Pub Date : 2024-03-06DOI: 10.1038/s44303-023-00005-z
Okyaz Eminaga, Fred Saad, Zhe Tian, Ulrich Wolffgang, Pierre I. Karakiewicz, Véronique Ouellet, Feryel Azzi, Tilmann Spieker, Burkhard M. Helmke, Markus Graefen, Xiaoyi Jiang, Lei Xing, Jorn H. Witt, Dominique Trudel, Sami-Ramzi Leyh-Bannurah
Malignancy grading of prostate cancer (PCa) is fundamental for risk stratification, patient counseling, and treatment decision-making. Deep learning has shown potential to improve the expert consensus for tumor grading, which relies on the Gleason score/grade grouping. However, the core problem of interobserver variability for the Gleason grading system remains unresolved. We developed a novel grading system for PCa and utilized artificial intelligence (AI) and multi-institutional international datasets from 2647 PCa patients treated with radical prostatectomy with a long follow-up of ≥10 years for biochemical recurrence and cancer-specific death. Through survival analyses, we evaluated the novel grading system and showed that AI could develop a tumor grading system with four risk groups independent from and superior to the current five grade groups. Moreover, AI could develop a scoring system that reflects the risk of castration resistant PCa in men who have experienced biochemical recurrence. Thus, AI has the potential to develop an effective grading system for PCa interpretable by human experts.
{"title":"Artificial intelligence unravels interpretable malignancy grades of prostate cancer on histology images","authors":"Okyaz Eminaga, Fred Saad, Zhe Tian, Ulrich Wolffgang, Pierre I. Karakiewicz, Véronique Ouellet, Feryel Azzi, Tilmann Spieker, Burkhard M. Helmke, Markus Graefen, Xiaoyi Jiang, Lei Xing, Jorn H. Witt, Dominique Trudel, Sami-Ramzi Leyh-Bannurah","doi":"10.1038/s44303-023-00005-z","DOIUrl":"10.1038/s44303-023-00005-z","url":null,"abstract":"Malignancy grading of prostate cancer (PCa) is fundamental for risk stratification, patient counseling, and treatment decision-making. Deep learning has shown potential to improve the expert consensus for tumor grading, which relies on the Gleason score/grade grouping. However, the core problem of interobserver variability for the Gleason grading system remains unresolved. We developed a novel grading system for PCa and utilized artificial intelligence (AI) and multi-institutional international datasets from 2647 PCa patients treated with radical prostatectomy with a long follow-up of ≥10 years for biochemical recurrence and cancer-specific death. Through survival analyses, we evaluated the novel grading system and showed that AI could develop a tumor grading system with four risk groups independent from and superior to the current five grade groups. Moreover, AI could develop a scoring system that reflects the risk of castration resistant PCa in men who have experienced biochemical recurrence. Thus, AI has the potential to develop an effective grading system for PCa interpretable by human experts.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-023-00005-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140043207","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}
Pub Date : 2024-03-04DOI: 10.1038/s44303-024-00008-4
Raina M. Borum, Maurice Retout, Matthew N. Creyer, Yu-Ci Chang, Karlo Gregorio, Jesse V. Jokerst
We report noncovalent assemblies of iRGD peptides and methylene blue dyes via electrostatic and hydrophobic stacking. These resulting nanomaterials could bind to cancer cells, image them with photoacoustic signal, and then treat them via photodynamic therapy. We first assessed the optical properties and physical properties of the materials. We then evaluated their utility for live cell targeting, in vivo imaging, and in vivo photodynamic toxicity. We tuned the performance of iRGD by adding aspartic acid (DD) or tryptophan doublets (WW) to the peptide to promote electrostatic or hydrophobic stacking with methylene blue, respectively. The iRGD-DD led to 150-nm branched nanoparticles, but iRGD-WW produced 200-nm nano spheres. The branched particles had an absorbance peak that was redshifted to 720 nm suitable for photoacoustic signal. The nanospheres had a peak at 680 nm similar to monomeric methylene blue. Upon continuous irradiation, the nanospheres and branched nanoparticles led to a 116.62% and 94.82% increase in reactive oxygen species in SKOV-3 cells relative to free methylene blue at isomolar concentrations suggesting photodynamic toxicity. Targeted uptake was validated via competitive inhibition. Finally, we used in vivo bioluminescent signal to monitor tumor burden and the effect of for photodynamic therapy: The nanospheres had little impact versus controls (p = 0.089), but the branched nanoparticles slowed SKOV-3 tumor burden by 75.9% (p < 0.05).
