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Biology subjects

Khokhar, S.

Publications and source records attributed to Khokhar, S..

2 recordsLinked to original sources

Magnetic Resonance Imaging for Improved Brain Tumor Detection

Precise demarcation of brain tumor boundaries is critical for optimizing treatment strategies and improving patient outcomes. In vivo characterization of tumor using PET/CT and MRI is clinical standard. PET/CT highlights the metabolic aspects of the tumor, while MRI provides information on functional, metabolic and structural changes. Even with technological advancements in both PET/CT and MRI, a method that can precisely delineate infiltrative tumor boundaries from normal-appearing brain regions (NABR) in vivo is still lacking. To address this limitation, we explored a relatively new MR imaging method, the Nuclear Overhauser Effect Magnetization Transfer Ratio (NOEMTR), in conjunction with a gadolinium-based contrast agent (Gd-DOTA), to precisely delineate the tumor boundaries in a rat model of infiltrative gliosarcoma. NOEMTR imaging was performed in the rat model (n=5) before and after Gd-DOTA administration. The post-Gd-DOTA NOEMTR map was subtracted from the pre-Gd-DOTA map and compared with contrast-enhanced T1-weighted images and immuno-histological findings. The resulting NOEMTR difference map clearly highlighted both the tumor core and infiltrative boundaries, which was not discernible on the post-contrast T1-weighted images. The extended tumor boundaries observed on the NOEMTR difference map corroborated with the IHC image, which confirmed the presence of infiltrative tumor cells and macrophages in these regions. Guided by the NOEMTR difference map, regions of interest (ROI) were drawn to quantify NOEMTR signal changes in the tumor core, tumor boundaries, and NABR post-Gd-DOTA. Tumor core showed a significant [~]43% reduction in NOEMTR signal (plJ=lJ0.003), while the tumor periphery exhibited a moderate reduction of [~]10%, (plJ=lJ0.045). No appreciable change in was observed in the NABR (plJ=lJ0.371). In contrast, the post contrast T1-weighted signal changes in tumor core, tumor periphery and NABR were, 33.32% (p = 0.092), 3.8% (p = 0.478), and 8.7% (p = 0.464) respectively. These findings suggest that NOEMTR imaging provides enhanced tumor contrast, particularly at the infiltrative tumor margins, where conventional contrast enhanced T1-weighted MRI may underestimate tumor extent. Histological validation confirmed the presence of infiltrative tumor cells and macrophages in the tumor periphery, as highlighted by the NOEMTR difference map. Overall, NOEMTR imaging, in combination with Gd-DOTA administration, demonstrates superior delineation of brain tumor boundaries compared to conventional MRI. As NOEMTR imaging is a fast acquisition scan (under 10 minutes) and performed on standard 3 Tesla, it can be easily integrated into clinical protocols. By improving visualization of tumor infiltration and distinguishing tumor regions from NABR, NOEMTR imaging holds promise for advancing neuro-oncological diagnostics and treatment planning.

bioengineering↗

Non-invasive imaging of gene expression and protein secretion dynamics in living mice

The topology of gene expression and protein localization is a crucial characteristic of life, where the spatiotemporal dynamic of secretory proteins instruct higher order organization, including the orchestration of developmental and adaptive programs. However tools to non-invasively interrogate the fate of secretory proteins in vivo are scarce. Here we introduce a genetic tagging strategy for in vivo imaging of the secretion and expression dynamics of secretory proteins in living animals. Applying this to a prototypical liver-derived secretory protein, we demonstrate that this approach, combined with optical in-vivo imaging, uncovers extrahepatic prothrombin expression in multiple novel anatomical sites (including testes, placenta, brain, kidney, heart and lymphatic system) and in emerging tumors, resulting in significant amounts of tumor-derived prothrombin in the blood with procoagulant properties. Syngeneic cell lines from this mouse model enable unravelling regulatory mechanisms in high resolution, and in a scalable format ex vivo. Beyond discovering new functions of proteins in a targeted manner, this model allows identifying rheostats in the cross-talk between gene expression and availability of a secretory protein. It is also a valuable resource for uncovering novel (tissue-specific) therapeutic vulnerabilities.

cell biology↗