Hannah Fels-Palesandro, Sophie Heuer, Berin Boztepe, Yannik Streibel, Johannes Ungermann, Chenchen Pan, Jonas G Scheck, Manuel Fischer, Volker J Sturm, Daniel D Azorín, Kianush Karimian-Jazi, Giacomo Annio, Amir Abdollahi, Ina Weidenfeld, Wolfgang Wick, Varun Venkataramani, Sabine Heiland, Frank Winkler, Martin Bendszus, Ralph Sinkus, Michael O Breckwoldt, Katharina Schregel
{"title":"通过磁共振弹性成像评估实验性胶质瘤的肿瘤细胞侵袭和放疗反应","authors":"Hannah Fels-Palesandro, Sophie Heuer, Berin Boztepe, Yannik Streibel, Johannes Ungermann, Chenchen Pan, Jonas G Scheck, Manuel Fischer, Volker J Sturm, Daniel D Azorín, Kianush Karimian-Jazi, Giacomo Annio, Amir Abdollahi, Ina Weidenfeld, Wolfgang Wick, Varun Venkataramani, Sabine Heiland, Frank Winkler, Martin Bendszus, Ralph Sinkus, Michael O Breckwoldt, Katharina Schregel","doi":"10.1002/jmri.29567","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Gliomas are highly invasive brain neoplasms. MRI is the most important tool to diagnose and monitor glioma but has shortcomings. In particular, the assessment of tumor cell invasion is insufficient. This is a clinical dilemma, as recurrence can arise from MRI-occult glioma cell invasion.</p><p><strong>Hypothesis: </strong>Tumor cell invasion, tumor growth and radiotherapy alter the brain parenchymal microstructure and thus are assessable by diffusion tensor imaging (DTI) and MR elastography (MRE).</p><p><strong>Study type: </strong>Experimental, animal model.</p><p><strong>Animal model: </strong>Twenty-three male NMRI nude mice orthotopically implanted with S24 patient-derived glioma cells (experimental mice) and 9 NMRI nude mice stereotactically injected with 1 μL PBS (sham-injected mice).</p><p><strong>Field strength/sequence: </strong>2D and 3D T2-weighted rapid acquisition with refocused echoes (RARE), 2D echo planar imaging (EPI) DTI, 2D multi-slice multi-echo (MSME) T2 relaxometry, 3D MSME MRE at 900 Hz acquired at 9.4 T (675 mT/m gradient strength).</p><p><strong>Assessment: </strong>Longitudinal 4-weekly imaging was performed for up to 4 months. Tumor volume was assessed in experimental mice (n = 10 treatment-control, n = 13 radiotherapy). The radiotherapy subgroup and 5 sham-injected mice underwent irradiation (3 × 6 Gy) 9 weeks post-implantation/sham injection. MRI-/MRE-parameters were assessed in the corpus callosum and tumor core/injection tract. Imaging data were correlated to light sheet microscopy (LSM) and histology.</p><p><strong>Statistical tests: </strong>Paired and unpaired t-tests, a P-value ≤0.05 was considered significant.</p><p><strong>Results: </strong>From week 4 to 8, a significant callosal stiffening (4.44 ± 0.22 vs. 5.31 ± 0.29 kPa) was detected correlating with LSM-proven tumor cell invasion. This was occult to all other imaging metrics. Histologically proven tissue destruction in the tumor core led to an increased T2 relaxation time (41.65 ± 0.34 vs. 44.83 ± 0.66 msec) and ADC (610.2 ± 12.27 vs. 711.2 ± 13.42 × 10<sup>-6</sup> mm<sup>2</sup>/s) and a softening (5.51 ± 0.30 vs. 4.24 ± 0.29 kPa) from week 8 to 12. Radiotherapy slowed tumor progression.</p><p><strong>Data conclusion: </strong>MRE is promising for the assessment of key glioma characteristics.</p><p><strong>Evidence level: </strong>NA TECHNICAL EFFICACY: Stage 2.</p>","PeriodicalId":3,"journal":{"name":"ACS Applied Electronic Materials","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Assessment of Tumor Cell Invasion and Radiotherapy Response in Experimental Glioma by Magnetic Resonance Elastography.\",\"authors\":\"Hannah Fels-Palesandro, Sophie Heuer, Berin Boztepe, Yannik Streibel, Johannes Ungermann, Chenchen Pan, Jonas G Scheck, Manuel Fischer, Volker J Sturm, Daniel D Azorín, Kianush Karimian-Jazi, Giacomo Annio, Amir Abdollahi, Ina Weidenfeld, Wolfgang Wick, Varun Venkataramani, Sabine Heiland, Frank Winkler, Martin Bendszus, Ralph Sinkus, Michael O Breckwoldt, Katharina Schregel\",\"doi\":\"10.1002/jmri.29567\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Gliomas are highly invasive brain neoplasms. MRI is the most important tool to diagnose and monitor glioma but has shortcomings. In particular, the assessment of tumor cell invasion is insufficient. This is a clinical dilemma, as recurrence can arise from MRI-occult glioma cell invasion.</p><p><strong>Hypothesis: </strong>Tumor cell invasion, tumor growth and radiotherapy alter the brain parenchymal microstructure and thus are assessable by diffusion tensor imaging (DTI) and MR elastography (MRE).</p><p><strong>Study type: </strong>Experimental, animal model.