High Standardized Uptake Value Research Articles

1168Role of 18FDG(fluorodeoxyglucose)-PET (positron emission tomography) for differential diagnosis of pericardial disease

Abstract Background Pericardial disease is frequently associated with systemic diseases. Diagnosis is often troublesome because pericardial fluid does not always give an answer and limited assessment for the acquisition of tissue in effusive-constrictive or constrictive pericarditis. Even after biopsy of pericardium, diagnostic yield is very low without further information for the underlying case. 18FDG-PET can visualize both the inflammation and malignancy through whole body assessment; therefore, it can visualize both pericardium and other organs to provide further insight to the systemic disease. Purpose To assess the role of 18FDG-PET for differential diagnosis of pericardial disease in real clinical practice. Methods Patients who admitted to our pericardial disease clinic who underwent 18FDG-PET for diagnostic methods were derived from electrical medical system database and reviewed. Exclusion criteria were known the advanced stage of malignancy, or already diagnosed from pericardial effusion analysis (positive for malignancy or bacterial culture) by pericardiocentesis. Results Forty patients were finally analyzed. Most common final diagnosis was Idiopathic (n=13, 33%) and tuberculosis (n=12, 28%). Malignancy was diagnosed in 6 patients (15%). Diagnosis of malignancy in all the patients was not confirmed in pericardial effusion. One patient was diagnosed by pericardial biopsy and one by pericardial effusion. Other four were diagnosed by biopsy of other organs. Post-radiation therapy associated pericarditis in two patients, post-operative pericarditis in 5 patients, and transudate, hematoma associated pericarditis, parasite infection in one patient each. Lymph node uptake was found in 28 cases, and four of them was “suggestive malignancy”, 18 was “suggestive benign” and other 6 was “need further evaluation”. All of the patients categorized as “suggestive malignancy” was helped by 18FDG-PET which indicated the optimal biopsy site and 3 of them finally diagnosed as malignancy and one as parasite infection. All of the patients who were categorized as “suggestive benign” were finally diagnosed as a non-malignant disease. Pericardial biopsy was performed in 19 cases (48%) and only 4 were diagnostic. Other 15 specimen showed “chronic inflammation”. Guiding the optimal biopsy site by 18FDG-PET was achieved in 6 patients. 19 cases had normal SUV in the pericardium and 7 patients had very high pericardial SUV more than 10. 6 patients with benign LV pattern was finally diagnosed as tuberculosis pericarditis and one patient with the malignant pattern was finally diagnosed as angiosarcoma Conclusion 18FDG-PET is helpful in the initial assessment of pericardial disease in the aspects of 1) presumptive diagnosis of malignancy in especially in nondiagnostic pericardial effusion or technically risky for pericardiocentesis, 2) Selection of optimal biopsy site with a higher yield of disease, and 3) possibly non-invasive diagnosis of tuberculosis pericarditis. Acknowledgement/Funding None

Significance of CT attenuation and F-18 fluorodeoxyglucose uptake of visceral adipose tissue for predicting survival in gastric cancer patients after curative surgical resection

BackgroundThe purpose of this study was to investigate the prognostic significance of computed tomography (CT) attenuation and F-18 fluorodeoxyglucose (FDG) uptake of visceral adipose tissue (VAT) to predict peritoneal recurrence-free survival (RFS) as well as RFS and overall survival (OS) in patients with advanced gastric cancer (AGC).MethodsWe retrospectively enrolled 117 patients with AGC who underwent staging FDG positron emission tomography (PET)/CT and subsequent curative surgical resection. CT attenuation and FDG uptake (SUV) of VAT and maximum FDG uptake of primary tumor (SUVmaxT) were measured from PET/CT images. The relationship of VAT attenuation and SUV with clinico-histopathologic factors and survival was assessed.ResultsThere was a significant positive correlation between VAT attenuation and SUV (p < 0.001, r = 0.799). In correlation analyses, both VAT attenuation and SUV showed significant positive correlations with T stage, TNM stage, tumor size, and platelet-to-lymphocyte ratio (p < 0.05), and patients who experienced recurrence during the first 3-year after surgery had significantly higher VAT attenuation and SUV than those who had no recurrence (p < 0.05). Patients with high VAT attenuation and SUV showed significantly worse RFS, peritoneal RFS, and OS than those with low values (p < 0.05). On multivariate survival analysis, VAT attenuation was significantly associated with peritoneal RFS and OS and VAT SUV was significantly associated with OS (p < 0.05).ConclusionsCT attenuation and FDG uptake of VAT on staging FDG PET/CT were correlated with tumor characteristics and were significant predictive factors for peritoneal RFS and OS in patients with AGC.

