MR-BASED SIMULATION + MR-GUIDED HIGH INTENSITY FOCUSED ULTRASOUND FOR RADIATION ONCOLOGY

Melanie Traughber, D.Sc.

Conflicts of interest

• I am an employee of Philips Healthcare• I am an MR physicist

“The Role of the Physicist in State of the Art Radiation Therapy and Imaging Techniques”

MR

ˇ

The Radiation Oncology Learning CurveFrom the perspective of an MR physicist

MR can be used outside of Radiology.

“Oncology” is a general term. So is “Medical Physics”.

In RT, “simulation” does not involve MatLab or the Bloch equation.

RT has nothing to do with diagnosis or staging.

The existing MR technology will work for RT.

The existing MR workflow will notwork for RT.

MR should play a bigger role in RT.

MR-guided RTPotential Applications

• MR-only Simulation• Future workflow• Basic components• QA assessment tools

• Cortical bone imaging• Dose calculation• DRR generation

• MR-HIFU• Basic principles• Real-time monitoring • Volumetric heat deposition

• Clinical uses• Uterine Fibroids

• Bone metastases, Liver lesions• Hyperthermia

• Drug Delivery

Streamlined workflow for Therapy Planning with CTand MR

Localization/markingPatient positioning CT scanning

CT

Delineation

Patient positioning MR scanning

MR

TreatmentPatient positioning

Dosimetry DRR creationDelineationFusion

Localization/marking

Workflow for MR-only sim, without CT registration

Treatment

Patient positioning MR scanning

MR

Delineation/segmentation

DRR creationDose calculation

Patient positioning

Density assignment

Quality assurance for geometric deformation

Laser positioning system

Flat table top

Coil solutions for imaging in treatment position

RT software release•Dedicated ExamCards•Travel-to-Scan•QA analysis programs

Basic components of an MR SimulatorMR System dedicated for Radiation Therapy Planning

*Works-in-Progress

Quality Assurance for Radiation OncologyGeometric integrity and laser alignment

Phantom and analysis program• Provides geometric deformation

analysis of imaged phantom• Available on MR console• Dimensions 45 x 35 cm

Laser alignment• Guidance for the operator

throughout procedure • Calibration and alignment protocols

available on MR console

MR-only SimulationMR imaging in treatment position

Courtesy Henry Ford Health Systems, Detroit, USA

Bone imagingCalculation of bone-enhanced images

• Subtraction of IP from TE1

generates complete segemention of cortical bone.

• BE image is anatomically accurate in fine detail.

TE1

IP

BE

Slice 1 Slice 2

Clemente Anatomy, 4th Edition

Spongy bone

Inner table Outer table

Single acquisition UTE-mDIXONSequence specifics

• 3D isotropic acquisition with radial readout• Start FID acquisition on upslope of readout gradient (UTE)• Follow with 2-3 gradient echoes

11

Rahmer, et. al. Merging UTE Imaging, Water-Fat Separation, and T2* Mapping in a Single 3D MSK Scan. Abstract #3224, ISMRM 2010.

MR-only SimulationDelineation and segmentation

Improved delineation on MR

Investigational use only

MR auto-segmentation

Courtesy Henry Ford, Detroit, USA

BE water IP OP fat

In collaboration with University Hospitals, Cleveland, USA

Dose calculated on MR images

MR-only SimulationDose calculation and DRR generation

DRRs generated from MR images

In collaboration with Henry Ford Health System, Detroit, USA In collaboration with University Hospitals, Cleveland, USA

MR-only SimulationHow close are we?

• All of the pieces seem to be available• What is still needed?

