Decomposition of spontaneous fluctuations in tumour oxygenation using BOLD MRI and independent component analysis.
BACKGROUND
Solid tumours can undergo cycles of hypoxia, followed by reoxygenation, which can have significant implications for the success of anticancer therapies. A need therefore exists to develop methods to aid its detection and to further characterise its biological basis. We present here a novel method for decomposing systemic and tumour-specific contributions to fluctuations in tumour deoxyhaemoglobin concentration, based on magnetic resonance imaging measurements.


METHODS
Fluctuations in deoxyhaemoglobin concentration in two tumour xenograft models of colorectal carcinoma were decomposed into distinct contributions using independent component analysis. These components were then correlated with systemic pulse oximetry measurements to assess the influence of systemic variations in blood oxygenation in tumours, compared with those that arise within the tumour itself (tumour-specific). Immunohistochemical staining was used to assess the physiological basis of each source of fluctuation.


RESULTS
Systemic fluctuations in blood oxygenation were found to contribute to cycling hypoxia in tumours, but tumour-specific fluctuations were also evident. Moreover, the size of the tumours was found to influence the degree of systemic, but not tumour-specific, oscillations. The degree of vessel maturation was related to the amplitude of tumour-specific, but not systemic, oscillations.


CONCLUSIONS
Our results provide further insights into the complexity of spontaneous fluctuations in tumour oxygenation and its relationship with tumour pathophysiology. These observations could be used to develop improved drug delivery strategies.
Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London WC1E 6DD, UK.
Miguel R
MR
Gonçalves
Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London WC1E 6DD, UK.|Cancer Institute, University College London, London WC1E 6DD, UK.
S Peter
SP
Johnson
Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London WC1E 6DD, UK.
Rajiv
R
Ramasawmy
Cancer Institute, University College London, London WC1E 6DD, UK.
R Barbara
RB
Pedley
Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London WC1E 6DD, UK.
Mark F
MF
Lythgoe
Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London WC1E 6DD, UK.
Simon
S
Walker-Samuel
D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism*
D006454:Hemoglobins; C100003:deoxyhemoglobin; D010100:Oxygen