Diagnostic And Prognostic Value Of MR In Preterm Infants With White Matter Lesions

Objective:Punctate white matter lesions?PWML?are frequently recognized on magnetic resonance imaging?MRI?in unmyelinated white matter as hyperintensity on T1-weighted images with or without hypointensity on T2-weighted images.The incidence of PWML in preterm newborns with low and extremely low birth weight is50%.Among survivors,5%–10%exhibit cerebral palsy and 50%have deficits in cognition,behaviors or attention.PWML are important cause of neurodevelopmental impairment in preterm newborns.Preterm newborns have unstable cerebral blood pressure,which leads to brain injuries or ischemical reperfusion injury after cerebrovascular autoregulation.Assessment of the hemodynamics in the brains of newborns and quantification of brain development are critical for evaluating brain injury,choosinganappropriatetreatmentstrategyandpredicting neurodevelopmental deficits.It is important to detect the effects on cerebral microstructure and neurodevelopment.Conventional qualitative MRI is only an anatomic assessment of the brain.It could not offer hemodynamic and metabolic assessment and give a quantitative measurement of microstructure and pathologic basis.Phase contrast?PC?MRI and T2-relaxation-under-spin-tagging?TRUST?MRI are the most reliable way to measure global cerebral blood flow?CBF?,venous oxygen saturation fractions?Yv?,oxygen extraction fraction?OEF?and cerebral metabolic rate of oxygen?CMRO₂?,in healthy newborns,which has been successfully used to determine cerebral energy metabolism.Diffusion tensor imaging?DTI?could assess random motion?Brownian motion?of water molecules within biologic tissue and could provide insight into the information about the microstructural integrity of the white matter,their development and their severity of tract disruption in disease states.It could provide information on the apparent diffusion coefficient?ADC?and the directionality of diffusion fractional anisotropy?FA?.Magnetic resonance spectroscopy?MRS?is a common non-invasive method in vivo for cerebral metabolic and biochemistry assessment.Cerebral metabolism is associated with perinatal asphyxia and development of nervous system.The first purpose of this study was to investigate the hemodynamic and metabolic assessment of PWML in preterm neonates using PC MRI and TRUST MRI.The second purpose was to evaluate the grade of PWML using CMRO₂,CBF,Yv and OEF.The third purpose was to detect the effects of PWML on cerebral microstructure and brain development using DTI and neurodevelopmental assessment.Methods:1.23 cases of preterm infants with PWML and 28 matched controls were enrolled and scanned by PC MRI and TRUST MRI.CMRO₂,CBF,Yv,OEF and brain volume were calculated.The CMRO₂,CBF,Yv and OEF values were compared between groups,and their associations with age and TMS were evaluated.To evaluate the group difference with the consideration of age effect,multi-linear regression analyses were performed with the measured physiological parameter?Yv,OEF,CMRO₂,CBF and brain volume,respectively?as dependent variable,and group?PWML or control?and PMA at MRI scan as independent variables.Similar analyses were also performed with group category and TMS as independent variables.The receiver operating characteristic curve?ROC?was used to validate CMRO₂,CBF,Yv,OEF and brain volume in diagnosis of PWML.2.27 cases of preterm infants with PWML and 24 matched controls were enrolled and scanned by PC MRI,TRUST MRI and MRS.PWML were graded from I to IV based the method reported by Childs.The CMRO₂,CBF,Yv,OEF,brain volume,NAA/Cr,Cho/Cr,Lac/Cr,m I/Cr,Glx-?/Cr and Glx-?/Cr were compared between groups.3.25 cases of preterm infants with PWML and 12 matched controls were enrolled and scanned by PC MRI,TRUST MRI and DTI.FA and ADC values in 20 ROIs were compared between groups.All 87 cases of preterm infants with PWML and 35 matched controls were enrolled,graded from I to IV and followed-up by MRI and neurodevelopmental assessment during the period of postmenstrual age?PMA?at term,3-6,6-12,12-18 and 18-24 months.Results:1.Significant differences between PWML group and control group were found in CMRO₂?P=0.020?,CBF?P=0.027?,Yv?P=0.012?,OEF?P=0.018?.Considering all neonates together,the multi-linear regression analysis showed that both Yv and OEF had significant correlation with group?P=0.022 and P=0.028,respectively?,while had no dependence on PMA at MRI scan?P=0.993 and P=0.862,respectively?.CMRO₂ demonstrated a significant increase with PMA at MRI scan?P<0.05?,but