Standardized Uptake Value Measurements Research Articles

Hepatic 18F-FDG Uptake Measurements on PET/MR: Impact of Volume of Interest Location on Repeatability.

Background To investigate same day 18F-FDG (Fluorodeoxyglucose) PET (Positron Emission Tomography)/MR (Magnetic Resonance) test-retest repeatability of Standardized Uptake Value measurements normalized for body weight (SUV) and lean body mass (SUL) in different locations in the liver. Methods This prospective study was IRB approved with written informed consent obtained. 35 patients (20 women and 15 men, 61 ± 11.2 years) that performed a whole-body 18F-FDG PET/MR followed by liver-dedicated contrast-enhanced 18F-FDG PET/MR were included. SUV/L max, mean, and peak were measured inferior to, superior to, and at the right portal vein and in the left lobe of the liver. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated and Bland-Altman plots were obtained. Results The variability for SUV/L's measurements was lowest inferior to the portal vein (<9.2%) followed by measurements performed at the level of the portal vein (<14.6%). Conclusion The area inferior to the portal vein is the most reliable location for hepatic 18F-FDG uptake measurements on PET/MR.

Impact of moving target on measurement accuracy in 3D and 4D PET imaging—a phantom study

PurposeThe purpose of this study was to evaluate the impact of tumor motion on maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) measurements in both 3-dimensional and respiratory-correlated, 4-dimensional positron emission tomography (PET) imaging. We also evaluated the effect of implementing different attenuation correction methods in 4-dimensional PET image reconstruction on SUVmax and MTV. Methods and materialsAn anthropomorphic thorax phantom with a spherical ball as a surrogate for a tumor was used. Different types of motion were imposed on the ball to mimic a patient's breathing motion. Three-dimensional PET imaging of the phantom without tumor motion was performed and used as the reference. The ball was then set in motion with different breathing motion traces and imaged with both 3- and 4-dimensional PET methods. The clinical 4-dimensional PET imaging protocol was modified so that 3 different types of attenuation correction images were used for reconstructions: the same free-breathing computed tomography (CT) for all PET phases, the same average intensity projection CT for all PET phases, and 4-dimensional CT for phase-matched attenuation correction. Tumor SUVmax and MTV values that were measured from the moving phantom were compared with the reference values. ResultsSUVmax that was measured in 3-dimensional PET imaging was different from the reference value by 20.4% on average for the motions that were investigated; this difference decreased to 2.6% with 4-dimensional PET imaging. The measurement of MTV in 4-dimensional PET also showed a similar magnitude of reduction of deviation compared with 3-dimensional PET. Four-dimensional PET with use of phase-matched 4-dimensional CT for attenuation correction showed less variation in SUVmax and MTV among phases compared with 4-dimensional PET with free-breathing CT or average intensity projection CT for attenuation correction. ConclusionsFour-dimensional PET imaging reduces the impact of motion on measured SUVmax and MTV when compared with 3-dimensional PET imaging. Clinical 4-dimensional PET imaging protocols should consider phase-matched 4-dimensional CT imaging for attenuation correction to achieve more accurate measurements.

P3. The influence of reconstruction parameters on PET image quality

Introduction The PET image quality is directly related to the reconstruction algorithm. The statistical reconstruction methods can improve the image quality by improving the spatial resolution. This may change the image contrast and the quantitative measurement of SUV (standardized uptake value) in small structures. The aim of this study is to determine the changes in SUV, image contrast, recovery coefficient and spatial resolution within the reconstruction parameters such as iterations and subsets number and also the applied corrections. Material and method The measurements of SUV (average and maximum), contrast, recovery coefficient and spatial resolution were obtained through a Jaszczak Deluxe phantom image, acquired on a PET-CT GE scanner Discovery 710®. The phantom was filled with a 18F-FDG solution of 22 MBq. These parameters were studied based on the corrections applied during the reconstruction, including the Point Spread Function (PSF) and the Time-Of-Flight (TOF) option. Comparisons have also been made in terms of number of iterations and subsets: OSEM (2.4 and 10 iterations, 1.12 and 24 subsets). Results Reconstruction results for 4 iterations and 24 subsets showed that the average SUV value, with TOF function is reduced by 5.2%, 2.1% and 4.2% compared to non-TOF, PSF and TOF-PSF reconstructions respectively. With PSF, the average SUV value is reduced by 3% and 2% compared to the non-PSF and TOF-PSF reconstructions respectively. However the average SUV value is increased by 2% compared to the reconstruction integrating the TOF function. The contrast measurement is reduced by 80%, 75% and 45% compared to the expected absolute value for the reconstructions with TOF, PSF and TOF-PSF respectively. The recovery coefficient is improved with the correction of TOF and PSF however improvements become less important when the diameter of the sphere is large. The spatial resolution with the full width at half maximum (FWHM) measured on the largest sphere is underestimated by 5.5%, 0.6% and 5.6% for TOF, PSF and TOF-PSF reconstructions respectively. Conclusion The reconstruction parameters can improve image quality, however any image reconstruction protocol should be validated before clinical routine or research use.

A method to assess image quality for Low-dose PET: analysis of SNR, CNR, bias and image noise.

