MRI IN RADIATION TREATMENT PLANNING AND ASSESSMENT · CURRENT MRI IN RADIATION TREAMENT PLANNING...

MRI IN RADIATION TREATMENT PLANNING

AND ASSESSMENTYue Cao1 and Lili Chen2

Departments of Radiation Oncology and Radiology, University of Michigan1

Department of Radiation Oncology, Fox Chase Cancer Center2

OutlineI. OVERVIEW OF MR IMAGING

I.1 Principles of Magnetic Resonance ImagingI.2 Contrasts of MRII.3 Radiographic ResponseI.4 Artifacts and Geometric distortions

II. CURRENT MRI IN RADIATION TREATMENT PLANNINGII.1 Target DefinitionII.2 Treatment planning and simulation II.2.1 MRI simulator II.2.2 Assessment and Correction for Geometric distortionII.2.3. Creation of MR DRRII.3 Use of MRI in place of CT for treatment planning

III. PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS

III.1 Physiological and metabolic MR techniquesIII.1.1 Diffusion MR techniqueIII.1.2 Cerebral blood volume MR techniqueIII.1.3 CBF MR techniqueIII.1.4 Vascular permeability MR techniqueIII.1.5 Proton MR spectroscopyIII.2 Applications of physiological and metabolic MR in Radiation Oncology

OVERVIEW OF MR IMAGINGI.1 Principles of Magnetic

Resonance ImagingI.1.1 Signal Source– Nuclear magnetic moments or

spins of water protons– randomly oriented – lining up with a external

magnetic field– precessing about the direction of

B0– Larmor relationship:

ϖ0=γB0– Magnetization:

Longitudinal Mz=MoTransverse Mxy=0

a) randomly oriented spins in a sample b) alignment of spins in a static magnetic field.

a b


Resonance ImagingI.1.2 RF Excitation

• Applying a small radiofrequency (RF) field of amplitude B1 to create the transverse magnetization Mxy

• B1 oscillating at the Larmorfrequency

• B1 perpendicular to B0• B1 rotates the magnetization away

from B0• The flip angle depends upon the

amplitude and duration of B1• Applying B1 long enough, the

transverse magnetization will be equal to M0

B0

M0

M

Mxy

α

OVERVIEW OF MR IMAGING

I.1 Principles of Magnetic Resonance ImagingI.1.3 Free Induction Decay– Following a 90o RF pulse, M0

freely precesses about B0

– Inducing oscillating voltage in the receiver coil

– Magnetization is decay due to the incoherent precessing frequencies of spins

• Some of spins precess about B0faster than others

The envelope of the FID signals can be described as

S=S0 exp(-t/T*2)

OVERVIEW OF MR IMAGINGI.1 Principles of Magnetic Resonance

ImagingI.1.4 The Spin Echo

• After a 90o RF pulse, spins start dephasing• Applying a 180o RF pulse τ seconds after

the 90o pulse, the fast spins will be behind the low spins

• Then, the spins will come back into phase with each other after another τ seconds.

• The varying magnetic field induced in the receiver coil will form an echo, therefore it is called a spin echo.

• The magnitude of spin echo– S= S0 exp( - TE/T2), TE=2τ

• The amplitude of SE is decreased with an increase in TE due to incomplete refocuses of some of incoherent processes


Resonance ImagingI.1.5 T1 Relaxation Time

• After FID or forming a SE, the magnetization eventually returns to its initial rest state (along B0) by a process called T1 or spin-lattice relaxation.

– Two methods to measure T1Saturation recovery

S=S0 [1-exp(-t/T1)]Inversion recovery

S=S0 [1-2 exp(-t/T1)]

OVERVIEW OF MR IMAGINGI.1 Principles of Magnetic Resonance Imaging

I.1.6 2D Fourier ImagingFrequency encoding

If a magnetic field gradient is applied along the x axis, the spins along the x axis will experience a differential magnetic field according to their position, rotate with different frequencies, and induce voltages with different oscillating frequencies in the receiver coils. Applying a one-dimensional FT to the induced voltages will yield MR signals resolved along the x axis.

