Optical Molecular Imaging Research Articles

Preparation and identification of a fluorescent probe with CsPbBr3perovskite quantum dots and CD44v6 specific peptide for gastric cancer imaging.

Since the sensitivity and accuracy of traditional detection for early gastric cancer diagnosis are still insufficient, it is significant to continuously optimize the optical molecular imaging detection technology based on an endoscopic platform. The signal intensity and stability of traditional chemical fluorescent dyes are low, which hinders the clinical application of molecular imaging detection technology. This work developed a probe based on perovskite quantum dots (PQDs) and peptide ligands. By utilizing CsPbBr3perovskite PQDs modified by azithromycin (AZI), combined with the specific polypeptide ligand of CD44v6, a gastric cancer biomarker, the perovskite-based probe (AZI-PQDs probe) which can specifically identify gastric cancer tumor was prepared. Owing to the high photoluminescence quantum yield of CsPbBr3PQDs, the naked eye can observe the imaging under the excitation of the hand-held ultraviolet light source. AZI-PQDs probe can accurately identify gastric cancer cells, tissues, and xenograft models with experiments ofex vivoandin vivofluorescence imaging detection. It also exhibited low toxicity and immunogenicity, indicating the safety of the probe. This work provides a probe combined with cancer specificity and a reliable fluorescent signal that has the potential for application in gastric cancer optical molecular imaging.

Dictionary Learning Method Based on K-Sparse Approximation and Orthogonal Procrustes Analysis for Reconstruction in Bioluminescence Tomography.

Bioluminescence tomography (BLT) is one kind of noninvasive optical molecular imaging technology, widely used to study molecular activities and disease progression inside live animals. By combining the optical propagation model and inversion algorithm, BLT enables three-dimensional imaging and quantitative analysis of light sources within organisms. However, challenges like light scattering and absorption in tissues, and the complexity of biological structures, significantly impact the accuracy of BLT reconstructions. Here, we propose a dictionary learning method based on K-sparse approximation and Orthogonal Procrustes analysis (KSAOPA). KSAOPA uses an iterative alternating optimization strategy, enhancing solution sparsity with k-coefficients Lipschitzian mappings for sparsity(K-LIMAPS) in the sparse coding stage, and reducing errors with Orthogonal Procrustes analysis in the dictionary update stage, leading to stable and precise reconstructions. We assessed the method performance through simulations and in vivo experiments, which showed that KSAOPA excels in localization accuracy, morphological recovery, and in vivo applicability compared to other methods.

Gold Nanoparticles for Retinal Molecular Optical Imaging.

The incorporation of gold nanoparticles (GNPs) into retinal imaging signifies a notable advancement in ophthalmology, offering improved accuracy in diagnosis and patient outcomes. This review explores the synthesis and unique properties of GNPs, highlighting their adjustable surface plasmon resonance, biocompatibility, and excellent optical absorption and scattering abilities. These features make GNPs advantageous contrast agents, enhancing the precision and quality of various imaging modalities, including photoacoustic imaging, optical coherence tomography, and fluorescence imaging. This paper analyzes the unique properties and corresponding mechanisms based on the morphological features of GNPs, highlighting the potential of GNPs in retinal disease diagnosis and management. Given the limitations currently encountered in clinical applications of GNPs, the approaches and strategies to overcome these limitations are also discussed. These findings suggest that the properties and efficacy of GNPs have innovative applications in retinal disease imaging.

Optical molecular imaging in cancer research: current impact and future prospect

Abstract Cancer has long been a major threat to human health. Recent advancements in molecular imaging have revolutionized cancer research by enabling early and precise disease localization, essential for effective management. In particular, optical molecular imaging is an invaluable cancer detection tool in preoperative planning, intraoperative guidance, and postoperative monitoring owing to its noninvasive nature, rapid turnover, safety, and ease of use. The tumor microenvironment and cells within it express distinct biomarkers. Optical imaging technology leverages these markers to differentiate tumor tissues from surrounding tissues and capture real-time images with high resolution. Nevertheless, a robust understanding of these cancer-related molecules and their dynamic changes is crucial for effectively managing cancer. Recent advancements in optical molecular imaging technologies offer novel approaches for cancer investigation in research and practice. This review investigates the modern optical molecular imaging techniques employed in both preclinical and clinical research, including bioluminescence, fluorescence, chemiluminescence, photoacoustic imaging, and Raman spectroscopy. We explore the current paradigm of optical molecular imaging modalities, their current status in preclinical cancer research and clinical applications, and future perspectives in the fields of cancer research and treatment.

