Neonatal  microstructural  development  of  le3  superior-­‐temporal  gyrus  and  cerebral  white  ma:er  correlates    with  cogni;ve  development  at  18-­‐20  months  in  very-­‐low-­‐birth-­‐weight  preterm  children      

   Rachel  Vassar  BA  1,  Naama  Barnea-­‐Goraly  MD  2,  Katelyn  Cahill-­‐Rowley  MS1,  David  K  Stevenson  MD2,  Susan  R  Hintz  MD,  MS  Epi2  ,  and  Jessica  Rose  PhD1    

1Department  of  Orthopaedic  Surgery,  2Center  for  Interdisciplinary  Brain  Sciences  Research,  3Division  of  Neonatology  and  Developmental  Medicine,  Stanford  University  School  of  Medicine,  Stanford,  CA,        

Neonatal Neural Correlates, Physiological Risk Factors, and Early Motor Development in Very Low Birth Weight Preterm Children: A Diffusion Imaging Study

Jessica Rose PhD1, 2, Rachel Vassar BA2,5, Katelyn Cahill-Rowley MS4, Susan R. Hintz MD, MS Epi3, David K. Stevenson MD3, Naama Barnea-Goraly MD5

1Motion & Gait Analysis Laboratory, Lucile Packard Children�s Hospital, 2Department of Orthopaedic Surgery, 3Division of Neonatology and Developmental Medicine, 4Department of BioEngineering, 5Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, Stanford, CA

Objectives Results

Discussion

Initial results suggest left PLIC MD may have prognostic value for early motor function. This WM region includes corticospinal tract descending motor pathways. The stronger association found in the left PLIC may be explained by a majority of participants who demonstrated right hand preference. Cortical GM regions that mediate motor control may also have prognostic value for later fine and gross motor function. Limitations include partial volume effects with the relatively small size of the cortex in preterm infants, thus our defined cortical regions likely contain both GM and WM. This line of research may reveal brain structure-function relations that influence motor development. Preliminary analysis of this ongoing research may provide neonatal clues to later motor deficits and ultimately, may guide early intervention to improve motor control and quality of life for preterm children.

Results Methods

Figure 2. Axial and Sagittal DTI showing motor regions of interest (ROI).

Figure 3. Partial correlation plots (N=30) of relationship between motor development on BSID-III Composite Motor score at 18-20 months in relation to neonatal brain DTI: A) Left PLIC MD B) Combined Left PLIC + Right Cuneus MD controlling for GA-at-scan.

Table 1 . Demographics and perinatal physiological risk factor data.

Acknowledgements: We wish to thank Sue Thiemann and Alex Sox-Harris for valuable statistical consultation. This research is supported in part by the NIH Clinical and Translational Science Award 1UL1 RR025744 for the Stanford Center for Clinical and Translational Education and Research (Spectrum) and by the Lucile Packard Foundation for Children's Health.

Acknowledgements

Cerebral palsy is the most prevalent childhood motor disorder, affecting approximately 3/1000 children in the US. and is defined as “a group of disorders affecting the development of movement and posture, attributed to non-progressive disturbances to the developing fetal or infant brain” (CDC 2012, Bax 2005). The incidence of CP is substantially higher in children born prematurely, affecting ~15% of very low birth weight (VLBW) preterm children (<1500g, <32 wks gestation). An additional number of preterm children (~ 40%) may develop mild to severe motor impairment by school age, a prevalence 3-4 times that of the general population (Williams et al., 2010, Spittle et al, 2011). Early prognosis of motor function in preterm infants can guide early treatment at a time when there i s o p t i m a l n e u r o p l a s t i c i t y, r a p i d musculoskeletal growth, and an opportunity to improve motor control and prevent growth-related deformities. Diffusion tensor imaging (DTI) provides quantitative regional analysis of brain microstructure based on patterns of water diffusion. DTI may offer more accurate neonatal prognosis of risk of motor deficits compared to structural MRI (Rose et al., 2007, 2009). As the brain develops, brain water content decreases, extracellular spaces diminish in size, and intra and intercellular microstructures become more complex and organized. With development, new barriers to water mobility are formed, such as cell membranes of axons, dendrites, and white matter (WM) myelination and coherence, and diffusion becomes more restricted. DTI may offer a more sensitive measure to detect microstructural abnormalities that lead to CP. Aim: To develop a neonatal prognostic index for upper and lower-limb motor function in preterm children, based on near-term brain DTI as well as other perinatal risk factors.

