Mis-estimation and bias of hyperpolarized apparent diffusion coefficient measurements due to slice profile effects

Abstract

Purpose: The purpose of this work was to explore the impact of slice profile effects on apparent diffusion coefficient (ADC) mapping of hyperpolarized (HP) substrates.

Methods: Slice profile effects were simulated using a Gaussian radiofrequency (RF) pulse with a variety of flip angle schedules and b-value ordering schemes. A long T₁ water phantom was used to validate the simulation results, and ADC mapping of HP [¹³ C,¹⁵ N₂ ]urea was performed on the murine liver to assess these effects in vivo.

Results: Slice profile effects result in excess signal after repeated RF pulses, causing bias in HP measurements. The largest error occurs for metabolites with small ADCs, resulting in up to 10-fold overestimation for metabolites that are in more-restricted environments. A mixed b-value scheme substantially reduces this bias, whereas scaling the slice-select gradient can mitigate it completely. In vivo, the liver ADC of hyperpolarized [¹³ C,¹⁵ N₂ ]urea is nearly 70% lower (0.99 ± 0.22 vs 1.69 ± 0.21 × 10^-3 mm² /s) when slice-select gradient scaling is used.

Conclusion: Slice profile effects can lead to bias in HP ADC measurements. A mixed b-value ordering scheme can reduce this bias compared to sequential b-value ordering. Slice-select gradient scaling can also correct for this deviation, minimizing bias and providing more-precise ADC measurements of HP substrates. Magn Reson Med 78:1087-1092, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Keywords: ADC; DNP; diffusion-weighted imaging; hyperpolarization; slice profile effects.

Figure 1

With a constant slice-select gradient, hyperpolarized signal is overestimated after the initial RF pulse because of excess signal in the transition band, regardless of the flip angle scheme (A,D,G). By scaling the slice-select gradient, the desired signal response can be achieved (B,E,H). The amount of excess signal is a function of the flip angle and RF excitation profile (C,F,I). RF flip angle used in each case: constant 30° (A-C); RF variable flip angle (D-F); RF and diffusion variable flip angle (G-I).

Figure 2

Measured vs. actual ADC in the presence of slice profile effects for the three flip angle schedules explored in this work. For a sequential b-value scheme, where b-values are acquired in decreasing value, the ADC is systematically overestimated regardless of the flip angle scheme used. In contrast, a mixed b-value ordering greatly reduces the bias caused by slice profile effects.

Figure 3

Representative ¹³C urea ADC maps measured in the murine liver neglecting slice profile effects (A) or accounting for them by scaling the slice select gradient (B). As evinced above, slice profile effects will lead to overestimation of the ADC with the sequential b-value scheme. The liver is highlighted with the dashed line, and the ADC is in units of 10⁻³ mm²/s.