Experimental and numerical study of heat transfer in an endovenous laser treatment

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UNIVERSIDADE FEDERAL DE SANTA CATARINA

PROGRAMA DE PÓS-GRADUAÇÃO EM

ENGENHARIA MECÂNICA

Jônatas Vicente

EXPERIMENTAL AND NUMERICAL STUDY OF

HEAT TRANSFER IN AN ENDOVENOUS LASER

TREATMENT

Florianópolis

2019

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Jônatas Vicente

EXPERIMENTAL AND NUMERICAL STUDY OF HEAT TRANSFER IN AN ENDOVENOUS LASER

TREATMENT

Dissertação submetida ao Programa de Pós-Graduação em Engenharia Mecânica da Universidade Federal de Santa Catarina para a obtenção do grau de Mestre em Engenharia Mecânica.

Orientador: Prof. Amir Antônio Martins de Oliveira Jr., Ph.D.

Florianópolis 2019

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Ficha de identificação da obra elaborada pelo autor,

através do Programa de Geração Automática da Biblioteca Universitária da UFSC.

Vicente, Jônatas

Experimental and Numerical Study of Heat Transfer in an Endovenous Laser Treatment / Jônatas Vicente ; orientador, Amir Antônio Martins de Oliveira Jr., 2019.

124 p.

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico, Programa de Pós Graduação em Engenharia Mecânica, Florianópolis, 2019. Inclui referências.

1. Engenharia Mecânica. 2. Endovenous laser treatment (EVLT). 3. Heat transfer in biological systems. 4. Biomechanics. I. Antônio Martins de Oliveira Jr., Amir. II. Universidade Federal de Santa Catarina. Programa de Pós-Graduação em Engenharia Mecânica. III. Título.

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Jônatas Vicente

EXPERIMENTAL AND NUMERICAL STUDY OF

HEAT TRANSFER IN AN ENDOVENOUS LASER

TREATMENT

Esta Dissertação foi julgada adequada para obtenção do Título de Mestre em Engenharia Mecânica e aprovada em sua forma final pelo Programa de Pós-Graduação em Engenharia Mecânica da Universidade Federal de Santa Catarina.

Florianópolis, 1 de julho de 2019.

Prof. Jonny Carlos da Silva, Dr.

Coordenador do Programa de Pós-Graduação em Engenharia Mecânica - POSMEC

Prof. Amir Antônio Martins de Oliveira Jr., Ph.D. Universidade Federal de Santa Catarina - Orientador

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Banca Examinadora:

Prof. Amir Antônio Martins de Oliveira Jr., Ph.D. Universidade Federal de Santa Catarina - Presidente

Prof. Saulo Guths, Dr.

Universidade Federal de Santa Catarina - UFSC

Prof. Fernando Marcelo Pereira, Dr. Universidade Federal do Rio Grande do Sul

-UFRGS

Dr. Wangner Paula Ferreira Centro de Tratamento Vascular

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To my grandfather,

Carlos Bonessi (in memorian). To my father, Celso Vicente and my mother, Maristela Bonessi Vicente.

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“One must be sane to think clearly, but one can think deeply and be quite insane.”

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AGRADECIMENTOS

Aos meus pais Celso Vicente e Maristela Bonessi Vicente por serem meus exemplos, sou imensamente grato pelo apoio e suporte para que eu possa seguir em busca dos meus objetivos e sonhos. Obrigado pai, obrigado mãe, eu amo vocês.!

Ao meu irmão Vanderson Vicente e minha cunhada Denise F. Vicente que sempre me motivaram e apoiaram a correr atrás dos meus objetivos, e que trouxeram ao mundo a minha sobrinha e afilhada Júlia F. Vicente, que trouxe ainda mais luz e alegria para a nossa família.

A minha namorada Sheron L. Wierzynski pelo apoio, carinho, afeto, amor e compreensão ao durante mais esta etapa, obrigado meu bem. Extendo meus agradecimentos aos teus familiares pelo apoio e motivação.

Ao Prof. Amir Antônio Martins de Oliveira Jr. pela amizade, apoio, orientação e auxílio no desenvolvimento deste trabalho. Deixo expresso aqui a minha grande admiração que tenho pelo Sr.

Aos professores membros da banca, Prof. Fernando Marcelo Pereira, Prof. Saulo Guths, Dr. Wagner Paula Ferreira pelas con-tribuições e discussões, também aos professores do Departamento de Engenharia Mecânica da UFSC pelos ensinamentos.

Ao Dr. Wagner Paula Ferreira do Centro de Tratamento Vas-cular de Ribeirão Preto - SP, pelo apoio financeiro e técnico no de-senvolvimento deste trabalho. Pelas discussões que foram de extrema importância para a compreensão da técnica e fatores envolvidos do ponto de vista médico, meu muito obrigado.

Aos amigos, colegas e professores do Laboratório de Combustão e Engenharia de Sistemas Térmicos (LabCET) por todo apoio, suporte, ajuda, companheirismo, discussões técnias, conversas acompanhadas de um café ou uma cerveja geleada, em especial Abílio, Álvaro, Amir De Toni, Augusto, Camila, Christian A., Edemar, Prof. Edson Bazzo, Fernando, Flávia, Fred, Guilherme M., Guilherme H., Herlon, João Miranda, Juan, Marcos O., Marina, Mateus A., Matheus F., Nury, Rafael Meier, Rafael Mezzalira, Renzo, Ricardo, Simone (IT), Thiago B., Thiago P., Thiago R.. Amizades que aqui fiz e espero levar para toda vida, obrigado galera.

Aos amigos de outros laboratórios e aos que fiz durante esse tempo em Florianópolis, Ana, Andreza, Arthur, Bárbara, Christian G., Elidiana, Gean, Jéssia, Laura, Lucas, Paulo, Renan (Tiozão).

Aos meus amigos que mesmo de longe me motivaram, apoiaram e proporcionaram conversas e momentos de descontração, Vini Feijó,

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Wilson, Natan, Lucas, Cíntia, Luan, Camila, Mateus Pasinato, Leo-nardo, Marcos, Greyson, Paquito, e a galera do futebol do SESI.

Ao Prof. Saulo Guths e ao Laboratório de Meios Porosos e Trans-ferência de Calor - LMPT, pelo auxílio técnico e empréstimo de equi-pamentos utilizados na bancada experimental.

Aos integrantes e professores do Laboratório de Polimeros e Com-pósitos - POLICON pela realização do teste para caracterização térmica do polimero utilizado neste trabalho.

A Universidade Federal de Santa Catarina - Departamento de Engenharia Mecânica pela oportunidade em desenvolver meus estudos e por tudo que me proporcionou nesses últimos anos.

A todas as pessoas que de qualquer modo me enviaram ener-gias positivas, apoiaram, motivaram e torceram por mim, sejam eles familiares, amigos, vizinhos,..., obrigado.

