A novel gas embolotherapy using microbubbles electrocoalescence for cancer treatment.

BACKGROUND AND OBJECTIVE: Embolotherapy has been increasingly used to disrupt tumor growth. Despite its success in the occlusion of microvessels, it has drawbacks such as limited access to the target location, limited control of the blocker size, and inattention to the tumor characteristics, especially high interstitial fluid pressure. The present work introduces a novel numerical method of gas embolotherapy for cancer treatment through tumor vessel occlusion. METHODS: The gas microbubbles are generated from Levovist bolus injection into the tumor microvessel. The microbubble movement in the blood flow is innovatively controlled by an electric field applied to the tumor-feeding vessel. The interaction between the Levovist microbubbles and the electric field is resolved by developing a fully coupled model using the phase-field model, Carreau model for non-Newtonian blood, Navier-Stokes equations and Maxwell stress tensor. Additionally, the critical effect of high interstitial fluid pressure as a characteristic of solid tumors is included. RESULTS: The findings of this study indicate that the rates of microbubble deformation and displacement increase with the applied potential intensity to the microvessel wall. Accordingly, the required time for a microbubble to join the upper microvessel wall reduces from 1.97ms to 22 µs with an increase of the electric potential from 3.5V to 12.5V. Additionally, an electric potential of 12.5V causes the microbubbles coalescence and formation of a gas column against the bloodstream. CONCLUSIONS: Clinically, our novel embolization procedure can be considered a non-invasive targeted therapy, and under a controlled electric field, the blocker size can be precisely controlled. Also, the proposed method has the potential to be used as a gradual treatment in advanced cancers as tumors develop resistance and relapse.

Exploring the benefits of functionally graded carbon nanotubes (FG-CNTs) as a platform for targeted drug delivery systems.

BACKGROUND AND OBJECTIVE: Modern therapeutic systems have benefited from the use of functionally graded carbon nanotubes (FG-CNTs) to enhance their efficiency. Various studies have shown that the study of dynamic response and stability of fluid-conveying FG-nanotubes can be improved by considering a Multiphysics framework for the modeling of such a complex biological environment. However, despite noticing important aspects in modeling, the previous studies have drawbacks such as underrepresenting the effect of varying composition of the nanotube on magnetic drug release in drug delivery systems. The present work has the novelty of studying the combined effects of fluid flow, magnetic field, small-scale parameters, and functionally graded material on the performance of FG-CNTs for drug delivery applications. Additionally, the lack of an inclusive parametric study is resolved in the present study by evaluating the significance of different geometrical and physical parameters. As such, the achievements support the development of an efficient drug delivery treatment. METHODS: The Euler-Bernoulli beam theory is implemented to model the nanotube and Hamilton's principle based on Eringen's nonlocal elasticity theory is used to derive the constitutive equations of motion. To add the effect of slip velocity on the CNT's wall, a correction factor is applied to velocity based on the Beskok-Karniadakis model. RESULTS: demonstrate that the dimensionless critical flow velocity increases by 227% as the magnetic field intensity increases from 0 to 20 T, and improves the system stability. On the contrary, drug loading on the CNT has the opposite effect, as the critical velocity decreases from 10.1 to 8.38 using a linear function for drug loading, and it decreases to 7.95 using an exponential function. By employing a hybrid load distribution, an optimum material distribution can be achieved. CONCLUSIONS: To benefit from the potential of CNTs in drug delivery systems while minimizing the instability problems, a suitable design for the drug loading is required prior to the clinical implementation of the nanotube.

Viscoelastic parameters of invasive breast cancer in correlation with porous structure and elemental analysis data.

