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Handout 1

Answers for life.Unrestricted © Siemens AG 2014 All rights reserved.

Brian M. Dale, PhD, MBA, MR R&D Collaborations, Siemens Healthcare, USA

Quantitative MR Imaging in Routine Practice

Unrestricted © Siemens AG 2014 All rights reserved.

Magnetic Resonance

Brian M. Dale, PhD MBA

PhD in Biomedical Engineering – 2004• Case Western Reserve University• Cleveland, OH• IDEA programming• Optimal design

Zone Research Manager • Siemens Healthcare• Southeast Zone• Cary, NC• Abdominal MRI at 3 T


Magnetic Resonance

Bands of America, Grand Nationals, Indianapolis 2014

• My daughter is in marching band• Panther Creek High School, Cary, NC• Made Semifinals, competing this afternoon!

• Lucky chance to combine business and pleasure


Magnetic ResonanceMagnetic Resonance

What is Quantitative MRI?

OpposedPhase

In Phase

These data were acquired with the equivalent WIPs.

Courtesy of Dr. Puneet Sharma and Dr. Diego Martin, University of Arizona, AZ, USA

*The product is currently under development; is not for sale in the U.S. and other countries. Its future availability cannot be guaranteed.

Fat Percentage

21.3 ± 2.9 %

The process of extracting meaningful numbers from MR Images


Magnetic Resonance

Biomarkers• Accuracy• Reproducibility• Referring physician demand• A range of applications and techniques: clinical to pure research

Large working groups• QIBA: Quantitative Imaging Biomarker Alliance (RSNA)• Standards in Quantitative MR (ISMRM)• Quantitative Imaging Network (NCI)• BIRN: Bioinformatics Research Network (NIH)• ADNI: Alzheimer's Disease Neuroimaging Initiative

Why care about quantitative MR?


Magnetic Resonance

1 Pennell Circulation-128:228

• Early identification of cardiac iron overload in Thalassemia Major

• Intervention with suitable treatment, before onset of symptomatic Heart Failure.

Recent improvements in life expectancy for TM patients in the United Kingdom can be explained by the increasing availability of T2* CMR and earlier escalation of therapy.

ExampleCardiac T2* <10 ms is the most important predictor of development of heart failure.1

Handout 2


Magnetic Resonance

Increasing demand for biopsies cannot be fulfilled

Radiologists say:

We cannot biopsy all these

patients.

Need to monitor this patient group over time.

LiverFailure

Steatosis

Fibrosis

Inflammation / Necrosis

Cirrhosis

HCC

Haemotomachrosis


Magnetic Resonance

Types of quantitative MR

• Anatomical • Length• Volume

• Tissue Characterization• Perfusion• Fat Percentage• Chemical Concentration• Stiffness

• Relaxation• T1• T2/T2*

• Motion• Velocity• Diffusion• Strain


Magnetic Resonance

Structure of Remainder of Talk

• For Each Type of Quantitative Imaging:

• Physical Basis

• Clinical Importance

• Workflow and Patient Management

• Quality Assurance Requirements

• Diffusion

• Perfusion

• Motion

• Elastography

• Relaxometery

• Spectroscopy

• Fat/Iron Quantification


Magnetic Resonance

Diffusion Weighted Imaging

Diffusion weighted imaging (DWI) measures random thermal motion of molecules in any fluid


Magnetic Resonance

Diffusion is limited in highly ordered structures such as white matter


Magnetic Resonance

ADC and Diffusion Tensor Imaging

Mori and Barker Med. Anat. 257:102–109, 1999

Handout 3



MR Men’s HealthReadout Segmented Diffusion

Apparent Diffusion Coefficient(ADC) as a marker for celldensity:

• tumor tissue typically has lowADC

• normal glandular tissuetypically has high ADC


Magnetic Resonance

3D fiber orientation

AP

HF

RL



64 Channel Diffusion ImagingPush the limits with diffusion spectrum imaging (DSI)*

Use up to 514 diffusiondirections for ultra-sensitive diffusionspectrum imaging

Image rendering courtesy of TrackVis

514Directions

withDSI

* May not be commercially available in all countries. Future availability cannot be guaranteed in all countries Unrestricted © Siemens AG 2014 All rights reserved.

