FDG-PET/CT after two cycles of R-CHOP in DLBCL predicts complete remission but has limited value in identifying patients with poor outcome - final result of a UK National Cancer Research Institute prospective study.

The UK National Cancer Research Institute initiated a prospective study (UKCRN-ID 1760) to assess the prognostic value of early fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in diffuse large B-cell lymphoma (DLBCL). In total, 189 patients with DLBCL treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) had baseline and post-cycle-2 PET (PET2) within a quality assurance framework. Treatment decisions were based on CT; PET2 was archived for central blinded reporting after treatment completion. The association of PET2 response with end-of-treatment CT, progression-free (PFS) and overall survival (OS) was explored. The end-of-treatment complete response rate on CT was 83·9%, 75·0%, 70·5%, 40·4% and 36·4% for Deauville score (DS) 1 (n = 34), 2 (n = 39), 3 (n = 46), 4 (n = 56) and 5 (n = 14) (P < 0·001); and 64·1% and 50·0% for the maximum standardised uptake value (∆SUVmax ) of ≥66% (n = 168) and <66% (n = 21), respectively (P = 0·25). After a median 5·4 years of follow-up, the 5-year PFS was 69·4%, 72·8%, 76·7%, 71·2% and 47·6% by DS 1-5 (P = 0·01); and 72·6% and 57·1% by ∆SUVmax of ≥66% and <66% (P = 0·03), respectively. The association with DS remained in multivariable analyses, and was consistent for OS. Early complete metabolic response (DS 1-3) at interim PET/CT after two cycles of R-CHOP in DLBCL was associated with a higher end-of-treatment complete and overall response rate; however, only DS-5 patients had inferior PFS and OS.

Routine restaging after primary non-surgical treatment of laryngeal squamous cell carcinoma-a review.

PURPOSE: Treatment of patients with laryngeal squamous cell carcinoma with radiotherapy or chemoradiation is an established alternative to laryngeal surgery in many cases, but particularly for advanced tumors without cartilage invasion. Imaging modalities face the challenge of distinguishing between posttherapeutic changes and residual disease in the complex anatomic subsite of the larynx. Guidelines concerning restaging of head and neck squamous cell carcinomas (HNSCC) are presented by the National Comprehensive Cancer Network (NCCN) and other national guidelines, but clearly defined recommendations for routine restaging particularly for laryngeal cancer are lacking. METHODS: A systematic search was carried out in PubMed to identify studies evaluating routine restaging methods after primary non-surgical treatment of laryngeal squamous cell carcinoma from 2009 to 2020. RESULTS: Only three studies were deemed eligible, as they included at least ≥50% patients with laryngeal squamous cell carcinoma and evaluated imaging modalities to detect residual cancer. The small number of studies in our review suggest restaging with fluoro-deoxy-glucose positron-emission tomography/computed tomography (FDG PET/CT) 3 months after initial treatment, followed by direct laryngoscopy with biopsy of the lesions identified by FDG PET/CT. CONCLUSION: Studies evaluating restaging methods after organ-preserving non-surgical treatment of laryngeal carcinoma are limited. As radiotherapy (RT), chemoradiotherapy (CRT), systemic therapy followed by RT and radioimmunotherapy are established alternatives to surgical treatment, particularly in advanced laryngeal cancers, further studies are needed to assess and compare different imaging modalities (e.g. PET/CT, MRI, CT, ultrasound) and clinical diagnostic tools (e.g., video laryngoscopy, direct laryngoscopy) to offer patients safe and efficient restaging strategies. PET or PET/CT 3 months after initial treatment followed by direct laryngoscopy with biopsy of the identified lesions has the potential to reduce the number of unnecessary laryngoscopies.

Prognostic impact of total metabolic tumor volume in large B-cell lymphoma patients receiving CAR T-cell therapy.

