Dual-modality Imaging Research Articles

Noninvasive Gastrointestinal Tract Imaging Using BSA-Ag2Te Quantum Dots as a CT/NIR-II Fluorescence Dual-Modal Imaging Probe in Vivo.

The combination of high-resolution computed tomography (CT) and the real-time sensitive second near-infrared window (NIR-II) fluorescence bioimaging can provide complementary information for the diagnosis, progression and prognosis of gastrointestinal disorders. Ag2Te quantum dots (QDs) are a kind of promising CT/NIR-II fluorescence dual-modal imaging probe due to their high atomic number and narrow bandgap. However, conventional Ag2Te QDs synthesized by oil phase approaches often suffer from complicated steps, harsh reaction conditions, and toxic organic solvents. Herein, we report the synthesis of bovine serum albumin (BSA)-Ag2Te QDs using a biomineralization approach for CT/NIR-II fluorescence dual-modal imaging of the gastrointestinal tract. The BSA-Ag2Te QDs are fabricated in a facile one-pot approach under mild conditions and exhibit homogeneous size, favorable monodispersity, admirable aqueous solubility, excellent X-ray attenuation properties, and outstanding NIR-II fluorescence performance. In vivo imaging experiments show that BSA-Ag2Te QDs can be used in gastrointestinal tract CT/NIR-II dual-modal imaging with high spatiotemporal resolution and sensitivity. In addition, in an intestinal obstruction mouse model, accurate lesion positioning and imaging-guided obstruction relief surgery are successfully realized based on BSA-Ag2Te QDs. Besides, BSA-Ag2Te QDs have outstanding biocompatibility in vitro and in vivo. This study presents a high-performance and biosafe CT/NIR-II fluorescence dual-modal imaging probe for visualizing the gastrointestinal tract in vivo.

Switchable preamplifier for dual modal photoacoustic and ultrasound imaging.

Photoacoustic (PA) imaging is a high-fidelity biomedical imaging technique based on the principle of molecular-specific optical absorption of biological tissue constitute. Because PA imaging shares the same basic principle as that of ultrasound (US) imaging, the use of PA/US dual-modal imaging can be achieved using a single system. However, because PA imaging is limited to a shallower depth than US imaging due to the optical extinction in biological tissue, the PA signal yields a lower signal-to-noise ratio (SNR) than US images. To selectively amplify the PA signal, we propose a switchable preamplifier for acoustic-resolution PA microscopy implemented on an application-specific integrated circuit. Using the preamplifier, we measured the increments in the SNR with both carbon lead and wire phantoms. Furthermore, in vivo whole-body PA/US imaging of a mouse with a preamplifier showed enhancement of SNR in deep tissues, unveiling deeply located organs and vascular networks. By selectively amplifying the PA signal range to a level similar to that of the US signal without contrast agent administration, our switchable amplifier strengthens the mutual complement between PA/US imaging. PA/US imaging is impending toward clinical translation, and we anticipate that this study will help mitigate the imbalance of image depth between the two imaging modalities.

Conjugate electro-spinning towards Janus nanofibers array synchronously endowed with conductive anisotropy, magnetism and luminescence

An unpolymerized [Tb(BA) 3 phen (TBP)/polymethylmethacrylate (PMMA)]//[aniline (ANI)/Fe 3 O 4 /PMMA] Janus nanofibers array (UJNA) is successfully prepared by conjugate electro-spinning technique, and a polymerized [TBP/PMMA]//[polyaniline (PANI)/Fe 3 O 4 /PMMA] Janus nanofibers array (PJNA) with tunable conductive anisotropy, tailored magnetism and enhancive green luminescence is prepared by post-polymerization method. Using conjugate electro-spinning can prevent the problem of mutual diffusion between spinning dopes and realize the effective separation of luminescent substances form conductive-magnetic substances. Meanwhile, Janus nanofibers have a directional arrangement that can reduce light loss during excitation and emission. Therefore, compared with comparison samples, the PJNA prepared by conjugate electro-spinning has the strongest luminescence intensity. PJNA can be composed and contained different amounts of luminescent-conductive-magnetic (LCM) substances to adjust its LCM properties. As PANI mass ratio exceeds 70%, the sample's conductivity in the conductive direction exceeds that in the insulation direction by 10 7 times. The PJNA assembled in this work has potential applications in drug delivery, dual-mode imaging, electromagnetic shielding and nanodevices due to its excellent multifunctional properties. Further, this technology can also be applied to other multifunctional one-dimensional Janus nanomaterials and two-dimensional films. • Janus nanofibers array is prepared by conjugate electrospinning and post-polymerization. • Janus nanofibers (JNs) array owns conductive anisotropy, magnetism and luninescence. • Conjugate electrospinning is superior to parallel electrospinning in making JNs. • Partitioned structures guarantee strong luminescence and high conductive anisotropy. • Other multifunctional nanomaterials can be constructed using these techniques.

