以磁纳米粒子为热源的双相滞后热传输
Dual-Phase-Lag Heat Transfer with Magnetic Nanoparticles as Heat Source
DOI: 10.12677/MOS.2020.93021, PDF, HTML, XML, 下载: 709  浏览: 1,294  科研立项经费支持
作者: 孙逸尧, 菅永军*:内蒙古大学数学科学学院,内蒙古 呼和浩特
关键词: 双相滞后模型磁纳米粒子分离变量法滞后参数Dual-Phase-Lag Heat Transfer Model Magnetic Nanoparticles Method of Separation of Variables Lag Parameters
摘要: 磁感应热疗逐渐成为肿瘤治疗的热点领域。本文研究了以磁纳米粒子为热源的双相滞后传热模型。引入了描述温度和热流量的两个滞后参数τt和τq对Pennes热传导方程进行修正。利用分离变量法对修正的方程进行求解,得到温度的解析解,并分析了不同磁化率和磁场频率对温度分布的影响。结果表明,当磁化率或磁场频率增加,会使磁纳米粒子产生更多的热量,同时温度也会有所升高。此外,当无量纲时间为0.7左右时温度达到最大值。本研究对于磁流体热疗具有一定的理论指导作用。
Abstract: Magnetic induction hyperthermia has gradually become a hot field of tumor therapy. In this paper, a dual-phase-lag heat transfer model with magnetic nanoparticles as the heat source is studied. Two time-lag parameters τt and τq, describing temperature and heat flux lag times respectively, are introduced to modify Pennes heat conduction equation. The method of separation of variables is used to solve the modified equation. The analytical solution of temperature is obtained, and the influence of magnetic susceptibility and external magnetic field frequency on the temperature distribution is analyzed. The results show that as the magnetic susceptibility or the magnetic field frequency increases, the magnetic nanoparticles will generate more heat, and the temperature will also increase. Moreover, the temperature has a peak when dimensionless time is about 0.7. This study has some theoretical importance of magnetic induction hyperthermia.
文章引用:孙逸尧, 菅永军. 以磁纳米粒子为热源的双相滞后热传输[J]. 建模与仿真, 2020, 9(3): 195-205. https://doi.org/10.12677/MOS.2020.93021

1. 引言

近年来,热疗法逐渐成为肿瘤治疗的新领域。其中磁感应热疗是新兴的一种热疗方法。磁感应热疗的核心方法是将磁纳米粒子通过直接注射、静脉注射等方式使磁性纳米颗粒聚集在肿瘤区域附近,然后施加一外部交变磁场,使材料因产生磁滞、弛豫或感应涡流等现象而被加热。利用热源使得肿瘤组织升温,通过精确控制热疗温度,在不伤害正常组织的前提下,使肿瘤细胞自然凋亡。Johanssen [1] 报导了一组临床试验数据,表明了磁热疗可使90%的前列腺肿瘤组织温度达到38.8℃~43.4℃。Bohara [2] 等人对乳腺癌细胞进行了体外热疗试验,证实了磁流体热疗治疗乳腺癌的潜在可能性。

在低温情况下,热是以有限的速度传播的。为描述这种非傅立叶导热现象,Cattaneo [3] 提出了双曲型模型。这种模型假定在一个控制体内,热量流动和温度变化是在不同的时间发生的,两者存在着时间上的延迟。该模型因其形式简单、物理意义明确,在分析非傅立叶导热现象时获得了广泛的应用。但是对于双曲型热传导方程,Bai等人 [4] 发现,在某些条件下得出的温度会低于绝对零度,而且非傅立叶导热与热波并非等价。Tzou等人 [5] [6] [7] 分析了采用双曲型模型描述温度场的基本原理,从宏观和微观的角度对传热现象进行了研究,发展了更为完善的双相滞后(Dual-Phase-Lag, DPL)模型来描述非傅立叶导热现象。Poor等人 [8] 通过分离变量法求得了具有恒定的、周期性的和脉冲热流条件的双相滞后生物传热方程的解析解,研究了时间独立的表面热通量下皮肤组织的温度响应情况。

