Memory-Augmented Capsule Network for Adaptable Lung Nodule Classification.

Computer-aided diagnosis (CAD) systems must constantly cope with the perpetual changes in data distribution caused by different sensing technologies, imaging protocols, and patient populations. Adapting these systems to new domains often requires significant amounts of labeled data for re-training. This process is labor-intensive and time-consuming. We propose a memory-augmented capsule network for the rapid adaptation of CAD models to new domains. It consists of a capsule network that is meant to extract feature embeddings from some high-dimensional input, and a memory-augmented task network meant to exploit its stored knowledge from the target domains. Our network is able to efficiently adapt to unseen domains using only a few annotated samples. We evaluate our method using a large-scale public lung nodule dataset (LUNA), coupled with our own collected lung nodules and incidental lung nodules datasets. When trained on the LUNA dataset, our network requires only 30 additional samples from our collected lung nodule and incidental lung nodule datasets to achieve clinically relevant performance (0.925 and 0.891 area under receiving operating characteristic curves (AUROC), respectively). This result is equivalent to using two orders of magnitude less labeled training data while achieving the same performance. We further evaluate our method by introducing heavy noise, artifacts, and adversarial attacks. Under these severe conditions, our network's AUROC remains above 0.7 while the performance of state-of-the-art approaches reduce to chance level.

Entinostat reverses cisplatin resistance in esophageal squamous cell carcinoma via down-regulation of multidrug resistance gene 1.

Cisplatin resistance frequently occurs in esophageal squamous cell carcinoma (ESCC). The underlying mechanism for cisplatin resistance in ESCC remains largely obscure. Here we report that entinostat reversed cisplatin resistance in ESCC both in vitro and in vivo by induction of apoptosis and inhibition of cell proliferation, accompanied by a decrease of multidrug resistance gene 1 (MDR1), P-Src, Mcl-1, Cyclin D1 and an increase of cleaved PARP. MDR1 expression was associated with worsen survival of ESCC patients with cisplatin-based chemotherapy. Dasatinib potentiated entinostat to overcome cisplatin resistance. By inhibiting Src, dasatinib reduced the expression of MDR1 and Mcl-1. Furthermore, Obatoclax, an inhibitor of Mcl-1, obviously decreased the expression of MDR1, suggesting that entinostat might surmount cisplatin resistance in ESCC via a Src-Mcl-1-MDR1 pathway. Interestingly, cisplatin also enhanced the effect of entinostat both in vitro and in vivo. Our data disclose a molecular basis that entinostat reverses cisplatin resistance, and provide a promising strategy with combinatorial drugs to treat cisplatin resistant ESCC patients.

Image-guided fiberoptic molecular imaging in a VX2 rabbit lung tumor model.

PURPOSE: To show the feasibility of computed tomography (CT) image-guided fiberoptic confocal fluorescence molecular imaging in a rabbit lung tumor model. MATERIALS AND METHODS: Eight lung tumor models were created by injection of a VX2 cell suspension. The fluorescent imaging agent IntegriSense 680 was given to the animals 3.5-4 hours before the procedure. CT images were obtained and transferred to the minimally invasive multimodality image-guided (MIMIG) system as a guidance map. A real-time electromagnetically tracked needle was inserted under the visual guidance of the MIMIG system. A second CT image was obtained to confirm the location of the needle tip. Next, fiberoptic fluorescence imaging was acquired along the needle track. Finally, tumor samples were obtained for histopathologic confirmation. RESULTS: All cases were performed during breath-hold. Tumor size was 12.5 mm ± 1.6; the distance from the chest wall was 2.1 mm ± 0.5. The needle tip reached the tumor in all cases with an accuracy of 3.3 mm ± 1.6. Only one skin entry point was necessary, and no needle adjustments were required. No pneumothorax was observed. At least two-fold α(v)ß(3) integrin image contrast was detected in the tumor compared with normal lung tissue. Tumor samples were confirmed to have viable VX2 cells and contrast uptake. CONCLUSIONS: The MIMIG system enables effective in situ fluorescence molecular imaging in a needle biopsy lung procedure. In situ α(v)ß(3) integrin molecular imaging allows molecular characterization of lung tumors at multiple regions and can be used to guide biopsy procedures.