BOLD MRI of human tumor oxygenation during carbogen breathing

An MRI method is described for demonstrating improved oxygenation of human tumors and normal tissues during carbogen inhalation (95% O2, 5% CO2). T  *2 ‐weighted gradient‐echo imaging was performed before, during, and after carbogen breathing in 47 tumor patients and 13 male volunteers. Analysis of artifacts and signal intensity was performed. Thirty‐six successful tumor examinations were obtained. Twenty showed significant whole‐tumor signal increases (mean 21.0%, range 6.5–82.4%), and one decreased (−26.5 ± 8.0%). Patterns of signal change were heterogeneous in responding tumors. Five of 13 normal prostate glands (four volunteers and nine patients with nonprostatic tumors) showed significant enhancement (mean 11.4%, range 8.4–14.0%). An increase in brain signal was seen in 11 of 13 assessable patients (mean 8.0 ± 3.7%, range 5.0–11.7%). T  *2 ‐weighted tumor MRI during carbogen breathing is possible in humans. High failure rates occurred due to respiratory distress. Significant enhancement was seen in 56%, suggesting improved tissue oxygenation and blood flow, which could identify these patients as more likely to benefit from carbogen radiosensitization. J. Magn. Reson. Imaging 2001;14:156–163. © 2001 Wiley‐Liss, Inc.

[1]  S. Dische,et al.  Clinical results of hypoxic cell radiosensitisation from hyperbaric oxygen to accelerated radiotherapy, carbogen and nicotinamide. , 1996, The British journal of cancer. Supplement.

[2]  J. Kruuv,et al.  Blood flow and oxygenation of tumors in mice. I. Effects of breathing gases containing carbon dioxide at atmospheric pressure , 1967, Cancer.

[3]  J C Gore,et al.  Physiologic basis for BOLD MR signal changes due to hypoxia/hyperoxia: Separation of blood volume and magnetic susceptibility effects , 1997, Magnetic resonance in medicine.

[4]  C. Grau,et al.  Improving the radiation response in a C3H mouse mammary carcinoma by normobaric oxygen or carbogen breathing. , 1992, International journal of radiation oncology, biology, physics.

[5]  R. Turner,et al.  Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[6]  H. Baddeley,et al.  Inspired and expired gas concentrations in man during carbogen breathing. , 1999, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[7]  H Baddeley,et al.  Gas exchange parameters in radiotherapy patients during breathing of 2%, 3.5% and 5% carbogen gas mixtures. , 2000, The British journal of radiology.

[8]  S. Ogawa,et al.  Oxygenation‐sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields , 1990, Magnetic resonance in medicine.

[9]  S. Dische.  What have we learnt from hyperbaric oxygen? , 1991, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[10]  J R Griffiths,et al.  The response of human tumors to carbogen breathing, monitored by Gradient-Recalled Echo Magnetic Resonance Imaging. , 1997, International journal of radiation oncology, biology, physics.

[11]  A. Rojas.  ARCON: accelerated radiotherapy with carbogen and nicotinamide. , 1992, BJR supplement.

[12]  R. Hill,et al.  The importance of the pre-irradiation breathing times of oxygen and carbogen (5% CO2: 95% O2) on the in vivo radiation response of a murine sarcoma. , 1977, International journal of radiation oncology, biology, physics.

[13]  SJ Falk,et al.  The influence of carbogen breathing on tumour tissue oxygenation in man evaluated by computerised p02 histography. , 1992, British journal of cancer.

[14]  P. Hoskin,et al.  Effect of carbogen breathing on tumour microregional blood flow in humans. , 1996, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[15]  P Vaupel,et al.  Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements. , 1991, Cancer research.

[16]  S. Hill,et al.  Temporal heterogeneity in microregional erythrocyte flux in experimental solid tumours. , 1995, British Journal of Cancer.

[17]  P. Hoskin,et al.  Improvement in human tumour oxygenation with carbogen of varying carbon dioxide concentrations. , 1999, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[18]  F. Howe,et al.  Modification of Tumour Perfusion and Oxygenation Monitored by Gradient Recalled Echo MRI and 31P MRS , 1996, NMR in biomedicine.

[19]  W. Tilley,et al.  Vascular endothelial growth factor (VEGF) expression in prostate cancer and benign prostatic hyperplasia. , 1997, The Journal of urology.

[20]  B Vojnovic,et al.  Tumour radiosensitization by high-oxygen-content gases: influence of the carbon dioxide content of the inspired gas on PO2, microcirculatory function and radiosensitivity. , 1998, International journal of radiation oncology, biology, physics.

[21]  V. Laudone,et al.  Angiogenesis and prostate cancer: in vivo and in vitro expression of angiogenesis factors by prostate cancer cells. , 1998, Urology.

[22]  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.

[23]  S. Dische.  Hyperbaric oxygen: the Medical Research Council trials and their clinical significance. , 1978, The British journal of radiology.

[24]  J C Gore,et al.  Quantification of intravascular and extravascular contributions to BOLD effects induced by alteration in oxygenation or intravascular contrast agents , 1998, Magnetic resonance in medicine.

[25]  P Lambin,et al.  Changes in the oxygenation of head and neck tumors during carbogen breathing. , 1993, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[26]  F. Howe,et al.  Noninvasive monitoring of carbogen-induced changes in tumor blood flow and oxygenation by functional magnetic resonance imaging. , 1995, International journal of radiation oncology, biology, physics.

[27]  P. Vaupel,et al.  Tumor tissue oxygenation as evaluated by computerized-pO2-histography. , 1990, International journal of radiation oncology, biology, physics.

[28]  O Henriksen,et al.  Functional MRI of CO2 induced increase in cerebral perfusion , 1994, NMR in biomedicine.