Ali Erturk's research while affiliated with Ludwig-Maximilians-University of Munich and other places

Publications (16)

Preprint
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Deep convolutional neural networks have proven to be remarkably effective in semantic segmentation tasks. Most popular loss functions were introduced targeting improved volumetric scores, such as the Sorensen Dice coefficient. By design, DSC can tackle class imbalance; however, it does not recognize instance imbalance within a class. As a result, a...
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The meninges of the brain are an important component of neuroinflammatory response. Diverse immune cells move from the calvaria marrow into the dura mater via recently discovered skull-meninges connections (SMCs). However, how the calvaria bone marrow is different from the other bones and whether and how it contributes to human diseases remain unkn...
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Spatial molecular profiling of complex tissues is essential to investigate cellular function in physiological and pathological states. However, methods for molecular analysis of biological specimens imaged in 3D as a whole are lacking. Here, we present DISCO-MS, a technology combining whole-organ imaging, deep learning-based image analysis, and ult...
Article
Microscopic fluorescence imaging serves as a basic tool in many research areas including biology, medicine, and chemistry. With the help of optical clearing, large volume imaging of a mouse brain and even a whole body has been enabled. However, constrained by the physical principles of optical imaging, volume imaging has to balance imaging resoluti...
Preprint
Despite high metabolic activity, the retina and optic nerve head lack traditional lymphatic drainage. We here identified a novel ocular glymphatic clearance route for fluid and wastes via the proximal optic nerve. Amyloid-β (Aβ) was cleared from the vitreous via a pathway driven by the ocular-cranial pressure difference. After traversing the lamina...
Preprint
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Deep learning technology enables us acquire high resolution image from low resolution image in biological imaging free from sophisticated optical hardware. However, current methods require a huge number of the precisely registered low-resolution (LR) and high-resolution (HR) volume image pairs. This requirement is challengeable for biological volum...
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Optical tissue transparency permits cellular and molecular investigation of complex tissues in 3D, a fundamental need in biomedical sciences. Adult human organs are particularly challenging for this approach, owing to the accumulation of dense and sturdy molecules in decades-aged human tissues. Here, we introduce SHANEL method utilizing a new tissu...
Preprint
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Tissue clearing methods enable imaging of intact biological specimens without sectioning. However, reliable and scalable analysis of such large imaging data in 3D remains a challenge. Towards this goal, we developed a deep learning-based framework to quantify and analyze the brain vasculature, named Vessel Segmentation & Analysis Pipeline (VesSAP)....
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Reliable detection of disseminated tumor cells and of the biodistribution of tumor-targeting therapeutic antibodies within the entire body has long been needed to better understand and treat cancer metastasis. Here, we developed an integrated pipeline for automated quantification of cancer metastases and therapeutic antibody targeting, named DeepMA...
Article
In this photo essay, we present a sampling of technologies from laboratories at the forefront of whole-brain clearing and imaging for high-resolution analysis of cell populations and neuronal circuits. The data presented here were provided for the eponymous Mini-Symposium presented at the Society for Neuroscience's 2018 annual meeting.
Preprint
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Analysis of entire transparent rodent bodies could provide holistic information on biological systems in health and disease. However, it has been challenging to reliably image and quantify signal from endogenously expressed fluorescent proteins in large cleared mouse bodies due to the low signal contrast. Here, we devised a pressure driven, nanobod...
Article
Unlabelled: After traumatic brain injury (TBI), neurons surviving the initial insult can undergo chronic (secondary) degeneration via poorly understood mechanisms, resulting in long-term cognitive impairment. Although a neuroinflammatory response is promptly activated after TBI, it is unknown whether it has a significant role in chronic phases of...
Article
Full-text available
Neuroinflammation, the inflammatory response in the central nervous system (CNS), is a major determinant of neuronal function and survival during aging and disease progression. Microglia, as the resident tissue-macrophages of the brain, provide constant support to surrounding neurons in healthy brain. Upon any stress signal (such as trauma, ischemi...

