Michael Simca Middleton1, William Haufe1, Jonathan Hooker1, Magnus Borga2,3,4, Olaf Dahlqvist Leinhard2,3,5, Thobias Romu2,3,4, Patrik Tunon2, Nickolas Szeverenyi6, Gavin Hamilton6, Tanya Wolfson6,7, Anthony Gamst6,7, Rohit Loomba8, and Claude B. Sirlin1
1Department of Radiology, UCSD, San Diego, CA, United States, 2Advanced MR Analytics AB (AMRA), Linkoping, Sweden, 3Center for Medical Image Science and Visualization, Linkoping University, Linkoping, Sweden, 4Department of Biomedical Engineering, Linkoping University, Linkoping, Sweden, 5Department of Medicine and Health, Linkoping University, Linkoping, Sweden, 6Radiology, UCSD, San Diego, CA, United States, 7Computational and Applied Statistics Laboratory (CASL), UCSD, San Diego, CA, United States, 8Department of Medicine, UCSD, San Diego, United Kingdom
Synopsis
Current MRI methods
to estimate body tissue compartment volumes rely on manual segmentation, which
is laborious, expensive, not widely available outside specialized centers, and
not standardized. To address these concerns, a novel, semi-automated image
analysis method has been developed. Image acquisition takes about six minutes,
and uses widely available MRI pulse sequences. We found that this method
permits comprehensive body compartment analysis and provides high repeatability
and accuracy. Current and future clinical and drug development studies may
benefit from this methodology, as may clinical settings where monitoring change
in these measures is desired.Introduction
Magnetic
resonance imaging (MRI) can be used to estimate adipose tissue and
muscle volumes
1,2. However, current MRI methods to estimate body tissue
compartment volumes rely on manual segmentation, which is laborious, expensive,
not widely available outside specialized centers, and not standardized. Thus,
currently implemented MRI-based tissue volume assessment techniques are
impractical for many research studies, and not feasible for clinical care. Rapid,
inexpensive, standardized methods are needed to reduce analysis time and cost,
and to enable the use of accurate and precise imaging biomarkers for research
and, perhaps in the future, clinical practice. To address the problems inherent
in manual analysis methods, a novel, semi-automated image analysis method has
been developed
3-6. Image acquisition takes about six minutes and
requires overlapping stacks of MRI fat-water separated images, now widely
available as product sequences. Thus, the aim of this study was to assess the
repeatability and accuracy of a semi-automated analysis method to estimate
abdominal adipose tissue and thigh muscle volumes.
Methods
In this
single-site, prospective, cross-sectional, observational study of 20
adults, an axial, 3D, dual
spoiled-gradient-echo, fat-water
separation MRI sequence was used to estimate adipose and thigh muscle tissue volumes
on a 3T scanner (GE Signa EXCITE HDxt, GE Medical Systems, Milwaukee, WI). Two MRI exams were performed. In
the first MRI exam, the sequence was acquired twice
(i.e., repeats 1 and 2). Then, the subject was taken off the table,
placed back on the table, and the second MRI exam was performed in which that
sequence was acquired again (i.e., repeat 3). Hence, this sequence was acquired
three times for each subject.
Source images were reconstructed
offline to generate water, and calibrated fat images. Each composite image
stack (repeats 1, 2, and 3) was segmented into tissue compartments using a novel,
semi-automated, 3D, non-rigid, multi-atlas segmentation method 3-6.
Sixteen labeled atlases were registered to the image volumes. A voting scheme
was then used to combine the 16 labels into a 3D segmentation of each
compartment. A subset of 20 images obtained in repeat 1 for each subject
was selected for assessment of volume estimation accuracy. As a reference
standard, these 20 images were also segmented manually (sliceOmatic software
package; Tomovision, Ontario, Canada).
Intra- and inter-examination
repeatability was assessed with Bland-Altman analysis, intra-class correlation
(ICC), and coefficient of variation (CV) for paired data. Accuracy was assessed
by linear regression using the manually-segmented tissue volume measurements as
reference.
Results
Cohort characteristics are
summarized in Table 1; subjects
spanned a broad range of body habitus. Examples of semi-automated adipose and
muscle tissue segmentations are shown in Figure
1.
Intra- and inter-examination volume
estimation repeatabilities based on all images in the composite image stacks
are summarized in Tables 2 and 3, respectively. Tissue volume repeatability was
excellent, with intra- and inter-examination ICCs ranging from 0.996 to 0.998,
and CVs ranging from 1.5 to 3.6%.
Tissue volume accuracy indices for
the semi-automated method, using manually-determined measurements as reference for
the 20 selected images, are summarized in Table 4.
Abdominal adipose and thigh muscle estimated volumes were close to the
corresponding manually-determined reference measurements. 95% confidence
intervals (CIs) for all regression slopes included 1, and 95% CIs for all
intercepts included 0. Regression bias
was small for all measures, in the range 28.8 to 100.5 cm3.
Discussion and Conclusion
One
limitation
of this study was that only a single 3T MR scanner from a single manufacturer
was used. Another limitation is that we assessed accuracy in only a subset of
non-randomly selected images, but accuracy of this method has been demonstrated
previously 4,7. We did not address intra- or inter-operator
repeatability using the semi-automated analysis method, but the tested method
requires minimal operator supervision, and intra- and inter-reader agreement was
previously shown to be high 7.
In summary, a
novel, semi-automated tissue segmentation and volume estimation method permits
comprehensive body compartment analysis and provides high repeatability and
accuracy. We are not aware of other segmentation methods with comparable levels
of repeatability. Current and future clinical and drug development studies may
benefit from this methodology, as may clinical settings where monitoring change
in these measures is desired. Future studies might address ways to further
develop, qualify, and validate semi-automated tissue volumes as possible
biomarkers of clinical endpoints.
Acknowledgements
This study was supported by a grant from
Pfizer, Inc. and by NIH grant R01 DK088925.References
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