Frequency and cause of disagreements in imaging diagnosis in children with ventriculomegaly diagnosed prenatally

Frequency and etiology of imaging diagnosis disagreements inchildren with prenatally diagnosed ventriculomegaly

GM Senapati1, D Levine2, C Smith3, JA Estroff4, CE Barnewolt4, RL Robertson4, TYPoussaint4, TS Mehta2, XQ Werdich2, D Pier5, HA Feldman6, and CD Robson4

1 Tufts University School of Medicine, Boston, MA2 Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA3 Hertzl, Jewish General Hospital, Montreal, QC4 Department of Radiology and Advanced Fetal Care Center, Children’s Hospital Boston5 Harvard Medical School, Boston, MA6 Clinical Research Program, Children’s Hospital Boston, Boston, MA

AbstractPurpose—To assess the frequency and etiology of variability in diagnoses on cranial ultrasound(US) and magnetic resonance (MR) imaging for children referred for prenatally diagnosedventriculomegaly (VM).

Materials and Methods—Between 9/19/03-3/16/07, 119 children with US and MR studiesperformed within 13 months (median 6 days) after birth, after prenatal referral for VM, werestudied as part of a prospective IRB-approved HIPAA-compliant study with written parentalconsent. 3 sonologists and 3 pediatric neuroradiologists interpreted the US and MR examinations,blinded to prenatal diagnosis. Final diagnosis was obtained by consensus (97 US, 53 MR and 31US/MR comparisons). Ventricular size, types of disagreements, and reasons for disagreementswere recorded. Disagreements on a per patient basis were categorized as major when they crosseddiagnostic categories and had potential to change patient counseling.

Results—There was prospective agreement on 42/97 (43%) US and on 9/53 (17%) MR readings.Prospective consensus was more likely when the number of CNS anomalies was lower (P<.001and =.002 for US and MR, respectively). In 24/55 (44%) of US and 11/44 (25%) MR withdisagreements, one of the disagreements concerned the presence of VM. In 22/97 (23%) USstudies and 22/53 (42%) MR studies the disagreements were potentially important. Reasons fordiscrepancies in reporting of major findings included errors of observation as well as modalitydifferences in depiction of abnormalities. In comparing prenatal to postnatal diagnoses, there were11/97 (11%) US and 27/53 (51%) MR examinations with newly-detected major findings, the mostcommon being migrational abnormalities, callosal dysgenesis/destruction and intervaldevelopment of hemorrhage.

Conclusion—Variability in postnatal CNS diagnosis is common after a prenatal diagnosis ofVM. This is due in part to a lack of standardization in definition of postnatal VM.

Corresponding author: Deborah Levine, MD, Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Ave,Boston, MA, 02215, Phone: 617-667-8901, Fax: 617-667-8212, [email protected].

NIH Public AccessAuthor ManuscriptUltrasound Obstet Gynecol. Author manuscript; available in PMC 2011 November 1.

Published in final edited form as:Ultrasound Obstet Gynecol. 2010 November ; 36(5): 582–595. doi:10.1002/uog.7680.

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IntroductionVentriculomegaly (VM), a frequent fetal central nervous system (CNS) finding, is acommon end-point for a variety of fetal pathologic processes. Determining an accurateprenatal CNS diagnosis is important for appropriate patient counseling and management. Inorder to assess the accuracy of prenatal diagnosis it is important to have a reliable referencestandard for comparison.

One would expect postnatal imaging to serve as the reference standard for final CNSdiagnosis in children with a fetal diagnosis of VM. However, the few published studies ofpostnatal imaging of children with fetal diagnosis of VM were limited by retrospectivereview 1–4 or single reader interpretations of the postnatal imaging5–8. To our knowledge,no large scale prospective studies have been performed to evaluate the accuracy of postnatalimaging by assessing inter-observer variability and how postnatal imaging diagnosiscompares to fetal imaging diagnosis. Our study was performed to assess the frequency andetiology of variability in diagnoses on cranial US and MR imaging in children referred forprenatally diagnosed VM.

Materials and MethodsSubjects and Imaging

The study was performed at Beth Israel Deaconess Medical Center and Children’s Hospital,Boston as part of an Institutional Review Board approved, HIPAA compliant studyevaluating fetal VM using US and MRI. Written informed consent was obtained frompregnant women who either had a referral diagnosis of VM or whom during an ultrasoundexamination were found to have VM (defined as a ventricular size measured on an axialview at the level of the atria greater than or equal to 10 mm). Prenatal US and MRexaminations were performed and consensus imaging diagnoses were obtained on 195women with 199 fetuses recruited from 7/1/03 – 8/20/06, as previously described9. Threewere excluded after review of records showed they never had VM. Gestational age byultrasound ranged from 16–41 weeks, with a mean of 26 weeks.

The imaging studies were grouped into 5 prenatal diagnostic categories to assess for attritionand bias in postnatal follow-up imaging: 1) normal prenatal imaging; 2) mild isolated VM(10–12 mm); 3) isolated VM 13–15mm; 4) isolated VM >15 mm; and 5) VM with otherCNS anomalies (Table 1). For pregnancies resulting in a live delivery, the first postnatalhead ultrasound (HUS) and/or brain MR examination were retrieved. If imaging was notperformed for a clinical indication in the first 3 months of life, it was offered as part of theresearch study. However, many parents who felt their child was normal did not elect to havepostnatal imaging. Postnatal imaging performed greater than 13 months of age wereexcluded from analysis. Our final population was 119 infants with postnatal imaging studiesperformed between 9/19/03-3/16/07. There were significantly fewer live births in the groupwith VM with other anomalies (p<0.0001, Table 1) compared to other diagnostic groups.There were significantly more postnatal MR examinations in the groups with >12 mmisolated VM and VM with other CNS anomalies groups than in the other diagnostic groups(p<0.001).

The postnatal HUS exams were performed from day of life 1 to 255 with a median age of 2days after birth. MRI exams were performed from day of life 1 to 388 with a median age of17 days after birth. Sonograms were performed on 61 male and 36 female children. MRexaminations were performed on 29 male and 24 female children. The distribution of age atimaging did not differ by sex for either US or MR.

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Figure 1 illustrates the overall study design. Postnatal neurodevelopmental follow-up of thiscohort is described in a separate manuscript.10

Sonogram performance, interpretation, and consensus—Prenatal sonograms wereperformed according to AIUM guidelines. Additional views of the head were obtainedtransvaginally when the fetus was in cephalic position. Sonograms were interpreted by oneof 4 ultrasonologists (initials withheld for review, with 12–21 years experience inultrasound) involved in patient care the day of the examination as well as by two blindedultrasonologists, who only knew of the referral diagnosis for VM. VM was diagnosed whenthe ventricles at the level of the atrium measured ≥ 10 mm. Note that although the entrycriteria for this study was referral for VM or the finding at time of sonography of VM (for areferral for some other indication), some fetuses at the time of confirmatory sonographywere felt not have VM, and thus were coded as normal. CNS abnormalities were recordedusing a modification of a coding system described by Van der Knaap et al.11 The consensusdiagnosis of prenatal subjects has been previously published9.

Postnatal HUS were performed according to institutional protocols and interpreted by 3ultrasonologists (DL, CB, JE) who were blinded to prenatal diagnosis and clinical postnatalimaging diagnosis. The size of the ventricles at the atrium was measured. Unlike theprenatal imaging diagnosis of VM, where a measurement of 10 mm at the level of the atriumwas used to define VM, no specific threshold was used for postnatal imaging, since, to ourknowledge, none has been established. Reviewers therefore used their standard clinicalpractice subjective impression to diagnosis VM. Two neonates with holoprosencephaly wereexcluded from the ventricular measurement analysis due to inability to accurately measurethe ventricles.

