Real-time intraoperative surgical guidance system in the da Vinci surgical robot based on transrectal ultrasound/photoacoustic imaging with photoacoustic markers: an ex vivo demonstration.

This paper introduces the first integrated real-time intraoperative surgical guidance system, in which an endoscope camera of da Vinci surgical robot and a transrectal ultrasound (TRUS) transducer are co-registered using photoacoustic markers that are detected in both fluorescence (FL) and photoacoustic (PA) imaging. The co-registered system enables the TRUS transducer to track the laser spot illuminated by a pulsed-laser-diode attached to the surgical instrument, providing both FL and PA images of the surgical region-of-interest (ROI). As a result, the generated photoacoustic marker is visualized and localized in the da Vinci endoscopic FL images, and the corresponding tracking can be conducted by rotating the TRUS transducer to display the PA image of the marker. A quantitative evaluation revealed that the average registration and tracking errors were 0.84 mm and 1.16°, respectively. This study shows that the co-registered photoacoustic marker tracking can be effectively deployed intraoperatively using TRUS+PA imaging providing functional guidance of the surgical ROI.

Hypophysitis Induced by Sintilimab in the Treatment of Bladder Cancer: A Case Report.

BACKGROUND: Immune checkpoint inhibitors (ICIs), as novel antitumor drugs, have been widely used in the clinic and have shown good antitumor effects. However, their widespread use has also led to the emergence of various immune-related adverse events (IrAEs). Hypophysitis is a rare but serious IrAE. Due to its complex and changeable clinical manifestations, hypophysitis may be easily overlooked, leading to delayed diagnosis and treatment. CASE PRESENTATION: A 68-year-old male patient was diagnosed with bladder cancer (T2bNXM0) in October 2021. He received two cycles of immunotherapy with sintilimab and chemotherapy with gemcitabine and cisplatin (GC). One month after the second treatment, he gradually developed recurrent fever, anorexia, drowsiness, and delirium. Laboratory examination revealed hyponatremia, decreased adrenocorticotropic hormone, and hypocortisolemia. The pituitary MRI showed no abnormality. The patient was diagnosed with immunotherapy-induced hypophysitis (IH) caused by sintilimab, leading to downstream endocrine disorders. With hormone replacement therapy, he was in a good mood, had a good appetite, and made an overall recovery. CONCLUSION: Immunotherapy-induced hypophysitis (IH) can result in a severe adrenal crisis, and prompt recognition and diagnosis are crucial. Clinicians must remain vigilant for the possibility of IH in patients who exhibit recurrent fever, anorexia, cognitive decline, and personality changes following ICI treatment. It is imperative to consider this diagnosis early to initiate appropriate management promptly.

A Flexible, High-Voltage (>100 V) Generating Device Based on Zebra-Like Asymmetrical Photovoltaic Cascade.

The mutual conversion between light and electricity lies at the heart of optoelectronic and photonic applications. Maximization of the photoelectric conversion is a long-term goal that can be pursued via the fabrication of devices with ad-hoc architectures. In this framework, it is of utter importance to harvest and transform light irradiation into high electric potential in specific area for driving functional dielectrics that respond to pure electric field. Here, a nano-fabrication technology has been devised featuring double self-alignment that is applied to construct zebra-like asymmetric heterojunction arrays. Such nanostructured composite, which covers a surface area of 5 × 4 mm2 and contains 500 periodic repeating units, is capable of photo generating voltages as high as 140 V on a flexible substrate. This approach represents a leap over the traditional functionalization process based on simply embedding materials into devices by demonstrating the disruptive potential of integrating oriented nanoscale device components into meta-material.

Wearable Mechatronic Ultrasound-integrated AR Navigation System for Lumbar Puncture Guidance.

