshold of 40 and 50% of SUVmax was used (VOI40 and VOI50). The SUVmax, SUVmean, SUVpeak, MTV and TLG were calculated. The measurements were compared between the two scanners.ResultsIn total, 80 tumor lesions from 35 patients were evaluated. There was no statistical difference observed in liver regions, whereas in tumor lesions, SUVmax, SUV mean, and SUVpeak of PET-MR were significantly underestimated (p < 0.001) in both VOI40 and VOI50. Among volume metrics, there was no statistical difference observed except TLG on VOI50 (p = 0.03). Correlation between PET-CT and PET-MR of each metrics were calculated. There was a moderate correlation of the liver SUV and SUL metrics (r = 0.63–0.78). In tumor lesions, SUVmax and SUVmean had a stronger correlation with underestimation in PET-MR on VOI 40 (SUVmax and SUVmean; r = 0.92 and 0.91 with slope = 0.71 and 0.72, respectively). In the evaluation of MTV and TLG, the stronger correlations were observed both on VOI40 (MTV and TLG; r = 0.75 and 0.92) and VOI50 (MTV and TLG; r = 0.88 and 0.95) between PET-CT and PET-MR.ConclusionPET metrics on TOF-PET-MR showed a good correlation with that of TOF-PET-CT. SUVmax and SUVpeak of tumor lesions were underestimated by 16% on PET-MRI. MTV with % threshold can be regarded as identical volumetric markers for both TOF-PET-CT and TOF-PET-MR.

Evaluation of FET PET Radiomics Feature Repeatability in Glioma Patients.

Simple SummaryInitial studies suggested the additional diagnostic value of amino acid positron emission tomography (PET) radiomics using the tracer O-(2-[18F]fluoroethyl)-L-tyrosine (FET) in brain tumor patient management. However, to ensure the reliable performance of the generated FET PET radiomics models for clinical diagnostics, repeatability of radiomics features is essential. Hence, we assessed the impact of brain tumor volumes and key molecular alterations such as an isocitrate dehydrogenase (IDH) mutation on the repeatability of FET PET radiomics features in 50 newly diagnosed glioma patients. In a test–retest approach based on routinely acquired FET PET scans, we identified 297 repeatable features. The IDH genotype did not affect feature repeatability. Moreover, these robust features were able to differentiate patients with IDH-wildtype glioma from those with an IDH mutation. Our results suggest that robust radiomics features can be obtained from routinely acquired FET PET scans, which are valuable for further standardization of radiomics analyses in neurooncology.Amino acid PET using the tracer O-(2-[18F]fluoroethyl)-L-tyrosine (FET) has attracted considerable interest in neurooncology. Furthermore, initial studies suggested the additional diagnostic value of FET PET radiomics in brain tumor patient management. However, the conclusiveness of radiomics models strongly depends on feature generalizability. We here evaluated the repeatability of feature-based FET PET radiomics. A test–retest analysis based on equivalent but statistically independent subsamples of FET PET images was performed in 50 newly diagnosed and histomolecularly characterized glioma patients. A total of 1,302 radiomics features were calculated from semi-automatically segmented tumor volumes-of-interest (VOIs). Furthermore, to investigate the influence of the spatial resolution of PET on repeatability, spherical VOIs of different sizes were positioned in the tumor and healthy brain tissue. Feature repeatability was assessed by calculating the intraclass correlation coefficient (ICC). To further investigate the influence of the isocitrate dehydrogenase (IDH) genotype on feature repeatability, a hierarchical cluster analysis was performed. For tumor VOIs, 73% of first-order features and 71% of features extracted from the gray level co-occurrence matrix showed high repeatability (ICC 95% confidence interval, 0.91–1.00). In the largest spherical tumor VOIs, 67% of features showed high repeatability, significantly decreasing towards smaller VOIs. The IDH genotype did not affect feature repeatability. Based on 297 repeatable features, two clusters were identified separating patients with IDH-wildtype glioma from those with an IDH mutation. Our results suggest that robust features can be obtained from routinely acquired FET PET scans, which are valuable for further standardization of radiomics analyses in neurooncology.