TRPV4 and chloride channels mediate volume sensing in trabecular meshwork cells.

Aqueous humor drainage from the anterior eye determines intraocular pressure (IOP) under homeostatic and pathological conditions. Swelling of the trabecular meshwork (TM) alters its flow resistance but the mechanisms that sense and transduce osmotic gradients remain poorly understood. We investigated TM osmotransduction and its role in calcium and chloride homeostasis using molecular analyses, optical imaging, and electrophysiology. Anisosmotic conditions elicited proportional changes in TM cell volume, with swelling, but not shrinking, evoking elevations in intracellular calcium concentration [Ca2+]TM. Hypotonicity-evoked calcium signals were sensitive to HC067047, a selective blocker of TRPV4 channels, whereas the agonist GSK1016790A promoted swelling under isotonic conditions. TRPV4 inhibition partially suppressed hypotonicity-induced volume increases and reduced the magnitude of the swelling-induced membrane current, with a substantial fraction of the swelling-evoked current abrogated by Cl- channel antagonists 4,4'-diisothiocyanato-2,2'-stilbenedisulfonic acid (DIDS) and niflumic acid. The transcriptome of volume-sensing chloride channel candidates in primary human was dominated by ANO6 transcripts, with moderate expression of ANO3, ANO7, and ANO10 transcripts and low expression of LTTRC genes that encode constituents of the volume-activated anion channel. Imposition of 190 mosM but not 285 mosM hypotonic gradients increased conventional outflow in mouse eyes. TRPV4-mediated cation influx thus works with Cl- efflux to sense and respond to osmotic stress, potentially contributing to pathological swelling, calcium overload, and intracellular signaling that could exacerbate functional disturbances in inflammatory disease and glaucoma.NEW & NOTEWORTHY Intraocular pressure is dynamically regulated by the flow of aqueous humor through paracellular passages within the trabecular meshwork (TM). This study shows hypotonic gradients that expand the TM cell volume and reduce the outflow facility in mouse eyes. The swelling-induced current consists of TRPV4 and chloride components, with TRPV4 as a driver of swelling-induced calcium signaling. TRPV4 inhibition reduced swelling, suggesting a novel treatment for trabeculitis and glaucoma.

Early detection of pulmonary arterial hypertension through [18F] positron emission tomography imaging with a vascular endothelial receptor small molecule.

The objective of this study is to provide a positron emission tomography (PET) imaging modality targeting vascular endothelial growth factor receptors (VEGFR) for the early noninvasive detection and assessment of pulmonary arterial hypertension (PAH) severity. To validate the effectiveness of the [18F]VEGFR PET tracer, we utilized a monocrotaline (MCT)-induced PAH rat model. Molecular optical imaging, using a Cy5.5-conjugated VEGFR targeting agent, was employed to demonstrate the uptake of the agent at pulmonary arterioles, correlating with the onset and progression of PAH. Histological examinations of the MCT-PAH rat lung revealed a significant correlation between VEGFR2 expression and the pathogenesis of PAH. Molecular optical imaging demonstrated heightened uptake of the Cy5.5-conjugated VEGFR targeting agent at pulmonary arterioles, corresponding with the onset and progression of PAH. [18F]VEGFR PET showed increased lung uptake detectable in early-stage PAH before increase in pulmonary artery pressures, and this uptake correlated with increased PAH severity. Moreover, when compared to [18F]FDG PET, [18F]VEGFR PET exhibited markedly lower background cardiac signal, enhancing imaging sensitivity for lung abnormalities. Our study provides a compelling evidence for the potential utility of the innovative [18F]VEGFR PET tracer, in non-invasively detecting early signs of PAH, and monitoring its progression. The observed correlations between VEGFR2 expression, molecular optical imaging results, and [18F]VEGFR PET findings support the use of this tracer for early detection, and assessment of PAH severity. The lower background cardiac signal observed with [18F]VEGFR PET further enhances its imaging sensitivity, emphasizing its potential clinical significance.

