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Abstract
This study introduces a cutting-edge fiber-optic dosimetry (FOD) sensor designed for measuring radiation in biological settings. The accuracy and precision of dosimeters for small animals, particularly prolonged exposure to nonuniform radiation fields, are always challenging. A state-of-the-art in-vivo dosimeter utilizing glass-encapsulated Thermoluminescence cylindrical detector (TLD) was introduced. The FODs are implanted into the rat during a prolonged irradiation scenario involving 137Cs where the rat has the freedom to move within a heterogeneous radiation domain. The implantation surgery was verified with X-ray computed tomography (CT) in addition to biochemical and pathological tests to assess the biocompatibility of FOD in vivo. A versatile FOD is designed for industrial and medical fields, which demand accurate and resilient radiation dosimeters. The dose measurements are associated with precise two-dimensional (2D) radiation distribution imaging. Three cylindrical FODs and three standards TLD_100 for each rat were tested. The measurements of peak irradiation before and after exposure reveal greater stability and superior sensitivity when compared to standard thermo-luminescence detectors in an in-vivo animal test. To the best of our knowledge, FOD testing on live animals is presented for the first time in this paper. Regarding the safety and biocompatibility of FOD, no morphological signs with any kind of inflammation or sensitivity toward the FOD material have been remarked. Moreover, with the current FOD, there is no oedema between the epidermal, dermal, and subdermal sections at the site of implantation. The results also show the stable levels of white blood cells (lymphocytes, granulocytes, MID) as blood inflammatory markers before surgery and at the time of extraction of the implanted dosimeters, thus confirming the biocompatibility for each optical fiber cylinder dosimeter. As a result, the new dosimeters have excellent biocompatibility in living tissues and have 100% accurate reusability intensity of the delivered radiation doses compared to TLD_100 which demonstrated a 45% reduction in its intensity accuracy.
© 2024 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement
1. Introduction
Radiotherapy, employing ionizing radiation, is a cornerstone in cancer treatment, benefiting over 50% of cancer patients to enhance their prognoses [1]. The efficacy of radiation therapy relies on the accurate prediction and measurement of dose distribution throughout the irradiated volume. Thus, there is a growing need for novel, real-time, in-vivo radiation monitors capable of precisely assessing bodily radiation doses [2–4]. Ensuring accuracy and precision in both dosimetry and irradiation experiments is paramount, especially in animal model studies [5]. While dose verification methodologies in radiotherapy have garnered considerable attention and can be partly applied to animal studies, particularly in larger animals like non-human primates [6], challenges arise when employing external radiation monitors on smaller animals such as rats. This is particularly evident in scenarios where animals are allowed freedom of movement within the irradiator during prolonged irradiation sessions [7].
Radiation dosimetry encompasses the measurement of radiation exposure, including various high-energy sources such as X-rays and gamma rays [8–10]. Among the myriad methods available for observing radiation levels, silica-based optical fibers stand out as thermoluminescence dosimeters [11]. These fibers boast several advantages, including high resolution, immunity to electromagnetic fields, consistent and linear response across a wide dose range, and cost-effectiveness. Recent advancements indicate their potential for detecting ionizing radiation via radiation-induced absorption, luminescence, and alterations in refractive index [12,13]. Small scintillating Fiber-Optic Dosimeters (FODs) show promise for irradiation measurements in diverse applications, from medical to industrial settings. Unlike conventional dosimeters like TLD-100, multiple FODs can be accommodated within a single unit, enabling more precise and localized dose assessments [14]. Optical fiber dosimeters also excel in measuring high radiation doses without saturation or loss of sensitivity [14].
Several research groups are actively exploring the potential of fiber optics for sensing purposes. They explore the design and analysis of photonic crystal fiber (PCF)-based biosensors for medical applications. A PCF sensor with elliptically split cores is introduced for refractive index sensing of various analytes, including cancer-causing agents and biomolecules [15]. Other research [16] introduces a double D-shaped dual-core PCF sensor specifically tailored for detecting blood components like white blood cells (WBCs), hemoglobin (HB), and red blood cells (RBCs). Both sensors [15,16] leverage finite element method (FEM) simulations and demonstrate high sensitivities, indicating their potential for medical diagnostics and biochemical sensing applications. The thermoluminescence (TL) dosimetric responses of collapsed PCF are investigated for external beam radiotherapy [17], and their findings enhance silica optical fiber TL materials for accurate ionizing radiation dosimetry in radiotherapy.
