A Quantitative Method for the Evaluation of Deep Vein Thrombosis in a Murine Model Using Three-Dimensional Ultrasound Imaging
and John A. Hossack 1,*
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors
The authors have used 3D high-frequency B-mode and Doppler ultrasound imaging to determine the volumes of implanted bovine blood clots in a mouse DVT model in order to evaluate candidate thrombolytic therapies in rodents. They validated the method by correlating the volume measurements with clot weights. The method was appropriately validated and will be a useful addition to the field. However, there should be more points between 5 and 15 mm3 in Figure 5. This would require some more in vitro data acquisition.
Author Response
Thank you for your suggestions. The data in Figure 5 were from the in vivo experiment of mouse. The stenosis of the IVC can generate great variance in the blood clot volume and each mouse generates blood clots of different size. We managed to perform the experiments in similar conditions. However, the responses of the mice were unpredictable. Two more new datapoints were added from our recent experiment and the corresponding results were updated in section 3.2.
Reviewer 2 Report
Comments and Suggestions for Authors
The authors present a 3D ultrasound approach for the quantitative assessment of clots in a mouse model of DVT.
The article is well written and it has an high quality of presentation.
Has this method a possible clinical applications? I suggest to explore the possible developments of this technique.
Author Response
We gratefully appreciate for your suggestions. Similar methods have been evaluated in clinical patient setting and are discussed in line 42. We added more discussion about its application starting at line 235. To further apply the method in clinics, it is essential to develop the implementation of 3D ultrasound, for example, mechanical translation of the transducer or freehand scan.
Reviewer 3 Report
Comments and Suggestions for Authors
I thought this to be an interesting and provacative study.In the paragraph beginning on line 205 you discuss some of the problems imaging the IVC. Although yoiu triy to overcome these issues how do you think they influence your results?
Eventually if this technique is used in patients do you believe the larger size of vessels will able to be imaged in the same way and with similar accuracy?
Author Response
- Thank you for pointing this out. The imaging artifacts can affect our segmentation of the thrombus. For example, if the shadowing in Figure 6h blocks the signal of the thrombus underneath, it is difficult to detect the boundary. In this situation, the size might not be accurate (line 206). However, imaging from multiple angles at different timing can acquire the ultrasound slices of the best quality. The proposed method therefore generates a reliable measurement of thrombus volume.
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Ultrasound has been used as a standard procedure in the detection of DVT in clinics, therefore, the resolution and accuracy are not an issue. For final clinical applications, the implementation of 3D ultrasound is usually performed by translating an ultrasound transducer. Additionally, there have been attempt to evaluate 3D thrombus volume discussed in the manuscript (line 42 and 238) using a similar technique. The details have been discussed manuscript in a new paragraph starting at line 235 in the revised manuscript.
