Correlation between Multiparametric MR Imaging and Molecular Genetics in Pontine Pediatric High-Grade Glioma

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FIG 1.
Differences in OS between variant histone profiles. A, Kaplan-Meier curves of a patient’s OS by histone H3 mutation: H3-3A (n = 50) versus H3C2/3 (n = 11). B, Kaplan-Meier curves of OS for patients with tumors with histone H3 mutation (H3-3A, H3C2/3, and H3-mutant, specific gene unknown) (n = 68) versus H3 wild-type (n = 15) tumors.
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FIG 2.
Differences in ADC histogram parameters among histone H3 K27–altered tumors. H3-3A-mutant tumor (A) shows lower ADC_total mode (1252.531 × 10^–6 mm²/s), higher ADC_total skewness (0.673), and higher ADC_total kurtosis (2.721) relative to H3C2/3-altered tumor (B) (ADC_total mode: 1703.875 × 10^–6 mm²/s; ADC_total skewness: −0.231; and ADC_total kurtosis: 0.399). H3-3A-mutated tumor (A) shows lower mean (PG) ADC_enhancement (1216.092 × 10 mm²/s), median (PG) ADC_enhancement (1206 × 10^–6 mm²/s), and mode (PG) ADC_enhancement (1103.723 × 10^–6 mm²/s), relative to H3C2/3-mutated tumor (B): mean (PG) ADC_enhancement (1461.677 × 10^–6 mm²/s), median (PG) ADC_enhancement (1500 × 10^–6 mm²/s), and mode (PG) ADC_enhancement (1665.322 × 10^–6 mm²/s). A, A 3-year-old girl with H3-3A-mutant diffuse midline glioma and OS = 217 days. B, An 8-year-old girl with H3C2/3-mutant diffuse midline glioma and OS = 761 days.

Table 1:

Baseline characteristics of patients with pontine pHGG (n = 83)

Patient Characteristic	No. (%) or Median (Range)
Sex
Male	43 (52)
Female	40 (48)
Race
White	60 (72)
Black	19 (23)
Other	4 (5)
Age at registration (yr)	6 (0.7–17)
Histone mutation status
H3-3A	50 (60)
H3C2/3	11 (13)
Wild-type	15 (18)
H3 K27–altered, specific gene unknown	7 (8)
Presence of enhancement
Yes	54
No	25
Unknown	4
Median follow-up time of surviving patients (mo)	10.3 (2.3–76.2)

Table 2:

Association of measures of continuous imaging features with variant histone H3–altered tumors

Imaging Metric	H3-3A		H3C2/3		P Value^{^a}
Imaging Metric	No.	Median (Range)	No.	Median (Range)	P Value^{^a}
ADC total (×10^–6 mm²/s)
Mean	46	1227.51 (538.06–1710.88)	9	1586.56 (1224.37–1797.58)	.001
Median	46	1185 (532–1755)	9	1654 (1215–1842)	.001
Mode	46	1168.14 (450.92–1902.53)	9	1703.88 (1263.52–1961.24)	.001
Skewness	38	0.91 (−0.49–2.16)	9	–0.20 (−0.89–0.88)	.003
Kurtosis	38	1.57 (−0.60–9.71)	9	0.40 (−0.78–1.79)	.002
ADC_enhancement (×10^–6 mm²/s)
Mean	33	1138.81 (689.44–1509.96)	7	1390.54 (1033.58–1898.26)	.004
Median	33	1085 (667–1532)	7	1364 (995–1890)	.003
Mode	33	1012.56 (577.86–1617.56)	7	1393.38 (966.31–1746.86)	.002
Skewness	31	1.27 (−0.56–2.82)	7	0.52 (−0.71–2.61)	.1
Kurtosis	31	2.08 (−0.94–13.03)	7	0.85 (−0.84–9.09)	.3
FLAIR/T2/T1 PG volume (×10³ mm³)
FLAIR/T2	44	35.75 (7.97–77.53)	10	41.10 (22.84–77.57)	.2
Enhancing	32	1.90 (0.07–14.10)	9	5.04 (0.04–8.25)	.6

Table 3:

Association of measures of continuous imaging features with variant histone H3–altered versus H3 wild-type tumors

Imaging Metric	Any Histone Mutation		Wild-Type		P Value^{^a}
Imaging Metric	No.	Median (Range)	No.	Median (Range)	P Value^{^a}
ADC total (×10^–6 mm²/s)
Mean	61	1302.42 (538.06–1797.58)	12	1350.77 (922.96–1729.62)	.98
Median	61	1245 (532–1842)	12	1345 (917–1781)	.97
Mode	61	1250.51 (450.92–1961.24)	12	1305.29 (863.39–1805.47)	.9
Skewness	52	0.68 (−0.89–3.11)	11	0.98 (−0.30–2.57)	.3
Kurtosis	52	1.4 (−0.78–15.62)	11	2.82 (−0.78–10.77)	.1
ADC_enhancement (×10^–6 mm²/s)
Mean	45	1152.88 (689.44–1898.26)	6	1199.86 (956.62–1723.18)	.7
Median	45	1142.00 (667–1890)	6	1187.00 (807–1762)	.7
Mode	45	1062.49 (577.86–1746.86)	6	1175.10 (719.70–1805.78)	.6
Skewness	43	0.86 (−0.85–4.73)	6	0.67 (−0.14–1.86)	.7
Kurtosis	43	1.69 (−0.94–29.06)	6	1.35 (0.098–12.45)	.9
FLAIR/T2/T1 PG volume (×10³ mm³)
FLAIR/T2	60	35.13 (7.97–77.57)	13	32.77 (10.13–79.62)	.8
Enhancing	46	1.96 (0.04–14.10)	8	1.95 (0.01–4.71)	.4