Prenatal MRI quantitative analysis of the nonlinear morphological changes of the choroid plexus during the progression of fetal ventriculomegaly

Abstract

Background

To quantify fetal choroid plexus (CP) morphological changes across ventriculomegaly (VM) grades using routine 1.5-T MRI and assess their association with lateral ventricle dilatation.

Methods

In this retrospective study, 135 singleton fetuses (24–37 weeks’ gestation) were categorized by atrial width (AW): normal, mild VM, moderate VM, severe VM). On coronal T2-weighted images, CP length, width, perimeter, and area were measured. The two-dimensional (2D) CP ratio (CPR-2D) and CP-to-ventricle width ratio were calculated. Analysis of covariance (ANCOVA) adjusted for gestational age and fetal biometrics, and intraclass correlation coefficients (ICC) were used for analysis.

Results

Absolute CP measurements exhibited non-linear, stage-specific alterations: CP length and perimeter increased in mild VM, decreased in moderate VM, and increased again in severe VM. CP width progressively decreased until moderate VM before rebounding in severe cases. Conversely, ratio-based indices demonstrated a consistent, monotonic linear decrease as VM severity increased, which remained significant after adjusting for covariates (p < 0.05). While morphological asymmetry existed, the downward trend of ratios remained consistent for both ventricles.

Conclusions

The fetal CP undergoes a non-linear change process during the expansion of the lateral ventricle. However, based on ratio-based indicators, especially CPR-2D, stable and reproducible imaging biomarkers can be provided.

Introduction

Fetal ventriculomegaly (VM) is the most common central nervous system anomaly detected during prenatal screening, with an estimated incidence of 0.3%–2.2% [1]. The diagnostic threshold is typically defined as an atrial width (AW) of ≥ 10 mm [1]. This measurement is easily obtainable, highly reproducible, and remains the standard first-line screening parameter. However, the etiological spectrum, clinical progression, and subsequent neurodevelopmental outcomes of VM, particularly isolated mild VM, exhibit considerable heterogeneity [2]. Consequently, reliance on a single linear parameter is limited in its capacity to achieve refined risk stratification and provide comprehensive prenatal counseling.

Fetal magnetic resonance imaging (MRI), owing to its superior soft-tissue contrast, has become an important adjunct to prenatal ultrasound [3, 4].The choroid plexus (CP), as the primary site of cerebrospinal fluid (CSF) production and a key structural component of the blood–CSF barrier, plays a central role in maintaining intracranial homeostasis and mediating neurodevelopmental signaling [5, 6]. Previous studies suggest that morphological and positional changes in the CP may reflect underlying disturbances in ventricular fluid dynamics, which are closely associated with the pathophysiology of VM [7]. However, current quantitative assessments of the CP predominantly rely on high-field (3.0 T) MRI or deep learning algorithms [8–10]. Furthermore, the majority of these advanced quantitative studies have been conducted in adult cohorts, while corresponding research focusing on the fetal CP remains relatively scarce. Additionally, these advanced methods are constrained by limited scanner availability and substantial post-processing requirements. This hampers their routine implementation in broader clinical settings, where 1.5-T MRI is still recommended by current fetal MRI guidelines [1]. Moreover, the quantitative relationship between two-dimensional CP morphologic features and VM severity, as well as interobserver reproducibility, has yet to be systematically validated.

This study aimed to develop a practical and reproducible two-dimensional coronal CP measurement protocol using routine 1.5-T fetal MRI. The proposed metrics include CP length, transverse diameter, perimeter, area, and the ratio of CP area to the ipsilateral lateral ventricular area (choroid plexus ratio, CPR-2D). This study systematically examine the associations between two-dimensional CP imaging phenotypes and the degree of lateral jventricular dilatation, and evaluates the robustness of this measurement approach. The goal is to provide a clinically accessible quantitative basis for imaging-based grading of fetal VM.

Materials and methods

Study population

This retrospective study analyzed data from singleton pregnancies that underwent fetal MRI between January 2018 and December 2023. The study protocol was approved by the institutional ethics committee (approval No. (B) KY2026062). The requirement for informed consent was waived due to the retrospective analysis of anonymized imaging data.