BackgroundLowering injected dose will have an effect on PET image quality. In this article, we aim to investigate this effect in terms of signal-to-noise ratio (SNR) in the liver, contrast-to-noise ratio (CNR) in the lesion, bias and ensemble image noise.MethodsWe present here our method and preliminary results using tuberculosis (TB) cases. Sixteen patients who underwent 18F-FDG PET/MR scans covering the whole lung and portion of the liver were selected for the study. Reduced doses were simulated by randomly discarding events in the PET list mode data stream, and ten realizations at each simulated dose were generated and reconstructed. The volumes of interest (VOI) were delineated on the image reconstructed from the original full statistics data for each patient. Four thresholds (20, 40, 60 and 80 % of SUVmax) were used to quantify the effect of the threshold on CNR at the different count level. Image metrics were calculated for each VOI. This experiment allowed us to quantify the loss of SNR and CNR as a function of the counts in the scan, in turn related to dose injected. Reproducibility of mean and maximum standardized uptake value (SUVmean and SUVmax) measurement in the lesions was studied as standard deviation across 10 realizations.ResultsAt 5 × 106 counts in the scan, the average SNR in the liver in the observed samples is about 3, and the CNR is reduced to 60 % of the full statistics value. The CNR in the lesion and SNR in the liver decreased with reducing count data. The variation of CNR across the four thresholds does not significantly change until the count level of 5 × 106. After correcting the factor related to subject’s weight, the square of the SNR in the liver was found to have a very good linear relationship with detected counts. Some quantitative bias appears with count reduction. At the count level of 5 × 106, bias and noise in terms of SUVmean and SUVmax are up to 10 and 20 %, respectively. To keep both bias and noise less than 10 %, 5 × 106 counts and 20 × 106 counts were required for SUVmean and SUVmax, respectively.ConclusionsInitial results with the given data of 16 patients diagnosed as TB demonstrated that 5 × 106 counts in the scan could be sufficient to yield good images in terms of SNR, CNR, bias and noise. In the future, more work needs to be done to validate the proposed method with a larger population and lung cancer patient data.

WE‐H‐207A‐03: The Universality of the Lognormal Behavior of [F‐18]FLT PET SUV Measurements

Purpose:Log transforming [F‐18]FDG PET standardized uptake values (SUVs) has been shown to lead to normal SUV distributions, which allows utilization of powerful parametric statistical models. This study identified the optimal transformation leading to normally distributed [F‐18]FLT PET SUVs from solid tumors and offers an example of how normal distributions permits analysis of non‐independent/correlated measurements.Methods:Forty patients with various metastatic diseases underwent up to six FLT PET/CT scans during treatment. Tumors were identified by nuclear medicine physician and manually segmented. Average uptake was extracted for each patient giving a global SUVmean (gSUVmean) for each scan. The Shapiro‐Wilk test was used to test distribution normality. One parameter Box‐Cox transformations were applied to each of the six gSUVmean distributions and the optimal transformation was found by selecting the parameter that maximized the Shapiro‐Wilk test statistic. The relationship between gSUVmean and a serum biomarker (VEGF) collected at imaging timepoints was determined using a linear mixed effects model (LMEM), which accounted for correlated/non‐independent measurements from the same individual.Results:Untransformed gSUVmean distributions were found to be significantly non‐normal (p&lt;0.05). The optimal transformation parameter had a value of 0.3 (95%CI: −0.4 to 1.6). Given the optimal parameter was close to zero (which corresponds to log transformation), the data were subsequently log transformed. All log transformed gSUVmean distributions were normally distributed (p&gt;0.10 for all timepoints). Log transformed data were incorporated into the LMEM. VEGF serum levels significantly correlated with gSUVmean (p&lt;0.001), revealing log‐linear relationship between SUVs and underlying biology.Conclusion:Failure to account for correlated/non‐independent measurements can lead to invalid conclusions and motivated transformation to normally distributed SUVs. The log transformation was found to be close to optimal and sufficient for obtaining normally distributed FLT PET SUVs. These transformations allow utilization of powerful LMEMs when analyzing quantitative imaging metrics.

Interobserver and Intraobserver Variability among Measurements of FDG PET/CT Parameters in Pulmonary Tumors.

18F-fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET/CT) provides information about metabolic and morphologic status of malignancies. Tumor size and standardized uptake value (SUV) measurements are crucial for cancer treatment monitoring. The purpose of our study was to assess the variability of these measurements performed by observers evaluating lung tumors. Retrospective cross-sectional study. FDG PET/CT images of 97 patients with pulmonary tumors were independently evaluated by two experienced nuclear medicine physicians. Primary tumor size (UDCT), maximum SUV (SUVmax), mean SUV (SUVmean) and maximum SUV normalized to liver mean SUV (SUVnliv max) were measured by each observer at two different times with an interval of at least 2 weeks. Interobserver and intraobserver variabilities of measurements were evaluated through statistical methods. Size of the lesions varied from 0.81 to 13.6 cm (mean 4.29±2.24 cm). Very good agreement was shown with correlation, Bland-Altman and regression analysis for all measured PET/CT parameters. In the interobserver and intraobserver variability analysis, the Pearson correlation coefficients were greater than 0.96 and 0.98, respectively. Semi-quantitative measurements of pulmonary tumors were highly reproducible when determined by experienced physicians with clinically available software for routine FDG PET/CT evaluation. Consistency may be improved if the same observer performs serial measurements for any one patient.

Relationship between the Temporal Changes in Positron-Emission-Tomography-Imaging-Based Textural Features and Pathologic Response and Survival in Esophageal Cancer Patients.