BACKGROUND AND OBJECTIVE: Invasive ductal carcinoma (IDC) is the most common and aggressive type of breast cancer. As many clinical diagnoses are concerned with the tumor behavior at the compression, the IDC characterization using a compression test is performed in the present study. In the field of tissue characterization, most of the previous studies have focused on healthy and cancerous breast tissues at the cellular level; however, characterization of cancerous tissue at the tissue level has been under-represented, which is the target of the present study. METHODS: Throughout this article, 18 IDC samples are tested using a ramp-relaxation test. The strain rate in the ramp phase is similar for all samples, whereas the strain level is set at 2,4 and 6%. The experimental stress-time data is interpolated by a viscoelastic model. Two relaxation times, as well as the instantaneous and long-term shear moduli, are calculated for each specimen. RESULTS: The results show that the long-term and instantaneous shear moduli vary in the range of 0.31-17.03 kPa and 6.03-55.13 kPa, respectively. Our assessment of the viscoelastic parameters is accompanied by observing structural images of the IDCs and inspecting their elemental composition. It is concluded that IDCs with lower Magnesium to Calcium ratio (Mg:Ca) have smaller shear modulus and longer relaxation time, with a p-value of 0.001 and 0.01 for the correlation between Mg:Ca and long-term shear modulus, and Mg:Ca and early relaxation time. CONCLUSIONS: Our identification of the IDC viscoelastic parameters can contribute to the IDC inspection at the tissue level. The results also provide useful information for modeling of breast cancer.

Optimization of polyethylene glycol-based hydrogel rectal spacer for focal laser ablation of prostate peripheral zone tumor.

PURPOSE: Focal Laser ablation therapy is a technique that exposes the prostate tumor to hyperthermia ablation and eradicates cancerous cells. However, due to the excessive heating generated by laser irradiation, there is a possibility of damage to the adjacent healthy tissues. This paper through in silico study presents a novel approach to reduce collateral effects due to heating by the placement of polyethylene glycol (PEG) spacer between the rectum and tumor during laser irradiation. The PEG spacer thickness is optimized to reduce the undesired damage at common laser power used in the clinical trials. Our study also encompasses novelty by conducting the thermal analysis based on the porous structure of prostate tumor. METHODS: The thermal parameters and two thermal phase lags between the temperature gradient and the heat flux, are determined by considering the vascular network of prostate tumor. The Nelder-Mead algorithm is applied to find the minimum thickness of the PEG spacer. RESULTS: In the absence of the spacer, the predicted results for the laser power of 4 W, 8 W, and 12 W show that the temperature of the rectum rises up to 58.6 °C, 80.4 °C, and 101.1 °C, while through the insertion of 2.59 mm, 4 mm, and 4.9 mm of the PEG spacer, it dramatically reduces below 42 °C. CONCLUSIONS: The results can be used as a guideline to ablate the prostate tumors while avoiding undesired damage to the rectal wall during laser irradiation, especially for the peripheral zone tumors.

Numerical analysis of non-Fourier thermal response of lung tissue based on experimental data with application in laser therapy.

BACKGROUND AND OBJECTIVE: The thermal therapy is a minimally invasive technique used as an alternative approach to conventional cancer treatments. There is an increasing concern about the accuracy of the thermal simulation during the process of tumor ablation. This study is aimed at investigating the effect of finite speed of heat propagation in the biological lung tissue, experimentally and numerically. METHODS: In the experimental study, a boundary heat flux is applied to the lung tissue specimens and the temperature variation is measured during a transient heat transfer procedure. In the numerical study, a code is developed based on the finite volume method to solve the classical bio-heat transfer, the Cattaneo and Vernotte, and the Dual-phase-lag (DPL) equations. The thermal response of tissue during the experiments is compared with the predictions of the three heat transfer models. RESULTS: It is found that the trend of temperature variation by the DPL model resembles the experimental results. The experimental observation in parallel with the numerical results reveals that the accumulated thermal energy diffuses to the surrounding tissue with a slower rate in comparison with the conventional bio-heat transfer model. The DPL model is implemented to study the temperature elevation in the laser irradiation to lung tissue in the presence of gold nanoparticles (GNPs). It is concluded that the extent of the necrotic tumoral region and the area of the damaged healthy tissue are reduced, when the non-Fourier heat transfer is taken into account. CONCLUSIONS: Results show that considering the phase lags is crucial in planning for an effective thermal treatment, in which the cancerous tissue is ablated and the surrounding tissues are preserved from irreversible thermal damage.