Inclusion criteria: (1) gestational age between 24 and 37 weeks (determined from the last menstrual period and/or adjusted by first-trimester ultrasonography); (2) fetal MRI including complete brain T2-weighted sequences in the axial, sagittal, and coronal planes.

Exclusion criteria comprised: (1) other major structural brain abnormalities (e.g., agenesis of the corpus callosum, schizencephaly, Dandy–Walker syndrome); (2) suboptimal image quality with motion artifacts precluding reliable identification of key structures; (3) maternal pregnancy complications (e.g., preeclampsia, severe diabetes) or fetal chromosomal abnormalities; and (4) space-occupying or destructive lesions that directly alter and distort the intrinsic morphology of the choroid plexus, such as peri-/intraventricular hemorrhage, choroid plexus cysts, or tumors.

A total of 215 fetuses were included in this study. After excluding 14 lateral ventricles due to significant image artifacts, a total of 416 assessable lateral ventricles were finally included. Because the sample size in specific subgroups (particularly the severe VM group) was relatively limited, these lateral ventricles were treated as separate, independent samples for the overall morphological and statistical analysis.

Data acquisition

Collection of clinical and demographic data

Demographic and clinical data were retrieved from the institutional Picture Archiving and Communication System (PACS). Collected parameters included maternal age, gestational age (GA), amniotic fluid volume (assessed via ultrasound), placental thickness, and fetal biometric indices, including head circumference (HC) and biparietal diameter (BPD).

MRI acquisition protocol

All fetal MRI examinations were performed on a 1.5-T scanner (Siemens) using a standard fetal brain imaging protocol. The primary sequence was Half-Fourier Acquisition Single-shot Turbo spin Echo (HASTE) T2-weighted imaging, acquired in the axial, sagittal, and coronal planes to cover the entire brain. Imaging parameters were as follows: repetition time/echo time (TR/TE), 1200/90 ms; slice thickness, 4 mm; interslice gap, 0 mm; field of view (FOV), 300 × 300 mm; matrix, 256 × 256; and number of excitations (NEX), 1.

Two-dimensional quantitative analysis of the choroid plexus

Quantitative assessment of the choroid plexus (CP) was performed on coronal T2-weighted images.Two radiologists with extensive experience in fetal MRI independently selected, on the PACS workstation, the coronal slice demonstrating the largest CP area. Manual tracing was performed to delineate the CP boundaries, followed by the measurement of morphometric parameters. All measurements were obtained from the original images without preprocessing. In cases where interobserver variability exceeded 10%, a consensus reading was conducted to establish the final values.

Measurement parameters

The following two-dimensional parameters were measured and recorded: (1) CP length, defined as the maximum longitudinal diameter on the coronal plane; (2) CP width, defined as the maximum transverse diameter on the coronal plane; (3) CP perimeter, automatically calculated by the system based on the manually delineated boundary; (4) CP area, automatically generated from the outlined region (mm²); (5) area of the ipsilateral lateral ventricle on the same slice, obtained by manually tracing the ventricular boundary with automatic area calculation (lateral ventricle area delineation included all visible dilated chambers on the selected coronal plane); and (6) the choroid plexus–to–lateral ventricle area ratio (CPR-2D), calculated as: CPR-2D = CP area / ipsilateral lateral ventricular area. In addition, the ratio of CP width to lateral ventricular width was calculated to provide further insight into the morphologic and spatial proportional characteristics.

Participants were categorized according to atrial width (AW). The normal group was defined as AW < 10 mm, and the ventriculomegaly (VM) group as AW ≥ 10 mm. In accordance with established guidelines, the VM group was further stratified into mild (10–12 mm), moderate (> 12–15 mm), and severe (> 15 mm) subgroups [11].

Consistency analysis

A random sample of 20% of the cases was selected, and measurements were repeated by both radiologists. Interobserver agreement was assessed using the intraclass correlation coefficient (ICC) for continuous variables and Cohen’s kappa coefficient for categorical variables.

