Extracellular volume with bolus-only technique in amyloidosis patients: Diagnostic accuracy, correlation with other clinical cardiac measures, and ability to track changes in amyloid load over time

Background: Extracellular volume (ECV) by T₁ mapping requires the contrast agent distribution to be at equilibrium. This can be achieved either definitively with a primed contrast infusion (infusion ECV), or sufficiently with a delay postbolus (bolus-only ECV). For large ECV, the bolus-only approach measures higher than the infusion ECV, causing some uncertainty in diseases such as amyloidosis.

Purpose: To characterize the relationship between the bolus-only and current gold-standard infusion ECV in patients with amyloidosis.

Study type: Bolus-only and infusion ECV were prospectively measured.

Population: In all, 186 subjects with systemic amyloidosis attending our clinic and 23 subjects with systemic amyloidosis who were participating in an open-label, two-part, dose-escalation, phase 1 trial.

Field strength: Avanto 1.5T, Siemens Medical Solutions, Erlangen, Germany.

Assessment: Bolus-only and infusion ECV were measured in all subjects using shortened modified Look-Locker inversion recovery (ShMOLLI) T₁ mapping sequence.

Statistical tests: Pearson correlation coefficient (r); Bland-Altman; receiver operating characteristic (ROC) curve analysis. Linear regression model with a fractional polynomial transformation.

Results: The difference between the bolus-only and infusion myocardial ECV increased as the average of the two measures increased, with the bolus-ECV measuring higher. For an average ECV of 0.4, the difference was 0.013. The 95% limits of agreement for the two methods, after adjustment for the bias, were ±0.056. However, cardiac diagnostic accuracy was comparable (bolus-only vs. infusion ECV area under the curve [AUC] = 0.839 vs. 0.836), as were correlations with other clinical cardiac measures, and, in the trial patients, the ability to track changes in the liver/spleen with therapy.

Data conclusion: In amyloidosis, with large ECVs, the bolus-only technique reads higher than the infusion technique, but clinical performance by any measure is the same. Given the work-flow advantages, these data suggest that the bolus-only approach might be acceptable for amyloidosis, and might support its use as a surrogate endpoint in future clinical trials.

Level of evidence: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;47:1677-1684.