Optimization of Cladding Diameter for Refractive Index Sensing in Tilted Fiber Bragg Gratings.

This work presents an experimental investigation of the effect of chemical etching on the refractive index (RI) sensitivity of tilted fiber Bragg gratings (TFBGs). Hydrofluoric acid (HF) was used stepwise in order to reduce the optical fiber diameter from 125 µm to 13 µm. After each etching step, TFBGs were calibrated using two ranges of RI solutions: the first one with high RI variation (from 1.33679 RIU to 1.37078 RIU) and the second with low RI variation (from 1.34722 RIU to 1.34873 RIU). RI sensitivity was analyzed in terms of wavelength shift and intensity change of the grating resonances. The highest amplitude sensitivities obtained are 1008 dB/RIU for the high RI range and 8160 dB/RIU for the low RI range, corresponding to the unetched TFBG. The highest wavelength sensitivities are 38.8 nm/RIU for a fiber diameter of 100 µm for the high RI range, and 156 nm/RIU for a diameter of 40 µm for the small RI range. In addition, the effect of the etching process on the spectral intensity of the cladding modes, their wavelength separation and sensor linearity (R2) were studied as well. As a result, an optimization of the etching process is provided, so that the best trade-off between sensitivity, intensity level, and fiber thickness can be obtained.

Laser-induced thermal response and controlled release of copper oxide nanoparticles from multifunctional polymeric nanocarriers.

Multifunctional nanocarriers have attracted considerable interest in improving cancer treatment outcomes. Poly(lactide-co-glycolide) (PLGA) nanospheres encapsulating copper oxide nanoparticles (CuO-NPs) are characterized by antitumor activity and exhibit dual-modal contrast-enhancing capabilities. An in vitro evaluation demonstrates that this delivery system allows controlled and sustained release of CuO-NPs. To achieve localized release on demand, an external stimulation by laser irradiation is suggested. Furthermore, to enable simultaneous complementary photothermal therapy, polydopamine (PDA) coating for augmented laser absorption is proposed. To this aim, two formulations of CuO-NPs loaded nanospheres are prepared from PLGA polymers RG-504 H (H-PLGA) and RG-502 H (L-PLGA) as scaffolds for surface modification through in situ polymerization of dopamine and then PEGylation. The obtained CuO-NPs-based multifunctional nanocarriers are characterized, and photothermal effects are examined as a function of wavelength and time. The results show that 808 nm laser irradiation of the coated nanospheres yields maximal temperature elevation (T = 41°C) and stimulates copper release at a much faster rate compared to non-irradiated formulations. Laser-triggered CuO-NP release is mainly depended on the PLGA core, resulting in faster release with L-PLGA, which also yielded potent anti-tumor efficacy in head and neck cancer cell line (Cal-33). In conclusion, the suggested multifunctional nanoplatform offers the integrated benefits of diagnostic imaging and laser-induced drug release combined with thermal therapy.

Closed-Loop Temperature Control Based on Fiber Bragg Grating Sensors for Laser Ablation of Hepatic Tissue.

Laser ablation (LA) of cancer is a minimally invasive technique based on targeted heat release. Controlling tissue temperature during LA is crucial to achieve the desired therapeutic effect in the organs while preserving the healthy tissue around. Here, we report the design and implementation of a real-time monitoring system performing closed-loop temperature control, based on fiber Bragg grating (FBG) spatial measurements. Highly dense FBG arrays (1.19 mm length, 0.01 mm edge-to-edge distance) were inscribed in polyimide-coated fibers using the femtosecond point-by-point writing technology to obtain the spatial resolution needed for accurate reconstruction of high-gradient temperature profiles during LA. The zone control strategy was implemented such that the temperature in the laser-irradiated area was maintained at specific set values (43 and 55 °C), in correspondence to specific radii (2 and 6 mm) of the targeted zone. The developed control system was assessed in terms of measured temperature maps during an ex vivo liver LA. Results suggest that the temperature-feedback system provides several advantages, including controlling the margins of the ablated zone and keeping the maximum temperature below the critical values. Our strategy and resulting analysis go beyond the state-of-the-art LA regulation techniques, encouraging further investigation in the identification of the optimal control-loop.