Recent research [18] introduces a novel approach to radiation detection using ultra-low loss pure-silica core optical fiber (ULL-PSCF), that demonstrated high transient X-ray radiation-induced attenuation levels across UV to IR spectra. Pre-irradiation stabilizes and enhances the fiber's response, offering promise for dose rate monitoring with tunable sensitivity and linear RIA response.
Moreover, Alawiah et al. [19] investigated the suitability of pure silica optical fibers for radiation therapy dosimetry. Their findings demonstrated a linear response of these fibers within a relevant dose range, highlighting their potential for accurate dose measurements [19]. Furthermore, Noor et al. [20] demonstrated the efficacy of a commercially available TL Ge-doped silica fiber for 3D dose mapping in Intensity Modulated Radiation Therapy (IMRT) phantoms. The fiber accurately verified high and low-dose regions for both 6 MV and 15 MV photon energies, demonstrating good agreement with conventional LiF thermoluminescent dosimeters. Similarly, Issa et al. [21]explored the feasibility of Ge-doped silica fibers for brachytherapy source dosimetry. Their study highlighted the fiber's sub-millimeter spatial resolution, linear response across a wide dose range (10 Gy to >1 kGy), and dose-rate independence. The measured data aligned well with treatment planning system simulations and dose mapping.
These studies showcase the immense potential of FOD for advanced radiotherapy planning. Their unique combination of high spatial resolution, miniaturization, durability, and cost-effectiveness paves the way for more precise treatment delivery and improved patient outcomes. On the other hand, FOD has several limitations that require careful consideration and further investigation such as: signal fading in Ge-doped SiO2 fibers of approximately 20.4% within 30 days post-irradiation [22]. Furthermore, there are other limitations such as: the energy dependence, The effective atomic number; Standardization and Reproducibility; Complex Dose Response; Directional Dependence; and Limited Commercial Availability [22,23].
However, direct handling of FODs can pose challenges due to their minuscule size, potentially leading to missed samples during measurements. Implementing proper handling protocols is crucial to ensure accurate measurements and prevent contamination or sample loss. Our previous research [14] has explored various approaches to address this issue, thereby enhancing the accuracy of dosimetry measurements across different applications. Furthermore, strategically deploying FODs across various locations for radiation mapping and monitoring can offer invaluable insights for emergency response planning and occupational safety. Additionally, software-based tools simplify the estimation of absorbed doses, further streamlining dosimetry procedures.
This study is devoted to evaluating the efficiency of FOD in two ways: by evaluating the efficiency and sensitivity of those dosimeters for radiation doses and by studying their biocompatibility in living tissue in vivo. The results will be used in different biological applications on animal radiotherapy sessions to evaluate the dosage for confirming the real dose which reaches to target organ (Effective dose in addition to evaluating their tissue weighting factor. It is worthwhile to note that optical fiber dosimeter can be utilized for dose mapping. Consequently, the proposed FOD could be used in different applications such as the personal safety for diplomatic and military members in international meetings to follow up on their safety and confirm that there are no irradiation methods used with them and maybe developed to be real-time measurement to detect the risk on time.
2. Materials and methods
2.1 FOD technology
Figure 1 depicts an optical fiber dosimeter used for dose mapping. The diameter of each FOD is almost 1 mm, and targets different kinds of radiation sources in small exposed areas. Consequently, the proposed FOD could be used in different applications such as personal safety. FLIXCAT FlexHD1 FOD; it’s a glass (silica) optical fiber doped by Germanium, (Ge-doped SiO2) manufactured by Flexilicate company (Malaya University, Malaysia) for various TL applications that covers a wide range of doses with linear response [24]. The main advantage of silica optical fiber to be used as a TL dosimeter is its small size, especially in radiation therapy, non-sensitive to humidity, and water resistant which is a more important advantage for in-vivo measurements. Flexilicate [24] FODs, characterized by their cylindrical shape (FlexHD1), boasting an outer diameter (OD) of 995 µm, an inner diameter (ID) of 870 µm, and a length (L) of 5 mm for a dose range 1mGy up to ∼100Gy, were purposefully selected for their as they are suitable in for low-dose applications, utilized as a main dosimeter in the experiment. To ensure the dosimeter data's accuracy and reliability we applied the calibrated procedure as follows: all samples were annealed at 400°C for one hour then all of them were irradiated for 1 Gy and measured this step was repeated three times. After calibration, samples with less than 2% variation were selected. The samples were annealed at 400°C for one hour and then cooled to room temperature to erase previous TL signals and boost their response. The annealing oven (Ney Co., type 6-525, USA) was employed for thermal treatment. A cesium-137 (137Cs) source was used as the gamma irradiation source (γ-Cell-40 manufactured by Atomic Energy of Canada) with a dose rate of 5.8 m Gy/sec. This source is available at the National Centre for Radiation Research and Technology of Cairo (NCRRT). The thermoluminescence properties of our Fiber-Optic Dosimeter (FOD) samples were measured using the Thermo Scientific Harshaw 3500 TLD Reader (Thermo Scientific, Ohio, USA) [25,26]. This reader is controlled by the WinREMS operating system on a PC and is equipped with a nitrogen supply for cooling purposes. Each FOD sample underwent individual measurement on a 7 × 7 mm2 planchet within the TLD reader [26].
