Image Quality Evaluation in Dual-Energy CT of the Chest, Abdomen, and Pelvis in Obese Patients With Deep Learning Image Reconstruction.

OBJECTIVE: The aim of this study was to evaluate image quality in vascular and oncologic dual-energy computed tomography (CT) imaging studies performed with a deep learning (DL)-based image reconstruction algorithm in patients with body mass index of ≥30. METHODS: Vascular and multiphase oncologic staging dual-energy CT examinations were evaluated. Two image reconstruction algorithms were applied to the dual-energy CT data sets: standard of care Adaptive Statistical Iterative Reconstruction (ASiR-V) and TrueFidelity DL image reconstruction at 2 levels (medium and high). Subjective quality criteria were independently evaluated by 4 abdominal radiologists, and interreader agreement was assessed. Signal-to-noise ratio (SNR) and contrast-to-noise ratio were compared between image reconstruction methods. RESULTS: Forty-eight patients were included in this study, and the mean patient body mass index was 39.5 (SD, 7.36). TrueFidelity-High (DL-High) and TrueFidelity-Medium (DL-Med) image reconstructions showed statistically significant higher Likert scores compared with ASiR-V across all subjective image quality criteria ( P < 0.001 for DL-High vs ASiR-V; P < 0.05 for DL-Med vs ASiR-V), and SNRs for aorta and liver were significantly higher for DL-High versus ASiR-V ( P < 0.001). Contrast-to-noise ratio for aorta and SNR for aorta and liver were significantly higher for DL-Med versus ASiR-V ( P < 0.05). CONCLUSIONS: TrueFidelity DL image reconstruction provides improved image quality compared with ASiR-V in dual-energy CTs obtained in obese patients.

Multimodality Imaging for the Staging of Pancreatic Cancer.

Imaging plays a key role in the diagnosis, staging, and follow-up of pancreatic ductal adenocarcinoma. The pancreatic protocol dual-phase multidetector computed tomography scan is the imaging modality of choice. A computed tomography scan is highly accurate for pancreatic tumor detection, assessment of resectability, and detection of metastatic disease. This article reviews key principles of the acquisition, interpretation, and reporting of pancreatic ductal adenocarcinoma imaging with computed tomography scanning and highlights potential roles for newer and supplemental imaging technologies. We discuss the importance of structured interpretation and reporting for providing the most complete and accurate assessment of tumor stage and resectability.

Cost-effectiveness analysis of universal germline testing for patients with pancreatic cancer.

BACKGROUND: Historically, germline testing of patients with pancreatic cancer was performed selectively in patients with a strong family history of cancer. Current guidelines recommend universal testing because some patients may have actionable germline pathogenic variants without family history. METHODS: We conducted a cost-effectiveness analysis using a decision-tree model to compare universal versus selective testing strategies for patients with pancreatic cancer. Costs, probabilities, and overall survival were estimated from the published literature and institutional data. One-way and probabilistic sensitivity analyses explored model uncertainty. RESULTS: Universal germline genetic testing had an incremental cost of $310 with an increase of 0.003 life-years. The incremental cost-effectiveness ratio was $121,924/life-years. Parameters which were most impactful (sensitivity analysis) included the median overall survival of patients with advanced disease treated with personalized therapy, cost of personalized therapy for advanced disease, and the probability of receiving personalized therapy in advanced disease. A strategy of selective testing was more cost-effective in 59% of iterations when the willingness-to-pay threshold was set to $100,000/life-years. CONCLUSION: Our model suggested that selective germline testing of patients with newly diagnosed pancreatic cancer is more cost-effective than universal testing. Additional research is needed to explore the impact of cascade testing of relatives on cost-effectiveness.

Structured Reporting in Ultrasound.

Structured reporting of ultrasound examinations can add value throughout the imaging chain. Reports may be created in a more efficient manner, with increased accuracy and clarity. Communication with referring providers and patients may be improved. Patient care can be enhanced through improved adherence with guidelines and local best practices. Radiology departments may benefit from improved billing and quality reporting. Consistent discrete data can enable research and collaborations between institutions. This article will review the multifaceted impact of structuring ultrasound reports.

Gleason Probability Maps: A Radiomics Tool for Mapping Prostate Cancer Likelihood in MRI Space.

