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ECR 2019 / C-2639
Certificate of Merit
MRI evaluation of fat, iron and fibrosis in liver - step by step
Congress: ECR 2019
Poster No.: C-2639
Type: Educational Exhibit
Keywords: Imaging sequences, MR-Elastography, MR, Liver, Gastrointestinal tract, Abdomen, Tissue characterisation
Authors: J. Miranda, R. O. F. Bezerra, R. L. D. Azambuja, C. V. D. Oliveira, G. R. Camerin, N. Horvat, G. G. Cerri; São Paulo/BR

Findings and procedure details



Inversion-Recovery Imaging (STIR)


  • Based on short T1 of FAT
  • Fat has a shorter T1 than almost all other materials in the body.
  • This technique takes advantage of this difference to suppress the fat signal.
  • No signal from the lipid protons, but there is signal from other tissues with different T1 values.[4]


  • 180° pulse (inverts longitudinal magnetization).
  • 90° excitation pulse after a specific inversion time (TI), when the recovery magnetization of fat protons exactly crosses the null point.
  • Various types of pulse sequence (spin echo, fast spin echo and single-shot fast spin echo).
  • 1.5 or 3.0 T.
  • Commonly used for T2-weighted and proton-density weighted imaging (Figures 5 and 6).


Frequency-selective Fat Suppression Imaging


  • Chemical Shift based technique
  • CHESS (Chemical Shift Selective); Fat saturation or “Fat Sat”.
  • There`s a slight difference in precessional frequency (chemical shift) between water and lipid protons.
  • Signal from macroscopic fat is saturated while the water signal is relatively unaffected. [4]


  • Fat-Sat pulses: short-duration radiofrequency pulses tuned to the resonance frequency of fat (Figure 7).
  • They are applied immediately before the start of an MR imaging sequence.
  • The fat magnetization is dephased by application of a strong spoiler gradient.
  • 1.5 T; 3 T is more effective (increases the chemical shit difference between water and fat).
  • Commonly used for T1-weighted contrast material-enhanced MR imaging (Figure 8).[4]


SPIR and SPAIR Imaging


  • Hybrid techniques (Fat Sat + STIR).
  • SPIR: spectral presaturation with inversion recovery.
  • SPAIR: spectral presaturation attenuated inversion recovery.
  • Selectively suppress fat (“Fat Sat”) + null the residual longitudinal fat magnetization through an inversion delay (STIR). [4]


  • SPIR: selective excitation of lipid with a flip angle >90 ° (100 ° -180° range).
  • SPAIR: selective excitation of lipid with a flip angle of 180°.

-Spoiler gradient destroys any inadvertent transverse magnetization components of fat.

  • Imaging is begun as the fat protons are crossing the null point of longitudinal magnetization (Figure 9).
  • SPIR and SPAIR are well suited for imaging at 3T.
  • SPIR may be better for T1-weighted imaging while SPAIR may be preferred for T2-weighted imaging (Figure 10).



Chemical Shift Imaging or In-Phase (IP)/Out-of-phase (OOP)


  • Based on differences in water and fat resonance frequencies
  • There`s a slight difference in precessional frequency (chemical shift) between water and lipid protons.
  • Fat protons precess slower than water protons.
  • This difference is exploited in chemical shift imaging to improve the depiction of lipid.[4][2]


  • Two Gradient-echo (GRE) images with the same repetition time (TR) and two different echo time (TE) values, one IP and the second OOP.
  • IP and OOP conditions occur approximately every 2.2 msec at 1.5 T (Figure 11).
  • At 3.0T the phase cycling is twice as fast, occurring every 1.1msec.

How to do it:

  • Compare the two sets of images.
  • Tissue that shows a loss of signal intensity on OOP images contains intracytoplasmatic lipid.
  • If the voxel contains no fat or is all fat, there will be no decrease in signal intensity (Figure 12).