What do the mushroom bodies do for the insect brain? Twenty-five years of progress.

In 1998, a special edition of Learning & Memory was published with a discrete focus of synthesizing the state of the field to provide an overview of the function of the insect mushroom body. While molecular neuroscience and optical imaging of larger brain areas were advancing, understanding the basic functioning of neuronal circuits, particularly in the context of the mushroom body, was rudimentary. In the past 25 years, technological innovations have allowed researchers to map and understand the in vivo function of the neuronal circuits of the mushroom body system, making it an ideal model for investigating the circuit basis of sensory encoding, memory formation, and behavioral decisions. Collaborative efforts within the community have played a crucial role, leading to an interactive connectome of the mushroom body and accessible genetic tools for studying mushroom body circuit function. Looking ahead, continued technological innovation and collaborative efforts are likely to further advance our understanding of the mushroom body and its role in behavior and cognition, providing insights that generalize to other brain structures and species.

Introduction to the Optical Molecular Probes, Imaging and Drug Delivery 2023 feature issue

A feature issue is being presented by a team of guest editors containing papers based on studies presented at the Optical Molecular Probes, Imaging and Drug Delivery conference as part of the Optica Biophotonics Congress in Vancouver, Canada from April 24–27, 2023.

Fluorescence molecular tomography based on an online maximum a posteriori estimation algorithm

Fluorescence molecular tomography (FMT) is a non-invasive, radiation-free, and highly sensitive optical molecular imaging technique for early tumor detection. However, inadequate measurement information along with significant scattering of near-infrared light within the tissue leads to high ill-posedness in the inverse problem of FMT. To improve the quality and efficiency of FMT reconstruction, we build a reconstruction model based on log-sum regularization and introduce an online maximum a posteriori estimation (OPE) algorithm to solve the non-convex optimization problem. The OPE algorithm approximates a stationary point by evaluating the gradient of the objective function at each iteration, and its notable strength lies in the remarkable speed of convergence. The results of simulations and experiments demonstrate that the OPE algorithm ensures good reconstruction quality and exhibits outstanding performance in terms of reconstruction efficiency.

Opto-Lipidomics of Tissues.

Lipid metabolism and signaling play pivotal functions in biology and disease development. Despite this, currently available optical techniques are limited in their ability to directly visualize the lipidome in tissues. In this study, opto-lipidomics, a new approach to optical molecular tissue imaging is introduced. The capability of vibrational Raman spectroscopy is expanded to identify individual lipids in complex tissue matrices through correlation with desorption electrospray ionization (DESI) - mass spectrometry (MS) imaging in an integrated instrument. A computational pipeline of inter-modality analysis is established to infer lipidomic information from optical vibrational spectra. Opto-lipidomic imaging of transient cerebral ischemia-reperfusion injury in a murine model of ischemic stroke demonstrates the visualization and identification of lipids in disease with high molecular specificity using Raman scattered light. Furthermore, opto-lipidomics in a handheld fiber-optic Raman probe is deployed and demonstrates real-time classification of bulk brain tissues based on specific lipid abundances. Opto-lipidomics opens a host of new opportunities to study lipid biomarkers for diagnostics, prognostics, and novel therapeutic targets.

Near-Infrared Chemiluminescence Imaging of Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) has a high prevalence but is poorly managed for cancer patients due to the lack of reliable and sensitive diagnostic techniques. Molecular optical imaging can provide a noninvasive way for real-time monitoring of CIPN; However, this is not reported, likely due to the absence of optical probes capable of imaging deep into the spinal canal and possessing sufficient sensitivity for minimal dosage through local injection into the dorsal root ganglia. Herein, a near-infrared (NIR) chemiluminophore (MPBD) with a chemiluminescence quantum yield higher than other reported probes is synthesized and a NIR activatable chemiluminescent probe (CalCL) is developed for in vivo imaging of CIPN. CalCL is constructed by caging MPBD with calpain-cleavable peptide moiety while conjugating polyethylene glycol chain to endow water solubility. Due to the deep-tissue penetration of chemiluminescence and specific turn-on response of CalCL toward calpain (a hallmark of CIPN), it allows for sensitive detection of paclitaxel-mediated CIPN in living mice, which is unattainable by fluorescence imaging. This study thus not only develops a highly efficient chemiluminescent probe, but also presents the first optical imaging approach toward high-throughput screening of neurotoxic drugs.

