Skip to main content
Erschienen in: European Radiology 3/2020

08.11.2019 | Experimental

DWI and IVIM are predictors of Ki67 proliferation index: direct comparison of MRI images and pathological slices in a murine model of rhabdomyosarcoma

verfasst von: Yuan Yuan, Dewei Zeng, Yajie Liu, Juan Tao, Yu Zhang, Jie Yang, Tsendjav Lkhagvadorj, Zhenzhen Yin, Shaowu Wang

Erschienen in: European Radiology | Ausgabe 3/2020

Einloggen, um Zugang zu erhalten

Abstract

Objectives

The purpose of this study was to investigate the correlation of diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) with the Ki67 proliferation index in a murine model of rhabdomyosarcoma.

Methods

The rhabdomyosarcoma model was established by injecting RD cells into the right hind flank of nude mice. The mice underwent 3.0T magnetic resonance imaging (MRI), including DWI and IVIM. The apparent diffusion coefficient (ADC), D, D*, and f were calculated with the ADW4.7 workstation. A specialized method was employed to ensure the pathological sections corresponded to the correct MRI slices. The Ki67 proliferation index was analyzed by immunohistochemistry, and any possible correlations were assessed between the DWI and IVIM parameters and Ki67 proliferation index.

Results

Twenty-seven rhabdomyosarcoma mice were established successfully. After 46 days, the average tumor volume reached 1094.78 ± 678.77 mm3. The average ADC, D, and D* values were 1.0470 ± 0.2036 × 10−3 mm2/s, 0.7237 ± 0.0971 × 10−3 mm2/s, and 4.8497 ± 1.6293 × 10−3 mm2/s, respectively. The range in f values was 0.102–0.229. The ADC and D values showed a moderate negative correlation with the Ki67 proliferation indexes (r = − 0.543, p = 0.003; r = − 0.491, p = 0.009, respectively). In addition, the f value showed a weak negative correlation with the Ki67 proliferation indexes (r = − 0.151, p = 0.451), while the D* value showed no association with the Ki67 proliferation indexes (r = − 0.037, p = 0.853).

Conclusions

The ADC value of DWI, along with the D value of IVIM, may be reflective of Ki67 proliferation indexes in murine models of rhabdomyosarcoma.

