1	Cerebral MR Imaging Evaluation of Preterm Infants: Standardized Assessment and Predicting the Relationship of Common Imaging Abnormalities to Overall Neurodevelopmental Outcome 08-eSE-1196-ASNR Supsupin, E. P.·Bonfante-Mejia, E. E.·Sitton, C.W. ·Parikh, N.·Cacayorin, E. D.·Hochhauser, L.
2	Disclosures N. Parikh: Principal Investigator in a Research Grant. Supsupin, E. P.·Bonfante-Mejia, E. E.·Sitton, C.W. ·Cacayorin, E. D.·Hochhauser: None.
3	What are the current neuroimaging recommendations for preterm newborns? Routine screening cranial ultrasonography (CUS) is recommended for: All infants < 30 weeks’ gestation. All infants between 7 and 14 days of age. Optimally repeated between 36 and 40 weeks’ postmenstrual age (PMA). Practice parameter: Neuroimaging of the neonate. Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.
4	What is the primary screening modality for preterm newborns? Cranial ultrasonography (CUS): remains the primary imaging modality to detect hemorrhage and white matter injury in preterm newborns.
5	What is the advantage of CUS? Widely available. Can be used at the bedside. Ability to detect severe lesions (e.g., cystic white matter injury, hemorrhage) which correlate well with neurologic outcome.
6	What is the problem with CUS? CUS is suboptimal when it comes to diagnosing varying degrees of brain injury and prediction of neurosensory impairment. Large variability noted in CUS detection of low grade hemorrhages and white matter damage (Hintz, SR, J Pediatr 2007; Harris DL, Arch Dis Child 2006) .
7	Is there a role for MRI? Is follow-up MRI required for all CUS abnormalities for purposes of management or long-term prognostication? Recommendation: There is not sufficient evidence that routine MRI should be performed on all VLBW infants with abnormal CUS findings. Practice parameter: Neuroimaging of the neonate. Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.
8	So, why do we need MRI? The previous recommendation must be treated with caution! It is becoming clear that MRI is superior to CUS when it comes to detecting subtle lesions. The subtle lesions detected by MRI but not by CUS may have potential impact on neurosensory outcome and prognostication.
9	Relevant Missed MRI Evidence (1) Comparison of MRI to US done at term-equivalent age (n=51 <34 weeks): MRI predicted CP at 18m with 82% sensitivity and 97% specificity (US: 58%Sn; 100%Sp) (Valkama AM, Acta Pediatr 2000) [Grade C evidence] Cranial US & MRI comparison study (n= 28) for 18m prediction: MRI more predictive of disability with non-cystic white matter lesions (Murgo S, J Radiol 1999) [D] 215 preterm with early US and MRI at 1 year of age correlated to 3 year outcomes (>90% f/u rate) (Hashimoto K, 2001) [D] MRI correlated well with outcome, r = 0.87 US correlation with neurodevelopmental outcomes not as accurate, r = 0.69
10	Relevant Missed MRI Evidence (2) Prospective evaluation of discharge MRI with 12-24m outcomes with early US Dx of IVH with unilateral parenchymal involvement (n = 26): De Vries LS, Neuropediatr 1999;30:317-19; De Vries LS, Eur J Ped Neurol 2001; 5:139-149) [C] Symmetric myelination of posterior limb of internal capsule (PLIC): normal exam at follow-up Asymmetric myelination of PLIC: 9 of 9 cases with hemiplegia Same day US and MRI compared in neonates with parenchymal injury and related to neurodevelopmental outcome (n=61): (Roelants-van Rijn AM, Neuropediatr 2001;32:80-89) [C] Early MRI (first 4 wk) showed additional information on all 8 infants with cPVL; 2 of 8 with IVH and PI Late MRI useful in predicting later hemiplegia accurately based on asymmetry of PLIC MRI able to detect lesion in the basal ganglia and cerebellum
11	Do MRI findings correlate with histology? There is good correlation between MRI and histo-pathological findings in ill preterm infants Felderhoff-Mueser U. Am J Neuroradiol ‘99; Schouman-Claeys E. Radiology ‘93; Roelants-van Rijn AM Neuropediatrics ’01; Maalouf EF, J Pediatr ’99 T1 weighted MR (Schouman-Claeys E. Radiology ’93) : low signal intensity (similar to CSF) – PVL moderately low signal – translucent sparsely cellular regions or small cavities high signal intensity – hemorrhagic lesions or gliosis T2 weighted MRI: low signal intensity – hemorrhagic lesions Felderhoff-Mueser U. Am J Neuroradiol ‘99
12	Does MRI correlate with outcome? The validity of MRI as an accurate modality in predicting outcome has been shown in multiple studies (Ref 3, 4, 5, 6, 7, 8.).
13	What is the problem in the interpretation of MRI of preterm neonates? The lack of standardization in interpreting MRI scans of preterm newborns from institution to institution is the main issue. If we as radiologists are to help clinicians and reduce reading variability, a standardized method of interpretation must be in place.