In vivo three-dimensional brain imaging with chemiluminescence probes in Alzheimer's disease models.

Optical three-dimensional (3D) molecular imaging is highly desirable for providing precise distribution of the target-of-interest in disease models. However, such 3D imaging is still far from wide applications in biomedical research; 3D brain optical molecular imaging, in particular, has rarely been reported. In this report, we designed chemiluminescence probes with high quantum yields, relatively long emission wavelengths, and high signal-to-noise ratios to fulfill the requirements for 3D brain imaging in vivo. With assistance from density-function theory (DFT) computation, we designed ADLumin-Xs by locking up the rotation of the double bond via fusing the furan ring to the phenyl ring. Our results showed that ADLumin-5 had a high quantum yield of chemiluminescence and could bind to amyloid beta (Aβ). Remarkably, ADLumin-5's radiance intensity in brain areas could reach 4 × 107 photon/s/cm2/sr, which is probably 100-fold higher than most chemiluminescence probes for in vivo imaging. Because of its strong emission, we demonstrated that ADLumin-5 could be used for in vivo 3D brain imaging in transgenic mouse models of Alzheimer's disease.

Logarithmic total variation regularization via preconditioned conjugate gradient method for sparse reconstruction of bioluminescence tomography

Background and objectiveBioluminescence Tomography (BLT) is a powerful optical molecular imaging technique that enables the noninvasive investigation of dynamic biological phenomena. It aims to reconstruct the three-dimensional spatial distribution of bioluminescent sources from optical measurements collected on the surface of the imaged object. However, BLT reconstruction is a challenging ill-posed problem due to the scattering effect of light and the limitations in detecting surface photons, which makes it difficult for existing methods to achieve satisfactory reconstruction results. In this study, we propose a novel method for sparse reconstruction of BLT based on a preconditioned conjugate gradient with logarithmic total variation regularization (PCG-logTV). MethodThis PCG-logTV method incorporates the sparsity of overlapping groups and enhances the sparse structure of these groups using logarithmic functions, which can preserve edge features and achieve more stable reconstruction results in BLT. To accelerate the convergence of the algorithm solution, we use the preconditioned conjugate gradient iteration method on the objective function and obtain the reconstruction results. We demonstrate the performance of our proposed method through numerical simulations and in vivo experiment. Results and conclusionsThe results show that the PCG-logTV method obtains the most accurate reconstruction results, and the minimum position error (LE) is 0.254mm, which is 26%, 31% and 34% of the FISTA (0.961), IVTCG (0.81) and L1-TV (0.739) methods, and the root mean square error (RMSE) and relative intensity error (RIE) are the smallest, indicating that it is closest to the real light source. In addition, compared with the other three methods, the PCG-logTV method also has the highest DICE similarity coefficient, which is 0.928, which means that this method can effectively reconstruct the three-dimensional spatial distribution of bioluminescent light sources, has higher resolution and robustness, and is beneficial to the preclinical and clinical studies of BLT.

Advances in optical molecular imaging for neural visualization.

Iatrogenic nerve injury is a significant complication in surgery, which can negatively impact patients' quality of life. Currently, the main clinical neuroimaging methods, such as computed tomography, magnetic resonance imaging, and high-resolution ultrasonography, do not offer precise real-time positioning images for doctors during surgery. The clinical application of optical molecular imaging technology has led to the emergence of new concepts such as optical molecular imaging surgery, targeted surgery, and molecular-guided surgery. These advancements have made it possible to directly visualize surgical target areas, thereby providing a novel method for real-time identification of nerves during surgery planning. Unlike traditional white light imaging, optical molecular imaging technology enables precise positioning and identifies the cation of intraoperative nerves through the presentation of color images. Although a large number of experiments and data support its development, there are few reports on its actual clinical application. This paper summarizes the research results of optical molecular imaging technology and its ability to realize neural visualization. Additionally, it discusses the challenges neural visualization recognition faces and future development opportunities.