Statistical analysis

Statistical analyses were performed using SPSS software (version 26.0, IBM Corp.). Continuous variables were analyzed using analysis of variance (ANOVA) or non-parametric tests, as appropriate based on their distribution. Categorical variables were compared using χ² tests or Fisher’s exact test, as appropriate. To compare differences in CP indicators across different lateral ventricle grades, analysis of covariance (ANCOVA) was used, with gestational age, head circumference, and biparietal diameter included as covariates. Correlation analyses were conducted using Pearson’s or Spearman’s methods, depending on data characteristics. A two-tailed α level of 0.05 was set as the threshold for statistical significance.

Results

Baseline data and consistency testing

No statistically significant differences were observed among the groups for baseline indicators, including maternal age, gestational age, fetal head circumference, biparietal diameter, and amniotic fluid volume, among the groups (P > 0.05) (Table 1). The intraclass correlation coefficients (ICCs) for the inter - observer measurements of all CP two - dimensional morphological indicators were greater than 0.85, indicating good measurement reproducibility.

Table 1.

General information of subjects at different grades of lateral ventricular enlargement

Variables	Total (n = 416)	1 (n = 299)	2 (n = 64)	3 (n = 33)	4 (n = 20)	Statistic	P
Age, Mean ± SD	29.84 ± 3.99	29.99 ± 4.03	29.08 ± 3.82	30.21 ± 3.62	29.35 ± 4.52	F = 1.11	0.343
GA, Mean ± SD	31.46 ± 3.21	31.85 ± 3.10	30.72 ± 3.23	32.18 ± 3.64	32.05 ± 3.44	F = 1.65	0.083
HC, Mean ± SD	301.64 ± 29.29	301.55 ± 26.85	298.23 ± 27.39	309.59 ± 28.70	300.81 ± 58.35	F = 1.11	0.346
BPD, Mean ± SD	84.52 ± 14.31	85.33 ± 9.86	83.20 ± 14.00	84.42 ± 9.24	85.78 ± 43.57	F = 2.15	0.067
Placental thickness, M (Q₁, Q₃)	36.80 (32.45, 44.00)	38.30 (35.00,46.10)	37.90 (34.18,45.00)	35.00 (32.90,41.00)	36.70 (30.88,48.78)	χ²=6.17#	0.053
Amniotic fluid volume, n(%)						-	0.224
0	34 (8.17)	30 (10.03)	4 (6.25)	0 (0.00)	0 (0.00)
1	366 (87.98)	257 (85.95)	57 (89.06)	33 (100.00)	19 (95.00)
2	16 (3.85)	12 (4.01)	3 (4.69)	0 (0.00)	1 (5.00)

F: ANOVA, #: Kruskal-waills test, -: Fisher exact

SD: standard deviation, M: Median, Q₁: 1st Quartile, Q₃: 3st Quartile

BPD: biparietal diameter; HC: head circumference; GA: gestational age

Note: ‘n’ refers to the number of lateral ventricles

Relationship between the evolution of choroid plexus structure and VM grading

Nonlinear evolution of morphological indicators

The length, perimeter, and area of the CP exhibit non-monotonic changes with increasing VM severity (the morphological evolution of the choroid plexus along with the expansion of the lateral ventricle is shown in Fig. 1(A1,A2,A3,A4,B1,B2,B3,B4), including MRI and schematic diagrams.). Compared to the normal group, the mild VM group showed an increasing trend in CP length and perimeter. In contrast, these indicators decreased in the moderate VM group and increased again in the severe VM group. No significant difference in CP area was observed between the mild VM and normal groups. However, the moderate VM group shows a significant reduction, followed by a rebound in the severe VM group. CP width decreases in the mild VM group and then gradually increased with the severity of enlargement in the moderate and severe groups (Table 2; Fig. 2(A-B)).

Fig. 1.