Key Points

DWI and IVIM parameters are correlated with Ki67 proliferation indexes in rhabdomyosarcoma mouse models.
• A specialized method ensured a strong correlation between pathological sections and MRI slices, resulting in a robust radiological-pathological correlation.
Literatur
1.
2.
3.
Zurück zum Zitat Gerber NK, Wexler LH, Singer S et al (2013) Adult rhabdomyosarcoma survival improved with treatment on multimodality protocols. Int J Radiat Oncol Biol Phys 86(1):58–63PubMedPubMedCentralCrossRef Gerber NK, Wexler LH, Singer S et al (2013) Adult rhabdomyosarcoma survival improved with treatment on multimodality protocols. Int J Radiat Oncol Biol Phys 86(1):58–63PubMedPubMedCentralCrossRef
4.
Zurück zum Zitat He LY, Zhang H, Wang ZK, Zhang HZ (2016) Diagnostic and prognostic significance of E-cadherin and Ki-67 expression in non-small cell lung cancer patients. Eur Rev Med Pharmacol Sci 20(18):3812–3817PubMed He LY, Zhang H, Wang ZK, Zhang HZ (2016) Diagnostic and prognostic significance of E-cadherin and Ki-67 expression in non-small cell lung cancer patients. Eur Rev Med Pharmacol Sci 20(18):3812–3817PubMed
5.
Zurück zum Zitat Jakobsen JN, Sørensen JB (2013) Clinical impact of ki-67 labeling index in non-small cell lung cancer. Lung Cancer 79(1):1–7PubMedCrossRef Jakobsen JN, Sørensen JB (2013) Clinical impact of ki-67 labeling index in non-small cell lung cancer. Lung Cancer 79(1):1–7PubMedCrossRef
6.
Zurück zum Zitat Ko GH, Go SI, Lee WS et al (2017) Prognostic impact of Ki-67 in patients with gastric cancer-the importance of depth of invasion and histologic differentiation. Medicine (Baltimore) 96(25):e7181CrossRef Ko GH, Go SI, Lee WS et al (2017) Prognostic impact of Ki-67 in patients with gastric cancer-the importance of depth of invasion and histologic differentiation. Medicine (Baltimore) 96(25):e7181CrossRef
7.
Zurück zum Zitat Klöppel G, La Rosa S (2018) Ki67 labeling index: assessment and prognostic role in gastroenteropancreatic neuroendocrine neoplasms. Virchows Arch 472(3):341–349PubMedCrossRef Klöppel G, La Rosa S (2018) Ki67 labeling index: assessment and prognostic role in gastroenteropancreatic neuroendocrine neoplasms. Virchows Arch 472(3):341–349PubMedCrossRef
8.
Zurück zum Zitat Zhao Y, Shen L, Huang X et al (2017) High expression of Ki-67 acts a poor prognosis indicator in locally advanced nasopharyngeal carcinoma. Biochem Biophys Res Commun 494(1-2):390–396PubMedCrossRef Zhao Y, Shen L, Huang X et al (2017) High expression of Ki-67 acts a poor prognosis indicator in locally advanced nasopharyngeal carcinoma. Biochem Biophys Res Commun 494(1-2):390–396PubMedCrossRef
9.
Zurück zum Zitat Tian Y, Ma Z, Chen Z et al (2016) Clinicopathological and prognostic value of Ki-67 expression in bladder cancer: a systematic review and meta-analysis. PLoS One 11(7):e0158891PubMedPubMedCentralCrossRef Tian Y, Ma Z, Chen Z et al (2016) Clinicopathological and prognostic value of Ki-67 expression in bladder cancer: a systematic review and meta-analysis. PLoS One 11(7):e0158891PubMedPubMedCentralCrossRef
10.
Zurück zum Zitat Fassnacht M, Dekkers OM, Else T et al (2018) European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol 179(4):G1–G46PubMedCrossRef Fassnacht M, Dekkers OM, Else T et al (2018) European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol 179(4):G1–G46PubMedCrossRef
11.
Zurück zum Zitat San Miguel-Fraile P, Carrillo-Gijón R, Rodriguez-Peralto JL, Badiola IA (2004) Prognostic significance of DNA ploidy and proliferative index (MIB-1 index) in childhood rhabdomyosarcoma. Am J Clin Pathol 121(3):358–365PubMedCrossRef San Miguel-Fraile P, Carrillo-Gijón R, Rodriguez-Peralto JL, Badiola IA (2004) Prognostic significance of DNA ploidy and proliferative index (MIB-1 index) in childhood rhabdomyosarcoma. Am J Clin Pathol 121(3):358–365PubMedCrossRef
