MRI of Lymphedema.

Lymphedema is a devastating disease that has no cure. Management of lymphedema has evolved rapidly over the past two decades with the advent of surgeries that can ameliorate symptoms. MRI has played an increasingly important role in the diagnosis and evaluation of lymphedema, as it provides high spatial resolution of the distribution and severity of soft tissue edema, characterizes diseased lymphatic channels, and assesses secondary effects such as fat hypertrophy. Many different MR techniques have been developed for the evaluation of lymphedema, and the modality can be tailored to suit the needs of a lymphatic clinic. In this review article we provide an overview of lymphedema, current management options, and the current role of MRI in lymphedema diagnosis and management. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 5.

Lung Cancer Recurrence: 18F-FDG PET/CT in Clinical Practice.

OBJECTIVE: The purpose of this article is to summarize the clinical utility of 18F-FDG PET/CT in the evaluation of lung cancer recurrence with an emphasis on typical anatomic and metabolic patterns of recurrence, expected posttherapeutic changes, and common pitfalls of FDG PET/CT. FDG PET/CT is useful in assessing therapeutic response and in determining the extent of recurrent disease and provides a guide for targeted biopsy. CONCLUSION: FDG PET/CT plays a crucial role in the evaluation of therapeutic response in lung cancer and guides management.

Noninvasive Physiologic Vascular Studies: A Guide to Diagnosing Peripheral Arterial Disease.

Noninvasive physiologic vascular studies play an important role in the diagnosis and characterization in peripheral arterial disease (PAD) of the lower extremity. These studies evaluate the physiologic parameters of blood flow through segmental arterial pressures, Doppler waveforms, and pulse volume recordings. Collectively, they comprise a powerful toolset for defining the functionality of the arterial system, localizing the site of disease, and providing prognostic data. This technology has been widely adopted by diverse medical specialty practitioners, including radiologists, surgeons, cardiologists, and primary care providers. The use of these studies increased substantially between 2000 and 2010. Although they do not employ imaging, they remain a critical component for a comprehensive radiologic vascular laboratory. A strong presence of radiology in the diagnosis of PAD adds value in that radiologists have shifted to noninvasive alternatives to diagnostic catheter angiography (DCA), such as computed tomography (CT) and magnetic resonance (MR) angiography, which provide a more efficient, less-expensive, and lower-risk alternative. Other specialties have increased the use of DCA during the same period. The authors provide a review of the relevant anatomy and physiology of PAD as well as the associated clinical implications. In addition, guidelines for interpreting the ankle-brachial index, segmental pressures, Doppler waveforms, and pulse volume recordings are reviewed as well as potential limitations of these studies. Noninvasive physiologic vascular studies are provided here for review with associated correlating angiographic, CT, and/or MR findings covering the segmental distribution of PAD as well as select nonatherosclerotic diagnoses. ©RSNA, 2016.

Isolated prostate amyloidosis; a case report.

Identification of amyloidosis on a prostate biopsy specimen raises suspicion for systemic amyloidosis. For patients at risk of prostate adenocarcinoma, a transrectal MRI ultrasound fusion (MRI-TRUS) guided biopsy of the prostate is often needed for further investigation. Our patient is a 70 year old male presenting from his primary care provider with an elevated PSA. The patient underwent MRI-TRUS fusion biopsy of the prostate, which demonstrated AL (lambda)-type amyloidosis, confirmed by mass spectrometry in addition to prostatic adenocarcinoma. He was subsequently diagnosed with primary amyloidosis of the prostate without evidence of other amyloid deposition sites.

LI-RADS treatment response algorithm after first-line DEB-TACE: reproducibility and prognostic value at initial post-treatment CT/MRI.