Chimeric antigen receptor (CAR) T-cell therapy provides long-term remissions in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). Total metabolic tumor volume (TMTV) assessed by 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) has a confirmed prognostic value in the setting of chemoimmunotherapy, but its predictive role with CAR T-cell therapy is not fully established. Thirty-five patients with R/R LBCL who received CAR T-cells were included in the study. TMTV and maximum standardized uptake value (SUVmax) were measured at baseline and 1-month after CAR T-cell infusion. Best response included 9 (26%) patients in complete metabolic response (CMR) and 16 (46%) in partial metabolic response (PMR). At a median follow-up of 7.6 months, median PFS and OS were 3.4 and 8.2 months, respectively. A high baseline TMTV (≥ 25 cm3) was associated with a lower PFS (median PFS, 2.3 vs. 8.9 months; HR = 3.44 [95% CI 1.18-10.1], p = 0.02). High baseline TMTV also showed a trend towards shorter OS (HR = 6.3 [95% CI 0.83-47.9], p = 0.08). Baseline SUVmax did not have a significant impact on efficacy endpoints. TMTV and SUVmax values showed no association with adverse events. Metabolic tumor burden parameters measured by 18FDG-PET before CAR T-cell infusion can identify LBCL patients who benefit most from this therapy.

Bone marrow tracer uptake pattern of PET-CT in multiple myeloma: image interpretation and prognostic value.

PURPOSE: To evaluate the prognostic value of bone marrow (BM) imaging pattern and other imaging findings assessed by 18F-FDG PET-CT in multiple myeloma(MM) and to find out the image interpretation cut-off to define different BM tracer uptake pattern. MATERIALS AND METHODS: We retrospectively studied PET-CT examinations and clinical data of 100 healthy individuals and 172 newly diagnosed MM patients. A BM uptake > liver SUVmean was selected as the positivity cut-off of pathological uptake in BM after comparing BM uptake in normal control and MM patients. With this interpretation cut-off, we defined the BM FDG uptake pattern as four types: normal, focal, diffuse, and mixed. The clinical correlation and prognostic value of BM uptake pattern were evaluated. The findings were validated in an independent prospective cohort with 72 MM patients. RESULTS: In MM cohort, 34.9% patients had focal BM uptake pattern, 3.5% had diffuse pattern, 38.4% had mixed pattern, and 23.3% had normal BM uptake. Diffuse/mixed pattern was correlated with clinical and imaging parameters indicating high tumor burden, and inferior progression free survival (PFS; 3-year-PFS 26.8%) and overall survival (OS; 3-year-OS 50.6%). BM uptake pattern was an independent prognostic factor and diffuse/mixed pattern was associated with inferior OS (P = 0.037, HR 7.16) and PFS (P = 0.015, HR 7.77). The prognostic value of BM uptake pattern was also confirmed in validation set. CONCLUSION: We propose an FDG uptake higher than liver as the positivity cut-off to discriminate between physiological and pathological uptake in BM and defined four BM FDG uptake pattern. BM FDG uptake pattern is a reliable prognostic predictor of MM.

PET/MRI for staging patients with Hodgkin lymphoma: equivalent results with PET/CT in a prospective trial.

To compare FDG-PET/unenhanced MRI and FDG-PET/diagnostic CT in detecting infiltration in patients with newly diagnosed Hodgkin lymphoma (HL). The endpoint was equivalence between PET/MRI and PET/CT in correctly defining the revised Ann Arbor staging system. Seventy consecutive patients with classical-HL were prospectively investigated for nodal and extra-nodal involvement during pretreatment staging with same-day PET/CT and PET/MRI. Findings indicative of malignancy with the imaging procedures were regarded as lymphoma infiltration; in case of discrepancy, positive-biopsy and/or response to treatment were evidenced as lymphoma. Sixty of the 70 (86%) patients were evaluable having completed the staging program. Disease staging based on either PET/MRI or PET/CT was correct for 54 of the 60 patients (90% vs. 90%), with difference between proportions of 0.0 (95% CI, -9 to 9%; P=0.034 for the equivalence test). As compared with reference standard, invasion of lymph nodes was identified with PET/MRI in 100% and with PET/CT in 100%, of the spleen with PET/MRI in 66% and PET/CT in 55%, of the lung with PET/MRI in 60% and PET/CT in 100%, of the liver with PET/MRI in 67% and PET/CT in 100%, and of the bone with PET/MRI in 100% and PET/CT in 50%. The only statistically significant difference between PET/MRI and PET/CT was observed in bony infiltration detection rates. For PET/CT, iodinate contrast medium infusions' average was 86 mL, and exposure to ionizing radiation was estimated to be 4-fold higher than PET/MRI. PET/MRI is a promising safe new alternative in the care of patients with HL.

Assessment of Waldeyer's ring in pediatric and adolescent Hodgkin lymphoma patients-Importance of multimodality imaging: Results from the EuroNet-PHL-C1 trial.

