Chapter 14 -- Medical Applications of Nuclear Technology

Xiaodong He

Radiotherapy Center

Shanghai Pulmonary Hospital

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.

prologueprologue

Today, both diagnostic and therapeutic medicine as well as medical research depend critically on many increasingly sophisticated applications of nuclear radiation and radioisotopes.

Nuclear medicine

核医学

Medical Applications of Nuclear Technology

Radiation Oncology

放射肿瘤治疗学

RadiationImage

+NMR

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

Nuclear medicineNuclear medicine

Positron Emission Tomography

Single Photon Emission Computerized Tomography SPECT

γ Camera ， Bone Scanning

Radioimmunoassay ， RIA in vitro

体

内Radionuclide Therapy Tumor, hyperthyroidism 甲亢 , etc.

PET/CT

Radionuclide analysis in vitro + in vivo

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

Radioimmunoassay （ 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 antigen and antibody which tagged by radioactive isotopes can 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 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 clinical imaging 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. The emission 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

PET imaging of an object surrounded by a ring of detectors. Annihilation photons γa are 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. 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 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.

BGO ： 锗酸铋 (Bismuth Germanium Oxide）PMT：光电倍增管 (Photo Multiplier Tube)

Radiation Imaging & NMRRadiation Imaging & NMR

4D fast CT and 4D fast NMR

Function NMR ， NMR spectrum analysation

Magnetic Resonance Imaging （ NMR ）

Computed Tomography （ CT ）计算机断层成像

X ray Radiography, and DSA （ Digital subtraction angiography 数字减影血管造影术）

Background & Rationale

Convolution

线性系统 h(t)，输入 e(t)，输出y(t)

卷积的来源： 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。

卷积可以描述为一个过程

卷积可以描述为一个过程

这两个可认为是经典的衍射问题，信号处理也会遇到类似的问题。

在晶体 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：

讲卷积离不开傅立叶变换。 在晶体衍射里，傅立叶变换关联着两个完全不同的空间：现实的笛卡儿空间和倒易的衍射空间。

Fourier transformation

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。

i( ) ( ) dtF f t e t

Laplace transformation

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 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 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 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

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 = hνradio frequency pulse, RF

核磁共振

The quantum mechanical describes for NMR

小结

Background & Rational

Quantum mechanics

Fourier transformation

Radiation OncologyRadiation Oncology

Brachytherapy

Teletherapy

TeletherapyTeletherapy

P, C P, C

X raysX rays

ElectronsElectrons

Elements used in teleradiotherapy

TeletherapyTeletherapy

4DRT4DRT

CRTCRT

IMRTIMRT

Techniques used in teleradiotherapy

BrachytherapyBrachytherapy

IodineIodine

Ir-192Ir-192Cobalt-60Cobalt-60

BNCTBNCT boron neutronboron neutron

capture therapycapture therapy

Elements used in brachytherapy

BrachytherapyBrachytherapy近距离放疗近距离放疗After loading After loading radiotherapyradiotherapy

后装放疗后装放疗

Intracavity Intracavity afterloading afterloading radiotherapyradiotherapy腔内后装放疗腔内后装放疗

(125)I implantation Brachytherapy碘近距离粒子种植放疗

Seeds implantSeeds implant

Interstitial implant Interstitial implant brachytherapybrachytherapy 组织间插植组织间插植

Techniques applied in brachyradiotherapy

After-loading Intracavitary unit

后装治疗机

A 点：宫颈口旁 2cm

上 2cm

B 点： A 点外 3cm

Paris Dosimetry System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组织间插植治疗

Synopsis of the Synopsis of the Tele-radiotherapyTele-radiotherapy

外外放射治疗简介放射治疗简介

What is Radiotherapy (RT)What is Radiotherapy (RT)

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 RadiWhat is Radiation ation ??

The most frequently used elements in RT

Candidate particles

靶分子

电离

SSB 单链断裂

诱发自由基击出电子

DSB 双链断裂

氧固定

电子转移

potential lethal damage潜在致死性损伤

乏氧 时相( 稳态 )

双链修复

lethal damage

致死性损伤

sublethal damage亚致死性损伤

单链复制

错误复制

致畸致癌

时相 组织

间期死亡

增殖期死

亡 急性反应

慢性反应

ionization

Why RT can cure cancer disease ？ -- 辐射损伤与修复

1. RT is based on ionizing radiation 2. Ionization can induce trauma （ injury ）

tumor

Normal tissue

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

More separating the curves in dose is,

more higher the curable probability be.