{"title":"Self-assembled peptide-dye nanostructures for in vivo tumor imaging and photodynamic toxicity","authors":"Raina M. Borum, Maurice Retout, Matthew N. Creyer, Yu-Ci Chang, Karlo Gregorio, Jesse V. Jokerst","doi":"10.1038/s44303-024-00008-4","DOIUrl":"10.1038/s44303-024-00008-4","url":null,"abstract":"We report noncovalent assemblies of iRGD peptides and methylene blue dyes via electrostatic and hydrophobic stacking. These resulting nanomaterials could bind to cancer cells, image them with photoacoustic signal, and then treat them via photodynamic therapy. We first assessed the optical properties and physical properties of the materials. We then evaluated their utility for live cell targeting, in vivo imaging, and in vivo photodynamic toxicity. We tuned the performance of iRGD by adding aspartic acid (DD) or tryptophan doublets (WW) to the peptide to promote electrostatic or hydrophobic stacking with methylene blue, respectively. The iRGD-DD led to 150-nm branched nanoparticles, but iRGD-WW produced 200-nm nano spheres. The branched particles had an absorbance peak that was redshifted to 720 nm suitable for photoacoustic signal. The nanospheres had a peak at 680 nm similar to monomeric methylene blue. Upon continuous irradiation, the nanospheres and branched nanoparticles led to a 116.62% and 94.82% increase in reactive oxygen species in SKOV-3 cells relative to free methylene blue at isomolar concentrations suggesting photodynamic toxicity. Targeted uptake was validated via competitive inhibition. Finally, we used in vivo bioluminescent signal to monitor tumor burden and the effect of for photodynamic therapy: The nanospheres had little impact versus controls (p = 0.089), but the branched nanoparticles slowed SKOV-3 tumor burden by 75.9% (p < 0.05).","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-024-00008-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140024832","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}
Pub Date : 2024-03-01DOI: 10.1038/s44303-024-00010-w
Johanna Bischof, Georgina Fletcher, Paul Verkade, Claudia Kuntner, Julia Fernandez-Rodriguez, Linda Chaabane, Leor Ariel Rose, Andreas Walter, Michiel Vandenbosch, Marc A. M. J. van Zandvoort, Assaf Zaritsky, Antje Keppler, Maddy Parsons
Multimodal bioimaging is a broad term used to describe experimental workflows that employ two or more different imaging modalities. Such approaches have been in use across life science domains for several years but these remain relatively limited in scope, in part due to the complexity of undertaking these types of analysis. Expanding these workflows to encompass diverse, emerging technology holds potential to revolutionize our understanding of spatial biology. In this perspective we reflect on the instrument and workflows in current use, emerging areas to consider and our experience of the barriers to broader adoption and progress. We propose several enabling solutions across the different challenge areas, emerging opportunities for consideration and highlight some of the key community activities to help move the field forward.