Magnetic ResonanceMasood. PhD Thesis, Imperial College London, 2003.

Measuring myocardial fiber orientation

Fiber tracking


Magnetic Resonance

Diffusion Workflow

• Qualitative Diffusion Weighted Imaging• ~5 min

• Diffusion Tensor Trace ADC• No additional time required (~5 min)

• Fractional Anisotropy• ~9 min

• Diffusion Tractography• ~6-15 min• Post processing requires user input

• Per-patient QA Processes• Good shimming required – EPI artifacts• Motion sensitive – patient coopearation• Internal Reference

• Most common clinical approach• No additional scanning required• “Relative quantification”


Magnetic Resonance

Other Diffusion Quality Assurance

• Other QA Processes• Reference phantom

• QIBA/NIST• Not yet commonly used

Dr. Michael Boss, QIBA/NIST

Handout 4


Magnetic Resonance

Quantitative Perfusion techniques

ASL • EPI, endogenous contrast• relCBF

T2* DSC perfusion• EPI with Gad injection (bolus decreases signal)• relCBF, relCBV, relMTT, TTP• T1 and LocalAIF leakage corrections for better quantification

T1 DCE perfusion (bolus increases signal)• fl3d with Gad injection• Wash-in wash-out curve classification of breast lesions

• Benign or malignant • Pharmacokinetic modeling

• Ktrans (transfer constant), etc.• Nonlinear fitting, requires a T1 map or a guess

No BBB disruption

leak

Acquired image


Magnetic Resonance

1. Tag inflowing blood by magnetic inversion

2. Acquire the tag image3. Repeat the experiment without the tag4. Acquire a control image5. Subtract image to get an image

proportional to blood flow6. Theory relates the ASL signal to

absolute blood flow

Magnetically tag hydrogen atoms as they course through the blood and image them as they course through the slice of interest.

Arterial spin labelling



ASL 3DAssessment of perfusion following stroke

The Prince Charles Hospital, Brisbane, AustraliaDWI, b1000 and ADC,TA 2:16

TSE T2 DarkFluid, TA 2:16 TOF, TA 5:00

ASL 3D, TA 3:16, 40slices, SL 3 mm



ASL 2D Assessment of perfusion in tumors

T2 TSE T2 DarkFluid

T1 FLASH, pre and post contrast

DWI, b1000, ADC and Colored FA

ASL 2D, relCBF



Neuro PerfusionFast assessment of CE perfusion with inline technology

• Visualization of temporal variations in dynamic susceptibility

• Provides signal intensity curves of the temporal variations in a user-defined region of interest

• Outputs parametric images for calculated parameters to support the diagnostic process:• TTP delay in contrast bolus arrival• relCBV relative Cerebral Blood Volume• relMTT relative Mean Transit Time• relCBF relative Cerebral Blood Flow

One-click Arterial Input Function selection and automatic parameter-map calculation and loading (e.g. relMTT and relCBF)



MR Men’s HealthAnalysis of prostate perfusion

Tumor tissue tends to exhibit fast wash-in and wash-out.

Analysis requires:

• Motion correction

• Alignment of pre-contrast and morphology to dynamic reference

• Calculation of the Tofts model (ktrans, kep, Ve and AUC)

The parametric image overlay showsspatial distribution of perfusioncharacteristics

University Medical Centre St. Radboud, Nijmegen, Netherlands

* May not be commercially available in all countries, future availability cannot be guaranteed.

Handout 5


Magnetic Resonance

Perfusion Workflow and QA Issues

Quality Assurance

• Changes in signal• Motion is critical• Look for artifact

• Lack of good phantoms• Most perfusion measures are relative• Simple “reality check”

Workflow

• Per Patient• Often source images used qualitatively

• High temporal, low spatial resolution• Good instructions, cooperation• DSC and DCE

• Contrast-based• First pass• No second chance


Magnetic Resonance

Magnitude Phase

Phase Subtraction Reference

Velocitysensitised

Motion Quantification: Phase contrast velocity


Magnetic Resonance

165 ms55 ms 110 ms 220 ms 275 ms 330 ms 385 ms 440 ms

-5

0

5

1 0

1 5

2 0

2 5

3 0

3 5

0 2 0 0 4 0 0 6 0 0 8 0 0 (m s )

A A

D A

Measuring blood flow

Page 30Restricted © Siemens AG 2014 All rights reserved.

