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Chapter 14 -- Medical Applications of Nuclear Technology. Xiaodong He Radiotherapy Center Shanghai Pulmonary Hospit al.

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Chapter 14 medical applications of nuclear technology
Chapter 14 -- Medical Applications of Nuclear Technology

Xiaodong He

Radiotherapy Center

Shanghai Pulmonary Hospital


Prologue

Just after the moment of discovery of X rays, the importance of X rays in medical diagnosis was immediately apparent , and within months of its discovery, the bactericidal action of X rays and their ability to destroy tumors were revealed.

prologue



Medical Applications of Nuclear Technology medical research depend critically on many increasingly sophisticated applications of nuclear radiation and radioisotopes.

Radiation Oncology

放射肿瘤

治疗学

Nuclear

medicine

核医学

Radiation

Image

+

NMR

Medical Applications of Nuclear Technology are constituted by three parts above.


Nuclear medicine
Nuclear medicine medical research depend critically on many increasingly sophisticated applications of nuclear radiation and radioisotopes.

in vitro

Radioimmunoassay,RIA

γ Camera ,Bone Scanning

Single Photon Emission Computerized

Tomography SPECT

Positron Emission Tomography

PET/CT

Radionuclide Therapy

Tumor, hyperthyroidism甲亢,etc.

Radionuclide analysis

in vitro + in vivo


Radionuclide analysis for human species

According to the radioactive isotope analysis results of the Oak Ridge(橡树岭) lab:

In one year, 98% of the atoms of organism (human body) is replaced.

The body does not have a constant material.

And, in certain time the materials inside body are to produce thousands of times biological chemical reactions every second.

Radionuclide analysis for human species


R adio i mmuno a ssay more compactly as ria
R Oak Ridge(adioimmunoassay (more compactly as RIA 放射免疫技术)

RIA as a kind of technology take the both advantages of accuracy and sensitivity of the radioactive isotope measurement and the specificity of the reaction of antigen and antibody.

It is a new in vitro technology for ultra trace (10-9~10-15g) material detection.

放射免疫技术为一种将放射性同位素测量的高度灵敏性、精确性和抗原抗体反应的特异性相结合的体外测定超微量(10-9~10-15g)物质的新技术。


Broadly, all the assay technologies via immune reactions by Oak Ridge(antigen and antibody which tagged by radioactive isotopescan be called RIA

广义来说,凡是应用放射性同位素标记的抗原或抗体,通过免疫反应测定的技术,都可称为放射免疫技术 。

So far has development to the fifth generation of RIA technology. It is characterised by the combination of magnetic particles and RIA or IRMA (immunoradiometric assay) .


Pet ct positron emission tomography ct
PET / CT Oak Ridge(Positron emission tomography + CT

PET/CT is a perfect fusing of PET and CT.

It can Provide detailed lesion function and metabolic information of moleculars by PET , and in the same time, provide the accurate lesion anatomic localization by CT.

It is characterised by sensitivity, accuration, specific and accurate location.

It is extensive used in radiotherapy, and also be called the “high-tech coronal of Modern medicine”.


The mechanics of pet
The Mechanics of Oak Ridge(PET

The clinicalimaging process of PET is as followes:

a. Mark the radioactive isotopes which can emit positrons (such as F-18) to compounds which be gonna to participate in tissue blood flow, or in metabolic process.

b. Inject the tagged compounds into human body.


c Oak Ridge(. Theemission positron from radio-isotope can shift 1 mm in human body, and then combined with an electron in tissues and annihilate to produce two equal energy (511 KeV) and opposite γ photons.

It was recognized that detection of these photons, using the property that they are emitted simultaneously in opposite directions, would permit description, in three dimensions, of the distribution of the radionuclides in the body.


Sketch map of pet
Sketch map of PET Oak Ridge(

PET imaging of an object surrounded by a ring of detectors. Annihilation photons γaare recorded by detectors on opposite sides of the ring,

the relative intensities allow determination of the mass thickness of the distances L1 and L2 in the patient through which these photons travel.


d Oak Ridge(. Annihilation photons leaving the body are detected by an array of detectors that surround the patient.

Events are recorded only when two detectors each detect an annihilation photon simultaneously, i.e., within 10 to 25 ns of each other. Events separated further in time are not recorded.


