Week 4. Image guided therapies.
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Transcript of Week 4. Image guided therapies.
2012.10.30.
1
Multimodal Imaging in Neurosciences Course
Image guided therapies inneurological sciences and VRDr. András Jakab, MD, PhD
COURSE FAQ
Forthcoming lectures:16. October – „IGT lecture”23. October – NO LECTURE, holiday30. October – MR Spectroscopy6. November – PET + Final Test
Test:- Basic imaging techniques, what are they- 5-10 easy, simple choice questions- If November 6. is not good for everyone, I will organize extra
time for getting the short test done
Study material:Lecture material will be distributed in PDF 2 wks before thetest.
Diagnostic neuroimaging modalities
CT – Computed TomographyBrain anatomyStereotactic reference frame
Structural MRIFine brain anatomyVascular structure
Diffusion, perfusion MRIFine pathologicalinformation
Intra-operative imagingmodalities, open MRI, low-field
MR SpectroscopyBrain metabolismBiochemical mapping
Positron EmissionTomography PETBrain metabolismBrain function
Functional MR imaging fMRIBrain function
Electro encephalography, LORETTA, Magnetoencephalography
Using multi-modal imaging for planningimage-guided neurological interventions
What is multimodality?Combining images and information from multipleimaging tools, devicesAnatomical alignment of imagesFusion display, co-analysis of multipleinformation sources
What is needed for multimodality?What is needed for multimodality?CT, PET, MRI, SPECT, EEG, …Hybrid devices – PET-CT, PET-MRIImage processing skills to create image fusions, etc.
Overview of the lecture
1. Image guided therapy – basicsand the modalities used
2. Stereotactic functionalneurosurgeryR di d l i3. Radiosurgery and planning
4. Focused ultrasoundneurosurgery
5. VR applications in surgery
1 Image guided therapy -1. Image guided therapy -basics
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Image guidance• Using preoperative images
to define target volumes ina reference space
• Using intraoperativeimaging to monitor treatment– Intraoperative
ultrasound– Intraoperative low-field
MRI– Intraoperative high-field
open MRI Intraoperative open MRI, Brighamand Women’s Hospital, Harvard, Boston (credits: Prof. Ferenc Jolesz)
AMIGO – Harvard, Boston
Surgical robot for biopsies
Treatment planning w/ preoperative imaging
Intraoperative imaging withMRI
Surgical robot for biopsies
Intraoperative MR imaging
• Medtronic Polestar• Low field (0.1-0.3T)• Brain shift – a real problem• Use of nonmagnetic tools 2 Stereotaxy in functional2. Stereotaxy in functional
neurosurgery
What is stereotactic?• Space, spatial• Coordinate frame
of the brain:– Intrinsic– extrinsic
Why use stereotaxy inneurosurgery?
• Very high (<1-2mm) precision needed• Minimal invasive procedures
– Electrode implantation for ablationElectrode implantation for ablation– Permanent electrode implantation (DBS)– Biopsy sampling from the brain
• Procedures without opening the skull– Radiosurgery, LINAC, Gamma Knife,
Cyberknife– Focused ultrasound surgery
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Brain biopsy• Indications
– Tumor suspect (enhancing CT, MRI, lesion)– Inflammation, Neurodegeneration, unknown
• Procedure (1-2 hours):St f tt h t– Stereo frame attachment
– Computed tomography– Planning– General anaesthesia– Small craniotomy– Dexamethasone– Control scan(s)
Imaging for brain biopsy
• CT• MRI (T1/T2+Contrast)• Pathology+Radiological
consultation – where to takeh l f ?the sample from?