Fig. 1. Schematic diagram of an optical fiber dosimeter used for dose mapping: the holder contains 4 samples targeting different kinds of radiation.
The integration of FODs into animal models allows for precise and localized dose measurements, which are invaluable for preclinical investigations in radiation therapy. Additionally, FOD technology has the potential to transform radiation therapy with real-time dose feedback during treatment. In a comparative analysis, three cylindrical FOD dosimeters were surgically implanted at different points within an experimental rat's body and their results were compared with those obtained using standard TLD_100 dosimeters. The dosimeters were positioned on two FODs and one TLD at distinct anatomical locations including the head, the abdomen, and the tail. The purpose of this experiment was to evaluate the performance of FOD dosimeters in measuring radiation dosage to typical TLD_100 dosimeters. The significance of this experiment lies in evaluating the reliability and accuracy of FODs in comparison with conventional thermoluminescent dosimeters like TLD_100.
Subsequently, both FOD and TLD_100 samples were subjected to gamma radiation while implanted inside the rat's body and were measured after extraction. The difference in measurement between the actual irradiation dose and the reconstructed dose inside the animal’s body is that the dosimeter received the true dose directly without a barrier outside the animal’s body in the air, while the various tissues inside the animal’s body acted as a barrier that attenuates the radiation starting from its entrance point in the animal’s body until the location of dosimeter. This dose depends obviously on the thickness of the tissue, its type and the depth of the dosimeter from the surface of the body exposed to the radiation. To ensure accurate measurements and to limit the various sources of error, a pre-calibrated radioactive source was used. The samples outside the mouse’s body and those implanted inside it were also irradiated at the same moment. The rat was anaesthetized to ensure its immobility and that the same dose was taken in the same location. Furthermore, the results of these samples irradiated at the same dose before implantation (off-animal) were compared to verify the measurements. The analysis revealed that the intensity of TLD_100 decreased by 45% of its original value and was detected within the rat's body, while the intensity of the FOD remained unchanged and intact, as illustrated in Fig. 2. These findings underscore the superior accuracy of FODs compared to TLD_100 dosimeters. This study contributes to the understanding of biological effect parameters both inside and outside animal models.
Fig. 2. Comparisons of FOD and TLD_100 samples measured within and outside the rat's body after 1 hour of annealing at 400 °C and 2 Gy irradiation.
2.1.1 Kinetics analysis
The desired sample's glow curve structure reveals one notable peak, measured at a heating rate of 5°Cs-1 and composed of overlapping peaks, which is seen at about 493 K as illustrated in Fig. 3. Because its peaks overlap, the glow curve makes it challenging to determine the trap parameter. Because of this, we employ techniques to analyze kinetic parameters by separating their peaks. The kinetic parameters such as activation energy or the depth of trap, E(eV), position of peak temperature, TM(K), frequency factor, S(s-1), and b is the kinetic order of TL which play an important role in TL dosimetry, since these parameters are crucial for material properties and defects. It is worth noting the importance of the kinetic parameters when considering trapping phenomena, escape probability, and recombination of electrons through the trap and recombination centers before light emission [27]. The kinetic parameters of the TL glow curves are determined via a Computerized Glow Curve Deconvolution (CGCD) method to evaluate the kinetic parameters of the TL materials [27–30], such as activation energy, order of kinetics, the CGCD method can be applied [31]. The current study matches our previous research [14] concerning the TL properties of the FOD.
