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Biosensors
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In Vivo Imaging and Sensing of Biomarkers
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In Vivo Imaging and Sensing of Biomarkers

A special issue of Biosensors (ISSN 2079-6374). This special issue belongs to the section "Biosensors and Healthcare".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 31163

Special Issue Editors

Dr. Guanshu Liu

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Guest Editor
Russell H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Interests: molecular imaging; MR imaging probes; MRI biosensors; theranostic agents
Dr. Xin Zhou

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Guest Editor
Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China
Interests: ultrasensitive magnetic resonance imaging (MRI); biosensors; molecular imaging; MRI instrument; MRI biosensors; MRI images
Dr. Xing Yang

E-Mail Website
Guest Editor
Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
Interests: fluorescence imaging; molecular imaging; pharmaceutical chemistry; tumor chemical biology; cardiovascular imaging; cell-based fluorescent assay

Special Issue Information

Dear Colleagues,

In vivo bioimaging has become an essential tool in modern biomedical research and medicine. Mounting evidence has shown the unprecedented role of in vivo bioimaging in that biosensors are administered to living subjects for specifically detecting important disease biomarkers and displaying their spatial distribution non-invasively. In recent decades, a radical development has been made for in vivo sensing of various disease biomarkers. While the majority of these technologies have been demonstrated on preclinical animal models, encouraging clinical applications have also been reported. Ultimately, in vivo imaging and sensing will become an indispensable tool in precision medicine and can provide more accurate diagnosis and real-time treatment monitoring directly through sensing the underlying molecular events.

This Special Issue aims to cover recent advances in the development of in vivo imaging using clinically translatable modalities such as MRI, nuclear imaging, optical imaging, etc. Given the broad spectrum of technologies existing in this field, we will focus specifically on how imaging science and chemistry can be designed based on cellular/molecular biology to invent imaging methods and probes for sensing previously undetectable biomarkers and how these new innovations are translated to clinical studies to advance the medical field. 

Dr. Guanshu Liu
Dr. Xin Zhou
Dr. Xing Yang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biosensors is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • in vivo imaging
  • in vivo sensing
  • molecular imaging
  • biomarker mapping
  • precision diagnosis
  • real-time treatment monitoring
  • MRI
  • nuclear imaging
  • optical imaging

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Published Papers (11 papers)

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Editorial

Jump to: Research, Review

3 pages, 187 KiB  
Editorial
In Vivo Biomarker Imaging: Paving the Way for Precision Medicine
by Guanshu Liu, Xing Yang and Xin Zhou
Biosensors 2023, 13(4), 454; https://doi.org/10.3390/bios13040454 - 3 Apr 2023
Viewed by 1818
Abstract
In vivo bioimaging has become an indispensable tool in contemporary biomedical research and medicine [...] Full article
(This article belongs to the Special Issue In Vivo Imaging and Sensing of Biomarkers)

