Fiber Optic Diffuser Research Articles

Abstract 2776: Real-time measurement of temperature and tissue damage during laser photothermal ablation

Abstract Hepatocellular carcinoma (HCC) is the sixth most common cancer and tumor resection is feasible in only 25±30% of these patients. Thermal ablation therapies using lasers, radiofrequency waves and microwaves are considered as an alternative treatment for unresectable tumors. Our goal was to develop optical fiber-based laser ablation while monitoring the changes in temperature and tissue properties in real-time. A portable diffuse reflectance spectroscopy (DRS) system consisting of a DRS probe with self-calibration and fiber optic temperature sensor was made. Tissue mimicking phantoms using human hemoglobin powders and polystyrene particles with fixed total number of scatterers were used to calibrate the system. In vivo studies were performed in 8 rats orthotopically implanted with HCC. Temperature sensor was inserted in the center of the tumor via hypodermic needle and DRS fiber was overlaid on the temperature sensor. Ablation was performed by a fiber optic diffuser connected to an 808nm laser using different power settings in pulse mode. The tissue temperature and optical properties were continuously monitored until both plateaued using a custom LabVIEW program. Rats were immediately euthanized, and the ablated liver tissues were collected for histological analysis. The DRS showed average errors of 6.31% and 4.74% in measuring the absorption (μa) and reduced scattering coefficients (μs) of the phantoms respectively. Tumor bearing liver tissues showed a decreasing trend in both μa and μs irrespective of the laser power (1W-2.5W) and the temperatures recorded (50°C to 88°C) in different animals. Histological analysis showed discrete zones of tissue damage from treated regions with hemorrhage in the outer most zone. Changes in optical properties of the ablated tumors with temperatures and histological changes needs further correlation by performing more in vivo studies. Citation Format: Faraneh Fathi, Dilip R. Maddirela, Venkateswara Rao Gogineni, Sarah B. White, Bing Yu. Real-time measurement of temperature and tissue damage during laser photothermal ablation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2776.

Experimental study of optical power effect on the structure of fiber-optical diffuser obtained by fiber core melting

Subject of Research. The paper presents experimental findings of a fiber-optic diffuser structure formed by optical fiber melting. Method. An optical scheme of ytterbium fiber laser is demonstrated consisting of such main components as: a laser pump diode (980 nm, with power up to 30 W), an active GTWave fiber (24 m), and two fiber Bragg gratings with reflection coefficients of 100 % and 30 %. The presented ytterbium radiation source is used to form a periodic structure of microcavities inside the fiber core using the melting effect of the material. The described technology application provides the creation of scattering structures with a given period without removing the protective acrylate fiber coating. Thus, there is no need for the optical fiber re-coating with a polymer composition, and its strength characteristics are maintained. Main Results. The experimental setup developed during the study gives the possibility to record the scattering structure in the core of the optical fiber by destroying the material using laser radiation. In order to determine the dependence of the properties of the created structures on the input radiation power, a number of samples was obtained recorded for various radiation characteristics. It was established experimentally that with an increase of laser radiation power, the period of localization of microcavities decreases. At the same time, their sizes are reduced, and the uniformity of the structure increases. The optimal radiation power value for the scattering structure formation is established to be about 2 W. Practical Relevance. The studied scattering structures can be used in medical research, laser photodynamic therapy, laser pacemakers, fluorescence diagnostics, and also as a backlight for minimally invasive operations. The fiber optic diffuser can be applicable as a sensor of physical quantities, in particular, for measuring high temperatures, since the upper limit of the diffuser working temperature is comparable to the melting temperature of the optical fiber quartz part.

Results of a phase 2a, multicenter, open-label, study of RM-1929 photoimmunotherapy (PIT) in patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC).