Unusual FDG PET/CT Uptake in Uterine Tumors in Cancer Survivor

18-Fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG PET/CT) has become the essential modality of imaging in diagnosis; it is used for assessment of treatment response, after chemotherapy, as well as for prognostic evaluation. Case 1 is a postmenopausal woman treated for the case of Langerhans cell sarcoma; she received chemotherapy; post-chemotherapy PET/CT scan was done to assess the response to chemotherapy with an SUV of 7.1 in the uterus. The rest of the report showed no uptake elsewhere in the body, and hysterectomy with BSO pathological report showed benign leiomyoma. Case 2 is treated for carcinoma thyroid by surgery and radioiodine ablation therapy. She was on regular follow-up, and she is a premenopausal multiparous woman with regular menstruation and on annual PET/CT examination incidentally showed an increased SUV of 8 in the uterus. There was no FDG uptake elsewhere in the body except for uterus. False-positive uptake of 18-FDG PET/CT in uterine tumors can be seen in leiomyoma which has high SUV of more than 6. Surgical management with histopathological confirmation of leiomyoma is needed in cases treated for malignancy elsewhere in the body; we report these two cases hoping to expand the existing knowledge on the topic and highlight the limitation of PET/CT in the diagnosis of leiomyoma.

High standardized uptake values of 18F-FDG PET/CT imaging but not MRI correlates to pathology findings in patients with cervical cancer.

This study was to explore the correlation between the standardized uptake value (SUV) of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging and the apparent diffusion coefficient (ADC) value of magnetic resonance imaging (MRI) to the pathological features of cervical cancer (CC). The maximum and mean SUV of 18F-FDG PET/CT (SUVmax and SUVmean) and the minimum ADC (ADCmin) were collected from 72 patients with CC. The correlation between SUVmax and ADCmin was also assessed. Furthermore, the relationship between SUVmax, SUVmin, ADCmin and the clinical pathological characteristics of CC was analyzed. A significant increase in the SUVmax was observed in the group of CC cases with lymph node metastases and in the group with distant metastases compared to those without metastases (F=6.782, P=0.002; F=4.483, P=0.015). Furthermore, in the low differentiation groups compared to high/middle differentiation groups (F=3.342,P=0.024), in the squamocellular carcinoma groups compared to the adenocarcinoma and adenosquamous carcinoma groups (F=3.295, P=0.026) and finally in the International Federation of Gynecology and Obstetrics (FIGO) stage III-IV groups compared with stage III-IV groups (F=3.123, P=0.020).The SUVmean values of the lymph node metastases and distant metastases groups were significantly higher than those without lymph node metastases (F=5.802, P=0.005; F=3.486, P=0.036). We saw no correlation between the ADCmin and lymph node metastases. The SUVmax value had weak correlation with the ADCmin (r=-0.306, P=0.036). The SUVmax is most closely related to the clinical pathological characteristics of CC. An increased SUVmax suggests lymph node metastases or distant metastases, low differentiation and FIGO stage III-IV. A low negative correlation was observed between the SUVmax and ADCmin, while we observed no correlation between the ADCmin and the clinical pathological characteristics of cervical cancer.

Noninvasive assessment and quantification of tumor vascularization using [18F]FDG-PET/CT and CE-CT in a tumor model with modifiable angiogenesis\u2014an animal experimental prospective cohort study

BackgroundThis study investigated the noninvasive assessment of tumor vascularization with clinical F-18-fluorodeoxyglucose positron emission tomography/computed tomography and contrast-enhanced computed tomography ([18F]FDG-PET/CT and CE-CT) in experimental human xenograft tumors with modifiable vascularization and compared results to histology. Tumor xenografts with modifiable vascularization were established in 71 athymic nude rats by subcutaneous transplantation of human non-small-cell lung cancer (NSCLC) cells. Four different groups were transplanted with two different tumor cell lines (either A549 or H1299) alone or tumors co-transplanted with rat glomerular endothelial (RGE) cells, the latter to increase vascularization. Tumors were assessed noninvasively by [18F]FDG PET/CT and contrast-enhanced CT (CE-CT) using clinical scanners. This was followed by histological examinations evaluating tumor vasculature (CD-31 and intravascular fluorescent beads).ResultsIn both tumor lines (A549 and H1299), co-transplantation of RGE cells resulted in faster growth rates [maximal tumor diameter of 20 mm after 22 (± 1.2) as compared to 45 (± 1.8) days, p < 0.001], higher microvessel density (MVD) determined histologically after CD-31 staining [171.4 (± 18.9) as compared to 110.8 (± 11) vessels per mm2, p = 0.002], and higher perfusion as indicated by the number of beads [1.3 (± 0.1) as compared to 1.1 (± 0.04) beads per field of view, p = 0.001]. In [18F]FDG-PET/CT, co-transplanted tumors revealed significantly higher standardized uptake values [SUVmax, 2.8 (± 0.2) as compared to 1.1 (± 0.1), p < 0.001] and larger metabolic active volumes [2.4 (± 0.2) as compared to 0.4 (± 0.2) cm3, p < 0.001] than non-co-transplanted tumors. There were significant correlations for vascularization parameters derived from histology and [18F]FDG PET/CT [beads and SUVmax, r = 0.353, p = 0.005; CD-31 and SUVmax, r = 0.294, p = 0.036] as well as between CE-CT and [18F]FDG PET/CT [contrast enhancement and SUVmax, r = 0.63, p < 0.001; vital CT tumor volume and metabolic PET tumor volume, r = 0.919, p < 0.001].ConclusionsIn this study, a human xenograft tumor model with modifiable vascularization implementable for imaging, pharmacological, and radiation therapy studies was successfully established. Both [18F]FDG-PET/CT and CE-CT are capable to detect parameters closely connected to the degree of tumor vascularization, thus they can help to evaluate vascularization in tumors noninvasively. [18F]FDG-PET may be considered for characterization of tumors beyond pure glucose metabolism and have much greater contribution to diagnostics in oncology.