{"title":"Multimodal bioimaging across disciplines and scales: challenges, opportunities and breaking down barriers","authors":"Johanna Bischof, Georgina Fletcher, Paul Verkade, Claudia Kuntner, Julia Fernandez-Rodriguez, Linda Chaabane, Leor Ariel Rose, Andreas Walter, Michiel Vandenbosch, Marc A. M. J. van Zandvoort, Assaf Zaritsky, Antje Keppler, Maddy Parsons","doi":"10.1038/s44303-024-00010-w","DOIUrl":"10.1038/s44303-024-00010-w","url":null,"abstract":"Multimodal bioimaging is a broad term used to describe experimental workflows that employ two or more different imaging modalities. Such approaches have been in use across life science domains for several years but these remain relatively limited in scope, in part due to the complexity of undertaking these types of analysis. Expanding these workflows to encompass diverse, emerging technology holds potential to revolutionize our understanding of spatial biology. In this perspective we reflect on the instrument and workflows in current use, emerging areas to consider and our experience of the barriers to broader adoption and progress. We propose several enabling solutions across the different challenge areas, emerging opportunities for consideration and highlight some of the key community activities to help move the field forward.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-024-00010-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140000826","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}
Pub Date : 2024-02-19DOI: 10.1038/s44303-024-00006-6
Alexander Czaja, Alice J. Jiang, Matt Zacchary Blanco, Olga E. Eremina, Cristina Zavaleta
Achieving complete tumor resection upon initial surgical intervention can lead to better patient outcomes by making adjuvant treatments more efficacious and reducing the strain of repeat surgeries. Complete tumor resection can be difficult to confirm intraoperatively. Methods like touch preparation (TP) have been inconsistent for detecting residual malignant cell populations, and fatty specimens like breast cancer lumpectomies are too fatty to process for rapid histology. We propose a novel workflow of immunostaining and topographic surface imaging of freshly excised tissue to ensure complete resection using highly sensitive and spectrally separable surface-enhanced Raman scattering nanoparticles (SERS NPs) as the targeted contrast agent. Biomarker-targeting SERS NPs are ideal contrast agents for this application because their sensitivity enables rapid detection, and their narrow bands enable extensive intra-pixel multiplexing. The adaptive focus capabilities of an advanced Raman instrument, combined with our rotational accessory device for exposing each surface of the stained specimen to the objective lens, enable topographic mapping of complete excised specimen surfaces. A USB-controlled accessory for a Raman microscope was designed and fabricated to enable programmatic and precise angular manipulation of specimens in concert with instrument stage motions during whole-surface imaging. Specimens are affixed to the accessory on an anti-slip, sterilizable rod, and the tissue surface exposed to the instrument is adjusted on demand using a programmed rotating stepper motor. We demonstrate this topographic imaging strategy on a variety of phantoms and preclinical tissue specimens. The results show detail and texture in specimen surface topography, orientation of findings and navigability across surfaces, and extensive SERS NP multiplexing and linear quantitation capabilities under this new Raman topography imaging method. We demonstrate successful surface mapping and recognition of all 26 of our distinct SERS NP types along with effective deconvolution and localization of randomly assigned NP mixtures. Increasing NP concentrations were also quantitatively assessed and showed a linear correlation with Raman signal with an R2 coefficient of determination of 0.97. Detailed surface renderings color-encoded by unmixed SERS NP abundances show a path forward for content-rich, interactive surgical margin assessment.
