Quantitative BOLD imaging at 3T: Temporal changes in hepatocellular carcinoma and fibrosis following oxygen challenge

Patterson, Andrew J.; Priest, Andrew N.; Bowden, David J.; Wallace, Tess E.; Patterson, Ilse; Graves, Martin J.; Lomas, David J.

doi:10.1002/jmri.25189

Cited by 21 publications

(22 citation statements)

References 23 publications

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“…Several preliminary studies have already shown the use of hyperoxic gas challenge to stimulate BOLD and/or TOLD MRI signal responses in tumors at distinct disease sites (breast [56, 57], cervix [49, 58, 59], brain [38, 60], prostate [61], and liver [62]). Breathing oxygen is particularly appropriate, since this is standard intervention in emergency medicine and thus it is quite straightforward to gain IRB approval.…”

Section: Discussionmentioning

confidence: 99%

Developing oxygen-enhanced magnetic resonance imaging as a prognostic biomarker of radiation response

White

Zhang

et al. 2016

Cancer Letters

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Oxygen-Enhanced Magnetic Resonance Imaging (OE-MRI) techniques were evaluated as potential non-invasive predictive biomarkers of radiation response. Semi quantitative blood-oxygen level dependent (BOLD) and tissue oxygen level dependent (TOLD) contrast, and quantitative responses of relaxation rates (ΔR1 and ΔR2*) to an oxygen breathing challenge during hypofractionated radiotherapy were applied. OE-MRI was performed on subcutaneous Dunning R3327-AT1 rat prostate tumors (n = 25) at 4.7 T prior to each irradiation (2Fx15 Gy) to the gross tumor volume. Response to radiation, while inhaling air or oxygen, was assessed by tumor growth delay measured up to four times the initial irradiated tumor volume (VQT). Radiation-induced hypoxia changes were confirmed using a double hypoxia marker assay. Inhaling oxygen during hypofractionated radiotherapy significantly improved radiation response. A correlation was observed between the difference in the 2nd and 1st ΔR1 (ΔΔR1) and VQT for air breathing rats. The TOLD response before the 2nd fraction showed a moderate correlation with VQT for oxygen breathing rats. The correlations indicate useful prognostic factors to predict tumor response to hypofractionation and could readily be applied for patient stratification and personalized radiotherapy treatment planning.

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Section: Discussionmentioning

confidence: 99%

Developing oxygen-enhanced magnetic resonance imaging as a prognostic biomarker of radiation response

White

Zhang

et al. 2016

Cancer Letters

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“…18 In humans, gas challenges have been used to elicit T * 2 signal changes in studying hepatocellular carcinoma. 24,32 This study had limitations for the gas challenge. The main drawback of a hypercapnic challenge is the patient tolerability of the inspired CO 2 , which limits the level of P ET CO 2 , resulting in a smaller change in liver hemodynamics compared with the animal studies.…”

Section: Discussionmentioning

confidence: 99%

Using MRI to study the alterations in liver blood flow, perfusion, and oxygenation in response to physiological stress challenges: Meal, hyperoxia, and hypercapnia

Cox

Palaniyappan

Aithal

et al. 2018

Magnetic Resonance Imaging

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Background Noninvasive assessment of dynamic changes in liver blood flow, perfusion, and oxygenation using MRI may allow detection of subtle hemodynamic alterations in cirrhosis. Purpose To assess the feasibility of measuring dynamic liver blood flow, perfusion, and T2* alterations in response to meal, hypercapnia, and hyperoxia challenges. Study Type Prospective. Subjects Ten healthy volunteers (HV) and 10 patients with compensated cirrhosis (CC). Field Strength/Sequence 3T; phase contrast, arterial spin labeling, and normalT2* mapping. Assessment Dynamic changes in portal vein and hepatic artery blood flow (using phase contrast MRI), liver perfusion (using arterial spin labeling), and blood oxygenation (normalT2* mapping) following a meal challenge (660 kcal), hyperoxia (target PETO2 of 500 mmHg), and hypercapnia (target increase PETCO2 of ∼6 mmHg). Statistical Tests Tests between baseline and each challenge were performed using a paired two‐tailed t‐test (parametric) or Wilcoxon‐signed‐ranks test (nonparametric). Repeatability and reproducibility were determined by the coefficient of variation (CoV). Results Portal vein velocity increased following the meal (70 ± 9%, P < 0.001) and hypercapnic (7 (5–11)%, P = 0.029) challenge, while hepatic artery flow decreased (–30 ± 18%, P = 0.005) following the meal challenge in HV. In CC patients, portal vein velocity increased (37 ± 13%, P = 0.012) without the decrease in hepatic artery flow following the meal. In both groups, the meal increased liver perfusion (HV: 82 ± 50%, P < 0.0001; CC: 27 (16–42)%, P = 0.011) with faster arrival time of blood (HV: –54 (–56‐30)%, P = 0.074; CC: –42 ± 32%, P = 0.005). In HVs, normalT2* increased after the meal and in response to hyperoxia, with a decrease in hypercapnia (6 ± 8% P = 0.052; 3 ± 5%, P = 0.075; –5 ± 6%, P = 0.073, respectively), but no change in CC patients. Baseline between‐session CoV <15% for blood flow and <10% for normalT2* measures. Data Conclusion Dynamic changes in liver perfusion, blood flow, and oxygenation following a meal, hyperoxic, and hypercapnic challenges can be measured using noninvasive MRI and potentially be used to stratify patients with cirrhosis. Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1577–1586.