Combining fluorine-18 fluorodeoxyglucose positron emission tomography and pathological risk factors to predict postoperative recurrence in stage I lung adenocarcinoma.

The aim of this study was to investigate the predictive value of qualitative assessment of tumor fluorine-18 fluorodeoxyglucose (F-FDG) uptake on PET and pathological risk factors for postoperative tumor recurrence in patients with stage I lung adenocarcinoma. Eighty-seven patients with stage I lung adenocarcinoma who had undergone F-FDG-PET and sequential surgical treatment without adjuvant chemotherapy were enrolled into this retrospective study. Qualitative assessment visually compared tumor F-FDG uptake with liver uptake. Tumors with one or more risk factors of tumor size of at least 4 cm, poorly differentiated, visceral pleural invasion, and lymphovascular invasion were defined as pathological high-risk tumors. Patients with pathological high-risk tumors had a significantly (P=0.015) higher standardized uptake value. A multivariable Cox's proportional hazard analysis showed that tumor F-FDG uptake>liver uptake (adjusted hazard ratio: 3.54; 95% confidence interval: 1.36-9.21, P=0.010) and pathological high-risk tumors (adjusted hazard ratio: 2.34; 95% confidence interval: 1.13-4.87, P=0.023) were significant independent predictors of postoperative tumor recurrence. Patients with tumor F-FDG uptake>liver uptake and pathological high-risk tumors had significantly (P=0.001) worse 5-year disease-free survival (38.8%) and significantly (P=0.011) worse overall survival (68.5%). Tumor F-FDG uptake>liver uptake and pathological high-risk tumors were significant independent predictors of postoperative tumor recurrence in stage I lung adenocarcinoma. Combining the two factors improves the prediction of disease-free and overall survivals, which could offer a feasible prediction model for clinically recommending adjuvant chemotherapy.

Quantitative computed tomography texture analysis: can it improve diagnostic accuracy to differentiate malignant lymph nodes?

Background and objectiveMediastinal lymph node (LN) staging in individuals with non-small-cell lung cancer plays an important role in staging and treatment planning. This study aimed to assess the accuracy of computed tomography (CT) texture analysis (CTTA) in differentiating benign and malignant mediastinal LNs.MethodsPathologically confirmed malignant and benign mediastinal LN samples, obtained using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), were retrospectively reviewed, in addition to chest CT and 18-fluorodeoxyglucose (FDG) uptake positron emission tomography (PET) data. For each LN, CTTA was performed using “AVIEW” software (Coreline Soft, Republic of Korea) by drawing a region of interest.ResultsA total of 132 LNs from 80 patients were included and classified into two groups according to pathology results: malignant (n = 61) and benign (n = 71). In EBUS, size > 1 cm, round shape, heterogeneous echogenicity, and presence of coagulation necrosis sign were more prevalent in malignant than in benign LNs; length was the only feature that distinguished the two groups. Among CTTA features, compactness and normalized standard deviation (SD) showed differences between the two groups. The ability to distinguish malignant LNs was higher using high standard uptake value (SUV) on FDG PET/CT (SUVmax ≥ 5) and normalized SD on CTTA (area under the receiver operating characteristic curve 0.739 versus 0.742, respectively); however, normalized SD demonstrated very low sensitivity despite high specificity.ConclusionsCTTA may be helpful in distinguishing between benign and malignant LNs; however, the diagnostic value was not high. Therefore, integrated evaluation with other imaging modalities is needed.

18F] Fluorodeoxyglucose positron emission (FDG-PET) in breast cancer: Clinical utility in neoadjuvant and metastatic setting.

e12584 Background: FDG-PET in clinical practice is based on the detection of a relapse and the initial staging but its role as a predictive factor or its correlation with biological parameters is very controversial. Methods: We analyzed the SUV of FDG-PET in a cohort with 36 patients in neoadjuvant setting and 112 with metastatic disease. Results: The median of SUV in neoadjuvant was 8,95 (range 2,8-30) with higher SUV in triple negative (11,7 range 2,8-18,8) than HER2 positive (8,75 range 4-30) and luminal patients (7,9 range 4,4-16). We don´t find a correlation between the SUV with either histological and clinical variables but there was a slightly correlation with residual tumor (p:0,068) and initial node involvement (p:0,069). In the 112 metastatic cohort the median SUV was 7,95 (range 2-28) with higher SUV in triple negative (10,1 range 3,4-19) than HER2 positive (9,7 range 4-28) and luminal patients (7,6 range 2.21). We found only a correlation between the SUV and progesterone receptor value (OR 0,875 p:0,005) but not in estrogen receptor, Ki67 index and HER2 status. In the survival analysis we don´t find a correlation between the SUV value and the disease free and overall survival included the analysis for different phenotypes. Conclusions: The SUV of the FDG-PET is very variable in all phenotypes of breast cancer being higher in the triple negative phenotype and lower in the luminal. The SUV value is very similar in neoadjuvant and metastatic setting. We only correlated the SUV value with the progesterone receptor in the metastatic cohort. We don´t find a prognostic value of the initial value of SUV in the two cohorts.

