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Background Prognostic modeling in health care has been predominantly statistical, despite a rapid growth of literature on machine-learning approaches in biological data analysis. We aim to assess the relative importance of variables in predicting overall survival among patients with non-small cell lung cancer using a Variable Importance (VIMP) approach in a machine-learning Random Survival Forest (RSF) model for posttreatment planning and follow-up. Methods A total of 935 non-small cell lung cancer patients were randomly and equally divided into 2 training and testing cohorts in an RFS model. The prognostic variables included age, sex, race, the TNM Classification of Malignant Tumors (TNM) stage, smoking history, Eastern Cooperative Oncology Group performance status, histologic type, treatment category, maximum standard uptake value of whole-body tumor (SUVmaxWB), whole-body metabolic tumor volume (MTVwb), and Charlson Comorbidity Index. The VIMP was calculated using a permutation method in the RSF model. We further compared the VIMP of the RSF model to that of the standard Cox survival model. We examined the order of VIMP with the differential functional forms of the variables. Results In both the RSF and the standard Cox models, the most important variables are treatment category, TNM stage, and MTVwb. The order of VIMP is more robust in RSF model than in Cox model regarding the differential functional forms of the variables. Conclusions The RSF VIMP approach can be applied alongside with the Cox model to further advance the understanding of the roles of prognostic factors, and improve prognostic precision and care efficiency.

T-cell/histiocyte-rich large B-cell lymphoma (TCRLBCL) is an aggressive variant of diffuse large B-cell lymphoma (DLBCL) characterized by rare malignant B cells within a robust but ineffective immune cell infiltrate. The mechanistic basis of immune escape in TCRLBCL is poorly defined and not targeted therapeutically. We performed a genetic and quantitative spatial analysis of the PD-1/PD-L1 pathway in a multi-institutional cohort of TCRLBCLs and found that malignant B cells harbored PD-L1/PD-L2 copy gain or amplification in 64% of cases, which was associated with increased PD-L1 expression (P = .0111). By directed and unsupervised spatial analyses of multiparametric cell phenotypic data within the tumor microenvironment, we found that TCRLBCL is characterized by tumor-immune "neighborhoods" in which malignant B cells are surrounded by exceptionally high numbers of PD-L1-expressing TAMs and PD-1+ T cells. Furthermore, unbiased clustering of spatially resolved immune signatures distinguished TCRLBCL from related subtypes of B-cell lymphoma, including classic Hodgkin lymphoma (cHL) and DLBCL-NOS. Finally, we observed clinical responses to PD-1 blockade in 3 of 5 patients with relapsed/refractory TCRLBCL who were enrolled in clinical trials for refractory hematologic malignancies (NCT03316573; NCT01953692), including 2 complete responses and 1 partial response. Taken together, these data implicate PD-1 signaling as an immune escape pathway in TCRLBCL and also support the potential utility of spatially resolved immune signatures to aid the diagnostic classification and immunotherapeutic prioritization of diverse tumor types.

PURPOSE: We hypothesized that whole-body metabolic tumor volume (MTVwb) could be used to supplement non-small cell lung cancer (NSCLC) staging due to its independent prognostic value. The goal of this study was to develop and validate a novel MTVwb risk stratification system to supplement NSCLC staging. METHODS: We performed an IRB-approved retrospective review of 935 patients with NSCLC and FDG avid tumor divided into modeling and validation cohorts based on the PET/CT scanner type used for imaging. In addition, sensitivity analysis was conducted by dividing the patient population into two randomized cohorts. Cox regression and Kaplan-Meier survival analyses were performed to determine the prognostic value of the MTVwb risk stratification system. RESULTS: The cutoff values (10.0, 53.4 and 155.0 mL) between the MTVwb quartiles of the modeling cohort were applied to both modeling and validation cohorts to determine each patient’s MTVwb risk stratum. The survival analyses showed that a lower MTVwb risk stratum was associated with better overall survival (all p

Stage IIIA non-small cell lung cancer (NSCLC) is heterogeneous in tumor burden, and its treatment is variable. Whole-body metabolic tumor volume (MTVWB) has been shown to be an independent prognostic index for overall survival (OS). However, the potential of MTVWB to risk-stratify stage IIIA NSCLC has previously been unknown. If we can identify subgroups within the stage exhibiting significant OS differences using MTVWB, MTVWB may lead to adjustments in patients’ risk profile evaluations and may, therefore, influence clinical decision making regarding treatment. We estimated the risk-stratifying capacity of MTVWB in stage IIIA by comparing OS of stratified stage IIIA with stage IIB and IIIB NSCLC. We performed a retrospective review of 330 patients with clinical stage IIB, IIIA, and IIIB NSCLC diagnosed between 2004 and 2014. The patients’ clinical TNM stage, initial MTVWB, and long-term survival data were collected. Patients with TNM stage IIIA disease were stratified by MTVWB. The optimal MTVWB cutoff value for stage IIIA patients was calculated using sequential log-rank tests. Univariate and multivariate cox regression analyses and Kaplan-Meier OS analysis with log-rank tests were performed. The optimal MTVWB cut-point was 29.2 mL for the risk-stratification of stage IIIA. We identified statistically significant differences in OS between stage IIB and IIIA patients (p

