Oi Lei Wong^{1}, Jing Yuan^{1}, Gladys Goh Lo^{2}, Thomas W. T. Leung^{3}, Wai Ki Chung^{2}, and Benny W. H. Ho^{2}

^{1}Medical Physics and Research Department, Hong Kong Sanatorium & Hospital, Hong Kong, Hong Kong, ^{2}Department of diagnostic & interventional radiology, Hong Kong Sanatorium & Hospital, Hong Kong, Hong Kong, ^{3}Comprehensive Oncology Center, Hong Kong Sanatorium & Hospital, Hong Kong, Hong Kong

### Synopsis

**The
use of IVIM in assessing the microcapillary perfusion and true diffusion has
attracted elevating attention. The segmented bi-exponential fitting has been
widely adopted to calculate IVIM metrics, in which a cut-off b-value is
pre-defined for perfusion and diffusion region separation. This study
calculated the corrected Akaike Information Criterion (AICc) for bi-exponential
IVIM model in the healthy human liver with varying cut-off b-values and then
compared to the AICc for the mono-exponential model. The statistical preference
of the bi-exponential model to mono-exponential model was demonstrated based on
the lowest AICc. This bi-exponential model preference was independent of the
choice of cut-off b-value and ROI location.**### Purpose

Apparent
diffusion coefficient (ADC) has widely been applied in the
clinic. However, the
micro-capillary perfusion effect is not considered in
mono-exponential model. Contrariwise, this effect is included in the
bi-exponential intravoxel incoherent motion (IVIM).
Despite the best fitting method for the bi-exponential IVIM model is
yet to determine, the segmented bi-exponential fit has been suggested
to be more robust than the simultaneous full bi-exponential fit

^{ [1]}.
Indeed, the estimate of true diffusion (D) and perfusion fraction
(f), using segmented bi-exponential fit, is dependent on the
pre-defined cut-off b-value to separate the perfusion and diffusion
region on DW signal decay curve. Such cut-off b-value, however, is
often heuristically chosen from a low b-value range (50 – 200
s/mm

^{2}) without a standardized value. For example, Koh et al. defined
the cut-off b-value to be 100 s/mm

^{2 [2]} while Cohen et al. used 50
s/mm

^{2} in the liver

^{[3]}. Also, the behaviour of the DW signal decay
curve may be regional dependent where different IVIM metrics between
the left and right liver lobe has been previously identified

^{[4]}. We,
thus, hypothesize that the model
preference (bi-exponential and mono-exponential)
may be affected by the choice of cut-off b-value and the selection of
ROI. We evaluated the model perference due to both effects using the
corrected Akaike Information Criterion (AICc).

### Methodology

Liver
imaging was performed on 7 healthy volunteers using a 1.5T MRI
(Optima MR450w, General Electric Healthcare, Milwaukee) and a
dedicated 32-channel phase array. A non-elastic belt was used to
minimize respiratory motion during free breathing. Coronal diffusion
scans (TE/TR=77/2200ms, 5 x 10mm slices, 35cm FOV, diffusion encoding
direction =LR, 6 NSA) were performed with the b-values of 0, 10, 20,
30, 40, 50, 100, 200, 300, 400, 500 s/mm

^{2}. The bulk respiratory
motion was first corrected with a rigid body transformation using
MCFLIRT (FSL, FMRIB, Oxford, UK). Voxel-based IVIM analysis was then
performed using a custom Matlab script (Mathworks Natick, MA) based
on a two-step segmented unconstrained analysis: (1) nine D were
obtained from a monoexponential fit with b-values no smaller than 10,
20, 30, 40, 50, 100, 200, 300 and 400 s/mm

^{2}, and the corresponding f
values were subsequently obtained using the intercept; (2) nine D*
were determined from the bi-exponential IVIM model with each set of f
and D values calculated in step one. Afterwards, AICc value for the
bi-exponential IVIM model was calculated using each set of IVIM
metrics. A mono-exponential fit using all b-values was also performed
to calculate ADC and the mono-exponential AICc value. The model
preference between bi-exponential and mono-exponential model was then
determined based on the lowest AICc value. The voxel map of the
cut-off b-value corresponding to the set of IVIM metrics with the
lowest AICc value (b

_{cut}) was also obtained. A circular ROI (diameter
= 10mm) was selected on the left and the right liver lobe separately
on the same slice (Figure1).
A ranksum test was performed to compare the IVIM metrics and b

_{cut}.

### Results

When
comparing with AICc using mono-exponential model, all voxels within
both left and right liver ROI presented with lower AICc using
bi-exponential model for all choices of cut-off b-value. As
illustrated in Figure 2, significant difference between left and
right liver lobe were observed in D (4.33±1.16 x 10

^{-3} mm

^{2}/s vs.
1.63±0.27 x 10

^{-3} mm

^{2}/s, p<0.01) and b

_{cut} (93.6±27.7 s/mm

^{2} vs.
170.1±34.2 s/mm

^{2}, p<0.05). Larger f was also observed in the left
liver lobe (0.16±0.02) when compared to the right (0.12±0.03)
(p=0.05).

### Discussion

When
compared with the mono-exponential model, the bi-exponential model
was noted to be the preferred model based on our results, which was
independent of the choice on the cut-off b-value. The model
preference was also observed to be independent of the ROI location
though a significant difference between left and right liver lobe was
obtained using D. Moreover, our calculated bcut
range for both liver lobe agreed with the typical value used in the
literature. However, a significant difference in the bcut value has
been observed in regional basis (Figure 3). The smaller bcut value
and the larger f value in the left liver lobe may indicate a more
prominent perfusion effect. Our voxel-wise IVIM metrics were
calculated based on these varying b

_{cut}, which could be different from
the traditional approach with a single fixed bcut. Whether this
approach could improve the accuracy of IVIM quantification needs to
be further investigated.

### Acknowledgements

No acknowledgement found.### References

[1] Cho G. et al.
Comparison of fitting methods and b-value sampling strategies for
intravoxel incoherent motion in breast cancer. MRM 2015;
74(4):1077-85

[2] Koh DM. Et al.
Intravoxel incoherent motion in body diffusion-weighted MRI: reality
and challenges. 2011 American Journal of Roentgenology 196(6):
1351-61.

[3] Cohen AD et al. The effect of low b-values on the intravoxel incoherent motion
derived pseudodiffusion parameter in liver 2015
MRM, 73: 306-311

[4] Wong OL et al.
Evaluation of Pseudo-hepatic anisotropy artifact in liver intravoxel
incoherent motion (IVIM) based on clustering technique. 2015 The
proceeding of 23rd ISMRM, Toronto, Canada.