Functional neurosurgery
• Alleviating symptoms by modifyingfunctional areas of the brain, subcortical areas
• Two main approaches:• Two main approaches:– Permanently cutting fiber pathways,
destroying specific nuclei
– Retuning / stimulating fiber pathways, specificnuclei in the brain
Thermoablation
Deep brain stimulation
Thalamotomy / pallidotomy• Parkinson disease – associated tremor
alleviation• Essential tremor (unkown ethiology)
Targets:VIM nucleusSubthalamicnucleus, PTTVentral Pallidum
Thalamotomy• Fantom pain (after amputation)• Intractable tumor / stroke pain in limbs etc.• CL / CM nucleus – central lateralis / centré median
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Deep brain stimulation (DBS)
• FDA approval: 1997
• Implant in brain+ subcutaneous+ subcutaneousstimulator(~pacemaker)
• Retuningfunctionalpathways(„arrhythmia”)
Deep brain stimulation
• Indications:– Chronic pain, PD tremor,
ET, dystonia– Tourette, OCD, Major
d idepression
– Parkinsons• Subthalamic nucleus• Globus pallidus interna• Zona incerta• Pallidothalamic fibers
Procedure• Localization,
stereotaxy• Electrode trajectory: • Trials and
monitoring• Pre/postop imaging
Targeting scheme• 1. Target definition using stereotactic atlas
of the human thalamus and basal ganglia(histology)
Getting x,y,z coordinatesfor yourtarget
Reference: AC-PC coordinatesystem
Targeting scheme• 2. Defining targets on the patient’s coordinate frame (using CT+MRI)
Manually finding AC, PC points on scans
Finding landmarks of the reference frame(stereotactic frameattached to the head)
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3. Radiosurgery
Gamma ART 6000N Rotating Gamma SystemAmerican Radiosurgery Inc., San Diego, CA,
USA
•only 30 Co60 sources•Rotating sources•Collimator size:
4, 8, 14, 18 mm•Stereotactic frame required•0,3 mm accuracy•Source half-life approx. 5 yrs
Challenges
• Morphological imaging by MRI– 3D isotrop voxel acquisitio
• Good tissue contrast• Good signal-to-noise• Minimal image distortion• Optimal image resolution
– MRI as reference system?• Robust CT method is necessary
Challenges of multimodality
– fMRI– DTI, fibertracking– MRS, MRSI
• Postprocessing– Registration, image fusion (need fast)
• PET, SPECT
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3D T1 weighted images• 1,2x1,2x1,2 mm• 140 slices• 6 minutes• Gd contrast agent
3D T2 weighted images
• 0,7x0,7x0,7 mm• 40-60 slices• 4 minutes
3D TOF acquisition• 1,2x1,2x1,2 mm• 190 slices• 6 minutes• Gd contrast agentg
Our imaging protocolls(+indications)
• Metastasis, meningeoma• AVM• Cavernoma• Cavernoma• Acustic neurinoma• Hypophysis microadenoma
AVM MRA Automatic radiologic image processing
CT/T1/T2
T1
Automated CT/MRI registration(gammaknife, neurosurgery
automatedstandardization, segmentation
(neurosurgery, neurology)
DIC
OM
server
ImageSorter
DWI, T1
fMRI, T1, T2
automatedTensor space calculations and
regularization(neurosurgery, neurology)
automatedSPM analízisfMRI, T1, T2automated
SPM analízisfMRI, T1, T2automated
SPM analysis(neurosurgery, neurology)
Pet & Mriautomated
PET-MR registrationand roi analysis
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T1-CT registration for radiosurgery(gamma-knife)
- Automatic (maximalisation relative entropy)- Manual correction (with internal „landmarks”)To this time, manual correction was necessary in 60% of
the cases- Optimalised automatic registration
Image registration, alignmentgamma knife
T1-CT Fiesta-CT TOF-CT
Extracranial metastasis Extracranial metastasis (epipharynx)(epipharynx)
Acoustic neurinoma treatment plan
• 1 kezelési tervet betenni
Acustic neurinoma
Pre-treatment 6 months post 12 months post
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Treating trigeminal neuralgiaTrigeminal neuralgia
CT and FIESTA imaging
Service available via a DICOM-serverDataflow
• 2D fusion
BrainCAD:•Dicom-minc conversion
MNI and M3I tools:
• 2D fusion
• 3D fusion
• Fiber visualizationSPM-analysis
INTERACTIVEIMAGE PROCESSING
•Segmentation
•Automatic registration
•Spatial standardization
•Automatic region analysis
AUTOMATICIMAGE PROCESSING PRESENTATION
(neuronavigation)
Validation of the T1-CT optimized registration method
S01
REFERENCE IMAGES AUTOMATICALLY REGISTERED IMAGES
S02
S03
SnMRI data revision by experts
(occassionaly manual registrations)
Comparison using normalized relative entropy
Further fancy options
PET/SPECT imagesT2, PD etc.
