Dinil Sasi S1, Rakesh K Gupta2, Indrajit Saha3, Anandh K Ramaniharan3, and Anup Singh4,5
1Indian Institute of Technology Delhi, New Delhi, India, 2Fortis Memorial Research Institute, Gurugram, India, 3Philips India Limited, Gurugram, India, 4Indian Institute of Technology Delhi, Hauz Khas, India, 5All India Institute of Medical Science, New Delhi, India
Synopsis
T1-perfusion
derived parameters have been utilized for brain tumor quantification and
grading. In this study, we have analyzed the potential of Compressed SENSE
(CSENSE) acceleration technique on high resolution T1-perfusion MRI for quantitative
analysis of brain tumor(glioma) and compared its performance and accuracy with
conventional acquisition protocol in terms of concentration-time curve, perfusion
parameters and glioma grading. A prospective analysis was also carried on
healthy subjects to analyze the spatial error propagation at different
acceleration factors(R). All derived perfusion parameters were able to quantify
and differentiate different tumor classes with improved concentration-time
curve(High grade and low grade glioma).
Introduction
T1-perfusion derived parameters acts as a biomarker in tumor
angiogenesis and hence clinicians and researchers have been utilizing its
potential for tumor analysis1. Several scan acceleration techniques such as SENSE2, compressed sensing(CS)3, compressed-SENSE(CSENSE)4etc. have been utilized in clinical practice to
improve the spatial coverage and resolution for MR perfusion imaging. A
preliminary study was previously reported5 on analyzing the effect of CSENSE enabled
T1-perfusion derived rCBV in differentiating high grade and low grade glioma on
25 patients. In this extension to previous study, we have prospectively
analyzed the spatial error propagation as a function of acceleration factor(R)
on healthy subjects and a retrospective analysis was carried on T1-perfusion
data of 100 treatment naïve subjects to evaluate the effect of CSENSE on
accuracy and performance of quantitative perfusion parameters and the behavior
of concentration-time curves(CTC) on contralesional healthy tissue as well as
on tumor tissue, and compared it with conventional acquisition
protocol(protocol-1). Methods
All
MRI experiments were carried out using 3.0 T whole body Ingenia MRI system(Philips Healthcare, The Netherlands)
using a 15 channel head coil. A retrospective analysis was carried on
T1-perfusion MRI data of 100 treatment naïve glioma subjects(50 subjects/protocol)
acquired using protocol-1 and CSENSE enabled protocol(protocol-2). Each
protocol subsumed equal number of HGG and LGG subjects. A prospective study,
which included acquisition of 3D T1-FFE images(20 slices and 8 dynamics) of 3
healthy volunteer without the injection of intravenous contrast agent was also
carried out to analyze the error propagation with respect to R. Repeatability
was measured using co-efficient of variation(COV) at different ROIs in white
matter. The MR parameters for both acquisition
protocols are given in table 1. All patients were intravenously administered
with 0.1 mmol/kg body weight of gadobenate dimeglumine Gd-BOPTA(Multihance,
Bracco) at the fourth time point. Protocol-2
took the advantage of SENSE enabled scan acceleration(R=1.5) for T1 mapping7. We have
considered the histologically confirmed grades based upon WHO 2016 classification
as a gold standard.
Normalized-Mean-Squared-Error(NMSE) was used to evaluate the
error propagated as a function of R in healthy volunteer data. Generalized-Tracer-Kinetic-model6 and first pass analysis was used for
T1-perfusion analysis. Quantitative perfusion parameters CBV(leakage
corrected CBV)2 and CBF used in
this study were normalized using their mean values in the
normal–appearing-white-matter tissue on the contralesional side to obtain rCBV
and rCBF maps. Glioma grading was carried out using independent perfusion
parameters as well as combination(using logistic regression) of different
parameters computed at tumor tissue(contrast-enhancing and non-enhancing area)
segmented using previously reported semi-automatic method6. Mean values
greater than 90th percentile was used for grading(ROC analysis) and
statistical analysis(t-test). Results
The acquisition of 20 slices 3D-T1-FFE images at 32
time points using protocol-2 took ~1.9 times less than the time taken for
acquiring the same images without any scan acceleration. Also, protocol-1 took
similar time of acquisition (same temporal resolution) for lesser spatial
coverage and resolution compared to protocol-2. Figure-1 shows the T1-FFE
images of a healthy subject acquired at different R. The NMSE of images at R =
2, 3 and 4 were (5.23±2.35)×10-4, (6.64±2.95)×10-4 and
(9.66±3.33)×10-4 respectively. Figure 2 shows the similar slices of
a 2 different subjects for different protocols and CTC corresponding to each
protocol. CTC exhibited more oscillations(noisy) in protocol-1. The mean CBV at
gray matter ROIs of 25 representative HGG data from each protocol were
statistically similar(p=0.23, mean rCBV at GM ROIs were 1.39±0.55 and 1.34±0.23
respectively for protocol-1 and 2). Figure 4 shows box-whisker plot of all
perfusion parameters of HGG data acquired using both protocols. Even if
most of the values comes under the inter-quartile range, the range of tracer
kinetic parameters were more in protocol-1, while the hemodynamic parameter has
shown a lesser range. The perfusion parameters of both protocols didn’t change
significantly(Ktrans(p=0.3971), Ve(p=0.4222), rCBV(p=0.1562) and rCBF (p=0.1621).
Figure 5 show the ROC plots for
differentiating glioma using individual perfusion parameters as well as
combining all parameters(rCBV, rCBF, Ktrans and Ve) for protocol-1 and protocol-2.
In protocol-2, combining all parameters has produced an AUC 0.962 with 88% sensitivity
and 95.83% specificity.Discussion
This
study evaluated the potential of CSENSE(at R=3.75) in improving the spatial
coverage and resolution of data acquired for T1-perfusion MRI for quantitative
analysis of glioma and compared it with conventional protocol. For CSENSE, on
increasing R(upto 4), even though the error in signal increases, it didn’t
effect much the behavior of concentration-curve. On the other hand it has
reduced the oscillations in CTC, since the increased resolution inversely
effects the presence of ringing related artefacts. Since there was no statistically
significant change observed for hemodynamic parameters at normal appearing
tissues and all perfusion parameters in tumor tissues, R=3.75 can be adopted in
to a clinical setting, which can either be used to improve the scan time,
spatial resolution or coverage. In
this study, better accuracy of grading was observed while combining all
parameters for both protocolsConclusion
For the
application of T1-perfusion MRI to brain tumour(glioma), compressed-SENSE can
be used at R=3.75 without compromising the data quality either to reduce the
scan time or to increase the resolution/coverage. Accuracy of quantitative
parameters as well as their performance in Glioma grading was similar to
conventional imaging protocol(Protocol-2).Acknowledgements
This
work was supported by SERB (Quantitative software tools for processing DCE
perfusion MRI data of patients with intracranial Mass lesions
(YSS/2014/000092)) and IIT Delhi. The authors would like to acknowledge Philips India Limited
in data acquisition and Dr. Pradeep Kumar Gupta and Dr. Mamta Gupta for data
handling. The authors also acknowledge Dr Rana Patir and Dr Sunita Ahlawat for clinical input.References
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