Physiological noise in murine solid tumours using T2*-weighted gradient-echo imaging: a marker of tumour acute hypoxia?
- 10 July 2004
- journal article
- research article
- Published by IOP Publishing in Physics in Medicine & Biology
- Vol. 49 (15) , 3389-3411
- https://doi.org/10.1088/0031-9155/49/15/006
Abstract
T2*-weighted gradient-echo magnetic resonance imaging (T2*-weighted GRE MRI) was used to investigate spontaneous fluctuations in tumour vasculature non-invasively. FSa fibrosarcomas, implanted intramuscularly (i.m.) in the legs of mice, were imaged at 4.7 T, over a 30 min or 1 h sampling period. On a voxel-by-voxel basis, time courses of signal intensity were analysed using a power spectrum density (PSD) analysis to isolate voxels for which signal changes did not originate from Gaussian white noise or linear drift. Under baseline conditions, the tumours exhibited spontaneous signal fluctuations showing spatial and temporal heterogeneity over the tumour. Statistically significant fluctuations occurred at frequencies ranging from 1 cycle/3 min to 1 cycle/h. The fluctuations were independent of the scanner instabilities. Two categories of signal fluctuations were reported: (i) true fluctuations (TFV), i.e., sequential signal increase and decrease, and (ii) profound drop in signal intensity with no apparent signal recovery (SDV). No temporal correlation between tumour and contralateral muscle fluctuations was observed. Furthermore, treatments aimed at decreasing perfusion-limited hypoxia, such as carbogen combined with nicotinamide and flunarizine, decreased the incidence of tumour T2*-weighted GRE fluctuations. We also tracked dynamic changes in T2* using multiple GRE imaging. Fluctuations of T2* were observed; however, fluctuation maps using PSD analysis could not be generated reliably. An echo-time dependency of the signal fluctuations was observed, which is typical to physiological noise. Finally, at the end of T2*-weighted GRE MRI acquisition, a dynamic contrast-enhanced MRI was performed to characterize the microenvironment in which tumour signal fluctuations occurred in terms of vessel functionality, vascularity and microvascular permeability. Our data showed that TFV were predominantly located in regions with functional vessels, whereas SDV occurred in regions with no contrast enhancement as the result of vessel functional impairment. Furthermore, transient fluctuations appeared to occur preferentially in neoangiogenic hyperpermeable vessels. The present study suggests that spontaneous T2*-weighted GRE fluctuations are very likely to be related to the spontaneous fluctuations in blood flow and oxygenation associated with the pathophysiology of acute hypoxia in tumours. The disadvantage of the T2*-weighted GRE MRI technique is the complexity of signal interpretation with regard to pO2 changes. Compared to established techniques such as intravital microscopy or histological assessments, the major advantage of the MRI technique lies in its capacity to provide simultaneously both temporal and detailed spatial information on spontaneous fluctuations throughout the tumour.Keywords
This publication has 43 references indexed in Scilit:
- Tumor-line specific pO2 fluctuations in human melanoma xenograftsInternational Journal of Radiation Oncology*Biology*Physics, 2004
- Temporal heterogeneity in oxygen tension in human melanoma xenograftsBritish Journal of Cancer, 2003
- Cluster analysis of BOLD fMRI time series in tumors to study the heterogeneity of hemodynamic response to treatmentMagnetic Resonance in Medicine, 2003
- Using High Spectral and Spatial Resolution Bold MRI to Choose the Optimal Oxygenating Treatment for Individual Cancer PatientsPublished by Springer Nature ,2003
- How does blood oxygen level‐dependent (BOLD) contrast correlate with oxygen partial pressure (pO2) inside tumors?Magnetic Resonance in Medicine, 2002
- Spectrally inhomogeneous BOLD contrast changes detected in rodent tumors with high spectral and spatial resolution MRINMR in Biomedicine, 2002
- Drug-induced alterations in tumour perfusion yield increases in tumour cell radiosensitivityBritish Journal of Cancer, 2001
- Analysis of subcutaneous angiogenesis by gradient echo magnetic resonance imagingMagnetic Resonance in Medicine, 1998
- Temporal heterogeneity in microregional erythrocyte flux in experimental solid tumoursBritish Journal of Cancer, 1995
- Acute hypoxia in tumors: Implications for modifiers of radiation effectsInternational Journal of Radiation Oncology*Biology*Physics, 1986