Quantitative Flow Measurements

4D Flow* Real Time Flow*

Aortic Valve Stenosis4D GRE

Aortic Valve StenosisReal Time Flow, EPI

*This product is currently under development; is not for sale in the U.S and other countries. It‘s future availability cannot be guaranteed.

Courtesy: Dr. Orlando SimonettiThe Ohio State University, Columbus, OH

Courtesy: Prof. DacherCHU Rouen, France


Magnetic Resonance

Quantitative tagged image analysis


Magnetic Resonance

Strain Analysis

Lima J. et al. American Journal of Physiology, 1995; 268(3, part 2): H1304-H1312.

Handout 6


Magnetic Resonance

Cine DENSE

1. Kim et al. Radiology 2004;230:862–871.

Multiple acquisitions throughout the cardiac cycle


Magnetic Resonance

DENSE Imaging

Displacement Encoding with Stimulated Echoes (DENSE): Encode the tissue displacement into the phase of the stimulated echo

+ =

Displacement map of left ventricle at end systoleX-encoded phase image Y-encoded phase image

1. Aletras et al. JMR 1999; 137(1):247-252.

2. Kim et al. Radiology 2004;230:862-871.


Magnetic Resonance

Motion Workflow and QA Issues

Quality Assurance

• Measure motion• Robust to motion

• Phase wrapping (phase contrast, DENSE)• Exceed allowable range• Phase unwrapping artifacts

• T1 decay (tagging)• Errors in late phases

• Phantoms exist• Expensive, bulky, inaccurate• Seldom used

Workflow

• Not useful for qualitative read• Increase exam duration up to 10 min• Cost benefit trade off

• Significant post processing effort (tagging, DENSE)• Not supplied by MR vendors• Data transfer issues


Magnetic Resonance

MR Elastography** for Abdominal Imaging

MR Elastography package

• Hardware and Software:• Active and passive drivers*• One sequence and protocols • Sequence: 2D gradient-echo

with motion-encoding gradients(MEG)

• Siemens features:• Inline Elastogram• Magnitude, Stiffness, Stiffness with Mask and

Wave images are ready to read• Reading of stiffness can be done with the cursor• Free windowing of stiffness maps

* Is a product of Resoundant Inc.

Active Driver

MR Elastography examination set-up

Passive Driver and Body 18

*The products/features (here mentioned) are not commercially available in all countries. Due to regulatoryreasons their future availability cannot be guaranteed.



MR Elastography* – Liver Fibrosis

Left Wave image• Obtained by the application of

mechanical waves• While measuring with a

motion-sensitive MR sequence

RightElastogram• Calculated from the wave

image• Providing data about tissue

stiffness

Northwestern Memorial Hospital Outpatient Imaging Center, Chicago, IL, U.S.The products/features (here mentioned) are not commercially available in all countries. Due to regulatoryreasons their future availability cannot be guaranteed.

Rel

ativ

e S

hea

r S

tiff

nes

s 8

04

* Unrestricted © Siemens AG 2014 All rights reserved.

Magnetic Resonance

Elastography Workflow and QA Issues

Quality Assurance

• Confidence maps• Show regions of poor fit• Usually only part of liver• Does not show cause

• Poor passive driver placement

• Phantoms do exist• Inexpensive to produce• Stiffen over time• Used by manufacturers/researchers only

Workflow

• Images not used clinically• Additional exam time, but short

• Passive driver• Additional device to place

• Requires more setup time• Positioning is critical

• Increases distance from coil• Reduced SNR

• Two approaches• Place at beginning – SNR hit on clinical images• Place at end – pull patient out and in again

Handout 7


Magnetic Resonance

Quantitative Myocardial Parametric Mapping – Why?

Motivations for quantification:

• Reproducible measure.

• Objective, user independent.

Clinical utility:

• Can be used to detect cardiac and systemic diseases (T1, T2, T2*).

• Niche application in diffuse diseases (T1), iron deposition (T2*).

• Identification of reversible myocardial injury and prediction of functional recovery in acute MI (T1, T2).



Cardiac T1 Mapping* - Technical Details

1 Xue et al. MRM 2013 .

* This feature is currently under development; it is not for sale in the U.S. and other countries. Its future availability cannot be guaranteed.

