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
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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
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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
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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
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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?
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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
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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
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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
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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
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Magnetic Resonance
Diffusion Weighted Imaging
Diffusion weighted imaging (DWI) measures random thermal motion of molecules in any fluid
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Magnetic Resonance
Diffusion is limited in highly ordered structures such as white matter
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Magnetic Resonance
ADC and Diffusion Tensor Imaging
Mori and Barker Med. Anat. 257:102–109, 1999
Handout 3
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Magnetic ResonanceMagnetic Resonance
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
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Magnetic Resonance
3D fiber orientation
AP
HF
RL
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Magnetic ResonanceMagnetic Resonance
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
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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”
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Magnetic Resonance
Other Diffusion Quality Assurance
• Other QA Processes• Reference phantom
• QIBA/NIST• Not yet commonly used
Dr. Michael Boss, QIBA/NIST
Handout 4
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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
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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
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Magnetic ResonanceMagnetic Resonance
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
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Magnetic ResonanceMagnetic Resonance
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
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Magnetic ResonanceMagnetic Resonance
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)
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Magnetic ResonanceMagnetic Resonance
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
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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
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Magnetic Resonance
Magnitude Phase
Phase Subtraction Reference
Velocitysensitised
Motion Quantification: Phase contrast velocity
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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
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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
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Magnetic Resonance
Quantitative tagged image analysis
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Magnetic Resonance
Strain Analysis
Lima J. et al. American Journal of Physiology, 1995; 268(3, part 2): H1304-H1312.
Handout 6
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Magnetic Resonance
Cine DENSE
1. Kim et al. Radiology 2004;230:862–871.
Multiple acquisitions throughout the cardiac cycle
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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.
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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
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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.
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Magnetic ResonanceMagnetic Resonance
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
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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).
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Magnetic ResonanceMagnetic Resonance
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
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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
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Magnetic ResonanceMagnetic Resonance
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
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Magnetic ResonanceMagnetic Resonance
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.
Magnetic ResonanceMagnetic Resonance
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
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Magnetic ResonanceMagnetic Resonance
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.
Magnetic ResonanceMagnetic Resonance
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.
Unrestricted © Siemens AG 2014 All rights reserved.
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
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Magnetic Resonance
MR spectroscopy
Non-invasively measures tissue biochemistry.
Metabolites identified as spectral peaks.
Myoinositol
Choline
Creatine
Glutamate, glutamine, GABA
N-acetyl aspartate
Lipids
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Magnetic Resonance
Reference
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Magnetic ResonanceMagnetic Resonance
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
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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
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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 : ∗
*The product is currently under development; is not for sale in the U.S. and other countries. Its future availability cannot be guaranteed.
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Magnetic ResonanceMagnetic Resonance
Multi-echo Dixon* at 1.5 T – Patient with Focal Iron Deposition
These data were acquired with the equivalent WIPs.
Courtesy of Dr. Puneet Sharma and Dr. Diego Martin, University of Arizona, AZ, USA
HISTO result:
R2*effFP
108.3 ±18.5 s-12.1 ± 2.1 %
37.2 ±8.9 s-14.9 ± 3.0 %
*The product is currently under development; is not for sale in the U.S. and other countries. Its future availability cannot be guaranteed.
Unrestricted © Siemens AG 2013 All rights reserved.
Magnetic ResonanceMagnetic Resonance
Multi-echo Dixon* at 1.5 T – Patient with Relatively Severe Fatty Liver
These data were acquired with the equivalent WIPs.
Courtesy of Dr. Puneet Sharma and Dr. Diego Martin, University of Arizona, AZ, USA
HISTO result:
R2*effFP
42.7 ±9.3 s-121.3 ± 2.9 %
*The product is currently under development; is not for sale in the U.S. and other countries. Its future availability cannot be guaranteed.
Unrestricted © Siemens AG 2013 All rights reserved.
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
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Magnetic Resonance
Answers for life.Unrestricted © Siemens AG 2013 All rights reserved.
Thank you for your attention!
*The product is currently under development; is not for sale in the U.S. and other countries. Its future availability cannot be guaranteed.
Acknowledgements:Chen LinBruce SpottiswoodeJohn GrinsteadXiaodong ZhongKecheng LiuBradley Bolster