12.
Zurück zum Zitat Jiang JX, Zhao JL, Zhang Q et al (2018) Endometrial carcinoma: diffusion-weighted imaging diagnostic accuracy and correlation with Ki-67 expression. Clin Radiol 73(4):413.e1–413.e6CrossRef Jiang JX, Zhao JL, Zhang Q et al (2018) Endometrial carcinoma: diffusion-weighted imaging diagnostic accuracy and correlation with Ki-67 expression. Clin Radiol 73(4):413.e1–413.e6CrossRef
13.
Zurück zum Zitat Li HM, Liu J, Qiang JW, Gu WY, Zhang GF, Ma FH (2017) Endometrial stromal sarcoma of the uterus: magnetic resonance imaging findings including apparent diffusion coefficient value and its correlation with Ki-67 expression. Int J Gynecol Cancer 27(9):1877–1887PubMedCrossRef Li HM, Liu J, Qiang JW, Gu WY, Zhang GF, Ma FH (2017) Endometrial stromal sarcoma of the uterus: magnetic resonance imaging findings including apparent diffusion coefficient value and its correlation with Ki-67 expression. Int J Gynecol Cancer 27(9):1877–1887PubMedCrossRef
14.
Zurück zum Zitat Cheng J, Wang Y, Zhang CF et al (2017) Chemotherapy response evaluation in a mouse model of gastric cancer using intravoxel incoherent motion diffusion-weighted MRI and histopathology. World J Gastroenterol 23(11):1990–2001PubMedPubMedCentralCrossRef Cheng J, Wang Y, Zhang CF et al (2017) Chemotherapy response evaluation in a mouse model of gastric cancer using intravoxel incoherent motion diffusion-weighted MRI and histopathology. World J Gastroenterol 23(11):1990–2001PubMedPubMedCentralCrossRef
15.
Zurück zum Zitat Sun M, Cheng J, Zhang Y et al (2018) Application of DWIBS in malignant lymphoma: correlation between ADC values and Ki-67 index. Eur Radiol 28(4):1701–1708PubMedCrossRef Sun M, Cheng J, Zhang Y et al (2018) Application of DWIBS in malignant lymphoma: correlation between ADC values and Ki-67 index. Eur Radiol 28(4):1701–1708PubMedCrossRef
16.
Zurück zum Zitat Shen L, Zhou G, Tong T et al (2018) ADC at 3.0 T as a noninvasive biomarker for preoperative prediction of Ki67 expression in invasive ductal carcinoma of breast. Clin Imaging 52:16–22PubMedCrossRef Shen L, Zhou G, Tong T et al (2018) ADC at 3.0 T as a noninvasive biomarker for preoperative prediction of Ki67 expression in invasive ductal carcinoma of breast. Clin Imaging 52:16–22PubMedCrossRef
17.
Zurück zum Zitat Fan M, He T, Zhang P, Zhang J, Li L (2017) Heterogeneity of diffusion-weighted imaging in tumours and the surrounding stroma for prediction of Ki-67 proliferation status in breast cancer. Sci Rep 7(1):2875PubMedPubMedCentralCrossRef Fan M, He T, Zhang P, Zhang J, Li L (2017) Heterogeneity of diffusion-weighted imaging in tumours and the surrounding stroma for prediction of Ki-67 proliferation status in breast cancer. Sci Rep 7(1):2875PubMedPubMedCentralCrossRef
18.
Zurück zum Zitat Xiao Z, Zhong Y, Tang Z et al (2018) Standard diffusion-weighted, diffusion kurtosis and intravoxel incoherent motion MR imaging of sinonasal malignancies: correlations with Ki-67 proliferation status. Eur Radiol 28(7):2923–2933PubMedCrossRef Xiao Z, Zhong Y, Tang Z et al (2018) Standard diffusion-weighted, diffusion kurtosis and intravoxel incoherent motion MR imaging of sinonasal malignancies: correlations with Ki-67 proliferation status. Eur Radiol 28(7):2923–2933PubMedCrossRef
19.
Zurück zum Zitat Yamanaka H, Oue T, Uehara S, Fukuzawa M (2011) Hedgehog signal inhibitor forskolin suppresses cell proliferation and tumor growth of human rhabdomyosarcoma xenograft. J Pediatr Surg 46(2):320–325PubMedCrossRef Yamanaka H, Oue T, Uehara S, Fukuzawa M (2011) Hedgehog signal inhibitor forskolin suppresses cell proliferation and tumor growth of human rhabdomyosarcoma xenograft. J Pediatr Surg 46(2):320–325PubMedCrossRef
20.
