David R Smith, Jesse W Wilson, Siddarth Shivkumar, Hervé Rigneault, Randy A Bartels
{"title":"Low-Frequency Coherent Raman Imaging Robust to Optical Scattering.","authors":"David R Smith, Jesse W Wilson, Siddarth Shivkumar, Hervé Rigneault, Randy A Bartels","doi":"10.1021/cbmi.4c00020","DOIUrl":"10.1021/cbmi.4c00020","url":null,"abstract":"<p><p>We demonstrate low-frequency interferometric impulsive stimulated Raman scattering (ISRS) imaging with high robustness to distortions by optical scattering. ISRS is a pump-probe coherent Raman spectroscopy that can capture Raman vibrational spectra. Recording of ISRS spectra requires isolation of a probe pulse from the pump pulse. While this separation is simple in nonscattering specimens, such as liquids, scattering leads to significant pump pulse contamination and prevents the extraction of a Raman spectrum. We introduce a robust method for ISRS microscopy that works in complex scattering samples. High signal-to-noise ISRS spectra are obtained even when the pump and probe pulses pass through many scattering layers.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 8","pages":"584-591"},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142117047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David R. Smith, Jesse W. Wilson, Siddarth Shivkumar, Hervé Rigneault and Randy A. Bartels*,
{"title":"Low-Frequency Coherent Raman Imaging Robust to Optical Scattering","authors":"David R. Smith, Jesse W. Wilson, Siddarth Shivkumar, Hervé Rigneault and Randy A. Bartels*, ","doi":"10.1021/cbmi.4c0002010.1021/cbmi.4c00020","DOIUrl":"https://doi.org/10.1021/cbmi.4c00020https://doi.org/10.1021/cbmi.4c00020","url":null,"abstract":"<p >We demonstrate low-frequency interferometric impulsive stimulated Raman scattering (ISRS) imaging with high robustness to distortions by optical scattering. ISRS is a pump–probe coherent Raman spectroscopy that can capture Raman vibrational spectra. Recording of ISRS spectra requires isolation of a probe pulse from the pump pulse. While this separation is simple in nonscattering specimens, such as liquids, scattering leads to significant pump pulse contamination and prevents the extraction of a Raman spectrum. We introduce a robust method for ISRS microscopy that works in complex scattering samples. High signal-to-noise ISRS spectra are obtained even when the pump and probe pulses pass through many scattering layers.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 8","pages":"584–591 584–591"},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142075613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Apeksha C. Rajamanthrilage, Unaiza Uzair, Paul W. Millhouse, Matthew J. Case, Donald W. Benza and Jeffrey N. Anker*,
{"title":"Spatial Resolution for X-ray Excited Luminescence Chemical Imaging (XELCI)","authors":"Apeksha C. Rajamanthrilage, Unaiza Uzair, Paul W. Millhouse, Matthew J. Case, Donald W. Benza and Jeffrey N. Anker*, ","doi":"10.1021/cbmi.4c0003910.1021/cbmi.4c00039","DOIUrl":"https://doi.org/10.1021/cbmi.4c00039https://doi.org/10.1021/cbmi.4c00039","url":null,"abstract":"<p >Measuring chemical concentrations at the surface of implanted medical devices is important for elucidating the local biochemical environment, especially during implant infection. Although chemical indicator dyes enable chemical measurements in vitro, they are usually ineffective when measuring through tissue because the background obscures the dye signal and scattering dramatically reduces the spatial resolution. X-ray excited luminescent chemical imaging (XELCI) is a recent imaging modality which overcomes these limitations using a focused X-ray beam to excite a small spot of red light on scintillator-coated medical implants with well-defined location (because X-rays are minimally scattered) and low background. A spectrochemical indicator film placed over the scintillator layer, e.g., a polymer film containing pH-indicator dyes, absorbs some of the luminescence according to the local chemical environment, and this absorption is then detected by measuring the light intensity/spectrum passing through the tissue. A focused X-ray beam is used to scan point-by-point with a spatial resolution mainly limited by the X-ray beam width with minimum increase from X-ray absorption and scattering in the tissue. X-ray resolution, implant surface specificity, and chemical sensitivity are the three key features of XELCI. Here, we study spatial resolution using optically absorptive targets. For imaging a series of lines, the 20–80% knife-edge resolution was ∼285 (±15) μm with no tissue and 475 ± 18 and 520 ± 34 μm, respectively, through 5 and 10 mm thick tissue. Thus, doubling the tissue depth did not appreciably change the spatial resolution recorded through the tissue. This shows the promise of XELCI for submillimeter chemical imaging through tissue.