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Accurate prediction of MCI-to-AD progression is an important yet challenging task. We introduce a new quantitative parameter: the atrophy-weighted standard uptake value ratio (awSUVR), defined as the PET SUVR divided by the hippocampal volume measured with MR, and evaluate whether it may provide better prediction of the MCI-to-AD progression. Materials and Methods: We used ADNI data to evaluate the prediction performances of the awSUVR against SUVR. 571, 363 and 252 18-F-Florbetaipir scans were selected based on criteria of conversion at the third, fifth and seventh year after the PET scans, respectively. Corresponding MR scans were segmented with Freesurfer and applied on PET for SUVR and awSUVR computation. We also searched for the optimal combination of target and reference regions. In addition to evaluating the overall prediction performances, we also evaluated the prediction for APOE4 carriers and non-carriers. For the scans with false predictions, we used 18-F-Flortaucipir scans to investigate the potential source of error. Results: awSUVR provides more accurate prediction than the SUVR in all three progression criteria. The 5-year prediction accuracy/sensitivity/specificity is 90/81/93% for awSUVR and 86/81/88% for SUV. awSUVR also yields good 3- and 7-year prediction accuracy/sensitivity/specificity of 91/57/96 and 92/89/93, respectively. APOE4 carriers generally are slightly more difficult to predict for the progression. False negative prediction is found to either due to a near-cutoff mis-classification or potentially non-AD dementia pathology. False positive prediction is mainly due to the slightly delayed progression than the expected progression time. Conclusion: We demonstrated with ADNI data that 18-F-Florbetapir SUVR weighted with hippocampus volume may provide good prediction power with over 90% accuracy in MCI-to-AD progression.

ObjectiveTo assess the presence of brain and systemic inflammation in subjects newly diagnosed with Parkinson’s disease (PD).BackgroundEvidence for a pathophysiologic role of inflammation in PD is growing. However, several key gaps remain as to the role of inflammation in PD, including the extent of immune activation at early stages, potential effects of PD treatments on inflammation, and whether pro-inflammatory signals are associated with clinical features and/or predict more rapid progression.MethodsWe enrolled subjects with de novo PD (n=58) and age-matched controls (n=62). Subjects underwent clinical assessments, including the Movement Disorder Society-United Parkinson’s Disease rating scale (MDS-UPDRS). Comprehensive cognitive assessment meeting MDS Level II criteria for mild cognitive impairment (MCI) testing was performed. Blood was obtained for flow cytometry and cytokine/chemokine analyses. Subjects underwent imaging with 18F-DPA-714, a translocator protein 18kd (TSPO) ligand, and lumbar puncture if eligible and consented.ResultsBaseline demographics and medical history were comparable between groups. PD subjects showed significant differences in University of Pennsylvania Smell Identification Test, Schwab and England Activities of Daily Living, Scales for Outcomes in PD autonomic dysfunction, and MDS-UPDRS scores. Cognitive testing demonstrated significant differences in cognitive composite, executive function, and visuospatial domain scores at baseline. PET imaging showed increased 18F-DPA-714 signal in PD subjects. 18F-DPA-714 signal correlated with several cognitive measures and some chemokines.Conclusions18F-DPA-714 imaging demonstrated increased central inflammation in de novo PD subjects compared to controls. Longitudinal follow-up will be important to determine whether the presence of inflammation predicts cognitive decline.

Rationale: Measuring amyloid and predicting tau status using a single amyloid positron emission tomography (PET) study would be valuable for assessing brain AD pathophysiology. We hypothesized that early-frame amyloid PET (efAP) correlates with the presence of tau pathology because the initial regional brain concentrations of radioactivity are primarily determined by blood flow, which is expected to be decreased in the setting of tau pathology. Methods: 120 participants (63 amyloid-positive/57 amyloid-negative) with dynamic 18F-florbetapir-PET and static 18F-flortaucipir-PET scans obtained within 6 months of each other were included. These subjects were predominantly cognitively intact in both the amyloid positive (63%) and amyloid negative (93%) groups. Parameters for efAP quantification were optimized for stratification of tau PET positivity, assessed by either a tauopathy score or Braak regions. The ability of efAP to stratify tau positivity was measured using receiver operating characteristics (ROC) analysis of area under the curve (AUC). Pearson's r and Spearman's ρ were used for parametric and non-parametric comparisons between efAP and tau PET, respectively. Standardized net benefit was used to evaluate improvement in utilizing efAP as an additional co-predictor over hippocampal volumes in predicting tau PET positivity. Results: Measuring efAP within the hippocampus and summing the first 3 minutes of brain activity post-injection showed the strongest discriminative ability to stratify for tau positivity (AUC 0.67-0.89 across tau PET Braak regions) in amyloid positive individuals. Hippocampal efAP correlated significantly with a global tau-PET tauopathy score in amyloid-positive participants (r = -0.57, P < 0.0001). Compared to hippocampal volumes, hippocampal efAP showed stronger association with tau PET Braak stage (ρ = -0.58 vs. -0.37) and superior stratification of tau PET tauopathy score (AUC: 0.86 vs. 0.66, P = 0.002). Conclusion: Hippocampal efAP can provide additional information to conventional amyloid-PET, including estimation of the likelihood of tau positivity in amyloid-positive individuals.

PURPOSE Previous studies have shown that SUVmax on F-FDG PET/CT predicts prognosis in patients with salivary gland carcinoma (SGC). Here, we sought to evaluate whether texture features extracted from F-FDG PET/CT images may provide additional prognostic information for SGC with high-risk histology. METHODS We retrospectively examined pretreatment F-FDG PET/CT images obtained from 85 patients with nonmetastatic SGC showing high-risk histology. All patients were treated with curative intent. We used the fixed threshold of 40% of SUVmax for tumor delineation. PET texture features were extracted by using histogram analysis, normalized gray-level co-occurrence matrix, and gray-level size zone matrix. Optimal cutoff points for each PET parameter were derived from receiver operating characteristic curve analyses. Recursive partitioning analysis was used to construct a prognostic model for overall survival (OS). RESULTS Receiver operating characteristic curve analyses revealed that SUVmax, SUV entropy, uniformity, entropy, zone-size nonuniformity, and high-intensity zone emphasis were significantly associated with OS. The strongest associations with OS were found for high SUVmax (>6.67) and high SUV entropy (>2.50). Multivariable Cox analysis identified high SUVmax, high SUV entropy, performance status, and N2c-N3 stage as independent predictors of survival. A prognostic model derived from multivariable analysis revealed that patients with high SUVmax and SUV entropy or with the presence of poor performance status or N2c-N3 were associated with worse OS. CONCLUSIONS A prognostic model that includes SUVmax and SUV entropy is useful for risk stratification and supports the additional benefit of texture analysis for SGC with high-risk histology.