Precise T1-CT registration
Structures defined in the space of a brain atlasDTI parametric images
SPM images
CT-DTI registration
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CT-DTI registration
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DTI + MRI data in the CT frame. Metastaticdisease, 55/M
( Gamma Radiosurgery Centre, Debrecen )
Proton therapy
100%
60%
PHOTONSMedulloblastoma“dose bath”
60%
10%
PROTONS
The proton advantage:Nasopharynx
Photons (IMRT) Protons
Dose bath
The proton advantage:Paraspinal
Photons Protons
Dose bath
4 Focused ultrasound4. Focused ultrasoundneurosurgery
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Energy Conversion and Transport in Biosystems (09.12.10)
Non-invasiveInterventions with
Beat WernerMR-CenterUniversity Children‘s HospitalZurich
Focused Ultrasound
WelcomeWelcome
Beat WernerMR-CenterUniversity Children’s Hospital Zurich
www.kispi.uzh.ch/mrbeat werner@kispi uzh [email protected]
dipl. phys. ETH
MR-Physics
HIFU surgery since 2005, research project as part of NCCR Co-Me
Slide credits: Beat Werner, Ernst Martin
Intro: Image guided interventionsIntro: Image guided interventions
Slide credits: Beat Werner, Ernst Martin
Intro: Image guided interventionsIntro: Image guided interventionsImage Guided Interventions
Improve accuracyDecrease intervention risks Minimally invasive / Non-invasive Interventions
Planning and navigation Complex interventions in cranio-maxillo-facial surgery. Slide credits: Beat Werner, Ernst Martin
Intro: Image guided interventionsIntro: Image guided interventions"Multimodal" Imaging
Multimodal: US, CT, MR, ...Multidomain: Anatomical, physiological, statistical information Multi-Timescales: Static (Pre-/intra-intervention), RealtimeRealtimeAugmented reality: condition, fuse, modelEnhanced visualization: 2D, 3D, ..., force feedback
Computer-assisted support in ORL surgerySlide credits: Beat Werner, Ernst Martin
Intro: Image guided interventionsIntro: Image guided interventionsEnabling technologies used here:
MRClosed-loop intervention controlUS field calibration
Focused UltrasoundMechanical / Thermal therapy(Targeted) drug delivery(Targeted) drug activation
Nano-ParticlesMolecular markersContrast agentsDrug carriersTherapeutic devicesSlide credits: Beat Werner, Ernst Martin
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Motivation: NonMotivation: Non--invasive HIFU Surgeryinvasive HIFU Surgery
Slide credits: Beat Werner, Ernst Martin
Motivation: Clinical value of Motivation: Clinical value of MR guided Focused US SurgeryMR guided Focused US Surgery
Excellent soft tissue contrast for target localizationLocal therapyNon-invasiveNon invasiveNo dose accumulation effectsNo long term toxicityImmediate result –no radiation necrosisTreatments can be repeated Closed-loop image guidance Real time monitoring
Imaging (Diagnostics): want wide field of view with uniform low acoustic intensity
Imaging <Imaging <--> Focused Ultrasound> Focused Ultrasound
HIFU (Intervention / Therapy): want small focal spot with high acoustic intensitySlide credits: Beat Werner, Ernst Martin
Phased-Array Transducer = Array of TransducersEach transducer element controlled individually Transducer phases define superposition pattern of waves -> Electronic steering
