Retinoblastoma: value of dynamic contrast-enhanced MR imaging and correlation with tumor angiogenesis

Abstract

Background and purpose: Noninvasive evaluation of retinoblastoma treatment response has become more important due to increased use of eye-sparing treatments. We evaluated the relation between DCE-MR imaging and histopathologic parameters to determine the value of DCE-MR imaging in assessing tumor angiogenesis and prognostic features.

Materials and methods: Fifteen consecutive patients with retinoblastoma (mean age, 24 months; range, 2-70 months) undergoing enucleation as the primary treatment (15 eyes) were scanned at 1.5T by using dedicated surface coils. Pretreatment DCE-MR imaging of the most affected eye was evaluated by 2 observers by using curve-pattern analysis, with the first 5 minutes of each curve and the full time-series described as κ(5min) and κ(17min), respectively. Assessed histopathologic and immunologic parameters included optic nerve invasion, choroid invasion, MVD, tumor necrosis, and expression of VEGF and Flt-1.

Results: The median value of κ(5min) was 1.28 (range, 0.87-2.07) and correlated positively with MVD (P = .008). The median value of κ(17min) was 1.33 (range, 0.35-3.08) and correlated negatively with tumor necrosis (P = .002). Other histopathologic and immunohistopathologic parameters did not correlate with DCE-MR imaging parameters. Interobserver agreement was 0.53 for κ(5min) and 0.91 for κ(17min).

Conclusions: In retinoblastoma, the early phase of the DCE time curve positively correlates with MVD, while the presence of late enhancement is correlated with necrosis. Thus, the potential for DCE-MR imaging to noninvasively assess tumor angiogenesis and necrosis in retinoblastoma is promising and warrants further investigation.

Fig 1.

Retinoblastoma tumor in the right eye (patient 9) with transverse T2-weighted spin-echo (A) and transverse contrast-enhanced T1-weighted spin-echo (B) MR images. Curve-pattern analyses of the signal intensity curve of 1 observer (C) shows slow initial uptake of contrast (κ_5min = 0.76) and slow further rising of the curve (κ_17min = 1.06). Immunohistochemical staining with CD-31 (original magnification ×10) (D) shows brown-stained microvessels on a background of blue tumor cells with a MVD of 11. Hematoxilin-eosin staining (E) illustrates 30% necrotic areas (arrow).

Fig 2.

Retinoblastoma tumor in the right eye (patient 2) with transverse T2-weighted spin-echo (A) and transverse contrast-enhanced T1-weighted spin-echo (B) MR images. Curve-pattern analysis of the signal intensity curve of 1 observer (C) shows fast uptake of contrast agent (κ_5min = 1.67) and early arrival at equilibrium (κ_17min = 2.79). Immunohistochemical staining with CD-31 (original magnification ×10) (D) shows a high MVD of 21, and hematoxilin-eosin staining shows only 10% necrosis (arrow) (E).

Fig 3.

Retinoblastoma tumor in the right eye (patient 5) with transverse T2-weighted spin-echo (A) and transverse contrast-enhanced T1-weighted fat-suppressed spin-echo (B) MR images. Curve-pattern analysis of the signal intensity curve of 1 observer (C) shows a moderate uptake of contrast agent (κ_5min = 1.22) and a continuing increase leading to κ_17min = 0.84. Immunohistochemical staining with CD-31 (original magnification ×10) (D) shows an MVD of 14. Hematoxilin eosin staining (E) shows a large area of necrosis (70%) (arrow I) in vital tumor tissue (arrow II).

Fig 4.

Graphs show the positive correlation (A) between κ_5min and mean MVD (P = .008) and the negative correlation (B) between κ_17min (a measure for late enhancement) and tumor necrosis (P = .002).