Evaluation of a marker-less, intra-operative, augmented reality guidance system for robot-assisted laparoscopic radical prostatectomy.

PURPOSE: Robot-assisted laparoscopic radical prostatectomy (RALRP) using the da Vinci surgical robot is a common treatment for organ-confined prostate cancer. Augmented reality (AR) can help during RALRP by showing the surgeon the location of anatomical structures and tumors from preoperative imaging. Previously, we proposed hand-eye and camera intrinsic matrix estimation procedures that can be carried out with conventional instruments within the patient during surgery, take < 3 min to perform, and fit seamlessly in the existing surgical workflow. In this paper, we describe and evaluate a complete AR guidance system for RALRP and quantify its accuracy. METHODS: Our AR system requires three transformations: the transrectal ultrasound (TRUS) to da Vinci transformation, the camera intrinsic matrix, and the hand-eye transformation. For evaluation, a 3D-printed cross-wire was visualized in TRUS and stereo endoscope in a water bath. Manually triangulated cross-wire points from stereo images were used as ground truth to evaluate overall TRE between these points and points transformed from TRUS to camera. RESULTS: After transforming the ground-truth points from the TRUS to the camera coordinate frame, the mean target registration error (TRE) (SD) was [Formula: see text] mm. The mean TREs (SD) in the x-, y-, and z-directions are [Formula: see text] mm, [Formula: see text] mm, and [Formula: see text] mm, respectively. CONCLUSIONS: We describe and evaluate a complete AR guidance system for RALRP which can augment preoperative data to endoscope camera image, after a deformable magnetic resonance image to TRUS registration step. The streamlined procedures with current surgical workflow and low TRE demonstrate the compatibility and readiness of the system for clinical translation. A detailed sensitivity study remains part of future work.

A partial augmented reality system with live ultrasound and registered preoperative MRI for guiding robot-assisted radical prostatectomy.

We propose an image guidance system for robot assisted laparoscopic radical prostatectomy (RALRP). A virtual 3D reconstruction of the surgery scene is displayed underneath the endoscope's feed on the surgeon's console. This scene consists of an annotated preoperative Magnetic Resonance Image (MRI) registered to intraoperative 3D Trans-rectal Ultrasound (TRUS) as well as real-time sagittal 2D TRUS images of the prostate, 3D models of the prostate, the surgical instrument and the TRUS transducer. We display these components with accurate real-time coordinates with respect to the robot system. Since the scene is rendered from the viewpoint of the endoscope, given correct parameters of the camera, an augmented scene can be overlaid on the video output. The surgeon can rotate the ultrasound transducer and determine the position of the projected axial plane in the MRI using one of the registered da Vinci instruments. This system was tested in the laboratory on custom-made agar prostate phantoms. We achieved an average total registration accuracy of 3.2 â€¯±â€¯ 1.3 mm. We also report on the successful application of this system in the operating room in 12 patients. The average registration error between the TRUS and the da Vinci system for the last 8 patients was 1.4 â€¯±â€¯ 0.3 mm and average target registration error of 2.1 â€¯±â€¯ 0.8 mm, resulting in an in vivo overall robot system to MRI mean registration error of 3.5 mm or less, which is consistent with our laboratory studies.

On the feasibility of transperineal 3D ultrasound image guidance for robotic radical prostatectomy.

PURPOSE: Prostate cancer is the most prevalent form of male-specific cancers. Robot-assisted laparoscopic radical prostatectomy (RALRP) using the da Vinci surgical robot has become the gold-standard treatment for organ-confined prostate cancer. To improve intraoperative visualization of anatomical structures, many groups have developed techniques integrating transrectal ultrasound (TRUS) into the surgical workflow. TRUS, however, is intrusive and does not provide real-time volumetric imaging. METHODS: We propose a proof-of-concept system offering an alternative noninvasive transperineal view of the prostate and surrounding structures using 3D ultrasound (US), allowing for full-volume imaging in any anatomical plane desired. The system aims to automatically track da Vinci surgical instruments and display a real-time US image registered to preoperative MRI. We evaluate the approach using a custom prostate phantom, an iU22 (Philips Healthcare, Bothell, WA) US machine with an xMATRIX X6-1 transducer, and a custom probe fixture. A novel registration method between the da Vinci kinematic frame and 3D US is presented. To evaluate the entire registration pipeline, we use a previously developed MRI to US deformable registration algorithm. RESULTS: Our US calibration technique yielded a registration error of 0.84 mm, compared to 1.76 mm with existing methods. We evaluated overall system error with a prostate phantom, achieving a target registration error of 2.55 mm. CONCLUSION: Transperineal imaging using 3D US is a promising approach for image guidance during RALRP. Preliminary results suggest this system is comparable to existing guidance systems using TRUS. With further development and testing, we believe our system has the potential to improve patient outcomes by imaging anatomical structures and prostate cancer in real time.

