Maher Salloum

Controlling nanoparticle delivery in magnetic nanoparticle hyperthermia for cancer treatment: Experimental study in agarose gel

In magnetic nanoparticle hyperthermia for cancer treatment, controlling the heat distribution and temperature elevations is an immense challenge in clinical applications. In this study we evaluate magnetic nanofluid transport and heat distribution induced by commercially available magnetic nanoparticles injected into the extracellular space of biological tissue using agarose gel with porous structures similar to human tissue. The nanofluid distribution in the gel is examined via digital images of the nanofluid spreading in the gel. A radio-frequency electromagnetic field is applied to the gel following the nanofluid injection and the initial rates of temperature rise at various locations are measured to obtain the specific absorption rate (SAR) distribution. By adjusting the gel concentration and injection flow rate, the results have demonstrated that a relatively low injection rate leads to a spherically shaped nanofluid distribution in the gels which is desirable for controlling temperature elevations. The SAR distribution shows that the nanoparticle distribution in the gel is not uniform with a high concentration of the nanoparticles close to the injection site. We believe that the experimental study is the first step towards providing guidance for designing better treatment protocol for future clinical applications.

Enhancement in treatment planning for magnetic nanoparticle hyperthermia: Optimization of the heat absorption pattern

In clinical applications of magnetic nanoparticle hyperthermia for cancer treatment it is very important to ensure a maximum damage to the tumor while protecting the normal tissue. The resultant heating pattern by the nanoparticle distribution in tumor is closely related to the injection parameters. In this study we develop an optimization algorithm to inversely determine the optimum heating patterns induced by multiple nanoparticle injections in tumor models with irregular geometries. The injection site locations, thermal properties of tumor and tissue, and local blood perfusion rates are used as inputs to the algorithm to determine the optimum parameters of the heat sources for all nanoparticle injection sites. The design objective is to elevate the temperature of at least 90% of the tumor above 43°C, and to ensure only less than 10% of the normal tissue is heated to temperatures of 43°C or higher. The efficiency, flexibility and capability of this approach have been demonstrated in a case study of two tumors with simple or complicated geometry. An extensive experimental database should be developed in the future to relate the optimized heating pattern parameters found in this study to their appropriate nanoparticle concentration, injection amount, and injection rate. We believe that the optimization algorithm developed in this study can be used as a guideline for physicians to design an optimal treatment plan in magnetic nanoparticle hyperthermia.

An in-vivo experimental study of temperature elevations in animal tissue during magnetic nanoparticle hyperthermia

In magnetic nanoparticle hyperthermia in cancer treatment, the local blood perfusion rate and the amount of nanofluid delivered to the target region are important factors determining the temperature distribution in tissue. In this study, we evaluate the effects of these factors on the heating pattern and temperature elevations in the muscle tissue of rat hind limbs induced by intramuscular injections of magnetic nanoparticles during in vivo experiments. Temperature distribution in the vicinity of the injection site is measured inside the rat limb after the nanoparticle hyperthermia. The measured temperature elevations at the injection site are 3.5° ± 1.8°C and 6.02° ± 0.8°C above the measured body temperature, when the injection amount is 0.1 cc and 0.2 cc, respectively. The full width of half maximum (FWHM) of the temperature elevation, an index of heat transfer in the radial direction from the injection site is found to be approximately 31 mm for both injection amounts. The temperature measurements, together with the measured blood perfusion rate, ambient air temperature, and limb geometry, are used as inputs into an inverse heat transfer analysis for evaluation of the specific absorption rate (SAR) by the nanoparticles. It has been shown that the nanoparticles are more concentrated in the vicinity of the injection site when the injection amount is bigger. The current in vivo experimental studies have demonstrated the feasibility of elevating the tissue temperature above 43°C under the experimental protocol and equipment used in this study.

