Characterisation of Lesions after Stereotactic Radiosurgery for Brain Metastases: Impact of Delayed Contrast Magnetic Resonance Imaging

Highlights

• After SRS, radiation injuries and malignancies have a statistically different signal-intensity time course on delayed MRI.

• By measuring signal-intensity at 15 and 55 min after administering Gd-DTPA, all lesions can be correctly categorised.

• An increase in signal-intensity indicates a radiation injury, whereas a marked decrease indicates malignancy.

Abstract

Aims

To investigate if brain metastases and radiation injuries after stereotactic radiosurgery (SRS) have different signal intensity (SI) time courses up to 55 min after contrast agent application and if delayed contrast magnetic resonance imaging (MRI) contributes to improve diagnostic accuracy.

Materials and methods

Thirty-four consecutive patients treated with SRS for cerebral metastases were prospectively enrolled in the study. T1-weighted images were acquired on a 3-Tesla MR unit at three time points, at 2 (TP1), 15 (TP2) and 55 (TP3) min after administering contrast agent. A simultaneous, matched-pairs approach was used for region of interest analysis of the entire contrast-enhancing lesion (SI-e), the centre (SI-c), the border of the lesion (SI-b) and the adjacent non-contrast-enhancing tissue (SI-p). SIs of brain metastases and radiation injuries after SRS were compared using a two-level, linear, mixed-effects regression model.

Results

In total, 41 lesions were analysed: 16 metastases and 25 radiation injuries. The SI time course of SI-e, SI-c and SI-b proved to be significantly different for both entities (P < 0.001) from TP2 to TP3. The SI of 39/41 lesions increased from TP1 to TP2 for the three parameters. Radiation injuries showed a further signal increase at least for SI-c from TP2 to TP3, whereas for all the three parameters SI decreased in all metastases.

Conclusion

Brain metastases and radiation injuries after SRS have a characteristic and statistically significantly different SI time course on sequential gadolinium enhancement MRI when late MR studies are included.

Introduction

Brain metastases affect 20–40% of patients with systemic cancer [1]. Prognosis varies according to primary tumour type, age, performance status, number of brain metastases and extracranial disease status [2]. Stereotactic radiosurgery (SRS) is an established treatment option for brain metastases in addition to surgery, whole brain radiation therapy, chemotherapy and combinations of these treatments. The evidence that SRS improves patient-relevant outcomes is for patients with up to three brain metastases, good performance status and controlled extracranial disease [2]. The goals of each treatment or combinations of treatments are better local tumour control, improved quality of life and prolonged survival [1], [2], [3], [4], [5], [6]. After radiation treatment, follow-up magnetic resonance imaging (MRI) can depict lesions of the brain with a high sensitivity, but it has limitations in distinguishing radiation injuries from a malignancy [7], [8], [9]. Clinically, this differentiation has significant implications for patient care and outcome and is mandatory for adequately adjusting therapeutic strategies as early as possible. Although most patients with radiation injuries stabilise or improve with symptomatic treatments, those patients with local or distant tumour recurrences require specific therapy [10].

Many studies have been carried out in an attempt to non-invasively distinguish benign from malignant lesions after SRS, but it remains a diagnostic challenge on standard anatomical MRI as the radiographic appearance of these two entities shows many of the same features. More sophisticated MR techniques and positron emission tomography have also been evaluated for this purpose [11], [12], [13], [14], [15]. Although lower apparent diffusion coefficient values have been found in benign as compared with malignant lesions with diffusion-weighted MRI, tumour recurrence could not be reliably distinguished from radiation necrosis [12]. Using dynamic susceptibility-weighted contrast-enhanced perfusion MRI, a cut-off relative cerebral blood volume ratio greater than 2.1 yielded a sensitivity and specificity for identifying malignancy at 100 and 95.2%, respectively [13]. A relative cerebral blood volume ratio below 1.35 was observed exclusively in radiation injuries [14], leaving much overlap in benign and malignant lesions. Lizarraga et al. [15] reported that delayed radiation injury (i.e. radiation necrosis) could be distinguished from progressive brain metastasis with a sensitivity of 81.3% and a specificity of 84.3% using 6-18F-fluoro-l-dopa.

So far, however, none of these techniques, individually or in combination, has been found to be a reliable tool to non-invasively distinguish benign from malignant lesions.

Contrast enhancement of the brain parenchyma on conventional MRI is a consequence of disruption or lack of a blood–brain barrier with exchange of contrast medium between different compartments. These exchanges are known to be time dependent [16] and in other fields, such as cardiac imaging, so-called late gadolinium enhancement studies [17] are already established for making differential diagnoses. MR signal changes caused by contrast agent extravasation are determined by several factors, including tissue perfusion and capillary permeability [18]. As the histopathology of radionecrosis and malignancy differ, analysis of MR signal changes over time may be able to provide additional valuable pathophysiological information.

The aim of our study was to determine if radiation injuries and metastases have significantly different signal intensity (SI) time courses up to 55 min after contrast agent application and, second, if delayed contrast MRI contributes to improve diagnostic accuracy.