Oxygen‐sensitive MRI assessment of tumor response to hypoxic gas breathing challenge

Abstract

Oxygen‐sensitive MRI has been extensively used to investigate tumor oxygenation based on the response (R2* and/or R1) to a gas breathing challenge. Most studies have reported response to hyperoxic gas indicating potential biomarkers of hypoxia. Few studies have examined hypoxic gas breathing and we have now evaluated acute dynamic changes in rat breast tumors. Rats bearing syngeneic subcutaneous (n = 15) or orthotopic (n = 7) 13762NF breast tumors were exposed to a 16% O2 gas breathing challenge and monitored using blood oxygen level dependent (BOLD) R2* and tissue oxygen level dependent (TOLD) T1‐weighted measurements at 4.7 T. As a control, we used a traditional hyperoxic gas breathing challenge with 100% O2 on a subset of the subcutaneous tumor bearing rats (n = 6). Tumor subregions identified as responsive on the basis of R2* dynamics coincided with the viable tumor area as judged by subsequent H&E staining. As expected, R2* decreased and T1‐weighted signal increased in response to 100% O2 breathing challenge. Meanwhile, 16% O2 breathing elicited an increase in R2*, but divergent response (increase or decrease) in T1‐weighted signal. The T1‐weighted signal increase may signify a dominating BOLD effect triggered by 16% O2 in the relatively more hypoxic tumors, whereby the influence of increased paramagnetic deoxyhemoglobin outweighs decreased pO2. The results emphasize the importance of combined BOLD and TOLD measurements for the correct interpretation of tumor oxygenation properties.

Non-Invasive Evaluation of Acute Effects of Tubulin Binding Agents: A Review of Imaging Vascular Disruption in Tumors

“…Sound waves are also subject to severe scattering by bones and do not transmit through air. US can be entirely non-invasive, but Doppler methods do require sufficient Hypoxia may be observed using oxygen-sensitive MRI including Blood Oxygen Level Dependent (BOLD) and Tissue Oxygen Level Dependent (TOLD) contrast [229][230][231][232][233]. In principle, vascular disruption causes ischemia and yields hypoxiation.…”

Physiological system analysis of the kidney by high‐temporal‐resolution monitoring of an oxygenation step response

“…This study enhances the amount of information by adding the time domain using high‐temporal‐resolution dynamic mapping of the kidney’s response to a test stimulus, including but not limited to changes in the inspiratory oxygenation fraction 49,50 . We hypothesize that high‐temporal‐resolution monitoring of a step‐like oxygenation stimulus facilitates physiological system analysis of the kidney.…”

“…[42][43][44][45][46][47][48] This study enhances the amount of information by adding the time domain using high-temporal-resolution dynamic T * 2 mapping of the kidney's response to a test stimulus, including but not limited to changes in the inspiratory oxygenation fraction. 49,50 We hypothesize that high-temporal-resolution T * 2 monitoring of a step-like oxygenation stimulus facilitates physiological system analysis of the kidney. The term "system analysis" is used in analogy to the well-known and widely used characterization of mechanical and electronic systems 51 that oscillate after perturbations from the steady state.…”

Non-Invasive Evaluation of Acute Effects of Tubulin Binding Agents: A Review of Imaging Vascular Disruption in Tumors

“…MR Elastography indicated reduction in tumor viscoelasticity 24 hrs after ZD6126 at which time no significant change in tumor apparent diffusion coefficient (ADC) was observed [220]. Hypoxia may be observed using oxygen-sensitive MRI including Blood Oxygen Level Dependent (BOLD) and Tissue Oxygen Level Dependent (TOLD) contrast [221][222][223][224][225]. In principle, vascular disruption causes ischemia and yields hypoxiation.…”

“…[3] However, high concentrations of Hb, e.g., accompanying hemorrhage can also accelerate R1, giving potentially anomalous results [225,226]. The signal changes observed using TOLD in response to a hyperoxic gas breathing challenge are much smaller than seen in DCE following Gd-contrast and thus TOLD must be performed first, as in Figure 7, or separate cohorts of animals used [95].…”