102 VLBW infants (<1500g BW;<32weeks GA) admitted to the NICU who had routine n e a r - t e r m b r a i n - M R I b e t w e e n 1/1/10-12/31/11 were recruited to participate, representing 74% of eligible infants, 68 of these infants also had DTI. To date, 45 infants (91% retention) returned for follow-up evaluation of neurodevelopment at 18-20 months corrected age, 30 also had DTI. Brain MRI scans performed on 3T MRI(GE-Discovery MR750,GE 8-Channel HD head coil) included T1, T2-weighted scans and diffusion-weighted scans. DTI was processed using an infant atlas and DiffeoMap (www.mristudio.org), thresholded for CSF, for calculations of mean diffusivity (MD). White matter motor tracts analyzed included posterior limb of internal capsule (PLIC). Grey matter (GM) regions known to mediate motor control were analyzed including medial and lateral frontal orbital gyri (FOG) and Cuneus.

Figure 1. Diffusion tensor image axial view showing corticospinal tracts traversing the posterior limb of internal capsule (PLIC). Motor development at 18-20 months adjusted-age was assessed on Bayley Scales of Infant Development (BSID-III). Age adjusted Composite Motor score and Fine and Gross Motor Scaled scores are reported. Directional hypotheses were tested and 2-tailed significance reported.

Initial findings are reported from an ongoing prospective study of neonatal brain structure on MRI and diffusion-tensor imaging (DTI), perinatal physiological risk factors, and early neurodevelopment at 18-20 months of age in VLBW preterm children.

BSI

D-I

II C

ompo

site

Mot

or S

core

Left PLIC MD

At 18-20 months of age the mean BSID-III Composite Motor Percentile score was 44%, Mean Fine Motor age equivalence was 19.5+3.6 months and Gross Motor was 16.6+2.5 months. Table 2. Correlations examined a prioi hypotheses regarding neonatal brain development on DTI MD at near-term age and motor function on BSID-III at 18-22 months of age.

BSI

D-I

II C

ompo

site

Mot

or S

core

Figure 3a.

Figure 3b.

Demographics:. Population!n=102!Female/male! 60/42!Birth!Weight,!g,!mean!±!SD! 1088!±!278!GA!at!birth,!weeks,!mean!±!SD! 28.7!±!2.4!GA!at!MRI,!weeks,!mean!±!SD! 36.6!±!1.8!Mean!maternal!age,!years! 31.6!±6.0!.Perinatal.Clinical.Measures:.

.Prevalence:.

Bronchopulmonary!dysplasia!(BPD)! 40%!Retinopathy!of!prematurity!(ROP)! 71%!Sepsis! 20%!Necrotizing!enterocolitis!(NEC)! 11%!Premature!rupture!of!maternal!membranes!(PPROM)! 31%!Mechanical!ventilation!required! 62%!Abnormal!structural!MRI! 37%!Mean!Total!Serum!Bilirubin!(TB)!in!first!two!weeks,!mg/dl,!mean!�!SD!(range)!

5.4!�1.3!(2.9\10.0)!

Mean!Peak!Total!Serum!Bilirubin!(PTB)!in!first!two!weeks!!mg/dl,!mean!�!SD!(range)!

7.9!�1.9!(4.5\16.3)!

!

Brain&Regions:&1°&Hypothesis&&

Mean%Diffusivity%Mean%±%SD%

Composite%Motor%Score%%

Fine%Motor%Score%%

Gross%Motor%Score&

Left%Posterior%Limb%of%Internal%Cap%Right%Posterior%Limb%of%Internal%Cap%

.00116%±.&00004%

.00116%±&.00004%E.474,%p=.009*%E.315,%p=.096%

E.417,%p=.025*%E.259,%p=.176%

E.258,%p=.177%E.167,%p=.387%

2°&Hypotheses&& % % & %Right%Cuneus% .00142%±&.00005%% E.443,%p=.016*% E.428,%p=.020*% E.206,%p=.283%

Right%Medial%Frontal%Orbital%Gyrus% .00148%±&.00007%% E.188,%p=..330% E.033,%p=.867% E.346,%p=.066%Right%Lateral%Frontal%Orbital%Gyrus& .00150%±&.00005% E.171,%p=.375% E.042,%p=.831% E.361,%p=.055%

*%Significance%p%<%%.05%

As expected, MD decreased with older GA-at-scan: Left PLIC MD vs GA-at-scan R= -.407, p=.001 Right Cuneus MD vs GA-at-scan R= -.528, p=.000. Thus, correlations between MD and BSID-III scores are reported controlling for GA-at-scan (Partridge et al. 2004, Rose et al 2007).