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 7","pages":"510–517 510–517"},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141955872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tracing the Chromatin: From 3C to Live-Cell Imaging","authors":"Arianna N. Lacen, and , Hui-Ting Lee*, ","doi":"10.1021/cbmi.4c0003310.1021/cbmi.4c00033","DOIUrl":"https://doi.org/10.1021/cbmi.4c00033https://doi.org/10.1021/cbmi.4c00033","url":null,"abstract":"<p >Chromatin organization plays a key role in gene regulation throughout the cell cycle. Understanding the dynamics governing the accessibility of chromatin is crucial for insight into mechanisms of gene regulation, DNA replication, and cell division. Extensive research has been done to track chromatin dynamics to explain how cells function and how diseases develop, in the hope of this knowledge leading to future therapeutics utilizing proteins or drugs that modify the accessibility or expression of disease-related genes. Traditional methods for studying the movement of chromatin throughout the cell relied on cross-linking spatially adjacent sections or hybridizing fluorescent probes to chromosomal loci and then constructing dynamic models from the static data collected at different time points. While these traditional methods are fruitful in understanding fundamental aspects of chromatin organization, they are limited by their invasive sample preparation protocols and diffraction-limited microscope resolution. These limitations have been challenged by modern methods based on high- or super-resolution microscopy and specific labeling techniques derived from gene targeting tools. These modern methods are more sensitive and less invasive than traditional methods, therefore allowing researchers to track chromosomal organization, compactness, and even the distance or rate of chromatin domain movement in detail and real time. This review highlights a selection of recently developed methods of chromatin tracking and their applications in fixed and live cells.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 10","pages":"659–682 659–682"},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142551112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tracing the Chromatin: From 3C to Live-Cell Imaging.","authors":"Arianna N Lacen, Hui-Ting Lee","doi":"10.1021/cbmi.4c00033","DOIUrl":"10.1021/cbmi.4c00033","url":null,"abstract":"<p><p>Chromatin organization plays a key role in gene regulation throughout the cell cycle. Understanding the dynamics governing the accessibility of chromatin is crucial for insight into mechanisms of gene regulation, DNA replication, and cell division. Extensive research has been done to track chromatin dynamics to explain how cells function and how diseases develop, in the hope of this knowledge leading to future therapeutics utilizing proteins or drugs that modify the accessibility or expression of disease-related genes. Traditional methods for studying the movement of chromatin throughout the cell relied on cross-linking spatially adjacent sections or hybridizing fluorescent probes to chromosomal loci and then constructing dynamic models from the static data collected at different time points. While these traditional methods are fruitful in understanding fundamental aspects of chromatin organization, they are limited by their invasive sample preparation protocols and diffraction-limited microscope resolution. These limitations have been challenged by modern methods based on high- or super-resolution microscopy and specific labeling techniques derived from gene targeting tools. These modern methods are more sensitive and less invasive than traditional methods, therefore allowing researchers to track chromosomal organization, compactness, and even the distance or rate of chromatin domain movement in detail and real time. This review highlights a selection of recently developed methods of chromatin tracking and their applications in fixed and live cells.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 10","pages":"659-682"},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"First Year of Chemical & Biomedical Imaging: Reflection and Prospect","authors":"Wenxi Lei, Juanjuan Jia, Deju Ye and Zijian Guo*, ","doi":"10.1021/cbmi.4c00043","DOIUrl":"https://doi.org/10.1021/cbmi.4c00043","url":null,"abstract":"","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 6","pages":"398–400"},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael C. Hart, Ritesh K. Isuri, Drew Ramos, Sofya A. Osharovich, Andrea E. Rodriguez, Stefan Harmsen, Grace C. Dudek, Jennifer L. Huck, David E. Holt, Anatoliy V. Popov, Sunil Singhal and Edward J. Delikatny*,