{"title":"A Raman topography imaging method toward assisting surgical tumor resection","authors":"Alexander Czaja, Alice J. Jiang, Matt Zacchary Blanco, Olga E. Eremina, Cristina Zavaleta","doi":"10.1038/s44303-024-00006-6","DOIUrl":"10.1038/s44303-024-00006-6","url":null,"abstract":"Achieving complete tumor resection upon initial surgical intervention can lead to better patient outcomes by making adjuvant treatments more efficacious and reducing the strain of repeat surgeries. Complete tumor resection can be difficult to confirm intraoperatively. Methods like touch preparation (TP) have been inconsistent for detecting residual malignant cell populations, and fatty specimens like breast cancer lumpectomies are too fatty to process for rapid histology. We propose a novel workflow of immunostaining and topographic surface imaging of freshly excised tissue to ensure complete resection using highly sensitive and spectrally separable surface-enhanced Raman scattering nanoparticles (SERS NPs) as the targeted contrast agent. Biomarker-targeting SERS NPs are ideal contrast agents for this application because their sensitivity enables rapid detection, and their narrow bands enable extensive intra-pixel multiplexing. The adaptive focus capabilities of an advanced Raman instrument, combined with our rotational accessory device for exposing each surface of the stained specimen to the objective lens, enable topographic mapping of complete excised specimen surfaces. A USB-controlled accessory for a Raman microscope was designed and fabricated to enable programmatic and precise angular manipulation of specimens in concert with instrument stage motions during whole-surface imaging. Specimens are affixed to the accessory on an anti-slip, sterilizable rod, and the tissue surface exposed to the instrument is adjusted on demand using a programmed rotating stepper motor. We demonstrate this topographic imaging strategy on a variety of phantoms and preclinical tissue specimens. The results show detail and texture in specimen surface topography, orientation of findings and navigability across surfaces, and extensive SERS NP multiplexing and linear quantitation capabilities under this new Raman topography imaging method. We demonstrate successful surface mapping and recognition of all 26 of our distinct SERS NP types along with effective deconvolution and localization of randomly assigned NP mixtures. Increasing NP concentrations were also quantitatively assessed and showed a linear correlation with Raman signal with an R2 coefficient of determination of 0.97. Detailed surface renderings color-encoded by unmixed SERS NP abundances show a path forward for content-rich, interactive surgical margin assessment.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-024-00006-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139901720","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}
Pub Date : 2024-02-19DOI: 10.1038/s44303-024-00007-5
Erin K. Zaluzec, Elizabeth Kenyon, Maximilian Volk, Hasaan Hayat, Katherine Powell, Alexander Loomis, Shatadru Chakravarty, Jeremy M. L. Hix, Josh Schipper, Chi Chang, Matti Kiupel, Ping Wang, Erik M. Shapiro, Lorenzo F. Sempere
There are limited options for primary prevention of breast cancer (BC). Experimental procedures to locally prevent BC have shown therapeutic efficacy in animal models. To determine the suitability of FDA-approved iodine-containing and various metal-containing (bismuth, gold, iodine, or tantalum) preclinical nanoparticle-based contrast agents for image-guided intraductal (ID) ablative treatment of BC in rodent models, we performed a prospective longitudinal study to determine the imaging performance, local retention and systemic clearance, safety profile, and compatibility with ablative solution of each contrast agent. At least six abdominal mammary glands (>3 female FVB/JN mice and/or Sprague-Dawley rats, 10–11 weeks of age) were intraductally injected with commercially available contrast agents (Omnipaque® 300, Fenestra® VC, MVivoTM Au, MVivoTM BIS) or in-house synthesized tantalum oxide (TaOx) nanoparticles. Contrast agents were administered at stock concentration or diluted in 70% ethanol (EtOH) and up to 1% ethyl cellulose (EC) as gelling agent to assess their compatibility with our image-guided ablative procedure. Mammary glands were serially imaged by microCT for up to 60 days after ID delivery. Imaging data were analyzed by radiologists and deep learning to measure in vivo signal disappearance of contrast agents. Mammary glands and major organs were ultimately collected for histopathological examination. TaOx-containing solutions provided best imaging performance for nitid visualization of ductal tree immediately after infusion, low outward diffusion (<1 day) and high homogeneity. Of all nanoparticles, TaOx had the highest local clearance rate (46% signal decay as stock and 36% as ablative solution 3 days after ID injection) and exhibited low toxicity. TaOx-containing ablative solution with 1% EC caused same percentage of epithelial cell death (88.62% ± 7.70% vs. 76.38% ± 9.99%, p value = 0.089) with similar minimal collateral damage (21.56 ± 5.28% vs. 21.50% ± 7.14%, p value = 0.98) in mouse and rat mammary glands, respectively. In conclusion, TaOx-nanoparticles are a suitable and versatile contrast agent for intraductal imaging and image-guided ablative procedures in rodent models of BC with translational potential to humans.
