Convolutional neural network advances in demosaicing for fluorescent cancer imaging with color-near-infrared sensors.

Significance: Single-chip imaging devices featuring vertically stacked photodiodes and pixelated spectral filters are advancing multi-dye imaging methods for cancer surgeries, though this innovation comes with a compromise in spatial resolution. To mitigate this drawback, we developed a deep convolutional neural network (CNN) aimed at demosaicing the color and near-infrared (NIR) channels, with its performance validated on both pre-clinical and clinical datasets. Aim: We introduce an optimized deep CNN designed for demosaicing both color and NIR images obtained using a hexachromatic imaging sensor. Approach: A residual CNN was fine-tuned and trained on a dataset of color images and subsequently assessed on a series of dual-channel, color, and NIR images to demonstrate its enhanced performance compared with traditional bilinear interpolation. Results: Our optimized CNN for demosaicing color and NIR images achieves a reduction in the mean square error by 37% for color and 40% for NIR, respectively, and enhances the structural dissimilarity index by 37% across both imaging modalities in pre-clinical data. In clinical datasets, the network improves the mean square error by 35% in color images and 42% in NIR images while enhancing the structural dissimilarity index by 39% in both imaging modalities. Conclusions: We showcase enhancements in image resolution for both color and NIR modalities through the use of an optimized CNN tailored for a hexachromatic image sensor. With the ongoing advancements in graphics card computational power, our approach delivers significant improvements in resolution that are feasible for real-time execution in surgical environments.

Characterization of DREB family genes in Lotus japonicus and LjDREB2B overexpression increased drought tolerance in transgenic Arabidopsis.

BACKGROUND: Drought stress affects plant growth and development. DREB proteins play important roles in modulating plant growth, development, and stress responses, particularly under drought stress. To study the function of DREB transcription factors (TFs), we screened key DREB-regulating TFs for drought in Lotus japonicus. RESULTS: Forty-two DREB TFs were identified, and phylogenetic analysis of proteins from L. japonicus classified them into five subfamilies (A1, A2, A4, A5, A6). The gene motif composition of the proteins is conserved within the same subfamily. Based on the cis-acting regulatory element analysis, we identified many growth-, hormone-, and stress-responsive elements within the promoter regions of DREB. We further analyzed the expression pattern of four genes in the A2 subfamily in response to drought stress. We found that the expression of most of the LjDREB A2 subfamily genes, especially LjDREB2B, was induced by drought stress. We further generated LjDREB2B overexpression transgenic Arabidopsis plants. Under drought stress, the growth of wild-type (WT) and overexpressing LjDREB2B (OE) Arabidopsis lines was inhibited; however, OE plants showed better growth. The malondialdehyde content of LjDREB2B overexpressing lines was lower than that of the WT plants, whereas the proline content and antioxidant enzyme activities in the OE lines were significantly higher than those in the WT plants. Furthermore, after drought stress, the expression levels of AtP5CS1, AtP5CS2, AtRD29A, and AtRD29B in the OE lines were significantly higher than those in the WT plants. CONCLUSIONS: Our results facilitate further functional analysis of L. japonicus DREB. LjDREB2B overexpression improves drought tolerance in transgenic Arabidopsis. These results indicate that DREB holds great potential for the genetic improvement of drought tolerance in L. japonicus.

RGB tri-luminescence in organic-inorganic zirconium halide perovskites.

