Potential for differentiation of pseudoprogression from true tumor progression with dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging using ferumoxytol vs. gadoteridol: a pilot study

Abstract

Purpose: We evaluated dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging (DSC-MRI) using gadoteridol in comparison to the iron oxide nanoparticle blood pool agent, ferumoxytol, in patients with glioblastoma multiforme (GBM) who received standard radiochemotherapy (RCT).

Methods and materials: Fourteen patients with GBM received standard RCT and underwent 19 MRI sessions that included DSC-MRI acquisitions with gadoteridol on Day 1 and ferumoxytol on Day 2. Relative cerebral blood volume (rCBV) values were calculated from DSC data obtained from each contrast agent. T1-weighted acquisition post-gadoteridol administration was used to identify enhancing regions.

Results: In seven MRI sessions of clinically presumptive active tumor, gadoteridol-DSC showed low rCBV in three and high rCBV in four, whereas ferumoxytol-DSC showed high rCBV in all seven sessions (p = 0.002). After RCT, seven MRI sessions showed increased gadoteridol contrast enhancement on T1-weighted scans coupled with low rCBV without significant differences between contrast agents (p = 0.9). Based on post-gadoteridol T1-weighted scans, DSC-MRI, and clinical presentation, four patterns of response to RCT were observed: regression, pseudoprogression, true progression, and mixed response.

Conclusion: We conclude that DSC-MRI with a blood pool agent such as ferumoxytol may provide a better monitor of tumor rCBV than DSC-MRI with gadoteridol. Lesions demonstrating increased enhancement on T1-weighted MRI coupled with low ferumoxytol rCBV are likely exhibiting pseudoprogression, whereas high rCBV with ferumoxytol is a better marker than gadoteridol for determining active tumor. These interesting pilot observations suggest that ferumoxytol may differentiate tumor progression from pseudoprogression and warrant further investigation.

Figure 1

Regression after radiochemotherapy (RCT) (Patient #1 in Table 1). (A, E, I) T1-weighted magnetic resonance imaging (MRI) before and (B, F, J) after gadoteridol (Gd) administration. (A, B) MRI after surgery but before RCT demonstrates area of enhancement in the right temporal lobe (arrow). Relative cerebral blood volume (rCBV) in the enhancing area was lower on the Gd-rCBV parametric map (C) compared to the ferumoxytol (Fe)-rCBV map (D) (bold arrow). (E, F) MRI after completion of RCT revealed decreased enhancement (F, arrow) with low rCBV on Gd-rCBV (G) and Fe-rCBV parametric maps (H) (arrow). (I, J) MRI 14 months after completion of RCT showed resolution of enhancement. (K) First-pass time-intensity curves of the perfusions C and D demonstrate post-bolus increasing signal above the baseline when Gd was used while ferumoxytol post-bolus signal intensity was below the baseline and remains stable.

Figure 2

Pseudoprogression followed by true tumor progression (Patient #2 in Table 1). (A, C, G, I) T1-weighted magnetic resonance imaging (MRI) before and (B, D, H, J) after gadoteridol (Gd). (A, B) MRI after surgery but before radiochemotherapy (RCT) demonstrates residual enhancement (arrow). (C, D) MRI 2 months after RCT shows increased area of enhancement with low relative cerebral blood volume (rCBV) on both Gd (E) and ferumoxytol (Fe) parametric maps (F) (arrow). (G, H) Adjuvant temozolomide treatment was continued and enhancement decreased on MRI 25 months after the end of RCT (arrow). (I, J) Area of increased enhancement on MRI 28 months after RCT (arrow) coincided with high Fe-rCBV (L) and low Gd-rCBV (K) (bold arrows).

Figure 3

Mixed response to radiochemotherapy (RCT) (Patient #14 in Table 1). (A) T1-weighted contrast enhanced magnetic resonance imaging (MRI) before surgery demonstrated glioblastoma multiforme lesion which decreased in size after surgery (B). (C) MRI 1 month after RCT showed increased enhancement, with low relative cerebral blood volume (rCBV) within the lesion and a thin rim of high rCBV with ferumoxytol (Fe) and lower with gadoteridol (Gd) (D) (E) (arrow).

Figure 4

Comparison of relative cerebral blood volume (rCBV) acquired by dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) using ferumoxytol versus gadoteridol. Rapidly growing tumors are assocated with rCBV > 1.75 , indicated by the starred arrows. The rCBV obtained using gadoteridol was always lower than using ferumoxytol in tumor (P=0.002) and the mixed response group (P=0.007), but there was no difference between contrast agents in the pseudoprogression group (P=0.9).

Figure 5

Comparison of relative cerebral blood volume (rCBV) between tumor, pseudoprogression and mixed response groups. (A) Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) using ferumoxytol revealed high rCBV in the tumor group (> 4.2), low in the pseudoprogression group (< 1.1) and intermediate in the mixed response group. Rapidly growing tumors are assocated with rCBV > 1.75, indicated by the starred arrows. (B) DSC-MRI using gadoteridol showed low rCBV (< 1.7) in 3 of 7 scans in the tumor group, low rCBV in all pseudoprogression scans (< 1.2), and low in 3 of 4 mixed response scans. Differences between groups were significant ( P<0.00001 for ferumoxytol; P=0.01 for gadoteridol).

Figure 6

Algorithm of evaluation and classification of response to radiochemotherapy by conventional magnetic resonance imaging (MRI) using gadolinium-based contrast agent and dynamic susceptibility contrast MRI using ferumoxytol.