Signal enhancement ratio of multi-phase contrast-enhanced MRI: an imaging biomarker for survival in pancreatic adenocarcinoma.

OBJECTIVES: To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard. METHODS: This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SIlt - SIpre)/(SIea - SIpre), where SIpre, SIea, and SIlt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves. RESULTS: The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001). CONCLUSION: SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC. CLINICAL RELEVANCE STATEMENT: The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC. KEY POINTS: Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.

Quantitative dynamic contrast-enhance MRI parameters for rectal carcinoma characterization: correlation with tumor tissue composition.

OBJECTIVE: To investigate the relationship between dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) measurements and the potential composition of rectal carcinoma. METHODS: Twenty-four patients provided informed consent for this study. DCE-MRI was performed before total mesorectal excision. Quantitative parameters were calculated based on a modified Tofts model. Whole-mount immunohistochemistry and Masson staining sections were generated and digitized at histological resolution. The percentage of tissue components area was measured. Pearson correlation analysis was used to evaluate the correlations between pathological parameters and DCE-MRI parameters. RESULTS: On the World Health Organization (WHO) grading scale, there were significant differences in extracellular extravascular space (Ktrans) (F = 9.890, P = 0.001), mean transit time (MTT) (F = 9.890, P = 0.038), CDX-2 (F = 4.935, P = 0.018), and Ki-67 (F = 4.131, P = 0.031) among G1, G2, and G3. ECV showed significant differences in extramural venous invasion (t = - 2.113, P = 0.046). Ktrans was strongly positively correlated with CD34 (r = 0.708, P = 0.000) and moderately positively correlated with vimentin (r = 0.450, P = 0.027). Interstitial volume (Ve) was moderately positively correlated with Masson's (r = 0.548, P = 0.006) and vimentin (r = 0.417, P = 0.043). There was a moderate negative correlation between Ve and CDX-2 (r = - 0.441, P = 0.031). The rate constant from extracellular extravascular space to blood plasma (Kep) showed a strong positive correlation with CD34 expression (r = 0.622, P = 0.001). ECV showed a moderate negative correlation with CDX-2 (r = - 0.472, P = 0.020) and a moderate positive correlation with collagen fibers (r = 0.558, P = 0.005). CONCLUSION: The dynamic contrast-enhanced MRI-derived parameters measured in rectal cancer were significantly correlated with the proportion of histological components. This may serve as an optimal imaging biomarker to identify tumor tissue components.

The use of quantitative T1-mapping to identify cells and collagen fibers in rectal cancer.

Aim: This study aimed to explore the value of T1 mapping in assessing the grade and stage of rectal adenocarcinoma and its correlation with tumor tissue composition. Methods: Informed consent was obtained from all rectal cancer patients after approval by the institutional review board. Twenty-four patients (14 women and 10 men; mean age, 64.46 years; range, 35 - 82 years) were enrolled in this prospective study. MRI examinations were performed using 3.0T MR scanner before surgery. HE, immunohistochemical, and masson trichrome-staining was performed on the surgically resected tumors to assess the degree of differentiation, stage, and invasion. Two radiologists independently analyzed native T1 and postcontrast T1 for each lesion, and calculated the extracellular volume (ECV) was calculated from T1 values. Intraclass correlation coefficient (ICC) and Bland-Altman plots were applied to analyze the interobserver agreement of native T1 values and postcontrast T1 values. Student's t-test and one-way analysis of variance (ANOVA) were used to test the differences between T1 mapping parameters and differentiation types, T and N stages, and venous and neural invasion. Pearson correlation coefficients were used to analyze the correlation of T1 mapping extraction parameters with caudal type homeobox 2 (CDX-2), Ki-67 index, and collagen expression. Results: Both the native and postcontrast T1 values had an excellent interobserver agreement (ICC 0.945 and 0.942, respectively). Postcontrast T1 values indicated significant differences in venous invasion (t=2.497, p=0.021) and neural invasion (t=2.254, p=0.034). Pearson's correlation analysis showed a significant positive correlation between native T1 values and Ki-67 (r=-0.407, p=0.049). There was a significant positive correlation between ECV and collagen expression (r=0.811, p=.000) and a significant negative correlation between ECV and CDX-2 (r=-0.465, p=0.022) and Ki-67 (r=-0.549, p=0.005). Conclusion: Postcontrast T1 value can be used to assess venous and neural invasion in rectal cancer. ECV measurements based on T1 mapping can be used to identify cells and collagen fibers in rectal cancer.

Correlation between diffusion kurtosis and intravoxel incoherent motion derived (IVIM) parameters and tumor tissue composition in rectal cancer: a pilot study.

PURPOSE: To correlate non-invasive quantitative diffusion kurtosis imaging (DKI) and intravoxel incoherent motion-derived (IVIM) parameters with rectal cancer composition assessed by the expression of caudal-type homeobox 2 (CDX-2), Vimentin (VIM), CD34 and Ki-67 on resected tissues, as well as the tumor stroma ratio (TSR) and the results of H&E and Masson staining. MATERIALS AND METHODS: A prospective study of 26 patients with rectal cancer who underwent magnetic resonance (MR) imaging, including DKI with 4 b values and IVIM at 3.0 T prior to surgery. Primary tumor was harvested and fixed for H&E, immunohistochemistry and Masson staining. One-way ANOVA was used to test the differences. Pearson correlation coefficients and multiple linear regression analyses were applied to evaluation the correlations. RESULTS: The apparent diffusion coefficient (ADCDKI) and MKDKI all exhibited significant differences in subgroups with different T stages (P < 0.05) and among high- and low- grade rectal cancer (P < 0.05). MDDKI showed a moderate negative correlation with CDX-2 (r = - 0.42, P = 0.040) and a moderate positive correlation with CD34 (r = 0.42, P = 0.041). ADCIVIM exhibited a moderate positive correlation with Masson staining (r = 0.426, P = 0.048) DIVIM showed a moderate negative correlation with CDX-2 (r = - 0.58, P = 0.005). [Formula: see text] showed a moderate positive correlation with VIM (r = 0.445, P = 0.033). CONCLUSION: ADCDKI and MKDKI demonstrated a higher correlation with T stages and histologic grades. MDDKI showed significant correlations with CDX-2 and CD34. ADCIVIM showed significant correlation with Masson. DIVIM showed significant correlations with CDX-2 and [Formula: see text] showed significant correlation with VIM. These findings should be validated in a larger study.