Can Na18F PET/CT bone scans help when deciding if early intervention is needed in patients being treated with a TSF attached to the tibia: insights from 41 patients

PurposeTo demonstrate the usefulness of positron emission tomography (PET)/computed tomography (CT) bone scans for gaining insight into healing bone status earlier than CT or X-ray alone.MethodsForty-one prospective patients being treated with a Taylor Spatial Frame were recruited. We registered data obtained from successive static CT scans for each patient, to align the broken bone. Radionuclide uptake was calculated over a spherical volume of interest (VOI). For all voxels in the VOI, histograms and cumulative distribution functions of the CT and PET data were used to assess the type and progress of new bone growth and radionuclide uptake. The radionuclide uptake difference per day between the PET/CT scans was displayed in a scatter plot. Superimposing CT and PET slice data and observing the spatiotemporal uptake of 18F− in the region of healing bone by a time-sequenced movie allowed qualitative evaluation.ResultsNumerical evaluation, particularly the shape and distribution of Hounsfield Units and radionuclide uptake in the graphs, combined with visual evaluation and the movies enabled the identification of six patients needing intervention as well as those not requiring intervention. Every revised patient proceeded to a successful treatment conclusion.ConclusionNumerical and visual evaluation based on all the voxels in the VOI may aid the orthopedic surgeon to assess a patient’s progression to recovery. By identifying slow or insufficient progress at an early stage and observing the uptake of 18F− in specific regions of bone, it might be possible to shorten the recovery time and avoid unnecessary late complications.

Multiparametric MRI and auto-fixed volume of interest-based radiomics signature for clinically significant peripheral zone prostate cancer

ObjectivesTo create a radiomics approach based on multiparametric magnetic resonance imaging (mpMRI) features extracted from an auto-fixed volume of interest (VOI) that quantifies the phenotype of clinically significant (CS) peripheral zone (PZ) prostate cancer (PCa).MethodsThis study included 206 patients with 262 prospectively called mpMRI prostate imaging reporting and data system 3–5 PZ lesions. Gleason scores > 6 were defined as CS PCa. Features were extracted with an auto-fixed 12-mm spherical VOI placed around a pin point in each lesion. The value of dynamic contrast-enhanced imaging(DCE), multivariate feature selection and extreme gradient boosting (XGB) vs. univariate feature selection and random forest (RF), expert-based feature pre-selection, and the addition of image filters was investigated using the training (171 lesions) and test (91 lesions) datasets.ResultsThe best model with features from T2-weighted (T2-w) + diffusion-weighted imaging (DWI) + DCE had an area under the curve (AUC) of 0.870 (95% CI 0.980–0.754). Removal of DCE features decreased AUC to 0.816 (95% CI 0.920–0.710), although not significantly (p = 0.119). Multivariate and XGB outperformed univariate and RF (p = 0.028). Expert-based feature pre-selection and image filters had no significant contribution.ConclusionsThe phenotype of CS PZ PCa lesions can be quantified using a radiomics approach based on features extracted from T2-w + DWI using an auto-fixed VOI. Although DCE features improve diagnostic performance, this is not statistically significant. Multivariate feature selection and XGB should be preferred over univariate feature selection and RF. The developed model may be a valuable addition to traditional visual assessment in diagnosing CS PZ PCa.Key Points• T2-weighted and diffusion-weighted imaging features are essential components of a radiomics model for clinically significant prostate cancer; addition of dynamic contrast-enhanced imaging does not significantly improve diagnostic performance.• Multivariate feature selection and extreme gradient outperform univariate feature selection and random forest.• The developed radiomics model that extracts multiparametric MRI features with an auto-fixed volume of interest may be a valuable addition to visual assessment in diagnosing clinically significant prostate cancer.