The staging and management of patients with newly diagnosed nonsmall cell lung cancer (NSCLC) in the setting of recently diagnosed other (metachronous or synchronous) primary cancer are challenging. This retrospective cohort study was carried out to test our hypothesis that baseline 2-deoxy-2-[F]fluoro-D-glucose (F-FDG) PET/CT parameters, including whole-body metabolic tumor volume (MTVWB), total lesion glycolysis (TLGWB), and maximum standardized uptake value (SUVmaxWB), are associated with the overall survival (OS) of such patients.A total of 110 NSCLC patients (52 men and 58 women, aged 68.6±7.8 years) with other primary malignant cancers who had baseline F-FDG PET/CT scans were retrospectively reviewed. MTVWB, TLGWB, and SUVmaxWB were measured. Kaplan-Meier analysis with the log-rank test and Cox regression models were used to assess the association of OS with F-FDG PET/CT parameters and clinical risk factors.Kaplan-Meier analysis and univariate Cox regression models showed significant associations of OS with ln(MTVWB), ln(TLGWB), ln(SUVmaxWB), TNM stage, and treatment type (surgery vs. no treatment). Multivariable Cox regression models showed a significant relationship of OS with ln(MTVWB) [hazard ratio (HR)=1.368, P=0.001], ln(TLGWB) (HR=1.313, P0.001), and ln(SUVmaxWB) (HR=1.739, P=0.006), adjusted for age, treatment type, tumor histology, and TNM stage. The TNM stage was not associated significantly with OS when MTVWB, TLGWB, or SUVmaxWB were included in the multivariable models.MTVWB, TLGWB, and SUVmaxWB from baseline F-FDG PET/CT are associated individually with OS of patients with both NSCLC and other primary malignant tumors independent of age, treatment type, tumor histology, and TNM stage.

As real-time and immediate feedback becomes increasingly important in tasks related to mobile information, big data stream processing systems are increasingly applied to process massive amounts of mobile data. However, when processing a drastically fluctuating mobile data stream, the lack of an elastic resource-scheduling strategy limits the elasticity and scalability of data stream processing systems. To address this problem, this paper builds a flow-network model, a resource allocation model, and a data redistribution model as the foundation for proposing Flink with an elastic resource-scheduling strategy (Flink-ER), which consists of a capacity detection algorithm, an elastic resource reallocation algorithm, and a data redistribution algorithm. The strategy improves the performance of the platform by dynamically rescaling the cluster and increasing the parallelism of operators based on the processing load. The experimental results show that the throughput of a cluster was promoted under the premise of meeting latency constraints, which verifies the efficiency of the strategy.

e21085 Background: The aim of this study is to model and validate a post-treatment PET/CT volumetric prognostic (ptPVP) index for risk assessment after definitive therapy for NSCLC. Methods: This IRB-approved retrospective cohort study included 1028 NSCLC patients diagnosed between 2004 and 2017. Variables included: pre-treatment whole-body metabolic tumor volume (MTVwb) measured on baseline FDG PET/CT, patient age, clinical TNM stage, ECOG performance status (PS), gender, tumor histology, treatment type, and survival outcomes. Patients were assigned to a modeling cohort (531 patients) for modeling ptPVP index and a clinical index with a multivariate Cox regression model. The ptPVP index was validated with a separate validation cohort (497 patients) by comparing the prognostic value of ptPVP index against its individual independent variables and the clinical index. Results: The ptPVP index generated from the modeling cohort was comprised of 5 variables including treatment type (surgery, no surgery, and no therapy), age, clinical TNM stage (stage I or II, III, and IV), PS ( 0, 1, and ≥ 2) and MTVwb. The clinical index was comprised of above 4 clinical variables without MTVwb. Univariate Cox models showed significant association of the ptPVP index with OS with Hazard ratio (HR) of 2.72 (95% CI = 2.39-3.09, p < 0.001). The C-statistic of ptPVP index (0.71) was significantly greater than that of clinical index (0.68) (p = 0.001). In the validation cohort, univariate Cox models showed significant association of the ptPVP index with OS (HR = 3.09, 95% CI = 2.64-3.61, p < 0.001). The ptPVP index showed greater prognostic power (C-statistic = 0.72) than that of the clinical index (C-statistic = 0.70, p = 0.001), treatment type (C-statistic = 0.66, p < 0.001), MTVwb (C-statistic = 0.67, p < 0.001), age (C-statistic = 0.58, p < 0.001), clinical 9-group TNM staging (C-statistic = 0.66, p < 0.001), and PS (C-statistic = 0.57, p < 0.001). Multivariate Cox regression analysis demonstrated a significant association of ptPVP index with OS (HR = 3.06, 95% CI of 2.60-3.61, p < 0.001) after adjusting gender and NSCLC histology. A better separation of Kaplan-Meier curves of patients grouped by ptPVP index than those grouped by clinical index, MTVwb, or clinical TNM stage was evident. Conclusions: The ptPVP index developed for NSCLC patients demonstrated moderately prognostic power and better prognostic ability than its individual independent variables and clinical index without MTVwb. It provides a practical quantitative risk assessment for the patient follow-up and management after initial treatment.

Objectives Whole-body metabolic tumor volume (MTVWB) and TNM staging are independent prognostic factors for overall survival (OS) in non-small cell lung cancer (NSCLC). We aimed to update and validate the PET/CT volumetric prognostic index (PVP index) using the new 8th edition TNM staging system to evaluate its prognostic power versus TNM staging and MTVWB alone. Materials and Methods This study was a retrospective analysis of 949 non-small cell lung cancer (NSCLC) patients diagnosed between 2004 and 2014. Clinical TNM stage, MTVWB, age and gender, tumor histology type at the initial staging PET/CT exam, as well as treatment history and long-term survival data were obtained. Patients were randomly assigned to modeling or validation group. Univariate and multivariate Cox regression analyses were performed to compare PVP index, TNM stage, and MTVWB in the validation group. Results The updated PVP index included the 3 variables TNM stage, and MTVWB and age. Univariate Cox models showed significant association of PVP index with overall survival (OS) in patients with NSCLC (with Hazard ratio HR = 2.88 in the validation group, p Conclusions The updated PVP index provides a quantitative risk assessment for NSCLC patients using 8th edition TNM staging, MTVWB, and age. The index provides a simple and practical way for the care team to incorporate the independent prognostic value of both the TNM stage and MTVWB. This approach can further improve the accuracy of overall survival prognosis.

