Novel Technologies in Radiotherapy: Protons and Magnetic … · · 2012-04-30Novel Technologies...

Novel Technologies in Radiotherapy: Protons and

Magnetic Resonance ImagingMagnetic Resonance Imaging

Todd Pawlicki

UC San DiegoUC San Diego

DisclosureDisclosure

• I have no conflicts of interest to discloseI have no conflicts of interest to disclose.

Learning ObjectivesLearning Objectives

• Understand the physics of protons beamsUnderstand the physics of protons beams

• Describe differences between proton & photon plans

• Summarize basic physics of MRI

• Discuss applications of MRI in radiotherapy• Discuss applications of MRI in radiotherapy

Question #1Question #1

• What are two methods to create a clinicalWhat are two methods to create a clinical proton beam?

a) Passive scattering and active scanninga) Passive scattering and active scanning

b) Blocks, bolus and wedges

c) Active scattering and passive scanningc) Active scattering and passive scanning

d) None of the above


• What property of tissues makes nuclearWhat property of tissues makes nuclear magnetic resonance useful for imaging?

a) Angular momentum is independent of RF energya) Angular momentum is independent of RF energy

b) Tissues have characteristic relaxation times

c) RF attenuation is linearly related to tissue densityc) RF attenuation is linearly related to tissue density


Proton TherapyProton Therapy

• Physics of protonsPhysics of protons– Dose deposition

– Creating a proton beam

• Proton beam planningp g

Some Proton HistorySome Proton History• Cyclotron invented in 1930

– Lawrence EO Livingston MS The production of high speed protons without the use of– Lawrence EO, Livingston MS. The production of high speed protons without the use of high voltages. Physical Review 1931.

• Suggested for medical use in 1946Wil RR R di l i l f f t t R di l 1946– Wilson RR. Radiological use of fast protons. Radiology 1946.

• First patients treated in 1958– Tobias CA et al. Pituitary irradiation with high-energy proton beams a preliminary report.

Cancer Research 1958.

– In 1961, the Harvard Cyclotron Laboratory started treating intracranial lesions

• First hospital-based system developed at the LLUMCp y p– First patient treated in 1991

– Slater JM et al. The proton treatment center at Loma Linda University Medical Center: rational for and description of its development. IJROBP 1991.

Physical PropertiesPhysical Properties

Particle Symbol Charge Rest Mass

Electron −1 0.511 MeV,e β− −

Positron +1 0.511 MeV

Proton +1 1836 ⋅ 0.511 MeV

,e β+ +

11,p H+ +

Neutron 0 1839 ⋅ 0.511 MeV10,n n

Proton InteractionsProton Interactions

• Electronic ppElectronic– Ionization

– Excitatione

pp

Proton InteractionsProton Interactions

• Nuclear(i) p`

p θNuclearI. Multiple Coulomb scattering

Small θII El ti l lli i

p

II. Elastic nuclear collisionLarge θ

III. Inelastic nuclear interaction p

p`

nucleus

(ii)

nucleus

p`e

γ, npnucleus

(iii)

Ionization DensityIonization Density

0 5 MeV Proton

10 MeV Proton

0.5 MeV Proton

1 MeV Electron

5 keV Electron

Hall. Radiology for the Radiologist. 4th ed. 1994.

5 keV Electron

Linear Energy Transfer (LET)Linear Energy Transfer (LET)

• Energy transferred per unit track lengthEnergy transferred per unit track length

LET dEdl

=

• Useful as a simple way to indicate radiation quality

dl

p y q yand biological effectiveness

Radiation LET (keV/μm)

Cobalt-60 γ-rays 0.2

250 keV x-rays 2.5

10 MeV protons 4.7

150 MeV protons 0.5

Hall. Radiology for the Radiologist. 4th ed. 1994.

LET versus DepthLET versus Depth

40 MeV 100 MeV 250 MeV40 MeV 100 MeV 250 MeV

Depth (cm)

Relative Biological EffectivenessRelative Biological Effectiveness

• Equal doses of difference types of radiation do notEqual doses of difference types of radiation do not produce equal biological effects

RBE x rayD −

• RBE depends on

RBE y

testD=

• RBE depends on – Dose

– Biological system (cell type) Hall. Radiology for the Radiologist. 4th ed. 1994.

