Elsevier

Oral Oncology

Volume 44, Issue 12, December 2008, Pages 1147-1154
Oral Oncology

Quantitative dynamic contrast-enhanced MRI for the assessment of mandibular invasion by squamous cell carcinoma

https://doi.org/10.1016/j.oraloncology.2008.02.009Get rights and content

Summary

The objective of this study was to determine the value of dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative assessment of mandibular invasion in squamous cell carcinomas (SCC), adjacent or fixed to the mandible. DCE-MRI was performed with gadolinium diethylene triamine pentaacetic acid (Gd-DTPA). Data were obtained from 25 patients. From pharmacokinetic analysis of the tissue uptake of Gd-DTPA, the DCE-MRI parameters (kep, Ktrans and ve) were determined, with kep representing the exchange rate constant, Ktrans the volume transfer constant and ve the volume of extracellular space per unit volume of tissue. The histology of the resection specimens was used as gold standard for the extent of mandibular invasion. SCC with medullary invasion showed higher mean kep and Ktrans compared with SCC without medullary invasion (ANOVA, p < 0.001). ROC analysis of kep and Ktrans revealed reliable threshold values for medullary invasion. In conclusion, DCE-MRI can discriminate SCC with medullary invasion from SCC without medullary invasion and may serve as a valuable tool in preoperative tumour staging with regard to the delineation of medullary invasion.

Introduction

Squamous cell carcinoma (SCC) of the oral cavity has a tendency to invade the mandible due to the close anatomical relation to the bone. The treatment of choice for SCC adjacent or fixed to the mandible is complete surgical removal of the tumour in the soft tissues “en bloc” with the involved bone. There are two types of mandibular resection: marginal and segmental resection. In marginal mandibular resections, the continuity of the mandible is left intact, whereas in segmental mandibular resection, the continuity of the mandible is interrupted. The choice between these two types of mandibular resection depends on the assumed extent of mandibular invasion and may have a significant impact on health related quality of life.1, 2, 3, 4, 5 The extent of the invasion, however, is often unclear, due to the lack of reliable imaging methods. This explains the high percentages (35–78%) of resected mandibles with no evidence of tumour invasion on histological examination.6, 7, 8, 9

At present, routine preoperative assessment usually consists of clinical examination, conventional radiography and CT and/or MRI scanning. With clinical examination, it is impossible to detect subtle cortical invasion.10, 11, 12 Conventional radiography has also limitations as at least 30–50% mineral loss must occur in the bone before any change is visible.7, 13 The value of CT scans in the detection of mandibular invasion is questionable.10, 14 False results are caused by the complex anatomy of the inner cortex of the mandible, irregular dental sockets and dental infections. Experiences with MRI are also not unequivocally positive.15, 16, 17, 18, 19 False positive results may be the result of dental infections, other inflammatory reactions, oedema or sclerosis as a reaction to the primary tumour. Bone scanning using Technetium (Tc)-99m-labelled diphosphonate is a highly sensitive technique for the detection of mandibular invasion.10, 20 Its specificity, however, is still in need of improvement.

All the above-mentioned preoperative examination methods have their shortcomings. Therefore, an imaging technique is needed that would further improve the assessment of mandibular invasion, preferably by quantitative analysis. Dynamic contrast-enhanced MRI (DCE-MRI) might be of use for that purpose.21, 22, 23 Its value has already been demonstrated for tumour detection, localisation, grading or staging in several tumours, such as in prostate,24, 25, 26, 27 breast,28, 29, 30, 31 brain,32 cervix33 and in the head and neck.34 Aspects of vascularity, in particular vascular permeability, vascular surface area and flow can be assessed by DCE-MRI using gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) as a contrast agent. SCC has been characterised as hypervascular and metabolically active tissue with increased perfusion. The uptake of Gd-DTPA is often more rapid and higher in tumour tissue compared to the normal or fibrotic tissue surrounding the tumour, because of enlarged, leaky vessels and increased interstitial space.

Data obtained by DCE-MRI can be used to gain insight in the underlying physiology of the tumour by applying a physiological pharmacokinetic model to the data. Such a model is commonly used to fit the concentration Gd-DTPA versus time data and consists in its simplest form of two compartments: a vascular compartment (blood plasma) and an extravascular compartment (EES) (Fig. 1).

The exchange of Gd-DTPA between blood plasma and the extravascular space is determined by the uptake rate constant kep (min−1) and volume transfer constant Ktrans (a.u. min−1), which are related by kep = Ktrans/ve, in which ve is the volume of extravascular space per unit volume of tissue and Ktrans = (1  ePS/F), with PS representing the vessel permeability surface area product and F representing the blood flow.21, 35 The Gd-DTPA uptake rate can be displayed as a map by applying the physiological model to DCE-MRI data on a pixel-by-pixel basis. In this way spatial information can be obtained to identify and characterise tumour tissue.

The aim of this study is to determine the value of DCE-MRI for the preoperative assessment of mandibular invasion in SCC, adjacent or fixed to the mandible. The hypothesis is that DCE-MRI will detect higher Gd-DTPA uptake rates in SCC with mandibular invasion compared to SCC without mandibular invasion.

Section snippets

Materials and methods

Approval for the study was given by the local ethical committee. Informed consent was obtained from all patients after the procedure had been fully explained. Initially, 33 consecutive patients were recruited for the study. According to the treatment protocol of the local Head and Neck tumour workgroup, these patients were planned to have a marginal or segmental resection for histologically confirmed SCC, adjacent or fixed to the mandible.

Each patient had an orthopantomogram (OPT) with

Results

DCE-MRIs were available from 25 patients with a mean age of 54 years (range, 48–76 years), 15 males and 10 females. The primary sites of SCC were floor of mouth (n = 12), alveolar process (n = 5), and retromolar area (n = 8). As an example, three different MR images and one CT image at the same level of a single patient with squamous cell carcinoma in the anterior floor of mouth with medullary invasion are shown in Figure 2.

Histological examination showed mandibular invasion through cortex into

Discussion

The results of this study confirm our hypothesis: DCE-MRI detects higher Gd-DTPA uptake rates in SCC with medullary invasion as compared to SCC without medullary invasion. This study also suggests that DCE-MRI may have added value over conventional CT and MRI. This added value is reflected by a number of cases where DCE-MRI would have predicted the medullary invasion, whereas conventional imaging was not able to detect mandibular invasion. One false positive diagnosis of medullary invasion by

Conflict of Interest Statement

All authors declare that there are no financial and personal relationships with other people or organisations that could inappropriately influence (bias) this work.

Acknowledgement

The authors thank Mrs. Maria Schipper for performing the statistical analyses.

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