Deep NIR-II optical imaging combined with minimally invasive interventional photothermal therapy for orthotopic bladder cancer

• An excellent NIR-II PTA (HAPO-1048) for actively-targeted PTT of orthotopic BC. • Combining dual-modality 3D NIR-II PA and OCTA molecular imaging for micro-BC. • High sensitivity and specificity (about 2 mm diameter) dynamic detecting of BC. • Designing a minimally invasive interventional PTT for deep orthotopic BC. • HAPO-1048 demonstrates improved NIR-II therapeutic efficiency. Surgical resection (SR) is the major method for treating invasive or recurrent noninvasive bladder cancer (BC). However, SR still causes additional risks of urinary tract infection, bleeding and some complications that may be life-threatening. Therefore, it is of urgent medical need for new diagnosis and therapy scheme for BC. Herein, we proposed a strategy that combines dual-modality three-dimensional (3D) NIR-II photoacoustic (PA) and optical coherence tomography angiography (OCTA) molecular imaging to guide visually interventional photothermal therapy (PTT) for BC. Additionally, we developed an excellent NIR-II hyaluronic acid-IR-1048 with liposome-coated (HAPO-1048) photothermal agent for PTT of CD44 overexpressing orthotopic BC, which showed strong NIR-II optical absorption, preferable tumor targeting, excellent biocompatibility and high PTT efficacy. Combined with the NIR-II PA/PTT response of the HAPO-1048, we can achieve high sensitivity and specificity (about 2 mm diameter) dynamic monitoring and investigate the precision therapy of PTT in deep orthotopic BC (4.38 mm). Simultaneously, we can map the dynamic changes of 3D PA signals and HAPO-1048 nanoparticles (HAPO-1048 NPs) enrichment, which is closely related to the PTT efficacy. Significantly, the whole changes of complex microvascular morphometrics and angiogenesis of BC were well surveilled and assessed in vivo using OCTA. Lastly, minimally invasive interventional PTT strategy was successfully implemented to achieve a controllable and precise therapy for orthotopic BC based on laparoscopy and US guidance. In conclusion, we present a multimodal NIR-II optical imaging synergy laparoscopy interventional oncologic scheme, which should expand the current PTT technology, leading to a significant ongoing in treatment of primary tumors of urinary system.

Engineering sialic acid-coated mesoporous polydopamine nanomaterials for MRI-guided photothermal-enhanced synergistic effect chemodynamic lung cancer therapy

The mortality and morbidity rates of lung cancer are extremely high. Thus, the development of efficient diagnostic and therapeutic agents for lung cancer is warranted. We aimed to construct a new theranostic drug based on mesoporous polydopamine (MP) for dual T1/T2 magnetic resonance imaging (MRI)-guided chemo-photothermal chemotherapy. MP-nanomaterials (MP-NMs) loaded with superparamagnetic iron oxide nanomaterials (MP@SPIONs) were co-loaded with sialic acid (SA) and Fe3+ (SA-MP@SPION/Fe3+). Subsequently, SA-MP@SPION/Fe3+/CTX was engineered for tumor theranostics using a cabazitaxel (CTX)-loaded prodrug. MTT analysis revealed that PEG-SA-MP@SPION/Fe3+/CTX was water soluble and biocompatible. Further, the new theranostic agent was demonstrated to have a great photothermal conversion/stability, with relaxivity of r1 = 4.31 mM−1s−1 and r2 = 104.64 mM−1s−1, respectively, based on its in vitro photothermal and relaxivity ability. SA-MP@SPION/Fe3+/CTX efficiently encapsulated CTX, enabling both pH- and thermally-induced drug release. Notably, SA-MP@SPION/Fe3+/CTX was found to efficiently target lung cancer cells in vitro. Moreover, SA-MP@SPION/Fe3+/CTX exhibited more accurate dual-mode T1-T2 contrast imaging, unlike those that did not undergo SA alteration, and exerted a more significant therapeutic efficacy owing to its dynamic targeting capabilities and the combination of chemotherapy and photothermal treatment based on SA-MP@SPION/Fe3+/CTX NMs. According to our findings, the targeted nanoplatform, SA-MP@SPION/Fe3+/CTX, is an excellent tumor theranostic tool that could be effectively applied for lung cancer treatment.