The aim of the study was to use a previously proposed mask region–based convolutional neural network (Mask R-CNN) for automatic abnormal liver density detection and segmentation based on hepatocellular carcinoma (HCC) computed tomography (CT) datasets from a radiological perspective. Training and testing datasets were acquired retrospectively from two hospitals of Taiwan. The training dataset contained 10,130 images of liver tumor densities of 11,258 regions of interest (ROIs). The positive testing dataset contained 1,833 images of liver tumor densities with 1,874 ROIs, and negative testing data comprised 20,283 images without abnormal densities in liver parenchyma. The Mask R-CNN was used to generate a medical model, and areas under the curve, true positive rates, false positive rates, and Dice coefficients were evaluated. For abnormal liver CT density detection, in each image, we identified the mean area under the curve, true positive rate, and false positive rate, which were 0.9490, 91.99%, and 13.68%, respectively. For segmentation ability, the highest mean Dice coefficient obtained was 0.8041. This study trained a Mask R-CNN on various HCC images to construct a medical model that serves as an auxiliary tool for alerting radiologists to abnormal CT density in liver scans; this model can simultaneously detect liver lesions and perform automatic instance segmentation.

Measuring amyloid and predicting tau status using a single amyloid PET study would be valuable for assessing brain AD pathophysiology. We hypothesized that early-frame amyloid PET (efAP) correlates with the presence of tau pathology because the initial regional brain concentrations of radioactivity are determined primarily by blood flow, which is expected to be decreased in the setting of tau pathology. Methods: The study included 120 participants (63 amyloid-positive and 57 amyloid-negative) with dynamic (18)F-florbetapir PET and static (18)F-flortaucipir PET scans obtained within 6 mo of each other. These subjects were predominantly cognitively intact in both the amyloid-positive (63%) and the amyloid-negative (93%) groups. Parameters for efAP quantification were optimized for stratification of tau PET positivity, assessed by either a tauopathy score or Braak regions. The ability of efAP to stratify tau positivity was measured using receiver-operating-characteristic analysis of area under the curve (AUC). Pearson r and Spearman ρ were used for parametric and nonparametric comparisons between efAP and tau PET, respectively. Standardized net benefit was used to evaluate improvement in using efAP as an additional copredictor over hippocampal volume in predicting tau PET positivity. Results: Measuring efAP within the hippocampus and summing the first 3 min of brain activity after injection showed the strongest discriminative ability to stratify for tau positivity (AUC, 0.67–0.89 across tau PET Braak regions) in amyloid-positive individuals. Hippocampal efAP correlated significantly with a global tau PET tauopathy score in amyloid-positive participants (r = −0.57, P

Objectives The aim of this study was to develop and validate a prognostic model incorporating [18F]FDG PET/CT radiomics for patients of minor salivary gland carcinoma (MSGC). Methods We retrospectively reviewed the pretreatment [18F]FDG PET/CT images of 75 MSGC patients treated with curative intent. Using a 1.5:1 ratio, the patients were randomly divided into a training and validation group. The main outcome measurements were overall survival (OS) and relapse-free survival (RFS). All of the patients were followed up for at least 30 months or until death. Following segmentation of tumors and lymph nodes on PET images, radiomic features were extracted. The prognostic significance of PET radiomics and clinical parameters in the training group was examined using receiver operating characteristic curve analysis. Variables showing a significant impact on OS and RFS were entered into multivariable Cox regression models. Recursive partitioning analysis was subsequently implemented to devise a prognostic index, whose performance was examined in the validation group. Finally, the performance of the index was compared with clinical variables in the entire cohort and nomograms for surgically treated cases. Results The training and validation groups consisted of 45 and 30 patients, respectively. The median follow-up time in the entire cohort was 59.5 months. Eighteen relapse, 19 dead, and thirteen relapse, eight dead events were found in the training and validation cohorts, respectively. In the training group, two factors were identified as independently associated with poor OS, i.e., (1) tumors with both high maximum standardized uptake value (SUVmax) and discretized intensity entropy and (2) poor performance status or N2c-N3 stage. A prognostic model based on the above factors was devised and showed significant higher concordance index (C-index) for OS than those of AJCC stage and high-risk histology (C-index: 0.83 vs. 0.65, P = 0.005; 0.83 vs. 0.54, P < 0.001, respectively). This index also demonstrated superior performance than nomogram for OS (C-index: 0.88 vs. 0.70, P = 0.017) and that for RFS (C-index: 0.87 vs. 0.72, P = 0.004). Conclusions We devised a novel prognostic model that incorporates [18F]FDG PET/CT radiomics and may help refine outcome prediction in patients with MSGC.

The unidentified presence of uterine smooth muscle malignancies poses a tremendous risk in women planning surgery for presumed benign leiomyomas. We sought to investigate whether preoperative FDG PET may be useful to identify leiomyosarcomas (LMS) and smooth muscle tumors of uncertain malignant potential (STUMP). Methods. We investigated patients with rapidly growing uterine masses which were suspected of being malignant on ultrasound or MRI. Among the 21 patients who underwent FDG PET, we identified 7 LMS, 1 STUMP, and 13 leiomyomas. PET-derived parameters and FDG uptake patterns were analyzed retrospectively. Results. The SUVmax values of LMS/STUMP (range: 3.7–11.8) were significantly higher than those observed in leiomyomas (range: 2.0–9.4; P=0.003) despite a significant overlap. The metabolic tumor/necrosis ratio was significantly higher in LMS/STUMP than in leiomyomas (P<0.001), with no significant intergroup overlaps. All LMS/STUMP revealed a characteristic pattern of FDG uptake, identifying a specific “hollow ball” sign (corresponding to areas of coagulative tumor necrosis). In contrast, this sign was invariably absent in patients with leiomyomas. Conclusion. The characteristic FDG uptake pattern instead of SUV on PET images allows identifying LMS/STUMP in patients with rapidly growing uterine masses, avoiding the deleterious consequences of regular surgery for presumed benign leiomyomas.