Research

Jump to: Editorial, Review

14 pages, 2734 KiB  
Article
The Dual-Targeted Peptide Conjugated Probe for Depicting Residual Nasopharyngeal Carcinoma and Guiding Surgery
by Wenhui Huang, Zicong He, Xuekang Cai, Jingming Zhang, Wei Li, Kun Wang and Shuixing Zhang
Biosensors 2022, 12(9), 729; https://doi.org/10.3390/bios12090729 - 5 Sep 2022
Cited by 2 | Viewed by 2250
Abstract
Detecting residual nasopharyngeal carcinoma (rNPC) can be difficult because of the coexistence of occult tumours and post-chemoradiation changes, which poses a challenge for both radiologists and surgeons using current imaging methods. Currently, molecular imaging that precisely targets and visualises particular biomarkers in tumours [...] Read more.
Detecting residual nasopharyngeal carcinoma (rNPC) can be difficult because of the coexistence of occult tumours and post-chemoradiation changes, which poses a challenge for both radiologists and surgeons using current imaging methods. Currently, molecular imaging that precisely targets and visualises particular biomarkers in tumours may exceed the specificity and sensitivity of traditional imaging techniques, providing the potential to distinguish tumours from non-neoplastic lesions. Here, we synthesised a HER2/SR-BI-targeted tracer to efficiently position NPC and guide surgery in living mice. This bispecific tracer contained the following two parts: IRDye 800 CW, as an imaging reagent for both optical and optoacoustic imaging, and a fusion peptide (FY-35), as the targeting reagent. Both in vitro and in vivo tests demonstrated that the tracer had higher accumulation and longer retention (up to 48 h) in tumours than a single-targeted probe, and realised sensitive detection of tumours with a minimum size of 3.9 mm. By visualising the vascular network via a customised handheld optoacoustic scan, our intraoperative fluorescence molecular imaging system provides accurate guidance for intraoperative tumour resection. Integrating the advantages of both optical and optoacoustic scanning in an intraoperative image-guided system, this method holds promise for depicting rNPC and guiding salvage surgery. Full article
(This article belongs to the Special Issue In Vivo Imaging and Sensing of Biomarkers)
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17 pages, 3878 KiB  
Article
A Mouse Holder for Awake Functional Imaging in Unanesthetized Mice: Applications in 31P Spectroscopy, Manganese-Enhanced Magnetic Resonance Imaging Studies, and Resting-State Functional Magnetic Resonance Imaging
by Lindsay C. Fadel, Ivany V. Patel, Jonathan Romero, I-Chih Tan, Shelli R. Kesler, Vikram Rao, S. A. Amali S. Subasinghe, Russell S. Ray, Jason T. Yustein, Matthew J. Allen, Brian W. Gibson, Justin J. Verlinden, Stanley Fayn, Nicole Ruggiero, Caitlyn Ortiz, Elizabeth Hipskind, Aaron Feng, Chijindu Iheanacho, Alex Wang and Robia G. Pautler
Biosensors 2022, 12(8), 616; https://doi.org/10.3390/bios12080616 - 8 Aug 2022
Cited by 4 | Viewed by 3641
Abstract
Anesthesia is often used in preclinical imaging studies that incorporate mouse or rat models. However, multiple reports indicate that anesthesia has significant physiological impacts. Thus, there has been great interest in performing imaging studies in awake, unanesthetized animals to obtain accurate results without [...] Read more.
Anesthesia is often used in preclinical imaging studies that incorporate mouse or rat models. However, multiple reports indicate that anesthesia has significant physiological impacts. Thus, there has been great interest in performing imaging studies in awake, unanesthetized animals to obtain accurate results without the confounding physiological effects of anesthesia. Here, we describe a newly designed mouse holder that is interfaceable with existing MRI systems and enables awake in vivo mouse imaging. This holder significantly reduces head movement of the awake animal compared to previously designed holders and allows for the acquisition of improved