DASFNet: Dense-Attention–Similarity-Fusion Network for scene classification of dual-modal remote-sensing images

• The cosine similarity and a gating mechanism are used by the SFM to fuse IRRG and DSM data and extract corresponding complementary features. • The MCFAM is used to extract multiscale context cues, solving the problem of object-scale variations in HRRSIs. • The DAMM forms a dense-attention branch that can adaptively capture both low- and high-level attentions. Although significant progress has been made in scene classification of high-resolution remote-sensing images (HRRSIs), dual-modal HRRSI scene classification is still an active and challenging issue. In this study, we introduce an end-to-end dense-attention–similarity-fusion network (DASFNet) for dual-modal HRRSIs. Specifically, we propose a dense-attention map module based on graph convolution, which adaptively captures long-range semantic cues and further directs shallow-attention cues to the deep level to guide the generation of high-level feature attention cues. At the encoder stage, DASFNet uses feature similarity to explore the correlation between dual-modal features; a similarity-fusion module extracts complementary information by fusing features from different modalities. A multiscale context-feature-aggregation module is used to strengthen the feature embedding of any two spatial scales; this solves the of scale change problem. A large number of experiments on two HRRSI benchmark datasets for scene classification indicate that the proposed DASFNet outperforms the outstanding scene classification approaches.

Unsupervised and quantitative intestinal ischemia detection using conditional adversarial network in multimodal optical imaging.

Intraoperative evaluation of bowel perfusion is currently dependent upon subjective assessment. Thus, quantitative and objective methods of bowel viability in intestinal anastomosis are scarce. To address this clinical need, a conditional adversarial network is used to analyze the data from laser speckle contrast imaging (LSCI) paired with a visible-light camera to identify abnormal tissue perfusion regions. Our vision platform was based on a dual-modality bench-top imaging system with red-green-blue (RGB) and dye-free LSCI channels. Swine model studies were conducted to collect data on bowel mesenteric vascular structures with normal/abnormal microvascular perfusion to construct the control or experimental group. Subsequently, a deep-learning model based on a conditional generative adversarial network (cGAN) was utilized to perform dual-modality image alignment and learn the distribution of normal datasets for training. Thereafter, abnormal datasets were fed into the predictive model for testing. Ischemic bowel regions could be detected by monitoring the erroneous reconstruction from the latent space. The main advantage is that it is unsupervised and does not require subjective manual annotations. Compared with the conventional qualitative LSCI technique, it provides well-defined segmentation results for different levels of ischemia. We demonstrated that our model could accurately segment the ischemic intestine images, with a Dice coefficient and accuracy of 90.77% and 93.06%, respectively, in 2560 RGB/LSCI image pairs. The ground truth was labeled by multiple and independent estimations, combining the surgeons' annotations with fastest gradient descent in suspicious areas of vascular images. The total processing time was 0.05s for an image size of . The proposed cGAN can provide pixel-wise and dye-free quantitative analysis of intestinal perfusion, which is an ideal supplement to the traditional LSCI technique. It has potential to help surgeons increase the accuracy of intraoperative diagnosis and improve clinical outcomes of mesenteric ischemia and other gastrointestinal surgeries.

Dual imaging modality of fluorescence and transmission X-rays for gold nanoparticle-injected living mice.