6014 Background: Patients with rHNSCC who have failed standard of care have poor prognoses and limited therapeutic options. In this study, final results are reported of a phase 2a trial of photoimmunotherapy (PIT) with a targeted drug RM-1929, consisting of the EGFR-directed antibody cetuximab conjugated to a photoactivatable dye (IRDye 700DX). Binding of the antibody-dye conjugate to cancer cells followed by photoactivation with nonthermal red light induces selective and rapid necrosis of the cancer cells, with minimal damage to surrounding tissue. Methods: A phase 2a, multicenter, open-label, study of RM-1929 PIT in patients with locoregional, rHNSCC who could not be satisfactorily treated with surgery, radiation, or platinum chemotherapy was conducted to evaluate the safety and efficacy of the drug, RM-1929. For each treatment, nonthermal red light (690 nm) was applied to the tumors 24 hours post IV infusion of the drug. Surface illumination was administered for superficial tumors and interstitial illumination via intratumoral placement of fiber optic diffusers for deep tumors. Therapeutic response was assessed using CT RECIST 1.1 by an independent blinded radiologist. Results: Thirty rHNSCC patients were enrolled. There were no dose-limiting toxicities and one Grade 1 photosensitivity reaction. Most reported AEs were mild to moderate in severity with 96.7% (29/30) of patients with Grade 1 and 83.3% (25/30) with Grade 2, respectively. There were 13 (43.3%) patients who had at least one SAE. 86% (19/22) of SAEs were deemed unlikely related to treatment, including all 3 fatal SAEs. Three SAEs were reported to be possibly/probably related to treatment (site/oral pain, tumor hemorrhage, and airway obstruction). ORR was 50% (15/30) with 16.7% (5/30) CR and 86.7% (26/30) DCR. Median PFS and OS results will be forthcoming. Conclusions: These data indicate that RM-1929 PIT treatment was generally well tolerated with majority of AEs as mild to moderate in severity. Preliminary data showed favorable response rates in a heavily pre-treated population. A global phase 3 clinical trial is currently underway. Clinical trial information: NCT02422979.

Near infrared photoimmunotherapy using a fiber optic diffuser for treating peritoneal gastric cancer dissemination.

Peritoneal dissemination (PD) of abdominal malignancies is a common form of metastasis and its presence signals a poor prognosis. New treatment is required for patients with PD. Near infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate (APC). In this study, we investigate in vitro and in vivo efficacy of trastuzumab (tra)-IR700DX NIR-PIT on a human epidermal growth factor receptor type 2 (HER2)-positive gastric cancer cell line. NIR-PIT effects were investigated in vitro and in vivo. Disseminated peritoneal implants mice were separated into 5 groups: (1) no treatment; (2) tra-IR700 i.v. only; (3) NIR light only; (4) NIR-PIT; (5) repeated NIR-PIT. The peritoneal cavity was irradiated with NIR light using a fiber optic diffuser delivered through the catheter. Specific binding and cell-specific killing was observed after NIR-PIT in vitro. In the in vivo study, fluorescence endoscopy showed high tumor accumulation of tra-IR700 within tumors. Significantly prolonged survival was achieved in the three treatment groups (tra-IR700 i.v. only, NIR-PIT, and repeated NIR-PIT groups) compared with control and NIR light only group (p < 0.05 for tra-IR700 i.v. only, p < 0.01 for NIR-PIT, and p < 0.0001 for repeated NIR-PIT). Moreover, most prolonged survival was shown for the repeated NIR-PIT group (p < 0.0001 vs tra-IR700 i.v. only, p < 0.01 vs NIR-PIT). NIR-PIT using a fiber optic diffuser to deliver light is a promising candidate for the treatment of disseminated peritoneal metastases and could be readily translated to humans.

Endoscopic near infrared photoimmunotherapy using a fiber optic diffuser for peritoneal dissemination of gastric cancer.

