Pradeep Kumar Gupta1, Jitender Saini2, Ashish Awasthi3, Chandra M Pandey 4, Shreelekha Mohapatra1, Anup Singh5, Rana Patir6, Sunita Ahlawat7, Manish Beniwal8, Anita Mahadevan 9, and Rakesh Kumar Gupta1
1Department of Radiology and Imaging, Fortis Memorial Research Institute, Gurgaon, India, 2Department of Neuroimaging & Interventional Radiology, National Institute of Mental Health and Neurosciences, Bangalore, India, 3Indian Institute of Public Health, Gandhinagar, India, 4Biostatistics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India, 5Center for Biomedical Engineering, Indian Institute of Technology Delhi, Delhi, India, 6Department of Neurosurgery, Fortis Memorial Research Institute, Gurgaon, India, 7SRL Diagnostics, Fortis Memorial Research Institute, Gurgaon, India, 8Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India, 9Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, India
Synopsis
Glioblastoma
and primary CNS lymphoma (PCNSL) need differentiation on pre operative imaging
as management strategies for these two pathologies are diverse. Due to the presence of atypical imaging findings in a significant number of cases, it becomes difficult to differentiate
these two pathologies on conventional MRI. We utilized multi-parametric imaging
methods (T1-perfusion, DWI, and SWI) for possible differentiation of these two
entities. In
linear discriminant analysis using various imaging parameters we achieved 84%
accuracy with AUC 90.14%. We conclude
that multi-parametric imaging may prove to be useful in accurate preoperative discrimination
of these two pathologies.
Introduction:
Primary Glioblastoma (GB) and primary
CNS lymphoma (PCNSL) are intracranial mass lesions which require pretreatment
differentiation because of substantial differences in the treatment strategies
used for these two tumors1-4. Aim of the study was to investigate
the diagnostic performance of multi parametric MRI for differentiation of glioblastoma
from lymphoma using multiple imaging indices derived from diffusion weighted
imaging (DWI), contrast enhanced T1-perfusion MRI and susceptibility weighted
imaging (SWI).Methods:
Total 100 (GB=70 and
PCNSL=30) adult patients (66M/34F; age range 18-82 years; mean age= 51.81±15.86
years) were included in this study. All the patients with PCNSL were
immunocompetent. Multi-parametric MRI including contrast enhanced T1-perfusion,
DWI, and SWI were performed on these patients at 3.0T MRI (Philips HealthTech,
The Netherlands) scanner using 15/32-channel head-coils. Following acquisition
parameters were used for various imaging sequences: T1-perfusion (3D TFE):
TR/TE/flip-angle=4.4/2.1/100, slice-thickness=6mm, FOV=240×240mm2,
matrix size=128×128, temporal-resolution=3.9s, dynamic=32, slices=12), SWI
(TR/TE =31/7.2 ms, slice thickness=2
mm over contiguous slices, flip angle =17°, acquisition matrix = 288 ×288,
FOV=230×230mm2), and DWI (TR/TE=4,156/114ms, number of signal
averages=4, flip angle=90°, slice thickness=5mm, acquisition matrix=152×121,
and FOV=230×184mm2 , b values= 0 and 1,000) were acquired in all the
included subjects. At the fourth time point of the T 1 perfusion data
acquisition, 0.1 mmol/kg body weight of Gd-BOPTA (Multihance, Bracco, Italy)
was administered intravenously at a rate of 3.0 ml/sec, followed by a 30-ml
saline flush.
Image processing and data analysis:
ADC
was quantified using vender supplied tool (Intellispace Portal, Philips Medical
systems, ver 9.0) while T1-perfusion indices i.e. relative CBV, permeability (Ktrans
and Kep), fractional
extracellular extravascular volume (Ve), fractional plasma volume (Vp)
and the leakage rate (λ tr) were estimated using in house
developed program5. CBV
value was normalized by the mean of normal white matter CBV value to generate
the normalized CBV_corr map6. Intratumoral
susceptibility signal (ITSS) scores on SWI images were calculated for each
tumor as described elsewhere7. Leakage corrected CBV (CBV_corr) maps
were co-registered with DWI derived ADC maps, FLAIR and SWI images, and
multiple ROIs were drawn to extract the highest CBV_corr values from the tumor.
Similarly, values for other kinetic parameters were extracted from the co-registered
maps and ROI’s were placed in the regions showing the highest values. DWI
derived ADC map s areas showing the lowest values were used for recording the
values from the ROI.