PURPOSE: To evaluate the inter-reader reproducibility and prognostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (LR-TR) at the time of initial post-treatment evaluation following drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC). METHODS: This retrospective study included patients with HCC who underwent first-line DEB-TACE between January 2011 and December 2015. Six readers (three fellowship-trained radiologists and three radiology trainees) independently assessed lesion-level response in up to two treated lesions per LR-TR and modified Response Evaluation Criteria in Solid Tumors (mRECIST)-target criteria, as well as patient-level response per mRECIST-overall criteria, on the initial post-treatment CT/MRI. Inter-reader agreement was calculated by Fleiss' multi-reader κ. We tested whether LR-TR, mRECIST-target, and mRECIST-overall response were associated with overall survival using Kaplan-Meier and Cox proportional hazard model analyses. RESULTS: A total of 82 patients with 113 treated target lesions were included. Inter-reader agreement was moderate for LR-TR and mRECIST-overall (κ range 0.42-0.57), and substantial for mRECIST-target (κ range 0.62-0.66), among all three reader-groups: all readers, experienced readers, and less-experienced readers. LR-TR and mRECIST-target response were not significantly associated with overall survival regardless of reader experience (P > 0.05). In contrast, mRECIST-overall response was significantly associated with overall survival when assessed by all readers (P = 0.02) and experienced readers (P = 0.03), but not by the less-experienced readers (P = 0.35). CONCLUSION: Although LR-TR algorithm has moderate inter-reader reproducibility, it alone may not predict overall survival on the initial post-treatment CT/MRI after first-line DEB-TACE for HCC.

Discovery of a Series of Pyrazinone RORγ Antagonists and Identification of the Clinical Candidate BI 730357.

The interleukin (IL)-23/T helper (Th)17 axis plays a critical role in autoimmune diseases, and there is an increasing number of biologic therapies that target IL-23 and IL-17. The transcription factor retinoic acid receptor-related orphan nuclear receptor γt (RORγt) is important for the activation and differentiation of Th17 cells and thus is an attractive pharmacologic target for the treatment of Th17-mediated diseases. A novel series of pyrazinone RORγ antagonists was discovered through hybridization of two distinct screening hits and scaffold hopping. The series offers attractive potency and selectivity in combination with favorable druglike properties, such as metabolic stability and aqueous solubility. Lead optimization identified a clinical candidate, compound (S)-11 (BI 730357), for the treatment of autoimmune diseases.

Deciphering Intratumoral Molecular Heterogeneity in Clear Cell Renal Cell Carcinoma with a Radiogenomics Platform.

PURPOSE: Intratumoral heterogeneity (ITH) challenges the molecular characterization of clear cell renal cell carcinoma (ccRCC) and is a confounding factor for therapy selection. Most approaches to evaluate ITH are limited by two-dimensional ex vivo tissue analyses. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can noninvasively assess the spatial landscape of entire tumors in their natural milieu. To assess the potential of DCE-MRI, we developed a vertically integrated radiogenomics colocalization approach for multi-region tissue acquisition and analyses. We investigated the potential of spatial imaging features to predict molecular subtypes using histopathologic and transcriptome correlatives. EXPERIMENTAL DESIGN: We report the results of a prospective study of 49 patients with ccRCC who underwent DCE-MRI prior to nephrectomy. Surgical specimens were sectioned to match the MRI acquisition plane. RNA sequencing data from multi-region tumor sampling (80 samples) were correlated with percent enhancement on DCE-MRI in spatially colocalized regions of the tumor. Independently, we evaluated clinical applicability of our findings in 19 patients with metastatic RCC (39 metastases) treated with first-line antiangiogenic drugs or checkpoint inhibitors. RESULTS: DCE-MRI identified tumor features associated with angiogenesis and inflammation, which differed within and across tumors, and likely contribute to the efficacy of antiangiogenic drugs and immunotherapies. Our vertically integrated analyses show that angiogenesis and inflammation frequently coexist and spatially anti-correlate in the same tumor. Furthermore, MRI contrast enhancement identifies phenotypes with better response to antiangiogenic therapy among patients with metastatic RCC. CONCLUSIONS: These findings have important implications for decision models based on biopsy samples and highlight the potential of more comprehensive imaging-based approaches.

Multimodality depiction of findings in branchio-oto-renal syndrome: two case reports.

Branchio-oto-renal syndrome is a rare genetic disorder that affects multiple organ systems. Temporal bone abnormalities include the unwound appearance of the cochlea which is common in this syndrome. This appearance can prompt renal imaging and evaluation. Presented here are two cases of branchio-oto-renal syndrome with dysplastic cochleae. A branchial cleft sinus and renal dysplasia were also present in one of the cases.

