Room: Room 207
Purpose: Tumor hypoxia is the result of limited oxygen delivery during uncontrolled proliferation and is a common indication of invasive and metastatic potential. Clinical imaging techniques have been used to measure hypoxic conditions, but most suffer from limited spatial and temporal resolutions (e.g. FMISO PET) or utilize highly invasive procedures (Eppendorf electrodes). In this work, we detail preliminary applications of in-vivo photoacoustic CT (PCT) to measure and distinguish acute and chronic hypoxia.
Methods: Ten mice were seeded with syngeneic MC38 tumors and imaged with PCT-spectroscopy over two weeks to determine local hemoglobin concentration (Hb) and oxygen saturation (SaO2) with growth. Additional PCT-S scans were acquired over two hours in 15-minute intervals to measure short-term fluctuations in SaO2 and Hb. Hypoxia classification was based on SaO2 levels in voxels containing hemoglobin. Voxels that never exceeded 0.2 SaO2 (equivalent to 10mmHg) were labelled chronically hypoxic. Voxels that oscillate above and below 0.2 were labelled as cycling, or acutely hypoxic.
Results: Notable regions of low Hb and low SaO2 were observed through the duration of scanning in all mice, indicating the presence of some form of hypoxia throughout growth. On average, the hypoxic fraction increased with tumor growth as SaO2/Hb decreased. Acute hypoxia was more prevalent in early time points, but regions of chronic hypoxia developed as tumor volumes increased.
Conclusion: Photoacoustic imaging is uniquely capable of concurrent hemoglobin and oxygen saturation measurement. Histology is in-progress to validate presence of hypoxia-specific factors (HIF-1alpha, HIF2alpha). Combined, these techniques provide a non-invasive method to assess metabolic and undifferentiated status within the tumor microenvironment. Further work will incorporate DCE-PCT to measure vascular perfusion and apply oxygen transport models to directly calculate interstitial pO2.
Not Applicable / None Entered.