Partially etched chirped fiber Bragg grating (pECFBG) for joint temperature, thermal profile, and refractive index detection.

In this work, a partially etched chirped fiber Bragg grating (pECFBG) is introduced, as a compact sensor for multi-parametric measurement of temperature, thermal gradients over the active length, and refractive index. The sensor is fabricated by wet-etching a portion of a 14-mm linearly chirped FBG with linear chirp profile. The resulting device has two active areas: the unetched part of the grating (2 mm) can be used either as a uniform temperature sensor, or to detect thermal gradients experienced through the grating length by means of a spectral reconstruction technique; the etched part (12 mm), besides having a similar thermal sensitivity, is exposed to refractive index sensing through the introduction of a sensitivity to external refractive index. Overall, the pECFBG structure behaves as a compact sensor with multi-parameter capability, that can both measure temperature and refractive index on the same grating, but also spatially resolve temperature detection through the grating section. The results have been validated through both a model and experimental setup, showing that the mutual correlation algorithm applied to different spectral parts of the grating is able to discriminate between uniform and gradient-shaped temperature profiles, and refractive index changes.

Fiber optic refractive index sensors through spectral detection of Rayleigh backscattering in a chemically etched MgO-based nanoparticle-doped fiber.

We demonstrate and experimentally validate a fiber optic refractive index (RI) sensor obtained by simply etching a high-scattering MgO-based nanoparticle-doped single-mode fiber in hydrofluoric acid (HF). The fiber has 32.3 dB stronger Rayleigh scattering than a standard fiber, allowing a detection of scattering spectral signatures with an optical backscatter reflectometer, even when the core is exposed to the outer RI. The obtained sensitivity is 1.53 nm/RIU (RI units), measured by correlating the scattering spectra. We prove the possibility of implementing a distributed RI detection (seven locations spaced by 1 mm). The fabrication method for this RI sensor is simplified, since it simply requires etching in an HF bath, without the need of inscribing reflective elements or fabricating microstructures in the fiber.

Largely tunable dispersion chirped polymer FBG.

We demonstrate a largely tunable dispersion fiber Bragg grating (FBG) inscribed in a microstructured polymer optical fiber (mPOF). The bandwidth of the chirped FBG (CFBG) was achieved from 0.11 to 4.86 nm, which corresponds to a tunable dispersion range from 513.6 to 11.15 ps/nm. Furthermore, thermal sensitivity is used to compensate for the wavelength shift due to the applied strain. These results demonstrate that a CFBG in a POF is a promising technology for future optical systems.

Non-Fourier Bioheat Transfer Analysis in Brain Tissue During Interstitial Laser Ablation: Analysis of Multiple Influential Factors.

This work presents the dual-phase lag-based non-Fourier bioheat transfer model of brain tissue subjected to interstitial laser ablation. The finite element method has been utilized to predict the brain tissue's temperature distributions and ablation volumes. A sensitivity analysis has been conducted to quantify the effect of variations in the input laser power, treatment time, laser fiber diameter, laser wavelength, and non-Fourier phase lags. Notably, in this work, the temperature-dependent thermal properties of brain tissue have been considered. The developed model has been validated by comparing the temperature obtained from the numerical and ex vivo brain tissue during interstitial laser ablation. The ex vivo brain model has been further extended to in vivo settings by incorporating the blood perfusion effects. The results of the systematic analysis highlight the importance of considering temperature-dependent thermal properties of the brain tissue, non-Fourier behavior, and microvascular perfusion effects in the computational models for accurate predictions of the treatment outcomes during interstitial laser ablation, thereby minimizing the damage to surrounding healthy tissue. The developed model and parametric analysis reported in this study would assist in a more accurate and precise prediction of the temperature distribution, thus allowing to optimize the thermal dosage during laser therapy in the brain.

Preliminary Results of Laser Ablation during In Vivo Experiments: Comparison of Thermal Effects Obtained with Bare and Diffuser Tip Applicators.