Citations

... Although mainly demonstrated here for single-cell total proteome measurements, the sensitivity gain achieved in our workflow will be advantageous in any situation that is sample limited. This includes investigation of other compound classes such as metabolites or drugs, post-translational modifications from small numbers of cells or from in vivo material, and measurements directly from paraffinembedded formalin-fixed (FFPE) pathology specimens, which we are already pursuing (preprint: Bhatia et al, 2021;preprint: Mund et al, 2021). ...
... Regarding deep−learning-based analyses, several fluorescence imaging applications have been reported, including super resolution on microscopy images [15][16][17][18], conversion of standard hematoxylin and eosin stained histology images to UV light fluorescence images [19] and particle detection [20] on sub-cellular sized molecules and virus structures. Additionally, deep−learning in pathology images has been successfully applied in cancer research [21,22], leading to state-of-the-art tissue sample characterization. ...
... SPIM requires samples to be optically clear which is time-consuming and often introduces tissue distortion (Dodt et al., 2007;Renier et al., 2014;Jensen and Berg, 2017;Wan et al., 2018;Qi et al., 2019; Figure 3C). Clearing technology itself also limits the size of the sample as it is difficult to remove lipids/penetrate larger volumes such as those of non-human primates and human brains (Tainaka et al., 2018;Zhao et al., 2019;Ueda et al., 2020a; Figure 3C). Even if these brains could be cleared, it is challenging to create an objective lens with a long enough working distance to collect signals from the entire sample (Ueda et al., 2020a). ...
... MR vascular fingerprinting is a promising first attempt to reduce noise by simulating the MR signal in realistic tissue and finding a best match to the measured signal (Lemasson et al., 2016), which may soon enable vessel size sensitive imaging at similarly high resolution presented here while reducing impact of noise. In the future, automated machine-learning analyses of comprehensive histological and MR angiograms may help overcome the limitations of previous and the present work and yield further insights into neurovascular imaging correlates with the possibility of reliable clinical translation (Di Giovanna et al., 2018;Todorov et al., 2019). ...
... To segment dispersive fluorescent stem cells in whole mouse cryo-imaging, Patiwet Wuttisarnwattana et al. 32 employed an algorithm for detection of candidate stem cells using sombrero filtering and top-hat transform, followed by bagging decision tree classification of candidates. Chenchen Pan et al. 33 recently utilized deep learning to segment fluorescent breast cancer metastases in a whole mouse body with light sheet microscopy and tissue clearing. They chunked the large dataset into sub-volumes of 350 × 350 × 350 voxels at 10 × 10 × 10 µm resolution and used three 2D U-Net-like neural networks to segment the maximum intensity projection images along three axes. ...
... Via stochastic electrotransport (Kim et al., 2015), fluorescent antibodies can be driven efficiently into cleared rodent brains to label specific neural populations. Via lightsheet microscopy (Mano et al., 2018;Migliori et al., 2018;Chakraborty et al., 2019;Hillman et al., 2019), the cleared tissue can be sectioned optically, thus eliminating registration issues and the need for manual manipulation of delicate tissue sections. Segmentation and image-analysis software makes it possible to trace single axons throughout the labeled, cleared brain (Berger et al., 2018;Gao et al., 2019). ...
... A different set of organic solvents-DBE (dibenzyl ether) and/or THF (tetrahydrofuran) and dichloromethane (DCM)-were combined in 3D imaging of solvent-cleared organs (3DISCO) to better preserve the fluorescence of GFP during the clearing process (Becker et al., 2012Ert€ urk et al., 2012Ert€ urk et al., , 2014. Since then, various other hydrophobic tissue-clearing reagents with different attributes have been developed to support various applications, including ultimate DISCO (uDISCO) (Pan et al., 2016), immunolabeling-enabled DISCO (iDISCO) (Belle et al., 2014;Renier et al., 2014), iDISCO+ , FluoClearBABB (Schwarz et al., 2015), ethyl cinnamate (ECi) (Klingberg et al., 2017), free-of-acrylamide SDS-based tissue clearing (FASTClear) (Perbellini et al., 2017), polyethylene glycol (PEG)associated solvent system (PEGASOS) (Jing et al., 2018), variable domain of heavy chain antibodies (nanobodies) DISCO (vDISCO) (Cai et al., 2018), multiscale architectonic staining of human cortex (MASH) (Hildebrand et al., 2018), and stabilized DISCO (sDISCO) (Hahn et al., 2019). ...
... WT mice, however, presented plastic changes of synaptic contacts following mTBI [42] (i.e., a decrease in the length and volume of the PSDs), which recovered at later time points (Figure 2). Importantly, we observed in WT mice that the loss of dendritic spines, excitatory synapses and PSD structures was found on the ipsilateral and contralateral side of the injury, indicating that the TBI effects are not restricted to the lesion site [43,44]. ...
... Tissue clearing techniques achieve transparency via the removal of lipids and/or increasing the refractive index of the sample. Tissue clearing techniques that effectively reduce light scattering [1,2] include aqueous-based methods such as CLARITY [3,4], CUBIC [5][6][7], TDE [8], SeeDB [9], Scale [10] and MYOCLEAR [11] and organic solvent based-clearing such as BABB [12], DISCO [13,14] and PEGASOS [15]. Combined with LSFM, an unobstructed view of a whole intact tissue can be obtained [16]. ...
... It has also been identified the significantly upregulated expression of HMGB1 in the serum and cerebral cortex of chronic unpredictable mild stress (CUMS)-induced depression model (26). HMGB1 has been considered to be the mediator to initiate the microglia sensitization and activation of proinflammatory cytokines (20,27,28). ...