The line joining the two recording detectors is a Oak Ridge(line of response (LOR) along which the annihilation photons have traveled and on which the positron decay occurred.

This coincident detection technique allows a determination of the direction of the annihilation photons without the physical collimation needed in SPECT. For this reason coincident detection is often called electronic collimation.


PMT Oak Ridge(:光电倍增管(Photo Multiplier Tube)

BGO: 锗酸铋(Bismuth Germanium Oxide)


Radiation imaging nmr
Radiation Imaging Oak Ridge(& NMR

X ray Radiography, and DSA

(Digital subtraction angiography 数字减影血管造影术)

Computed Tomography (CT)

计算机断层成像

Magnetic Resonance Imaging (NMR)

Function NMR,NMR spectrum analysation

4D fast CT and 4D fastNMR


Background rationale
Background & Rationale Oak Ridge(

  • Convolution

线性系统h(t),输入e(t),输出y(t)


  • 卷积的来源: Oak Ridge(

  • 物理中类似对于冲量不变的研究。在用t做横坐标、F做纵坐标的坐标系中,就如同一个面积不变的长方形,底边被挤的越窄,高度被挤的越高。在数学中它可以被挤到无限高,但即使它无限瘦、无限高、但它仍然保持面积不变。

  • 可以对它进行积分,求面积。于是“卷积” 这个数学怪物就这样诞生了。




  • 在晶体 Oak Ridge(X射线衍射中,实验测量出的衍射峰的线形h,包括两部分:晶体的贡献f和衍射仪器的贡献g,h、f和g三者的关系满足卷积运算:



  • Fourier transformation Oak Ridge(

  • 傅里叶变换能将满足一定条件的某个函数表示成三角函数(正弦和/或余弦函数)或者它们的积分的线性组合。

  • Two features:

    1. 傅立叶变换是线性算子,若赋予适当的范数,它还是酉算子;

    2. 正弦基函数是微分运算的本征函数,从而使得线性微分方程的求解可以转化为常系数的代数方程的求解.在线性时变复杂的卷积运算为简单的乘积运算,从而提供了计算卷积的一种简单手段。


  • Laplace transformation Oak Ridge(

  • 拉氏变换的物理意义:建立了时域和复频域之间的联系。

  • 其数学意义:将微分方程转化为代数方程,简化了计算。


傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而fourier变换是将连续的时间域信号转变到频率域;它可以说是laplace变换的特例;

拉氏存在条件比fourier变换要宽,是将连续的时间域信号变换到复频率域(整个复平面,而fourier变换此时可看成仅在jΩ轴);


  • Z傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而变换则是连续信号经过理想采样之后的离散信号的laplace变换,再令z=esT时的变换结果(T为采样周期),所对应的域为数字复频率域,此时数字频率ω=ΩT。

  • 它与拉氏变换一样,都是将时域映射到频域。

  • 拉普拉斯变换与Z变换的联系;其本质区别在于拉氏变换处理的是时间上连续的问题,Z变换处理的是时间上分立的问题。


  • Question 1傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而

  • What is the main difference between fourier transformation and laplace transformation ?

    main difference:laplace transformation is in whole complex plane,and fourier transformation is just in imaginary axis.

  • Question 2

  • What is the physical and mathematical significance of laplace transformation?

    physical significance: It establishes the relationship between the time domain and complex frequency domain.

    mathematical significance: Converts differential equation to Algebraic equation, so as to simplify the calculation.


NMR傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而

  • 原子核在外磁场作用下发生能级分裂,在一定射频场作用下吸收其能量发生能级跃迁的现象。

    塞曼能级分裂

    射频脉冲 E = hν

    radio frequency pulse, RF

    核磁共振


The quantum mechanical describes for nmr
The quantum mechanical describes for NMR傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而


小结傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而


Background rational
Background & Rational傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而

  • Quantum mechanics

  • Fourier transformation


Radiation oncology
Radiation Oncology傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而

