Dieter Meier

Institute for Biomedical Engineering

Future Trends in Clinical Diagnostics with Magnetic

Resonance

SNHTA Bern 12. November 2003

Topics

• The “International Competence and Reference Center for MRI Methodology”

• Advantages of MRI

• Functional Information

• Discussion and Outlook

Swiss Federal Institute of Technology (ETH)• natural and technical sciences • 83 institutes and laboratories, > 11’000 students

University Zurich• all major scientific disciplines (7 faculties)• > 20'000 students

University Hospital Zurich• education site for medical faculty• 130’000 ambulant, 35’000 stationary patients a

year, 960 beds, 5500 employees

Scientific Environment

International Relations• Excellent scientific and industrial relations

Biomechanics Biomedical Electronics

Biomechanics BioelectronicsMedical Optics

P. Niederer R. Müller

D-ITET D-ITET D-MAVT

Biomaterials Tissue Engineering

N.N.

International Zurich Magnetic Resonance Education Center

Biophysics MR Competence CenterMRI / MRS

P. Bösiger

Med. FacultyD-ELEK

MRITechnology

K.P. Prüssmann

D-ELEK

MRI inNeurosci.

N.N.

Med. Fak.

International Zurich Magnetic Resonance Education Center

Institute for Biomedical Engineering

Technical Director: Dieter Meier

Partners at University

• Dept. Radiology:Neuroradiology, Radiology, Nuclear Medicine

• Dept. Internal Medicine:Cardiology , Angiology, Gastroenterology

• Neuroscience:Neurology, Psychiatry, Psychology

Competence Center CCMRI

International Scientific Relations

Inst. for Biomedical EngineeringDivision Biophysics (MRI)

Univ. and ETH ZurichP. Boesiger, K.P. Pruessmann

Johns Hopkins Univ. Baltimore, MD P.van Zijl, X. GolayM. Stuber

Stanford University Stanford, CAC. Bammer

King’s College, London, UKS. Kozerke

German Heart InstituteBerlin, GermanyE. FleckE. Nagel, I. Paetsch

Univ. of CaliforniaSan Francisco, CAC. HigginsO.M. Weber

Harvard Med. School Boston, MAW. ManningR. Botnar

Univ. Hospital AarhusAarhus, Denmark E. Pedersen

Univ. of Minnesota Minneapolis, MN K. UgurbilR. Grütter

Technical Univ. Graz Graz, AustriaK. Perktold

Industrial Relations

Inst. for Biomedical EngineeringDivision Biophysics (MRI)

Univ. and ETH Zurich

Medtronic andBakken ResearchCenter Tolochenaz VD and Maastricht NL

Guerbet Pharmaceuticals Zurich und Paris F

Bracco Imaging Milano I

Roche Pharmaceuticals Basel

Philips Medical Systems Philips Research LaboratoryPhilips Med. Systems Schweiz AGBest NL, Hamburg DE, Zurich CH

Bitplane AGZurich

GyroTools GmbHZurich

ETH and University of Zurich

Philips Medical Systems

University Hospital of Zurich

Project related funding:

SEP; EUREKA / KTI; SNF; Dt. StifterverbandFurther partners from industry and science

Funding

Development of new and dedicated MRI techniques for applications in diagnostics and

therapy as well as in basic medical and clinical research.

Application of these procedures in medical research in collaboration with highly qualified local and international scientific and medical

research groups.