This work is a step towards the analysis of the effect of different laser applicator tips used for laser ablation of liver for in vivo experiments. As the thermal outcome of this minimally invasive treatment for tumors depends upon the interaction between the tissue and the light, the emission pattern of the laser applicator has a key role in the shape and size of the final treated region. Hence, we have compared two different laser applicators: a bare tip fiber (emitting light from the tip and forward) and a diffuser tip fiber (emitting light at 360° circumferentially from the side of the fiber). The experiments have been carried out percutaneously in a preclinical scenario (anesthetized pigs), under computed tomography (CT) guidance. The thermal effects of the two applicators have been assessed in terms of real-time temperature distribution, by means of an array of 40 fiber Bragg grating (FBG) sensors, and in terms of cavitation and ablation volumes, measured through CT post-temperature due to breathing motion has been analyzed and filtered out. Results show that the maximum temperature reached 50.5 °C for the bare tip fiber experiment (measured at 6.24 mm distance from the applicator) and 60.9 °C for the diffuser tip fiber experiment (measured at 5.23 mm distance from the applicator). The diffuser tip fiber allowed to achieve a more symmetrical heat distribution than the bare tip fiber, and without cavitation volume.Clinical Relevance-This work shows the analysis of the thermal effects of different laser fiber tips to improve laser ablation treatment. The results obtained in the preclinical scenario well represent the expected clinical outcome in the treatment of hepatic tumors. Moreover, these findings can be applied to other fields in which laser ablation is the optimal therapeutic choice, such as neurosurgery.

On the role of polymeric hydrogels in the thermal response of gold nanorods under NIR laser irradiation.

Hydrogels are 3D cross-linked networks of polymeric chains designed to be used in the human body. Nowadays they find widespread applications in the biomedical field and are particularly attractive as drug delivery vectors. However, despite many good results, their release performance is sometimes very quick and uncontrolled, being forced by the high in vivo clearance of body fluids. In this direction, the development of novel responsive nanomaterials promises to overcome the drawbacks of common hydrogels, inducing responsive properties in three-dimensional polymeric devices. In this study, we synthesized and then loaded gold nanorods (Au NRs) within an agarose-carbomer (AC)-based hydrogel obtained from a microwave-assisted polycondensation reaction between carbomer 974P and agarose. The photothermal effect of the composite device was quantified in terms of maximum temperature and spatial-temporal temperature distribution, also during consecutive laser irradiations. This work shows that composite Au NRs loaded within AC hydrogels can serve as a stable photothermal treatment agent with enhanced photothermal efficiency and good thermal stability after consecutive laser irradiations. These results confirm that the composite system produced can exhibit an enhanced thermal effect under NIR laser irradiation, which is expected to lead to great therapeutic advantages for the localized treatment of different diseases.

Characterization of susceptibility artifacts in magnetic resonance thermometry images during laser interstitial thermal therapy: dimension analysis and temperature error estimation.

Objective.Laser interstitial thermal therapy (LITT) is a minimally invasive procedure used to treat a lesion through light irradiation and consequent temperature increase. Magnetic resonance thermometry imaging (MRTI) provides a multidimensional measurement of the temperature inside the target, thus enabling accurate monitoring of the damaged zone during the procedure. In proton resonance frequency shift-based thermometry, artifacts in the images may strongly interfere with the estimated temperature maps. In our work, after noticing the formation of the dipolar-behavior artifact linkable to magnetic susceptibility changes duringin vivoLITT, an investigation of susceptibility artifacts in tissue-mimicking phantoms was implemented.Approach.The artifact was characterized: (i) by measuring the area and total volume of error regions and their evolution during the treatment; and (ii) by comparison with temperature reference provided by three temperature sensing needles. Lastly, a strategy to avoid artifacts formation was devised by using the temperature-sensing needles to implement a temperature-controlled LITT.Main results.The artifact appearance was associated with gas bubble formation and with unwanted treatment effects producing magnetic susceptibility changes when 2 W laser power was set. The analysis of the artifact's dimension demonstrated that in the sagittal plane the dipolar-shape artifact may consistently spread following the temperature trend until reaching a volume 8 times bigger than the ablated one. Also, the artifact shape is quite symmetric with respect to the laser tip. An absolute temperature error showing a negative Gaussian profile in the area of susceptibility artifact with values up to 64.4 °C was estimated. Conversely, a maximum error of 2.8 °C is measured in the area not-affected by artifacts and far from the applicator tip. Finally, by regulating laser power, susceptibility artifacts formation was avoided, and appreciable thermal damage was induced.Significance.These findings may help in improving the MRTI-based guidance of thermal therapies.