{"title":"Non-Small Cell Lung Cancer Imaging Using a Phospholipase A2 Activatable Fluorophore","authors":"Michael C. Hart, Ritesh K. Isuri, Drew Ramos, Sofya A. Osharovich, Andrea E. Rodriguez, Stefan Harmsen, Grace C. Dudek, Jennifer L. Huck, David E. Holt, Anatoliy V. Popov, Sunil Singhal and Edward J. Delikatny*, ","doi":"10.1021/cbmi.4c0002610.1021/cbmi.4c00026","DOIUrl":"https://doi.org/10.1021/cbmi.4c00026https://doi.org/10.1021/cbmi.4c00026","url":null,"abstract":"<p >Lung cancer, the most common cause of cancer-related death in the United States, requires advanced intraoperative detection methods to improve evaluation of surgical margins. In this study we employed DDAO-arachidonate (DDAO-A), a phospholipase A2 (PLA2) activatable fluorophore, designed for the specific optical identification of lung cancers in real-time during surgery. The <i>in vitro</i> fluorescence activation of DDAO-A by porcine sPLA2 was tested in various liposomal formulations, with 100 nm extruded EggPC showing the best overall characteristics. Extruded EggPC liposomes containing DDAO-A were tested for their stability under various storage conditions, demonstrating excellent stability for up to 4 weeks when stored at −20 °C or below. Cell studies using KLN 205 and LLC1 lung cancer cell lines showed DDAO-A activation was proportional to cell number. DDAO-A showed preferential activation by human recombinant cPLA2, an isoform highly specific to arachidonic acid-containing lipids, when compared to a control probe, DDAO palmitate (DDAO-P). <i>In vivo</i> studies with DBA/2 mice bearing KLN 205 lung tumors recapitulated these results, with preferential activation of DDAO-A relative to DDAO-P following intratumoral injection. Topical application of DDAO-A-containing liposomes to human (n = 10) and canine (n = 3) lung cancers <i>ex vivo</i> demonstrated the preferential activation of DDAO-A in tumor tissue relative to adjacent normal lung tissue, with fluorescent tumor-to-normal ratios (TNR) of up to 5.2:1. The combined results highlight DDAO-A as a promising candidate for clinical applications, showcasing its potential utility in intraoperative and back-table imaging and topical administration during lung cancer surgeries. By addressing the challenge of residual microscopic disease at resection margins and offering stability in liposomal formulations, DDAO-A emerges as a potentially valuable tool for advancing precision lung cancer surgery and improving curative resection rates.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 7","pages":"490–500 490–500"},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141959230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael C Hart, Ritesh K Isuri, Drew Ramos, Sofya A Osharovich, Andrea E Rodriguez, Stefan Harmsen, Grace C Dudek, Jennifer L Huck, David E Holt, Anatoliy V Popov, Sunil Singhal, Edward J Delikatny
{"title":"Non-Small Cell Lung Cancer Imaging Using a Phospholipase A2 Activatable Fluorophore.","authors":"Michael C Hart, Ritesh K Isuri, Drew Ramos, Sofya A Osharovich, Andrea E Rodriguez, Stefan Harmsen, Grace C Dudek, Jennifer L Huck, David E Holt, Anatoliy V Popov, Sunil Singhal, Edward J Delikatny","doi":"10.1021/cbmi.4c00026","DOIUrl":"10.1021/cbmi.4c00026","url":null,"abstract":"<p><p>Lung cancer, the most common cause of cancer-related death in the United States, requires advanced intraoperative detection methods to improve evaluation of surgical margins. In this study we employed DDAO-arachidonate (DDAO-A), a phospholipase A2 (PLA2) activatable fluorophore, designed for the specific optical identification of lung cancers in real-time during surgery. The <i>in vitro</i> fluorescence activation of DDAO-A by porcine sPLA2 was tested in various liposomal formulations, with 100 nm extruded EggPC showing the best overall characteristics. Extruded EggPC liposomes containing DDAO-A were tested for their stability under various storage conditions, demonstrating excellent stability for up to 4 weeks when stored at -20 °C or below. Cell studies using KLN 205 and LLC1 lung cancer cell lines showed DDAO-A activation was proportional to cell number. DDAO-A showed preferential activation by human recombinant cPLA2, an isoform highly specific to arachidonic acid-containing lipids, when compared to a control probe, DDAO palmitate (DDAO-P). <i>In vivo</i> studies with DBA/2 mice bearing KLN 205 lung tumors recapitulated these results, with preferential activation of DDAO-A relative to DDAO-P following intratumoral injection. Topical application of DDAO-A-containing liposomes to human (n = 10) and canine (n = 3) lung cancers <i>ex vivo</i> demonstrated the preferential activation of DDAO-A in tumor tissue relative to adjacent normal lung tissue, with fluorescent tumor-to-normal ratios (TNR) of up to 5.2:1. The combined results highlight DDAO-A as a promising candidate for clinical applications, showcasing its potential utility in intraoperative and back-table imaging and topical administration during lung cancer surgeries. By addressing the challenge of residual microscopic disease at resection margins and offering stability in liposomal formulations, DDAO-A emerges as a potentially valuable tool for advancing precision lung cancer surgery and improving curative resection rates.