Research

The Weis Lab employs a hybrid experimental/computational approach towards characterizing disease, employing tools of imaging, biophysics, and computational modeling to study disease progression and response to therapy in cancer and other diseases.

Research spans the length scale of disease from preclinical in vitro and in vivo model systems to translational clinical-based investigations within the scope of several overarching projects:

1. Multi-scale imaging-based biophysical modeling to predict the response of breast cancer to chemotherapy

We begin with the hypothesis that interactions between cancer and tissue at the macroscopic level can be described by a coupled reactive-diffusive mechanics system, where tumor cells grow and diffuse in space depending on their mechanical environment. Rather than use this system to simulate tumor growth de novo, the Weis Lab is interested in leveraging rich non-invasive imaging data sources available to make these models patient-specific. This has led to work developing a mathematical approach to interpret quantitative in vivo imaging data using biomathematical models of tumor growth in order to characterize and predict response to neoadjuvant chemotherapy based on early measurements. The Weis Lab investigates the use of these methods in both pre-clinical and clinical settings using 3D spheroid/organoid cancer model systems imaged using live-cell fluorescence microscopy and quantitative MRI in patients, respectively.

2. Imaging-based biophysical modeling to differentiate tumor recurrence from radiation necrosis following stereotactic radiosurgery for intracranial metastasis

Patients with intracranial metastases often undergo stereotactic radiosurgery (e.g. GammaKnife) for local control. Following treatment, some patients develop radiation-induced necrosis, which appears radiographically similar to tumor recurrence on follow-up imaging. Both may appear as an enhancing lesion in contrast-enhanced MR imaging with surrounding fluid abnormality, complicating diagnostic and therapeutic efforts. The Weis Lab has developed a spatiotemporal model of tumor growth to parameterize tumor growth kinetics, based on contrast-enhanced serial MR imaging. Differences between patients with tumor recurrence and radiation-induced necrosis can be identified when comparing the biophysical model-based parameters, suggesting the potential to non-invasively distinguish between diagnoses in a biophysical model-based image analysis framework.

3. Mechanical stiffness as a biomarker to evaluate and predict breast cancer therapeutic response

Mechanical investigations within the Weis Lab focus on studying cancer from a mechanics and mathematical modeling background to explore tissue-level mechanical stiffness imaging biomarkers in breast cancer. The Weis Lab has developed novel computational methodologies to assess tissue-level mechanical elasticity in breast cancer clinical and preclinical models based on anatomical magnetic resonance images collected before and after the application of a quasi-static mechanical compression. In an extension to the methodology, we have also investigated the use of the method in clinical cancer patients using gravitational excitation as a deformation source to drive model-based estimation of mechanical tissue stiffness markers.

5. Non-invasive imaging for biophysical indicators of neonatal intestinal health and disease

Imaging and biophysical computational characterization methods within the Weis Lab have also been extended to study the developing gastrointestinal system under a multi-disciplinary team-science approach. In this work, we are developing and deploying new advanced non-invasive imaging and image analysis methods for intestinal disease within the neonatal setting. The extension of quantitative imaging characterization methodology development to study intestinal health and disease into this setting presents significant translational opportunity to improve quality of care in neonatal and pediatric patients.