Ayan Debnath1, Prativa Sahoo2, Pradeep Gupta3, Rakesh Gupta3, and Anup Singh1
1Centre for Bio-Medical Engineering, Indian Institute of Technolgy Delhi, Delhi, India, 2Philips India Limited, New Delhi, India, 3Radiology, Fortis Memorial Research Institute, New Delhi, India
Synopsis
In the current study, Amide Proton Transfer (APT) and T1-weighted DCE
perfusion MRI was performed on patients
with intra-cranial mass lesions(low and high grade tumors, CNS tuberculoma, CNS
lymphoma) at 3T MRI. APT maps provided a significant difference between lesion
and its contra-lateral side. From the preliminary study it was observed that
APT contrast was low in infection lesion followed by tumor and lymphoma. APT values showed a
significant (P<0.01) difference between low and high grade tumors. A
weak Inter-class correlation was observed between APT and perfusion parameters (like
cbf, cbv, Ktr, Kep, ve). Therefore, APT mapping might improve diagnostic value
either alone or in combination with other MRI parameters. Purpose:
CEST
MRI (1) is a novel non-invasive molecular imaging technique having great
potential in molecular characterization of tissues and hence in disease
diagnosis. CEST contrast at offset frequency of +3.5ppm from water protons
resonance, at low saturation RF power, has been reported to be sensitive to
amide protons of peptides and small proteins (2, 3). This contrast is widely
known as amide proton transfer (APT) contrast. Objective of the study was to
compare APT maps with DCE perfusion parameters map and to evaluate its
diagnostic and grading value in intra-cranial mass lesions (low grade tumors,
high grade tumors, Central Nervous System (CNS) Tuberculosis,
CNS Lymphoma (6)).
Materials and Methods:
All
the MRI experiments were performed at 3T whole body Inginia MRI system (Philips
Healthcare, The Netherlands) using a body coil excite and a 8 channel head coil
for reception. Twenty-two patients with
pathologically proven, solitary, contrast-enhancing tumors and
having different kinds of intra-cranial mass lesion (low grade
tumor(n=9), high grade tumor(n=8), tuberculoma (n=1), tubercular abscess (n=1),
lymphoma(n=3)) were scanned for MRI data
in the current study. APT W images were acquired at following frequency
offsets:±2.5, ± 3, ± 3.5,
±4, ±4.5 ppm
from water. The WASSR approach was used to determine B0 maps (range,
-1.5 to1.5 ppm; interval, 0.125 ppm).
Data Processing: Pre-processing was
performed on APT-W images for background noise removal. B0 map were generated
and CEST or APT images were corrected for B0 inhomogeneity followed by
asymmetry analysis (8, 9) for computing APT map.
APT contrast = 100*[Msat
(-3.5ppm) – Msat (+3.5ppm)]/ Msat (-3.5ppm)
APT
map and perfusion weighted images was registered with T1-weighted images for
motion correction. Region of interest (ROI) analysis (mean and standard
deviation) was performed on combination of T1 weighted images, GD-CE images, T1
dynamic images. Same ROI are being applied on APT maps, and other perfusion
parameters (like cbf, cbv, cbv corrected, cbv corrected for ve, kinetic
parameters like(Ktr, Kep), leakage volume, ve and vp). Two ROI in WM and GM
were drawn on each patient. ROIs on lesion, contra-lateral side, core portion
and peripheral part of lesion were
also drawn. Signal intensities are being measured in different ROIs. We studied
Intra-class correlation co-efficient (ICC) between APT and other perfusion
parameters for entire lesion region (ROI-1), core region within lesion (ROI-2)
and peripheral portion of lesion (ROI-3) for twenty two patients having
intra-cranial mass lesions (Table no.1). T-test was also performed for
evaluating difference of APT values between low and high grade tumors.
Results and Discussion:
APT
maps (Second column in Figure 1) show a difference in values between white
matter (WM), gray matter (GM) and intracranial lesions. ROIs in the WM regions
showed –ve APT contrast value while GM regions mostly showed a +ve contrast
values. Intracranial lesions in the current study showed significantly higher
APT contrast compared to contra-lateral side, can be significantly
differentiated (P<0.01). From this we can
see that APT values are weakly correlated with all of the perfusion parameters;
thus it might have potential in improving diagnostic value alone or in
combination with other perfusion parameters. ICC between normalized APT and
normalized CBV was -0.364 which is non-significant .Significant
differences were observed between high- and low-grade tumors (P < 0.01). A
significant difference between low and high grade tumors are observed for APT.
Conclusion:
In conclusion, all types of intracranial lesions
in the current study showed significantly higher APT contrast compared to
contra-lateral side. APT images are weakly correlated with other perfusion
parameters; therefore, its inclusion might improve diagnostic and grading value
for different intra-cranial diseases.
Acknowledgements
The Authors acknowledge internal grant from
IIT-Delhi; NIH grant P41 EB015909 for APT pulse sequence and Philips India
Limited for technical support in MRI data acquisition. The authors thanks Drs.
Jinyuan Zhou, Peter C.M. van Zijl, Dr. Indrajit Saha. The authors thanks Prof.
RKS Rathore for technical support in DCE-perfusion analysis. References
[1] Ward
KM, et al. JMR 2000;[2] Zhou J, et al. Nat Med 2003;[3] Zhou J, et al., MRM
2003; [4] Craig K. Jones, et al., MRM 2006; [5] Zhou J, et al., JMRI 2013; [6]
Jiang S, et al., EurRadiol. 2015. [7] Zhu H, et al. MRM 2010; [8] Cai K, et al,
Nature Medicine 2012. [9] Singh A, et al, MRM, 2012, [10]Park J.E, et al., Radiology, 2015