Stereotactic radiosurgery (SRS) is a standard treatment method for patients with brain metastases, providing highly conformal, high-dose radiotherapy with limited cognitive side effects. Although it is an effective treatment method, after several months to over 1 year following SRS there are approximately 33% of treated brain metastases increase in size on imaging, which is suspicious tumor progression. However, based on findings obtained from the subjects with follow-up biopsies, the majority of the newly detected metastases on imaging were radiation treatment effects instead of active tumors. So far, the only gold standard to differentiate active tumor and radiation necrosis is surgical resection for pathologic confirmation, which is invasive and incompliant to those poor surgical candidates, and it should be avoidable in cases of necrosis. Unfortunately, existing non-invasive imaging techniques, including standard magnetic resonance imaging (MRI), perfusion-weighted MRI, MR spectroscopy, single photon emission computed tomography (SPECT), and positron emission tomography (PET), are still far inconsistent, inconvenient to obtain, or have poor sensitivity or specificity of differentiating these two type of tissues. Therefore, often patients are surveilled or undergo a trial of steroid therapy, which delays needed treatment before their brain metastasis has progressed. The discovery of non-invasive biomarkers that distinguish active tumors from radiation necrosis will permit targeted, intensified treatment to patient populations and facilitate clinical trials of new therapies.
Current clinical MRI is typically based on conventional qualitative contrast-weighted MRI images, and it lacks the ability to distinguish active tumors from necrosis. In contrast, quantitative measurement can provide a great deal of information about tissue properties, structures and pathological conditions. Recently, a novel MRI data acquisition approach, namely MR Fingerprinting (MRF), opens the door to multi-parametric MR analysis and thus utilization of T1 and T2 mapping for brain tumor imaging. By leveraging our extensive experience in MRF and fast MR imaging, we propose to develop a unique approach to further accelerate MRF scanning, and apply the developed approach for differentiation of tumor recurrence and radiation necrosis. In addition, quantitative diffusion MRI, such as the intravoxel incoherent motion (IVIM) technique, can provide a noninvasive and powerful tool to quantify microstructural information by measuring water diffusion and microcirculation perfusion in vivo.
In this proposal, we aim to 1) demonstrate the clinical feasibility of combining MRF with state-of-the-art parallel imaging techniques to achieve high-resolution quantitative imaging within a reasonable scan time of 5 min for whole brain coverage, and 2) apply the developed quantitative approach in combination with IVIM MRI for differentiation of tumor recurrence and radiation necrosis. Based on the new MRF technique development and the obtained quantitative patient MRI results in this study, we expect that 1) the combination of sequence optimization and parallel imaging will greatly reduce the scan time to less than 5 minutes while providing accurate quantification with a high spatial resolution (1×1×2 mm3) and whole-brain coverage (18-cm volume), and 2) the multi-parametric quantitative measures developed in this study could establish a new fundamental biomarker for the diagnosis and monitoring of brain tumors.