BACKGROUND: In the EuroNet Pediatric Hodgkin Lymphoma (EuroNet-PHL) trials, decision on Waldeyer's ring (WR) involvement is usually based on clinical assessment, that is, physical examination and/or nasopharyngoscopy. However, clinical assessment only evaluates mucosal surface and is prone to interobserver variability. Modern cross-sectional imaging technology may provide valuable information beyond mucosal surface, which may lead to a more accurate WR staging. PATIENTS, MATERIALS, AND METHODS: The EuroNet-PHL-C1 trial recruited 2102 patients, of which 1752 underwent central review including reference reading of their cross-sectional imaging data. In 14 of 1752 patients, WR was considered involved according to clinical assessment. In these 14 patients, the WR was re-assessed by applying an imaging-based algorithm considering information from 18 F-fluorodeoxyglucose positron emission tomography, contrast-enhanced computed tomography, and/or magnetic resonance imaging. For verification purposes, the imaging-based algorithm was applied to 100 consecutive patients whose WR was inconspicuous on clinical assessment. RESULTS: The imaging-based algorithm confirmed WR involvement only in four of the 14 patients. Of the remaining 10 patients, four had retropharyngeal lymph node involvement and six an inconspicuous WR. Applying the imaging-based algorithm to 100 consecutive patients with physiological appearance of their WR on clinical assessment, absence of WR involvement could be confirmed in 99. However, suspicion of WR involvement was raised in one patient. CONCLUSIONS: The imaging-based algorithm was feasible and easily applicable at initial staging of young patients with Hodgkin lymphoma. It increased the accuracy of WR staging, which may contribute to a more individualized treatment in the future.

Discrepancies between F-18-FDG PET/CT findings and conventional imaging in Langerhans cell histiocytosis.

BACKGROUND: Accurate risk stratification of Langerhans cell histiocytosis (LCH) is essential as management can range from conservative in single system, low risk for central nervous system (CNS) involvement lesions to intensive chemotherapy for multisystem or high-risk disease. Additionally, being able to differentiate metabolically active from inactive lesions is essential for both prognostic reasons and to avoid potentially unnecessary treatment. METHODS: A retrospective review was performed on all patients with histopathology-confirmed LCH at Cincinnati Children's Hospital Medical Center (CCHMC) between 2009 and 2019. RESULTS: One hundred seven positron emission tomography (PET)/computerized tomography (CT) images were included in the review. A discrepancy between PET/CT and conventional imaging occurred on 53 occasions. On 13 occasions, increased uptake was observed on PET in an area with no identifiable lesion on conventional imaging. On 40 occasions, lesions were found on conventional imaging where no increased uptake was observed on PET. On eight skeletal surveys, three other radiographs, four diagnostic CTs, five localization CTs, and one bone scan, no lesion was identified in an area with increased fluorodeoxyglucose (FDG) uptake. This occurred exclusively in bone. On nine skeletal surveys, one other radiograph, four diagnostic CTs, six localization CTs, 19 magnetic resonance imaging (MRI) scans, and one bone scan, a lesion was identified in a location without increased FDG uptake. This occurred in bone, CNS, and lungs. CONCLUSION: F-18-FDG PET/CT is vital in the evaluation of LCH lesions given its ability to detect LCH lesions not detectable on conventional imaging modalities, as well as its ability to distinguish metabolically active from inactive disease. MRI and diagnostic CT are still useful adjunctive tests for identification of CNS and lung lesions.

Clinical Perspectives of Theranostics.

Theranostics is a precision medicine which integrates diagnostic nuclear medicine and radionuclide therapy for various cancers throughout body using suitable tracers and treatment that target specific biological pathways or receptors. This review covers traditional theranostics for thyroid cancer and pheochromocytoma with radioiodine compounds. In addition, recent theranostics of radioimmunotherapy for non-Hodgkin lymphoma, and treatment of bone metastasis using bone seeking radiopharmaceuticals are described. Furthermore, new radiopharmaceuticals for prostatic cancer and pancreatic cancer have been added. Of particular, F-18 Fluoro-2-Deoxyglucose (FDG) Positron Emission Tomography (PET) is often used for treatment monitoring and estimating patient outcome. A recent clinical study highlighted the ability of alpha-radiotherapy with high linear energy transfer (LET) to overcome treatment resistance to beta--particle therapy. Theranostics will become an ever-increasing part of clinical nuclear medicine.

The effects of season change and fasting on Brown adipose tissue FDG-PET in mice.

