Dynamic Contrast-Enhanced MRI in the Abdomen of Mice with High Temporal and Spatial Resolution Using Stack-of-Stars Sampling and KWIC Reconstruction
Round 1
Reviewer 1 Report
The article is interesting and well written. The authors precisely explained its purpose, assumptions and the state of knowledge in the field of dynamic contrast enhanced MRI. Then they presented an original method of produce artifact free images with good SNR leading to robust estimation of DCE parameters. The originality of the work is based on an optimized DCE protocol consisting of three acquisitions. The selection of data for research was carried out in an appropriate manner. The test results are properly interpreter. The authors also indicated the limitation of their model and the possibilities of future work. The figures and table clearly present the data and are easy to interpret. The literature review has been provided in a fair and complete manner.There are several inaccuracies in the article which do not affect the understanding and quality of the article. I indicate them below.
1. In the "discussion" section, there is no direct comparison of the results with data published in similar studies.
2. The "conclusions" part is missing. Some of the text from the "discussion" chapter could be moved to this section.
3. Line 132: the values are highlighted.
4. Line 29, 168: double space.
Author Response
- In the “discussion” section there is no comparison of the results with data published in similar studies
Three paragraphs have been added to the discussion section (lines 467-495) in which this comparison is made. Note numerous additional citations were also added.
- The “conclusions” part is missing
A conclusions section was added.
- Line132: the values hare highlighted
The highlighting was removed
- Line 29, 168: double space
The superfluous spaces were removed.
Reviewer 2 Report
1The manuscript describes an application of existing methods to a novel application. The results are clearly presented. However, the improvements compared with the previous publications are unclear and the grammas should be checked.
1) Please add full name of “RF inhomogeneity”.
22) Please distinguish the different tissues in Fig. 4 with different colors. Please also add data points (scatter plot) on top of Fig. 4. Please add p values to support the claim in line 392-394.
33) The novelty is unclear. E.g., can the previous protocols in clinical DCE studies directly be applied to the preclinical DCE dataset? If yes, what’s the difference and what are the major improvements of the proposed method? What’s the difference between clinical & preclinical DCE (e.g., the flow velocities) and how could that affect the algorithm design and/or solved by the proposed method?
Author Response
- Please add full name of “RF inhomogeneity”
It is not clear what the reviewer is asking for here. No changes were made in response to this point.
- Please distinguish the different tissues in Fig 4 with different colors. Please also add data points to plot on top of fig 4. Please add p values to support claim in line 392-394
The figure was reworked to include 1) different colors for the different tissue types, 2) data points are included, 3) p-values were added for the NC<->B1 comparison. P-values were also added to the body of the manuscript for the B1 <-> B1+OVS comparison.
- The novelty is unclear, E.G. can the previous protocols in clinical studies directly be applied to preclinical dec dataset? If yes, what’s the difference and what are the major improvements of the proposed methods? What’s the difference between clinical & preclinical DCE (e.g. the flow velocities ) and how could that affect the algorithm design and/or solved by the proposed method.
Clinical DCE methods do not translate to pre-clinical studies for the following reasons: 1) respiration rates in mice are an order of magnitude more rapid than in humans (see lines 70-71). The rapid respiration motion leads to significant motion artifacts, especially in abdominal studies, 2) the bolus transit times are much more rapid in small animals and therefore the pre-clinical studies generally require higher temporal resolution than their clinical counter parts , 3) the vasculature in mice is small relative to the spatial resolution that can be achieved with fast imaging on pre-clinical scanners (see lines 58-60).
Our paper demonstrates that the combination of SoS sampling and KWIC image reconstruction can be used to address items (1) and (2) above. We employ the reference tissue method of analysis because of the difficulties in extracting an AIF from the dynamic data due to item (3) above.
A Conclusions section was added which states that this is the first demonstration of DCE with SoS + KWIC in mouse models in order to emphasize the novelty.
Reviewer 3 Report
In this study, the authors developed a quantitative DCE-MRI protocol for mouse abdominal imaging via integrated the SoS sampling with KWIC reconstruction. The development was demonstrated to provide motion-robust AFI B1 mapping and VFA T1 mapping, as well as achieve DCE images with both high-spatial and high-temporal resolution. Overall, this study is well designed and performed, the methods and results are clearly presented, and the development itself is an important contribution to the advances in quantitative DCE-MRI acquisition in abdomen. A few specific comments/suggestions are provided below.
1. Would the slice orientation affect the imaging robustness to motion?
2. Did you perform any comparison between the developed SoS+KWIC DCE acquisition strategy with the more conventional DCE acquisition? How much can your developed technique reduce the effect of motion in DCE acquisition and quantitative parameter estimation? These comparisons would be helpful supports to the value of your developed protocol.
3. Please label in Figure 4 to show observed significant differences between VFA, VFA+B1, and VFA+B1+OVS.
4. Please provide more comparisons between your developed protocols with previous studies on motion-robust dynamic imaging and high temporal resolution DCE imaging in the Discussion.
Author Response
- Would slice orientation affect the imaging robustness to motion?
The slice orientation relative to the predominant direction of motion is relevant. The motion robustness of the SoS sampling scheme is limited to in plane motion as phase encoding is employed in the slice dimension. However, motion sensitivity decreases as voxel size increases. Our protocol employs anisotropic resolution with the slice thickness (voxel dimension) being several times larger than the in-plane voxel size. The relatively large slice thickness reduces the sensitivity of the protocol to motion in the slice dimension.
- Did you perform any comparison between the developed SoS+Kwic DCE strategy with the more conventional DCE acquisition? How much can your developed technique reduce the effect of motion in DCE acquisition and quantitative parameter estimation? These comparisons would be helpful supports to the value of your developed protocol.
The spatial and/or temporal resolution that can be achieved with Cartesian sampling is significantly lower than that presented in our manuscript. As such it is not possible to make direct comparisons. In addition, motion corruption is an intermittent problem and varies significantly from study to study making it difficult to quantify.
The discussion section was expanded to include qualitative comparisons between the method presented in the current work and previous studies (lines 467-495).
- Please label in Figure 4 to show observed significant differences between VFA and …
P-values were added to the figure and to the body of the manuscript.
- Please provide more comparisons between your developed protocols with previous studies
The discussion section was expanded to include comparisons of our method to previous studies of DCE in mouse abdomen (lines 467-495).
Round 2
Reviewer 2 Report
The authors partially solved my questions.
1) Please add "radiofrequency field (RF)" to the 1st appearance of "RF".
2) For point 3), please double check the usage of reference [27] in lines 81-90. It is still not clear to me whether the previous method (line 89-91, ref27 & 29) can be applied to this pre-clinical dataset? Adding a comparative study may help solve this concern.
Author Response
1) The requested change was made (line 52)
2) The reviewer is correct, the citation 27 (now 31), is not appropriate in this context and was removed. Note that this citation is used in the methods section (line 190) to describe the image reconstruction method.
The following was added to the first paragraph in the discussion section (lines 442-9) in order to clarify the relationship between previous work and the current manuscript.
"Our method is a direct translation of the previously demonstrated clinical technique for DCE in the chest to abdominal studies in mice [27] without the use of self-gated respiratory phase binning for motion compensation. The motion correction methods used in the clinical study are not feasible in small animals because the interval between consecutive samples of the center of k-space is long relative to the respiration period in small animals. The present study relies on the oversampling of the center of k-space and fact that the magnitude of the respiration motion is significantly reduced in the abdomens of anesthetized animals relative to that in the chest."