{"title":"Tantalum oxide nanoparticles as versatile and high-resolution X-ray contrast agent for intraductal image-guided ablative procedure in rodent models of breast cancer","authors":"Erin K. Zaluzec, Elizabeth Kenyon, Maximilian Volk, Hasaan Hayat, Katherine Powell, Alexander Loomis, Shatadru Chakravarty, Jeremy M. L. Hix, Josh Schipper, Chi Chang, Matti Kiupel, Ping Wang, Erik M. Shapiro, Lorenzo F. Sempere","doi":"10.1038/s44303-024-00007-5","DOIUrl":"10.1038/s44303-024-00007-5","url":null,"abstract":"There are limited options for primary prevention of breast cancer (BC). Experimental procedures to locally prevent BC have shown therapeutic efficacy in animal models. To determine the suitability of FDA-approved iodine-containing and various metal-containing (bismuth, gold, iodine, or tantalum) preclinical nanoparticle-based contrast agents for image-guided intraductal (ID) ablative treatment of BC in rodent models, we performed a prospective longitudinal study to determine the imaging performance, local retention and systemic clearance, safety profile, and compatibility with ablative solution of each contrast agent. At least six abdominal mammary glands (>3 female FVB/JN mice and/or Sprague-Dawley rats, 10–11 weeks of age) were intraductally injected with commercially available contrast agents (Omnipaque® 300, Fenestra® VC, MVivoTM Au, MVivoTM BIS) or in-house synthesized tantalum oxide (TaOx) nanoparticles. Contrast agents were administered at stock concentration or diluted in 70% ethanol (EtOH) and up to 1% ethyl cellulose (EC) as gelling agent to assess their compatibility with our image-guided ablative procedure. Mammary glands were serially imaged by microCT for up to 60 days after ID delivery. Imaging data were analyzed by radiologists and deep learning to measure in vivo signal disappearance of contrast agents. Mammary glands and major organs were ultimately collected for histopathological examination. TaOx-containing solutions provided best imaging performance for nitid visualization of ductal tree immediately after infusion, low outward diffusion (<1 day) and high homogeneity. Of all nanoparticles, TaOx had the highest local clearance rate (46% signal decay as stock and 36% as ablative solution 3 days after ID injection) and exhibited low toxicity. TaOx-containing ablative solution with 1% EC caused same percentage of epithelial cell death (88.62% ± 7.70% vs. 76.38% ± 9.99%, p value = 0.089) with similar minimal collateral damage (21.56 ± 5.28% vs. 21.50% ± 7.14%, p value = 0.98) in mouse and rat mammary glands, respectively. In conclusion, TaOx-nanoparticles are a suitable and versatile contrast agent for intraductal imaging and image-guided ablative procedures in rodent models of BC with translational potential to humans.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-024-00007-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139901723","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}
Pub Date : 2024-01-11DOI: 10.1038/s44303-023-00004-0
Kevin M. Brindle
The challenge in clinical oncology is to select the most appropriate treatment for an individual patient. Transcriptome and metabolite profiling have revealed that tumours can display metabolic subtypes with different therapeutic vulnerabilities1–4. Metabolic imaging has the potential to distinguish these subtypes and therefore those treatment(s) that should be most effective. Moreover, since changes in tumour metabolism can occur early during treatment, metabolic imaging can also be used subsequently to detect early evidence of treatment response. In this Perspective I briefly review and discuss the relative advantages and disadvantages of magnetic resonance imaging of tumour metabolism using hyperpolarized 13C- and 2H-labelled substrates.