Teletherapy

Brachytherapy


P, C 傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而

Teletherapy

X rays

Electrons

Elements used in teleradiotherapy


4DRT傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而

CRT

IMRT

Teletherapy

Techniques used in teleradiotherapy


Iodine傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而

BNCT

boron neutron

capture therapy

Ir-192

Cobalt-60

Brachytherapy

Elements used in brachytherapy


(125)I implantation 傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而

Brachytherapy

碘近距离粒子种植放疗

Brachytherapy

近距离放疗

After loading

radiotherapy

后装放疗

Intracavity afterloading radiotherapy

腔内后装放疗

Techniques applied in brachyradiotherapy

Seeds implant

Interstitial implant

brachytherapy

组织间插植


After-loading Intracavitary unit 傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而

后装治疗机

A点:宫颈口旁2cm

上2cm

B点:A点外3cm


Paris dosimetry system
Paris Dosimetry System傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而巴黎剂量学系统

植入辐射源呈直线型、彼此相互平行、各线源等分中心位于同一平面、各源相互等间距、排布呈正方形或等边三角形、源的线性活度均匀且等值、线源与过中心点的平面垂直。


Interstitial radiation
Interstitial Radiation傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而组织间插植治疗


Synopsis of the tele radiotherapy
Synopsis of the 傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而Tele-radiotherapy外放射治疗简介


What is radiotherapy rt
What is Radiotherapy (RT)傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而

RT is a clinical subject of treating cancers by applying the theories and means of high energy rays to irradiate tumor targets.

研究、应用高能放射线治疗肿瘤的原理和方法的临床治疗学科


What is Radi傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而ation ?


The most frequently used elements in RT傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而


Candidate particles傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而


Why RT can cure cancer disease傅氏与拉氏变换的区别在于,拉氏变换是处理微分方程的,它的最初目的是将微分运算转化为容易求解的代数运算。而?--辐射损伤与修复

1. RT is based on ionizing radiation

2. Ionization can inducetrauma(injury)

靶分子

ionization

电离

固定

电子转移

lethal damage致死性损伤

SSB单链断裂

诱发自由基击出电子

DSB双链断裂

错误

复制

时相

(稳态)

单链

复制

乏氧

组织

时相

双链修复

间期死亡

增殖期死亡

急性反应

慢性反应

致畸

致癌

sublethal damage

亚致死性损伤

potential lethal damage潜在致死性损伤


3. Some type of cancer more sensitive to ionization irradiation than normal cells (sigmoid curves)

tumor

Normal tissue

More separating the curves in dose is,

more higher the curable probability be.


The role of RT in irradiation than normal cells (tumor treatment

Out of control

Till now, surgery, RT and chemotherapy are the major three ways to treat cancers. Nearly 2/3 of cancer patients need RT.

But radiotherapy has no good response for some patients, the main reason is that the 10%- 50 % of hypoxic cells in solid tumors have low response to radiotherapy


How the rt is performed the flow chart of rt
How the RT is performed? irradiation than normal cells (The flow chart of RT 放疗流程图

treatment

follow up

随访

TPS计划设计

Virtual simulation and image fusion

虚拟模拟和图像融合

CT SCAN

PET/CT MRI

To localization

Medical evaluation

评估 (include pathology,physical,lab test, image)

Portal verification

射野验证

QA


Simplified Radiotherapy Treatment Flow irradiation than normal cells (


The composition of rt
The composition of RT irradiation than normal cells (放疗学构成

Radiotherapy includes four branches:

1. Radiation Oncology (放射肿瘤学)

2. Radiation Physics (放射物理学)

3. Radiobiology (放射生物学)

4. Radiation Technology (放射技术学)


A. irradiation than normal cells (Some important concepts


1 liner energy transfer let for short

1. irradiation than normal cells (Liner Energy Transfer. (线性能量传输)

LET for short

△E

LET =

KeV/μm

△X


2. Ionization induced Direct and Indirect effects irradiation than normal cells (

电离对靶分子的间接作用与直接作用

Direct :Directly act on target molecules

( Break DNA double strands )

直接作用: 直接引起DNA双链断裂

Indirect:Affect target molecules via ionized

& excitated water molecules H2O

间接作用:通过水分子电离、激发 再作 用到靶分子


3 oxygen enhancement ratio oer

3. Oxygen Enhancement Ratio . OER irradiation than normal cells (

(氧增强比)

D0(dose for killing hypoxic cells乏氧细胞)

OER =

D0 (dose for killing aerobic cells有氧细胞)


4 relative biological effect rbe

4. Relative Biological Effect . RBE irradiation than normal cells (

(相对生物效应)

