Semi-quantitative F-18-FDG PET/computed tomography parameters for prediction of grade in patients with renal cell carcinoma and the incremental value of diuretics.

OBJECTIVE: The primary objective of the study was to evaluate the correlation between semi-quantitative F-18 FDG PET parameters and renal cell carcinoma (RCC) grade and its role in predicting the histopathological grade in RCC. The secondary objective was to evaluate the role of forced diuresis in improving the diagnostic accuracy of F-18 FDG for RCC. METHODS: Thirty-three patients with radiologically proven RCC were included in the study. All patients underwent PET/CT on a dedicated PET/CT scanner (Biograph mCT; Siemens Medical Solutions, Erlangen, Germany) 45-60 min post-injection F-18-FDG. Patients were then injected 1 mg/kg body weight furosemide (upto 40 mg) and regional PET/CT images of abdomen were acquired after 2 h. For both baseline and post-diuretic F-18-FDG PET/CT scans, maximum standardized uptake value for tumor (SUVmax), mean SUV for tumor, metabolic tumor volume (MTV), tumor-to-liver (T/L) and tumor-to-kidney ratio (T/K) were calculated. Histopathology findings were considered as the reference standard. To assess the incremental value of diuresis in scan interpretation, visual analysis of scans was done. RESULTS: Of 33 patients, histopathology grading was available for comparison with metabolic tumor markers in all except four. Of 29 patients (mean age = 51.89 ± 13.54 years), 20 patients had clear cell (cc) type while rest had non-cc RCC. Difference between the mean values among the categories was insignificant for all parameters except T/K. Fuhrman grading was obtained in 25 patients (17 low and eight high). SUVmax, MTV and T/L were found to be significantly different between low and high grade patients. Significantly strong positive correlation was observed between Furhman grades and tumor metabolism (r ≥ 0.5). No significant difference was observed between baseline and post-diuretic scan in any of the patients. CONCLUSION: Semi-quantitative F-18 FDG PET parameters (SUVmax, MTV and T/L) were found to be significantly correlated with Fuhrman grade in patients with RCC and are important markers for differentiation between low- and high-grade tumors. Furthermore, forced diuresis had no incremental value in characterization of primary RCC lesions.

Breaking and Fixing Origin-Based Access Control in Hybrid Web/Mobile Application Frameworks.

Hybrid mobile applications (apps) combine the features of Web applications and "native" mobile apps. Like Web applications, they are implemented in portable, platform-independent languages such as HTML and JavaScript. Like native apps, they have direct access to local device resources-file system, location, camera, contacts, etc. Hybrid apps are typically developed using hybrid application frameworks such as PhoneGap. The purpose of the framework is twofold. First, it provides an embedded Web browser (for example, WebView on Android) that executes the app's Web code. Second, it supplies "bridges" that allow Web code to escape the browser and access local resources on the device. We analyze the software stack created by hybrid frameworks and demonstrate that it does not properly compose the access-control policies governing Web code and local code, respectively. Web code is governed by the same origin policy, whereas local code is governed by the access-control policy of the operating system (for example, user-granted permissions in Android). The bridges added by the framework to the browser have the same local access rights as the entire application, but are not correctly protected by the same origin policy. This opens the door to fracking attacks, which allow foreign-origin Web content included into a hybrid app (e.g., ads confined in iframes) to drill through the layers and directly access device resources. Fracking vulnerabilities are generic: they affect all hybrid frameworks, all embedded Web browsers, all bridge mechanisms, and all platforms on which these frameworks are deployed. We study the prevalence of fracking vulnerabilities in free Android apps based on the PhoneGap framework. Each vulnerability exposes sensitive local resources-the ability to read and write contacts list, local files, etc.-to dozens of potentially malicious Web domains. We also analyze the defenses deployed by hybrid frameworks to prevent resource access by foreign-origin Web content and explain why they are ineffectual. We then present NoFrak, a capability-based defense against fracking attacks. NoFrak is platform-independent, compatible with any framework and embedded browser, requires no changes to the code of the existing hybrid apps, and does not break their advertising-supported business model.

Using Frankencerts for Automated Adversarial Testing of Certificate Validation in SSL/TLS Implementations.