Noninvasive Strategies for the Treatment of Tiny Liver Cancer: Integrating Photothermal Therapy and Multimodality Imaging EpCAM-Guided Nanoparticles

Surgical resection and ablation therapy have been shown to achieve the purpose of a radical cure for liver cancer with a size of less than 3 cm; however, tiny liver cancer lesions of diameters smaller than 2 cm remain challenging to diagnose and cure due to the failure of the generation of new blood vessels within tumors. Emerging evidence has revealed that optical molecular imaging combined with nanoprobes can detect tiny cancer from the perspective of molecular and cellular levels and kill cancer cells by the photothermal effect of nanoparticles in real time, thereby achieving radical goals. In the present study, we designed and synthesized multicomponent and multifunctional ICG-CuS-Gd@BSA-EpCAM nanoparticles (NPs) with a potent antineoplastic effect on tiny liver cancer. Using subcutaneous and orthotopic liver cancer xenograft mouse models, we found that the components of the NPs, including ICG and CuS-Gd@BSA, showed synergistic photothermal effects on the eradication of tiny liver cancer. We also found that the ICG-CuS-Gd@BSA-EpCAM NPs exhibited triple-modal functions of fluorescence imaging, magnetic resonance imaging, and photoacoustic imaging, with targeted detection and photothermal treatment of tiny liver cancer under near-infrared light irradiation. Together, our study demonstrates that the ICG-CuS-Gd@BSA-EpCAM NPs in combination with optical imaging technique might be a potential approach for detecting and noninvasively and radically curing tiny liver cancer by the photothermal effect.

Ex vivo near-infrared targeted imaging of human bladder carcinoma by ICG-anti-CD47.

The low detection rate of early-stage and small tumors remains a clinical challenge. A solution to this unmet need is urgently warranted for the accurate diagnosis and treatment of bladder cancer (BC). This study aimed to evaluate the feasibility of CD47 as a target for optical molecular imaging of human BC and conduct preliminary ex vivo imaging experiments. Using indocyanine green (ICG) and a CD47 antibody (anti-CD47), we synthesized a new targeted fluorescent probe ICG-anti-CD47. A total of 25 patients undergoing radical cystectomy were prospectively included in ex vivo imaging experiments. Following surgery, the freshly isolated bladder specimens were incubated with ICG-anti-CD47, and images were captured under white light and near-infrared (NIR) light. Standard histopathologic evaluation was performed, and findings were correlated with those of CD47-targeted NIR molecular imaging. Based on the ex vivo imaging experiments, 23 and 2 patients were pathologically diagnosed with bladder urothelial carcinoma and bladder squamous cell carcinoma, respectively. There were no adverse effects of ICG-anti-CD47 on the histological structure of the tumor and normal uroepithelium. In the NIR grayscale images, the mean fluorescence intensity of the tumor tissue was significantly higher than that of the adjacent normal background tissue, which markedly improved tumor visualization. Anti-CD47-targeted NIR molecular imaging may be a feasible and powerful strategy for the accurate diagnosis of BC. Nevertheless, larger-scale randomized trials are warranted to verify the present findings.

CD40-targeting magnetic nanoparticles for MRI/optical dual-modality molecular imaging of vulnerable atherosclerotic plaques

