Featured
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| Open AccessA fluorogenic probe for granzyme B enables in-biopsy evaluation and screening of response to anticancer immunotherapies
Granzyme B is found in activated T cells and can be used as a marker of T cell activation. Here, the authors generate a fluorescent probe that can detect Granzyme B levels in tumours, and has the potential to be used as a biomarker of response to immunotherapy.
- Jamie I. Scott
- , Lorena Mendive-Tapia
- & Marc Vendrell
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Article
| Open AccessDissecting extracellular and intracellular distribution of nanoparticles and their contribution to therapeutic response by monochromatic ratiometric imaging
Detailed quantification of nanoparticle distribution in tumor tissues can provide the prediction of drug delivery efficacy and therapeutic outcome. Here the authors develop a pH/light dual responsive monochromatic ratiometric-imaging nanoparticle which can quantify extracellular and intracellular nanoparticle distribution in several tumor models.
- Yue Yan
- , Binlong Chen
- & Yiguang Wang
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Article
| Open AccessCarbonized paramagnetic complexes of Mn (II) as contrast agents for precise magnetic resonance imaging of sub-millimeter-sized orthotopic tumors
Improving the imaging of cancer may enhance the treatment of patients, Here, the authors develop a Mn(II) based nanoparticle contrast agent for MRI imaging and show that the nanoparticles can cross the brain barrier and image glioma cells.
- Ruixue Qin
- , Shi Li
- & Hongmin Chen
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Article
| Open AccessZebrafish imaging reveals TP53 mutation switching oncogene-induced senescence from suppressor to driver in primary tumorigenesis
It is unclear how a single oncogenic cell primes tumorigenesis. Here the authors visualised this behaviour using a zebrafish larval skin as a model and show that RasG12V oncogenic cell is eliminated through oncogene-senescence while a gain of function mutation in p53 alters this behaviour from tumour suppressive to tumour promoting.
- Yukinari Haraoka
- , Yuki Akieda
- & Tohru Ishitani
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| Open AccessHyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer
Your paper will be accompanied by the following editor’s summary. Please let us know if there are any inaccuracies: ‘Hyperpolarised ¹³C-MRI is used to image cancer metabolism. Here the authors use this technique in prostate cancer and show that it can differentiate distinct disease states.
- Nikita Sushentsev
- , Mary A. McLean
- & Ferdia A. Gallagher
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| Open AccessA bioactivated in vivo assembly nanotechnology fabricated NIR probe for small pancreatic tumor intraoperative imaging
Fluorescence probes for detecting tumours during surgery can suffer from poor accumulation and short imaging windows. Here, the author develop fluorescence probes with multiple motifs that permit enhanced circulation times, tumour targeting and use the probes to image pancreatic cancer in mice
- Han Ren
- , Xiang-Zhong Zeng
- & Li-Li Li
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Article
| Open AccessLive tumor imaging shows macrophage induction and TMEM-mediated enrichment of cancer stem cells during metastatic dissemination
Intravital imaging reveals macrophage-driven de novo induction of cancer stem cells in vivo, and their dramatic enrichment on dissemination through TMEM doorways. These findings provide a mechanism for the validated ability of TMEM doorway density to be prognostic for distant recurrence of metastatic tumors in breast cancer patients.
- Ved P. Sharma
- , Binwu Tang
- & Maja H. Oktay
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Article
| Open AccessKRas-transformed epithelia cells invade and partially dedifferentiate by basal cell extrusion
The ability to visualise stochastic invasion events is limited in murine models of metastatic cancers. Here the authors use a transparent zebrafish epidermis model to follow the invasion events of K-Ras transformed epithelial cells and show that these cells invade through basal cell extrusion.
- John Fadul
- , Teresa Zulueta-Coarasa
- & Jody Rosenblatt
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Article
| Open AccessDeep learning for the prediction of early on-treatment response in metastatic colorectal cancer from serial medical imaging
Evaluation of tumor response to antivascular endothelial growth factor therapies in metastatic colorectal cancer (mCRC) is limited because morphological change in tumor may occur earlier or be more critical than tumor size change. Here, the authors present an analysis utilizing a deep learning network to characterize tumor morphological change as well as tumor size changes for response assessment in mCRC patients.
- Lin Lu
- , Laurent Dercle
- & Lawrence H. Schwartz
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Article
| Open AccessAggregation-induced emission luminogens for image-guided surgery in non-human primates
Most applications of aggregation-induced emission luminogens (AIEgens) have been limited in small animal models. Here, the authors show the versatility of AIEgens-based imaging-guided surgical operation from small animals to rhesus macaque, in support of the clinical translation of AIEgens.