Symmetry and spatial distribution of muscle glucose uptake in the lower limbs during walking measured using FDG-PET.

PurposeThis study aimed to elucidate whether muscle activity (in terms of glucose uptake) between the legs can be considered symmetrical during walking. Furthermore, we aimed to determine whether the [18F]-fluorodeoxyglucose was distributed heterogeneously throughout each muscle, and if so, whether areas of high uptake would be clustered.MethodsTen healthy participants walked on a treadmill at self-selected comfortable walking speed for a total of 90 minutes, 60 minutes before and 30 minutes after intravenous injection of 50 MBq [18F]-fluorodeoxyglucose. Thereafter, a positron emission tomography/computed tomography scan of the lower limb was acquired. Three-dimensional muscle contours of 78 (= 39x2) muscles of the left and right lower limb were semi-automatically determined from magnetic resonance imaging scans. After non-rigid registration, those muscle contours were used to extract [18F]-fluorodeoxyglucose uptake from the positron emission tomography scans.ResultsLarge asymmetries were observed in the lower leg muscles (e.g. median absolute asymmetry index of 42% in the gastrocnemius medialis) and in the gluteus minimus (30% asymmetry) and gluteus medius (15% asymmetry), whereas the uptake in the thighs was relatively symmetrical between the limbs (<6% asymmetry). These were not related to limb-dominance nor to inter-limb differences in muscle volume. The [18F]-fluorodeoxyglucose distribution was not distributed normally; most voxels had a relatively low standardized uptake value, and a minority of voxels had a relatively high standardized uptake value. The voxels with higher [18F]-fluorodeoxyglucose uptake were distributed heterogeneously; they were clustered in virtually all muscles.ConclusionThe findings in this study challenge the common assumption of symmetry in muscle activity between the limbs in healthy subjects. The clustering of voxels with high uptake suggests that even in this prolonged repetitive task, different spatial regions of muscles contribute differently to walking than others.

Utility of EBUS-TBNA in PET-positive mediastinal lymph nodes in subjects with extra-thoracic malignancy.

Background/AimPatients with primary extra-thoracic malignancy (ETM) often have hyper-metabolic mediastinal lymph nodes (HM-MLN) in the PET-scan done for initial staging or post treatment follow-up. There is scant data on the etiology of HM-MLN in such patients, which can also be due to non-malignant causes. We used endobronchial ultrasound (EBUS) guided sampling to determine the etiology of HM-MLN in patients with ETM and study the relationship between PET-SUV values and a diagnosis of malignancy in this population.Materials and methods65 consecutive patients, from March 2013 to March 2017 with either known ETM for primary staging or post-treatment follow-up, with PET CT showing HM-MLN (SUV > 2.5) were included in the study.Results65 patients with ETM had EBUS-TBNA for HM-MLN. 20/65 (30.7%) were malignant, 45/65 (69.23%) were benign MLN. In patients with benign etiology of HM-MLN, 6/45 (13.3%) had necrotising granulomatous, 24/45 (53.3%) had non- necrotising granulomatous MLN and 15/45 (33.3%) had reactive MLN. We found discordance (i.e. primary ETM responded to treatment and a new HM-MLN was detected) in 21/65 (32.3%) patients with PET-CT done for initial ETM staging, and 44/65 (67.7%) with a post-treatment PET-CT. showed. Correlating SUV with diagnoses, the SUV values in EBUS-proven malignant MLN were 8.9 ± 4.1, while they were 10.2 ± 5.57 in benign MLN. There was no statistically significant difference between the SUV of benign and malignant MLNs.ConclusionThis study shows a significant incidence of EBUS-TBNA proven benign diagnoses 45/65 (69.2%) in ‘SUV-deemed-malignant MLN’ and a poor relationship between high SUV and malignant MLN, in patients with known ETM. The ETM related HM-MLN have a significant chance of being benign, and a tissue diagnosis is imperative as it impacts on the treatment plan and prognosis.

