TY - JOUR
T1 - Pancreatic Intraepithelial Neoplasia Revealed by Diffusion-Tensor MRI
AU - Bilreiro, Carlos
AU - Fernandes, Francisca F.
AU - Simões, Rui V.
AU - Henriques, Rafael
AU - Chavarrías, Cristina
AU - Ianus, Andrada
AU - Castillo-Martin, Mireia
AU - Carvalho, Tânia
AU - Matos, Celso
AU - Shemesh, Noam
N1 - Funding Information:
Conflicts of interest and sources of funding: N.S. serves on the Scientific Advisory Board of Bruker Biospin. No other potential conflicts of interest are reported from remaining authors. Champalimaud Foundation funded this work; R.V.S.'s work was supported by H2020-MSCA-IF-2018, ref: 844776; A.I.'s work received the support of a fellowship from \u201CLa Caixa\u201D Foundation (ID 100010434) and from the European Union's Horizon 2020 research and innovation programme under the Marie Sk\u0142odowska-Curie grant agreement no. 847648, fellowship code LCF/BQ/PI20/11760029.
Publisher Copyright:
© 2024 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2024
Y1 - 2024
N2 - Objectives Detecting premalignant lesions for pancreatic ductal adenocarcinoma, mainly pancreatic intraepithelial neoplasia (PanIN), is critical for early diagnosis and for understanding PanIN biology. Based on PanIN's histology, we hypothesized that diffusion tensor imaging (DTI) and T2∗ could detect PanIN. Materials and Methods DTI was explored for the detection and characterization of PanIN in genetically engineered mice (KC, KPC). Following in vivo DTI, ex vivo ultrahigh-field (16.4 T) MR microscopy using DTI, T2∗ was performed with histological validation. Sources of MR contrasts and histological features were investigated, including histological scoring for disease burden (lesion span) and severity (adjusted score). To test if findings in mice can be translated to humans, human pancreas specimens were imaged. Results DTI detected PanIN and pancreatic ductal adenocarcinoma in vivo (6 KPC, 4 KC, 6 controls) with high discriminative ability: fractional anisotropy (FA) and radial diffusivity with area under the curve = 0.983 (95% confidence interval: 0.932-1.000); mean diffusivity and axial diffusivity (AD) with area under the curve = 1 (95% confidence interval: 1.000-1.000). MR microscopy with histological correlation (20 KC/KPC; 5 controls) revealed that sources of MR contrasts likely arise from microarchitectural signatures: high FA, AD in fibrotic areas surrounding lesions, high diffusivities within cysts, and high T2∗ within lesions' stroma. The strongest histological correlations for lesion span and adjusted score were obtained with AD (R = 0.708, P < 0.001; R = 0.789, P < 0.001, respectively). Ex vivo observations in 5 human pancreases matched our findings in mice, revealing substantial contrast between PanIN and normal pancreas. Conclusions DTI and T2∗ are useful for detecting and characterizing PanIN in genetically engineered mice and in the human pancreas, especially with AD and FA. These are encouraging findings for future clinical applications of pancreatic imaging.
AB - Objectives Detecting premalignant lesions for pancreatic ductal adenocarcinoma, mainly pancreatic intraepithelial neoplasia (PanIN), is critical for early diagnosis and for understanding PanIN biology. Based on PanIN's histology, we hypothesized that diffusion tensor imaging (DTI) and T2∗ could detect PanIN. Materials and Methods DTI was explored for the detection and characterization of PanIN in genetically engineered mice (KC, KPC). Following in vivo DTI, ex vivo ultrahigh-field (16.4 T) MR microscopy using DTI, T2∗ was performed with histological validation. Sources of MR contrasts and histological features were investigated, including histological scoring for disease burden (lesion span) and severity (adjusted score). To test if findings in mice can be translated to humans, human pancreas specimens were imaged. Results DTI detected PanIN and pancreatic ductal adenocarcinoma in vivo (6 KPC, 4 KC, 6 controls) with high discriminative ability: fractional anisotropy (FA) and radial diffusivity with area under the curve = 0.983 (95% confidence interval: 0.932-1.000); mean diffusivity and axial diffusivity (AD) with area under the curve = 1 (95% confidence interval: 1.000-1.000). MR microscopy with histological correlation (20 KC/KPC; 5 controls) revealed that sources of MR contrasts likely arise from microarchitectural signatures: high FA, AD in fibrotic areas surrounding lesions, high diffusivities within cysts, and high T2∗ within lesions' stroma. The strongest histological correlations for lesion span and adjusted score were obtained with AD (R = 0.708, P < 0.001; R = 0.789, P < 0.001, respectively). Ex vivo observations in 5 human pancreases matched our findings in mice, revealing substantial contrast between PanIN and normal pancreas. Conclusions DTI and T2∗ are useful for detecting and characterizing PanIN in genetically engineered mice and in the human pancreas, especially with AD and FA. These are encouraging findings for future clinical applications of pancreatic imaging.
KW - animals, genetically modified
KW - carcinoma in situ
KW - diffusion tensor imaging
KW - pancreatic intraepithelial neoplasia
KW - pancreatic neoplasms
UR - http://www.scopus.com/inward/record.url?scp=85212677245&partnerID=8YFLogxK
U2 - 10.1097/RLI.0000000000001142
DO - 10.1097/RLI.0000000000001142
M3 - Article
C2 - 39668406
AN - SCOPUS:85212677245
SN - 0020-9996
JO - Investigative Radiology
JF - Investigative Radiology
M1 - 10.1097/RLI.0000000000001142
ER -