Objectives Human papillomavirus-negative oropharyngeal squamous cell carcinoma (OPSCC) has unfavorable survival outcomes. Two outcomes have been identified based on smoking history and tumor stage. We investigate the prognostic role of pre-treatment positron emission tomography (PET) in high-risk OPSCC. Materials and Methods We enrolled 147 M0 OPSCC patients with p16-negative staining and a history of heavy smoking (>10 pack-years) or T4 disease. All patients completed primary chemoradiotherapy, and 42% maximum standard uptake values (SUVmax) were used as the threshold for primary tumor. Patients were classified into training and validation cohorts with a ratio of 1:1.5 according to the PET date. Heterogeneity and irregularity indices were obtained. PET parameters with significant impact on progression-free survival (PFS) in receiver operating characteristic curves and univariate Cox models were identified and included in recursive partitioning analysis (RPA) for constructing a prognostic model. The RPA-based prognostic model was further tested in the validation cohort using multivariate Cox models. Results Fifty-eight and 89 patients were in the training and validation groups, respectively. Heterogeneity parameter, SUV-entropy (derived from histogram analysis), and irregularity index, and asphericity were significantly associated with PFS. The RPA model revealed that patients with both high SUV-entropy and high asphericity experienced the worst PFS. Results were confirmed in the validation group. The overall concordance index for PFS of the model was 0.75, which was higher than the clinical stages, performance status, SUVmax, and metabolic tumor volume of PET. Conclusions PET prognostic model provided useful prediction of PFS for patients with high-risk OPSCC.

In this study, a new computer-aided system was proposed to automatically reconstruct the spine model. The bi-planar EOS X-ray imaging was adopted as the scanning technology, which is capable of a simultaneous capture of bi-planar X-ray images by slot scanning of the whole body using ultra-low radiation doses. High quality and high contrast anteroposterior (AP) and lateral (LAT) X-ray images will be acquired during scanning period and these two radiographs enable a precise three-dimensional reconstruction of vertebrae, pelvis and other parts of the skeletal system. To overcome the timeconsuming issue of spine reconstruction using EOS system, a generative adversarial network (GAN) was applied to reconstruct the entire spine model, which is consist of generator and discriminator and training by unsupervised learning approach. Nowadays, GAN model has already been adopted in the transformation from 2D image to 3D scenes. Therefore, our approach represents a potential alternative for EOS reconstruction while still maintaining a clinically acceptable diagnostic accuracy.

In this retrospective review of prospectively collected data, we sought to investigate whether early FDG-PET assessment of treatment response based on total lesion glycolysis measured using a systemic approach (TLG-S) would be superior to either local assessment with EORTC (European Organization for Research and Treatment of Cancer) criteria or single-lesion assessment with PERCIST (PET Response Criteria in Solid Tumors) for predicting clinical outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib. We also examined the effect of bone flares on tumor response evaluation by single-lesion assessment with PERCIST in patients with metastatic bone lesions. We performed a retrospective review of prospectively collected data from 23 patients with metastatic lung adenocarcinoma treated with erlotinib. All participants underwent FDG-PET imaging at baseline and on days 14 and 56 after completion of erlotinib treatment. In addition, diagnostic CT scans were performed at baseline and on day 56. FDG-PET response was assessed with TLG-S, EORTC, and PERCIST criteria. Response assessment based on RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) from diagnostic CT imaging was used as the reference standard. Two-year progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. We identified 13 patients with bone metastases. Of these, four (31 %) with persistent bone uptake due to bone flares on day 14 were erroneously classified as non-responders according to the PERCIST criteria, but they were correctly classified as responders according to both the EORTC and TLG-S criteria. Patients who were classified as responders on day 14 based on TLG-S criteria had higher rates of 2-year PFS (26.7 % vs. 0 %, P = 0.007) and OS (40.0 % vs. 7.7 %, P = 0.018). Similar rates were observed in patients who showed a response on day 56 based on CT imaging according to the RECIST criteria. Patients classified as responders on day 14 according to the EORTC criteria on FDG-PET imaging had better rates of 2-year OS than did non-responders (36.4 % vs. 8.3 %, P = 0.015). TLG-S criteria may be of greater help in predicting survival outcomes than other forms of assessment. Bone flares, which can interfere with the interpretation of treatment response based on PERCIST criteria, are not uncommon in patients with metastatic lung adenocarcinoma treated with erlotinib.

Objective: Detection of focal cortical dysplasia (FCD) is of paramount importance in epilepsy presurgical evaluation. Our study aims at utilizing quantitative positron emission tomography (QPET) analysis to complement magnetic resonance imaging (MRI) postprocessing by a morphometric analysis program (MAP) to facilitate automated identification of subtle FCD. Methods: We retrospectively included a consecutive cohort of surgical patients who had a negative preoperative MRI by radiology report. MAP was performed on T1-weighted volumetric sequence and QPET was performed on PET/computed tomographic data, both with comparison to scanner-specific normal databases. Concordance between MAP and QPET was assessed at a lobar level, and the significance of concordant QPET-MAP(+) abnormalities was confirmed by postresective seizure outcome and histopathology. QPET thresholds of standard deviations (SDs) of -1, -2, -3, and -4 were evaluated to identify the optimal threshold for QPET-MAP analysis. Results: A total of 104 patients were included. When QPET thresholds of SD = -1, -2, and -3 were used, complete resection of the QPET-MAP(+) region was significantly associated with seizure-free outcome when compared with the partial resection group (P = 0.023, P

BACKGROUND Kinesio tape (KT) is an elastic therapeutic tape used for treating sports-related injuries and a number of other disorders. To date, the objective evidence to link pathophysiological effects and actual reactions triggered by KT is limited. PURPOSE To explore the effect of KT on the lumbar paraspinal muscles by magnetic resonance (MR) elastography. STUDY TYPE Prospective observational study. POPULATION Sixty-six asymptomatic volunteers with 31 women and 35 men. FIELD STRENGTH/SEQUENCE 3.0T MRI and elastography with vibration frequency of 120 Hz. ASSESSMENT The 5-cm-width KT with full tension was placed on a single side of the lumbar paraspinal muscle. The taping side and adhering direction were randomly decided. Two rectangular regions of interest (ROIs) of 5- and 2.5-cm-width were positioned at the bilateral paraspinal regions from the L2 to L4 level on the confidence map of MR elastography before and after KT taping. The mean shear stiffness values of the ROIs at the superficial, middle, and deep depths were recorded; then the differences between the taping and reference sides were calculated. STATISTICAL TESTS Paired t-test and Pearson correlations were used to evaluate the stiffness changes after KT application and intraoperator errors of the stiffness measures on the reference side, respectively. RESULTS A significant decrease in the muscle stiffness value between taping and reference sides (-0.71 kPa ± 0.60 with KT and -0.25 kPa ± 0.78 without KT, P