- Danni Zhong
- , Weiyu Chen
- & Min Zhou
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Article
| Open AccessAccurate recognition of colorectal cancer with semi-supervised deep learning on pathological images
Machine-assisted recognition of colorectal cancer has been mainly focused on supervised deep learning that suffers from a significant bottleneck of requiring massive amounts of labeled data. Here, the authors propose a semi-supervised model based on the mean teacher architecture that provides pathological predictions at both patch- and patient-levels.
- Gang Yu
- , Kai Sun
- & Hong-Wen Deng
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Article
| Open AccessGeneration of hydroxyl radical-activatable ratiometric near-infrared bimodal probes for early monitoring of tumor response to therapy
The hydroxyl radical is generated during radiotherapy and ferroptosis and accurate imaging of this reactive oxygen species may permit the monitoring of response to therapy. Here, the authors develop a ratiometric probe for accurate imaging of hydroxyl radical generation in vivo.
- Luyan Wu
- , Yusuke Ishigaki
- & Deju Ye
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Article
| Open AccessHigh-resolution positron emission microscopy of patient-derived tumor organoids
Positron emission tomography (PET) radiotracers measure the metabolic activity in cancer cells in patients. Here, the authors develop a microscopy method to image organoids using clinical radiotracers, which allows a direct comparison to PET imaging in patients.
- Syamantak Khan
- , June Ho Shin
- & Guillem Pratx
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Article
| Open AccessA prostate-specific membrane antigen activated molecular rotor for real-time fluorescence imaging
Detection of the tumour boundary in prostate cancer is required for surgery. Here the authors present a fluorescent molecular rotor probe to target a prostate cancer marker, prostate-specific membrane antigen (PSMA), which they use in a xenograft mouse model to show it can be used for in vivo imaging.
- Jingming Zhang
- , Anastasia Rakhimbekova
- & Xing Yang
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| Open AccessNodal immune flare mimics nodal disease progression following neoadjuvant immune checkpoint inhibitors in non-small cell lung cancer
Granulomatous/sarcoid-like lesions have been reported in patients treated with immune checkpoint inhibitors (ICIs). Here the authors report the occurrence of “nodal immune flare”, an apparent radiological cancer progression in the nodes characterized by the absence of cancer and the presence of non-caseating granulomas, in patients with non-small cell lung cancer following neoadjuvant ICI treatment.
- Tina Cascone
- , Annikka Weissferdt
- & Boris Sepesi
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Article
| Open AccessChemical tools for epichaperome-mediated interactome dysfunctions of the central nervous system
Here, the authors show structural, biochemical, and functional insights into the discovery of epichaperome‐ directed chemical probes for use in central nervous system diseases. Probes emerging from this work have translated to human clinical studies in Alzheimer’s disease and cancer.
- Alexander Bolaender
- , Danuta Zatorska
- & Gabriela Chiosis
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Article
| Open AccessSubcellular localization of biomolecules and drug distribution by high-definition ion beam imaging
Multiplexed ion beam imaging can provide subcellular localisation information but with limited resolution. Here the authors report an ion beam imaging method with nanoscale resolution which they use to assess the subcellular distribution of cisplatin.
- Xavier Rovira-Clavé
- , Sizun Jiang
- & Garry P. Nolan
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| Open AccessThe impact of site-specific digital histology signatures on deep learning model accuracy and bias
Deep learning models have been trained on The Cancer Genome Atlas to predict numerous features directly from histology, including survival, gene expression patterns, and driver mutations. Here, the authors demonstrate that site-specific histologic signatures can lead to biased estimates of accuracy for such models, and propose a method to minimize such bias.
- Frederick M. Howard
- , James Dolezal
- & Alexander T. Pearson
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| Open AccessArtificially engineered antiferromagnetic nanoprobes for ultra-sensitive histopathological level magnetic resonance imaging
Ultra-high-field (UHF) magnetic resonance imaging (MRI) has potential for imaging disease including cancer metastasis. Here, the authors develop an ultra-sensitive antiferromagnetic nanoparticle probe with a small magnetisation for use in UHF MRI and demonstrate the ability to detect small primary tumours and micrometastases in mice.
