Long-term outcomes of endoscopic ultrasound-guided laser ablation for liver tumors in the caudate lobe: 5 years of experience.

OBJECTIVES: Liver tumor in the caudate lobe is challenging to treat, partly due to its deep location. Endoscopic ultrasound-guided laser ablation (EUS-LA) is a new attractive option for tumors in high-risk or difficult-to-reach locations. This prospective study investigated the long-term efficacy of EUS-LA for tumors in the caudate lobe, and factors that predict outcomes. METHODS: From June 2016 to July 2021, twenty consecutive patients (aged 56.95 ± 10.06 years) with 25 caudate lobe tumors (15.64 ± 6.37 mm) underwent EUS-LA. Treatment outcomes were assessed and predictive factors were calculated via univariate and multivariate analyses. RESULTS: Twenty-five tumors achieved complete ablation after the first or second session of EUS-LA. The treatment effectiveness was 100%. During a median follow up of 27 months (3-60), four tumors (16%) developed local tumor progression and 15 patients (75%) experienced intrahepatic distant recurrence. According to univariate and multivariate analyses, the significant prognostic factor of local tumor progression was tumor size >2 cm (p = 0.047). Significant prognostic factors of intrahepatic distant recurrence were: tumor number, alpha-fetoprotein level, and total bilirubin level (p = 0.020, 0.019, 0.010, respectively). No adverse events related to EUS-LA were observed. CONCLUSION: EUS-LA is a viable, safe, and effective treatment option for patients with liver tumor in the caudate lobe. Tumor size >2 cm increases the risk of post-procedural local tumor progression. Intrahepatic tumor number, and pretreatment alpha-fetoprotein level and total bilirubin level are associated with intrahepatic distant recurrence. REGISTRATION: Clinicaltrials.gov, ID: NCT02816944(June 29, 2016).

Fabrication error tolerant broadband mode converters and their working principles.

Computational inverse design techniques have shown potential to become reliable means for designing compact nanophotonic devices without compromising the performance. Much effort has been made to reduce the computation cost involved in the optimization process and obtain final designs that are robust to fabrication imperfections. In this work, we experimentally demonstrate TE0-TE1 and TE1-TE3 mode converters (MCs) on the silicon-on-insulator platform designed using the computationally efficient shape optimization method. These MCs have mode conversion efficiencies above 95%, and the insertion loss ranges from 0.3 dB to 1 dB over a wavelength span of 80 nm ranging from 1.5 µm to 1.58 µm. Maximum modal crosstalk found experimentally in the C-band is -19 dB. The conversion efficiency drops at most by 2.2% at 1.55 µm for 10 nm over/under etch, implying good robustness to dimensional variations. We present the mode conversion mechanism of these MCs by studying the simulated electromagnetic field patterns and validate with supportive data. We also demonstrate their performance in the time domain with a 28 Gbps OOK and a 20 GBaud PAM-4 payload transmissions, which supports their utility for high throughput data communications. The open eye diagrams exhibit Q-factors of 8 dB.

Efficient mode exchanger-based silicon photonic switch enabled by inverse design.

A novel and energy efficient mode insensitive switch building block is proposed and experimentally demonstrated on a silicon-on-insulator platform. Based on a Mach-Zehnder interferometer, the switch uses a relatively compact mode insensitive phase shifter which includes a mode exchanger. The novel structure realizes the exact same phase shift for all modes by exchanging the modes midway within the phase shifter. The design approach leads to reduced power consumption otherwise not possible. Switching the first two quasi transverse electric (TE) modes simultaneously consumes 25.6 mW of power, an approximately 30% reduction from previous reported demonstrations. The measured insertion loss is 3.1 dB on average with a worst-case crosstalk of -14.9 dB over a 40 nm optical bandwidth from 1530 nm to 1570 nm. The design methodology enables scalability up to four optical modes.

Athermal echelle grating and tunable echelle grating demultiplexers using a Mach-Zehnder interferometer launch structure.

