Thermal Ablation Of Tumors Research Articles

Early Clinical Feasibility Evaluation of an Augmented Reality Platform for Guidance and Navigation during Percutaneous Tumor Ablation

An augmented reality platform with a head-mounted display and electromagnetic tracking of instruments was developed for percutaneous procedural guidance. Earlier work had demonstrated bench and first-in-human feasibility of the platform. This report further evaluated the clinical usability and benefits of this technology. The platform was used in 12 patients who had been referred for percutaneous thermal ablation of abdominal soft tissue tumors. In 10 cases, the intraprocedural holographic guidance agreed with the standard imaging guidance. The evaluation was limited in 2 cases because of anatomic and workflow issues. Overall, this series demonstrated the clinical feasibility of this platform and the potential benefits of its use in percutaneous procedures.

Thermal shielding performance of self-healing hydrogel in tumor thermal ablation

Thermal ablation therapy is widely used in the surgical treatment of tumors. Clinically, normal saline is generally used as an insulator to protect adjacent tissues from local high-temperature burns caused by thermal ablation. However, the flow of saline causes fluid loss, requiring frequent injections and complex operation, which is easy to lead to complications such as secondary injury and hematoma. Here, a self-healing chitosan-PEG (CP) hydrogel was proposed as a protective medium to challenge the clinical preparations. Compared with saline and non-self-healing hydrogel F127, CP hydrogel exhibited outstanding thermal shielding performance in the thermal ablation of thyroid nodule in a Beagle dog model. The transient plane source (TPS) method is used to measure thermal properties, including thermal conductivity, thermal diffusivity and specific heat capacity. The thermal shielding mechanism and clinical advantages including operability, biodegradability, and biological safety of self-healing hydrogel are then revealed in-depth. Therefore, self-healing hydrogel can achieve much better thermal management in tumor thermal ablation.

Analysis of Coil Configurations for a Contactless Thermal Tumor Ablation With Implanted Devices.

In the wide field of tumor treatment, thermal ablation procedures are very promising. Alternating magnetic fields are used to transfer the energy from outside the patient to the tumor area located anywhere in the body. This energy is converted to heat by implanted devices located in the tumor area. In this paper, the spatial distribution of the magnetic field of different circular coil configurations is analyzed and optimized with focus on patients' safety and on coil configuration performance. The analysis is based on several performance criteria and is conducted with respect to the worst case scenario of a contactless thermal tumor ablation of deep-seated tumors, in which the energy has to be transferred over a considerably large distance. The magnetic field and the specific absorption rate (SAR) are calculated numerically and the performance criteria are evaluated based on a model of a human body including a tumor area. The most suitable coil configurations for different application scenarios are presented and a thermal analysis is done. Based on this, the minimum required heating power, coil current and number of coil windings, and the corresponding maximum SAR to achieve an adequate rise of tissue temperature are evaluated. For a heating power of 1.45 W, a minimum SAR of 130 mW/kg, a maximum power transfer efficiency of 1.05%, and a maximum coupling coefficient of 0.00695 is achieved. This paper shows the potential to enhance the safety of the patients significantly by choosing the appropriate coil configuration for a specific application scenario.

A New Thermal Damage-Controlled Protocol for Thermal Ablation Modeled with Modified Porous Media-Based Bioheat Equation with Variable Porosity

Thermal ablation of tumors is a minimally invasive technique more and more employed in cancer treatments. The main shortcomings of this technique are, on the one hand, the risk of an incomplete ablation, and on the other hand, the destruction of the surrounding healthy tissue. In this work, thermal ablation of a spherical hepatocellular carcinoma tumor (HCC) surrounded by healthy tissue is modeled. A modified porous media-based bioheat model is employed, including porosity variability from tumor core to healthy tissue, following experimental in vivo measures. Moreover, three different protocols are investigated: a constant heating protocol, a pulsating protocol, and a new developed damage-controlled protocol. The proposed damage-controlled protocol changes the heating source from constant to pulsating according to the thermal damage probability on the tumor rim. The equations are numerically solved by means of the commercial software COMSOL Multiphysics, and the outcomes show that the new proposed protocol is able to achieve the complete ablation in less time than the completely pulsating protocol, and to reach tissue temperature on the tumor rim 10 °C smaller than the constant protocol. These results are relevant to develop and improve different patient-based and automated protocols which can be embedded in medical devices’ software or in mobile applications, supporting medical staff with innovative technical solutions.