Background and aimsAcute coronary syndrome caused by vulnerable plaque rupture or erosion is a leading cause of death worldwide. CD40 has been reported to be highly expressed in atherosclerotic plaques and closely related to plaque stability. Therefore, CD40 is expected to be a potential target for the molecular imaging of vulnerable plaques in atherosclerosis. We aimed to design a CD40-targeted magnetic resonance imaging (MRI)/optical multimodal molecular imaging probe and explore its ability to detect and target vulnerable atherosclerotic plaques. MethodsCD40-Cy5.5 superparamagnetic iron oxide nanoparticles (CD40-Cy5.5-SPIONs), which comprise a CD40-targeting multimodal imaging contrast agent, were constructed by conjugating CD40 antibody and Cy5.5-N-hydroxysuccinimide ester with SPIONs. During this in vitro study, we observed the binding ability of CD40-Cy5.5-SPIONs with RAW 264.7 cells and mouse aortic vascular smooth muscle cells (MOVAS) after different treatments, using confocal fluorescence microscopy and Prussian blue staining. An in vivo study involving ApoE−/− mice fed a high-fat diet for 24–28 weeks was performed.24 h after intravenous injection of CD40-Cy5.5-SPIONs, fluorescence imaging and MRI were performed. ResultsCD40-Cy5.5-SPIONs bind specifically to tumor necrosis factor (TNF)-α-treated macrophages and smooth muscle cells. Fluorescence imaging results showed that, compared with the control group and the atherosclerosis group injected with non-specific bovine serum albumin (BSA)-Cy5.5-SPIONs, the atherosclerotic group injected with CD40-Cy5.5-SPIONs had a stronger fluorescence signal. T2-weighted images showed that the carotid arteries of atherosclerotic mice injected with CD40-Cy5.5-SPIONs had a significant substantial T2 contrast enhancement effect. ConclusionsCD40-Cy5.5-SPIONs could potentially serve as an effective MRI/optical probe for vulnerable atherosclerotic plaques during non-invasive detection.

Practical Guidance for Developing Small-Molecule Optical Probes for In Vivo Imaging.

The WMIS Education Committee (2019-2022) reached a consensus that white papers on molecular imaging could be beneficial for practitioners of molecular imaging at their early career stages and other scientists who are interested in molecular imaging. With this consensus, the committee plans to publish a series of white papers on topics related to the daily practice of molecular imaging. In this white paper, we aim to provide practical guidance that could be helpful for optical molecular imaging, particularly for small molecule probe development and validation in vitro and in vivo. The focus of this paper is preclinical animal studies with small-molecule optical probes. Near-infrared fluorescence imaging, bioluminescence imaging, chemiluminescence imaging, image-guided surgery, and Cerenkov luminescence imaging are discussed in this white paper.

A FRET-Based Ratiometric H2S Sensor for Sensitive Optical Molecular Imaging in Second Near-Infrared Window.

Second near-infrared (NIR-II) window optical molecular imaging kicks off a new revolution in high-quality imaging invivo, but always suffers from the hurdles of inevitable tissue autofluorescence background and NIR-II probe development. Here, we prepare a Förster resonance energy transfer-based ratiometric NIR-II window hydrogen sulfide (H2S) sensor through the combination of an H2S-responsive NIR-II cyanine dye (acceptor, LET-1055) and an H2S-inert rhodamine hybrid polymethine dye (donor, Rh930). This sensor not only exhibits high sensitivity and selectivity, but also shows rapid reaction kinetics (~20 min) and relatively low limit of detection (~96 nM) toward H2S, allowing invivo ratiometric NIR-II fluorescence imaging of orthotopic liver and colon tumors and visualization of the drug-induced hepatic H2S fluctuations. Our findings provide the potential for advancing the feasibility of NIR-II activity-based sensing for invivo clinical diagnosis.

Molecular Imaging for Early-Stage Disease Diagnosis.

With the development of cellular biology, molecular biology, and other subjects, targeted molecular probe was combined with medical imaging technologies to launch a new scientific disciplineof molecular imaging that is a research discipline to visualize, characterize, and analyze biological process at the cellular and molecular levels for real-time tracking and precision therapy, also termed as the medical imaging in the twenty-first century. An array of imaging techniques has been developed to image specific targets of living cells or tissues by molecular probes, including optical molecular imaging (OI), magnetic resonance molecular imaging, ultrasound (US) molecular imaging, nuclear medicine molecular imaging, X-ray molecular imaging, and multi-mode molecular imaging. These imaging techniques make the early diagnosis of various diseases possible by means of visualization of gene expression, interactions between proteins, signal transduction, cell metabolism, cell traces, and other physiological or pathological processes in the living system, which bridge the gap between molecular biology and clinical medicine. This chapter will lay the emphasis on the early-stage diagnosis of fatal diseases, such as malignant tumors, cardio- or cerebrovascular diseases, digestive system disease, central nervous system disease, and other diseases employing molecular imaging in a real-time visualized manner.