另外,在生物传热研究中,传统的Pennes方程因其简洁性得到了最为广泛的应用。但Pennes方程也有一定的局限性。对于常规条件下的热传导方程,人们通常用傅里叶定律来描述热流密度与温度梯度之间的关系,但在其描述瞬态导热过程时,与能量方程的结合得到的抛物线型温度方程由于热扰动现象将出现温度传播速度无限大的情况 [9],显然是不符合物理实际的。因此对传统的Pennes方程利用双相滞后模型对其修正是有必要的。Liu等人采用广义的双相滞后生物传热模型来描述激光辐照活组织的热行为 [10] 和在生物组织中被高度吸收的激光照射现象 [11],利用Laplace变换和改进的离散化技术研究了血液与组织的耦合系数、孔隙率和相位滞后时间对温度的影响。

基于以上研究,本文将引入双相滞后时间τtτq的傅里叶传热方程与Pennes方程联立得到修正的Pennes方程。将磁纳米粒子作为热源,考虑修正的Pennes方程中的热源项随磁化率和磁场频率的变化。使用分离变量法对修正的方程进行求解,给出温度分布的解析解。讨论了磁纳米粒子的磁化率,外磁场频率和滞后时间对温度分布的影响。该研究对磁感应热疗的相关实验有一定的指导意义。

2. 模型建立

首先,一维傅里叶热传导定律可表示为 [12]:

q ( x , t ) = k T x , (1)

其中,k为组织热导率,T是组织温度,q为热流量。将傅里叶定律中的热流量q和温度T看作时间t和空间x的函数,并引入双相滞后时间τtτq,式(1)变为:

q ( x , t + τ q ) = k T ( x , t + τ t ) x (2)

对很小的滞后时间τtτq,将方程两边分别在t点进行泰勒展开,并保留一阶偏导数,得:

q + τ q q t = k x ( T + τ t T t ) , (3)

式(3)中τq为热松弛时间,τt是温度弛豫时间 [13] [14] [15]。

引入一维Pennes热传导方程 [16]:

ρ c T t = x ( k x T ) + ρ b c b ω b ( T a T ) + Q m , (4)

其中,ρ是组织密度,c是组织比热,ρbcbωb分别为血液密度、比热和灌注率,Ta是动脉温度为常数 [17]。此外,Qm为磁纳米粒子在外磁场条件下产生的热源,其表达式可表示为 [18]:

Q m = μ 0 π χ 0 f H 0 2 2 π f τ 1 + ( 2 π f τ ) 2 , (5)

其中f是磁场频率,H0为磁场强度,μ0是真空的磁导率,χ0磁化率,τ为磁纳米粒子的有效弛豫时间。联立式(3)和(4),消去热流量q得:

( 1 + τ q t ) ( ρ c T t ) x ( k τ t 2 T t x ) = x ( k x T ) + τ q ( ρ b c b ω b T t + Q m t ) + ρ b c b ω b ( T a T ) + Q m (6)

3. 方程的求解

假设热源为定常与时间无关,将式(6)重新整理,可化简为:

( 1 + τ q t ) T t + ρ b c b ω b ρ c ( 1 + τ q t ) ( T T a ) = k ρ c 2 T 2 x + k τ t ρ c 3 T t 2 x + Q m ρ c , (7)

式(7)是线性非齐次偏微分方程,且关于时间和空间的最高偏导数都是二阶。故需要给出两个初始条件和两个边界条件。设初始时刻温度为T0且温度不发生变化:

T | t = 0 = T 0 , T t | t = 0 = 0 ; (8)

边界条件满足:

k ( T x | x = 0 ) = q 0 , T x | x = L = 0 , ( 0 x L , t > 0 ) , (9)