Left PLIC + Right Cuneus MD

R = -.474 p = .009

R = -.566 p = .004

Neonatal Neural Correlates, Physiological Risk Factors, and Early Motor Development in Very Low Birth Weight Preterm Children: A Diffusion Imaging Study

Jessica Rose PhD1, 2, Rachel Vassar BA2,5, Katelyn Cahill-Rowley MS4, Susan R. Hintz MD, MS Epi3, David K. Stevenson MD3, Naama Barnea-Goraly MD5

1Motion & Gait Analysis Laboratory, Lucile Packard Children�s Hospital, 2Department of Orthopaedic Surgery, 3Division of Neonatology and Developmental Medicine, 4Department of BioEngineering, 5Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, Stanford, CA

Objectives Results

Discussion

Initial results suggest left PLIC MD may have prognostic value for early motor function. This WM region includes corticospinal tract descending motor pathways. The stronger association found in the left PLIC may be explained by a majority of participants who demonstrated right hand preference. Cortical GM regions that mediate motor control may also have prognostic value for later fine and gross motor function. Limitations include partial volume effects with the relatively small size of the cortex in preterm infants, thus our defined cortical regions likely contain both GM and WM. This line of research may reveal brain structure-function relations that influence motor development. Preliminary analysis of this ongoing research may provide neonatal clues to later motor deficits and ultimately, may guide early intervention to improve motor control and quality of life for preterm children.

Results Methods

Figure 2. Axial and Sagittal DTI showing motor regions of interest (ROI).

Figure 3. Partial correlation plots (N=30) of relationship between motor development on BSID-III Composite Motor score at 18-20 months in relation to neonatal brain DTI: A) Left PLIC MD B) Combined Left PLIC + Right Cuneus MD controlling for GA-at-scan.

Table 1 . Demographics and perinatal physiological risk factor data.

Acknowledgements: We wish to thank Sue Thiemann and Alex Sox-Harris for valuable statistical consultation. This research is supported in part by the NIH Clinical and Translational Science Award 1UL1 RR025744 for the Stanford Center for Clinical and Translational Education and Research (Spectrum) and by the Lucile Packard Foundation for Children's Health.

Acknowledgements

Cerebral palsy is the most prevalent childhood motor disorder, affecting approximately 3/1000 children in the US. and is defined as “a group of disorders affecting the development of movement and posture, attributed to non-progressive disturbances to the developing fetal or infant brain” (CDC 2012, Bax 2005). The incidence of CP is substantially higher in children born prematurely, affecting ~15% of very low birth weight (VLBW) preterm children (<1500g, <32 wks gestation). An additional number of preterm children (~ 40%) may develop mild to severe motor impairment by school age, a prevalence 3-4 times that of the general population (Williams et al., 2010, Spittle et al, 2011). Early prognosis of motor function in preterm infants can guide early treatment at a time when there i s o p t i m a l n e u r o p l a s t i c i t y, r a p i d musculoskeletal growth, and an opportunity to improve motor control and prevent growth-related deformities. Diffusion tensor imaging (DTI) provides quantitative regional analysis of brain microstructure based on patterns of water diffusion. DTI may offer more accurate neonatal prognosis of risk of motor deficits compared to structural MRI (Rose et al., 2007, 2009). As the brain develops, brain water content decreases, extracellular spaces diminish in size, and intra and intercellular microstructures become more complex and organized. With development, new barriers to water mobility are formed, such as cell membranes of axons, dendrites, and white matter (WM) myelination and coherence, and diffusion becomes more restricted. DTI may offer a more sensitive measure to detect microstructural abnormalities that lead to CP. Aim: To develop a neonatal prognostic index for upper and lower-limb motor function in preterm children, based on near-term brain DTI as well as other perinatal risk factors.