We present a comparative experimental study of three silicon photonic echelle grating demultiplexers that are integrated with a Mach-Zehnder interferometer (MZI) launch structure. By appropriate choice of the MZI configuration, the temperature induced shift of the demultiplexer channel wavelengths can be suppressed (athermal) or enhanced (super-thermal) or be controlled by an on-chip micro-heater. The latter two configurations allow the channel wavelengths to be actively tuned using lower power than possible by temperature tuning a conventional echelle demultiplexer. In the athermal configuration, the measured channel spectral shift is reduced to less than 10 pm/°C, compared to the 83 pm/°C shift for an unmodified echelle device. In super-thermal operation an enhanced channel temperature tuning rate of 170 pm/°C is achieved. Finally, by modulating the MZI phase with an on-chip heater, the demultiplexer channels can be actively tuned to correct for ambient temperature fluctuations up to 20 °C, using a drive current of less than 20 mA.

Neutrophil membrane-coated nanoparticles for enhanced nanosecond pulsed electric field treatment of pancreatic cancer.

OBJECTIVE: Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. Poor prognosis and low survival rates have driven the development of novel therapeutic strategies. Nanosecond pulsed electric field has emerged as a novel, minimal invasive and non-thermal treatment for solid tumors. It is of great significance to study the combination therapy of nsPEF and other treatment strategies for pancreatic cancer. METHODS: We developed neutrophil membrane-wrapped liposomal nanoparticles loaded with gemcitabine (NE/Lip-GEM) and investigated their use as a complementary agent for nsPEF treatment. RESULTS: Our results showed that neutrophil-mediated delivery of liposomal-gemcitabine (NE/Lip-GEM) efficiently inhibited the growth of pancreatic tumors in mice whose has been treated with incomplete nsPEF ablation. CONCLUSIONS: The combination of nsPEF and NE/Lip-GEM may be a promising synergistic strategy for pancreatic cancer therapy.

Topological inverse design of nanophotonic devices with energy constraint.

In this paper, we introduce an energy constraint to improve topology-based inverse design. Current methods typically place the constraints solely on the device geometry and require many optimization iterations to converge to a manufacturable solution. In our approach the energy constraint directs the optimization process to solutions that best contain the optical field inside the waveguide core medium, leading to more robust designs with relatively larger minimum feature size. To validate our method, we optimize two components: a mode converter (MC) and a wavelength demultiplexer. In the MC, the energy constraint leads to nearly binarized structures without applying independent binarization stage. In the demultiplexer, it also reduces the appearance of small features. Furthermore, the proposed constraint improves the robustness to fabrication imperfections as shown in demultiplexer design. With energy constraint optimization, the corresponding spectrum shifts under ±10 nm dimensional variations are reduced by 17% to 30%. The proposed constraint is unique in simultaneously taking both geometry and electric field into account, opening the door to new ideas and insights to further improve the computationally intensive topology-based optimization process of nanophotonic devices.

Efficient Bloch mode calculation of periodic systems with arbitrary geometry and open boundary conditions in the complex wavevector domain.

We show how existing iterative methods can be used to efficiently and accurately calculate Bloch periodic solutions of Maxwell's equations in arbitrary geometries. This is carried out in the complex-wavevector domain using a commercial frequency-domain finite-element solver that is available to the general user. The method is capable of dealing with leaky Bloch mode solutions, and is extremely efficient even for 3D geometries with non-trivial material distributions. We perform independent finite-difference time-domain simulations of Maxwell's equations to confirm our results. This comparison demonstrates that the iterative mode finder is more accurate, since it provides the true solutions in the complex-wavevector domain and removes the need for additional signal processing and fitting. Due to its efficiency, generality and reliability, this technique is well suited for complex and novel design tasks in integrated photonics, and also for a wider range of photonics problems.

Fiber Fabry-Perot astrophotonic correlation spectroscopy for remote gas identification and radial velocity measurements.

