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Advanced Imaging TechniquesX-Nuclei Imaging

Prof. Dr. Frank G. ZöllnerComputer Assisted Clinical MedicineMedical Faculty Mannheim Heidelberg University

Theodor-Kutzer-Ufer 1-3D-68167 Mannheim, Germany

Frank.Zoellner@medma.uni-heidelberg.dewww.ma.uni-heidelberg.de/inst/cbtm/ckm

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Learning Goals

� introduction to advanced imaging techniques in MR, CT and CBCT

� basic MRI principles -> Physics of Imaging Techniques

� Goals:

1. How does the technique work ?

2. What kind of images do we receive?

3. Where is this applied to ?

� Literature is given in the respective lectures

� Slides of the lectures at https://www.umm.uni-heidelberg.de/inst/cbtm/ckm/lehre/index.html

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Reading� Wetterling et al., Sodium-23 magnetic resonance imaging during and

after transient cerebral ischemia: multinuclear stroke protocols fordouble-tuned 23Na/1H resonator systems . Phys. Med. Biol. 2012(57) 6929

� Konstandin & Schad. 30 years of sodium/X-nuclei magnetic resonance imaging. Magn Reson Mater Phy (2014) 27: 1

� Konstandin, S. Development of 2D Radial Techniques for Sodium MRI with Application to Abdominal Imaging at 3Tesla.PhD Thesis, Heidelberg University, 2012

� Konstandin & Nagel. Measurement techniques for magnetic resonance imaging of fast relaxing nuclei. Magn Reson Mater Phy(2014) 27: 5

� Eisele, et al. Heterogeneity of acute multiple sclerosis lesions on sodium (23Na) MRI. Multiple Sclerosis.(2016). http://doi.org/10.1177/1352458515609430

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Outline

�Motivation

�Challenges of X-Nuclei MRI

� Imaging Techniques of 23Na

�Applications

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Motivation

� Ion fluxes in cells play an important role of cell activity� sodium–potassium pump (Na+–K+-ATPase), which pumps

3 Na+ ions out of and 2 K+ into the cell. � active transport mechanism is one factor

to keep the resting membrane potentialin cells at about −70 mV

https://www.slideshare.net/Amirrezagholizadeh1/sodium-potassium-pump

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Motivation

� Different ion-specific channels are able to transmit information via electrical signals by gating the flow of ions across the cell membrane.

� pathological change in concentration canbe visualized by X-nuclei MRI

� can give additional functional information Dr. John W. Kimball,

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html

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MR Properties of X-nuclei

nucleus spin Igyromagnetic

ratio γ[108 rad s-1 T-1]

natural abundanceof isotope

in %

sensitivityfor B0 = const.in % (rel. to 1H)

1H 1/2 2,675 99,98 100,00 MRI: 111 mol

25Mg 5/2 -0,164 10,00 2,68 × 10-2

33S 3/2 0,205 0,75 1,70 × 10-3

23Na23Na 3/23/2 0,7080,708 100,00100,00 9,279,27 MRI: 45 mmol

19F 1/2 2,518 100,00 83,40

31P 1/2 1,084 100,00 6,65

2H 1 0,410 0,01 9,60 × 10-1

1 0,193 99,63 1,00 × 10-114N16O 0 - 99,76 -17O 5/2 -0,363 0,04 1,11 × 10-3

13C 1/2 0,673 1,11 1,75 × 10-2

12C 0 - 98,89 -

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MR Properties of X-Nuclei – Exp. Sodium

Konstandin, S., PhD Thesis, Heidelberg University, 2012

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MR properties of X-nuclei

� low in vivo signal 10 000 – 50 000 times lowerthan 1H-signal

� short relaxation timesbrain tissue: T2f

* ≈ 4 ms, T2s* ≈ 30 ms, T1 ≈ 30 ms

relative sensitivity 19.27 ⋅ 10-2

in-vivo concentration [M] 11145 ⋅ 10-3

in-vivo sensitivity 14.59 ⋅ 10-5

signal deficit 22 000 0

Na23

11H1

1

Chalifa Tower, Dubai1H - 830 m

23Na - 183 mm35Cl - 48 mm39K - 4 mm

high SNR-efficiency & short echo times !!

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Imaging of 23Na

� broadband transmitter

� dedicated rf coils needed

� single tuned coils vs. double resonant coils

� dual-RF resonator allows for

� homogeneous transmit B+1

field

� highly sensitive receive B-1

field

preclinical coils

clinical coilsZöllner et al., NMR Biomed 2015

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Imaging of 23Na

� aim to record a proton density weighted image

� quantification of tissue sodium concentration

� relatively long TRs and UTEs are required to avoid T1 and T2* weighting in the images

� need for UTE sequences, radial readouts, rectangular RF pulse

� SNR increased by uniform k-space sampling

� measurement time: twisted projection, density adapted, etc.