As one of the most commonly performed spinal interventions in routine clinical practice, lumbar punctures are usually done with only hand palpation and trial-and-error. Failures can prolong procedure time and introduce complications such as cerebrospinal fluid leaks and headaches. Therefore, an effective needle insertion guidance method is desired. In this work, we present a complete lumbar puncture guidance system with the integration of (1) a wearable mechatronic ultrasound imaging device, (2) volume-reconstruction and bone surface estimation algorithms and (3) two alternative augmented reality user interfaces for needle guidance, including a HoloLens-based and a tablet-based solution. We conducted a quantitative evaluation of the end-to-end navigation accuracy, which shows that our system can achieve an overall needle navigation accuracy of 2.83 mm and 2.76 mm for the Tablet-based and the HoloLens-based solutions, respectively. In addition, we conducted a preliminary user study to qualitatively evaluate the effectiveness and ergonomics of our system on lumbar phantoms. The results show that users were able to successfully reach the target in an average of 1.12 and 1.14 needle insertion attempts for Tablet-based and HoloLens-based systems, respectively, exhibiting the potential to reduce the failure rates of lumbar puncture procedures with the proposed lumbar-puncture guidance.

AutoInFocus, a new paradigm for ultrasound-guided spine intervention: a multi-platform validation study.

PURPOSE: Ultrasound-guided spine interventions often suffer from the insufficient visualization of key anatomical structures due to the complex shapes of the self-shadowing vertebrae. Therefore, we propose an ultrasound imaging paradigm, AutoInFocus (automatic insonification optimization with controlled ultrasound), to improve the key structure visibility. METHODS: A phased-array probe is used in conjunction with a motion platform to image a controlled workspace, and the resulting images from multiple insonification angles are combined to reveal the target anatomy. This idea is first evaluated in simulation and then realized as a robotic platform and a miniaturized patch device. A spine phantom (CIRS) and its CT scan were used in the evaluation experiments to quantitatively and qualitatively analyze the advantages of the proposed method over the traditional approach. RESULTS: We showed in simulation that the proposed system setup increased the visibility of interspinous space boundary, a key feature for lumbar puncture guidance, from 44.13 to 67.73% on average, and the 3D spine surface coverage from 14.31 to 35.87%, compared to traditional imaging setup. We also demonstrated the feasibility of both robotic and patch-based realizations in a spine phantom study. CONCLUSION: This work lays the foundation for a new imaging paradigm that leverages redundant and controlled insonification to allow for imaging optimization of the complex vertebrae anatomy, making it possible for high-quality visualization of key anatomies during ultrasound-guided spine interventions.

Construction of Laterally Asymmetric Heterojunctions with Sub-Micrometer Resolution by Hierarchical Self-Assembly of Polythiophene Nanofibers.

Polymeric semiconductors are crucial candidates for the construction of next-generation flexible and printable electronic devices. By virtue of the successful preparation of monodispersed colloidal solution in orthogonal solvent, poly(3-hexylthiophene) (P3HT) nanofibers are developed into versatile building blocks for nanoelectronics and their compatibilities are verified with photolithographic lift-off technology. Then, the joint efforts from both the bottom-up hierarchical self-assembly and top-down self-alignment technology have led to the realization of lateral asymmetric heterojunctions with resolution better than 1 µm. As a result, planar photovoltaic devices incorporating N,N'-dioctyl-3,4,9,10-perylenedicarboximide and P3HT supramolecular nanowires as active components are constructed with the cathode-to-anode distance being tuned from ≈0.1 to 1-2 µm. Based on such a novel device configuration, an interesting phenomenon of channel-length-dependent photovoltaic efficiency is observed for the first time, strongly suggesting the impact of near-field light intensity on the performance of nanophotonic devices.

Wafer-Scale and Full-Coverage Two-Dimensional Molecular Monolayers Strained by Solvent Surface Tension Balance.

Inspired by the outstanding properties discovered in two-dimensional materials, the bottom-up generation of molecular monolayers is becoming again extremely popular as a route to develop novel functional materials and devices with tailored characteristics and minimal materials consumption. However, achieving a full-coverage over a large-area still represents a grand challenge. Here we report a molecular self-assembly protocol at the water surface in which the monolayers are strained by a novel solvent surface tension balance (SSTB) instead of a physical film balance as in the conventional Langmuir-Blodgett (LB) method. The obtained molecular monolayers can be transferred onto any arbitrary substrate including rigid inorganic oxides and metals, as well as flexible polymeric dielectrics. As a proof-of-concept, their application as ideal modification layers of a dielectric support for high-performance organic field-effect transistors (OFETs) has been demonstrated. The field-effect mobilities of both p- and n-type semiconductors displayed dramatic improvements of 1-3 orders of magnitude on SSTB-derived molecular monolayer, reaching values as high as 6.16 cm2 V-1 s-1 and 0.68 cm2 V-1 s-1 for pentacene and PTCDI-C8, respectively. This methodology for the fabrication of wafer-scale and defect-free molecular monolayers holds potential toward the emergence of a new generation of high-performance electronics based on two-dimensional materials.