Microstructure-based non-Fourier heat transfer modeling of HIFU treatment for thyroid cancer.

BACKGROUND AND OBJECTIVES: High intensity focused ultrasound is an emerging non-invasive technique for the thermal ablation of cancer. Modeling of high intensity focused ultrasound as a method to induce hyperthermia, by considering non-equilibrium convective heat transfer has been under-represented in the previous studies. Therefore, in the present study, we aimed to study the effect of blood vessels during high intensity focused ultrasound ablation of thyroid cancer. In addition, high intensity focused ultrasound modeling was greatly improved by considering non-Fourier heat transfer. METHODS: The modified dual-phase-lag model was used for the modeling of heat transfer in thyroid cancer during the ultrasound irradiation. The model parameters were linked with the tissue's microstructure parameters. Meanwhile, an interfacial convective heat transfer was considered between the blood vessels and the extravascular matrix. The extent of the vascular region was determined using the field emission scanning electron microscopy images. The non-linear Westervelt equation was solved for the sound wave to determine the heat source for the induced hyperthermia treatment. RESULTS: Referring to the acoustic results, sharp-wave ripples were observed due to the inclusion of notable amplitudes of excited harmonics. The thermal results showed a maximum temperature rise of 25.08°C and 51.47°C at the powers of 5 W and 10 W using the modified dual-phase-lag model, while the Pennes model predicted a temperature rise of 28.77°C and 55.5°C at the same powers. It was also concluded that a constant blood temperature, overestimates the dissipated energy and the temperature reduction during the cooling period, as a 15% deviation in the tumor temperature was observed from the non-equilibrium state at 10.65 s exposure and 10 W power. Eventually, the calculation of the ablated volumes indicated that the volumes were up to 4.5 times larger by the Pennes model compared to the modified dual-phase-lag model. CONCLUSIONS: It can be concluded from the results that there should be a serious concern on the high intensity focused ultrasound modeling based on the parameters of blood vessels. Based on the thermal maps, the cancerous tissue should be exposed to a higher energy level of ultrasound waves in order to cause the desired damage against the estimated energy level predicted by the Pennes model.

Simultaneous localization of multiple tumors from thermogram of tissue phantom by using a novel optimization algorithm inspired by hunting dogs.

The objective of this study is to couple the contact thermography method with a novel optimization algorithm to rapidly detect and localize the soft tissue tumor. To this end, experiments are carried out on tissue-mimicking phantoms containing resistance heaters to simulate the embedded tumors. An examiner robot is used to measure the temperature of the tissue surface. The time required for the examination of the tissue surface is reduced by developing a novel optimization algorithm called the Hunter Algorithm (HA). In the HA, population individuals are called the hunters, and the global maximum is referred to as the prey. The maximum temperature occurs at the location of the tumor. By the end of the hunting procedure, a flock of hunters converges to the maximum temperature and reaches the tumor while the examination time is significantly reduced. Performance of the HA is evaluated by applying the Genetic Algorithm (GA) and the Particle Swarm Optimization (PSO) algorithm to 11 test functions as minimization problems. It is observed that for the Ackley's function, as an example, the HA finds the global minimum after the 10th iteration with an accuracy of 10-4, while the PSO converges with the same accuracy after the 30th iteration and the accuracy of the GA remains about 0.002. In addition, the results show that the contact thermography in conjunction with the HA is of clinical importance in accurate detection of multiple tumors and small and deeply located tumors with insignificant thermal effects on the tissue surface.

A numerical study on thermal ablation of brain tumor with intraoperative focused ultrasound.

Focused ultrasound surgery (FUS) is a non-invasive thermal therapeutic method which has been emerged in the field of brain tumors treatment. During intraoperative brain surgery, application of FUS can significantly increase the accuracy of thermal ablation of tumor while reducing undesirable damage to healthy brain tissue. The main objective of this study is acquiring acoustic transducer specifications to achieve optimum thermal treatment in the tumoral tissue. 2D and 3D models are constructed from patient-specific brain MRI images which consist of a malignant vascular tumor. Acoustic pressure and temperature are obtained by using homogenous Helmholtz and bio-heat transfer equations according to insignificant nonlinear effect. Besides that, thermal lesion induced by FUS is obtained by the thermal dose function. Results show the significance of blood vessels' cooling effect on the temperature profile. Moreover, correlation between temperature profile and transducer's operating parameter including power, frequency and duty cycle is obtained. Artificial neural network analysis is conducted to estimate required transducer parameters for optimum temperature rise.

