High-Resolution Cranial Defect Reconstruction by Iterative, Low-Resolution, Point Cloud Completion Transformers

Each year thousands of people suffer from various types of cranial injuries and require personalized implants whose manual design is expensive and time-consuming. Therefore, an automatic, dedicated system to increase the availability of personalized cranial reconstruction is highly desirable. The problem of the automatic cranial defect reconstruction can be formulated as the shape completion task and solved using dedicated deep networks. Currently, the most common approach is to use the volumetric representation and apply deep networks dedicated to image segmentation. However, this approach has several limitations and does not scale well into high-resolution volumes, nor takes into account the data sparsity. In our work, we reformulate the problem into a point cloud completion task. We propose an iterative, transformer-based method to reconstruct the cranial defect at any resolution while also being fast and resource-efficient during training and inference. We compare the proposed methods to the state-of-the-art volumetric approaches and show superior performance in terms of GPU memory consumption while maintaining high-quality of the reconstructed defects

Deep learning-based framework for automatic cranial defect reconstruction and implant modeling

Background and Objective: This article presents a robust, fast, and fully automatic method for personalized cranial defect reconstruction and implant modeling. Methods: We propose a two-step deep learning-based method using a modified U-Net architecture to perform the defect reconstruction, and a dedicated iterative procedure to improve the implant geometry, followed by an automatic generation of models ready for 3-D printing. We propose a cross-case augmentation based on imperfect image registration combining cases from different datasets. Additional ablation studies compare different augmentation strategies and other state-of-the-art methods. Results: We evaluate the method on three datasets introduced during the AutoImplant 2021 challenge, organized jointly with the MICCAI conference. We perform the quantitative evaluation using the Dice and boundary Dice coefficients, and the Hausdorff distance. The Dice coefficient, boundary Dice coefficient, and the 95th percentile of Hausdorff distance averaged across all test sets, are 0.91, 0.94, and 1.53 mm respectively. We perform an additional qualitative evaluation by 3-D printing and visualization in mixed reality to confirm the implant’s usefulness. Conclusion: The article proposes a complete pipeline that enables one to create the cranial implant model ready for 3-D printing. The described method is a greatly extended version of the method that scored 1st place in all AutoImplant 2021 challenge tasks. We freely release the source code, which together with the open datasets, makes the results fully reproducible. The automatic reconstruction of cranial defects may enable manufacturing personalized implants in a significantly shorter time, possibly allowing one to perform the 3-D printing process directly during a given intervention. Moreover, we show the usability of the defect reconstruction in a mixed reality that may further reduce the surgery time

Trinucleotide mRNA Cap Analogue <i>N</i>6‑Benzylated at the Site of Posttranscriptional ^m6A_m Mark Facilitates mRNA Purification and Confers Superior Translational Properties In Vitro and In Vivo

Eukaryotic mRNAs undergo cotranscriptional 5′-end modification with a 7-methylguanosine cap. In higher eukaryotes, the cap carries additional methylations, such as m6Ama common epitranscriptomic mark unique to the mRNA 5′-end. This modification is regulated by the Pcif1 methyltransferase and the FTO demethylase, but its biological function is still unknown. Here, we designed and synthesized a trinucleotide FTO-resistant N6-benzyl analogue of the m6Am-cap–m7GpppBn6AmpG (termed AvantCap) and incorporated it into mRNA using T7 polymerase. mRNAs carrying Bn6Am showed several advantages over typical capped transcripts. The Bn6Am moiety was shown to act as a reversed-phase high-performance liquid chromatography (RP-HPLC) purification handle, allowing the separation of capped and uncapped RNA species, and to produce transcripts with lower dsRNA content than reference caps. In some cultured cells, Bn6Am mRNAs provided higher protein yields than mRNAs carrying Am or m6Am, although the effect was cell-line-dependent. m7GpppBn6AmpG-capped mRNAs encoding reporter proteins administered intravenously to mice provided up to 6-fold higher protein outputs than reference mRNAs, while mRNAs encoding tumor antigens showed superior activity in therapeutic settings as anticancer vaccines. The biochemical characterization suggests several phenomena potentially underlying the biological properties of AvantCap: (i) reduced propensity for unspecific interactions, (ii) involvement in alternative translation initiation, and (iii) subtle differences in mRNA impurity profiles or a combination of these effects. AvantCapped-mRNAs bearing the Bn6Am may pave the way for more potent mRNA-based vaccines and therapeutics and serve as molecular tools to unravel the role of m6Am in mRNA