We present a novel, to the best of our knowledge, remote gas detection and identification technique based on correlation spectroscopy with a piezoelectric tunable fiber-optic Fabry-Perot filter. We show that the spectral correlation amplitude between the filter transmission window and gas absorption features is related to the gas absorption optical depth, and that different gases can be distinguished from one another using their correlation signal phase. Using a previously captured telluric-corrected high-resolution near-infrared spectrum of Venus, we show that the radial velocity of Venus can be extracted from the phase of higher order harmonic lock-in signals. This correlation spectroscopy technique has applications in the detection and radial velocity determination of weak spectral features in astronomy and remote sensing. We experimentally demonstrate a remote CO2 detection system using a lock-in amplifier, fiber-optic Fabry-Perot filter, and single channel avalanche photodiode.

Spectrum-free integrated photonic remote molecular identification and sensing.

Absorption spectroscopy is widely used in sensing and astronomy to understand remote molecular compositions. However, dispersive techniques require multichannel detection, reducing detection sensitivity while increasing instrument cost when compared to spectrophotometric methods. We present a novel non-dispersive infrared molecular detection and identification scheme that performs spectral correlation optically using a specially tailored integrated silicon ring resonator. We show experimentally that the correlation amplitude is proportional to the number of overlapping ring resonances and gas lines, and that molecular specificity can be achieved from the phase of the correlation signal. This strategy can enable on-chip detection of extremely faint remote spectral signatures.

Photonic temperature and wavelength metrology by spectral pattern recognition.

Spectral pattern recognition is used to measure temperature and generate calibrated wavelength/frequency combs using a single silicon waveguide ring resonator. The ring generates two incommensurate interleaving TE and TM spectral combs that shift independently with temperature to create a spectral pattern that is unique at every temperature. Following an initial calibration, the ring temperature can be determined by recognizing the spectral resonance pattern, and as a consequence, the wavelength of every resonance is also known. Two methods of pattern-based temperature retrieval are presented. In the first method, the ring is locked to a previously determined temperature set-point defined by the coincidence of only two specific TE and TM cavity modes. Based on a prior calibration at the set-point, the ring temperature and hence all resonance wavelengths are then known and the resulting comb can be used as a wavelength calibration reference. In this configuration, all reference comb wavelengths have been reproduced within a 5 pm accuracy across an 80 nm range by using an on-chip micro-heater to tune the ring. For more general photonic thermometry, a spectral correlation algorithm is developed to recognize a resonance pattern across a 30 nm wide spectral window and thereby determine ring temperature continuously to 50 mK accuracy. The correlation method is extended to simultaneously determine temperature and to identify and correct for wavelength calibration errors in the interrogating light source. The temperature and comb wavelength accuracy is limited primarily by the linewidth of the ring resonances, with accuracy and resolution scaling with the ring quality factor.

Perfectly vertical surface grating couplers using subwavelength engineering for increased feature sizes.

We present perfectly vertical grating couplers for the 220 nm silicon-on-insulator platform incorporating subwavelength metamaterials to increase the minimum feature sizes and achieve broadband low back-reflection. Our study reveals that devices with high coupling efficiencies are distributed over a wide region of the design space with varied back-reflections, while still maintaining minimum feature sizes larger than 100 nm and even 130 nm. Using 3D-finite-difference time-domain simulations, we demonstrate devices with broadband low back-reflection of less than -20dB over more than 100 nm bandwidth centered around the C-band. Coupling efficiencies of 72% and 67% are achieved for minimum feature sizes of 106 nm and 130 nm, respectively. These gratings are also more fabrication tolerant compared to similar designs not using metamaterials.

Highly efficient optical antenna with small beam divergence in silicon waveguides.

Optical antennas are key components in optical phased arrays for light detection and ranging technology requiring long sensing range and high scanning resolution. To achieve a narrow beam width in the far-field region, antenna lengths of several millimeters or more are required. To date, such long antennas have been impossible to achieve in silicon waveguides because currently demonstrated technologies do not allow accurate control of grating strength. Here, we report on a new type of surface-emitting silicon waveguide with a dramatically increased antenna length of L=3.65mm. This is achieved by using a subwavelength metamaterial waveguide core evanescently coupled with radiative segments laterally separated from the core. This results in a far-field diffracted beam width of 0.025°, which is a record small beam divergence for a silicon photonics surface-emitting device. We also demonstrate that by using a design with L-shaped surface-emitting segments, the radiation efficiency of the antenna can be substantially increased compared to a conventional design, with an efficiency of 72% at the wavelength of 1550 nm.