Luminescent cyclometalated iridium(III) polypyridine indole complexes--synthesis, photophysics, electrochemistry, protein-binding properties, cytotoxicity, and cellular uptake.

A series of luminescent cyclometalated iridium(III) polypyridine indole complexes, [Ir(N--C)(2)(N--N)](PF(6)) (HN--C = 2-phenylpyridine (Hppy), N--N = 4-((2-(indol-3-yl)ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine (bpy-ind) (1a), N--N = 4-((5-((2-(indol-3-yl)ethyl)aminocarbonyl)pentyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine (bpy-C6-ind) (1b); HN--C = 7,8-benzoquinoline (Hbzq), N--N = bpy-ind (2a), N--N = bpy-C6-ind (2b); and HN--C = 2-phenylquinoline (Hpq), N--N = bpy-ind (3a), N--N = bpy-C6-ind (3b)), have been synthesized, characterized, and their photophysical and electrochemical properties and lipophilicity investigated. Photoexcitation of the complexes in fluid solutions at 298 K and in alcohol glass at 77 K resulted in intense and long-lived luminescence (lambda(em) = 540-616 nm, tau(o) = 0.13-5.15 mus). The emission of the complexes has been assigned to a triplet metal-to-ligand charge-transfer ((3)MLCT) (dpi(Ir) --> pi*(N--N)) excited state, probably with some mixing of triplet intraligand ((3)IL) (pi --> pi*) (pq) character for complexes 3a,b. Electrochemical measurements revealed that all the complexes showed an irreversible indole oxidation wave at ca. +1.1 V versus SCE, a quasi-reversible iridium(IV/III) couple at ca. +1.3 V, and a reversible diimine reduction couple at ca. -1.3 V. The interactions of these complexes with an indole-binding protein, bovine serum albumin (BSA), have been studied by emission titrations, and the K(a) values are on the order of 10(4) M(-1). Additionally, the cytotoxicity of the complexes toward human cervix epithelioid carcinoma (HeLa) cells has been examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The IC(50) values of the complexes ranged from 1.1 to 6.3 microM, which are significantly smaller than that of cisplatin (30.7 microM) under the same experimental conditions. Furthermore, the cellular uptake of the complexes has been investigated by flow cytometry and laser-scanning confocal microscopy. The microscopy images indicated that complex 3a was localized in the perinuclear region upon interiorization. Temperature-dependence experiments suggested that the internalization of the complex was an energy-requiring process such as endocytosis. This has been confirmed by cellular-uptake experiments involving the luminescent conjugates Ir-BSA and Ir-TF (TF = holo-transferrin), which were prepared by conjugation of the proteins with the complex [Ir(pq)(2)(phen-NCS)](PF(6)) (phen-NCS = 5-isothiocyanato-1,10-phenanthroline).

Utilization of the highly environment-sensitive emission properties of rhenium(I) amidodipyridoquinoxaline biotin complexes in the development of biological probes.

We report the synthesis and characterization of luminescent rhenium(I) amidodipyridoquinoxaline biotin complexes [Re(CO)3(dpqa)(L)](PF6) (dpqa = 2-(n-butylamido)dipyrido[3,2-f:2',3'-h]quinoxaline; L = 4-(biotinamidomethyl)pyridine (py-4-CH2-NH-biotin) (1), 3-(N-((2-biotinamido)ethyl)amido)pyridine (py-3-CO-NH-en-NH-biotin) (2), 4-(N-((6-biotinamido)hexanoyl)aminomethyl)pyridine (py-4-CH2-NH-cap-NH-biotin) (3)), and their biotin-free counterpart [Re(CO)3(dpqa)(py)](PF6) (py = pyridine (4)). Upon irradiation, these complexes exhibited intense triplet metal-to-ligand charge-transfer (3MLCT) (dpi(Re) --> pi(dpqa)) emission in fluid solutions at 298 K and in alcohol glass at 77 K. However, the emission became much weaker in aqueous buffer, probably due to the interactions of water molecules with the amide substituent of the dpqa ligand. These properties render the complexes good candidates as luminescent probes for hydrophobic media, such as the substrate-binding sites of proteins. The avidin-binding properties of the new biotin complexes have been studied by 4'-hydroxyazobenzene-2-carboxylic acid (HABA) assays, emission titrations, and competitive association and dissociation assays. Most importantly, the complexes showed a profound increase in emission intensities upon binding to avidin. Additionally, we found that the fluorescence of anthracene was quenched by these rhenium(I) complexes, and the 3MLCT emission of the complexes was also quenched by anthracene. On the basis of these findings, new homogeneous assays for biotin using these complexes, avidin, and anthracene-labeled avidin have been designed.

