Effect of measured Hematocrit value on Glioma grading using Dynamic contrast enhanced  derived MR perfusion parameter
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 mm2 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 (Cp = Cb/(1-Hct)). Perfusion para meters (CBF, CBV, Ktrans, Kep, Ve, Vp 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

1. Liu P et. Al. Magn. Reson. Med., 2015 [Epub ahead of print]

2. Cheng HL. J. Magn. Reson. Imaging, 2007, vol. 25, no. 5, pp. 1073–8

3. Gupta RK, Kumar S. Magnetic Resonance Imaging of Neurological Diseases in Tropics, JP Medical Ltd, 2014, pp. 89–118

4. Sahoo P et al. J. Magn. Reson. Imaging, 2013, vol. 38, no. 3, pp. 677–88

Figures

Figure 1: Scatter plot demonstrating the relation between relative errors introduced in Hct and that in the kinetic parameters derived from simulation. AIF and C(t) kept constant and anly the Hct value was varied from 20-50%.

Figure 2: Box plot shows the fluctuation in blood Hct value of 10 patients during the time interval of treatment.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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