Irreversible electroporation in patients with liver tumours: treated-area patterns with contrast-enhanced ultrasound.

BACKGROUND: Familiarity with post-IRE imaging interpretation is of considerable importance in determining ablation success and detecting recurrence. CEUS can be used to assess the tumour response and characteristics of the ablation zone. It is of clinical interest to describe the ultrasonographic findings of liver tumours after irreversible electroporation (IRE) percutaneous ablation. METHODS: A prospective study of 24 cases of malignant liver tumours (22 cases of primary liver tumours and 2 cases of liver metastases) treated by IRE ablation was conducted. Two inspectors evaluated the ablation zone in a consensus reading performed immediately, 1 day, and 1 month after IRE ablation. The gold standard method, magnetic resonance imaging (MRI), was used to evaluate the effectiveness of the treatment at 1 month. RESULTS: Immediately after IRE ablation and up to 1 month later, the ablation zones gradually changed from hypo-echogenicity to hyper-echogenicity on conventional ultrasound and showed non-enhancement on contrast-enhanced ultrasound (CEUS). One month after IRE ablation, CEUS and MRI results were highly consistent (κ = 0.78, p < 0.05). CONCLUSIONS: We conclude that CEUS may be an effective tool for assessing post-IRE ablation changes after 1 month. CEUS enables the depiction of tumour vascularity in real time and serves as an easy, repeatable method.

Empirical model for the temperature dependence of silicon refractive index from O to C band based on waveguide measurements.

An accurate model for the silicon refractive index including its temperature and wavelength dependence is critically important for many disciplines of science and technology. Currently, such a model for temperatures above 22°C in the optical communication bands is not available. The temperature dependence in the spectral response of integrated echelle grating filters made in silicon-on-insulator is solely determined by the optical properties of the slab waveguide, making it largely immune to dimensional uncertainties. This feature renders the echelle filters a reliable tool to evaluate the thermo-optic properties of silicon. Here we investigate the temperature dependence of silicon echelle filters for the wavelength range of both O and C bands, measured between 22°C to 80°C. We show that if a constant thermo-optic coefficient of silicon is assumed for each band, as is common in the literature, the predictions show an underestimate of up to 10% in the temperature-induced channel wavelength shift. We propose and assess a model of silicon refractive index that encompasses both the wavelength and temperature dependence of its thermo-optic coefficients. We start from literature data for bulk silicon and further refine the model using the echelle filter measurement results. This model is validated through accurate predictions of device channel wavelengths and their temperature dependence, including the quadratic term, over a wide wavelength and temperature range. This work also demonstrates a new high-precision method for characterizing the optical properties of a variety of materials.

On-chip Fourier-transform spectrometers and machine learning: a new route to smart photonic sensors.

Miniaturized silicon photonics spectrometers capable of detecting specific absorption features have great potential for mass market applications in medicine, environmental monitoring, and hazard detection. However, state-of-the-art silicon spectrometers are limited by fabrication imperfections and environmental conditions, especially temperature variations, since uncontrolled temperature drifts of only 0.1°C distort the retrieved spectrum precluding the detection and classification of the absorption features. Here we present a new strategy that exploits the robustness of machine learning algorithms to signal imperfections, enabling recognition of specific absorption features in a wide range of environmental conditions. We combine on-chip spatial heterodyne Fourier-transform spectrometers and supervised learning to classify different input spectra in the presence of fabrication errors, without temperature stabilization or monitoring. We experimentally show the differentiation of four different input spectra under an uncontrolled 10°C range of temperatures, about $ 100\times $100× increase in operational range, with a success rate up to 82.5% using state-of-the-art support vector machines and artificial neural networks.

Bragg filter bandwidth engineering in subwavelength grating metamaterial waveguides.