Trabecular bone structure scales allometrically in the foot of four human groups

The human foot is highly derived relative to that of other hominoids and therefore a topic of intense research in paleoanthropology. While trabecular bone is thought to be highly plastic in response to habitual behavior, knowledge of how trabecular structure scale with body size is essential for making functional inferences from trabecular bone morphology. Trabecular bone properties scale with negative allometry in interspecific studies that includes a wide range of body size; however, intraspecific scaling patterns often differ from interspecific trends. In this paper we examine patterns of trabecular bone scaling in the calcaneus, talus, and first metatarsal of four human populations with different subsistence strategies and associated levels of terrestrial mobility. We report Bayesian linear regressions between the natural logarithms of femoral head diameter and five standard trabecular variables calculated in five spherical volumes of interest. We additionally report regressions on population-specific z-scores of femoral head diameter and trabecular variables as a way of placing the four populations on a common scale. Results show that with increasing body size there is no change in bone volume fraction (BV/TV) and trabecular thickness (Tb.Th), a slight increase in trabecular spacing (Tb.Sp), and a sharp decrease in connectivity density (Conn.D). Degree of anisotropy was found to scale with positive allometry in the calcaneus, negative allometry in the talar trochlea, and shows no relationship with femoral head diameter in the talar and first metatarsal heads. These results show that scaling of the degree of anisotropy can vary substantially within and between bones. Degree of anisotropy is often used as a proxy for directionality in joint loading when interpreting variation in trabecular structures of fossils and extant primates. Body size should therefore be an important consideration when trabecular bone structure is used to interpret function from fossil morphology.

Differences between primary central nervous system lymphoma and glioblastoma: topographic analysis using voxel-based morphometry

To evaluate the diagnostic feasibility of probabilistic analysis using voxel-based morphometry (VBM) in differentiating primary central nervous system lymphoma (PCNSL) from glioblastoma (GBM). In total, 118 patients with GBM (57 males, 61 females; mean [± standard deviation] age, 56.9±19.3 years; median, 61 years) and 52 patients with PCNSL (37 males, 15 females; mean age, 62±13.3 years, median, 66 years) were studied retrospectively. Each patient underwent preoperative contrast-enhanced T1-weighted imaging (CE-T1WI) using a 1.5 or 3 T magnetic resonance imaging (MRI) system. To assess preferential occurrence sites, images from CE-T1WI were co-registered and spatially normalised using the MNI152 T1 template. Subsequently, a region of interest (ROI) was placed in the centre of the enhancing tumour in normalised images with 1-mm isotropic resolution. The same ROI between normalised and T1 template images was set up using an ROI manager function in ImageJ software. A spherical volume of interest (VOI) with a radius of 10 mm was determined. A probability map was created by overlaying each image with the VOI. Each VOI was removed from T1 template images for VBM analysis. VBM analysis was performed using statistical parametric mapping (SPM) 12 software under default settings. VBM analysis showed significantly higher frequency in the splenium of the corpus callosum among PCNSL patients than among GBM patients (p<0.05; family-wise error correction). Topographic analysis using VBM provides useful information for differentiating PCNSL from GBM.

Diffusely Decreased Liver Uptake on FDG PET and Cancer-Associated Cachexia With Reduced Survival.

We investigated clinical characteristics of patients with extremely increased or decreased physiologic F-FDG uptake of the liver and their prognosis. One thousand four hundred eighty-seven PET/CT scans of patients with known or suspected malignancy were retrospectively analyzed. A spherical volume of interest (3 cm in diameter) was set on the right lobe of the liver to calculate the SUVmean. Scans with extremely high (SUVmean >97.5th percentile) and low (SUVmean <2.5th percentile) FDG uptake in the liver were evaluated. Physical and laboratory data among a control group (n = 30), the extremely high liver uptake group (HG, n = 36), and the extremely low liver uptake group (LG, n = 36) were compared. Overall survival (OS) of the 3 groups was also compared. Body weight and body mass index in the HG (SUVmean ≥3.04) were significantly higher than those in the control group. The LG cases (SUVmean ≤1.78) had anemia, impaired liver function, and systemic inflammation. They were also in a poor nutritional state. The characteristics of LG cases had many things in common with those of cachectic patients. Indeed, 36.1% of LG cases met the diagnostic criteria for cachexia. Moreover, in LG cases with viable and/or recurrent malignant lesions on FDG PET, the proportion of cachexia increased by 52.6%. The OS of LG cases (median, 33 months) was significantly worse than that of controls and HG cases. Our data indicate that cancer patients with extremely decreased liver FDG uptake were likely to have cancer cachexia and a lower OS.