14	How do you interpret the MRI studies of preterm infants? The following parameters are used in our institution to standardize the interpretation of the MRI scans of preterm newborns: Gray Matter White Matter Atrophy Signal Abnormalities
15	MRI Reader’s Comprehensive Checklist* Gray Matter G0 Frontal and occipital cortex completely smooth, insula widely open G1 Frontal cortex still smooth, but some sulci in the occipital cortex G2 Frontal and occipital cortex with some convolutions, frontal sulci shallow G3 Frontal and occipital cortex folded and rich in sulci, insula more convoluted and infolded G4 Secondary gyri present; transverse and inferior temporal; anterior and posterior orbital gyri G5 Tertiary inferior temporal and inferior occipital gyri and sulci present. White matter isointense with gray matter on T1 White Matter W0 Immature (<30 week) myelination pattern (e.g., brainstem not myelinated) W1 Brainstem, dorsal aspect of pons myelinated W2 Ventral pons, cerebellar medulla myelinated W3 PLIC (posterior limb of internal capsule), lenticular nucleus, thalamus myelinated W4 Corona radiata myelinated W5 Corticospinal tracts of the precentral and postcentral gyri myelinated Degree of Generalized Atrophy None Mild Moderate Severe Signal Changes DEHSI Other signal abnormalities. Others, e.g., presence of shunt, etc.
16	MRI Reader’s Comprehensive Checklist Gray Matter G0 Frontal and occipital cortex completely smooth, insula widely open G1 Frontal cortex still smooth, but some sulci in the occipital cortex G2 Frontal and occipital cortex with some convolutions, frontal sulci shallow G3 Frontal and occipital cortex folded and rich in sulci, insula more convoluted and infolded G4 Secondary gyri present; transverse and inferior temporal; anterior and posterior orbital gyri G5 Tertiary inferior temporal and inferior occipital gyri and sulci present. White matter isointense with gray matter on T1
17	MRI Reader’s Comprehensive Checklist White Matter W0 Immature (<30 week) myelination pattern (e.g., brainstem not myelinated) W1 Brainstem, dorsal aspect of pons myelinated W2 Ventral pons, cerebellar medulla myelinated W3 PLIC (posterior limb of internal capsule), lenticular nucleus, thalamus myelinated W4 Corona radiata myelinated W5 Corticospinal tracts of the precentral and postcentral gyri myelinated
18	MRI Reader’s Comprehensive Checklist Degree of Generalized Atrophy None Mild Moderate Severe Signal Changes DEHSI (Diffuse Excessive High Signal Intensity) Other signal abnormalities Others, e.g., presence of shunt, etc.
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20	"B" B A
21	"B" B A
22	31-week old infant at 3 days of life. Frontal and occipital cortex completely smooth Insula widely open Answer: G0 How do you rate the gray matter maturation of this premature brain?
23	Infant born at 33 weeks Frontal cortex smooth Some sulci in occipital cortex Insula widely open Gray matter maturation level – G1
24	Which brain is more developed?
25	The answer is D, which shows a more advanced sulcation and myelination pattern.
26	Infant prematurely born at 26 weeks. Corrected age is 36 weeks. Frontal and occipital cortex folded with some convolutions Frontal cortex shallow Gray matter maturation level - G2 Describe the gray matter findings.
27	Describe the development of the gray matter. Frontal and occipital cortex rich in sulci Insula more convoluted and infolded Gray matter maturation level - G3
28	Which brain is more mature?
29	E shows secondary gyri in the temporal lobes (G4). F demonstrates tertiary gyri and sulci (G5). F shows more advanced myelination of the posterior limb of the internal capsule.
30	Answer is F
31	How is the gray matter development rated in this neonate? Secondary gyri present in the temporal lobes Answer: G4
32	Describe the gray matter findings. Findings: Tertiary gyri and sulci present Gray matter maturation level - G5
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34	Describe the myelination finding. How is this classified based on white matter maturation level?
35	The dorsal pons is myelinated. White matter maturation level – W1
36	Describe the myelination pattern?
37	Ventral pons and cerebellar medulla are myelinated. White matter maturation level – W2
38	Which structures are myelinated? What is the white matter maturation level? Answer: Lenticular nuclei, thalami, and posterior limbs of both internal capsules are myelinated. White matter maturation level – W3.
39	Which structure is myelinated? How is this classified based on white matter maturation level?
40	Answer: Myelination of the corona radiata (shown as bright signal on T1, dark signal on T2). White matter maturation level – W4
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44	Grade the degree of generalized atrophy.
45	Degree of generalized atrophy.
46	What is an example of an abnormal signal in the white matter? Answer – DEHSI. DEHSI: Diffuse excessive high signal intensity may be present in up to 80% of preterm neonates. This may be a form of diffuse white matter injury. This has been shown to impact neurocognitive outcome (9).
47	Summary A standardized, objective, and reproducible way of reading MRI scans of preterm newborns must be in place. This will aid clinicians in accurate diagnosis and prognostication.
48	References
49	References