Kalman filter-based EM-optical sensor fusion for needle deflection estimation.

PURPOSE: In many clinical procedures such as cryoablation that involves needle insertion, accurate placement of the needle's tip at the desired target is the major issue for optimizing the treatment and minimizing damage to the neighboring anatomy. However, due to the interaction force between the needle and tissue, considerable error in intraoperative tracking of the needle tip can be observed as needle deflects. METHODS: In this paper, measurements data from an optical sensor at the needle base and a magnetic resonance (MR) gradient field-driven electromagnetic (EM) sensor placed 10 cm from the needle tip are used within a model-integrated Kalman filter-based sensor fusion scheme. Bending model-based estimations and EM-based direct estimation are used as the measurement vectors in the Kalman filter, thus establishing an online estimation approach. RESULTS: Static tip bending experiments show that the fusion method can reduce the mean error of the tip position estimation from 29.23 mm of the optical sensor-based approach to 3.15 mm of the fusion-based approach and from 39.96 to 6.90 mm, at the MRI isocenter and the MRI entrance, respectively. CONCLUSION: This work established a novel sensor fusion scheme that incorporates model information, which enables real-time tracking of needle deflection with MRI compatibility, in a free-hand operating setup.

Real-time probe tracking using EM-optical sensor for MRI-guided cryoablation.

BACKGROUND: A method of real-time, accurate probe tracking at the entrance of the MRI bore is developed, which, fused with pre-procedural MR images, will enable clinicians to perform cryoablation efficiently in a large workspace with image guidance. METHODS: Electromagnetic (EM) tracking coupled with optical tracking is used to track the probe. EM tracking is achieved with an MRI-safe EM sensor working under the scanner's magnetic field to compensate the line-of-sight issue of optical tracking. Unscented Kalman filter-based probe tracking is developed to smooth the EM sensor measurements when occlusion occurs and to improve the tracking accuracy by fusing the measurements of two sensors. RESULTS: Experiments with a spine phantom show that the mean targeting errors using the EM sensor alone and using the proposed method are 2.21 mm and 1.80 mm, respectively. CONCLUSION: The proposed method achieves more accurate probe tracking than using an EM sensor alone at the MRI scanner entrance.

Accommodative responses under different stimulus conditions.

PURPOSE: The method and the sequence of accommodative stimuli are two factors affecting the steady-state accommodative response. This study investigated the possible effects of these two factors on the accommodative stimulus response curves (ASRCs) and compared three indexes to evaluate ASRC in the different stimulus conditions. METHODS: In this study, we investigated the difference in the accommodative stimulus response curves under six stimulus conditions. The ASRCs of 10 emmetropes were measured when the accommodative stimulus (AS) was induced using three methods: negative lenses, positive lenses, and a Badal stimulator; and the stimulus was presented using two sequences: ascending and descending sequences. Three indexes, accommodative error area (AEA), accommodative error index (AEI), and the slope of ASRC, were used for comparison. RESULTS: The accommodative error was larger when accommodative stimulus was presented in the ascending sequence than in the descending sequence (p < 0.05) in the Badal stimulator method whenever AEI, AEA, or the slope of ASRC was used. The ASRCs elicited with positive lenses were more accurate than that elicited with negative lenses or the Badal stimulator when AEA and AEI were used. However, when the slope of the ASRC was used, the result was not significant. CONCLUSIONS: The results suggest that the accommodative response in the steady state may be affected by the method used for inducing AS and the sequence of AS presented. The AEA is suggested to be used in the evaluation of the accuracy of the ASRC in future studies.

BDNF and NT-3 expression by using glucocorticoid-induced bicistronic expression vector pGC-BDNF-IRES-NT3 protects apoptotic cells in a cellular injury model.