Interventional radiology in the management of thoracic duct injuries: Anatomy, techniques and results.

Disruption of the thoracic duct can have devastating consequences and be associated with a high morbidity and mortality. Conservative therapies have been attempted to treat chylothorax without much success. Surgical management has traditionally been necessary to provide definitive treatment at the expense of increased morbidity. Lymphatic interventions have recently emerged as a new frontier for interventional radiologists to add value and provide minimally invasive therapies for debilitating conditions. The goal of this manuscript is to review the anatomy of the thoracic duct, describe various percutaneous techniques for accessing the duct, and briefly discuss outcomes as reported in the literature.

Identification of Gene Expression Differences between Lymphangiogenic and Non-Lymphangiogenic Non-Small Cell Lung Cancer Cell Lines.

It is well established that lung tumors induce the formation of lymphatic vessels. However, the molecular mechanisms controlling tumor lymphangiogenesis in lung cancer have not been fully delineated. In the present study, we identify a panel of non-small cell lung cancer (NSCLC) cell lines that induce lymphangiogenesis and use genome-wide mRNA expression to characterize the molecular mechanisms regulating tumor lymphangiogenesis. We show that Calu-1, H1993, HCC461, HCC827, and H2122 NSCLC cell lines form tumors that induce lymphangiogenesis whereas Calu-3, H1155, H1975, and H2073 NSCLC cell lines form tumors that do not induce lymphangiogenesis. By analyzing genome-wide mRNA expression data, we identify a 17-gene expression signature that distinguishes lymphangiogenic from non-lymphangiogenic NSCLC cell lines. Importantly, VEGF-C is the only lymphatic growth factor in this expression signature and is approximately 50-fold higher in the lymphangiogenic group than in the non-lymphangiogenic group. We show that forced expression of VEGF-C by H1975 cells induces lymphangiogenesis and that knockdown of VEGF-C in H1993 cells inhibits lymphangiogenesis. Additionally, we demonstrate that the triple angiokinase inhibitor, nintedanib (small molecule that blocks all FGFRs, PDGFRs, and VEGFRs), suppresses tumor lymphangiogenesis in H1993 tumors. Together, these data suggest that VEGF-C is the dominant driver of tumor lymphangiogenesis in NSCLC and reveal a specific therapy that could potentially block tumor lymphangiogenesis in NSCLC patients.

4,5-Disubstituted cis-pyrrolidinones as inhibitors of type II 17beta-hydroxysteroid dehydrogenase. Part 2. SAR.

4,5-Disubstituted cis-pyrrolidinones were investigated as inhibitors of type II 17beta-hydroxysteroid dehydrogenase (17beta-HSD). Early structure-activity relationship patterns for this class of compounds are discussed.

A novel estrogen receptor ligand template.

Three synthetic routes towards a novel estrogen receptor ligand template based on a rigid bicyclo-[3.3.1]-nonene core have been investigated. The prototype compound exhibits potent binding at the ERbeta receptor and promising estrogen receptor subtype selectivity.

Synthesis and pharmacological characterization of a potent, orally active p38 kinase inhibitor.

Inhibitors of the MAP kinase p38 provide a novel approach for the treatment of osteoporosis, inflammatory disorders, and cancer. We have identified N-(3-tert-butyl-1-methyl-5-pyrazolyl)-N'-(4-(4-pyridinylmethyl)phenyl)urea as a potent and selective p38 kinase inhibitor in biochemical and cellular assays. This compound is orally active in two acute models of cytokine release (TNF-induced IL-6 and LPS-induced TNF) and a chronic model of arthritis (20-day murine collagen-induced arthritis).

Omega-carboxypyridyl substituted ureas as Raf kinase inhibitors: SAR of the amide substituent.

Bis-aryl ureas have been disclosed previously as a potent class of Raf kinase inhibitors. Modifications in the amide portion led to an improvement in aqueous solubility, an important characteristic for an oral drug. Based on this finding, we hypothesize that this portion of the molecule is directed towards the solvent in Raf-1.