102 VLBW infants (<1500g BW;<32weeks GA) admitted to the NICU who had routine n e a r - t e r m b r a i n - M R I b e t w e e n 1/1/10-12/31/11 were recruited to participate, representing 74% of eligible infants, 68 of these infants also had DTI. To date, 45 infants (91% retention) returned for follow-up evaluation of neurodevelopment at 18-20 months corrected age, 30 also had DTI. Brain MRI scans performed on 3T MRI(GE-Discovery MR750,GE 8-Channel HD head coil) included T1, T2-weighted scans and diffusion-weighted scans. DTI was processed using an infant atlas and DiffeoMap (www.mristudio.org), thresholded for CSF, for calculations of mean diffusivity (MD). White matter motor tracts analyzed included posterior limb of internal capsule (PLIC). Grey matter (GM) regions known to mediate motor control were analyzed including medial and lateral frontal orbital gyri (FOG) and Cuneus.

Figure 1. Diffusion tensor image axial view showing corticospinal tracts traversing the posterior limb of internal capsule (PLIC). Motor development at 18-20 months adjusted-age was assessed on Bayley Scales of Infant Development (BSID-III). Age adjusted Composite Motor score and Fine and Gross Motor Scaled scores are reported. Directional hypotheses were tested and 2-tailed significance reported.

Initial findings are reported from an ongoing prospective study of neonatal brain structure on MRI and diffusion-tensor imaging (DTI), perinatal physiological risk factors, and early neurodevelopment at 18-20 months of age in VLBW preterm children.

BSID

-III C

ompo

site

Mot

or S

core

Left PLIC MD

At 18-20 months of age the mean BSID-III Composite Motor Percentile score was 44%, Mean Fine Motor age equivalence was 19.5+3.6 months and Gross Motor was 16.6+2.5 months. Table 2. Correlations examined a prioi hypotheses regarding neonatal brain development on DTI MD at near-term age and motor function on BSID-III at 18-22 months of age.

BSID

-III C

ompo

site

Mot

or S

core

Figure 3a.

Figure 3b.

Demographics:. Population!n=102!Female/male! 60/42!Birth!Weight,!g,!mean!±!SD! 1088!±!278!GA!at!birth,!weeks,!mean!±!SD! 28.7!±!2.4!GA!at!MRI,!weeks,!mean!±!SD! 36.6!±!1.8!Mean!maternal!age,!years! 31.6!±6.0!.Perinatal.Clinical.Measures:.

.Prevalence:.

Bronchopulmonary!dysplasia!(BPD)! 40%!Retinopathy!of!prematurity!(ROP)! 71%!Sepsis! 20%!Necrotizing!enterocolitis!(NEC)! 11%!Premature!rupture!of!maternal!membranes!(PPROM)! 31%!Mechanical!ventilation!required! 62%!Abnormal!structural!MRI! 37%!Mean!Total!Serum!Bilirubin!(TB)!in!first!two!weeks,!mg/dl,!mean!�!SD!(range)!

5.4!�1.3!(2.9\10.0)!

Mean!Peak!Total!Serum!Bilirubin!(PTB)!in!first!two!weeks!!mg/dl,!mean!�!SD!(range)!

7.9!�1.9!(4.5\16.3)!

!

Brain&Regions:&1°&Hypothesis&&

Mean%Diffusivity%Mean%±%SD%

Composite%Motor%Score%%

Fine%Motor%Score%%

Gross%Motor%Score&

Left%Posterior%Limb%of%Internal%Cap%Right%Posterior%Limb%of%Internal%Cap%

.00116%±.&00004%

.00116%±&.00004%E.474,%p=.009*%E.315,%p=.096%

E.417,%p=.025*%E.259,%p=.176%

E.258,%p=.177%E.167,%p=.387%

2°&Hypotheses&& % % & %Right%Cuneus% .00142%±&.00005%% E.443,%p=.016*% E.428,%p=.020*% E.206,%p=.283%

Right%Medial%Frontal%Orbital%Gyrus% .00148%±&.00007%% E.188,%p=..330% E.033,%p=.867% E.346,%p=.066%Right%Lateral%Frontal%Orbital%Gyrus& .00150%±&.00005% E.171,%p=.375% E.042,%p=.831% E.361,%p=.055%

*%Significance%p%<%%.05%

As expected, MD decreased with older GA-at-scan: Left PLIC MD vs GA-at-scan R= -.407, p=.001 Right Cuneus MD vs GA-at-scan R= -.528, p=.000. Thus, correlations between MD and BSID-III scores are reported controlling for GA-at-scan (Partridge et al. 2004, Rose et al 2007).

