Diagnostic value of multimodal functional MRI indicators combined with clinical features for delayed brain function development in children

doi:10.3877/cma.j.issn.1673-5250.2025.06.007

Objective

To explore the diagnostic value of multimodal functional magnetic resonance imaging (fMRI) indicators combined with clinical features for delayed brain function development in children.

Methods

A total of 241 children with delayed brain function development admitted to the Children′s Hospital of Soochow University from January 2022 to December 2024 were retrospectively selected as the study group. Another 200 healthy children who underwent physical examination during the same period in the same hospital were selected as the control group. All the children underwent multimodal fMRI to obtain the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values in the subcortical white matter of the frontal, parietal, and occipital lobes (SWM-FPOL), as well as the ratios of N-acetylaspartate (NAA) to creatine (Cr) (NAA/Cr) and glutamate/glutamine complex (Glx) to Cr (Glx/Cr). Clinical data of all subjects were collected retrospectively. Univariate and multivariate analyses were performed using independent-samples t test, chi-square test, and multivariate unconditional logistic regression to identify influencing factors (multimodal fMRI indicators and clinical features) of delayed brain function development in children. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of multivariate unconditional logistic regression results based on multimodal fMRI indicators combined with clinical features for delayed brain function development in children. There were no statistically significant differences in general clinical data such as age and gender ratio between two groups (P>0.05). This study was approved by the Ethics Committee of the Children′s Hospital of Soochow University (Approval No. 2025cs129).

Results

①The proportion of neonatal asphyxia, maternal complications during pregnancy and perinatal period, premature birth, infant diseases, parental mental retardation, ADC values and Glx/sCr of SWM-FPOL in study group were higher than those in control group, while the parents′ education level, birth weight, and FA values and NAA/Cr level of SWM-FPOL were significantly lower than those in control group, and all the differences were statistically significant (P<0.05). ②Multivariate unconditional logistic regression analysis showed that maternal complications during pregnancy and perinatal period (OR=2.635, 95%CI: 1.388-5.002), preterm birth (OR=3.047, 95%CI: 1.712-5.422), parental mental retardation (OR=4.533, 95%CI: 2.323-8.844), high ADC value of SWM-FPOL (OR=3.642, 95%CI: 2.253-5.887), high Glx/Cr of SWM-FPOL (OR=6.487, 95%CI: 3.430-12.265) were independent risk factors for delayed brain function development in children, while high NAA/Cr of SWM-FPOL (OR=0.152, 95%CI: 0.084-0.275) was its independent protective factor (P<0.05). ③The ROC curve analysis results showed that the area under the curve (AUC) of maternal complications during pregnancy and perinatal period, preterm birth, parental mental retardation, and ADC value, NAA/Cr, Glx/Cr of SWM-FPOL alone and these six indicators combined diagnoses of delayed brain function development in children were 0.617, 0.636, 0.616, 0.731, 0.803, 0.787 and 0.919 respectively (all P<0.05).

Conclusions

The combination of clinical features of child such as maternal complications during pregnancy and perinatal period, preterm birth, and parental mental retardation with fMRI indicators of child (ADC value, Glx/Cr, and NAA/Cr of SWM-FPOL) has a relatively high value in the diagnosis of delayed brain function development in children.

Key words: Magnetic resonance imaging, multimodal, Brain function, Developmental disabilities, Magnetic resonance spectroscopy, ROC curve, Diagnostic value, Child

表1 颅脑多模态fMRI检查序列参数

检查序列	TR(ms)	TE(ms)	FOV(mm×mm)	矩阵	层厚(mm)	层间距(mm)	b值(s/mm²)
T1WI	389	15	220×220	182×256	5	2.5	－
T2WI	3 035	100	220×220	128×128	5	2.5	－
T2-FLAIR	3 035	100	220×220	128×128	5	2.5	－
DWI	2 144	56	220×220	128×128	5	2.5	1 000
DTI	6 600	80	240×240	128×128	3	2.5	1 000

表1 颅脑多模态fMRI检查序列参数

检查序列	TR(ms)	TE(ms)	FOV(mm×mm)	矩阵	层厚(mm)	层间距(mm)	b值(s/mm²)
T1WI	389	15	220×220	182×256	5	2.5	－
T2WI	3 035	100	220×220	128×128	5	2.5	－
T2-FLAIR	3 035	100	220×220	128×128	5	2.5	－
DWI	2 144	56	220×220	128×128	5	2.5	1 000
DTI	6 600	80	240×240	128×128	3	2.5	1 000

