MRI Brain Mets Breast (FIESTA)

Official Title

Towards Improved Detection of BRain Metastatses in Breast Cancer Patients: a Pilot Study of Magnetic Resonance Imaging (MRI) in Detecting Vascular Permeable and Non-Permeable Brain Metastases

Summary:

Women diagnosed with metastatic HER-2 positive breast cancer are usually treated with trastuzumab (a HER-2 monoclonal antibody). This therapy is effective against extra-cranial metastases and extends survival. However, these women have up to a 40% risk of developing and succumbing to brain metastases, because antibodies are too large to cross the blood brain barrier. Pre-clinical work by Drs. Foster and Chambers suggests that current MRI diagnostic imaging techniques for these patients, which rely on permeability of brain metastases to gadolinium contrast agent, may underestimate metastatic burden. Balanced steady-state free precession (bSSFP) is an option on clinical MRI units, typically used to image the heart or individual nerves due to its speed and high spatial resolution; this sequence has not been used to image human brain tumours. Our work in a mouse model showed that bSSFP detects more brain metastases than standard contrast enhanced MRI. The purpose of this study is to determine if these findings translate to the human setting. If this is the case, our work may lead to improved detection of brain metastases and a more accurate description of true metastatic burden in these patients, a way to diagnose brain metastases earlier, enabling earlier interventions to improve outcomes.

Trial Description

Primary and Secondary Outcomes:

• Number of new lesions documented by FIESTA but occult to conventional MRI
• Number of  conventional MRI lesions occult to  FIESTA
• Assessment of changes in bSSFP only detected brain metastases.

The main purpose of the proposed study is to determine if a new MRI imaging technique detects additional brain metastases compared to the standard MRI techniques. Magnetic Resonance Imaging (MRI) with intravenous contrast is the present standard for the assessment of brain metastases. MRI employs strong magnetic fields with radiofrequency pulses to detect changes in local magnetic fields associated with protons in the nuclei of atoms. The perturbations in the magnetic fields of hydrogen nuclei are most often studied, given their abundance, especially in water molecules. While CT imaging relies on a single parameter, the difference in electron density between various tissues, MRI uses several features of the changing local magnetic fields to generate a much wider range of contrast between tissues. In imaging brain metastases with MRI, intravenous contrast (gadolinium) is used as it generates a signal since it extravasates where the blood brain barrier is leaky.
The most common MRI techniques use changes in spin echoes to generate various levels of contrast between tissues. Less often used are angular radiofrequency pulses affecting magnetic field gradients. The latter approach leads to much faster data acquisition and a greater signal to noise ratio. MRI gradient echo – instead of spin echo – techniques are most often used to image vascular flow. Recent MRI imaging of brain metastases in mice, by Dr. Paula Foster’s laboratory, comparing 3-dimensional balanced steady-state free precession (bSSFP), a gradient echo technique, against contrast-enhanced T1 weighted MRI, a spin echo technique, demonstrated that early brain metastases up to day twenty were nonpermeable and only detected by the bSSFP technique. Over time, brain metastases in mice became increasingly permeable and detectable by the contrast-enhanced spin echo technique.
In the proposed clinical study, women presenting with brain metastases will be imaged with standard contrast-enhanced MRI and also with the bSSFP technique. The images for the bSSFP technique will be read by the reference radiologist but the results will not be made known to physicians managing the patient’s care. The main objective of this phase of study is to determine if the bSSFP technique detects additional brain metastases over and above the standard MRI. If this is the case, our work may lead to improved detection of brain metastases and a more accurate description of true metastatic burden in these patients, a way to diagnose brain metastases earlier, enabling earlier interventions to improve outcomes.