Modified Dixon Imaging


  •  Chemical Shift based technique
  • IP and OOP are combined and water-only and fat-only images are reconstructed by postprocessing the image data.
  • A third image phase is designed to allow the correction of phase errors.
  • The fat-only images offer the potential for fat-quantification.[4]



  • Dixon method combines 3 echoes acquired at different TE`s to create water-only and fat-only images (Figure 13). 
  • Phase 3 is obtained at the next 180° phase shift, when the water and fat protons are again in phase, any differences between the two in-phase images can be attributed to phase errors and corrected.
  • Single acquisition.
  • Various types of pulse sequences.


How to do it:

  • Comparison between water-only image and fat-only image highlights the differences in fat and water content of the various tissues imaged (Figure 14).
  • Relatively insensitive to inhomogeneities.

The figure 15 summarizes the advantages and limitations of the qualitative MRI methods to assess fat on liver.




It is known that MR Spectroscopy is the gold standard technique to quantify fat, however it has some disadvantages. Figure 16 shows come concepts about this technique.


Basic Chemical Shift Imaging


  • Based on differences in water and fat resonance frequencies
  • Fat protons precess slower than water protons.
  • Only the abnormal accumulation of fat (triglycerides within vacuoles) is “visible” with MRI.
  • Fat fraction = liver signal attributable to fat.[2][5]



  • Two GRE images and two different TE values, one when fat and water signal are OOP and 1 when they are IP.

How to do it:

  • Fat Fraction: estimated by applying the signal intensities in an equation (Figure 17).
  • There are numerous theoretical biases with this technique (Figure 18). In the presence of iron, the signal on IP and OOP can behave completely different and if we try to quantify fat using this equation, we will be wrong. 


Advanced Chemical Shift Imaging - Proton Density Fat Fraction (PDFF)


  • Multiple Gradient Echo sequences and correction of confounding factors
  • Fat quantification technique that takes into account the multiple spectral peaks of fat and the presence of iron in addition to other corrections.
  • PDFF: ratio of the density of mobile triglycerides to the total density of mobile triglycerides and mobile water.
  • PDFF of 5.56% or greater: abnormal high fat fraction.
  • R2* maps are also created.[6]


  • Breath-hold.
  • Magnitude and Phase information from three or more images acquired at echo times appropriate for separation of water and fat signals.
  • The signal curve is fit into a mathematical model (Figure 19).
  • All biases are corrected.

How to do it:

  • Put the ROI in the region if interest. The result is the PDFF map (Figure 20) and also R2* map. 
  • This technique has a dynamic range of 100%. PDFF has a grat correlation with histological steatosis, triglyceride concentration and MR Spectroscopy. 


The figure 21 summarizes the advantages and limitations of quantitative MRI methods to asses fat on liver.




T2 Fast Spin echo and Gradient echo MR Imaging


  • Based on T2 and T2* decay
  • Iron has a paramagnetic effect and creates a local susceptibility induced distortion in the local magnetic field.
  • Iron causes faster decay of the transverse magnetization and shorter T2 and T2* (Figure 22).
  • The result is a signal loss on T2-weighted fast spin-echo and gradient echo MR imaging (in phase), respectively.[3][7]

 How to do it:

  • Note the signal loss on the liver more than expected.
  • Signal loss on the liver and spleen on IP image. This occurs because the TE of the IP sequence is usually higher than that of the OOP sequence; therefore, the IP pulse sequence is more sensitive to iron deposits because of the increased T2* effect. 
  • Note: when elevated fat and iron coexist in the liver, signal loss due to fat-water signal cancelation on the opposed-phase echo can mask T2* decay on the in-phase echo (Figure 23).




Liver-to-Muscle-Signal Intensity Ratio


  • Based on T2* decay compared to a reference tissue.
  • Based on relative signal intensities between the liver and a reference tissue (usually the skeletal muscle).
  • The higher the iron content in a voxel, the faster the signal decreases as the echo time is increased.[2][5][3]


  • 5 GRE sequences with increasing echo time.
  • Separate breath holds.
  • Body coil.
  • 1,0T 1,5T and 3T.