– Clinical endpoint (early or late effects)

RBE for ProtonsRBE for Protons

• RBE is a function of LETRBE is a function of LET– RBE is not constant with depth

– Must be careful at the distal end of the target and/or near critical structurescritical structures

• Clinical RBE for protons ≅ 1.1– 1 Gy proton dose ≅ 1.1 Gy Cobalt dose – A single value might not be sufficient

Carabe A Moteabbed M Depauw N Schuemann J Paganetti HCarabe A, Moteabbed M, Depauw N, Schuemann J, Paganetti H. Range uncertainty in proton therapy due to variable biological effectiveness. Phys Med Biol. 2012;57(5):1159-72.

1.7

1.3

1.5 160 MeVRB

Ehigh

0 9

1.1

low

Clinical RBE

0.9

1.0Modulated beam

dose

0.6

0.2Rela

tive

d

4 6 8 12 14 16 18 200 102

Depth [cm]Source: S.M. Seltzer, NISTIIR 5221

Depth DoseDepth Dose

PhotonsBragg Peak

SOBP

Photons

Electrons Protons

http://commons.wikimedia.org/wiki/Category:Radiation_therapy

Schulz-Ertner et al. Semin Radiat Oncol, 2006.

Cobalt-60

20 MV X-rays

160 MeV Protons

Koehler and Preston. Radiology(104)191-195, 1972.

Proton Beam RequirementsProton Beam Requirements

• Maximum energy should be about 250 MeVMaximum energy should be about 250 MeV

• Energy should be variable starting at ∼70 MeV

• The accelerator should be as small as possible with minimum weight

CyclotronCyclotronMagnet

“Dees”

RF

Magnetic Field

Proton Source

Proton Beam ( )magF q v B= ⋅ ×r rr

eleF q E= ⋅r r

Proton BeamsProton Beams

• Currently, two proton accelerator options basedCurrently, two proton accelerator options based on the cyclotron

Cyclotron– Cyclotron• Protons revolve at the same frequency regardless of energy

or orbit radius

– Synchrotron• The magnetic field strength and RF frequency are increased

in synchrony with the increase in beam energyin synchrony with the increase in beam energy

Cyclotron versus SynchrotronCyclotron versus Synchrotron

• CyclotronCyclotron– Fixed-energy accelerator

– Capable of high beam currents

d l l b– Neutrons created in clinical beams

• Synchrotron– Produces proton beams of variable energies

– Lower weight and power consumption

– Low neutron production in clinical beams

Clinically Useful Proton BeamsClinically Useful Proton Beams

• There are two main approachesThere are two main approaches

• Passive scattering systemsFixed depth of penetration– Fixed depth of penetration

– Fixed modulation

• Active scanning systems• Active scanning systems– Irradiation the target using a narrow beam

– Beam controlled in three dimensions

Passive ScatteringPassive Scattering

Goitein et al. Physics Today. 2002.

Active ScanningActive Scanning

Goitein et al. Physics Today. 2002.

Active (Raster) ScanningActive (Raster) Scanning

Schulz-Ertner et al. Semin Radiat Oncol, 2006.

Treatment PlanningTreatment Planning

• Acquisition of imaging data (CT, MRI)Acquisition of imaging data (CT, MRI)

• Conversion of CT values into stopping power

• Delineation of regions of interest

• Selection of proton beam directions• Selection of proton beam directions

Treatment PlanningTreatment Planning

• Design of each beamDesign of each beam

• Optimization of the plan Including variable energy with each beam– Including variable energy with each beam

• Dose calculation models– Broad beam (measurement)

– Pencil beam

– Monte Carlo

Dose DistributionsDose Distributions

Photons

Protons

MacDonald et al. Cancer Investigation. 2006.


Greco & Wolden. Cancer. 2007.


Suit et al. Acta Oncologica. 2003.

Kase et al. A Treatment Planning Comparison of Passive-Scattering and Intensity-ModulatedProton Therapy for Typical Tumor Sites. J Radiat Res, 2011.

PET Treatment VerificationPET Treatment Verification

Remmele et al. A deconvolution approach for PET-based dose reconstruction in proton radiotherapy. PMB 2011.

Challenges in Proton TherapyChallenges in Proton Therapy

• Patient related• Patient related– Patient setup/movements, Organ motion, Body contour, Target definition

• Biolog related• Biology related– Relative biological effectiveness (RBE)

Ph i l t d• Physics related– CT number conversion, Dose calculation

M hi l t d• Machine related– Device tolerances, Beam energy

Final CommentsFinal Comments

Magnetic Resonance ImagingMagnetic Resonance Imaging

• Physics of magnetic resonance imagingPhysics of magnetic resonance imaging– Nuclear magnetic resonance