It is widely reported that BAT is more frequently observed in patients during the winter season, and its activities could vary significantly under different conditions. However, whether this phenomenon is entirely caused by low temperature or other factors is not very clear. In this study, we tried to explore the seasonal fluctuation of FDG-PET BAT using mouse models that were from the same genetic breed and raised in a well-controlled environment. We also compared these variations with the effects of fasting and cold stimulation on BAT activities in these mice. In overnight fasted mice, the FDG-PET BAT was the highest in standardized uptake value (SUV) in the winter season. The values were much lower in all other seasons, especially in the summer. Compared to regular feeding, overnight fasting reduced BAT SUV, and refeeding after fasting could fully recover BAT activities. Fasted mice also did not respond to cold environment stimulation. After refeeding, their BAT thermogenic activities became normal. These results suggest that BAT FDG-PET SUV measurements vary significantly with the season and highlight the importance of taking into account the seasonal effect and fasting status in BAT evaluation studies using FDG-PET imaging.

Impact of 18F-FDG-PET/CT on the identification of regional lymph node metastases and delineation of the primary tumor in esophageal squamous cell carcinoma patients.

PURPOSE: In patients undergoing chemoradiation for esophageal squamous cell carcinoma (ESCC), the extent of elective nodal irradiation (ENI) is still discussed controversially. This study aimed to analyze patterns of lymph node metastases and their correlation with the primary tumor using 18F­fludeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans. METHODS: 102 ESCC patients with pre-treatment FDG-PET/CT scans were evaluated retrospectively. After exclusion of patients with low FDG uptake and patients without FDG-PET-positive lymph node metastases (LNM), 76 patients were included in the final analysis. All LNM were assigned to 16 pre-defined anatomical regions and classified according to their position relative to the primary tumor (above, at the same height, or below the primary tumor). In addition, the longitudinal distance to the primary tumor was measured for all LNM above or below the primary tumor. The craniocaudal extent (i.e., length) of the primary tumor was measured using FDG-PET imaging (LPET) and also based on all other available clinical and imaging data (endoscopy, computed tomography, biopsy results) except FDG-PET (LCT/EUS). RESULTS: Significantly more LNM were identified with 18F­FDG-PET/CT (177 LNM) compared to CT alone (131 LNM, p < 0.001). The most common sites of LNM were paraesophageal (63% of patients, 37% of LNM) and paratracheal (33% of patients, 20% of LNM), while less than 5% of patients had supraclavicular, subaortic, diaphragmatic, or hilar LNM. With regard to the primary tumor, 51% of LNM were at the same height, while 25% and 24% of lymph node metastases were above and below the primary tumor, respectively. For thirty-three LNM (19%), the distance to the primary tumor was larger than 4 cm. No significant difference was seen between LCT/EUS (median 6 cm) and LPET (median 6 cm, p = 0.846) CONCLUSION: 18F­FDG-PET can help to identify subclinical lymph node metastases which are located outside of recommended radiation fields. PET-based involved-field irradiation might be the ideal compromise between small treatment volumes and decreasing the risk of undertreatment of subclinical metastatic lymph nodes and should be further evaluated.

Longitudinal FDG-PET scan study of brain changes in mice with cancer-induced bone pain and after morphine analgesia.

Morphine is the most commonly used drug for treating physical and psychological suffering caused by advanced cancer. Although morphine is known to elicit multiple supraspinal analgesic effects, its behavioral correlates with respect to the whole-brain metabolic activity during cancer-induced bone pain have not been elucidated. We injected 4T1 mouse breast cancer cells into the left femur bone marrow cavity of BALB/c mice. All mice developed limb use deficits, mechanical allodynia, and hypersensitivity to cold, which were effectively suppressed with morphine. Serial 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was performed for each mouse before cancer induction (0 day), after cancer-induced bone pain was established (14 days), and during effective morphine treatment (16 days). The longitudinal FDG-PET imaging analysis demonstrated that cancer-induced bone pain increased glucose uptake in the insular cortex and hypothalamus and decreased the activity of the retrosplenial cortex. Morphine reversed the activation of the insular cortex and hypothalamus. Furthermore, morphine activated the amygdala and rostral ventromedial medulla and suppressed the activity of anterior cingulate cortex. Our findings of hypothalamic and insular cortical activation support the hypothesis that cancer-induced bone pain has strong inflammatory and affective components in freely moving animals. Morphine may provide descending inhibitory and facilitatory actions in the treatment of cancer-induced bone pain in a clinical setting.