Left PLIC + Right Cuneus MD

R = -.474 p = .009

R = -.566 p = .004

IntroducNon   Results  

At  near-­‐term  age,  the  brain  undergoes  rapid  growth  and   microstructural   development.   AbnormaliNes  idenNfied  during   this   period   have   been   recognized  as   potenNal   predictors   of   neurodevelopment   in  children   born   preterm.1,2   Children   born   preterm  with   very-­‐low-­‐birth-­‐weight   (VLBW)   are   at   high   risk  for   neuromotor   problems   including   cerebral   palsy,  developmental   and   cogniNve   impairment   and  language  delay.2  The   incidence  of  auNsm  spectrum  disorder   is   2-­‐3  Nmes  higher   among  VLBW  preterm  infants   compared   to   term   infants.3,4   Certain  morbidiNes   and   clinical   factors,   including  bronchopulmonary   dysplasia   (BPD),   have   been  shown  to  be  associated  with  higher  risk  for  adverse  outcomes.  Previous  studies  have  also  demonstrated  widespread   differences   in   white   maZer   (WM)  development   and   regional   corNcal   volumes   in  infants   born   VLBW   compared   to   age-­‐matched   full-­‐term   infants.5   Near-­‐term   brain   MRI   has   been  suggested   as   a   potenNal   tool   for   enhanced  prognosis   for   VLBW   infants   and   to   guide   early  intervenNon   at   a   Nme   of   opNmal   neuroplasNcity.  Diffusion   tensor   imaging   (DTI)   allows   analysis   of  brain   microstructure   based   on   paZerns   of   water  diffusion.   As   the   brain   develops,   brain   water  content   decreases,   extracellular   spaces   diminish,  and  cellular  microstructures  become  more  complex  and  organized,  all  changes  quanNfiable  with  DTI.          

To   examine   the   relaNonship   between   brain  development   at   near-­‐term,   clinical   variables,   and  cogniNve  development  at  18-­‐20  months.      

Subjects:  102  VLBW  infants  (≤1500g  BW;  ≤32  weeks  GA)   admiZed   to   the   NICU   who   had   rouNne   near-­‐term   brain   MRI   between   1/1/10-­‐12/31/11   were  recruited  to  parNcipate,  represenNng  74%  of  eligible  infants;   66   of   these   infants   also   had   DTI.   This  analysis   examined   the   sub-­‐populaNon   of   59  neonates  who  received  DTI   scans  at  near-­‐term  age  and  were  administered  the  CogniNve  subtest  of  the  Bayley   Scales   of   Infant   Development-­‐III   (BSID-­‐III)  assessment   at   18-­‐20  months   of   age,   corrected   for  prematurity.    

Methods  

References  1.  Rose  J,  Butler  EE,  Lamont  LE,  et  al.  Neonatal  brain  structure  on  MRI  and  diffusion  tensor  imaging,  sex,  and  neurodevelopment  in  VLBW  preterm  children.  Dev  Med  Child  Neurol.  2009;  51(7):526–535.    2.  Woodward  LJ,  Clark  CAC,  Bora  S,  et  al.  Neonatal  White  MaZer  AbnormaliNes  an  Important  Predictor  of  NeurocogniNve  Outcome  for  Very  Preterm  Children.  PLoS  ONE.  2012;  7(12):e51879.    3.  Movsas  TZ,  Pinto-­‐MarNn  JA,  Whitaker  AH,  et  al.  AuNsm  Spectrum  Disorder  Is  Associated  with  Ventricular  Enlargement  in  a  Low  Birth  Weight  PopulaNon.  The  Journal  of  Pediatrics.  2013;  163(1):73-­‐8.  4.  Limperopoulos  C,  Bassan  H,  Sullivan  NR,  et  al.  PosiNve  Screening  for  AuNsm  in  Ex-­‐preterm  Infants:  Prevalence  and  Risk  Factors.  Pediatrics.  2008;  121(4):758–765.    5.  Lee  AY,  Jang  SH,  Lee  E,  et  al.  Radiologic  differences  in  white  maZer  maturaNon  between  preterm  and  full-­‐term  infants:  TBSS  study.  Pediatric  Radiology.  2012;  43(5):612-­‐9.    6.  Oishi  K,  Mori  S,  Donohue  PK,  et  al.  MulN-­‐contrast  human  neonatal  brain  atlas:  applicaNon  to  normal  neonate  development  analysis.  Neuroimage.  2011;5  6(1):8–20.    