The readers rated their confidence in their diagnosis with regards to presence, character, andspecific nature of the abnormality on a 5 point scale (1 = very confident to 5 = notconfident).

The US diagnoses of the three ultrasonologists were compared for differences in opinion.Each disagreement was recorded as specified in appendix table 1. Disagreements of “noclinical difference” were those where similar abnormalities were being described, but withdifferent codes, for example, codes for agenesis of the septum pellucidum and defect of theseptum pellucidum. Errors of omission were those where by the description of the finding,the reviewer clearly saw the abnormality, but did not code for it. Errors of observation werethose where neither description nor coding recorded the finding.

Disagreements due to issues other than coding were settled by majority opinion of threeprenatal sonologists at a consensus conference with image review. For a given child, alldisagreements were evaluated to determine what potential impact the disagreement(s) hadon each case. Major disagreements were those felt to be potentially clinically important, thatcould change patient counseling, as determined by our referring maternal fetal medicineguidelines, utilized in prior publications9, 12–14. For example, a disagreement about thepresence of a cyst in a fetus with agreement about the presence of agenesis of the corpuscallosum was a minor change in diagnosis, but not clinically important. However, adisagreement about the diagnosis of dysgenesis of the corpus callosum when there wasagreement about a midline cyst was a major new finding, with a potentially clinicallyimportant difference of opinion. The reason for a difference in opinion and the impact of thedisagreements on the case are summarized in appendix table 1.



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MR imaging performance, interpretation, and consensusFetal MR examinations were performed at 1.5 T typically using an 8 channel surface coil (inrare occasions with large patients in the third trimester, the body coil was utilized if asurface coil would not fit in the scanner). Sequence parameters varied during the study butalways included single shot fast spin echo sequences in the fetal sagittal, coronal, and axialplanes with 3–5 mm slice thickness, depending on gestational age and maternal bodyhabitus. A typical sequence had echo spacing 4.2 msec, TEeffective 60 msec, matrix of 128 ×256, flip angle of 130 degrees and echotrain length of 72. Breathhold T1 weightedsequences were obtained in one or two fetal planes. A typical T1 sequence was turbo fastlow angle shot technique with TR/TE of 15.4/4.2 ms, matrix 160 × 256, and slice thicknessof 5 mm. Field of view for each sequence was tailored to the fetus and maternal bodyhabitus. Other imaging sequences were performed at the discretion of the radiologistsupervising the examination. Prenatal fetal MR examinations were interpreted by theradiologist supervising the examination (typically the ultrasonologist who performed theprenatal scan (DL, TM, JE, or CB) and by 3 pediatric neuroradiologists (CR, TYP, RR). Theneuroradiologists were initially blinded to sonographic diagnosis and then re-interpreted thestudies after knowledge of sonographic findings. Coded CNS abnormalities, ventricularmeasurements, and confidence ratings were recorded in the same manner described for US.

Postnatal MR examinations were performed according to institutional guidelines at 1.5T,typically with an 8 channel phased array brain coil and the following parameters: sagittaland axial SE T1 weighted MR images (TR/TE 450–550/9–14 msec; flip angle 90 degrees; 1excitation; field of view 20× 24 cm; matrix 224 × 256; slice thickness 3.5 mm/skip 1 mm)and FSE T2 weighted images (TR/TE 2800 – 5000/98–108 msec; echo train length 16; 1excitation, field of view 20× 24 cm, matrix 256 × 320 cm; slice thickness 4 mm/skip 1 mm).Additional sequences obtained on some neonates included coronal FSE T2, axial diffusionweighted images (B value of 1000, TR/TE 100000/85 msec; field of view 24 × 24 cm;matrix 128 × 128; slice thickness 4 mm skip 1 mm) and a susceptibility sequence (TR/TE567/40 msec; flip angle 30 degrees; 1 excitation; field of view 20 × 24 cm; matrix 128 ×245; slice thickness 4 mm skip 1 mm). Neonatal images were typically obtained afterfeeding and wrapping the infant, without sedation. 50/53 (94%) neonatal MRs wereperformed without intravenous contrast and 3/53 (6%) were performed with contrast.

Postnatal brain MRI exams were independently reviewed by the same 3 pediatricneuroradiologists who interpreted the prenatal studies. They performed this review at least 3months after prenatal imaging and without knowledge of prenatal diagnosis. Coded CNSabnormalities, ventricular measurements, and confidence ratings were recorded in the samemanner described for US.

MR findings were compared for differences in coded diagnoses. Final postnatal MRdiagnosis consensus was achieved by majority opinion of the pediatric neuroradiologistsduring a second image review session. The coding of disagreements as well as the etiologyand/or impact of the disagreement were recorded in the same manner described for US.

Comparison of US and MRA final postnatal consensus diagnosis was determined for each case. For subjects who hadeither an US or MR (and not both), the consensus diagnosis from that particular imagingmodality was used as the final diagnosis. For neonates where both US and MR wereperformed postnatally, the US and MR consensus diagnoses were compared to one another.When the final diagnosis was ambiguous, one of the ultrasonologists (DL) with consultationfrom one of the pediatric neuroradiologists (CR) determined the final postnatal diagnosis.Studies with disagreements were coded as shown in appendix table 1. The etiology and/or



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impact of all the disagreements for each case were recorded in the same manner as forultrasound.

Comparison of prenatal to postnatal imagingPrenatal US, MR, and final diagnoses determined from our companion study.9 werecompared to postnatal US, MR and final consensus diagnoses. Final prenatal to postnatalconsensus diagnosis was performed at a separate image review session with two of theauthors (DL, CR). For subjects with changes in diagnosis between prenatal and postnataldiagnoses, an explanation for the variability as well as the etiology or impact of thedifference in diagnosis were tallied as described in appendix table 1. In cases whereventricular shunts had been placed and there was disagreement between the studies on thepresence of VM, the assessment of VM was taken from the imaging study where the shuntwas not present. For studies where VM was coded as being present prenatally but notpresent postnatally, the ventricular diameters were compared to assess if the measurement atthe ventricular atrium had decreased or if it had remained at a similar level but was notcoded as VM postnatally.

Statistical AnalysisPostnatal measurements of ventricular diameter were compared across categories of rateragreement by mixed-model analysis of variance (ANOVA), adjusting for within-subject andwithin-rater correlation. Where US and MR measurements were analyzed together, theANOVA was also adjusted for imaging mode. Comparing studies with consensus withstudies with disagreement, the rater’s confidence scores were analyzed by mixed-modelANOVA (adjusting for within-rater correlation) and the age at imaging and number of finaldiagnoses (including normal as a diagnosis) per patient by the Wilcoxon two-sample test toallow for the skewed distribution of those variables.

The number of children with structural abnormalities not visualized prenatally (choroidplexus cysts and hemorrhage were not included as structural abnormalities) were comparedbetween different prenatal VM groups using Fisher’s exact test. Impact of gestational age atprenatal imaging, interval between prenatal and postnatal imaging, and age at postnatalimaging, and ventricular diameter (median of 3 measurements obtained at prenatal US) wereindividually assessed by Poisson regression analysis for association with the number ofdisagreements between pre-and postnatal imaging. SAS software version 9.1 (Cary, NC)was used for all computations. A p value of .05 was taken for statistical significance.

ResultsFor those fetuses with postnatal imaging, gestational age at prenatal ultrasound ranged from17–41 weeks, with a mean of 27 weeks (Figure 2). Diagnoses are listed in Table 2 for theprenatal and postnatal imaging. In the final postnatal consensus 42/119 (35%) brains werejudged normal. VM was present among the final diagnoses in 70/119 children (59%).