18F-FDG PET/CT Quantitative Parameters and Texture Analysis Effectively Differentiate Endometrial Precancerous Lesion and Early-Stage Carcinoma.

OBJECTIVE: This study evaluated the metabolic parameters and texture features of fluorodeoxyglucose positron emission tomography-computed tomography (PET/CT) for the diagnosis and differentiation of endometrial atypical hyperplasia (EAH), EAH with field cancerization (FC), and stage 1A endometrial carcinoma (EC 1a). MATERIALS AND METHODS: We retrospectively analyzed the metabolic parameters of PET/CT in 170 patients with diagnoses confirmed by pathology, including 57 cases of EAH (57/170, 33.53%), 45 cases of FC (45/170, 26.47%), and 68 cases of EC 1a (68/170, 40.0%). Then, the texture features of each tumor were extracted and compared with the metabolic parameters and pathological results using nonparametric tests and linear regression analysis. The diagnostic performance was assessed by the area under the curve (AUC) values obtained from receiver operating characteristic analysis. RESULTS: There were moderate positive correlations between the PET standardized uptake values (SUVpeak, SUVmax, and SUVmean) and postoperative pathological features with correlation coefficients (rs) of 0.663, 0.651, and 0.651, respectively (P < .001). Total lesion glycolysis showed relatively low correlation with pathological characteristics (rs = 0.476), whereas metabolic tumor volume and age showed the weakest correlations (rs = 0.186 and 0.232, respectively). To differentiate between the diagnosis of EAH and FC, SUVmax displayed the largest AUC of 0.857 (sensitivity, 82.2%; specificity, 84.2%). Five texture features were screened out as Percentile 40, Percentile 45, InverseDifferenceMoment_AllDirection_offset 1, InverseDifferenceMoment_angle 45_offset 4, and ClusterProminence_angle 135_offset 7 (P < .001) by linear model of texture analysis (AUC = 0.851; specificity = 0.692; sensitivity = 0.871). To differentiate between the diagnoses of FC and EC 1a, SUVpeak displayed the largest AUC of 0.715 (sensitivity, 67.6%; specificity, 77.8%), and 2 texture features were identified as Percentile 10 and CP_angle 135_offset 7 (AUC = 0.819; specificity = 0.871; sensitivity = 0.766; P < .001). CONCLUSIONS: SUVmax and SUVpeak had the highest diagnostic values for EAH, FC, and EC 1a compared with the other tested parameters. SUVmax, Percentile 40, Percentile 45, InverseDifferenceMoment_AllDirection_offset 1, InverseDifferenceMoment_angle 45_offset 4, and ClusterProminence_angle 135_offset 7 distinguished EAH from FC. SUVpeak, Percentile 10, and ClusterProminence_angle 135_offset 7 distinguished FC from EC 1a. This study showed that the addition of texture features provides valuable information for differentiating EAH, FC, and EC 1a diagnoses.

Predicting Alzheimer Disease From Mild Cognitive Impairment With a Deep Belief Network Based on 18F-FDG-PET Images.

OBJECTIVE: Accurate diagnosis of early Alzheimer disease (AD) plays a critical role in preventing the progression of memory impairment. We aimed to develop a new deep belief network (DBN) framework using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) metabolic imaging to identify patients at the mild cognitive impairment (MCI) stage with presymptomatic AD and to discriminate them from other patients with MCI. METHODS: 18F-fluorodeoxyglucose-PET images of 109 patients recruited in the ongoing longitudinal Alzheimer's Disease Neuroimaging Initiative study were included in this analysis. Patients were grouped into 2 classes: (1) stable mild cognitive impairment (n = 62) or (2) progressive mild cognitive impairment (n = 47). Our framework is composed of 4 steps: (1) image preprocessing: normalization and smoothing; (2) identification of regions of interest (ROIs); (3) feature learning using deep neural networks; and (4) classification by support vector machine with 3 kernels. All classification experiments were performed with a 5-fold cross-validation. Accuracy, sensitivity, and specificity were used to validate the results. RESULT: A total of 1103 ROIs were obtained. One hundred features were learned from ROIs using the DBN. The classification accuracy using linear, polynomial, and RBF kernels was 83.9%, 79.2%, and 86.6%, respectively. This method may be a powerful tool for personalized precision medicine in the population with prediction of early AD progression.