The Ang's risk profile (based on p16, smoking and cancer stage) is a well-known prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC). Whether heterogeneity in (18)F-fluorodeoxyglucose (FDG) positron emission tomographic (PET) images and epidermal growth factor receptor (EGFR) expression could provide additional information on clinical outcomes in advanced-stage OPSCC was investigated. Patients with stage III-IV OPSCC who completed primary therapy were eligible. Zone-size nonuniformity (ZSNU) extracted from pretreatment FDG PET scans was used as an index of image heterogeneity. EGFR and p16 expression were examined by immunohistochemistry. Disease-specific survival (DSS) and overall survival (OS) served as outcome measures. Kaplan-Meier estimates and Cox proportional hazards regression models were used for survival analysis. A bootstrap resampling technique was applied to investigate the stability of outcomes. Finally, a recursive partitioning analysis (RPA)-based model was constructed. A total of 113 patients were included, of which 28 were p16-positive. Multivariate analysis identified the Ang's profile, EGFR and ZSNU as independent predictors of both DSS and OS. Using RPA, the three risk factors were used to devise a prognostic scoring system that successfully predicted DSS in both p16-positive and -negative cases. The c-statistic of the prognostic index for DSS was 0.81, a value which was significantly superior to both AJCC stage (0.60) and the Ang's risk profile (0.68). In patients showing an Ang's high-risk profile (N = 77), the use of our scoring system clearly identified three distinct prognostic subgroups. It was concluded that a novel index may improve the prognostic stratification of patients with advanced-stage OPSCC.

Purpose This study was conducted to investigate the correlation between the number of vascularized lymph nodes (LN) transferred and resolution of hind limb lymphedema in a rat model. Methods Unilateral hind limb lymphedema was created in 18 male Sprague–Dawley rats following inguinal and popliteal LN resection and radiation. A para-aortic LN flap based on the celiac artery was subsequently transferred to the affected groin. The three study groups consisted of Group A (no LN transfer), Group B (transfer of a single vascularized LN), and Group C (transfer of three vascularized LNs). Volumetric analysis of bilateral hind limbs was performed using micro-CT imaging at 1, 2, and 3 months postoperatively. Lymphatic drainage was assessed with Tc99 lymphoscintigraphy preoperatively and at 3 months postoperatively. Results A statistically significant volume reduction was seen in Groups B and C compared to Group A at all time points. Volume reduction of Group A vs.Group B at 1 month (8.6% ± 2.0% vs. 2.7% ± 2.6%, P

The question as to whether the regional textural features extracted from PET images predict prognosis in oropharyngeal squamous cell carcinoma (OPSCC) remains open. In this study, we investigated the prognostic impact of regional heterogeneity in patients with T3/T4 OPSCC.We retrospectively reviewed the records of 88 patients with T3 or T4 OPSCC who had completed primary therapy. Progression-free survival (PFS) and disease-specific survival (DSS) were the main outcome measures. In an exploratory analysis, a standardized uptake value of 2.5 (SUV 2.5) was taken as the cut-off value for the detection of tumour boundaries. A fixed threshold at 42 % of the maximum SUV (SUVmax 42 %) and an adaptive threshold method were then used for validation. Regional textural features were extracted from pretreatment (18)F-FDG PET/CT images using the grey-level run length encoding method and grey-level size zone matrix. The prognostic significance of PET textural features was examined using receiver operating characteristic (ROC) curves and Cox regression analysis.Zone-size nonuniformity (ZSNU) was identified as an independent predictor of PFS and DSS. Its prognostic impact was confirmed using both the SUVmax 42 % and the adaptive threshold segmentation methods. Based on (1) total lesion glycolysis, (2) uniformity (a local scale texture parameter), and (3) ZSNU, we devised a prognostic stratification system that allowed the identification of four distinct risk groups. The model combining the three prognostic parameters showed a higher predictive value than each variable alone.ZSNU is an independent predictor of outcome in patients with advanced T-stage OPSCC, and may improve their prognostic stratification.

Human papillomavirus-negative oropharyngeal squamous cell carcinoma (OPSCC) has unfavorable survival outcomes. Two outcomes have been identified based on smoking history and tumor stage. We investigate the prognostic role of pre-treatment positron emission tomography (PET) in high-risk OPSCC.We enrolled 147 M0 OPSCC patients with p16-negative staining and a history of heavy smoking (10 pack-years) or T4 disease. All patients completed primary chemoradiotherapy, and 42% maximum standard uptake values (SUVFifty-eight and 89 patients were in the training and validation groups, respectively. Heterogeneity parameter, SUV-entropy (derived from histogram analysis), and irregularity index, and asphericity were significantly associated with PFS. The RPA model revealed that patients with both high SUV-entropy and high asphericity experienced the worst PFS. Results were confirmed in the validation group. The overall concordance index for PFS of the model was 0.75, which was higher than the clinical stages, performance status, SUVPET prognostic model provided useful prediction of PFS for patients with high-risk OPSCC.

Cell sheet technology has been widely employed for the treatment of myocardial infarction (MI), but cell sheet fabrication generally requires the use of thermo-responsive dishes. Here we developed a method for the preparation of adipose-derived stem cell (ASC) sheet that obviated the need of thermo-responsive dishes. This method only required the seeding of rabbit ASC onto 6-well plates at an appropriate cell density and culture in appropriate medium, and the cells were able to develop into ASC sheet in 2 days. The ASC sheet allowed for transduction with the hybrid baculovirus at efficiencies >97%, conferring robust and prolonged (>35 days) overexpression of vascular endothelial growth factor (VEGF). The ASC sheet was easily detached by brief (10 s) trypsinization and saline wash, while retaining the extracellular matrix and desired physical properties. The ASC sheet formation and VEGF expression promoted cell survival under hypoxia in vitro. Epicardial implantation of the VEGF-expressing ASC sheet to rabbit MI models reduced the infarct size and improved cardiac functions to non-diseased levels, as judged from the left ventrical ejection fraction/myocardial perfusion. The VEGF-expressing ASC sheet also effectively prevented myocardial wall thinning, suppressed myocardium fibrosis and enhanced blood vessel formation. These data implicated the potential of this method for the preparation of genetically engineered ASC sheet and future MI treatment.