Prostate cancer is the most common noncutaneous cancer in men in the United States. The current paradigm for screening and diagnosis is imperfect, with relatively low specificity, high cost, and high morbidity. This study aims to generate new image contrasts by learning a distribution of unique image signatures associated with prostate cancer. In total, 48 patients were prospectively recruited for this institutional review board-approved study. Patients underwent multiparametric magnetic resonance imaging 2 weeks before surgery. Postsurgical tissues were annotated by a pathologist and aligned to the in vivo imaging. Radiomic profiles were generated by linearly combining 4 image contrasts (T2, apparent diffusion coefficient [ADC] 0-1000, ADC 50-2000, and dynamic contrast-enhanced) segmented using global thresholds. The distribution of radiomic profiles in high-grade cancer, low-grade cancer, and normal tissues was recorded, and the generated probability values were applied to a naive test set. The resulting Gleason probability maps were stable regardless of training cohort, functioned independent of prostate zone, and outperformed conventional clinical imaging (area under the curve [AUC] = 0.79). Extensive overlap was seen in the most common image signatures associated with high- and low-grade cancer, indicating that low- and high-grade tumors present similarly on conventional imaging.

Sonographic Appearances of Portal Vein Abnormalities.

Portal venous system evaluation is required in many clinical circumstances, as substantial morbidity and mortality can be associated with a spectrum of portal vein abnormalities. Portal venous system pathologies can be congenital or acquired, and the knowledge of their imaging appearances will allow for a confident diagnosis and appropriate treatment options. In addition, a firm understanding of anatomical variants is important for planning surgical procedures and percutaneous interventions of the liver. This article will review various imaging appearances of portal venous systems abnormalities.

Magnetic Resonance-Guided Focused Ultrasound: A Brief Review With Emphasis on the Treatment of Extra-abdominal Desmoid Tumors.

Magnetic resonance-guided focused ultrasound (MRgFUS) utilizes high-intensity focused ultrasound to noninvasively, thermally ablate lesions within the body while sparing the intervening tissues. Magnetic resonance imaging provides treatment planning and guidance, and real-time magnetic resonance thermometry provides continuous monitoring during therapy. Magnetic resonance-guided focused ultrasound is ideally suited for the treatment of extra-abdominal desmoid fibromatosis due to its noninvasiveness, lack of ionizing radiation, low morbidity, and good safety profile. Conventional treatments for these benign tumors, including surgery, radiation, and chemotherapy, can carry significant morbidity. Magnetic resonance-guided focused ultrasound provides a safe and effective alternative treatment in this often-young and otherwise healthy patient population. While there is considerable experience with MRgFUS for treatment of uterine fibroids, painful bone lesions, and essential tremor, there are few reports in the literature of its use for treatment of benign or malignant soft tissue tumors. This article reviews the principles and biologic effects of high-intensity focused ultrasound, provides an overview of the MRgFUS treatment system and use of magnetic resonance thermometry, discusses the use of MRgFUS for the treatment of extra-abdominal desmoid tumors, and provides several case examples.

Distal splenorenal and mesocaval shunting at the time of pancreatectomy.

BACKGROUND: When pancreatic neoplasms occlude or encase the superior mesenteric-portal-splenic vein confluence with abutment of the posterior lateral wall of the superior mesenteric artery, a mesocaval shunt with or without a distal splenorenal shunt allows for safe dissection of the porta hepatis and separation of the pancreatic tumor from the superior mesenteric artery. Herein we report long-term results of the largest known series of portosystemic shunts performed at the time of pancreatectomy. METHODS: All patients who underwent pancreatic resection with a mesocaval shunt or distal splenorenal shunt were identified from our prospective database. Demographics, perioperative treatment, and outcomes were reviewed. RESULTS: A total of 34 patients underwent mesocaval shunt or distal splenorenal shunt, including 25 at the time of pancreatoduodenectomy, 6 during total pancreatectomy, and 3 after prior pancreatectomy. There were 15 mesocaval shunts, 16 distal splenorenal shunts, 2 combined mesocaval/distal splenorenal shunts, and 1 distal splenoadrenal vein shunt. The mesocaval group included 11 temporary and 6 permanent (3 delayed) shunts. Median operative time was 9 hours (range 6.5-13), median estimated blood loss was 950 mL (range 200-5,000), and median duration of hospital stay was 11 days (range 7-35). Four patients experienced complications that required intervention (Clavien-Dindo grade ≥III), but there were no 90-day mortalities. For patients with adenocarcinoma, median overall survival was 31 months at a median follow-up of 19 months. All but 1 shunt (distal splenorenal) were patent at last follow-up. CONCLUSION: Mesenteric venous shunting facilitates a safe and complete tumor resection in patients who require a complex pancreatectomy, many of whom would otherwise be deemed inoperable.

Characterizing indeterminate liver lesions in patients with localized pancreatic cancer at the time of diagnosis.