Mission

• MRI Scanner Philips Gyroscan Intera 1.5 Tesla Worldwide fastest MRI commercially available scanner, equipped with parallel imaging technique SENSE

• MRI Scanner Philips Gyroscan Intera 3.0 Tesla Worldwide first 3 T scanner with compact magnet; presently being further developed in collaboration with IBT

Equipment

• High soft tissue contrast

• Contrast adaption

• High spatial resolution

• Arbitrary slice direction

• No known hazards

Advantages of MRI

• Functional information

MRI of the Brain

• anatomy

• angiography

• perfusion, fMRI

• diffusion

• metabolite imaging

Magnetic Resonance Imaging

T2-TSE512 matrix, 2 mm

Sagital Head Images 3Tesla

y

z2D SENSEScan time 26 s

y

z

NONSENSEScan time 106 s

M. Weiger, K. Pruessmann, IBTZ

3D Imaging with 2D SENSE

3D, Inflow MRA

3DI/TONETR 28ms, TE 4.6ms, Flip 20o

scan time 7.30 min100 slices, thickness 1.0/-0.5 matrix 1024

IBTZ, Neuroradiology USZ

High Resolution MRA 3Tesla

High Resolution MRA 3Tesla

Venogram

High Resolution MRA 3Tesla

Arteriovenous Malformation (AVM)

3.0 T1.5 T

Inflow Angiography 1.5 vs. 3.0T

M. Huber, S. Kozerke, IBTZ

NONSENSE R = 2.0 R = 3.0

3D FFE, 3 TeslaTE=3.8ms, TR=19ms

Flip angle=10o

velocity encod = 50cm/s (RL-AP-FH )

slice thickn=0.5 mm120 slices

FOV=190mmmatrix=163x256

SENSE Phase Contrast MRA @ 3T

Decrease of relative concentration of desoxygenated blood, acting as a contrast agent

Increase of T2*, increase of signal amplitude

Activation of brain area:

Raise of metabolic activity

Raise of blood flow

Raise of concentration of oxygenated blood

Brain Activation: BOLD fMRI

Activation of Neurons

Activation of Motor Cortex

C. Schmidt, K. Pruessmann, IBTZ

high-res SENSE sshEPIlow-res conventional sshEPI

stimulation: bilateral opposite finger tapping, 4 x 20s on/off

SENSE: fMRI 3T

Visual Stimulation

4.0

0

A [%]1 2 3

4 5 6

Courtesy: S. Sunaert, Leuven

BOLD fMRI 1.5 vs 3T: Auditory Stimulation

1.5 T

3.0 T

PDw/TSETR 3500 TE 16

T2w/TSETR 3500 TE 110

T1w/IR-TSETR 1400 TE 12 TI 700

T1w/IR-TSETR 1400 TE 12 TI 700

after IV Gd-DOTA

MRI and Perfusion

Direction field mapFractional anisotropy (ordering of fibers)

T. Jaerman, IBTZ, Neurorad USZ

SENSE: Diffusion Tensor Imaging

Diffusion Tensor Imaging

forceps minor

forceps major

external capsule

optic radiation

ant. limb of internal capsule

post. limb of internal capsule(corticospinal tracts)

Characterizing the ORIENTATION of the ellipsoid

Talk T. Jaermann et al, today, 15.00 pm

3T SENSE-DTI: Tracking Results

Functionality:• oblique rotations• introduce new slices• slice shifting• zooming

T. Jaermann, IBTZ, Neurorad USZ Meiyappan Solaiyappan,

Johns Hopkins University

3T SENSE-DTI: White Matter Segmentation

radiation of corpus callosum

volume: 200x200x108mm3

anatomy: 256x256x180SENSE-DWIs: 128x128x36

T. Jaermann, IBTZ, Neurorad USZ

Scan time: 1:04 min, VOI 45 cc

4.0 1.03.0 2.0

Chemical shift (ppm)

NAA

CrCho

MI NAA+Glx

Cr

Glx Lac

Metabolites in 1H MR Spectroscopy

NAA, (P)Cr

NAA: Neuronal marker (neuronal density); concentration correlates with neuronal function

: Tumor, Stroke, Epilepsy, Hyp-/Anoxia, Inflammation, Dementia, Trauma

: Brain Development and Maturation

Cr (PCr): Energy buffer H + PCr + ADP ATP + Cr Energy shuttle: “Energy transport”

The Cr peak is often stable and used as internal reference

: Acute and subacute stroke, brain tumor, brain metastasis, abscesses, inborn errors of Cr synthesis

