Why does second trimester demise of a monochorionic twin not result in acardiac twinning?

BACKGROUND: We previously explained why acardiac twinning occurs in the first trimester. We raised the question why a sudden demised monochorionic twin beyond the first trimester does not lead to acardiac twinning. We argued that exsanguinated blood from the live twin would strongly increase the demised twins' vascular resistance, preventing its perfusion and acardiac onset. However, our current hypothesis is that perfusion of the demised twin does occur but that it is insufficient for onset of acardiac twinning. METHODS: We analyzed blood pressures and flows in a vascular resistance model of a monochorionic twin pregnancy where one of the fetuses demised. The resistance model consists of a demised twin with a (former) placenta, a live twin and its placenta, and arterioarterial (AA) and venovenous placental anastomoses. We assumed that only twins with a weight of at least 33% of normal survived the first trimester and that exsanguination of more than 50% of its blood volume is fatal for the live twin. RESULTS: At 20 weeks, only AA anastomoses with radii ≲1 mm keep the exsanguinated blood volume below 50%. Then, perfusion of the deceased body with arterial blood from the live fetus is about 5-40 times smaller than when that body was alive. Beyond 20 weeks, this factor is even smaller. At 14 weeks, this factor is at most 2. CONCLUSION: We hypothesize that this small perfusion flow of arterial blood prevents further growth of the deceased body and hence precludes onset of acardiac twinning.

Mathematical modeling of the thermal effects of irreversible electroporation for in vitro, in vivo, and clinical use: a systematic review.

Introduction: Irreversible electroporation (IRE) is a relatively new ablation method for the treatment of unresectable cancers. Although the main mechanism of IRE is electric permeabilization of cell membranes, the question is to what extent thermal effects of IRE contribute to tissue ablation.Aim: This systematic review reviews the mathematical models used to numerically simulate the heat-generating effects of IRE, and uses the obtained data to assess the degree of mild-hyperthermic (temperatures between 40 °C and 50 °C) and thermally ablative (TA) effects (temperatures exceeding 50 °C) caused by IRE within the IRE-treated region (IRE-TR).Methods: A systematic search was performed in medical and technical databases for original studies reporting on numerical simulations of IRE. Data on used equations, study design, tissue models, maximum temperature increase, and surface areas of IRE-TR, mild-hyperthermic, and ablative temperatures were extracted.Results: Several identified models, including Laplace equation for calculation of electric field distribution, Pennes Bioheat Equation for heat transfer, and Arrhenius model for thermal damage, were applied on various electrode and tissue models. Median duration of combined mild-hyperthermic and TA effects is 20% of the treatment time. Based on the included studies, mild-hyperthermic temperatures occurred in 30% and temperatures ≥50 °C in 5% of the IRE-TR.Conclusions: Simulation results in this review show that significant mild-hyperthermic effects occur in a large part of the IRE-TR, and direct thermal ablation in comparatively small regions. Future studies should aim to optimize clinical IRE protocols, maintaining a maximum irreversible permeabilized region with minimal TA effects.

Periocular CO2 laser resurfacing: severe ocular complications from multiple unintentional laser impacts on the protective metal eye shields.

BACKGROUND AND OBJECTIVES: A 36-year-old woman underwent CO2 laser resurfacing for periocular rhytides using protective stainless steel Cox II ocular shields. Immediately after the treatment, corneal lesions were seen in both eyes. The left eye subsequent developed corneal ulceration and scarring, a deformed iris, cataract, and lower eye lashes showing signs of acute burns. The right cornea had a small inferior mid-peripheral superficial lesion and concomitant lower mid-peripheral burned eye lashes. Our objective was to determine the most likely cause of these ocular complications. STUDY: We estimated temperature-time combinations that could induce corneal injury and cataract. Heat conduction effects from a heated cornea to the lens and from a heated ring of periocular skin to the cornea were computed. The temperature response of a shield following CO2 laser irradiation was determined. RESULTS: We computed that cataract can develop when the corneal temperature reaches, for example, 80 °C for 14 seconds. A periocular ring of heated skin contributes little to the corneal temperature. After 7 pulses of consecutive CO2 laser bursts in 7.5 seconds, the total shield area already reached a homogeneous temperature of 63 °C. CONCLUSION: Despite uncertainties in procedural details and modeling of cataract temperatures, the eye injuries were caused beyond doubt by heating of tear-covered metal eye shields by at least 10 consecutive but unintentional laser impacts. Lasers Surg. Med. 50:980-986, 2018. © 2018 Wiley Periodicals, Inc.

The Influence of a Metal Stent on the Distribution of Thermal Energy during Irreversible Electroporation.