其中T0为初始温度,q0为初始热流量,L为皮肤组织的厚度。为计算简便,引入如下的无量纲变量 [19]

t = ρ b c b ω b ρ c t , x = ρ b c b ω b ρ c x , θ ( x , t ) = T T a q 0 ρ b c b ω b k , ψ = k ρ b c b ω b Q m q 0 (10)

则控制方程、初始条件和边界条件(7)~(9)化为:

A 2 θ t 2 + B θ t + θ = ( 1 + D t ) 2 θ x 2 + ψ , (11)

θ | t = 0 = 0 , θ t | t = 0 = 0 , (12)

θ x | x = 0 = 1 , θ x | x = x L = 0 , ( 0 x x L , t > 0 ) ,(13)

式中, A = ρ b c b ω b ρ c τ q B = 1 + A D = ρ b c b ω b ρ c τ t x L = ρ b c b ω b k L

首先,为了将非齐次方程(11)齐次化,令 θ * = θ ψ ,带入式(11)~(13)得:

A 2 θ * t 2 + B θ * t + θ * = ( 1 + D t ) 2 θ * x 2 , (14)

θ * | t = 0 = ψ , θ * t | t = 0 = 0 ,(15)

θ * x | x = 0 = 1 , θ * x | x = x L = 0 , ( 0 x x L , t > 0 ) . (16)

由于边界条件(16)是非齐次的,根据叠加原理,(14)可分解成两个问题,假设 θ * ( x , t ) = θ 1 ( x , t ) + θ 2 ( x ) ,带入方程(14)~(16),使得θ2满足:

d 2 θ 2 d x 2 θ 2 = 0 , (17)

d θ 2 d x | x = 0 = 1 , d θ 2 d x | x = x L = 0 , (18)

容易求得它的解为:

θ 2 = cosh ( x L x ) sinh ( x L ) (19)

另外,由式(14)~(18)可知θ1满足如下问题:

A 2 θ 1 t 2 + B θ 1 t + θ 1 2 θ 1 x 2 D 3 θ 1 t x 2 = 0 , (20)

θ 1 x | x = 0 = 0 , θ 1 x | x = x L = 0 , (21)

θ 1 | t = 0 + θ 2 = ψ , θ 1 t | t = 0 = 0 (22)

注意到方程是线性齐次方程且边界条件是齐次的,所以可以利用分离变量法对方程进行求解,具体求解过程见附录A。最后解得:

θ = θ * + ψ = θ 1 + θ 2 + ψ . (23)

式中θ1θ2,ψ由附录A给出。

4. 结果与讨论

本文研究了磁纳米粒子为热源的双相滞后修正的Pennes传热方程,利用分离变量法求得了温度分布的解析解。考虑磁感应热疗中的实际问题,相关参数使用文献 [17] [20] [21] 中给定的参数:组织密度 ρ = 1000 kg / m 3 ,组织热导率 k = 0.628 J / ( m K ) ,组织比热 c = 4187 J / ( kg K ) ,血液密度、比热和灌注率分别为 ρ b = 1000 kg / m 3 c b = 4187 J / ( kg K ) ω b = 1.87 × 10 3 s 1 ,动脉温度 T a = 37 ˚ C ,初始热流量 q 0 = 1.9 × 10 4 W / m ,皮肤组织厚度 L = 5 × 10 2 m ,由此可知x'的取值范围为0~5.5829。真空的磁导率 μ 0 = 4 π × 10 7 N / A 2 。另外,我们考虑肿瘤热疗使用Fe3O4磁性纳米粒子 [22],其中有效弛豫时间 τ = 10 6 s ,磁化率χ0的量级为10−4~10−3,磁场强度 H 0 = 5 × 10 4 A / m ,磁场频率f的量级为105 Hz。由式(23)可求得此时的温度分布。