Evaluation of Effectiveness of Er,Cr:YSGG Laser For Root Canal Disinfection: Theoretical Simulation of Temperature Elevations in Root Dentin

Erbium, chromium: yttrium, scandium, gallium, garnet (Er,Cr:YSGG) lasers are currently being investigated for disinfecting the root canal system. Prior to using laser therapy, it is important to understand the temperature distribution and to assess thermal damage to the surrounding tissue. In this study, a theoretical simulation using the Pennes bioheat equation is conducted to evaluate how heat spreads from the canal surface using an Er,Cr:YSGG laser. Results of the investigation show that some of the proposed treatment protocols for killing bacteria in the deep dentin are ineffective, even for long heating durations. Based on the simulation, an alternative treatment protocol is identified that has improved effectiveness and is less likely to introduce collateral damage to the surrounding tissue. The alternative protocol uses 350 mW laser power with repeating laser tip movement to achieve bacterial disinfection in the deep dentin (800 microm lateral from the canal surface), while avoiding thermal damage to the surrounding tissue (T<47 degrees C). The alternative treatment protocol has the potential to not only achieve bacterial disinfection of deep dentin but also shorten the treatment time, thereby minimizing potential patient discomfort during laser procedures.

Temperature Distribution During ICG-Dye-Enhanced Laser Photocoagulation of Feeder Vessels in Treatment of AMD-Related Choroidal Neovascularization

Laser photocoagulation of the feeder vessels of age-related macula degeneration-related choroidal neovascularization (CNV) membranes is a compelling treatment modality, one important reason being that the treatment site is removed from the fovea in cases of sub- or juxtafoveal CNV. To enhance the energy absorption in a target feeder vessel, an indocyanine green dye bolus is injected intravenously, and the 805 nm wavelength diode laser beam is applied when the dye bolus transits the feeder vessel; this tends to reduce concomitant damage to adjacent tissue. A 3D theoretical simulation, using the Pennes bioheat equation, was performed to study the temperature distribution in the choroidal feeder vessel and its vicinity during laser photocoagulation. The results indicate that temperature elevation in the target feeder vessel increases by 20% in dye-enhanced photocoagulation, compared to just photocoagulation alone. The dye bolus not only increases the laser energy absorption in the feeder vessel but also shifts the epicenter of maximum temperature away from the sensitive sensory retina and retinal pigment epithelial layers and toward the feeder vessel. Two dominant factors in temperature elevation of the feeder vessel are location of the feeder vessel and blood flow velocity through it. Feeder vessel temperature elevation becomes smaller as distance between it and the choriocapillaris layer increases. The cooling effect of blood flow through the feeder vessel can reduce the temperature elevation by up to 21% of the maximum that could be produced. Calculations were also performed to examine the effect of the size of the laser spot. To achieve the same temperature elevation in the feeder vessel when the laser spot diameter is doubled, the laser power level has to be increased by only 60%. In addition, our results have suggested that more studies are needed to measure the constants in the Arrhenius integral for assessing thermal damage in various tissues.

Evaluation of Effectiveness of Er,Cr:YSGG Laser for Root Canal Disinfection: Theoretical Simulation of Temperature Elevations in Root Dentin

Lasers have been used in dentistry for removing hard tooth tissue for more than twenty years. Erbium, chromium: yttrium, scandium, gallium, garnet (Er, Cr: YSGG) lasers are currently being investigated for disinfecting the root canal system, since bacteria can spread from the root canal surface to the deep dentin via the dentin tubules [1]. It is expected that temperature elevation in the deep dentin is sufficient to eradicate bacteria there. Prior to using laser therapy, it is important to understand the temperature distribution and to assess thermal damage to the surrounding tissue. In this study, we develop a heat transfer model to estimate the temperature elevations in both the tooth root and surrounding tissue during Er,Cr:YSGG laser disinfection of the root canal surface. The laser power level, pulse setting, as well as laser duration are incorporated into the Pennes bioheat equation for the theoretical study. We propose a treatment protocol that achieves better heat penetration with shorter treatment time than the existing protocols used in dentistry [2].© 2009 ASME