PhasedPhased--Array TransducersArray Transducers
Constructive Destructive Shift
Slide credits: Beat Werner, Ernst Martin
Beam Forming / FocusingBeam Forming / Focusing
Geometric focusing Lens focusing
Electronic beam forming Electronic steering
Slide credits: Beat Werner, Ernst Martin
PhasedPhased--Array TransducersArray TransducersLinear Array -> Plane Wave
Spherical Array -> Focus
Slide credits: Beat Werner, Ernst Martin
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PhasedPhased--Array TransducersArray Transducers
Spherical Array
Pressure Distribution Temperature Distribution
Slide credits: Beat Werner, Ernst Martin
PhasedPhased--Array TransducersArray Transducers
Spherical Array
Electronic Steering
Slide credits: Beat Werner, Ernst Martin
The effects of Ultrasound on biological tissue are a field of active researchMany effects are not well understoodEffects include:
Biological EffectsBiological Effects
th l non thermalultrasoundthermal mechanisms
non-thermal mechanisms
cavitation mechanismsnon-cavitation mechanisms
non-inertial cavitation inertial cavitationtemperature increase radiation force
energy absorption
ablation enhanced Delivery lithothripsy
Slide credits: Beat Werner, Ernst Martin
Medical applicationsMedical applications
LithotrypsyPhysiotherapyHIFU Surgery (Tissue ablation)Blood-Brain-Barrier-OpeningCell sonoporation Targeted Cell sonoporationLocal drug activationVessel occlusionThrombolysisNerve activation / blockage
gdrug delivery
Slide credits: Beat Werner, Ernst Martin
1880 1880 Piezoelectric effect (P. & J. Curie)Piezoelectric effect (P. & J. Curie)1918 1918 Sonar (Langevin)Sonar (Langevin)1927 1927 Effects on biological tissues (Looms, Wood)Effects on biological tissues (Looms, Wood)1942 1942 First HIFU lesions in animal brains (J.Lynn, T.Putnam)First HIFU lesions in animal brains (J.Lynn, T.Putnam)19501950––2000 2000 Pioneer work on (a) HIFU effects on tissue (brain Pioneer work on (a) HIFU effects on tissue (brain
tumors) and (b) LIU for soft tissue visualization (W Frytumors) and (b) LIU for soft tissue visualization (W Fry
Development of HIFU TechnologyDevelopment of HIFU Technology
tumors) and (b) LIU for soft tissue visualization (W.Fry tumors) and (b) LIU for soft tissue visualization (W.Fry & F.Fry).& F.Fry).
19511951––1960 1960 Technical development at MGH (Cosman)Technical development at MGH (Cosman)19511951––1967 1967 HIFU stereotactic neurosurgery against pain, psychoHIFU stereotactic neurosurgery against pain, psycho--
neuroses, anxiety, depression and epilepsy (Lindstrom) neuroses, anxiety, depression and epilepsy (Lindstrom) and Radiosurgery (Leksell) gamma knife and Radiosurgery (Leksell) gamma knife
Mid Mid 19701970ss First stereotactic HIFU brain surgery with open cranium First stereotactic HIFU brain surgery with open cranium (F.Fry & R.Heimburger).(F.Fry & R.Heimburger).
Slide credits: Beat Werner, Ernst Martin
W.Fry, circa 1960, with 4W.Fry, circa 1960, with 4--beam HIFU system for neurobeam HIFU system for neuro--surgery in his surgery in his bioacoustics bioacoustics laboratory.laboratory.
Development of HIFU TechnologyDevelopment of HIFU Technology
Slide credits: Beat Werner, Ernst Martin
2012.10.30.