Doses which create a certain bio-effect by one standard ray

产生一定生物效应标准射线剂量

RBE =

Doses which create the same bio-effect by another ray

产生同样生物效应另一种射线剂量


5. The characteristic of irradiation than normal cells (high LET rays

高LET射线的特点

a. There is a Bragg Peak

b. RBE 大,OER 小

c. Direct effects is major

直接作用为主,致死性损伤


Cell phase independent only for high let

Cell phase independent irradiation than normal cells (

细胞时相差异小(Only for high LET)


6 absorbed dose d e ab m e ab is absorbed energy m is mass

6 irradiation than normal cells (、Absorbed Dose 吸收剂量

D = ∆Eab / ∆m

∆Eab is absorbed energy;∆m is mass;


7 irradiation than normal cells (、Kerma(比释动能)

Kinetic energy released per unit mass

K = dEtr / dm

It applies to indirect ionizing radiation

It is differ from the Karma业障 in Buddhism.

它是一个适用于间接电离辐射,如光子和中子的非随机量。它计算从间接电离辐射转移到直接电离辐射的平均数量值,不考虑转移后的发生的情况。下列讨论将局限于光子。

光子的能量分两步授予给物质。

第一步,光子辐射通过多种光子相互作用(光电效应,康普顿效应及电子对生成)将能量转移给次级带电粒子(电子)。

第二步,带电粒子通过原子激发或和电离将能量转移给介质。


8 cema converted energy per unit mass it applies to direct ionizing radiation d e c d m

8 irradiation than normal cells (、Cema (比释能)

Converted energy per unit mass

It applies to direct ionizing radiation

此处dEc 是带电粒子在质量为dm 的材料中碰撞损失的能量,不包括次级电子的损失。


  • Question 3 irradiation than normal cells (

    Please describe the definitions and formulasof concepts “ Cema” & “Kerma”?


9 the relative dominant area of three main effects of photon media interaction s

9 irradiation than normal cells (、The relative dominant area of three main effects of photon-media interactions

光子与介质相互作用中三种主要作用相对占优势区域

These three effects are other than three actions, so called electromagnetic action,

weak action,

strong action.

Photoelectric effect


10 irradiation than normal cells (、“4R”concept in RT

Cells be irradiated will experience four occurrences which named 4R.

4R --- Repair 修复

Regeneration 再增殖

Redistribution 细胞周期再分布

Reoxygenation 再氧合


Question 4
Question 4 irradiation than normal cells (

  • What is 4R in radiobiology?


物理因素导致放射治疗 irradiation than normal cells (5年生存率的提高


Three aspects in modern rt
Three aspects in modern RT irradiation than normal cells (

host

servant

servant

Position verification

Irradiation techniques

Dose verification


“If you can’t see it , you can’t hit it irradiation than normal cells (

If you can’t hit it, you can’t cure it”


Historical Review irradiation than normal cells (

Experimental aspects

Theoretical aspects


Historical review irradiation than normal cells (

1. Experimental Discovery

1.1 In 1895, Roentgen discovered X rays

In 1901, He won the first Nobel Prize

1.2 In 1896, Becquerel discovered radioactive element of uranium

1.3 In July 1898, Madame Curie and her husband got a great success that they discovered the radioactive element, polonium, which Marie named after Poland.

伟大的居里夫妇发现钋

1.4 The discoveries of α、β、γ rays

Rutherford‘s atomic model (1911)


Historical review irradiation than normal cells (

2. Theoretic Discovery

---Full of seminal ideas


2 1 microcosmic scale quantum mechanics
2.1 Microcosmic Scale irradiation than normal cells (-Quantum Mechanics 微观尺度-量子力学

  • layer of structure

D~ћ/mc

10-14m

(10fm)

Nucleus

10-10m

Atom

10-15m

(fm)

Nucleon

10-18m

quark

Wave-Particle Duality, Probbility, Entanglement


Schödinger- equation irradiation than normal cells ((introduce operator & complex number)

Klein-Gordon- equation

Dirac- equation (import spin matrix & Quaternions 四元数)

非相对论-相对论;时空非对称-时空对称;

狄喇克方程,引入自旋自由度(波函数由单分量到多分量)

E→ i∂/∂t, P→ -i∂/∂r

E=p2/2m

E2=p2c2+m2c4

E=±(p2+m2)1/2

=αpc+βmc2


2 2 high energy relativity
2.2 High energy irradiation than normal cells (-Relativity

High energy particles belong to

Relative territory.