Materials with two or more fluorescence features under different excitation sources have great potential in optical applications, but luminous materials with three emission characteristics have been largely undeveloped. Here, we report a novel zero-dimensional (0D) organic-inorganic hybrid ((C2H5)4N)2ZrCl6 perovskite with multiple emissions. The zirconium-based perovskite exhibits a red emission around 620 nm, a green emission at 527 nm, and a blue emission around 500 nm. The red and green emissions come from self-trapped excitons (STEs) and the d-d transitions of Zr(iv), respectively, which are caused by distortion of the [ZrCl6]2- octahedra. The blue emission is caused by thermally activated delayed fluorescence (TADF), which is similar to that of Cs2ZrCl6. The absolute photoluminescence quantum yield (PLQY) of the red and blue double emission is up to 83% and the PLQY of the green emission is 27%. With different combinations of ((C2H5)4N)2ZrCl6 samples, we achieve a variety of applications, including a two-color luminescent anti-counterfeiting device, a white light-emitting diode (WLED) with a color rendering index (CRI) of 95 and information encryption with different excitations. We also synthesize other hybrid zirconium perovskites with tri-luminescence through a similar method. Our work provides a potential set of excitation-dependent luminescent materials and is expected to expand the basic research and practical applications of multi-luminescence materials.

Biomimetic-Membrane-Protected Plasmonic Nanostructures as Dual-Modality Contrast Agents for Correlated Surface-Enhanced Raman Scattering and Photoacoustic Detection of Hidden Tumor Lesions.

Optical imaging and spectroscopic modalities are of considerable current interest for in vivo cancer detection and image-guided surgery, but the turbid or scattering nature of biomedical tissues has severely limited their abilities to detect buried or occluded tumor lesions. Here we report the development of a dual-modality plasmonic nanostructure based on colloidal gold nanostars (AuNSs) for simultaneous surface-enhanced Raman scattering (SERS) and photoacoustic (PA) detection of tumor phantoms embedded (hidden) in ex vivo animal tissues. By using red blood cell membranes as a naturally derived biomimetic coating, we show that this class of dual-modality contrast agents can provide both Raman spectroscopic and PA signals for the detection and differentiation of hidden solid tumors with greatly improved depths of tissue penetration. Compared to previous polymer-coated AuNSs, the biomimetic coatings are also able to minimize protein adsorption and cellular uptake when exposed to human plasma without compromising their SERS or PA signals. We further show that tumor-targeting peptides (such as cyclic RGD) can be noncovalently inserted for targeting the ανß3-integrin receptors expressed on metastatic cancer cells and tracked via both SERS and PA imaging (PAI). Finally, we demonstrate image-guided resections of tumor-mimicking phantoms comprising metastatic tumor cells buried under layers of skin and fat tissues (6 mm in thickness). Specifically, PAI was used to determine the precise tumor location, while SERS spectroscopic signals were used for tumor identification and differentiation. This work opens the possibility of using these biomimetic dual-modality nanoparticles with superior signal and biological stability for intraoperative cancer detection and resection.

The overexpression of SlBRI1 driven by Atrd29A promoter-transgenic plants improves the chilling stress tolerance of tomato.

MAIN CONCLUSION: Overexpression of SlBRI1 driven by the Atrd29A promoter could increase the cold resistance of tomato plants during chilling stress but did not improve the expression of SlBRI1 and plant growth under normal conditions. Low temperature is the main limiting factor severely affecting tomato plant development, growth, and fruit quality in winter and spring. Brassinosteroids (BRs) and key BR signaling genes positively regulate tomato plant development and response to chilling stress. Brassinosteroid-insensitive 1 (BRI1) is a major BR receptor that initiates BR signaling. Our results showed that overexpression of SlBRI1 driven by the Atrd29A promoter in transgenic plants did not increase the expression of SlBRI1 under normal conditions but rapidly induced the expression of SlBRI1 during chilling stress. The degree of wilting was lower in Atrd29A promoter-transgenic plants than in wild-type (WT) plants after chilling stress. Atrd29A promoter-transgenic plants exhibited low relative electrolyte leakage and reactive oxygen species (ROS) accumulation under chilling stress. Transgenic plants showed higher photosynthetic ability and antioxidant enzyme activity than WT plants under chilling stress. The BR content and expression levels of key genes involved in BR biosynthesis in Atrd29A-promoter transgenic plants were significantly lower than those in WT plants during chilling stress. The abscisic acid (ABA) content and expression levels of key ABA biosynthesis genes in the Atrd29A promoter-transgenic plants were significantly higher than those in the WT plants during chilling stress. In addition, Atrd29A promoter-transgenic plants positively enhanced the expression levels of ICE-CBF-COR cold-responsive pathway genes. Therefore, the overexpression of SlBRI1 driven by the Atrd29A promoter in transgenic plants can be a valuable tool for reducing chilling stress.