Ultrasound diagnoses and agreementOf 97 children with postnatal HUS, there were 42 (43%) with prospective consensus (Table3). Among these, 27/42 (64%) had normal final diagnosis, while the other 15/42 (33%) had1–4 abnormal final diagnoses with a median of 1.

Of 55 neonates without prospective consensus, 15 (27%) had normal final diagnosis, and theother 40 (73%) had a range of 1–4 final abnormal diagnoses, with a median of 2. Thenumber of final diagnoses was significantly greater in children without consensus (p<0.001).



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In 24/55 (44%) sonograms with disagreements, one of the disagreements concerned thepresence of VM (Figure 3). Measurements of ventricular diameter varied significantlyaccording to whether the sonographers agreed on the presence of VM (Table 4, p<0.01).

In the majority of studies with sonographic disagreements (44/55, 80%), at least one of thedisagreements was a difference in opinion about diagnosing VM (N = 24) and/or had noclinical importance (N=23, Table 3). There were 22/55 (40%) subjects with potentiallyimportant disagreements. There were 114 disagreements on specific CNS diagnoses in the55 subjects (Table 5). The most common type of disagreement was error of observation(N=45/114, 39%).

The median age at postnatal US imaging was 2 days and did not differ between those withand without consensus (p>0.50).

In the 42 subjects with consensus, the sonologists’ confidence was higher with regard to thetypes of abnormality (p<0.05) than in the 55 subjects without consensus (Figure 4). Thelevel of confidence in additional findings associated with the anomaly was generally not ashigh as that in the presence or nature of the anomaly itself, but was significantly higher insubjects with consensus than without (p<0.001).

MR diagnoses and agreementOf the 53 postnatal MRI examinations, consensus was reached prospectively by 3 pediatricneuroradiologists in 9 infants (17%, Table 3). Two subjects were normal, while the other 7had 1–4 abnormal final diagnoses, with a median of 2. There were 44/53 subjects (83%)without consensus. These had a range of 1–6 abnormal final diagnoses, with a median of 3.The number of final diagnoses was significantly greater in subjects without consensus(p=0.013).

In 11/44(25%) of MR subjects without consensus, there was disagreement regarding thepresence of VM (Table 3). Ventricular diameter did not differ significantly between ratersindicating VM present and those indicating VM absent (Table 4).

The majority of disagreements on MR (30/44 = 68%) either had no clinical importance(N=27) and/or involved a disagreement about whether or not to diagnose VM (N=11, Table3). In 22/44 instances (50%), the disagreements were categorized as being potentiallyimportant.

On MR exams there were 139 disagreements on specific CNS diagnoses (Table 5). The mostcommon types of disagreements were coding issues (N=77, 55%). The neuroradiologists’level of confidence in MR findings with respect to the presence and nature of abnormalitiesand associated findings was generally higher than that for US readings (Figure 4).Confidence in MR findings did not differ between subjects with or without consensus.

The median age at postnatal MR imaging was not significantly greater in children ofconsensus (21 days, range 1–388 days) than in those with disagreement (10 days, range 1–383) (p>0.40).

Comparing US and MR postnatal interpretationsThere were 31 subjects where both a postnatal HUS and MRI were performed. There were27 subjects without consensus (87%, Table 3). These had a range of 2–7 final diagnoses,with a median of 4. The number of final diagnoses was significantly greater in subjectswithout consensus (p=0.007).



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Among the 27 HUS/MR examination pairs with disagreements, the disagreement concernedcalling VM (N=3) or had no clinical importance (N=5); one or both of these accountedentirely for the difference of opinion in 4 instances (15%). In the remaining 23 studies therewere 21 major new findings, two overcalls of a major finding, and 1 minor change indiagnosis. The common findings seen on postnatal MR which were not recognized onpostnatal HUS were migrational abnormalities (N=8), hemorrhage (N=7), and infarction(N=4).

Comparison of Prenatal to Postnatal imagingPrenatal and postnatal final diagnoses agreed in 35/119 studies (29%, Table 3). The majorityof these (30/35, 86%) were either normal (N=9) or isolated VM (N=21). In the remaining 84studies (71%) there was initial difference in diagnostic coding. The group with consensushad fewer diagnoses than the group without consensus (p<0.001).

The range of interval between prenatal and postnatal US imaging was 1–338 (mean 106,median 100) days. In US imaging (prenatal vs. postnatal) there was agreement in 26/97studies (27%), with the majority of these having final CNS diagnosis of either isolated VM(N=16) or normal (N=8). In 71/97 (73%) studies there were differences in diagnoses and thefinal diagnoses varied from normal (N=34) up to 5 coded CNS abnormalities, mostcommonly dysgenesis of the corpus callosum (N=16).

The range of interval between prenatal and postnatal MR imaging was 5–455 (mean 129,median 98) days. In MR imaging (prenatal vs. postnatal) there was agreement in 13/53studies (25%). In 5 of those studies (38%) the final MR diagnosis was either normal (N=1)or isolated VM (N=4). There were 40/53 studies (75%) with differences in final diagnosis(Figure 5–8). In 20/40 (50%) of those studies with there were 3 or more codedabnormalities, the most frequent being dysgenesis of the corpus callosum (N=15) andpolymicrogyria (N=9).

In 38/53 (72%) studies, the postnatal MR diagnoses matched the final diagnoses. Anexample of a lesion present, but not noted on prenatal imaging, is shown in figure 6.However, in one instance the prenatal diagnosis was felt to be more accurate, i.e., thepostnatal MRI suggested the diagnosis of schizencephaly whereas the fetal MRI diagnosiswas encephaloclastic porencephaly (Figure 7). In this case, the postnatal diagnosis wasschizencephaly since cortex seemed to line the defect. However, since by prenatal imagingthis was in the process of developing, it was felt to be encephaloclastic event, rather than agenetic event.

Low signal intensity lesions were a relatively common cause of difference in final diagnosis.For example, nodular subependymal T2 shortening could be due to germinal matrixhemorrhage or neuronal heterotopia in a fetus with hemimegalencephaly. The case ofhemimegalencephaly was interpreted on prenatal MR as germinal matrix hemorrhage withdilatation of the ipsilateral ventricle as a result of hemorrhage. More extensive associatedcortical malformation and the correct diagnosis only became apparent as the brain matured(Figure 5).

Ventricular diameter on prenatal imaging was significantly associated with the number ofdisagreements needing reconciliation in the final prenatal-postnatal consensus conference(p<0.001). Median diameter ranged from 10.5 mm in those with consensus in the finalconference (n=36) to 24 mm in those with 5–6 disagreements. The number of disagreementswas not associated with gestational age at prenatal imaging, interval between prenatal andpostnatal imaging, or age at postnatal imaging.



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There were 12 fetuses categorized as normal prenatally. In 10 of these postnatal diagnosiswas normal. Two were felt to have VM as neonates, one with a small choroid plexus cyst(Table 6). Of 52 fetuses with isolated mild VM 10–12 mm prenatally, 28 had normalpostnatal imaging, 17 had isolated VM, 3 had intracranial hemorrhage, 2 had small choroidplexus cysts and 2 (4%) had structural abnormalities not diagnosed prenatally (Table 6). Of11 fetuses with isolated VM 13–15 mm prenatally, 2 had normal postnatal imaging, 3 hadisolated VM, and 4 (37%) had structural abnormalities not diagnosed prenatally. 1 fetus withVM >15 mm prenatally was diagnosed with a tumor postnatally. In these three groupswithout additional abnormalities prenatally, there were increasing numbers of structuralabnormalities seen postnatally as the degree of VM increased (p<.0001).