- Zeyu Liang
- , Qiyue Wang
- & Daishun Ling
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Article
| Open AccessRational construction of a reversible arylazo-based NIR probe for cycling hypoxia imaging in vivo
Most fluorescence probes to measure hypoxia are irreversible. Here, the authors develop a near infrared luminescent probe to measure hypoxia which is reversible and use the probe to monitor hypoxia-reoxygenation in several animal models.
- Yuming Zhang
- , Wenxuan Zhao
- & Weijiang He
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Article
| Open AccessInterleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer
The stromal fibroblast population in the colon is composed of heterogeneous and distinct cell subtypes that play a crucial role in the development of colitis and colon cancer. Here the authors generate IL-11 reporter mice and characterize the origin and phenotype of inflammatory IL-11+ fibroblasts in colitis and colon cancer preclinical models.
- Takashi Nishina
- , Yutaka Deguchi
- & Hiroyasu Nakano
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| Open AccessHuman-interpretable image features derived from densely mapped cancer pathology slides predict diverse molecular phenotypes
Computational methods have made progress in improving classification accuracy and throughput of pathology workflows, but lack of interpretability remains a barrier to clinical integration. Here, the authors present an approach for predicting clinically-relevant molecular phenotypes from whole-slide histopathology images using human-interpretable image features.
- James A. Diao
- , Jason K. Wang
- & Amaro Taylor-Weiner
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| Open AccessAn annotation-free whole-slide training approach to pathological classification of lung cancer types using deep learning
Deep learning for digital pathology is hindered by the extremely high spatial resolution of whole slide images (WSIs), which requires researchers to adopt patch-based methods and laborious free-hand contouring. Here, the authors develop a whole-slide training method to classify types of lung cancers using slide-level diagnoses with deep learning.
- Chi-Long Chen
- , Chi-Chung Chen
- & Cheng-Yu Chen
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| Open AccessSelf-assembled organic nanomedicine enables ultrastable photo-to-heat converting theranostics in the second near-infrared biowindow
Organic agents with activity in the second near infrared region (NIR-II) are needed for precise treatment of cancer. Here, the authors develop boron difluoride formazanate nanosystem as a theranostic agent active in the NIR-II region for treating deep-seated hepatocellular carcinoma in mice.
- Huijing Xiang
- , Lingzhi Zhao
- & Yanli Zhao
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Article
| Open AccessNon-invasive assessment of telomere maintenance mechanisms in brain tumors
Telomerase expression and the alternative lengthening of telomeres pathway are hallmarks of cancer. Here, the authors show that, in primary brain tumors, these features are correlated with metabolic signatures detectable by metabolic imaging, suggesting that they can be used to non-invasively monitor telomere maintenance in brain tumours.
- Pavithra Viswanath
- , Georgios Batsios
- & Sabrina M. Ronen
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| Open AccessA deep learning diagnostic platform for diffuse large B-cell lymphoma with high accuracy across multiple hospitals
Replacing diagnostic histopathology with AI-based tools requires large training datasets and robustness to sample variability. Here, the authors present a deep learning platform with high accuracy in large diffuse B-cell lymphoma diagnosis across multiple hospitals, trained on small datasets.
- Dongguang Li
- , Jacob R. Bledsoe
- & Shaoguang Li
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Article
| Open AccessCo-administered antibody improves penetration of antibody–dye conjugate into human cancers with implications for antibody–drug conjugates
Antibody-drug conjugates targeting high expression receptors can suffer from poor tumour penetration. Here, the authors use unconjugated antibody to improve the penetration of an antibody-dye conjugate in a clinical study, supporting further clinical investigation of the co-administration strategy.
- Guolan Lu
- , Naoki Nishio
- & Eben L. Rosenthal
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Article
| Open AccessNon-invasive decision support for NSCLC treatment using PET/CT radiomics
EGFR mutations are common in non-small cell lung cancer and patients with these mutations are treated with tyrosine kinase inhibitors. Here, the authors show that EGFR mutation status can be predicted from 18F-FDG-PET/CT images, which may enable the stratification of patients for treatment.
- Wei Mu
- , Lei Jiang
- & Matthew B. Schabath
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| Open AccessUltralong purely organic aqueous phosphorescence supramolecular polymer for targeted tumor cell imaging
Room-temperature phosphorescence has attracted attention for bioimaging, but quenching in aqueous systems is an issue. Here, the authors report on the synthesis of a water soluble organic phosphorescent polymer and demonstrate application is cancer cell targeting and imaging.