2.1.2 Deconvolution method:
The kinetic parameters of the glow curve are matched theoretically to the following relation derived by Kitis et al. [32] as:
The FOM of the fitted data is almost 1.78%, and the kinetic order for all the peaks is approximately a second-order kinetic (b ≈ 2) from the glow curve deconvolution. Table 1 summarizes the findings of the glow curve deconvolution analysis, which shows that, the activation energy of the six overlapping glow peaks occurs at 0.879, 0.717, 0.861, 1.168, 0.892, and 0.899 eV, respectively, with a corresponding frequency factor and order of kinetics.
Table 1. Trapping parameters of FOD for various glow peaks after γ irradiated 100 Gy using CGCD.
2.2 Animal preparation
Six Sprague Dawley male rats with 150 g body weight (10 weeks aged, 3 as normal control and 3 for implantation) were housed three days before surgery and implantation of the new radio-dosimeter under the skin at different three points. The rats were housed in a standard plastic cage separately and maintained in conditions of good ventilation, normal temperature, and humidity range. The rat was fed on standard pellets, containing all nutritive elements with 23% protein. Drinking water and food were provided ad libitum throughout the study. All the rats were irradiated with gamma rays by a single exposure to 2 Gy at a dose rate of 5.8 mGy /sec. using a 137Cs source (Gamma-cell-40 Exactor; NCRRT, EAEA, Cairo, Egypt) [35,36].
3. Experimentation
Three dosimeters (3 cylinders) were transplanted with three standards TLD_100 along the body of a rat after washing with Betadine (Povidone-iodine) for sterilization. The dosimeter insertion surgery was done in a septic condition and under general anesthesia using Thiopental sodium 50 mg/kg and Atropine 50 µg/kg injected intraperitoneally [35]. The dosimeters were transplanted aseptically subcutaneously by making three small incisions (ca. 4 mm) at three different spots on the same animal; namely, the neck, abdomen, and right femur, at each position. One sample of TLD_100 is placed with the cylindrical dosimeter for comparison purposes.
3.1 Surgical steps for dosimeters implantation
The small incisions were wide enough to allow for the transplantation of the tiny dosimeters (dimensions; 1* 0.5 ml). Right after the insertion, the incisions were closed using surgical sutures (two stitches, not dissolved), and the incisions were then cleaned aseptically. The surgical fields were then kept dry using surgical dressing. The animals remained under full medical care until the anesthesia wore off and recovery was complete as shown in Fig. 4. The next day, the wounds were sterilized and cleaned with Betadine (Povidone-iodine) after assuring the stability and existence of the stitches. On the third day after the operation, the stitches were sterilized.
Fig. 4. The diagram showed the surgical implantation of two fiber optical dosimeters (Ro and Ri symbol) and one standard (S symbol) sub-dermal layer of rat’s skin at three points: the neck A, abdomen B, and right femur C as shown in Fig. 4(e).
3.2. X-ray computed tomography (CT)
On the fourth day, one of the three animals is labeled for CT imaging to validate the existence of implants (dosimeters) as shown in Fig. 5, and this rat is not used in evaluating the absorbed dose to avoid any conflict between the Gamma irradiated dose and the CT dose. The animal was under complete anesthesia and the heart rate was checked. The rat is then covered with sterile surgical gowns and fixed on the CT table. The sagittal and axial sections were done to detect the dosimeters in vivo.
Fig. 5. X-ray computed tomography (CT) scans reveal the different points of the subdermal implantation of the radio-dosimeter. (A) the lateral view of the mouse before implantation; (B) the three points of implantation: B1 is at the neck region above the cervical vertebrae, B2 is right femur, and B3 is between the external oblique and abdominal midline abdomen; and (C) Three-dimensional rendered image showing the implants and indicated by red arrows. (D), (E) and (F) represent transversal images of the rat neck, abdomen, and right femur, respectively showing the implant in subdermal regions.
3.3 Whole body gamma irradiation
After seven days, the rat was then sent to the animal irradiation unit (Gamma cell – 137Cs), where it was placed under complete anesthesia in the whole-body gamma irradiation and was irradiated to 2Gy (dose rate 5.8 m Gy/sec.).