In 37 fetuses VM was coded as being present prenatally, but not present postnatally. In12/37 (32%) of these the ventricular atrium measured a similar amount prenatally comparedto postnatally but these were not coded as VM in the postnatal study. In 25/37 (68%) thedegree of ventricular dilatation decreased between the examinations.

DiscussionDisagreements are common among readers of postnatal imaging studies after a fetaldiagnosis of VM, and are more likely as the degree of VM increases and as the complexityof CNS anomalies increases. In addition to differences of opinion and error of observation,there are a number of reasons for discrepancies between prenatal and postnatal imaging.These include interval resolution of VM (25/200, 12.5% of our population), differences incriteria for diagnosis of VM (12/200, 6%) ventricles measured a similar amount but were notcoded as VM postnatally, new development of a CNS abnormality over time (i.e.,porencephaly); certain abnormalities becoming more apparent at a later gestational age (i.e.,a cortical migrational abnormality and dysgenesis of the corpus callosum), and resolution ofan abnormality, such as hemorrhage. Importantly, additional MRI sequences (for example,susceptibility sequences showing hemorrhage that can be utilized in neonatal MRI but arenot as easily adapted to the rapid imaging needed for fetal MRI) and contrast medium (forexample in a fetus with a brain neoplasm) can be utilized postnatally, and not in fetal MRI,may allow for improved visualization of previously unsuspected abnormalities.

The diagnosis of VM was a frequent area of disagreement (25% and 21% in US and MRsubjects, respectively). In the prenatal population, VM is clearly defined as atrium of thelateral ventricle measuring 10 mm. However, to our knowledge, there is no such definitionfor VM in the postnatal population. There are a wide variety of methods for characterizingneonatal ventricles using US (such as the ratio of the distance from the falx to the lateralwall of the ventricle to the hemispheric width, ratio of ventricular diameter to the diameterof the brain at the same level, displacement of the medial wall of the ventricle toward themidline, and subjective assessment)15–26. Similarly, on neonatal MRI, ventricular size hasbeen assessed using a ventricular/brain ratio27. We found a significant difference of opinion(p<.01) between radiologists interpreting postnatal HUS as to when VM should bediagnosed postnatally. The prenatal definition cannot be utilized in postnatal HUS studiesbecause imaging through the anterior fontanelle of the neonate does not give the sonologistthe same axial plane of view. Even on postnatal MR with axial imaging planes, ventriclescan measure larger than 10 mm and not be classified as enlarged. Therefore, without aninterval change in the size of the ventricles, an individual could be given the diagnosis ofVM in utero, but after delivery (even on the same day) be considered normal because of thelack of a standardized definition. However, the clinical importance of this difference indiagnosis is not yet established. Our companion paper10 assesses the outcome of fetuseswith varying degrees of prenatally diagnosed VM in our population.



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It is well recognized that VM can resolve in utero. In our study, of 12 fetuses referred forVM who were felt to be normal at prenatal imaging, 2 had postnatal studies showing VM.This suggests that even when VM resolves in utero, postnatal follow-up should be obtained.Structural abnormalities have been reported postnatally in up to 10% of subjects withisolated mild VM diagnosed prenatally.28–30 We demonstrated that the risk of postnataldiagnosis of structural abnormalities increases as the degree of VM increases, with newstructural abnormalities seen in 0% of fetuses judged to be normal prenatally, 4% of fetuseswith VM 10–12 mm prenatally, and 37% of fetuses with VM 13–15 mm prenatally.

An important limitation of our study is the bias in the study population due to attrition offetuses with complex CNS anomalies who did not survive to birth to undergo postnatalimaging. In addition, there were differences in performance and modality of imaging afterbirth that were driven by prenatal diagnosis. While the group with prenatally diagnosed VMwith associated CNS anomalies had the largest prenatal attrition, they also had the highestpercentage of postnatal imaging when liveborn (93%) and the highest likelihood of having apostnatal MRI (88%). Subjects in the normal or mild isolated VM groups often did notcomplete postnatal follow-up. In addition, there was a higher percentage of disagreement inthe MR subjects (83%) compared to the US subjects (57%). Much of this discrepancy can beexplained by the fact that the children with more abnormalities prenatally had postnatal MRexaminations more often than those with fewer anomalies. This biases our results to studieswith more diagnoses, and thus more discrepancies. Migrational abnormalities, hemorrhage,and infarctions were better visualized on postnatal MR compared to US. In children withoutMR imaging, such abnormalities could have been missed. Recall bias is a possibility, asreaders overlapped between prenatal and postnatal imaging studies. However, the length oftime between obtaining these studies should have decreased this potential bias. A finallimitation is lack of correlation of our diagnoses with developmental outcomes. This isaddressed in a prior publication from our study.10

Normal brain development continues throughout pregnancy and even postnatally, thereforeit is often not possible prenatally to tell if a structure will be normal, merely that it appearsnormal for that stage in gestation. Furthermore, abnormalities detected antenatally canevolve, e.g. mild VM may become severe VM, and new abnormalities may evolve, forexample a region of hemorrhage may become an area of porencephaly. Also, head sizeincreases so there is improvement from the imaging perspective since larger structures ingeneral are easier to evaluate. These issues will affect the comparison of prenatal topostnatal findings, and are thus important concepts to understand when counseling patientsafter a diagnosis of fetal VM. In this study we have assessed congenital findings that have ofnecessity changed in character and appearance over time. It is possible that some lesionswere acquired after a postnatal event. However this type of information is also important toconsider when counseling the parents.

In conclusion, disagreements among radiologists are common with regard to the final CNSdiagnosis for children with a prenatal diagnosis of VM. This leads to difficulty inestablishing a reference standard for accuracy of prenatal diagnosis. This is particularlyproblematic in the postnatal characterization of VM. Understanding the variability inpostnatal diagnosis after a prenatal diagnosis of VM is important to clinicians who care forand counsel these patients. An imaging standard for postnatal diagnosis of VM is needed toimprove consistency in reporting. However, it should be recognized that change inappearance over time, and clinical outcome are needed to assess the clinical importance offetal VM.



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AcknowledgmentsThis study was funded by NIH NIBIB 01998. Medical student research support was from RSNA Research andEducation Foundation Medical Student Research Grant and the Clinical Research Fellowship Program at HarvardMedical School offered by the Doris Duke Charitable Foundation in conjunction with the Harvard PASTEURProgram.

References1. Patel TR, Bannister CM, Thorne J. A study of prenatal ultrasound and postnatal magnetic imaging

in the diagnosis of central nervous system abnormalities. Eur J Pediatr Surg. 2003; 13 (Suppl1):S18–22. [PubMed: 14758562]

2. Breeze AC, Alexander PM, Murdoch EM, Missfelder-Lobos HH, Hackett GA, Lees CC. Obstetricand neonatal outcomes in severe fetal ventriculomegaly. Prenat Diagn. 2007; 27:124–129.[PubMed: 17152115]

3. Ouahba J, Luton D, Vuillard E, Garel C, Gressens P, Blanc N, Elmaleh M, Evrard P, Oury JF.Prenatal isolated mild ventriculomegaly: outcome in 167 cases. Bjog. 2006; 113:1072–1079.[PubMed: 16956339]

4. Launay S, Robert Y, Valat AS, Thomas D, Devisme L, Rocourt N, Vaast P. [Cerebral fetal MRI andventriculomegaly]. J Radiol. 2002; 83:723–730. [PubMed: 12149589]

