A DTI study to probe tumor microstructure and its connection with hypoxia

Solid tumors have chaotic organization of blood vessels, disruptive nerve paths and muscle fibers that result in a hostile and heterogeneous microenvironment. These tumor regions are often hypoxic and resistant to radiation therapy. The knowledge of partial pressure of oxygen concentration (pO2), in conjunction with the information about tissue organization, can predict tissue health and may eventually be used in combination with intensity-modulated radiation therapy (IMRT) for targeted destruction of radiation-resistant areas, while sparing healthy tissues. Diffusion tensor imaging (DTI) based parameter fractional anisotropy (FA) can be used to assess organization of tissue microstructure, whereas the pO2 can be measured using electron paramagnetic resonance oxygen imaging (EPROI). This study is our first step to connect these two important physiological parameters. We calculated FA in fixed fibrosarcoma (FSa) grown in hind leg of nude mice (n = 6) using preclinical 9.4 T MRI. The FA in tumor region (0.34 ± 0.014) was found to be lower when compared to normal surrounding region (0.36 ± 0.013). We hypothesized that the change in FA is directly correlated with the change in oxygen concentration in tumor. We present preliminary in vivo results showing a positive correlation (R = 0.85, p = 0.017) between the FA and pO2 values acquired for MCa4 tumor (n = 1) using DTI and EPROI.

[1]  David J. Collins,et al.  SUMMARY Technology Insight: water diffusion MRI—a potential new biomarker of response to cancer , 2008 .

[2]  Rakesh K. Jain,et al.  Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy , 2001, Nature Medicine.

[3]  R. Jain,et al.  Delivering nanomedicine to solid tumors , 2010, Nature Reviews Clinical Oncology.

[4]  S. Jewell,et al.  Copyright © American Society for Investigative Pathology Review Effect of Fixatives and Tissue Processing on the Content and Integrity of Nucleic Acids , 2022 .

[5]  Martijn Froeling,et al.  DTI of human skeletal muscle: the effects of diffusion encoding parameters, signal‐to‐noise ratio and T2 on tensor indices and fiber tracts , 2013, NMR in Biomedicine.

[6]  P. Basser,et al.  Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. 1996. , 1996, Journal of magnetic resonance.

[7]  G. Johnson,et al.  Peritumoral diffusion tensor imaging of high-grade gliomas and metastatic brain tumors. , 2003, AJNR. American journal of neuroradiology.

[8]  Derek K. Jones,et al.  Diffusion‐tensor MRI: theory, experimental design and data analysis – a technical review , 2002 .

[9]  L. H. Gray,et al.  The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. , 1953, The British journal of radiology.

[10]  K A Il'yasov,et al.  Contribution of diffusion tensor MR imaging in detecting cerebral microstructural changes in adults with neurofibromatosis type 1. , 2007, AJNR. American journal of neuroradiology.

[11]  P. Basser,et al.  Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. , 1996, Journal of magnetic resonance. Series B.

[12]  Howard J. Halpern,et al.  Electron paramagnetic resonance oxygen imaging in vivo , 2012 .

[13]  Colin Mailer,et al.  Absolute oxygen R1e imaging in vivo with pulse electron paramagnetic resonance , 2014, Magnetic resonance in medicine.

[14]  P. Sundgren,et al.  Diffusion tensor imaging of the brain: review of clinical applications , 2004, Neuroradiology.

[15]  Brian O'Rourke,et al.  Hypoxic tumor microenvironments reduce collagen I fiber density. , 2010, Neoplasia.

[16]  Martyna Elas,et al.  EPR oxygen images predict tumor control by a 50% tumor control radiation dose. , 2013, Cancer research.

[17]  J Martin Brown,et al.  Tumor hypoxia in cancer therapy. , 2007, Methods in enzymology.

[18]  Elias R. Melhem,et al.  Diffusion Tensor Imaging: Introduction and Applications to Brain Tumor Characterization , 2014 .

[19]  David J Collins,et al.  Technology Insight: water diffusion MRI—a potential new biomarker of response to cancer therapy , 2008, Nature Clinical Practice Oncology.

[20]  P. Choyke,et al.  Diffusion-weighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations. , 2009, Neoplasia.