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RESUMO

O presente trabalho tem como objetivo investigar por meio experimental e numérico os mecanismos da transferência de calor na aplicação do pro-cedimento cirúrgico de ablação endovenosa a laser (EVLA) assim como a influência de parâmetros termofísicos no campo de temperatura na face interna de um modelo de veia artificial. A ablação a laser é uma téc-nica cirúrgica minimamente invasiva de cauterização de veias, a fim de interromper o escoamento sanguíneo e eliminar a formação de êbolos e varizes. A motivação para o desenvolvimento deste trabalho é, além de ampliar o conhecimento sobre os fenômenos envolvidos no procedimento, disponibilizar uma ferramenta e resultados que sirvam de auxílio ao médico no aprimoramento da técnica e obtenção de melhores resultados. A bancada experimental consiste em um cilindro moldado em um polímero e imerso em um reservatório com controle térmico. O cilindro com diâmetro externo de 34 _{mm e comprimento 250 mm possui um orifício central na direção axial} com diâmetro 8 mm que simula uma veia, o qual é preenchido por sangue humano ou soro fisiológico durante os experimentos. O cilindro é instrumen-tado com termopares nas direçôes axial e radial. O feixe de laser é conduzido por uma fibra óptica para o interior da veia. A fibra é deslocada com velocidade constante durante o experimento, simulando a aplicação cirúrgica do método. Utiliza-se um sistema de laser contínuo, com potência ajustável entre 1 e 30 W, nos comprimentos de onda 810 nm e 1470 nm. Opera-se com fibras óticas com diâmetro de 600 µm. O modelo numérico emprega a equação da condução de calor em coordenadas cilíndricas e um modelo para o fluxo de calor móvel na parede da veia. A equação da condução de calor é resolvida por um método de volumes finitos. O modelo é utilizado para correlacionar o campo de temperatura na veia com as características do feixe de laser e sua interação com o sangue humano. As medições de temperatura identificaram assimetrias no campo de temperatura. Dependendo da inten-sidade das assimetrias observadas, elas foram relacionadas com os seguintes efeitos: (1) Movimentação da extremidade da fibra ótica para fora da linha de centro da veia durante o teste; (2) contato direto da ponta da fibra na parede interna da veia e (3) geração de bolhas de vapor que se originam e se deslocam da ponta da fibra para a parte superior devido aos efeitos da gravidade. Com a utilização do modelo teórico, obteve-se a intensidade do fluxo de calor na parede da veia e com isso, determinou-se a importância relativa de cada fenômeno na ablação da parede da veia.

Palavras-chave: Tratamento endovenoso a laser (EVLT), Transferência de calor em sistemas biológicos, Biomecanica.

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ABSTRACT

The present work had the aim to investigate through experimental and numerical the heat transfer mechanisms evolved at the endovenous laser ablation (EVLA or EVLT) surgical procedure application as well as the thermophysics parameters that influence at the temperature field at an in-ternal wall of an artificial vein model. Laser ablation is a minimally invasive surgical technique to vein cauterization, in order to interrupt the blood flow and eliminating the varicose veins and plungers formation. The motivation to develop this study was on to increase the knowledge about the phenomena evolved at the procedure as well as to provide materials and a tool to assist doctors to improve the technique and through these, attainment to strive higher standards. The experimental workbench consists of a cylinder molded in a polymer (PVC-P), attached to a reservoir with thermal control. The cylinder had an external diameter of 34 mm and 250 mm of length, at the center have an orifice in the axial direction with a diameter of 8 mm that simulate the vein, it was filled with human blood or saline solution during the experimental test. The instrumentation at the vein model was with thermocouples at the axial and radial directions. The conduction of laser beam to the interior of the vein was through an optical fiber. The fiber was displaced with constant velocity (pullback) at the test performed, simulating the surgical procedure application. Draw on a continuous laser system with adjustable power between 1 to 30 W, at the wavelength of 810 nm and 1470_{nm. The optical fibers used were with a diameter of 600 µm, bare and} radial fiber. The numerical model employs the heat conduction equation in cylindrical coordinates and another model to the mobile heat source at the vein wall. A Finite Volumes Method (FVM) was used to solve the heat conduction equation. The model was used to correlate the temperature field at the vein with the laser beam characteristics and human blood interac-tion. The measures obtained identify asymmetries at the temperature field. Depending on the intensity of the asymmetries observed, these were related with the following effects: (1) Movement of the fiber tip out of the vein centerline during the test; (2) direct contact of the fiber tip at the internal wall, and (3) steam bubbles formation that originates and move at the fiber tip to the top of the vein by buoyancy. With the theoretical model use, was obtained the heat flux intensity at the vein wall and with it, the rela-tive importance with each phenomenon at vein wall ablation was determined. Keywords: Endovenous laser treatment (EVLT), Heat transfer in biological systems, Biomechanical.

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λ λ

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LIST OF FIGURES

1.1 Evolution of the surgeries unilateral and bilateral per-formed . . . 2 2.1 Representation of (A) a normal vein with normal valves

and blood ﬂow, and (B) a varicose veins with deformed valves and, abnormal and retrograde blood ﬂow. . . 6 2.2 Stripping surgical procedure representation.. . . 9 2.3 Foam sclerotherapy treatment representation. (A)

Injec-tion of sclerosing drug followed by ultrasound guidance. (B) Vein closing through reaction with the solution. (C) Vein after treatment. . . 10 2.4 Example of catheter used to perform the RFA procedure. 12 2.5 Radiofrequency treatment representation. (A) Catheter

stationary during treatment at saphenofemoral junction. (B) Slight overlap between treatments. (C) Vein treated stepwise along the length. . . 13 2.6 Thermal eﬀects at vein after EVLT procedure. . . 15 2.7 Representation of EVLT procedure application. . . 17 2.8 Electromagnetic radiation spectrum. . . 18 2.9 Laser system representation. . . 19 2.10 Laser beam interaction representation with tissue. . . 21 2.11 Absorption spectrum by tissue chromophores. . . 23 2.12 Schematic overview of the experimental set-up. . . 27 2.13 Temperature-time histories measured in thermocouples

close to the center-line, distance of 1 mm. . . 28 2.14 Temperature-time histories measured in thermocouples

further away to the center-line, distance of 1.5 mm. . . 29 2.15 Representation of the geometry used for simulation . . . 30 2.16 Isodamage distribution inside tissues (Power = 15 W,

pull-back speed = 1.5 mm/s, vein diameter = 3 mm, λ = 980 nm). . . 31 3.1 Rendering of the experimental workbench concept. . . 35 3.2 Reservoir with the cooper serpentine ﬁxed. . . 36 3.3 Lauda Alpha RA8 thermal bath. . . 37 3.4 Holes distribution (A) at the circular section; (B) at the

length. (C) The tube perforated. . . 38 3.5 (A) Connectors and tube mold. (B) Set assembled with

couplers, tube and support. (C) Set ﬁxed into support to be poured. . . 39 3.6 Artiﬁcial vein manufactured into the support. . . 40

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3.7 Angular distribution of the thermocouples, location of the tips at the vein model, and reading distribution for each acquisition unit. . . 41 3.8 Representation of thermocouples distribution along

sec-tions and length of the model. . . 42 3.9 Equipment Novadiode 30 manufactured by Synus Laser

Technologies with λw= 810 nm. . . 43 3.10 Equipment innova touch DUO manufactured by ORlight

Laser with λw= 1470 nm and λw= 532 nm. . . 44 3.11 Bare ﬁber: (A.1) dimensions; (A.2) Light emission

pat-tern at the side; (A.3) Light emission frontal patpat-tern. Radial ﬁber: (B.1) dimensions; (B.2) light emission pat-tern at the side; (B.3) light emission frontal patpat-tern. . . 45 3.12 Experimental workbench assembled according to the

conceptual projetct. . . 46 4.1 Rendering of the physical model. . . 47 4.2 Heat wave moving along the domain. . . 50 4.3 Balances of the convection and conduction ﬂuxes into

the analysis domain. . . 55 4.4 Representation of the radius divided in control volumes. . 60 4.5 Representation of the length divided in control volumes. . 60 5.1 Rendering of ﬁber position at the instrumented region. . . 65 5.2 Evolution of the temperature proﬁles with the time at

the section 1, the further away section in front of the bare ﬁber tip. . . 66 5.3 Evolution of the temperature proﬁles with the time at

the section 3, the adjacent section in front of the bare ﬁber tip. . . 67 5.4 Evolution of the temperature proﬁles with the time at

the section 4, the adjacent section behind the bare ﬁber tip. . . 67 5.5 Evolution of the temperature proﬁles with the time at

the section 6, the further away section behind the bare ﬁber tip. . . 68 5.6 Maximum temperatures disposed at the angles in each

section in a static test with the bare ﬁber positioned at the center of the instrumented region. . . 68 5.7 Evolution of the temperature proﬁles with the time at

the section 1, the further away section in front of the radial ﬁber tip. . . 69

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5.8 Evolution of the temperature profiles with the time at the section 3, the adjacent section in front of the radial fiber tip. . . 69 5.9 Evolution of the temperature profiles with the time at

the section 4, the adjacent section behind the radial ﬁber tip. . . 70 5.10 Evolution of the temperature proﬁles with the time at

the section 6, the further away section behind the radial ﬁber tip. . . 70 5.11 Maximum temperatures disposed at the angles in each

section in a static test with the radial fiber positioned at the center of the instrumented region. . . 71 5.12 Rendering of fiber moving at the tests. . . 74 5.13 Temperature profile evolution at Section 1 with Q =