5. Falip C, Blanc N, Maes E, Zaccaria I, Oury JF, Sebag G, Garel C. Postnatal clinical and imagingfollow-up of infants with prenatal isolated mild ventriculomegaly: a series of 101 cases. PediatrRadiol. 2007; 37:981–989. [PubMed: 17724586]

6. Kinzler WL, Smulian JC, McLean DA, Guzman ER, Vintzileos AM. Outcome of prenatallydiagnosed mild unilateral cerebral ventriculomegaly. J Ultrasound Med. 2001; 20:257–262.[PubMed: 11270530]

7. Breeze AC, Dey PK, Lees CC, Hackett GA, Smith GC, Murdoch EM. Obstetric and neonataloutcomes in apparently isolated mild fetal ventriculomegaly. J Perinat Med. 2005; 33:236–240.[PubMed: 15914347]

8. Blaicher W, Bernaschek G, Deutinger J, Messerschmidt A, Schindler E, Prayer D. Fetal and earlypostnatal magnetic resonance imaging--is there a difference? J Perinat Med. 2004; 32:53–57.[PubMed: 15008387]

9. Levine D, Feldman HA, Tannus JF, Estroff JA, Magnino M, Robson CD, Poussaint TY, BarnewoltCE, Mehta TS, Robertson RL. Frequency and cause of disagreements in diagnoses for fetusesreferred for ventriculomegaly. Radiology. 2008; 247:516–527. [PubMed: 18430880]

10. Beeghly M, Ware J, Soul J, duPlessis A, Khwaja O, Senapati GM, Robson CD, Robertson RL,Poussaint TY, Barnewolt CE, Feldman HA, Estroff JA, Levine D. Neurodevelopmental outcomesof fetuses referred for ventriculomegaly. Ultrasound in Obstetrics and Gynecology. 9999 n/a.

11. van der Knaap MS, Valk J. Classification of congenital abnormalities of the CNS. AJNR Am JNeuroradiol. 1988; 9:315–326. [PubMed: 3128080]

12. Levine D, Barnes PD, Madsen JR, Abbott J, Mehta T, Edelman RR. Central nervous systemabnormalities assessed with prenatal magnetic resonance imaging. Obstet Gynecol. 1999;94:1011–1019. [PubMed: 10576192]

13. Levine D, Barnes PD, Robertson RR, Wong G, Mehta TS. Fast MR imaging of fetal centralnervous system abnormalities. Radiology. 2003; 229:51–61. [PubMed: 12920177]

14. Levine D, Barnes PD, Madsen JR, Li W, Edelman RR. Fetal central nervous system anomalies:MR imaging augments sonographic diagnosis. Radiology. 1997; 204:635–642. [PubMed:9280237]

15. Levene MI. Measurement of the growth of the lateral ventricles in preterm infants with real-timeultrasound. Arch Dis Child. 1981; 56:900–904. [PubMed: 7332336]

16. Liao MF, Chaou WT, Tsao LY, Nishida H, Sakanoue M. Ultrasound measurement of theventricular size in newborn infants. Brain Dev. 1986; 8:262–268. [PubMed: 3532852]

17. van de Bor M, Ruys JH. [Normal values of the diameter of the lateral ventricles in newborn infantsdetermined with ultrasound]. Tijdschr Kindergeneeskd. 1983; 51:54–57. [PubMed: 6879584]



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18. Soni JP, Singhania RU, Sharma A. Measurement of ventricular size in term and preterm infants.Indian Pediatr. 1992; 29:55–59. [PubMed: 1601497]

19. Saliba E, Bertrand P, Gold F, Vaillant MC, Laugier J. Area of lateral ventricles measured oncranial ultrasonography in preterm infants: reference range. Arch Dis Child. 1990; 65:1029–1032.[PubMed: 2241221]

20. Fiske CE, Filly RA, Callen PW. Sonographic measurement of lateral ventricular width in earlyventricular dilation. J Clin Ultrasound. 1981; 9:303–307. [PubMed: 6788811]

21. Davies MW, Swaminathan M, Chuang SL, Betheras FR. Reference ranges for the lineardimensions of the intracranial ventricles in preterm neonates. Arch Dis Child Fetal Neonatal Ed.2000; 82:F218–223. [PubMed: 10794790]

22. Poland RL, Slovis TL, Shankaran S. Normal values for ventricular size as determined by real timesonographic techniques. Pediatr Radiol. 1985; 15:12–14. [PubMed: 3881723]

23. Grasby DC, Esterman A, Marshall P. Ultrasound grading of cerebral ventricular dilatation inpreterm neonates. J Paediatr Child Health. 2003; 39:186–190. [PubMed: 12654141]

24. Csutak R, Unterassinger L, Rohrmeister C, Weninger M, Vergesslich KA. Three-dimensionalvolume measurement of the lateral ventricles in preterm and term infants: evaluation of astandardised computer-assisted method in vivo. Pediatr Radiol. 2003; 33:104–109. [PubMed:12557066]

25. Graziani L, Dave R, Desai H, Branca P, Waldroup L, Goldberg B. Ultrasound studies in preterminfants with hydrocephalus. J Pediatr. 1980; 97:624–630. [PubMed: 7420230]

26. Reeder JD, Kaude JV, Setzer ES. The occipital horn of the lateral ventricles in premature infants.An ultrasonographic study. Eur J Radiol. 1983; 3:148–150. [PubMed: 6873077]

27. McArdle CB, Richardson CJ, Nicholas DA, Mirfakhraee M, Hayden CK, Amparo EG.Developmental features of the neonatal brain: MR imaging. Part II. Ventricular size andextracerebral space. Radiology. 1987; 162:230–234. [PubMed: 3786768]

28. Goldstein I, Reece EA, Pilu GL. Sonographic evaluation of the normal developmental anatomy ofthe fetal cerebral ventricles. IV. The posterior horn. Am J Perinatol. 1990; 7:79. [PubMed:2403796]

29. Bromley B, Frigoletto FD Jr, Benacerraf BR. Mild fetal lateral cerebral ventriculomegaly: clinicalcourse and outcome. Am J Obstet Gynecol. 1991; 164:863–867. [PubMed: 2003552]

30. Patel MD, Filly AL, Hersh DR, Goldstein RB. Isolated mild cerebral ventriculomegaly: Clinicalcourse and outcome. Radiology. 1994; 192:759–764. [PubMed: 7520183]



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Figure 1.Consensus study design.



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Figure 2.Histogram of weeks of gestational age when prenatal imaging was performed for the 119subjects in the final study population.



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Figure 3.Coronal neonatal head ultrasound with the right ventricle measuring 9–11 mm and the leftventricle measuring 11–14 mm, diagnosed as normal by two sonologists and asventriculomegaly by one sonologist.



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Figure 4.Confidence of US and MR readers in postnatal diagnosis of fetal CNS abnormalities. Barsindicate mean ± standard error on a five-point scale from very confident to not confident. P-values from analysis of variance, adjusted for inter-reader and inter-subject variability.



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Figure 5.Hemimegalencephaly misdiagnosed as hemorrhage on prenatal imaging. A. Axial singleshot fast spin echo (SSFSE) T2WI at 22 weeks gestational age shows some areas of lowsignal intensity (arrowheads) felt to represent subependymal hemorrhage with dilatation ofthe right lateral ventricle at initial prenatal interpretation. The region of asymmetricenlargement and irregularity of the cortex (arrows) and generalized enlargement of the rightcerebral hemisphere was not prospectively noted. B. Axial fast spin echo (FSE) T2WI onday 1 of life shows a mildly larger right cerebral hemisphere and polymicrogyria that is mostmarked in the right frontal lobe (arrows). There is abnormal hypointense signal within theright frontal white matter and basal ganglia. These findings are consistent withhemimegalencephaly.