• Workflow• Proven benefits• Clinical outcomes Localization/mar

king

Workflow for MR-only simulation, without CT registration

Treatment

Patient positioning

MR scanning

MR

Delineation/segmentation DRR creation

Dose calculation

Patient positioning

Density assignment

High Intensity Focused Ultrasound (HIFU)Physical Interaction with tissue

Tissue Ablation/Hyperthermia@ the Focal Spot

Tissue Ablation/Hyperthermia@ the Focal Spot

Vibration of MoleculesVibration of Molecules

Energy AbsorptionEnergy Absorption

Temperature ElevationTemperature Elevation2 x 7 mm Focal spot

UltrasoundUltrasoundTransducer

Tissue

Non-invasive &Precise Treatment

1.2 -1.4 MHzGeometric Gain

Other Localizedeffects

Cavitationand/or

Mechanical Effects

MR-HIFU Paradigm

MR PlanningMR imaging for 3D planning and treatment simulation

HIFU Tissue Ablation or Hyperthermia

Focused ultrasound heats the target non-invasively

MR Therapy ControlSimultaneous MR is used

to guide, monitor, control, and assess HIFU therapy

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Image GuidedTherapy

Real-timeTemperature monitoring

ThermalAblation

Real-timecontrol

Ultrasound TransducerIn Therapy Tabletop

Therapy Console

HIFU Components1) Console2) Tabletop & Trolley3) Electronics Cabinet4) Cabling

Phased Array controlledby 5DOF Robot

MR with integrated HIFU

MR Multi-slice monitoring for Safety6 Simultaneous T monitoring planes

• 3 coronal + 1 sagittal• 1 skin + 1 sacral surface• 1 slice along the beam axis• Every 2.9 sec

Allows Optimal Target heating while monitoring critical Structures

x 6 speed

Courtesy Y. Kim, Samsung MC

Nearfield

Farfield

Focal Plane

Cavitation Detection

Early MR-HIFU Challenges

1) Slow Treatment Speed• Treating large tumors (2 – 20 cm) with

a small HIFU focal spot (mm)• Treatment Times 3-4 hours

2) Ablation Variability • Dependence on tissue properties• Unpredictable lesion sizes & shapes

3) Indication Expansion: Treatment around Scars, Bowel Loops & moving organs

4) Clinical Evidence: RCTs, Trials with Latest Technology

5) Healthcare System: Complex Regulatory, Turf Battles, Which Specialty?

Courtesy Nathan McDannold

Courtesy Y. Kim, Samsung MC, Korea

Volumetric HeatingIncreased Ablation Volume

Cell

Electronic beam steering:

Outwards-movingconcentric circles

4 – 16 mm ØFor details see:M. Köhler et al., Med.Phys. 36 (8),3521, August 2009

Diameter (mm)

Length (mm)

Volume (ml)

4 10 0.1

8 20 0.6

12 30 2.3

16 40 5.4

Real Time FeedbackReliable necrosis volume

Thermal map & Dose map

Real time visualization+ Feedback

T > 65°C* or Dose >240 EM

Stop heating

Reliable necrosis volume

Thermal map Dose map

Threshold

Non-perfused volumeJ. Enholm et al., IEEE Trans.Biomed.Eng. accepted

Reliable necrosis volumeNo a-priori knowledge needed

Simple and robust

* Applies to the border of the cell. Temperatures at the center are higher, especially for larger cells.

Beam Shaping to Avoid Scars & Bowel

Beam Shaping enables selective blocking of part of the ultrasound cone in user-specified region

� Organ Avoidance Region or OAR

Allows ultrasound delivery in the presence of :

� Scars� Umbilicus� Skin folds � Air bubbles on the

skin� Bowel

Umbilicus

OAR

Shaped Beam

MR-HIFU Applications

Ablation• Uterine fibroids (Phase III Trials)• Bone metastases (Phase II Trials)

• Prostate (Phase II starting 8/2012)• Breast tumors (Phase I enrolling)

• Liver & Kidney• Neurology & Cardiac

Conformal Hyperthermia (Translational)