Phase encodingIf a gradient is applied along y axis for a short time period before recording the induced voltages, the spins along the y axis will have different phases due to that the spins that experience a larger field will rotate faster than the spins that are exposed to a smaller field. If this process is done N times and magnitude of y gradient-is different for each time, we will obtain N signals with N different phases. Again, applying a one-dimensional Fourier transform to the N signals with N different phases will yield the MR signals resolved along the y axis.

time

RF pulse

time

RF pulse

time

Freq

uenc

ygr

adie

nt

time

Freq

uenc

ygr

adie

nt

time

Pha

segr

adie

nt

time

Pha

segr

adie

nt

OVERVIEW OF MR IMAGINGI.2 Basic MRI Contrasts

– T1 weighted image• TE short, TR ~<T1• Brighter for tissue w shorter T1

– T2 weighted image• TE ~<T2, TR long• Brighter for tissue w longer T2

– FLAIR T2 weighted image• Fluid-attenuation inversion recovery

– Post Gd-DTPA T1 weighted image• Brighter for tissue that is uptake contrast

– Contrast agent – Gd-DTPA• Shortening T1 increase SI in T1WI• Shortening T2* or T2 decrease SI in

T2*WI or T2WI

OVERVIEW OF MR IMAGINGI.3 Treatment (radiographic)

Response• Surrogate measure

– Longest dimension, two longest dimensions, and volume of the tumor

– 2000 NCI guideline• Longest dimension

CR: disappearing tumorPR: decrease > 30%SD: increase <20% or decrease <30%PD: increase >20% or new lesions

Pre Tx Post Tx

OVERVIEW OF MR IMAGINGI.4 Artifact and Geometric distortion• Artifact and geometric distortion

– Inhomogeneity in the external magnetic field – Inhomogeneity in the RF field– any non-linearity and asymmetry in gradients– Eddy currents– a large change in magnetic susceptibility

around tissue boundaries – Chemical shifts of water and fat– surgical clips and dental work– High field worse, fast sequences worse

(EPI, GE, …)• Motion artifacts

– Respiration motion– Cardiac motion– Involuntary motion

CURRENT MRI IN RADIATION TREAMENT PLANNING

II.1 Target Definition– Advantages of MRI

• Superior soft tissue contrasts • Richness in various contrasts• Widely available• One stop to obtain anatomic, metabolic and functional images

– Radiation treatment planning• Routinely used in brain tumor including primary and metastasis• Increasing its use in prostate cancer better delineation of prostate

and rectal volume• a leaser extent in H/N, liver, pancreas, …


?

CT Post-Gd T1W FLAIR


II.2 Treatment planning and simulation II.2.1 MRI simulator– A system at FCCC

• 0.23 T • Flat patient table top• 47 cm separation between

two poles• Patient weight up to 400

lb

A Philips 0.23 permanent magnet


II.2 Treatment planning and simulationII.2.2 Assessment and Correction for Geometric

distortion• Sources of geometric distortion

– Hardware and software of the scanner– Patient induced

• System dependent factors– Field strength: the lower field the less distortion– Filed of view: the smaller FOV the less distortion

» The farther distance from the isocenter results in the large distortion


II.2 Treatment planning and simulationII.2.2 Assessment and Correction for Geometric

distortion• FCCC 0.23 system

– 139 Hz/pixel in FE insignificant distortion caused by chemical shifting and susceptibility

– Distortion caused by imperfect gradient systems» Distortion of 2-3 mm if 12-18 cm is offset from the

isocenter» Gradient distortion correction program negligible distortion for the patient lateral size < 38 cm7 mm distortion for the patient later size > 38 cm


CT Uncorrected MRI GDC MRI


II.3 Use of MRI in place of CT for treatment planning– II.2.3. Creation of MR DRR

• Bony structures appear as signal voids on MRI • Bony structures can be contoured and assigned a bulk

density– e.g., 2.0g/cm3 to pubic symphysis, femoral heads, acetabulum

and sacrum for prostate patient– Accuracy of this method 2-4 mm compared to CT DRR


MRI-DRR CT-DRR


II.3 Use of MRI in place of CT for treatment planning– gold standard

• MR and CT image fusion with CT-based dose calculation

– MRI-based treatment planning for prostate • Additional errors induced by the fusion process• substantial differences in bladder and rectal filling • redundant CT imaging session


II.3 Use of MRI in place of CT for treatment planning– MRI-based treatment planning for prostate

• Major concern: lack of electron density information for accurate dose calculation and heterogeneous anatomy

• Several Monte Carlo studies have shown that there is no clinically significant difference in dose calculation between homogeneous and heterogeneous geometry for the pelvic region.