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Figure 6.



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Congenital CNS tumor as an error of observation. A. Sagittal SSFSE T2 weighted MRI at 36weeks gestational age showed VM and a very subtle area of low signal intensity above thetectum (arrow). This was only noted in retrospect after postnatal MRI. B. Postnatal spinecho (SE) T1WI without contrast shows a mildy hyperintense mass above the tectum(arrow). This was felt to be a hamartoma or low grade glioma causing hydrocephalus due toobstruction at the level of the aqueduct.



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Figure 7.Example of prenatal diagnosis being more accurate than postnatal diagnosis. A. CoronalSSFSE T2WI at 33 weeks gestational age shows ventriculomegaly and a region ofporencephaly with slightly higher signal intensity fluid (arrow). B. Axial fast spin echo(FSE) T2 weighted MRI on day of life 27 (with a 2 month interval from fetal MRI) showsthe extra-axial fluid appears contiguous with the ventricular system (arrow). Initialinterpretation of the postnatal MR (blinded to prenatal diagnosis) included schizencephalysince the parenchyma appears to have a cortical rim (arrow) in the region of the defect.However, when interpreted in conjunction with the fetal MRI, the finding was felt torepresent porencephaly. Additional findings on this image are dysmorphic ventriculomegalywith absence of the septum pellucidum and a large extra-axial fluid collection with midlineshift. The patient had other features (not shown) consistent with lobar holoprosencephaly.



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Figure 8.Example of new development of an abnormality and error of observation. A. Sagittal (A)and axial (B) SSFSE T2 weighted MR at 31 weeks gestational age show the corpus callosum(arrowhead on A, short black arrow in B). Note also absent leaflets of the septumpellucidum (*) and left temporal schizencephaly (long arrow) with ventriculomegaly. C.Sagittal SE T1-weighted MR at 3 months of age shows deficiency in the anterior genu androstrum of the corpus callosum (arrows) that was not appreciated on the prenatal MR. Notenormal appearing body of corpus callosum, as seen prenatally (arrowhead). D,E. Axial FSET2-weighted MR at 3 months of age show absent septal leaflets, deficiency of the anteriorgenu of the corpus callosum (black arrowhead) with associated dysmorphism of the frontalhorns of the lateral ventricles and schizencephaly (long arrow). In addition there aresubependymal neuronal heterotopia (white arrowheads) not visible on the prenatal study andnot recorded by one of the neuroradiologists.



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Tabl

e 1

Pren

atal

dia

gnos

es o

f sub

ject

s and

enr

ollm

ent i

n po

stna

tal i

mag

ing

porti

on o

f stu

dy

N (%

)

Nor

mal

Isol

ated

VM

10–

12 m

mIs

olat

ed V

M 1

3–15

mm

Isol

ated

VM

>15

mm

VM

with

oth

er C

NS

findi

ngs

All

Pren

atal

imag

ing†

2185

152

7319

6

Te

rmin

atio

n, st

illbi

rth, n

eona

tal d

emis

e0

(0)

7 (8

)2

(13)

1 (5

0)27

(37)

37 (1

9)

Li

vebo

rn, s

urvi

ving

neo

nata

l per

iod,

abl

e to

be

imag

edpo

stna

tally

21 (1

00)

78 (9

2)13

(87)

1 (5

0)46

(63)

159

(81)

Liv

ebor

n, w

ith p

oten

tial f

or p

ostn

atal

imag

ing†

2178

131

4615

9

N

ot p

erfo

rmed

bef

ore

age

13 m

o or

imag

es n

ot a

vaila

ble

for

revi

ew9

(43)

26 (3

3)2

(15)

0 (0

)3

(7)

40 (2

5)

Pe

rfor

med

12 (5

7)52

(67)

11 (8

5)1

(100

)43

(93)

119

(75)

Post

nata

l im

agin

g †

1252

111

4311

9

H

ead

ultra

soun

d10

(83)

50 (9

6)8

(73)

1 (1

00)

28 (6

5)97

(82)

M

RI

3 (2

5)6

(12)

5 (4

5)1

(100

)38

(88)

53 (4

5)

B

oth

1 (8

)4

(8)

2 (1

8)1

(100

)23

(53)

31 (2

6)

† Nor

mal

and

less

seve

re d

iagn

oses

wer

e as

soci

ated

with

gre

ater

pot

entia

l for

live

born

, sur

vivi

ng th

e ne

onat

al p

erio

d, a

ble

to b

e im

aged

pos

tnat

ally

than

wer

e th

ose

with

mor

e se

vere

dia

gnos

es. A

mon

gpo

tent

ial s

ubje

cts f

or p

ostn

atal

imag

ing,

nor

mal

and

less

seve

re d

iagn

oses

wer

e as

soci

ated

with

low

er li

kelih

ood

of a

ctua

l per

form

ance

of i

mag

ing;

and

am

ong

thos

e im

aged

, hig

her l

ikel

ihoo

d of

ultr

asou

ndan

d lo

wer

like

lihoo

d of

MR

I, co

mpa

red

with

mor

e se

vere

dia

gnos

es. A

ll as

soci

atio

ns si

gnifi

cant

at p

<0.0

01.


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Tabl

e 2

Pren

atal

and

pos

tnat

al d

iagn

oses

, by

US

and

MR

read

ers,

sepa

rate

ly a

nd b

y co

nsen

sus.

Dia

gnos

is*

Pre-

nata

l

Post

nata

lFi

nal P

rena

tal t

opo

stna

tal c

onse

nsus

US,

any

rea

der

US

final

con

sens

us N

(% o

f US,

any

rea

der)

MR

, any

rea

der

MR

fina

l con

sens

us N

(% o

f MR

, any

read

er)

Fina

l Pos

tnat

al U

S/M

R c

onse

nsus

Tota

l sub

ject

s11

997

9753

5311

911

9

VM

105

6750

(75%

)48

45 (9

4%)

7070

Nor

mal

1249

42 (8

6%)

32

(67%

)42

42

Dys

gene

sis c

orpu

s cal

losu

m18

2219

(86%

)23

22 (9

6%)

2828

Hem

orrh

age

914

7 (5

0%)

1412

(86%

)18

18

Cys

t6

99

(100

%)

65

(83%

)12

12

Mig

ratio

nal a

bnor

mal

ity/p

olym

icro

gyria

54

2 (5

0%)

1311

(85%

)12

12

Chi

ari m

alfo

rmat

ion*

*8

65

(83%

)7

7 (1

00%

)9

9**

Pore

ncep

haly

76

3 (5

0%)

65

(83%

)5

7

Het

erot

opia

13

1 (3

3%)

66(

100%

)6

7

Def

ect s

epti

pellu

cidi

45

3 (6

0%)

87

(88%

)6

6

Con

geni

tal i

nfar

ctio

n3

00

5***

5 (1

00%

)5

5

Dan

dy W

alke

r var

iant

/mal

form

atio

n3

53

(60%

)6

4 (6

7%)

44

Cer

ebel

lar h

ypop

lasi

a2

51

(20%

)4

3 (7

5%)

33

* Subj

ects

may

hav

e m

ore

than

one

fina

l dia

gnos

is. T

his t

able

list

s onl

y th

ose

diag

nose

s tha

t occ

urre

d 5

or m

ore

times

at a

ny p

oint

ing

the

revi

ew p

roce

ss. F

or a

list

ing

of le

ss fr

eque

nt a

bnor

mal

ities

, see

appe

ndix

Tab

le 2

.