Bioinspired, vertically stacked, and perovskite nanocrystal-enhanced CMOS imaging sensors for resolving UV spectral signatures.

Imaging and identifying target signatures and biomedical markers in the ultraviolet (UV) spectrum is broadly important to medical imaging, military target tracking, remote sensing, and industrial automation. However, current silicon-based imaging sensors are fundamentally limited because of the rapid absorption and attenuation of UV light, hindering their ability to resolve UV spectral signatures. Here, we present a bioinspired imaging sensor capable of wavelength-resolved imaging in the UV range. Inspired by the UV-sensitive visual system of the Papilio xuthus butterfly, the sensor monolithically combines vertically stacked photodiodes and perovskite nanocrystals. This imaging design combines two complementary UV detection mechanisms: The nanocrystal layer converts a portion of UV signals into visible fluorescence, detected by the photodiode array, while the remaining UV light is detected by the top photodiode. Our label-free UV fluorescence imaging data from aromatic amino acids and cancer/normal cells enables real-time differentiation of these biomedical materials with 99% confidence.

Properties of Carbon Dots versus Small Molecules from "Bottom-up" Synthesis.

A major challenge in the "bottom-up" solvothermal synthesis of carbon dots (CDs) is the removal of small-molecule byproducts, noncarbonized polyamides, or other impurities that confound the optical properties. In previously reported benzene diamine-based CDs, the observed fluorescence signal already has been shown to arise from free small molecules, not from nanosized carbonized dots. Here we have unambiguously identified the small-molecule species in the synthesis of CDs starting with several isomers of benzene diamine by directly matching their NMR, mass spectrometry, and optical data with commercially available small organic molecules. By combining dialysis and chromatography, we have sufficiently purified the CD reaction mixtures to measure the CD size by TEM and STM, elemental composition, optical absorption and emission, and single-particle blinking dynamics. The results can be rationalized by electronic structure calculations on small model CDs. Our results conclusively show that the purified benzene diamine-based CDs do not emit red fluorescence, so the quest for full-spectrum fluorescence from isomers of a single precursor molecule remains open.

Cell-Membrane Coated Nanoparticles for Tumor Delineation and Qualitative Estimation of Cancer Biomarkers at Single Wavelength Excitation in Murine and Phantom Models.

Real-time guidance through fluorescence imaging improves the surgical outcomes of tumor resections, reducing the chances of leaving positive margins behind. As tumors are heterogeneous, it is imperative to interrogate multiple overexpressed cancer biomarkers with high sensitivity and specificity to improve surgical outcomes. However, for accurate tumor delineation and ratiometric detection of tumor biomarkers, current methods require multiple excitation wavelengths to image multiple biomarkers, which is impractical in a clinical setting. Here, we have developed a biomimetic platform comprising near-infrared fluorescent semiconducting polymer nanoparticles (SPNs) with red blood cell membrane (RBC) coating, capable of targeting two representative cell-surface biomarkers (folate, αυß3 integrins) using a single excitation wavelength for tumor delineation during surgical interventions. We evaluate our single excitation ratiometric nanoparticles in in vitro tumor cells, ex vivo tumor-mimicking phantoms, and in vivo mouse xenograft tumor models. Favorable biological properties (improved biocompatibility, prolonged blood circulation, reduced liver uptake) are complemented by superior spectral features: (i) specific fluorescence enhancement in tumor regions with high tumor-to-normal tissue (T/NT) ratios in ex vivo samples and (ii) estimation of cell-surface tumor biomarkers with single wavelength excitation providing insights about cancer progression (metastases). Our single excitation, dual output approach has the potential to differentiate between the tumor and healthy regions and simultaneously provide a qualitative indicator of cancer progression, thereby guiding surgeons in the operating room with the resection process.