anatomical images. In addition to applications in anatomical T2-weighted magnetic resonance imaging (MRI), we also describe applications in acquiring 31P spectra, manganese-enhanced magnetic resonance imaging (MEMRI) transport rates and resting-state functional magnetic resonance imaging (rs-fMRI) in awake animals and describe a successful conditioning paradigm for awake imaging. These data demonstrate significant differences in 31P spectra, MEMRI transport rates, and rs-fMRI connectivity between anesthetized and awake animals, emphasizing the importance of performing functional studies in unanesthetized animals. Furthermore, these studies demonstrate that the mouse holder presented here is easy to construct and use, compatible with standard Bruker systems for mouse imaging, and provides rigorous results in awake mice. Full article
(This article belongs to the Special Issue In Vivo Imaging and Sensing of Biomarkers)
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15 pages, 2754 KiB  
Article
Cardiac and Respiratory Influences on Intracranial and Neck Venous Flow, Estimated Using Real-Time Phase-Contrast MRI
by Maria Marcella Laganà, Alice Pirastru, Francesca Ferrari, Sonia Di Tella, Marta Cazzoli, Laura Pelizzari, Ning Jin, Domenico Zacà, Noam Alperin, Giuseppe Baselli and Francesca Baglio
Biosensors 2022, 12(8), 612; https://doi.org/10.3390/bios12080612 - 8 Aug 2022
Cited by 7 | Viewed by 2133
Abstract
The study of brain venous drainage has gained attention due to its hypothesized link with various neurological conditions. Intracranial and neck venous flow rate may be estimated using cardiac-gated cine phase-contrast (PC)-MRI. Although previous studies showed that breathing influences the neck’s venous flow, [...] Read more.
The study of brain venous drainage has gained attention due to its hypothesized link with various neurological conditions. Intracranial and neck venous flow rate may be estimated using cardiac-gated cine phase-contrast (PC)-MRI. Although previous studies showed that breathing influences the neck’s venous flow, this aspect could not be studied using the conventional segmented PC-MRI since it reconstructs a single cardiac cycle. The advent of real-time PC-MRI has overcome these limitations. Using this technique, we measured the internal jugular veins and superior sagittal sinus flow rates in a group of 16 healthy subjects (12 females, median age of 23 years). Comparing forced-breathing and free-breathing, the average flow rate decreased and the respiratory modulation increased. The flow rate decrement may be due to a vasoreactive response to deep breathing. The respiratory modulation increment is due to the thoracic pump’s greater effect during forced breathing compared to free breathing. These results showed that the breathing mode influences the average blood flow and its pulsations. Since effective drainage is fundamental for brain health, rehabilitative studies might use the current setup to investigate if respiratory exercises positively affect clinical variables and venous drainage. Full article
(This article belongs to the Special Issue In Vivo Imaging and Sensing of Biomarkers)
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10 pages, 1543 KiB  
Article
Simultaneous Observation of Mouse Cortical and Hippocampal Neural Dynamics under Anesthesia through a Cranial Microprism Window
by Rujin Zhang, Chaowei Zhuang, Zilin Wang, Guihua Xiao, Kunsha Chen, Hao Li, Li Tong, Weidong Mi, Hao Xie and Jiangbei Cao
Biosensors 2022, 12(8), 567; https://doi.org/10.3390/bios12080567 - 26 Jul 2022
Cited by 3 | Viewed by 2413
Abstract
The fluorescence microscope has been widely used to explore dynamic processes in vivo in mouse brains, with advantages of a large field-of-view and high spatiotemporal resolution. However, owing to background light and tissue scattering, the single-photon wide-field microscope fails to record dynamic neural [...] Read more.