Although change in standardized uptake value (SUV) measures and PET-based textural features during treatment have shown promise in tumor response prediction, it is unclear which quantitative measure is the most predictive. We compared the relationship between PET-based features and pathologic response and overall survival with the SUV measures in esophageal cancer. Fifty-four esophageal cancer patients received PET/CT scans before and after chemoradiotherapy. Of these, 45 patients underwent surgery and were classified into complete, partial, and non-responders to the preoperative chemoradiation. SUVmax and SUVmean, two cooccurrence matrix (Entropy and Homogeneity), two run-length matrix (RLM) (high-gray-run emphasis and Short-run high-gray-run emphasis), and two size-zone matrix (high-gray-zone emphasis and short-zone high-gray emphasis) textures were computed. The relationship between the relative difference of each measure at different treatment time points and the pathologic response and overall survival was assessed using the area under the receiver-operating-characteristic curve (AUC) and Kaplan-Meier statistics, respectively. All Textures, except Homogeneity, were better related to pathologic response than SUVmax and SUVmean. Entropy was found to significantly distinguish non-responders from the complete (AUC = 0.79, p = 1.7 × 10(-4)) and partial (AUC = 0.71, p = 0.01) responders. Non-responders can also be significantly differentiated from partial and complete responders by the change in the run-length and size-zone matrix textures (AUC = 0.71-0.76, p ≤ 0.02). Homogeneity, SUVmax, and SUVmean failed to differentiate between any of the responders (AUC = 0.50-0.57, p ≥ 0.46). However, none of the measures were found to significantly distinguish between complete and partial responders with AUC <0.60 (p = 0.37). Median Entropy and RLM textures significantly discriminated patients with good and poor survival (log-rank p < 0.02), while all other textures and survival were poorly related (log-rank p > 0.25). For the patients studied, temporal changes in Entropy and all RLM were better correlated with pathological response and survival than the SUV measures. The hypothesis that these metrics can be used as clinical predictors of better patient outcomes will be tested in a larger patient dataset in the future.

Role of Optimal Quantification of FDG PET Imaging in the Clinical Practice of Radiology.

The combination of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) for dual-modality imaging (PET/CT) plays a key role in the diagnosis and staging of FDG-avid malignancies. FDG uptake by the tumor cells offers an opportunity to detect cancer in organs that appear normal at anatomic imaging and to differentiate viable tumor from posttreatment effects. Quantification of FDG uptake has multiple clinical applications, including cancer diagnosis and staging. Dedicated FDG PET/CT-based visual and quantitative criteria have been developed to evaluate treatment response. Furthermore, the level of tumor FDG uptake reflects the biologic aggressiveness of the tumor, predicting the risk of metastasis and recurrence. FDG uptake can be measured with qualitative, semiquantitative, and quantitative methods. Qualitative or visual assessment of PET/CT images is the most common clinical approach for describing the level of FDG uptake. Standardized uptake value (SUV) is the most commonly used semiquantitative tool for measuring FDG uptake. SUV can be measured as maximum, mean, or peak SUV and may be normalized by using whole or lean body weight. SUV measurements provide the basis for quantitative response criteria; however, SUVs have not been widely adopted as diagnostic thresholds for discriminating malignant and benign lesions. Volumetric FDG uptake measurements such as metabolic tumor volume and total lesion glycolysis have shown substantial promise in providing accurate tumor assessment. SUV measurement and other quantification techniques can be affected by many technical, physical, and biologic factors. Familiarity with FDG uptake quantification approaches and their pitfalls is essential for clinical practice and research.

Impact and correction of the bladder uptake on 18F-FCH PET quantification: a simulation study using the XCAT2 phantom

The spill-in counts from neighbouring regions can significantly bias the quantification over small regions close to high activity extended sources. This effect can be a drawback for 18F-based radiotracers positron emission tomography (PET) when quantitatively evaluating the bladder area for diseases such as prostate cancer. In this work, we use Monte Carlo simulations to investigate the impact of the spill-in counts from the bladder on the quantitative evaluation of prostate cancer when using 18F-Fluorcholine (FCH) PET and we propose a novel reconstruction-based correction method. Monte Carlo simulations of a modified version of the XCAT2 anthropomorphic phantom with 18F-FCH biological distribution, variable bladder uptake and inserted prostatic tumours were used in order to obtain simulated realistic 18F-FCH data. We evaluated possible variations of the measured tumour Standardized Uptake Value (SUV) for different values of bladder uptake and propose a novel correction by appropriately adapting image reconstruction methodology. The correction is based on the introduction of physiological background terms on the reconstruction, removing the contribution of the bladder to the final image. The bladder is segmented from the reconstructed image and then forward-projected to the sinogram space. The resulting sinograms are used as background terms for the reconstruction. SUVmax and SUVmean could be overestimated by 41% and 22% respectively due to the accumulation of radiotracer in the bladder, with strong dependence on bladder-to-lesion ratio. While the SUVs measured under these conditions are not reliable, images corrected using the proposed methodology provide better repeatability of SUVs, with biases below 6%. Results also showed remarkable improvements on visual detectability. The spill-in counts from the bladder can affect prostatic SUV measurements of 18F-FCH images, which can be corrected to less than 6% using the proposed methodology, providing reliable SUV values even in the presence of high radioactivity accumulation in the bladder.