Modern network security rests on the Secure Sockets Layer (SSL) and Transport Layer Security (TLS) protocols. Distributed systems, mobile and desktop applications, embedded devices, and all of secure Web rely on SSL/TLS for protection against network attacks. This protection critically depends on whether SSL/TLS clients correctly validate X.509 certificates presented by servers during the SSL/TLS handshake protocol. We design, implement, and apply the first methodology for large-scale testing of certificate validation logic in SSL/TLS implementations. Our first ingredient is "frankencerts," synthetic certificates that are randomly mutated from parts of real certificates and thus include unusual combinations of extensions and constraints. Our second ingredient is differential testing: if one SSL/TLS implementation accepts a certificate while another rejects the same certificate, we use the discrepancy as an oracle for finding flaws in individual implementations. Differential testing with frankencerts uncovered 208 discrepancies between popular SSL/TLS implementations such as OpenSSL, NSS, CyaSSL, GnuTLS, PolarSSL, MatrixSSL, etc. Many of them are caused by serious security vulnerabilities. For example, any server with a valid X.509 version 1 certificate can act as a rogue certificate authority and issue fake certificates for any domain, enabling man-in-the-middle attacks against MatrixSSL and GnuTLS. Several implementations also accept certificate authorities created by unauthorized issuers, as well as certificates not intended for server authentication. We also found serious vulnerabilities in how users are warned about certificate validation errors. When presented with an expired, self-signed certificate, NSS, Safari, and Chrome (on Linux) report that the certificate has expired-a low-risk, often ignored error-but not that the connection is insecure against a man-in-the-middle attack. These results demonstrate that automated adversarial testing with frankencerts is a powerful methodology for discovering security flaws in SSL/TLS implementations.

Eternal Sunshine of the Spotless Machine: Protecting Privacy with Ephemeral Channels.

Modern systems keep long memories. As we show in this paper, an adversary who gains access to a Linux system, even one that implements secure deallocation, can recover the contents of applications' windows, audio buffers, and data remaining in device drivers-long after the applications have terminated. We design and implement Lacuna, a system that allows users to run programs in "private sessions." After the session is over, all memories of its execution are erased. The key abstraction in Lacuna is an ephemeral channel, which allows the protected program to talk to peripheral devices while making it possible to delete the memories of this communication from the host. Lacuna can run unmodified applications that use graphics, sound, USB input devices, and the network, with only 20 percentage points of additional CPU utilization.

Therapeutically targeting cyclin D1 in primary tumors arising from loss of Ini1.

Rhabdoid tumors (RTs) are rare, highly aggressive pediatric malignancies with poor prognosis and with no standard or effective treatment strategies. RTs are characterized by biallelic inactivation of the INI1 tumor suppressor gene. INI1 directly represses CCND1 and activates cyclin-dependent kinase (cdk) inhibitors p16(Ink4a) and p21(CIP). RTs are exquisitely dependent on cyclin D1 for genesis and survival. To facilitate translation of unique therapeutic strategies, we have used genetically engineered, Ini1(+/-) mice for therapeutic testing. We found that PET can be used to noninvasively and accurately detect primary tumors in Ini1(+/-) mice. In a PET-guided longitudinal study, we found that treating Ini1(+/-) mice bearing primary tumors with the pan-cdk inhibitor flavopiridol resulted in complete and stable regression of some tumors. Other tumors showed resistance to flavopiridol, and one of the resistant tumors overexpressed cyclin D1, more than flavopiridol-sensitive cells. The concentration of flavopiridol used was not sufficient to down-modulate the high level of cyclin D1 and failed to induce cell death in the resistant cells. Furthermore, FISH and PCR analyses indicated that there is aneuploidy and increased CCND1 copy number in resistant cells. These studies indicate that resistance to flavopiridol may be correlated to elevated cyclin D1 levels. Our studies also indicate that Ini1(+/-) mice are valuable tools for testing unique therapeutic strategies and for understanding mechanisms of drug resistance in tumors that arise owing to loss of Ini1, which is essential for developing effective treatment strategies against these aggressive tumors.

Benign tongue FDG uptake in a patient with tardive dyskinesia.

Fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography (F-18 FDG PET-CT) is the modality of choice for diagnosis, staging, and restaging of many malignancies. The importance of eliminating false positives cannot be underestimated because they can dramatically alter the clinical course. We present a case of benign uptake in the tongue secondary to tardive dyskinesia in a 62-year-old woman referred for staging of ductal carcinoma of the breast who was concurrently receiving oral therapy for schizoaffective disorder. This case emphasizes the importance of direct clinical interview and adequate history taking in the formulation of an appropriate diagnosis.