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First US-image guided HIFU system to treat brain cancer patients.W.Fry in the 1970s
F.Fry and R.Heimburger 1974
Development of HIFU TechnologyDevelopment of HIFU Technology
Slide credits: Beat Werner, Ernst Martin
Image guidanceImage guidance
US-ImagingCheapLimited feedback
MRMRExpensiveHigh-resolution imagingClosed loop process
Slide credits: Beat Werner, Ernst Martin
Key technologies: Key technologies: 1.1. Phased array transducersPhased array transducers2.2. Acoustic field modellingAcoustic field modelling33. MR imaging for accurate real time monitoring. MR imaging for accurate real time monitoring
ll 990990 l d h d ( )l d h d ( )
Development of HIFU TechnologyDevelopment of HIFU Technology
Early Early 19901990s s Ultrasound phased arrays (Hynynen)Ultrasound phased arrays (Hynynen)MidMid––19901990s s MRI thermometry (Jolesz)MRI thermometry (Jolesz)20012001 First integrated MRgHIFU system (InSightec)First integrated MRgHIFU system (InSightec)20012001 Fibroadenoma of Breast and Uterine FibroidsFibroadenoma of Breast and Uterine Fibroids20042004 FDA approval for Uterine Fibroid ApplicationFDA approval for Uterine Fibroid Application……20082008 Functional NeurosurgeryFunctional Neurosurgery
Slide credits: Beat Werner, Ernst Martin
HIFU Surgery for Uterine FibroidsHIFU Surgery for Uterine Fibroids
Slide credits: Beat Werner, Ernst Martin
InSightec Exablate InSightec Exablate 20002000
InSightec Haifa, IsraelTechnology originally GE
FDA approvedFirst & only worldwide
GE MR-ScannersCa. 200 systems installed
Slide credits: Beat Werner, Ernst Martin
Treatment process for Treatment process for Uterine FibroidsUterine Fibroids
benign (non-cancerous) tumors most common pelvic tumors in women20-40% in women of reproductive age Classical procedure: Hysterectomy
Slide credits: Beat Werner, Ernst Martin
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Patient interfacePatient interfaceMR-coil
Patient
Transducer
Ultrasound
Coupling Target
Slide credits: Beat Werner, Ernst Martin
TransducerTransducer16 element array
vertical electronic steeringfocal depth 12cm – 19cm
Mechanical positioning4 axesComputer controlled
MR-compatibleCeramic step motors
Slide credits: Beat Werner, Ernst Martin
Safety checksSafety checks
Air bubbles?Metallic clips?Scars?Bowels?Bl dd ?Bladder?Nerves?
Slide credits: Beat Werner, Ernst Martin
Treatment planningTreatment planning
Delineate region of treatmentSystem createstreatment planp(array of sonicationsto be done)Plan can be changed manuallyby operator
Slide credits: Beat Werner, Ernst Martin
RealReal--time temperature monitoringtime temperature monitoringMR-ThermometryProton resonance frequency shift ~ TemperaturePhase difference ~ Temperature difference
1.1 seconds 4.5 seconds 7.9 seconds 11.3 seconds
Slide credits: Beat Werner, Ernst Martin
Treatment assessmentTreatment assessment
Very good agreement
Blue dots = Cell ablation as calculated by thermal dose
Treatment control by contrast enhanced MR
Slide credits: Beat Werner, Ernst Martin
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MRgFUS = Magnetic Resonance guidedFocused UltraSound
Closed loop controlClosed loop control
Planing Safetychecks
Real-TimeMonitoring
Assement
Closed LoopSlide credits: Beat Werner, Ernst Martin Slide credits: Beat Werner, Ernst Martin
Clinical applications and researchClinical applications and research
Brain Tumors
Breast Cancer
Brain Functional
Liver TumorsUterine Fibroids
Prostate
Bone Tumors
Slide credits: Beat Werner, Ernst Martin
T1w contrast enhanced image before treatment
T2w planning
Uterine fibroidsUterine fibroids
Courtesy of Sheba Medical Center, Tel Aviv, Israel
T1w contrast enhanced image immediately post-treatment
T2w planning image with dose overlay
Slide credits: Beat Werner, Ernst Martin
Treatment effects in canine prostate
Prostate Prostate
Thermal dose estimate
T1w contrast enhanced image imaging
TTC stained tissue
Courtesy InSightec Slide credits: Beat Werner, Ernst Martin
Liver tumors Liver tumors
Courtesy of St. Mary’s Hospital, London, UK
Sagittal, Axial and coronal post treatment dose maps (in blue) and post treatment T1W+C
Slide credits: Beat Werner, Ernst Martin
2012.10.30.