To test the hypothesis that whole-body metabolic tumor burden (MTBWB) on postsurgical fluorodeoxyglucose (FDG) positron emission tomographic (PET)/computed tomographic (CT) images in patients with non-small cell lung cancer (NSCLC) is associated with their overall survival (OS).The institutional review board approved this study and waived the requirement for obtaining informed consent. One hundred forty-two patients with NSCLC (69 men, 73 women; median age, 67.7 years) who underwent postsurgical FDG PET/CT were retrospectively reviewed. The whole-body metabolic tumor volume (MTVWB), whole-body total lesion glycolysis (TLGWB), and whole-body maximum standardized uptake value (SUVWBmax) were measured. OS served as the primary end point of the study. Kaplan-Meier curves and Cox regression were used to assess the association between PET/CT markers and OS.The interobserver variability was low, as demonstrated with intraclass correlation coefficients higher than 0.94 for SUVWBmax, MTVWB, and TLGWB. When compared with those with negative postsurgical FDG PET/CT findings, a significant decrease of OS was found in patients with the presence of FDG-avid tumor on the basis of both a log-rank test (P = .001) and a univariate Cox model (hazard ratio = 2.805, P = .001). In patients with FDG-avid tumor, there was a significant association between OS and ln MTVWB (P.001), ln TLGWB (P.001), and ln SUVWBmax (P.010) in either univariate or multivariate analysis, after adjusting for patient age, sex, TNM restage, and therapy after postsurgical PET/CT studies. The OS differences between the groups dichotomized by the median value of MTVWB (11.54 mL, P = .004), TLGWB (32.38 mL, P.001), or SUVWBmax (4.93, P = .023) were significant.MTBWB and tumor maximum standardized uptake at postsurgical FDG PET/CT are related to the patient's OS in NSCLC, independent of age, sex, TNM restaging, and therapy after postsurgical PET/CT studies.

Cerebral vasospasm (CVS) is a severe complication that occurs following aneurysmal subarachnoid hemorrhage (SAH). Magnetic resonance angiography (MRA) has been used to evaluate brain injury following SAH in humans. The present study was designed to assess a rabbit model of symptomatic CVS (SCVS) and the utility of MRA in evaluating SCVS in rabbits. Japanese white rabbits (n=24) were randomly divided into 2 equal groups: A sham group and a SAH group. Neurological scores were evaluated for 7 days following SAH. Basilar artery (BA) diameters were measured using MRA preoperatively and 7 days postoperatively. Rabbits were sacrificed 7 days following SAH and the BA diameter of each rabbit was determined using histological evaluation. Compared with the Sham group, neurological function was significantly reduced in the SAH group at all time points (P

Purpose TNM Stage 3B encompasses a wide range of primary tumor and nodal metastatic tumor burden. This study aimed to evaluate the prognostic value of quantitative FDG PET/CT parameters in patients with newly diagnosed Stage 3B Non-Small Cell Lung Cancer (NSCLC). Materials and Methods Institutional review board approved retrospective study identified patients diagnosed with Stage 3B NSCLC (8th edition TNM classification) on baseline FDG PET/CT at two medical centers (Medical centers A and B), between Feb 2004 and Dec 2014. Patients were excluded if they had prior NSCLC treatment or recent diagnosis of a second primary cancer. Quantitative FDG PET/CT parameters including whole body metabolic tumor volume (MTVwb), total lesion glycolysis (TLGwb), and maximum standardized uptake value (SUVmaxwb) were measured from baseline PET/CT using Edge method with Mimvista software. The primary endpoint was overall survival (OS). Cox proportional hazard regression and Kaplan-Meier overall survival analyses were used to test for an association between OS and quantitative FDG PET/CT parameters. The distributions of MTVwb, TLGwb, SUVmaxwb were skewed, so a natural logarithm transformation was applied and the transformed variables [(ln(MTVwb), ln(TLGwb), and ln(SUVmaxwb)] were used in the analysis. Results The training set included 110 patients from center A with Stage 3B NSCLC. 78.2% of patients expired during follow-up. Median OS was 14 months. 1-year, 2-year, and 5-year OS was 56.5%, 34.6% and 13.9%, respectively. Univariate Cox regression analysis showed no significant difference in OS on the basis of age, gender, histology, ln(TLGwb), or ln(SUVmaxwb). ln(MTVwb) was positively associated with OS [hazard ratio (HR) of 1.23, p = 0.037]. This association persisted on multivariate Cox regression analysis (HR 1.28, p = 0.043), with adjustments for age, gender, treatment and tumor histology. External validation with 44 patients from center B confirmed increasing MTVwb was associated significantly worse OS. An MTVwb cut-off point of 85.6 mL significantly stratified Stage 3B NSCLC patient prognosis. Conclusion MTVwb is a prognostic marker for OS in patients with Stage 3B NSCLC, independent of age, gender, treatment, and tumor histology.

Background The purpose of this study is to describe the preliminary findings of 99mTc-labeled ethylene dicysteine deoxyglucose (99mTc-EC-DG) performed four weeks after chemoradiotherapy in patients with locally advanced head and neck squamous cell carcinoma. Methods Review of nine patients with locally advanced head and neck squamous cell carcinomas imaged with 99mTc-EC-DG single photon emission computed tomography-computed tomography (SPECT-CT) at baseline before treatment and at four weeks after treatment completion was performed. Results At four weeks post-treatment, five patients had either decreased activity or no significant activity on 99mTc-EC-DG SPECT-CT and were considered to have responded to treatment, whereas four patients did not have significantly decreased uptake on 99mTc-EC-DG SPECT-CT and were considered to have not adequately responded to treatment. Among the five patients considered to have treatment response at four weeks, all were free of disease (true-negative). Among the four patients considered to have stable activity on 99mTc-EC-DG SPECT-CT at four weeks, two were designated as having no response or incomplete response (true-positive), and two were designated as having complete response (false-positive) on subsequent composite assessment. Conclusions The pilot data is promising but warrants further investigation of 99mTc-EC-DG SPECT-CT for the assessment of locoregional treatment response at four weeks in patients with locally advanced head and neck squamous cell carcinomas.