X-ray fluorescence (XRF) imaging for metal nanoparticles (MNPs) is a promising molecular imaging modality that can determine dynamic biodistributions of MNPs. However, it has the limitation that it only provides functional information. In this study, we aim to show the feasibility of acquiring functional and anatomic information on the same platform by demonstrating a dual imaging modality of pinhole XRF and computed tomography (CT) for gold nanoparticle (GNP)-injected living mice. By installing a transmission CT detector in an existing pinhole XRF imaging system using a two-dimensional (2D) cadmium zinc telluride (CZT) gamma camera, XRF and CT images were acquired on the same platform. Due to the optimal X-ray spectra for XRF and CT image acquisition being different, XRF and CT imaging were performed by 140 and 50kV X-rays, respectively. An amount of 40mg GNPs (1.9nm in diameter) suspended in 0.20ml of phosphate-buffered saline were injected into the three BALB/c mice via a tail vein. Then, the kidney and tumor slices of mice were scanned at specific time points within 60min to acquire time-lapse in vivo biodistributions of GNPs. XRF images were directly acquired without image reconstruction using a pinhole collimator and a 2D CZT gamma camera. Subsequently, CT images were acquired by performing CT scans. In order to confirm the validity of the functional information provided by the XRF image, the CT image was fused with the XRF image. After the XRF and CT scan, the mice were euthanized, and major organs (kidneys, tumor, liver, and spleen) were extracted. The ex vivo GNP concentrations of the extracted organs were measured by inductively coupled plasma mass spectrometry (ICP-MS) and L-shell XRF detection system using a silicon drift detector, then compared with the in vivo GNP concentrations measured by the pinhole XRF imaging system. Time-lapse XRF images were directly acquired without rotation and translation of imaging objects within an acquisition time of 2min per slice. Due to the short image acquisition time, the time-lapse in vivo biodistribution of GNPs was acquired in the organs of the mice. CT images were fused with the XRF images and successfully confirmed the validity of the XRF images. The difference in ex vivo GNP concentrations measured by the L-shell XRF detection system and ICP-MS was 0.0005-0.02% by the weight of gold (wt%). Notably, the in vivo and ex vivo GNP concentrations in the kidneys of three mice were comparable with a difference of 0.01-0.08wt%. A dual imaging modality of pinhole XRF and CT imaging system and L-shell XRF detection system were successfully developed. The developed systems are a promising modality for in vivo imaging and ex vivo quantification for preclinical studies using MNPs. In addition, we discussed further improvements for the routine preclinical applications of the systems.

Cone-beam X-ray luminescence computed tomography based on MLEM with adaptive FISTA initial image

Background and objectiveAs an emerging dual-mode optical molecular imaging, cone-beam X-ray luminescence computed tomography (CB-XLCT) has shown potential in early tumor diagnosis and other applications with increased depth and little autofluorescence. However, due to the low transfer efficiency of PNPs to convert X-ray energy to visible or near-infrared (NIR) light and X-ray dose limitation, the signal to noise ratio of projections is quite low, making the quality of CB-XLCT relatively poor. MethodsTo improve the reconstruction quality of low-counts CB-XLCT imaging, an adaptive reconstruction algorithm (named ADFISTA-MLEM) based on the maximum likelihood expectation estimation (MLEM) framework is proposed for CB-XLCT reconstruction from Poisson distributed projections. In the proposed framework, the image reconstructed by fast iterative shrinkage-thresholding algorithm (FISTA) is used as the initial image for MLEM iterations to improve reconstruction accuracy, in which both the projection noise model and the sparsity constraint of the image could be considered. For relative quantitative imaging, a specific normalization is applied to the projection data and system matrix. To determine the hyperparameter of FISTA, which may be different for different projections, an adaptive strategy (ADFISTA) is then designed for adaptive update of the hyperparameter with reconstructed image in each iteration. Results and conclusionsResults from numerical simulations and phantom experiments indicate that the proposed framework can obtain superior reconstruction accuracy in terms of contrast to noise ratio and shape similarity. In addition, high intensity-concentration linearity between different probe targets indicates its potential for quantitative CB-XLCT imaging.

Dual-Modality Molecular Imaging of Tumor via Quantum Dots-Liposome-Microbubble Complexes.

Molecular imaging has demonstrated promise for evaluating the expression levels of biomarkers for the early prediction of tumor progression and metastasis. However, most of the commonly used molecular imaging modalities are relatively single and have difficulties imaging complex biological processes. Here, we fabricated αvβ3-integrin-targeted quantum-dots-loaded liposome-microbubble (iRGD-QDLM) complexes that combined ultrasound imaging with optical imaging. The resulting iRGD-QDLM has excellent binding capability to 4T1 breast cancer cells. Ultrasound molecular imaging of 4T1 tumors demonstrated that significantly enhanced ultrasound molecular signals could be observed in comparison with non-targeted QDLM. Importantly, our study also suggested that iRGD-QDL on the surface of microbubbles could be delivered into a tumor by ultrasound-mediated microbubble destruction and adhered to αvβ3 integrin on breast cancer cells, achieving transvascular fluorescent imaging. Our study provides a novel approach to dual-modality molecular imaging of αvβ3 integrin in the tumor tissue.