MRI and schematic diagram of the fetal choroid plexus morphological evolution along with the expansion of the lateral ventricle. (A) MRI Findings of Choroid Plexus Morphology in Lateral Ventricular Enlargement of Different Grades; (B) Morphological Evolution Patterns of the Choroid Plexus. The figure shows, in coronal view, four characteristic stages of the choroid plexus as lateral ventricular enlargement progresses: (A1, B1) Normal control (AW < 10 mm): The lateral ventricles have a regular shape. The choroid plexus fills the atrium, exhibits smooth margins, and adheres closely to the ventricular wall. (A2, B2) Mild enlargement (Mild VM, 10–12 mm): The lateral ventricles are mildly enlarged. The choroid plexus appears elongated, and an increase in its length is observed. (A3, B3) Moderate enlargement (Moderate VM, 12–15 mm): The choroid plexus appears overall reduced in size. The width and area show a significant decrease compared to the mild enlargement group (Key Finding). (A4, B4) Severe enlargement (Severe VM, > 15 mm): Extreme ventricular enlargement is observed, and the choroid plexus exhibits an irregular morphology and altered spatial configuration

Table 2.

Choroid plexus morphometry by ventriculomegaly grade

Variables	Total (n = 416)	1 (n = 299)	2 (n = 64)	3 (n = 33)	4 (n = 20)	Statistic	P
CP length, Mean ± SD	16.27 ± 3.50	16.65 ± 3.37	17.66 ± 3.39	13.50 ± 3.52	14.97 ± 3.04	F = 13.05	< 0.001
CP perimeter, Mean ± SD	37.37 ± 7.23	37.96 ± 6.97	38.62 ± 7.05	32.23 ± 7.44	33.97 ± 6.77	F = 10.92	< 0.001
CP width, M (Q₁, Q₃)	2.20 (1.80, 2.60)	2.30 (1.90,2.60)	2.00 (1.70,2.40)	2.10 (1.70,2.50)	2.25 (1.67,3.10)	χ²=10.30#	0.016
CP area, M (Q₁, Q₃)	31.15 (24.17, 38.73)	31.50 (24.55,38.85)	31.50 (25.55,40.20)	25.60 (21.40,33.60)	27.45 (21.95,34.85)	χ²=13.07#	0.004
CPR-2D, M (Q₁, Q₃)	0.20 (0.12, 0.25)	0.22 (0.18,0.27)	0.13 (0.09,0.15)	0.08 (0.06,0.10)	0.07 (0.05,0.08)	χ²=172.97#	< 0.001
CP width/lateral ventricle width, M (Q₁, Q₃)	0.31 (0.21, 0.43)	0.37 (0.29,0.48)	0.19 (0.15,0.22)	0.16 (0.12,0.19)	0.13 (0.10,0.19)	χ²=209.06#	< 0.001

F: ANOVA, #: Kruskal-waills test, χ²: Chi-square test, -: Fisher exact

SD: standard deviation, M: Median, Q₁: 1st Quartile, Q₃: 3st Quartile

CP: choroid plexus; CPR: choroid plexus ratio

Note: ‘n’ refers to the number of lateral ventricles

Fig. 2.

Comparison box plot of two-dimensional morphology of choroid plexus and CPR-2D in different grades of fetal lateral ventricle dilation. A. Comparison of two-dimensional morphology of choroid plexus in different grades of fetal lateral ventricle dilation; B. Comparison of proportion indicators of choroid plexus in different grades of fetal lateral ventricle dilation. The vertical axis represents the measured values of two-dimensional morphology indicators (unit: mm), the horizontal axis represents different grades of lateral ventricle dilation, and the Color Bar represents different indicators. CP = choroid plexus, CPR-2D = ratio of choroid plexus to lateral ventricle area

Discriminatory efficacy of ratio indicators

The CPR-2D and the CP width-to-lateral ventricle width ratio exhibit a linear decrease with increasing severity of lateral ventricular enlargement (P < 0.05). This trend remained statistically significant after adjusting for gestational age, head circumference, and biparietal diameter (Table 3).

Table 3.

