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Journal ArticleDOI

Multimodal Contrast Agents for Optoacoustic Brain Imaging in Small Animals.

Xue-feng Shi, Bin Ji1, Yanyan Kong1, Yihui Guan1, Ruiqing Ni2 
28 Sep 2021-Frontiers in Bioengineering and Biotechnology (Frontiers Media SA)-Vol. 9, pp 746815-746815
TL;DR: In this paper, a review of contrast agents including chemical dyes and nanoparticles applied in multimodal optoacoustic brain imaging integrated with other modalities in small animals, and provide outlook for further research.
Abstract: Optoacoustic (photoacoustic) imaging has demonstrated versatile applications in biomedical research, visualizing the disease pathophysiology and monitoring the treatment effect in an animal model, as well as toward applications in the clinical setting. Given the complex disease mechanism, multimodal imaging provides important etiological insights with different molecular, structural, and functional readouts in vivo. Various multimodal optoacoustic molecular imaging approaches have been applied in preclinical brain imaging studies, including optoacoustic/fluorescence imaging, optoacoustic imaging/magnetic resonance imaging (MRI), optoacoustic imaging/MRI/Raman, optoacoustic imaging/positron emission tomography, and optoacoustic/computed tomography. There is a rapid development in molecular imaging contrast agents employing a multimodal imaging strategy for pathological targets involved in brain diseases. Many chemical dyes for optoacoustic imaging have fluorescence properties and have been applied in hybrid optoacoustic/fluorescence imaging. Nanoparticles are widely used as hybrid contrast agents for their capability to incorporate different imaging components, tunable spectrum, and photostability. In this review, we summarize contrast agents including chemical dyes and nanoparticles applied in multimodal optoacoustic brain imaging integrated with other modalities in small animals, and provide outlook for further research.

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Posted ContentDOI
TL;DR: This study revealed an increased [18F]RoSMA-18-d6 measure of CB2R and a reduced [18f]FDG measure of CMRglc in ischemic striatum of tMCAO mice at subacute stage and might be a promising PET tracer for detectingCB2R alterations in animal models of neuroinflammation without neuronal loss.
Abstract: Stroke is one of the most prevalent vascular diseases. Non-invasive molecular imaging methods have the potential to provide critical insights into the temporal dynamics and follow alterations of receptor expression and metabolism in ischemic stroke. The aim of this study was to assess the cannabinoid type 2 receptor (CB2R) levels in transient middle cerebral artery occlusion (tMCAO) mouse models at subacute stage using positron emission tomography (PET) with our novel tracer [18F]RoSMA-18-d6 and structural imaging by magnetic resonance imaging (MRI). Our recently developed CB2R PET tracer [18F]RoSMA-18-d6 was used for imaging neuroinflammation at 24 h after reperfusion in tMCAO mice. The RNA expression levels of CB2R and other inflammatory markers were analyzed by quantitative real-time polymerase chain reaction using brain tissues from tMCAO (1 h occlusion) and sham-operated mice. [18F]fluorodeoxyglucose (FDG) was included for evaluation of the cerebral metabolic rate of glucose (CMRglc). In addition, diffusion-weighted imaging and T2-weighted imaging were performed for anatomical reference and delineating the lesion in tMCAO mice. mRNA expressions of inflammatory markers TNF-α, Iba1, MMP9 and GFAP, CNR2 were increased to 1.3–2.5 fold at 24 h after reperfusion in the ipsilateral compared to contralateral hemisphere of tMCAO mice, while mRNA expression of the neuronal marker MAP-2 was markedly reduced to ca. 50 %. Reduced [18F]FDG uptake was observed in the ischemic striatum of tMCAO mouse brain at 24 h after reperfusion. Although higher activity of [18F]RoSMA-18-d6 in ex vivo biodistribution studies and higher standard uptake value ratio (SUVR) were detected in the ischemic ipsilateral compared to contralateral striatum in tMCAO mice, the in vivo specificity of [18F]RoSMA-18-d6 was confirmed only in the CB2R-rich spleen. This study revealed an increased [18F]RoSMA-18-d6 measure of CB2R and a reduced [18F]FDG measure of CMRglc in the ischemic striatum of tMCAO mice at subacute stage. [18F]RoSMA-18-d6 might be a promising PET tracer for detecting CB2R alterations in animal models of neuroinflammation without neuronal loss.

10 citations

Journal ArticleDOI
27 Jan 2023-Medicine
TL;DR: In this article , a global bibliometric and visualization analysis was used to comprehensively review the published research related to multimodal molecular imaging and point out the developing areas of this field.

1 citations

Journal ArticleDOI
TL;DR: The current PAT/US dual-modal imaging systems are discussed in detail, and their promising clinical applications are presented and compared systematically and the potential impacts of these combined systems in the coming future are described.
Abstract: 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.