A versatile metal–organic nanoplatform in combination with CXCR4 antagonist and PD-L1 inhibitor for multimodal synergistic cancer therapy and MRI-guided tumor imaging

Currently, multimodal synergistic nanoplatform emerges as an important cancer therapy paradigm, however, multimodal synergistic theranostic nanoplatform remains to be developed. Herein, using the mouse model of breast cancer, a versatile multimodal synergistic theranostic nanoplatform is rationally designed and synthesized for enhancing chemodynamic therapy (CDT), overcoming immunosuppression within tumor microenvironment, and inhibiting metastasis as well as tracking tumor. To fulfill our design, a composite Fe/Mn magnetic nanoparticle is first synthesized by loading with Fe3O4 and BMS-202 (PD-L1 inhibitor) within a poly(lactide-co-glycolide)-based nanoparticle core, which are further modified with in situ synthesis of MnO2 layer. Then, the composite metal-organic nanoparticle is coated with two targeting moieties hyaluronic acid (HA) and AMD3100 (CXCR4 antagonist), respectively, to achieve the multimodal synergistic theranostic nanoplatform (FMN-BMS@HA+AMD). With surface targeting modification, FMN-BMS@HA+AMD exhibits enhanced tumor accumulation, where it effectively consumes endogenous glutathione to generate Mn2+ allowing for the enhanced CDT effect, alleviates tumor hypoxia by O2 generation and reverses the tumor immunosuppression. FMN-BMS@HA+AMD blocks CXCR4 receptor on cancer cells, thus suppressing the CXCR4-mediated cancer metastasis and invasion. Additionally, FMN-BMS@HA+AMD would synchronously be achieving tumor tracking by T1-T2 dual-mode magnetic resonance imaging. Collectively, this strategy holds a novel multimodal synergistic theranostics for effective cancer management.

Abstract 14699: Effect of Shear Stress on Arterial Inflammation and Development of Healed Plaque: A Comprehensive Shear Stress-Molecular Imaging Study Based on a Novel Multispectral Fluorescence Lifetime Imaging Catheter

Introduction and Hypothesis: Endothelial shear stress (ESS) is the tangential force produced by luminal blood flow on arterial endothelium. Both high ESS and low ESS are known to have atherogenic effects, however, it remains poorly understood how these different forces influence coronary atherosclerosis. We evaluated the impact of ESS changes on biochemical and phenotypic difference of coronary atheroma, as assessed by a novel dual-modal optical coherence tomography-fluorescence lifetime imaging (OCT-FLIm) in vivo in beating human coronary arteries. Methods and Results: We constructed a fully-integrated OCT and multispectral FLIm system based on a low-profile dual-modal imaging catheter. High-speed OCT-FLIm could be performed safely in patients undergoing coronary revascularization (Pullback speed: 10-20mm/sec). 3D artery model for computational fluid dynamics was reconstructed by fusion of OCT and angiography. We analyzed spatial associations between ESS and multispectral FLIm information: ch.3(542nm) = fibroatheroma with inflammation; ch.1 (390nm) = loose fibrous tissue (healed plaque). OCT-FLIm visualized coronary microstructure clearly and offered correctly-coregistered biochemical readouts of coronary atherosclerotic plaque in vivo in a label-free manner. Fibroatheromas with increased inflammation activity, as assessed by ch.3 FLIm, were found in low ESS area. On the other hands, high ESS area colocalized with regions with increased ch.1 lifetime, a FLIm signature of loose fibrous tissue (healed plaque). Based on a coregistered ESS-FLIm data, we found a statistically significant negative correlation between ESS and ch.3 lifetime (p>0.001) and a positive correlation between ESS and ch.1 lifetime (p>0.001). Conclusions: Low ESS was associated with lipid and macrophage infiltration whereas high ESS was associated with presence of loose fibrous tissue, a histologic marker of recent plaque disruption leading to rapid plaque progression. Our novel imaging strategy enabling comprehensive evaluation of complex interaction between ESS and biochemical phenotype of plaques is expected to enhance understanding of coronary atherosclerosis biology.

