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Editorial: Optical Molecular Imaging in Cancer Research

1 Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China, 2 Xi’an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi’an, China, 3 Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China, 4 School of Precision Instruments and Optoelectronics Engineering, Tianjin University, Tianjin, China, 5 Thayer School of Engineering, Dartmouth College, Hanover, NH, United States

background for differentiation between the tumors and brain tissue. Experiments using tumors from both rats and patients demonstrated substantial differences between the malignant tumors and normal tissues.

Breast Cancer
Li et al. prepared a novel ultrasound contrast agent VEGFR2targeting iron-doped silica (SiO2) hollow nanoparticles (VEGFR2-PEG-HSNs-Fe NPs) and applied it in microwave ablation for breast cancer to investigate its value in the evaluation of effectiveness after tumor ablation. The subcutaneous xenograft tumor was established to simulate the microenvironment of mouse breast cancer. After the xenograft tumor was treated with microwave ablation, the extent of perfusion defect was evaluated by injecting VEGFR2-PEG-HSNs-Fe NPs, and an enhanced ultrasound signal was detected in the tumor. Experiments showed that the nano-targeted VEGFR2-PEG-HSNs-Fe NPs had good biosafety and ability for specific imaging, which had the potential to evaluate the efficacy of tumor ablation.
Li et al. designed new types of nanocarriers, the cascade release near-infrared imaging (NIFI) and thermal-chemo combination nanoparticles (CNC NPs), which can release drugs through the cascade of ultrasound triggering and pH responding to achieve synchronous tumor accumulation, monitoring, and the synergistic treatment of two functional molecules. The NPs can effectively perform cascade drug release through ultrasound triggering and pH responding. The CNC NPs have good in vivo biological safety and excellent fluorescence imaging, drug delivery, and therapeutic abilities in triple-negative breast cancer models.

Gastric Cancer
Yin et al. prepared 68Ga-DOTA-KEK-(GX1)2 and applied it to PET and Cerenkov imaging of gastric cancer. Its tumor-targeting ability was determined by nano PET/CT and Cerenkov imaging, standardized uptake value, signal-to-background ratio (SBR) quantification, and a bio-distribution study in tumor-bearing nude mice. Experiments showed that GX1 was modified successfully, and the in vivo and in vitro properties of the GX1 dimer were significantly better than those of GX1. The imaging probe 68Ga-DOTA-KEK-(GX1)2 is a potential candidate probe for PET and Cerenkov diagnosis of gastric cancer.

Liver Cancer
Yan et al. performed a phage-displayed bio-panning to identify a specific binding peptide targeting Glypican-3 (GPC-3), which could be used as a biomarker in hepatocellular carcinoma (HCC). In this bio-distribution study, a higher accumulation of F3 peptides was observed in HepG-2 tumors compared to PC-3 tumors in xenograft models. Furthermore, the F3 peptide tracer enabled the specific detection of tumors in HCC tumor models with PET imaging after labeling with radioactive 68Ga. This cyclic peptide targeting GPC-3 may be an alternative to serve as an imaging probe or a targeting domain in the drug conjugate.
Zhou et al. utilized IR780 as the near-infrared fluorescence imaging, photoacoustic imaging, and photothermal therapy (PTT) agent, and utilized paclitaxel (PTX), which is a broad-spectrum chemotherapy drug, together to build the NIF/PA dual-mode imaging and PTT/chemo synergistic theranostic nanoparticles (DIST NPs). Experiment results showed that the DIST NPs had a long circulation in vivo, high bioavailability, high biocompatibility, and low effective dose. Thus, the DIST NPs showed an excellent NIFI/PAI dual-mode imaging and signifi cant synergistic antitumor effect in hepatic carcinoma models.

Lung Cancer
Chen et al. proposed to utilize habitat imaging-based 18 Ffluorodeoxyglucose ( 18 F-FDG) PET/CT radiomics for preoperatively discriminating non-small cell lung cancer (NSCLC) and benign inflammatory diseases (BIDs). Their study included 317 18 F-FDG PET/CT scans from patients who underwent aspiration biopsy or surgical resection. They constructed radiomics models based on clustering-based habitat radiomics method, conventional habitat-based method, and nonhabitat method. Experimental results showed that their adaptive habitat imaging-based method showed significantly improved discrimination performance compared to the conventional methods. This study implied that the microenvironmental variations in NSCLC and BID could be captured by PET/CT.

CLT Imaging
Wang et al. proposed a prior compensation algorithm to carry out Cerenkov luminescence tomography (CLT) reconstruction based on depth calibration strategy. Since the attenuation of light in the tissue depends heavily on the depth, a depth calibration matrix was designed to calibrate the attenuation between the surface light flux and the density of the internal light source. The feature of the proposed algorithm was that the depth calibration matrix directly acts on the system matrix, rather than modifying the regularization penalty items. The experiment results showed that the proposed method could locate the radiation sources accurately by using single-view measurements.
Wei et al. proposed a probabilistic energy distribution density region scaling (P-EDDRS) framework to implement CLT reconstruction. In this framework, multiple reconstruction iterations were performed, and the Cerenkov source distribution of each reconstruction was treated as random variables. The size of the region required for the next operation was determined dynamically by combining intensity characteristics. Besides, each reconstruction source distribution was given a probability weight value. Experimental results showed that this reconstruction framework had better positioning accuracy and shape recovery ability.

DOT Imaging
Wang et al. proposed a data self-calibration method based on a high-density (HD) parallel-plate diffuse optical tomography (DOT) system. Based on their proposed scheme, the reference predicted data can be constructed directly from the measurement data with the support of the HD-DOT system, which has nearly a hundred sets of measurements at each SD distance. The proposed scheme had been validated by Monte Carlo simulation, breast-size phantom experiments, and clinical trials, and results showed that the scheme had feasibility in ensuring the quality of the DOT reconstruction while effectively reducing the complexity.

XLCT Imaging
Liu et al. proposed a new finite element mesh regrouping strategy-based hybrid light transport model for X-ray luminescence computed tomography (XLCT). In their scheme, two separate meshes were obtained and the system matrixes and source weight matrixes were separately calculated. Then, the two system matrixes with different dimensions were coupled, and the two meshes were combined to establish the hybrid optical transmission model. The proposed method can reduce the computational memory consumption significantly, thus achieving a good balance between computational accuracy and efficiency.

Pathology Imaging
Zeng et al. proposed a wide-field pixel super-resolution color lensfree microscopy by performing wavelength scanning pixel super-resolution and phase retrieval simultaneously on the three channels of red, green, and blue (RGB), respectively. A highresolution RGB three-channel composite color image is converted to the YUV space for separating the color component and the brightness component, keeping the brightness component unchanged as well as enhancing the color component through an average filter. The proposed method can eliminate the common rainbow artifacts of holographic color reconstruction and maintain the highresolution details under different color illuminations.

REVIEWS FOR OPTICAL IMAGING
Wang et al. reviewed recent advances in hybrid light propagation models, with particular emphasis on their powerful use for 3D optical imaging in cancer detection. Since traditional optical imaging can only qualitatively detect 2D biomedical information, 3D imaging technology is explored to provide 3D quantitative information. For 3D imaging, the light propagation models that reflect the interaction between light and biological tissues are important bases and extensively reviewed in this paper.