图1图2是当空间位置 x = 2 时,分别令 χ 0 = 6.14 × 10 4 χ 0 = 5.02 × 10 3 ,对于不同的弛豫时间τt (0 s和16 s)无量纲温度随时间的变化分布图。此时,热流量松弛时间τq统一取16 s。由式(5)和上述参数取值可知,两图中的热源分别为 Q m = 7.5 × 10 5 W / m 3 Q m = 6.15 × 10 6 W / m 3 。可以看出,温度随时间的变化是具有相同趋势的,首先快速增长并在 t = 0 .7 左右到达其峰值,而后缓慢下降,并在 t = 3 左右逐渐趋于稳态。即在达到稳态之前,温度会出现波动行为。式(23)中给出的解析解中的余弦项恰好也说明了温度会随时间发生波动。但随着时间的增加,解析解中的余弦项产生的影响会逐渐减弱,因此,温度会趋于某一固定值。

同时可以发现,不同磁化率下, τ t = τ q = 16 s 时的最大值总是小于 τ t = 0 s τ q = 16 s 时的最大值,这

Figure 1. θ changes with t' at x = 2 , χ 0 = 6.14 × 10 4 , τ q = 16 s , τ t = 0 s and 16 s respectively

图1. 当 x = 2 χ 0 = 6.14 × 10 4 τ q = 16 s τ t = 0 s 或16 s时,θ随t'的变化

Figure 2. θ changes with t' at x = 2 , χ 0 = 5.02 × 10 3 , τ q = 16 s , τ t = 0 s and 16 s respectively

图2. 当 x = 2 χ 0 = 5.02 × 10 3 τ q = 16 s τ t = 0 s 或16 s时,θ随t'的变化

说明考虑两个滞后时间的双相滞后模型要比只考虑单个弛豫时间的模型得到的温度峰值小。另外,随着磁化率χ0的增大,即热源Qm的升高,温度有大幅度的增加,但温度θ随t'的变化趋势没有发生改变。也就是说,外加磁场强度不变,磁纳米粒子的磁化率升高,会使磁纳米粒子产生更多的热量。因此,在实际磁感应热疗中,可以考虑使用不同磁纳米粒子进行温度控制。

图3是当空间位置 x = 2 时,令磁化率 χ 0 = 6.14 × 10 4 τ q = 16 s τ t = 16 s ,对于不同磁场频率f (3 × 105 Hz, 3.5 × 105 Hz, 4 × 105 Hz, 4.5 × 105 Hz)条件下温度随时间的变化分布图。从图3可以发现,与磁化率对温度的影响相似,随着f的增大,热源Qm升高,会使函数曲线整体上升。式(5)给出的热源Qm的表达式也说明了随Qm会随f的增大而升高。也就是说,磁纳米粒子的磁化率不变,外加磁场频率升高,会使磁纳米粒子产生更多的热量。因此,在实际磁感应热疗中,控制外加磁场频率对达到治疗的目的也有重要影响,这一点可能比使用不同磁纳米粒子更容易操作。

Figure 3. θ changes with t' at x = 2 , χ 0 = 6.14 × 10 4 , τ q = 16 s , τ t = 16 s , f = 3 × 10 5 Hz and 3.5 × 105 Hz and 4 × 105 Hz and 4.5 × 105 Hz respectively

图3. 当 x = 2 χ 0 = 6.14 × 10 4 τ q = 16 s τ t = 16 s f = 3 × 10 5 Hz 或3.5 × 105 Hz或4 × 105 Hz或4.5 × 105 Hz时,θ随t'的变化

5. 结论

本文考虑磁纳米粒子作为热源,双相滞后修正的Pennes热传问题,利用分离变量法对修正的Pennes方程进行求解,得到了温度的解析解。分析了热源项Qm中不同取值的参数χ0,f和不同弛豫时间τt对温度分布的影响,主要结论如下:

相对于只考虑热流量弛豫时间τq的模型,考虑两个滞后时间τt,τq的双相滞后模型得到的温度变化较为迟缓,更加符合实际情况。磁纳米粒子的磁化率和磁场频率大小会对其作为热源产生的热量有较为明显的影响。当磁场频率或磁化率增加,会使磁纳米粒子产生更多的热量,但会存在一个峰值,并且会随着时间的增加趋于固定值。因此,选取具有合适的磁化率的磁纳米粒子和合适的外加磁场尤为重要。本研究中使用的模型只讨论了一维情形,实际问题较之更为复杂。在计算热源时只考虑了磁纳米粒子热源,所以计算温度可能比实际结果偏低。但该模型优点在于通过对温度函数进行了一些假设的前提下得到了温度与时间空间的精确解,为后来的实验和理论研究奠定了基础。

基金项目

本研究由国家级大学生创新创业训练计划“磁纳米粒子热源的生物热传输分析(201910126021)”项目资助。

附录A

求解方程(20)~(22),假设解的形式为:

θ 1 ( x , t ) = X ( x ) T ( t ) , (A.1)

带入式(20)化简得:

( A d 2 T d t 2 + B d T d t + T ) X = ( T + D d T d t ) d 2 X d x 2 = 0 , (A.2)

令: λ = A d 2 T d t 2 + B d T d t + T T + D d T d t = d 2 X d x 2 X

λ为常数。

求解二阶线性常微分方程组:

X ( x ) + λ X ( x ) = 0 , (A.3)

X ( 0 ) = 0 , X ( x L ) = 0 . (A.4)

1) 若 λ < 0 ,此时只有零解。

2) 若 λ = 0 ,得:

X ( x ) = m x + n , (A.5)

由边界条件(A.4)得:

X ( x ) = n , (A.6)

再求解关于t的常微分方程: A d 2 T d t 2 + B d T d t + T = 0

B 2 4 A > 0 时:

T ( t ) = d 1 e ( B + B 2 4 A 2 A ) t + d 2 e ( B B 2 4 A 2 A ) t , (A.7)

θ 1 n 1 ( x , t ) = X ( x ) T ( t ) = C 0 e ( B + B 2 4 A 2 A ) t + D 0 e ( B B 2 4 A 2 A ) t . (A.8)

B 2 4 A = 0 时:

T ( t ) = ( d 1 + d 2 t ) e ( B 2 A ) t , (A.9)

θ 1 n 1 ( x , t ) = X ( x ) T ( t ) = ( C 0 + D 2 t ) e ( B 2 A ) t . (A.10)

B 2 4 A < 0 时:

T ( t ) = e B 2 A t ( d 1 cos ( B 2 4 A 2 A t ) + d 2 sin ( B 2 4 A 2 A t ) ) , (A.11)

θ 1 n 1 ( x , t ) = X ( x ) T ( t ) = e B 2 A t ( C 0 cos ( B 2 4 A 2 A t ) + D 0 sin ( B 2 4 A 2 A t ) ) . (A.12)

3) 若 λ = 0 ,解得:

X ( x ) = c 1 cos ( λ x ) + c 2 sin ( λ x ) .(A.13)

由边界条件(A.4),若 c 1 0 ,则:

λ n = ( n π x L ) 2 , ( n = 1 , 2 , 3 , ) , (A.14)

X ( x ) = c 1 cos ( n π x L x ) . (A.15)

下解 A d 2 T d t 2 + B d T d t + T + λ n ( T + D d T d t ) = 0

a n = A b n = B + λ n D c n = 1 + λ n

b n 2 4 a n c n < 0 时:

T ( t ) = e b n 2 a n t ( d 1 cos ( b n 2 4 a n c n 2 a n t ) + d 2 sin ( b n 2 4 a n c n 2 a n t ) ) , (A.16)

θ 1 n 2 ( x , t ) = X ( x ) T ( t ) = e b n 2 a n t ( A n cos ( b n 2 4 a n c n 2 a n t ) + B n sin ( b n 2 4 a n c n 2 a n t ) ) cos ( n π x L x ) , (A.17)

b n 2 4 a n c n = 0 时:

