Nicholas Majtenyi1, Thanh B. Nguyen2,3, Gerd Melkus2, Ryan Gotfrit4, Gregory O. Cron2,3,5, and Ian G. Cameron1,2,3
1Department of Physics, Carleton University, Ottawa, ON, Canada, 2Medical Imaging, The Ottawa Hospital, Ottawa, ON, Canada, 3Radiology, University of Ottawa, Ottawa, ON, Canada, 4Department of Undergraduate Medical Education, University of Ottawa, Ottawa, ON, Canada, 5The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Synopsis
Intravoxel incoherent motion (IVIM) is
an MR-based diffusion-weighted imaging technique that can measure both diffusion
and perfusion. Currently, no link has been established between the perfusion
parameters obtained from IVIM to those from dynamic contrast-enhanced (DCE)-MRI,
particularly in the human brain. This study
determined that no correlation exists between these two perfusion measurement
techniques in patients with glioblastomas. This indicates that these two
imaging techniques measure two separate effects; however, IVIM may be able to
provide complementary, additional perfusion information that can potentially
aid clinical diagnoses when used in conjunction with DCE-MRI parameters.
Introduction
Several methods are used to measure perfusion effects with MRI. In this work, two of these methods will
be considered: intravoxel incoherent motion (IVIM) and dynamic
contrast-enhanced (DCE)-MRI. It stands to reason that, since they both measure
perfusion, a close relationship should exist between the two sets of perfusion
parameters. Conversely, if this is not the case, then they characterize different,
possibly complimentary, tissue parameters. Currently, there is no reported link
between perfusion parameters obtained from IVIM and DCE-MRI. The purpose of
this work was to investigate the relationship between these two MR perfusion
acquisitions in glioblastomas.
DCE-MRI
is a well-established technique for detecting contrast agents as they pass through
tissues by relating associated signal changes to tissue perfusion
characteristics1. IVIM is a non-contrast diffusion-weighted imaging (DWI) technique
that differentiates signal contributions due to diffusion from those due to perfusion2.
On a macroscopic scale, blood flow through the
microvasculature can be considered incoherent due to the pseudorandom structure
of the vessels2; this process is called pseudo-diffusion and manifests
as an additional component to the diffusion decay.
To observe the
IVIM effect, sequentially stronger diffusion gradients differentiate stationary
molecules from those undergoing diffusion3. This is modelled by
S(b)=S0[f⋅e−bD∗+(1−f)⋅e−bD] (1)
where S(b) is the signal-intensity for a given b-value, S0
is the signal-intensity at b=0, f is the perfusion fraction, D is the diffusion
coefficient, and D* is the pseudo-diffusion coefficient. Several different
methods to evaluate IVIM parameters using Eq. 1 are reported in the literature2,4,5.
Methods
Both IVIM and DCE-MRI were
performed pre-operatively on ten patients (median age = 68, 60% male) with glioblastomas.
All data was acquired using a 3T MRI system (Magnetom Trio, Siemens) with a
32-channel head coil. For IVIM, DWI images (in trace mode) were acquired using
16 b-values in total (0-900 s/mm2) with 10 values being less than 200
s/mm2. Image data was corrected for both noise and eddy currents. IVIM
parameters were evaluated from Eq. 1 using MATLAB and a robust, two-step approach.
Parameters f and D were obtained using a mono-exponential function for b≥200
s/mm2. These values were then used with the full bi-exponential fit
to determine D*. DCE-MRI was performed using a FLASH sequence with TR=6.5 ms,
TE=1.65 ms, and flip angle=30°. DCE-MRI parameters (vp, Ktrans,
ve, and kep=Ktrans/ve) were obtained
using commercial software. The perfusion parameters from IVIM (f, D*, and their
product fD*) were measured for regions of interest (ROIs) on tumour volumes after
co-registration to the DCE-MRI data. The ROIs were drawn manually on the
DCE-MRI images by a medical student under the supervision of a neuroradiologist.
Correlation coefficients between IVIM and DCE-MRI parameters were computed using
Spearman’s rank correlation for total tumour tissue (enhancing and necrotic) volumes.Results
IVIM perfusion parameters, in general, did not correlate with
the perfusion parameters obtained from DCE-MRI. Figure 1 shows a weak negative
correlation (ρ=-0.058,
P=0.573) of the IVIM perfusion fraction (f) to DCE-MRI percent
plasma volume (vp). Figure 2 similarly shows a weakly negative correlation
(ρ=-0.173, P=0.093) for the
comparison of two parameters related to flow (fD* and Ktrans). All
reported parameter correlations are shown in Fig. 3 for noise-corrected data
measured in this study, along with those reported from two others studies4-5.
None of the three studies indicate a trend towards positive correlation between
any two sets of parameters.Discussion
Comparisons
between IVIM and DCE-MRI quantitative parameters have not been well studied,
especially within the human brain. The framework for each of these acquisitions
is that they both measure perfusion, albeit by different means. The most
intuitive comparison is between blood volume measurements (f versus vp)
where the expected positive correlation was clearly not observed (Fig. 1);
Figure 3 indicates that none of the three studies report a positive
correlation. No discernible pattern appears to emerge from these studies for
nearly all parameter comparisons. Bisdas et al. obtained IVIM parameters from a
modified bi-exponential decay (perfusion term included D+D*) using a different fit
method5. This indicates that regardless of the fitting technique chosen
to obtain IVIM parameters, no significant correlation exists. Conclusion
The
results presented in this study show that perfusion parameters obtained with
IVIM and DCE-MRI are poorly correlated in glioblastomas. This suggests that
they are in fact describing different tissue properties and can perhaps be
considered complimentary parameters rather than redundant ones. The results
further suggest that it may be beneficial to obtain both sets of parameters,
rather than one or the other, since they appear to characterize different
tissue properties - possibly different aspects of the perfusion process.Acknowledgements
The authors would like to thank Christian Federau for his guidance in establishing our IVIM protocol and data processing methods.
References
1. Padhani AR and Husband JE. Dynamic Contrast-enhanced MRI
Studies in Oncology with an Emphasis on Quantification, Validation and Human
Studies. Clin Radiol. 2001;56(8):607-620.
2. Le Bihan D, Breton E, Lallemand D, et
al. Separation of Diffusion and Perfusion in Intravoxel Incoherent Motion MR
Imaging. Radiology. 1988;168(2):497-505.
3. Sigmund EE and Jensen J. (2011). Basic
physical principles of body diffusion-weighted MRI. In B. Taouli (Ed.), Extra-Cranial Applications of Diffusion-Weighted
MRI (pp. 1-17). New York, NY: Cambridge University Press.
4. Keil VC, Mädler B, Gielen GH, et al. Intravoxel
Incoherent Motion MRI in the Brain: Impact of the Fitting Model on Perfusion
Fraction and Lesion Differentiability. J Magn Reson Imaging. 2017;46(4):1187-1199.
5. Bisdas S, Braun C, Skardelly M, et al. Correlative
assessment of tumor microcirculation using contrast-enhanced perfusion MRI and
intravoxel incoherent motion diffusion-weighted MRI: is there a link between
them? NMR Biomed. 2014;27(10):1184-1191.
6. Lee EY, Hui ES, Chan KK, et al. Relationship between
intravoxel incoherent motion diffusion-weighted MRI and dynamic
contrast-enhanced MRI in tissue perfusion of cervical cancers. J Magn Reson Imaging.
2015;42(2):454-459.