Paper Info Reviews Meta-review Author Feedback Post-Rebuttal Meta-reviews

Authors

Robin Mieling, Sarah Latus, Martin Fischer, Finn Behrendt, Alexander Schlaefer

Abstract

Compression-based optical coherence elastography (OCE) enables characterization of soft tissue by estimating elastic properties. However, previous probe designs have been limited to surface applications. We propose a bevel tip OCE needle probe for percutaneous insertions, where biomechanical characterization of deep tissue could enable precise needle placement, e.g., in prostate biopsy. We consider a dual-fiber OCE needle probe that provides estimates of local strain and load at the tip. Using a novel setup, we simulate deep tissue indentations where frictional forces and bulk sample displacement can affect biomechanical characterization. Performing surface and deep tissue indentation experiments, we compare our approach with external force and needle position measurements at the needle shaft. We consider two tissue mimicking materials simulating healthy and cancerous tissue and demonstrate that our probe can be inserted into deep tissue layers. Compared to surface indentations, external force-position measurements are strongly affected by frictional forces and bulk displacement and show a relative error of 49.2% and 42.4% for soft and stiff phantoms, respectively. In contrast, quantitative OCE measurements show a reduced relative error of 26.4% and 4.9% for deep indentations of soft and stiff phantoms, respectively. Finally, we demonstrate that the OCE measurements can be used to effectively discriminate the tissue mimicking phantoms.

Link to paper

DOI: https://doi.org/10.1007/978-3-031-43996-4_58

SharedIt: https://rdcu.be/dnwP2

Link to the code repository

N/A

Link to the dataset(s)

N/A


Reviews

Review #1

  • Please describe the contribution of the paper

    The authors propose a bevel tip dual fiber OCE needle probe to estimate the local strain and load at tip for biomechanical characterization of deep tissue. They simulate percutaneous insertions using two tissue mimicking phantoms with similar elastic properties to healthy and cancerous prostate tissue and a customized experimental setup. The authors demonstrate that their probe can be inserted into deep tissue layers for biomechanical characterization due to the bevel tip design. The quantitative results show that OCE measurements provide a better agreement between surface and deep tissue indentations compared to external force-position measurements and allows for robust discriminate between two different tissue mimicking phantoms.

  • Please list the main strengths of the paper; you should write about a novel formulation, an original way to use data, demonstration of clinical feasibility, a novel application, a particularly strong evaluation, or anything else that is a strong aspect of this work. Please provide details, for instance, if a method is novel, explain what aspect is novel and why this is interesting.

    The authors propose a new bevel tip dual fiber OCT needle probe design for biomechanical characterization of deep tissue. It has three strengths:

    1. The OCE probe has a bevel tip which enables the insertion into deep tissue and addresses the limitations of previous OCE probes that have been limited to surface applications.

    2. The OCE probe contains dual fibers which enable simultaneous estimations of tissue compression and force, and thus enable estimations of the tissue elastic properties.

    3. The OCE probe measures tissue compression and force both at the needle tip, and thus address the limitation of external force-position measurements which suffer from additional friction force and bulk motion.

  • Please list the main weaknesses of the paper. Please provide details, for instance, if you think a method is not novel, explain why and provide a reference to prior work.
    1. The paper does not provide in vivo validation of their method, which could limit the practical use of the proposed method.

    2. The paper does not compare the performance of the proposed OCE probe with other OCE techniques, which may provide a better understanding of its advantages and limitations.

    3. The paper only tests two tissue-mimicking phantoms to simulate healthy and cancerous tissue, which may not fully represent the variability of real prostate tissue.

  • Please rate the clarity and organization of this paper

    Very Good

  • Please comment on the reproducibility of the paper. Note, that authors have filled out a reproducibility checklist upon submission. Please be aware that authors are not required to meet all criteria on the checklist - for instance, providing code and data is a plus, but not a requirement for acceptance

    The OCE probe design and the experimental setup can be easily reproduced based on the detailed descriptions in the manuscript. However, the data processing scheme lacks clarity due to the inappropriate usage of notations.