Abstract P6-02-08: SUV max of 18F FDG-PET/CT: A predictive factor associated with pathologic complete response in luminal HER2–negative breast cancer patients (receiving neoadjuvant chemotherapy)

Abstract Purpose Neoadjuvant chemotherapy (NAC) is considered to be the standard of care for locally advanced breast cancer. When pathological complete response (pCR) is obtained with NAC it is a predictor of better outcome and often used as a surrogate for survival. However, response to NAC of luminal type breast cancer is variable and mostly limited. This study investigated the predictive relevance of several clinicopathological factors, including parameters of 18F FDG-PET/CT, on the pCR to NAC in patients with luminal HER2–negative breast cancer. Methods From 2009 to 2015, 117 hormone receptor-positive, HER2-negative breast cancer patients who were treated with NAC followed by curative surgery at the Kyungpook National University Hospital (Daegu, Korea) were retrospectively analyzed. pCR was defined as the absence of cancer cells in breast and axillary node. 18F FDG-PET/CT maximum standardized uptake value (SUV max) was measured at baseline. Patients received from 6 to 8 cycles of anthracycline-based and taxane-based NAC. Results The median age of the patients was 48 years (range-29-68 years). 104 patients (88.9%) were PR-positive, and forty-nine (41.9%) patients showed high ki-67 expression at initial diagnosis. After NAC, nine patients (7.7%) achieved pCR and patients who had high initial SUV max (≥ 9.09) achieved improved pCR rate compared to low initial SUV max (&amp;lt; 9.09) patients (77.8 % vs. 22.2%). Conclusion In luminal HER2-negative breast cancer, 18F FDG-PET/CT SUV max was useful for predicting pathologic complete response after NAC Table 1Characteristics of study populationMedian, range48 (29-68)Initial clinical T stage 1 2 3 48 (6.8) 83 (70.9) 19 (16.2) 7 (6.0)Initial clinical N stage 0 1 2 310 (8.5) 49 (41.9) 47 (40.2) 11 (9.4)Initial ER expression Negative (0-2) Weak (3-5) Strong (6-8)8 (6.8) 14 (12) 95 (81.2)Initial PR expression Negative (0-2) Weak (3-5) Strong (6-8)13 (11.1) 20 (17.1) 84 (71.8)Initial Ki-67 expression &amp;lt;14% ≥14% Not assessed55 (47) 49 (41.9) 13 (11.1)Pathologic T stage 0 I II III16 (13.7) 50 (42.7) 42 (35.9) 9 (7.7)Pathologic Stage (AJCC) pCR 1A 1B 2A 2B 3A 3C9 (7.7) 23 (19.7) 7 (6.0) 27 (23.1) 21 (17.9) 23 (19.7) 7 (6.0)Histologic grade 1 2 322 (18.8) 61 (52.1) 14 (12)Nuclear Grade 1 2 316 (13.7) 9 (7.7) 50 942.7)Pathologic complete response Yes9 (7.7)Recurrence18 (15.4)Death10 (8.5)table 2Association between pathologic complete response and clinicopathologic featuresFactorsPathologic CR NoPathologic CR YesP- valueAll patients108 (92.3)9 (7.7) Age &amp;lt;40 40-55 56-7016 (18.2) 54(61.4) 18 (20.5)2 (22.2) 6 (66.7) 1 (11.1)0.789Initial clinical T stage 1 2 3 48 (7.4) 76 (70.4) 7 (6.5) 17 (15.7)0 (0) 7 (77.8) 2 (22.2) 0 (0)0.676Initial ER expression Negative (0-2) Weak (3-5) Strong (6-8)7 (6.5) 12 (11.1) 89 (8.4)1 (11.1) 2 (22.2) 6 (66.7)0.504Initial PR expression Negative (0-2) Weak (3-5) Strong (6-8)11 (10.2) 20 (18.5) 77 (71.3)2 (22.2) 0 (0) 7 (77.8)0.247Initial Ki-67 expression &amp;lt;14% ≥14%52 (54.7) 43 (45.3)3 (33.3) 6 (66.7)0.301SUV max (tumor) &amp;lt; 9.09 ≥ 9.0972 (66.7) 36 (33.3)2 (22.2) 7 (77.8)0.012SUV max (axilla) &amp;lt; 6.08 ≥ 6.0858 (67.4) 28 (32.6)3 (42.9) 4 (57.1)0.228 Citation Format: Lee IH, Lee SJ, Lee J, Lee RK, Jung J, Park H, Lee S-w, Chae YS. SUV max of 18F FDG-PET/CT: A predictive factor associated with pathologic complete response in luminal HER2–negative breast cancer patients (receiving neoadjuvant chemotherapy) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-02-08.

Abstract WP547: FTY720 (Fingolimod) Ameliorates Ischemia Reperfusion Injury in Experimental Stroke Model

Background: Fingolimod (FTY720), a widely known sphingosine-1-phosphate (S1P) receptor agonist, was approved as a treatment for multiple sclerosis due to its strong anti-inflammatory effect. Methods: In-vivo study, FTY720 was injected intraperitoneally just before reperfusion. Neurological score and infarct volume were evaluated at Day0, 1, 3, 5, and 7 after MCAO. Evans Blue analysis and immunohistochemistry were conducted at day1 and day7. [18F]DPA-714 PET was performed 2 and 9 days after MCAO. In vitro study, in order to perform OGD, Bovine Brain Microvascular Endothelial Cells (BBMVECs) were incubated in a glucose-free medium under 1% oxygen condition, and then reperfused for 4 hours. In vitro models of ischemia/reperfusion injury were exposed to FTY720, FTY720-P, S1P and SEW (100 nM) immediately after reperfusion. The effects of FTY720 on the blood brain barrier were examined by real-time PCR analysis and immunofluorescence staining. Results: In this study, we observed that FTY720 reduced infarction size and improved neurological score after MCAO. [18F]DPA-714 PET showed a high standardized uptake value (SUV) around the ischemic area 2 days after MCAO. Although SUV was increased further 9 days after MCAO in both treatment groups, the increase was significantly inhibited in 1.5mg/kg group. In addition, FTY720 recovered the integrity of blood brain barrier which has been disrupted by ischemia/reperfusion injury. However, we observed that FTY720 can improve the integrity of blood brain barrier by inducing the translocation of tight junction and adherins junction, but FTY720 cannot ameliorate the expression of tight junction and adherins junction. Conclusions: The present results suggest that FTY720 improves neurological score, reduces infarction size, inflammatory activation and neuronal apoptosis. Especially ameliorates the integrity of Blood-Brain Barrier by inducing the translocation of tight junction and adherins junction after transient MCAO.