• Radiation & Chemotherapy Sensitization

Local Drug Delivery (Translational)• Temperature or Mechanical Force induced

local drug release

• Partnerships with Pharma to develop novel drugs

Investigational Device in USA

Ablation Innovations in the Clinic: FibroidsAblation on or near a blood vessel

Courtesy: UMC Utrecht, The Netherlands

T1-w CE image post-treatment

T1-w CE image pre-treatment

= Non-Perfused Volume Post-treatment: Large fibroid 84% NPV Complete devascularization of four small fibroids

Ablated Area

T2-w image pre-treatment

Vessel & Perfusion Guided AblationNon-Contrast sequence

• Pre-Treatment perfusion and large vessel visualization (3-5 minute acquisition)

Delay = 1.5s Delay = 1.0s

Smaller Vessels Larger Vessels

Investigational Device in USA

First Oncology Application: Bone Mets Palliation

Palliation of Painful Bone Metastases•HIFU can be used to treat painful Bone Mets

• Pelvis, Sacrum, Scapula, Ribs, long bones• osteolytic & osteoblastic • RT failure or RT naïve

•HIFU is non-ionizing option potentially co-administered during RT of primary tumor

Bone & US/MR Physics•High US absorption in cortical bone

• Allows efficient & safe Tx at lower HIFU power• Potentially limits whole tumor treatment

•Low water content in Bone• Reduces MR SNR for traditional thermometry• T2,T1 approaches can be used to compensate

Pain Relief Mechanisms•Death of periosteal nerves•Tumor necrosis -> reduced mass effect

Courtesy: G. Czarnota, Sunnybrook Medical Center, Toronto, Canada

Planning: Scapula Met in 61F

Treatment: Pain VAS 8�2

Investigational Device in USA

Bone Pain PalliationFemur with Intact Cortical Bone

Low power (20 W)Excellent response: Pain score 8 � 0

Sunnybrook Health Sciences Center/Dr. G. Czarnota

Post TxT2 Imaging

AblationZone

Bone pain therapy – heating of bone surface, ablation of periosteal nerves

Large volume Hyperthermia in vivoMR-HIFU with Temperature Feedback and

Electrical & Robotic HIFU beam steerability allows precise conformal hyperthermia

Large Volume Hyperthermia is feasible• Vx2 tumor in rabbit hind muscle• 5 cm2 cross-sectional area (~ 50 cm3 ellipsoid)

Target Volume

Power/deflection limits

0 5 10 15 2036

37

38

39

40

41

42

43

Sonication Cooldown

Ttarget

Time (min)

Tem

per

atu

re (

°° °°C)

Max

T10

Mean

MinT90

Power and Temperature

43

39

°C

30

W

0

MR-HIFU Drug Delivery With Low Temperature Sensitive Liposomes(LTSL) – Hyperthermia Release

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Drug circulates toTumor

Drug extravasates under HIFU Heat & Pressure

Drug released locally byHIFU Heat

Duke U

niversity

Key Benefits: Potentially high dose (10x) of Chemotherapy targeted at tumor sites with reduced systemic toxicity

AddHeat

Drug: ThermDox® (Celsion)

<39<39ooCC >39>39ooCC

Status•In 2008, Philips & Celsion initiated Partnership to develop MR-HIFU + ThermoDox•In July 2012, FDA IND for phase II Bone MR-HIFU + ThermoDox Study•Pre-clinical studies & Regulatory process underway for Pancreas

Towards an Integrated Workflow MR-HIFU+RT

MR with integrated HIFU transducer array

Integrated Planning &

Therapy RT Delivery System

Integrate the two therapies for simultaneous planni ng & time saving while offering inter-fraction imaging f or adaptive therapy as a “side benefit”.

30-60 minutes Hours to days

(CT,PET/CT, MR)

Simulation(CT,PET/CT, MR)

(CBCT, X-Ray)

60 - 90 minutes for Tx & plan adaptation

10 minutes 5-15 minutes

Focal Ablation and/or Hyperthermia

Thank you