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 7","pages":"490-500"},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nancy Sharma, Walaa Mohammad, Xavier Le Guével* and Asifkhan Shanavas*,
{"title":"Gold Nanoclusters as High Resolution NIR-II Theranostic Agents","authors":"Nancy Sharma, Walaa Mohammad, Xavier Le Guével* and Asifkhan Shanavas*, ","doi":"10.1021/cbmi.4c0002110.1021/cbmi.4c00021","DOIUrl":"https://doi.org/10.1021/cbmi.4c00021https://doi.org/10.1021/cbmi.4c00021","url":null,"abstract":"<p >In the realm of nanomaterials, atomically precise quasi-molecular gold nanoclusters (AuNCs) play a prime role due to their unique, stable, and highly tunable optical properties. They are extensively structure-engineered for modulation of surface electronic states toward long wavelength photoluminescence, particularly in the NIR-II (1000 to 1700 nm) window. Contrast agents with NIR-II emission can potentially transform optical imaging in terms of higher spatial resolution, deeper tissue penetration, and reduced tissue autofluorescence. These advantages allow real-time imaging in living organisms for observing disease progression and treatment response. In this short review, we discuss origin of NIR-II emission in rationally designed AuNCs and their application toward high resolution imaging of vasculatures and hard and soft tissue structures for identification of pathological conditions such as stroke and injury. Further, recent employment of these AuNCs in the rapidly growing field of tumor theranostics is also summarized. Final remarks are provided on the scope for improvement in their optical properties and persisting challenges for clinical translation.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 7","pages":"462–480 462–480"},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141959070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nischal Sharma, Antoine M. van Oijen, Lisanne M. Spenkelink* and Stefan H. Mueller*,
{"title":"Insight into Single-Molecule Imaging Techniques for the Study of Prokaryotic Genome Maintenance","authors":"Nischal Sharma, Antoine M. van Oijen, Lisanne M. Spenkelink* and Stefan H. Mueller*, ","doi":"10.1021/cbmi.4c0003710.1021/cbmi.4c00037","DOIUrl":"https://doi.org/10.1021/cbmi.4c00037https://doi.org/10.1021/cbmi.4c00037","url":null,"abstract":"<p >Genome maintenance comprises a group of complex and interrelated processes crucial for preserving and safeguarding genetic information within all organisms. Key aspects of genome maintenance involve DNA replication, transcription, recombination, and repair. Improper regulation of these processes could cause genetic changes, potentially leading to antibiotic resistance in bacterial populations. Due to the complexity of these processes, ensemble averaging studies may not provide the level of detail required to capture the full spectrum of molecular behaviors and dynamics of each individual biomolecule. Therefore, researchers have increasingly turned to single-molecule approaches, as these techniques allow for the direct observation and manipulation of individual biomolecules, and offer a level of detail that is unattainable with traditional ensemble methods. In this review, we provide an overview of recent in vitro and in vivo single-molecule imaging approaches employed to study the complex processes involved in prokaryotic genome maintenance. We will first highlight the principles of imaging techniques such as total internal reflection fluorescence microscopy and atomic force microscopy, primarily used for in vitro studies, and highly inclined and laminated optical sheet and super-resolution microscopy, mainly employed in in vivo studies. We then demonstrate how applying these single-molecule techniques has enabled the direct visualization of biological processes such as replication, transcription, DNA repair, and recombination in real time. Finally, we will showcase the results obtained from super-resolution microscopy approaches, which have provided unprecedented insights into the spatial organization of different biomolecules within bacterial organisms.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 9","pages":"595–614 595–614"},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}