PURPOSE: Irreversible electroporation (IRE) uses short duration, high-voltage electrical pulses to induce cell death via nanoscale defects resulting from altered transmembrane potential. The technique is gaining interest for ablations in unresectable pancreatic and hepatobiliary cancer. Metal stents are often used for palliative biliary drainage in these patients, but are currently seen as an absolute contraindication for IRE due to the perceived risk of direct heating of the metal and its surroundings. This study investigates the thermal and tissue viability changes due to a metal stent during IRE. METHODS: IRE was performed in a homogeneous tissue model (polyacrylamide gel), without and with a metal stent placed perpendicular and parallel to the electrodes, delivering 90 and 270 pulses (15-35 A, 90 µsec, 1.5 cm active tip exposure, 1.5 cm interelectrode distance, 1000-1500 V/cm, 90 pulses/min), and in-vivo in a porcine liver (4 ablations). Temperature changes were measured with an infrared thermal camera and with fiber-optic probes. Tissue viability after in-vivo IRE was investigated macroscopically using 5-triphenyltetrazolium chloride (TTC) vitality staining. RESULTS: In the gel, direct stent-heating was not observed. Contrarily, the presence of a stent between the electrodes caused a higher increase in median temperature near the electrodes (23.2 vs 13.3°C [90 pulses]; p = 0.021, and 33.1 vs 24.8°C [270 pulses]; p = 0.242). In-vivo, no temperature difference was observed for ablations with and without a stent. Tissue examination showed white coagulation 1mm around the electrodes only. A rim of vital tissue remained around the stent, whereas ablation without stent resulted in complete tissue avitality. CONCLUSION: IRE in the vicinity of a metal stent does not cause notable direct heating of the metal, but results in higher temperatures around the electrodes and remnant viable tissue. Future studies should determine for which clinical indications IRE in the presence of metal stents is safe and effective.

Irreversible electroporation: just another form of thermal therapy?

BACKGROUND: Irreversible electroporation (IRE) is (virtually) always called non-thermal despite many reports showing that significant Joule heating occurs. Our first aim is to validate with mathematical simulations that IRE as currently practiced has a non-negligible thermal response. Our second aim is to present a method that allows simple temperature estimation to aid IRE treatment planning. METHODS: We derived an approximate analytical solution of the bio-heat equation for multiple 2-needle IRE pulses in an electrically conducting medium, with and without a blood vessel, and incorporated published observations that an electric pulse increases the medium's electric conductance. RESULTS: IRE simulation in prostate-resembling tissue shows thermal lesions with 67-92°C temperatures, which match the positions of the coagulative necrotic lesions seen in an experimental study. Simulation of IRE around a blood vessel when blood flow removes the heated blood between pulses confirms clinical observations that the perivascular tissue is thermally injured without affecting vascular patency. CONCLUSIONS: The demonstration that significant Joule heating surrounds current multiple-pulsed IRE practice may contribute to future in-depth discussions on this thermal issue. This is an important subject because it has long been under-exposed in literature. Its awareness pleads for preventing IRE from calling "non-thermal" in future publications, in order to provide IRE-users with the most accurate information possible. The prospect of thermal treatment planning as outlined in this paper likely aids to the important further successful dissemination of IRE in interventional medicine. Prostate 75:332-335, 2015. © 2014 The Authors. The Prostate Published by Wiley Periodicals, Inc.

Optical-thermal mathematical model for endovenous laser ablation of varicose veins.

Endovenous laser ablation (EVLA) is successfully used to treat varicose veins. However, the exact working mechanism is still not fully identified and the clinical procedure is not yet standardized. Mathematical modeling of EVLA could strongly improve our understanding of the influence of the various EVLA processes. The aim of this study is to combine Mordon's optical-thermal model with the presence of a strongly absorbing carbonized blood layer on the fiber tip. The model anatomy includes a cylindrically symmetric blood vessel surrounded by an infinite homogenous perivenous tissue. The optical fiber is located in the center of the vessel and is withdrawn with a pullback velocity. The fiber tip includes a small layer of strongly absorbing material, representing the layer of carbonized blood, which absorbs 45% of the emitted laser power. Heat transfer due to boiling bubbles is taken into account by increasing the heat conduction coefficient by a factor of 200 for temperatures above 95 °C. The temperature distribution in the blood, vessel wall, and surrounding medium is calculated from a numerical solution of the bioheat equation. The simulations were performed in MATLAB™ and validated with the aid of an analytical solution. The simulations showed, first, that laser wavelength did virtually not influence the simulated temperature profiles in blood and vessel wall, and, second, that temperatures of the carbonized blood layer varied slightly, from 952 to 1,104 °C. Our improved mathematical optical-thermal EVLA model confirmed previous predictions and experimental outcomes that laser wavelength is not an important EVLA parameter and that the fiber tip reaches exceedingly high temperatures.

Some controversies in endovenous laser ablation of varicose veins addressed by optical-thermal mathematical modeling.