{"title":"Imaging cancer metabolism using magnetic resonance","authors":"Kevin M. Brindle","doi":"10.1038/s44303-023-00004-0","DOIUrl":"10.1038/s44303-023-00004-0","url":null,"abstract":"The challenge in clinical oncology is to select the most appropriate treatment for an individual patient. Transcriptome and metabolite profiling have revealed that tumours can display metabolic subtypes with different therapeutic vulnerabilities1–4. Metabolic imaging has the potential to distinguish these subtypes and therefore those treatment(s) that should be most effective. Moreover, since changes in tumour metabolism can occur early during treatment, metabolic imaging can also be used subsequently to detect early evidence of treatment response. In this Perspective I briefly review and discuss the relative advantages and disadvantages of magnetic resonance imaging of tumour metabolism using hyperpolarized 13C- and 2H-labelled substrates.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-023-00004-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139419853","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}
Pub Date : 2023-12-06DOI: 10.1038/s44303-023-00003-1
Vito Ko, Marie C. Goess, Lukas Scheel-Platz, Tao Yuan, Andriy Chmyrov, Dominik Jüstel, Jürgen Ruland, Vasilis Ntziachristos, Selina J. Keppler, Miguel A. Pleitez
Conventional histology, as well as immunohistochemistry or immunofluorescence, enables the study of morphological and phenotypical changes during tissue inflammation with single-cell accuracy. However, although highly specific, such techniques require multiple time-consuming steps to apply exogenous labels, which might result in morphological deviations from native tissue structures. Unlike these techniques, mid-infrared (mid-IR) microspectroscopy is a label-free optical imaging method that retrieves endogenous biomolecular contrast without altering the native composition of the samples. Nevertheless, due to the strong optical absorption of water in biological tissues, conventional mid-IR microspectroscopy has been limited to dried thin (5–10 µm) tissue preparations and, thus, it also requires time-consuming steps—comparable to conventional imaging techniques. Here, as a step towards label-free analytical histology of unprocessed tissues, we applied mid-IR optoacoustic microscopy (MiROM) to retrieve intrinsic molecular contrast by vibrational excitation and, simultaneously, to overcome water-tissue opacity of conventional mid-IR imaging in thick (mm range) tissues. In this proof-of-concept study, we demonstrated application of MiROM for the fast, label-free, non-destructive assessment of the hallmarks of inflammation in excised white adipose tissue; i.e., formation of crown-like structures and changes in adipocyte morphology.
{"title":"Fast histological assessment of adipose tissue inflammation by label-free mid-infrared optoacoustic microscopy","authors":"Vito Ko, Marie C. Goess, Lukas Scheel-Platz, Tao Yuan, Andriy Chmyrov, Dominik Jüstel, Jürgen Ruland, Vasilis Ntziachristos, Selina J. Keppler, Miguel A. Pleitez","doi":"10.1038/s44303-023-00003-1","DOIUrl":"10.1038/s44303-023-00003-1","url":null,"abstract":"Conventional histology, as well as immunohistochemistry or immunofluorescence, enables the study of morphological and phenotypical changes during tissue inflammation with single-cell accuracy. However, although highly specific, such techniques require multiple time-consuming steps to apply exogenous labels, which might result in morphological deviations from native tissue structures. Unlike these techniques, mid-infrared (mid-IR) microspectroscopy is a label-free optical imaging method that retrieves endogenous biomolecular contrast without altering the native composition of the samples. Nevertheless, due to the strong optical absorption of water in biological tissues, conventional mid-IR microspectroscopy has been limited to dried thin (5–10 µm) tissue preparations and, thus, it also requires time-consuming steps—comparable to conventional imaging techniques. Here, as a step towards label-free analytical histology of unprocessed tissues, we applied mid-IR optoacoustic microscopy (MiROM) to retrieve intrinsic molecular contrast by vibrational excitation and, simultaneously, to overcome water-tissue opacity of conventional mid-IR imaging in thick (mm range) tissues. In this proof-of-concept study, we demonstrated application of MiROM for the fast, label-free, non-destructive assessment of the hallmarks of inflammation in excised white adipose tissue; i.e., formation of crown-like structures and changes in adipocyte morphology.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-023-00003-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138866984","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}
Pub Date : 2023-11-29DOI: 10.1038/s44303-023-00001-3
Lydia M. Smith, Hannah E. Greenwood, Will E. Tyrrell, Richard S. Edwards, Vittorio de Santis, Friedrich Baark, George Firth, Muhammet Tanc, Samantha Y. A. Terry, Anne Herrmann, Richard Southworth, Timothy H. Witney
Mouse models are invaluable tools for radiotracer development and validation. They are, however, expensive, low throughput, and are constrained by animal welfare considerations. Here, we assessed the chicken chorioallantoic membrane (CAM) as an alternative to mice for preclinical cancer imaging studies. NCI-H460 FLuc cells grown in Matrigel on the CAM formed vascularized tumors of reproducible size without compromising embryo viability. By designing a simple method for vessel cannulation it was possible to perform dynamic PET imaging in ovo, producing high tumor-to-background signal for both 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and (4S)-4-(3-18F-fluoropropyl)-L-glutamate (18F-FSPG). The pattern of 18F-FDG tumor uptake were similar in ovo and in vivo, although tumor-associated radioactivity was higher in the CAM-grown tumors over the 60 min imaging time course. Additionally, 18F-FSPG provided an early marker of both treatment response to external beam radiotherapy and target inhibition in ovo. Overall, the CAM provided a low-cost alternative to tumor xenograft mouse models which may broaden access to PET and SPECT imaging and have utility across multiple applications.
