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Analytical Chemistry Dec 2021Raman spectroscopy enables nondestructive, label-free imaging with unprecedented molecular contrast, but is limited by slow data acquisition, largely preventing...
Raman spectroscopy enables nondestructive, label-free imaging with unprecedented molecular contrast, but is limited by slow data acquisition, largely preventing high-throughput imaging applications. Here, we present a comprehensive framework for higher-throughput molecular imaging via deep-learning-enabled Raman spectroscopy, termed DeepeR, trained on a large data set of hyperspectral Raman images, with over 1.5 million spectra (400 h of acquisition) in total. We first perform denoising and reconstruction of low signal-to-noise ratio Raman molecular signatures via deep learning, with a 10× improvement in the mean-squared error over common Raman filtering methods. Next, we develop a neural network for robust 2-4× spatial super-resolution of hyperspectral Raman images that preserve molecular cellular information. Combining these approaches, we achieve Raman imaging speed-ups of up to 40-90×, enabling good-quality cellular imaging with a high-resolution, high signal-to-noise ratio in under 1 min. We further demonstrate Raman imaging speed-up of 160×, useful for lower resolution imaging applications such as the rapid screening of large areas or for spectral pathology. Finally, transfer learning is applied to extend DeepeR from cell to tissue-scale imaging. DeepeR provides a foundation that will enable a host of higher-throughput Raman spectroscopy and molecular imaging applications across biomedicine.
Topics: Deep Learning; Molecular Imaging; Neural Networks, Computer; Signal-To-Noise Ratio; Spectrum Analysis, Raman
PubMed: 34797972
DOI: 10.1021/acs.analchem.1c02178 -
Current Opinion in Chemical Biology Aug 2021Phospholipid-coated microbubbles are ultrasound contrast agents that, when functionalized, adhere to specific biomarkers on cells. In this concise review, we highlight... (Review)
Review
Phospholipid-coated microbubbles are ultrasound contrast agents that, when functionalized, adhere to specific biomarkers on cells. In this concise review, we highlight recent developments in strategies for targeting the microbubbles and their use for ultrasound molecular imaging (UMI) and therapy. Recently developed novel targeting strategies include magnetic functionalization, triple targeting, and the use of several new ligands. UMI is a powerful technique for studying disease progression, diagnostic imaging, and monitoring of therapeutic responses. Targeted microbubbles (tMBs) have been used for the treatment of cardiovascular diseases and cancer, with therapeutics either coadministered or loaded onto the tMBs. Regardless of which disease was treated, the use of tMBs always resulted in a better therapeutic outcome than non-tMBs when compared in vitro or in vivo.
Topics: Animals; Cardiovascular Diseases; Contrast Media; Drug Carriers; Drug Therapy, Combination; Humans; Microbubbles; Molecular Imaging; Molecular Targeted Therapy; Neoplasms; Phospholipids; Treatment Outcome; Ultrasonography
PubMed: 34102582
DOI: 10.1016/j.cbpa.2021.04.013 -
Bioconjugate Chemistry Mar 2020Enzymatic reactions and self-assembly are two fundamental attributes of cells. It is not surprising that one can use enzyme-instructed self-assembly (EISA)-the... (Review)
Review
Enzymatic reactions and self-assembly are two fundamental attributes of cells. It is not surprising that one can use enzyme-instructed self-assembly (EISA)-the integration of enzymatic transformation and molecular self-assembly-to modulate the emergent properties of supramolecular assemblies for controlling cell behaviors. The exploration of EISA for developing cancer therapy and imaging has made considerable progress over the last five years. In this Topical Review, we discuss these exciting results and the future promise of EISA. After describing several key studies to illustrate the progress of EISA in developing cancer therapy, we discuss the use of EISA for molecular imaging. Then, we give the outlook of EISA for developing supramolecular anticancer medicine that inhibits multiple hallmark capabilities of cancer.