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“…Profound changes to liver tissue composition may exist in certain hepatic diseases. While the oxygen‐enhanced hepatic BOLD approach eliminates confounding factors from liver tissue composition, the measurement is still sensitive to variations in the liver hemodynamic response to hyperoxia in different diseases …”

Section: Discussionmentioning

confidence: 99%

“…For example, in healthy controls with intact vascular autoregulatory mechanisms, an oxygen‐challenge induces negligible changes to liver R 2 * , because breathing pure oxygen causes no changes to hepatic blood flow and hepatic tissue oxygenation . In patients with liver fibrosis and HCC, significant but variable responses have been observed . Therefore, oxygen‐enhanced hepatic BOLD is highly dependent on the hepatic vascular response and may not be able to accurately assess tissue oxygenation.…”

Section: Discussionmentioning

confidence: 99%

“…While the oxygen-enhanced hepatic BOLD approach eliminates confounding factors from liver tissue composition, the measurement is still sensitive to variations in the liver hemodynamic response to hyperoxia in different diseases. 46 For example, in healthy controls with intact vascular autoregulatory mechanisms, an oxygen-challenge induces negligible changes to liver R 2 * , because breathing pure oxygen causes no changes to hepatic blood flow and hepatic tissue oxygenation. 47 In patients with liver fibrosis and HCC, significant but variable responses have been observed.…”

Section: Discussionmentioning

confidence: 99%

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Mapping hepatic blood oxygenation by quantitative BOLD (qBOLD) MRI

Wengler

Wang

Sosa

et al. 2019

Magnetic Resonance in Med

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Purpose Abnormalities in hepatic oxygen delivery and oxygen consumption may serve as a significant indicator of hepatic cellular dysfunction and may predict treatment response. However, conventional and oxygen‐enhanced hepatic BOLD MRI can only provide semiquantitative assessment of hepatic oxygenation. Methods A hepatic quantitative BOLD (qBOLD) model was proposed for noninvasive mapping of hepatic venous blood oxygen saturation (Yv) and deoxygenated blood volume (DBV) in human subjects. The validity and the estimation bias of the proposed model were evaluated by Monte Carlo simulations. Eight healthy subjects were scanned after written consent with institutional review board approval. Results Monte Carlo simulations demonstrated that the proposed single‐compartment hepatic qBOLD model leads to significant deviation of the predicted T2* decay profile from the simulated signal due to high hepatic blood volume fraction. Small relative estimation bias for hepatic Yv and significant overestimation for hepatic DBV were observed, which can be corrected by applying the calibration curves established from simulations. After correction, the mean hepatic Yv in human subjects was 56.8 ± 6.8%, and the mean hepatic DBV was 0.190 ± 0.035, consistent with measurements from other invasive approaches. Except in regions with significant vascular contamination, the maps for hepatic Yv and DBV were relatively homogenous. Conclusions With estimation bias correction, the hepatic qBOLD approach enables noninvasive mapping of hepatic blood volume and oxygenation in human subjects. The established protocol may be used to quantitatively assess hepatic tissue hypoxia in multiple liver diseases.

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Quantitative BOLD imaging at 3T: Temporal changes in hepatocellular carcinoma and fibrosis following oxygen challenge

Cited by 21 publications

References 23 publications

Developing oxygen-enhanced magnetic resonance imaging as a prognostic biomarker of radiation response

Developing oxygen-enhanced magnetic resonance imaging as a prognostic biomarker of radiation response

Using MRI to study the alterations in liver blood flow, perfusion, and oxygenation in response to physiological stress challenges: Meal, hyperoxia, and hypercapnia

Mapping hepatic blood oxygenation by quantitative BOLD (qBOLD) MRI

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