Noninvasive Imaging of Cycling Hypoxia in Head and Neck Cancer Using Intrinsic Susceptibility MRI

Abstract

Purpose: To evaluate intrinsic susceptibility (IS) MRI for the identification of cycling hypoxia, and the assessment of its extent and spatial distribution, in head and neck squamous cell carcinoma (HNSCC) xenografts and patients.Experimental Design: Quantitation of the transverse relaxation rate, R 2 Ã , which is sensitive to paramagnetic deoxyhemoglobin, using serial IS-MRI acquisitions, was used to monitor temporal oscillations in levels of paramagnetic deoxyhemoglobin in human CAL R xenografts and patients with HNSCC at 3T. Autocovariance and power spectrum analysis of variations in R 2 Ã was performed for each imaged voxel, to assess statistical significance and frequencies of cycling changes in tumor blood oxygenation. Pathologic correlates with tumor perfusion (Hoechst 33342), hypoxia (pimonidazole), and vascular density (CD31) were sought in the xenografts, and dynamic contrast-enhanced (DCE) MRI was used to assess patient tumor vascularization. The prevalence of fluctuations within patient tumors, DCE parameters, and treatment outcome were reported.Results: Spontaneous R 2 Ã fluctuations with a median periodicity of 15 minutes were detected in both xenografts and patient tumors. Spatially, these fluctuations were predominantly associated with regions of heterogeneous perfusion and hypoxia in the

Imaging tumour hypoxia with oxygen-enhanced MRI and BOLD MRI

“…[91][92][93] Given the sensitivity of R 2 * to deoxygenated erythrocytes, continuous BOLD MRI measurements have been exploited pre-clinically to non-invasively image cyclical hypoxia through changes in the oxy/ deoxyhaemoglobin ratio at high spatial and temporal resolution in both xenografts and patient tumours in vivo. [94][95][96] Frequencies in the range of 0.00027-0.001 Hz (corresponding to 15 to 60 min) were measured, comparable to the periodicity originally reported from classical pre-clinical invasive measurements of cyclical hypoxia. 97,98 Interestingly, in patients with head and neck squamous cell carcinoma, R 2 * fluctuations spatially correlated with parts of lymph nodes with low K trans values, typically in the vicinity of necrotic nodes.…”

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

“…Because of this, blood in such vessels periodically changes its route [83], which results in tumor segmentation into hypoxia areas that re-oxygenate after some time [116] ( Figure 3). This process loops every few minutes [116,117] for up to several hours [118,119]. This type of hypoxia is called cycling (intermittent, transient) hypoxia and is characteristic of a malignant tumor.…”

Quantitative photoacoustic imaging study of tumours in vivo: baseline variations in quantitative measurements

“…(while O 2 breathing) and sO 2 (difference in measured sO 2 between airand oxygen-breathing) decreased with tumour growth, from a 30 mm 3 volume to time of culling. The CAL R model used for this project has also been shown to be aggressive[36] and hypoxic, using MRI and histology evidence (pimonidazole for hypoxia and Hoechst staining for perfusion)[49], so a decrease in sO 2, as observed by Tomaszewski et al[41], might have been expected. However, this was not the case, either during air-or oxygen-breathing imaging, for the CAL R tumour model.The intra-and inter-tumour CoVs for the 6 day imaging study, Table A 5, were >19.3±8.7% and >27.0±4.1%, respectively, for the haemoglobin parameters (Hb, HbO 2 and HbT).…”