**8

pren

atal

Chi

ari I

I dia

gnos

es in

fetu

ses w

ith n

eura

l tub

e de

fect

s; 1

pos

tnat

al C

hiar

i I m

alfo

rmat

ion

as a

new

find

ing

*** In

clud

es o

ne c

ase

of c

onge

nita

l inf

arct

ion

diag

nose

d at

con

sens

us c

onfe

renc

e


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Tabl

e 3

Dis

agre

emen

t in

post

nata

l ass

essm

ent,

US-

MR

reco

ncili

atio

n, a

nd p

rena

tal-p

ostn

atal

reco

ncili

atio

n.

Post

nata

l ass

essm

ent

Pren

atal

-pos

tnat

al r

econ

cilia

tion

US

MR

US-

MR

US

MR

Fina

l

Tota

l sub

ject

s97

5331

9753

119

No

disa

gree

men

t, N

(%)

42 (4

3%)

9 (1

7%)

4 (1

3%)

26 (2

7%)

13 (2

5%)

35 (2

9%)

At l

east

one

dis

agre

emen

t N (%

)55

(57%

)44

(83%

)27

(87%

)71

(73%

)40

(75%

)84

(71%

)

Num

ber o

f dis

agre

emen

ts m

edia

n, (r

ange

)*2

(1–6

)3

(1–7

)3

(1–7

)1

(1–6

)2

(1–6

)2

(1–6

)

Type

s of d

isag

reem

ent:

N (%

)†

(a) D

ecis

ion

to d

iagn

ose

VM

24 (4

4)11

(25)

3 (1

1)25

(35)

0 (0

)22

(26)

(b) N

o cl

inic

al d

iffer

ence

23 (4

2)27

(61)

5 (1

9)16

(23)

4 (1

0)10

(12)

(a

) or (

b)44

(80)

30 (6

8)8

(30)

41 (5

8)4

(10)

32 (3

8)

(c) M

ajor

new

find

ing

13 (2

4)11

(25)

21 (7

8)11

(15)

27 (6

8)31

(37)

(d) O

verc

all,

maj

or fi

ndin

g5

(9)

1 (2

)2

(7)

2 (3

)2

(5)

2 (2

)

(e) M

inor

dia

gnos

tic c

hang

e12

(22)

11 (2

5)1

(4)

5 (7

)10

(25)

9 (1

1)

(c

) or (

d)16

(29)

12 (2

7)22

(81)

13 (1

8)28

(70)

32 (3

8)

A

ny o

f (c)

–(e)

22 (4

0)22

(50)

23 (8

5)18

(25)

37 (9

3)40

(48)

(f) N

ow n

orm

al—

——

13 (1

8)1(

3)14

(17)

Num

ber o

f fin

al d

iagn

oses

per

pat

ient

All,

med

ian

(ran

ge)

1 (1

–4)

3 (1

–6)

3 (1

–7)

1 (1

–5)

3 (1

–6)

1 (1

–7)

No

disa

gree

men

t, m

edia

n (r

ange

)1

(1–2

)2

(1–4

)2

(1–2

)1

(1–3

)2

(1–3

)1

(1–3

)

At l

east

one

dis

agre

emen

t, m

edia

n (r

ange

)2

(1–4

)3

(1–6

)4

(2–7

)1

(1–5

)3

(1–6

)2

(1–7

)

p‡<0

.001

0.01

30.

007

0.00

2<0

.001

<0.0

01

* amon

g th

ose

with

at l

east

one

dis

agre

emen

t.

† type

s are

not

mut

ually

exc

lusi

ve.

‡ p co

mpa

res t

hose

with

and

with

out d

isag

reem

ent.


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Tabl

e 4

Post

nata

l mea

sure

men

ts o

f ven

tricu

lar d

iam

eter

, by

imag

ing

mod

e an

d pr

ospe

ctiv

e ag

reem

ent o

r dis

agre

emen

t con

cern

ing

pres

ence

of v

entri

culo

meg

aly.

Mod

eA

gree

men

t*E

xam

inat

ions

†M

easu

rem

ents

Ven

tric

ular

dia

met

er, m

m‡

Ven

tric

ular

dia

met

er, r

ange

US

All

9527

012

.9 ±

0.5

1–49

Rat

ers a

gree

, VM

pre

sent

4111

818

.3 ±

1.0

5–49

Rat

ers a

gree

, VM

abs

ent

3084

7.6

± 1.

21–

11

Rat

ers d

isag

ree

2468

10.2

± 1

.33–

16

• Rat

er in

dica

tes V

M p

rese

nt—

3411

.0 ±

1.3

6–15

• Rat

er in

dica

tes V

M a

bsen

t—

349.

4 ±

1.3

3–16

• Diff

eren

ce1.

6 ±

0.6

(p<0

.01)

MR

All

5115

317

.9 ±

0.6

3–46

Rat

ers a

gree

, VM

pre

sent

3410

220

.2 ±

1.2

11–4

6

Rat

ers a

gree

, VM

abs

ent

515

8.5

± 3.

05–

13

Rat

ers d

isag

ree

1236

15.2

± 2

.03–

30

• Rat

er in

dica

tes V

M p

rese

nt—

2715

.5 ±

2.0

3–30

• Rat

er in

dica

tes V

M a

bsen

t—

914

.3 ±

2.2

4–19

• Diff

eren

ce1.

2 ±

1.2

(p=0

.29)

US-

MR

com

paris

on

All

2917

019

.4 ±

0.7

3–46

US/

MR

con

sens

us, V

M p

rese

nt24

140

20.3

± 1

.44–

46

US/

MR

con

sens

us, V

M a

bsen

t2

129.

8 ±

4.7

7–13

US/

MR

con

sens

us d

isag

ree

318

18.7

± 3

.83–

46

• Rat

er in

dica

tes V

M p

rese

nt—

1124

.0 ±

3.9

3–46

• Rat

er in

dica

tes V

M a

bsen

t—

710

.6 ±

4.1

8–12

• Diff

eren

ce13

.3 ±

2.6

(p<0

.01)

* Cas

es o

f agr

eem

ent i

nclu

de th

ose

whe

re ra

ters

dis

agre

ed c

once

rnin

g di

agno

ses o

ther

than

VM

.

† Num

ber o

f inf

ants

, eac

h m

easu

red

by 3

rate

rs. T

wo

inst

ance

s of h

olop

rose

ncep

haly

are

exc

lude

d.


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Senapati et al. Page 31‡ M

ean

or d

iffer

ence

± st

anda

rd e

rror

from

ana

lysi

s of v

aria

nce,

adj

uste

d fo

r with

in-in

fant

and

with

in-r

ater

cor

rela

tion.

US-

MR

resu

lts a

lso

adju

sted

for i

mag

ing

mod

e. M

ean

diam

eter

var

ied

sign

ifica

ntly

acro

ss c

ateg

orie

s of r

ater

agr

eem

ent,

p<0.

002,

for e

ach

mod

e.


