Global sensitivity study for irreversible electroporation:Towards treatment planning under uncertainty

Background: Electroporation-based cancer treatments are minimally invasive, nonthermal interventional techniques that leverage cell permeabilization to ablate the target tumor. However, the amount of permeabilization is susceptible to the numerous uncertainties during treatment, such as patient-specific variations in the tissue, type of the tumor, and the resolution of imaging equipment. These uncertainties can reduce the extent of ablation in the tissue, thereby affecting the effectiveness of the treatment. Purpose: The aim of this work is to understand the effect of these treatment uncertainties on the treatment outcome for irreversible electroporation (IRE) in the case of colorectal liver metastasis (CRLM). Understanding the nature and extent of these effects can help us identify the influential treatment parameters and build better models for predicting the treatment outcome. Methods: This is an in silico study using a static computational model with a custom applicator design, spherical tissue, and tumor geometry. A nonlinear electrical conductivity, dependent on the local electric field, is considered. Morris analysis is used to identify the influential treatment parameters on the treatment outcome. Seven treatment parameters pertaining to the relative tumor location with respect to the applicator, the tumor growth pattern, and the electrical conductivity of tissue are analyzed. The treatment outcome is measured in terms of the relative tumor ablation with respect to the target ablation volume and total ablation volume. Results: The Morris analysis was performed with 800 model evaluations, sampled from the seven dimensional input parameter space. Electrical properties of the tissue, especially the electrical conductivity of the tumor before ablation, were found to be the most influential parameter for relative tumor ablation and total ablation volume. This parameter was found to be about 4–15 times more influential than the least influential parameter, depending on the tumor size. The tumor border configuration was identified as the least important parameter for treatment effectiveness. The most desired treatment outcome is obtained by a combination of high healthy liver conductivity and low tumor conductivity. This information can be used to tackle worst-case scenarios in treatment planning. Finally, when the safety margins used in the clinical applications are accounted for, the effects of uncertainties in the treatment parameters reduce drastically. Conclusions: The results of this work can be used to create an efficient surrogate estimator for uncertainty quantification in the treatment outcome, that can be utilized in optimal real-time treatment planning solutions.</p

Aorto-atrial fistula formation and therapy

Aorta-atrial fistulas (AAF) are a rare but complex pathological condition. These fistulas are characterised by aberrant blood flow between the aorta and either atrium. In the present manuscript, we present a comprehensive overview of the clinical characteristics, formation and treatment of this condition. A literature review was conducted using PubMed. Aorta-Atrial Fistula was used as the primary search term. The clinical presentation of AAF encompasses a wide range of signs and symptoms of heart failure including dyspnoea, chest pain, palpitations, fatigue, weakness coughing or oedema. Causes of fistulas can be congenital or acquired, whilst diagnosis is normally achieved via echocardiography or MRI. Due to the low incidence of AAF, no clinical trials have been performed in AAF patients and treatment strategies are based on expert opinion and consensus amongst the treating physicians. Uncorrected AAF may continue to impose a risk of progression to overt heart failure. The repair of an AAF can either be surgical or percutaneous. AAF is a relatively rare but very serious condition. Clinicians should consider the possibility of AAF, when a new continuous cardiac murmur occurs, especially in patients with a history of cardiac surgery or with signs of heart failure. Closure of the AAF fistula tract is generally recommended. Further studies are required to define optimal therapeutic strategies, but these are hindered by the rarity of the occurrence of this disorde

Simulation study of the cooling effect of blood vessels and blood coagulation in hepatic radio-frequency ablation

Purpose Computer simulations of hepatic radio-frequency ablation (RFA) were performed to: (i) determine the dependence of the vessel wall heat transfer coefficient on geometrical parameters; (ii) study the conditions required for the occurrence of the directional effect of blood; and (iii) classify blood vessels according to their effect on the thermal lesion while considering blood coagulation. The information thus obtained supports the development of a multi-scale bio-heat model tailored for more accurate prediction of hepatic RFA outcomes in the vicinity of blood vessels. Materials and methods The simulation geometry consisted of healthy tissue, tumor tissue, a mono-polar RF-needle, and a single cylindrical blood vessel. The geometrical parameters of interest were the RF-needle active length and those describing blood vessel configuration. A simple, novel method to incorporate the effects of blood coagulation into the simulation was developed and tested. Results A closed form expression giving the dependence of the vessel wall heat transfer coefficient on geometrical parameters was obtained. Directional effects on the thermal lesion were found to occur for blood vessel radii between 0.4 mm and 0.5 mm. Below 0.4 mm blood coagulation blocked the flow. Conclusions The closed form expression for the heat transfer coefficient can be used in models of RFA to speed up computation. The conditions on vessel radii required for the occurrence of directional effects on the thermal lesion were determined. These conditions allow the classification of blood vessels. Different approximations to the thermal equation can thus be used for these vessel classes

Tuning the Pennes Perfusion Rate to Model Large Vessel Cooling Effects in Hepatic Radiofrequency Ablation

Radio frequency ablation (RFA) has become a popular method for the minimally invasive treatment of liver cancer. However, the success rate of these treatments depends heavily on the amount of experience the clinician possesses. Mathematical modeling can help mitigate this problem by providing an indication of the treatment outcome. Thermal lesions in RFA are affected by the cooling effect of both fine-scale and large-scale blood vessels. The exact model for large-scale blood vessels is advection-diffusion, i.e., a model capable of producing directional effects, which are known to occur in certain cases. In previous research, in situations where directional effects do not occur, the advection term in the blood vessel model has been typically replaced with the Pennes perfusion term, albeit with a higher-than-usual perfusion rate. Whether these values of the perfusion rate appearing in literature are optimal for the particular vessel radii in question, has not been investigated so far. This work aims to address this issue. An attempt has been made to determine, for values of vessel radius between 0.55 mm and 5 mm, best estimates for the perfusion rate which minimize the error in thermal lesion volumes between the perfusion-based model and the advection-based model. The results for the best estimate of the perfusion rate presented may be used in existing methods for fast estimation of RFA outcomes. Furthermore, the possible improvements to the presented methodology have been highlighted.</p

Simulation study of the cooling effect of blood vessels and blood coagulation in hepatic radio-frequency ablation

Purpose Computer simulations of hepatic radio-frequency ablation (RFA) were performed to: (i) determine the dependence of the vessel wall heat transfer coefficient on geometrical parameters; (ii) study the conditions required for the occurrence of the directional effect of blood; and (iii) classify blood vessels according to their effect on the thermal lesion while considering blood coagulation. The information thus obtained supports the development of a multi-scale bio-heat model tailored for more accurate prediction of hepatic RFA outcomes in the vicinity of blood vessels. Materials and methods The simulation geometry consisted of healthy tissue, tumor tissue, a mono-polar RF-needle, and a single cylindrical blood vessel. The geometrical parameters of interest were the RF-needle active length and those describing blood vessel configuration. A simple, novel method to incorporate the effects of blood coagulation into the simulation was developed and tested. Results A closed form expression giving the dependence of the vessel wall heat transfer coefficient on geometrical parameters was obtained. Directional effects on the thermal lesion were found to occur for blood vessel radii between 0.4 mm and 0.5 mm. Below 0.4 mm blood coagulation blocked the flow. Conclusions The closed form expression for the heat transfer coefficient can be used in models of RFA to speed up computation. The conditions on vessel radii required for the occurrence of directional effects on the thermal lesion were determined. These conditions allow the classification of blood vessels. Different approximations to the thermal equation can thus be used for these vessel classes