小鼠模型是放射性示踪剂开发和验证的宝贵工具。然而，小鼠模型价格昂贵、通量低，而且受到动物福利因素的限制。在这里，我们评估了鸡绒毛膜（CAM）作为小鼠临床前癌症成像研究的替代品。在CAM上的Matrigel中生长的NCI-H460 FLuc细胞形成了大小可重复的血管化肿瘤，而不会影响胚胎的存活率。通过设计一种简单的血管插管方法，可以在胚胎中进行动态 PET 成像，为 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) 和 (4S)-4-(3-18F-fluoropropyl)-L-glutamate (18F-FSPG) 产生较高的肿瘤-背景信号。18F-FDG的肿瘤摄取模式在体内和体外相似，但在60分钟的成像过程中，CAM生长的肿瘤中肿瘤相关放射性更高。此外，18F-FSPG 还是体外放疗反应和体内靶点抑制的早期标记物。总之，CAM 为肿瘤异种移植小鼠模型提供了一种低成本的替代方法，它可以拓宽 PET 和 SPECT 成像的应用范围，并在多种应用中发挥作用。
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Pub Date : 2023-11-28DOI: 10.1038/s44303-023-00002-2
Bo-Jui Chang, Douglas Shepherd, Reto Fiolka
Structured illumination microscopy (SIM) can double the spatial resolution of a fluorescence microscope and video rate live cell imaging in a two-dimensional format has been demonstrated. However, rapid implementations of 2D SIM typically only cover a narrow slice of the sample immediately at the coverslip, with most of the cellular volume out of reach. Here, we implement oblique plane structured illumination microscopy (OPSIM) in a projection format to rapidly image an entire cell in a 2D SIM framework. As no mechanical scanning of the sample or objective is involved, this technique has the potential for rapid projection imaging with doubled resolution. We characterize the spatial resolution with fluorescent nanospheres, compare projection and 3D imaging using OPSIM and image mitochondria and ER dynamics across an entire cell at up to 2.7 Hz. To our knowledge, this represents the fastest whole cell SIM imaging to date.
{"title":"Projective oblique plane structured illumination microscopy","authors":"Bo-Jui Chang, Douglas Shepherd, Reto Fiolka","doi":"10.1038/s44303-023-00002-2","DOIUrl":"10.1038/s44303-023-00002-2","url":null,"abstract":"Structured illumination microscopy (SIM) can double the spatial resolution of a fluorescence microscope and video rate live cell imaging in a two-dimensional format has been demonstrated. However, rapid implementations of 2D SIM typically only cover a narrow slice of the sample immediately at the coverslip, with most of the cellular volume out of reach. Here, we implement oblique plane structured illumination microscopy (OPSIM) in a projection format to rapidly image an entire cell in a 2D SIM framework. As no mechanical scanning of the sample or objective is involved, this technique has the potential for rapid projection imaging with doubled resolution. We characterize the spatial resolution with fluorescent nanospheres, compare projection and 3D imaging using OPSIM and image mitochondria and ER dynamics across an entire cell at up to 2.7 Hz. To our knowledge, this represents the fastest whole cell SIM imaging to date.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-023-00002-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138866983","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}
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