Choline Containing Compounds = Cho,

Myo-InositolCho: Involved in pathways of phospholipid synthesis

and degradation. => reflecting membrane synthesis and degradation

: Brain Tumors, MS-Plaques, Stroke, Inflammation, White Matter Diseases

: Hepatic Encephalopathy, Necrosis

: Alzheimers’ disease, renal failure, Diabetes mellitus

: Abscesses, Hepatic encephalopathy, tumors, stroke

MI: Astrocyte marker, second messenger

Glutamate and Glutamine = Glx; Lactate

Glutamate: excitatory neurotransmitter, substrate for Krebs-Cycle,Protein Biosynthesis

Glutamine: Substrate for neurotransmitter synthesis (GABA, Glutamate), Protein Biosynthesis

Glx: Stroke, hyp-/anoxia, epilepsy, neurodegenerative diseases, hepatic encephalopathy

Lac: Sign of impaired energy metabolism, impaired oxygen delivery (anaerobic glycolysis).

: Stroke, An-/Hypoxia, mitochondrial diseases, tumors,epileptic discharges, abscesses/infection, prolonged neuronal

activation

Hardly detectable in normal brain tissue (~1 mM)

Single Voxel Spectroscopy @ 3T

TE = 288 ms

VOI = 20 x 20 x 20 mm3

Cerebellum (AMS study)

U. Dydak, IBTZ

NAA

CrCho

Lactate

Mi

before treatment

after treatment

4 3 2 1

NAACr

Cho

Lactate

4 3 2 1

NAACr

Cho

Lactate

Courtesy: Dept. of Radiology, University of Bonn, GermanyCourtesy: Dept. of Radiology, University of Bonn, Germany

Scan time: 4.16 min (35cc)

SVS: tumor treatment

MiMi

Subacute

Acute

Normal

Normal

Courtesy: Tim Roberts, Toronto

FLAIR - ROIs

Cerebral Infarction

Alzheimer’s Disease

The increase () of MI seems to differentiate Alzheimer’s Disease from other forms of dementia

Whole brain TSI

6 slices, 20x20x6 isotropic voxel (1.33ml), = 8.8 Hz

Cho

Cr

NAA

TSI6: Meningioma

NAA

Cho

Single slice, 32 x 32 matrix, TR=2000 ms, 0.8 ml voxel => 5:12 min

U. Dydak, IBTZ

Visualization of 3D MRSI Data

visualization software: IMARIS by Bitplane, Switzerland

NAA maps

3D SENSE-SI

Talk U. Dydak et al, Friday, 10.45 am

SENSE Extremity Imaging @ 3T

3D T1w FFE3.0 TeslaSENSE factor 2150 microns in-plane1mm slice thicknessScantime 8 min.

K.P. Pruessmann, IBTZ D. Weishaupt, Radiology, USZ

Scan time: 4 s / 3D frame

SENSE R=3.0

1.6 × 2.1 × 2.4 mm3

Time-Resolved 3D CE-MRA

SENSE Angiography

M. Weiger, K. Pruessmann, IBTZ

Time-Resolved 3D CE-MRA

ibt / mw kp

4 s / 3D frame1.6 × 2.1 × 2.4 mm3

SENSE R=3.0

SENSE Angiography

Motion Artefact Reduction

Standard Breathhold: 24 sec

SENSE R = 2.0Breathhold: 12 sec

Dep. of Veterans Affairs, Durham

Problem:

• Morphological imaging for many problems insufficient

• Functional diagnostics on a strongly moving organ (heart motion, breathing) at rest and under stress needed.

“One stop shop”.

