Tumor Biomechanics Quantified Using MR Elastography to Predict Response to Neoadjuvant Chemotherapy in Individuals with Breast Cancer

Aaditya Sinha; Arnie Purushotham; Patriek Jurrius; Anne-Sophie van Schelt; Omar Darwish; Belul Shifa; Giacomo Annio; Zhane Peterson; hannah jeffrey; Karen Welsh; Anna Metafa; John  Spence; Ashutosh Kothari; Hisham Hamed; Georgina Bitsakou; Vasileios Karydakis; Mangesh Thorat; Elina Shaari; Ali Sever; Anne Rigg; Tony Ng; Sarah Pinder; Ralph Sinkus

doi:10.1148/rycan.240138

Tumor Biomechanics Quantified Using MR Elastography to Predict Response to Neoadjuvant Chemotherapy in Individuals with Breast Cancer

Aaditya Sinha, Arnie Purushotham^*, Patriek Jurrius, Anne-Sophie van Schelt, Omar Darwish, Belul Shifa, Giacomo Annio, Zhane Peterson, hannah jeffrey, Karen Welsh, Anna Metafa, John Spence, Ashutosh Kothari, Hisham Hamed, Georgina Bitsakou, Vasileios Karydakis, Mangesh Thorat, Elina Shaari, Ali Sever, Anne RiggTony Ng, Sarah Pinder, Ralph Sinkus

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Purpose To evaluat

Purpose

To evaluate the ability of MR elastography (MRE) to noninvasively quantify tissue biomechanics and determine the added diagnostic value of biomechanics for predicting response throughout neoadjuvant chemotherapy (NAC).

Materials and Methods

In this prospective study (between September 2020 and August 2023; registration no. NCT03238144), participants with breast cancer scheduled to undergo NAC underwent five MRE scans at different time points alongside clinical dynamic contrast-enhanced MRI (DCE MRI). Regions of interest were drawn over the tumor region for the first two scans, while for the post-NAC scan, the initial pre-NAC tumor footprint was used. Biomechanics, specifically tumor stiffness and phase angle within these regions of interest, were quantified as well as the corresponding ratios relative to before NAC (tumor-stiffness ratio and phase-angle ratio, respectively). Postsurgical pathologic analysis was used to determine complete and partial responders. Furthermore, a repeatability analysis was performed for 18 participants.

Results

Datasets of 41 female participants (mean age, 47 years ± 12.5 [SD]) were included in this analysis. The tumor-stiffness ratio following NAC decreased significantly for complete responders and increased for partial responders (0.76 ± 0.16 and 1.14 ± 0.24, respectively; P < .001). The phase-angle ratio after the first cycle of the first NAC regimen compared with before NAC predicted pathologic response (1.23 ± 0.31 vs 0.91 ± 0.34; P < .001). Combining the tumor stiffness ratio with DCE MRI improved specificity compared with DCE MRI alone (96% vs 44%) while maintaining the high sensitivity of DCE MRI (94%). Repeatability analysis showed excellent agreement for elasticity (repeatability coefficient, 8.3%) and phase angle (repeatability coefficient, 5%).

Conclusion

MRE–derived phase-angle ratio and tumor stiffness ratio were associated with pathologic complete response in participants with breast cancer undergoing NAC, and a combined DCE MRI plus MRE approach significantly enhanced specificity for identification of complete responders after NAC, while maintaining high sensitivity.e the ability of MR elastography (MRE) to noninvasively quantify tissue biomechanics and determine the added diagnostic value of biomechanics for predicting response throughout neoadjuvant chemotherapy (NAC). Materials and Methods In this prospective study (between September 2020 and August 2023; registration no. NCT03238144), participants with breast cancer scheduled to undergo NAC underwent five MRE scans at different time points alongside clinical dynamic contrast-enhanced MRI (DCE MRI). Regions of interest were drawn over the tumor region for the first two scans, while for the post-NAC scan, the initial pre-NAC tumor footprint was used. Biomechanics, specifically tumor stiffness and phase angle within these regions of interest, were quantified as well as the corresponding ratios relative to before NAC (tumor-stiffness ratio and phase-angle ratio, respectively). Postsurgical pathologic analysis was used to determine complete and partial responders. Furthermore, a repeatability analysis was performed for 18 participants. Results Datasets of 41 female participants (mean age, 47 years ± 12.5 [SD]) were included in this analysis. The tumor-stiffness ratio following NAC decreased significantly for complete responders and increased for partial responders (0.76 ± 0.16 and 1.14 ± 0.24, respectively; P < .001). The phase-angle ratio after the first cycle of the first NAC regimen compared with before NAC predicted pathologic response (1.23 ± 0.31 vs 0.91 ± 0.34; P < .001). Combining the tumor stiffness ratio with DCE MRI improved specificity compared with DCE MRI alone (96% vs 44%) while maintaining the high sensitivity of DCE MRI (94%). Repeatability analysis showed excellent agreement for elasticity (repeatability coefficient, 8.3%) and phase angle (repeatability coefficient, 5%). Conclusion MRE-derived phase-angle ratio and tumor stiffness ratio were associated with pathologic complete response in participants with breast cancer undergoing NAC, and a combined DCE MRI plus MRE approach significantly enhanced specificity for identification of complete responders after NAC, while maintaining high sensitivity. Keywords: Breast Cancer, MR Elastography, Neoadjuvant Chemotherapy, Dynamic Contrast-enhanced MRI Supplemental material is available for this article. Clinical trials registration no. NCT03238144 Published under a CC BY 4.0 license.