The fluorescence microscope has been widely used to explore dynamic processes in vivo in mouse brains, with advantages of a large field-of-view and high spatiotemporal resolution. However, owing to background light and tissue scattering, the single-photon wide-field microscope fails to record dynamic neural activities in the deep brain. To achieve simultaneous imaging of deep-brain regions and the superficial cortex, we combined the extended-field-of-view microscopy previously proposed with a novel prism-based cranial window to provide a longitudinal view. As well as a right-angle microprism for imaging above 1 mm, we also designed a new rectangular-trapezoidal microprism cranial window to extend the depth of observation to 1.5 mm and to reduce brain injury. We validated our method with structural imaging of microglia cells in the superficial cortex and deep-brain regions. We also recorded neuronal activity from the mouse brains in awake and anesthesitized states. The results highlight the great potential of our methods for simultaneous dynamic imaging in the superficial and deep layers of mouse brains. Full article
(This article belongs to the Special Issue In Vivo Imaging and Sensing of Biomarkers)
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14 pages, 2217 KiB  
Article
Real-Time Phase-Contrast MRI to Monitor Cervical Blood and Cerebrospinal Fluid Flow Beat-by-Beat Variability
by Giuseppe Baselli, Federica Fasani, Laura Pelizzari, Marta Cazzoli, Francesca Baglio and Maria Marcella Laganà
Biosensors 2022, 12(6), 417; https://doi.org/10.3390/bios12060417 - 15 Jun 2022
Cited by 11 | Viewed by 2547
Abstract
Beat-by-beat variability (BBV) rhythms are observed in both cardiovascular (CV) and intracranial (IC) compartments, yet interactions between the two are not fully understood. Real-Time Phase-Contrast (RT-PC) MRI sequence was acquired for 30 healthy volunteers at 1st cervical level on a 3T scanner. The [...] Read more.
Beat-by-beat variability (BBV) rhythms are observed in both cardiovascular (CV) and intracranial (IC) compartments, yet interactions between the two are not fully understood. Real-Time Phase-Contrast (RT-PC) MRI sequence was acquired for 30 healthy volunteers at 1st cervical level on a 3T scanner. The arterial (AF), venous (VF), and cerebrospinal fluid (CSF) flow (CSFF) were computed as velocity integrals over the internal carotid artery, internal jugular vein, and CSF. AF, VF, and CSFF signals were segmented in inspiration and expiration beats, to assess the respiration influence. Systolic and diastolic BBV, and heart period series underwent autoregressive power spectral density analysis, to evaluate the low-frequency (LF, Mayer waves) and high frequency (HF, respiratory waves) components. The diastolic VF had the largest BBV. LF power was high in the diastolic AF series, poor in all CSFF series. The pulse wave analyses revealed higher mean amplitude during inspiration. Findings suggests a possible role of LF modulation of IC resistances and propagation of HF waves from VF to AF and CCSF. PC-RT-MRI could provide new insight into the interaction between CV and IC regulation and pave the way for a detailed analysis of the cerebrovascular effects of varied respiration patterns due to exercise and rehabilitation. Full article
(This article belongs to the Special Issue In Vivo Imaging and Sensing of Biomarkers)
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10 pages, 3936 KiB  
Article
Cell-Membrane Biomimetic Indocyanine Green Liposomes for Phototheranostics of Echinococcosis
by Xinxin Xiong, Jun Li, Duyang Gao, Zonghai Sheng, Hairong Zheng and Wenya Liu
Biosensors 2022, 12(5), 311; https://doi.org/10.3390/bios12050311 - 9 May 2022
Cited by 8 | Viewed by 2399
Abstract
Echinococcosis is an important zoonotic infectious disease that seriously affects human health. Conventional diagnosis of echinococcosis relies on the application of large-scale imaging equipment, which is difficult to promote in remote areas. Meanwhile, surgery and chemotherapy for echinococcosis can cause serious trauma and [...] Read more.