Bragg gratings are fundamental building blocks for integrated photonic circuits. In the high-index contrast silicon-on-insulator material platform, it is challenging to accurately control the grating strength and achieve narrow spectral bandwidths. Here we demonstrate a novel Bragg grating geometry utilizing a silicon subwavelength grating (SWG) waveguide with evanescently coupled periodic Bragg loading segments placed outside the SWG core. We report experimental 3 dB filter bandwidths in a range from 8 nm to 150 pm by adjusting the distance of the Bragg loading segments from the core and the relative phase shift of the segments on the two sides of the waveguide, with a structure that has a minimum feature size of 100 nm.

Athermal echelle grating filter in silicon-on-insulator using a temperature-synchronized input.

Athermal design of integrated photonic devices can reduce the need for active temperature stabilization and consequently the energy required to operate photonic integrated circuits. For silicon photonic filters such as AWGs which employ wire or ridge waveguides, temperature insensitivity can be achieved using cladding materials with negative thermo-optic coefficients. On the other hand, in echelle grating filters the inteference takes place in the slab free-propagation region, and therefore the modal overlap with the cladding is small, rendering this method ineffective. In this work we present an approach to design an athermal echelle grating filter exploiting a temperature-synchronized Mach-Zehnder interferometer as input. This reduces the spectral shift over a temperature range of 20 K to less than ±45 pm compared to the 1.6 nm shift for the same echelle grating with a conventional waveguide input. Furthermore, the proposed design relies exclusively on a standard fabrication process for silicon-on-insulator photonic devices and exhibits a good tolerance to fabrication uncertainties.

Value of Two-Dimensional Shear Wave Elastography for Assessing Acute Liver Congestion in a Bama Mini-Pig Model.

BACKGROUND: To date, liver congestion is one of the most significant clinical diseases. However, few studies have profoundly investigated the development, pathology, and prognosis of the important problems associated with acute hepatic congestion. AIMS: To explore the value of noninvasive two-dimensional shear wave elastography (2D-SWE) for assessing acute liver congestion in an animal model. METHODS: Six healthy Bama mini-pigs were used for this research and randomly divided into the experimental group and control group. We measured the basal liver stiffness (LS) by 2D-SWE and then clamped the inferior vena cava (IVC). LS was measured after 1, 5, 10, and 15 min. We reopened the IVC of experimental group pigs and detected the LS again. All pigs were killed and obtained for a pathological microscopic examination. RESULTS: LS was distinctly increased from 7.03 ± 0.48 to 17.18 ± 3.40 kPa (p < 0.01) within 15 min and reversed to almost normal values of 7.59 ± 0.77 kPa (p < 0.01) within 5 min. In addition, two-dimensional ultrasound images demonstrated the interesting phenomenon of spontaneous echo contrast. Most importantly, the pathologic results of experimental group pigs showed the central veins of the hepatic lobules and hepatic sinusoids were enlarged and filled with numerous erythrocytes; central lobular hepatocytic necrosis and edema were noted. CONCLUSIONS: In conclusion, 2D-SWE is a valuable, reliable, and quantitative approach to successfully assess acute liver congestion, and it is well consistent with histopathological characteristics. Besides, acute liver congestion is an important factor influencing LS that increases LS in a reversible way.

Temperature dependence mitigation in stationary Fourier-transform on-chip spectrometers.

We present two techniques for mitigating the effects of temperature drifts in waveguide spatial heterodyne Fourier-transform on-chip spectrometers. In high-resolution devices, large optical path length differences result in an increased sensitivity to temperature variations and impose stringent requirements on the thermal stabilization system. In order to overcome this limitation, here we experimentally demonstrate two new temperature mitigation techniques based on a temperature-sensitive calibration and phase error correction. The spectrometer chip under analysis comprises an array of 32 Mach-Zehnder interferometers fabricated on a silicon-on-insulator platform. The optical path delays are implemented as microphotonic spirals of linearly increasing length up to 3.779 cm, yielding a spectral resolution of 17 pm. We demonstrate that the degradation in retrieved spectra caused by temperature drift is effectively eliminated by temperature-sensitive calibration and phase error correction.