IR prepared single shot

trueFISP images

Motion

correction1

3 parameter PSIR

fitting1

Inline T1 mapgeneration

0 500 1000 1500 2000 2500 3000 3500 4000-400

-300

-200

-100

0

100

200

300

400

TI (ms)

Inte

nsity

ECG

Readout

TD

TI

1

IR prep

TI

2

TI3 TI

4

TI5 TI6 TI7 TI8

MZ

1

0

-1 TI

A

TI

B

IR prep 1

IR prep 2

Images

Developed in collaboration with Drs. Arai and Kellman, NHLBI, Bethesda, MD, USA


Magnetic Resonance

T1 mapping megastudies

UK Biobank: 100,000 healthy volunteersNative T1

Canadian: 9,700 healthy volunteersNative T1 all+ ECV: 2,200

HCMR: 2,750 HCM patientsNative T1 and ECV

Courtesy: Dr. James MoonSCMR 2014, O005The Heart Hospital London, UK

Biomarker for cardiac amyloidosis



Cardiac T1 Mapping* – clinical case: Amyloid

* This features is currently under development; it is not for sale in the U.S. and other countries. Its future availability cannot be guaranteed.

Amyloid patient: Native T1 map (ms)

Amyloid patient: IR image

Late-enhancement image nulled reasonably well on a global level, and may appear normal.

Mean T1 values in the septum for this case and a healthy volunteer were 1140 and 1040 ms, respectively.

Images courtesy of Drs. Arai and Kellman, NHLBI, Bethesda, MD, US



Cardiac T2 Mapping* - Technical Details

Giri et al. JCMR 2009

Developed in collaboration with: Dr. Simonetti, The Ohio State University, Columbus, OH

T2-prepared single shot trueFISP or

GRE images

Motion

correction

Robust 2 parameter pixel-

wise fitting

Inline T2 map generation

Recovery duration Recovery duration

TD1 TD2 TD3

Image 2 Image 3Image 1

No T2 prep, TE = 0 ms T2 prep, TE = 25 ms T2 prep, TE = 55 ms

ECG

T2 prep ( )and readout ( )

Images

* This feature is currently under development; is not for sale in the U.S. and other countries. Its future availability cannot be guaranteed. Unrestricted © Siemens AG 2014 All rights reserved.


Helios Klinik Berlin-Buch, Berlin, Germany

Cardiac T2 Mapping* – clinical case: Acute infarction

T2 Map

• To assess conditions which alter the myocardial water content and consequently prolong T2 relaxation times

• T2 values (ms) > 65ms indicative of pathology (edema)

• Potential clinical benefit of T2 Map: Differentiate chronic from acute pathology

* This feature is currently under development; is not for sale in the U.S. and other countries. Its future availability cannot be guaranteed.

Handout 8



Cardiac T2* Mapping* - Technical Details

1 Shah et al. Proc. Of SCMR / EuroCMR Joint Scientific Sessions, 2011

…

1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8

RF1 RF2

Monopolar multi-echo readout

…

Optional

black-blood

preparation

…

TE: 1 2 3 4 5 6 7 8

Multi-echo segmented

gradient echo

Robust pixel-wise fitting1

Inline T2* map generation

0 10 20 30 40 50 60 70 80 90 1000

20

40

60

80

100

120

140

160

180

T2St ar-Linear-LSE-Cos t=123.3013-T2Star=41. 4238

T2St ar-NonLinear-LSE -Cost =123. 3013-T2St ar=41.4238

T2St ar-NonLinear-LAD-Cost =123. 0776-T2St ar=40.9759T2St ar-Linear-LSE-robust -Cost =123. 3013-T2St ar=41.4238

T2St ar-NonLinear-LSE -robust -Cos t=123. 3013-T2S tar=41.4238

T2St ar-NonLinear-LAD-robust -Cos t=122. 8753-T2S tar=41.0475

* This feature is currently under development; is not for sale in the U.S. and other countries. Its future availability cannot be guaranteed. Unrestricted © Siemens AG 2014 All rights reserved.


Cardiac T2* Mapping* – Thallassemia Major

• GRE image showing hypointensesignal in the liver.