Figure   1.   Neonatal   brain   white   maZer   regions  idenNfied   in   a   representaNve   parNcipant   on   trace  image,   based   on   the   JHU   neonatal   atlas   and  LDDMM  transformaNon.      DTI   Parameters   and   Processing:   Brain   MRI   was  performed  on  3T  MRI  at  LPCH.  DTI  raw  images  were  processed   using   DTIStudio   and   DiffeoMap  (www.mristudio.org)   using   the   FA   and   trace   maps  to   perform   a   large   deformaNon   diffeomorphic  metric   mapping   (LDDMM)   transformaNon.   Each  brain  was  normalized  to  map  onto  the  JHU  neonatal  atlas6   and   automaNcally   segmented   into   126  regions,  using  threshold  values  of  trace  <0.006  mm2  

s−1  and  FA  >0.15.  Regions  analyzed  (Fig.  1)  included  WM   regions   that   are   well-­‐visualized   at   near-­‐term  age   and   thought   to   be   related   to   motor   and  cogniNve  funcNon.  Regional  FA  and  MD  values  were  analyzed   and   correlaNons   were   assessed   between  DTI   values   and   cogniNve   score   on   the   BSID-­‐III   at  18-­‐20  months  corrected  age.  (Table  2).      

 Diffusion   tensor   imaging   (DTI):   reflects   fiber   coherence,  direcNonality,  diameter,  density,  and  myelinaNon  Frac;onal  anisotropy  (FA):  direcNonality  of  diffusion  Mean  diffusivity  (MD):    mean  diffusion  on  3  axes,  (λ1+λ2  +λ3)  /3    

λ1    

λ2    

λ3    

Bundle  of  fibers  

 

  Total  population     Neonates  with  BSID,  DTI,  without  BPD    

Neonates  with  BSID,          DTI,  with  BPD    

Total  n=   102   34   25  

Males/Females,  (%)   41%  /  59%   32%  /  68%   44%  /  56%  

Birthweight  (g),  mean  (SD)   1087  (279)   1179  (248)   915  (217)  

GA-­‐at-­‐birth  (wks),  mean  (SD)     28.7  (2.4)   30.0  (2.0)   27.0  (1.7)  

PMA-­‐at-­‐scan  (wks),  mean  (SD)   36.6  (1.8)   36.1  (1.0)   37.2  (1.4)  

Cognitive  score,  BSID-­‐III  at  18-­‐mo   95.4  (12.3)   99.0  (12.8)   92.0  (12.7)  

Bronchopulmonary  dysplasia  (%)     37%   0%   100%  

   

Table  1.  ParNcipant  demographics    

Discussion  

 We  wish  to  thank  Alex  Sox-­‐Harris  for  staNsNcal  consultaNon  and  Dr.  Ximena  Stecher  Guzman  for  neuroradiological  consultaNon.  This  research   is  supported   in  part  by  the  NIH  Clinical  and  TranslaNonal   Science   Award   1UL1   RR025744   for   the   Stanford   Center   for   Clinical   and  TranslaNonal   EducaNon   and   Research   (Spectrum)   and   by   the   Lucile   Packard   FoundaNon   for  Children's   Health.   This   material   is   based   upon   work   supported   by   the   NaNonal   Science  FoundaNon  Graduate  Research  Fellowship  under  Grant  No.  DGE-­‐1147470.    

Methods  

Table  2.  CorrelaNons  between  near-­‐term  brain  DTI  values  of  FA  and  MD  and  BSID-­‐III  cogniNve  subscore  at  18-­‐20  months,  corrected  for  PMA-­‐at-­‐scan.  