Prognostic and Predictive Values of Metabolic Parameters of 18F-FDG PET/CT in Patients With Non-Small Cell Lung Cancer Treated With Chemotherapy.

OBJECTIVES: Increasing interests have been focused on using artificial intelligence (AI) to extend prognostic value of medical imaging. Feature extraction is a critical step for successful application of AI. The aim of this study was to explore several metabolic parameters measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) as potential AI features in predicting the effectiveness of chemotherapy in patients with non-small cell lung cancer (NSCLC). METHODS: A set of metabolic parameters of PET/CT and clinical characteristics were detected from 137 patients with NSCLC treated with at least 1 cycle of chemotherapy. Survival receiver-operating characteristic (ROC) analysis was used to define the more significant parameters chosen for the following survival analysis. Patient survival was analyzed by Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: Survival ROC showed that maximum standardized uptake value (SUVmax), metabolic tumor volume 50% (MTV50), and total lesion glycolysis 50% (TLG50) had larger area under the curve, and the optimal cutoff values were 11.72, 4.04, and 34.55, respectively. Univariate and multivariate analyses synergistically showed that late PET/CT stage and MTV50 >4.04 were independent factors of poor survival in patients with NSCLC who received chemotherapy. CONCLUSIONS: Several potential prognostic biomarkers of PET/CT imaging have been extracted for predicting survival and selecting patients with NSCLC who are more likely to benefit from chemotherapy. The identification may accelerate the development of AI methods to improve treatment outcome for NSCLC.

Extracellular cold inducible RNA-binding protein mediates binge alcohol-induced brain hypoactivity and impaired cognition in mice.

BACKGROUND: Alcohol abuse affects the brain regions responsible for memory, coordination and emotional processing. Binge alcohol drinking has shown reductions in brain activity, but the molecular targets have not been completely elucidated. We hypothesized that brain cells respond to excessive alcohol by releasing a novel inflammatory mediator, called cold inducible RNA-binding protein (CIRP), which is critical for the decreased brain metabolic activity and impaired cognition. METHODS: Male wild type (WT) mice and mice deficient in CIRP (CIRP-/-) were studied before and after exposure to binge alcohol level by assessment of relative brain glucose metabolism with fluorodeoxyglucose (18FDG) and positron emission tomography (PET). Mice were also examined for object-place memory (OPM) and open field (OF) tasks. RESULTS: Statistical Parametric Analysis (SPM) of 18FDG-PET uptake revealed marked decreases in relative glucose metabolism in distinct brain regions of WT mice after binge alcohol. Regional analysis (post hoc) revealed that while activity in the temporal (secondary visual) and limbic (entorhinal/perirhinal) cortices was decreased in WT mice, relative glucose metabolic activity was less suppressed in the CIRP-/- mice. Group and condition interaction analysis revealed differing responses in relative glucose metabolism (decrease in WT mice but increase in CIRP-/- mice) after alcohol in brain regions including the hippocampus and the cortical amygdala where the percent changes in metabolic activity correlated with changes in object discrimination performance. Behaviorally, alcohol-treated WT mice were impaired in exploring a repositioned object in the OPM task, and were more anxious in the OF task, whereas CIRP-/- mice were not impaired in these tasks. CONCLUSION: CIRP released from brain cells could be responsible for regional brain metabolic hypoactivity leading to cognitive impairment under binge alcohol conditions.

Use of 18F-FDG PET/CT texture analysis to diagnose cardiac sarcoidosis.