Bioinspired color-near infrared endoscopic imaging system for molecular guided cancer surgery.

Significance: Fluorescently guided minimally invasive surgery is improving patient outcomes and disease-free survival, but biomarker variability hinders complete tumor resection with single molecular probes. To overcome this, we developed a bioinspired endoscopic system that images multiple tumor-targeted probes, quantifies volumetric ratios in cancer models, and detects tumors in ex vivo samples. Aim: We present a new rigid endoscopic imaging system (EIS) that can capture color images while simultaneously resolving two near-infrared (NIR) probes. Approach: Our optimized EIS integrates a hexa-chromatic image sensor, a rigid endoscope optimized for NIR-color imaging, and a custom illumination fiber bundle. Results: Our optimized EIS achieves a 60% improvement in NIR spatial resolution when compared to a leading FDA-approved endoscope. Ratio-metric imaging of two tumor-targeted probes is demonstrated in vials and animal models of breast cancer. Clinical data gathered from fluorescently tagged lung cancer samples on the operating room's back table demonstrate a high tumor-to-background ratio and consistency with the vial experiments. Conclusions: We investigate key engineering breakthroughs for the single-chip endoscopic system, which can capture and distinguish numerous tumor-targeting fluorophores. As the molecular imaging field shifts toward a multi-tumor targeted probe methodology, our imaging instrument can aid in assessing these concepts during surgical procedures.

Ultra-small α-CsPbI3 perovskite quantum dots with stable, bright and pure red emission for Rec. 2020 display backlights.

The synthesis of α-CsPbI3 perovskite quantum dots (QDs) with pure red emission around 630 nm is in high demand for display backlight application. However, the phase transition of α-CsPbI3 to yellow non-emitting δ-CsPbI3 has been proven to be a great challenge for the classic colloidal synthesis route for perovskite QDs in octadecene (ODE). Herein, we report a novel colloidal synthesis route by replacing ODE with lauryl methacrylate (LMA) as the reaction solvent to improve the solubility of precursors, resulting in small sized α-CsPbI3 QDs with a diameter of only 4.2 nm, which are the smallest red PQDs reported so far. The corresponding CsPbI3 QD films exhibit a tunable photoluminescence (PL) emission peak in the bright pure red region of 627 to 638 nm. The CsPbI3 QD polymer composite films with PL emission at 630 nm exhibit a superior photoluminescence quantum yield (PLQY) and photostability to mixed halide CsPbBrI2 films under intense illumination. Perovskite light emitting diodes (LED) with the color gamut reaching 96% of the Rec. 2020 standard are achieved using these films. This study provides a high-performance pure red fluorescent material with a robust, low-cost, and reproducible colloidal chemistry that will pave the way for the adoption of perovskite QDs in display backlight application.

Genome-wide analysis of the homeodomain-leucine zipper family in Lotus japonicus and the overexpression of LjHDZ7 in Arabidopsis for salt tolerance.

The homeodomain-leucine zipper (HD-Zip) family participates in plant growth, development, and stress responses. Here, 40 HD-Zip transcription factors of Lotus japonicus were identified and gave an overview of the phylogeny and gene structures. The expression pattern of these candidate genes was determined in different organs and their response to abiotic stresses, including cold, heat, polyethylene glycol and salinity. The expression of the LjHDZ7 was strongly induced by abiotic stress, especially salt stress. Subsequently, LjHDZ7 gene was overexpressed in Arabidopsis. The transgenic plants grew obviously better than Col-0 plants under salt stress. Furthermore, LjHDZ7 transgenic lines accumulated higher proline contents and showed lower electrolyte leakage and MDA contents than Col-0 plants under salt stress. Antioxidant activities of the LjHDZ7 overexpression lines leaf were significantly higher than those of the Col-0 plants under salt stress. The concentration of Na+ ion in LjHDZ7 overexpression lines was significantly lower than that of Col-0 in leaf and root parts. The concentration of K+ ion in LjHDZ7 overexpression lines was significantly higher than that of Col-0 in the leaf parts. Therefore, these results showed that overexpression of LjHDZ7 increased resistance to salt stress in transgenic Arabidopsis plants, and certain genes of this family can be used as valuable tools for improving abiotic stresses.