Variability and Reliability of Normal Liver 18F-FDG Standardized Uptake Value in Relation to Placement of Volume of Interest

Background: The impact of volume-of-interest (VOI) placement on liver standardized-uptake-value (SUV) measurement remains unclear. Objectives: To investigate variability and reliability of liver SUV in relation to placement of VOI within the right lobe of the liver. Patients and Methods: Positron emission tomography-computed tomography (PET/CT) of 343 patients with normal liver were retrieved. Liver mean SUV (SUVmean) were measured by placing spherical VOIs at upper, portal vein and lower level of the right-lobe liver. The general linear model, Bland-Altman analysis, one-way ANOVA were performed and the intraclass correlation coefficients (ICC) were calculated to identify impacts of reader and VOI position on variations of liver SUVmean. Results: The liver SUVmean at the upper, lower and portal vein level were 1.85 ± 0.435, 1.88 ± 0.409, and 1.89 ± 0.414, respectively, with no significant inter-location difference (P = 0.449). The coefficients of variation were close among locations (21.9% - 23.5%). The inter-location ICCs controlling for reader were 0.955 for reader 1 and 0.980 for reader 2, while the inter-reader ICCs controlling for location were between 0.930 and 0.937, indicating great reliability and reproducibility. However, inter-reader bias of SUVmean were significantly different among locations (P < 0.001). Bias at portal vein level (0.069 ± 0.112) was significantly larger than those at the upper level (0.004 ± 0.144, P < 0.001) and lower level (0.002 ± 0.136, P < 0.001). Conclusion: Liver SUVmean measured by placing VOI at the portal vein level exhibited a relatively larger variation and less precision between readers, which was not recommended.

Quantitative performance of 124I PET/MR of neck lesions in thyroid cancer patients using 124I PET/CT as reference

BackgroundIn patients with differentiated thyroid cancer (DTC), serial 124I PET/CT imaging is, for instance, used to assess the absorbed (radiation) dose to lesions. Frequently, the lesions are located in the neck and they are close to or surrounded by different tissue types. In contrast to PET/CT, MR-based attenuation correction in PET/MR may be therefore challenging in the neck region. The aim of this retrospective study was to assess the quantitative performance of 124I PET/MRI of neck lesions by comparing the MR-based and CT-based 124I activity concentrations (ACs). Sixteen DTC patients underwent PET/CT scans at 24 and 120 h after administration of about 25 MBq 124I. Approximately 1 h before or after PET/CT examination, each patient additionally received a 24-h PET/MR scan and sometimes a 120-h PET/MR scan. PET images were reconstructed using the respective attenuation correction approach. Appropriate reconstruction parameters and corrections were used to harmonize the reconstructed PET images to provide, for instance, similar spatial resolution. For each lesion, two types of ACs were ascertained: the maximum AC (max-AC) and an average AC (avg-AC). The avg-AC is the average activity concentration obtained within a spherical volume of interest with a diameter of 7 mm, equaling the PET scanner resolution. For each type of AC, the percentage AC difference between MR-based and CT-based ACs was determined and Lin’s concordance correlation analysis was applied. Quantitative performance was considered acceptable if the standard deviation was ± 25% (precision), and the mean value was within ± 10% (accuracy).ResultsThe avg-ACs (max-ACs within parentheses) of 74 lesions ranged from 0.20 (0.33) to 657 (733) kBq/mL. Excluding two lesions with ACs of approximately 1 kBq/mL, the mean (median) ± standard deviation (range) was − 4% (− 5%) ± 14% (− 28 to 29%) for the avg-AC and − 9% (− 11%) ± 14% (− 33 to 33%) for the max-AC. Lin’s concordance correlation coefficients were ≥ 0.97, indicating substantial AC agreement.ConclusionsQuantification of lesions in the neck region using 124I PET/MR showed acceptable quantitation performance to 124I PET/CT for AC above 1 kBq/mL. The PET/MRI-based 124I ACs in the neck region can be therefore reliably used in pre-therapy dosimetry planning.