Trinucleotide mRNA Cap Analogue <i>N</i>6‑Benzylated at the Site of Posttranscriptional ^m6A_m Mark Facilitates mRNA Purification and Confers Superior Translational Properties In Vitro and In Vivo

Eukaryotic mRNAs undergo cotranscriptional 5′-end modification with a 7-methylguanosine cap. In higher eukaryotes, the cap carries additional methylations, such as m6Ama common epitranscriptomic mark unique to the mRNA 5′-end. This modification is regulated by the Pcif1 methyltransferase and the FTO demethylase, but its biological function is still unknown. Here, we designed and synthesized a trinucleotide FTO-resistant N6-benzyl analogue of the m6Am-cap–m7GpppBn6AmpG (termed AvantCap) and incorporated it into mRNA using T7 polymerase. mRNAs carrying Bn6Am showed several advantages over typical capped transcripts. The Bn6Am moiety was shown to act as a reversed-phase high-performance liquid chromatography (RP-HPLC) purification handle, allowing the separation of capped and uncapped RNA species, and to produce transcripts with lower dsRNA content than reference caps. In some cultured cells, Bn6Am mRNAs provided higher protein yields than mRNAs carrying Am or m6Am, although the effect was cell-line-dependent. m7GpppBn6AmpG-capped mRNAs encoding reporter proteins administered intravenously to mice provided up to 6-fold higher protein outputs than reference mRNAs, while mRNAs encoding tumor antigens showed superior activity in therapeutic settings as anticancer vaccines. The biochemical characterization suggests several phenomena potentially underlying the biological properties of AvantCap: (i) reduced propensity for unspecific interactions, (ii) involvement in alternative translation initiation, and (iii) subtle differences in mRNA impurity profiles or a combination of these effects. AvantCapped-mRNAs bearing the Bn6Am may pave the way for more potent mRNA-based vaccines and therapeutics and serve as molecular tools to unravel the role of m6Am in mRNA

Trinucleotide mRNA Cap Analogue <i>N</i>6‑Benzylated at the Site of Posttranscriptional ^m6A_m Mark Facilitates mRNA Purification and Confers Superior Translational Properties In Vitro and In Vivo

Eukaryotic mRNAs undergo cotranscriptional 5′-end modification with a 7-methylguanosine cap. In higher eukaryotes, the cap carries additional methylations, such as m6Ama common epitranscriptomic mark unique to the mRNA 5′-end. This modification is regulated by the Pcif1 methyltransferase and the FTO demethylase, but its biological function is still unknown. Here, we designed and synthesized a trinucleotide FTO-resistant N6-benzyl analogue of the m6Am-cap–m7GpppBn6AmpG (termed AvantCap) and incorporated it into mRNA using T7 polymerase. mRNAs carrying Bn6Am showed several advantages over typical capped transcripts. The Bn6Am moiety was shown to act as a reversed-phase high-performance liquid chromatography (RP-HPLC) purification handle, allowing the separation of capped and uncapped RNA species, and to produce transcripts with lower dsRNA content than reference caps. In some cultured cells, Bn6Am mRNAs provided higher protein yields than mRNAs carrying Am or m6Am, although the effect was cell-line-dependent. m7GpppBn6AmpG-capped mRNAs encoding reporter proteins administered intravenously to mice provided up to 6-fold higher protein outputs than reference mRNAs, while mRNAs encoding tumor antigens showed superior activity in therapeutic settings as anticancer vaccines. The biochemical characterization suggests several phenomena potentially underlying the biological properties of AvantCap: (i) reduced propensity for unspecific interactions, (ii) involvement in alternative translation initiation, and (iii) subtle differences in mRNA impurity profiles or a combination of these effects. AvantCapped-mRNAs bearing the Bn6Am may pave the way for more potent mRNA-based vaccines and therapeutics and serve as molecular tools to unravel the role of m6Am in mRNA

The LHCb upgrade I

International audienceThe LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software

The LHCb upgrade I

International audienceThe LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software

The LHCb upgrade I

The LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software

The LHCb upgrade I

International audienceThe LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software

The LHCb upgrade I

International audienceThe LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software