• T2* map showing a T2* value of 6.6 ms in the myocardium and 1.3 ms in the liver, both below the normal range.

Images courtesy of Drs. Taigang He, David Firmin, Dudley Pennell, Royal Brompton Hospital, London, UK

T2* map (ms)T2* map (ms) GRE image TE 0.9 msGRE image TE 2 ms

* This feature is currently under development; it is not for sale in the U.S. and other countries. Its future availability cannot be guaranteed.


Magnetic Resonance

Relaxometry Workflow and QA Issues

Quality Assurance

• Many different techniques• Details may change

• Often motion sensitive• Check source images • Reality check on output results• Some techniques automatically correct

• Phantoms do exist• Inexpensive to produce

• Challenging to calibrate• Commercial phantoms available

Workflow

• Images not used for qualitative reads• Increased exam time several (~6) minutes• Cost/benefit analysis

• Post processing analysis• Often automated

• Calibration• Phantom scan

• Daily or weekly basis• Special processing may be required

• External reference• Additional setup time


Magnetic Resonance

MR spectroscopy

Non-invasively measures tissue biochemistry.

Metabolites identified as spectral peaks.

Myoinositol

Choline

Creatine

Glutamate, glutamine, GABA

N-acetyl aspartate

Lipids


Magnetic Resonance

Reference



MR Men’s HealthProstate spectroscopy – MR Spectroscopy Analysis

Healthy glandular tissue: ratio(Choline + Creatinine) / Citrate typically < 0.5

Tumors: (Choline + Creatinine) / Citrate typically ≥ 0.5

Comprehensive tool forresearch and routine alike.

Fakultní nemocnice Plzen, Plzen, Czech Republic

Handout 9


Magnetic Resonance

Spectroscopy Workflow and QA Issues

Quality Assurance

• Spectral features• Linewidth• Baseline• Noise level

• Phantoms do exist• Materials can be hazardous

• Sensitive to • Motion• Shimming• B1 variations

• Slice chemical shift

Workflow

• Spectra can also be used qualitatively• Rarely part of routine practice

• Substantial pre- and post-processing required• Shimming is critical• Post processing automation is minimal

• Reference• Internal – relative quantification• External – additional setup

• Calibration scans• Daily or weekly


Magnetic Resonance

Fat/Iron Quantification: HISTO*

T2 correction:

• The T2-corrected peak areas of water and fat were derived from the areas of water and fat at each TE using an exponential least-squares fitting algorithm

• Fat fraction : ∗




Multi-echo Dixon* at 1.5 T – Patient with Focal Iron Deposition



HISTO result:

R2*effFP

108.3 ±18.5 s-12.1 ± 2.1 %

37.2 ±8.9 s-14.9 ± 3.0 %




Multi-echo Dixon* at 1.5 T – Patient with Relatively Severe Fatty Liver



HISTO result:

R2*effFP

42.7 ±9.3 s-121.3 ± 2.9 %



Magnetic Resonance

Fat/Iron Quantification Workflow and QA Issues

Quality Assurance

• Motion sensitive• Long breath hold• Check source images

• Limited range of R2*• Check source images

• Early echoes bright• Late echoes dark• Intermediate echoes

• Phantoms• Fat/water – easy, inexpensive• Fat emulsification – more challenging• Iron concentration – much less common

Workflow

• Images not used for qualitative read• Additional exam time ~1 min• Long breath hold• Can be post-contrast for fat only

• No additional calibration scans needed

• Automated post processing• Many series generated• R2* not directly iron concentration

© Siemens AG 2012. All rights reserved.

Diagnose comprehensively

Early disease detection in less than 30 minutes

Characterize uniquely

Quantitative tissue characterization for early assessment of disease status or treatment response

Treat individually

Personalized outcome prediction and therapy adjustment based on imaging biomarkers

Personalized healthcare in medical imaging

Today Tomorrow Future

Image Courtesy: OncoTreat: Mount Vernon Cancer Centre, London, UK, Prof. A Padhani

Conclusion: The Big Picture

Handout 10


Magnetic Resonance

Answers for life.Unrestricted © Siemens AG 2013 All rights reserved.

Thank you for your attention!


Acknowledgements:Chen LinBruce SpottiswoodeJohn GrinsteadXiaodong ZhongKecheng LiuBradley Bolster

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