Multivariate linear regression analysis of lateral ventricular enlargement grading

Variables	single factor					multi-factor
	β	S.E	t	P	β (95%CI)	β	S.E	t	P	β (95%CI)
CP length	-0.06	0.01	-5.11	< 0.001	-0.06 (-0.08 ~ -0.04)	-0.03	0.03	-0.79	0.431	-0.03 (-0.09 ~ 0.04)
CP width	-0.09	0.07	-1.39	0.164	-0.09 (-0.23 ~ 0.04)	0.33	0.17	1.91	0.056	0.33 (-0.01 ~ 0.66)
CP perimeter	-0.02	0.01	-4.34	< 0.001	-0.02 (-0.03 ~ -0.01)	0.00	0.01	0.15	0.879	0.00 (-0.02 ~ 0.03)
CP area	-0.01	0.00	-3.11	0.002	-0.01 (-0.02 ~ -0.01)	0.00	0.01	0.18	0.860	0.00 (-0.01 ~ 0.01)
CPR-2D	-5.24	0.38	-13.62	< 0.001	-5.24 (-6.00 ~ -4.49)	-1.24	0.62	-1.85	0.045	-1.14 (-2.36 ~ -0.17)
CP width/lateral ventricle width	-3.19	0.22	-14.58	< 0.001	-3.19 (-3.62 ~ -2.76)	-3.66	0.39	-9.43	< 0.001	-3.66 (-4.42 ~ -2.90)
GA	0.01	0.01	0.71	0.480	0.01 (-0.02 ~ 0.03)	0.02	0.02	1.10	0.271	0.02 (-0.02 ~ 0.06)
HC	0.00	0.00	0.52	0.607	0.00 (-0.00 ~ 0.00)	0.00	0.00	0.90	0.369	0.00 (-0.00 ~ 0.01)
BPD	0.01	0.00	3.62	< 0.001	0.01 (0.01 ~ 0.02)	0.00	0.00	0.86	0.389	0.00 (-0.00 ~ 0.01)

BPD: biparietal diameter; CP: choroid plexus; CPR: choroid plexus ratio; CI: Confidence Interval; HC: head circumference; GA: gestational age

Lateral differences analysis

Lateral analysis revealed asymmetry in CP morphological changes. The two-dimensional morphological indicators of the right CP exhibited a trend of initial decrease followed by an increase with VM progression, whereas the left CP showed a continuous decreasing trend. Despite lateral differences in absolute values, the CPR − 2D maintained a consistent decreasing trend with increasing VM severity on both sides (Table 4).

Table 4.

Comparative analysis of bilateral CP 2D morphology and ventricular indices across ventriculomegaly grades

Variables	Total (n = 209)	1 (n = 128)	2 (n = 48)	3 (n = 24)	4 (n = 9)	Statistic	P
Left CP length, Mean ± SD	16.06 ± 3.56	17.38 ± 3.46	16.03 ± 3.27	13.43 ± 3.47	13.37 ± 2.64	F = 8.42	< 0.001
Left CP width, Mean ± SD	2.34 ± 0.63	2.39 ± 0.63	2.30 ± 0.59	2.23 ± 0.63	2.21 ± 0.60	F = 2.83	0.040
Left CP perimeter, Mean ± SD	36.34 ± 7.44	37.26 ± 7.15	36.53 ± 7.11	32.14 ± 7.13	31.20 ± 5.82	F = 7.85	< 0.001
Left CP area, Mean ± SD	32.51 ± 11.31	33.25 ± 11.54	32.46 ± 11.38	28.06 ± 9.45	27.93 ± 9.03	F = 2.42	0.068
Left CPR-2D, Mean ± SD	0.18 ± 0.09	0.22 ± 0.08	0.18 ± 0.06	0.16 ± 0.03	0.13 ± 0.21	F = 18.69	< 0.001
Left CP width/lateral ventricle width, Mean ± SD	0.31 ± 0.15	0.38 ± 0.14	0.21 ± 0.08	0.17 ± 0.05	0.13 ± 0.04	F = 43.31	< 0.001
Right CP length, Mean ± SD	14.24 ± 3.43	14.67 ± 3.36	12.91 ± 3.20	12.97 ± 3.42	14.47 ± 3.37	F = 5.03	0.002
Right CP width, Mean ± SD	2.25 ± 0.57	2.10 ± 0.55	2.04 ± 0.49	2.14 ± 0.60	2.45 ± 0.97	F = 2.74	0.044
Right CP perimeter, Mean ± SD	31.75 ± 6.98	31.03 ± 6.76	29.04 ± 6.76	31.42 ± 7.81	34.42 ± 7.41	F = 3.99	0.009
Right CP area, Mean ± SD	25.52 ± 10.13	24.48 ± 10.27	22.02 ± 9.84	22.78 ± 6.74	27.65 ± 7.79	F = 3.32	0.021
Right CPR-2D, Mean ± SD	0.19 ± 0.08	0.19 ± 0.07	0.16 ± 0.07	0.17 ± 0.02	0.17 ± 0.04	F = 3.34	0.024
Right CP width/lateral ventricle width, Mean ± SD	0.24 ± 0.15	0.25 ± 0.13	0.16 ± 0.11	0.16 ± 0.05	0.15 ± 0.07	F = 24.04	< 0.001

