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International Journal of Molecular... Oct 2021Diabetic foot infection is the leading cause of non-traumatic lower limb amputations worldwide. In addition, diabetes mellitus and sequela of the disease are increasing... (Review)
Review
Diabetic foot infection is the leading cause of non-traumatic lower limb amputations worldwide. In addition, diabetes mellitus and sequela of the disease are increasing in prevalence. In 2017, 9.4% of Americans were diagnosed with diabetes mellitus (DM). The growing pervasiveness and financial implications of diabetic foot infection (DFI) indicate an acute need for improved clinical assessment and treatment. Complex pathophysiology and suboptimal specificity of current non-invasive imaging modalities have made diagnosis and treatment response challenging. Current anatomical and molecular clinical imaging strategies have mainly targeted the host's immune responses rather than the unique metabolism of the invading microorganism. Advances in imaging have the potential to reduce the impact of these problems and improve the assessment of DFI, particularly in distinguishing infection of soft tissue alone from osteomyelitis (OM). This review presents a summary of the known pathophysiology of DFI, the molecular basis of current and emerging diagnostic imaging techniques, and the mechanistic links of these imaging techniques to the pathophysiology of diabetic foot infections.
Topics: Animals; Diabetes Complications; Diabetes Mellitus; Diabetic Foot; Humans; Molecular Imaging; Osteomyelitis
PubMed: 34768982
DOI: 10.3390/ijms222111552 -
CA: a Cancer Journal For Clinicians Jul 2022The authors define molecular imaging, according to the Society of Nuclear Medicine and Molecular Imaging, as the visualization, characterization, and measurement of... (Review)
Review
The authors define molecular imaging, according to the Society of Nuclear Medicine and Molecular Imaging, as the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Although practiced for many years clinically in nuclear medicine, expansion to other imaging modalities began roughly 25 years ago and has accelerated since. That acceleration derives from the continual appearance of new and highly relevant animal models of human disease, increasingly sensitive imaging devices, high-throughput methods to discover and optimize affinity agents to key cellular targets, new ways to manipulate genetic material, and expanded use of cloud computing. Greater interest by scientists in allied fields, such as chemistry, biomedical engineering, and immunology, as well as increased attention by the pharmaceutical industry, have likewise contributed to the boom in activity in recent years. Whereas researchers and clinicians have applied molecular imaging to a variety of physiologic processes and disease states, here, the authors focus on oncology, arguably where it has made its greatest impact. The main purpose of imaging in oncology is early detection to enable interception if not prevention of full-blown disease, such as the appearance of metastases. Because biochemical changes occur before changes in anatomy, molecular imaging-particularly when combined with liquid biopsy for screening purposes-promises especially early localization of disease for optimum management. Here, the authors introduce the ways and indications in which molecular imaging can be undertaken, the tools used and under development, and near-term challenges and opportunities in oncology.
Topics: Animals; Humans; Magnetic Resonance Imaging; Medical Oncology; Molecular Imaging; Positron-Emission Tomography
PubMed: 34902160
DOI: 10.3322/caac.21713 -
European Journal of Cancer (Oxford,... Mar 2021Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission... (Review)
Review
Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT) have been used in clinical trials and approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs). NETs form in cells that interact with the nervous system or in glands that produce hormones. These cells, called neuroendocrine cells, can be found throughout the body, but NETs are most often found in the abdomen, especially in the gastrointestinal tract. These tumours may also be found in the lungs, pancreas and adrenal glands. In addition to being rare, NETs are also complex and may be difficult to diagnose. Most NETs are non-functioning; however, a minority present with symptoms related to hypersecretion of bioactive compounds. NETs often do not cause symptoms early in the disease process. When diagnosed, substantial number of patients are already found to have metastatic disease. Several societies' guidelines address Neuroendocrine neoplasms (NENs) management; however, many issues are still debated, due to both the difficulty in acquiring strong clinical evidence in a rare and heterogeneous disease and the different availability of diagnostic and therapeutic options across countries. EANM Focus 3 reached consensus on employing gallium-labelled somatostatin analogue ([Ga]Ga-DOTA-SSA)-based PET/CT with diagnostic CT or magnetic resonance imaging (MRI) for unknown primary NET detection, metastatic NET, NET staging/restaging, suspected extra-adrenal pheochromocytoma/paraganglioma and suspected paraganglioma. Consensus was reached on employing fluorine-fluoro-2-deoxyglucose ([F]FDG) PET/CT in neuroendocrine carcinoma, G3 NET and in G1-2 NET with mismatched lesions (CT-positive/[Ga]Ga-DOTA-SSA-negative). Peptide receptor radionuclide therapy (PRRT) was recommended for second line treatment for gastrointestinal NET with [Ga]Ga-DOTA-SSA uptake in all lesions, in G1/G2 NET at disease progression, and in a subset of G3 NET provided all lesions are positive at [F]FDG and [Ga]Ga-DOTA-SSA. PRRT rechallenge may be used for in patients with stable disease for at least 1 year after therapy completion. An international consensus is not only a prelude to a more standardised management across countries but also serves as a guide for the direction to follow when designing new research studies.