12 W; Sq= 2 mm/s; λw= 1470 nm; bare ﬁber. . . 74 5.14 Temperature proﬁle evolution at Section 2 with Q =

12 W; Sq= 2 mm/; λw= 1470 nm; bare ﬁber. . . 75 5.16 Temperature proﬁle evolution at Section 4 with Q =

12 W; Sq= 2 mm/s; λw= 1470nm; bare ﬁber. . . 76 5.18 Temperature proﬁle evolution at Section 6 with Q =

12 W; Sq= 2 mm/s; λw= 1470nm; bare ﬁber. . . 76 5.19 Temperature proﬁle evolution at Section 1 with Q =

12 W; Sq= 2 mm/s; λw= 1470 nm; radial ﬁber. . . 77 5.20 Temperature proﬁle evolution at Section 2 with Q =

12 W; Sq= 1.4 mm/s; λw= 810 nm; bare ﬁber. . . 80 5.26 Temperature proﬁle evolution at Section 2 with Q =

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5.27 Temperature profile evolution at Section 3 with Q = 12 W; Sq= 1.4 mm/s; λw= 810 nm; bare fiber. . . 81 5.28 Temperature profile evolution at Section 4 with Q =

12 W; Sq= 1.4 mm/s; λw= 810 nm; bare ﬁber. . . 81 5.29 Temperature proﬁle evolution at Section 5 with Q =

12 W; Sq= 1.4 mm/s; λw= 810nm; bare ﬁber. . . 81 5.30 Temperature proﬁle evolution at Section 6 with Q =

12 W; Sq= 1.4 mm/s; λw= 810nm; bare ﬁber. . . 82 5.31 Temperature proﬁle evolution at Section 1 with Q =

12 W; Sq= 2 mm/s; λw= 810 nm; radial ﬁber. . . 84 5.37 Bare ﬁber at the endovenous catheter presenting a clot

of carbonized blood at the tip. (A) The ﬁber tip cove-red by the clot. (B) The clot formed around the tip, allowing the laser beam passage. (C) No propagation of the laser beam due to the clot at the tip. (D) Laser beam propagated to a surface with a clean tip. . . 85 5.38 Radial ﬁber at the endovenous catheter presenting a clot

of carbonized blood at the tip. (A) The fiber tip covered by the clot. (B) The clot formed around the tip, allowing partially the laser beam passage. (C) Propagation of the partially laser to a surface. (D) Laser beam propagated to a surface with a clean tip. . . 86 5.39 Temperature profile calculated using different numbers

of uniformly spaced control volumes along the radial di-rection m. . . 90 5.40 Temperature proﬁle at the inner wall of the model with

simulation time from t = 0 s to t = 100 s with mesh reﬁ-nement at the radius coordinate. . . 92 5.41 θ at η = ηias a function of ξ for diﬀerent values of Pe at

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5.42 θ at ξ = 0 as a function of η for diﬀerent values of Pe at aspect ratio a = 6 and ηi= 0.24. . . 95 5.43 θ at ξ = −5,−10, and −20, and maximum value of θ as

a function of Pe at ηi= 0.24 for diﬀerent values of Pe at aspect ratio a = 1 and ηi= 0.24. . . 96 5.44 Q∗ _{as a function of Pe at aspect ratio a = 1 and η = 1}

presenting the heat ﬂuxes of conduction and convection that cross the boundary. . . 97 5.45 Temperature proﬁle θ at η = ηi of the simulation with

Q = 4 W and σ = 2.5 and the experimental result with the following set Q = 12 W; Sq= 1 mm/s; bare ﬁber. . . . 98 5.46 Temperature proﬁle θ at η = ηi of the simulation with

Q = 4.2 W and σ = 4.2 and the experimental result with the following set Q = 12 W; Sq= 2.5 mm/s; radial ﬁber. . 99 5.47 Example of temperature proﬁle not optimized and the

final convergence of the model fitting for a thermocouple positioned at the first section (S1) at angle 0◦ _{with the}

parameter Pe= 276.6. . . 101 5.48 Model-ﬁtting representation with the model prediction

and disperses points of the measured temperatures for a thermocouple positioned at the ﬁrst section (S1) and at the angle of 225◦_{, with the parameters: Pe= 276.57;}

a= 0.48; q = 0.25 W/rad; σ = 34.7 mm. . . 102 5.49 Model-ﬁtting representation with a good convergence of

the prediction with the measured temperatures for a thermocouple positioned at the third section (S3) and at the angle of 180◦_{, with the parameters: Pe= 276.57;}

a= 5.09; q = 0.24 W/rad; σ = 3.3 mm.. . . 103 5.51 Predicted scattering of the heat wave, σ (mm), as a

func-tion of the temperature diﬀerence between the maximum surface and the initial temperatures, ∆T = Tmax− To (o_{C), for the data in Tables (5.5), (5.6) and (5.7). . . 105} 5.50 Predicted surface heat ﬂuxes at the center of the heat

wave, q′′

o (W/m2), as a function of the temperature diﬀe-rence between the maximum surface and the initial tem-peratures, ∆T = Tmax− To (oC), for the data in Tables (5.5), (5.6) and (5.7). . . 106 A.1 Set-up of the thermocouples calibration assembled at the

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LIST OF TABLES

2.1 Commonly lasers for medical application . . . 20 2.2 Laser-tissue interactions: thermal eﬀects. . . 22 4.1 Summary of the small and large Fourier approximations

for the temperature characteristic scale and amplitude of the heat wave. . . 55 5.1 Thermal properties of the PVC-P material. . . 88 5.2 Grid convergence in steady state using the temperature

at the inner diameter as convergence criterion. . . 91 5.3 Grid convergence in the radial direction using the

tem-perature at t = 100 s as convergence criterion. . . 92 5.4 Time-step convergence of the temperature in the inner

surface at elapsed times of 1, 5, 10, 20, 40, and 80 s. The temperature calculated with ∆t = 10−4 _{s is taken}

as reference temperature. . . 93 5.5 Results of the heat ﬂux and other parameters for each

thermocouple obtained with the model-ﬁtting, through the temperature measurements at the inner surface for the Sections 1, 2, and 3 in an experiment with: ri = 4 mm; ro = 17 mm; Sq= 2 mm/s; λ = 0.17 W/m-K; α = 1.23.10−7 m2/s; Pe= 276.57, and ηi= 0.235; λw= 810 nm; Q = 12 W. . . 102 5.6 Results of the heat ﬂux and other parameters for each

thermocouple obtained with the model-ﬁtting, through the temperature measurements at the inner surface for the Sections 4, 5, and 6 in an experiment with: ri = 4 mm; ro = 17 mm; Sq= 2 mm/s; λ = 0.17 W/m-K; α = 1.23.10−7 _m2_{/s; Pe= 276.57, and η}

i= 0.235; λw= 810 nm; Q = 12 W. . . 104 5.7 Results of the model ﬁtting to the temperature

measu-rements at the inner surface: ri= 4 mm; ro= 17 mm; Sq = 2 mm/s; λ = 0.17 W/m-K; α = 1.23.10−7 m2/s; Pe= 276.57, and ηi= 0.235. . . 105 A.1 Uncertainties of measurement for each

thermocou-ple used at the experimental workbench for the ﬁrst acquisition unit (AU1). . . 121

A.2 Uncertainties of measurement for each thermocouple used at the experimental workbench for the second acquisition unit (AU2). . . 122

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GLOSSARY

1D One-Dimensional. 2D Two-Dimensional. AU Acquisition unit.

CVI Chronic Venous Insuﬃciency. DAq Data acquisition.

EVLA Endovenous Laser Ablation. EVLT Endovenous Laser Treatment. FVM Finite Volumes Method. GSV Great Saphenous Vein.

ICD International Classiﬁcation of Diseases. PLA Polylactic Acid.