Methods of monitoring thermal ablation of soft tissue tumors - A comprehensive review.

Thermal ablation is a form of hyperthermia in which oncologic control can be achieved by briefly inducing elevated temperatures, typically in the range 50-80°C, within a target tissue. Ablation modalities include high intensity focused ultrasound, radiofrequency ablation, microwave ablation, and laser interstitial thermal therapy which are all capable of generating confined zones of tissue destruction, resulting in fewer complications than conventional cancer therapies. Oncologic control is contingent upon achieving predefined coagulation zones; therefore, intraoperative assessment of treatment progress is highly desirable. Consequently, there is a growing interest in the development of ablation monitoring modalities. The first section of this review presents the mechanism of action and common applications of the primary ablation modalities. The following section outlines the state-of-the-art in thermal dosimetry which includes interstitial thermal probes and radiologic imaging. Both the physical mechanism of measurement and clinical or pre-clinical performance are discussed for each ablation modality. Thermal dosimetry must be coupled with a thermal damage model as outlined in Section 4. These models estimate cell death based on temperature-time history and are inherently tissue specific. In the absence of a reliable thermal model, the utility of thermal monitoring is greatly reduced. The final section of this review paper covers technologies that have been developed to directly assess tissue conditions. These approaches include visualization of non-perfused tissue with contrast-enhanced imaging, assessment of tissue mechanical properties using ultrasound and magnetic resonance elastography, and finally interrogation of tissue optical properties with interstitial probes. In summary, monitoring thermal ablation is critical for consistent clinical success and many promising technologies are under development but an optimal solution has yet to achieve widespread adoption.

HIGH-INTENSITY FOCUSED ULTRASOUND (HIFU) ENERGIZED NANOPARTICLES-MEDIATED ENHANCED THERMAL ABLATION OF TUMORS: REVIEW OF RECENT PROGRESS AND A PROPOSED METHODOLOGY FOR DISTINGUISHING HEAT SOURCES

HIGH-INTENSITY FOCUSED ULTRASOUND (HIFU) ENERGIZED NANOPARTICLES-MEDIATED ENHANCED THERMAL ABLATION OF TUMORS: REVIEW OF RECENT PROGRESS AND A PROPOSED METHODOLOGY FOR DISTINGUISHING HEAT SOURCES

Versatile multi-constrained planning for thermal ablation of large liver tumors.

The surgical planning of large hepatic tumor ablation remains a challenging task that relies on fulfilling multiple medical constraints, especially for the ablation based on configurations of multiple electrodes. The placement of the electrodes to completely ablate the tumor as well as their insertion trajectory to their final position have to be planned to cause as little damage to healthy anatomical structures as possible to allow a fast rehabilitation. In this paper, we present a novel, versatile approach for the computer-assisted planning of multi-electrode thermal ablation of large liver tumors based on pre-operative CT data with semantic annotations. This involves both the specification of the number of required electrodes and their distribution to adequately ablate the tumor region without damaging too much healthy tissue. To determine the insertion trajectory of the electrodes to their final position, we additionally incorporate a series of medical constraints into our optimization, which allows a global analysis where obstacles such as bones are taken into account and damage to healthy tissue is mitigated. Compared with the state-of-the-art method, our method achieves compact ablation regions without relying on assumptions on a potential needle path for optimal global search and, hence, is suitable for guiding clinicians through the planning of the tumor ablation. We also demonstrate the feasibility of our approach in various experiments of clinical data and demonstrate that our approach not only allows completely ablating the tumor region but also reducing the damage of healthy tissue in comparison to the previous state-of-the-art method.

Clinical practice guidelines:image-guided thermal ablation of primary and metastatic lung tumors (2021 edition)

Image-guided thermal ablation (IGTA) has been applied in the treatment of primary and metastatic lung tumors, and the number of patients treated is increasing rapidly every year. The Ablation Expert Committee of the Chinese Society of Clinical Oncology, the Expert Group on Tumor Ablation Therapy of the Chinese Medical Doctors Association, the Tumor Ablation Committee of the Chinese College of Interventionalists, and the Society of Tumor Ablation Therapy of the Chinese Anti-Cancer Association provided the platform for multidisciplinary experts to formulate the"Clinical Practice Guidelines:Image-Guided Thermal Ablation of Primary and Metastatic Lung Tumors (2021 Edition)". The main contents of the Clinical Practice Guidelines include: (1)epidemiology of primary and metastatic lung tumors; (2) IGTA concepts and common technical features; (3) procedures, indications, contraindications, outcomes evaluation, and related complications of IGTA for primary and metastatic lung tumors.

