Apparent Diffusion Coefficient: a quantitative parameter for in vivo tumor characterization

https://doi.org/10.1016/S0720-048X(02)00310-8Get rights and content

Abstract

Purpose: The purpose of the this study was to evaluate the potential of diffusion weighted imaging (DWI) to distinguish different tissue compartments in early, intermediate and advanced tumor stages. Materials and methods: Twenty-two male mice were induced with squamous cell tumor (SCCVII) and scanned with a clinical 1.5 T scanner. T1-SE, T2-FSE, diffusion weighted Line-Scan-MRI and contrast enhanced T1-SE were obtained from mice with early (tumor volume 10–100 mm3), intermediate (200–600 mm3), advanced tumors (600–1000 mm3) and tumor necrosis (>1500 mm3). The apparent diffusion coefficient (ADC) of different tumor compartments was calculated offline with a pixel-by-pixel method. The animals were sacrificed immediately after scanning and histopathologic correlation was performed. Results: In early stages of tumor development, tumors appeared homogeneous on diffusion weighted images with an ADC of 0.64±0.06×10−3 mm2/s. With tumor progression the ADC in the rim areas of tumor increased significantly (intermediate stage: 0.70±0.11×10−3 mm2/s; advanced stage: 0.88±0.11×10−3 mm2/s; tumor necrosis 1.03±0.06×10−3 mm2/s), whereas the ADC in viable tumor remained constant. Histologically the areas with an increased ADC correlated well with areas of necrosis (reduced cell density). Conclusion: The ADC is a non-invasive technique to monitor changes in the biological structure of tumor tissue during tumor progression. Thus, DWI is a potential diagnostic tool for in-vivo tissue characterization.

Introduction

Magnetic resonance imaging (MRI) has evolved as an important diagnostic tool for assessing neoplasm due to its excellent soft tissue contrast and multiplanar reconstruction capabilities [1], [2]. However, conventional MRI is limited in providing clinically satisfactory information about lesion characterization and the presence and extent of viable tumor tissue and/or tumor necrosis [3], [4], [5]. To obtain these critical elements for tumor diagnosis, tumor staging and determining tumor prognosis invasive techniques such as needle or surgical biopsy were required [6]. These invasive methods leave a potential risk of infection and/or hemorrhage to the patient and, furthermore, are subject to sampling error [7].

Diffusion weighted imaging (DWI) is a non-invasive technique, that is capable of probing the structure of biologic tissues at a microscopic level and may therefore be used for in vivo tissue characterization [4]. The principle of DWI exploits the random, translational motion of water protons in biologic tissues [8]. On diffusion sensitive sequences this motion causes phase dispersion of the spins resulting in signal loss [6], [9]. This signal loss can be quantified by calculating the apparent diffusion coefficient (ADC), which refers to the specific diffusion capacity of a biologic tissue [5], [10].

In the presence of diffusion-hindering obstacles such as membranes, tight junctions, fibers, macromolecules, and cell organelles, the mobility of water protons is hindered, resulting in a decreased ADC [11]. Accordingly, in viable tumor tissue with densely packed diffusion hindering obstacles low ADC values can be found, whereas, in tissues with less densely packed obstacles (i.e. necrosis, non-neoplastic tissue) the ADC values is expected to be higher and may therefore, be used to distinguish viable tumor from tumor necrosis and/or benign tissue [5], [12], [13].

The cellular structure of a tumor is considered to be an indicator of tumor aggressiveness, and to influence the response to tumor therapy [14]. Currently, these features can only be evaluated from invasively obtained specimen [7]. Furthermore, in advanced tumors several different compartments of viable and necrotic tissue may be present, and thus guiding the biopsy needle to an area of viable tumor is crucial for accurate tumor assessment [3]. The purpose of this study was to evaluate the power of DWI to distinguish different tissue compartments in early, intermediate and advanced tumor stages.

Section snippets

Mouse tumor model

The squamous cell carcinoma VII (SCCVII) is a syngeneic transplantable, tumor that arises spontaneously in the abdominal wall of C3H/Km mice. It has subsequently been adapted for in vitro growth. We chose this tumor because it is considered to mimic realistically de novo human head and neck tumors. In vitro cultured tumor cells were transplanted in the right flank of 32 8–9-week-old male mice by subcutaneous injection of a suspension containing 0.05 ml Hank's solution and 2×105 SCCVII cells.

Results

Histologically, the SCCVII is a hypercellular tumor composed of sheets of moderately pleomorphic large cells with eccentrically placed nuclei, abundant eosinophilic cytoplasma and distinct cell borders (Fig. 1f). There are low numbers of fibroblast-like cells and blood vessels present. With tumor progression, necrosis develops presenting with reduced cell density, haemorrage, fibrin and cell debris.

In early stages of tumor growth (stage I) only viable tumor was present without any distinct

Discussion

DWI is considered to be a potential tool for diagnosing neoplasm and for monitoring treatment effects by exploiting the structural differences of biological tissue [4]. Quantitative diffusion measurements can aid to determination of different tissue types and tissue characteristics [12], [15]. In the present study viable tumor tissue was reliably discriminated from tumor necrosis and from benign tissue based on significant differences in the ADC. The ADC of viable tumor was significantly lower

Acknowledgements

The authors thank Drs. Roland Bammer, Stanford University, and Stephan Maier, Harvard Medical School, for their technical support with LSDI.

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