PVC-P Polyvinyl Chloride with Plasticizer. SFJ Saphenofemoral Junction.

SIH Sistema de Informações Hospitalares. SSV Small Saphenous Vein.

SUS Sistema Único de Saúde.

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NOMENCLATURE

µa,λ Absorption coeﬃcient [1/cm] µs,λ Scattering coeﬃcient [1/cm] µt,λ Total attenuation factor [1/cm] Ω Damaged cells [nond.]

A Frequency factor [1/s] Ea Energy activation [J/mole] R Universal gas constant [J/mole-K] T Temperature [K]

C0 Concentration of undamaged molecules at the beginning

[nond.]

Ct Concentration of undamaged molecules at time τ [nond.]

τ Time [s] ◦_C _{Degree Celsius [}◦_C] λw Wavelength [nm] ρ Density [kg/m3] cp Speciﬁc heat [J/kg-K] λ Thermal conductivity [W/m-K]

wb Mass ﬂux of blood per unit of tissue volume [kg/s-m3] cpb Speciﬁc heat of the blood [J/kg-K]

Tb Blood temperature [K]

qm Thermal energy conversion rate by metabolism [W/m3] qe Thermal energy generation by external source [W/m3] α Thermal diﬀusivity [m2_/s]

q Heat transfer rate per radian [W/rad] ri Inner radius of the model [m]

σ Standard deviation of the wave function scattering [m] z Axial position [m]

zq Center position of the heat wave [m] q′′

(t, z) Heat wave function [W/m2-rad] Q(t) Heat transfer rate [W]

E Thermal energy deposited [J]

zo Initial position of the heat ﬂux proﬁle center [m] Sq Pullback velocity [m/s]

t Current time of the interactions [s] To Initial temperature [K]

Fo Fourier number [nond.]

δ Thickness of heat penetration [m]

qc Heat transfer rate at the inner surface [W/rad] qk Heat transfer rate by conduction [W/rad]

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tC Characteristic time scale for convection [s] tD Characteristic time scale for diﬀusion [s] Ra Rayleigh number [nond.]

e Eﬀusivity [W-s1/2/m-K] σs Standard deviation

P Perimeter of the internal diameter [m] L Length of the domain [m]

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TABLE OF CONTENTS 1 INTRODUCTION . . . 1 1.1 Motivation. . . 3 1.2 Objectives . . . 3 1.2.1 General objective. . . 3 1.2.2 Specific objetives . . . 3 1.3 Structure of the Document . . . 4 2 FUNDAMENTALS AND LITERATURE REVIEW . . . 5 2.1 Varicose Veins Disease and Treatments. . . 5 2.1.1 Historical background. . . 5 2.1.2 Evolution of varicose veins treatments. . . 7 2.1.2.1 Stripping and ligation . . . 8 2.1.2.2 Foam sclerotherapy . . . 9 2.1.2.3 Radiofrequency ablation . . . 11 2.1.2.4 Endovenous laser ablation . . . 14 2.1.3 Endovenous laser treatment - Surgical procedure . . . 15 2.2 Laser. . . 18 2.2.1 Laser fundamentals . . . 18 2.2.2 Biologic materials . . . 20 2.2.3 Laser-tissue interactions. . . 20 2.2.3.1 Absorption . . . 22 2.2.3.2 Scattering . . . 23 2.2.4 Mechanisms of action . . . 24 2.2.4.1 Steam bubble . . . 24 2.2.4.2 Direct contact . . . 25 2.2.4.3 Direct energy absorption of the vein wall . . . 25 2.2.4.4 Heat pipe eﬀect . . . 26 2.3 State of Art . . . 27 2.3.1 Experimental studies. . . 27 2.3.2 Numerical and mathematical studies. . . 30 2.3.3 Clinical studies. . . 32 2.4 Concluding Remarks . . . 33 3 EXPERIMENT . . . 35 3.1 Workbench overview. . . 35 3.1.1 Reservoir and thermal control. . . 36 3.1.2 Artificial vein model . . . 37 3.1.3 Temperature measurement and DAq system. . . 40 3.2 Laser System and Fibers . . . 43 3.2.1 Equipments. . . 43 3.2.2 Fibers. . . 44

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3.3 Test Procedure. . . 45 4 MODELING . . . 47 4.1 Physical Model . . . 47 4.2 Mathematical Model. . . 48 4.2.1 Formulation . . . 48 4.2.2 Nondimensionalization . . . 51 4.2.3 Final equations. . . 58 4.3 Numerical Solution . . . 59 4.3.1 Grid and discretization. . . 59 4.3.2 Solution of the system of linear equations. . . 62 4.3.3 Curve-fitting of model to measurements . . . 63 5 RESULTS AND ANALYSIS . . . 65 5.1 Experimental Results . . . 65 5.1.1 Static fiber tests. . . 65 5.1.2 Moving fiber tests . . . 73 5.2 Numerical Results . . . 87 5.2.1 Thermal properties of the material. . . 88 5.2.2 Grid and time-step convergence . . . 88 5.2.2.1 Mesh in steady state . . . 89 5.2.2.2 Mesh in unsteady state . . . 91 5.2.2.3 Time-step . . . 93 5.2.3 Dimensionless results. . . 93 5.2.4 Comparison to measurements . . . 97 5.2.5 Model fitting to measurements . . . 100 6 CONCLUSION . . . 107 6.1 General Conclusions. . . 107 6.2 Recommendations for Future Works. . . 108 Bibliography . . . 110 Appendix A – DAq Calibration and Uncertainty Analysis . . . 117 A.1 Thermocouples Calibration Procedure . . . 117 A.2 Uncertainties Analysis. . . 118 A.3 Temperature Uncertainty. . . 120

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1 1 INTRODUCTION

Chronic venous insufficiency (CVI) is a common disease with the worldwide prevalence. People affected are more predisposed to develop specific conditions like CVI of lower limbs, commonly known as varicose veins of lower extremities. Varicose veins are a degenerative disease of the venous system, in which the strength of the vein’s wall is reduced, with associated valvular dysfunction. It results in reflux (reverse or retrograde) flow in affected areas of the superficial venous system of the legs, (BERGAN, 2007;HEGER et al., 2014).

According to Golledge & Quigley (2003), varicose veins affect 10 to 40 % of the world population aged 30 to 70 years old. The early symptoms reported include pain and fatigue, followed by twisted and bulging veins. More severe cases are followed by venous ulcers, which are superficial injuries arising from local trauma, affecting the people quality of life directly, (HEGER et al., 2014;RASMUSSEN et al., 2007).

In Brazil, according to data of the Hospital Information System (SIH) from the Uniﬁed Health System (SUS), more than ﬁfty thou-sand unilateral surgical procedures were undergone in the period from January 2013 to October 2014. During this period more than ninety thousand bilateral surgical procedures were also performed, (Portal Bra-sil, 2014). Figure 1.1 presents the historical evolution of the surgeries

that were conducted in the lasts years, including unilateral and bilateral procedures.

Aside from the direct eﬀects in the welfare of patients, the econo-mical impact is also considerable. The data of National Social Welfare Council, available on Digital Observatory of Security and Health Work, shows that there were 5763 medical leaves due to this disease from 2013 to 2017, of which 1890 (32,8 %) were male patients and 3873 (67,2 %) were female, (Secretaria da Previdência, 2017).

The direct treatment of this condition is to eliminate the reﬂux at the vein. Historically, the usual treatment for this illness has been an open surgery with the complete extraction (stripping) and ligation of the defective vein. Recently, less invasive treatments have been develo-ped as alternatives to treat these conditions and complications. Exam-ples of these new treatments are the sclerotherapy, radiofrequency and laser ablation, (HEGER et al., 2014).

To implement the new treatments eﬀectively, doctors are seeking to develop less invasive and ambulatory surgical procedures, without the need of complex infrastructure and a team of specialists. One of these minimally invasive procedures is the endovenous thermal

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abla-2 1 INTRODUCTION

Figure 1.1: Evolution of the surgeries unilateral and bilateral performed Source: Adapted from Ministério da Saúde (2019).

tion with laser energy, used most frequently to treat varicose veins of lower limbs, mainly the great saphenous vein (GSV) and small saphe-nous vein (SSV). This treatment has demonstrated a great acceptance by patients and doctors, having shown eﬃciency, safety, and less pos-toperative complications, (RASMUSSEN et al., 2007; RASMUSSEN et al.,

2010).