Spinal cord injury (SCI) is a severe traumatic disease in the central nervous system with high incidence and high morbidity. Recent study demonstrated that cell transplantation therapy may improve local microenvironment of the injury site and promote nerve regeneration to restore spinal cord functions. In this study, we constructed a glucocorticoid-induced bicistronic eukaryotic expression vector pGC-BDNF-IRES-NT3 by using molecular cloning techniques and examined the protective effect of neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) expressed by this vector in a rat spinal cord injury (SCI) model. We first connected glucocorticoid response element (GRE) to cytomegalovirus (CMV) promoter and then the GRE-CMV gene was inserted into pEGFP-1 vector to construct the eukaryotic expression vector pGC-EGFP. Western blot analysis was used to confirm the expression of EGFP by transfecting this vector in RN-DSC cells. The IRES was used to connect BDNF gene and NT-3 gene and replaced the EGFP gene in pGC-EGFP plasmid to form the bicistronic expression vector-pGC-BDNF-IRES-NT3. After RN-DSC cells were transfected with the plasmid and treated with glucocorticoid, BDNF and NT-3 expression in the culture medium were measured by ELISA method. Finally, we found that combination therapy with the transfection of this vector and glucocorticoid had an anti-apoptotic effect in a cellular SCI model of RN-DSC cells. Therefore, the co-expression of BDNF and NT-3 by using this vector rescued the injured cells. This provided useful information for the gene-modification cell transplantation combined with glucocorticoid for the treatment of SCI.

A comparative study of the preventive effects of mitomycin C and chitosan on intraarticular adhesion after knee surgery in rabbits.

We sought to compare the preventive effects of mitomycin-C(MMC) and chitosan on intraarticular adhesion after knee surgery in rabbits. For this purpose, 48 New-Zealand rabbits were randomly and equally divided into MMC, chitosan, and control groups. Approximately 10 × 10 mm(2) of the cortical bone was removed from both sides of left femoral condyle and the cancellous bone underneath was exposed. The decorticated areas were topically treated with MMC and chitosan while control group was treated with physiological saline. The lower left limb was fixed in flexed position with Kirschner-wire for 4 weeks postoperatively. After 4 weeks, gross and histopathological examination, biochemical analysis, and fibroblast counts were performed on knee intraarticular adhesion in each group. The data show mild membrane-like fibrous intraarticular adhesion, presented in loose, in MMC group. There was moderate intraarticular adhesion in chitosan group while in controls; there was large-size compact fibrous tissue adhesion. Hydroxyproline contents and fibroblast quantity of MMC and chitosan groups were lower (P < 0.05) than that of control group. We, therefore, concluded that MMC and chitosan could prevent intraarticular adhesion of the knee in rabbits by inhibiting fibroblast proliferation and reducing collagenous fiber formation while MMC had a better preventive effect than that of chitosan.

The effects of spherical aberration on static accommodative responses in emmetropes and myopes.

PURPOSE: To compare the effects of spherical aberration (SA) on accommodative responses between emmetropes (EMs), stable myopes (SMs), and progressing myopes (PMs). METHODS: The accommodative responses (AR) induced by negative lenses from 0 to -5 D in 1 D steps were measured with a Complete Ophthalmic Analysis System (COAS) for 10 emmetropes (EMs), 13 stable myopes (SMs), and 9 progressing myopes (PMs). Three types of AR were calculated from wavefront aberration data based on ocular foci within a paraxial area, natural pupil area, and a 3.5 mm-diameter annular pupil area. The accommodative stimulus response curves (ASRCs) were compared between the three groups and between the three AR conditions. RESULTS: The difference in the slope of ASRC was significant between the three AR conditions (p < 0.0001) but it was not significant between the three refractive groups. In each group, the slope of ASRC for the accommodative response measured within the paraxial area of the pupil (paraxial AR) was significantly steeper than that measured for the natural pupil (total AR) and also for that estimated for the 3.5 mm-diameter annular pupil (p < 0.01). The difference in the y-intercept of ASRC between the three AR conditions was also significant (p = 0.02) but not between the three refractive groups. The y-intercept of ASRC for paraxial AR was more positive than that for total AR in SMs (p < 0.01) and in PMs (p < 0.05); the y-intercept of ASRC for the 3.5 mm peripheral AR was more positive than that for total AR in SMs (p < 0.05). CONCLUSIONS: The spherical aberration of the eye has a significant effect on the slope of ASRC and is less in PMs than in EMs and SMs.