Endometrioma presenting as a cavitary lung mass with intense 18F-FDG uptake on PET-CT.

[18F]-fluoro-2-deoxy-D-glucose positron emission tomography computed tomography is a useful tool to suggest the diagnosis of malignant processes. However, false positive results are known to occur in benign lesions that have a high metabolic activity. Here we describe the unusual diagnosis of a pulmonary endometrioma in a 47-year-old woman, presenting as a cavitary lung mass with intense (18)F-FDG uptake on PET-CT.

Limited myocardial muscle necrosis model allowing for evaluation of angiogenic treatment modalities.

The currently accepted model for creating infarcted cardiac tissue in a rat model involves ligation of the left anterior descending artery (LAD), either proximally or at the bifurcation level. This procedure requires significant technical expertise and, even in skilled hands, commonly results in a 30% to 60% animal mortality. The authors propose a new model for creating a limited area of myocardial muscle necrosis that can be effectively studied. It involves a distal electrocautery occlusion of the LAD terminal branches and coagulation of the surrounding muscle. The model is consistently reproducible and decreases the morbidity of the study animals. It provides a cardiac muscle necrosis model not dependent on survival, while allowing study of the post injured state of the muscle and surrounding scar. This allows researchers to evaluate neovascularization and healing of the scar and peri-necrotic muscle, to assess improving blood flow with treatment by techniques designed to improve and stimulate angiogenesis, and to measure the outcome of stem-cell transplants for potential clinical use.

Positron emission tomography in gynecological malignancies.

Positron emission tomography (PET) is a functional diagnostic imaging technique. F-18 fluoro-2-deoxy-d-glucose (FDG) is a commonly used radiopharmaceutical that is an analog of glucose. PET with FDG is now the standard of care in initial staging, monitoring the response to the therapy and management of various cancers. There is not sufficient data to support the use of PET in the initial diagnosis of cervical cancer; however, FDG-PET has a role in initial staging in the detection of distant metastases in patients with cervical cancer. PET has limited value in lesion localization in early stages of ovarian cancer, but plays a significant role in identifying recurrent tumors in patients with rising tumor markers. In this article, the clinical application of PET in gynecological malignancies is reviewed.

FDG-PET and CT characterization of adrenal lesions in cancer patients.

PURPOSE: Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) may differentiate benign from malignant adrenal lesions. In this study, standardized uptake values (SUVs), visual interpretation, and computed tomography (CT) data were correlated with the final diagnosis to determine the contribution of adrenal FDG-PET in patients with known non-adrenal cancer. METHODS: Ninety-two patients with adrenal lesions on CT underwent FDG-PET. Eighty adrenals in 74 patients met the inclusion criteria (PET scan within 4 weeks of CT plus >1 year of follow-up after PET scan with repeat CT or biopsy for final diagnosis). CT was considered positive for metastases (CT+) based on two of the following three criteria: >4 cm, Hounsfield units (HU) >30, and delayed contrast enhancement. Lesions with <2 cm, with HU <20, and showing no enhancement were considered benign (CT-). Remaining lesions were considered indeterminate (CT-Ind). Visually, adrenal uptake exceeding liver uptake was considered PET positive (PET+). Diagnosis of metastases was based on biopsy or interval CT growth (unchanged >1 year=benign). SUV(max) and SUV(avg) were calculated from a 4 x 4 pixel region of interest drawn from CT, PET, and fused images. A receiver operator curve (ROC) determined the SUV with the best sensitivity and specificity. RESULTS: Overall, PET was 93% sensitive and 96% specific for metastases. A SUV(max) of 3.4 was 95% sensitive and 86% specific. A SUV(avg) of 3.1 was 95% sensitive and 90% specific. There was no significant difference between visual interpretation and SUV (SUV(max) or SUV(avg)). Among CT+ and CT- lesions, PET was 100% sensitive and 96% specific; CT was 86% sensitive and 100% specific. In the CT-Ind group, PET was 88% sensitive and 96% specific. CONCLUSION: PET accurately characterized adrenal lesions. Visual interpretation was as accurate as SUV. FDG-PET was most useful in the 52.5% of cancer patients with inconclusive adrenal lesions on CT.

Nuclear medicine studies of the prostate, testes, and bladder.