Cardiovascular MRI

• Coronary artery angiography

• Viability and perfusion

• Wall motion, ejection fraction

• Flow (coronary flow reserve, valvular flow, regurgitation)

Heart functions:

Cardiovascular MRI

Ischemic Cascade

Hypoperfusion

Metabolic changes

Diastolic dysfunction

Regional systolic dysfunction

ECGchanges

Chestpain

Time

spectroscopy

coronary

MRA, flow,

perfusion

motion

viability

Frank H. Netter

Balanced FFE, SENSE R=1.5, 1 breathhold

Courtesy R. Springorum, PMS

MitralValve

TricuspidValve

High Contrast Cardiac Imaging

Chronic Myocardial Injury

S. Flamm, Texas Heart Institute

M. Schaer, S. Kozerke, K.P. Pruessmann, IBTZ

TR = 3.8 ms, Matrix = 213 x 160

Slice = 8 mm, 20 phases

No SENSE15 sec

SENSE 2 x 7 sec

SENSE 3 x 5 sec

Balanced FFE @ 3T

8 k-t SENSE5 coils

8 k-t BLAST1 coil

J. Tsao, K.P. Pruessmann, IBTZ

Real-time SSFP with k-t

No SENSE 9 sec BH, 25 fphb

SENSE R=2 5 sec BH, 25 fphb

SENSE R=2 9 sec BH, 50 fphb

Courtesy M. Kouwenhoven, PMS

fphb = frames per heart beat

Balanced FFE, breathhold

SENSE Cardiac Imaging

ibt

35 ms / frameResol 2.5 mmSENSE R=2.7

Rest Stress 155 bpm

SENSE Real Time Cardiac Imaging

Coronary Arteries

0.75 x 1.0 x 1.5 mm3 0.75 x 1.0 x 0.75 mm3

No SENSE, 20 slices SENSE 2 x, 40 slices

RCA

Coronary Angiography @ 3T

Talk M.E. Huber et al, Friday, 11.30 am

Left coronary arteries;intravascular contrast agent

Right coronary artery;without contrast agent

IBT Zurich / BIDMC Boston / DHZ Berlin / Bracco Milan

Coronary Artery Angiography

• 2D Selective real-time NAV• Free-breathing • VECG• 3D TFE• 600m in-plane resolution• 3mm slice thickness

LAD

Ao

LCX

M. Stuber, BIDMC Boston

Coronary Angiography 3T

IBT Zurich / BIDMC Boston /

A

FED

CB

Coronary Artery Angiography

Myocardial Tagging• 45 heart phases with interval of 13ms• 8mm grid width, 2.8mm x 2.8mm resolution • spiral readout: 12 spirals, acquisition window 5ms

S. Ryf, M. Spiegel, IBTZM. Stuber, BIDMC

Heart Wall Motion

basal level apikal level

Stuber M. et al, Circulation 100, 361, 1999

Heart Wall Motion

anatomy flow

Regurgitation

S. Kozerke, IBTZ

Heart Valve Function : STrack

Heart ValveProsthesis:Particle Tracing

Flow Imaging: STrack

S. Kozerke, IBTZ

Outlook and Discussions

• Higher field strength

• Faster techniques

• Cardiac functions

• Brain organization

And the costs ???

New techniques will be more expensive!BUT:

Modern technique allows for a much better diagnosis!

It is not the medical equipment, which will influence the cost!

The medical staff has to choose the appropriate methods for an

optimal diagnosis and to propose the best therapy or surgery!

• Doctoral StudentsChristof Baltes, el. eng.

Holger Eggers, el. eng.

Michael Huber, el. eng.

Thomas Jaermann, phys.

Thomas Lange, phys.

Roger Luechinger, phys.

Markus Oelhafen, el. eng.

Salome Ryf, phys.

Michael Schär, phys.

Conny Schmidt, phys.

Rolf Schulte, phys.

Andreas Steingoetter, el. eng

Reto Treier, phys.

Florian Wiesinger, phys.

• ChairmenPeter Boesiger, PhD

Klaas Pruessmann, PhD

• Research AssistantsUlrike Dydak, PhD

Roger Luechinger, PhD

Jeff Tsao, PhD

Andreas Trabesinger, PhD

Gérard Crelier, PhD

• Project LeadersDieter Meier, PhD

Sebastian Kozerke, PhD

Markus Scheidegger, PhD

Present Team