Deformable registration of lateral cephalogram and cone-beam computed tomography image.

PURPOSE: This study aimed to design and evaluate a novel method for the registration of 2D lateral cephalograms and 3D craniofacial cone-beam computed tomography (CBCT) images, providing patient-specific 3D structures from a 2D lateral cephalogram without additional radiation exposure. METHODS: We developed a cross-modal deformable registration model based on a deep convolutional neural network. Our approach took advantage of a low-dimensional deformation field encoding and an iterative feedback scheme to infer coarse-to-fine volumetric deformations. In particular, we constructed a statistical subspace of deformation fields and parameterized the nonlinear mapping function from an image pair, consisting of the target 2D lateral cephalogram and the reference volumetric CBCT, to a latent encoding of the deformation field. Instead of the one-shot registration by the learned mapping function, a feedback scheme was introduced to progressively update the reference volumetric image and to infer coarse-to-fine deformations fields, accounting for the shape variations of anatomical structures. A total of 220 clinically obtained CBCTs were used to train and validate the proposed model, among which 120 CBCTs were used to generate a training dataset with 24k paired synthetic lateral cephalograms and CBCTs. The proposed approach was evaluated on the deformable 2D-3D registration of clinically obtained lateral cephalograms and CBCTs from growing and adult orthodontic patients. RESULTS: Strong structural consistencies were observed between the deformed CBCT and the target lateral cephalogram in all criteria. The proposed method achieved state-of-the-art performances with the mean contour deviation of 0.41 ± 0.12 mm on the anterior cranial base, 0.48 ± 0.17 mm on the mandible, and 0.35 ± 0.08 mm on the maxilla, respectively. The mean surface mesh ranged from 0.78 to 0.97 mm on various craniofacial structures, and the LREs ranged from 0.83 to 1.24 mm on the growing datasets regarding 14 landmarks. The proposed iterative feedback scheme handled the structural details and improved the registration. The resultant deformed volumetric image was consistent with the target lateral cephalogram in both 2D projective planes and 3D volumetric space regarding the multicategory craniofacial structures. CONCLUSIONS: The results suggest that the deep learning-based 2D-3D registration model enables the deformable alignment of 2D lateral cephalograms and CBCTs and estimates patient-specific 3D craniofacial structures.

Investigation of the weak binding of a tetrahistidine-tagged peptide to quantum dots by using capillary electrophoresis with fluorescence detection.

Capillary electrophoresis with fluorescence detection was utilized to probe the self-assembly between cyanine group dye labeled tetrahistidine containing peptide and CdSe/ZnS quantum dots, inside the capillary. Quantum dots and cyanine group dye labeled tetrahistidine containing peptide were injected into the capillary one after the other and allowed to self-assemble. Their self-assembly resulted into a measurable Förster resonance energy transfer signal between quantum dots and cyanine group dye labeled tetrahistidine containing peptide. The Förster resonance energy transfer signal increased upon increasing the cyanine group dye labeled tetrahistidine containing peptide/quantum dot molar ratio and reached a plateau at the 32/1 molar ratio. Additionally, the Förster resonance energy transfer signal was also affected by the increment of the interval time of injection and the sampling time. Online ligand exchange experiments were used to assess, the potential of a monovalent ligand of imidazole and a hexavalent ligand peptide, to displace surface bound cyanine group dye labeled peptide ligands from the quantum dots surface. Under optimal conditions, a linear relationship between the integrated peak areas and hexavalent ligand peptide was obtained at a hexavalent ligand concentration range of 0-0.5 mM. Therefore, the present assay has the potential to be applied in the online ligands detection.

Simultaneous detection of assembly and disassembly of multivalent HA tag and anti-HA antibody in single in-capillary assay.

Herein, we have developed an in-capillary assay for simultaneous detection of the assembly and disassembly of the multivalent HA tag peptide and antibody. HA tag with hexahistidine at C terminus (YPYDVPDYAG4 H6 , termed YPYDH6 ) was conjugated with quantum dots (QDs) by metal-affinity force to form a multivalent HA tag (QD-YPYDH6 ). QD-YPYDH6 and monoclonal anti-HA antibody (anti-HA) were sequentially injected into the capillary. They were mixed and assembled inside the capillary. The reaction products were online discriminated and detected by fluorescence coupled capillary electrophoresis (CE-FL). For the in-capillary assay, the binding efficiency of the multivalent HA tag and antibody on was influenced by the molar ratio and injection time. Such novel assay could even give out the self-assembly kinetic constant of QDs and YPYDH6 as KD of 34.1 µM with n (binding cooperativeness) of 2.2 by Hill equation. More importantly, the simultaneous detection of the assembly and imidazole (Im) induced disassembly of the QD-YPYDH6 -anti-HA complex was achieved in a single in-capillary assay. Our study demonstrated a new method for the online detection of antigen-antibody interactions.

Simultaneous monitoring of quantum dots and their assembly and disassembly with PreScission protease using capillary electrophoresis with fluorescence detection.

A novel assay was developed for the simultaneous monitoring of quantum dots and their assembly and disassembly with PreScission protease using capillary electrophoresis with fluorescence detection. Quantum dots and PreScission protease were injected into a capillary sequentially, then mixed and assembled via a thioether bond upon coupling to glutathione S-transferase tag inside the capillary. The in-capillary assembly was influenced by the molar ratio and the time interval of injection. Furthermore, the simultaneous monitoring of quantum dots and their assembly with PreScission protease and glutathione induced disassembly was achieved by adjusting the sampling sequence and the time interval of injection. More importantly, the in-capillary assay could be also applied to the online detection of glutathione.

In-capillary detection of fast antibody-peptide binding using fluorescence coupled capillary electrophoresis.

Herein, we report a technique for detecting the fast binding of antibody-peptide inside a capillary. Anti-HA was mixed and interacted with FAM-labeled HA tag (FAM-E4 ) inside the capillary. Fluorescence coupled capillary electrophoresis (CE-FL) was employed to measure and record the binding process. The efficiency of the antibody-peptide binding on in-capillary assays was found to be affected by the molar ratio. Furthermore, the stability of anti-HA-FAM-E4 complex was investigated as well. The results indicated that E4 YPYDVPDYA (E4) or TAMRA-E4 YPYDVPDYA (TAMRA-E4) had the same binding priorities with anti-HA. The addition of excess E4 or TAMRA-E4 could lead to partial dissociation of the complex and take a two-step mechanism including dissociation and association. This method can be applied to detect a wide range of biomolecular interactions.