Original language	English
Article number	e240138
Pages (from-to)	e240138
Journal	Radiology. Imaging cancer
Volume	7
Issue number	2
Early online date	14 Feb 2025
DOIs	https://doi.org/10.1148/rycan.240138
Publication status	Published - Mar 2025

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Sinha, A., Purushotham, A., Jurrius, P., van Schelt, A.-S., Darwish, O., Shifa, B., Annio, G., Peterson, Z., jeffrey, H., Welsh, K., Metafa, A., Spence, J., Kothari, A., Hamed, H., Bitsakou, G., Karydakis, V., Thorat, M., Shaari, E., Sever, A., ... Sinkus, R. (2025). Tumor Biomechanics Quantified Using MR Elastography to Predict Response to Neoadjuvant Chemotherapy in Individuals with Breast Cancer. Radiology. Imaging cancer, 7(2), e240138. Article e240138. https://doi.org/10.1148/rycan.240138

@article{f9b67bcaa3ad486caaee1b8d9d277809,

title = "Tumor Biomechanics Quantified Using MR Elastography to Predict Response to Neoadjuvant Chemotherapy in Individuals with Breast Cancer",

abstract = "Purpose To evaluatPurposeTo evaluate the ability of MR elastography (MRE) to noninvasively quantify tissue biomechanics and determine the added diagnostic value of biomechanics for predicting response throughout neoadjuvant chemotherapy (NAC).Materials and MethodsIn this prospective study (between September 2020 and August 2023; registration no. NCT03238144), participants with breast cancer scheduled to undergo NAC underwent five MRE scans at different time points alongside clinical dynamic contrast-enhanced MRI (DCE MRI). Regions of interest were drawn over the tumor region for the first two scans, while for the post-NAC scan, the initial pre-NAC tumor footprint was used. Biomechanics, specifically tumor stiffness and phase angle within these regions of interest, were quantified as well as the corresponding ratios relative to before NAC (tumor-stiffness ratio and phase-angle ratio, respectively). Postsurgical pathologic analysis was used to determine complete and partial responders. Furthermore, a repeatability analysis was performed for 18 participants.ResultsDatasets of 41 female participants (mean age, 47 years ± 12.5 [SD]) were included in this analysis. The tumor-stiffness ratio following NAC decreased significantly for complete responders and increased for partial responders (0.76 ± 0.16 and 1.14 ± 0.24, respectively; P < .001). The phase-angle ratio after the first cycle of the first NAC regimen compared with before NAC predicted pathologic response (1.23 ± 0.31 vs 0.91 ± 0.34; P < .001). Combining the tumor stiffness ratio with DCE MRI improved specificity compared with DCE MRI alone (96% vs 44%) while maintaining the high sensitivity of DCE MRI (94%). Repeatability analysis showed excellent agreement for elasticity (repeatability coefficient, 8.3%) and phase angle (repeatability coefficient, 5%).ConclusionMRE–derived phase-angle ratio and tumor stiffness ratio were associated with pathologic complete response in participants with breast cancer undergoing NAC, and a combined DCE MRI plus MRE approach significantly enhanced specificity for identification of complete responders after NAC, while maintaining high sensitivity.e the ability of MR elastography (MRE) to noninvasively quantify tissue biomechanics and determine the added diagnostic value of biomechanics for predicting response throughout neoadjuvant chemotherapy (NAC). Materials and Methods In this prospective study (between September 2020 