npj ImagingPub Date : 2024-12-04DOI: 10.1038/s44303-024-00055-x
Brice Wang, Tianle Ma, Theresa Chen, Trinh Nguyen, Ethan Crouse, Stephen J. Fleming, Alison S. Walker, Vera Valakh, Ralda Nehme, Evan W. Miller, Samouil L. Farhi, Mehrtash Babadi
{"title":"Robust self-supervised denoising of voltage imaging data using CellMincer","authors":"Brice Wang, Tianle Ma, Theresa Chen, Trinh Nguyen, Ethan Crouse, Stephen J. Fleming, Alison S. Walker, Vera Valakh, Ralda Nehme, Evan W. Miller, Samouil L. Farhi, Mehrtash Babadi","doi":"10.1038/s44303-024-00055-x","DOIUrl":"10.1038/s44303-024-00055-x","url":null,"abstract":"Voltage imaging is a powerful technique for studying neuronal activity, but its effectiveness is often constrained by low signal-to-noise ratios (SNR). Traditional denoising methods, such as matrix factorization, impose rigid assumptions about noise and signal structures, while existing deep learning approaches fail to fully capture the rapid dynamics and complex dependencies inherent in voltage imaging data. Here, we introduce CellMincer, a novel self-supervised deep learning method specifically developed for denoising voltage imaging datasets. CellMincer operates by masking and predicting sparse pixel sets across short temporal windows and conditions the denoiser on precomputed spatiotemporal auto-correlations to effectively model long-range dependencies without large temporal contexts. We developed and utilized a physics-based simulation framework to generate realistic synthetic datasets, enabling rigorous hyperparameter optimization and ablation studies. This approach highlighted the critical role of conditioning on spatiotemporal auto-correlations, resulting in an additional 3-fold SNR gain. Comprehensive benchmarking on both simulated and real datasets, including those validated with patch-clamp electrophysiology (EP), demonstrates CellMincer’s state-of-the-art performance, with substantial noise reduction across the frequency spectrum, enhanced subthreshold event detection, and high-fidelity recovery of EP signals. CellMincer consistently outperforms existing methods in SNR gain (0.5–2.9 dB) and reduces SNR variability by 17–55%. Incorporating CellMincer into standard workflows significantly improves neuronal segmentation, peak detection, and functional phenotype identification, consistently surpassing current methods in both SNR gain and consistency.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-21"},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-024-00055-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789399","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}
npj ImagingPub Date : 2024-11-21DOI: 10.1038/s44303-024-00057-9
Siyang Cheng, Yuya Nakatani, Gabriella Gagliano, Nahima Saliba, Anna-Karin Gustavsson
{"title":"Light sheet illumination in single-molecule localization microscopy for imaging of cellular architectures and molecular dynamics","authors":"Siyang Cheng, Yuya Nakatani, Gabriella Gagliano, Nahima Saliba, Anna-Karin Gustavsson","doi":"10.1038/s44303-024-00057-9","DOIUrl":"10.1038/s44303-024-00057-9","url":null,"abstract":"Single-molecule localization microscopy has revealed cellular architectures and molecular dynamics beyond the diffraction limit of light. However, imaging thick samples presents challenges from increased fluorescence background. Light sheet illumination, which utilizes a plane of light for optical sectioning, is effective in reducing fluorescence background, photobleaching, and photodamage. Here, we present the principles of single-molecule localization microscopy and light sheet illumination, followed by an introduction to light sheet microscopy geometries and their imaging applications. Finally, we discuss light sheet illumination approaches for high- and super-resolution imaging of biological structures and dynamics.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-024-00057-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142679997","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}
npj ImagingPub Date : 2024-11-13DOI: 10.1038/s44303-024-00053-z
Yuriko Mori, Emil Novruzov, Dominik Schmitt, Jens Cardinale, Tadashi Watabe, Peter L. Choyke, Abass Alavi, Uwe Haberkorn, Frederik L. Giesel
{"title":"Clinical applications of fibroblast activation protein inhibitor positron emission tomography (FAPI-PET)","authors":"Yuriko Mori, Emil Novruzov, Dominik Schmitt, Jens Cardinale, Tadashi Watabe, Peter L. Choyke, Abass Alavi, Uwe Haberkorn, Frederik L. Giesel","doi":"10.1038/s44303-024-00053-z","DOIUrl":"10.1038/s44303-024-00053-z","url":null,"abstract":"The discovery of fibroblast activation protein inhibitor positron emission tomography (FAPI-PET) has paved the way for a new class of PET tracers that target the tumor microenvironment (TME) rather than the tumor itself. Although 18F-fluorodeoxyglucose (FDG) is the most common PET tracer used in clinical imaging of cancer, multiple studies have now shown that the family of FAP ligands commonly outperform FDG in detecting cancers, especially those known to have lower uptake on FDG-PET. Moreover, FAPI-PET will have applications in benign fibrotic or inflammatory conditions. Thus, even while new FAPI-PET tracers are in development and applications are yet to enter clinical guidelines, a significant body of literature has emerged on FAPI-PET, suggesting it will have important clinical roles. This article summarizes the current state of clinical FAPI-PET imaging as well as potential uses as a theranostic agent.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-21"},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-024-00053-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637014","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}