Feedback-controlled laser ablation for cancer treatment: comparison of On-Off and PID control strategies.

Laser ablation is a rising technique used to induce a localized temperature increment for tumor ablation. The outcomes of the therapy depend on the tissue thermal history. Monitoring devices help to assess the tissue thermal response, and their combination with a control strategy can be used to promptly address unexpected temperature changes and thus reduce unwanted thermal effects. In this application, numerical simulations can drive the selection of the laser control settings (i.e., laser power and gain parameters) and allow evaluating the thermal effects of the control strategies. In this study, the influence of different control strategies (On-Off and PID-based controls) is quantified considering the treatment time and the thermal effect on the tissue. Finite element model-based simulations were implemented to model the laser-tissue interaction, the heat-transfer, and the consequent thermal damage in liver tissue with tumor. The laser power was modulated based on the temperature feedback provided within the tumor safety margin. Results show that the chosen control strategy does not have a major influence on the extent of thermal damage but on the treatment duration; the percentage of necrosis within the tumor domain is 100% with both strategies, while the treatment duration is 630 s and 786 s for On-Off and PID, respectively. The choice of the control strategy is a trade-off between treatment duration and unwanted temperature overshoot during closed-loop laser ablation. Clinical Relevance-This work establishes that different temperature-based control of the laser ablation procedure does not have a major influence on the extent of thermal damage but on the duration of treatment.

Thermomechanical Modeling of Laser Ablation Therapy of Tumors: Sensitivity Analysis and Optimization of Influential Variables.

In cancer treatment, laser ablation is a promising technique used to induce localized thermal damage. Different variables influence the temperature distribution in the tissue and the resulting therapy efficacy; thus, the optimal therapy settings are required for obtaining the desired clinical outcome. In this work, thermomechanical modeling of contactless laser ablation was implemented to analyze the sensitivity of independent variables on the optimal treatment conditions. The Finite Element Method was utilized to solve the governing equations, i.e., the bioheat, mechanical deformation, and the Navier-Stokes equations. Validation of the model was performed by comparing experimental and simulated temperatures, which indicated high accuracy for estimating temperature. In particular, the results showed that the model can estimate temperature with a good correlation factor (R = 0.98) and low Mean Absolute Error (3.9 °C). A sensitivity analysis based on laser irradiation time, power, beam distribution, and the blood vessel depth on temperature distribution and fraction of necrotic tissue was performed. An optimization process was performed based on the most significant variables, i.e., laser irradiation time and power. This resulted in an indication of the optimal therapy settings for achieving maximum procedure efficiency i.e., the required fraction of necrotic tissue within the target volume, constituted by tumor and safety margins around it.

Experimental Evaluation of Radiation Response and Thermal Properties of NPs-Loaded Tissues-Mimicking Phantoms.