  • Please provide detailed and constructive comments for the authors. Please also refer to our Reviewer’s guide on what makes a good review: https://conferences.miccai.org/2023/en/REVIEWER-GUIDELINES.html

    Major comments:

    1. In the OCE probe, there is a small spatial gap between fiber 1 and fiber 2, and the applied force is not uniform due to the bevel tip design. It is not clear how to ensure that the compression and the force are measured at the exact same location. And if not, will this cause some systematic errors in determining the elastic properties of deep tissue?

    2. The OCT image in Fig. 3 does not seem to have a good quality. Is it possible to consider doing A-scan average to improve the signal to noise ratio for better compression and force estimations?

    Minor comments:

    1. In Fig. 1 Right, it may be better to label which is before needle insertion and which is after.

    2. The notations in Eq. 4 are a little messy. the authors use $\delta u_i (z,t)$ in Eq. 3, then use $u_i (z,t)$ for deformation in the paragraph between Eq. 3 and Eq. 4, and then use $\Delta u_i (z,t)$ in Eq. 4. It is not clear what their differences are.

    3. Following the previous concern, the authors mention that spatial averaging is performed to reduce noise. It is not clear how the spatial average is done. And if $\Delta u_i (z,t)$ is after the spatial average, why is it still a function of $z$?

    4. In Eq. 5, it is not clear why there is a bar over $\Delta \bar{u}_2$ and what the difference is between $\Delta \bar{u}_2$ and $\Delta u_1$ without the bar in Eq. 4.

    5. The authors mention that $a_F$ is calibrated based on force-position curves. Since the authors mention logging motor positions in the same paragraph, it is easy to get confused whether the position in this force-position curve is measured from the motor or from the OCT.

    6. In Results section, first paragraph line 2, “external force-position curves are shown in Fig. 4a” should be “external force-position curves are shown in Fig. 5a”.

    7. In Fig. 5a, it is not explained why two trails in “Mat. B Deep” are different from the rest.

  • Rate the paper on a scale of 1-8, 8 being the strongest (8-5: accept; 4-1: reject). Spreading the score helps create a distribution for decision-making

    6

  • Please justify your recommendation. What were the major factors that led you to your overall score for this paper?

    The paper has detailed description about the OCE probe design, system calibration and data processing steps. It demonstrates the feasibility of using the OCE probe to discriminate between two different tissue mimicking phantoms by measuring accurate elastic properties in deep tissue, which suggests its potential usage in clinical diagnosis. However, no in-vivo tests are performed and evaluated.

  • Reviewer confidence

    Confident but not absolutely certain

  • [Post rebuttal] After reading the author’s rebuttal, state your overall opinion of the paper if it has been changed

    6

  • [Post rebuttal] Please justify your decision

    The authors have addressed the primary concerns raised by the reviewer. However, they still need to refine specific details to enhance the overall quality of the manuscript.



Review #2

  • Please describe the contribution of the paper

    The authors propose a bevel tip OCE needle probe for percutaneous insertions. They propose a novel and pertinent setup to simulate deep tissue indentations where frictional forces and bulk sample displacement can affect biomechanical characterization. In this study, the authors show that the OCE measurements can be used to effectively discriminate hepatic tissue mimicking phantoms.

  • Please list the main strengths of the paper; you should write about a novel formulation, an original way to use data, demonstration of clinical feasibility, a novel application, a particularly strong evaluation, or anything else that is a strong aspect of this work. Please provide details, for instance, if a method is novel, explain what aspect is novel and why this is interesting.

    The method proposed here is most relevant and responds to a real problem. Performing OCE in deep tissue structures is a real challenge and the proposed solution is pertinent for the biomechanical characterization during needle insertions.

  • Please list the main weaknesses of the paper. Please provide details, for instance, if you think a method is not novel, explain why and provide a reference to prior work.