Results   indicate   that   BSID-­‐III   cogniNve   subscore   at  18-­‐20  months  was   lower   in   infants  with  history  of  BPD,  although  they  were  also  of   lower  BW  and  GA  and   more   likely   to   be   male.     Mean   motor   and  language  subscore  were  not  different  between  the  group  with  and  without  BPD.    CorrelaNons   between   cogniNve   composite   score  and   brain   DTI   values   differed   between   the   group  with  and  without  BPD.  The  sub-­‐populaNon  without  BPD   demonstrated   strong   posiNve   correlaNons  between  near-­‐term  FA  and   cogniNve  development  at  18-­‐20  months.    

    Correlations  between  FA  and  BSID-­‐III  Cognitive  Score   Correlations  between  MD  and  BSID-­‐III  Cognitive  Score  

Brain  Region    

Without  BPD  (n=34)    

With  BPD    (n=25)    

Total    (n=59)    

Without  BPD  (n=34)    

With  BPD    (n=25)    

Total    (n=59)    

CC  Genu                                                                  

0.359*    (p  =  .040)  

-­‐0.576**  (p  =  .003)  

-­‐0.058  (p  =  .667)  

0.126    (p  =  .484)  

0.203  (p  =  .343)  

0.193  (p  =  .761)  

CC  Body   0.112  (p  =  .537)  

-­‐0.272  (p  =  .199)  

-­‐0.041  (p  =  .762)  

0.189  (p  =  .293)  

0.162  (p  =  .449)  

0.196  (p  =  .141)  

CC  Splenium                                                    

0.075  (p  =  .680)  

-­‐0.237  (p  =  .264)  

-­‐0.042  (p  =  .755)  

0.039  (p  =  .831)  

0.133  (p  =  .535)  

0.041  (p  =  .141)  

SCR                  L                                    R                                                    

0.390*  (p  =  .025)  

-­‐0.117  (p  =  .588)  

0.115  (p  =  .390)  

-­‐0.127  (p  =  .483)  

-­‐0.208  (p  =  .328)  

-­‐0.089  (p  =  .505)  

0.326  (p  =  .064)  

-­‐0.368  (p  =  .077  )  

-­‐0.052  (p  =  .697)  

-­‐0.065  (p  =  .717)  

-­‐0.115  (p  =  .  592)  

-­‐0.035  (p  =  .796)    PCR                  L  

                                 R                                                  

0.340  (p  =  .053)  

-­‐0.426*  (p  =  .038)  

-­‐0.056  (p  =  .677)  

-­‐0.247  (p  =  .166)  

-­‐0.007  (p  =  .973)  

-­‐0.111  (p  =  .407)  

0.446**  (p  =  .009)  

-­‐0.325  (p  =  .122)  

0.103  (p  =  .441)  

-­‐0.169  (p  =  .346)  

-­‐0.080  (p  =  .710)  

-­‐0.085  (p  =  .526)  

ALIC                L                                    R                                                                        

0.403*  (p  =  .020)    

-­‐0.252  (p  =  .235)  

0.153  (p  =  .251)  

-­‐0.181  (p  =  .313)    

0.083  (p  =  .701)  

-­‐0.042  (p  =  .752)  

0.271  (p  =  .128)    

-­‐0.221  (p  =  .300)  

0.078  (p  =  .563)  

-­‐0.312  (p  =  .077)    

0.043  (p  =  .844)  

-­‐0.105  (p  =.435)  

PLIC                  L                                    R  

0.386*  (p  =  .026)  

-­‐0.171  (p  =  .425)  

0.122  (p  =  .360)  

-­‐0.437*  (p  =  .011)  

-­‐0.289  (p  =  .171)  

-­‐0.356**  (p  =  .006)  

0.344  (p  =  .050)  

-­‐0.210  (p  =  .324)  

0.069  (p  =  .609)  

-­‐0.303  (p  =  .086)  

-­‐0.149  (p  =  .287)  

-­‐0.211  (p  =.112)  

RLC                    L                                                                    R                                                                

0.530**  (p  =  .002)  

-­‐0.385  (p  =  .064)  

0.169  (p  =  .206)  

-­‐0.284  (p  =  .109)  

-­‐0.186  (p  =  .384)  

-­‐0.177  (p  =  .184)  )  0.395*  

(p  =  .023)  -­‐0.217  (p  =  .309)  