3.4 Dosimeter extraction
After being irradiated, the rat was subjected to another surgery to extract the implanted dosimeters after half an hour of irradiation. The dosimeters were then extracted, labeled as per their insertion site, and placed in protective capsules. The dosimeters were sent right back to the dosimetry lab for 1 h to assess their absorbed doses of gamma radiation as shown in Fig. 6. It is found that there aren’t any diffusion or edema in the point of implantation and there isn’t any type of abscess or necrosis in addition the animal skin doesn’t have any sign for inflammation, this indicates a good biological biocompatibility for those dosimeters. All extracted dosimeters were evaluated except those extracted from the rat exposed to CT dose to avoid the interference between radiation doses of the CT device and Gamma irradiation unit.
Fig. 6. Excellent healing of wounds after implantation without any sign of inflammation. (a), (b), and (c) represent the neck region, right femur, and abdomen, respectively; (d) represents the rat under anesthesia at the Gamma cell rack to prevent movement and avoid change in irradiation-ray direction; (e) represents the extraction of lithium fluoride standard; (f) represents the extraction of cylinder optical fiber; and (g) represents the ring optical fiber.
3.5 Sample collection for hematological assay
Blood samples were collected from the right eye by micro-hematocrit sodium-heparinized capillary tubes for complete blood count (CBC) assay [24,37,38] and at the end of the experiment, the blood samples were collected from the heart puncture after dosimeter extraction. Blood samples of around 200 µl of whole blood were taken on Ethylenediaminetetraacetic acid (EDTA) vacuum tubes.
3.6 Histopathological examination
The skin tissues were extracted from the surgery and non-surgery area of the same animal then fixed in 10% formalin saline for 24 h, washed in tap water, and followed for dehydration by serial dilutions of alcohol (methyl, ethyl, and absolute ethyl). Samples were embedded in paraffin after being cleared in xylene and at 56°C in a hot air oven for 24 h. By slides microtome, paraffin beeswax tissue blocks were prepared for sectioning at 4μ thickness. The obtained sections were collected on glass slides, deparaffinized, and stained using hematoxylin and eosin (H and E) for routine light electronic microscope examination [38]. Figure 7 shows the histopathological images for both normal skin and skin under radio dosimeter implantation at the implantation site. After imaging the sections, no edema or cell infiltration or inflammation in pathological sections have been detected, moreover the thickness of skin layers didn’t change, thus confirming the biocompatibility of the dosimeters in living tissue.
Fig. 7. Histopathological images for both: normal skin and skin of animals under radio dosimeter implantation at the site of implantation. Images from (a) to (c) show normal skin with normal thickness between the epidermal, dermal and subdermal sections. Images from (d) to (f) show the skin at the site of implantation, no oedema or inflammation at the site of implantation.
4. Results
4.1 Statistical analysis
All experiments were performed at least in triplicate and the results were expressed as the mean ± standard error (SEM). The software package (SPSS, 20, Inc., Chicago, IL) was used for statistical analysis. Statistical significance between all groups was analyzed by using the P < 0.001, P < 0.01 and P < 0.05. Statistical analysis were performed using Prism, version 7 (GraphPad Software, La Jolla, CA).
4.2 Morphological changes of the whole body and psychological behavior
There are no morphological changes in animals, in addition, the excellent healing of the surgery sits without any inflammations. The animals start feeding normally without any psychological observations or loss of appetite. The rat does not try to remove the stitches and there are no irritation symptoms on wounds from the third day.
4.3 Wound tissue morphology
There are no inflammation signs in wound tissue during dosimeter extraction, in addition after microscopic investigations there are no bus cells or bacterial and fungal infections, this proves a very good biocompatibility of those dosimeters with living tissue.
4.4 Blood and inflammatory markers
The mean value of the Hemoglobin before the surgery was 12.4 g/dL, and after dosimeter extraction, it was 12.5 g/dl, thus no significant changes (P value = 0.585); this confirms that there aren’t any immunological changes after dosimeter implantation, namely no induced Hemoglobin breakdown has been detected. Moreover, there aren’t any significant changes in the white blood cells (lymphocytes, granulocytes, MID) and platelets before implantation and after extraction of the dosimeters, this indicates good biocompatibility of the dosimeters. Note that MID refers to white blood cells not classified as lymphocytes or granulocytes. C-reactive protein (CRP) values before implantation and after extraction are: 5.8 ± 0.21 and 6.1 ± 0.25 respectively (P value = 0.667), this indicates the absence of inflammation and contamination. Table 2 indicates an increase in white blood cells (lymphocytes low, granulocytes high, MID low) with platelets, as well as an increase in markers of inflammation after the insertion of dosimeters in rats. The results also showed a decrease in the levels of white blood cells (lymphocytes high, granulocytes low, MID high), and inflammation markers as well as a decrease in the levels of platelets before the extraction of dosimeters from rats to normal levels before surgery. Also, there is no significant alteration in histopathological parameters as shown in Fig. 7.