How to do it:

  • 3 ROIs in the liver parenchyma (excluding vascular structures) and 1 in each paraspinal muscle (Figure 24).
  • Repeat the process with the five MR sequences mentioned above.
  • The values obtained with the measurement of the ROIs will be analyzed with the algoritm developed by Gandon et al available online on the website of the university of Rennes and liver iron concentration (LIC) will be estimated. 

  Relaxometry methods


  • Based on T2 and T2* decay.
  • The higher the iron content in a voxel, the faster the signal decreases as the echo time is increased.
  • Images acquired with increasing echo time.
  • Liver signal intensity is modeled as a function of echo time -> signal decay constants are calculated (R2 or R2*).
  • T2 and T2* are inversely proportional to iron concentrations, and, therefore, the inverse values are often reported, R2 and R2*(Figure 25).[8][3]


  • Spin-echo or GRE sequences with growing TE.
  • Surface coil.
  • R2: 1.5 T; free breathing; long acquisition time.
  • R2*: 1.5 T or 3.0 T; single breath hold; fast acquisition time.
  • The time and decay constant calculations will generate a map.

How to do it:

  • R2 relaxometry: ROI covering the right liver lobe on the largest axial section.
  • R2* relaxometry: on a single mid hepatic section drawn an ROI excluding hilar vessels.
  • R2: centralized analysis. R2*: apply R2* value in some of the equations, depending on what protocol was used (Figure 26).
  • Note: for onde R2* measurement we can get different LIC depending on what protocol was used, because these methods require calibration and the gold standard liver biopsy is highly variable. 
  • The same Relaxometry technique should be used when following patients over time. 

Relaxometry R2* and PDFF: figure 27 shows an example of a patient with hepatic fat and iron overload.


The figure 28 summarizes the advantages and limitations of quantitative MRI methods to asses iron on liver.




Conventional MRI


  • Hepatic fibrosis has traditionally been diagnosed at MR imaging by assessment of morphologic abnormalities.
  • Morphologic features: good at diagnosing cirrhosis and advanced fibrosis, but they suffer from low sensitivity and are not always present at early stages of fibrosis (Figure 29).




MR Elastography (MRE)


  • MRI based technique for quantitatively assessing the mechanical properties of tissues.
  • Displace/vibrate tissue with sound waves.
  • Observe the wave motion.
  • Convert "wavelength"into "stiffness". 
  • Create stiffness maps- "Elastograms" (Figure 30).
  • Patients with fibrosis: waves go faster and speed is reflected in the wavelentgh (Figure 31).[1][9][10]


Mechanical shear waves (Figure 32):

  • Waves at typically 60 Hz transmitted through a passive driver.

MR Elastography sequence:

  • Allow shear waves to be imaged.
  • Phase-contrast sequence with cyclic motion-encoding.
  • Gradient-recalled echo, spin echo or echo planar imaging.

Inversion algorithm:

  • Wave image: two-dimensional displacement map that shows propagation of shear waves.
  • Elastogram: two-dimensional gray or color-coded map of liver stiffness in units of kilopascals. High stiffness are depicted as red areas.

Confidence algorithm:

  • Indicates the highest regions of statistical confidence.

How to do it

Generating mechanical waves 

  • Active driver outside the scanner room generates waves.
  • Flexible plastic tube transmits pressure waves to a passive driver inside the scanner room.  
  • Passive driver is placed on the patient`s abdome and secured with an elastic strap (Figures 33 and 34).

Measuring stiffness values

  • Drawn ROI`s in the elastograms (geographic or elliptical areas): guided by the magnitude image avoid liver edge, fissures, gallbladder fossa, lesions and large vessels (Figure 35).
  • Report stiffness values as a mean and range.
  • Excellent correlation between stiffness values and pathologic degree of fibrosis (Metavir score) (Figure 36).
  • The mechanical properties do not depend on the magnetic field, but on the mechanical frequency. The stiffness will be the same on 1.5 or 3T.

Figure 37 summarizes advantages and limitations of MRE.



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