An Introduction to Molecular Imaging in Radia-

tion Oncology :A report by the AAPM Working Group on Molecular Imaging in Radiation

Oncology(WGMIR)

Tuesday Seminar

24th, Dec, 2013

Radiological Physics Lab,

Seoul national university

Seongmoon Jung

Outline

• Introduction

• Molecular Imaging Modalities and Techniques

• Molecular Imaging Challenges in Clinical Radiation

Oncology

• Conclusion

Introduction• Definition

“ Directly or indirectly monitor and record the spatiotemporal distribution

of molecular or cellular processes for biochemical, biologic, diagnos-

tic, therapeutic applications.”

– Radiological Society of North America(2005)

“ The visualization, characterization, and measurement of biological

processes at the molecular and cellular levels in human and other liv-

ing things……”

– Society of Nuclear Medicine(2007)

Molecular Imaging

Tumor cells

Biological Character

Physiological

change

Spatial ex-tent

Define Target

Treatment Planning

Introduction• Background

Accurate &

Optimized

• Interest to the radiation oncology community

- Imaging of biological tumor characteristics

Such as presence of hypoxia, proliferation rate

- diagnosis, radiation treatment, evaluation in the

molecular manner

Introduction

Molecular Imaging Modalities

and Techniques

Molecular Imaging Modalities and Techniques

• 5 devices for molecular imaging

(a) PET

(b) SPECT

(c) MRI

(d) Optical imaging

(e) Ultrasound

Molecular Imaging Modalities and Tech-niques

A. PET – (1) Basic Principle

• Simultaneous detection of annihilation X-rays ( two 511 KeV) of a positron

- coincident event

- random(false) event

- scatter event

• Positron emitting Radionuclides(Short half life) + biological tracer molecule(Ligand) to localize in vivo in tissues

Molecular Imaging Modalities and Tech-niques

A. PET – (2) Spatial Resolution

• The finite positron range

- depends on the radioisotope, the type of tissue

• Noncolinearity of the annihilation photons

• Pet scanner itself (detector size)

Molecular Imaging Modalities and Tech-niques

A. PET – (3) application in oncology

• FDG to image metabolically active, increased glycolysis

- presence of tumor, inflammation

• Cerebral blood flow using 15O H2O, tumor hypoxia with 18F fluo-romisonidazole, cell proliferation with 11C thymidine

• The hybrid PET-CT

A. PET – (4) application in oncology

Molecular Imaging Modalities and Tech-niques

B. SPECT –(1) basic principle

• Detection of gamma decay X-rays by radiolabeled agents

• Gamma emitting radioisotopes + Ligand

(99mTc, 111In, 67Ga, 131I, 201Tl )

• Detector called the Anger gamma camera rotated around the object

3 or 6 degree, 120 or 60 projection data

mathematically reconstruction

Molecular Imaging Modalities and Tech-niques

B. SPECT – (2) Compared to PET

• Disadvantage

- Using a collimator reduction of sensitivity

- Less radiation event poorer spatial resolution

• Advantage

- Multiple radiotracers can be administered and detected

- Relatively long half life radioisotopes slow biological pro-cesses

- Availability for research even at labs far away from cyclotron

facilities

Molecular Imaging Modalities and Tech-niques

B. SPECT – (3) application in oncology

• A number of radiolabeled tracer for specific tumors

• In early work, pre- & post- optimization of lung treatment plans

also in brain tumor and malignant lymphoma

• Different organs or functions monitored simultaneously

• Hybrid SPECT-CT in oncology, cardiology and neuropsychiatry

B. SPECT – (3) application in oncology

Molecular Imaging Modalities and Tech-niques

C. MRI – (1) Basic Principle

• The origin of signal is the magnetic dipole moment

- External magnetic field(B0)

- RF coil

- Gradient coil

• Signals (SNR, signal-to-noise ratio)

- T1, T2, T2* relaxation time

Molecular Imaging Modalities and Tech-niques

C. MRI – (2) Four types of MR

• MRSI

• Perfusion MRI

• Diffusion MRI

• Functional MR(fMRI)

