Issues in flow and oxygenation dependent contrast (FLOOD) imaging of tumours

Abstract

The sensitivity of blood oxygenation level dependent (BOLD) contrast techniques to changes to tumour deoxyhaemoglobin concentration is of relevance to many strategies in cancer treatments. In the context of tumour studies, which frequently involve the use of agents to modify blood flow, there are underlying physiological changes different to those of BOLD in the brain. Hence we use the term, flow and oxygenation dependent (FLOOD) contrast, to emphasize this difference and the importance of flow effects. We have measured the R 2 * changes in a prolactinoma tumour model for a variety of vasoactive challenges [carbogen, 100% oxygen and 100% nitrogen as different breathing gases, and administration of tumour blood flow modifiers such as calcitonin gene related peptide (CGRP), hydralazine and nicotinamide]. In addition we have measured other relevant physiological parameters, such as bioenergetic status from 31 P MRS, and blood pH and glucose, that may change during a vasoactive challenge. Here we discuss how they relate to our understanding of FLOOD contrast in tumours. We frequently observe R 2 * changes that match the expected action of the vascular stimulus: R 2 * decreases with agents expected to improve tumour oxygenation and blood flow, and increases with agents designed to increase tumour hypoxia. Unlike most normal tissues, tumours have a chaotic and poorly regulated blood supply, and a mix of glycolytic and oxidative metabolism; thus the response to a vasoactive challenge is not predictable. Changes in blood volume can counteract the effect of blood oxygenation changes, and changes in blood pH and glucose levels can alter oxygen extraction. This can lead to R 2 * changes that are smaller or the reverse of those expected. To properly interpret FLOOD contrast changes these effects must be accounted for.

Quantification of the magnetic resonance signal response to dynamic (C)O2‐enhanced imaging in the brain at 3 T: R*2 BOLD vs. balanced SSFP

“…Because the bSSFP signal approximately scales with the R 1 /R 2 ratio (46), this can also be explained by a reduced dHb concentration (R 2 decrease) as well as by an increase in PO 2 and an elevated inflow of unsaturated spins: both manifest in an enhancement of the true and apparent R 1 , respectively (16,30). With long TE and TR, the bSSFP signal further exhibits a considerable T* 2 contrast and Miller et al have shown that gradientecho and passband bSSFP signals behave similarly at long TR (34,35), which could be another explanation of the bSSFP signal increase.…”

Influence of body temperature on the BOLD effect in murine SCC tumors†

“…The tip angle chosen in the GRE pulse sequences in the imaging experiments was sufficient to elicit BOLD contrast caused by changes in both tissue oxygen concentration and blood flow (15,16). The present study shows that the core temperature of a female C3H mouse steadily decreases from 37°C to 30°C within ϳ20 min.…”

Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

“…Apart from its very large application in neuroscience, the use of BOLD contrast in tumor brings with it new challenges of understanding and interpretation. 100 The underlying physiological changes are different from those of BOLD in the brain. In the brain, blood vessel size, density and distribution are well characterized, in contrast to tumors.…”

“…113 Changes in R Ã 2 in response to a vasoactive challenge are not always predictable. 100 An R Ã 2 decrease is expected in response to agents aimed at improving tumor oxygenation and blood flow, and conversely an increase in R Ã 2 is expected with agents designed to increase tumor hypoxia. However, changes in blood volume can counteract the effect of blood oxygenation changes.…”