• Adequate to use homogeneous density in prostate


II.3 Use of MRI in place of CT for treatment planning– MRI-based treatment planning for prostate

• Compared to the plan based upon CT and heterogeneous geometry for 15 plans

– The mean differences: » <2.6% for isocenter dose» 1.25 ± 0.83 % for the maximum doses » 0.54 ± 0.4% for D95 of the PTV » 1.0± 0.49% for D17 of the rectum» 1.09 ± 0.31% D35 of the rectum » 0.96 ± 0.53% for D25 of the bladder» 0.66 ± 0.71% and D50 of the bladder


CT - based plan MRI - based planCT - based plan MRI - based planCT - based plan MRI - based planCT - based plan MRI - based plan

100% 100%90% 90%

CT-based and MRI-based IMRT plans. The isodose lines are 100%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20% and 10%.


0

20

40

60

80

100

0 10 20 30 40 50 60 70 80 90 100

Dose (Gy)

Volu

me

(%)

CT-based PTVMR-based PTVCT-based rectumMR-base rectumCT-based bladderMR-based bladder

PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS

III.1 Physiological and metabolic MR techniques– Diffusion imaging– Diffusion tensor imaging– Vascular imaging including blood volume, blood flow,

mean transit time, and vascular permeability– Metabolic imaging (1H, 31P, 13C, 19F,…)– Do not blindly use commercial software without evaluation

(e.g., XXX)– Understand limitations of technologies


III.1 Physiological and metabolic MR techniquesIII.1.1 Diffusion MR

• The random motion of the water protons and the inhomogeneity of a magnetic field cause de-phasing of spins

• Applying dephasing and refocused field gradients to sensitize an image to water proton motion

• The diffusional signal loss by the gradient application is given– S=S0 exp(-bD)– large diffusion results in great in signal loss

Low diffusion in tumor


III.1 Physiological and metabolic MR techniquesIII.1.2 Cerebral blood volume and Cerebral blood

flow MR techniques– Using DCE imaging, several vascular properties

such as CBV, CBF, MTT(=CBV/CBF) and vascular permeability can be estimated.


III.1 Physiological and metabolic MR techniquesIII.1.2 Cerebral blood volume MR

techniques– DCE T2* weighted images with

an i.v. injected contrast bolus– An image volume can be

acquired within 1-2 seconds– The acquisition continues for 1-2

minutes– The equation on the right hand

side provides a good estimate of CBV

– An overestimate or underestimate can occur in abnormal conditions

dttS

SCBV ∫ ⎥⎦

⎤⎢⎣

⎡∝

)(ln 0

400

500

600

700

800

900

1000

1100

0 20 40 60 80

time (s)

S(t)


III.1 Physiological and metabolic MR techniquesIII.1.2 Cerebral blood flow MR techniques– CBF can be estimated from DCE T2* weighted MRI and a artery input

function

– The residual function R is determined by deconvolusion computation (SVD)

– The amplitude of the residual function R is proportional to blood flow.

⎥⎦

⎤⎢⎣

⎡=

)(ln1)( 0

tSS

TEtAIF

MCA

MCA

τττ dtRAIFtTisst

)()()(0

−= ∫

⎥⎦

⎤⎢⎣

⎡=

)(ln1)( 0

tSS

TEtTiss

tiss

tiss


CBV

CBF


III.1.4 Vascular permeability MR technique– Vascular permeability is

estimated from T1-weighted or T2* weighted DCE images and a compartmental model

– Two compartmental model• Vascular space and

extravascular extracellularspace

– AssumptionΔR1 =constant*C orΔSI =constant*C

artery veincapillary

Kin

bloodinflow

bloodoutflow

extra-vascular space

Kout


Kin

bloodinflow

bloodoutflow


Kout


Kin

bloodinflow

bloodoutflow


Kout

Two compartmental model

)()()(0

)( tCvdCeKtC pp

t

ptk

intb += ∫ −− τττ


III.1.4 Vascular permeability MR technique

Vascular permeability images


III.1.5 Proton MR spectroscopy– Proton MR spectroscopy (MRS) is a technique that is able

to detect proton metabolites and chemical compounds in tissue

– In an organic compound, electron bindings of each of protons with neighbor atoms are different, and generate a slight different but characteristic magnetic field offset.