PURPOSE: 18F-fluorodeoxyglocose positron emission tomography (FDG PET) plays a significant role in the diagnosis of cardiac sarcoidosis (CS). Texture analysis is a group of computational methods for evaluating the inhomogeneity among adjacent pixels or voxels. We investigated whether texture analysis applied to myocardial FDG uptake has diagnostic value in patients with CS. METHODS: Thirty-seven CS patients (CS group), and 52 patients who underwent FDG PET/CT to detect malignant tumors with any FDG cardiac uptake (non-CS group) were studied. A total of 36 texture features from the histogram, gray-level co-occurrence matrix (GLCM), gray-level run length matrix (GLRLM), gray-level zone size matrix (GLZSM) and neighborhood gray-level difference matrix (NGLDM), were computed using polar map images. First, the inter-operator and inter-scan reproducibility of the texture features of the CS group were evaluated. Then, texture features of the patients with CS were compared to those without CS lesions. RESULTS: Twenty-eight of the 36 texture features showed high inter-operator reproducibility with intraclass correlation coefficients (ICCs) over 0.80. In addition, 17 of the 36 showed high inter-scan reproducibility with ICCs over 0.80. The SUVmax showed no difference between the CS and non-CS group [7.36 ± 2.77 vs. 8.78 ± 4.65, p = 0.45, area under the curve (AUC) = 0.60]. By contrast, 16 of the 36 texture features could distinguish CS from non-CS grsoup with AUC > 0.80. Multivariate logistic regression analysis after hierarchical clustering concluded that long-run emphasis (LRE; P = 0.0004) and short-run low gray-level emphasis (SRLGE; P = 0.016) were significant independent factors that could distinguish between the CS and non-CS groups. Specifically, LRE was significantly higher in CS than in non-CS (30.1 ± 25.4 vs. 11.4 ± 4.6, P < 0.0001), with high diagnostic ability (AUC = 0.91), and had high inter-operator reproducibility (ICC = 0.98). CONCLUSIONS: The texture analysis had high inter-operator and high inter-scan reproducibility. Some of texture features showed higher diagnostic value than SUVmax for CS diagnosis. Therefore, texture analysis may have a role in semi-automated systems for diagnosing CS.

Low hexokinase-2 expression-associated false-negative 18F-FDG PET/CT as a potential prognostic predictor in patients with multiple myeloma.

PURPOSE: False-negative 18F-FDG PET/CT, which is associated with low hexokinase-2 (HK2) expression in multiple myeloma (MM), is a new concept that is relevant for diagnosis and treatment response assessment. This study aimed to investigate the prognostic relevance of low HK2 expression-associated false-negative PET/CT in patients with MM. METHODS: Ninety consecutive patients, with newly diagnosed MM, receiving novel agents during induction therapy were enrolled in this retrospective study. Patients were divided into three groups according to the combination of the positivity of PET/CT and whole-body diffusion-weighted magnetic resonance imaging (DWMRI), namely, negative DWMRI, false-negative PET/CT, and positive PET/CT. RESULTS: False-negative PET/CT was observed in 12% patients who were older, had documented clinical history of smouldering MM, and showed lower HK2 expression levels than the positive PET/CT patients. False-negative PET/CT patients showed a clear trend of longer time to next treatment (TTNT) and progression-free survival (PFS) than the positive PET/CT patients (P = 0.035 and 0.071, respectively). Furthermore, TTNT and PFS of false-negative PET/CT patients were similar to those of patients without established high-risk PET/CT findings and significantly longer than those of high-risk PET/CT patients (P = 0.013 and 0.047, respectively). CONCLUSIONS: This study showed, for the first time, that low HK2 expression-associated false-negative PET/CT was associated with relatively better prognosis in patients with newly diagnosed MM, suggesting that this phenomenon may not undermine the established PET/CT-based prognostication. Furthermore, this phenomenon may be useful for identifying patients at lower risk of disease progression among those with myelomatous lesions on DWMRI.

Pretreatment 18F-FDG PET/CT combined with quantification of clonal circulating plasma cells as a potential risk model in patients with newly diagnosed multiple myeloma.

PURPOSE: Both 18F-FDG PET/CT and clonal circulating plasma cell (CPC) quantification are emerging tools for multiple myeloma (MM) prognostication that have been validated in recent studies. This study investigated the value of PET/CT coupled with CPC quantification for MM prognostication that may contribute to future risk-adapted treatment. METHODS: We retrospectively analysed the prognostic relevance of a combination of pretreatment PET/CT findings and CPC levels in 163 consecutive patients with newly diagnosed, symptomatic MM receiving novel agents during induction therapies. RESULTS: High-risk PET/CT findings and elevated CPC levels were defined by the presence of >3 focal lesions with or without extramedullary disease and CPCs ≥0.10% of the total mononuclear cells evaluated, respectively. Subsequently, patients were divided into three groups: PET-CPC stage I included patients with no high-risk PET/CT findings and low CPC levels; stage III included patients with high-risk PET/CT findings and high CPC levels; and stage II included the remaining patients. The three groups of patients differed significantly in terms of both progression-free survival (PFS) and overall survival (OS) (median PFS: not reached [NR] and 36.4 and 15.9 months, and median OS: NR, NR, and 40.4 months for stages I, II, and III, respectively; P < 0.001 for both PFS and OS). This system discriminated both PFS and OS even among younger (age < 75 years) or older (≥ 75 years) patients, patients with Revised International Staging System stage II or III, and patients with or without high-risk cytogenetic characteristics. In the multivariate analysis, the PET-CPC staging system remained prognostic for both PFS and OS. CONCLUSIONS: The PET-CPC staging system predicted survival outcomes independently of established risk factors in patients with newly diagnosed MM. Pretreatment 18F-FDG PET/CT assessment combined with CPC quantification may improve the prognostication of MM and facilitate the development of novel risk-adapted approaches for MM.