Regarding the stripping procedure, it is important to emphasize that the total removal of the GSV can cause the destruction of other veins that drain to the saphenous vein causing bleeding and extensive hematomas, moreover, possible injury in the saphenous nerve. Indeed, after the recovery period, these symptoms improve, but the procedure always has trauma. After this procedure, the patient usually stays in recovery for 7 to 30 days. On the other hand, in the EVLT proce-dure, the period of recovery is markedly shorter than the traditional treatment, usually 4 days, (NEJM JR., 2015;BOOTUN et al., 2016).

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1.1 Motivation 3

treatment (EVLT) procedures, several studies regarding the elucidation of the physical mechanisms of this technique were developed. Examples are the works of Proebstle et al. (2002), Disselhoff et al. (2008), and Malskat et al. (2014a). The focus of earlier studies was on comparisons on the efficiency of the procedure when compared to other procedures, and differences in the corresponding postoperative. Recent efforts focus investigations of EVLT’s mechanism of action, heat transfer, tempera-ture field and, damage in the vein wall.

1.1 Motivation

Given the irreversible character of this procedure, any possible enhancement of the technique must be thoroughly investigated in−vitro with experimental and numerical tools before clinical trials (in−vivo tests).

Considering the background discussed above, there is still a need to understand better the mechanisms and phenomena involved with and, also to help and bring support to doctors to improve the applica-tion of the technique and thus obtaining more satisfying results. 1.2 Objectives

1.2.1 General objective

To investigate the effects of mechanical and thermal aspects in the EVLT surgical procedure more specifically, the effects of retraction velocity (pullback), power of laser energy source, optical fiber model in the temperature field at the vein wall with the assistance of an experi-mental apparatus and a numerical model.

1.2.2 Specific objetives

• To develop an experimental apparatus to study EVLT;

• To manufacture an artiﬁcial vein, instrument it and, mount in the workbench;

• To perform an in-vitro surgical procedure with a variation of the wavelength of the system, ﬁber type and, pullback;

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4 1 INTRODUCTION • To analyze the eﬀects of selected parameters on the temperature

ﬁeld in a model of the vein wall;

• To develop a numerical model that can reproduce the experimen-tal results;

• To elaborate conclusions about the eﬀects of the heat transfer mechanisms from laser to vein and general recommendations for clinical applications of the technique.

1.3 Structure of the Document

This document is divided into six chapters as follows.

Chapter one describes the motivation, objectives and general aspects of this work.

Chapter two presents the fundamental theories and concepts of the disease and surgical procedures, the physics of laser and laser-tissue interactions and, a review of the state of the art describing the foremost studies in experimental, numerical and clinical research in this ﬁeld.

Chapter three describes the experimental concepts, an overview of the experimental apparatus and the instrumentation, including an account of all components and their functions.

Chapter four presents the numerical method used including the governing equations, boundary conditions, and the nondimensionaliza-tion of the governing equanondimensionaliza-tions.

Chapter ﬁve presents the results, discussion, and comparisons with other studies.

Finally, chapter six presents the conclusions and recommendati-ons for further work.

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5 2 FUNDAMENTALS AND LITERATURE REVIEW

This chapter provides an overview of the varicose veins disease and historical evolution of surgical treatments. It covers a concise des-cription of the main treatments oﬀered nowadays and basic concepts of the mechanism of action as well as a detailed explanation of the EVLT technique and surgical procedure. The chapter includes an elucidation on the laser fundamentals and laser-tissue interactions and, a descrip-tion of thermophysical mechanisms involved. Finally, the state of the art in the experimental, numerical and clinical studies is presented. 2.1 Varicose Veins Disease and Treatments

2.1.1 Historical background

The circulatory system of human body is composed of blood, conductors, and heart. The conductors form the vascular system, which is formed of arteries, veins, and capillaries. Blood ﬂows through the arteries by heart pumping, and after permeating within tissues and organs it returns to the heart at lower pressure through the veins. There is no pumping in the vein system and valves prevent retrograde blood ﬂow.

Later in adult life, these valves begins to fail, and local blood reﬂux occurs between the chambers formed by the valves. The re-ﬂux leads to a deformation of the vein by stretching, tortuosity and abnormal diameter increase, normally appearing in the legs. These manifestations can jeopardize the functional mobility of the patient. Treatment of the varicose veins, in general, relieve these symptoms and improve the quality of life of patients. This dysfunction of the valves is aggravated in people with CVI and is associated with poor food ha-bits and sedentary lifestyle, (BEEBE-DIMMER et al., 2005). Figure 2.1

presents a rendering of a healthy vein and a varicose vein.

The cause of development of varicose veins in the legs is usually the venous blood reﬂux in the GSV and/or in the SSV. The disease is a worldwide public health problem, resgistered in the International Classiﬁcation of Diseases (ICD) from OMS with the code I83 (Varicose veins of lower extremities).

Earlier reports of varicose veins date approximately from 460 − 377 b.C. These reports mention that Hippocrates developed one of the

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6 2 FUNDAMENTALS AND LITERATURE REVIEW

Figure 2.1: Representation of (A) a normal vein with normal valves and blood ﬂow, and (B) a varicose veins with deformed valves and, abnormal and retrograde blood ﬂow.

Source: Adapted from Beebe-Dimmer et al. (2005).

first treatments by cauterizing the defective veins with a hot iron. He was the first to observe the association between the varicose veins and the ulcers in the leg. Through history, the disease and treatments have evolved. During the Roman era, Aurelius Cornelius Celsius (53 b.C − 7 a.C.) described in detail removing a varicose vein by surgery. The procedure was improved considerably in the past centuries. A breakth-rough happens with the description by Mayo (1904) about a metallic instrument in a ring shape to extraluminal extraction of the SSV. In the next year, Keller (1905) used an intraluminal device that inverts the vein upon the vein was pulled, being Babcock (1907) that deve-loped the fleboextrator, which consists of a metallic rod with a tip in an olive shape, this is the prototype of the materials used by doctors nowadays.

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2.1 Varicose Veins Disease and Treatments 7

the techniques have improved a lot, from the total extraction of the vein (stripping and ligation) up to the current treatments available on thermal, non-thermal and non-tumescent methods for vein occlusion. Regarding the thermal treatments, the use of the ﬁrsts few treatments began around the year of 1999 with the laser herewith the radiofre-quency ablation treatment, (MEDEIROS, 2006).

2.1.2 Evolution of varicose veins treatments

As previously mentioned, the history of varicose veins treatments comes from many centuries ago followed by a huge evolution and mo-dernization of the techniques.

The stripping was for decades the principal treatment to this disease. The treatment consists of open surgery with a complete with-drawal of the GSV or SSV by which breaks all other veins that drain into the saphenous vein. Bleeding, extensive bruising and, signs and symptoms of saphenous nerve injury are common symptoms because of the removal of the vein. In fact, these complaints usually improve up to six months, but these are an unwanted outcome of the procedure, (NEJM JR., 2015).

Over time, several segments of medicine obtained an expressive evolution due to the searching by doctors for less invasive surgical pro-cedures. In the same direction, with less invasive procedures it is possi-ble the realization in ambulatory or medical practices without support from a big physical structure and personal team. The introduction of minimally invasive techniques to treat varicose veins was towards the end of the twentieth century. These have dramatically changed the management of varicose veins.

Nowadays, besides the stripping, doctors are using other treat-ments divided into thermal and non-thermal treattreat-ments. Foam scle-rotherapy is the main used in relation to non-thermal treatment. Con-cerning the thermal treatments, the alternatives are the radiofrequency ablation and endovenous laser ablation. The treatment is selected by the doctor, being speciﬁc for each case according to the illness stage and/or inﬂuencing factors to the outcome, (BOOTUN et al., 2016).