Analysis of thyroid thermographic images for detection of thyroid tumor: An experimental-numerical study.

Thermography is a developing and noninvasive medical imaging technique that can be used for diagnosis of body disorders based on temperature deviation from normal body temperature. This research investigates the feasibility of thermography method in conjunction with artificial neural networks (ANNs) for detection of thyroid tumors. For this purpose, first, a 3-D model of the healthy human neck is constructed based on patient-specific computed tomography (CT) images. This model is used for analyzing bio-heat transfer in the human neck. The healthy thyroid gland is considered as a heat source and generates heat according to its temporal temperature. Finite element results verify the thermography potential for detection of thyroid gland location and estimation of its butterfly shape on the neck thermogram. The numerical analysis is carried out on 35 models with varying thermo-physical parameters of the healthy thyroid gland, including heat generation and blood perfusion. The acquired thermograms are used to develop an ANN for correlating the thermo-physical parameters of the gland and temperature profile on the neck surface. In the next stage, dynamic thermal images are captured from 10 healthy and three cancerous human cases. The experimental thermal images are analyzed by the developed ANN and the corresponding thermo-physical parameters are obtained. Results show that the estimated heat generation values for the healthy cases are about 3000 Wm3 while it increases to more than 12 000 Wm3 for the cases with tumors. This significant variation confirms the potential of dynamic thermography in diagnosis of thyroid tumors.

A Patient-Specific Three-Dimensional Hemodynamic Model of the Circle of Willis.

Circle of Willis (CoW) is one of the most important cerebral arteries in the human body and various attempts have been made to study the hemodynamic of blood flow in this vital part of the brain. In the present study, blood flow in a patient specific CoW is numerically modeled to predict disease-prone regions of the CoW. Medical images and computer aided design software are used to construct a realistic three-dimensional model of the CoW for this particular case. The arteries are considered as elastic conduits and the interactions between arterial walls and the blood flow are taken into account. Mooney-Rivlin hyperelastic model is used to describe the behavior of arterial walls and blood is considered as a non-Newtonian fluid obeying the Carreau model. An available experimental-based pulsatile velocity profile is used at the entrance of the CoW. The finite element-based commercial software, ADINA, is used to solve the governing equations. Blood pressure and velocity and arterial wall shear stress are calculated in different regions of the CoW. A simplified form of the model is also compared with the available published data. Results affirmed that the proposed computational model has the potential to capture the hemodynamic characteristics of the CoW. The computational results can be used to determine disease-prone locations for a given CoW.

Finite element modeling of haptic thermography: A novel approach for brain tumor detection during minimally invasive neurosurgery.

Intraoperative Thermal Imaging (ITI) is a novel neuroimaging method that can potentially locate tissue abnormalities and hence improves surgeon's diagnostic ability. In the present study, thermography technique coupled with artificial tactile sensing method called "haptic thermography" is utilized to investigate the presence of an abnormal object as a tumor with an elevated temperature relative to the normal tissue in the brain. The brain tissue is characterized as a hyper-viscoelastic material to be descriptive of mechanical behavior of the brain tissue during tactile palpation. Based on a finite element approach, Magnetic Resonance Imaging (MRI) data of a patient diagnosed to have a brain tumor is utilized to simulate and analyze the capability of haptic thermography in detection and localization of brain tumor. Steady-state thermal results prove that temperature distribution is an appropriate outcome of haptic thermography for the superficial tumors while heat flux distribution can be used as an extra thermal result for deeply located tumors.

A novel robotic tactile mass detector with application in clinical breast examination.

