Diffusion-weighted imaging in rectal carcinoma patients without and after chemoradiotherapy: A comparative study with histology
Introduction
Diffusion-weighted MRI (DWI) is a technique that exploits differences in the extracellular movement of water protons to discriminate between tissues of varying properties depending on the respective cellular microenvironment. For oncologic imaging, DWI has shown promise for identification of malignant tumor and is frequently used as reliable tool for assessment of tumor response [1], [2]. It has been shown previously that diffusion values correlate inversely with tissue cellularity in many tumors such as in brain [3], but not in others, e.g. in multiple myeloma [4]. For rectal carcinoma, recent studies showed that DWI was useful to identify tumor in the rectum and differentiate between cancer and residual scar tissue after chemoradiotherapy (CRT) [5], [6].
Modern approaches to cancer therapy, e.g. anti-angiogenic and anti-tumor effects of therapy require a therapy-adapted response monitoring [7]. Currently monitoring is mostly based on the change in size of the tumor as assessed according to the response evaluation criteria in solid tumors (RECIST) [8], [9]. As therapy may, however, result in constant tumor size but modified tissue composition, it is expected therefore that functional techniques such as DWI, that reflect these alterations in tissue micro- rather than macrostructure may replace the current standards [10]. To support the use of DWI parameters in decision-making about pharmaceuticals, it is important to link DWI derived parameters to underlying pathophysiological processes both before and after therapeutic interventions. In patients with rectal carcinoma receiving neoadjuvant CRT, a significant increase of the apparent diffusion coefficient (ADC) was reported [11], while others contradictorily showed a decrease in ADC [12], [13].
The ADC derived from DWI reflects functional processes in tumor tissue including a combined measure of the molecular movement of water (diffusion) and microcirculation of blood in the capillaries (perfusion). Le Bihan et al. proposed the intravoxel incoherent motion (IVIM) model to separate perfusion and diffusion effects [14], which can be applied to oncologic imaging [15], [16]. In brief, the IVIM theory exploits the differences in signal decay between the blood and tissue compartments, i.e. the blood magnetization dominates the signal decay at low b-values enabling a differentiation between the perfusion fraction f and perfusion-free diffusion D [14]. Recently, the IVIM model was used for the differentiation between chronic pancreatitis and pancreatic carcinoma [15] or healthy pancreatic tissue and pancreatic carcinoma by the perfusion fraction f, respectively [16]. To the best of our knowledge, no correlation for parameters of cellularity and vascularization has been performed for rectal carcinoma between DWI and histological properties. Therefore, we applied the IVIM model to patients with rectal carcinoma with and without preceding CRT for correlation of DWI values of diffusion and perfusion with postoperative histological parameters including cellularity, vascular area fraction and vessel diameter.
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Patients
This prospective study was approved by our institutional review board, and informed consent was obtained from all patients (registration number: S-242/2008). Patients with primary histologically proven T3 to T4 adenocarcinoma of the rectum (without any further histological specification), any nodal-stage without metastatic spread who were scheduled to undergo surgery with and without neoadjuvant CRT according to the guidelines [17] were included in this study. The tumor spread (T-stage) was
DWI parameters
In patients that did not receive CRT, D was highest in rectum (1.29 × 10−3 mm2/s), followed by tumor (0.96 × 10−3 mm2/s) and fat (0.37 × 10−3 mm2/s; p < 0.001 for all comparisons; Fig. 2a, Table 1). Values for f were significantly lower in tumor (9.12%) as compared to fat (16.05%), without any further differences between the tissues (Fig. 2b, Table 1). In patients receiving CRT, D was higher in tumor (1.10 × 10−3 mm2/s) as compared to fat (0.33 × 10−3 mm2/s) as well as higher in rectum (1.26 × 10−3 mm2/s) in
Discussion
DWI is sensitive to microscopic motion of water molecules, which occur in each voxel whereby signal attenuation is influenced not only by diffusion processes but also by perfusion and other kinds of motion, summarized as IVIM. High ADCs of a tumor region might be due to the influence of tumor perfusion [15], [20], which could explain conflicting results on ADC changes in rectal carcinoma reported earlier. Perfusion leads to water molecule motion during data acquisition and often shifts signal
Conclusions
In rectal carcinoma and the adjacent tissues rectum wall and fat, DWI can be correlated to cellularity and vascularization, but such associations depend clearly on the microscopic environment and the administered treatment. As a result, many structural and functional tissue characteristics are beyond histological ascertainability. Using the IVIM model, however, we found correlations between diffusion and perfusion with histological parameters cellularity and vascular area fraction in rectal
Author contributions
T. Bäuerle, M. Münter, A. Jensen, H.P. Schlemmer, B. Stieltjes, and M. Ganten had done study conception and design works. The team of T. Bäuerle, L. Seyler, K.H. Fritzsche, M. Schüssler, B. Stieltjes, and M. Ganten had done data acquisition, and apart from that this team excluding M. Schüssler and including A. Kopp-Schneider and H.P. Schlemmer had done data analysis and interpretation. Then T. Bäuerle, B. Stieltjes, and M. Ganten had done works related to quality control of data and algorithms
Conflict of interest statement
None of the authors has any actual or potential conflict of interest including financial, personal or other relationships with other people or organizations within three (3) years of beginning the work submitted that could inappropriately influence (bias) their work.
Acknowledgements
This study was supported by the grant GA-765/2-1 of the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG). The DFG did not influence the decision to submit the manuscript.
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