Background No study to test the feasibility and prognostic value of the number of primary tumors, the number of positive lymph nodes, and the total number of tumors in the whole body as tumor burden measurements on FDG PET/CT imaging has been reported. Purpose To determine whether the number of tumors seen in 18F-FDG PET scans can be a prognostic factor in non-surgical patients with non-small cell lung cancer (NSCLC). Material and Methods One hundred and forty patients with histologically proven NSCLC and baseline 18F-FDG PET scan before therapy were identified in this retrospective analysis. The total number of tumors (TTn) in the whole body, the number of primary tumors (Tn), positive lymph nodes (Nn), and distant metastases (Mn), along with the maximum standardized uptake values (SUVmax) of the tumors were measured. Inter-observer variability of the total number of tumors, counted by two radiologists, was assessed. Survival analyses were performed to determine the prognostic value of the number of tumors. Results Concordance correlation coefficients for the TTn, Tn, Nn, and Mn were all greater than 0.85. TTn and Nn were strong prognostic factors of NSCLC patients' overall survival (OS). In univariate Cox regression models, gender, stage, TTn, Nn, and Mn were statistically significant factors ( P = 0.016, 0.032, , respectively, after adjusting for clinical stage based 7th edition of TNM staging system, age, gender, and SUVmax. Patients with a TTn ≤4 (cutpoint based on median value) had a median OS of 15.2 months compared with 9.0 months for those with TTn >4. Conclusion Measuring the number of tumors on FDG PET imaging is easy to perform with minimal inter-observer variability. The total number of tumors and number of nodal metastases, as metabolic tumor burden measurements in 18F-FDG PET/CT, are prognostic markers independent of clinical stage, age, gender, and SUV measurement in non-surgical patients with NSCLC.

Objective To determine the accuracy of nonattenuation corrected (NAC) 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) images in the evaluation of solitary pulmonary lesion as compared with more established methods. Methods Fifty-six patients received 18F-FDG PET/CT for diagnosing solitary pulmonary nodules or mass lesions based on histopathology (n=39) and clinical follow-up (n=17). Visual pulmonary lesion FDG uptake was graded by consensus of two nuclear medicine physicians on both attenuation corrected (AC) [absent, less than mediastinal blood pool (MBP), equal to MBP, greater than MBP] and NAC (absent, less than skin, equal to skin, greater than skin) images. Standardized uptake values (SUV) were also measured from AC images. SUV, visual AC, and visual NAC methods' diagnostic performances were compared, distinguishing benign from malignant pulmonary nodules. Results There were 34 malignant and 22 benign lesions. Lesion diameter varied from 5 to 100 mm (mean±SD, 24.0±17.9 mm). The NAC, AC, and SUV method sensitivities and specificities were 100/64%, 91/59%, and 79/77%, respectively. For lesions less than 3 cm, NAC, AC, and SUV methods yielded accuracies of 85%, 78%, and 73%, respectively. The NAC method was the most sensitive and accurate especially for small nodules. Conclusion Visual assessment of NAC 18F-FDG PET images alone may provide a more accurate characterization of solitary pulmonary lesions.

In order to aid radiologists’ routine work for interpreting bone scan images, we developed a computerized method for temporal subtraction (TS) images which can highlight interval changes between successive whole-body bone scans, and we performed a prospective clinical study for evaluating the clinical utility of the TS images. We developed a TS image server which includes an automated image-retrieval system, an automated image-conversion system, an automated TS image-producing system, a computer interface for displaying and evaluating TS images with five subjective scales, and an automated data-archiving system. In this study, the radiologist could revise his/her report after reviewing the TS images if the findings on the TS image were confirmed retrospectively on our clinical picture archiving and communication system. We had 256 consenting patients of whom 143 had two or more whole-body bone scans available for TS images. In total, we obtained TS images successfully in 292 (96.1%) pairs and failed to produce TS images in 12 pairs. Among the 292 TS studies used for diagnosis, TS images were considered as “extremely beneficial” or “somewhat beneficial” in 247 (84.6%) pairs, as “no utility” in 44 pairs, and as “somewhat detrimental” in only one pair. There was no TS image for any pairs that was considered “extremely detrimental.” In addition, the radiologists changed their initial reported impression in 18 pairs (6.2%). The benefit to the radiologist of using TS images in the routine interpretation of successive whole-body bone scans was significant, with negligible detrimental effects.

e21164Background: Comorbidities reflect patients’ underlying multiple-disease growth curve and influence outcomes of treatment. However, it is unclear if there is and how much independent prognosti...

e21118Background: It is unclear how comorbidities are associated with the stage of non-small cell lung cancer (NSCLC) at cancer diagnosis. We aimed to evaluate the association between Charlson Como...

OBJECTIVES The objective of this study was to test the hypothesis that the metabolic tumor volume (MTV) of primary non-small-cell lung cancer is not sensitive to differences in F-fluorodeoxyglucose (F-FDG) uptake time, and to compare this consistency of MTV measurements with that of standardized uptake value (SUV) and total lesion glycolysis (TLG). METHODS Under Institutional Review Board approval, 134 consecutive patients with histologically proven non-small-cell lung cancer underwent F-FDG PET/computed tomography scanning at about 1 h (early) and 2 h (delayed) after intravenous injection of F-FDG. MTV, SUV, and TLG of the primary tumor were all measured. Student's t-test and Wilcoxon's signed-rank test for paired data were used to compare MTV, SUV, and TLG between the two scans. The intraclass correlation coefficient (ICC) was used to assess agreement in PET parameters between the two scans and between the measurements made by two observers. RESULTS MTV was not significantly different (P=0.17) between the two scans. However, SUVmax, SUVmean, SUVpeak, and TLG increased significantly from the early to the delayed scans (P