Abstract 14778: Combined Shear Stress-Molecular Imaging for the Evaluation of Early Arterial Healing Responses Following Implantation of Bioresorbable Scaffold With Different Strut Thickness

Introduction and Hypothesis: Arterial healing following stent implantation involves a series of biological reactions such as thrombosis, inflammation, neointimal regeneration. Clinical evidences have shown favorable arterial healing after thin-strut stents, however, there has been a lack of in vivo imaging evidence on how strut thickness affect vascular healing process. We evaluated local endothelial shear stress (ESS) and healing response of a thin-strut bioresorbable scaffold (BRS, 100μm) compared to first-generation 157μm-thickness ABSORB. Methods and Results: BRS and ABSORB were simultaneously implanted in left coronary arteries of the same pigs (n=7). Detailed scaffolded-artery 3D model was reconstructed based on OCT and angiography. Scaffold-related inflammation response was serially assessed by dual-modal OCT-near-infrared fluorescence (OCT-NIRF) molecular imaging using macrophage-mannose receptor-Cy7 as an inflammation-targeting agent. On ESS analysis, regions with athero-prone low ESS were significantly greater in thick-ABSORB compared to BRS. Dual-modal OCT-NIRF imaging visualized arterial inflammation activity at peri-strut regions in vivo (Figure). Based on coregistered ESS-NIRF data, we found a significant inverse correlation was found between ESS and NIRF activity (p<0.0001), suggesting immune-modulating effect of ESS during early stent healing phase. Arterial inflammation, quantified as target-to-background ratio, was significantly lower in thin-strut BRS than ABSORB at 2 weeks (p<0.01). At week 3, unlike ABSORB with residual peri-strut NIRF signals, inflammation activity dissipated significantly in BRS. Ex vivo confocal fluorescence microscopy (Figure) and immunohistochemical analysis well corroborated the findings in vivo . Conclusions: Thin-strut BRS was associated with less inflammation and rapid resolution of inflammation compared to thicker-strut ABSORB. This study provides in vivo imaging insights into how strut thickness affects early arterial healing and the importance of ESS as an inflammatory modulator. Our comprehensive imaging strategy enabling evaluation of complex interplay between scaffold, ESS, and artery is expected to enhance understanding of stent healing.

Targeted OUM1/PTPRZ1 silencing and synergetic CDT/enhanced chemical therapy toward uveal melanoma based on a dual-modal imaging-guided manganese metal–organic framework nanoparticles

Metastasis and chemical resistance are the most serious problems in the treatment of highly aggressive uveal melanoma (UM). The newly identified lncRNA OUM1 is overexpressed in UM, functions as a catalyst and regulates protein tyrosine phosphatase (PTP) activity by binding to PTP receptor type Z1 (PTPRZ1), which plays an important role in cell proliferation, metastasis and chemotherapy resistance in the UM microenvironment. Hence, siRNAs that selectively knocking down the lncRNA OUM1 (siOUM1) and its target gene PTPRZ1 (siPTPRZ1) were designed to inhibit the OUM1/PTPRZ1 pathway to reduce PTP activity, and this reduction in activity interrupts protein tyrosine phosphorylation, suppresses UM proliferation and metastasis and improves cisplatin sensitivity in UM cells. Then, to overcome the limitations of the difficulty of drug administration and traditional therapeutics, the indocyanine green (ICG)-labeled manganese metal–organic framework (MOF) nanoparticles (NPs) were fabricated and linked with arginine-glycine-aspartate (RGD) peptide to carry siOUM1/siPTPRZ1 and cisplatin to achieve targeted siRNA interference-mediated therapy, enhanced cisplatin therapy and chemodynamic therapy. This NP system also has a dual-modal imaging ability because ICG is a near-infrared region fluorescent dye and manganese has the potential to be used in magnetic resonance imaging. This study verifies the significance of the newly discovered lncRNA OUM1 as a new therapeutic target for aggressive UM and provides a drug delivery NP system for precise treatment of UM accompanied with a dual-modal imaging ability.Graphical

Photoacoustic mediated multifunctional tumor antigen trapping nanoparticles inhibit the recurrence and metastasis of ovarian cancer by enhancing tumor immunogenicity