Topics: Animals; Consensus; Humans; Molecular Imaging; Neuroendocrine Tumors; Radiopharmaceuticals
PubMed: 33588146
DOI: 10.1016/j.ejca.2021.01.008 -
Molecular Cell Dec 2019Visualizing the location and dynamics of RNAs in live cells is key to understanding their function. Here, we identify two endonuclease-deficient, single-component...
Visualizing the location and dynamics of RNAs in live cells is key to understanding their function. Here, we identify two endonuclease-deficient, single-component programmable RNA-guided and RNA-targeting Cas13 RNases (dCas13s) that allow robust real-time imaging and tracking of RNAs in live cells, even when using single 20- to 27-nt-long guide RNAs. Compared to the aptamer-based MS2-MCP strategy, an optimized dCas13 system is user friendly, does not require genetic manipulation, and achieves comparable RNA-labeling efficiency. We demonstrate that the dCas13 system is capable of labeling NEAT1, SatIII, MUC4, and GCN4 RNAs and allows the study of paraspeckle-associated NEAT1 dynamics. Applying orthogonal dCas13 proteins or combining dCas13 and MS2-MCP allows dual-color imaging of RNAs in single cells. Further combination of dCas13 and dCas9 systems allows simultaneous visualization of genomic DNA and RNA transcripts in living cells.
Topics: CRISPR-Cas Systems; Cell Line, Tumor; Fluorescent Dyes; Humans; Molecular Imaging; Mucin-4; Protein Engineering; RNA; RNA, Guide, CRISPR-Cas Systems; RNA, Long Noncoding; Ribonucleases; Single Molecule Imaging; Staining and Labeling
PubMed: 31757757
DOI: 10.1016/j.molcel.2019.10.024 -
Neuron Oct 2020Visualizing and perturbing neural activity on a brain-wide scale in model animals and humans is a major goal of neuroscience technology development. Established... (Review)
Review
Visualizing and perturbing neural activity on a brain-wide scale in model animals and humans is a major goal of neuroscience technology development. Established electrical and optical techniques typically break down at this scale due to inherent physical limitations. In contrast, ultrasound readily permeates the brain, and in some cases the skull, and interacts with tissue with a fundamental resolution on the order of 100 μm and 1 ms. This basic ability has motivated major efforts to harness ultrasound as a modality for large-scale brain imaging and modulation. These efforts have resulted in already-useful neuroscience tools, including high-resolution hemodynamic functional imaging, focused ultrasound neuromodulation, and local drug delivery. Furthermore, recent breakthroughs promise to connect ultrasound to neurons at the genetic level for biomolecular imaging and sonogenetic control. In this article, we review the state of the art and ongoing developments in ultrasonic neurotechnology, building from fundamental principles to current utility, open questions, and future potential.