    The main limiting points that I would see are the following:

    The forces taken into account here result in an estimation of the Young’s modulus (equations 2 and 3). However, as specified, the stress field is unknown and not measurable, so it is not the elasticity but the stiffness that is evaluated here. On the other hand, the expressions used assume that all the forces exerted are in compression, but clearly, most of the forces used here and involved in the measurements are in shear, which does not make this expression correct. It is quite difficult for me to understand both the device and the assumptions used here.

    On the other hand, the forces considered are up to strains of the order of 20ù, which is well beyond the linear behavior of the tissue, for which the liver tissue appears as hyperelastic (non linear elasticity), with a dependence of the stiffness with the level of deformation, which risks to distort the measurements. I would recommend not to exceed 8 to 10% of deformation for the method proposed here. This works here because gelatin is highly linear (up to 200 or even 300% deformation), which does not correctly simulate the behavior of liver tissue. I would suggest to the authors to use rather PVC plastisol type gels, hyperelastic, as well as incorporating a significant viscous phase, or even to test directly on ex vivo liver pieces (the phantom is of interest only if it is characterized in parallel by another method taken as reference).

    Finally, the indentation speeds do not seem to be specified. This is a crucial point because liver tissue has an eminently viscous behavior (and even more so in the case of NASH), greatly influencing the measurement of its mechanical properties as a function of the loading speed, the strain rate, but also the measurement times (with possible relaxation phenomena). The measurements will be all the more impacted as, in the set up proposed here, it is not the stress-strain relation but the force-strain relation that is used, the latter being highly sensitive to the phenomena of viscous relaxation and dependence on the loading speed. Here again, gelatin cannot account for this kind of behavior, which is found very strongly in liver tissue.

  • Please rate the clarity and organization of this paper

    Very Good

  • Please comment on the reproducibility of the paper. Note, that authors have filled out a reproducibility checklist upon submission. Please be aware that authors are not required to meet all criteria on the checklist - for instance, providing code and data is a plus, but not a requirement for acceptance

    I think that as long as one remains on a purely elastic, highly linear and non-viscous (and a fortiori very homogeneous) gel, the approach works very well and I consider it to be highly relevant, very well thought out and very well done. However, I have serious reservations about its application and reproducibility on liver tissue, whether ex or in vivo (for the reasons previously mentioned in the limiting points). In my opinion, the proofs as to the reproducibility on liver tissue (or in a general way on biological tissue) remain entirely to be made (even if this first very preliminary stage on gel remains obviously necessary). To sum up: the tests presented here are clearly enough to be completely reproducible, but in my opinion not yet proven to be exportable on biological tissue, and in the first place in the liver (which remains the first stated objective).

  • Please provide detailed and constructive comments for the authors. Please also refer to our Reviewer’s guide on what makes a good review: https://conferences.miccai.org/2023/en/REVIEWER-GUIDELINES.html

    The authors use gelatin fantom, that is highly linear (up to 200 or even 300% deformation), non-viscous, and which does not correctly simulate the behavior of liver tissue in large strain. I would suggest to the authors to use rather PVC plastisol type gels, hyperelastic, as well as incorporating a significant viscous phase, or even to test directly on ex vivo liver pieces (the phantom is of interest only if it is characterized in parallel by another method taken as reference). I think that as long as one remains on a purely elastic, highly linear and non-viscous (and a fortiori very homogeneous) gel, the approach works very well and I consider it to be highly relevant, very well thought out and very well done. However, I have serious reservations about its application and reproducibility on liver tissue, whether ex or in vivo (for the reasons previously mentioned in the limiting points). In my opinion, the proofs as to the reproducibility on liver tissue (or in a general way on biological tissue) remain entirely to be made (even if this first very preliminary stage on gel remains obviously necessary).

  • Rate the paper on a scale of 1-8, 8 being the strongest (8-5: accept; 4-1: reject). Spreading the score helps create a distribution for decision-making

    4

  • Please justify your recommendation. What were the major factors that led you to your overall score for this paper?