Many efforts have recently concentrated on constructing and developing nanoparticles (NPs) as promising thermal agent for optical hyperthermia and photothermal therapy. However, thermal energy transfer in biological tissue is a complex process involving different mechanisms such as conduction, convection, radiation. Therefore, having information about thermal properties of tissue especially when NPs are embedded in is a necessity for predicting the heat transfer during hyperthermia. In this work, the thermal properties of solid phantom based on agar in the presence of three different nanoparticles (BPSi, tNAs, GNRs) and alone were measured and reported as a function of temperature (ranging from 22 to 62 °C). The thermal response of these NPs to an 808 nm laser beam with three different powers were studied in the water comparatively. Agar and tNAs have almost constant thermal properties in the considered range. Among the three NPs, gold has the highest conductivity and diffusivity. At 62 °C BPSi NPs have the similar amount of increase for the diffusivity. The thermal parameters reported in this paper can be useful for the mathematical modeling. Irradiation of the NPs-loaded water phantom displayed the highest radiosensitivity of gold among the three mentioned NPs. However, for the higher power of irradiation, BPSi and tNAs NPs showed the increased absorption of heat during shorter time and the increased temperature gradient slope for the initial 15 s after the irradiation started. The three NPs showed different thermal and irradiation response behavior; however, this comparison study notes the worth of having information about thermal parameters of NPs-loaded tissue for pre-clinical planning.

Analysis of cavitation artifacts in Magnetic Resonance Imaging Thermometry during laser ablation monitoring.

Magnetic Resonance Thermometry Imaging (MRTI) holds great potential in laser ablation (LA) monitoring. It provides the real-time multidimensional visualization of the treatment effect inside the body, thus enabling accurate intraoperative prediction of the thermal damage induced. Despite its great potential., thermal maps obtained with MRTI may be affected by numerous artifacts. Among the sources of error producing artifacts in the images., the cavitation phenomena which could occur in the tissue during LA induces dipole-structured artifacts. In this work., an analysis of the cavitation artifacts occurring during LA in a gelatin phantom in terms of symmetry in space and symmetry of temperature values was performed. Results of 2 Wand 4 W laser power were compared finding higher symmetry for the 2 W case in terms of both dimensions of artifact-lobes and difference in temperature values extracted in specular pixels in the image. This preliminary investigation of artifact features may provide a step forward in the identification of the best strategy to correct and avoid artifact occurrence during thermal therapy monitoring. Clinical Relevance- This work presents an analysis of cavitation artifacts in MRTI from LA which must be corrected to avoid error in the prediction of thermal damage during LA monitoring.

Quasi-distributed fiber optic sensor-based control system for interstitial laser ablation of tissue: theoretical and experimental investigations.

This work proposes the quasi-distributed real-time monitoring and control of laser ablation (LA) of liver tissue. To confine the thermal damage, a pre-planning stage of the control strategy based on numerical simulations of the bioheat-transfer was developed to design the control parameters, then experimentally assessed. Fiber Bragg grating (FBG) sensors were employed to design the automatic thermometry system used for temperature feedback control for interstitial LA. The tissue temperature was maintained at a pre-set value, and the influence of different sensor locations (on the direction of the beam propagation and backward) on the thermal outcome was evaluated in comparison with the uncontrolled case. Results show that the implemented computational model was able to properly describe the temperature evolution of the irradiated tissue. Furthermore, the realized control strategy allowed for the accurate confinement of the laser-induced temperature increase, especially when the temperature control was actuated by sensors located in the direction of the beam propagation, as confirmed by the calculated fractions of necrotic tissues (e.g., 23 mm3 and 53 mm3 for the controlled and uncontrolled LA, respectively).

Laser-induced optothermal response of gold nanoparticles: From a physical viewpoint to cancer treatment application.

Gold nanoparticles (GNPs)-based photothermal therapy (PTT) is a promising minimally invasive thermal therapy for the treatment of focal malignancies. Although GNPs-based PTT has been known for over two decades and GNPs possess unique properties as therapeutic agents, the delivery of a safe and effective therapy is still an open question. This review aims at providing relevant and recent information on the usage of GNPs in combination with the laser to treat cancers, pointing out the practical aspects that bear on the therapy outcome. Emphasis is given to the assessment of the GNPs' properties and the physical mechanisms underlying the laser-induced heat generation in GNPs-loaded tissues. The main techniques available for temperature measurement and the current theoretical simulation approaches predicting the therapeutic outcome are reviewed. Topical challenges in delivering safe thermal dosage are also presented with the aim to discuss the state-of-the-art and the future perspective in the field of GNPs-mediated PTT.

Functionalized etched tilted fiber Bragg grating aptasensor for label-free protein detection.