npj ImagingPub Date : 2024-11-06DOI: 10.1038/s44303-024-00052-0
Xiaoyi Zhu, Luca Menozzi, Soon-Woo Cho, Junjie Yao
{"title":"High speed innovations in photoacoustic microscopy","authors":"Xiaoyi Zhu, Luca Menozzi, Soon-Woo Cho, Junjie Yao","doi":"10.1038/s44303-024-00052-0","DOIUrl":"10.1038/s44303-024-00052-0","url":null,"abstract":"Photoacoustic microscopy (PAM) is a key implementation of photoacoustic imaging (PAI). PAM merges rich optical contrast with deep acoustic detection, allowing for broad biomedical research and diverse clinical applications. Recent advancements in PAM technology have dramatically improved its imaging speed, enabling real-time observation of dynamic biological processes in vivo and motion-sensitive targets in situ, such as brain activities and placental development. This review introduces the engineering principles of high-speed PAM, focusing on various excitation and detection methods, each presenting unique benefits and challenges. Driven by these technological innovations, high-speed PAM has expanded its applications across fundamental, preclinical, and clinical fields. We highlight these notable applications, discuss ongoing technical challenges, and outline future directions for the development of high-speed PAM.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-024-00052-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142588296","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}
npj ImagingPub Date : 2024-11-06DOI: 10.1038/s44303-024-00047-x
Denzel Fusco, Emmanouil Xypakis, Ylenia Gigante, Lorenza Mautone, Silvia Di Angelantonio, Giorgia Ponsi, Giancarlo Ruocco, Marco Leonetti
{"title":"Stochastically structured illumination microscopy scan less super resolution imaging","authors":"Denzel Fusco, Emmanouil Xypakis, Ylenia Gigante, Lorenza Mautone, Silvia Di Angelantonio, Giorgia Ponsi, Giancarlo Ruocco, Marco Leonetti","doi":"10.1038/s44303-024-00047-x","DOIUrl":"10.1038/s44303-024-00047-x","url":null,"abstract":"In super-resolution, a varying illumination image stack is required. This enriched dataset typically necessitates precise mechanical control and micron-scale optical alignment and repeatability. Here, we introduce a novel methodology for super-resolution microscopy called stochastically structured illumination microscopy (S2IM), which bypasses the need for illumination control exploiting instead the random, uncontrolled movement of the target object. We tested our methodology within the clinically relevant ophthalmoscopic setting, harnessing the inherent saccadic motion of the eye to induce stochastic displacement of the illumination pattern on the retina. We opted to avoid human subjects by utilizing a phantom eye model featuring a retina composed of human induced pluripotent stem cells (iPSC) retinal neurons and replicating the ocular saccadic movements by custom actuators. Our findings demonstrate that S2IM unlocks scan-less super-resolution with a resolution enhancement of 1.91, with promising prospects also beyond ophthalmoscopy applications such as active matter or atmospheric/astronomical observation.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-024-00047-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142588291","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}
npj ImagingPub Date : 2024-11-06DOI: 10.1038/s44303-024-00043-1
Segos Ioannis, Van Eeckhoven Jens, Greig Alan, Redd Michael, Thrasivoulou Christopher, Conradt Barbara
{"title":"Impact of photobleaching on quantitative, spatio-temporal, super-resolution imaging of mitochondria in live C. elegans larvae","authors":"Segos Ioannis, Van Eeckhoven Jens, Greig Alan, Redd Michael, Thrasivoulou Christopher, Conradt Barbara","doi":"10.1038/s44303-024-00043-1","DOIUrl":"10.1038/s44303-024-00043-1","url":null,"abstract":"Super-resolution (SR) 3D rendering allows superior quantitative analysis of intracellular structures but has largely been limited to fixed or ex vivo samples. Here we developed a method to perform SR live imaging of mitochondria during post-embryonic development of C. elegans larvae. Our workflow includes the drug-free mechanical immobilisation of animals using polystyrene nanobeads, which has previously not been used for in vivo SR imaging. Based on the alignment of moving objects and global threshold-based image segmentation, our method enables an efficient 3D reconstruction of individual mitochondria. We demonstrate for the first time that the frequency distribution of fluorescence intensities is not affected by photobleaching, and that global thresholding alone enables the quantitative comparison of mitochondria along timeseries. Our composite approach significantly improves the study of biological structures and processes in SR during C. elegans post-embryonic development. Furthermore, the discovery that image segmentation does not require any prior correction against photobleaching, a fundamental problem in fluorescence microscopy, will impact experimental strategies aimed at quantitatively studying the dynamics of organelles and other intracellular compartments in any biological system.