Rationale and Objectives We evaluated the usefulness of temporal subtraction images obtained from two successive whole-body bone scans, in terms of improvement in radiologists’ diagnostic accuracy in detecting interval changes and of a reduction in reading time, by use of a jackknife free-response receiver operating characteristic (JAFROC) analysis method. Materials and Methods Twenty pairs of successive whole-body bone scans (72 consented interval changes) and their temporal subtraction images were used for an observer performance study. Our institutional review board approved the use of this database and the participation of radiologists in this study. In the first session of the observer study, without temporal subtraction images, the previous and current images were shown to five radiologists independently for their marking of the locations on current images and confidence ratings on potential interval changes from previous images. In the second session, temporal subtraction images were shown together with the modified previous and current images. JAFROC analysis was used for assessing the statistical significance of differences between radiologists’ performance without and with temporal subtraction images. Results The average sensitivity for detecting interval changes was improved from 58.6% to 73.2% at a false-positive rate of two per case by use of temporal subtraction images, and the difference was statistically significant by use of JAFROC analysis ( P = .035). In addition, the mean reading time per case was reduced considerably from 134 seconds to 91 seconds ( P Conclusions Temporal subtraction imaging for successive whole-body bone scans has the potential greatly to assist radiologists by increasing both their accuracy and productivity.

Patients 90% overall survival following treatment with chemotherapy and surgery. We report two infants with favorable biology, stage 4 neuroblastoma with refractory disease after standard intermediate-risk chemotherapy and additional retrieval chemotherapy. One patient was treated with six additional cycles of isotretinoin and the other observed. Both remain clinically well with persistent disease but no evidence of tumor progression for 28 and 13 months following completion of cytotoxic treatment. Similar to residual tumor in primary sites, refractory metastatic disease may not portend a poor outcome in patients with favorable biology, intermediate-risk neuroblastoma.

Whole-body metabolic tumor volume (MTVWB) has been shown of prognostic value for non-small cell lung cancer (NSCLC) beyond that of TNM stage, age, gender, performance status, and treatment selection. The current TNM staging system does not incorporate tumor volumetric information. We propose a new PET/CT volumetric prognostic (PVP) index that combines the prognostic value of MTVWB and TNM stage.Based on 328 consecutive NSCLC patients with a baseline PET/CT scan before treatment, from which MTVWB was measured semi-automatically, we estimated hazard ratios (HRs) for ln(MTVWB) and TNM stage from a Cox proportional hazard regression model that consisted of only ln(MTVWB) and TNM stage as prognostic variables of overall survival. We used the regression coefficients, which gave rise to the HRs, as weights to formulate the PET/CT volumetric prognostic (PVP) index. We also compared the prognostic value of the PVP index against that of TNM stage alone and ln(MTVWB) alone with univariate and multivariate survival analyses and C-statistics.Univariate analysis C-statistic for the PVP index (C=0.71) was statistically significantly greater than those for TNM stage alone (C=0.67, p0.01) and for ln(MTVWB) alone (C=0.69, p=0.033). Multivariate analyses showed that the PVP index yielded significantly greater discriminatory power (C=0.74) than similar models based on either TNM stage (C=0.72, p0.01) or ln(MTVWB) (C=0.73, p0.01). Lower values of the PVP index were associated with significantly better overall survival (adjusted HR=2.70, 95%CI [2.16, 3.37]).The PVP index provides a practical means for clinicians to combine the prognostic value of MTVWB and TNM stage and offers significantly better prognostic accuracy for overall survival of NSCLC patients than the current TNM staging system or metabolic tumor burden alone.

Event-related functional MRI (ER-fMRI) based on both blood oxygen level-dependent (BOLD) contrast and perfusion contrast has been recently developed to study human brain activation due to brief stimulation. In this report, both BOLD- and perfusion-based ER-fMRI were directly compared using repeated single-trial, short visual stimulation (1 sec) in six human volunteers. The results show that the cerebral blood flow change reached a maximum approximately 1 sec earlier than the BOLD signal change (4.2 ± 0.2 sec vs. 5.1 ± 0.2 sec after the stimulation, P < 0.05). The full width at half maximum of the hemodynamic response measured by perfusion was not significantly different from that measured with BOLD (5.1 ± 0.6 sec vs. 5.9 ± 0.6 sec). A positive linear correlation was found between the maximum perfusion and maximum BOLD signal changes (r = 0.77, P = 0.07). Magn Reson Med 43:768–772, 2000. © 2000 Wiley-Liss, Inc.

Singular value decomposition (SVD) is a promising deconvolution technique for use in dynamic contrast agent magnetic resonance perfusion imaging. Computer simulations, however, show that the selection of the threshold for SVD affects the accuracy of the cerebral blood flow measurements and may distort the shape of the vascular residue function. In this report, a pixel-by-pixel thresholding method is proposed based on the signal-to-noise ratio of the concentration time curve at maximum concentration (SNRC). Monte Carlo simulations were used to determine the optimal threshold for different SNRC. This technique was used to analyze data from six healthy volunteers, resulting in a mean gray to white matter cerebral blood flow ratio of 2.67 +/- 0.07. This value is in excellent agreement with values published in the literature.

A double-echo magnetic resonance (MR) phase imaging method was used to measure the time-dependent changes in regional cerebral venous blood oxygenation during neural stimulation. Our results showed that a finger opposition task induced an absolute increase of blood oxygenation level of DY 5 0.16 6 0.05 (n 5 6), which was measured in the small veins located in the left central sulcus. It was observed that there is a long temporal delay of approximately 27 sec after the onset of the task to reach the steady-state venous oxygenation. This work demonstrated that MRI is a powerful clinical tool for in vivo monitoring of the dynamic nature of organ-specific venous blood oxygenation. Magn Reson Med 41:407‐411, 1999.

8548Background: We developed a PET/CT volumetric prognostic staging system (PVP index) using risk-based models integrating hazard of death from both whole-body metabolic tumor volume (MTVWB ) and T...