Active contour algorithm with discriminant analysis for delineating tumors in positron emission tomography.

In the context of cancer delineation using positron emission tomography datasets, we present an innovative approach which purpose is to tackle the real-time, three-dimensional segmentation task in a full, or at least nearly full automatized way. The approach comprises a preliminary initialization phase where the user highlights a region of interest around the cancer on just one slice of the tomographic dataset. The algorithm takes care of identifying an optimal and user-independent region of interest around the anomalous tissue and located on the slice containing the highest standardized uptake value so to start the successive segmentation task. The three-dimensional volume is then reconstructed using a slice-by-slice marching approach until a suitable automatic stop condition is met. On each slice, the segmentation is performed using an enhanced local active contour based on the minimization of a novel energy functional which combines the information provided by a machine learning component, the discriminant analysis in the present study. As a result, the whole algorithm is almost completely automatic and the output segmentation is independent from the input provided by the user. Phantom experiments comprising spheres and zeolites, and clinical cases comprising various body districts (lung, brain, and head and neck), and two different radio-tracers (18 F-fluoro-2-deoxy-d-glucose, and 11C-labeled Methionine) were used to assess the algorithm performances. Phantom experiments with spheres and with zeolites showed a dice similarity coefficient above 90% and 80%, respectively. Clinical cases showed high agreement with the gold standard (R2 = 0.98). These results indicate that the proposed method can be efficiently applied in the clinical routine with potential benefit for the treatment response assessment, and targeting in radiotherapy.

18F-FDG-PET-based radiomics features to distinguish primary central nervous system lymphoma from glioblastoma.

The differential diagnosis of primary central nervous system lymphoma from glioblastoma multiforme (GBM) is essential due to the difference in treatment strategies. This study retrospectively reviewed 77 patients (24 with lymphoma and 53 with GBM) to identify the stable and distinguishable characteristics of lymphoma and GBM in 18F-fluorodeocxyglucose (FDG) positron emission tomography (PET) images using a radiomics approach. Three groups of maps, namely, a standardized uptake value (SUV) map, an SUV map calibrated with the normal contralateral cortex (ncc) activity (SUV/ncc map), and an SUV map calibrated with the normal brain mean (nbm) activity (SUV/nbm map), were generated, and a total of 107 radiomics features were extracted from each SUV map. The margins of the ROI were adjusted to assess the stability of the features, and the area under the curve (AUC) of the receiver operating characteristic curve of each feature was compared with the SUVmax to evaluate the distinguishability of the features. Nighty-five radiomics features from the SUV map were significantly different between lymphoma and GBM, 46 features were numeric stable after marginal adjustment, and 31 features displayed better performance than SUVmax. Features extracted from the SUV map demonstrated higher AUCs than features from the further calibrated maps. Tumors with solid metabolic patterns were also separately evaluated and revealed similar results. Thirteen radiomics features that were stable and distinguishable than SUVmax in every circumstance were selected to distinguish lymphoma from glioblastoma, and they suggested that lymphoma has a higher SUV in most interval segments and is more mathematically heterogeneous than GBM. This study suggested that 18F-FDG-PET-based radiomics is a reliable noninvasive method to distinguish lymphoma and GBM.

Significance of Metabolic Tumor Volume and Total Lesion Glycolysis Measured Using ¹⁸F-FDG PET/CT in Locally Advanced and Metastatic Gallbladder Carcinoma.

PurposeThis study aimed to determine the prognostic value of new quantitative parameters of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), including metabolic tumor volume (MTV), in patients with locally advanced and metastatic gallbladder cancer (GBC).Materials and MethodsIn total, 83 patients initially diagnosed with locally advanced and metastatic GBC and who underwent 18F-FDG PET/CT at the time of initial diagnosis were retrospectively reviewed. The metabolic volume-based PET parameters of primary tumors and metastatic lesions were measured, including maximum and average standardized uptake values (SUV), MTV, and total lesion glycolysis. An overall survival (OS) analysis was performed using the Kaplan-Meier method with PET and clinical parameters. A Cox proportional hazards regression analysis was performed to determine independent prognostic factors.ResultsIn univariate analysis, pathologic differentiation (p<0.001), performance status (PS; p=0.003), C-reactive protein (CRP) level (p=0.009), and PET-related SUVmt max (the highest SUV among the metastatic lesions) (p=0.040) and MTVtotal (the sum of the MTVs of both the primary and metastatic lesions) (p=0.031), were significant for OS. In multivariate analysis, MTVtotal (hazard ratio: 2.07; 95% confidence interval: 1.23–3.48; p=0.006) remained significant for the prediction of OS, as did differentiation (p=0.001), PS (p=0.001), and CRP (p=0.039).ConclusionIn locally advanced and metastatic GBC, volume-based PET/CT parameters of the total tumor burden of malignancy, such as MTVtotal, were found to be useful for the identification of patients with poor prognosis.