During the last decade, there has been a significant advancement in imaging of urologic diseases. Transrectal ultrasound (TRUS), computerized tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET) are still experiencing new developments in urology. Despite these many technological advances, the initial diagnostic procedure for a patient with suspected prostate cancer (PC) is multiple site blind prostate biopsies. There is a need for a noninvasive metabolic imaging modality to direct the site of biopsy to decrease the sampling error. MRS seems promising but as it is a costly and more time-consuming test, further studies are needed to evaluate its clinical utility. Currently, PET does not play any role to direct biopsy. Acetate and choline appear to be better tracers than FDG for the detection of a prostate lesion, however, further well-organized studies are needed before any of these agents can be used clinically. Incidental detection of intense focal uptake in the prostate during whole body PET scanning should be evaluated with prostate-specific antigen (PSA) and TRUS-guided biopsy. Although FDG is inferior to other tracers for primary staging, it may be useful in selected patients with suspected high-grade cancer. The role of ProstaScint scan is still controversial for detection of recurrent PC. This study may be helpful for evaluating nodal metastases when PSA is elevated and bone scan is negative. Bone scan remains the study of choice when bone metastases are suspected (PSA>15-20 ng/mL+/-bone pain). Acetate and choline provide better accuracy than FDG in the detection of local soft tissue disease, nodal involvement, and distant metastases. High FDG uptake may be indicative of more aggressive and possibly androgen-independent disease. PET/CT with any of the above PET tracers will most likely be preferred to the PET scan alone due to better localization of a hot lesion in PET/CT. Nuclear medicine studies also have been used to evaluate acute scrotum and testicular neoplasms. Scrotal scintigraphy has lost its popularity to Doppler ultrasound in the evaluation of the acute scrotum. In testicular tumors, FDG-PET appears to be superior to conventional imaging modalities in initial staging, detection of residual/recurrence, and monitoring treatment response. Tumor markers after treatment occasionally are elevated and cannot locate the site of recurrence, FDG-PET can play a very important role in this regard. Nuclear medicine studies also have been used to evaluate diseases of the urinary bladder. Radionuclide cystography is more sensitive and has less than 1/20 the radiation exposure of the conventional contrast enhanced micturating cystourethrogram (MCU). However, the utility of FDG-PET in the evaluation of bladder cancer seems to be limited to the evaluation of distant metastases. 11C-Methionine and choline may be a better option for local and nodal disease due to their negligible excretion in the urine.

Retrospective analysis of sentinel node localization in multifocal, multicentric, palpable, or nonpalpable breast cancer.

UNLABELLED: Multicentric or multifocal breast cancer is considered as one of the limitations for sentinel lymph node (SLN) localization. We did a retrospective analysis to evaluate the success rate, sensitivity, accuracy, and negative predictive values of SLN localization in multicentric or multifocal breast lesions. METHODS: Fifty-nine patients with multifocal or multicentric breast lesions proven by either fine-needle aspiration (19/59), core biopsy (39/59), or lumpectomy (8/59) underwent SLN localization. Of these patients, 46 had SLN localization by both radiocolloid and blue dye, and 13 had SLN localization by radiocolloid alone. Approximately 10 MBq (99m)Tc-labeled unfiltered sulfur colloid in 0.3-0.4 mL were injected intradermally over the 1 or 2 breast tumor locations 2-4 h before surgery. During surgery, vital blue dye was injected intraparenchymally in 4-6 places around the tumor. All lymph nodes with counts of >10 times that of the background counts, whether or not blue dye positive, and all blue dye-positive lymph nodes, whether or not radiocolloid positive, were excised and labeled accordingly. All lymph nodes underwent frozen sectioning and were examined by hematoxylin and eosin and immunohistologic (cytokeratin) staining. RESULTS: Of the 59 patients, 48 had axillary lymph node dissection irrespective of the results of pathologic examination of the SLN. The success rate, sensitivity, negative predictive value, and accuracy were 93%, 100%, 100%, and 100% using the radiocolloid probe, 87%, 100%, 100%, and 100% using blue dye, and 93.5%, 100%, 100%, and 100% using combined methods, respectively. Concordance between blue dye and radiocolloid was 91% (the incidence of the number of sentinel nodes detected was 37.5%, 30.3%, 10.7%, and 21.4% for 1, 2, 3, and 4 or more lymph nodes, respectively). Metastatic lymph node involvement was found in 39.5% of patients. CONCLUSION: The sentinel node localization approach showed a high negative predictive value in breast cancer patients with multifocal or multicentric lesions, contrary to the common belief of significant false-negative results in these patients.

Transient postischemic stunning evaluation by stress gated Tl-201 SPECT myocardial imaging: Effect on systolic left ventricular function.