Near infrared photoimmunotherapy (NIR‐PIT) is a highly selective tumor treatment that employs an antibody‐photo‐absorber conjugate (APC) which is activated by near infrared light. Here, we describe the efficacy of endoscopic NIR‐PIT using the APC trastuzumab‐IR700DX (tra‐IR700) in the setting of human epidermal growth factor 2 positive (HER2 + ) gastric carcinoma with peritoneal disseminations. In this in vivo study, fluorescence endoscopy showed high tumor accumulation of tra‐IR700 within disseminated peritoneal implants. Mice with disseminated peritoneal gastric cancer were separated into 4 groups: (i) control (no treatment); (ii) tra‐IR700 i.v. only; (iii) NIR light only; and (iv) endoscopic NIR‐PIT. NIR light irradiation was carried out through a fiber optic diffuser under endoscopic guidance. In vivo bioluminescence images showed significantly greater therapeutic effect in the endoscopic NIR‐PIT group than that in the control groups (P < .01 vs other control groups). Histological analysis showed diffuse cancer cell death in NIR‐PIT‐treated tumors. In conclusion, NIR‐PIT with NIR light delivered via an endoscopic fiber optic diffuser is a promising method for the treatment of peritoneal dissemination of gastric cancer. Moreover, this technique could be readily used in other types of cancers with peritoneal dissemination provided that suitable antibodies could be found.

A Phase 2a, Multicenter, Open-Label Study of RM-1929 Photoimmunotherapy in Patients With Recurrent Head And Neck Cancer

Patients with recurrent head and neck squamous cell cancer (rHNSCC) have poor prognoses and limited treatment options after they have failed standard therapies. We are investigating photoimmunotherapy (PIT) for the treatment of rHNSCC using a novel targeted light-activated drug conjugate RM1929, consisting of the EGFR-directed monoclonal antibody cetuximab conjugated to the phthalocyanine dye, IRDye 700DX. This is a multi-institutional open-label Phase 2a study of rHNSCC patients who cannot be satisfactorily treated with surgery, radiation, or platinum chemotherapy. PIT, using a previously determined optimal drug dose and light treatment dose, was performed to evaluate the safety and efficacy associated with repeat dosing of up to 4 treatment cycles, 4-8 weeks apart, in patients with persistence of disease. For each treatment, nonthermal red light was applied to the tumors 24 hours after intravenous infusion of the photoactivated conjugate. The light was applied on the surface for superficial mucosal/cutaneous disease or within the tumor (via fiber optic diffusers placed by ultrasound guidance) for submucosal/subcutaneous or nodal disease. Responses and Progression-Free Survival (PFS) were calculated using CT RECIST 1.1. All CT RECIST 1.1 measurements were determined by an independent blinded radiologist. Nineteen patients with rHNSCC who were treated with RM-1929 PIT and have been followed for at least 3 months were included in the outcome analysis. There were no dose-limiting toxicities or skin photosensitivity reactions observed. No toxicity was noted for normal tissues exposed to therapeutic light treatment. Two reported SAEs, tumor hemorrhage and tumor pain, were assessed as possibly or probably related to treatment. CT RECIST 1.1 demonstrated a PFS of 153 days (5.1 months). Objective response rate (ORR), complete response (CR) and disease control rate (DCR) by CT RECIST 1.1 were 42% (8/19), 26% (5/19) and 84% (16/19) respectively. Photoimmunotherapy with RM1929 in patients with rHNSCC is safe and well-tolerated. CT RECIST 1.1 PFS, ORR, and CR response rates are improved over those of standard of care therapies and encouraging in these patients who have failed standard therapies and have typically recalcitrant disease. Further investigation of this novel therapeutic strategy is warranted and a Phase 3 clinical trial is planned.

Interstitial near-infrared photoimmunotherapy: effective treatment areas and light doses needed for use with fiber optic diffusers.

