Three-dimensional susceptibility-weighted imaging and two-dimensional T2*-weighted gradient-echo imaging of intratumoral hemorrhages in pediatric diffuse intrinsic pontine glioma

Abstract

Introduction: We compared the sensitivity and specificity of T2*-weighted gradient-echo imaging (T2*-GRE) and susceptibility-weighted imaging (SWI) in determining prevalence and cumulative incidence of intratumoral hemorrhages in children with diffuse intrinsic pontine glioma (DIPG) undergoing antiangiogenic and radiation therapy.

Methods: Patients were recruited from an institutional review board-approved prospective phase I trial of vandetanib administered in combination with radiation therapy. Patient consent was obtained before enrollment. Consecutive T2*-GRE and SWI exams of 17 patients (F/M: 9/8; age 3-17 years) were evaluated. Two reviewers (R1 and R2) determined the number and size of hemorrhages at baseline and multiple follow-ups (92 scans, mean 5.4/patient). Statistical analyses were performed using descriptive statistics, graphical tools, and mixed-effects Poisson regression models.

Results: Prevalence of hemorrhages at diagnosis was 41% and 47%; the cumulative incidences of hemorrhages at 6 months by T2*-GRE and SWI were 82% and 88%, respectively. Hemorrhages were mostly petechial; 9.7% of lesions on T2*-GRE and 5.2% on SWI were hematomas (>5 mm). SWI identified significantly more hemorrhages than T2*-GRE did. Lesions were missed or misinterpreted in 36/39 (R1/R2) scans by T2*-GRE and 9/3 scans (R1/R2) by SWI. Hemorrhages had no clinically significant neurological correlates in patients.

Conclusions: SWI is more sensitive than T2*-GRE in detecting hemorrhages and differentiating them from calcification, necrosis, and artifacts. Also, petechial hemorrhages are more common in DIPG at diagnosis than previously believed and their number increases during the course of treatment; hematomas are rare.

Figure 1

T2*-GRE and SWI images that were used for data evaluation. T2*-GRE images included magnitude (a) and phase (b) images; SWI included magnitude (c), phase (d), SWI (e) and minimum intensity projection images (f). For both sequences, the image quality was rated as slight susceptibility artifacts or image deformity without interference.

Figure 2

Cumulative incidence of hemorrhagic lesions in patients who showed a marked nonlinear increase in the number of hemorrhagic lesions during the course of the disease. Results of T2*-GRE scans are displayed in red and those of SWI in black (R1 solid lines, R2 dashed lines). The gray vertical lines represent the time interval of cRT, and the red vertical line the point when the patient was taken off the study. The symbol # above the curves marks scans performed on a 1.5T scanner.

Figure 3

Number of hemorrhagic lesions identified by T2*-GRE and SWI (R1 black circles; R2 red stars). Each circle/star represents the lesion count by T2*-GRE and SWI of a single patient study.

Figure 4

Hemorrhage versus calcification. The two index lesions show identical signal properties on both T2*-GRE magnitude (a) and phase (b) images, suggesting hemorrhagic nature. The SWI magnitude image (c) allows better delineation of the lesions and the corresponding phase image (d) shows that the lesion within the ventral pons corresponds to a petechial hemorrhage, whereas the lesion within left posterolateral pons is likely a calcification because it exhibits a hyposignal (confirmed by CT).

Figure 5

Hemorrhage versus areas of necrosis. T2*-GRE magnitude (a) and phase (b) images suggest a hemorrhagic lesion within the ventral pons. On SWI magnitude (c), the hyposignal is less conspicuous and the corresponding phase image (d) does not show a hypersignal, which formally rules out the presence of deposits of magnetically susceptible substances within the lesion.

Figure 6

SWI images with the phase-encoding direction set from anterior to posterior. Flow artifacts from the basilar artery project directly onto the tumor area on the magnitude image (a) which may lead to misinterpretation. However, the phase image (b) does not show a corresponding hypersignal to indicate a true hemorrhage.

Figure 7

Hematoma versus cluster of petechial hemorrhages. T2*-GRE magnitude (a) and phase (b) images suggest a hematoma. SWI, magnitude (c) and phase (d) images reveal a cluster of petechial hemorrhages within an area of tumor necrosis.