Evaluation of the Effects of Anti‐PD‐1 Therapy on Triple‐Negative Breast Cancer in Mice by Diffusion Kurtosis Imaging and Dynamic Contrast‐Enhanced Imaging

Abstract

Background The monitoring of immunotherapies is still based on changes in the tumor size in imaging, with a long evaluation period and low sensitivity. Purpose To investigate the effectiveness of diffusion kurtosis imaging (DKI) and dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) in assessing the therapeutic efficacy of anti‐programmed death‐1 (PD‐1) therapy in a mouse triple negative breast cancer (TNBC) model. Study Type Prospective. Animal Model A total of 54 BALB/c mouse subcutaneous 4 T1 transplantation models of TNBC. Field Strength/Sequence A 3.0‐T; turbo spin echo (TSE) T2‐weighted imaging, DKI with seven b values (0, 500, 1000, 1500, 2000, 2500, and 3000 sec/mm2) and T1‐twist DCE acquisition series. Assessment DKI and DCE‐MRI parameters were evaluated by two radiologists independently. Regions of interest (ROIs) were drawn manually on the maximum cross‐sectional area of the lesion; care was taken to avoid necrotic areas. The tumor cell density, the CD45 and CD31 levels were analyzed by two pathologists. Statistical Tests The two‐tailed unpaired t‐test, Mann–Whitney U test, Fisher's exact test and Pearson correlation coefficient were performed. A P < 0.05 was considered statistically significant. Results The apparent diffusion coefficient (ADC), mean diffusivity (MD), Ktrans and Kep values were significantly different between the two groups at each time point after treatment. There were significant differences in the mean kurtosis (MK) and Ve values between the two groups at 5 and 10 days after treatment but no significant differences at 15 days (P = 0.317 and 0.183, respectively). The ADC and MD values were significantly correlated with tumor cell density (ADC, r = −0.833; MD, r = 0.890) and the CD45 level (ADC, r = 0.720; MD, r = 0.718). The Ktrans and Kep values were significantly correlated with the CD31 level (Ktrans, r = 0.820; Kep, r = 0.683). Data Conclusion DKI and DCE‐MRI could reflect the changes in tumor microstructure and tumor tissue vasculature after anti‐PD‐1 therapy, respectively. Level of Evidence 1 Technical Efficacy Stage 4.

Clinically feasible liver tumour cell size measurement through histology-informedin vivodiffusion MRI

“…S8 shows standard dMRI metrics, namely ADC and kurtosis excess 𝐾𝐾, in the same mouse livers. Visual trends highlight that the higher cell density of sample Patinf1 translated to remarkably reduced ADC and increased 𝐾𝐾 compared to the Control, is in line with known correlations with cellularity (38,39). Lastly, Fig.…”

Diffusion kurtosis imaging as a biomarker of breast cancer

“…Tang and colleagues compared an antiprogrammed death receptor-1(PD-1) therapy group with a control group in a triple negative breast cancer mouse model and found significant differences in K and ADC 0 between the two groups at 5 and 10 days after treatment. 26 Additionally, ADC 0 was significantly different between the two groups at 15 days after treatment and correlated positively with histological CD45 levels, suggesting immune effects. 26 …”

“… 26 Additionally, ADC 0 was significantly different between the two groups at 15 days after treatment and correlated positively with histological CD45 levels, suggesting immune effects. 26 …”

Molecular MRI-Based Monitoring of Cancer Immunotherapy Treatment Response

“…DKI can be calculated from standard DWI-acquired data, after additional post-processing that is not currently included in standard MRI software [78]. The potential benefits of this technique for immunotherapy monitoring were reported in several recent studies, including on dendritic cell treatment [79], and anti-PD-1 ICI monitoring [80]. A recent study of DKI in metastatic melanoma patients reported that cell death can be detected as early as 3-12 weeks after treatment initiation [81].…”