and August 2023; registration no. NCT03238144), participants with breast cancer scheduled to undergo NAC underwent five MRE scans at different time points alongside clinical dynamic contrast-enhanced MRI (DCE MRI). Regions of interest were drawn over the tumor region for the first two scans, while for the post-NAC scan, the initial pre-NAC tumor footprint was used. Biomechanics, specifically tumor stiffness and phase angle within these regions of interest, were quantified as well as the corresponding ratios relative to before NAC (tumor-stiffness ratio and phase-angle ratio, respectively). Postsurgical pathologic analysis was used to determine complete and partial responders. Furthermore, a repeatability analysis was performed for 18 participants. Results Datasets of 41 female participants (mean age, 47 years ± 12.5 [SD]) were included in this analysis. The tumor-stiffness ratio following NAC decreased significantly for complete responders and increased for partial responders (0.76 ± 0.16 and 1.14 ± 0.24, respectively; P < .001). The phase-angle ratio after the first cycle of the first NAC regimen compared with before NAC predicted pathologic response (1.23 ± 0.31 vs 0.91 ± 0.34; P < .001). Combining the tumor stiffness ratio with DCE MRI improved specificity compared with DCE MRI alone (96% vs 44%) while maintaining the high sensitivity of DCE MRI (94%). Repeatability analysis showed excellent agreement for elasticity (repeatability coefficient, 8.3%) and phase angle (repeatability coefficient, 5%). Conclusion MRE-derived phase-angle ratio and tumor stiffness ratio were associated with pathologic complete response in participants with breast cancer undergoing NAC, and a combined DCE MRI plus MRE approach significantly enhanced specificity for identification of complete responders after NAC, while maintaining high sensitivity. Keywords: Breast Cancer, MR Elastography, Neoadjuvant Chemotherapy, Dynamic Contrast-enhanced MRI Supplemental material is available for this article. Clinical trials registration no. NCT03238144 Published under a CC BY 4.0 license.",

author = "Aaditya Sinha and Arnie Purushotham and Patriek Jurrius and {van Schelt}, Anne-Sophie and Omar Darwish and Belul Shifa and Giacomo Annio and Zhane Peterson and hannah jeffrey and Karen Welsh and Anna Metafa and John Spence and Ashutosh Kothari and Hisham Hamed and Georgina Bitsakou and Vasileios Karydakis and Mangesh Thorat and Elina Shaari and Ali Sever and Anne Rigg and Tony Ng and Sarah Pinder and Ralph Sinkus",

year = "2025",

month = mar,

doi = "10.1148/rycan.240138",

language = "English",

volume = "7",

pages = "e240138",

journal = "Radiology. Imaging cancer",

issn = "2638-616X",

publisher = "Radiological Society of North America Inc.",

number = "2",

}

Sinha, A , Purushotham, A , Jurrius, P , van Schelt, A-S , Darwish, O, Shifa, B, Annio, G, Peterson, Z, jeffrey, H, Welsh, K, Metafa, A, Spence, J, Kothari, A, Hamed, H, Bitsakou, G, Karydakis, V, Thorat, M, Shaari, E, Sever, A, Rigg, A, Ng, T , Pinder, S & Sinkus, R 2025, 'Tumor Biomechanics Quantified Using MR Elastography to Predict Response to Neoadjuvant Chemotherapy in Individuals with Breast Cancer', Radiology. Imaging cancer, vol. 7, no. 2, e240138, pp. e240138. https://doi.org/10.1148/rycan.240138

TY - JOUR

T1 - Tumor Biomechanics Quantified Using MR Elastography to Predict Response to Neoadjuvant Chemotherapy in Individuals with Breast Cancer