Synthesis, characterization, crystal structure, and electrochemical, photophysical, and protein-binding properties of luminescent rhenium(I) diimine indole complexes.

We report the synthesis, characterization, and photophysical and electrochemical properties of a series of luminescent rhenium(I) diimine indole complexes, [Re(N-N)(CO)3(L)](CF3SO3) (N-N = 3,4,7,8-tetramethyl-1,10-phenanthroline (Me4-phen), L = N-(3-pyridoyl)tryptamine (py-3-CONHC2H4-indole) (1a), N-[N-(3-pyridoyl)-6-aminohexanoyl]tryptamine, (py-3-CONHC5H10CONHC2H4-indole) (1b); N-N = 1,10-phenanthroline (phen), L = py-3-CONHC2H4-indole (2a), py-3-CONHC5H10CONHC2H4-indole (2b); N-N = 2,9-dimethyl-1,10-phenanthroline (Me2-phen), L = py-3-CONHC2H4-indole (3a), py-3-CONHC5H10CONHC2H4-indole (3b); N-N = 4,7-diphenyl-1,10-phenanthroline (Ph2-phen), L = py-3-CONHC2H4-indole (4a), py-3-CONHC5H10CONHC2H4-indole (4b)), and their indole-free counterparts, [Re(N-N)(CO)3(py-3-CONH-Et)](CF3SO3) (py-3-CONH-Et = N-ethyl-(3-pyridyl)formamide; N-N = Me4-phen (1c), phen (2c), Me2-phen (3c), Ph2-phen (4c)). The X-ray crystal structure of complex 3a has also been investigated. Upon irradiation, most of the complexes exhibited triplet metal-to-ligand charge-transfer (3MLCT) (d pi(Re) --> pi*(diimine)) emission in fluid solutions at 298 K and in low-temperature glass. However, the structural features and long emission lifetimes of the Me4-phen complexes in solutions at room temperature suggest that the excited state of these complexes exhibited substantial triplet intraligand (3IL) (pi --> pi*) (Me4-phen) character. The binding interactions of these complexes to indole-binding proteins including bovine serum albumin and tryptophanase have been examined.

Luminescent rhenium(I) diimine indole conjugates--photophysical, electrochemical and protein-binding properties.

Two novel luminescent rhenium(I) diimine indole complexes have been designed and their properties studied; these conjugates can be recognised by indole-binding proteins including bovine serum albumin, lysozyme and tryptophanase.

New luminescent cyclometalated iridium(III) diimine complexes as biological labeling reagents.

We report the synthesis, characterization, and photophysical and electrochemical properties of thirty luminescent cyclometalated iridium(III) diimine complexes [Ir(N-C)(2)(N-N)](PF(6)) (HN-C = 2-phenylpyridine, Hppy; 2-(4-methylphenyl)pyridine, Hmppy; 3-methyl-1-phenylpyrazole, Hmppz; 7,8-benzoquinoline, Hbzq; 2-phenylquinoline, Hpq; N-N = 4-amino-2,2'-bipyridine, bpy-NH(2); 4-isothiocyanato-2,2'-bipyridine, bpy-ITC; 4-iodoacetamido-2,2'-bipyridine, bpy-IAA; 5-amino-1,10-phenanthroline, phen-NH(2); 5-isothiocyanato-1,10-phenanthroline, phen-ITC; 5-iodoacetamido-1,10-phenanthroline, phen-IAA). The X-ray crystal structure of [Ir(mppz)(2)(bpy-NH(2))](PF(6)) has also been investigated. Upon irradiation, all the complexes display intense and long-lived luminescence under ambient conditions and in 77-K glass. On the basis of the photophysical and electrochemical data, the emission of most of these complexes is assigned to an excited state of predominantly triplet metal-to-ligand charge-transfer ((3)MLCT) (dpi(Ir) --> pi(N-N)) character. In some cases, triplet intraligand ((3)IL) (pi --> pi)(N-N or N-C(-)) excited states have also been identified. In view of the specific reactivity of the isothiocyanate and iodoacetamide moieties toward the primary amine and sulfhydryl groups, respectively, we have labeled various biological molecules with a selection of these luminescent iridium(III) complexes. The photophysical properties of the luminescent conjugates have been investigated. In addition, a heterogeneous assay for digoxin has also been designed on the basis of the recognition of biotinylated anti-digoxin by avidin labeled with one of the luminescent iridium(III) complexes.