Simultaneous FDG-PET/MRI detects hippocampal subfield metabolic differences in AD/MCI.

The medial temporal lobe is one of the most well-studied brain regions affected by Alzheimer's disease (AD). Although the spread of neurofibrillary pathology in the hippocampus throughout the progression of AD has been thoroughly characterized and staged using histology and other imaging techniques, it has not been precisely quantified in vivo at the subfield level using simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI). Here, we investigate alterations in metabolism and volume using [18F]fluoro-deoxyglucose (FDG) and simultaneous time-of-flight (TOF) PET/MRI with hippocampal subfield analysis of AD, mild cognitive impairment (MCI), and healthy subjects. We found significant structural and metabolic changes within the hippocampus that can be sensitively assessed at the subfield level in a small cohort. While no significant differences were found between groups for whole hippocampal SUVr values (p = 0.166), we found a clear delineation in SUVr between groups in the dentate gyrus (p = 0.009). Subfield analysis may be more sensitive for detecting pathological changes using PET-MRI in AD compared to global hippocampal assessment.

Bone Marrow and Tumor Radiomics at 18F-FDG PET/CT: Impact on Outcome Prediction in Non-Small Cell Lung Cancer.

Background Primary tumor maximum standardized uptake value is a prognostic marker for non-small cell lung cancer. In the setting of malignancy, bone marrow activity from fluorine 18-fluorodeoxyglucose (FDG) PET may be informative for clinical risk stratification. Purpose To determine whether integrating FDG PET radiomic features of the primary tumor, tumor penumbra, and bone marrow identifies lung cancer disease-free survival more accurately than clinical features alone. Materials and Methods Patients were retrospectively analyzed from two distinct cohorts collected between 2008 and 2016. Each tumor, its surrounding penumbra, and bone marrow from the L3-L5 vertebral bodies was contoured on pretreatment FDG PET/CT images. There were 156 bone marrow and 512 tumor and penumbra radiomic features computed from the PET series. Randomized sparse Cox regression by least absolute shrinkage and selection operator identified features that predicted disease-free survival in the training cohort. Cox proportional hazards models were built and locked in the training cohort, then evaluated in an independent cohort for temporal validation. Results There were 227 patients analyzed; 136 for training (mean age, 69 years ± 9 [standard deviation]; 101 men) and 91 for temporal validation (mean age, 72 years ± 10; 91 men). The top clinical model included stage; adding tumor region features alone improved outcome prediction (log likelihood, -158 vs -152; P = .007). Adding bone marrow features continued to improve performance (log likelihood, -158 vs -145; P = .001). The top model integrated stage, two bone marrow texture features, one tumor with penumbra texture feature, and two penumbra texture features (concordance, 0.78; 95% confidence interval: 0.70, 0.85; P < .001). This fully integrated model was a predictor of poor outcome in the independent cohort (concordance, 0.72; 95% confidence interval: 0.64, 0.80; P < .001) and a binary score stratified patients into high and low risk of poor outcome (P < .001). Conclusion A model that includes pretreatment fluorine 18-fluorodeoxyglucose PET texture features from the primary tumor, tumor penumbra, and bone marrow predicts disease-free survival of patients with non-small cell lung cancer more accurately than clinical features alone. © RSNA, 2019 Online supplemental material is available for this article.

[18F] FDG Positron Emission Tomography (PET) Tumor and Penumbra Imaging Features Predict Recurrence in Non-Small Cell Lung Cancer.

We identified computational imaging features on 18F-fluorodeoxyglucose positron emission tomography (PET) that predict recurrence/progression in non-small cell lung cancer (NSCLC). We retrospectively identified 291 patients with NSCLC from 2 prospectively acquired cohorts (training, n = 145; validation, n = 146). We contoured the metabolic tumor volume (MTV) on all pretreatment PET images and added a 3-dimensional penumbra region that extended outward 1 cm from the tumor surface. We generated 512 radiomics features, selected 435 features based on robustness to contour variations, and then applied randomized sparse regression (LASSO) to identify features that predicted time to recurrence in the training cohort. We built Cox proportional hazards models in the training cohort and independently evaluated the models in the validation cohort. Two features including stage and a MTV plus penumbra texture feature were selected by LASSO. Both features were significant univariate predictors, with stage being the best predictor (hazard ratio [HR] = 2.15 [95% confidence interval (CI): 1.56-2.95], P < .001). However, adding the MTV plus penumbra texture feature to stage significantly improved prediction (P = .006). This multivariate model was a significant predictor of time to recurrence in the training cohort (concordance = 0.74 [95% CI: 0.66-0.81], P < .001) that was validated in a separate validation cohort (concordance = 0.74 [95% CI: 0.67-0.81], P < .001). A combined radiomics and clinical model improved NSCLC recurrence prediction. FDG PET radiomic features may be useful biomarkers for lung cancer prognosis and add clinical utility for risk stratification.