Abstract 05: Genetic heterogeneity in rectal cancer - Identification of subpopulations of tumor cells resistant to neoadjuvant CRT

Abstract One of the benefits of neoadjuvant chemotherapy and radiation therapy (CRT) for the management of rectal cancer is tumor downstaging that can ultimately lead to complete tumor regression (known as complete pathological response - pCR). In a previous study using PET/CT imaging to assess tumor response to CRT, 50% of rectal cancers showed a continuous decrease in metabolic activity (estimated by standard uptake value measurements) between 6 and 12 weeks from CRT completion. However the remaining 50% of the cases showed increased metabolic activity within that period. We reasoned that the increased metabolic activity observed in these later patients could be determined by the clonal expansion of a genetically distinct subpopulation of tumor cells resistant to CRT. To address this question we performed exome sequencing and mutation detection analysis on normal tissue, primary tumor and residual tumor from 7 patients with rectal cancer that exhibited an increase in metabolic activity after CRT. Overall, about 20Gb of unambiguously mapped sequences were generated for each sample resulting in an average fold-coverage of 30X. Captured sequences mapped to the reference human genome were then used for the detection of SNPs and non-synonymous somatic point mutations in all three samples from each patient. Approximately 30,000 single nucleotide variants (SNVs) were identified in each sample and most of these SNVs were common to all samples. As expected, the majority of these common inherited variants (96%) have already been described in dbSNP. To identify non-synonymous somatic mutations occurring in primary and residual tumor samples, we excluded those present in the normal sample and those already described as a known SNP in dbSNP resulting in a mean of 243 SNVs per patient. Noteworthy, a significant number of non-synonymous somatic mutations were exclusively found in the primary and residual tumor samples of each patient, 30 and 32 SNVs on average respectively, revealing a high degree of tumor genetic heterogeneity. Furthermore, we were able to identify non-synonymous somatic mutations that were presented in both samples (mean of 107 SNVs), and for these mutations we determined the mutant allele frequency (number of reads representing the mutation/total number of reads covering the mutated base) in the primary and the residual tumor. We then searched for mutations with significantly different allele frequencies in the two samples, as these mutations would likely represent genetically distinct subpopulations of tumor cells selected during CRT. We were able to identify, on average, 4 SNVs enriched in primary tumor and 37 SNVs enriched in residual tumor per patient. In conclusion, based on exome sequencing of rectal tumors that exhibit incomplete response to CRT and have increased tumor metabolism we were able to identify non-synonymous mutations that may be associated with specific mechanisms of resistance or sensitivity to CRT. Functional analysis of these mutations and mutated genes will be presented, providing new insights into the molecular events influencing response to neoadjuvant CRT in rectal cancer. Citation Format: Fabiana Bettoni, Elisa R. Donnard, Bruna R. S. Correa, Paula F. Asprino, Fernanda C. Koyama, Natália M. Felício, Bruna H. Hessel, Pedro A. F. Galante, Anamaria A. Camargo, Angelita Habr-Gama, Rodrigo O. Perez. Genetic heterogeneity in rectal cancer - Identification of subpopulations of tumor cells resistant to neoadjuvant CRT. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr 05.

FDG PET/CT for Initial Staging of Diffuse Large B-Cell Lymphoma: Is Diffuse Bone Marrow Uptake a Reflection of Disease Involvement?

Objectives: Bone marrow assessment is a diagnostic challenge in staging diffuse large B-cell lymphoma (DLBCL). Diffuse bone marrow uptake (BMU) can be observed on FDG PET/CT performed for initial staging of DLBCL, but remains difficult to analyze. The aim of this study was to evaluate the meaning of this diffuse BMU, and especially to assess its correlation with bone marrow involvement (BMI). Methods: Patients who underwent FDG PET/CT for initial staging of DLBCL were analyzed. Diffuse BMU was assessed using a visual qualitative analysis according to liver uptake (grade 1=below liver uptake, 2=equal to liver uptake, 3=above liver uptake), and a semi-quantitative analysis, by measurement of maximum standardized uptake value (SUV) in the sacral promontory. We compared the BMU with BMI, parameters of disease extension and inflammatory markers. Results: 86 patients (median age 59, range: 19-91, 54 men, 32 women) were included. BMU grade was 1, 2 and 3 in 45, 28 and 13 cases respectively. Bone marrow was considered involved in 13 patients. No statistical correlation was found between diffuse BMU and BMI, using qualitative (p=0.594) or semi-quantitative method (p=0.116). Diffuse BMU visual grading was correlated with inflammatory markers: biological systemic symptoms (p=0.003), CRP (p=0.002) and fibrinogen (p=0.020). Conclusions: Our study suggests that a diffuse BMU seen on FDG PET/CT at initial staging of DLBCL is not representative of bone marrow involvement, but can be due to inflammatory changes.

