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.

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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.

◥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.