27. Harmonization of 18F-FDG PET images for multicenter radiomic studies

Introduction Radiomics is a promising method which has undergone rapid development over the last few years. However, it has been shown that different acquisition/reconstruction parameters could introduce biases in PET-based textural feature calculation [1] , [2] . The aim of this study was (i) to evaluate the impact of voxel size, spatial resolution (SR) and signal-to-noise ratio (SNR) on feature values, (ii) to propose a harmonization method of 18F-FDG PET images based on phantom acquisitions to reduce the impact of SR and SNR on radiomic indices. Methods 115 cervical cancer patients were included retrospectively. Two groups were defined according to the PET scanner used for baseline image acquisition (G1: Siemens Biograph I; G2: GE Discovery-690). Eleven radiomic features were extracted from a spherical non-pathological hepatic volume of interest (VOI). The impact of voxel size was investigated by resampling all images into three different matrix sizes: 5.3 mm × 5.3 mm × 3.4 mm (G1 grid size), 2.7 mm × 2.7 mm × 3.4 mm (G2 grid size), 2.0 mm × 2.0 mm × 2.0 mm. In addition, two FDG-filled phantoms (homogeneous: HP, triple-line: TLP) were acquired on a GE Discovery-690 PET/CT with seven acquisition and reconstruction protocols, by changing the iteration number and post-filtering FWHM and with or without PSF modeling. SR was evaluated for all sets using TLP and all images were convolved by a 3D-Gaussian function (referred to harmonization filter HF hereafter) with a specific standard deviation so that all filtered images had the same SR as when using the clinical protocol. SNR was evaluated using the homogeneous phantom before and after HF. Radiomic features were also calculated in 22 spherical VOI (19.5 mL) before and after HF on the homogeneous phantom. Bland-Altman plots were used to characterize the dispersion of values between original and HF images. P-values from permutation tests were calculated between the two sets. Results At least 4 features (SUVmax, SUVpeak, Homogeneity, SRE) were highly dependent on the PET scanner in the three sets of patient images (p Original images of the phantoms showed large differences in both SR (3.3–7.9 mm) and SNR (9.2–25.7). A large variability of radiomic feature values was observed between different reconstruction protocols, especially for those with point-spread function correction. After filtering all images to the clinical SR (7.9 mm), feature values were less scattered according to Bland-Altman analysis (Figure 1). The difference in feature values between 2 mm and 6.4 mm FWHM post-filtering was highly significant on original images (permutation test, p 0.05). The whole analysis will be reproduced on a Philips Gemini PET device (work in progress). Conclusions A high variability of feature values was observed on clinical data due to the gap in technology between the two imaging devices. Gaussian filtering showed promising results on phantom data, by reducing the differences in textural feature values between protocols. When applied on highly different PET devices, this method might eliminate some biological signal. A combination of Gaussian filtering and voxel resampling will be investigated on patient data to assess the clinical use of such method on more recent devices.

Influence of region-of-interest determination on measurement of signal-to-noise ratio in liver on PET images.

On 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET), signal-to-noise ratio in the liver (SNRliver) is used as a metric to assess image quality. However, some regions-of-interest (ROIs) are used when measuring the SNRliver. The purpose of this study is to examine the different ROIs and volumes of interest (VOIs) to obtain a reproducible SNRliver. This study included 108 patients who underwent 18F-FDG-PET/CT scans for the purpose of cancer screening. We examined four different ROIs and VOIs; a 3-cm-diameter and a 4-cm-diameter circular ROI and a 3-cm-diameter and a 4-cm-diameter spherical VOI on the right lobe of the patients' livers. The average of SUV (SUVmean), standard deviation (SD) of SUV (SUVSD), SNRliver and SD of the SNRliver obtained using ROIs and VOIs were then compared. Although the SUVmean was not different among the ROIs and VOIs, the SUVSD was small with a 3-cm-diameter ROI. The largest SUVSD was obtained with a 4-cm-diameter spherical VOI. The SNRliver and the SD of the SNRliver with a 4-cm-diameter spherical VOI were the smallest, while those with a 3-cm-diameter circular ROI were the largest. These results suggest that a small ROI may be placed on a relatively homogeneous region not representing whole liver unintentionally. The SNRliver varied according to the shape and size of ROIs or VOIs. A 4-cm-diameter spherical VOI is recommended to obtain stable and reproducible SNRliver.

Towards standardization of 18F-FET PET imaging: do we need a consistent method of background activity assessment?