PCI Alternative Using Sustained Exercise (PAUSE): Rationale and trial design.

Cardiovascular disease (CVD) currently claims nearly one million lives yearly in the US, accounting for nearly 40% of all deaths. Coronary artery disease (CAD) accounts for the largest number of these deaths. While efforts aimed at treating CAD in recent decades have concentrated on surgical and catheter-based interventions, limited resources have been directed toward prevention and rehabilitation. CAD is commonly treated using percutaneous coronary intervention (PCI), and this treatment has increased exponentially since its adoption over three decades ago. Recent questions have been raised regarding the cost-effectiveness of PCI, the extent to which PCI is overused, and whether selected patients may benefit from optimal medical therapy in lieu of PCI. One alternative therapy that has been shown to improve outcomes in CAD is exercise therapy; exercise programs have been shown to have numerous physiological benefits, and a growing number of studies have demonstrated reductions in mortality. Given the high volume of PCI, its high cost, its lack of effect on survival and the potential for alternative treatments including exercise, the current study is termed "PCI Alternative Using Sustained Exercise" (PAUSE). The primary aim of PAUSE is to determine whether patients randomized to exercise and lifestyle intervention have greater improvement in coronary function and anatomy compared to those randomized to PCI. Coronary function and anatomy is determined using positron emission tomography combined with computed tomographic angiography (PET/CTA). Our objective is to demonstrate the utility of a non-invasive technology to document the efficacy of exercise as an alternative treatment strategy to PCI.

Variable activation of the DNA damage response pathways in patients undergoing single-photon emission computed tomography myocardial perfusion imaging.

BACKGROUND: Although single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) has improved the diagnosis and risk stratification of patients with suspected coronary artery disease, it remains a primary source of low-dose radiation exposure for cardiac patients. To determine the biological effects of low-dose radiation from SPECT MPI, we measured the activation of the DNA damage response pathways using quantitative flow cytometry and single-cell gene expression profiling. METHODS AND RESULTS: Blood samples were collected from patients before and after SPECT MPI (n=63). Overall, analysis of all recruited patients showed no marked differences in the phosphorylation of proteins (H2AX, protein 53, and ataxia telangiectasia mutated) after SPECT. The majority of patients also had either downregulated or unchanged expression in DNA damage response genes at both 24 and 48 hours post-SPECT. Interestingly, a small subset of patients with increased phosphorylation had significant upregulation of genes associated with DNA damage, whereas those with no changes in phosphorylation had significant downregulation or no difference, suggesting that some patients may potentially be more sensitive to low-dose radiation exposure. CONCLUSIONS: Our findings showed that SPECT MPI resulted in a variable activation of the DNA damage response pathways. Although only a small subset of patients had increased protein phosphorylation and elevated gene expression postimaging, continued care should be taken to reduce radiation exposure to both the patients and operators.

Circulating tumor microemboli diagnostics for patients with non-small-cell lung cancer.

INTRODUCTION: Circulating tumor microemboli (CTM) are potentially important cancer biomarkers, but using them for cancer detection in early-stage disease has been assay limited. We examined CTM test performance using a sensitive detection platform to identify stage I non-small-cell lung cancer (NSCLC) patients undergoing imaging evaluation. METHODS: First, we prospectively enrolled patients during 18F-FDG PET-CT imaging evaluation for lung cancer that underwent routine phlebotomy where CTM and circulating tumor cells (CTCs) were identified in blood using nuclear (DAPI), cytokeratin (CK), and CD45 immune-fluorescent antibodies followed by morphologic identification. Second, CTM and CTC data were integrated with patient (age, gender, smoking, and cancer history) and imaging (tumor diameter, location in lung, and maximum standard uptake value [SUVmax]) data to develop and test multiple logistic regression models using a case-control design in a training and test cohort followed by cross-validation in the entire group. RESULTS: We examined 104 patients with NSCLC, and the subgroup of 80 with stage I disease, and compared them to 25 patients with benign disease. Clinical and imaging data alone were moderately discriminating for all comers (Area under the Curve [AUC] = 0.77) and by stage I disease only (AUC = 0.77). However, the presence of CTM combined with clinical and imaging data was significantly discriminating for diagnostic accuracy in all NSCLC patients (AUC = 0.88, p value = 0.001) and for stage I patients alone (AUC = 0.87, p value = 0.002). CONCLUSION: CTM may add utility for lung cancer diagnosis during imaging evaluation using a sensitive detection platform.