The role of RT in The role of RT in tumor treatmenttumor treatment

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

Out of control

How the RT is performed?How the RT is performed? The flow chart of RT The flow chart of RT 放疗流程图放疗流程图

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

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

QAQA Portal

verification射野验证

Portal verification射野验证

treatment treatment follow up随访

follow up随访

TPS 计划设计TPS 计划设计CT SCAN

PET/CT MRITo localization

CT SCANPET/CT MRITo localization

Virtual simulation and image fusion

虚拟模拟和图像融合

Virtual simulation and image fusion

虚拟模拟和图像融合

Simplified Radiotherapy Treatment FlowSimplified Radiotherapy Treatment Flow

The composition of RT The composition of RT 放疗学构成放疗学构成

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. Some important concepts

1. Liner Energy Transfer. （线性能量传输）

LET for short

LET =△E

△X

KeV/μ ｍ

2. Ionization induced Direct and Indirect effects

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

（氧增强比）

OER =

D0 (dose for killing hypoxic cells 乏氧细胞 )

D0 (dose for killing aerobic cells 有氧细胞 )

4. Relative Biological Effect . RBE

（相对生物效应）

RBE =

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

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 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

d. Cell phase independent

细胞时相差异小 (Only for high LET)

6 、 Absorbed Dose 吸收剂量

D = ∆Eab / ∆m ∆Eab is absorbed energy ；∆ m is mass ；

物理量 定义 SI单位 旧单位 换算 Exposure (X)

Dose (D)

Equivalent Dose (H)

Activity (A)

7 、 Kerma （比释动能） Kinetic energy released per unit mass

K = dEtr / dmIt 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 ( 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。

cdEC

dm

Question 3 Please describe the definitions and formulas of

concepts “ Cema” & “Kerma”?

9 、 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

Photoelectric effect These three effects are other than three actions, so called electromagnetic action,weak action,strong action.

10 “、 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

What is 4R in radiobiology?

肿瘤 五年生存率（％）kV级 X 射线 高能 X （ γ ）射线

霍奇金氏病 30～ 35 70 ～ 75

食管癌 0 ～ 2 8 ～ 16

宫颈癌 35 ～ 45 55 ～ 65前列腺癌 5 ～ 15 55 ～ 60鼻咽癌 20 ～ 25 45 ～ 50膀胱癌 0 ～ 5 25 ～ 35卵巢癌 15 ～ 20 50 ～ 60

视网膜母细胞瘤 30 ～ 40 80 ～ 85精原细胞瘤 65 ～ 70 90 ～ 95睾丸胚胎瘤 20 ～ 25 55 ～ 70扁桃体癌 25 ～ 30 40 ～ 50

物理因素导致放射治疗 5 年生存率的提高

Three aspects in modern RTThree aspects in modern RT

容积调强VMAT

调强 IMRT

适形照射“刀”

常规照射

IGRT(3D KV)

EPID(2D MV)

film胶片

剂量验证

Irradiation techniques

Dose verificationPosition verification

hostservant servant

“If you can’t see it , you can’t hit it

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

B. Historical Review

1. Experimental aspects2. Theoretical aspects

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 1. Experimental Discovery

Historical review

2. Theoretic Discovery

---Full of seminal ideas

2.1 Microcosmic Scale － Quantum Mechanics 微观尺度－量子力学

10-10mAtom

10-14m(10fm)Nucleus

10-15m(fm)Nucleon

10-18mquark

2~ , ,

hn A E h p k

Wave-Particle Duality, Probbility, Entanglement

D~ћ/mc

,Ei ti tAe Ae E h

•layer of structure

Schödinger- equation (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）

21( ) 0 (2.01)

2it m

22 2

2( ) 0 (2.02)mt

0 (2.03)imt

E=p2/2m

E→ i∂/∂t, P→ -i∂/∂r

E2=p2c2+m2c4

E=±(p2+m2)1/2

=αpc+βmc2

2.2 High energy － Relativity

High energy particles belong to

Relative territory.

~

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

4 810 ~ 10 eV

Nucleus

Particles

8 1010 ~ 10 eV Q+L

1010 eV

1 1P E

E M

P E MFor particles, the criteria to distinguish whether it is a relative particle or not is:

2.3 Particles creating & annihilating — Quantum Field Theory

There are three types of quantum field theories

In 1934 ， Pauli and Weisskopf pointed out that 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

12

1

0

基本粒子的四要素自旋、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

循证医疗

Highlight some of the technologies

Just like a robot

Tomotherapy( 断层扫描式放疗 ) can irradiate while rotating

Can check position while irradiating

Proton Radiotherapy

LET & RBE

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

Electronbeam

电子线用于浅表组织的治疗

How to treat moving target?

Movement and deformation

RPM — Real-time Position Management

Respiration synchronised 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

4D real time tracing system 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 Thank you for your

kind attention !kind attention !