0.086  (p  =  .522)    

-­‐0.105  (p  =  .562)  

-­‐0.343  (p  =  .101)  

-­‐0.069  (p  =  .604)  )    

EC                        L                                    R                                                    

0.467**  (p  =  .006)  

-­‐0.271  (p  =  .200)  

0.087  (p  =  .517)  

-­‐0.151  (p  =  .400)  

-­‐0.268  (p  =  .205)  

-­‐0.109  (p  =  .414)    0.519**  

(p  =  .002)  -­‐0.215  (p  =  .312)  

0.131  (p  =  .328)  

-­‐0.062  (p  =  .733)  

-­‐0.209  (p  =  .328)  

-­‐0.035  (p  =  .796)    StriaT            L  

                                   R                                                    

0.377*  (p  =  .031)  

-­‐0.427*  (p  =  .037)  

0.069  (p  =  .607)  

-­‐0.212  (p  =  .237)  

0.251  (p  =  .236)  

-­‐0.005  (p  =  .968)  )  0.473**  

(p  =  .005)  -­‐0.193  (p  =  .366)  

0.212  (p  =  .109)  

-­‐0.106  (p  =  .558)  

0.245  (p  =  .248)  

0.046  (p  =  .732)  

ST  Gyrus  L                                      R      

-­‐0.036  (p  =  .842)  

.021  (p  =  .922)  

-­‐0.031  (p  =  .820)  

-­‐0.351*  (p  =  .045)  

0.066  (p  =  .760)  

-­‐0.219  (p  =.098)  

-­‐0.114  (p  =.528)  

-­‐0.021  (p  =  .924)  

-­‐0.090  (p  =  .502)  

-­‐0.168  (p  =  .349)  

-­‐0.123    (p  =.567)  

-­‐0.131  (p  =  .328)      

*  Significant  correlations,  p<  0.05  **  Significant  correlations,  p<  0.01  

     

Preliminary   results   suggest   that   the   observed  a s so c i aNon   be tween   BPD   and   adve r se  neurodevelopmental  outcome  may  be  explained   in  part   by   brain   microstructural   WM   injury.   The  ongoing   research  may   further   elucidate   these   links  to   guide  NICU-­‐based  quality   of   care   improvements  and  targeted  post-­‐discharge  early  intervenNon.    

Acknowledgments  Aim  

CC  Genu      CC  Body      CC  Splenium      Superior  Corona  Radiata  (SCR)      Posterior  Corona  Radiata  (PCR)    Anterior  Limb  of  Internal  Capsule  (ALIC)      Posterior  Limb  of  Internal  Capsule  (PLIC)      RetrolenNcular  Part  of  Internal  Capsule  (RLC)      Stria  Terminalis  (StriaT)      External  Capsule  (EC)      Superior  Temporal  Gyrus  (ST  Gyrus)  

R²  =  0.22854  R²  =  0.27778  

0.17  

0.18  

0.19  

0.2  

0.21  

0.22  

0.23  

65   75   85   95   105   115   125  

Frac;o

nal  anisotrop

y  (FA)    

BSID-­‐III  Cogni;ve  Score  

EC  (lew)  

EC  (right)  

R²  =  0.28808  

0.21  

0.23  

0.25  

0.27  

0.29  

0.31  

0.33  

0.35  

0.37  

65   75   85   95   105   115   125  

Frac;o

nal  anisotrop

y  (FA)    

BSID-­‐III  Cogni;ve  Score  

RLC  (lew)  

R²  =  0.19214  

1.00E-­‐03  

1.05E-­‐03  

1.10E-­‐03  

1.15E-­‐03  

1.20E-­‐03  

1.25E-­‐03  

1.30E-­‐03  

65   75   85   95   105   115   125  

Mean  diffu

sivity  (M

D)  

BSID-­‐III  Cogni;ve  Score  

ST  Gyrus  (lew)  

Figure  2.  DTI  of  the  (A)  external  capsule  FA                                            (B)  retrolenNcular  capsule  FA,  and  (C)  lew  superior  temporal  gyrus  MD,  in  relaNon  to  BSID-­‐III  cogniNve  score  at  18-­‐20  months  among  infants  without  BPD  

A  

B  

C  

A

P