    These reasons have been already detailed above (absence of clear validation on a realistic fantome or tissue, weakness/limitation of some of the assumptions that are not fully representative of the biological soft tissue in the current sollicitations)

  • Reviewer confidence

    Somewhat confident

  • [Post rebuttal] After reading the author’s rebuttal, state your overall opinion of the paper if it has been changed

    N/A

  • [Post rebuttal] Please justify your decision

    N/A



Review #3

  • Please describe the contribution of the paper

    This work demonstrates the feasibility of use a needle of beveled tip to estimate OCE elasticity for deep tissue needle insertions and show good agreement between surface and deep tissue indentations compared to external measurements.

  • Please list the main strengths of the paper; you should write about a novel formulation, an original way to use data, demonstration of clinical feasibility, a novel application, a particularly strong evaluation, or anything else that is a strong aspect of this work. Please provide details, for instance, if a method is novel, explain what aspect is novel and why this is interesting.

    proposed a beveled tip needle to faciliate the estimation of deep tissue elastography.

  • Please list the main weaknesses of the paper. Please provide details, for instance, if you think a method is not novel, explain why and provide a reference to prior work.

    the needle based OCE and their appliations have been demonstrated before.

  • Please rate the clarity and organization of this paper

    Good

  • Please comment on the reproducibility of the paper. Note, that authors have filled out a reproducibility checklist upon submission. Please be aware that authors are not required to meet all criteria on the checklist - for instance, providing code and data is a plus, but not a requirement for acceptance

    Not be able to comment since this is mainly an engineering and hardware work.

  • Please provide detailed and constructive comments for the authors. Please also refer to our Reviewer’s guide on what makes a good review: https://conferences.miccai.org/2023/en/REVIEWER-GUIDELINES.html

    two tissue mimicking materials are not enough, demonstration on ex vivo tissues will help.

  • Rate the paper on a scale of 1-8, 8 being the strongest (8-5: accept; 4-1: reject). Spreading the score helps create a distribution for decision-making

    5

  • Please justify your recommendation. What were the major factors that led you to your overall score for this paper?

    New OCE needle design

  • Reviewer confidence

    Very confident

  • [Post rebuttal] After reading the author’s rebuttal, state your overall opinion of the paper if it has been changed

    N/A

  • [Post rebuttal] Please justify your decision

    N/A




Primary Meta-Review

  • Please provide your assessment of this work, taking into account all reviews. Summarize the key strengths and weaknesses of the paper and justify your recommendation. In case you deviate from the reviewers’ recommendations, explain in detail the reasons why. In case of an invitation for rebuttal, clarify which points are important to address in the rebuttal.

    The authors propose a bevel tip dual fiber OCE needle probe for the biomechanical characterization of deep tissue stiffness. This could potentially be useful in accurately sampling the tumor while avoiding inaccuracies in sampling the neighboring healthy tissue. The reviewers agree that there is significant clinical potential. However, there were several questions raised about the methodology and validation – specifically on the use of only two tissue-mimicking phantoms for validation. The authors are encouraged to address the reviewers’ comments in this rebuttal phase.




Author Feedback

Dear Reviewers, Area Chairs, and Program Chairs,

Thank you for your time and effort. We greatly appreciate the detailed insights and comments.

Reviewers #1, #2, and #3 criticize that the method has not yet been validated on soft tissue.

We agree that experiments with soft tissue samples will be important for further validation of the proposed method. However, in our current study, we primarily demonstrate the feasibility of OCE measurements at different depths by taking frictional forces and bulk tissue motion into account. Therefore, we designed an experiment that allows systematic and reproducible analysis of elasticity estimation in deeper tissue layers. Our results show that external force and position measurements, as often proposed in similar experimental setups, do not enable the robust characterization even in this simplified experiment with two phantom materials. In contrast, we illustrate that the proposed approach that considers measurements at the needle tip can overcome this limitation. Real tissue has a much more complex structure and exhibits greater variation between measurements, making it difficult to establish a local ‘ground truth’ for comparison. Therefore, we consider the current work, including the experimental approach, to be an important first step demonstrating the feasibility of deep tissue characterization using OCE.