Adipose-derived stem cells (ASCs) hold promise for cartilage regeneration but their chondrogenesis potential is inferior. Here, we used a baculovirus (BV) system that exploited FLPo/Frt-mediated transgene recombination and episomal minicircle formation to genetically engineer rabbit ASCs (rASCs). The BV system conferred prolonged and robust TGF-β3/BMP-6 expression in rASCs cultured in porous scaffolds, which critically augmented rASCs chondrogenesis and suppressed osteogenesis/hypertrophy, leading to the formation of cartilaginous constructs with improved maturity and mechanical properties in 2-week culture. Twelve weeks after implantation into full-thickness articular cartilage defects in rabbits, these engineered constructs regenerated neocartilages that resembled native hyaline cartilages in cell morphology, matrix composition and mechanical properties. The neocartilages also displayed cartilage-specific zonal structures without signs of hypertrophy and degeneration, and eventually integrated with host cartilages. In contrast, rASCs that transiently expressed TGF-β3/BMP-6 underwent osteogenesis/hypertrophy and resulted in the formation of inferior cartilaginous constructs, which after implantation regenerated fibrocartilages. These data underscored the crucial role of TGF-β3/BMP-6 expression level and duration in rASCs in the cell differentiation, constructs properties and in vivo repair. The BV-engineered rASCs that persistently express TGF-β3/BMP-6 improved the chondrogenesis, in vitro cartilaginous constructs production and in vivo hyaline cartilage regeneration, thus representing a remarkable advance in cartilage engineering.

Purpose: The authors report a novel measurement strategy to obtain both rest and stress blood flow during a single, relatively short, scan session. Methods: Measurement of rest-stress myocardial blood flow with long-lived tracers usually requires separate scan sessions to remove the confounding effects of residual radioactivity concentration in the blood and tissue. The innovation of this method is to treat the rest-stress scan as a single entity in which the flow parameters change due to pharmacological challenge. With this approach the fate of a tracer molecule is naturally accounted for, no matter if it was introduced during the rest or stress phase of the study. Two new dual-injection kinetic models are considered that represent the response to pharmacological stress as a transitional or transient increase of myocardial blood flow. The authors present the theory of the method followed by the specific application of the theory to18F-Flurpiridaz, a new myocardial flow-imaging agent. Results: Myocardial blood flow was accurately and precisely estimated from a single-scan rest/stress study for the long half-lived tracer18F-Flurpiridaz. By accounting for the time-dependence of the kinetic parameters, the proposed models achieved good accuracy and precision (5%) under different vasodilators and different ischemic states. Conclusions: Detailed simulations predict that accurate and precise rest-stress blood flow measurements can be obtained in 20–30 min.

Objectives/Hypothesis Plasma Epstein-Barr virus (EBV) DNA concentrations predict prognosis in patients with nasopharyngeal carcinoma (NPC). Recent evidence also indicates that intratumor heterogeneity on F-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) scans is predictive of treatment outcomes in different solid malignancies. Here, we sought to investigate the prognostic value of heterogeneity parameters in patients with primary NPC. Study Design Retrospective cohort study. Methods We examined 101 patients with primary NPC who underwent pretreatment 18F-FDG PET/computed tomography. Circulating levels of EBV DNA were measured in all participants. The following PET heterogeneity parameters were collected: histogram-based heterogeneity parameters, second-order texture features (uniformity, contrast, entropy, homogeneity, dissimilarity, inverse difference moment), and higher-order (coarseness, contrast, busyness, complexity, strength) texture features. Results The median follow-up time was 5.14 years. Total lesion glycolysis (TLG), tumor heterogeneity measured by histogram-based parameter skewness, and the majority of second-order or higher-order texture features were significantly associated with overall survival (OS) and/or recurrence-free survival (RFS). In multivariate analysis, age (P =.005), EBV DNA load (P = .0002), and uniformity (P = .001) independently predicted OS. Only skewness retained the independent prognostic significance for RFS. Tumor stage, standardized uptake value, or TLG did not show an independent association with survival endpoints. The combination of uniformity, EBV DNA load, and age resulted in a more reliable prognostic stratification (P < .001). Conclusions Tumor heterogeneity is superior to traditional PET parameters for predicting outcomes in primary NPC. The combination of uniformity with EBV DNA load can improve prognostic stratification in this clinical entity. Level of Evidence 4 Laryngoscope, 127:E22–E28, 2017

The Ang's risk profile (based on p16, smoking and cancer stage) is a well-known prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC). Whether heterogeneity in (18)F-fluorodeoxyglucose (FDG) positron emission tomographic (PET) images and epidermal growth factor receptor (EGFR) expression could provide additional information on clinical outcomes in advanced-stage OPSCC was investigated. Patients with stage III-IV OPSCC who completed primary therapy were eligible. Zone-size nonuniformity (ZSNU) extracted from pretreatment FDG PET scans was used as an index of image heterogeneity. EGFR and p16 expression were examined by immunohistochemistry. Disease-specific survival (DSS) and overall survival (OS) served as outcome measures. Kaplan-Meier estimates and Cox proportional hazards regression models were used for survival analysis. A bootstrap resampling technique was applied to investigate the stability of outcomes. Finally, a recursive partitioning analysis (RPA)-based model was constructed. A total of 113 patients were included, of which 28 were p16-positive. Multivariate analysis identified the Ang's profile, EGFR and ZSNU as independent predictors of both DSS and OS. Using RPA, the three risk factors were used to devise a prognostic scoring system that successfully predicted DSS in both p16-positive and -negative cases. The c-statistic of the prognostic index for DSS was 0.81, a value which was significantly superior to both AJCC stage (0.60) and the Ang's risk profile (0.68). In patients showing an Ang's high-risk profile (N = 77), the use of our scoring system clearly identified three distinct prognostic subgroups. It was concluded that a novel index may improve the prognostic stratification of patients with advanced-stage OPSCC.