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IDECaution-Investigational Device
Limited by United States Law to Investigational Use.
Breast Cancer Breast Cancer
Pre treatment T1w+C MIP image
2 weeks post treatment T1w+C MIP image
Courtesy of Breastopia Namba Hospital, Japan Slide credits: Beat Werner, Ernst Martin
10.0Screening
Bone tumors (Pain palliation) Bone tumors (Pain palliation)
1.5
7
0
1.5
00.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
0 10 20 30 40 50 60 70 80 90
Days post treatment
VAS
scor
e
ScreeningAverage
1 Month Follow Up
3 Months Follow Up
Courtesy InSightec Slide credits: Beat Werner, Ernst Martin
NonNon--invasive neuroinvasive neuro--surgery surgery in the MRin the MR--suitesuite
Skull: Anisotropic AberrationSkull: Anisotropic Aberration
Focused waves are distrorted after skull
Courtesy of ESPCI, Paris, F
Focused waves … … are distrorted after skull
Phase corrected waves … … are refocused after skull
InSightec ExAblate InSightec ExAblate 40004000FrontendAmplifier
3D-Positioner
InSightec ExAblate 4000 / 3.0T GE Signa HDxHemispheric 1024-element phased-array transducer (650kHz)
Transducer
(650kHz)Stereotactic frameWater cooling of skull surfaceCT-based acoustic modelingPRS-ThermometryInstallation June 2006
Degassed water used for acoustic coupling & coolingStereotactic frame for patient immobillization
PatientPatient InterfaceInterface
Sealing membraneSealing membraneTransducerTransducer
WaterWater Stereotactic frameStereotactic frame
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MRIMRI--HIFU ConsoleHIFU Console Clinical phase I studyClinical phase I studyCentro-Lateral Thalamotomy against chronic, therapy resistant, neuropathic pain
Established procedure: RF-ablationo minimally invasiveo n (pain) > 100 interventions
New procedure: Non-invasive TcMRgHIFUo Minimize intervention risks (Collateral
damage, infections, bleeding, tissue shift)
o Enhanced efficacy (no trajectory restrictions, anatomically adapted volume ablation, image guidance)
o Outpatient process
Bildfolge der Behandlung (sonication procedure)Bildfolge der Behandlung (sonication procedure)
X+20’: Stereotactic frame
Bildfolge der Behandlung (sonication procedure)Bildfolge der Behandlung (sonication procedure)
X+50: Positioning
X+1h20: Imaging X+3h: Verification sonications
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X+3h: Verification sonications X+4h: Ablation
Dosemap Dosemap 17 17 CEM CEM 4343°°CC
Dosemap Dosemap 240 240 CEM CEM 4343°°CC
X+6h: End of treatment
X+7h: Happy End
Patient #Patient #44immediately afterimmediately afterthe interventionthe intervention
Patient #Patient #2248 48 h afterh afterthe interventionthe intervention
Trigeminal neuralgiaTrigeminal neuralgia Chronic lumbar pain syndrome Chronic lumbar pain syndrome following disc hernia op Lfollowing disc hernia op L44/L/L5 5
Slide credits: Beat Werner, Ernst Martin
2012.10.30.