We suggest changing the last paragraph in the Discussion as follows:

“Further experiments need to include biological soft tissue to validate the approach for clinical application, as our evaluation is currently limited to homogeneous gelatin.”

Reviewer #1 questions whether the offset between the two optical fibers will result in a systematic error.

We agree that the positioning of the fibers (as well as the tip geometry) affects the measurements. However, we still provide reproducible measurements because the tip geometry and fiber position are constants of the needle probe. Hence, the computed quantitative values are reproducible and already allow distinguishing tissue. Moreover, we are working on applying machine learning methods to map the values to common physical quantities, i.e.., to essentially calibrate the needle.

Reviewer #2 questions the validity of our approach for non-linear materials.

Our goal was to prove the reproducibility of OCE measurements at different depths, where both friction forces and bulk tissue motion are present. To this end, the mostly linear behavior of gelatin gels is no substantial limitation. However, we agree that consideration of non-linearity will be important for the characterization of biomedical soft tissue samples. We also agree that our simplification of assuming a linear relationship between the tip force and strain measured at the OCE needle tip in Eq. 2 cannot represent the complex biomechanics of soft tissue. For future studies with soft tissue samples, we expect that we can measure non-linear behavior via separate estimation of strain and tip force, envisioning a machine learning-based approach for data processing and thus considering non-linear models for tissue characterization.

We propose to change the beginning of page 4 as follows:

“[…] we hypothesize instead that the elasticity is relative to the applied tip force F_T and the resulting local strain. To obtain a single parameter for comparing two measurements, we assume a linear relation

E_{OCE} (F_T, epsilon_l) ≈ F_T / epsilon_l (2)

in the context of this work.”

Finally, we would like to thank reviewer #2 for the suggested use of plastisol and the detailed information on non-linear behavior of liver tissue, which is very relevant for future experiments.

We hope to have addressed the major concerns of the reviewers and will address minor concerns in the camera-ready manuscript.

Thank you for considering our manuscript.




Post-rebuttal Meta-Reviews

Meta-review # 1 (Primary)

  • Please provide your assessment of the paper taking all information into account, including rebuttal. Highlight the key strengths and weaknesses of the paper, clarify how you reconciled contrasting review comments and scores, indicate if concerns were successfully addressed in the rebuttal, and provide a clear justification of your decision. If you disagree with some of the (meta)reviewer statements, you can indicate so in your meta-review. Please make sure that the authors, program chairs, and the public can understand the reason for your decision.

    The authors have addressed the reviewers’ comments sufficiently. I recommend accepting the paper.



Meta-review #2

  • Please provide your assessment of the paper taking all information into account, including rebuttal. Highlight the key strengths and weaknesses of the paper, clarify how you reconciled contrasting review comments and scores, indicate if concerns were successfully addressed in the rebuttal, and provide a clear justification of your decision. If you disagree with some of the (meta)reviewer statements, you can indicate so in your meta-review. Please make sure that the authors, program chairs, and the public can understand the reason for your decision.

    The major limitations arise from the limited validation combined with incorrect conclusions (largely explained by R2). The rebuttal addresses these concerns to some extent, and while I am in favor of leaning positively on this one, I feel that the suggested changes to the manuscript are insufficient to adequately address the limitations and caveats outlined by the reviewers.

    I explicitly and stronlgy urge the authors to seriously revise their manuscript to clearly highlight the limitations outlined by the reviewers, and their implications for future studies/work.



Meta-review #3

  • Please provide your assessment of the paper taking all information into account, including rebuttal. Highlight the key strengths and weaknesses of the paper, clarify how you reconciled contrasting review comments and scores, indicate if concerns were successfully addressed in the rebuttal, and provide a clear justification of your decision. If you disagree with some of the (meta)reviewer statements, you can indicate so in your meta-review. Please make sure that the authors, program chairs, and the public can understand the reason for your decision.

    This remains a borderline paper with weaknesses overweighing strengths.



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