表2 2组受试儿与其父母相关临床资料比较

组别	例数	性别[例数(%)]		年龄(岁，±s)	新生儿窒息[例数(%)]	孕母发生孕期与围产期并发症[例数(%)]	新生儿早产[例数(%)]	合并婴幼儿疾病[例数(%)]
组别	例数	男	女	年龄(岁，±s)	新生儿窒息[例数(%)]	孕母发生孕期与围产期并发症[例数(%)]	新生儿早产[例数(%)]	合并婴幼儿疾病[例数(%)]
研究组	241	140(58.1)	101(41.9)	4.8±1.2	50(20.7)	96(39.8)	110(45.6)	63(26.1)
对照组	200	106(53.0)	94(47.0)	4.9±1.2	21(10.5)	33(16.5)	37(18.5)	28(14.0)
统计量		χ²＝1.15		t＝1.12	χ²＝8.50	χ²＝28.75	χ²＝36.24	χ²＝9.84
P值		0.284		0.265	0.004	<0.001	<0.001	0.002
组别	例数	父母受教育年限(年，±s)	新生儿出生体重(g，±s)	父母智力低下[例数(%)]	受试儿ADC值(×10^－3 mm²/s，±s)	受试儿FA值(±s)	受试儿NAA/Cr(±s)	受试儿Glx/Cr(±s)
研究组	241	9.5±3.8	3 024.6±378.1	80(33.2)	0.82±0.11	0.41±0.11	1.23±0.31	0.84±0.22
对照组	200	11.2±4.5	3 151.9±406.5	20(10.0)	0.73±0.10	0.45±0.12	1.66±0.42	0.63±0.16
统计量		t＝4.52	t＝3.39	χ²＝33.54	t＝8.91	t＝3.65	t＝12.35	t＝11.25
P值		<0.001	0.001	<0.001	<0.001	<0.001	<0.001	<0.001

表2 2组受试儿与其父母相关临床资料比较

组别	例数	性别[例数(%)]		年龄(岁，±s)	新生儿窒息[例数(%)]	孕母发生孕期与围产期并发症[例数(%)]	新生儿早产[例数(%)]	合并婴幼儿疾病[例数(%)]
组别	例数	男	女	年龄(岁，±s)	新生儿窒息[例数(%)]	孕母发生孕期与围产期并发症[例数(%)]	新生儿早产[例数(%)]	合并婴幼儿疾病[例数(%)]
研究组	241	140(58.1)	101(41.9)	4.8±1.2	50(20.7)	96(39.8)	110(45.6)	63(26.1)
对照组	200	106(53.0)	94(47.0)	4.9±1.2	21(10.5)	33(16.5)	37(18.5)	28(14.0)
统计量		χ²＝1.15		t＝1.12	χ²＝8.50	χ²＝28.75	χ²＝36.24	χ²＝9.84
P值		0.284		0.265	0.004	<0.001	<0.001	0.002
组别	例数	父母受教育年限(年，±s)	新生儿出生体重(g，±s)	父母智力低下[例数(%)]	受试儿ADC值(×10^－3 mm²/s，±s)	受试儿FA值(±s)	受试儿NAA/Cr(±s)	受试儿Glx/Cr(±s)
研究组	241	9.5±3.8	3 024.6±378.1	80(33.2)	0.82±0.11	0.41±0.11	1.23±0.31	0.84±0.22
对照组	200	11.2±4.5	3 151.9±406.5	20(10.0)	0.73±0.10	0.45±0.12	1.66±0.42	0.63±0.16
统计量		t＝4.52	t＝3.39	χ²＝33.54	t＝8.91	t＝3.65	t＝12.35	t＝11.25
P值		<0.001	0.001	<0.001	<0.001	<0.001	<0.001	<0.001