Purpose. We aimed at improving the existing methods for the fully automatic quantification of striatal uptake of [Tc99m]-TRODAT with SPECT imaging.Procedures. A normal [Tc99m]-TRODAT template was first formed based on 28 healthy controls. Images from PD patients (n=365) and nPD subjects (28 healthy controls and 33 essential tremor patients) were spatially normalized to the normal template. We performed an inverse transform on the predefined striatal and reference volumes of interest (VOIs) and applied the transformed VOIs to the original image data to calculate the striatal-to-reference ratio (SRR). The diagnostic performance of the SRR was determined through receiver operating characteristic (ROC) analysis.Results. The SRR measured with our new and automatic method demonstrated excellent diagnostic performance with 92% sensitivity, 90% specificity, 92% accuracy, and an area under the curve (AUC) of 0.94. For the evaluation of the mean SRR and the clinical duration, a quadratic function fit the data withR2=0.84.Conclusions. We developed and validated a fully automatic method for the quantification of the SRR in a large study sample. This method has an excellent diagnostic performance and exhibits a strong correlation between the mean SRR and the clinical duration in PD patients.

Metabolic heterogeneity is a recognized characteristic of malignant tumors. Positron emission tomography (PET) texture analysis evaluated intratumoral heterogeneity in the uptake of (18)F-fluorodeoxyglucose. There were recent evidences that PET textural features were of prognostic significance in patients with different solid tumors. Unfortunately, there are still crucial standardization challenges to transform PET texture parameters from their current use as research tools into the arena of validated technologies for use in oncology practice. Testing its generalizability, robustness, consistency, and limitations is necessary before implementing it in daily patient care.

This article demonstrates a gateway system for converting image fusion results to digital imaging and communication in medicine (DICOM) objects. For the purpose of standardization and integration, we have followed the guidelines of the Integrated Healthcare Enterprise technical framework and developed a DICOM gateway. The gateway system combines data from hospital information system, image fusion results, and the information generated itself to constitute new DICOM objects. All the mandatory tags defined in standard DICOM object were generated in the gateway system. The gateway system will generate two series of SOP instances of each PET-MR fusion result; SOP (Service Object Pair) one for the reconstructed magnetic resonance (MR) images and the other for position emission tomography (PET) images. The size, resolution, spatial coordinates, and number of frames are the same in both series of SOP instances. Every new generated MR image exactly fits with one of the reconstructed PET images. Those DICOM images are stored to the picture archiving and communication system (PACS) server by means of standard DICOM protocols. When those images are retrieved and viewed by standard DICOM viewing systems, both images can be viewed at the same anatomy location. This system is useful for precise diagnosis and therapy.

This study was to compare our input function estimation methods with the standard blood sampling and other competing methods. We have developed two input function estimation methods, namely simplified simultaneous estimation method and regression estimated input function method for FDG-PET model. The derivation of input functions from both methods requires no blood sample. Our results show that both methods have high correlation with the standard blood sampling method using nonlinear least squares method for parameter estimation. There were no significant differences in error percentage among the proposed methods and the existing methods such as image derived input function method, standard input function method, and simultaneous estimation method. Accordingly, our methods can reliably measure cerebral metabolic rate of glucose and provide patients and physicians with simple and noninvasive ways in FDG-PET quantitative studies.

This study was conducted to investigate the correlation between the number of vascularized lymph nodes (LN) transferred and resolution of hind limb lymphedema in a rat model.Unilateral hind limb lymphedema was created in 18 male Sprague-Dawley rats following inguinal and popliteal LN resection and radiation. A para-aortic LN flap based on the celiac artery was subsequently transferred to the affected groin. The three study groups consisted of Group A (no LN transfer), Group B (transfer of a single vascularized LN), and Group C (transfer of three vascularized LNs). Volumetric analysis of bilateral hind limbs was performed using micro-CT imaging at 1, 2, and 3 months postoperatively. Lymphatic drainage was assessed with Tc(99) lymphoscintigraphy preoperatively and at 3 months postoperatively.A statistically significant volume reduction was seen in Groups B and C compared to Group A at all time points. Volume reduction of Group A vs.Group B at 1 month (8.6% ± 2.0% vs. 2.7% ± 2.6%, P0.05), 2 months (9.3% ± 2.2% vs. -4.3% ± 2.7%, P0.05), and 3 months (7.6% ± 3.3% vs. -8.9% ± 5.2%, P0.05). Volume reduction of Group A vs. Group C at 1 month (8.6% ± 2.0% vs. -6.6% ± 3.1%, P0.05), 2 months (9.3% ± 2.2% vs. -10.2% ± 4.6%, P0.05), and 3 months (7.6% ± 3.3% vs. -9.1% ± 3.1%, P0.05). Of note, comparison of Groups B and C demonstrated greater volume reduction in Group C at 1 (P0.02) and 2 (P = 0.07) months postoperatively.LN flap transfer is an effective procedure for the treatment of lymphedema. The number of vascularized LNs transferred correlates positively with the degree of volume reduction.

Background. The quantification of tumor heterogeneity with molecular images, by analyzing the local or global variation in the spatial arrangements of pixel intensity with texture analysis, possesses a great clinical potential for treatment planning and prognosis. To address the lack of available software for computing the tumor heterogeneity on the public domain, we develop a software package, namely, Chang-Gung Image Texture Analysis (CGITA) toolbox, and provide it to the research community as a free, open-source project.Methods. With a user-friendly graphical interface, CGITA provides users with an easy way to compute more than seventy heterogeneity indices. To test and demonstrate the usefulness of CGITA, we used a small cohort of eighteen locally advanced oral cavity (ORC) cancer patients treated with definitive radiotherapies.Results. In our case study of ORC data, we found that more than ten of the current implemented heterogeneity indices outperformed SUVmeanfor outcome prediction in the ROC analysis with a higher area under curve (AUC). Heterogeneity indices provide a better area under the curve up to 0.9 than the SUVmeanand TLG (0.6 and 0.52, resp.).Conclusions. CGITA is a free and open-source software package to quantify tumor heterogeneity from molecular images. CGITA is available for free for academic use athttp://code.google.com/p/cgita.