Zurück zum Zitat Le Bihan D (1995) Molecular diffusion, tissue microdynamics and microstructure. NMR Biomed 8(7–8):375–386PubMedCrossRef Le Bihan D (1995) Molecular diffusion, tissue microdynamics and microstructure. NMR Biomed 8(7–8):375–386PubMedCrossRef
21.
Zurück zum Zitat Le Bihan D, Breton E, Lallemand D, Aubin ML, Vignaud J, Laval-Jeantet M (1988) Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. Radiology 168(2):497–505PubMedCrossRef Le Bihan D, Breton E, Lallemand D, Aubin ML, Vignaud J, Laval-Jeantet M (1988) Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. Radiology 168(2):497–505PubMedCrossRef
22.
Zurück zum Zitat Meng X, Li H, Kong L et al (2016) MRI in rectal cancer: correlations between MRI features and molecular markers Ki-67, HIF-1a, and VEGF. J Magn Reson Imaging 44(3):594–600PubMedCrossRef Meng X, Li H, Kong L et al (2016) MRI in rectal cancer: correlations between MRI features and molecular markers Ki-67, HIF-1a, and VEGF. J Magn Reson Imaging 44(3):594–600PubMedCrossRef
23.
Zurück zum Zitat Surov A, Caysa H, Wienke A, Spielmann RP, Fiedler E (2015) Correlation between different ADC fractions, cell count, Ki-67, total nucleic areas and average nucleic areas in meningothelial meningiomas. Anticancer Res 35(12):6841–6846PubMed Surov A, Caysa H, Wienke A, Spielmann RP, Fiedler E (2015) Correlation between different ADC fractions, cell count, Ki-67, total nucleic areas and average nucleic areas in meningothelial meningiomas. Anticancer Res 35(12):6841–6846PubMed
24.
Zurück zum Zitat Mao X, Zou X, Yu N, Jiang X, Du J (2018) Quantitative evaluation of intravoxel incoherent motion diffusion-weighted imaging (IVIM) for differential diagnosis and grading prediction of benign and malignant breast lesions. Medicine (Baltimore) 97(26):e11109CrossRef Mao X, Zou X, Yu N, Jiang X, Du J (2018) Quantitative evaluation of intravoxel incoherent motion diffusion-weighted imaging (IVIM) for differential diagnosis and grading prediction of benign and malignant breast lesions. Medicine (Baltimore) 97(26):e11109CrossRef
25.
Zurück zum Zitat Dyvorne HA, Galea N, Nevers T et al (2013) Diffusion-weighted imaging of the liver with multiple b values: effect of diffusion gradient polarity and breathing acquisition on image quality and intravoxel incoherent motion parameters--a pilot study. Radiology 266(3):920–929PubMedPubMedCentralCrossRef Dyvorne HA, Galea N, Nevers T et al (2013) Diffusion-weighted imaging of the liver with multiple b values: effect of diffusion gradient polarity and breathing acquisition on image quality and intravoxel incoherent motion parameters--a pilot study. Radiology 266(3):920–929PubMedPubMedCentralCrossRef
26.
Zurück zum Zitat Wang F, Wu LM, Hua XL, Zhao ZZ, Chen XX, Xu JR (2018) Intravoxel incoherent motion diffusion-weighted imaging in assessing bladder cancer invasiveness and cell proliferation. J Magn Reson Imaging 47(4):1054–1060PubMedCrossRef Wang F, Wu LM, Hua XL, Zhao ZZ, Chen XX, Xu JR (2018) Intravoxel incoherent motion diffusion-weighted imaging in assessing bladder cancer invasiveness and cell proliferation. J Magn Reson Imaging 47(4):1054–1060PubMedCrossRef
27.
Zurück zum Zitat Kralik SF, Haider KM, Lobo RR, Supakul N, Calloni SF, Soares BP (2018) Orbital infantile hemangioma and rhabdomyosarcoma in children: differentiation using diffusion-weighted magnetic resonance imaging. J AAPOS 22(1):27–31PubMedCrossRef Kralik SF, Haider KM, Lobo RR, Supakul N, Calloni SF, Soares BP (2018) Orbital infantile hemangioma and rhabdomyosarcoma in children: differentiation using diffusion-weighted magnetic resonance imaging. J AAPOS 22(1):27–31PubMedCrossRef
28.