</p><p><strong>Animal model: </strong>Twenty-three male NMRI nude mice orthotopically implanted with S24 patient-derived glioma cells (experimental mice) and 9 NMRI nude mice stereotactically injected with 1 μL PBS (sham-injected mice).</p><p><strong>Field strength/sequence: </strong>2D and 3D T2-weighted rapid acquisition with refocused echoes (RARE), 2D echo planar imaging (EPI) DTI, 2D multi-slice multi-echo (MSME) T2 relaxometry, 3D MSME MRE at 900 Hz acquired at 9.4 T (675 mT/m gradient strength).</p><p><strong>Assessment: </strong>Longitudinal 4-weekly imaging was performed for up to 4 months. Tumor volume was assessed in experimental mice (n = 10 treatment-control, n = 13 radiotherapy). The radiotherapy subgroup and 5 sham-injected mice underwent irradiation (3 × 6 Gy) 9 weeks post-implantation/sham injection. MRI-/MRE-parameters were assessed in the corpus callosum and tumor core/injection tract. Imaging data were correlated to light sheet microscopy (LSM) and histology.</p><p><strong>Statistical tests: </strong>Paired and unpaired t-tests, a P-value ≤0.05 was considered significant.</p><p><strong>Results: </strong>From week 4 to 8, a significant callosal stiffening (4.44 ± 0.22 vs. 5.31 ± 0.29 kPa) was detected correlating with LSM-proven tumor cell invasion. This was occult to all other imaging metrics. Histologically proven tissue destruction in the tumor core led to an increased T2 relaxation time (41.65 ± 0.34 vs. 44.83 ± 0.66 msec) and ADC (610.2 ± 12.27 vs. 711.2 ± 13.42 × 10<sup>-6</sup> mm<sup>2</sup>/s) and a softening (5.51 ± 0.30 vs. 4.24 ± 0.29 kPa) from week 8 to 12. Radiotherapy slowed tumor progression.</p><p><strong>Data conclusion: </strong>MRE is promising for the assessment of key glioma characteristics.</p><p><strong>Evidence level: </strong>NA TECHNICAL EFFICACY: Stage 2.</p>\",\"PeriodicalId\":3,\"journal\":{\"name\":\"ACS Applied Electronic Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-08-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Electronic Materials\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/jmri.29567\",\"RegionNum\":3,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, ELECTRICAL & ELECTRONIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Electronic Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/jmri.29567","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, ELECTRICAL & ELECTRONIC","Score":null,"Total":0}
Assessment of Tumor Cell Invasion and Radiotherapy Response in Experimental Glioma by Magnetic Resonance Elastography.
Background: Gliomas are highly invasive brain neoplasms. MRI is the most important tool to diagnose and monitor glioma but has shortcomings. In particular, the assessment of tumor cell invasion is insufficient. This is a clinical dilemma, as recurrence can arise from MRI-occult glioma cell invasion.
Hypothesis: Tumor cell invasion, tumor growth and radiotherapy alter the brain parenchymal microstructure and thus are assessable by diffusion tensor imaging (DTI) and MR elastography (MRE).
Study type: Experimental, animal model.
Animal model: Twenty-three male NMRI nude mice orthotopically implanted with S24 patient-derived glioma cells (experimental mice) and 9 NMRI nude mice stereotactically injected with 1 μL PBS (sham-injected mice).
Field strength/sequence: 2D and 3D T2-weighted rapid acquisition with refocused echoes (RARE), 2D echo planar imaging (EPI) DTI, 2D multi-slice multi-echo (MSME) T2 relaxometry, 3D MSME MRE at 900 Hz acquired at 9.4 T (675 mT/m gradient strength).
Assessment: Longitudinal 4-weekly imaging was performed for up to 4 months. Tumor volume was assessed in experimental mice (n = 10 treatment-control, n = 13 radiotherapy). The radiotherapy subgroup and 5 sham-injected mice underwent irradiation (3 × 6 Gy) 9 weeks post-implantation/sham injection. MRI-/MRE-parameters were assessed in the corpus callosum and tumor core/injection tract. Imaging data were correlated to light sheet microscopy (LSM) and histology.
Statistical tests: Paired and unpaired t-tests, a P-value ≤0.05 was considered significant.
Results: From week 4 to 8, a significant callosal stiffening (4.44 ± 0.22 vs. 5.31 ± 0.29 kPa) was detected correlating with LSM-proven tumor cell invasion. This was occult to all other imaging metrics. Histologically proven tissue destruction in the tumor core led to an increased T2 relaxation time (41.65 ± 0.34 vs. 44.83 ± 0.66 msec) and ADC (610.2 ± 12.27 vs. 711.2 ± 13.42 × 10-6 mm2/s) and a softening (5.51 ± 0.30 vs. 4.24 ± 0.29 kPa) from week 8 to 12. Radiotherapy slowed tumor progression.
Data conclusion: MRE is promising for the assessment of key glioma characteristics.
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