Lymphedema is a debilitating condition that is characterized by the abnormal collection of fluid and proteins within the interstitium. Dysfunctional lymphatic vessels cause lymphatic fluid stasis, decreased macrophage function, and chronic inflammation and fibrosis.1 It is often a surgical complication following oncologic resection and lymph node dissection. Approximately 16–39% of breast cancer and 20–49% of genital cancer patients suffer from upper extremity lymphedema and lower extremity lymphedema, respectively.2,3 The management of lymphedema is complex and includes decongestive physiotherapy and various surgical options. However, no option has been shown to be completely effective and most may provide only temporary relief of symptoms. Evolving surgical techniques in the management of extremity lymphedema have shown promise with lymphovenous bypass and vascularized lymph node (VLN) flap transfer procedures.4,5 In our clinical series,3,6,7 VLN flap transfer from groin area has been shown to effectively improve the lymphatic drainage from lymphedematous limbs in patients with postmastectomy upper extremity lymphedema. To further investigate effective management strategies for the treatment of lymphedema, a stable and reproducible animal model is needed. Currently, lymphedema models have been previously established in various animal models. In canine and sheep models, variable removal of popliteal lymph nodes and connected lymphatic vessels were performed to replicate lymphedema in the hind limb.8,9 In Lahteenvuo’s porcine model, lymphatic vessel stripping was performed only to identify lymphatic vessels connected to lymph nodes.10 In a forelimb model, Mendez et al11 dissected axillary lymph nodes to develop lymphedema. In a hind limb model proposed by Kanter et al,12 radiation therapy of 45 Gy was coupled with the removal of lymph nodes to replicate lymphedema. Among these models, the hind limb location of the rat model is economically and technically reproducible allowing for further investigation of the surgical treatment of chronic lymphedema. But, previous studies using this model have not shown reproducible lymphedema and have used imprecise limb circumference measurement techniques.12 The purpose of this study was to establish a consistent hind limb lymphedema model by combining lower limb lymphadenectomy and assessing effects with differing doses of radiation therapy. In addition, microcomputed tomography (micro-CT) imaging was used to precisely evaluate volumetric changes of lymphedematous and contralateral healthy limbs. Lymphoscintigraphy was then used to assess lymphatic drainage patterns.

In recent decades, we have witnessed an explosive growth of diagnostic tools that have changed the face of modern medicine. Among these diagnostic tools, medical imaging is indeed one of the most representative fields that have been growing fast, used extensively, and regarded as an irreplaceable part of clinical routines. With a very different scale, “omics” refers to the study of cellular- or DNA-level molecules including their functions, structures, interactions, and involvement in disease development. Similar to imaging, the “omics” fields such as genomics, proteomics, and metabolomics have also advanced drastically in recent decades. The “omics” data obtained from a patient reveal a much more microscaled world that allows the practitioner to see what is going on in the genomic and proteomic levels. As imaging and omics technologies look at human physiology in quite different scales, physicians and scientists are currently attempting to integrate imaging and omics data for tailored therapies and research purposes. This special issue provides original research and review on the potential role and value of imaging in the context of personalized medicine based on omics information. Imaging can be used as a tool to directly measure the omics data. As pointed out by the comprehensive review by G. Lin and Y. L. Chung on the use of molecular imaging methods to study metabolomics in this issue, recent technological advancements of parallel imaging and high-field magnets have largely propelled the advancement of metabolomics for MR spectroscopy to measure the amount and exchange of multiple metabolites. Such imaging technologies can also be applied to in vivo imaging for both small animals and humans. Imaging the living organisms allows investigators to observe the metabolism and molecular exchange in both the spatial and temporal domains. In addition to measuring the omics data with imaging, clinical oncology continues to use medical images for treatment planning. G. C. Pereira et al. have given a comprehensive review on the role and importance of imaging in radiation therapies in this special issue. In this review, the critical role of imaging in radiation therapy is reviewed for the application of dose calculation, lesion location, and delineation. The combination of omics information and the image-derived lesion information has a high potential to further enhance the treatment efficacy for oncological applications. Image quantification and information extraction remain to be a challenge for integrating imaging and omics information. In this special issue, Y.-H. D. Fang et al. described an example in the open-source software development for quantifying the intratumoral heterogeneity. Such quantification based on texture analysis has been reported to be helpful for prognosis in oncological applications. However, currently there is no free software for such quantification in the public domain. Therefore, Y.-H. D. Fang et al. developed and shared a software package to fill this void and demonstrated its usefulness in a small cohort of oral cavity cancer patients. There are also many practical limitations for medical imaging that is modality-dependent. Ionizing radiation is one major concern for CT and radionuclide imaging such as PET and SPECT. MR does not require ionizing radiation and owns a great potential in molecular imaging, but it has its own limitations in speed, cost, and potential renal toxicity with the use of Gd-based contrast agents. In this special issue, H. M. Huang and Y. Y. Shih gave a review on the recent technical advancement of dose reduction for CT and acceleration for MR. From their review, it could be optimistically expected that such practical limitations will gradually be resolved to make those two modalities more commonly used in the integration of imaging and omics research in the future. To fully exploit the omics data in personalized medicine, new advancements for instrumentation to extract omics data play a critical role. A review article by C.-S. A. Gong and K. F. Lei in this special issue will discuss the recent advancement of miniaturized devices for genomics, which may further advance the clinical popularity for gene sequencing. One of the striking examples is the use of electrochemical impedance spectroscopy as the electrical detection of DNA hybridization in microfluidic devices. The combination of microfluidic and impedimetric technologies shows an alternative and attractive method for detecting the genomic signal. In conclusion, the dramatic advancements of the omics knowledge have further propelled the development of personalized medicine. The original and review articles in this special issue show that there will be a significant role of medical images in the future of personalized medicine. It can be optimistically expected that imaging will continue to evolve as part of the omics data as well as serving as a tool for omics measurements. Although integration of imaging and omics data is a challenging task for the imaging community, such efforts will truly benefit personalized medicine by allowing us to see an individual from macro- to microscale levels. Tzu-Chen Yen Dimitris Visvikis Tinsu Pan Yu-Hua Dean Fang

The aim of this study is to develop and evaluate a novel direct reconstruction method to improve the signal-to-noise ratio (SNR) of parametric images in dynamic positron-emission tomography (PET), especially for applications in myocardial perfusion studies.Simulation studies were used to test the performance in SNR and computational efficiency for different methods. The NCAT phantom was used to generate simulated dynamic data. Noise realization was performed in the sinogram domain and repeated for 30 times with four different noise levels by varying the injection dose (ID) from standard ID to 1/8 of it. The parametric images were calculated by (1) three direct methods that compute the kinetic parameters from the sinogram and (2) an indirect method, which computes the kinetic parameter with pixel-by-pixel curve fitting in image space using weighted least-squares. The first direct reconstruction maximizes the likelihood function using trust-region-reflective (TRR) algorithm. The second approach uses tabulated parameter sets to generate precomputed time-activity curves for maximizing the likelihood functions. The third approach, as a newly proposed method, assumes separable complete data to derive the M-step for maximizing the likelihood.The proposed method with the separable complete data performs similarly to the other two direct reconstruction methods in terms of the SNR, providing a 5%-10% improvement as compared to the indirect parametric reconstruction under the standard ID. The improvement of SNR becomes more obvious as the noise level increases, reaching more than 30% improvement under 1/8 ID. Advantage of the proposed method lies in the computation efficiency by shortening the time requirement to 25% of the indirect approach and 3%-6% of other direct reconstruction methods.With results provided from this simulation study, direct reconstruction of myocardial blood flow shows a high potential for improving the parametric image quality for clinical use.