The effect of mitomycin C in reducing intraarticular adhesion after knee surgery in rabbits.

Mitomycin C (MMC) is known to inhibit fibroblast proliferation through suppressing DNA dependent RNA synthesis. Based on this knowledge, we illustrated the effect of MMC on inhibiting fibroblast collagen synthesis and reducing intraarticular fibrous adhesion in a rabbit model. Forty-eight New Zealand white rabbits were randomly divided into four groups. Approximately 10 x 10 mm squares of the cortical bone was removed from both sides of the femoral condyle, and the underneath cancellous bone was exposed. MMC in various concentrations or saline were then applied to the decorticated areas. The intraarticular adhesions were evaluated after four weeks by macroscopic evaluation, histological evaluation and biochemical analysis of hydroxyproline content. The results demonstrated that MMC could suppress the formation of intraarticular fibrous adhesion in a dose-dependent manner. The intraarticular adhesion score, the hydroxyproline content and the fibroblast number in 0.1mg/ml MMC group were significantly less than those in 0.05 mg/ml MMC group, 0.01 mg/ml MMC group and control group. However, dense adhesions were found in 0.01 mg/ml MMC group and control group. These results indicated that topical application of 0.1mg/ml MMC could reduce intraarticular adhesion through inhibiting fibroblast proliferation in rabbits.

Objective depth-of-focus is different from subjective depth-of-focus and correlated with accommodative microfluctuations.

In this study, we investigated whether the objective depth-of-focus (DOF) is different from the subjective DOF and whether it correlates to accommodative microfluctuations (AMF). The objective DOF and subjective DOF at 1.5 D accommodative stimulus (AS) level were compared in the same group of subjects. The objective DOF and magnitude of AMF were measured at 5 AS levels from 0 D to 4 D. Results showed that there was a significant difference and no correlation between the objective DOF and the subjective DOF. The objective DOF was correlated to the magnitude of AMF. The results suggest that objective DOF and subjective DOF represent the blur sensitivity of two different systems. AMF are correlated with the blur sensitivity of the accommodative system.

Visual field does not affect steady-state accommodative response and near-work induced transient myopia.

To investigate whether or not peripheral retinal defocus contributes to the refractive development of myopia by influencing the overall accommodative function. The steady-state accommodative stimulus response curve (ASRC) and the near-work induced transient myopia (NITM) after a near visual task were compared between different visual field conditions in emmetropes (EMMs), stable myopes (SMs) and progressing myopes (PMs). Results showed that visual field had no effect on the ASRC and NITM but PMs exhibited greater NITM than EMMs and SMs. The results of this study suggest that peripheral defocus does not influence the overall accommodative system so its probable contribution to myopia development is not via the accommodative system.

Optimal dioptric value of near addition lenses intended to slow myopic progression.

PURPOSE: The purpose of this study was to determine the optimal power value of near addition lenses, which would create the least error in accommodative and vergence responses. METHODS: We evaluated accommodative response, phoria, and fixation disparity when the subject viewed through various addition lenses at three working distances for 30 young adults (11 emmetropic, 17 myopic, and 2 hyperopic). Accommodative response was determined with a Canon R-1 infrared optometer under binocular viewing conditions, phoria was determined by the alternating cover test with prism neutralization, and fixation disparity was measured with a Sheedy disparometer. RESULTS: We found that the optimal powers of near addition lenses for the young adult subjects associated with zero retinal defocus were +0.92 D, +1.04 D, and +1.28 D at three viewing distances, 50 cm, 40 cm, and 30 cm, respectively. The optimal powers associated with -3 prism diopters (Delta) near phoria were +0.58 D, +0.35 D, and +0.20 D at the three distances, 50 cm, 40 cm, and 30 cm, respectively. In addition, we found high correlations between the initial accommodative error and the optimal power of the near addition lenses and between the initial near phoria and the optimal power of the near addition lenses. CONCLUSIONS: The results suggest that when the effects of near addition lenses on the accommodative and vergence systems are both considered, the optimal dioptric power of the near addition lens is in a range between +0.20 D and +1.28 D for the three viewing distances. Using progressive lenses to delay the progression of myopia may have promising results if each subject's prescription is customized based on establishing a balance between the accommodative and vergence systems. Formulas derived from this study provide a basis for such considerations.

