Jeff L Zhang1, Christopher C Conlin2, Xiaowan Li2, Gwenael Layec3,4, Ken Chang1, Jayashree Kalpathy-Cramer1,5, and Vivian S Lee6
1A.A. Martinos Center for Biomedical Imaging; Radiology, Massachusetts General Hospital, Charlestown, MA, United States, 2Radiology and Imaging Science, University of Utah, Salt Lake City, UT, United States, 3Department of Kinesiology, University of Massachusetts, Amherst, MA, United States, 4Institute for Applied Life Sciences, University of Massachusetts, Amherst, MA, United States, 5MGH and BWH Center for Clinical Data Science, Massachusetts General Hospital, Charlestown, MA, United States, 6Verily Life Sciences, Cambridge, MA, United States
Synopsis
We tested the feasibility
of using artificial neural network (NN) to rapidly map calf-muscle perfusion,
and assessed the importance of data diversity in NN training. Forty-eight DCE
MRI data were collected from healthy and diseased subjects stimulated by
plantar flexion. Results: the NN method was much faster than model fitting. The
NN trained with diverse data gave estimates with mean absolute error (MAE) of
15.9 ml/min/100g, significantly more accurate than regular model fitting or NN
trained with homogeneous data (MAE 22.3 and 24.9 ml/min/100g, P<0.001). Conclusion:
properly trained NN is capable of estimating muscle perfusion with high
accuracy and speed.
Introduction
Tissue-perfusion
maps from DCE MRI can reveal regional tissue heterogeneity and improve the diagnosis
of various pathological conditions [1-7].
For perfusion mapping, voxel-wise fitting to a tracer kinetic model is conventionally
done with least-mean-square optimization. Hence, perfusion mapping is a
time-consuming process that is mostly done off-line. In addition, converge to
local optimum often leads to inaccurate perfusion estimates.
Artificial neural network (NN) shows
promise in multiple applications of medical imaging. With simple operations, NN
can be easily programmed on any computer platform, and does not rely on
optimization. In this study, we tested the feasibility of the NN approach for
quantifying exercise-stimulated perfusion of calf muscles from DCE MRI. Different
from other organs, muscle perfusion can vary dramatically with exercise
intensity, pathologic condition, and even aging. To accurately estimate
perfusion with such large variations, we assessed the importance of training NN
with diverse data.Materials and Methods
DCE
MRI for calf muscles
This IRB-approved study recruited 13
young healthy subjects, 5 elderly healthy and 3 patients with peripheral artery
disease (PAD), and used a 3T MRI scanner (TimTrio; Siemens). Calf muscles were
first stimulated by plantar flexion. The exercise protocols included load of 4,
8 or 16 lbs for 3 minutes, and exercise to exhaustion [8].
For each subject, we performed MRI after two or four of the exercise protocols,
so collected 48 MRI data. Immediately after exercise, dynamic images of an
axial calf slice were acquired after 0.05 mmol/kg gadoteridol (Prohance;
Bracco), using 2D SR-prepared turboFLASH [8].
Voxel-wise model fitting was applied to tracer concentration
curves of each tissue voxel (TC) and an arterial region (AIF) [9]. The model fitting was
implemented with optimization initialized with one set of parameter values (termed
“regular fit”), and 25 sets of initial values (“multi-grid fit”). The 25 sets
of values were the combinations of 5 perfusion values and 5 bolus arrival time
values. The perfusion estimates from the multi-grid fit were used as reference values
for both NN training and testing evaluation.
Training
of NN for quantifying muscle perfusion
We
performed the training and testing of NN in TensorFlow (version 1.13; Python
3.7.3), using a fully connected feed-forward network with 7 hidden layers and
70 nodes per layer. Each node used the rectified linear unit as the activation
function. The input for the network was the vector that concatenated voxel TC
and AIF, and the output was perfusion value. Two groups of data were separately
used for training: a) a diverse group of 20 MRI data including 2 young healthy
subjects (each stimulated by 4 different exercises), 4 elderly healthy subjects
and 2 PAD patients (each by 2 different exercises); b) a homogeneous group of
20 data including 10 young healthy subjects (each repeated a same exercise
twice). Both the trained networks were tested on the remaining 8 data sets that
included 1 young healthy subject (stimulated by 4 different exercises), 1
elderly healthy subject and 1 PAD patient (stimulated by 2 exercises). Using the perfusion values from multi-grid fit
as reference, mean absolute error (MAE) and correlation coefficient (R) were
computed for the estimates by each estimation method. Results
Compared to the reference values, the regular-fit estimates differed
by MAE of 22.3 ml/min/100g and correlation coefficient R of 0.889. The NN
trained by the diverse group performed significantly better with lower MAE of
15.9 (P value<0.001) and higher R 0.949. The NN trained with homogeneous
data gave error (MAE 24.9; R 0.850) significantly higher than the other two
methods (P value <0.001). While all the three methods gave estimates with
low error for perfusion less than 100 ml/min/100g (Figure 1), the NN trained
with diverse data outperformed the other two methods substantially in estimating
higher perfusion values.
For a same
dataset, perfusion maps were generated by all the four methods (Figure 2). To
generate the map, the multi-grid fit took 79 minutes 34 seconds, the regular
fit 2 minutes 41 seconds, and the NN methods each took less than 1 second. All
the activated muscle groups, including medial and lateral gastrocnemius and
anterior tibial muscles, and even the arterial regions inside the muscles were accurately
enhanced in the map generated by the NN method (Figure 2C).Discussion
With the NN method, perfusion maps of 8 testing data (about
25,000 voxels) were generated almost instantaneously, and the estimates were
comparable to the values from multi-grid fit that took about 70-80 minutes for
each data set. For NN training, the diverse group included all three types of
subjects: young healthy, elderly healthy and PAD, and each subject was
stimulated by exercise of at least two different intensities. In contrast, the homogeneous
group included only 20 young healthy subjects, stimulated by a same exercise
only. This result indicates that to estimate tissue perfusion accurately with
the NN method, training data should match to those of the target data, or the
more diverse the collection of the training data, the more robust the network.
In conclusion, the NN
method is capable of providing perfusion estimates with comparable accuracy as
conventional model fitting, and its extremely fast implementation would make
real-time perfusion mapping possible. Acknowledgements
No acknowledgement found.References
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