had no significant relationship with group?P=0.093?.Similarly,a significant increase in CBF and brain volume were found with PMA?P<0.05?,but not with category?P=0.748?.Their areas-undercurve?AUC?were 0.71?confidence interval?C.I.?:0.55-0.86?,0.70?0.54-0.86?,0.69?0.54-257 0.84?,0.68?0.53-0.83?and 0.52?0.36-0.68?,respectively suggesting a fair diagnostic value of Yv.2.27infants with PWML contained none in Grade I,12 cases in Grade II,7 cases in Grade III and 8 cases in Grade IV.PWML in Grade II-IV had significantly lower CMRO₂,CBF and OEF,higher Yv than those in control group?P<0.05?.Grade II had similar CMRO₂,CBF,Yv and OEF to those in Grade IV.The lowest CMRO₂,CBF and OEF,and the highest Yv were measured in Grade III.CMRO₂ and CBF demonstrated significant increases with NAA/Cr measured by MRS?r=0.66,P<0.001;r=0.58,P=0.001?.3.Only in centrum ovale and parietal watershed white matter,infants with PWML had significantly lower FA than that in controls?P=0.024,P=0.007?.ADC in infants with lesions was higher than that in controls.However,there was no significant difference of FA and ADC between the infants with PWML and infants in controls in other ROIs?P>0.05?.There were 7 infants with Grade I,37 infants with Grade II,23 infants with Grade III and 20 infants with Grade IV were followed up.Corresponding to the classification,there were 27,28 and 23 infants followed up respectively.7 infants with lesions in Grade I were followed up once,MRI showing the lesions disappear and 7 cases?7/7?with no abnormalities on the follow-up MRI.There was only 1 case?1/7,14.24%?with mild mental developmental delayed performance?MDI<70,PDI>85?and others with normal neurodevelopment?MDI,PDI>85?by BSID II.37 infants with lesions in Grade II were followed up once by28 cases,twice by 5 cases and three times by 4 cases.8?8/37?cases'signal of the lesions weakened or/and disappeared.4?4/37?cases'signal of the lesions didn't chang.There were 25 cases?25/37?with cystic PVL,ventriculomegaly or ventricular deformation.There were 7?7/37?cases with mental and psychomotor developmental delayed performance?MDI,PDI<70 or 70-85?,9?9/37?with cerebral palsy?MDI,PDI<50?and 4 cases with normal neurodevelopment?MDI,PDI>85,one case with rehabilitated function exercises before 6 months after birth?by BSID II.23 infants with lesions in Grade III were followed up once by 15 cases,twice by 7 cases and three times by one case.One?1/23?case's signal of the lesions weakened or/and disappeared.There were 22 cases?22/23?with cystic PVL,ventriculomegaly or ventricular deformation.There were 7?11/22?cases with mental and psychomotor developmental delayed performance?MDI,PDI<70 or 70-85?,10?10/22?with cerebral palsy?MDI,PDI<50?and one case with normal neurodevelopment?MDI,PDI>85?by BSID II.20 infants with lesions in Grade IV were followed up once by12 cases,twice by 4 cases and three times by 2 cases.4?4/20?cases'signal of the lesions weakened or/and disappeared.8?8/20?cases'signal of the lesions weakened and hyperintensity appeared around lesions.There were 8 cases?8/20?with cystic PVL,ventriculomegaly or ventricular deformation.There were 6?6/20?cases with mental and psychomotor developmental delayed performance?MDI,PDI<70?,12?12/20?with cerebral palsy?MDI,PDI<50?and 2 cases with normal neurodevelopment?MDI,PDI>85?by BSID II.The morbidities of PVL,ventricular dilation,atrophy of the white matter and/or neurodevelopmental delay were 14.29%?1/7?,67.56%?25/37?and 95.65%?22/23?and 90%?18/20?accordingly.Conclusion:1.It is feasible to use non-invasive MRI methods of PC MRI and TRUST MRI to measure CMRO₂,CBF,Yv and OEF in preterm infants with PWML.It is helpful for assessmet cerebral oxygen supply and consumption in neonates with PWML.CMRO₂ and CBF are helpful in assessing brain development and maturation in newborns.2.It is feasible to evaluate the grade of PWML using PC MRI and TRUST MRI.CMRO₂,CBF,Yv and OEF are effective for assessment of cerebral oxygen supply,consumption and nerve cell damage in neonates.PWML in Grade II-IV had significantly lower CMRO₂,CBF and OEF,and higher Yv.Grade II had similar CMRO₂,CBF,Yv and OEF to those in Grade IV.The lowest CMRO₂,CBF and OEF,and the highest Yv were measured in Grade III.3.PWML in Grade II and III might interfer the myelinization in cerebral microstructure of preterm infants,notablely in corticospinal tract.The infants with lesions in Grade?often have normal outcomes of MRI and neurodevelopment.The infants with lesions in Grade II-IV often have cerebral palsy or neurodevelopmental delay,especially,in Grade III.