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8 2 FUNDAMENTALS AND LITERATURE REVIEW 2.1.2.1 Stripping and ligation

The removal of GSV from the circulation system is one of two essential steps in varicose veins of lower limbs treatment. Incompetent valves along the GSV allow blood to reﬂux down the vein and into its tributaries (veins connected to the defective one), transmitting high pressure into smaller tributaries, which become varicose development as a result. Traditionally, the treatment was accomplished surgically by ligation of an incompetent saphenofemoral or saphena popliteal junc-tion (SFJ or SPJ) along with stripping of the reﬂuxing truncal vein.

As other procedures, that will be addressed in the sequence, it is followed by detailed preoperative steps. The preoperative evaluates the patient history, the mapping and demarcation of defectives veins segments at the patient.

The procedure involves making incisions at the beginning and at the end of the defective vein and other tributaries. These tributaries are connected to another deeper vein which takes care of the large volume of blood, in this way, the circulation not becomes so complicated. A flexible instrument is threaded up to the vein to the first incision at the end. The vein is grasped and removed. Then, the defective vein is fixed to the instrument and with the aid of a tool, removed, (MAYO CLINIC,, 2019;BOOTUN et al., 2016;BERGAN, 2007). Figure 2.2 presents

an exempliﬁcation of the procedure.

Are described in sequence at Figure 2.2, (A) the vein is cathe-terized with a downstream stripper towards the groin. (B) A strong thread is knotted on the stripper. (C) The stripper is withdrawn from the groin to the malleolus and the thread takes its place. (D) This wire is attached to the great saphenous vein in the groin. (E) Trac-tion on the distal end of the wire allows vein stripping by invaginaTrac-tion, (PERRIN, 2007).

In this procedure, the postoperative is followed by compression bandaging or socks. With it, most patients experience little downtime, but some, however, do experience hematomas, pain, and extensive brui-sing, (BERGAN, 2007).

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Figure 2.2: Stripping surgical procedure representation.

Source: Adapted from Perrin (2007).

2.1.2.2 Foam sclerotherapy

Foam sclerotherapy is the original thermal and non-tumescent (NTNT) method. The treatment uses a combination of sclerosing drug and air (“air block” technique). The technique initially was described by Orbach in 1994, (FRULLINI; CAVEZZI, 2002). In

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10 2 FUNDAMENTALS AND LITERATURE REVIEW thermal procedures, the heating can cause some complications and unwanted outcomes, i.e, damaging superﬁcial nerves. Non-thermal ablation technique was introduced in an attempt to avoid potential complications of thermal ablation, (BOOTUN et al., 2016).

Sclerotherapy, one of these minimally invasive procedures, uses an injection of a special chemical (sclerosant) into a varicose vein to da-mage and scars the inside lining of the vein. Two of the most common solutions used are polidocanol (POL) and sodium tetradecyl sulfate (STS), (TEKIN et al., 2016;BOOTUN et al., 2016). These solutions have

been shown to react with venous endothelium. The mechanism of ac-tion of these soluac-tions is causing damage (endosclerosis) and ﬁbrosis (endoﬁbrosis) of the vessel lumen, (GOLDMAN, 2002).

Sclerosing foam displaces venous blood, increasing contact with endothelium, thereby, increasing their power. The solution causes in-tense spasm to the vein. A greater volume can be injected without using too much of the drug due to this foam characteristic. The performance is followed by ultrasound as well as RFA and EVLT, (TESSARI et al.,

2001;TEKIN et al., 2016). The treatment is exempliﬁed in Figure 2.3.

Figure 2.3: Foam sclerotherapy treatment representation. (A) Injection of sclerosing drug followed by ultrasound guidance. (B) Vein closing through reaction with the solution. (C) Vein after treatment.

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The initial results were very promising with the application of foam sclerotherapy to treat varicose veins. This method of treatment offers a possible alternative to surgery. In the beginning, this was effective for the treatment of smaller veins (spider veins). These spider veins are damaged veins that appear at the surface of the legs or face. They usually are not painful or harmful, and the treatment becomes more for cosmetic reasons. Furthermore, over the years, ultrasound guidance was introduced to the treatment, increasing the efficiency of the technique. Nowadays, the treatment is used to treat bigger veins with the same results, (TEKIN et al., 2016;BOOTUN et al., 2016).

2.1.2.3 Radiofrequency ablation

Radiofrequency (RF) waves are a portion of the electromagnetic spectrum bordered by the frequencies of 3 Hz and 300 GHz. The in-teraction of electromagnetic waves with materials can be very different and dependent on the material frequency reaction. The radiofrequency application in medicine causes thermal ablation of a defined volume of tissue. The procedure is performed using a specific electrode that delivers energy. The electrode produces a very high energy flux around the tip due to the small cross-sectional area.

On the other hand, the energy delivered by the electrode dis-perses through the large cross-sectional area that surrounds the tip, minimizing the ﬂux. As a result, the damage is limited to the part that surrounds the electrode tip. Thus, the ablation results in coagulative necrosis of the tissue from high temperatures. The dipole molecules immediately next to the tip of the RF electrode attempt to remain aligned in the direction of the current. Applying alternating current, the molecules are forced to vibrate rapidly because of this excitation. Molecules farther away from the electrode are set into motion by other vibrating molecules near them. Local energy deposition and tempe-rature increasing are a result of the frictional energy losses between adjacent molecules, (HONG; GEORGIADES, 2010).

Roth (2007) describes that endovenous radiofrequency ablation (RFA) is a catheter-based endovascular intervention with RF energy de-livered in continuous or sinusoidal wave mode. Also, when high energy is used (between 200 and 3000 kHz) there is no stimulation of neuro-muscular cells. The mechanism by which RF current heats tissue is resistive (or ohmic), heating a narrow rim of tissue that is in direct contact with the electrode. Controlling the rate of heating can be

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achi-12 2 FUNDAMENTALS AND LITERATURE REVIEW eved subtle gradations of either controlled collagen contraction or total thermocoagulation of the vein wall. The RF technique is considered also a minimally surgical procedure to treat varicose veins. One of the catheters used to perform this procedure is shown in Figure 2.4.

Figure 2.4: Example of catheter used to perform the RFA procedure.

Source: (ROTH, 2007).

The surgical procedure of radiofrequency ablation is similar to the laser ablation, and will be described in the sequence. Figure 2.5 presents an illustration of the procedure.

Through the RFA, the heat is generated by the passage of electri-cal current through the tissue, resulting in resistive heating. Therefore, during this resistive heating, the heat is generated in the vein wall and not in the catheter tip. Through this procedure application, is possible to obtain precise tissue destruction with endothelial denudation, media,

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Figure 2.5: Radiofrequency treatment representation. (A) Catheter stationary during treatment at saphenofemoral junction. (B) Slight overlap between treatments. (C) Vein treated stepwise along the length.

Source: (ROTH, 2007).

and intramural collagen denaturation, with a subsequent ﬁbrotic seal of the vein lumen with minimal formation of thrombus and coagulum, (GOLDMAN, 2000; ROTH, 2007).

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14 2 FUNDAMENTALS AND LITERATURE REVIEW 2.1.2.4 Endovenous laser ablation

The ﬁrsts experience related to the use of laser energy technology in medicine comes from 1964. From then on, the idea about to use this technology in surgery arises. The ﬁrst’s results were not satisfactory even with a good perspective on the use of laser. The progress regarding laser uses in surgery appears at the beginning of the 1970 decade with the manufacturing of a CO2 surgical laser by Polanyi, (MEDEIROS,

2006).

Endovenous laser ablation was introduced towards the turn of the century with Boné (1999) and Navarro et al. (2001) describing the first clinical trial. For a study, there were recruited and treated 33 patients (44 GSV) having SFJ reflux with GSV incompetence. The technique appeared safe and very effective in the short-term of time due to the occlusion of all treated GSV segments. The ablative procedure consisting of laser energy delivered at a wavelength of 810 nm along the GSV while the laser fiber was being slowly pulled back in 3 −5 mm increments.