AU - Sinha, Aaditya

AU - Purushotham, Arnie

AU - Jurrius, Patriek

AU - van Schelt, Anne-Sophie

AU - Darwish, Omar

AU - Shifa, Belul

AU - Annio, Giacomo

AU - Peterson, Zhane

AU - jeffrey, hannah

AU - Welsh, Karen

AU - Metafa, Anna

AU - Spence, John

AU - Kothari, Ashutosh

AU - Hamed, Hisham

AU - Bitsakou, Georgina

AU - Karydakis, Vasileios

AU - Thorat, Mangesh

AU - Shaari, Elina

AU - Sever, Ali

AU - Rigg, Anne

AU - Ng, Tony

AU - Pinder, Sarah

AU - Sinkus, Ralph

PY - 2025/3

Y1 - 2025/3

N2 - Purpose To evaluatPurposeTo evaluate the ability of MR elastography (MRE) to noninvasively quantify tissue biomechanics and determine the added diagnostic value of biomechanics for predicting response throughout neoadjuvant chemotherapy (NAC).Materials and MethodsIn this prospective study (between September 2020 and August 2023; registration no. NCT03238144), participants with breast cancer scheduled to undergo NAC underwent five MRE scans at different time points alongside clinical dynamic contrast-enhanced MRI (DCE MRI). Regions of interest were drawn over the tumor region for the first two scans, while for the post-NAC scan, the initial pre-NAC tumor footprint was used. Biomechanics, specifically tumor stiffness and phase angle within these regions of interest, were quantified as well as the corresponding ratios relative to before NAC (tumor-stiffness ratio and phase-angle ratio, respectively). Postsurgical pathologic analysis was used to determine complete and partial responders. Furthermore, a repeatability analysis was performed for 18 participants.ResultsDatasets of 41 female participants (mean age, 47 years ± 12.5 [SD]) were included in this analysis. The tumor-stiffness ratio following NAC decreased significantly for complete responders and increased for partial responders (0.76 ± 0.16 and 1.14 ± 0.24, respectively; P < .001). The phase-angle ratio after the first cycle of the first NAC regimen compared with before NAC predicted pathologic response (1.23 ± 0.31 vs 0.91 ± 0.34; P < .001). Combining the tumor stiffness ratio with DCE MRI improved specificity compared with DCE MRI alone (96% vs 44%) while maintaining the high sensitivity of DCE MRI (94%). Repeatability analysis showed excellent agreement for elasticity (repeatability coefficient, 8.3%) and phase angle (repeatability coefficient, 5%).ConclusionMRE–derived phase-angle ratio and tumor stiffness ratio were associated with pathologic complete response in participants with breast cancer undergoing NAC, and a combined DCE MRI plus MRE approach significantly enhanced specificity for identification of complete responders after NAC, while maintaining high sensitivity.e the ability of MR elastography (MRE) to noninvasively quantify tissue biomechanics and determine the added diagnostic value of biomechanics for predicting response throughout neoadjuvant chemotherapy (NAC). Materials and Methods In this prospective study (between September 2020 and August 2023; registration no. NCT03238144), participants with breast cancer scheduled to undergo NAC underwent five MRE scans at different time points alongside clinical dynamic contrast-enhanced MRI (DCE MRI). Regions of interest were drawn over the tumor region for the first two scans, while for the post-NAC scan, the initial pre-NAC tumor footprint was used. Biomechanics, specifically tumor stiffness and phase angle within these regions of interest, were quantified as well as the corresponding ratios relative to before NAC (tumor-stiffness ratio and phase-angle ratio, respectively). Postsurgical pathologic analysis was used to determine complete and partial responders. Furthermore, a repeatability analysis was performed for 18 participants. Results Datasets of 41 female participants (mean age, 47 years ± 12.5 [SD]) were included in this analysis. The tumor-stiffness ratio following NAC decreased significantly for complete responders and increased for partial responders (0.76 ± 0.16 and 1.14 ± 0.24, respectively; P < .001). The phase-angle ratio after the first cycle of the first NAC regimen compared with before NAC predicted pathologic response (1.23 ± 0.31 vs 0.91 ± 0.34; P < .001). Combining the tumor stiffness ratio with DCE MRI improved specificity compared with DCE MRI alone (96% vs 44%) while maintaining the high sensitivity of DCE MRI (94%). Repeatability analysis showed excellent agreement for elasticity (repeatability coefficient, 8.3%) and phase angle (repeatability coefficient, 5%). Conclusion MRE-derived phase-angle ratio and tumor stiffness ratio were associated with pathologic complete response in participants with breast cancer undergoing NAC, and a combined DCE MRI plus MRE approach significantly enhanced specificity for identification of complete responders after NAC, while maintaining high sensitivity. Keywords: Breast Cancer, MR Elastography, Neoadjuvant Chemotherapy, Dynamic Contrast-enhanced MRI Supplemental material is available for this article. Clinical trials registration no. NCT03238144 Published under a CC BY 4.0 license.