The hypoimmunogenicity of tumors is one of the main bottlenecks of cancer immunotherapy. Enhancing tumor immunogenicity can improve the efficacy of tumor immunotherapy by increasing antigen exposure and presentation, and establishing an inflammatory microenvironment. Here, a multifunctional antigen trapping nanoparticle with indocyanine green (ICG), aluminum hydroxide (Al(OH)3) and oxaliplatin (OXA) (PPIAO) has been developed for tumor photoacoustic/ultrasound dual-modality imaging and therapy. The combination of photothermal/photodynamic therapy and chemotherapy induced tumor antigen exposure and release through immunogenic death of tumor cells. A timely capture and storage of antigens by aluminum hydroxide enabled dendritic cells to recognize and present those antigens spatiotemporally. In an ovarian tumor model, the photoacoustic-mediated PPIAO NPs combination therapy achieved a transition from “cold tumor” to “hot tumor” that promoted more CD8+ T lymphocytes activation in vivo and intratumoral infiltration, and successfully inhibited the growth of primary and metastatic tumors. An in situ tumor vaccine effect was produced from the treated tumor tissue, assisting mice against the recurrence of tumor cells. This study provided a simple and effective personalized tumor vaccine strategy for better treatment of metastatic and recurrent tumors. The developed multifunctional tumor antigen trapping nanoparticles may be a promising nanoplatform for integrating multimodal imaging monitoring, tumor treatment, and tumor vaccine immunotherapy.

Targeted Therapy of Atherosclerosis Vulnerable Plaque by ROS-Scavenging Nanoparticles and MR/Fluorescence Dual-Modality Imaging Tracing.

Early diagnosis and treatment of atherosclerosis (AS) vulnerable plaque has important clinical significance for the prognosis of patients. In this work, the integrated diagnosis and treatment nanoparticles based on Gd-doped Prussian blue (GPB) were constructed for the fluorescence/MR dual-mode imaging and anti-ROS treatment of vulnerable AS plaques in vitro and in vivo. To fabricate the theranostic NPs, GPB was modified with water-soluble polymer polyethyleneimine (PEI), fluorescence molecule rhodamine (Rd), and targeted molecule dextran sulfate (DS) step by step via electrostatic adsorption to construct GPRD NPs. The fluorescence/MR imaging ability and various nano-enzymes activity of GPRD NPs were detected, and the biocompatibility and safety of GPRD were also evaluated. Subsequently, RAW264.7 cells and ApoE -/- model mice were used to evaluate the effect of GPRD NPs on the targeted dual-mode imaging and anti-ROS treatment of vulnerable plaque in vitro and in vivo. The experimental results showed that our fabricated GPRD NPs not only displayed excellent MR/fluorescence dual-modality imaging of vulnerable plaque in vivo but also effectively utilized the nano-enzyme activity of GPB to inhibit the AS progress by ROS scavenging and the following reduction of inflammation, apoptosis, and foam cells' formation, providing a new avenue for the diagnosis and treatment of AS vulnerable plaque. The fabricated multimodal imaging nanoparticles with ROS-scavenging ability provided a new avenue for the diagnosis and treatment of AS vulnerable plaques.

Automated Lung Cancer Segmentation Using a Dual-Modality Deep Learning Network with PET and CT Images

<h3>Purpose/Objective(s)</h3> To develop an automated lung cancer segmentation method using dual-modality imaging and deep learning, and to perform clinical evaluation of the method. <h3>Materials/Methods</h3> A 3D neural network with dual inputs from diagnostic PET and simulation CT was constructed based on U-Net. The architecture consisted of two parallel convolution paths for independent feature extractions from PET and CT at multiple resolution levels and a single deconvolution path. At each resolution level, the extracted features from the convolution arms were concatenated and fed into the deconvolution path through skip connections. The network was trained/validated/tested by a 3:1:1 split on a dataset of 290 pairs of PET and CT from lung cancer patients treated at our institution, with manual physician contours as the ground truth. The performance of the 3D dual-modality network was compared against that of a CT-only network. evaluated both the manual and the network-produced tumor contours of a randomly selected subset of 20 cases (10 large and 10 small) in a blinded fashion. <h3>Results</h3> The mean Dice similarity coefficient (DSC), Hausdorff Distance (HD), and bi-directional local distance (BLD) comparing the automatic contours versus the ground truth were 0.77 ± 0.12, 7.6 ± 4.7 mm, and 2.9 ± 1.4 mm, and 0.79 ± 0.10, 5.8 ± 3.2 mm, and 2.8 ± 1.5 mm for dual modality inputs, respectively. The stratification method delivered the best results when the model for the large GTV subset (> 25 ml) was trained with GTVs of all sizes (DSC, HD, BLD of 0.85 ± 0.05, 9.5 ± 3.8 mm, and 3.8 ± 1.8 mm), and that for the small GTV subset (< 25 ml) was trained with small GTVs only (DSC, HD, BLD of 0.82 ± 0.08, 3.7 ± 1.7 mm, and 2.2 ± 1.1 mm). From the stratified results, the best combined overall DSC, HD, and BLD were 0.83 ± 0.07, 5.9 ± 2.5 mm, and 2.8 ± 1.4 mm, respectively. In the multi-observer review, on average 91.25% of manual vs. 88.75% of automatic contours were Accepted or Accepted with Modifications. (50% Accepted, 41.25% Accepted w/ Mods and 6.25% Rejected for manual vs. 18.75%, 70%, and 8.75% for automatic), the modifications on the automatic contours were relatively minor with a mean DSC of 0.92 ± 0.04 between the original and modified, comparable to the mean DSC of 0.90 ± 0.04 between all the modified contours and their manual ground truths. <h3>Conclusion</h3> By utilizing an expansive clinical PET and CT image database and a dual-modality architecture, the proposed 3D network with a novel GTV volume-based stratification strategy was able to generate clinically useful lung cancer contours that were quantitatively similar to the ground truth and highly acceptable in physician review.