Injectable and Biodegradable Chitosan Hydrogel-Based Drug Depot Contributes to Synergistic Treatment of Tumors.

Combined therapy provides a more effective method in the treatment of tumors and becomes a research hotspot. To improve treatment outcomes and reduce serious side effects, hydrogel-based local delivery was developed herein to form a drug depot in suit to eliminate tumors. Indocyanine green and imiquimod were coencapsulated in the novel temperature-sensitive chitosan hydrogel. After intratumoral injection of the hydrogel, indocyanine green that accumulated in the tumor area could induce thermal ablation of primary tumors under laser irradiation. In the presence of imiquimod, the immune effects increased the probability of complete ablation of primary tumors and inhibition of metastases. Combined with cyclophosphamide, the enhanced immunological responses would further inhibit tumors and prolong the survival time. In a word, this work offered an excellent local delivery platform that enabled a remarkable combined antitumor strategy and achieved synergistic therapeutic effects.

3D Quantitative Ablation Margins for Prediction of Ablation Site Recurrence After Stereotactic Image-Guided Microwave Ablation of Colorectal Liver Metastases: A Multicenter Study.

BackgroundThree-dimensional (3D) volumetric ablation margin assessment after thermal ablation of liver tumors using software has been described, but its predictive value on treatment efficacy when accounting for other factors known to correlate ablation site recurrence (ASR) remains unknown.PurposeTo investigate 3D quantitative ablation margins (3D-QAMs) as an algorithm to predict ASR within 1 year after stereotactic microwave ablation (SMWA) for colorectal liver metastases (CRLM).Materials and MethodsSixty-five tumors in 47 patients from a prospective multicenter study of patients undergoing SMWA for CRLM were included in this retrospective 3D-QAM analysis. Using a previously developed algorithm, 3D-QAM defined as the distribution of tumor to ablation surface distances was assessed in co-registered pre- and post-ablation CT scans. The discriminatory power and optimal cutoff values for 3D-QAM were assessed using receiver operating characteristic (ROC) curves. Multivariable logistic regression analysis using generalized estimating equations was applied to investigate the impact of various 3D-QAM outputs on 1-year ASR while accounting for other known influencing factors.ResultsTen of the 65 (15.4%) tumors included for 3D-QAM analysis developed ASR. ROC analyses identified i) 3D-QAM <1 mm for >23% of the tumor surface, ii) 3D-QAM <5 mm for >45%, and iii) the minimal ablation margin (MAM) as the 3D-QAM outputs with optimal discriminatory qualities. The multivariable regression model without 3D-QAM yielded tumor diameter and KRAS mutation as 1-year ASR predictors. When adding 3D-QAM, this factor became the main predictor of 1-year ASR [odds ratio (OR) 21.67 (CI 2.48, 165.21) if defined as >23% <1 mm; OR 0.52 (CI 0.29, 0.95) if defined as MAM].Conclusions3D-QAM allows objectifiable and standardized assessment of tumor coverage by the ablation zone after SMWA. Our data shows that 3D-QAM represents the most important factor predicting ASR within 1 year after SMWA of CRLM.

Numerical Study of Bubble Cloud and Thermal Lesion Evolution During Acoustic Droplet Vaporization Enhanced HIFU Treatment.