Statistical
analysis: Discriminant function analysis was used to identify
discriminatory variables using a multivariable procedure. The independent variables
identified by this correlation analysis were used in the model for
classification using discriminant function analysis. Receiver operating
characteristic (ROC) curve analysis was used to evaluate the performance of
various parameter and discriminant function to predict GB. All the statistical
computations were carried out using Statistical Package for the Social Sciences
(IBM, SPSS version 23.0). A p value of ≤0.05 indicated a statistically
significant difference for two tailed alternate hypothesis.
Results:
Figure 1 shows multiparametric images of atypical GB
and PCNSL on conventional MRI. Various imaging indices used for classification using ROC analysis are summarized
in table 1. A discriminant function was derived for
differentiating between PCNSL and GB using multiple imaging parameters. The
form of the function estimated is
“D=0.355*CBV_corr+0.002*ADC+1.087*ITSS-0.6091*Ve-5.055”. This function
classified overall 84 % of the cases correctly, with 84.3% sensitivity and
73.3% specificity and area under curve as 0.90 (p<0.01).Discussion:
In this study, T1-perfusion derived hemodynamic and kinetic metrics
along with diffusion and SWI were used for characterizing and differentiating the
GB from PCNSL. Our study showed that T1-perfusion metrics Ve,
CBV_corr, DWI derived ADC maps along with ITSS score derived from SWI are
useful indices to discriminate PCNSL from GB. DSC perfusion is the most
commonly used perfusion method in previous study which has some inherent
limitations such as presence of blood, postsurgical artifacts, calcifications, or
lesions proximity to skull-base8. While T1-perfusion is less
susceptible to above mentioned conditions and provides both blood brain barrier
permeability and hemodynamic information thus allowing more reliable characterization
of lesions4,9.Conclusion:
We conclude that differentiating of PCNSL
from GB using multi-parametric imaging can be improved by combining T1
perfusion, DWI derived ADC maps and ITSS score derived from SWI in the imaging
protocol.Acknowledgements
NoneReferences
-
Mansour
A, Qandeel M, Abdel-Razeq H, Abu Ali HA. MR imaging features of intracranial
primary CNS lymphoma in immune competent
patients. Cancer Imaging. 2014;14:22.
- Ding
Y, Xing Z, Liu B, Lin X, Cao D. Differentiation of primary central nervous
system lymphoma from high grade glioma
and brain metastases using susceptibility-weighted imaging. Brain Behav.
2014;4:841-9.
- Lu
S, Wang S, Gao Q, Zhou M, Li Y, Cao P, Hong X, Shi H. Quantitative Evaluation of Diffusion
and Dynamic Contrast-Enhanced Magnetic Resonance Imaging for
Differentiation Between Primary Central Nervous System Lymphoma and
Glioblastoma. J Comput Assist
Tomogr. 2017 Aug 12. doi: 10.1097/RCT.0000000000000622. [Epub ahead of print]
- Gupta
PK, Saini J, Sahoo P, et al. Role of Dynamic Contrast-Enhanced Perfusion
Magnetic Resonance Imaging in Grading of Pediatric Brain Tumors on 3T. Pediatr
Neurosurg. 2017; 52: 298-305.
- Singh
A, Singh A, Haris M, et al. Quantification of physiological and hemodynamic
indices using T(1) dynamic contrast-enhanced MRI in intracranial mass lesions.
J Magn Reson Imaging. 2007; 26: 871-880.
- Sahoo
P, Gupta RK, Gupta PK et al. Diagnostic accuracy of automatic normalization of
CBV in glioma grading using T1- weighted
DCE-MRI. Magn Reson Imaging 2017;44:32–37.
- Saini
J, Gupta PK, Sahoo P, Singh A, Patir
R, Ahlawat S,Beniwal M, Thennarasu K, Santosh
V, Gupta RK.Differentiation
of grade II/III and grade IV glioma by combining “T1 contrast-enhanced brain
perfusion imaging” and susceptibility-weighted quantitative imaging.
Neuroradiology, 2017 (online) [https://doi.org/10.1007/s00234-017-1942-8]
- Conte
GM, Castellano A, Altabella L, et al. Reproducibility of dynamic
contrast-enhanced MRI and dynamic susceptibility contrast MRI in the study of
brain gliomas: a comparison of data obtained using different commercial software. Radiol Med. 2017; 122: 294-302.
- Sahoo
P, Gupta PK, Awasthi A, et al. Comparison of actual with default hematocrit
value in dynamic contrast enhanced MR
perfusion quantification in grading of
human glioma. Magn Reson Imaging. 2016; 34: 1071-7.