Zöllner et al., NMR Biomed 2015

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k-space

2D

3D

TEmin ~ 0.4 ms !!

• radial projection technique• nonuniform k-space coverage

• SNR loss of 25.5 %α

readout

phase

TE

Lauterbur Nature 1973

23Na-Imaging: Radial Readout

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23Na-Imaging: Radial Readout

Konstandin & Nagel. Magn Reson Mater Phy (2014) 27: 5

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Imaging of 23Na: Quantification

� PD weighted images needed

� reference vials + CSF

� estimate T1 and T2 relaxation time

� T2reff= 7.15 msec, T2refl

= 33.7 msec

� tissue T1 and T2 relaxation time

� T1 = 34 ms

� T2tissf= 2.2 msec, T2tissl

= 20.4 msec

correction for T1 effects correction for T2 effectsHaneder et al, Radiology 2011Maril et al, Kidney Int., 2004

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Imaging of 23Na: Quantification

� accurate TSC quantification requires a reliable correction of the RF excitation field and coil sensitivity

� 3% deviation in B1 map → 5% error in concentration

� different techniques in 1H MRI proposed

� phase sensitive (PS)

� double angle method(DAM)

Lommen et al, NMR Biomed 2015Paschke et al, ESMRMB 2015

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Renal Sodium Imaging – Initial Studies in Human

� coronal projection of a 3D 23Na image of the human abdomen @3T

� (a) 25-min � (b) 12-min

� in-house build quadrature surface coil

� 3D gradient-echo sequence � TR/TE 30/1.8 ms, FOV 38 x 38 x

24 cm, and matrix 128x128 x16

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Renal Sodium Imaging – Cortico-Medullary SodiumGradient

normal condition 12h water deprivation

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Renal Sodium Imaging – Quantitative Approaches

� 3D DA-RAD sequence� TR/TE 120/0.55ms, FA

85°,FOV 320x320 mm� readout length per spoke was

20 msec, and 8000 projections

� total acquisition time of 16 minutes

� quantification of 23Na

T2w 23Na

normal condition water load

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Renal Sodium Imaging – Quantitative Approaches

T2w 23Na

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Renal Sodium Imaging – Quantitative Approaches

23Na concentration[mmol/l WTV]

Slope 23Na gradient[mmol/l /mm WTV]

cortex medulla

59 ± 17 99 ± 26 3.2 [1.5 6.3]

Conclusion� cortico-medullary sodium concentration gradient� wide inter-individual ranges � no significant correlations with age, gender, [23Na]serum, BMI, GFR, ADC, or

R2* values

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Renal Sodium Imaging – Studies of PathophysiologicProcesses

� assess post-radiotherapeuticrenal changes� 56-year-old patient

after adrenal stereotactic body radiotherapy

� cortico-medullary sodium gradient and sodium concentration are decreased in the left kidney

Haneder et al, Strahlenther. Onkol. 2012

[23Na] map 23Na/1H fusion 1H T2w

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Renal Sodium Imaging – Studies of PathophysiologicProcesses

� central diabetes insipidus� intranasal

administration of 20 µg desmopressin

Haneder et al, Magn. Reson. Mater. Phys. 2014

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Renal Sodium Imaging – Studies of PathophysiologicProcesses

� sodium removal from tissue stores in hemodialysis patients�

23Na-MRI quantitatively detects sodium stored in skin and muscle

� allows studying sodium storage reduction in ESRD patients

Dahlmann et al, Kidney Int. 2014

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Renal Sodium Imaging – Studies of PathophysiologicProcesses

� transplanted kidneys/ renal allograft loss� Sodium concentration was

lower in transplanted kidneys than in native kidneys(153.5± 11.9 vs. 192.9±9.6 mM)

� Sodium gradient of transplanted kidneys was lower than for native kidneys(8.9±1.5 vs. 10.5±0.9 mM/ mm)

Moon et al, Eur. Radiol. 2014

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Bain Sodium Imaging – Multiple Sclerosis

� MRI the most practical and widely applied biomarker to detect signs of pathological change and inflammatory activity

� sodium MRI is a sensitive marker of very subtle tissue normalities

� recent studies that identified elevated TSC values in chronic lesions

Eisele, et al. Multiple Sclerosis.(2016)

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Bain Sodium Imaging – Stroke

� final infarction in acute stroke dependent on several factors

� individual vascular collateral flow,

� admission glucose levels, hematocrit level and blood pressure,

� the most determining factor though is the time until recanalization and reperfusion is achieved

� concept of DWI/PWI mismatch strongly underestimates the amount of still viable tissue

Neumaier-Probst et al. (2015). International Journal of Stroke, 10(SA100), 56–61

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Sodium Cancer Imaging

Madelin and Regatte J Magn Reson Imaging. 2013

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Muscle Skeleton Imaging

Madelin and Regatte J Magn Reson Imaging. 2013

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Muscle Skeleton Imaging

Madelin and Regatte J Magn Reson Imaging. 2013