~

The relative particles should suffice 1. Lorentz-transform invariance; 2. Curved space time.

Q+L

Particles

Nucleus

For particles, the criteria to distinguish

whether it is a relative particle or not is:


2 3 particles creating annihilating quantum field theory
2.3 Particles creating & annihilating irradiation than normal cells ( — Quantum Field Theory

There are three types of quantum field theories

In 1934,Pauliand Weisskopf pointed outthat just like Maxwell equation, K-G equation as well as Dirac equation are all the field equations.

K-G’s is for scalar field, which spin is most meson

Dirac’s is for rotary field(旋量场), which spin is

Maxwell’s is for vector field, which spin is photon

*粒子是相应的场的一种激发态,反粒子是相应的复共轭场的一种激发态。不同的场(复共轭场)的激发态代表不同数目的粒子(反粒子)态;场(复共轭场)由激发态变到基态表示相应粒子(反粒子)消灭(湮灭),场(复共轭场)由基态变到激发态表示相应粒子(反粒子)产生

*场论的‘真空’充满了各种粒子(反粒子)场(复共轭场)的基态


基本粒子的四要素 irradiation than normal cells (自旋、静质量、电荷量和磁矩

自旋是量子力学的术语,是讨论物质波对称性质的一种表述,并非真的粒子自己在旋转。

从量子理论定义上来讲,自旋半圈后看起来和原来一样的粒子,自旋量子数为二;自旋一圈时的粒子,量子数为一;而自旋两圈才和原来一样的粒子,自旋量子数为二分之一。

自旋本无特定的方向,只有在测量时才显示确定的方向

已发现的粒子中,自旋为整数的,最大自旋为4;自旋为半奇数的,最大自旋为3/2。 电子的自旋是1/2,光子的自旋是1。


c. The Revolution in Radiotherapy irradiation than normal cells (


循证医疗 irradiation than normal cells (


Highlight some of the technologies
Highlight some of the technologies irradiation than normal cells (


Just like a robot
Just like a robot irradiation than normal cells (


Tomotherapy can irradiate while rotating
Tomotherapy irradiation than normal cells ((断层扫描式放疗)can irradiate while rotating


Can check position while irradiating
Can check position while irradiating irradiation than normal cells (


Proton radiotherapy
Proton Radiotherapy irradiation than normal cells (


Let rbe
LET & RBE irradiation than normal cells (

低LET射线,RBE值低(≤1.0),高LET射线,RBE值高(≥2.0)。高LET射线的RBE,在达20keV/μm以上时,随LET升高而迅速上升,同时OER下降,但当超过160keV/μm时,RBE值反又减小,而OER下降到1。高LET射线的RBE大,在细胞存活曲线上体现D0值(平均致死量)低,且其RBE值随分割照射时的分次剂量大小而改变,即每次剂量越小,RBE值越大。


The pdd comparisons of varies rays
The PDD comparisons of varies rays irradiation than normal cells (

Electron

beam


电子线用于浅表组织的治疗 irradiation than normal cells (


How to treat moving target? irradiation than normal cells (


Movement and deformation irradiation than normal cells (


RPM — Real-time Position Management irradiation than normal cells (

Respirationsynchronised imaging and treatment


The Real-time Position Management™ (RPM) system is a non-invasive, video based system that allows for clean imaging and treatment of lung, breast, and upper abdominal sites.

The RPM system is accurate, easy to use and fast. It is comfortable for the patient and accommodates both breath hold and free breathing protocols.


The problem of rpm
The problem of RPM non-invasive, video based system that allows for clean imaging and treatment of lung, breast, and upper abdominal sites.


4D real time tracing system non-invasive, video based system that allows for clean imaging and treatment of lung, breast, and upper abdominal sites. 四维实时跟踪放疗

4D Tx delivery “Visualization”:

Internal magnetic marker displacement (Calypso)

Calypso system: response

Next step after RPM


Thank you for your kind attention

Thank you for your kind attention ! non-invasive, video based system that allows for clean imaging and treatment of lung, breast, and upper abdominal sites.


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