Feasibility and reproducibility of BOLD and TOLD measurements in the liver with oxygen and carbogen gas challenge in healthy volunteers and patients with hepatocellular carcinoma

Abstract

Purpose: To quantify baseline relaxation rates R2* and R1 in the abdomen, their changes after respiratory challenges, and their reproducibility in healthy volunteers and patients with hepatocellular carcinoma (HCC) at 1.5T and 3.0T.

Materials and methods: R2* measurements were acquired in the liver in 8 volunteers and 27 patients with 34 HCCs using multiecho T2* at baseline and after respiratory challenges with 100% oxygen (O2 ) and carbogen (CB = 95%O2 /5%CO2 ). R1 was measured at 1.5T in one volunteer and 21 patients with 23 HCCs. Test-retest coefficient of variation (CV) was assessed in 10 subjects. Intra- and interobserver variability of R2* and R1 measurements was assessed in 12 and 10 patients, respectively. Parameters for HCC, liver, and muscle were compared between baseline and after gas challenges.

Results: We observed that R2* and R1 imaging of HCCs with O2 and CB is feasible and reproducible (test-retest CV R2*<15%/R1 <5%; intra- and interobserver intraclass correlation coefficient R2*>0.88/R1 >0.7 and CV R2*<7%/R1 <3% at 1.5T). R2* measurements were observed to be less reproducible at 3.0T (CV<35%). There was a statistically significant decrease in R2* values in HCC before and after O2 (P = 0.02) and increase in R1 after O2 (P = 0.004). CB had no significant effect (P R2* = 0.47/R1 = 0.278).

Conclusion: R2* measurements in HCC and liver parenchyma are more reproducible at 1.5T than at 3.0T, and with O2 than with CB challenge. We observed a decrease in R2* and an increase in R1 of HCCs from baseline in response to O2 challenge, as expected with increased tissue and blood oxygenation.

Keywords: R1; R2*; hepatocellular carcinoma; liver.

FIGURE 1

MRI acquisition protocol demonstrating the succession of respiratory challenges for BOLD and TOLD imaging.

FIGURE 2

A 67-year-old male patient with left hepatic lobe HCC measuring 5.4 cm (arrow on postcontrast T₁WI), which demonstrates a decrease in ${\mathrm{R}}_2^{\ast }$ after O₂ ($\Delta {\mathrm{R}}_2^{\ast }$ O₂=18.7%) and carbogen ($\Delta {\mathrm{R}}_2^{\ast }$ CB=20%) gas challenges. HCC shows no significant change in R₁ (ΔR₁ O₂=−1.7%), below the level of physiological variation denoted by test–retest CV=3.6%. The decrease in ${\mathrm{R}}_2^{\ast }$ above the level of physiological variation, accompanied by no significant change in R₁, is consistent with baseline hypoxia.

FIGURE 3

A 68-year-old male patient with right hepatic lobe HCC treated with chemoembolization. There is central tumor necrosis on postcontrast T₁WI (arrow). The viable tumor at the periphery of the lesion demonstrates response to hyperoxia (arrows), with a decrease in ${\mathrm{R}}_2^{\ast }$ under O₂ ($\Delta {\mathrm{R}}_2^{\ast }$ O₂=17%) and carbogen ($\Delta {\mathrm{R}}_2^{\ast }$ CB=23.7%). The tumor also shows overall increase in R₁ under O₂ (ΔR₁ O₂=−8.5%). This lesion may be normoxic or mildly hypoxic, since the R₁ increase with O₂ challenge is also substantial.

FIGURE 4

Histogram distribution of changes in ${\mathrm{R}}_2^{\ast }$ observed in HCC lesions at 3.0T (patients 1–5) and 1.5T (patients 4–27) with oxygen (O₂) and carbogen (CB) gas challenges. The horizontal lines mark the threshold for response ±9% (1.5T CV ${\mathrm{R}}_2^{\ast }$ baseline=±9.1%, 3.0T CV ${\mathrm{R}}_2^{\ast }$ baseline=±8.8%). $\Delta {\mathrm{R}}_2^{\ast }$ >0 denotes decrease in ${\mathrm{R}}_2^{\ast }$ from baseline with respiratory challenge ($\Delta {\mathrm{R}}_2^{\ast }$ (%)=100*[(${\mathrm{R}}_2^{\ast }$ baseline − ${\mathrm{R}}_2^{\ast }$ gas)/${\mathrm{R}}_2^{\ast }$ baseline). Lesions are indexed by patient number and ordered by superior-to-inferior anatomical location. The changes in ${\mathrm{R}}_2^{\ast }$ with O₂ are highly variable between individual lesions. With CB, 6/18 lesions at 1.5T and 2/3 lesions at 3T have paradoxical response (increase in ${\mathrm{R}}_2^{\ast }$, $\Delta {\mathrm{R}}_2^{\ast }$ <0).

FIGURE 5

Histogram distribution of changes in R₁ observed in HCC lesions at 1.5T, with oxygen (O₂) and carbogen (CB) gas challenges. The horizontal lines mark the threshold for response, CV R₁ baseline=3.6%; ΔR₁<0 denotes increase in R₁ from baseline with respiratory challenge (ΔR₁ (%)=100 *[(R_1baseline − R_{1 gas})/R_{1 baseline}). Lesions are indexed by patient number and ordered by superior-to-inferior anatomical location. The majority of lesions show the expected response with O₂, increase in R₁ (ΔR₁<0), while response with CB is variable.

FIGURE 6

Histogram distribution comparing ${\mathrm{R}}_2^{\ast }$ and R₁ response in HCCs to oxygen (O₂) challenge in 22 HCCs. Some tumors show substantial decrease in ${\mathrm{R}}_2^{\ast }$ with oxygen from baseline, and modest/no increase in R₁; these are possibly hypoxic (thin arrows). Other tumors show a modest decrease in ${\mathrm{R}}_2^{\ast }$ and substantial increase in R₁ (thick arrows); these are possibly normoxic/mildly hypoxic/hyperoxic tumors.