– Each of the protons in a compound has a slightly different resonance frequency even though the compound is immersed in the same external magnetic field.

– Using this characteristic resonance frequency each proton can be uniquely identified on a spectrum, and the concentration of a compound can be estimated relatively to another compound.


III.1.5 Proton MR spectroscopy– Chemical compounds

and metabolites commonly detected in brain tissue

• choline-containing compounds, creatine, lactate, lipid, and N-acetylaspartate (NAA)

• Proton spectra can be obtained by 2D or 3D

NAAcholine


III.2 Applications of physiological and metabolic MR in Radiation Oncology– Applications of physiological and metabolic MR

in radiation therapy are emerging• Target definition• Early prediction for treatment response• Early prediction for treatment toxicity• optimizing treatment strategies• Endpoints – clinical, pathological, …


III.2 Applications of physiological and metabolic MR in Radiation Oncology– Assessment for treatment response

• A study of 28 patients with newly diagnosed GBM treated by fractionated radiotherapy and chemotherapy, the pre-radiotherapy volume of the metabolic abnormality (the region with choline/NAA > 2.5) within the T2 defined tumor volume predicted survival.


III.2 Applications of physiological and metabolic MR in Radiation Oncology–Early assessment for treatment response• Another recent study of 23

high-grade gliomas found that the fractional tumor volume with high CBV prior to radiotherapy (RT) predicted survival

(month)

P=0.002

fTV w High-CBV <0.07

fTV w High-CBV >0.07


Pre RT 1 week 3 weeksSubsequent decreases in the fractional tumor volumes with high-CBV at week 3 of RT were associated with better survival


III.2 Applications of physiological and metabolic MR in Radiation Oncology– Early prediction for treatment toxicity

• assessment of blood-brain or blood-tumor barrier opening in high-grade gliomas during radiation therapy using high-resolution post contrast MRI

– A significant increase in the contrast uptake in the initially non-contrast enhanced portion of the tumor after ~30 Gy and up to 1 month post RT

– A graduate decrease in the contrast uptake in the initially contrast enhanced portion of the tumor during RT


-2.00

0.00

2.00

4.00

6.00

8.00

10.00

12.00

pre-RT 1wk 3wk 1 mon pst 3 mon pst 6 mon pst

Gd-

DTP

A U

ptak

e In

dex

Pre RT After ~30Gy


III.2 Applications of physiological and metabolic MR in Radiation Oncology– Early prediction for hepatic venous perfusion

dysfunction• Decreases in the regional portal vein perfusion one

month post RT were predicted by the local doses and the decreases observed after received ~45 Gy in patients who underwent focal liver radiation

• CT only allows us to acquire DCE images from a small slab (~2cm) of liver, but MRI allows to us to image the whole liver


250 ml/100g/min 250 ml/100g/min45 ml/100g/min

Total perfusion Arterial perfusion Portal vein perfusion0 ml/100g/min 0 ml/100g/min0 ml/100g/min


ΔFp

v% 1

mon

th a

fter

RT

ΔFpv% after 3 weeks RT Regional dose (end of RT in cGy)


III.2 Applications of physiological and metabolic MR in Radiation Oncology– Early prediction for hepatic venous perfusion

dysfunction• CT only allows us to acquire DCE images from a

small slab (~2cm) of liver, but MRI allows to us to image the whole liver

• Prediction of hepatic venous perfusion dysfunction post RT might have a significant impact on optimizing or re-optimizing radiation dose in individual patients

SUMMARY

• Roles of MRI in radiation oncology will continue increasing, including target definition for treatment planning, boost volume definition, early assessment for response, early prediction for radiation toxicity, and re-optimization for radiation treatment based upon normal tissue toxicity and tumor response.

• Applications of physiological and metabolic MRI to RO will increase substantially.

MRI IN RADIATION TREATMENT PLANNING AND ASSESSMENT · CURRENT MRI IN RADIATION TREAMENT PLANNING...

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