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Patient #Patient #44immediately afterimmediately afterthe interventionthe intervention
Patient #Patient #2248 48 h afterh afterthe interventionthe intervention
TT11WI + GdWI + Gd TT11WI + GdWI + Gd
Patient #Patient #44immediately afterimmediately afterthe interventionthe intervention
Patient #Patient #2248 48 h afterh afterthe interventionthe intervention
DTIDTI DTIDTI
TumorvolumeTumorvolume
HIFUHIFU--AblationAblation
Combined Tumor therapy:Combined Tumor therapy:HIFUHIFU--Ablation & LIFU BBBDAblation & LIFU BBBD
McDannold et al. McDannold et al. Neurosurgery 2010 Neurosurgery 2010
BBBBBB--Opening with Low Intensity Opening with Low Intensity Focused Ultrasound (LIFU)Focused Ultrasound (LIFU)and Adjuvant Chemotherapyand Adjuvant Chemotherapy
Slide credits: Beat Werner, Ernst Martin
Blood Brain BarrierBlood Brain BarrierBrain protected by BBB:
Structural and functional barrier in the vessel wallsControls transport and diffusion from the vasculature to the central nervous system Severely limits ability to deliver drugs to the brain
Slide credits: Beat Werner, Ernst Martin
Reversible BBBReversible BBB--Disruption using Disruption using FUS and Microbubble UCAFUS and Microbubble UCA
MicrobubblesPhospholipid / Hexafluorid (2-4um)Commercial CE / FDA
Lipid monolayer
Reversible opening of BBB byCavitationShear stress (Acoustic streaming, radiation force, ...)Slide credits: Beat Werner, Ernst Martin
TcMRgFUS BBBTcMRgFUS BBB--DisruptionDisruptionUS freq. 220kHz – 1MHzAcc.Power < 1WSonication 10 – 200sDuty cycle 1%Tail vein injection
Inj.
Dru
g
Inj. Micro bubbles
MR
I
His
to
MR
I
Low Intensity US (Bursts of 10ms/1000ms)
MR-contrast agent / drugMicro bubbles
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TcMRgFUS BBBTcMRgFUS BBB--DisruptionDisruption
P iti MR C il
MR-Scanner: GE 3.0TTransducer: Imasonic (Aperture 8cm, f# 0.8)Microbubbles: Bracco
WatertankTransducer
Positioner MR-Coil
Mouse
TcMRgFUS BBBTcMRgFUS BBB--DisruptionDisruptionDuration
several hours
ApplicationNeuro-PhamacologyPhamacologyTumorsAlzheimerNeuron regeneration
Targeted Drug DeliveryTargeted Drug DeliveryTargeted Drug Delivery
Bubble constructsAdd specificityAdd payloadRemote activation
Targeted Drug DeliveryTargeted Drug DeliveryTarget specificCarries contrast agents (Dye, fluorescent, magnetic, ...)Carries drugsRemote activation
Targeted Drug DeliveryTargeted Drug DeliveryReleasing drug by Ultrasound
HeatCavitation
Gene DeliveryGene Delivery
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Gene Activation: hspGene Activation: hsp--8080
Slide credits: Beat Werner, Ernst Martin
SummarySummaryImage guided FUS is a new modality for non-invasive interventions deep in soft tissueThermal ablation clinically establishedIntense research on treatment strategies based on mechanical effectsVery promising results in animal models for targetedVery promising results in animal models for targeted drug delivery based on transient BBBD / SonoporationIntense research on development of nano-constructs for imaging and therapy Clinical studies to come soon
Slide credits: Beat Werner, Ernst Martin
Targeted Drug Delivery
In-vitro T2W MRI before [l] and after[r] sonication
Clot Lyses for StrokeNeurological Disorders
OutlookOutlook
Slide credits: Beat Werner, Ernst Martin
Thank you !
Slide credits: Beat Werner, Ernst Martin
Thank you for your attention!
Presentation credits:
Dr. András Jakab, M.D. Ph.D.Dr. Ervin Berényi, M.D. Ph.D.Dr. Miklós Emri (Nuclear Medicine Institute, UD)Prof. Ernst Martin – Uni. Zürich (Focused Ultrasound)Beat Werner – Uni. Zürich (Focused Ultrasound)