An observational study of circulating tumor cells and (18)F-FDG PET uptake in patients with treatment-naive non-small cell lung cancer.

INTRODUCTION: We investigated the relationship of circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) with tumor glucose metabolism as defined by (18)F-fluorodeoxyglucose (FDG) uptake since both have been associated with patient prognosis. MATERIALS & METHODS: We performed a retrospective screen of patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell Adhesion Molecule (EpCAM) independent fluid biopsy based on cell morphology for CTC detection and enumeration (defined here as High Definition CTCs or "HD-CTCs"). We then correlated HD-CTCs with quantitative FDG uptake image data calibrated across centers in a cross-sectional analysis. RESULTS: We assessed seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile range, IQR, 2.0-3.6) and median maximum standardized uptake value (SUVmax) was 7.2 (IQR 3.7-15.5). More than 2 HD-CTCs were detected in 63% of patients, whether across all stages (45 of 71) or in stage I disease (27 of 43). HD-CTCs were weakly correlated with partial volume corrected tumor SUVmax (r = 0.27, p-value = 0.03) and not correlated with tumor diameter (r = 0.07; p-value = 0.60). For a given partial volume corrected SUVmax or tumor diameter there was a wide range of detected HD-CTCs in circulation for both early and late stage disease. CONCLUSIONS: CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, in vivo tumor biology in the early stages of this deadly disease.

A case of three synchronous primary tumors demonstrated by F-18 FDG PET.

We present an F-18 FDG PET scan which demonstrates 3 synchronous primary malignancies. The patient is a 61-year-old man who presented with weight loss and dysphagia. He was initially diagnosed with squamous cell carcinoma of the midesophagus, and was then found to have an adenocarcinoma in the right lung. A staging PET scan additionally showed increased left tonsillar uptake. Subsequent biopsy confirmed squamous cell carcinoma of the left tonsil. The demonstration of 3 synchronous primaries by PET is probably rare.

F-18 fluorodeoxyglucose PET/CT as an imaging tool for staging and restaging cutaneous angiosarcoma of the scalp.

Cutaneous angiosarcoma of the scalp is a rare highly aggressive malignant tumor that typically afflicts elderly patients and commonly presents with extensive local spread and distant metastasis. Distant metastases favor lung, liver, lymph nodes, and skin. Overall, the prognosis is poor. It differs from other soft tissue sarcomas in that the size of the lesion at presentation instead of tumor grade is the important prognostic factor. Optimal treatment is yet to be determined. Wide-margin complete excision with postoperative radiotherapy has been the most effective therapy. Chemotherapy and gene therapy have been used with some success. Local extent is critical in surgical planning, especially in the head and face, and is difficult to determine accurately with clinical examination and morphologic imaging tools. We report the case of a 70-year-old man diagnosed with multifocal angiosarcoma of the scalp. PET/CT imaging with F-18 2-fluoro-2-deoxyglucose (F-18 FDG) not only showed avid FDG uptake by an angiosarcoma (SUVmax = 10.7), but also simultaneously showed local extension of multifocal lesions with periosteal involvement and excluded metastatic abdominal nodal disease. PET/CT imaging after chemotherapy and before radiation therapy showed complete resolution of FDG uptake in the scalp and osseous lesions. Evaluation of more cases of this subset of soft tissue sarcoma with FDG PET/CT may suggest a possible role in not only staging angiosarcomas to determine the extent of local as well as distant disease, but also to potentially help determine response to therapy and early recognition of local or distant recurrence.

Positively labeled white blood cell scan with eosinophilia and absence of infection.

PURPOSE: The authors describe the variability of Tc-99m exametazime-labeled leukocyte distribution as a function of the relative frequency of white cell types in the labeled blood. MATERIALS AND METHODS: A 76-year-old man who was hospitalized with fever and possible postoperative osteomyelitis underwent scintigraphic imaging with Tc-99m exametazime-labeled leukocytes. RESULTS: The white cell scan excluded any discrete focus of infection and revealed diffuse involvement of the lymph nodes and skin. The pathologic diagnosis was angioimmunoblastic T-cell lymphoma. The atypical infiltrates seen on the white cell scan can be explained by the severe eosinophilic blood count on the day of leukocyte labeling (total leukocyte count: 8,100 cells/microl with 63% neutrophils, 8.9% lymphocytes, and 22.2% eosinophils). CONCLUSION: In the labeling of the leukocyte moiety, a higher presence of any leukocyte subpopulation will modify the biodistribution and thus the image interpretation.