AB - Purpose To evaluatPurposeTo evaluate the ability of MR elastography (MRE) to noninvasively quantify tissue biomechanics and determine the added diagnostic value of biomechanics for predicting response throughout neoadjuvant chemotherapy (NAC).Materials and MethodsIn this prospective study (between September 2020 and August 2023; registration no. NCT03238144), participants with breast cancer scheduled to undergo NAC underwent five MRE scans at different time points alongside clinical dynamic contrast-enhanced MRI (DCE MRI). Regions of interest were drawn over the tumor region for the first two scans, while for the post-NAC scan, the initial pre-NAC tumor footprint was used. Biomechanics, specifically tumor stiffness and phase angle within these regions of interest, were quantified as well as the corresponding ratios relative to before NAC (tumor-stiffness ratio and phase-angle ratio, respectively). Postsurgical pathologic analysis was used to determine complete and partial responders. Furthermore, a repeatability analysis was performed for 18 participants.ResultsDatasets of 41 female participants (mean age, 47 years ± 12.5 [SD]) were included in this analysis. The tumor-stiffness ratio following NAC decreased significantly for complete responders and increased for partial responders (0.76 ± 0.16 and 1.14 ± 0.24, respectively; P < .001). The phase-angle ratio after the first cycle of the first NAC regimen compared with before NAC predicted pathologic response (1.23 ± 0.31 vs 0.91 ± 0.34; P < .001). Combining the tumor stiffness ratio with DCE MRI improved specificity compared with DCE MRI alone (96% vs 44%) while maintaining the high sensitivity of DCE MRI (94%). Repeatability analysis showed excellent agreement for elasticity (repeatability coefficient, 8.3%) and phase angle (repeatability coefficient, 5%).ConclusionMRE–derived phase-angle ratio and tumor stiffness ratio were associated with pathologic complete response in participants with breast cancer undergoing NAC, and a combined DCE MRI plus MRE approach significantly enhanced specificity for identification of complete responders after NAC, while maintaining high sensitivity.e the ability of MR elastography (MRE) to noninvasively quantify tissue biomechanics and determine the added diagnostic value of biomechanics for predicting response throughout neoadjuvant chemotherapy (NAC). Materials and Methods In this prospective study (between September 2020 and August 2023; registration no. NCT03238144), participants with breast cancer scheduled to undergo NAC underwent five MRE scans at different time points alongside clinical dynamic contrast-enhanced MRI (DCE MRI). Regions of interest were drawn over the tumor region for the first two scans, while for the post-NAC scan, the initial pre-NAC tumor footprint was used. Biomechanics, specifically tumor stiffness and phase angle within these regions of interest, were quantified as well as the corresponding ratios relative to before NAC (tumor-stiffness ratio and phase-angle ratio, respectively). Postsurgical pathologic analysis was used to determine complete and partial responders. Furthermore, a repeatability analysis was performed for 18 participants. Results Datasets of 41 female participants (mean age, 47 years ± 12.5 [SD]) were included in this analysis. The tumor-stiffness ratio following NAC decreased significantly for complete responders and increased for partial responders (0.76 ± 0.16 and 1.14 ± 0.24, respectively; P < .001). The phase-angle ratio after the first cycle of the first NAC regimen compared with before NAC predicted pathologic response (1.23 ± 0.31 vs 0.91 ± 0.34; P < .001). Combining the tumor stiffness ratio with DCE MRI improved specificity compared with DCE MRI alone (96% vs 44%) while maintaining the high sensitivity of DCE MRI (94%). Repeatability analysis showed excellent agreement for elasticity (repeatability coefficient, 8.3%) and phase angle (repeatability coefficient, 5%). Conclusion MRE-derived phase-angle ratio and tumor stiffness ratio were associated with pathologic complete response in participants with breast cancer undergoing NAC, and a combined DCE MRI plus MRE approach significantly enhanced specificity for identification of complete responders after NAC, while maintaining high sensitivity. Keywords: Breast Cancer, MR Elastography, Neoadjuvant Chemotherapy, Dynamic Contrast-enhanced MRI Supplemental material is available for this article. Clinical trials registration no. NCT03238144 Published under a CC BY 4.0 license.

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U2 - 10.1148/rycan.240138

DO - 10.1148/rycan.240138

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Tumor Biomechanics Quantified Using MR Elastography to Predict Response to Neoadjuvant Chemotherapy in Individuals with Breast Cancer

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