An aptasensor based on etched tilted fiber Bragg grating (eTFBG) is developed on a single-mode optical fiber targeting biomolecule detection. TFBGs were chemically etched using hydrofluoric acid (HF) to partially remove the fiber cladding. The sensor response was coarsely interrogated, resulting on a sensitivity increase from 1.25 nm/RIU (refractive index unit) at the beginning of the process, up to 23.38 nm/RIU at the end of the etching, for a RI range from 1.3418 to 1.4419 RIU. The proposed aptasensor showed improved RI sensitivity as compared to the unetched TFBG, without requiring metal depositions on the fiber surface or polarization control during the measurements. The proposed sensor was tested for the detection of thrombin-aptamer interactions based on silane-coupling surface chemistry, with thrombin concentrations ranging from 2.5 to 40 nM. Functionalized eTFBGs provided a competitive platform for biochemical interaction measurements, showing sensitivity values ranging from 2.3 to 3.3 p.m./nM for the particular case of thrombin detection.

Multi-fiber distributed thermal profiling of minimally invasive thermal ablation with scattering-level multiplexing in MgO-doped fibers.

We propose a setup for multiplexed distributed optical fiber sensors capable of resolving temperature distribution in thermo-therapies, with a spatial resolution of 2.5 mm over multiple fibers interrogated simultaneously. The setup is based on optical backscatter reflectometry (OBR) applied to optical fibers having backscattered power significantly larger than standard fibers (36.5 dB), obtained through MgO doping. The setup is based on a scattering-level multiplexing, which allows interrogating all the sensing fibers simultaneously, thanks to the fact that the backscattered power can be unambiguously associated to each fiber. The setup has been validated for the planar measurement of temperature profiles in ex vivo radiofrequency ablation, obtaining the measurement of temperature over a surface of 96 total points (4 fibers, 8 sensing points per cm2). The spatial resolution obtained for the planar measurement allows extending distributed sensing to surface, or even three-dimensional, geometries performing temperature sensing in the tissue with millimeter resolution in multiple dimensions.

Temperature Profiling of ex-vivo Organs during Ferromagnetic Nanoparticles-Enhanced Radiofrequency Ablation by Fiber Bragg Grating Arrays.

In this paper, we present real-time profiles of temperature during a ferromagnetic nanoparticles (NPs)enhanced radiofrequency ablation (RFA). A minimally invasive RFA setup has been prepared and applied ex vivo on a liver phantom; NPs (with concentration of 5 mg/mL) have been synthetized and injected within the tissue prior to perform the ablation, in order to facilitate the heat distribution to the peripheral sides of the ablated tissue. Temperature detection has been realized in situ with a network of 15 fiber Bragg grating (FBG) sensors in order to highlight the impact of the NPs on the RFA mechanism. Obtained temperature profiles and thermal maps confirm that nanoparticles injection ensures better heat penetration than in case of pristine RFA procedure. The results show that adding NPs solution leads to extending the successfully ablated area achieving a double-sized lesion.

Linearly chirped fiber Bragg grating response to thermal gradient: from bench tests to the real-time assessment during in vivo laser ablations of biological tissue.

The response of a fiber optic sensor [linearly chirped fiber Bragg grating (LCFBG)] to a linear thermal gradient applied on its sensing length (i.e., 1.5 cm) has been investigated. After these bench tests, we assessed their feasibility for temperature monitoring during thermal tumor treatment. In particular, we performed experiments during ex vivo laser ablation (LA) in pig liver and in vivo thermal ablation in animal models (pigs). We investigated the following: (i) the relationship between the full width at half maximum of the LCFBG spectrum and the temperature difference among the extremities of the LCFBG and (ii) the relationship between the mean spectrum wavelength and the mean temperature acting on the LCFBG sensing area. These relationships showed a linear trend during both bench tests and LA in animal models. Thermal sensitivity was significant although different values were found with regards to bench tests and animal experiments. The linear trend and significant sensitivity allow hypothesizing a future use of this kind of sensor to monitor both temperature gradient and mean temperature within a tissue undergoing thermal treatment.