Acoustic droplet vaporization (ADV) has been proven to enhance high intensity focused ultrasound (HIFU) thermal ablation of tumor. It has also been demonstrated that triggering droplets before HIFU exposure could be a potential way to control both the size and the shape of the thermal lesion. In this paper, a numerical model is proposed to predict the thermal lesion created in ADV enhanced HIFU treatment. Bubble oscillation was coupled into a viscoelastic medium in the model to more closely represent real applications in tissues. Several physical processes caused by continuous wave ultrasound and elevated temperature during the HIFU exposure were considered, including rectified diffusion, gas solubility variation with temperature in the medium, and boiling. Four droplet concentrations spanning two orders of magnitude were calculated. The bubble cloud formed from triggering of the droplets by the pulse wave ultrasound, along with the evolution of the shape and location of the bubble cloud and thermal lesion during the following continuous wave exposure was obtained. The increase of bubble void fraction caused by continuous wave exposure was found to be consistent with the experimental observation. With the increase of droplet concentration, the predicted bubble cloud shapes vary from tadpole to triangular and double triangular, while the thermal lesions move toward the transducer. The results show that the assumptions used in this model increased the accuracy of the results. This model may be used for parametrical study of ADV enhanced HIFU treatment and be further used for treatment planning and optimization in the future.

Abstract 25 - Percutaneous thermal ablation of small renal tumours: A single centre experience

Abstract 25 - Percutaneous thermal ablation of small renal tumours: A single centre experience

On the Design of a Microwave Imaging System to Monitor Thermal Ablation of Liver Tumors

Thermal ablation treatment of cancer is increasingly adopted in the clinical practice, being minimally invasive and highly specific. However, a significant drawback of the technique is the lack of effective imaging modalities for monitoring the changes undergoing in the thermally treated tissue. In this respect, microwave imaging has been proposed as a possible candidate, owing to its portability, low-cost, non-ionizing nature, and capability to detect changes in dielectric properties of tissues induced by the temperature. The goal of this paper is to provide the guidelines for the design of a microwave imaging system for thermal ablation monitoring of liver tumors. To this end, an analytical study is performed to determine the proper working conditions, in terms of frequency band and matching medium. Then, three antipodal Vivaldi antennas on different dielectric substrates are designed and numerically assessed. Among those antennas, the Vivaldi antenna on RT/duroid 6010LM substrate proved to be the most suitable choice. The results of this study pave the way to an experimental assessment of microwave imaging as a modality to monitor thermal ablation treatments.

Second Near-Infrared Light-Activatable Polymeric Nanoantagonist for Photothermal Immunometabolic Cancer Therapy.

Immunometabolic modulation offers new opportunities to treat cancers as it is highly associated with cancer progression and immunosuppressive microenvironment. However, traditional regimens using nonselective small-molecule immunomodulators lead to the off-target adverse effects and insufficient therapeutic outcomes. Herein a second near-infrared (NIR-II) photothermally activatable semiconducting polymeric nanoantagonist (ASPA) for synergistic photothermal immunometabolic therapy of cancer is reported. ASPA backbone is obtained by conjugating vipadenant, an antagonist to adenosine A2A receptor, onto NIR-II light-absorbing semiconducting polymer via an azo-based thermolabile linker. Under deep-penetrating NIR-II photoirradiation, ASPA induces tumor thermal ablation and subsequently immunogenic cell death, triggers the cleavage of thermolabile linker, and releases the antagonist to block the immunosuppressive adenosinergic pathway. Such a remotely controlled immunometabolic regulation potentiates cytotoxic T cell functions while suppresses regulatory T cell activities, leading to efficient primary tumor inhibition, pulmonary metastasis prevention, and long-term immunological memory. Thereby, this work provides a generic polymeric approach for precise spatiotemporal regulation of cancer immunometabolism.

Combined utility of one lung ventilation and artificial pneumothorax in thermal ablation of hepatic dome tumor: a technical note.

Radiofrequency ablation and microwave ablation are established treatment modalities for smaller (<3 cm) or isolated hepatic tumors. Transthoracic ablation of hepatic dome lesions is a well described technique. We report the use of one lung ventilation to facilitate the successful percutaneous transthoracic microwave ablation of a segment 8 hepatic dome lesion after induction of artificial pneumothorax. This involved the use of general anesthesia and insertion of a double lumen endotracheal tube to allow isolated ventilation of one lung, followed by creation of an artificial pneumothorax under computed tomography (CT) guidance. Complete ablation of the lesion was confirmed on CT liver at 1 and 7 months with no local recurrence. The combined techniques of one lung ventilation and artificial pneumothorax enabled a safe and accurate transthoracic targeting of the hepatic dome lesion.

Hepatic Hilar Nerve Block for Hepatic Interventions: Anatomy, Technique, and Initial Clinical Experience in Thermal Ablation of Liver Tumors.