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Tabl

e 5

Dis

agre

emen

t on

parti

cula

r dia

gnos

es in

pos

tnat

al a

sses

smen

t, U

S-M

R re

conc

iliat

ion,

and

pre

nata

l-pos

tnat

al re

conc

iliat

ion

Typ

e of

dis

agre

emen

t*U

SM

RU

S-M

R

Post

nata

l ass

essm

ent†

114

139

98

Er

ror o

f obs

erva

tion

45 (3

8)24

(17)

0 (0

)

Er

ror o

f int

erpr

etat

ion

16 (1

4)25

(18)

4 (4

)

Er

ror o

f om

issi

on7

(6)

13 (9

)1

(1)

C

odin

g is

sue

25 (2

2)77

(55)

23 (2

3)

D

isag

reem

ent r

egar

ding

obs

erva

tion

12 (1

0)0

(0)

—

D

isag

reem

ent r

egar

ding

inte

rpre

tatio

n9

(8)

1 (1

)—

N

euro

radi

olog

ist e

xper

ienc

e w

ould

hav

e he

lped

——

2 (2

)

Ex

pect

to se

e be

tter o

n U

S—

—11

(11)

Ex

pect

to se

e be

tter o

n M

R—

—48

(48)

O

ther

0 (0

)0

(0)

10 (1

0)

Pren

atal

-pos

tnat

al re

conc

iliat

ion

109

107

175

V

M re

solv

ed28

(25)

4 (4

)27

(15)

V

M w

orse

ned

2 (2

)2

(2)

4 (2

)

V

M si

ze u

ncha

nged

, not

cod

ed a

s VM

pos

tnat

ally

11 (1

0)1

(1)

12 (7

)

C

ortic

al m

igra

tion

mor

e ap

pare

nt3

(3)

18 (1

7)19

(11)

N

ew C

NS

abno

rmal

ity d

evel

oped

late

r15

(13)

33 (3

0)38

(22)

Pr

enat

al a

bnor

mal

ity re

solv

ed3

(3)

5 (5

)8

(5)

C

allo

sal d

ysge

nesi

s now

app

aren

t10

(9)

4 (4

)11

(6)

C

odin

g is

sue

17 (1

5)20

(18)

21 (1

2)

In

adeq

uate

vie

w p

oste

rior f

ossa

1 (1

)0

(0)

0 (0

)

Er

rors

5 (4

)2

(2)

7 (4

)

O

ther

10 (9

)18

(17)

26 (1

5)

* Num

ber (

%) o

f dia

gnos

es o

n w

hich

rate

rs d

isag

reed

ent

erin

g co

nsen

sus c

onfe

renc

e; m

ay in

clud

e m

ore

than

one

per

pat

ient

.

† Type

s of d

isag

reem

ent a

re n

ot m

utua

lly e

xclu

sive

in p

ostn

atal

ass

essm

ent.


NIH


NIH


NIH



Tabl

e 6

Post

nata

l dia

gnos

es w

ith re

spec

t to

pren

atal

dia

gnos

tic g

roup

Pren

atal

dia

gnos

isPo

stna

tal d

iagn

osis

, N (%

)

All

Nor

mal

Isol

ated

VM

VM

with

oth

er a

bnor

mal

ities

(N)

Nor

mal

1210

(83)

1 (8

)1

(8):

Cho

roid

ple

xus c

yst (

1)

Isol

ated

VM

, 10–

12m

m52

28 (5

4)17

(33)

7 (1

3): H

emor

rhag

e (3

)C

horo

id p

lexu

s cys

t (2)

Cys

t with

het

erot

opia

(1)

Abn

orm

al m

idbr

ain

with

dys

gene

sis o

f cor

pus c

allo

sum

and

mig

ratio

nal a

bnor

mal

ity (1

)

Isol

ated

VM

, 13–

15m

m11

2 (1

8)3

(27)

6 (5

5): D

efec

t of s

eptu

m p

ellu

cidu

m (2

)C

hiar

i mal

form

atio

n (1

)H

emor

rhag

e an

d sc

alp

mas

s (1)

Hem

orrh

age

and

meg

a ci

ster

na m

agna

(1)

Dys

gene

sis o

f cor

pus c

allo

sum

(1)

Isol

ated

VM

, >15

mm

10

(0)

0 (0

)1

(100

): H

emor

rhag

e an

d tu

mor

(1)

VM

with

oth

er C

NS

findi

ngs

432

(5):

Cer

ebel

lar h

ypop

lasi

a (1

)M

ega

cist

erna

mag

na (1

)0

(0)

41 (9

5)

All

119

42 (3

5)21

(18)

56 (4

7)


NIH


NIH


NIH



Appendix Table 1

Reasons for disagreements and impact of disagreements used in this study

Reasons for disagreements (scored once for each disagreement)

error of observation

error of interpretation

error of omission

coding issue (two similar diagnoses have separate codes on the scale for example septo-optic dysplasia versus defect of the septumpellucidum versus agenesis of the septum pellucidum)

disagreement regarding observation (still do not agree after consensus conference)*

disagreement regarding interpretation (finding was seen by all in consensus conference, but no agreement on interpretation)*

expected to be seen better at US (such as the wall of an arachnoid cyst)*

expected to be seen better at MRI (i.e., parenchymal changes) *

neuroradiologist experience would aid in diagnosis*

Reasons for a difference in opinion and the impact of the disagreements on the case (score as many as indicated for each case)

decision to diagnose VM (difference of opinion as to whether VM was present)

no clinical difference due to disagreement (agenesis of the corpus callosum versus damage of the corpus callosum)

minor new finding

major new finding

overcall of a minor finding

overcall of a major finding

neonatal brain now appears normal*

Reasons for disagreement between prenatal and postnatal imaging

resolution of VM

worsening of VM

ventricular size similar to prenatal examination but not coded as VM postnatally

intervention (i.e., surgery or shunt placement);

cortical migrational abnormalities more apparent at a later gestational age/postnatally;

new CNS abnormality developed later (i.e., hemorrhage, tumor, or porencephaly);

prenatal CNS abnormality resolved postnatally (i.e., hemorrhage);

spinal neural tube defect not visualized on brain imaging

corpus callosum dysgenesis more apparent

coding issue

inadequate view of the posterior fossa on postnatal HUS

error

abnormality of the type not expected to be seen on the imaging modality utilized (i.e., cortical migrational abnormality detected prenatallymay be missed postnatally if only a HUS was done after birth and no brain MRI)

other

*Used only for prenatal to postnatal comparisons


NIH


NIH


NIH



App

endi

x ta

ble

2

Unc

omm

on a

bnor

mal

ities

, pre

nata

l and

pos

tnat

al d

iagn

oses

, by

US

and

MR

read

ers,

sepa

rate

ly a

nd b

y co

nsen

sus.

Dia

gnos

is*

Pre-

nata

lPo

stna

tal

Fina

l Pre

nata

l to

post

nata

l con

sens

us

US,

any

rea

der

US

final

con

sens

us N

(%of

US,

any

rea

der)

MR

, any

rea

der

MR

fina

l con

sens

us N

(% o

f MR

, any

rea

der)

Fina

l Pos

tnat

al U

S/M

R c

onse

nsus

Periv

entri

cula

r leu

kom

alac

ia1

10

(0%

)4*

(100

%)

44

Con

geni

tal c

ereb

ral c

alci

ficat

ion

01

1 (1

00%

)1

1 (1

00%

)2

2

Hol

opro

senc

epha

ly1

20

(0%

)2

2 (1

00%

)2

2

Meg

acis

tern

a m

agna

30

02

1(50

%)

22

Abn

orm

al m

idbr

ain/

thal

amus

00

02

2(10

0%)

22

Cra

nios

ynos

tosi

s1

00

22(

100%

)2

2

Ecto

pic

post

erio

r pitu

itary

00

01

1(10

0%)

11

Schi

zenc

epha

ly1

00

22(

100%

)2

1

Mic

renc

epha

ly1

00

11(

100%

)1

1

Tum

or0

00

11

(100

%)

11

Scal

p m

ass

00

01

1 (1

00%

)1

1

Hem

imeg

alen

ceph

aly

00

01

1 (1

00%

)1

1

* incl

udes

one

cas

e of

PV

L di

agno

sed

at ti

me

of c

onse

nsus

con

fere

nce.


Documents

Frequency and cause of disagreements in imaging diagnosis in children with ventriculomegaly diagnosed prenatally