Echinococcosis is an important zoonotic infectious disease that seriously affects human health. Conventional diagnosis of echinococcosis relies on the application of large-scale imaging equipment, which is difficult to promote in remote areas. Meanwhile, surgery and chemotherapy for echinococcosis can cause serious trauma and side effects. Thus, the development of simple and effective treatment strategies is of great significance for the diagnosis and treatment of echinococcosis. Herein, we designed a phototheranostic system utilizing neutrophil-membrane-camouflaged indocyanine green liposomes (Lipo-ICG) for active targeting the near-infrared fluorescence diagnosis and photothermal therapy of echinococcosis. The biomimetic Lipo-ICG exhibits a remarkable photo-to-heat converting performance and desirable active-targeting features by the inflammatory chemotaxis of the neutrophil membrane. In-vitro and in-vivo studies reveal that biomimetic Lipo-ICG with high biocompatibility can achieve in-vivo near-infrared fluorescence imaging and phototherapy of echinococcosis in mouse models. Our research is the first to apply bionanomaterials to the phototherapy of echinococcosis, which provides a new standard for the convenient and noninvasive detection and treatment of zoonotic diseases. Full article
(This article belongs to the Special Issue In Vivo Imaging and Sensing of Biomarkers)
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17 pages, 3395 KiB  
Article
Radiometal-Based PET/MRI Contrast Agents for Sensing Tumor Extracellular pH
by Alyssa C. Pollard, Jorge de la Cerda, F. William Schuler, Tyler R. Pollard, Aikaterini Kotrotsou, Federica Pisaneschi and Mark D. Pagel
Biosensors 2022, 12(2), 134; https://doi.org/10.3390/bios12020134 - 20 Feb 2022
Cited by 8 | Viewed by 3376
Abstract
Acidosis is a useful biomarker for tumor diagnoses and for evaluating early response to anti-cancer treatments. Despite these useful applications, there are few methods for non-invasively measuring tumor extracellular pH, and none are routinely used in clinics. Responsive MRI contrast agents have been [...] Read more.
Acidosis is a useful biomarker for tumor diagnoses and for evaluating early response to anti-cancer treatments. Despite these useful applications, there are few methods for non-invasively measuring tumor extracellular pH, and none are routinely used in clinics. Responsive MRI contrast agents have been developed, and they undergo a change in MRI signal with pH. However, these signal changes are concentration-dependent, and it is difficult to accurately measure the concentration of an MRI contrast agent in vivo. PET/MRI provides a unique opportunity to overcome this concentration dependence issue by using the PET component to report on the concentration of the pH-responsive MRI agent. Herein, we synthesized PET/MRI co-agents based on the design of a pH-dependent MRI agent, and we have correlated pH with the r1 relaxivity of the MRI co-agent. We have also developed a procedure that uses PET radioactivity measurements and MRI R1 relaxation rate measurements to determine the r1 relaxivity of the MRI co-agent, which can then be used to estimate pH. This simultaneous PET/MRI procedure accurately measured pH in solution, with a precision that depended on the concentration of the MRI co-agent. We used our procedure to measure extracellular pH in a subcutaneous flank model of MIA PaCa-2 pancreatic cancer. Although the PET co-agents were stable in serum, post-imaging studies showed evidence that the PET co-agents were degraded in vivo. These results showed that tumor acidosis can be evaluated with simultaneous PET/MRI, although improvements are needed to more precisely measure MRI R1 relaxation rates, and ensure the in vivo stability of the agents. Full article
(This article belongs to the Special Issue In Vivo Imaging and Sensing of Biomarkers)
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Review