Comparing diagnostic accuracy of 18F-FDG-PET/CT, contrast enhanced CT and combined imaging in patients with suspected vascular graft infections.

BACKGROUND: To evaluate the diagnostic accuracy of positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (PET/CT), contrast-enhanced CT (CE-CT), and a combined imaging approach (CE-PET/CT) in patients with suspected vascular graft infection (VGI). METHODS: PET/CT and CE-CT were performed prospectively in 23 patients with suspected VGI. Diagnostic accuracy for PET/CT was assessed by using previously suggested cut-off points for maximum standardized uptake values (SUVmax) measured in the vicinity of the graft. Using a new 4-point scale for visual grading, two readers independently assessed the diagnostic accuracy for CE-CT and combined CE-PET/CT. Microbiological culture, obtained after open biopsy or graft explantation, and clinical follow-up of the patients served as the standard of reference. RESULTS: Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of PET/CT for the diagnosis of VGI was 100%, 50%, 100%, 72.2%, and 78.3%, using the most favorable SUVmax cut-off ≥ 4.9. Respective values for CE-CT were 100%, 50%, 100%, 72.2%, and 78.3% for reader 1, and 92.3%, 80%, 88.9%, 85.7%, and 86.9% for reader 2; while respective values for combined CE-PET/CT were 100%, 70%, 100%, 81.3%, and 86.9% for reader 1, and 100%, 80%, 100%, 86.7%, and 91.3% for reader 2. Additionally, imaging provided a conclusive clinical diagnosis in patients without graft infection (i.e., other sites of infection): five of ten patients with CE-CT, six of ten patients with PET/CT, and seven of ten patients with combined CE-PET/CT. CONCLUSION: The diagnostic accuracy of combined CE-PET/CT in patients with suspected VGI is very high. The combination of the high sensitivity of PET/CT in detecting metabolically active foci in infection, and the high specificity of CE-CT in detecting anatomic alterations, appears to be the reason why combined imaging outperforms stand-alone imaging in diagnosing VGI and may be supportive in future decision-making of difficult cases of suspected VGI. Clinical Trials.gov Identifier: NCT01821664.

Clinical value of FDG-PET/CT in bacteremia of unknown origin with catalase-negative gram-positive cocci or Staphylococcus aureus.

INTRODUCTION: Bacteremia is associated with high mortality, especially when the site of infection is unknown. While conventional imaging usually focus on specific body parts, FDG-PET/CT visualizes hypermetabolic foci throughout the body. PURPOSE: To investigate the ability of FDG/PET-CT to detect the site of infection and its clinical impact in bacteremia of unknown origin with catalase-negative Gram-positive cocci (excluding pneumococci and enterococci) or Staphylococcus aureus (BUOCSA). METHODS: We retrospectively identified 157 patients with 165 episodes of BUOCSA, who subsequently underwent FDG-PET/CT. Data were collected from medical records. Decision regarding important sites of infection in patients with bacteremia was based on the entire patient course and served as reference diagnosis for comparison with FDG-PET/CT findings. FDG-PET/CT was considered to have high clinical impact if it correctly revealed site(s) of infection in areas not assessed by other imaging modalities or if other imaging modalities were negative/equivocal in these areas, or if it established a new clinically relevant diagnosis, and/or led to change in antimicrobial treatment. RESULTS: FDG-PET/CT detected sites of infection in 56.4% of cases and had high clinical impact in 47.3%. It was the first imaging modality to identify sites of infection in 41.1% bacteremia cases, led to change of antimicrobial therapy in 14.7%, and established a new diagnosis unrelated to bacteremia in 9.8%. Detection rate and clinical impact were not significantly influenced by duration of antimicrobial treatment preceding FDG-PET/CT, days from suspicion of bacteremia to FDG-PET/CT-scan, type of bacteremia, or cancer. CONCLUSION: FDG-PET/CT appears clinically useful in BUOCSA. Prospective studies are warranted for confirmation.