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-024-00043-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142588277","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}
npj ImagingPub Date : 2024-11-06DOI: 10.1038/s44303-024-00051-1
Veronica Clavijo Jordan, André F. Martins, Erica Dao, Kalotina Geraki, Sara Chirayil, Xiaodong Wen, Pooyan Khalighinejad, Daniel Parrott, Xiaojing Wang, Patricia Gonzalez Pagan, Neil Rofsky, Michael Farquharson, A. Dean Sherry
{"title":"Impact of dietary zinc on stimulated zinc secretion MRI in the healthy and malignant mouse prostate","authors":"Veronica Clavijo Jordan, André F. Martins, Erica Dao, Kalotina Geraki, Sara Chirayil, Xiaodong Wen, Pooyan Khalighinejad, Daniel Parrott, Xiaojing Wang, Patricia Gonzalez Pagan, Neil Rofsky, Michael Farquharson, A. Dean Sherry","doi":"10.1038/s44303-024-00051-1","DOIUrl":"10.1038/s44303-024-00051-1","url":null,"abstract":"Previous studies have shown that the zinc-responsive MRI probe, GdL1, can distinguish healthy versus malignant prostate tissues based upon differences in zinc content and secretion. In this study, mice were fed chow containing low, normal, or high zinc content for 3 weeks before imaging glucose stimulated zinc secretion (GSZS) by MRI. The distribution of zinc in prostate tissue in these three groups was imaged by synchrotron radiation X-ray fluorescence (SR-XRF). A zinc deficiency caused systemic and organ-level dysregulation, weight loss, and altered zinc bioavailability. Zinc efflux from the prostate increased in parallel to dietary zinc in healthy mice but not in TRAMP mice, consistent with a lowered capacity to store dietary zinc in malignant cells. This differential zinc efflux suggests that a dietary supplement of zinc prior to a GSZS study may enhance image contrast between healthy and malignant prostate tissue, thereby improving the accuracy of prostate cancer detection in man.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-024-00051-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142588292","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}
npj ImagingPub Date : 2024-11-06DOI: 10.1038/s44303-024-00048-w
Luca Menozzi, Junjie Yao
{"title":"Deep tissue photoacoustic imaging with light and sound","authors":"Luca Menozzi, Junjie Yao","doi":"10.1038/s44303-024-00048-w","DOIUrl":"10.1038/s44303-024-00048-w","url":null,"abstract":"Photoacoustic computed tomography (PACT) can harvest diffusive photons to image the optical absorption contrast of molecules in a scattering medium, with ultrasonically-defined spatial resolution. PACT has been extensively used in preclinical research for imaging functional and molecular information in various animal models, with recent clinical translations. In this review, we aim to highlight the recent technical breakthroughs in PACT and the emerging preclinical and clinical applications in deep tissue imaging.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-024-00048-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142588265","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}
npj ImagingPub Date : 2024-10-07DOI: 10.1038/s44303-024-00046-y
Biqi Chen, Zi Yin, Billy Wai-Lung Ng, Dan Michelle Wang, Rocky S. Tuan, Ryoma Bise, Dai Fei Elmer Ker
{"title":"Label-free live cell recognition and tracking for biological discoveries and translational applications","authors":"Biqi Chen, Zi Yin, Billy Wai-Lung Ng, Dan Michelle Wang, Rocky S. Tuan, Ryoma Bise, Dai Fei Elmer Ker","doi":"10.1038/s44303-024-00046-y","DOIUrl":"10.1038/s44303-024-00046-y","url":null,"abstract":"Label-free, live cell recognition (i.e. instance segmentation) and tracking using computer vision-aided recognition can be a powerful tool that rapidly generates multi-modal readouts of cell populations at single cell resolution. However, this technology remains hindered by the lack of accurate, universal algorithms. This review presents related biological and computer vision concepts to bridge these disciplines, paving the way for broad applications in cell-based diagnostics, drug discovery, and biomanufacturing.","PeriodicalId":501709,"journal":{"name":"npj Imaging","volume":" ","pages":"1-26"},"PeriodicalIF":0.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44303-024-00046-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383541","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}