Topics: Animals; Enzymes; Humans; Molecular Imaging; Neoplasms
PubMed: 31995365
DOI: 10.1021/acs.bioconjchem.0c00025 -
Molecules (Basel, Switzerland) Nov 2020Molecular imaging has rapidly developed to answer the need of image contrast in medical diagnostic imaging to go beyond morphological information to include functional... (Review)
Review
Molecular imaging has rapidly developed to answer the need of image contrast in medical diagnostic imaging to go beyond morphological information to include functional differences in imaged tissues at the cellular and molecular levels. Vibrational (infrared (IR) and Raman) imaging has rapidly emerged among the molecular imaging modalities available, due to its label-free combination of high spatial resolution with chemical specificity. This article presents the physical basis of vibrational spectroscopy and imaging, followed by illustration of their preclinical in vitro applications in body fluids and cells, ex vivo tissues and in vivo small animals and ending with a brief discussion of their clinical translation. After comparing the advantages and disadvantages of IR/Raman imaging with the other main modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography/single-photon emission-computed tomography (PET/SPECT), ultrasound (US) and photoacoustic imaging (PAI), the design of multimodal probes combining vibrational imaging with other modalities is discussed, illustrated by some preclinical proof-of-concept examples.
Topics: Algorithms; Animals; Humans; Infrared Rays; Magnetic Resonance Imaging; Models, Theoretical; Molecular Imaging; Positron-Emission Tomography; Spectrum Analysis, Raman; Tomography, X-Ray Computed; Ultrasonography
PubMed: 33256052
DOI: 10.3390/molecules25235547 -
Biological & Pharmaceutical Bulletin 2024Both nuclear and optical imaging are used for in vivo molecular imaging. Nuclear imaging displays superior quantitativity, and it permits imaging in deep tissues. Thus,... (Review)
Review
Both nuclear and optical imaging are used for in vivo molecular imaging. Nuclear imaging displays superior quantitativity, and it permits imaging in deep tissues. Thus, this method is widely used clinically. Conversely, because of the low permeability of visible to near-IR light in living animals, it is difficult to visualize deep tissues via optical imaging. However, the light at these wavelengths has no ionizing effect, and it can be used without any restrictions in terms of location. Furthermore, optical signals can be controlled in vivo to accomplish target-specific imaging. Nuclear medicine and phototherapy have also evolved to permit targeted-specific imaging. In targeted nuclear therapy, beta emitters are conventionally used, but alpha emitters have received significant attention recently. Concerning phototherapy, photoimmunotherapy with near-IR light was approved in Japan in 2020. In this article, target-specific imaging and molecular targeted therapy utilizing nuclear medicine and optical technologies are discussed.
Topics: Humans; Animals; Optical Imaging; Molecular Imaging; Nuclear Medicine; Phototherapy; Molecular Targeted Therapy; Neoplasms
PubMed: 38825459
DOI: 10.1248/bpb.b24-00008 -
Stroke and Vascular Neurology Mar 2021Stem cells (SCs) are cells with strong proliferation ability, multilineage differentiation potential and self-renewal capacity. SC transplantation represents an... (Review)
Review
Stem cells (SCs) are cells with strong proliferation ability, multilineage differentiation potential and self-renewal capacity. SC transplantation represents an important therapeutic advancement for the treatment strategy of neurological diseases, both in the preclinical experimental and clinical settings. Innovative and breakthrough SC labelling and tracking technologies are widely used to monitor the distribution and viability of transplanted cells non-invasively and longitudinally. Here we summarised the research progress of the main tracers, labelling methods and imaging technologies involved in current SC tracking technologies for various neurological diseases. Finally, the applications, challenges and unresolved problems of current SC tracing technologies were discussed.