1 citations

References
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Journal ArticleDOI
TL;DR: Recent studies examining spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal of functional magnetic resonance imaging as a potentially important and revealing manifestation of spontaneous neuronal activity are reviewed.
Abstract: The majority of functional neuroscience studies have focused on the brain's response to a task or stimulus. However, the brain is very active even in the absence of explicit input or output. In this Article we review recent studies examining spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal of functional magnetic resonance imaging as a potentially important and revealing manifestation of spontaneous neuronal activity. Although several challenges remain, these studies have provided insight into the intrinsic functional architecture of the brain, variability in behaviour and potential physiological correlates of neurological and psychiatric disease.

6,135 citations

Journal ArticleDOI
23 Mar 2012-Science
TL;DR: A review of the state of the art of photoacoustic tomography for both biological and clinical studies can be found in this paper, where the authors discuss the current state-of-the-art and discuss future prospects.
Abstract: Photoacoustic tomography (PAT) can create multiscale multicontrast images of living biological structures ranging from organelles to organs. This emerging technology overcomes the high degree of scattering of optical photons in biological tissue by making use of the photoacoustic effect. Light absorption by molecules creates a thermally induced pressure jump that launches ultrasonic waves, which are received by acoustic detectors to form images. Different implementations of PAT allow the spatial resolution to be scaled with the desired imaging depth in tissue while a high depth-to-resolution ratio is maintained. As a rule of thumb, the achievable spatial resolution is on the order of 1/200 of the desired imaging depth, which can reach up to 7 centimeters. PAT provides anatomical, functional, metabolic, molecular, and genetic contrasts of vasculature, hemodynamics, oxygen metabolism, biomarkers, and gene expression. We review the state of the art of PAT for both biological and clinical studies and discuss future prospects.

3,518 citations

Journal ArticleDOI
TL;DR: Tumour fluorescence derived from 5-aminolevulinic acid enables more complete resections of contrast-enhancing tumour, leading to improved progression-free survival in patients with malignant glioma.
Abstract: Summary Background 5-aminolevulinic acid is a non-fluorescent prodrug that leads to intracellular accumulation of fluorescent porphyrins in malignant gliomas—a finding that is under investigation for intraoperative identification and resection of these tumours. We aimed to assess the effect of fluorescence-guided resection with 5-aminolevulinic acid on surgical radicality, progression-free survival, overall survival, and morbidity. Methods 322 patients aged 23–73 years with suspected malignant glioma amenable to complete resection of contrast-enhancing tumour were randomly assigned to 20 mg/kg bodyweight 5-aminolevulinic acid for fluorescence-guided resection (n=161) or to conventional microsurgery with white light (n=161). The primary endpoints were the number of patients without contrast-enhancing tumour on early MRI (ie, that obtained within 72 h after surgery) and 6-month progression-free survival as assessed by MRI. Secondary endpoints were volume of residual tumour on postoperative MRI, overall survival, neurological deficit, and toxic effects. We report the results of an interim analysis with 270 patients in the full-analysis population (139 assigned 5-aminolevulinic acid, 131 assigned white light), which excluded patients with ineligible histological and radiological findings as assessed by central reviewers who were masked as to treatment allocation; the interim analysis resulted in termination of the study as defined by the protocol. Primary and secondary endpoints were analysed by intention to treat in the full-analysis population. The study is registered at http://www.clinicaltrials.gov as NCT00241670. Findings Median follow-up was 35·4 months (95% CI 1·0–56·7). Contrast-enhancing tumour was resected completely in 90 (65%) of 139 patients assigned 5-aminolevulinic acid compared with 47 (36%) of 131 assigned white light (difference between groups 29% [95% CI 17–40], p vs 21·1% [14·0–28·2]; difference between groups 19·9% [9·1–30·7], p=0·0003, Z test). Groups did not differ in the frequency of severe adverse events or adverse events in any organ system class reported within 7 days after surgery. Interpretation Tumour fluorescence derived from 5-aminolevulinic acid enables more complete resections of contrast-enhancing tumour, leading to improved progression-free survival in patients with malignant glioma.

2,838 citations

Journal ArticleDOI
28 Jan 2020-ACS Nano
TL;DR: Prominent authors from all over the world joined efforts to summarize the current state-of-the-art in understanding and using SERS, as well as to propose what can be expected in the near future, in terms of research, applications, and technological development.
Abstract: The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article.

1,768 citations

Journal ArticleDOI
TL;DR: This Review discusses promising photonic methods that have the ability to visualize cellular and subcellular components in tissues across different penetration scales, according to the tissue depth at which they operate.
Abstract: Optical microscopy has been a fundamental tool of biological discovery for more than three centuries, but its in vivo tissue imaging ability has been restricted by light scattering to superficial investigations, even when confocal or multiphoton methods are used. Recent advances in optical and optoacoustic (photoacoustic) imaging now allow imaging at depths and resolutions unprecedented for optical methods. These abilities are increasingly important to understand the dynamic interactions of cellular processes at different systems levels, a major challenge of postgenome biology. This Review discusses promising photonic methods that have the ability to visualize cellular and subcellular components in tissues across different penetration scales. The methods are classified into microscopic, mesoscopic and macroscopic approaches, according to the tissue depth at which they operate. Key characteristics associated with different imaging implementations are described and the potential of these technologies in biological applications is discussed.

1,607 citations