Background Image-guided procedures for treatment of liver diseases can be painful and require heavy sedation of the patient. Local-regional nerve blocks improve pain control and reduce oversedation risks, but there are no documented liver-specific nerve blocks. Purpose To develop a safe and technically simple liver-specific nerve block. Materials and Methods Between March 2017 and October 2019, three cadavers were dissected to evaluate the hepatic hilar anatomy. The hepatic hilar nerves were targeted with transhepatic placement of a needle adjacent to the main portal vein, under US guidance, and evaluated with use of an injection of methylene blue. A hepatic nerve block, using similar technique and 0.25% bupivacaine, was offered to patients undergoing liver tumoral ablation. In a prospective pilot study, 12 patients who received the nerve block were compared with a control group regarding complications, safety, pain scores, and intraoperative opioid requirement. Student t tests were used to compare the groups' characteristics, and Mann-Whitney U tests were used for the measured outcomes. Results Cadaver results confirmed that the hepatic nerves coursing in the hepatic hilum can be targeted with US for injection of anesthetic agents, with adequate spread of injected methylene blue around the nerves in the hepatic hilar perivascular space. The 12 participants (mean age ± standard deviation, 66 years ± 13; eight men) who received a hepatic hilar block before liver thermal ablations demonstrated reduced pain compared with a control group of 12 participants (mean age, 63 years ± 15; eight men) who received only intravenous sedation. Participants who received the nerve block had a lower mean visual analog scale score for pain than the control group (3.9 ± 2.4 vs 7.0 ± 2.8, respectively; P = .01) and decreased need for intraprocedural fentanyl (mean dose, 152 μg ± 78.0 vs 235.4 μg ± 58.2, respectively; P = .01). No major complications occurred in the hepatic hilar nerve block group. Conclusion A dedicated hepatic hilar nerve block with 0.25% bupivacaine can be safely performed to provide anesthesia during liver tumoral ablation. © RSNA, 2021.

Stereotactic Thermal Ablation of Liver Tumors: 3D Planning, Multiple Needle Approach, and Intraprocedural Image Fusion Are the Key to Success—A Narrative Review

Simple SummaryThermal ablation is a minimally invasive, potentially curative approach for the treatment of primary and secondary liver tumors. Different technologies are available, with radiofrequency ablation (RFA) and microwave ablation (MWA) being the most widely used. Both methods induce an irreverible destruction of the tumor tissue by applying thermal energy. Conventionally, a single ablation probe is placed using ultrasound (US) or computed tomography (CT). Using these standard guidance techniques the creation of necrosis zones to treat large tumors (i.e., >2–3 cm) is hampered by technical limitations. These limitations can be overcome by stereotactic thermal ablation: a multiple needle approach with 3D treatment planning and precise stereotactic needle placement combined with immediate verification of treatment success by means of image fusion. The stereotactic multi-needle technique allows for local curative treatment of multiple and large tumors within a single session. Ultimately, due to the application of these sophisticated tools and advanced techniques, a local curative treatment option can be offered to a higher number of patients suffering of primary and secondary liver tumors. This article provides an overview of the current stereotactic techniques for thermal ablation and summarizes the available clinical evidence for this approach.Thermal ablation is an emerging, potentially curative approach in treating primary and metastatic liver cancer. Different technologies are available, with radiofrequency ablation (RFA) and microwave ablation (MWA) being the most widely used. Regardless of the technique, destruction of the entire tumor, including an adequate safety margin, is key. In conventional single-probe US- or CT-guided thermal ablation, the creation of such large necrosis zones is often hampered by technical limitations, especially for large tumors (i.e., >2–3 cm). These limitations have been overcome by stereotactic RFA (SRFA): a multiple needle approach with 3D treatment planning and precise stereotactic needle placement combined with intraprocedural image fusion of pre- and post-interventional CT scans for verification of treatment success. With these sophisticated tools and advanced techniques, the spectrum of locally curable liver malignancies can be dramatically increased. Thus, we strongly believe that stereotactic thermal ablation can become a cornerstone in the treatment of liver malignancies, as it offers all the benefits of a minimally invasive method while providing oncological outcomes comparable to surgery. This article provides an overview of current stereotactic techniques for thermal ablation, summarizes the available clinical evidence for this approach, and discusses its advantages.