Molecular Imaging Modalities and Tech-niques

C. MRI – (3) fMRI & MRSI application

• MRSI detect, quantify, differentiate neo-plastic disease processes in the brain, breast and prostate

- By changes of

N-acetylaspartate(NAA) choline lactate, creatine citrate

• fMRI

- Using BOLD (blood oxygen level-dependent) contrast

Relative concentration of deoxyhemoglobin and oxyhemoglobin

C. MRI – (3) fMRI , MRSI application

Molecular Imaging Modalities and Tech-niques

D. Optical Imaging – (1) Basic Principle

• Detection of visible and infrared photons transmitted through biological tissues

• Short penetration depth

- In vitro measurements

- Surface in vivo of small animals

Molecular Imaging Modalities and Tech-niques

D. Optical Imaging – (2) Four types

1. Bioluminescence

2. Fluorescence – GFP

3. Diffuse optical tomography(DOT)

4. Optical coherence tomography(OCT)

Molecular Imaging Modalities and Tech-niques

E. Ultrasound

• Development of ultrasound

- Characterization of tissues through Spectral analysis

- Enhancing image quality by the use of specialized contrast agents

• High spatial resolution, real-time imaging• But poor image quality

Molecular Imaging Modalities and Tech-niques

E. Ultrasound• Contrast Agent, Microbubbles

- Small gas-filled bubbles(1~10μm diameter, 10~200nm shell thickness)

- Provide contrast due to echogenicity of its gas or shell

- Attachment of antibodies, peptides, ligands

• Application

- Blood vessel detection

- Assessment of perfusion and vascular delivery of drugs

- Detection of inflammation and angiogenesis of tumors

Summary

Summary

Molecular Imaging Challenges in

Clinical Radiation Oncology

A. Spatial scale in molecular imaging

B. Image quality

C.Biologic structure definition and response

D.Biological modeling & application for treatment planning and response assessment

Molecular Imaging Challenges in Clinical Radiation Oncology

A. Spatial scale in molecular imaging

• Spatial scale covers 4 orders of magnitude

presents challenges with respect to integrating such data into

a clinical radiation treatment system

• Although resolution is improving due to technological advantages,

fundamental physical limits exist

Molecular Imaging Challenges in Clinical Radiation Oncology

B. Imaging Quality• It depends on a number of complex interacting factors including

- the physical processes affecting the signal

- origination(depth and surrounding tissues)

- spatial & temporal resolution

- noise …..

• Each modality requires specialized QA and quality control

- individual calibration or QA for each patient

• Standardized phantoms, QA tests and benchmark data for various lesion locations would be valuable for future work

Molecular Imaging Challenges in Clinical Radiation Oncology

C. Biologic structure definition and response

• Challenges in radiation treatment

1. Image transmission

2. Registration of multimodality images

3. Image interpretation

4. Composition of the target and critical volumes from a set of multi-modality image

Molecular Imaging Challenges in Clinical Radiation Oncology

C. Biologic structure definition and response• Accurate image interpretation is required

- Experts

- Software tools

• Even above challenges are accepted,

the clinical use of molecular images is still challenged by the needs to define a target volume

• Biological target volumes for multimodality image sets will not be con-gruent in size or shape

• Temporal effects must also be addressed when defining the target

Molecular Imaging Challenges in Clinical Radiation Oncology

D. Biological modeling & application for treatment planning and response assessment

• Predicted models based on biological data from molecular images

provide information to therapeutic decisions and prognoses

• Standardized image acquisition and processing techniques required

To routinely use in biological modeling of radiation dose response

Conclusion• Molecular imaging is not only imaging a specific cell or molecular di-

mensional objects, but also imaging their molecular or biological pro-cesses

• High resolution anatomical imaging + high sensitivity molecular imaging can achieve volumetric tumor characterization and quantitative model-ing of tissue irradiation

• For the clinical application

- accurate registration

- clinical interpretation of data

- target definition

- image quality

• Great challenges and opportunities for collaborations through the con-vergence of molecular biology, diagnostic radiology, radiation oncology, physics, imaging science, chemistry, and other fields

Discussion & Question

Thank you for your attention !

MRI