Changes in accommodative and vergence responses when viewing through near addition lenses.

It has been proposed that near addition lenses reduce the lag of accommodation and may slow myopia progression. In this study, we investigated the differences in accommodative response and near phoria in subjects with and without near addition lenses. Fourteen subjects (7 emmetropic and 7 myopic) participated in the study. Monocular and binocular accommodative responses to a target at 40 cm were measured with and without +2.00 diopter (D) lenses using a Canon R-1 optometer (Canon Europe N.V., Amsterdam, The Netherlands). Near dissociated phoria was measured using 3 testing methods: Maddox rod, cover test, and Von Graefe technique. The differences in accommodative response and near phoria between the 2 viewing conditions with and without the near addition lens were significant (P < 0.0001). No significant differences were revealed in accommodative response and near phoria between refractive error groups. The average accommodative responses of all subjects were 2.03 +/- 0.06 (SE) D (without +2.00 D lens) and 0.60 +/- 0.07 D (with +2.00 D lens) under monocular viewing conditions and 2.11 +/- 0.06 D (without +2.00 D lenses) and 0.77 +/- 0.07 D (with +2.00 D lenses) under binocular viewing conditions. The average near phorias of all subjects were -2.08 +/- 0.69 prism diopters (PD, without +2.00 D lenses) and -7.90 +/- 0.68 PD (with +2.00 D lenses). We discuss the effect of near addition lenses on the defocus of the retinal image, accommodative response, and near phoria. In addition, we propose that the observed difference between binocular and monocular accommodation, when viewing through near addition lenses, is caused by an increased vergence accommodation.

Myopic progression and dark focus variation in optometric students during the first academic year.

BACKGROUND: The aim of this research was to investigate the change in refractive error (RE) of optometric students during their first academic year and whether these changes relate to changes in their dark focus (DF). METHOD: The RE and DF of 64 students were measured objectively every three months during the first academic year, a total of four times, using a Canon R-1 infrared optometer. Thirty-five of the 64 students had an additional RE and DF measurement three weeks immediately after their Summer vacation. Students completed a survey regarding the near work demands they experienced during the Winter break and the teaching semesters. RESULTS: Over nine months, the average RE of the students changed significantly from -2.22 +/- 1.93 (SD) D to -2.50 +/- 2.05 D (p = 0.0002). The rate of myopic progression averaged -0.37 dioptres per year. Inclusion of measurements taken on 35 students immediately after the Summer vacation showed that their change in RE during the Summer vacation was not significant (p = 0.79). For these subjects, the DF measured immediately after the vacation was significantly lower than the DF measured before the vacation (p = 0.007). The reduction in the DF after the vacations corresponded to a period of relative myopic stability in these subjects. CONCLUSIONS: The results of this study suggest that optometric students performing extensive near work are at risk of developing myopia. The variation of their DF values indicates the changing demand for near work during different periods of the year. After Winter and Summer vacations, the DF was lower and the myopic progression was suspended. These findings further support the notion that myopic progression is related to high near work demands and suggest that this progression can be slowed by a period of reduced near work, for example, vacation periods.

The adaptive effect of narrowing the interocular separation on the AC/A ratio.

The purpose of this study was to determine whether the response AC/A ratio could be altered when the subject's interpupillary distance (IPD) was optically halved. We measured the changes in the AC/A ratio for 10 subjects after using the optical device for 30 min. Accommodative response was measured using a Canon R-1 optometer, and vergence response was measured with an ASL 210 Eye Movement Monitor. The average AC/A ratios were 1.20+/-0.35 (SD) (MA/D) and 0.84+/-0.39 (MA/D) before and after wearing the device, respectively. The decrease in AC/A ratio was statistically significant (p=0.01). This was mainly caused by a reduction in the slope of the accommodative vergence. The results of this study suggest that the AC/A ratio can be decreased if an IPD-narrowing device is used. A possible application of this mechanism in the study of myopia is discussed.