Multiparametric MR for non‐invasive evaluation of tumour tissue histological characteristics after radionuclide therapy

Abstract

Early non‐invasive tumour therapy response assessment requires methods sensitive to biological and physiological tumour characteristics. The aim of this study was to find and evaluate magnetic resonance imaging (MRI) derived tumour tissue parameters that correlate with histological parameters and that reflect effects of radionuclide therapy. Mice bearing a subcutaneous human small‐intestine neuroendocrine tumour were i.v . injected with 177 Lu‐octreotate. MRI was performed (7 T Bruker Biospec) on different post‐therapy intervals (1 and 13 days) using T2‐weighted imaging, mapping of T2* and T1 relaxation time constants, as well as diffusion and dynamic contrast enhancement (DCE‐MRI) techniques. After MRI, animals were killed and tumours excised. Four differently stained histological sections of the most central imaged tumour plane were digitized, and segmentation techniques were used to produce maps reflecting fibrotic and vascular density, apoptosis, and proliferation. Histological maps were aligned with MRI‐derived parametric maps using landmark‐based registration. Correlations and predictive power were evaluated using linear mixed‐effects models and cross‐validation, respectively. Several MR parameters showed statistically significant correlations with histological parameters. In particular, three DCE‐MRI‐derived parameters reflecting capillary function additionally showed high predictive power regarding apoptosis (2/3) and proliferation (1/3). T1 could be used to predict vascular density, and perfusion fraction derived from diffusion MRI could predict fibrotic density, although with lower predictive power. This work demonstrates the potential to use multiparametric MRI to retrieve important information on the tumour microenvironment after radiotherapy. The non‐invasiveness of the method also allows longitudinal tumour tissue characterization. Further investigation is warranted to evaluate the parameters highlighted in this study longitudinally, in larger studies, and with additional histological methods.

Hyperfractionated Treatment with 177Lu-Octreotate Increases Tumor Response in Human Small-Intestine Neuroendocrine GOT1 Tumor Model

“…Since GOT1 cell proliferation is slow, most GOT1 animal studies are performed in the model based on serial transplantation of small tissue pieces from one tumor to several younger mice, which was the case in the present study. Due to some heterogeneity in GOT1 tumors [ 32 , 41 ], there is a risk that a mouse may be transplanted with a tumor piece having cells with altered SSTR expression, which was most probably the case in the present study, and explains the lower SSTR 2 expression in this non-responding mouse. We reported similar findings in a previous study [ 32 ].…”

Joint total variation‐based reconstruction of multiparametric magnetic resonance images for mapping tissue types

“…In the proposed algorithm, parameter maps are estimated from reconstructed images at each iteration, which provides an additional constraint on pixel values in the form of the relaxation model equation, in addition to information from the JTV, and improves the accuracy of the end results of the reconstruction process. Accelerated mpMRI parametric mapping will enable objective mapping of tissue histological characteristics [3][4][5]7,49 and intratumoral habitats, 6,[8][9][10]50 which in turn will enable the development of better imaging biomarkers for understanding tumor resistance to therapies and the development of adaptive anticancer therapy regimens. 41,42 Alternate approaches being investigated to this end include MR fingerprinting (MRF), which is a dictionary-based technique that is gaining popularity for accelerated acquisition of mpMR images in research settings.…”

“…Accelerated mpMRI parametric mapping will enable objective mapping of tissue histological characteristics 3–5,7,49 and intratumoral habitats, 6,8–10,50 which in turn will enable the development of better imaging biomarkers for understanding tumor resistance to therapies and the development of adaptive anticancer therapy regimens 41,42 . Alternate approaches being investigated to this end include MR fingerprinting (MRF), which is a dictionary‐based technique that is gaining popularity for accelerated acquisition of mpMR images in research settings.…”

Apparent diffusion coefficient for the prediction of tumor response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer

“…The DWI-derived ADC is a quantitative parameter that can be used to evaluate properties of molecules, including cell density, cell membrane integrity, and interactions with macromolecules. Generally, ADC values are negatively related to cell density and positively related to extracellular space [ 25 ]. It has been proven that the ADC can reflect histological changes in primary tumors after neoadjuvant chemo-radiotherapy [ 26 ].…”