Optical Property Measurement and Temperature Monitoring in High-Intensity Focused Ultrasound Therapy by Diffuse Optical Tomography: A Correlation Study

Round 1

Reviewer 1 Report

The present attempts to present a novel approach DOCT for imaging volumetric temperature distribution of tissue in HIFU by measuring the temperature-dependent tissue reduced scattering coefficient. The performance was well evaluated using the excised porcine and chicken breast muscle tissues, and the experimental results tried to prove the temperature increase of the tissue samples with the validation of thermocouples. Overall, this work is interesting and the manuscript is well written. Following are the comments which should be addressed for further improvement of the overall quality of the manuscript.

 

The length and number of the figure are quite not enough to be an article. Moreover, Figures 2 and 3 are bringing the same concept as Figures 4 and 5, but the only difference is the target sample. These experiments look redundant. It might be better to submit as "Communication", not "Article". You can take a look at journal guidelines at https://www.mdpi.com/journal/applsci/instructions

 

As the author mentioned in the manuscript, the fast DOT system was developed in the previous article, "Zhang T, Zhou J, Jiang R, Yang H, Carney PR, Jiang H. Pre-seizure state identified by diffuse optical tomography. Scientific reports. 2014”. Even though the same device was used, it still was very interesting to present a new approach as alternative thermometry to measure the temperature caused by HIFU. However, more information about HIFU should be included such as acoustic parameters generated from RF generators and amplifiers. If you used the same acoustic parameters, how is the treated area of porcine and chicken breast different after HIFU? The treated area of chicken breast is much larger as shown in Fig 4 (a). Any reason? Can you also show the cross-section view of the treated target to validate Figures 2 (b) and 4 (b)?

 

There is no information on how thermocouple is co-aligned with HIFU focus. As shown in Figure 1, the medium was water. How did control the impact of water temperature on the tissue sample during HIFU treatment? Is there any layer between the DOT system and water?

 

Correct some typo such as line 140 and 145 (Mhz -> MHZ, 5cm -> 5 cm, and Omega engineering Inc., TJC36-CPSS- 020G-6 ->Omega engineering Inc., TJC36-CPSS-020G-6). Please re-check the grammar and typo.

Comments for author File: Comments.pdf

Author Response

The present attempts to present a novel approach DOCT for imaging volumetric temperature distribution of tissue in HIFU by measuring the temperature-dependent tissue reduced scattering coefficient. The performance was well evaluated using the excised porcine and chicken breast muscle tissues, and the experimental results tried to prove the temperature increase of the tissue samples with the validation of thermocouples. Overall, this work is interesting and the manuscript is well written. Following are the comments which should be addressed for further improvement of the overall quality of the manuscript.

The length and number of the figure are quite not enough to be an article. Moreover, Figures 2 and 3 are bringing the same concept as Figures 4 and 5, but the only difference is the target sample. These experiments look redundant. It might be better to submit as "Communication", not "Article". You can take a look at journal guidelines at https://www.mdpi.com/journal/applsci/instructions

R: Thanks very much for the reviewer’s valuable comments. After reading the journal guidelines, we found that it seems like there are only two article types: “articles” and “reviews”. However, we have no problem to change to “Communication” if it’s acceptable.

As the author mentioned in the manuscript, the fast DOT system was developed in the previous article, "Zhang T, Zhou J, Jiang R, Yang H, Carney PR, Jiang H. Pre-seizure state identified by diffuse optical tomography. Scientific reports. 2014”. Even though the same device was used, it still was very interesting to present a new approach as alternative thermometry to measure the temperature caused by HIFU. However, more information about HIFU should be included such as acoustic parameters generated from RF generators and amplifiers. If you used the same acoustic parameters, how is the treated area of porcine and chicken breast different after HIFU? The treated area of chicken breast is much larger as shown in Fig 4 (a). Any reason? Can you also show the cross-section view of the treated target to validate Figures 2 (b) and 4 (b)?

R:

More details about HIFU were added to the revision (Line 118-122 on page 3).

“We noticed the difference in the fitting results between the chicken breast and porcine samples. The reason for this difference should be due to the nonlinear relationship between temperature and optical properties. It may also be related to the difference in acoustic properties (especially acoustic absorption coefficient) of the two different tissues.”  (Line 219-222 on page 6).

The confusions seen in Figures 2(a) and 4(b) are now corrected. Because the tissue samples are sliced and piled up together, the ablation zone often crossed the interface of two tissue slices. The old pictures we used are improper because they do not show the center of the focal point. In the revised Figure 2, the cross-section view of the treated tissue along HIFU direction (z-axis) was used to replace the old ones. The ruler shown in the pictures indicates the size of the ablation zone (~5 mm) of HIFU in the tissue. However, we also want to point out that the pressure applied to the tissue samples when we cut them would cause some deformation of the ablated area.

There is no information on how thermocouple is co-aligned with HIFU focus. As shown in Figure 1, the medium was water. How did control the impact of water temperature on the tissue sample during HIFU treatment? Is there any layer between the DOT system and water?

R: The confusion seen in Figure 1 is corrected. In this study, neither the tissue samples nor DOT interface were immersed in water. Therefore, the impact of water temperature on the sample tissue was minimal. As shown in the revised Figure 1, “A membrane attached to the bottom of DOT interface was used not only to hold the sample tissues but also insulate the tissues from water. The water level was carefully adjusted to just reach to the membrane in order to realize a good coupling of acoustic signal between water and sample tissues. Because the focal length of the HIFU transducer is known and it was easy to determine the focal zone in the water, the relative positions of HIFU transducer and DOT interface, and thermocouple could be set and fixed prior to the HIFU experiments in the water tank without a tissue sample. The HIFU focal point was set at the center of the DOT interface. Then, the water level was adjusted to the same height as the membrane attached to the DOT interface, which also served as a position marker for the DOT interface in the subsequent experiments.  The thermocouple was fixed on a manual translation stage which could move vertically. A marker indicating the insert depth in the tissue was made on the probe to make sure that the thermocouple reached to the focal point of HIFU.” (Line 128-140 on page 3 and 4).

