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Updated: May 16, 2026
Longitudinal Intravital Imaging of Brain Tumor Cell Behavior in Response to an Invasive Surgical Biopsy
Published on: May 3, 2019
Real-time multi-modality imaging of glioblastoma tumor resection and recurrence
Shawn Hingtgen1, Jose-Luiz Figueiredo, Christian Farrar
1Molecular Neurotherapy and Imaging Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Abstract:
The lack of relevant pre-clinical animal models incorporating the clinical scenario of Glioblastoma multiforme (GBM) resection and recurrence has contributed significantly to the inability to successfully treat GBM. A multi-modality imaging approach that allows real-time assessment of tumor resection during surgery and non-invasive detection of post-operative tumor volumes is urgently needed. In this study, we report the development and implementation of an optical imaging and magnetic resonance imaging (MRI) approach to guide GBM resection during surgery and track tumor recurrence at multiple resolutions in mice. Intra-operative fluorescence-guided surgery allowed real-time monitoring of intracranial tumor removal and led to greater than 90 % removal of established intracranial human GBM. The fluorescent signal clearly delineated tumor margins, residual tumor, and correlated closely with the clinically utilized fluorescence surgical marker 5-aminolevulinic acid/porphyrin. Post-operative non-invasive optical imaging and MRI confirmed near-complete tumor removal, which was further validated by immunohistochemistry (IHC). Longitudinal non-invasive imaging and IHC showed rapid recurrence of multi-focal tumors that exhibited a faster growth rate and altered blood-vessel density compared to non-resected tumors. Surgical tumor resection significantly extended long-term survival, however mice ultimately succumbed to the recurrent GBM. This multi-modality imaging approach to GBM resection and recurrence in mice should provide an important platform for investigating multiple aspects of GBM and ultimately evaluating novel therapeutics.
Insights
Developing advanced imaging techniques for Glioblastoma multiforme (GBM) resection and recurrence in mice improves surgical outcomes. This multi-modal approach aids in tracking tumor regrowth and evaluating new therapies.
Area of Science:
- Neuro-oncology
- Medical imaging
- Pre-clinical research
Background:
- Glioblastoma multiforme (GBM) treatment is hindered by a lack of effective pre-clinical models that replicate clinical resection and recurrence.
- There is a critical need for imaging methods enabling real-time surgical assessment and non-invasive post-operative tumor monitoring.
Purpose of the Study:
- To develop and implement a multi-modal optical imaging and MRI approach for guiding GBM resection and tracking tumor recurrence in mice.
- To assess the efficacy of intra-operative fluorescence-guided surgery in achieving maximal tumor removal.
- To evaluate the capability of post-operative imaging in detecting tumor recurrence and characterizing its features.
Main Methods:
- Development of an integrated optical and MRI system for intra-operative guidance and post-operative monitoring of GBM in a mouse model.
- Utilization of intra-operative fluorescence imaging to delineate tumor margins during resection.
- Application of longitudinal non-invasive optical imaging and MRI for tracking tumor recurrence, validated by immunohistochemistry (IHC).
Main Results:
- Intra-operative fluorescence-guided surgery achieved >90% removal of intracranial human GBM, with clear delineation of tumor margins.
- Post-operative imaging confirmed near-complete tumor removal, with subsequent detection of rapid, multi-focal tumor recurrence.
- Recurrent tumors exhibited faster growth and altered vascularity compared to non-resected tumors, despite initial survival extension from resection.
Conclusions:
- The developed multi-modal imaging approach effectively guides GBM resection and tracks tumor recurrence in mice.
- This platform provides a valuable tool for investigating GBM biology and evaluating novel therapeutic strategies.
- While surgical resection improves survival, recurrent GBM remains a significant challenge, necessitating further research into effective treatments.