Metachronous Malingnancy, 27 Years After Teflon Cordal Injection

We report a rare case of a patient known for a long-time history of iatrogenic VC paralysis, with unusual PET-CT findings. Due to a bilateral paragangliomas (PGLs), 27 years before the patient underwent a left jugulo-petrosectomy. After admission for contralateral sudden hearing loss, MRI and PET-CT scans were acquired. We tried to critically analyze the clinical relevance of multimodal imaging in an unusual condition of comorbities. Moreover, we suggested a physiopathological interpretation of collecting imagings and clinical otorhinolaryngological aspects. We could determine that high SUV in paralyzed left VC was related to a foreign-body reaction after laryngeal injection by polytetrafluoroethylene fluoropolymer resin (Teflon) performed 27 years before. Moreover, an asymptomatic pT1c mixed lung adenocarcinoma was serendipitously detected in the left lung. The SUVs of these two lesions were both compatible with neoplasms. A further possible lesion in the right lung highlighted by MRI was not confirmed by PET-CT imaging (MRI artifact). Although Teflon is no longer in use for laryngeal injection, clinicians should be aware of the potential misinterpretation laryngeal findings in patients with such a clinical history, even long time after the procedure.

FDG PET/CT as a survival prognostic factor in patients with advanced renal cell carcinoma

Accurate prediction of the outcome of molecular target-based treatment in advanced renal cell carcinoma (RCC) is an important clinical problem. Positron emission tomography/computed tomography using [18F]-2-fluoro-2-deoxyglucose (FDG PET/CT) is a noninvasive tool for the assessment of glucose accumulation which can be a marker of the biological characteristics of the tumor. In this paper, we assess FDG PET/CT as a survival prognostic marker in patients with advanced RCC. The study included 121 patients treated in the years 2011–2016 with a diagnosis of advanced renal cell carcinoma (stage IV, multifocal metastases in all patients). Assessment using FDG PET/CT was conducted by measuring the maximum standard uptake value (SUVmax) for the marker used (the highest SUV measurement result for each patient in a single examination). SUVmax measurements were compared with various clinical risk factors used as prognostic markers. The median follow-up period was 19 months (ranging from 3 to 61 months). SUVmax measurements in all patients ranged from 1.3 to 30.0 (median 6.9). Higher SUVmax was correlated with poorer prognosis. Multi-way analysis with standard risk factors revealed that SUVmax was an independent factor for overall survival (OS; p < 0.003, hazard ratio 1.312, 95% CI 1.147–1.346). For SUVmax < 7.0, median OS was 32 months. For 7.0 ≤ SUVmax < 12.0, median OS was 12.5 months. For SUVmax ≥ 12.0, median OS was 10 months. The differences were statistically significant. A preliminary SUVmax assessment conducted using FDG PET/CT can provide information useful in the prediction of survival of patients with advanced RCC.

Histone deacetylase-1 as a prognostic factor and mediator of gastric cancer progression by enhancing glycolysis

Histone deacetylase 1 (HDAC1) has been shown to be closely associated with tumor development. We investigated its effects on survival and biological behavior in gastric cancer (GC). HDAC1 expression and glycolysis activity were analyzed in a cohort of 252 samples of primary GC tumors and in vitro study. High HDAC1 (HDAC1High) staining was seen in 60.7% patients with GCs, which was significantly greater than was seen in normal epithelial cells (19.4%; P < .005). HDAC1High expression was associated with larger tumor size (P = .001), advanced T stage (P = .001), lymph node metastases (N stage; P < .001), and lymphovascular invasion (P = .005). Univariate and multivariate survival analyses showed HDAC1 expression to be an independent prognostic factor for both disease-free survival and overall survival (P < .05). In vitro studies showed a notably decreased glycolysis rate in HDAC1 knockdown cells. In patients' samples, HDAC1High expression was always accompanied with high Maximal standardized uptake value (SUVmax) value (P < .05). A hypoxia-inducible factor (HIF)-1α response element-luciferase reporter system showed HDAC1 to affect HIF1α activity in a dose-dependent manner. In conclusion, HDAC1 promotes glycolysis in GC and affects HIF-1α activity in tumor progression and metastasis. HDAC1High expression was also an independent adverse prognostic factor for overall survival and disease-free survival.

Low PR in ER(+)/HER2(-) breast cancer: high rates of TP53 mutation and high SUV.