Background Radiolabeled metaiodobenzylguanidine (MIBG) is sensitive and specific for detecting neuroblastoma. The extent of MIBG-avid disease is assessed using Curie scores. Although Curie scoring is prognostic in patients with high-risk neuroblastoma, there is no standardized method to assess the response of specific sites of disease over time. The goal of this study was to develop approaches for Curie scoring to facilitate the calculation of scores and comparison of specific sites on serial scans. Procedure We designed three semiautomated methods for determining Curie scores, each with increasing degrees of computer assistance. Method A was based on visual assessment and tallying of MIBG-avid lesions. For method B, scores were tabulated from a schematic that associated anatomic regions to MIBG-positive lesions. For method C, an anatomic mesh was used to mark MIBG-positive lesions with automatic assignment and tallying of scores. Five imaging physicians experienced in MIBG interpretation scored 38 scans using each method, and the feasibility and utility of the methods were assessed using surveys. Results There was good reliability between methods and observers. The user-interface methods required 57 to 110 seconds longer than the visual method. Imaging physicians indicated that it was useful that methods B and C enabled tracking of lesions. Imaging physicians preferred method B to method C because of its efficiency. Conclusions We demonstrate the feasibility of semiautomated approaches for Curie score calculation. Although more time was needed for strategies B and C, the ability to track and document individual MIBG-positive lesions over time is a strength of these methods.

8516Background: We previously developed a PET/CT volumetric prognostic staging system (PVP index) using Cox regression models to predict the hazard of death using both whole-body metabolic tumor vo...

To determine whether whole-body metabolic tumor burden, measured as either metabolic tumor volume (MTVWB) or total lesion glycolysis (TLGWB), using FDG-PET/CT is an independent prognostic marker in non-small cell lung cancer (NSCLC).328 patients with histologically proven NSCLC were identified for this retrospective analysis. This study was approved by our Institutional Review Board. All patients underwent baseline (18)F-FDG-PET/CT scan imaging before therapy. The MTVWB, TLGWB, maximum standardized uptake value (SUVmaxWB) and mean standardized uptake value (SUVmeanWB) of tumors throughout the whole body were measured from FDG-PET images with semi-automated 3D contouring software.In univariate analysis, there was a statistically significant association of overall survival (OS) with the MTVWB (hazard ratio (HR) = 1.62, p 0.001), TLGWB (HR = 1.47, p 0.001). The patients with a MTVWB ≤ median of 65.7 ml and TLGWB ≤ median of 205.11 SUVmean * ml had a median OS of 41.1 and 35.4 months compared with 9.5 and 9.7 months for those with a MTVWB 65.7 ml and TLGWB 205.11 SUVmean * ml, respectively. From a series of multivariate Cox regression models, the MTVWB and TLGWB were significantly better than SUVmaxWB and SUVmeanWB at prognostication and significantly associated with patients' OS with HRs of 1.50 (p 0.001) and 1.42 (p 0.001), respectively, after adjustment for patient's age, gender and treatment intent as well as the tumor SUVmaxWB, histology and stage.MTVWB and TLGWB as metabolic tumor burden measurements in (18)F-FDG-PET/CT are independent prognostic markers and are significantly better than SUVmaxWB and SUVmeanWB at prognostication.

The utility of magnetic resonance imaging (MRI) in the diagnosis of acute cholecystitis was evaluated in 72 consecutive individuals (5 healthy, 13 with chronic cholecystitis and silent gallbladder stones, 43 without biliary or diffuse liver disease, and 11 with acute cholecystitis and gallbladder stones) with a 0.5-T superconducting unit. On the T1-weighted (500/20) and less T1-weighted axial spin-echo images (620/25), the liver/gallbladder signal intensity ratio (mean +/- SD) was 2.5 +/- 0.51 (n = 5) and 1.8 +/- 0.29 (n = 8) in acute cholecystitis; 0.9 +/- 0.42 (n = 6) and 1.0 +/- 0.29 (n = 9) in chronic cholecystitis; and 0.9 +/- 0.14 (n = 5) and 0.8 +/- 0.19 (n = 43) in normal gallbladder, respectively. Our results indicate that the liver/gallbladder signal intensity ratio on the T1-weighted image may be a simple and reliable indicator for the diagnosis of acute cholecystitis; we suggest further investigation to confirm these results.

To assess the prognostic value of metabolic tumor burden as measured with metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT), independent of current Union Internacional Contra la Cancrum/American Joint Committee on Cancer tumor, node, and metastasis (TNM) stage; in comparison with that of standardized uptake value (SUV) in surgical patients with non-small-cell lung cancer (NSCLC).This study retrospectively reviewed 104 consecutive surgical patients (47 males, 57 females, median age at PET/CT scan of 67.92 years) with diagnosed stage I to IV NSCLC who had baseline (18)F-FDG PET/CT scans. The (18)F-FDG PET/CT scans were performed in accordance with National Cancer Institute guidelines. The MTV of tumors in the whole body (MTV(WB)), TLG of tumors in the whole body (TLG(WB)), the maximum standardized uptake value of tumors in the whole body (SUV(maxWB)) as well as the mean standardized uptake value of tumor in the whole body (SUV(meanWB)) were measured. The median follow-up among 67 survivors was 42.07 months from the PET/CT (range 2.82-80.95 months). Statistical methods included Kaplan-Meier curves, Cox regression, and C-statistics. The interobserver variability of SUV(maxWB), SUV(meanWB), MTV(WB), and TLG(WB) between two observers was analyzed using concordance correlation coefficients (CCCs).The interobserver variability of SUV(maxWB), SUV(meanWB), MTV(WB) and TLG(WB) was very low with CCCs greater than 0.882. There was a statistically significant association of stage with overall survival (OS). The hazard ratio (HR) of stage III and stage IV as compared with stage I was 3.60 (P = .001) and 4.00 (P = .013), respectively. The MTV(WB) was significantly associated with OS with a HR for 1-unit increase of ln(MTV(WB)) of 1.40/1.32 (P = .004/.039), before/after adjusting for stage and other prognostic factors including chemoradiation therapy, and surgical procedure, respectively. TLG(WB) had a statistically significant association with OS before and after adjusting for stage and the other prognostic factors. The HR for 1-unit increase in ln(TLG(WB)) was 1.26 (P = .011) and 1.25 (P = .031), before and after the adjustment, respectively. Subjects with conditions that led to pneumonectomy (HR = 2.82, P = .035) or segmental resection (HR = 3.44, P = .044) had significantly worse survival than those needing lobectomy. There was no statistically significant association between OS and age, gender, tumor histology, ln(SUV(maxWB)), and ln(SUV(meanWB)) (all P.05). There were 37 deaths during follow-up.Baseline whole-body metabolic tumor burden as measured with MTV(WB) and TLG(WB) on FDG PET is a prognostic measure independent of clinical stage and other prognostic factors including chemoradiation therapy and surgical procedure with low interobserver variability and may be used to further risk stratify surgical patients with NSCLC. This study also suggests that MTV and TLG are better prognostic measures than SUV(max) and SUV(mean). These results will need to be validated in larger cohorts in a prospective study.