F: ANOVA, χ²: Chi-square test, -: Fisher exact

CP: choroid plexus; CPR: choroid plexus ratio; HC: head circumference; GA: gestational age; SD: standard deviation

Note: ‘n’ refers to the number of lateral ventricles

Discussion

This study quantitatively analyzed the conventional 1.5 T magnetic resonance imaging (MRI) characteristics of the choroid plexus (CP) in fetuses with varying degrees of ventriculomegaly (VM), revealing the dynamic morphological evolution of the CP with disease progression. The main findings are as follows: (1) Absolute morphological parameters (e.g., length, perimeter, area) exhibited non-monotonic fluctuations with varying degrees of lateral ventricle enlargement, following a complex pattern of “extension—compression—morphological disarray”; (2) Relative ratio indicators (e.g., choroid plexus-lateral ventricle area ratio (CPR-2D)) demonstrated a robust linear decline and good inter-observer reproducibility; (3) Significant left-right asymmetry was observed in CP morphological changes, yet the ratio indicators maintained consistent trends bilaterally. These findings suggest that quantitative analysis of the CP based on conventional MRI can provide new imaging perspectives for the pathophysiological assessment of VM, helping to complement the existing single-width atrial (AW) screening system.

Nonlinear dynamic characteristics of absolute morphological changes in the choroid plexus

Contrary to the view held by some previous studies [12] that the choroid plexus undergoes simple compression and atrophy with lateral ventricle enlargement, the results of this study demonstrate that the two - dimensional morphological changes of the CP exhibit distinct stage - specific characteristics.In the mild VM stage, CP length and perimeter increase, while width and width - to - length ratio decrease, with no significant change in CP area. This pattern suggests that, in the early stages, a slight increase in cerebrospinal fluid pressure within the lateral ventricles may generate a longitudinal fluid shear or tensile force [13], we speculate that this force might cause the soft CP to undergo a passive “stretching” deformation. On two-dimensional imaging, this manifests as longitudinal elongation and lateral thinning, leading to increased length and perimeter while the width decreases, yet the overall volume (as reflected in the area) does not undergo substantial changes. This physical ‘stretching’ is primarily a mechanical response related to the expansion of the lateral ventricle, as the CP remains anchored by its attachment at the foramen of Monro, creating a passive ‘tethering effect’ [7].

As the condition progresses to the moderate VM stage, a significant decrease was observed in CP length, perimeter, width, and area. This may be attributed to a marked increase in intraventricular hydrostatic pressure. The elevated pressure is presumed to exert direct compression on the CP. As suggested by previous neuropathological models. this prolonged pressure might lead to the collapse of the trabecular spaces and a subsequent reduction in tissue volume. This results in an overall “atrophic” appearance on two-dimensional imaging, which may reflect the failure of compensatory mechanisms [12].