Topics: Animals; Blood-Brain Barrier; Brain; Drug Delivery Systems; Echoencephalography; Functional Neuroimaging; Hemodynamics; Humans; Molecular Imaging; Proteins; Ultrasonic Therapy; Ultrasonic Waves; Ultrasonography; Ultrasonography, Doppler, Transcranial
PubMed: 33058769
DOI: 10.1016/j.neuron.2020.09.003 -
Annual Review of Physical Chemistry Apr 2021Mass spectrometry imaging (MSI) is a powerful, label-free technique that provides detailed maps of hundreds of molecules in complex samples with high sensitivity and... (Review)
Review
Mass spectrometry imaging (MSI) is a powerful, label-free technique that provides detailed maps of hundreds of molecules in complex samples with high sensitivity and subcellular spatial resolution. Accurate quantification in MSI relies on a detailed understanding of matrix effects associated with the ionization process along with evaluation of the extraction efficiency and mass-dependent ion losses occurring in the analysis step. We present a critical summary of approaches developed for quantitative MSI of metabolites, lipids, and proteins in biological tissues and discuss their current and future applications.
Topics: Animals; Brain; Brain Chemistry; Humans; Kidney; Liver; Mass Spectrometry; Molecular Imaging; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tandem Mass Spectrometry
PubMed: 33441032
DOI: 10.1146/annurev-physchem-061020-053416 -
The Quarterly Journal of Nuclear... Mar 2021
Topics: Humans; Molecular Imaging
PubMed: 33494586
DOI: 10.23736/S1824-4785.21.03329-X -
Nature Communications Mar 2022Non-invasive visualization of dynamic molecular events in real-time via molecular imaging may enable the monitoring of cascade catalytic reactions in living systems,...
Non-invasive visualization of dynamic molecular events in real-time via molecular imaging may enable the monitoring of cascade catalytic reactions in living systems, however effective imaging modalities and a robust catalytic reaction system are lacking. Here we utilize three-dimensional (3D) multispectral photoacoustic (PA) molecular imaging to monitor in vivo cascade catalytic therapy based on a dual enzyme-driven cyclic reaction platform. The system consists of a two-dimensional (2D) Pd-based nanozyme conjugated with glucose oxidase (GOx). The combination of nanozyme and GOx can induce the PA signal variation of endogenous molecules. Combined with the PA response of the nanozyme, we can simultaneously map the 3D PA signals of dynamic endogenous and exogenous molecules associated with the catalytic process, thus providing a real-time non-invasive visualization. We can also treat tumors under the navigation of the PA imaging. Therefore, our study demonstrates the imaging-guided potential of 3D multispectral PA imaging in feedback-looped cascade catalytic therapy.
Topics: Catalysis; Glucose Oxidase; Humans; Molecular Imaging; Neoplasms; Photoacoustic Techniques
PubMed: 35277519
DOI: 10.1038/s41467-022-29082-1 -
JACC. Cardiovascular Imaging Nov 2022
Topics: Humans; Molecular Imaging; Cardiovascular Diseases
PubMed: 36357149
DOI: 10.1016/j.jcmg.2022.10.001 -
Journal of Nuclear Medicine : Official... Jun 2021The genetic code to life is balanced on a string of DNA that is under constant metabolic and physical stress from environmental forces. Nearly all diseases have a... (Review)
Review
The genetic code to life is balanced on a string of DNA that is under constant metabolic and physical stress from environmental forces. Nearly all diseases have a genetic component caused by or resulting in DNA damage that alters biology to drive pathogenesis. Recent advancements in DNA repair biology have led to the development of imaging tools that target DNA damage response and repair proteins. PET has been used for early detection of oncogenic processes and monitoring of tumor response to chemotherapeutics that target the DNA repair machinery. In the field of precision medicine, imaging tools provide a unique opportunity for patient stratification by directly measuring drug target expression or monitoring therapy to identify early responders. This overview discusses the state of the art on molecular imaging of DNA damage and repair from the past 5 years, with an emphasis on poly[adenosine diphosphate ribose]polymerase-1 as an imaging target and predictive biomarker of response to therapy.
Topics: DNA Damage; DNA Repair; Humans; Molecular Imaging; Poly (ADP-Ribose) Polymerase-1
PubMed: 33579802
DOI: 10.2967/jnumed.120.243287