This paper presents a novel tactile sensing robot designed to detect breast lesions with minimum invasiveness to the tissue while providing exact documentation to make therapeutic and surgical decisions. The robot named "Robotic Tactile Breast Mass Identifier (Robo-Tac-BMI) consists of an indentation probe controlled by a robotic system and a visualization interface to manipulate the end-effecter. Geometrical maps of the test points with related tension-relaxation curves are provided during clinical examinations. Utilizing the curves, three functional stiffness parameters are extracted locally for each test point. These parameters are employed to provide objective information to facilitate the surgeon's task in the diagnostic procedure. Computational analysis is proposed for a real breast tissue model to study the capability of artificial tactile sensing in the mass detection. Indications of the mass existence are determined and employed as the basis of the Robo-Tac-BMI design and construction. Clinical trials are executed by the Robo-Tac-BMI on 161 cases. The results show that the robot has the potential to provide tissue mechanical properties unlike the conventional screening modalities carried out either by the surgeon or the imaging techniques which are not quantitative and lack documentation. Sonography with and without mammography is chosen as the "gold standard" tests.

A novel haptic robotic viscogram for characterizing the viscoelastic behaviour of breast tissue in clinical examinations.

BACKGROUND: This paper presents a novel tactile sensing robot designed to characterize the viscoelastic behaviour of breast tissue during clinical breast examination (CBE). The robot, named the 'robotic tactile breast mass identifier' (Robo-Tac-BMI), mainly consists of an indentation probe controlled by a robotic system and a visualization interface to manipulate the end-effector. Major high order mechanical parameters are extracted to characterize the viscoelastic behaviour of the tissue in order to certify mass detection and judge the mass type. By fusing the measurements over both breasts, the probe can generalize a mechanical image to visualize the viscoelastic distribution within the internal tissue. The viscoelastic properties provide additional and objective information to facilitate the surgeon's task in the decision-making process. METHODS: A new computational method is presented for characterizing mass existence in a real breast model. The effect of the strain rate on the mechanical properties is considered to study the viscoelastic behaviour of different mass types. A creative method is proposed to find the optimum strain rate for different mass positions and consistencies, which improves nodule detection. The computational results would be used as the basis for the design and set-up of the Robo-Tac-BMI. Clinical tests with statistical analyses were performed on 161 cases, using the Robo-Tac-BMI. RESULTS: The results include analysis of two high-order mechanical properties. Robo-Tac-BMI's capability of nodule detection and differentiation between benign and malignant mass types are investigated. The results were validated by 'gold standard' tests. CONCLUSION: The results show that Robo-Tac-BMI has the potential to provide high-order mechanical parameters, unlike the conventional screening modality carried out by the surgeon, which is not inclusive or quantitative and lacks effectiveness and documentation. The nodule detection ability of this device is confirmed statistically in clinical breast examinations. Differentiation between different mass types is reported as the preliminary result of Robo-Tac-BMI utilization.

A medical tactile sensing instrument for detecting embedded objects, with specific application for breast examination.

BACKGROUND: In this paper, having considered the tactile sensing and palpation of a physician in order to detect abnormal masses in the breast, we simplified and then modelled the tissue containing a mass and used contact elements to analyse the tactile sensor function. METHODS: By using the finite element method, the effects of the mass existence appeared on the surface of the tissue. This was due to exerting mechanical load on the modelled tissue surface. Following this, a tactile sensing instrument called the 'tactile tumour detector' (TTD) was designed and constructed. This device is able to detect abnormal objects in the simulated models by making contact with model surfaces. In order to perform a series of precise experiments, a robot that could hold the tactile probe was used. The velocity of the linear movement of the probe is low enough to ensure that the tissue behaves in the linear elastic range, so that dynamic effects can be neglected. RESULTS AND DISCUSSION: The maximum value of stresses was chosen as the comparison criterion. The variation of this criterion vs. the mass parameter changes was investigated and good agreements between numerical and experimental results were obtained. Moreover, the sensitivity and specificity of TTD and clinical breast examination (CBE) in the detection of breast masses, in comparison to sonography as the 'gold standard', were calculated by performing clinical trials on 55 cases.