Topics: Cell Differentiation; Cell Tracking; Magnetic Resonance Imaging; Stem Cells
PubMed: 33122254
DOI: 10.1136/svn-2020-000408 -
European Journal of Nuclear Medicine... Jun 2020
Topics: Humans; Molecular Imaging; Nuclear Medicine
PubMed: 32157428
DOI: 10.1007/s00259-020-04750-w -
Molecules (Basel, Switzerland) Dec 2020Recent progress realized in the development of optical imaging (OPI) probes and devices has made this technique more and more affordable for imaging studies and... (Review)
Review
Recent progress realized in the development of optical imaging (OPI) probes and devices has made this technique more and more affordable for imaging studies and fluorescence-guided surgery procedures. However, this imaging modality still suffers from a low depth of penetration, thus limiting its use to shallow tissues or endoscopy-based procedures. In contrast, positron emission tomography (PET) presents a high depth of penetration and the resulting signal is less attenuated, allowing for imaging in-depth tissues. Thus, association of these imaging techniques has the potential to push back the limits of each single modality. Recently, several research groups have been involved in the development of radiolabeled fluorophores with the aim of affording dual-mode PET/OPI probes used in preclinical imaging studies of diverse pathological conditions such as cancer, Alzheimer's disease, or cardiovascular diseases. Among all the available PET-active radionuclides, F stands out as the most widely used for clinical imaging thanks to its advantageous characteristics (t = 109.77 min; 97% β emitter). This review focuses on the recent efforts in the synthesis and radiofluorination of fluorescent scaffolds such as 4,4-difluoro-4-bora-diazaindacenes (BODIPYs), cyanines, and xanthene derivatives and their use in preclinical imaging studies using both PET and OPI technologies.
Topics: Animals; Disease; Fluorescence; Fluorescent Dyes; Fluorine Radioisotopes; Humans; Molecular Imaging; Neoplasms; Optical Imaging; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 33371284
DOI: 10.3390/molecules25246042 -
Theranostics 2021In recent years, a paradigm shift from single-photon-emitting radionuclide radiotracers toward positron-emission tomography (PET) radiotracers has occurred in nuclear... (Review)
Review
In recent years, a paradigm shift from single-photon-emitting radionuclide radiotracers toward positron-emission tomography (PET) radiotracers has occurred in nuclear oncology. Although PET-based molecular imaging of the kidneys is still in its infancy, such a trend has emerged in the field of functional renal radionuclide imaging. Potentially allowing for precise and thorough evaluation of renal radiotracer urodynamics, PET radionuclide imaging has numerous advantages including precise anatomical co-registration with CT images and dynamic three-dimensional imaging capability. In addition, relative to scintigraphic approaches, PET can allow for significantly reduced scan time enabling high-throughput in a busy PET practice and further reduces radiation exposure, which may have a clinical impact in pediatric populations. In recent years, multiple renal PET radiotracers labeled with C, Ga, and F have been utilized in clinical studies. Beyond providing a precise non-invasive read-out of renal function, such radiotracers may also be used to assess renal inflammation. This manuscript will provide an overview of renal molecular PET imaging and will highlight the transformation of conventional scintigraphy of the kidneys toward novel, high-resolution PET imaging for assessing renal function. In addition, future applications will be introduced, e.g. by transferring the concept of molecular image-guided diagnostics and therapy (theranostics) to the field of nephrology.
Topics: Animals; Humans; Kidney; Molecular Imaging; Positron-Emission Tomography; Precision Medicine; Radioisotopes; Radionuclide Imaging; Radiopharmaceuticals; Urology
PubMed: 33897902
DOI: 10.7150/thno.58682 -
Nature Communications Dec 2020Zebrafish embryos provide a unique opportunity to visualize complex biological processes, yet conventional imaging modalities are unable to access intricate biomolecular...
Zebrafish embryos provide a unique opportunity to visualize complex biological processes, yet conventional imaging modalities are unable to access intricate biomolecular information without compromising the integrity of the embryos. Here, we report the use of confocal Raman spectroscopic imaging for the visualization and multivariate analysis of biomolecular information extracted from unlabeled zebrafish embryos. We outline broad applications of this method in: (i) visualizing the biomolecular distribution of whole embryos in three dimensions, (ii) resolving anatomical features at subcellular spatial resolution, (iii) biomolecular profiling and discrimination of wild type and ΔRD1 mutant Mycobacterium marinum strains in a zebrafish embryo model of tuberculosis and (iv) in vivo temporal monitoring of the wound response in living zebrafish embryos. Overall, this study demonstrates the application of confocal Raman spectroscopic imaging for the comparative bimolecular analysis of fully intact and living zebrafish embryos.
Topics: Animals; Animals, Genetically Modified; Embryo, Nonmammalian; Molecular Imaging; Multivariate Analysis; Mycobacterium Infections, Nontuberculous; Mycobacterium marinum; Spectrum Analysis, Raman; Time-Lapse Imaging; Wound Healing; Zebrafish
PubMed: 33268772
DOI: 10.1038/s41467-020-19827-1