BACKGROUND: In patients with newly diagnosed pancreatic cancer, the classification of indeterminate liver lesions is an unanswered clinical dilemma as misclassification of these lesions can impact the assignment of clinical stage and subsequent treatment planning. Our objective was to design a standardized classification system to more accurately define the risk of malignancy in indeterminate liver lesions. METHODS: In this retrospective study, patients with localized, non-metastatic pancreatic cancer were identified and pre-treatment computed tomography (CT) scans were evaluated for the presence or absence of liver lesions. Liver lesions were defined as definitely benign (1) or indeterminate (2). Indeterminate lesions were further sub-classified as either indeterminate probably benign (2B) or indeterminate possibly malignant (2M). The index liver lesion was evaluated on follow-up imaging for stability or unequivocal disease progression. RESULTS: From 2008 to 2015, 304 patients with localized, non-metastatic pancreatic cancer were identified and 125 (41%) patients had liver lesions. Of the 125 patients, the liver lesions in 35 (28%) were classified as definitely benign and in 90 (72%) patients they were classified as indeterminate. The 90 patients with indeterminate lesions included 80 (89%) classified as indeterminate probably benign (2B) and 10 (11%) classified as indeterminate possibly malignant (2M). After a median follow-up of 56 weeks, no patient with a definitely benign lesion had metastatic disease progression of the index lesion. Of the 90 patients with indeterminate liver lesions, the index lesion progressed to unequivocal liver metastasis in 8 (9%) patients; 5 (6%) of the 80 lesions classified as indeterminate probably benign (2B), and 3 (30%) of the ten lesions classified as indeterminate possibly malignant (2M). The sensitivity of the classification system was 38% and the specificity was 91%. The positive predictive value was 30% and the negative predictive value was 94%. CONCLUSIONS: A significant proportion of patients with localized pancreatic cancer will have liver lesions identified at the time of diagnosis and most of these lesions will have indeterminate characteristics. A classification system which further stratifies indeterminate liver lesions by malignant potential can assist clinicians in determining optimal treatment plan and is associated with a high negative predictive value.

Tetracycline compounds with non-antimicrobial organ protective properties: possible mechanisms of action.

Tetracyclines were developed as a result of the screening of soil samples for antibiotics. The first(t) of these compounds, chlortetracycline, was introduced in 1947. Tetracyclines were found to be highly effective against various pathogens including rickettsiae, as well as both gram-positive and gram-negative bacteria, thus becoming the first class of broad-spectrum antibiotics. Many other interesting properties, unrelated to their antibiotic activity, have been identified for tetracyclines which have led to widely divergent experimental and clinical uses. For example, tetracyclines are also an effective anti-malarial drug. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Another tetracycline, doxycycline is known to exert anti-protease activities. Doxycycline can inhibit matrix metalloproteinases which contribute to tissue destruction activities in diseases such as periodontitis. A large body of literature has provided additional evidence for the "beneficial" actions of tetracyclines, including their ability to act as reactive oxygen species scavengers and anti-inflammatory agents. This review provides a summary of tetracycline's multiple mechanisms of action as a means to understand their beneficial effects.

Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature.

There must be something unique about a class of drugs (discovered and developed in the mid-1940s) where there are more than 130 ongoing clinical trials currently listed. Tetracyclines were developed as a result of the screening of soil samples for antibiotic organisms. The first of these compounds chlortetracycline was introduced in 1948. Soon after their development tetracyclines were found to be highly effective against various pathogens including rickettsiae, Gram-positive, and Gram-negative bacteria, thus, becoming a class of broad-spectrum antibiotics. The mechanism of action of tetracyclines is thought to be related to the inhibition of protein synthesis by binding to the 30S bacterial ribosome. Tetracyclines are also an effective anti-malarial drug. Over time, many other "protective" actions have been described for tetracyclines. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Its mechanism of action appears to relate to specific effects exerted on apoptosis signaling pathways. Another tetracycline, doxycycline is known to exert antiprotease activities. Doxycycline can inhibit matrix metalloproteinases, which contribute to tissue destruction activities in diseases such as gingivitis. A large body of literature has provided additional evidence for the "beneficial" actions of tetracyclines, including their ability to act as oxygen radical scavengers and anti-inflammatory agents. This increasing volume of published work and ongoing clinical trials supports the notion that a more systematic examination of their possible therapeutic uses is warranted. This review provides a summary of tetracycline's multiple mechanisms of action and while using the effects on the heart as an example, this review also notes their potential to benefit patients suffering from various pathologies such as cancer, Rosacea, and Parkinson's disease.

Platelet-derived growth factor receptor antagonist STI571 (imatinib mesylate) inhibits human vascular smooth muscle proliferation and migration in vitro but not in vivo.