Clinical photoacoustic/ultrasound dual-modal imaging: Current status and future trends.

Photoacoustic tomography (PAT) is an emerging biomedical imaging modality that combines optical and ultrasonic imaging, providing overlapping fields of view. This hybrid approach allows for a natural integration of PAT and ultrasound (US) imaging in a single platform. Due to the similarities in signal acquisition and processing, the combination of PAT and US imaging creates a new hybrid imaging for novel clinical applications. Over the recent years, particular attention is paid to the development of PAT/US dual-modal systems highlighting mutual benefits in clinical cases, with an aim of substantially improving the specificity and sensitivity for diagnosis of diseases. The demonstrated feasibility and accuracy in these efforts open an avenue of translating PAT/US imaging to practical clinical applications. In this review, the current PAT/US dual-modal imaging systems are discussed in detail, and their promising clinical applications are presented and compared systematically. Finally, this review describes the potential impacts of these combined systems in the coming future.

Nimotuzumab iodine-131 conjugated with MnFe2O4 for potential dual-modality (MRI/SPECT) imaging nanoprobe

Manganese ferrite nanoparticle (MnFe2O4 NPs) has introduced a versatile platform to develop a multifunctional nanosystem for Magnetic Resonance Imaging (MRI) and Single-Photon Emission Computed Tomography (SPECT) modalities. Herein, we develop novel iodine-131-labeled-nimotuzumab conjugated with MnFe2O4 NPs as multimodalities of MRI and SPECT nanoprobe. The synthesis of MnFe2O4 NPs was mediated by Piper nigrum seed extract (PNE) consisting of alkaloids and terpenoids which play essential roles as a weak base source and stabilizing agent in the formation of MnFe2O4 NPs. anti-epidermal Growth Factor Receptor (EGFR) nimotuzumab was conjugated with MnFe2O4 NPs via a heterobifunctional PEG-linker. The radiolabeling of nimotuzumab/MnFe2O4 with iodine-131 was performed using the iodogen method. The vibrational, optical, magnetic, and morphological properties of MnFe2O4 NPs were characterized. MnFe2O4 NPs exhibited a spherical shape with an average particle size of 21 nm with a magnetization value of 23.4 emu/g. The vibrational and structural analyses verify that the MnFe2O4-nimotuzumab was conjugated using a linker. As a result, 131I-labeled-MnFe2O4-nimotuzumab NPs represents an excellent radiochemical purity of 99.32 ± 0.22 %, suggesting that radiopharmaceutical product generates a high imaging quality and unnecessary radiation. In this study, we offer a novel approach to design 131I-labeled-MnFe2O4-nimotuzumab NPs for potential dual-modality MRI and SPECT imaging nanoprobe.

Retraction: Versatile Molecule for Single-Laser-Triggered Redox-Responsive Enhanced Dual-Modal Imaging and Synergistic Photothermal-Photodynamic Therapy.

Mingli Han, Zhongxing Jiang Macromol. Biosci. 2022, 2200353 https://doi.org/10.1002/mabi.202200353 Retraction: "Versatile Molecule for Single-Laser-Triggered Redox-Responsive Enhanced Dual-Modal Imaging and Synergistic Photothermal-Photodynamic Therapy", by Mingli Han and Zhongxing Jiang, Macromolecular Bioscience 2022, 2200353 (https://doi.org/10.1002/mabi.202200353). The above article, published online on October 10, 2022, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief Anne Pfisterer, and Wiley-VCH GmbH. The article has been retracted because the manuscript was submitted and published with neither the knowledge nor consent of the listed coauthor and thus lacked the proper authorization for publication.