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Evaluation of Single Bolus, Multi-Echo Dynamic Susceptibility Contrast Protocols in Brain Tumor Patients
Ashley M Stokes1, Ashley Nespodzany1, Lea Alhilali2, Leland Hu3, C. Chad Quarles1, and Leslie C. Baxter1

1Neuroimaging Research, Barrow Neurological Institute, Phoenix, AZ, United States, 2Radiology, Barrow Neurological Institute, Phoenix, AZ, United States, 3Department of Radiology, Mayo Clinic Arizona, Phoenix, AZ, United States

Synopsis

Relative cerebral blood volume (rCBV) obtained from dynamic susceptibility contrast (DSC) MRI is adversely impacted by contrast agent leakage in brain tumors. Using a digital reference object, we previously demonstrated that multi-echo DSC-MRI protocols provide advantages in terms of contrast agent dosing, pulse sequence flexibility, and rCBV accuracy. The purpose of this study is to assess the in-vivo performance of multi-echo acquisitions in patients with brain tumors. Multi-echo rCBV obtained without a preload is compared to the standard single-echo rCBV obtained with preload. In addition, two contrast agent doses and two flip angles are compared for the multi-echo acquisition.

Introduction

Relative cerebral blood volume (rCBV) measures obtained from dynamic susceptibility contrast (DSC) MRI are widely used in the diagnosis and treatment of brain tumors [1,2]. Unfortunately, contrast agent leakage effects are often observed in this population and can limit the reliability of rCBV measurements [1,3]. To reduce contaminating T1 effects, current recommendations include preload administration of a single dose of contrast agent, given 5–10 minutes before dynamic imaging [4]. However, this double bolus strategy has multiple drawbacks, including higher cost, larger contrast dose and the potential for increased protocol variability, due to multiple timed injections. Thus, a single bolus scheme would largely simplify and facilitate standardized clinical applications. Multiple echo acquisitions have been shown to remove T1 leakage effects without the need for a contrast preload and may provide more robust rCBV measures [5]. Using simulations [6], we recently demonstrated that multi-echo acquisitions allow for significant flexibility in acquisition protocols with improved accuracy [7]. Currently, it is unclear if the advantages of multi-echo acquisitions identified through simulations will translate to clinical scans obtained in patients. The purpose of this study is to assess the in vivo performance of a no preload, multi-echo acquisition compared to the current preload, single-echo standard.

Methods

We previously evaluated a wide array of multi-echo acquisitions (two dosing schemes, 2 field strengths, three TRs, three flip angles (FA), 29 echo time combinations, and with and without leakage correction) using a digital reference object (DRO) [7]. We found that multi-echo acquisitions do not require a preload injection and provide significant pulse sequence flexibility, essentially decoupling both TR and FA from rCBV accuracy. To test this hypothesis in vivo, brain tumor patients (n = 11) underwent a conventional MRI protocol with DSC perfusion at 3T (Philips). To compare the no-preload multi-echo (single bolus) and preload single-echo (double bolus) techniques, two contrast doses of gadobutrol were given during consecutive DSC-MRI acquisitions. During the first bolus, a multi-echo DSC protocol was performed (TE1/TE2 = 7.3/33.3ms, TR = 1.4s, FA = 75° (n = 8) or 30°) (n = 3). This simultaneously permits evaluation of the single bolus, multi-echo technique and serves as preload for the double bolus technique. The preload was either ½ dose (0.05mmol/kg, n = 4) or full dose (0.1 mmol/kg, n = 7). After a delay of 6 minutes, a full dose (0.1 mmol/kg) contrast bolus was given during a standard protocol single-echo DSC acquisition (TE = 30ms, TR = 1.4s, FA = 75° for all 11 patients). Leakage correction was performed using the standard Boxerman-Schmainda-Weisskoff (BSW) method [8,9]. Maps of rCBV were compared across bolus injections for dual-echo and single-echo acquisitions.

Results/Discussion

Figure 1 shows the dual-echo (no preload, full dose) and single-echo (with preload, full dose) signals (left) and ΔR2* curves (right) (FA = 75°, TR = 1.4s). T1 effects are evident in the dual-echo signals (blue and red) due to the lack of preload, while the single-echo curve does not exhibit appreciable leakage effects due to the preload. The T1 leakage effects can be effectively removed for the dual-echo ΔR2*, and similar ΔR2* curves result from each injection. Figures 2 and 3 demonstrate two representative cases, where the dual-echo rCBV and single-echo rCBV are highly similar. Finally, Figure 4 illustrates the correlation between the dual-echo (no preload) and single-echo (with preload) rCBV, across multiple doses and flip angles. Overall, these results suggest that multi-echo acquisitions may obviate the need for preload dosing in a clinical setting, verifying our previous simulation results. For multi-echo protocols, the pulse sequence parameters (including TR and FA) have little impact on the resulting rCBV, indicating the potential for significant flexibility in acquisition parameters. Work is ongoing to acquire this data in more patients using a range of pulse sequence parameters.