Correct some typo such as line 140 and 145 (Mhz -> MHZ, 5cm -> 5 cm, and Omega engineering Inc., TJC36-CPSS- 020G-6 ->Omega engineering Inc., TJC36-CPSS-020G-6). Please re-check the grammar and typo.

R: Corrected as suggested.

Author Response File: Author Response.docx

Reviewer 2 Report

 

This paper describes the use of DOCT for temperature control in HIFU.

I do have a fundamental problem with this paper. While the authors suggest they perform temperature measurements, what they do is they access thermal tissue damage, which is a temperature- treatment time relation and highly dependent of tissue characteristics. With the dead tissue samples used this is just protein denaturation. The authors mist fully reframe their paper. The present version in not acceptable. Accessing thermal damage may be a valid way to control HIFU is case tissue ablation is aimed for. But this has nothing to do with thermometry.

Line 25: “a rapidly developing …”. HIFU for hyperthermia is in a steady decline, only new applications like treatment of tremors, opening the BBB and helping immunotherapy flourish. So please adjust this image. Also line 28, omit “successfully”.

Lines 46-55, also the absolute calibration stays a problem.

Lines 60-65: caution, the tissue changes induced by high temperatures are now being described as thermometry. There is no linearity in these effects. So using these optical properties as thermometry is questionable, it is more tissue damage characterization. Tissue damage is dependent on thermal dose, which is a temperature – treatment duration relation.

Lines 90-116 unnecessary details for this paper. While the important part line 117-120 almost gets no attention.

Author Response

This paper describes the use of DOCT for temperature control in HIFU.

I do have a fundamental problem with this paper. While the authors suggest they perform temperature measurements, what they do is they access thermal tissue damage, which is a temperature- treatment time relation and highly dependent of tissue characteristics. With the dead tissue samples used this is just protein denaturation. The authors mist fully reframe their paper. The present version in not acceptable. Accessing thermal damage may be a valid way to control HIFU is case tissue ablation is aimed for. But this has nothing to do with thermometry.

R: We agree with the review’s comments that the optical property change due to thermal damage caused by HIFU could be used to monitor and control HIFU treatment directly. In this study, we tried to further correlate the optical property (Us ) with the temperature. However, we do notice some drawbacks of this method as indicated below. Therefore, we deleted the term “thermometry” and related statements throughout the revised manuscript.

Line 25: “a rapidly developing …”. HIFU for hyperthermia is in a steady decline, only new applications like treatment of tremors, opening the BBB and helping immunotherapy flourish. So please adjust this image. Also line 28, omit “successfully”.

R:

More descriptions and references about those applications of HIFU were added to the revision. (Line 27-30 on page 1).

“a rapidly developing” was replaced by “mature”

The word “successfully” was deleted.

 

Lines 46-55, also the absolute calibration stays a problem.

R: More descriptions and references were added to the revision. (Line 54-57 on page 2).

 

Lines 60-65: caution, the tissue changes induced by high temperatures are now being described as thermometry. There is no linearity in these effects. So using these optical properties as thermometry is questionable, it is more tissue damage characterization. Tissue damage is dependent on thermal dose, which is a temperature – treatment duration relation.

R: Yes, we agree with the review’s comment that optical properties change is related to the thermal dose/tissue damage. We believe that it is the reason why the relationship between optical property and temperature is not linear but nonlinear. More discussion was added to the revision：

“Additionally, we noticed that a limitation of this approach is that the relationship between temperature and  is nonlinear, which adds the complexity of this approach. The primary reason is that the change of optical properties is directly related to thermal dose. Therefore, it may cause the delay of optical property change over temperature. However, if all parameters associated with HIFU keep the same, the whole treatment process should be repeatable which has been demonstrated by the extensive experiments presented in this work. Thus, this nonlinear relationship between temperature and optical property ( ) still could be used to predict the temperature changes during HIFU treatment.” (Line 241-249 on page 7).

 

Lines 90-116 unnecessary details for this paper. While the important part line 117-120 almost gets no attention.

R: Lines 90-116 (introduction to the DOT reconstruction algorithm) is now deleted in the revision. 

 

 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

The manuscript has been improved to a satisfactory level. I thank the authors for diligently and thoroughly addressing my comments.

Minor comments:

1. Please put a space before the number of reference and before unit. I could see a lot of similar errors like these.

For example, page 1, line 27 -- fibroids(7) -> fibroids (7)

For example, page 2 line 80 -- 850nm -> 850 nm

 

2. For temperature unit, be consistent using either use °C or degree

 

3. T in Table 1 should be capitalized. 

 

Author Response

The manuscript has been improved to a satisfactory level. I thank the authors for diligently and thoroughly addressing my comments.

R: Thanks very much for the reviewer’s valuable comments.

 

Minor comments:

1. Please put a space before the number of reference and before unit. I could see a lot of similar errors like these.

For example, page 1, line 27 -- fibroids(7) -> fibroids (7)

For example, page 2 line 80 -- 850nm -> 850 nm

 R: Corrected as suggested.

 

2. For temperature unit, be consistent using either use °C or degree

 R: Corrected as suggested. All “Degree” were replaced by “°C” 

 

3. T in Table 1 should be capitalized. 

 R: Corrected as suggested. (Line 182, 216)

Author Response File: Author Response.docx