An Acceptor-π-Donor Structured Organic Chromophore for NIR Triggered Thermal Ablation of Tumor via DNA Damage-Mediated Apoptosis.

IntroductionIt will be challenging to develop high-performance organic chromophores for light-triggered thermal ablation of the tumor. Besides, the mechanisms of organic chromophores for tumor therapy remain unclear. Herein, an acceptor-π-donor (A-π-D) structured organic chromophore based on 2-dicyanomethylenethiazole named PTM was developed for photothermal therapy (PTT) of tumors.Methods and ResultsBiocompatible PTM nanoparticles (PTM NPs) were fabricated by enclosing PTM with Pluronic F-127. The results of optical and photothermal properties of PTM NPs showed robust near-infrared (NIR) absorption, excellent photostability and high photothermal conversion efficiency (56.9%). The results of flow cytometry, fluorescence microscopy, apoptosis, CCK-8 assays and animal experiments showed that PTM NPs had a good killing effect on tumors under NIR laser irradiation. Furthermore, mechanistic studies, RNA-seq and biological analysis revealed that PTM NPs can cause tumor cell death via DNA damage-mediated apoptosis.ConclusionLight-induced thermal ablation effects of PTM NPs in vitro and vivo were surveyed. Collectively, our studies provided a new approach to developing a safe and effective photothermal agent for cancer treatment.

The Role of Conventional and Stereotactic Microwave Ablation for Intrahepatic Cholangiocarcinoma.

Background: The incidence and mortality of intrahepatic cholangiocarcinoma (ICCA) is increasing worldwide and curative treatment options are limited due to the aggressive tumor biology and often late diagnosis. Resection of the primary tumor remains the only curative therapy available, as the benefit of palliative chemotherapy and radiotherapy is relatively small. In contrast to hepatocellular carcinoma, minimal-invasive thermal tumor ablation, and in particular stereotactic tumor ablation for small primary cancers or metastases, is not established and data are scarce. Methods: We conducted a literature review in the field of ICCA ablation and retrospective analysis of 10 patients treated by stereotactic microwave ablation (SMWA) for either primary ICCA or liver metastases of ICCA. Results: While current guidelines have no consensus for ablation of primary ICCA, some state that it might be an option in inoperable patients or those with recurrent disease. The literature review revealed 11 studies on microwave ablation for ICCA reporting that MWA for ICCA ≤ 5 cm might be safe and could be a treatment option for patients who are not candidates for surgery. No data has been published on stereotactic microwave ablation (SMWA) for ICCA. The analyses of our own data of 10 patients treated by SMWA for primary ICCA (n = 5) or recurrent ICCA (n = 5) show that the treatment is safe and efficient with short hospital stays and low complication rates. Conclusion: Although thermal ablation, and in particular SMWA, might be a minimally invasive and tissue-sparing curative treatment alternative for small ICCA in the diseased liver and ICCA metastases, the oncologic benefit still needs to be shown in larger studies with longer follow-up.

Preparation of multifunctional polyvinyl alcohol microspheres by electrospinning and its properties and application

In this paper, MnO2-polydopamine (PDA)/polyvinyl alcohol (PVA) and MnO2-PVA-5-fluorouracil (5-Fu)/PVA composite microspheres were prepared by electrospinning. Specifically, dopamine (DA) and KMnO4 were added to the PVA solution, where a redox reaction happened between DA and KMnO4 to form PDA and MnO2. Thus, the MnO2-PDA/PVA microspheres were prepared by electrospinning the MnO2-PDA/PVA solution. MnO2-PDA-5-Fu/PVA microspheres were prepared by electrospinning the MnO2-PDA-5-Fu/PVA solution, which was prepared by directly dissolving 5-Fu in the MnO2-PDA/PVA solution. The water stability of the electrospun microspheres was given by a glutaraldehyde crosslinking method. The composite microspheres have excellent photothermal conversion, controlled drug release and good biosafety, which were used to prevent the recurrence of tumor after the operation. The photothermal conversion efficiency of MnO2-PDA-5-Fu/PVA microspheres reaches 24.5% under the irradiation of 808 nm NIR laser, which can achieve the efficient tumor thermal ablation; on the other hand, the released 5-Fu can kill the residual tumor cells after operation. This study confirms the application potential of the microspheres in the field of preventing tumor recurrence, and provides a new strategy for the design of multifunctional composite nanomaterials.