Near-infrared photoimmunotherapy (NIR-PIT), a promising cancer therapy utilizing an antibody-photoabsorber conjugate (APC) and NIR light, which induces rapid necrotic cell death only in APC-bound cells. Effective NIR-PIT in mouse models has been achieved using superficial light illumination (SLI) with light emitting diodes (LEDs) or lasers, but in the clinical setting, fiber optic diffusers have been employed to deliver light to deeper tumors. However, the performance of NIR light in tissue delivered by fiber optic diffusers is poorly understood. Here, we investigated NIR-PIT using a cylindrical fiber optic diffuser in a mouse model of A431 tumors. NIR-PIT with 100 J/cm, the same light dose used in clinical trials of NIR-PIT, was applied after insertion of the diffuser within the tumor bed, and then both bioluminescence and fluorescence imaging were analyzed to assess the therapeutic efficacy. The diffuser can deliver adequate NIR light dose for effective NIR-PIT to the A431 tumor at a distance of approximately 1 cm around the light source at 100 J/cm. At 50 J/cm NIR light effective NIR-PIT was reduced to a distance of 5 – 7 mm diameter around the light source. These results indicate that the energy of interstitial light (measured in Joules/cm) administered via a fiber diffuser determines the depth of effective NIR-PIT around the diffuser and determines the spacing at which such diffusers should be placed to entirely cover the tumor. Thermal measurements demonstrate that interstitial light for NIR-PIT does not cause damage to the skin overlying the diffuser.

Investigation on dip coating process by mathematical modeling of non-Newtonian fluid coating on cylindrical substrate

A mathematical model for the dip coating process has been developed for cylindrical geometries with non-Newtonian fluids. This investigation explores the effects of the substrate radius and hydrodynamic behavior of the non-Newtonian viscous fluid on the resulting thin film on the substrate. The coating fluid studied, Dymax 1186-MT, is a resin for fiber optics and used as a matrix to suspend 1 vol. % titanium dioxide particles. The coating substrate is a 100 μm diameter fiber optic diffuser. Ellis viscosity model is applied as a non-Newtonian viscous model for coating thickness prediction, including the influence of viscosity in low shear rates that occurs near the surface of the withdrawal film. In addition, the results of the Newtonian and power law models are compared with the Ellis model outcomes. The rheological properties and surface tension of fluids were analyzed and applied in the models and a good agreement between experimental and analytical solutions was obtained for Ellis model.

Empirical Evaluation of the Effect of Heat Gain from Fiber Optic Daylighting System on Tropical Building Interiors

A fiber optic daylighting system is an evolving technology for transporting illumination from sunlight into building interiors. This system is a solution developed by daylighting designers to reduce operational costs and enhance comfort. As an innovative technology, fiber optic daylighting systems can illuminate building interiors efficiently compared with other daylighting strategies. However, as a transmission medium in daylighting systems, optical fibers require uniform light distribution in sunlight concentration, which could generate heat. Therefore, this study aims to investigate the effect of heat buildup produced by end-emitting fiber optic daylighting systems in tropical buildings. The applied method adopts a new fiber optic daylighting system technology from Sweden called Parans SP3, with a 10 m cable to be tested in an actual room size under the Malaysian climatic environment, particularly within the vicinity of the main campus of the Universiti Sains Malaysia. Results show that the system generated a temperature of 1.3 °C under average conditions through fiber optic diffusers and increases indoor temperature by 0.8 °C in a 60 m3 room. According to the results, applying fiber optic daylighting systems, as renewable energy sources, generates extra heat gain in building interiors in the tropics.

Development of novel tunable light scattering coating materials for fiber optic diffusers in photodynamic cancer therapy