The eﬃcacy of EVLT was conﬁrmed in a second study developed by Proebstle et al. (2002), using a similar technique as Navarro et al., with a variation, a laser system with a wavelength of 940 nm. They treated 26 patients (31 limbs) with GSV incompetence. One patient had an incomplete occlusion giving a complete occlusion rate of 97 %, (BOOTUN et al., 2016).

The procedure consists of using laser energy to cause injury at the vein wall, and also to develop thrombosis due to the blood re-action with temperature. After the procedure, blood vessels become thrombotically occluded within minutes, which trigger a chronic type inﬂammatory response that mediates tissue remodeling (cicatrization) and ultimately permanent closure, (HEGER et al., 2014). The laser is

conducted through an optical ﬁber, which can be bare or radial tip. Figure 2.6 presents illustrate the response of the treated vein to the laser energy.

Regarding the response of EVLT application presented in Fi-gure 2.6 it follows a sequence established as (A) The response of the laser energy cause photothermal conversion in erythrocytes and vas-cular wall affected, protein and collagen denaturation, followed by en-dothelial cell activation/denudation, thermal coagulum formation, and mural cell death. (B) Infiltration of immune cells and fibroblasts, th-rombus organization, obliterative remodeling which results in fibrosis

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Figure 2.6: Thermal eﬀects at vein after EVLT procedure.

Source: Adapted from Heger et al. (2014).

of vascular lumen and ﬁnally, no blood ﬂow.

2.1.3 Endovenous laser treatment - Surgical procedure

For Gibson et al. (2007), the first step is followed by careful pre-paration, n the preoperative is necessary a complete surgical history and a physical examination of the patient. The investigation of the history of the patient surgeries aims to verify if was carried some pro-cedure to treat the veins (stripping, sclerotherapy or ablation) or other in the vascular system. In addition, is obtained a survey about familiar historic linked to circulatory system diseases. The physical exam is to verify the presence, distribution, and dimensions of varicose veins. In practice, are made photos during the evaluation that precedes the sur-gery as in the post-evaluation to attach to the patient documentation. The second step is still in the preoperative stage, is an exam by duplex ultrasound. The exam aims to obtain a detailed anatomy map-ping of the local blood flow and the location of the defective segments with local blood reflux. The exam also allows evaluating other veins in the early stages of the disease. Following this, the treatment planning is carried. As the final step of the preoperative, the patient is placed in a specific position, lying turned upwards when the treatment is in the GSV and turned downwards when is in the SSV, (GIBSON et al., 2007).

The third step can be deﬁned as the following topics: anesthesia, vascular access, and ﬁber positioning. It is held local anesthesia accor-ding to which vein will be treated. Usually, is administered a 500 mL of saline solution with 35 mL 1 % lidocaine diluted, also containing 5 mL of epinephrine and 5 mL of bicarbonate. The vascular access is

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16 2 FUNDAMENTALS AND LITERATURE REVIEW performed with aid from a coaxial puncture needle, which consists of a type of tube with a needle inside. The vein is perforated with the instrument and after positioned, take the needle oﬀ and the access is done, (BOS et al., 2008).

Through the access, is introduced a guideline until the sapheno-femoral junction (SFJ). The use of this guideline is to obtain a reference that helps the positioning of the ﬁber inside the vein. Usually, the po-sitioning of the ﬁber and the other steps of the procedure are followed by ultrasound guidance, (THEIVACUMAR et al., 2008).

With the guideline positioned, a bigger catheter is introduced taking off the access. This bigger catheter allows the introduction of the fiber maintaining the guideline. The fiber is inserted and positioned in a distance of 25 mm above the SFJ. This distance is recommended with the purpose to not cause junction damage and unwanted local thrombosis. The guideline is removed before the procedure starts. The fiber position is followed by ultrasound, but also, it is possible to observe the fiber tip position under the skin caused by laser illumination.

The fourth and last step consists of the laser triggering and the energy delivery according to the parameters set in the equipment (power and delivering mode). The fiber is moved by retraction in a variable velocity. The velocity is dependent on the results observed in the ultrasound screen, as example the vein contraction due to the ef-fect of heating. The vein contraction is observed, and according to the contraction, moves the fiber, performing in this way, the vein ablation. When the vein it is not reacting with the heating the fiber tip can be with a clot of carbonized blood at the tip, thus, the doctor removes the fiber, clean it and introduces at the last position, and returns to perform the procedure. The movement of the fiber is called pullback.

It is common the manufacturer of the equipment to provide gui-delines with reference values for each method of use, as for example, the range of power for endovenous treatments. However, usually these parameters are set by doctors according to his technique and experi-ence, (BERGAN, 2007). Figure 2.7 presents an exempliﬁcation of the

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Figure 2.7: Representation of EVLT procedure application.

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18 2 FUNDAMENTALS AND LITERATURE REVIEW 2.2 Laser

2.2.1 Laser fundamentals

The term laser is the acronym for Light Ampliﬁcation by Stimu-lated Emission of Radiation. Light and other electromagnetic energy sources are composed of elementary particles known as photons. Pho-tons travel in the light velocity at the speed of light in vacuum. The pro-pagation of photons can also be described as an electromagnetic wave with wavelengths varying from gamma rays, for small wavelengths, to radio waves, for large wave lengths.

The visible light takes a relatively small region in the spectrum of electromagnetic radiation. This visible light is located between 390 nanometers (nm) and 700 nm. These wavelengths correspond to the human eye perception of the colors violet and red, respectively. Fi-gure 2.8 presents the full spectrum of electromagnetic radiation and a description of the visible range in terms of the corresponding colors.

Figure 2.8: Electromagnetic radiation spectrum.

All lasers devices are monochromatic, i.e., they emit light in just one speciﬁc wavelength. Basically, the laser systems have four parts: a system of energy source, an optical resonant cavity, the active medium and the delivery system involving optic ﬁber or mirrors. Vuylsteke & Mordon (2012a) emphasize that diode lasers systems are the most used in endovenous treatment, which are compact, provides a continuous light emission and, are relatively cheap.

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2.2 Laser 19

In the laser operation, the energy delivered by the source is used to excite charged particles that emit the laser light when they return to their ground states. This energy delivered can be in the form of a lamp, electrical current, or even as another laser beam. In the optic resonant cavity, the active medium is enclosed in a sealed tube with two mirrors, one of these totally opaque and the other partially transmissible.

When electrons in an excited state match a photon containing similar energy, they will emit a new photon with the same wavelength without absorbing this additional photon. Therefore, a chain reaction starts causing a further increase in the volumetric density of photons. Photons that are moving in a parallel direction leave the cavity through the partially transmissive mirror, taking the shape of a laser beam. The laser beam is conducted by other mirrors or optical ﬁbers. Franck et al. (2016) presents additional details of the equipment operation. Figure 2.9 presents the laser system components.

Figure 2.9: Laser system representation.

Source: Adaptade from Bergan (2007), Franck et al. (2016).

Table 2.1 presents the most common lasers found in medical applications and, and their characteristic range of wavelengths.

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20 2 FUNDAMENTALS AND LITERATURE REVIEW Table 2.1: Commonly lasers for medical application

Laser Active medium λ[ nm ] Power [ W ] GaAlAs Semiconductor 780 − 870 1 − 100

Nd:YAG Solid state 1064 100

Nd:YAP Solid state 1080 − 1341 10 − 100

Ho:YAG Solid state 2100 10 − 100

HF Chemical 2600 − 3000 150

CO2 Gas 10600 100

Source: (PENG et al., 2008).

2.2.2 Biologic materials

During EVLT, the laser interacts with blood and vein wall. Sil-verthorn (2010) describes that the blood is the portion of extracellular liquid that is circulating in the body, and is responsible to transport substances from a body part to another. Its composition can be sepa-rated into two groups. One is the plasma, composed of water, ions, or-ganic molecules, trace elements, vitamins, and gases. The other group is formed by cellular elements, such as erythrocytes, leukocytes, and platelets.

The vein is laid out in three layers denominated endothelium, smooth muscle and connective tissue. These biological materials can be described as complex combination of cells, liquids, and intercellular substances.