T ( t ) = ( d 1 + d 2 t ) e ( b n 2 a n ) t , (A.18)

θ 1 n 2 ( x , t ) = X ( x ) T ( t ) = e b n 2 a n t ( A n + B n t ) cos ( n π x L x ) , (A.19)

b n 2 4 a n c n > 0 时:

T ( t ) = d 1 e ( b n + b n 2 4 a n c n 2 a n ) t + d 2 e ( b n b n 2 4 a n c n 2 a n ) t , (A.20)

θ 1 n 2 ( x , t ) = X ( x ) T ( t ) = ( A n e ( b n + b n 2 4 a n c n 2 a n ) t + B n e ( b n b n 2 4 a n c n 2 a n ) t ) cos ( n π x L x ) .(A.21)

综合 λ < 0 λ = 0 λ > 0 三种情况得:

1) 当 b n 2 4 a n c n < 0 B 2 4 A > 0 时:

θ 1 ( x , t ) = n = 1 [ θ 1 n 1 ( x , t ) + θ 1 n 2 ( x , t ) ] = n = 1 ( e b n 2 a n t ( A n cos ( b n 2 4 a n c n 2 a n t ) + B n sin ( b n 2 4 a n c n 2 a n t ) ) cos ( n π x L x ) ) + C 0 e ( B + B 2 4 A 2 A ) t + D 0 e ( B B 2 4 A 2 A ) t (A.22)

其中 A n = 2 x L n 2 π 2 + x L 2 B n = b n b n 2 4 a n c n 2 x L n 2 π 2 + x L 2 C 0 = ( ψ 1 x L ) B 2 4 A + B 2 B 2 4 A D 0 = ( ψ 1 x L ) B 2 4 A B 2 B 2 4 A

2) 当 b n 2 4 a n c n > 0 时:

θ 1 ( x , t ) = n = 1 [ θ 1 n 1 ( x , t ) + θ 1 n 2 ( x , t ) ] = n = 0 ( ( A n e ( b n + b n 2 4 a n c n 2 a n ) t + B n e ( b n b n 2 4 a n c n 2 a n ) t ) cos ( n π x L x ) ) , (A.23)

其中 A n = 2 x L n 2 π 2 + x L 2 ( b n 2 b n 2 4 a n c n + 1 2 ) B n = 2 x L n 2 π 2 + x L 2 ( 1 2 b n 2 b n 2 4 a n c n )

3) 当 b n 2 4 a n c n = 0 B 2 4 A > 0 时:

θ 1 ( x , t ) = n = 1 [ θ 1 n 1 ( x , t ) + θ 1 n 2 ( x , t ) ] = n = 1 ( e b n 2 a n t ( A n + B n t ) cos ( n π x L x ) ) + C 0 e ( B + B 2 4 A 2 A ) t + D 0 e ( B B 2 4 A 2 A ) t , (A.24)

其中 A n = 2 x L n 2 π 2 + x L 2 B n = b n 2 a n 2 x L n 2 π 2 + x L 2 C 0 = ( ψ 1 x L ) B 2 4 A + B 2 B 2 4 A D 0 = ( ψ 1 x L ) B 2 4 A B 2 B 2 4 A

4) 当 b n 2 4 a n c n < 0 B 2 4 A = 0 时:

θ 1 ( x , t ) = n = 1 [ θ 1 n 1 ( x , t ) + θ 1 n 2 ( x , t ) ] = n = 1 ( e b n 2 a n t ( A n cos ( b n 2 4 a n c n 2 a n t ) + B n sin ( b n 2 4 a n c n 2 a n t ) ) cos ( n π x L x ) ) + ( C 0 + D 2 t ) e ( B 2 A ) t (A.25)

其中 A n = 2 x L n 2 π 2 + x L 2 B n = b n b n 2 4 a n c n 2 x L n 2 π 2 + x L 2 C 0 = ψ 1 x L D 0 = ( ψ 1 x L ) B 2 A

NOTES

*通讯作者。

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