Rationale and Objectives Stage IV non–small-cell lung cancer (NSCLC) consists of a heterogeneous group of patients with different prognoses. We assessed the prognostic value of baseline whole body tumor burden as measured by metabolic tumor volume (MTV), total lesion glycolysis (TLG), and standardized uptake values (SUV max and SUV mean ) of all tumors in nonsurgical patients with Stage IV NSCLC. Materials and Methods Ninety-two consecutive patients with newly diagnosed Stage IV NSCLC who had a pretreatment F-18 fludeoxyglucose positron emission tomography/computed tomography scan were retrospectively reviewed. The MTV, TLG, SUV mean , and SUV max of whole-body (WB) tumors were measured with the MIMvista workstation with manual adjustment. Results There was a statistically significant association between overall survival (OS) and ln(MTV)/ln(TLG) at the level of WB tumor burden (MTV WB ) and of primary tumor (MTV T ). The hazard ratio (HR) for a 1-unit increase of ln(MTV WB ) and ln(MTV T ) before and after adjusting for age and gender was 1.48/1.48 (both P P = .006, .007), respectively. The HR for a 1-unit increase of ln(TLG WB ) and ln(TLG T ) before and after adjusting for age and gender was 1.37/1.37 (both P = .001) and 1.19/1.19 ( P = .001, .017), respectively. There was no statistically significant association between OS and ln(SUV max ) and ln(SUV mean ) at WB tumor burden, primary tumor, nodal metastasis, or distant metastasis ( P > .05). There was low interobserver variability between two radiologists with concordance correlation coefficients of 0.90 for ln(MTV WB ) and greater than 0.90 for SUV maxWB , SUV meanWB , and ln(TLG WB ). Conclusion Baseline WB metabolic tumor burden, as measured with MTV and TLG, is a prognostic measurement in patients within Stage IV NSCLC with low interobserver variability. This study also suggests pretreatment MTV and TLG measurements may be used to further stratify patients with Stage IV NSCLC and are better prognostic measures than SUV max and SUV mean measurements.

Six patients with hepatic laceration underwent magnetic resonance imaging (MRI) at 0.5T. Acute hepatic laceration was slightly hypointense on T1-weighted spin-echo (SE) image, and hyperintense on T2- and proton-weighted SE images. Subacute laceration was heterogeneously intense on T1-weighted image and hyperintense on T2- and proton-weighted images. Consistent changes in signal intensity of postoperative hepatic laceration were observed. On T1-weighted image, the signal intensity at first increased and then decreased from periphery to the center. On the T2- and proton-weighted images, the laceration was uniformly hyperintense relative to the liver prior to the appearance and growth of a hypointense ring at its periphery. The appearance of the above changes in signal intensity was also observed in postoperative recurrent hemorrhage. The postoperative biloma had none of the above changes in signal intensity. Our cases show that MRI is effective in the evaluation of hepatic laceration and in the assessment of the course of healing after operation.

Background:18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET) imaging has been shown to be an accurate method for diagnosing pulmonary lesions, and the standardized uptake value (SUV) has been shown to be useful in differentiating benign from malignant lesions. Purpose: To survey the interobserver variability of SUVmax and SUVmean measurements on 18F-FDG PET/CT scans and compare them with tumor size measurements on diagnostic CT scans in the same group of patients with focal pulmonary lesions. Material and Methods: Forty-three pulmonary nodules were measured on both 18F-FDG PET/CT and diagnostic chest CT examinations. Four independent readers measured the SUVmax and SUVmean of the 18F-FDG PET images, and the unidimensional nodule size of the diagnostic CT scans (UDCT) in all nodules. The region of interest (ROI) for the SUV measurements was drawn manually around each tumor on all consecutive slices that contained the nodule. The interobserver reliability and variability, represented by the intraclass correlation coefficient (ICC) and coefficient of variation (COV), respectively, were compared among the three parameters. The correlation between the SUVmax and SUVmean was also analyzed. Results: There was 100% agreement in the SUVmax measurements among the 4 readers in the 43 pulmonary tumors. The ICCs for the SUVmax, SUVmean, and UDCT by the four readers were 1.00, 0.97, and 0.97, respectively. The root-mean-square values of the COVs for the SUVmax, SUVmean, and UDCT by the four readers were 0%, 13.56%, and 11.03%, respectively. There was a high correlation observed between the SUVmax and SUVmean (Pearson's r=0.958; P Conclusion: This study has shown that the SUVmax of lung nodules can be calculated without any interobserver variation. These findings indicate that SUVmax is a more valuable parameter than the SUVmean or UDCT for the evaluation of therapeutic effects of chemotherapy or radiation therapy on serial studies.

The authors report the fluorodeoxyglucose (FDG)-positron emission tomography(PET)/computed tomography (CT) findings of a rare case of growth hormone-secreting pituitary carcinoma with multiple metastatic lesions to the skeleton. A 31-year-old male had presented with acromegaly and had received transsphenoidal resection of a pituitary tumor and adjuvant radiotherapy. However, the tumor recurred with local invasions and the patient underwent more resections and adjuvant chemotherapy. Several months later, the patient developed rising levels of insulin-like growth factor 1 and whole-body FDG-PET/CT scanning revealed multiple hypermetabolic lesions throughout the skeleton compatible with metastasis.