表3 影响儿童脑功能发育迟缓因素的多因素非条件logistic回归分析

影响因素	B	SE	Wald值	P值	OR值	OR值95%CI
孕母发生孕期与围产期并发症(vs孕母未发生孕期与围产期并发症)	0.968	0.327	8.779	0.003	2.635	1.388~5.002
新生儿早产(vs足月产)	1.114	0.294	14.361	<0.001	3.047	1.712~5.422
父母智力低下(vs父母智力正常)	1.511	0.341	19.644	<0.001	4.533	2.323~8.844
受试儿SWM-FPOL ADC值(连续变量)	1.293	0.245	27.832	<0.001	3.642	2.253~5.887
受试儿SWM-FPOL NAA/Cr(连续变量)	－1.884	0.304	38.402	<0.001	0.152	0.084~0.275
受试儿SWM-FPOL Glx/Cr(连续变量)	1.869	0.325	33.099	<0.001	6.487	3.430~12.265

表3 影响儿童脑功能发育迟缓因素的多因素非条件logistic回归分析

影响因素	B	SE	Wald值	P值	OR值	OR值95%CI
孕母发生孕期与围产期并发症(vs孕母未发生孕期与围产期并发症)	0.968	0.327	8.779	0.003	2.635	1.388~5.002
新生儿早产(vs足月产)	1.114	0.294	14.361	<0.001	3.047	1.712~5.422
父母智力低下(vs父母智力正常)	1.511	0.341	19.644	<0.001	4.533	2.323~8.844
受试儿SWM-FPOL ADC值(连续变量)	1.293	0.245	27.832	<0.001	3.642	2.253~5.887
受试儿SWM-FPOL NAA/Cr(连续变量)	－1.884	0.304	38.402	<0.001	0.152	0.084~0.275
受试儿SWM-FPOL Glx/Cr(连续变量)	1.869	0.325	33.099	<0.001	6.487	3.430~12.265

图1 孕母发生孕期与围产期并发症、新生儿早产、父母智力低下与受试儿SWM-FPOL ADC值、NAA/Cr、Glx/Cr单独及6项指标联合诊断儿童脑功能发育迟缓的ROC曲线图注：ROC曲线为受试者工作特征曲线。SWM-FPOL为额叶、顶叶与枕叶皮质下白质，ADC为表观扩散系数，NAA/Cr为N-乙酰天冬氨酸与肌酸水平比值，Glx/sCr为谷氨酸及谷氨酰胺复合物与肌酸水平比值

表4 孕母发生孕期与围产期并发症、新生儿早产、父母智力低下与受试儿SWM-FPOL ADC值、NAA/Cr、Glx/Cr单独及6项指标联合对诊断儿童脑功能发育迟缓的临床价值

指标	ROC曲线			最佳临界值	敏感度(%)	特异度(%)
指标	AUC	AUC 95%CI	P值	最佳临界值	敏感度(%)	特异度(%)
孕母发生孕期与围产期并发症	0.617	0.565~0.669	<0.001	－	39.8	83.5
新生儿早产	0.636	0.584~0.687	<0.001	－	45.6	81.5
父母智力低下	0.616	0.564~0.668	<0.001	－	33.2	90.0
受试儿SWM-FPOL ADC值	0.731	0.684~0.778	<0.001	0.77×10^－3 mm²/s	66.0	70.5
受试儿SWM-FPOL NAA/Cr	0.803	0.763~0.843	<0.001	1.36	72.2	75.0
受试儿SWM-FPOL Glx/Cr	0.787	0.745~0.828	<0.001	0.7	71.8	68.0
以上6项指标联合	0.919	0.894~0.944	<0.001	－	85.5	78.5

指标	ROC曲线			最佳临界值	敏感度(%)	特异度(%)
指标	AUC	AUC 95%CI	P值	最佳临界值	敏感度(%)	特异度(%)
孕母发生孕期与围产期并发症	0.617	0.565~0.669	<0.001	－	39.8	83.5
新生儿早产	0.636	0.584~0.687	<0.001	－	45.6	81.5
父母智力低下	0.616	0.564~0.668	<0.001	－	33.2	90.0
受试儿SWM-FPOL ADC值	0.731	0.684~0.778	<0.001	0.77×10^－3 mm²/s	66.0	70.5
受试儿SWM-FPOL NAA/Cr	0.803	0.763~0.843	<0.001	1.36	72.2	75.0
受试儿SWM-FPOL Glx/Cr	0.787	0.745~0.828	<0.001	0.7	71.8	68.0
以上6项指标联合	0.919	0.894~0.944	<0.001	－	85.5	78.5

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