BackgroundPET with O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) has reached increasing clinical significance for patients with brain neoplasms. For quantification of standard PET-derived parameters such as the tumor-to-background ratio, the background activity is assessed using a region of interest (ROI) or volume of interest (VOI) in unaffected brain tissue. However, there is no standardized approach regarding the assessment of the background reference. Therefore, we evaluated the intra- and inter-reader variability of commonly applied approaches for clinical 18F-FET PET reading.The background activity of 20 18F-FET PET scans was independently evaluated by 6 readers using a (i) simple 2D-ROI, (ii) spherical VOI with 3.0 cm diameter, and (iii) VOI consisting of crescent-shaped ROIs; each in the contralateral, non-affected hemisphere including white and gray matter in line with the European Association of Nuclear Medicine (EANM) and German guidelines. To assess intra-reader variability, each scan was evaluated 10 times by each reader. The coefficient of variation (CoV) was assessed for determination of intra- and inter-reader variability. In a second step, the best method was refined by instructions for a guided background activity assessment and validated by 10 further scans.ResultsCompared to the other approaches, the crescent-shaped VOIs revealed most stable results with the lowest intra-reader variabilities (median CoV 1.52%, spherical VOI 4.20%, 2D-ROI 3.69%; p < 0.001) and inter-reader variabilities (median CoV 2.14%, spherical VOI 4.02%, 2D-ROI 3.83%; p = 0.001). Using the guided background assessment, both intra-reader variabilities (median CoV 1.10%) and inter-reader variabilities (median CoV 1.19%) could be reduced even more.ConclusionsThe commonly applied methods for background activity assessment show different variability which might hamper 18F-FET PET quantification and comparability in multicenter settings. The proposed background activity assessment using a (guided) crescent-shaped VOI allows minimization of both intra- and inter-reader variability and might facilitate comprehensive methodological standardization of amino acid PET which is of interest in the light of the anticipated EANM technical guidelines.

Simplifying volumes-of-interest (VOIs) definition in quantitative SPECT: Beyond manual definition of 3D whole-organ VOIs.

We investigated the feasibility of using simpler methods than manual whole-organ volume-of-interest (VOI) definition to estimate the organ activity concentration in single photon emission computed tomography (SPECT) in cases where the activity in the organ can be assumed to be uniformly distributed on the scale of the voxel size. In particular, we investigated an anatomic region-of-interest (ROI) defined in a single transaxial slice, and a single sphere placed inside the organ boundaries. The evaluation was carried out using Monte Carlo simulations based on patient indium 111 In pentetreotide SPECT and computed tomography (CT) images. We modeled constant activity concentrations in each organ, validating this assumption by comparing the distribution of voxel values inside the organ VOIs of the simulated data with the patient data. We simulated projection data corresponding to 100, 50, and 25% of the clinical count level to study the effects of noise level due to shortened acquisition time. Images were reconstructed using a previously validated quantitative SPECT reconstruction method. The evaluation was performed in terms of the accuracy and precision of the activity concentration estimates. The results demonstrated that the non-uniform image intensity observed in the reconstructed images in the organs with normal uptake was consistent with uniform activity concentration in the organs on the scale of the voxel size; observed non-uniformities in image intensity were due to a combination of partial-volume effects at the boundaries of the organ, artifacts in the reconstructed image due to collimator-detector response compensation, and noise. Using an ROI defined in a single transaxial slice produced similar biases compared to the three-dimensional (3D) whole-organ VOIs, provided that the transaxial slice was near the central plane of the organ and that the pixels from the organ boundaries were not included in the ROI. Although this slice method was sensitive to noise, biases were less than 10% for all the noise levels studied. The use of spherical VOIs was more sensitive to noise. The method was more accurate for larger spheres and larger organs such as the liver in comparison to the kidneys. Biases lower than 7% were found in the liver when using large enough spheres (radius ≥ 28 mm), regardless of the position, of the VOI inside the organ even with shortened acquisition times. The biases were more position-dependent for smaller organs. Both of the simpler methods provided suitable surrogates in terms of accuracy and precision. The results suggested that a spherical VOI was more appropriate for estimating the activity concentration in larger organs such as the liver, regardless of the position of the sphere inside the organ. Larger spheres resulted in better estimates. A single-slice ROI was more suitable for activity estimation in smaller organs such as the kidneys, providing that the transaxial slice selected was near the central plane of the organ and that voxels from the organ boundaries were excluded. Under those conditions, activity concentrations with biases lower than 5% were observed for all the studied count levels and coefficients of variation were less than 9% and 5% for the 25% and 100% count levels, respectively.