Genome-wide identification and expression analysis of the CBF transcription factor family in Lolium perenne under abiotic stress.

C-repeat binding factor (CBF) subfamily genes encoding transcriptional activators are members of the AP2/ERF superfamily. CBFs play important roles in plant tolerance to abiotic stress. In this study, we identified and analyzed the structure, phylogeny, conserved motifs, and expression profiles of 12 CBFs of the grass species Lolium perenne cultured under abiotic stress. The identified LpCBFs were grouped into three phylogenetic clades according to their protein structures and motif organizations. LpCBF expression was differentially induced by cold, heat, water deficit, salinity, and abscisic acid, among which cold treatment induced LpCBF gene expression significantly. Furthermore, association network analysis indicated that different proteins, including certain stress-related proteins, potentially interact with LpCBFs. Altogether, these findings will enhance our understanding of LpCBFs protein structure and function in the regulation of L. perenne stress responses. Our results will provide valuable information for further functional research of LpCBF proteins in L. perenne stress resistance.

Enhanced brassinosteroid signaling via the overexpression of SlBRI1 positively regulates the chilling stress tolerance of tomato.

Brassinosteroids (BRs) regulate plant development and response to stress. BRASSINOSTEROID INSENSITIVE 1 (BRI1) is a BR receptor that activates BR signaling. Although the function of the tomato BR receptor SlBRI1 in regulating growth and drought resistance has been examined, that of SlBRI1 in cold tolerance is unclear. This study indicated that the expression of SlBRI1 in tomato was rapidly induced and reached its highest level at 3 h under chilling treatment and then decreased. The overexpression of SlBRI1 displayed low relative electrolyte leakage, malondialdehyde content, and reactive oxygen species (ROS) accumulation under chilling stress. The proline content and activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in SlBRI1OE plants were higher than those in the wild-type (WT) plants after chilling stress. The transcript abundances of five cold-responsive genes were higher in SlBRI1OE plants than in WT plants during chilling stress. RNA sequence analysis showed that the expression of the majority of genes encoding photosystem I and II were downregulated. The degree of suppression in SlBRI1OE plants was weaker than that in WT plants. Additionally, the Pn and Fv/Fm of SlBRI1OE plants were significantly higher than those of WT plants under chilling stress. We identified several genes encoding key enzymes in BRs; indole acetic acid (IAA), gibberellin (GA), and abscisic acid (ABA) biosynthesis or signaling were upregulated or downregulated during chilling stress. Chilling stress decreased the BRs and GA3 content, and increased IAA and ABA content. The contents were lower or higher in SlBRI1OE than in WT plants. Furthermore, chilling stress regulated the expression levels of 43 transcription factors. The expression of seven cold-regulated protein genes was higher or lower in SlBRI1OE plants than in WT plants under chilling stress. These results suggest that SlBRI1 positively regulates chilling tolerance mainly through ICE1-CBF-COR pathway in tomato.

Biomimetic Surface-Enhanced Raman Scattering Nanoparticles with Improved Dispersibility, Signal Brightness, and Tumor Targeting Functions.