Table 2. Hematological indices and CRP before, after insertion, and before extraction of dosimeters.
5. Discussion
Biocompatibility is the crucial requirement for the clinical use in radiodosometers. It refers to the ability of a biomaterial to perform its function without eliciting toxic or injurious effects on biological systems, but producing an appropriate host response in a specific case. Today, the biocompatibility concept includes not only bio-inertia, but also bio-functionality and biostability [39,40]. High biocompatibility and functional properties are highly desirable for new biomaterials. The structural, chemical, mechanical properties of biomaterials, their interaction with biological-environment or even the methodology of assessment can influence the biocompatibility [39–41]. The biological evaluation of biomaterials includes a broad spectrum of in vitro and in vivo tests related to the cytocompatibility, genotoxicity, sensitization, irritation, acute and chronic toxicity, hemocompatibility, reproductive and developmental toxicity, carcinogenicity, implantation, and degradation as specified in different international standards. A brief review of the main assays used in the biocompatibility testing of orthopedic biomaterials is presented. In addition, their main biocompatibility issues are overviewed [39,40].
Using the FOD as a new dosimeter especially in biological systems in vivo required biocompatibility studies to evaluate their real tissue interaction in vivo, in addition to their impact on inflammatory markers in the blood. The current study started with the surgical operation of 3 cylinders’ format FOD implantation, in addition to the three standards TLD_100, where points were used in vivo (behind the neck, right femur, and abdomen point). For implant validation, a Magnetic Resonance imaging (MRI) was performed to detect the dosimeters in three points all over the animal’s body. MRI shows the implants (dosimeters) in the three points without oedema and/or inflammation; in addition, there isn’t cell infiltration that confirms the sterility and biocompatibility of dosimeters. The MRI didn't reveal any abscess or water at the point of implantation that can be detected by T2 weighted MR sequences; where in case of inflammation, the immune system is activated and characterized by a high water content and can be viewed in MRI [42,43]. The validation of implantation surgery and the sterility processes taken by MR imaging shows the insertion of dosimeters in three points without any type of edema or cell infiltration, this confirms that there is no inflammation, since in case of inflammation, the immune system is activated and thus high water content would be detected by T2 weighted MR sequences as free water shows hyperintense indicating on the biocompatible of FOD in vivo [42,43].
The biocompatibility of the dosimeters was investigated in vivo. A subcutaneous implantation model was utilized using Sprague-Dawley rats to detect preliminary in-vivo biocompatibility. Dosimeters were implanted for 7 days followed by histological preparation and staining. H&E staining was used to characterize oedema, cell infiltration, fibrotic capsule formation, and changes in skin dimensions. The material system of the current FOD would be biocompatible because the individual components have been reported to be biocompatible as previously reported by Elsharkawi et al. [14] and Guo et al. [44].
H&E staining is a conventional and practical method to assess tissue changes, cell infiltration and oedema formation. Histopathological changes for both normal skin and skin of animals under radio dosimeter implantation at the site of implantation show normal thickness between the epidermal, dermal, and sub-dermal sections without any type of oedema or inflammation sign at the site of implant, confirming the biocompatibility for each cylinder dosimeter of optical fibers.
Hematological parameters are invaluable indicators for assessing changes in the immune system. Therefore, CBC and CRP values were meticulously evaluated to gauge inflammation and ascertain the biocompatibility status. The CBC, a widely utilized diagnostic tool, is particularly recommended during the initial stages of infectious diseases to identify potential pathological complications such as anemia, thrombocytopenia, bleeding disorders, and thrombosis. Moreover, analyzing blood cell subtype ratios, including WBC count, lymphocyte (L) count, platelet-lymphocyte ratio (PLR), and red blood cell distribution width (RDW), offers valuable prognostic and diagnostic insights into various diseases. Notably, PLR has emerged as a significant marker of chronic inflammation, serving as both a thrombosis and inflammation biomarker. The results of the CBC analysis underscore the outstanding biocompatibility of our FOD implants. There were no significant differences observed in CBC parameters before and after extraction, including all inflammatory markers such as white blood cell counts (lymphocytes, granulocytes, MID). Additionally, the stability of hemoglobin levels post-extraction serves as a testament to the quality and efficiency of the implantation surgery, indicating the absence of bleeding or adverse reactions related to the implanted materials.