Both the blood and the tissue that composes the vein wall con-tain light absorption elements known as chromophores, which present strong absorption of laser light at speciﬁc wavelengths in the electro-magnetic spectrum. Vuylsteke & Mordon (2012a) presents as examples of chromophores usually found in tissue the melanin, hemoglobin, ca-rotenoids, proteins, and water.

2.2.3 Laser-tissue interactions

The interaction between the laser and biologic materials, or in this case, biologic tissue occurs by absorption and scattering of pho-tons. The absorption fraction consists of those photons whose energy excite transition states in the tissue molecules. The scattering fraction correspond to those photons that are reﬂected and diﬀracted from the

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2.2 Laser 21

tissue and are eventually absorbed by molecules around the laser focus. Figure 2.10 presents these interactions during tissue irradiation with a laser beam.

Figure 2.10: Laser beam interaction representation with tissue.

Source: (STEINER, 2011).

During EVLT, the laser beam irradiates the blood. Blood has chromophores that absorb photons in speciﬁcs wavelengths. After the laser beam is absorbed and scattered by blood, a fraction of it reaches the vein wall that also absorbs and scatters laser radiation. Part of the laser radiation that reaches the vein wall may be scattered back to the blood.

When photons are absorbed by biological components, the energy transfer of the photon to the chromophore leads to several inte-ractions mechanisms, such as the photothermal, photomechanical and photochemical eﬀects, (FRANCK et al., 2016). As a ﬁrst approximation,

the main mechanism in venus ablation is the photothermal effect. The photothermal effect can produce direct damage to the tissue, cells and adjacent structures because of the temperature rise. Due to the heating, the tissue suffers reversible and irreversible damages. These

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22 2 FUNDAMENTALS AND LITERATURE REVIEW damages are described with more details in Table 2.2 correlated to the respective temperatures.

Table 2.2: Laser-tissue interactions: thermal eﬀects. Temperature Molecules and Tissue Reaction

◦_C

42 − 45 Hyperthermia leading to protein structural changes, hy-drogen bond breaking, retraction

45 − 50 More drastical conformational changes, enzyme inacti-vation, changes in membrane

50 − 60 Coagulation, protein denaturation ∼ 80 Collagen denaturation

80 − 100 Dehydration

> 100 Boiling, steaming

100 − 300 Vaporization, tissue ablation

> 300 Carbonization

Source: (PENG et al., 2008).

Next section presents a description of the mechanisms of absorp-tion and scattering in the tissue and biologic materials.

2.2.3.1 Absorption

Is the primary event that provides a laser or other light source to cause a potential therapeutic eﬀect (or damage) in a tissue, ( VUYLS-TEKE; MORDON, 2012a). The absorbents molecular components are

melanin, hemoglobin, flavin, porphyrin, nucleic acids, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), nicotinamide adenine dinucleotide reduced (NADH) and water. The photon absorption by a chromophore produces changes in eletronic (electron transition caused by ultravio-let visible spectrum) and vibrational states of the molecule (vibration transition caused by near infrared). The coefficient that characterizes the absorption coefficient is µa,λ[1/cm], (STEINER, 2011). Figure 2.11 presents the absorption coefficient relative to the wavelength of some chromophores.

It is possible to observe, that up to the wavelength 1000 nm some substances as eumelanin, hemoglobin and melanin have an absorption coefficient larger than that for water. From this wavelength coefficient, the water coefficient remains dominant over other substances. The wa-ter presents the maximum value of absorption between the wavelength

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2.2 Laser 23

Figure 2.11: Absorption spectrum by tissue chromophores.

Source: (STEINER, 2011).

of 1350 nm and 1600 nm. 2.2.3.2 Scattering

The diﬀusion of light in biological tissue is a result of the la-ser beam scattering by cells, lysosomes, mitochondria, macromolecules, membranes, and other biological components, (ANSARI; MOHAJERANI,

2011).

The scattering behavior of biological tissue is important because it determines the volume distribution of light intensity in the tissue. The scattering is the primary step for tissue interactions, which is fol-lowed by absorption and heat generation. Scattering of a photon is accompanied by a change in the propagation direction without loss of energy. According to the size of the scatterer, this mechanism can be represented as Rayleigh or Mie scattering. Scattering of tissue is always a combination of Rayleigh and Mie coeﬃcients. The scattering

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24 2 FUNDAMENTALS AND LITERATURE REVIEW coeﬃcient is represented by µs,λ [1/cm].

With the values of absorption and scattering, it is possible to establish an attenuation factor by arrangement between absorption and scattering processes. The total attenuation factor is represented by µt,λ [1/cm], (STEINER, 2011).

2.2.4 Mechanisms of action

In the medical applications of EVLT for varicose veins, the ob-jective is to cause irreversible damage of the vein wall in such a way to eliminate the blood reﬂux. Therefore, the knowledge about the me-chanisms of action is of utmost importance, not just in improving the eﬃciency of clinical results through the treatment, but also in avoiding complications to the patient in the postoperative.

According to Bergan (2007), laser energy is considered recent to treat varicose veins, being the mechanisms of action sill under dis-cussion and not fully understood. The combination of intense thermal reaction and blood heating at the water evaporation point, in general, can be considered as mechanisms of injury caused by EVLT.

Disselhoﬀ et al. (2008), Fan & Rox-Anderson (2008), and Vuyls-teke & Mordon (2012a) present discussions of the mechanisms and this is discussed next.

2.2.4.1 Steam bubble

Based on the studies by Fan & Rox-Anderson (2008) and Vuyls-teke & Mordon (2012a), during the procedure, either in in-vitro as well as in in-vivo treatments by ultrasound, it is possible to observe bubble formation inside of the vein. These bubbles originate from the evaporation of the water fraction of the blood.

The steam bubbles move through the blood by buoyancy, colli-ding, heating and condensing at the vein wall. In this process, a high amount of energy is delivered to the vein causing irreversible damage by protein and collagen denaturation followed by dehydration, which favors thrombosis of the vessel and its occlusion. This heating is con-sidered an indirect mechanism.

The work of Proebstle et al. (2002) presents one of the ﬁrsts EVLT experiments and a discussion on the formation of steam bub-bles. In a histology of treated vein segment damage at the top of the

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2.2 Laser 25

circumference section was observed.

The experimental set-up consisted of a tube with known dimen-sions instrumented with a ruler and coupled to another silicone tube ﬁlled with heparinized blood. During the laser energy deposition inside of this tube it was observed the variation of the blood volume by the ruler and the bubbles within the tube. The author concludes that this is the primary mechanism of action of vein damage.

2.2.4.2 Direct contact

This is a mechanism addressed by Fan & Rox-Anderson (2008) and Vuylsteke & Mordon (2012a). When the fiber is introduced into a saphenous vein, due to the tortuosities and bends, the fiber has the tendency to stretch the vein. As a consequence of this stretching, the fiber tip frequently hits the vein wall. When the fiber tip is hot, the direct heating may cause ulceration and vein perforation.

This perforation can cause damage to the surrounding tissues and peripheral ligations, and other traumas. This deviation of the ﬁber with respect to the vein centerline, can result in non-integral and irregular damage, increasing the possibility of recanalization. Though these complications that the direct contact can cause to the vein, the mechanism of action is important to the success of the procedure.

Disselhoff et al. (2008) opposes the findings of Proebstle et al. (2002), in their work, they suggested that the direct contact of the fiber with the vein wall is the primary mechanism of action. This conclusion derived from an analysis of treated tissue, where no signs of denaturation were found between damaged points. The presence of heavily damaged points suggest that the fiber did not carry out circumferential denaturation, just punctual, in the places where the fiber touches the vein wall.

2.2.4.3 Direct energy absorption of the vein wall

Vuylsteke & Mordon (2012a) also discuss the direct energy ab-sorption by the vein wall. The light energy delivered inside of the vein by the fiber tip can be absorbed by the blood, water, or the vein wall. If the light is absorbed by the blood, the initial effect will be a throm-botic occlusion. However, this light energy can be absorbed directly by the vein wall, without direct contact occurring between the fiber tip