Live volumetric (4D) visualization and guidance of in vivo human ophthalmic surgery with intraoperative optical coherence tomography.

Minimally-invasive microsurgery has resulted in improved outcomes for patients. However, operating through a microscope limits depth perception and fixes the visual perspective, which result in a steep learning curve to achieve microsurgical proficiency. We introduce a surgical imaging system employing four-dimensional (live volumetric imaging through time) microscope-integrated optical coherence tomography (4D MIOCT) capable of imaging at up to 10 volumes per second to visualize human microsurgery. A custom stereoscopic heads-up display provides real-time interactive volumetric feedback to the surgeon. We report that 4D MIOCT enhanced suturing accuracy and control of instrument positioning in mock surgical trials involving 17 ophthalmic surgeons. Additionally, 4D MIOCT imaging was performed in 48 human eye surgeries and was demonstrated to successfully visualize the pathology of interest in concordance with preoperative diagnosis in 93% of retinal surgeries and the surgical site of interest in 100% of anterior segment surgeries. In vivo 4D MIOCT imaging revealed sub-surface pathologic structures and instrument-induced lesions that were invisible through the operating microscope during standard surgical maneuvers. In select cases, 4D MIOCT guidance was necessary to resolve such lesions and prevent post-operative complications. Our novel surgical visualization platform achieves surgeon-interactive 4D visualization of live surgery which could expand the surgeon's capabilities.

Characterization of genomic structure and polymorphisms in the human carbamyl phosphate synthetase I gene.

Human carbamyl phosphate synthetase I (CPSI) is an essential hepatic enzyme that initiates the urea cycle. Deficiency of this enzyme usually results in lethal hyperammonemia. CPSI is encoded by the CPSI gene located on chromosome 2q35. In the present study, we report the coding sequence and define the intron-exon structure of the human CPSI gene. These data are compared to the previously defined rat CPSI gene structure. This work was generated from direct sequence determination of human genomic DNA (35 introns) and comparison to public domain sequence of anonymous BACs (2 introns). The human CPSI gene spans >120kb of genomic DNA. CPSI has 38 exons and 37 introns, and all adhere to the consensus splicing sequences. Comparison of the human and rat CPSI genes reveals that the nucleotide sequences, amino acid sequences, and intron-exon organizations are highly similar. We report the primers and conditions for screening the human CPSI exonic and bordering intronic sequences. We also screened 100 individuals for polymorphisms in the human CPSI gene and identified 14 polymorphisms in the CPSI message. The knowledge of the CPSI gene structure and the 14 polymorphisms presented in this study will greatly facilitate future molecular studies involving the CPSI gene and the enzyme it encodes.