Prativa Sahoo1, Pradeep Kumar Gupta2, Ashish Awasthi3, Chandra Mani Pandey3, Rana Patir4, Sandeep Vaishya5, and Rakesh Kumar Gupta2
1Healthcare, Philips India ltd, Bangalore, India, 2Radiology and Imaging, Fortis Memorial Research Institute, Gurgaon, India, 3Biostatistics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India, 4Neuorsurgury, Fortis Memorial Research Institute, Gurgaon, India, 5Neuorsurgury, Fortis Memorial Research Institute, Lucknow, India
Synopsis
Quantification of DCE-MRI
assumes a constant blood hematocrite (Hct ) of 45% for adult human papulation.
However Hct varies with disease condition and more with chemotherapy. Correction of the measured signal for blood Hct level
is important as blood T1, quantification
of contrast agent and arterial input function is dependent on it. Purpose
of this study was to investigate the influence of Hct values on glioma grading
using DCE-MRI derived perfusion parameters. Study suggest that even though
grading of glioma not influenced by Hct values it does affect the kinetic
parameters and might be important for monitoring
serial assessment of disease progressions.Purpose
Dynamic contrast enhanced (DCE) MRI is a valuable tool for glioma
grading and monitoring response to therapy. However; post processing of DCE-MRI
depends upon factors like pre-contrast tissue relaxation time T1 estimation (T10), arterial input
function (AIF), post-processing models (e.g., Patlak model, Toft Model, Leaky
Tracer Kinetic Model), fitting algorithms and blood hematocrit (Hct) and that
may influence the estimation of perfusion parameters. Among all these, blood Hct is the most
commonly overlooked factor and generally a fixed value of Hct = 45% is assumed
for adult human population. However; Hct can vary from patient to patient with
disease conditions and more so in cancer patients who are on chemotherapy
treatment where the Hct level may reduce significantly. Furthermore it can
influence blood T1 relaxation time hence the quantification of concentration of
contrast agent and AIF
1, 2. Since MRI contrast agent only occupies
the blood plasma space; concentration of contrast measured at a voxel is the
concentration in blood plasma (Cp) rather than the whole blood (Cb)
3. Hence correction of the measured signal for blood Hct level is
important to get reliable estimation of the perfusion parameters. The purpose
of this study was to investigate the influence of Hct values on DCE-MRI derived
perfusion parameters and how it can affect the grading of glioma in clinical
practice.
Method
This retrospective
study included IRB approved analysis of 50 treatment naïve patients (38 high grades, 12 low grades with mean age 48.92±11.81 year) with
histologically confirmed glioma. All imaging was done on 3.0T MRI scanner
(Ingenia, Philips Healthcare, The Netherlands).
Imaging Protocol: DCE-MRI (TR/TE=4.4/2.1ms, 10o flip angle,
240 ×
240 mm
2 FOV,
128×128 matrix, 12
slice with 6mm thickness, 32 dynamic with 3.9s temporality, contrast dose 0.1
mmol/kg body weight, 3.5 ml/sec injection rate, contrast used Gd-BOPTA ),
conventional MRI (T1 weighted , post contrast T1 weighted, T2 weighted, FLAIR)
Surgery was performed within 48 hours of imaging and hematocrit estimation with
no history of blood loss between imaging and surgery. For each patient Hct was
estimated from the venous blood from the left median cubital vein. For 10
patients who were undergoing chemotherapy Hct was measured multiple times. Pre
contrast T1 was quantified and used for estimation of contrast time profile
voxelwise. An automated AIF was extracted and corrected for Hct using (C
p =
C
b/(1-Hct)). Perfusion para meters (CBF, CBV, K
trans, K
ep,
V
e, V
p and λtr) were quantified
4. Relative maps (rCBV, rCBF) were generated by placing ROI on contralateral
normal brain parenchyma. Each patient data was processed once with assumed Hct
value (45%) and once with measured Hct value. Simulation was done to see the
effect of extreme variation in Hct on the perfusion derived metrics by keeping
AIF and blood T1 constant. Statistical analysis was performed to decide the
cutoff value of each parameter for glioma grading and inter method reliability
between two tests.
Results
The Hct range of patients population included in
this study was found to be 40.4±4.28. ROC analysis shows that the sensitivity and
specificity of DCE-MRI parameters in glioma grading using rCBF and rCBV were
not influenced with actual Hct, however, grading using kinetic parameters were
influenced. Simulations demonstrated that, except Kep rest of the
kinetic parameters (Ktrans, Ve,Vp and λtr) were influenced
by Hct and the error incorporated in the kinetic parameters approximately o.5
times of the error in Hct values (Figure 1). The serial study of individual
patients demonstrated that actual blood Hct fluctuates 15-20% with treatment
(Figure 2).
Discussion
In the current study glioma grading is not
influenced significantly with actual Hct as the variation of actual Hct over
the patient population is less and also effect of Hct on grading can be removed
by using relative parameter rCBV values for glioma grading. However, Hct does
influence AIF and kinetic parameters. Kinetic parameters might play an
important role in serial assessment of disease progression, and CBV leakage
correction. Even though the grade of glioma will remain same with follow-up
studies, to monitor response to therapy measured Hct value taking into account
could be more reliable as Hct fluctuate 15-20% with treatment. Our study suggest that use of actual Hct in
DCE-MRI data quantification might be important for serial studies to correct
the kinetic parameters and remove the leakage effect from the hemodynamic
parameters which play major role in glioma grading.
Acknowledgements
No acknowledgement found.References
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