WB-DWI MRI Scanning Outperforms FDG PET-CT for the Assessment of Myeloma Disease Burden

▪Introduction:Whole body MRI is recommended for all patients suspected of having smouldering myeloma for detection of disease defining lesions (Dimopoulos et al. 2015). The speed, sensitivity and quantitative capabilities of Whole body Diffusion Weighted MRI (WB-DWI) have seen this increasingly used as the MRI sequence of choice for detection and response assessment in myeloma (Messiou and Kaiser 2015). 18-F-fluorodeoxyglucose positron emission tomography-CT (FDG PET-CT) also offers whole body coverage with standard uptake value (SUV) measurements of individual lesions. In previous studies the sensitivity and specificity of conventional MRI superseded FDG PET-CT due to improved detection of small focal lesions and diffuse disease (Zamagni et al. 2007, Shortt et al. 2009). However, WB-DWI and FDG PET-CT comparisons in patients with myeloma have not previously been investigated. We compared the assessment of myeloma using these two modalities and determined the relationship to laboratory estimates of disease burden.Method:Patients who had undergone paired WB-DWI and FDG PET-CT scans for myeloma at our institution were included. Scans were excluded if there was clinical or biochemical evidence of change in disease status between scans. Expert radiologists (WB-DWI = CM, AR; FDG PET-CT = BS, LF) scored disease burden by consensus using a previously described system (Giles et al. 2014) based on the number, size and pattern (diffuse/focal) of disease. Whole body and per region scores were compared. Bone marrow trephine assessments of % plasma cell (PC) infiltration were correlated to the imaging scores and compared to the assessment of disease infiltration at the iliac crests.Results:20 pairs of scans were performed in 17 patients. Scans took place within a median of 9.5 days (range 0-78), mean 14 days ±18.15. There was a positive correlation between WB-DWI and FDG PET-CT scores (Spearman r = 0.35, 95% C.I. [-0.12,0.69]) but the whole body score for WB-DWI was significantly higher than for FDG PET-CT (WB-DWI mean 17.65±12.24 vs FDG PET-CT mean 8.45±8.70. P =0.0023 Wilcoxon signed rank). In all regions scores for WB-DWI (Table 1) were higher than FDG PET-CT with statistical significance in all except for pelvis and long bones.Diffuse disease was reported in 36% (51/140) of regions on WB-DWI scans compared to only 7% (10/140) on FDG PET-CT. The regions reported as having diffuse disease on WB-DWI were reported on FDG PET-CT as 'no disease' for most (36/51) regions (Figure 1A). Whole body scores were reanalyzed including only focal lesions. The scores for FDG PET-CT and WB-DWI were no longer significantly different (FDG PET-CT mean 6.45±7.06, WB-DWI mean 7.45±10.32, P =0.92) (Figure 1Bi-ii) suggesting the ability of WB-DWI to detect more disease is largely due to the increased ability to detect diffuse marrow involvement.For 10 WB-DWI scans on which there was activity a follow up WB-DWI was available and demonstrated a change in disease burden (e.g. Figure 1B). This supports the presence of active lesions on the initial MRI and indicates the utility of WB-DWI as a response assessment tool.15/20 pairs had bone marrow trephines with adequate tissue for the calculation of PC % performed close to the FDG PET-CT and WB-DWI scans. The PC % was better correlated to WB-DWI scores than FDG PET-CT. In 93% of patients the trephine PC % was similar to the WB-DWI report of activity at the iliac crests compared with only 67% for FDG PET-CT.Conclusions:In paired scans WB-DWI reports a higher burden of myeloma disease than FDG PET-CT. This is largely due to the increased ability for WB-DWI to detect diffuse marrow disease. WB-DWI also outperforms FDG PET-CT in the assessment of disease infiltration in the iliac bones, essential for good clinical correlation of trephine results. We are in the process of validating these results in a prospective study but our results support guidance that MRI should be the investigation of choice for detection of myeloma marrow infiltration.Table 1RegionScoreMean (±SD)P value*FDG PET-CTWB-DWIWhole body8.45 (±8.70)17.65 (±12.24)0.002C spine0.47 (±1.17)1.68 (±1.92)0.016D spine1.20 (±1.64)2.60 (±2.04)0.011L spine1.00 (±1.62)2.50 (±2.04)0.007Pelvis2.40 (±2.54)3.30 (±1.95)NS, 0.13Long bones1.85 (±2.35)2.80 (±2.71)NS, 0.19Skull0.21 (±0.63)1.95 (±1.96)0.004Ribs/other1.35 (±1.90)3.00 (±1.97)0.006*Wilcoxon matched-pairs signed rank test [Display omitted] DisclosuresPawlyn:Celgene: Honoraria, Other: Travel support; The Institute of Cancer Research: Employment. Off Label Use: vorinostat for treatment of myeloma. Kaiser:Amgen: Consultancy, Honoraria; Janssen: Honoraria; Chugai: Consultancy; BristolMyerSquibb: Consultancy; Celgene: Consultancy, Honoraria, Research Funding. Jones:Celgene: Other: Travel support, Research Funding. Davies:Takeda-Milenium: Honoraria; Celgene: Honoraria; Onyx-Amgen: Honoraria; University of Arkansas for Medical Sciences: Employment. Morgan:Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda-Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; CancerNet: Honoraria; Weisman Institute: Honoraria; University of Arkansas for Medical Sciences: Employment; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MMRF: Honoraria.

Partial volume correction and image segmentation for accurate measurement of standardized uptake value of grey matter in the brain.