Radiotherapy (RT) using ultra-high dose rate (UHDR) radiation, has shown promising results in reducing normal tissue toxicity while maintaining tumor control. However, implementing FLASH RT in clinical settings presents technical challenges, including limited depth penetration and complex treatment planning [45]. Accurate dosimetry is essential for RT, and radiation detectors play a crucial role in measuring dose delivery. In conclusion, FOD simulation provides accurate dose calculation and optimization for RT determination, while radiation detectors, including ionization chambers, and radio chromic films, offer valuable tools for dosimetry in UHDR environments [14,45]. Further research is needed to refine treatment planning techniques and improve detector performance to facilitate the widespread implementation of RT, potentially revolutionizing cancer treatment [14,45].
FODs are a novel technology with significant potential for measuring radiation exposure, particularly in biological environments. Their advantages over traditional methods include miniaturization: Unlike bulky traditional dosimeters (e.g., TLDs), FODs are thin and flexible due to their fiber optic construction. This miniaturized size makes them ideal for implantation into small animals, enabling in-vivo measurements of radiation dose distribution throughout the body. FODs can be designed for various functionalities. They can provide real-time data on radiation exposure, crucial for treatment monitoring in radiotherapy, or be designed for later analysis in research settings. The small diameter of the optical fiber allows for highly precise measurements of radiation dose within a small area. This is essential for detailed mapping of dose distribution within complex biological systems.
Besides, FODs potentially offer further benefits which are their Immunity to electromagnetic interference, ensuring accurate readings, the wider dose range detection without saturation which allows for a broader range of applications, and their proven biocompatibility for safe implantation within living organisms.
The unique properties of FODs hold promise for significant advancements in radiation dosimetry, particularly in biological environments. Their potential for in-vivo measurements, real-time monitoring, and high spatial resolution can revolutionize various fields. FODs can provide crucial data for understanding the biological effects of radiation exposure in animal research which improves the in-vivo dosimetry. Real-time monitoring with FODs can lead to more precise radiotherapy techniques, minimizing damage to healthy tissue. On the other hand, FOD technology has the potential to be adapted for comfortable and potentially more sensitive wearable personal dosimeters.
6. Conclusion
In this study, we employed the FLIXCAT FlexHD1 Fiber-Optic Dosimeter (FOD) irradiated by a 137Cs γ-rays irradiator, revealing a discrepancy of up to 61% between the actual irradiated dose and the reconstructed dose inside animals, underscoring the importance of precise dose estimation for effective radiation management. Biocompatibility assessments affirmed the excellent compatibility of FOD materials within living tissue, with no significant changes observed in skin layers or blood parameters, indicating their safety for in-vivo applications.
Our results underscore the potential of the novel FOD in accurately measuring effective radiation doses for various organs in vivo, without inducing adverse effects. Furthermore, the versatile nature of FODs suggests promising applications in security, enabling regular health monitoring for radiation exposure, particularly in high-risk contexts. Future research will focus on extending these findings to assess effective doses in different organs of live animals and compare them with numerically calculated doses using simulation methods like the Monte Carlo method.
Funding
National Science and Technology Council (NTSC), Taiwan (number: NSTC 112-2811-E-006-047).
Acknowledgements
The authors would like to extend their sincere gratitude to Flexilicate, Malaya University, Malysia, for their invaluable support and provision of materials essential for the successful completion of this study.
Author Contributions. A. S. A. Elsharkawi, and A. Arafa conceptualization, formal analysis, H. Alazab investigation, writing–original draft, M. Asker, I. Yousef biological work, Y. L. LO and L. R. Gomaa Conceptualization, formal analysis, investigation, review, and editing.
Ethics Approval. The in vivo study was approved by the research ethics committee for experimental studies (Human and Animal subjects) at NCRRT, EAEA, (Cairo, Egypt), following the 3Rs principle for animal experimentation (Replace, Reduce, and Refine) and is organized and operated according to the Council for International Organizations of Medical Sciences and the International Council for Laboratory Animal Science International Guiding Principles for Biomedical Research Involving Animals 2012 (serial number:58A/23).
Consent to Participate. No requirement for informed consent for this study.
Consent to Publish. Not applicable.
Disclosures
The authors declare that they have no conflicts of interest.
Data availability
All data generated or analyzed during this study are included in this manuscript.
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