Enhancement in Treatment Planning for Magnetic Nanoparticle Hyperthermia: Optimization of the Heat Absorption Pattern

In clinical applications of magnetic nanoparticle hyperthermia for cancer treatment it is very important to ensure a maximum damage to the tumor while protecting the normal tissue. The resultant heating pattern by the nanoparticle distribution in tumor is closely related to the injection parameters. In this study we develop an optimization algorithm to inversely determine the optimum heating patterns induced by multiple nanoparticle injections in tumor models with irregular geometries. The injection site locations, thermal properties of tumor and tissue, and local blood perfusion rates are used as inputs to the algorithm to determine the optimum parameters of the heat sources for all nanoparticle injection sites. The design objective is to elevate the temperature of at least 90% of the tumor above 43 � C, and to ensure only less than 10% of the normal tissue is heated to temperatures of 43 � C or higher. The efficiency, flexibility and capability of this approach have been demonstrated in a case study of two tumors with simple or complicated geometry. An extensive experimental database should be developed in the future to relate the optimized heating pattern parameters found in this study to their appropriate nanoparticle concentration, injection amount, and injection rate. We believe that the optimization algorithm developed in this study can be used as a guideline for physicians to design an optimal treatment plan in magnetic nanoparticle hyperthermia.

An In-Vivo Experimental Study of Temperature Elevations in Animal Tissue During Magnetic Nanoparticle Hyperthermia

Magnetic nanoparticle hyperthermia has potential to achieve optimal therapeutic results due to its ability to deliver adequate heating power to irregular and/or deep-seated tumor at low magnetic field frequency and amplitude [1]. Iron oxides magnetite Fe3O4 and maghemite γ-Fe2O3 nanoparticles are the most studied to date [2] due to their biocompatibilty [3] for hyperthermia application. The heat generated by the particles when exposed to an external alternating magnetic field is mainly due to the Neel relaxation mechanism and/or Brownian motion of the particles [4]. The superparamagnetic particles (10–40 nm) are recommended in clinical application as they are able to generate substantial heat within a small magnetic field strength and frequency [5].Copyright

Theoretical Evaluation of Tissue Damage Using Er,Cr:YSGG Laser for Root Canal Preparation

Lasers have been used in dentistry for removing hard tooth tissue for more than twenty years. In particular, the arbium, chromium: yttrium, scandium, gallium, garnet (Er,Cr:YSGG) laser, which has a wavelength of 2.78 μm, has been shown to offer the advantages of straight, clean and precise hard tissue cuts [1]. Due to its long wavelength, the absorbed laser energy is limited within a very thin layer of the irradiated tissue and therefore, high temperature elevations (>100°C) at the surface results in hard tissue ablation. Recently, lasers have also been used to prepare a clean root canal surface as well as in disinfection and elimination of bacteria from the root canal system [2].Copyright

Experimental and Computational Study of Nanoparticle Transport in Agarose Gel

In magnetic nanoparticle hyperthermia for cancer treatment, controlling heat deposition and temperature elevations is an immense challenge in clinical applications. In this study, we evaluate magnetic nanofluid transport using agarose gel that has porous structures similar to human tissue by injecting magnetic nanoparticle solution into the extracellular space of gel. The nanofluid distribution in the gel is examined via digital images of the nanofluid spreading in the gel. By adjusting the gel concentration and injection flow rate, the results have demonstrated that a relatively low injection rate leads to a spherically shaped nanofluid distribution in the gels which is desirable for controlling temperature elevations. In parallel to the experimental study, a particle tracking model is developed to study the migration and deposition of nanoparticles in the porous structure under multiple forces including Brownian motion, London-Van der Waals attraction, electrostatic forces, gravitational body force, viscous force, and inertial force. This model allows for the determination of the rate of nanoparticle deposition on the porous structure for various particle sizes, surface potentials, and local fluid velocity. In the future, the information obtained in this study can be used with continuous porous medium theory to predict the evolution of the concentration and deposition profiles of nanoparticles in porous structure during infusion process.Copyright