Our aim was to explore a novel quantitative method [based upon an MRI-based image segmentation that allows actual calculation of grey matter, white matter and cerebrospinal fluid (CSF) volumes] for overcoming the difficulties associated with conventional techniques for measuring actual metabolic activity of the grey matter. We included four patients with normal brain MRI and fluorine-18 fluorodeoxyglucose (F-FDG)-PET scans (two women and two men; mean age 46±14 years) in this analysis. The time interval between the two scans was 0-180 days. We calculated the volumes of grey matter, white matter and CSF by using a novel segmentation technique applied to the MRI images. We measured the mean standardized uptake value (SUV) representing the whole metabolic activity of the brain from the F-FDG-PET images. We also calculated the white matter SUV from the upper transaxial slices (centrum semiovale) of the F-FDG-PET images. The whole brain volume was calculated by summing up the volumes of the white matter, grey matter and CSF. The global cerebral metabolic activity was calculated by multiplying the mean SUV with total brain volume. The whole brain white matter metabolic activity was calculated by multiplying the mean SUV for the white matter by the white matter volume. The global cerebral metabolic activity only reflects those of the grey matter and the white matter, whereas that of the CSF is zero. We subtracted the global white matter metabolic activity from that of the whole brain, resulting in the global grey matter metabolism alone. We then divided the grey matter global metabolic activity by grey matter volume to accurately calculate the SUV for the grey matter alone. The brain volumes ranged between 1546 and 1924 ml. The mean SUV for total brain was 4.8-7. Total metabolic burden of the brain ranged from 5565 to 9617. The mean SUV for white matter was 2.8-4.1. On the basis of these measurements we generated the grey matter SUV, which ranged from 8.1 to 11.3. The accurate metabolic activity of the grey matter can be calculated using the novel segmentation technique that we applied to MRI. By combining these quantitative data with those generated from F-FDG-PET images we were able to calculate the accurate metabolic activity of the grey matter. These types of measurements will be of great value in accurate analysis of the data from patients with neuropsychiatric disorders.

Regional Lymph Node Uptake of [18F]Fluorodeoxyglucose After Definitive Chemoradiation Therapy Predicts Local-Regional Failure of Locally Advanced Non-Small Cell Lung Cancer: Results of ACRIN 6668/RTOG 0235

The American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group (RTOG) 0235 study demonstrated that standardized uptake values (SUV) on post-treatment [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET) correlated with survival in locally advanced non-small cell lung cancer (NSCLC). This secondary analysis determined whether SUV of regional lymph nodes (RLNs) on post-treatment FDG-PET correlated with patient outcomes. Included for analysis were patients treated with concurrent chemoradiation therapy, using radiation doses ≥60 Gy, with identifiable FDG-avid RLNs (distinct from primary tumor) on pretreatment FDG-PET, and post-treatment FDG-PET data. ACRIN core laboratory SUV measurements were used. Event time was calculated from the date of post-treatment FDG-PET. Local-regional failure was defined as failure within the treated RT volume and reported by the treating institution. Statistical analyses included Wilcoxon signed rank test, Kaplan-Meier curves (log rank test), and Cox proportional hazards regression modeling. Of 234 trial-eligible patients, 139 (59%) had uptake in both primary tumor and RLNs on pretreatment FDG-PET and had SUV data from post-treatment FDG-PET. Maximum SUV was greater for primary tumor than for RLNs before treatment (P<.001) but not different post-treatment (P=.320). Post-treatment SUV of RLNs was not associated with overall survival. However, elevated post-treatment SUV of RLNs, both the absolute value and the percentage of residual activity compared to the pretreatment SUV were associated with inferior local-regional control (P<.001). High residual metabolic activity in RLNs on post-treatment FDG-PET is associated with worse local-regional control. Based on these data, future trials evaluating a radiation therapy boost should consider inclusion of both primary tumor and FDG-avid RLNs in the boost volume to maximize local-regional control.

Abstract 1486: Fatty acid and phospholipid profiling of liver tumor tissue: correlation with in vivo molecular PET imaging of phosphocholine synthesis

Abstract Alterations in phospholipid and fatty acid metabolism may play key roles in hepatocarcinogenesis. Phosphocholine synthesis can be imaged and quantified in-vivo by positron emission tomography (PET) using radiopharmaceuticals bearing the choline moiety. Results from this PET assessment of tissue phospholipid metabolism were compared to phospholipid and fatty acid profiles of both tumor and liver parenchymal tissues in patients with liver cancer undergoing hepatectomy. Fluorine-18 fluorocholine PET/CT of the liver was completed &amp;lt;2 weeks prior to surgery as part of a clinicaltrials.gov-registered (NCT01395030) IRB-approved clinical study with written informed consent. Paired tumor and parenchymal tissue samples were collected in liquid nitrogen (20 hepatocellular carcinoma, 3 with intrahepatic cholangiocarcinoma), freeze-dried, homogenized and extracted with methanol/CHCl3/water containing BHT as preservative. The organic phase was analyzed by orbitrap LCMS after electrospray ionization in positive mode to quantify fatty acids (after derivatization) and phospholipid metabolites. Tumor and liver standardized uptake value (SUV) measurements were obtained from static PET images. Tumors exhibited significantly lower levels of docosahexaenoic acid, docasopentanoic acid, alpha-linolenic acid and significantly higher levels of palmitoleic acid, eicosadienoic acid, arachadonic acid, and linoleic acid than peritumoral liver tissue. Tumors also exhibited significantly higher SUVs than surrounding liver. Highest tumor SUV correlated significantly with tumor levels of palmitoleic acid, gamma linolenic acid, CDP choline, phosphatidylcholine, phosphatidylethanolamine and phosphatidylinsolitol. In contrast, no significant correlations were noted between tumor SUV and peri-tumoral levels of these compounds. Peritumoral liver SUV was significantly correlated with levels of myristic acid, eicosaptaenoic acid, gamma-linolenic acid, palmitoleic acid, docosapentaenoic acid, linoleic acid, oleic acid, and palmitic acid in peritumoral liver tissue. Furthermore, parenchymal liver SUV was inversely correlated with the Knodell histologic activity index (HAI), as well as histologic features of portal inflammation, piecemeal necrosis, and fibrosis. These histology features were also inversely correlated with liver tissue concentrations of docosahexaenoic acid, CDP-choline, total phosphaticylcholine, and total phosphatidylinositol. No significant correlations were found between tumor fatty acid/phospholipid levels and Edmonson-Steiner tumor grade. These preliminary results may indicate multiple inter-related metabolic alterations involving phospholipid and fatty acid metabolism in primary liver cancer. Chronic liver disease appears to be associated with diminishing hepatic phospholipid reserve. Note: This abstract was not presented at the meeting. Citation Format: Sandi Alexander Kwee, Adrian A. Franke, Laurie J. Custer, Xingnan Li, Linda L. Wong. Fatty acid and phospholipid profiling of liver tumor tissue: correlation with in vivo molecular PET imaging of phosphocholine synthesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1486. doi:10.1158/1538-7445.AM2015-1486