Conclusions

Contrast agent extravasation reduces the reliability of DSC-MRI perfusion measures in brain tumors. We hypothesized, based on prior simulations, that multi-echo acquisitions in the absence of a preload dose would provide similar rCBV to standard single-echo acquisitions with a preload dose of contrast agent. Moreover, we hypothesized that the rCBV accuracy would be independent of pulse sequence parameters, such as FA. Using in vivo data from brain tumor patients, we showed that the use of a no preload, multi-echo DSC-MRI protocol gave comparable rCBV to single-echo DSC-MRI with a preload. This correlation was maintained across two dosing protocols and two flip angles. The use of multi-echo acquisitions provides significant pulse sequence flexibility and negates the need for a preload injection.

Acknowledgements

This work was supported by the Arizona Biomedical Research Commission (ADHS16-162414) and Philips Healthcare.

References

[1] Boxerman JL, Schmainda KM, Weisskoff RM. Relative cerebral blood volume maps corrected for contrast agent extravasation significantly correlate with glioma tumor grade, whereas uncorrected maps do not. AJNR Am J Neuroradiol 2006;27:859–67.

[2] Schmainda KM, Prah M, Connelly J, Rand SD, Hoffman RG, Mueller W, et al. Dynamic-susceptibility contrast agent MRI measures of relative cerebral blood volume predict response to bevacizumab in recurrent high-grade glioma. Neuro Oncol 2014;16:880–8. doi:10.1093/neuonc/not216.

[3] Stokes AM, Semmineh N, Quarles CC. Validation of a T1 and T2* leakage correction method based on multiecho dynamic susceptibility contrast MRI using MION as a reference standard. Magn Reson Med 2016;76:613–25. doi:10.1002/mrm.25906.

[4] Welker K, Boxerman J, Kalnin A, Kaufmann T, Shiroishi M, Wintermark M, et al. ASFNR recommendations for clinical performance of MR dynamic susceptibility contrast perfusion imaging of the brain. AJNR Am J Neuroradiol 2015;36:E41-51. doi:10.3174/ajnr.A4341.

[5] Paulson ES, Schmainda KM. Comparison of Dynamic Susceptibility-weighted Contrast-enhanced MR Methods: Recommendations for Measuring Relative Cerebral Blood Volume in Brain Tumors. Radiology 2008;249:601–13. doi:doi:10.1148/radiol.2492071659.

[6] Semmineh NB, Stokes AM, Bell LC, Boxerman JL, Quarles CC. A Population-Based Digital Reference Object (DRO) for Optimizing Dynamic Susceptibility Contrast (DSC)-MRI Methods for Clinical Trials. Tomography 2017;3:41–9. doi:10.18383/j.tom.2016.00286.

[7] Stokes AM, Semmineh NB, Quarles CC. Systematic Assessment of Multi-Echo Dynamic Susceptibility Contrast (DSC) MRI using a Digital Reference Object (DRO). Proc. 26th Annu. Meet. ISMRM, 2018, p. 2188.

[8] Boxerman JL, Schmainda KM, Weisskoff RM. Relative Cerebral Blood Volume Maps Corrected for Contrast Agent Extravasation Significantly Correlate with Glioma Tumor Grade, Whereas Uncorrected Maps Do Not. Am J Neuroradiol 2006;27:859–67.

[9] Weisskoff RM, Boxerman JL, Sorensen AG, Kulke SM, Campbell TA, Rosen BR. Simultaneous blood volume and permeability mapping using a single Gd-based contrast injection. Proc. 2nd Annu. Meet. SMRM, San Francisco, CA, USA: 1994, p. 279.

Figures

Dual-echo (no preload) and single-echo (with preload) signals (left) and ΔR2* curves (right) in a brain tumor ROI (full-dose/full-dose, TR = 1.4s, FA = 75°, TEs = 7.3/33ms for dual-echo and TE = 30 for single-echo). T1 leakage effects can be observed in the signals for the dual-echo acquisitions, which are removed in the dual-echo ΔR2*.

T1-weighted post-contrast image (left) and rCBV maps for dual-echo (middle) and single-echo (right) in a patient with glioma. The dual-echo rCBV was acquired in the absence of a preload (full-dose bolus, 30° flip angle). Both rCBV maps show similar patterns, including the rim of enhancement. T1 leakage effects have been removed (dual-echo) or minimized (single-echo, due to preload), and remaining leakage effects are removed using BSW leakage correction.

T1-weighted post-contrast image (left) and rCBV maps for dual-echo (middle) and single-echo (right) in a patient with glioma. The dual-echo rCBV was acquired in the absence of a preload (full-dose bolus) and with a higher flip angle (75°). Both rCBV maps show similar patterns, including hot spots.

Plot of single-echo vs. dual-echo mean tumor rCBV across all 11 glioma patients. Blue circles indicate patients with ½ dose preload (FA = 75°, n = 4), red circles indicate full dose preload and 75° FA, and yellow circles indicated full dose preload with 30° FA. Across all multi-echo acquisition protocols, high agreement was observed with the single-echo (with preload) rCBV.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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