BACKGROUND: Transient postischemic stunning (TIS) has been reported in images obtained (1/2) to 1 hour after stress with technetium 99m tracers but has not been investigated in images obtained shortly after stress with thallium 201. We also quantified the global extent and severity of TIS, which has not been done previously. METHODS AND RESULTS: We evaluated 82 patients with either treadmill or dobutamine stress Tl-201 myocardial perfusion imaging. Images were semiquantitatively examined with a 20-segment model. The extent and severity of myocardial ischemia and TIS were assessed by the summed difference score from the early and delayed scores of perfusion, wall motion (WM), and wall thickening (WT). The mean left ventricular ejection fraction (LVEF) was significantly lower in early images than in delayed images in patients with ischemia (P <.01), TIS by WM (P <.001), and TIS by WT (P <.001), and the LVEF difference was more significantly different as the summed difference score of perfusion, WM, or WT increased. No significant LVEF difference was seen in patients with ischemia who did not have TIS. CONCLUSIONS: In stress gated Tl-201 single photon emission computed tomography myocardial perfusion imaging, early TIS is frequently seen in patients with ischemia and is equivalently detected by WM and WT assessments. Significant exercise-induced transient left ventricular global dysfunction is associated with more severe and extensive ischemia and can be predicted by the measurement of the extent and severity of TIS from the same images.

Transient ischemic stunning of the myocardium in stress thallium-201 gated SPET myocardial perfusion imaging: segmental analysis of myocardial perfusion, wall motion and wall thickening changes.

Prolonged and persistent myocardial stunning has recently been demonstrated using technetium-99m sestamibi gated single-photon emission tomography (SPET) myocardial perfusion imaging post exercise or pharmacological stress test. In this study, we investigated the early postischemic transient myocardial stunning on early and delayed poststress thallium-201 gated SPET myocardial perfusion imaging using segmental wall motion (WM) and wall thickening (WT) analysis. A total of 1,680 segments from 84 patients' studies (53 men and 31 women, mean age 60 years) were evaluated on both early and delayed thallium-201 gated SPET treadmill exercise (59) or dobutamine stress (25) myocardial perfusion imaging. Semiquantitative analysis of perfusion, WM and WT in all segments was performed by two observers. Segments were classified according to changes in WM and WT between early and delayed images into normal, fixed abnormality, or improved abnormality (transient stunning), and were further classified according to changes in perfusion into normal, fixed defects, or ischemic. There were significant correlations between perfusion and WM, perfusion and WT, and WM and WT segmental scores on both early and delayed images. Transient stunning was seen significantly ( P < 0.001) more often in ischemic segments than were normal or fixed perfusion defects using WM (58%) and WT (50%) assessments. There was also a significant correlation between the severity of ischemia and transient stunning with either WM ( P < 0.05) or WT ( P < 0.005) evaluation. Segmental myocardial contractility assessment from gated SPET (201)Tl myocardial perfusion imaging using WM and WT was comparable, and results correlated well with the myocardial perfusion assessment. Early transient myocardial stunning was frequently observed in ischemic segments and was related to the severity of myocardial ischemia.

Role of Fluorine-18-Fluorodeoxyglucose in the Work-up of Febrile AIDS Patients. Experience with Dual Head Coincidence Imaging.

OBJECTIVE AND METHODS: This study was undertaken to find the role of fluorine-18-fluorodeoxyglucose (F18-FDG) in the diagnostic work-up of febrile Acquired Immune Deficiency Syndrome (AIDS) patients. Forty-seven (42 male and 5 female; mean age = 40.3 years) febrile patients with AIDS underwent imaging with F18-FDG by Dual Head Coincidence Imaging (DHCI). Findings were correlated with other imaging modalities.RESULTS: Our data show good sensitivity for scanning with F18-FDG by DHCI in determining the extent of Castleman's disease, lymphoma, Kaposi's sarcoma (KS), adenocarcinoma, and germ cell carcinoma. Various opportunistic infections also manifest with increased F18-FDG uptake.CONCLUSION: Total-body imaging can be done with F18-FDG with better resolution and a shorter procedure time compared to imaging with Gallium-67 (Ga-67). Furthermore, F18-FDG is more sensitive than Ga-67 for evaluating extent of involvement in various pathologies affecting AIDS patients. The new technology of DHCI is a good alternative for hospitals with no dedicated positron emission tomography (PET) scanner.