Zurück zum Zitat Sun J, Zhang XP, Li XT et al (2014) Applicable apparent diffusion coefficient of an orthotopic mouse model of gastric cancer by improved clinical MRI diffusion weighted imaging. Sci Rep 4:6072PubMedPubMedCentralCrossRef Sun J, Zhang XP, Li XT et al (2014) Applicable apparent diffusion coefficient of an orthotopic mouse model of gastric cancer by improved clinical MRI diffusion weighted imaging. Sci Rep 4:6072PubMedPubMedCentralCrossRef
29.
Zurück zum Zitat Ma T, Yang S, Jing H et al (2018) Apparent diffusion coefficients in prostate cancer: correlation with molecular markers Ki-67, HIF-1α and VEGF. NMR Biomed 31(3)CrossRef Ma T, Yang S, Jing H et al (2018) Apparent diffusion coefficients in prostate cancer: correlation with molecular markers Ki-67, HIF-1α and VEGF. NMR Biomed 31(3)CrossRef
30.
Zurück zum Zitat Hu XX, Yang ZX, Liang HY et al (2017) Whole-tumor MRI histogram analyses of hepatocellular carcinoma: correlations with Ki-67 labeling index. J Magn Reson Imaging 46(2):383–392PubMedCrossRef Hu XX, Yang ZX, Liang HY et al (2017) Whole-tumor MRI histogram analyses of hepatocellular carcinoma: correlations with Ki-67 labeling index. J Magn Reson Imaging 46(2):383–392PubMedCrossRef
31.
Zurück zum Zitat Bae H, Yoshida S, Matsuoka Y et al (2014) Apparent diffusion coefficient value as a biomarker reflecting morphological and biological features of prostate cancer. Int Urol Nephrol 46(3):555–561PubMedCrossRef Bae H, Yoshida S, Matsuoka Y et al (2014) Apparent diffusion coefficient value as a biomarker reflecting morphological and biological features of prostate cancer. Int Urol Nephrol 46(3):555–561PubMedCrossRef
32.
Zurück zum Zitat Ginat DT, Mangla R, Yeaney G, Wang HZ (2010) Correlation of diffusion and perfusion MRI with Ki-67 in high-grade meningiomas. AJR Am J Roentgenol 195(6):1391–1395PubMedCrossRef Ginat DT, Mangla R, Yeaney G, Wang HZ (2010) Correlation of diffusion and perfusion MRI with Ki-67 in high-grade meningiomas. AJR Am J Roentgenol 195(6):1391–1395PubMedCrossRef
33.
Zurück zum Zitat Calvar JA, Meli FJ, Romero C et al (2005) Characterization of brain tumors by MRS, DWI and Ki-67 labeling index. J Neurooncol 72(3):273–280PubMedCrossRef Calvar JA, Meli FJ, Romero C et al (2005) Characterization of brain tumors by MRS, DWI and Ki-67 labeling index. J Neurooncol 72(3):273–280PubMedCrossRef
Metadaten
Titel
DWI and IVIM are predictors of Ki67 proliferation index: direct comparison of MRI images and pathological slices in a murine model of rhabdomyosarcoma
verfasst von
Yuan Yuan
Dewei Zeng
Yajie Liu
Juan Tao
Yu Zhang
Jie Yang
Tsendjav Lkhagvadorj
Zhenzhen Yin
Shaowu Wang
Publikationsdatum
08.11.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
European Radiology / Ausgabe 3/2020
Print ISSN: 0938-7994
Elektronische ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-019-06509-w

Weitere Artikel der Ausgabe 3/2020

European Radiology 3/2020 Zur Ausgabe

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Screening-Mammografie offenbart erhöhtes Herz-Kreislauf-Risiko

26.04.2024 Mammografie Nachrichten

Routinemäßige Mammografien helfen, Brustkrebs frühzeitig zu erkennen. Anhand der Röntgenuntersuchung lassen sich aber auch kardiovaskuläre Risikopatientinnen identifizieren. Als zuverlässiger Anhaltspunkt gilt die Verkalkung der Brustarterien.

S3-Leitlinie zu Pankreaskrebs aktualisiert

23.04.2024 Pankreaskarzinom Nachrichten

Die Empfehlungen zur Therapie des Pankreaskarzinoms wurden um zwei Off-Label-Anwendungen erweitert. Und auch im Bereich der Früherkennung gibt es Aktualisierungen.

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

18.04.2024 Pädiatrische Notfallmedizin Nachrichten

Im Choosing-Wisely-Programm, das für die deutsche Initiative „Klug entscheiden“ Pate gestanden hat, sind erstmals Empfehlungen zum Umgang mit Notfällen von Kindern erschienen. Fünf Dinge gilt es demnach zu vermeiden.

Update Radiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.