Multiparametric magnetic resonance imaging for radiation therapy response monitoring in soft tissue sarcomas: a histology and MRI co-registration algorithm

Abstract

Rationale: To establish a spatially exact co-registration procedure between in vivo multiparametric magnetic resonance imaging (mpMRI) and (immuno)histopathology of soft tissue sarcomas (STS) to identify imaging parameters that reflect radiation therapy response of STS. Methods: The mpMRI-Protocol included diffusion-weighted (DWI), intravoxel-incoherent motion (IVIM), and dynamic contrast-enhancing (DCE) imaging. The resection specimen was embedded in 6.5% agarose after initial fixation in formalin. To ensure identical alignment of histopathological sectioning and in vivo imaging, an ex vivo MRI scan of the specimen was rigidly co-registered with the in vivo mpMRI. The deviating angulation of the specimen to the in vivo location of the tumor was determined. The agarose block was trimmed accordingly. A second ex vivo MRI in a dedicated localizer with a 4 mm grid was performed, which was matched to a custom-built sectioning machine. Microtomy sections were stained with hematoxylin and eosin. Immunohistochemical staining was performed with anti-ALDH1A1 antibodies as a radioresistance and anti-MIB1 antibodies as a proliferation marker. Fusion of the digitized microtomy sections with the in vivo mpMRI was accomplished through nonrigid co-registration to the in vivo mpMRI. Co-registration accuracy was qualitatively assessed by visual assessment and quantitatively evaluated by computing target registration errors (TRE). Results: The study sample comprised nine tumor sections from three STS patients. Visual assessment after nonrigid co-registration showed a strong morphological correlation of the histopathological specimens with ex vivo MRI and in vivo mpMRI after neoadjuvant radiation therapy. Quantitative assessment of the co-registration procedure using TRE analysis of different pairs of pathology and MRI sections revealed highly accurate structural alignment, with a total median TRE of 2.25 mm (histology - ex vivo MRI), 2.22 mm (histology - in vivo mpMRI), and 2.02 mm ( ex vivo MRI - in vivo mpMRI). There was no significant difference between TREs of the different pairs of sections or caudal, middle, and cranial tumor parts, respectively. Conclusion: Our initial results show a promising approach to obtaining accurate co-registration between histopathology and in vivo MRI for STS. In a larger cohort of patients, the method established here will enable the prospective identification and validation of in vivo imaging biomarkers for radiation therapy response prediction and monitoring in STS patients via precise molecular and cellular correlation.

Non-invasive monitoring of neoadjuvant radiation therapy response in soft tissue sarcomas by multiparametric MRI and quantification of circulating tumor DNA—A study protocol

“…In the literature [24,58,59] and previous works by our group [28][29][30][31][32][33][34]45], ctDNA is described as a potential biomarker for the prediction of STS, its recurrence, and minimal residual disease PLOS ONE after resection. However, it has not been shown if ctDNA can be used as a biomarker for therapy response and how ctDNA correlates with vital tumor mass during NRT.…”

“…Hence, we have developed a prospective study protocol that considers previous studies’ limitations and uses a highly sensitive and optimized NGS-based panel design for liquid biopsies. Combining this data with mpMRI and immunohistological findings of the resected tumor, large interdisciplinary data sets are generated to characterize the STS [ 45 ]. In addition, tumor response to NRT and morphological changes in the course of treatment can be monitored.…”

“…Four representative ROIs—one per cluster–are defined in the co-registered histology and mpMRI section. One-way ANOVA with post hoc pairwise t-tests (Bonferroni-Holm adjusted) is performed to compare differences in mpMRI parameters [ 45 ].…”

Biomarker-driven molecular imaging probes in radiotherapy

“…Functional multiparametric magnetic resonance imaging (mpMRI) and 2-[ 18 F]fluoro-2-deoxy-D-glucose ( 18 F-FDG) PET/CT are two major methods to detect early metabolic responses after radiotherapy 39 , 40 . These imaging results as early predictors, such as apparent diffusion coefficient (ADC), magnetic resonance spectroscopy (MRS), standardized uptake value (SUV) and total lesion glycolysis (TLG), have been frequently explored in radiotherapy for a variety of tumor indications (e.g., esophageal cancer, soft tissue sarcoma) 41 , 42 . Furthermore, these imaging results in radiotherapy have been reported to be correlated with end points such as recurrence-free survival (RFS) or overall survival (OS) in several prospective/retrospective studies 43 - 45 .…”

[68Ga]Ga-PSMA and [68Ga]Ga-RM2 PET/MRI vs. Histopathological Images in Prostate Cancer: A New Workflow for Spatial Co-Registration

“…Several approaches have been implemented to validate the in vivo images with histological slices [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Some authors suggested the use of the acquisition of the MRI or Computed Tomography (CT) ex vivo specimen as an intermediate step [ 11 , 15 , 16 , 17 , 18 , 19 , 23 , 25 , 26 ] since the histopathological specimen is acquired with the same contrast of the in vivo image, while maintaining the deformation due to resection of the histopathology images.…”