- Wei-Lei Zhou
- , Yong Chen
- & Yu Liu
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Article
| Open AccessPredicting distant metastasis and chemotherapy benefit in locally advanced rectal cancer
Distant metastasis (DM) is the main cause of treatment failure in locally advanced rectal cancer. Here, the authors developed and validated a radiomic signature (RS) for prediction of DM within a multicenter dataset, and suggest that it may help with stratification of patients who might benefit from adjuvant chemotherapy for DM.
- Zhenyu Liu
- , Xiaochun Meng
- & Jie Tian
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| Open AccessExploiting metabolic acidosis in solid cancers using a tumor-agnostic pH-activatable nanoprobe for fluorescence-guided surgery
It is well known that the pH of tumor tissue is lower than that of the corresponding normal adjacent tissue. Here, the authors report a clinical trial of a pH activatable nanoparticle for imaging tumours.
- F. J. Voskuil
- , P. J. Steinkamp
- & S. A. H. J. de Visscher
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Article
| Open AccessEarly stratification of radiotherapy response by activatable inflammation magnetic resonance imaging
Non-invasive approaches to stratify early responses to therapy are of great value to improve cancer patient management. Here the authors design a hybrid nanovesicle-based activatable inflammation magnetic resonance method for the early prediction of response to radiotherapy.
- Zijian Zhou
- , Hongzhang Deng
- & Xiaoyuan Chen
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Article
| Open AccessSuper-resolution imaging reveals the evolution of higher-order chromatin folding in early carcinogenesis
Aberrant chromatin structure is often found in cancer. Here, the authors optimise super-resolution microscopy for pathological tissue and discovered a significant decompaction of chromatin folding in early carcinogenesis prior to tumour formation.
- Jianquan Xu
- , Hongqiang Ma
- & Yang Liu
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| Open AccessDeep learning radiomics can predict axillary lymph node status in early-stage breast cancer
Breast cancer is frequently diagnosed using ultrasound. Here, the authors show that, in addition to ultrasound, shear wave elastography can be used to diagnose breast cancer and, in conjunction with deep learning and radiomics, can predict whether the disease has spread to axillary lymph nodes.
- Xueyi Zheng
- , Zhao Yao
- & Jianhua Zhou
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| Open AccessA case report of multiple primary prostate tumors with differential drug sensitivity
Prostate cancer is often a multifocal disease but how best to manage this clinically remains unclear. Here, the authors report a single case study of a patient with two genetically diverse tumours which showed differential response to therapy.
- Scott Wilkinson
- , Stephanie A. Harmon
- & Adam G. Sowalsky
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| Open AccessTissue pO2 distributions in xenograft tumors dynamically imaged by Cherenkov-excited phosphorescence during fractionated radiation therapy
Hypoxia in solid tumors is an important factor in radiation therapy resistance, but partial pressures of oxygen in the tissue are heterogenous and difficult to measure. Here the authors develop Cherenkov excited phosphorescence imaging using oxygen probe Oxyphor PtG4 to spatially track oxygen distributions in tumors during fractionated radiotherapy.
- Xu Cao
- , Srinivasa Rao Allu
- & Brian W. Pogue
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| Open AccessTargeting the tumor vasculature with engineered cystine-knot miniproteins
Cystine-knot miniprotein are small, highly stable, disulfide-rich peptides with increasing potential as drugs and tumor imaging agents. Here the authors develop cystine-knot miniproteins targeting the vascular tumor marker EDB, and use them as probes for in vivo tumor vasculature imaging.
- Bonny Gaby Lui
- , Nadja Salomon
- & Ugur Sahin
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Article
| Open AccessAutomated acquisition of explainable knowledge from unannotated histopathology images
Technologies for acquiring explainable features from medical images need further development. Here, the authors report a deep learning based automated acquisition of explainable features from pathology images, and show a higher accuracy of their method as compared to pathologist based diagnosis of prostate cancer recurrence.
- Yoichiro Yamamoto
- , Toyonori Tsuzuki
- & Go Kimura
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Article
| Open AccessOptical molecular imaging can differentiate metastatic from benign lymph nodes in head and neck cancer
Imaging metastatic disease burden in lymph nodes is important for surgical decision making. Here, the authors use an antibody-dye conjugate to distinguish between metastatic and benign lymph nodes in head and neck cancer.