AbstractTo homogenize light emitted from fiber optic diffusers for photodynamic therapy (PDT), novel coating materials with tunable properties were designed. A class VI medical grade UV‐curable acrylic resin for biomedical applications was used for the polymer matrix, and titanium dioxide (TiO2) was added to the resin as a scattering agent. UV‐curability of coatings containing TiO2 was significantly influenced by the grade and surface treatment of the TiO2 studied. Despite using a free‐radical system without inert gas protection, all samples demonstrated considerable thermal postcuring. A novel TiO2 surface treatment methodology was developed based on unsaturated alkoxyorganosilanes combined with unsaturated carboxylic acids for compatibilizing TiO2 for use in the resin material studied. By adjusting the concentration of the surface‐modifying agent, the scattering efficiency and UV curability can be controlled by decreasing the effective particle size and enhancing the dispersibility of the powder filler within the resin. This modification will enable fine‐tuning of the effective size of TiO2 particles to the wavelength of laser light to be scattered to maximize scattering efficiency in photodynamic cancer therapy and possibly also in other forms of cancer treatment (interstitial laser hyperthermia or interstitial laser photocoagulation). © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

Performance evaluation of cylindrical fiber optic light diffusers for biomedical applications

Dosimetry for intracavity and interstitial light delivery requires next to the knowledge of tissue optical properties and models describing light propagation in tissue also exact knowledge of the spatial light source emission characteristics. However, the emission characteristics of cylindrical diffusers are often ill defined by the manufacturer, and not regularly determined by the end user, thus limiting the attainable dosimetry accuracy. Commercial cylindrical diffusers, with active diffusive lengths of 1-2 cm and outer diameters of </=1 mm, were evaluated regarding their photometric emission characteristics. In addition to traditional tests of homogeneity such as light intensity emitted along the diffuser length and around its circumference (polar angle), azimuth emission was also measured. It was demonstrated that the light emission distribution is specific to the diffuser manufacturer, and while good polar isotropy is often attained, azimuth isotropy can vary by more than a factor of 5. In hollow organs the latter can result in over treatment of tissue distal to the actual placement of the cylindrical diffusers. To enable light dosimetry and treatment planning for applications such as photodynamic therapy or interstitial laser hyperthermia or photocoagulation, standardization of emission properties reporting for optical fiber diffusers is required.

3416 Photodynamic therapy probes: can they be reused?

Background: Fiber optic diffuser probes used in photodynamic therapy (PDT) are marketed as single-use disposable items. The relatively simple design of these probes (i.e. no moving parts, no open lumens) suggests that they might be safely sterilized and reused, without significant degradation in function.We prospectively evaluated PDT probes for sterility and loss of function in vivo and in vitro. Methods: Three patients underwent a total of five PDT treatments for esophageal cancer, with treatment time averaging 19 minutes per session. PDT probes were reused on two patients, but never shared between patients. Light transmission was evaluated prior to each treatment. After use, the PDT probe was cultured and sent for manual cleaning and sterilization using the STERIS system (Steris Corp., Mentor, Ohio). The probes were then recultured to assess sterility, and light transmission was measured to test for degradation in function. All cultures were incubated aerobically and anaerobically for more than 48 hours. To further evaluate the potential for sterilization and reuse, a separate probe was exposed in vitro to a suspension of 2.1 × 10 7 B. Stearothermophilus spores. The probe was cultured to ensure contamination by the spores. After manual cleaning and sterilization, the probe was recultured and tested for light transmission. This procedure was repeated five times. Results: Cultures of PDT probes following treatment in vivo grew numerous colonies of oropharyngeal flora. Culture of the probe exposed to B. Stearothermophilus spores grew numerous colonies of this organism. After sterilization, all probe cultures showed no growth, including eradication of B. Stearothermophilus spores. Light transmission did not change significantly in any probes following two treatments in vivo and up to five sterilizations in vitro. Conclusions: 1) Sterilization of PDT probes was achieved by manual cleaning followed by STERIS system reprocessing. 2) Reuse and reprocessing of PDT probes did not affect light transmission or probe function after up to five sterilizations. 3) The number of procedures which may be performed before significant deterioration in probe function has yet to be determined.

Speckle reduction in pulsed-laser photographs

A carbon disulfide cell and fiber-optic diffuser have been used in the beam from a pulsed ruby laser to reduce the spatial coherence of the beam and enable nearly speckle-free photographs of transient phenomena to be obtained.