In the severe VM stage, the further increase in CP width, length, and area may be related to the failure of the CP’s tethered structure, the development of substantial edema [14], or compensatory hyperplasia in response to severe ventricular enlargement. Under conditions of severe hydrocephalus, the attachment of the choroid plexus to the surrounding ventricular wall is altered. Fixation may occur only at the proximal stalk, while the distal part folds or gathers within the enlarged ventricle, assuming a floating state [7]. The increased degrees of freedom of this spatial configuration may lead to an enlargement of the projected area on two-dimensional imaging. Additionally, prolonged severe compression may result in interstitial edema or structural remodeling of the choroid plexus itself [15], contributing to a further increase in morphological parameters. The changes in CP morphology across different stages of ventricular enlargement reflect not merely volume fluctuations, but rather the dynamic interplay between intraventricular pressure conditions and tissue compliance.

Robustness and clinical value of ratio-based indicators

Compared to the complex fluctuations observed in absolute morphological parameters, ratio-based indicators exhibited a more stable trend across different grades of lateral ventricle enlargement. The results of this study demonstrate that the CPR − 2D and the ratio of choroid plexus width to lateral ventricle width, after adjustment for biological parameters, can effectively distinguish between different degrees of VM, demonstrating a monotonic linear decreasing trend. A significant decrease in CPR − 2D suggests that the rate of cerebrospinal fluid production or accumulation far exceeds the development or compensatory capacity of the choroid plexus [16].Compared to measuring CP volume or area alone, incorporating the lateral ventricle area as the denominator effectively constructs a spatial occupancy model reflecting the “parenchyma-to-cavity” ratio. This approach provides a substantial incremental value over the standard clinical measurement of atrial width (AW). While AW is a simple, highly reproducible, and well-established one-dimensional linear marker for first-line screening, it primarily registers localized spatial expansion. In contrast, ratio-based indices such as CPR-2D offer a dimensionless, comprehensive reflection of the multi-dimensional imbalance between intraventricular cerebrospinal fluid accumulation and choroid plexus structural alterations, bypassing the confounding effects of inter-individual growth variations. The primary clinical utility and applicable scenario of these ratio-based indices lie in the refined assessment of isolated mild or borderline ventriculomegaly (10–12 mm). Mild VM exhibits high clinical heterogeneity, making risk stratification and prenatal counseling using a single linear parameter exceptionally challenging. In these borderline scenarios, CPR-2D can serve as an auxiliary biomarker ; by capturing early morphological shifts (such as passive elongation or thinning under initial pressure changes), it provides clinicians with additional, subtle insights into intraventricular homeostasis and compensatory states. We acknowledge that area tracing is inherently more complex than a single linear width measurement and could potentially introduce greater measurement errors in less standardized settings. However, the excellent inter-observer reproducibility demonstrated in this study (ICC > 0.85) underscores that under a rigorously defined measurement protocol, these errors remain well-controlled. Furthermore, because these ratio indicators utilize internal normalization within the same slice, they intrinsically minimize diagnostic biases induced by developmental asymmetry or local structural distortions, ensuring robust clinical generalizability. It’s worth noting that, it should be noted that while these ratio-based indices reliably reflect the overall severity of ventricular dilatation, they cannot currently differentiate the specific underlying etiologies, particularly in moderate and severe VM. The etiologies at these advanced stages are highly heterogeneous. CPR-2D primarily captures the spatial imbalance between cerebrospinal fluid accumulation and the choroid plexus parenchyma, rather than the primary mechanism of the disease.

Lateral differences and asymmetry in cerebral development

Our lateral analysis further confirmed the presence of laterality in fetal brain development [17]. The results showed that the morphological “rebound” trend of the right choroid plexus during the severe enlargement stage was more pronounced than that of the left side. This asymmetry may be related to the temporal differences in the development of the fetal cerebral hemispheres (Yakovlevian torque) [18], as well as hemodynamic differences between the bilateral ventricular systems [19]. It may also be influenced by fetal position, local anatomical variations, and the inherent limitations of a two-dimensional measurement plane.The right lateral ventricle may exhibit different compliance under severe enlargement, leading to distinct morphological adaptations in its internal structure (CP). Despite Despite the observed left-right morphological differences, the CPR-2D and related ratio indicators maintained a consistent decreasing trend on both sides, further validating their robustness. This finding suggests that, in clinical practice, the stability and reliability of ratio-based indicators in reflecting the degree of lateral ventricle enlargement can help minimize diagnostic bias caused by cerebral anatomical asymmetry.