- Naoki Nishio
- , Nynke S. van den Berg
- & Eben L. Rosenthal
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Article
| Open AccessEvaluation of integrin αvβ6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis
Knottin is a cystine knot peptide. Here, the authors develop a knottin-based tracer for positron emission tomography and demonstrate its ability to detect cancer and idiopathic pulmonary fibrosis through selective binding to integrin αvβ6.
- Richard H. Kimura
- , Ling Wang
- & Sanjiv S. Gambhir
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Article
| Open AccessCamouflaging bacteria by wrapping with cell membranes
The use of engineered bacteria for biomedical applications is limited by side effects such as inflammatory response. Here the authors engineer cell membrane coated bacteria as in vivo tumor imaging agents, and show that these generate a lower inflammatory response and reduced macrophage clearance.
- Zhenping Cao
- , Shanshan Cheng
- & Jinyao Liu
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Article
| Open AccessMulticenter study demonstrates radiomic features derived from magnetic resonance perfusion images identify pseudoprogression in glioblastoma
MRI scans of glioblastoma patients can be misleading and some patients appear to show features of progressive disease although they respond to treatment. Here, the authors use MRI images of progressive disease or pseudoprogression and build a classifier using machine learning to distinguish the two.
- Nabil Elshafeey
- , Aikaterini Kotrotsou
- & Rivka R. Colen
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Article
| Open AccessSuper-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19 CAR-T
CD19 CAR-T cells have achieved some success in treating myeloma patients despite the limited detection of the CD19 antigen. Here, the authors show using dSTORM that 10/14 myeloma samples studied express ultra-low levels of CD19, which are sufficient for engaging CAR-T cells in vitro.
- Thomas Nerreter
- , Sebastian Letschert
- & Michael Hudecek
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Article
| Open AccessAlbumin tailoring fluorescence and photothermal conversion effect of near-infrared-II fluorophore with aggregation-induced emission characteristics
There is a balance between the fluorescence and photothermal properties of fluorescent molecules. Here, the authors report on an NIR-II fluorophore which binds with human serum albumin changing the equilibrium, increasing the photothermal efficiency, and demonstrate application of this for tumour ablation.
- Shuai Gao
- , Guoguang Wei
- & Wei Lu
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Article
| Open AccessDNA-enabled rational design of fluorescence-Raman bimodal nanoprobes for cancer imaging and therapy
Currently available Raman scanners are limited in speed to acquire images of clinically relevant sizes in cancer imaging. Here, the authors developed a DNA based design principle for Raman-Fluorescence bimodal nanoparticles and demonstrate real-time, high precision image-guided tumor resections and photothermal ablation of cancer.
- Suchetan Pal
- , Angana Ray
- & Moritz F. Kircher
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Article
| Open AccessMultimodal interference-based imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm
Methods to track molecular motion in eukaryotic cells mostly rely on fluorescent labels, transfection or photobleaching. Here the authors use multimodal partial wave spectroscopy to perform label-free live cell measurements of nanoscale structure and macromolecular motion with millisecond temporal resolution.
- Scott Gladstein
- , Luay M. Almassalha
- & Vadim Backman
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Article
| Open AccessBioengineered bacterial vesicles as biological nano-heaters for optoacoustic imaging
Bacterial outer membrane vesicles (OMVs) are increasingly used as carriers for drug delivery. Here the authors encapsulate biopolymer melanin into OMVs, extending their use to optoacoustic imaging both in vitro and in vivo, and demonstrate the potential of this tool for photothermal therapy applications.
- Vipul Gujrati
- , Jaya Prakash
- & Vasilis Ntziachristos
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Article
| Open AccessA mathematical-descriptor of tumor-mesoscopic-structure from computed-tomography images annotates prognostic- and molecular-phenotypes of epithelial ovarian cancer
Radiomics—the quantification of features within tumor images—has shown prognostic potential in cancer. Here, the authors use a machine learning approach to develop a radiomic-based small set of descriptors to predict ovarian cancer patient survival based on CT scans acquired pre-operatively in 364 patients.
- Haonan Lu
- , Mubarik Arshad
- & Eric O. Aboagye
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Article
| Open AccessWhole body PD-1 and PD-L1 positron emission tomography in patients with non-small-cell lung cancer
Assessment of PD-1 and PD-L1 expression can be predictive of immunotherapy response in lung cancer. Here the authors assess the clinical toxicity, safety and quality of non-invasive imaging of PD-1 and PD-L1 expression in 13 patients with advanced lung cancer prior to treatment with immunotherapy and show it correlates with response.
- A. N. Niemeijer
- , D. Leung
- & A. J. de Langen