BACKGROUND: Cell-specific inhibition of vascular smooth muscle cells, the primary constituent of neointima following arterial injury, without deleterious effects on vascular endothelial cell function may be a critical requirement for drug-eluting stents that are not prone to excess late thrombosis. We hypothesized that imatinib mesylate (Gleevec, Glivec, formerly known as STI571), a relatively selective inhibitor of protein tyrosine kinases including platelet-derived growth factor receptor (PDGFR), would inhibit hCASMC proliferation and migration in vitro with little effect on endothelial cell proliferation and prevent restenosis in a swine balloon injury model. METHODS: Proliferation and migration of stimulated human vascular smooth muscle and endothelial cells were quantified in cell culture in the presence of imatinib (0.001 to 10 M). Imatinib-loaded drug-eluting stents were implanted in swine coronary arteries after predilatation with an oversized balloon, and neointimal proliferation was measured by quantitative angiography and histopathology. RESULTS: Increasing doses of imatinib-inhibited autophosphorylation of the PDGFR and its downstream effects of proliferation and migration of human CASMC in a dose-responsive manner, yet had no effect on stimulated human aortic endothelial cells. However, imatinib-eluting stents had no effect on neointimal proliferation and restenosis in a standard porcine in-stent restenosis model compared to bare-metal or unloaded polymer-coated stents. CONCLUSION: We conclude that imatinib is a potent inhibitor of proliferation and migration of human vascular smooth muscle cells in vitro, but has no effect on human vascular endothelial cell proliferation. However, the lack of an in vivo effect on neointimal proliferation in a standard porcine coronary overstretch model does not support the use of imatinib mesylate for localized drug delivery in the prevention of in-stent restenosis.

Heterocyclic zinc-binding groups for use in next-generation matrix metalloproteinase inhibitors: potency, toxicity, and reactivity.

In an effort to improve the zinc-chelating portion of matrix metalloproteinase (MMP) inhibitors, we have developed a family of heterocyclic zinc-binding groups (ZBGs) as alternatives to the widely used hydroxamic acid moiety. Elaborating on findings from an earlier report, we performed in vitro inhibition assays with recombinant MMP-1, MMP-2, and in a cell culture assay using neonatal rat cardiac fibroblast cells. In both recombinant and cell culture assays, the new ZBGs were found to be effective inhibitors, typically 10-100-fold more potent than acetohydroxamic acid. The toxicity of these chelators was examined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt cytotoxicity assays, which demonstrate that most of these compounds are nontoxic at concentrations of almost 100 microM. To address the possible interaction of sulfur-containing ZBGs with biological reductants, the reactivity of these chelators with 5,5'-dithiobis(2-nitrobenzoic acid) was examined. Finally, thione ZBGs were shown to be effective inhibitors of cell invasion through an extracellular matrix membrane. The data presented herein suggest these heterocyclic ZBGs are potent, nontoxic, and biocompatible compounds that show promise for incorporation into a new family of MMP inhibitors.

Reduction of myocardial infarct size by doxycycline: a role for plasmin inhibition.

Myocardial ischemia-reperfusion (I/R) is associated with the activation of matrix metalloproteinases (MMPs) and serine proteases. We hypothesized that activation of MMPs and the serine protease plasmin contribute to early cardiac myocyte death following I/R and that broad-spectrum protease inhibition with doxycycline (DOX) preserves myocyte viability. Rats treated daily with or without DOX beginning 48 h prior to experimentation were subjected to 30 min of coronary occlusion and 2 days of reperfusion. DOX pre-treatment reduced infarct size by 37%. DOX attenuated increases in MMP-9 and plasmin levels as determined by gelatin zymography and immunoblot, respectively. Neutrophil extravasation was unaltered by DOX as assessed by myeloperoxidase (MPO) activity. To examine the contribution of MMP-9 and plasmin to myocyte injury, cultures of neonatal rat ventricular myocytes (NRVMs) were treated for 48 h with 83 kDa MMP-9 or plasminogen in the presence or absence of DOX. MMP-9 treatment did not affect myocyte viability. Plasminogen treatment led to increased plasmin activity, resulting in loss of beta1-integrin, NRVM detachment and apoptosis. DOX co-treatment inhibited plasmin activity and preserved NRVM attachment, whereas co-treatment with the broad-spectrum MMP inhibitor GM6001 had no effect. These results indicate that plasmin causes disruption of myocyte attachment and viability independently of MMP activation in vitro and that inhibition of plasmin by DOX may reduce I/R-induced myocyte death in vivo through the inhibition of plasmin.