– Image creation

• Uses of MRI in radiotherapy– In-room systems and functional imaging

A Bit of MRI HistoryA Bit of MRI History• Found a method to tune in on magnetic fields of

spinning nuclei in 1946spinning nuclei in 1946– Purcell E.M., Torrey H.C., Pound R.V., Resonance Absorption by Nuclear Magnetic

Moments in a Solid, Phys Rev 69, 37-38 (1946). [Harvard]

– Bloch F Hansen WW Packard M E Nuclear induction Phys Rev 69 127 (1946)Bloch F., Hansen W.W., Packard M.E., Nuclear induction, Phys Rev 69, 127 (1946) [Stanford]

• First MR image formed in 19731973 h t bli h d i N t titl d "I f ti b i d d l l– 1973 a short paper was published in Nature entitled "Image formation by induced local interaction; examples employing magnetic resonance". The author was Paul Lauterbur, a Professor of Chemistry at the State University of New York at Stony Brook.

• The first commercial MR scanner installed in 1983• The first commercial MR scanner installed in 1983– The Department of Diagnostic Radiology at the University of Manchester Medical School

in Europe (from Picker Ltd.)

Another Use of RadiationAnother Use of Radiation

mynasadata.larc.nasa.gov

Constituents of MatterConstituents of Matter

• Atoms → Nucleus + Electrons → ProtonsAtoms → Nucleus + Electrons → Protons

• Charged particle’s spin– Angular momentum suggested by Pauli in 1924

– A spinning charge creates a magnetic field, Br

BrB

Br

Br

No external magnetic field

B

Bushburg et al. The Essential Physics of Medical Imaging. 2nd Ed, 2002. Fig 14-2 .

Apply External Magnetic FieldApply External Magnetic Field

• Charged particles precessCharged particles precess about the magnetic field

• Net magnetic momentg

External magnetic field ( ) applied0Br

Bushburg et al. The Essential Physics of Medical Imaging. 2nd Ed, 2002. Fig 14-3.

Magnetic PropertiesMagnetic Properties

• Processional frequency depends on field strengthProcessional frequency depends on field strength and type of nucleus,– is the gyromagnetic ratio

0 0Bω γ=γ

Nuclei γ/2π (MHz/T)11H 42.58

23Na 11.313C 10.7

Pykett. NMR Imaging in Medicine. Sci Am, 1982.

Bushburg et al. The Essential Physics of Medical Imaging. 2nd Ed, 2002.

Pykett. NMR Imaging in Medicine. Sci Am, 1982.

RF PulseαM

a

α

α

u se

Mb

e

TIME

αM

M M

cd

TIMETIME

T2 DephasingT1 Relaxation

α

α

/ 2( ) t TxM t e− ( )/ 1

0( ) ( ) 1 t TzM t M t e−⋅ −

M MTIME

T1 Relaxation

T1 and T2T1 and T2

• T1, longitudinal relaxation timeT1, longitudinal relaxation time– Restoration of the precession of the nuclei in the static B field

• T2, transverse relaxation time– Following the RF excitation, the free induction signal vanishes because

the transverse component of the magnetization decaysthe transverse component of the magnetization decays

• T1 and T2 are tissue specific– Distinguishing characteristic of tissues that makes nuclear magnetic

resonance useful for imaging

Bloch and PurcellBloch and Purcell

• Detecting energy changes

• All modern MRI signals work on these principles

Purcell’s arrangementBloch’s arrangementPake. Magnetic Resonance. Sci Am, 1958.

Magnetic FieldsMagnetic Fields

• Units of magnetic field strengthUnits of magnetic field strength– Tesla (SI units); (newton ⋅ second) / (coulomb ⋅ meter)– Gauss (cgs units); 1 tesla = 10,000 gauss

Item Magnetic field strength

Earth’s magnetic field** 0.000025 – 0.000065 Tg

Hair dryer, Electric shaver* 0.000065 T

Really strong refrigerator magnet** 0.01 T

T i l li i l MRI 0 5 3 0 TTypical clinical MRI 0.5 – 3.0 T

* Running 60Hz at 15 cm distance; EPA Doc 402-R-92-008, Dec 1992.**http://www.magnet.fsu.edu/education/tutorials/magnetminute/tesla-transcript.html

Pulse SequencesPulse Sequences• Spin Echo

• Inversion recovery– First tip by 180o, then let decay (longitudinally) for TI (∼300ms)

Then add on a standard spin echo (90o + 180o)– Then add on a standard spin echo (90o + 180o)

– Can repeat for several TI’s.

