Matthew Van Houten1, Xue Feng1, Yang Yang2, Austin Robinson3, Craig Meyer1, and Michael Salerno1,3
1Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States, 2Biomedical Engineering and Imaging Institute and Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States, 3Department of Medicine, University of Virginia, Charlottesville, VA, United States
Synopsis
While quantitative first-pass quantitative perfusion imaging is an
excellent non-invasive tool for the evaluation of coronary artery disease, current
processing shortcomings have kept it from widespread clinical use. In this
study, we developed a pipeline which robustly and automatically segments,
registers, and quantifies flow with our ultra-high resolution quantitative
perfusion sequence.
Introduction
Quantitative first-pass myocardial perfusion imaging
has demonstrated great diagnostic and prognostic utility1,2. However, shortcomings of the
current techniques include incomplete ventricular coverage, limited
spatial-temporal resolution, unsatisfactory motion correction, and unreliable
segmentation of the myocardium for pixel-wise quantitative perfusion
calculations. We previously developed a spiral first-pass quantitative sequence
with whole heart coverage to address the acquisition limitations. To address
the processing hurdles, we developed an automatic pipeline that (1) segments
the myocardium with a neural network, (2) robustly registers the segmented
contours, and (3) generates quantitative perfusion maps.Methods
Adenosine stress CMR exams were performed on 12
patients for the evaluation of CAD on a 3T scanner with a Dotarem bolus (0.075
mmol/kg) after a three minute adenosine infusion (140μg/kg/min). We used our interleaved
spiral, dual contrast, ultra-high resolution quantitative perfusion sequence as
described previously (Figure 1)3. The imaging parameters were:
FOV 340mm, TE/TR 1.0/7.0 ms, and saturation recovery time (SRT) 90 ms, with 6
slices (thickness=10mm) for whole-heart coverage. We acquired four PD images
without a saturation preparation pulse (FA=5°) before collecting the remaining
images (FA=15°). The AIF images use FA=15°
and FA=45° for the PD and remaining images, respectively.
Additionally, the AIF images were 2x accelerated single-shot spiral
trajectories, with 6.95 mm2 in-plane resolution and with an SRT of
10 ms.
We reconstructed the images using L1-SPIRiT4 by defining the sparsity
transform as the finite temporal difference (Figure 2). Manual contours were
drawn for all frames for both the training set and validation to train a 2D U-Net5 for myocardial segmentation6. The output contours were then
used as a direct input for deformable ANTs7 registration of the image
set. Signal intensity was converted to gadolinium concentration8, where the PD images were
denoised by a Poisson NL means filter9.
Quantitative perfusion values were then calculated on
a pixel-by-pixel basis using three different approaches: (1) manually fitting
the Fermi function on each segment before using those parameters as the initial
point for pixel fits, (2) automatically fitting the Fermi function10 to each pixel with a coarse
grid search as the initial guess, and (3) automatically fitting the distributed
parameter11 (DP) model. A Fermi function was
fit to the concentration-time data through a deconvolution of the AIF and the
tissue function, while the DP model was fit in the Laplace domain to estimate
flow. The AIF time-concentration curve was fit to the gamma-variate function. In
the manual Fermi fit, the end of first-pass was chosen by the user. For the
automatic Fermi fit, the end of first pass was defined as the first time point
in the gamma-variate that was less than 5% of the maximum AIF value. The
automatic Fermi’s coarse grid was defined as t0 = [0:0.25:5] s, A =
[0:0.01:0.5] 1/s, k = [0:0.02:0.5] 1/s, and tau = [0:0.5:10] s, where t0 is the
contrast arrival time, A is the amplitude scale factor, and k and tau are Fermi
shape parameters. Flow was determined from the Fermi function amplitude at t=0.
The automatic DP’s coarse grid was defined as Fp = [0:0.1:8] mg/min/mL, Tc =
[0:0.25:4] min, Te = [0:0.5:10] min, and T= [0:0.5:5] min, where Fp is the plasma
flow, Tc is the mean capillary time, Te is the mean interstitial transit time,
and T is the mean transit time.Results
Figure 3 shows an example quantitative perfusion fit
(Figure 3A), along with a segmental Bland-Altman comparison of the automatic
Fermi fit (Figures 3B-C) in comparison to the manual Fermi fit. Over the 36
segments, the mean adjusted-R2 values were 0.87±0.12, 0.94±0.11,
and 0.96±0.04 for the manual Fermi, auto Fermi, and DP model fitting routines,
respectively.
Figure 4 is an
example output from the automatic processing pipeline. The subject had a large ischemic
region in the inferoseptal and inferior segments of their heart (Figure 4A).
The flow is reduced in the ischemic region, which is shown in the three
compared methods (Figures 4B-D). Figure 4B shows our prior pipeline, where the
ROIs were drawn by hand and the Fermi fits were segmentally tweaked by hand to
produce the maps. Figures 4C and 4D show quantitative perfusion maps from our
proposed pipeline, where the U-Net ROIs were used to register the images before
fitting the models. Figure 4C shows the automatic Fermi function maps, while
Figure 4D shows the DP maps.Discussion
The
automatic Fermi and automatic DP fitting methods both produced high quality
flow maps. The automatic DP method had higher adjusted-R2 values in comparison to automatic
Fermi. DP may be more advantageous since it uses all of the time points, as
opposed to Fermi, which requires a defined cut-off timepoint for the end of
first pass perfusion. Both methods performed better than the manual Fermi
fitting routine. While the DP model slightly underestimated stress flow values
in comparison with the manual Fermi function, it is in agreement with prior art11.Conclusion
We
developed an automatic pipeline for ultra-high resolution first-pass myocardial
perfusion, which robustly fits the automatic Fermi and DP models to pixelwise
concentration-time curves with superior R2 values to the manual fitting algorithm.
The pipeline employs DCNN-based automatic LV segmentation for ANTs
registration, which improves the accuracy of the fits.Acknowledgements
This
work was supported by NIH R01 HL131919 and T32 EB003841. References
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