The development of biocompatible and nontoxic surface-enhanced Raman scattering (SERS) nanoparticles is of considerable current interest because of their attractive biomedical applications such as ultrasensitive in vitro diagnostics, in vivo tumor imaging, and spectroscopy-guided cancer surgery. However, current SERS nanoparticles are prepared and stored in aqueous solution, have limited stability and dispersibility, and are not suitable for lyophilization and storage by freeze-drying or other means. Here, we report a simple but robust method to coat colloidal SERS nanoparticles by naturally derived biomimetic red blood cell membranes (RBCM), leading to a dramatic improvement in stability and dispersibility under freeze-thawing, lyophilization, heating, and physiological conditions. The results demonstrate that the lyophilized SERS nanoparticles in the solid form can be readily dissolved and dispersed in physiological buffer solutions. A surprising finding is that the RBCM-coated SERS particles are considerably brighter (by as much as 5-fold) than PEGylated SERS particles under similar experimental conditions. This additional enhancement is believed to arise from the hydrophobic nature of RBCM's hydrocarbon chains, which is known to reduce electronic dampening and boost electromagnetic field enhancement. A further advantage in using biomimetic membrane coatings is that the bilayer membrane structure allows nonvalent insertion of molecular ligands for tumor targeting. In particular, we show that cyclic-RGD, a tumor-targeting peptide, can be efficiently inserted into the membrane coatings of SERS nanoparticles for targeting the ανß3 integrin receptors expressed on cancer cells. Thus, biomimetic RBCMs provide major advantages over traditional polyethylene glycols for preparing SERS nanoparticles with improved dispersibility, higher signal intensity, and more efficient biofunctionalization.

Accelerated Digital Biodetection Using Magneto-plasmonic Nanoparticle-Coupled Photonic Resonator Absorption Microscopy.

Rapid, ultrasensitive, and selective quantification of circulating microRNA (miRNA) biomarkers in body fluids is increasingly deployed in early cancer diagnosis, prognosis, and therapy monitoring. While nanoparticle tags enable detection of nucleic acid or protein biomarkers with digital resolution and subfemtomolar detection limits without enzymatic amplification, the response time of these assays is typically dominated by diffusion-limited transport of the analytes or nanotags to the biosensor surface. Here, we present a magnetic activate capture and digital counting (mAC+DC) approach that utilizes magneto-plasmonic nanoparticles (MPNPs) to accelerate single-molecule sensing, demonstrated by miRNA detection via toehold-mediated strand displacement. Spiky Fe3O4@Au MPNPs with immobilized target-specific probes are "activated" by binding with miRNA targets, followed by magnetically driven transport through the bulk fluid toward nanoparticle capture probes on a photonic crystal (PC). By spectrally matching the localized surface plasmon resonance of the MPNPs to the PC-guided resonance, each captured MPNP locally quenches the PC reflection efficiency, thus enabling captured MPNPs to be individually visualized with high contrast for counting. We demonstrate quantification of the miR-375 cancer biomarker directly from unprocessed human serum with a 1 min response time, a detection limit of 61.9 aM, a broad dynamic range (100 aM to 10 pM), and a single-base mismatch selectivity. The approach is well-suited for minimally invasive biomarker quantification, enabling potential applications in point-of-care testing with short sample-to-answer time.

Rational Design of Surface-State Controlled Multicolor Cross-Linked Carbon Dots with Distinct Photoluminescence and Cellular Uptake Properties.

We disclose for the first time a facile synthetic methodology for the preparation of multicolor carbon dots (CDs) from a single source barring any chromatographic separations. This was achieved via sequential intraparticle cross-linking of surface abundant carboxylic acid groups on the CDs synthesized from a precursor to control their photoluminescence (PL) spectra as well as affect their degree of cellular internalization in cancer cells. The change in PL spectra with sequential cross-linking was projected by theoretical density functional theory (DFT) studies and validated by multiple characterization tools such as X-ray photoelectron spectroscopy (XPS), PL spectroscopy, ninhydrin assay, etc. The variation in cellular internalization of these cross-linked CDs was demonstrated using inhibitor assays, confocal microscopy, and flow cytometry. We supplemented our findings with high-resolution dark-field imaging to visualize and confirm the colocalization of these CDs into distinct intracellular compartments. Finally, to prove the surface-state controlled PL mechanisms of these cross-linked CDs, we fabricated a triple-channel sensor array for the identification of different analytes including metal ions and biologically relevant proteins.