– Images are heavily T1-weighted RFEcho

Slide Courtesy Shantanu Sinha, PhD, UC San DiegoInversion Time

(TI)

90o

180o

TE/2

180o

TE/2( )

Typical T1 and T2 ValuesTypical T1 and T2 ValuesTissue T1 for 0.5 T

(msec)T1 for 1.5 T

(msec)T2

(msec)

Fat 210 260 80

Muscle 550 870 45

White matter 500 780 90White matter 500 780 90

Gray matter 650 900 100

CSF 1800 2400 160

T1 Weighted


T1 Weighted

ImageImage Contrast

T2 Weighted


T2 Weighted

ImageImage Contrast

Proton Density Weighted


Proton Density Weighted

ImageImage Contrast

FLAIR

Bushburg et al. The Essential Physics of Medical Imaging. 2nd Ed, 2002. Fig 14-25, 14-26, and 14-27.

FLAIR

RFEcho

90o

RF

180o180o

Inversion Time(TI)

TE/2 TE/2

NMR: A Perspective on Imaging. General Electric Company, 1982. Fig 14.Brown. NMR Imaging: Principles and Recent Progress. SCA Conference Paper Number 8812, 1988. Fig 21.

Single frequency

An image of NxN pixels requires N independent projections, each defined by N points.

Two frequencies

Time Domain

Frequency Domain

MR image reconstruction by back projection of the MR frequency domain signal is equivalent to using the CTsignal is equivalent to using the CT attenuation profiles to create a CT image.

No B-field gradient

B-field gradient

Both vials resonate at:

Vials resonate at:

Bω γ ( ) Bδ⎛ ⎞⎜ ⎟

r

Brown. NMR Imaging: Principles and Recent Progress. SCA Conference Paper Number 8812, 1988. Fig 24.

0 0Bω γ= ( ) 0x xx

ω ω γδ

= ⎜ ⎟⎝ ⎠

Image Construction

Smith and Ranallo. A non-mathematical approach to basic MRI. 1989. Fig 18-1.

Image Construction

• To make a “slice” (i.e., constrain z), make the RFTo make a slice (i.e., constrain z), make the RF excitation itself spatially-selective

0ω ω>

0ω ω=

0B B>

0B B= 0

0ω ω<

0

0B B<

0 0Bω γ=

Slice Thickness

Slide Courtesy Shantanu Sinha, PhD, UC San Diego

Slice Thickness

Slice Thk: 3 mm Slice Thk: 10 mm Slice Thk: 20 mm

•Signal is proportional to then number of protons per voxel.•As slice thickness Increases, the number of protons increases linearly with slice thickness.•Partial volume effects also increases with slice thickness.•Thinner slices always preferred since better resolution but limited by SNR and gradients.

Enhanced ContrastEnhanced Contrast

Gadolinium T1 contrast enhancement by IV injection of exogenousGadolinium T1 contrast enhancement by IV injection of exogenous contrast agent.

lesion


Contrast From FlowContrast From Flow

MR Angiography utilizes inherent differences in contrast between g g p yflowing (blood) spins and stationary tissue.

Time-of-Flight MRA for visualization of vasculature.


MRSI• MR spectroscopy and MR imaging methods

MRSI

– Produce a spectrum identifying different chemical compounds (metabolites) in various tissues

M t b lit ti diff ti t b t ti• Metabolite ratios differentiate between active tumor, normal tissue, and necrosis

Hunjan et al. IJROBP, 2003.

MRSI

Delorme and Weber. Applications of MRS in the evaluation of focal malignant brain lesions. Cancer Imaging, 2006.

MRSI

In Room MR TechnologiesIn-Room MR Technologies

Oborn et al. Med Phys, 2010.Courtesy of Viewray, Inc.

In Room MR TechnologiesIn-Room MR Technologies

Raaymakers et al. Integrating a 1.5 T MRI scanner with a 6 MV accelerator: proof of concept. PMB, 2009.

Pyket. NMR Imaging in Medicine. Sci Am, 1982.


• What are two methods to create a clinicalWhat are two methods to create a clinical proton beam?

a) Passive scattering and active scanninga) Passive scattering and active scanning

b) Blocks, bolus and wedges

c) Active scattering and passive scanningc) Active scattering and passive scanning



• What property of tissues makes nuclearWhat property of tissues makes nuclear magnetic resonance useful for imaging?

a) Angular momentum is independent of RF energya) Angular momentum is independent of RF energy

b) Tissues have characteristic relaxation times

c) RF attenuation is linearly related to tissue densityc) RF attenuation is linearly related to tissue density


Novel Technologies in Radiotherapy: Protons and Magnetic … · · 2012-04-30Novel Technologies...

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