DCE derived kinetic perfusion indices predict seizure control in single calcified Neurocysticercosis
Alok Kumar Singh1, Ravindra Kumar Garg1, Prativa Sahoo2, Hardeep S Malhotra1, Pradeep Kumar Gupta3, Nuzhat Husain4, and Rakesh Kumar Gupta3

1Department of Neurology, KG Medical University, Lucknow, India, 2Healthcare, Philips India ltd, Bangalore, India, 3Radiology and Imaging, Fortis Memorial Research Institute, Gurgaon, India, 4Pathology, Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India

Synopsis

The purpose of this study was to investigate the utility of DCE derived kinetic parameters and serum MMP-9 in predicting the control of seizures in patients with calcified NCC while these are on AED therapy. We found that during follow up, Kep and Ktrans values decreased significantly in no recurrence group while increased in recurrence group. The serum MMP-9, a marker of BBB breakdown also supported the DCE derived kinetic metrics. Our results suggest that DCE derived kinetic parameters, might be able to predict the control of seizures in patients with single calcified NCC while these are on AED therapy

Purpose

The calcified neurocysticercosis (NCC) lesion is considered as a major cause of chronic epilepsy in the endemic regions. Currently, there is no definite objective criterion to decide the termination time point for anti epileptic drugs (AED) in these patients. Recently it has been shown that dynamic contrast enhanced (DCE-MRI) derived Kep, a marker of quantitative BBB disruption can be used as an imaging biomarker to differentiate asymptomatic from symptomatic calcified NCC1. Increased blood-brain barrier (BBB) permeability in neuro-inflammation is associated with up-regulation of expression of various inflammatory molecules like MMP-9 2.The purpose of this study was to investigate the utility of DCE derived kinetic parameters and serum MMP-9 in predicting the control of seizures in patients with calcified NCC while these are on AED therapy.

Methods

A total of 32 patients with new onset seizures and single calcified lesion on CT scan were prospectively analyzed. All patients were subjected to conventional as well as DCE-MRI and serum MMP-9 levels measurement at base line. Imaging and quantification of serum MMP-9 were repeated every 6 month for 2 years while they were being monitored on AED for the control of seizures. All patients were divided into two groups based on recurrence (n=8) and no recurrence of seizers (n=24) on AED therapy. Imaging was done on a 3T scanner with a 12-channel head coil. Imaging protocol: T2-weighted (TE/TR= 88/4400 ms); T2-weighted FLAIR (TE/TR/TI =140/9000/2250ms); pre and post contrast T1-weighted FLAIR (TE/TR/TI = 75/1600/820ms), 240×240mm2 FOV, 3mm slice thickness, no gap. SWI sequence (TE/TR=25/47ms, flip angle 15°, slice thickness 2.4 mm, matrix 320×224, FOV 240×240 mm2 ) was used to ensure that the lesion was solitary and to demonstrate the scolex in the lesion that is pathognomonic of NCC 3. DCE-MR imaging was done using a 3D-SPGR (TR/TE=5.0/2.1, flip angle 10°, slice thickness 6 mm; FOV 240×240 mm2; matrix size, 128×128; number of dynamics=32, number of slice 12, temporal resolution 5.65s). Gd-DTPA was administered intravenously through a power injector at 5 mL/s in a dose of 0.1mmol/kg body weight, followed by 30 mL of saline flush at the start of fourth acquisition. Kinetic parameters (Kep, Ktrans, Ve and Leakage) were estimated from DCE MRI data using in-house developed Java based software 4. Contrast enhancing lesions were segmented and mean signal intensity in the segmented region was measured from post-contrast T1-weighted images. Mean and standard deviation of kinetic parameters were estimated by placing ROIs on the lesion to conform to the area of pathological enhancement. Repeated measure with ANOVA analysis was performed using SPSS

Results

The perfusion indices (Kep, Ktrans, Ve and Leakage) differed in recurrence and no recurrence groups. During follow up, Kep and Ktrans values decreased significantly in no recurrence group (p<0.001) while increased in recurrence group (p=0.005 and 0.114 respectively) ( Figure 1). Though decrease in Ve values in no recurrence group was significant (p=0.041) but not linear while recurrence group showed no significant increase in Ve. Leakage volume also decreased significantly in no recurrence group (p<0.001) but increased in recurrence group. Signal intensity of the contrast enhanced region as well as hemodynamic parameters did not show significant change with time in both of the groups. Figure 2 shows examples of perfusion parameters, post-contrast T1 and SWI for No Recurrence and recurrence groups. Serum MMP-9 also showed similar trend in both groups.

Discussion and Conclusion

Our results suggest that DCE derived kinetic parameters, a quantitative measure of blood brain barrier disruption (BBB) are able to predict the control of seizures in patients with single calcified NCC while these are on AED therapy. The serum MMP-9, a marker of BBB breakdown also supported the DCE derived kinetic metrics. It was interesting to note that quantification of signal intensity on post contrast images did not show any significant difference between the two groups. This is due to the fact that contrast enhancement in the brain lesions represents a combination of lesion vasculature and BBB disruption in varying proportion and is probably responsible for the insignificant difference between the two groups. Insignificant differences in the hemodynamic parameters (rCBV and rCBF) also support the results of signal intensity measure of contrast enhancement in the calcified NCC.

Acknowledgements

No acknowledgement found.

References

1. Gupta RK, et al. Neurology. 2012;78(9):618-25.

2. Tsenova L, et al. Proc Natl Acad Sci USA 1999; 96:5657–62.

3. Del Brutto OH, et al. eurology 2001;57:177–83.

4. Sahoo P, et al. J Magn Reson Imaging. 2013;38(3):677-88.

Figures

Line diagram showing kinetic parameters, MMP-9 and contrast Measurement at each follow-up in No recurrence and recurrence groups.

Showing DCE-MRI derived kinetic parameters overlayed on post-contrast T1 image and SWI image for No Recurrence (a) and recurrence group(b).



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