Quantification, Variability, and Reproducibility of Basal Skeletal Muscle Glucose Uptake in Healthy Humans Using 18F-FDG PET/CT.

The quantification and variability of skeletal muscle glucose utilization (SMGU) in healthy subjects under basal (low insulin) conditions are poorly known. This information is essential early in clinical drug development to effectively interrogate novel pharmacologic interventions that modulate glucose uptake. The aim of this study was to determine test-retest characteristics and variability of SMGU within and between healthy subjects under basal conditions. Furthermore, different kinetic modeling strategies were evaluated to find the best-fitting model to assess SMGU studied by 18F-FDG. Six healthy male volunteers underwent 2 dynamic 18F-FDG PET/CT scans with an interval of 24 h. Subjects were admitted to the clinical unit to minimize variability in daily activities and food intake and restrict physical activity. 18F-FDG PET/CT scans of gluteal and quadriceps muscle area were obtained with arterial input. Regions of interest were drawn over the muscle area to obtain time-activity curves and standardized uptake values (SUVs) between 60 and 90 min. Spectral analysis of the data and kinetic modeling was performed using 2-tissue-irreversible (2T3K), 2-tissue-reversible, and 3-tissue-sequential-irreversible (3T5KS) models. Reproducibility was assessed by intraclass correlation coefficients (ICCs) and within-subject coefficient of variation (WSCV). SUVs in gluteal and quadriceps areas were 0.56±0.09 and 0.64±0.07. ICCs (with 90% confidence intervals in parentheses) were 0.88 (0.64-0.96) and 0.96 (0.82-0.99), respectively, for gluteal and quadriceps muscles, and WSCV for gluteal and quadriceps muscles was 2.2% and 3.6%, respectively. The rate of glucose uptake into muscle was 0.0016±0.0004 mL/mL⋅min, with an ICC of 0.94 (0.93-0.95) and WSCV of 6.6% for the 3T5KS model, whereas an ICC of 0.98 (0.92-1.00) and WSCV of 2.8% was obtained for the 2T3K model. 3T5KS demonstrated the best fit to the measured experimental points. Minimal variability in skeletal muscle glucose uptake was observed under basal conditions in healthy subjects. SUV measurements and rate of glucose uptake values were reproducible, with an average WSCV of less than 5%. Compared with SUV, the 3-tissue model adds information about kinetics between blood, intra- and intercellular compartments, and phosphorylation that may highlight the exact mechanisms of metabolic changes after pharmacologic intervention.

Added Value of Dual-Time-Point 18F-FDG PET/CT With Delayed Imaging for Detecting Aortic Graft Infection: An Observational Study.

18F-FDG PET/CT is a promising tool in detecting aortic graft infection. Present study investigated the value of dual-time-point 18F-FDG PET/CT imaging (DTPI) with delayed imaging in assessing aortic graft infection.Twenty-nine patients with suspected aortic graft infection were prospectively enrolled in this DTPI study. Two nuclear medicine physicians read all the images and achieved consensus about the measurement of maximal standardized uptake value (SUVmax) and grading of image quality. The percentages of SUVmax change between initial and delayed images were recorded as retention index (RI); sensitivity, specificity, and accuracy were calculated based on reference standard.All the 5 infected aortic grafts had positive RIs, which were generally higher than that of noninfected grafts. Those noninfected grafts had variable RIs. Seven patients had improved image quality in delayed imaging. DTPI with delayed image detected all the infected grafts with improved specificity (88%) and accuracy (90%), providing conspicuous delineation of the infected graft extent.In conclusion, noninfected aortic grafts had more variable RIs than infected ones. DTPI might be useful for detecting aortic graft infection, improving image quality, and enhancing delineation of the infected aortic grafts.