Function-adaptive clustered nanoparticles reverse Streptococcus mutans dental biofilm and maintain microbiota balance.

Dental plaques are biofilms that cause dental caries by demineralization with acidogenic bacteria. These bacteria reside inside a protective sheath which makes any curative treatment challenging. We propose an antibiotic-free strategy to disrupt the biofilm by engineered clustered carbon dot nanoparticles that function in the acidic environment of the biofilms. In vitro and ex vivo studies on the mature biofilms of Streptococcus mutans revealed >90% biofilm inhibition associated with the contact-mediated interaction of nanoparticles with the bacterial membrane, excessive reactive oxygen species generation, and DNA fragmentation. An in vivo examination showed that these nanoparticles could effectively suppress the growth of S. mutans. Importantly, 16S rRNA analysis of the dental microbiota showed that the diversity and richness of bacterial species did not substantially change with nanoparticle treatment. Overall, this study presents a safe and effective approach to decrease the dental biofilm formation without disrupting the ecological balance of the oral cavity.

Hexachromatic bioinspired camera for image-guided cancer surgery.

Cancer affects one in three people worldwide. Surgery remains the primary curative option for localized cancers, but good prognoses require complete removal of primary tumors and timely recognition of metastases. To expand surgical capabilities and enhance patient outcomes, we developed a six-channel color/near-infrared image sensor inspired by the mantis shrimp visual system that enabled near-infrared fluorescence image guidance during surgery. The mantis shrimp's unique eye, which maximizes the number of photons contributing to and the amount of information contained in each glimpse of its surroundings, is recapitulated in our single-chip imaging system that integrates arrays of vertically stacked silicon photodetectors and pixelated spectral filters. To provide information about tumor location unavailable from a single instrument, we tuned three color channels to permit an intuitive perspective of the surgical procedure and three near-infrared channels to permit multifunctional imaging of optical probes highlighting cancerous tissue. In nude athymic mice bearing human prostate tumors, our image sensor enabled simultaneous detection of two tumor-targeted fluorophores, distinguishing diseased from healthy tissue in an estimated 92% of cases. It also permitted extraction of near-infrared structured illumination enabling the mapping of the three-dimensional topography of tumors and surgical sites to within 1.2-mm error. In the operating room, during surgical resection in 18 patients with breast cancer, our image sensor further enabled sentinel lymph node mapping using clinically approved near-infrared fluorophores. The flexibility and performance afforded by this simple and compact architecture highlights the benefits of biologically inspired sensors in image-guided surgery.

Ultracompact Iron Oxide Nanoparticles with a Monolayer Coating of Succinylated Heparin: A New Class of Renal-Clearable and Nontoxic T1 Agents for High-Field MRI.

Herein, we present a new magnetic iron oxide nanoparticle (MION) with a succinylated heparin monolayer coating, which exhibits the highest T1 relaxivity at 7 T and the lowest r2/r1 reported for any MION at these high-field conditions. While the recent proliferation of 7 T MRI instruments in hospitals worldwide has enabled widespread access to higher quality, more finely detailed, diagnostic imaging, clinically available contrast agents have not kept pace due to the general phenomenon of reduced efficacy of T1 relaxation as magnetic field strength is increased. Development of new MION agents is one strategy to address this need, and to this end, we demonstrate the in vitro magnetic properties of the MIONs reported here to extend to in vivo applications, providing greatly increased contrast in tumor imaging in a murine xenograft subject at 7 T. While MION-based contrast agents can have side effects in clinical application, these are generally thought to be less than those of gadolinium-based agents and here are further reduced by the small size allowing direct glomerular filtration from the blood followed by renal-excretion. Finally, we show the succinylated heparin monolayer coating to provide class leading magnetic properties over a homologous series of particles with core size ranging from 2 to 18 nm and show the properties to be strongly related to the surface area. We suggest the increased porosity and hydrophilicity of the coating to increase water accessibility to the surface resulting in the increased magnetic properties.