Minimally invasive treatment of varicose veins by endovenous laser ablation (EVLA) becomes more and more popular. However, despite significant research efforts performed during the last years, there is still a lack of agreement regarding EVLA mechanisms and therapeutic strategies. The aim of this article is to address some of these controversies by utilizing optical-thermal mathematical modeling. Our model combines Mordon's light absorption-based optical-thermal model with the thermal consequences of the thin carbonized blood layer on the laser fiber tip that is heated up to temperatures of around 1,000 °C due to the absorption of about 45% of the laser light. Computations were made in MATLAB. Laser wavelengths included were 810, 840, 940, 980, 1,064, 1,320, 1,470, and 1,950 nm. We addressed (a) the effect of direct light absorption by the vein wall on temperature behavior, comparing computations by using normal and zero wall absorption; (b) the prediction of the influence of wavelength on the temperature behavior; (c) the effect of the hot carbonized blood layer surrounding the fiber tip on temperature behavior, comparing wall temperatures from using a hot fiber tip and one kept at room temperature; (d) the effect of blood emptying the vein, simulated by reducing the inside vein diameter from 3 down to 0.8 mm; (e) the contribution of absorbed light energy to the increase in total energy at the inner vein wall in the time period where the highest inner wall temperature was reached; (f) the effect of laser power and pullback velocity on wall temperature of a 2-mm inner diameter vein, at a power/velocity ratio of 30 J/cm at 1,470 nm; (g) a comparison of model outcomes and clinical findings of EVLA procedures at 810 nm, 11 W, and 1.25 mm/s, and 1,470 nm, 6 W, and 1 mm/s, respectively. Interestingly, our model predicts that the dominating mechanism for heating up the vein wall is not direct absorption of the laser light by the vein wall but, rather, heat flow to the vein wall and its subsequent temperature increase from two independent heat sources. The first is the exceedingly hot carbonized layer covering the fiber tip; the second is the hot blood surrounding the fiber tip, heated up by direct absorption of the laser light. Both mechanisms are about equally effective for all laser wavelengths. Therefore, our model concurs the finding of Vuylsteke and Mordon (Ann Vasc Surg 26:424-433, 2012) of more circumferential vein wall injury in veins (nearly) devoid of blood, but it does not support their proposed explanation of direct light absorption by the vein wall. Furthermore, EVLA appears to be a more efficient therapy by the combination of higher laser power and faster pullback velocity than by the inverse combination. Our findings suggest that 1,470 nm achieves the highest EVLA efficacy compared to the shorter wavelengths at all vein diameters considered. However, 1,950 nm of EVLA is more efficacious than 1,470 nm albeit only at very small inner vein diameters (smaller than about 1 mm, i.e., veins quite devoid of blood). Our model confirms the efficacy of both clinical procedures at 810 and 1,470 nm. In conclusion, our model simulations suggest that direct light absorption by the vein wall is relatively unimportant, despite being the supposed mechanism of action of EVLA that drove the introduction of new lasers with different wavelengths. Consequently, the presumed advantage of wavelengths targeting water rather than hemoglobin is flawed. Finally, the model predicts that EVLA therapy may be optimized by using 1,470 nm of laser light, emptying of the vein before treatment, and combining a higher laser power with a greater fiber tip pullback velocity.

Endovenous laser ablation (EVLA): a review of mechanisms, modeling outcomes, and issues for debate.

Endovenous laser ablation (EVLA) is a commonly used and very effective minimally invasive therapy to manage leg varicosities. Yet, and despite a clinical history of 16 years, no international consensus on a best treatment protocol has been reached so far. Evidence presented in this paper supports the opinion that insufficient knowledge of the underlying physics amongst frequent users could explain this shortcoming. In this review, we will examine the possible modes of action of EVLA, hoping that better understanding of EVLA-related physics stimulates critical appraisal of claims made concerning the efficacy of EVLA devices, and may advance identifying a best possible treatment protocol. Finally, physical arguments are presented to debate on long-standing, but often unfounded, clinical opinions and habits. This includes issues such as (1) the importance of laser power versus the lack of clinical relevance of laser energy (Joule) as used in Joule per centimeter vein length, i.e., in linear endovenous energy density (LEED), and Joule per square centimeter vein wall area, (2) the predicted effectiveness of a higher power and faster pullback velocity, (3) the irrelevance of whether laser light is absorbed by hemoglobin or water, and (4) the effectiveness of reducing the vein diameter during EVLA therapy.

The heat-pipe resembling action of boiling bubbles in endovenous laser ablation.

Endovenous laser ablation (EVLA) produces boiling bubbles emerging from pores within the hot fiber tip and traveling over a distal length of about 20 mm before condensing. This evaporation-condensation mechanism makes the vein act like a heat pipe, where very efficient heat transport maintains a constant temperature, the saturation temperature of 100 degrees C, over the volume where these non-condensing bubbles exist. During EVLA the above-mentioned observations indicate that a venous cylindrical volume with a length of about 20 mm is kept at 100 degrees C. Pullback velocities of a few mm/s then cause at least the upper part of the treated vein wall to remain close to 100 degrees C for a time sufficient to cause irreversible injury. In conclusion, we propose that the mechanism of action of boiling bubbles during EVLA is an efficient heat-pipe resembling way of heating of the vein wall.