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16 pages, 1676 KiB  
Review
Toward In Vivo MRI of the Tissue Proton Exchange Rate in Humans
by Mehran Shaghaghi and Kejia Cai
Biosensors 2022, 12(10), 815; https://doi.org/10.3390/bios12100815 - 1 Oct 2022
Cited by 2 | Viewed by 1892
Abstract
Quantification of proton exchange rate (kex) is a challenge in MR studies. Current techniques either have low resolutions or are dependent on the estimation of parameters that are not measurable. The Omega plot method, on the other hand, provides a [...] Read more.
Quantification of proton exchange rate (kex) is a challenge in MR studies. Current techniques either have low resolutions or are dependent on the estimation of parameters that are not measurable. The Omega plot method, on the other hand, provides a direct way for determining kex independent of the agent concentration. However, it cannot be used for in vivo studies without some modification due to the contributions from the water signal. In vivo tissue proton exchange rate (kex) MRI, based on the direct saturation (DS) removed Omega plot, quantifies the weighted average of kex of the endogenous tissue metabolites. This technique has been successfully employed for imaging the variation in the kex of ex vivo phantoms, as well as in vivo human brains in healthy subjects, and stroke or multiple sclerosis (MS) patients. In this paper, we present a brief review of the methods used for kex imaging with a focus on the development of in vivo kex MRI technique based on the DS-removed Omega plot. We then review the recent clinical studies utilizing this technique for better characterizing brain lesions. We also outline technical challenges for the presented technique and discuss its prospects for detecting tissue microenvironmental changes under oxidative stress. Full article
(This article belongs to the Special Issue In Vivo Imaging and Sensing of Biomarkers)
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13 pages, 580 KiB  
Review
Lineage Tracing and Molecular Real-Time Imaging of Cancer Stem Cells
by Xiaohua Jia, Guodong Shen, Jia Jia, Yan Zhang, Dan Zhang, Wanjun Li, Jianjun Zhang, Xinglu Huang and Jie Tian
Biosensors 2022, 12(9), 703; https://doi.org/10.3390/bios12090703 - 1 Sep 2022
Cited by 3 | Viewed by 2696
Abstract
The cancer stem cells (CSC) are the roots of cancer. The CSC hypothesis may provide a model to explain the tumor cell heterogeneity. Understand the biological mechanism of CSC will help the early detection and cure of cancer. The discovery of the dynamic [...] Read more.
The cancer stem cells (CSC) are the roots of cancer. The CSC hypothesis may provide a model to explain the tumor cell heterogeneity. Understand the biological mechanism of CSC will help the early detection and cure of cancer. The discovery of the dynamic changes in CSC will be possible by the using of bio-engineering techniques-lineage tracing. However, it is difficult to obtain real-time, continuous, and dynamic live-imaging information using the traditional approaches that take snapshots of time points from different animals. The goal of molecular imaging is to monitor the in situ, continuous molecular changes of cells in vivo. Therefore, the most advanced bioengineering lineage tracing approach, while using a variety of molecular detection methods, will maximize the presentation of CSC. In this review, we first introduce the method of lineage tracing, and then introduce the various components of molecular images to dynamic detect the CSC. Finally, we analyze the current situation and look forward the future of CSC detection. Full article
(This article belongs to the Special Issue In Vivo Imaging and Sensing of Biomarkers)
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87 pages, 18737 KiB  
Review
Dual-Mode Tumor Imaging Using Probes That Are Responsive to Hypoxia-Induced Pathological Conditions
by S. A. Amali S. Subasinghe, Robia G. Pautler, Md. Abul Hassan Samee, Jason T. Yustein and Matthew J. Allen
Biosensors 2022, 12(7), 478; https://doi.org/10.3390/bios12070478 - 30 Jun 2022
Cited by 12 | Viewed by 4359
Abstract
Hypoxia in solid tumors is associated with poor prognosis, increased aggressiveness, and strong resistance to therapeutics, making accurate monitoring of hypoxia important. Several imaging modalities have been used to study hypoxia, but each modality has inherent limitations. The use of a second modality [...] Read more.
Hypoxia in solid tumors is associated with poor prognosis, increased aggressiveness, and strong resistance to therapeutics, making accurate monitoring of hypoxia important. Several imaging modalities have been used to study hypoxia, but each modality has inherent limitations. The use of a second modality can compensate for the limitations and validate the results of any single imaging modality. In this review, we describe dual-mode imaging systems for the detection of hypoxia that have been reported since the start of the 21st century. First, we provide a brief overview of the hallmarks of hypoxia used for imaging and the imaging modalities used to detect hypoxia, including optical imaging, ultrasound imaging, photoacoustic imaging, single-photon emission tomography, X-ray computed tomography, positron emission tomography, Cerenkov radiation energy transfer imaging, magnetic resonance imaging, electron paramagnetic resonance imaging, magnetic particle imaging, and surface-enhanced Raman spectroscopy, and mass spectrometric imaging. These overviews are followed by examples of hypoxia-relevant imaging using a mixture of probes for complementary single-mode imaging techniques. Then, we describe dual-mode molecular switches that are responsive in multiple imaging modalities to at least one hypoxia-induced pathological change. Finally, we offer future perspectives toward dual-mode imaging of hypoxia and hypoxia-induced pathophysiological changes in tumor microenvironments. Full article
(This article belongs to the Special Issue In Vivo Imaging and Sensing of Biomarkers)
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