Correlation between the Uptake of 18F-Fluorodeoxyglucose (18F-FDG) and the Expression of Proliferation-Associated Antigen Ki-67 in Cancer Patients: A Meta-Analysis

ObjectiveTo study the correlation between 18F-FDG uptake and cell proliferation in cancer patients by meta-analysis of published articles.MethodsWe searched PubMed (MEDLINE included), EMBASE, and Cochrane Database of Systematic Review, and selected research articles on the relationship between 18F-FDG uptake and Ki-67 expression (published between August 1, 1994-August 1, 2014), according to the literature inclusion and exclusion criteria. The publishing language was limited to English. The quality of included articles was evaluated according to the Quality Assessment of Diagnosis Accuracy Studies-2 (QUADAS-2). The correlation coefficient (r) was extracted from the included articles and processed by Fisher's r-to-z transformation. The combined correlation coefficient (r) and the 95% confidence interval (CI) were calculated with STATA 11.0 software under a random-effects model. Begg's test was used to analyze the existence of publication bias and draw funnel plot, and the sources of heterogeneity were explored by sensitivity and subgroup analyses.ResultsAccording to the inclusion and exclusion criteria, 79 articles were finally included, including 81 studies involving a total of 3242 patients. All the studies had a combined r of 0.44 (95% CI, 0.41-0.46), but with a significant heterogeneity (I2 = 80.9%, P<0.01). Subgroup analysis for different tumor types indicated that most subgroups showed a reduced heterogeneity. Malignant melanoma (n = 1) had the minimum correlation coefficient (-0.22) between 18F-FDG uptake and Ki-67 expression, while the thymic epithelial tumors (TETs; n = 2) showed the maximum correlation coefficient of 0.81. The analytical results confirmed that correlation between 18F-FDG uptake and Ki-67 expression was extremely significant in TETs, significant in gastrointestinal stromal tumors (GISTs), moderate in patients with lung, breast, bone and soft tissue, pancreatic, oral, thoracic, and uterine and ovarian cancers, average in brain, esophageal and colorectal cancers, and poor in head and neck, thyroid, gastric and malignant melanoma tumors. Subgroup analysis indicated that positron emission tomography (PET) or PET/CT imaging technology or Ki-67 and standardized uptake value (SUV) measurement technology did not significantly affect the results of r values, and Begg's test showed no significant publication bias.ConclusionIn cancer patients, 18F-FDG uptake showed a moderate positive correlation with tumor cell proliferation. Different tumor types exhibited varied degree of correlation, and the correlation was significant in TETs and GSTs. However, our results need further validation by clinical trials with a large sample of different tumor types.

SU‐E‐J‐258: Prediction of Cervical Cancer Treatment Response Using Radiomics Features Based On F18‐FDG Uptake in PET Images

Purpose:Radiomics have shown potential for predicting treatment outcomes in several body sites. This study investigated the correlation between PET Radiomics features and treatment response of cervical cancer outcomes.Methods:our dataset consisted of a cohort of 79 patients diagnosed with cervical cancer, FIGO stage IB‐IVA, age range 25–86 years, (median age at diagnosis: 50 years) all treated between: 2009–14 with external beam radiation therapy to a dose range between: 45–50.4 Gy (median= 45 Gy), concurrent cisplatin chemotherapy and MRI‐based brachytherapy to a dose of 20–30 Gy (median= 28 Gy). Metabolic Tumor Volume (MTV) in patient's primary site was delineated on pretreatment PET/CT by two board certified Radiation Oncologists. The features extracted from each patient's volume were: 26 Co‐occurrence matrix (COM) Feature, 11 Run‐Length Matrix (RLM), 11 Gray Level Size Zone Matrix (GLSZM) and 33 Intensity‐based features (IBF). The treatment outcome was divided based on the last follow up status into three classes: No Evidence of Disease (NED), Alive with Disease (AWD) and Dead of Disease (DOD). The ability for the radiomics features to differentiate between the 3 treatments outcome categories were assessed by One‐Way ANOVA test with p‐value &lt; 0.05 was to be statistically significant. The results from the analysis were compared with the ones obtained previously for standard Uptake Value (SUV).Results:Based on patients last clinical follow‐up; 52 showed NED, 17 AWD and 10 DOD. Radiomics Features were able to classify the patients based on their treatment response. A parallel analysis was done for SUV measurements for comparison.Conclusion:Radiomics features were able to differentiate between the three different classes of treatment outcomes. However, most of the features were only able to differentiate between NED and DOD class. Also, The ability or radiomics features to differentiate types of response were more significant than SUV.

Characterization of PET image using global and local entropy

In the clinical practice PET imaging provides semi-quantitative information about metabolic activities in human body, using the Standardized Uptake Value (SUV). The SUV scale, by itself, does not to establish thresholds between benign and malignant uptake in high-level analyses, such as pattern recognition. The objective of this work is to investigate in PET image volume with high-uptake regions, two additional descriptors, besides the SUV measurements: the amount of information given by the Hartley function ( I Hartley ) and its expected value, the Shannon entropy ( H ). To estimate these descriptors, two models of the probability distribution were obtained from a high-uptake region of interest (ROI): (i) the normalized grayscale histogram from SUV intensity levels ( P i ), which provides global I HG and H G ; and (ii) the normalized gray level co-occurrence matrix (GLCM) of these graylevels ( P g,k ) at the same range, which provides local I HL and H L . The beginning results have shown that for the ROI (12x12 pixels) and for mean SUV ranging of 6.6213±0. 5196 g/ml, with SUV Max = 14,7372 g/ml, the global entropy (2,3778±0,0364) has a higher average uncertainty that local entropy (2,2069±0,0758), with a confidence interval of 99.95% (p value < 0,05%). This can be explained by analysing the sample from the amount of information, I Hartley , noting that on average local P g,k provides up to 90,55±9,18% more information when compared to the amount of information given by global P i. Therefore, these initial results suggest that, for build algorithms for PET image segmentations using threshold based in entropy measures, it is more appropriate to use a distribution functions estimator which considers the local information of the pixels intensities. The main application of this approach will be for, among other things, to construct pathological phantoms from PET images for dosimetry applications.