BACKGROUND AND PURPOSE: Although the prevalence of pineal cysts in autopsy series has been reported as being between 25% and 40%, MR studies have documented their frequency to range between 1.5% and 10.8%. The purpose of this high-resolution brain MR imaging study at 1.9T was to determine the prevalence of pineal cysts in healthy adults. MATERIALS AND METHODS: Brain MR images of 100 healthy young volunteers were randomly selected from our International Consortium for Brain Mapping project data base. Cysts were detected as circular areas of isointensity relative to CSF on both 3D gradient-echo T1-weighted and 2D fast spin-echo T2-weighted images. The inner diameters of all visualized pineal cysts were measured, and a criterion of 2.0 mm of the largest inner cross-sectional diameter was used to categorize cysts as being either small cystic changes (2.0-mm diameter). RESULTS: Twenty-three percent (23/100) of the volunteers had pineal cysts with a mean largest inner cross-sectional diameter of 4.3 mm (range, 2–14 mm); 13% (13/100) demonstrated cystic changes involving the pineal gland with the largest inner cross-sectional diameter of less than 2.0 mm. There was a slight female predominance. Two subjects with long-term follow-up scans showed no symptoms or changes in the size of their pineal cysts. CONCLUSION: On high-resolution MR imaging, the prevalence of pineal cysts was 23% in our healthy group of adults, which is consistent with previous autopsy studies. Long-term follow-up studies of 2 cases demonstrated the stability of the cysts.

We developed a computer-aided diagnostic (CAD) scheme for assisting radiologists in the detection of asymmetric abnormalities on a single whole-body bone scintigram by applying a contralateral subtraction (CS) technique. Twenty whole-body bone scans including 107 abnormal lesions in anterior and/or posterior images (the number of lesions per case ranged from 1 to 16, mean 5.4) were used in this study. In our scheme, the original bone scan image was flipped horizontally to provide a mirror image. The mirror image was first rotated and shifted globally to match the original image approximately, and then was nonlinearly warped by use of an elastic matching technique in order to match the original image accurately. We applied a nonlinear lookup table to convert the difference in pixel values between the original and the warped images to new pixel values for a CS image, in order to enhance dark shadows at the locations of abnormal lesions where uptake of radioisotope was asymmetrically high, and to suppress light shadows of the lesions on the contralateral side. In addition, we applied a CAD scheme for the detection of asymmetric abnormalities by use of rule-based tests and sequential application of artificial neural networks with 25 image features extracted from the original and CS images. The performance of the CAD scheme, which was evaluated by a leave-one-case-out method, indicated an average sensitivity of 80.4 % with 3.8 false positives per case. This CAD scheme with the contralateral subtraction technique has the potential to improve radiologists' diagnostic accuracy and could be used for computerized identification of asymmetric abnormalities on whole-body bone scans.

The magnetic resonance imaging (MRI) differential diagnosis of intrahepatic biloma from intrahepatic subacute hematoma has been reported in two cases. The biloma was heterogenously intense on T1-weighted images and homogenously hyperintense on T2-weighted images. The hematoma was hyperintense on the both T1- and T2-weighted MR images. The clinical significance of this MRI difference is that intrahepatic biloma needs drainage, whereas intrahepatic hematoma can heal spontaneously.

The diagnosis of hemobilia is difficult. Computed tomography and ultrasonography generally yield only contributory information about blood or clots in the gallbladder but cannot demonstrate bleeding. This case report shows that magnetic resonance imaging (MRI) can not only demonstrate traumatic hemobilia in the gallbladder, and its origin, but can also determine active bleeding from liver lacerations and hematoma.

Functional MRI (fMRI) utilizing both perfusion and blood oxygenation level-dependent (BOLD) contrast has been extensively used in human brain mapping. In most cases, techniques based on both contrasts have been performed using a blocked task paradigm. Most recently, both perfusion and BOLD based event-related fMRI (ER-fMRI) were developed to study the transient hemodynamic response to a short stimulus. A direct comparison of these two ER-fMRI techniques will improve our understanding of the hemodynamic response due to brain activation. In this study, we compare the temporal response in perfusion and BOLD based ER-fMRI. Experiments were performed on a 1.9 T MRI scanner, on 6 healthy human subjects. For perfusion based imaging, a flow-sensitive alternating inversion recovery (FAIR) EPI technique was used, with a temporal resolution of 1 s. For the BOLD based imaging, a T/sub 2/*weighted gradient-echo EPI was used with the same temporal resolution. A checkerboard flashing at 8 Hz was presented as the short visual stimulus. Ten trials were averaged. Percent maximum change, time-to-peak (TTP) and FWHM of the responses were determined on the activated voxels. FAIR signal changes are much higher than BOLD signal changes. The mean TTP occurs 0.9 s earlier for perfusion than BOLD. No significant difference was observed between the FWHM of the perfusion and which of the BOLD responses. A positive linear correlation was found between the maximum perfusion and maximum BOLD signal changes.

Comparative functional neuroimaging studies using the block design paradigm have previously demonstrated that there are no significant differences in the location of areas of cerebral activation when native Chinese speakers independently process single words or sentences in both the Chinese (first) and English (second) languages. While it has also been documented that significant domains of brain response include the inferior to middle left frontal lobe, the latency, amplitude and duration of the associated hemodynamic changes during isolated neural processing of Chinese and English languages still remain unknown. The aim of this study, therefore, was to examine the characteristics of the hemodynamic alterations in the above-mentioned regions with event-related functional MRI (ER-fMRI) when native Chinese speakers performed verb generation tasks in both the Chinese (first) and English (second) languages. Our results demonstrate the presence of a similar neural activity-induced hemodynamic response in the inferior to middle left frontal lobe during both tasks. Further, there were also no statistically significant differences among the variables that described the hemodynamic response curves. These findings strongly imply that the underlying neural mechanism for Chinese (first) and English (second) language processing may be similar in native Chinese speakers.