Statistical Evaluation of Different Mathematical Models for Diffusion Weighted Imaging of Prostate Cancer Xenografts in Mice

Harri Merisaari; Hanne Laakso; Heidi Liljenbäck; Helena Virtanen; Hannu J Aronen; Heikki Minn; Matti Poutanen; Anne Roivainen; Timo Liimatainen; Ivan Jambor

doi:10.3389/fonc.2021.583921

Statistical Evaluation of Different Mathematical Models for Diffusion Weighted Imaging of Prostate Cancer Xenografts in Mice

Front Oncol. 2021 May 26:11:583921. doi: 10.3389/fonc.2021.583921. eCollection 2021.

Authors

Harri Merisaari^{1

2}, Hanne Laakso³, Heidi Liljenbäck⁴, Helena Virtanen^{4

5}, Hannu J Aronen^{1

6}, Heikki Minn^{4

7}, Matti Poutanen⁵, Anne Roivainen^{4

5}, Timo Liimatainen^{3

8

9

10}, Ivan Jambor^{1

6}

Affiliations

¹ Department of Radiology, University of Turku, Turku, Finland.
² Turku Brain and Mind Center, University of Turku, Turku, Finland.
³ Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, Kuopio, Finland.
⁴ Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.
⁵ Turku Center for Disease Modeling, University of Turku, Turku, Finland.
⁶ Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland.
⁷ Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland.
⁸ Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland.
⁹ Department of Clinical Radiology, Oulu University Hospital, Oulu, Finland.
¹⁰ Department of Radiology, University of Oulu, Oulu, Finland.

Abstract

Purpose: To evaluate fitting quality and repeatability of four mathematical models for diffusion weighted imaging (DWI) during tumor progression in mouse xenograft model of prostate cancer.

Methods: Human prostate cancer cells (PC-3) were implanted subcutaneously in right hind limbs of 11 immunodeficient mice. Tumor growth was followed by weekly DWI examinations using a 7T MR scanner. Additional DWI examination was performed after repositioning following the fourth DWI examination to evaluate short term repeatability. DWI was performed using 15 and 12 b-values in the ranges of 0-500 and 0-2000 s/mm², respectively. Corrected Akaike information criteria and F-ratio were used to evaluate fitting quality of each model (mono-exponential, stretched exponential, kurtosis, and bi-exponential).

Results: Significant changes were observed in DWI data during the tumor growth, indicated by ADC_m, ADC_s, and ADC_k. Similar results were obtained using low as well as high b-values. No marked changes in model preference were present between the weeks 1-4. The parameters of the mono-exponential, stretched exponential, and kurtosis models had smaller confidence interval and coefficient of repeatability values than the parameters of the bi-exponential model.

Conclusion: Stretched exponential and kurtosis models showed better fit to DWI data than the mono-exponential model and presented with good repeatability.

Keywords: Akaike information criteria (AIC); F-ratio; PC-3 xenograft prostate tumors; diffusion weighted imaging; prostate cancer mouse model; repeatability.