On the basis of TP53 mutations and standardized uptake values (SUVs) from 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET), we sought to enhance our knowledge of the biology underlying low progesterone receptor (PR) expression in estrogen receptor (ER)-positive/human epidermal growth factor receptor-2 (HER2)-negative tumors. This study included 272 patients surgically treated for ER-positive, HER2-negative breast cancer and who had undergone TP53 gene sequencing. Of these, 229 patients also underwent 18F-FDG PET or PET/CT. Mutational analysis of exons 5–9 of the TP53 gene was conducted using PCR amplification and direct sequencing. The SUVs were measured using 18F-FDG-PET scan images. Twenty-eight (10.3%) tumors had a somatic TP53 mutation. The TP53 mutation rate was significantly higher in low-PR tumors than in high-PR tumors (17.1% vs 7.9%, P = 0.039). Low-PR tumors had significantly higher median SUVs than high-PR tumors (P = 0.046). The multivariable analysis revealed that SUV and age remained independent variables associated with low PR expression. An adverse impact of low PR expression on recurrence-free survival was observed in the multivariable Cox regression hazard model. We provide clinical evidence that genetic alteration of the TP53 gene and dysregulated glucose metabolism partly involve low PR expression in ER-positive and HER2-negative breast cancer.

THYMIC HYPERPLASIA AS A CASE OF FALSE-POSITIVE PET CT IN A FEMALE WITH LYNCH SYNDROME

SESSION TITLE: Disorders of the Mediastinum 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 pm - 02:15 pm INTRODUCTION: Lynch syndrome is an autosomal dominant genetic condition of defective DNA mismatch repair predisposing for malignancies. Here we present a case of Lynch syndrome with endometrial cancer and a hypermetabolic superior mediastinal lymph node on positron emission tomography-computed tomography (PET- CT). CASE PRESENTATION: An Asymptomatic 59-year old female tested positive for Lynch syndrome (PMS2 mutation) during family screening prompted by the death of her son by colon cancer after being diagnosed with Lynch syndrome. She underwent a prophylactic hysterectomy and was found to have well-differentiated adenocarcinoma of the endometrium, pT1b NxM0. Screening mammogram, colonoscopy, and upper endoscopy were negative. CT chest/abdomen/pelvis showed several lung nodules, some of which were calcified suggesting granulomas. PET-CT showed an isolated nodule (1.6 x 1.1 cm) in the upper left paratracheal area with standardized uptake values (SUV) of 11.1. She underwent ultrasound-guided biopsy of the nodule. Histopathology demonstrated scant lymphoid tissue. Flow cytometry was negative for lymphoma. Due to her Lynch syndrome and high activity on PET-CT, she underwent a second ultrasound-guided biopsy the result was suggestive of benign thymic tissue. There was no evidence of metastatic carcinoma. Repeat PET CT showed persistent hypermetabolic activity. She was referred to a thoracic surgeon for mediastinoscopy. She chose conservative observation strategy and is being followed closely. DISCUSSION: Superior mediastinal masses range from benign thymic hyperplasia to malignant etiologies such as lymphoma. Patients with Lynch syndrome are at increased risk for colorectal, endometrial, ovarian, gastric, brain, and skin cancers. However, they are not associated with chest or mediastinal malignancies.The thymus is a lymphoid organ that is active in the early years of life and atrophies in adults. Thymic hyperplasia is the proliferation of cells and increase in activity and size with normal histology seen on biopsy and is seen in young adults. Rebound thymic hyperplasia has been described in young patients treated for malignancy. (1) Increased FDG uptake was previously reported, however, the SUV ranged from 1.1 to 2.2 (2). Sakasi et al (3) reported the mean SUV to be 7.2 ± 2.9 in patients with thymic cancer. Thymic hyperplasia with SUV of 11.1 has not been reported before.Our patient had two negative core biopsies for malignancy despite having a very high SUV on PET-CT, thereby confirming a false positive scan. Our patient also did not have any obvious reasons for hyperplasia and was never treated with chemotherapy, adding to the uniqueness of the case. CONCLUSIONS: Thymic malignancies are typically associated with highly elevated SUVs on PET-CT however, on occasion, hyperplasia can cause mild elevations of an SUV. Our patient had a strongly positive PET CT but benign thymic tissue on biopsy. Reference #1: Sarji A. Physiological uptake in FDG PET simulating disease. Biomed Imaging Interv J. 2006 Oct-Dec; 2(4): e59. Reference #2: Wittram C, Fischman A, Mark E, et al. Thymic Enlargement and FDG Uptake in Three Patients: CT and FDG Positron Emission Tomography Correlated with Pathology. American Journal of Roentgenology. 2003; 180: 519-522. Reference #3: Sasaki M, Kuwabara Y, Ichiya Y, et al. Differential diagnosis of thymic tumors using a combination of 11C-methionine PET and FDG PET. J Nucl Med 1999; 40:1595-1601. DISCLOSURES: No relevant relationships by Amit Diwakar, source=Web Response No relevant relationships by Ahmad JABRI, source=Web Response no disclosure on file for Jason Lane; No relevant relationships by Colin McLaughlin, source=Web Response