Previous studies have shown that total lesion glycolysis (TLG) may serve as a prognostic indicator in oropharyngeal squamous cell carcinoma (OPSCC). We sought to investigate whether the textural features of pretreatment 18 F-FDG PET/CT images can provide any additional prognostic information over TLG and clinical staging in patients with advanced T-stage OPSCC. Methods: We retrospectively analyzed the pretreatment 18 F-FDG PET/CT images of 70 patients with advanced T-stage OPSCC who had completed concurrent chemoradiotherapy, bioradiotherapy, or radiotherapy with curative intent. All of the patients had data on human papillomavirus (HPV) infection and were followed up for at least 24 mo or until death. A standardized uptake value (SUV) of 2.5 was taken as a cutoff for tumor boundary. The textural features of pretreatment 18F-FDG PET/CT images were extracted from histogram analysis (SUV variance and SUV entropy), normalized gray-level cooccurrence matrix (uniformity, entropy, dissimilarity, contrast, homogeneity, inverse different moment, and correlation), and neighborhood gray-tone difference matrix (coarseness, contrast, busyness, complexity, and strength). Receiver-operating-characteristic curves were used to identify the optimal cutoff values for the textural features and TLG. Results: Thirteen patients were HPV-positive. Multivariate Cox regression analysis showed that age, tumor TLG, and uniformity were independently associated with progression-free survival (PFS) and disease-specific survival (DSS). TLG, uniformity, and HPV positivity were significantly associated with overall survival (OS). A prognostic scoring system based on TLG and uniformity was derived. Patients who presented with TLG . 121.9 g and uniformity # 0.138 experienced significantly worse PFS, DSS, and OS rates than those without (P , 0.001, , 0.001, and 0.002, respectively). Patients with TLG . 121.9 g or uniformity # 0.138 were further divided according to age, and different PFS and DSS were observed. Conclusion: Uniformity extracted from the normalized gray-level cooccurrence matrix represents an independent prognostic predictor in patients with advanced T-stage OPSCC. A scoring system was developed and may serve as a risk-stratification strategy for guiding therapy.

The authors report a novel measurement strategy to obtain both rest and stress blood flow during a single, relatively short, scan session.Measurement of rest-stress myocardial blood flow with long-lived tracers usually requires separate scan sessions to remove the confounding effects of residual radioactivity concentration in the blood and tissue. The innovation of this method is to treat the rest-stress scan as a single entity in which the flow parameters change due to pharmacological challenge. With this approach the fate of a tracer molecule is naturally accounted for, no matter if it was introduced during the rest or stress phase of the study. Two new dual-injection kinetic models are considered that represent the response to pharmacological stress as a transitional or transient increase of myocardial blood flow. The authors present the theory of the method followed by the specific application of the theory to (18)F-Flurpiridaz, a new myocardial flow-imaging agent.Myocardial blood flow was accurately and precisely estimated from a single-scan rest∕stress study for the long half-lived tracer (18)F-Flurpiridaz. By accounting for the time-dependence of the kinetic parameters, the proposed models achieved good accuracy and precision (5%) under different vasodilators and different ischemic states.Detailed simulations predict that accurate and precise rest-stress blood flow measurements can be obtained in 20-30 min.

It has been suggested that Bayesian estimation methods may be used to improve the signal-to-noise ratio of parametric images. However, there is little experience with the method and some of the underlying assumptions and performance properties of Bayesian estimation remain to be investigated. We used a sample population of 54 subjects, studied previously with (11)C-Altropane, to empirically evaluate the assumptions, performance and some practical issues in forming parametric images. By using normality tests, we showed that the underpinning normality assumptions of data and parametric distribution apply to more than 80% of voxels. The standard deviation of the binding potential can be reduced 30-50% using Bayesian estimation, without introducing substantial bias. The sample size required to form the a priori information was found to be modest; as little as ten subjects may be sufficient and the choice of specific subjects has little effect on Bayesian estimation. A realistic simulation study showed that detection of localized differences in parametric images, e.g. by statistical parametric mapping (SPM), could be made more reliable and/or conducted with smaller sample size using Bayesian estimation. In conclusion, Bayesian estimation can improve the SNR of parametric images and better detect localized changes in cohorts of subjects.

77 Objectives To evaluate the role of high resolution quantitative PET/CT with MRI for early monitoring of treatment response to TNF-α inhibitor in human patients with rheumatoid arthritis (RA). Methods A PET/CT extremity scanner has been built at our institution. High resolution fused and co-registered PET/CT images of the wrist are obtained from this device. The patient lies prone on top of the PET/CT gantry, with the most symptomatic hand (locked by an immobilizer) suspended through a hole on the table-top. The hand immobilizer is compatible with MRI allowing the acquisition of clinical MR images at the same time points as extremity PET/CT. To date, three RA patients who were candidates for TNF-α blocker etanercept have been scanned with FDG-PET/CT and MRI at baseline and two at one month after initiation of treatment. This is a 10 patient study and recruitment is ongoing. Results For patient 1 (57f) at 1 month, marked reduction compared to baseline of 20-40% in maximum PET signal intensity (Imax) in the synovium and at sites of erosions, and of 82% in PET metabolic synovial volume was measured. MRI contrast enhancement correlated with this finding. This patient was hence classified as a responder to the drug. Rheumatologist examination at the end of three months confirmed this finding. For patient 2 (63f), an increase of 20-30% in Imax was measured in the synovium and at erosion sites at 1 month compared to baseline. We predict that this patient is a non-responder to the drug. Clinical examination for this patient is pending. Conclusions From initial studies, high resolution FDG-PET/CT with MRI shows significant promise for quantitative monitoring of early response to anti-TNF-α therapy in RA. Research Support This work was funded by the NIH grants UL1-RR024146, R01CA129561, R01EB002138, and the UC Davis Imaging Research Center