Practical application and clinical significance

Previous quantitative studies on the choroid plexus often relied on high-field strength equipment, three-dimensional volume reconstruction, or deep learning algorithms [20–22]. Although these methods are highly accurate, they have stringent requirements for specialized hardware and advanced technical expertise.This study, conducted in a real-world clinical setting, demonstrated that a two-dimensional measurement approach using conventional 1.5-T MRI coronal images has good operability and inter-observer consistency. This method avoids complex post - processing workflows, enabling radiologists to obtain additional quantitative information beyond the lateral ventricle atrial width (AW) during routine image interpretation. In previous clinical practice, the atrial width (AW) mainly reflected the degree of local ventricular enlargement. Particularly in cases of isolated mild lateral ventricle enlargement, a single linear measurement was insufficient to comprehensively capture the heterogeneity of the condition [23].This study demonstrates that ratio - based indicators offer distinct advantages in reflecting the overall effect of ventricular enlargement. They contribute to a more comprehensive information base for imaging-based stratified assessment. In prenatal counseling and follow - up management, the introduction of two - dimensional and ratio - based CP indicators is expected to provide a more objective quantitative reference for multidisciplinary teams.

Limitations

This study has several limitations. First, because simple two-dimensional measurements cannot fully capture the complex three-dimensional distortions of the choroid plexus, our mechanistic hypotheses regarding “stretching” or “compression” require future validation through 3D volumetric analysis or cerebrospinal fluid dynamic modeling. Second, the cross-sectional design lacks longitudinal and postnatal follow-up, preventing direct verification of the temporal morphological sequence and the establishment of reliable clinical cutoffs based on true neurodevelopmental outcomes. Consequently, future studies with long-term follow-up are necessary to definitively correlate these choroid plexus changes with postnatal cognitive and motor functions and to validate their clinical predictive value. Third, strict ethical regulations and the use of cranial-only MRI protocols precluded the identification of fetal sex, preventing us from exploring potential sex-related morphological differences. Future studies could investigate these differences if such data becomes ethically and clinically accessible. Fourth, our rigorous exclusion of fetuses with maternal complications or confirmed chromosomal abnormalities introduces selection bias, limiting the generalizability of our findings to real-world clinical settings where such factors frequently coexist. Future prospective studies using unselected cohorts are necessary to validate whether these morphological trajectories remain consistent across diverse etiological backgrounds.

Conclusions

In conclusion, the choroid plexus in fetuses with lateral ventricular enlargement does not merely undergo atrophy but instead demonstrates a complex morphological evolution characterized by “stretching—compression—remodeling.” Compared to absolute morphological indicators, which are more susceptible to fluctuations, ratio - based indicators such as CPR − 2D provide a more stable, objective, and developmentally independent assessment. These indicators hold significant clinical value for the prenatal MRI evaluation of developmental abnormalities of the fetal ventricular system.

Abbreviations

2D

Two-dimensional

ANCOVA

Analysis of covariance

ANOVA

Analysis of variance

AW

Atrial width

BPD

Biparietal diameter

CP

Choroid plexus

CPR-2D

Two-dimensional choroid plexus ratio/Choroid plexus-to-lateral ventricle area ratio

CSF

Cerebrospinal fluid

FOV

Field of view

FSE

Fast spin-echo

GA

Gestational age

HC

Head circumference

ICC

Intraclass correlation coefficient

MRI

Magnetic resonance imaging

NEX

Number of excitations

PACS

Picture Archiving and Communication System

TE

Echo time

TR

Repetition time

VM

Ventriculomegaly

Author contributions

Conceptualization: Mingshan Du, Wei Chen, Yan Li, Li Zeng；Data curation: Yuhan Zhang, Fengwei Yu；Formal analysis: Yuhan Zhang, Fengwei Yu, Meng Zeng；Investigation: Yuhan Zhang；Methodology: Mingshan Du, Chen Liu, Fengwei Yu；Project administration: Mingshan Du；Resources: Mingshan Du, Ping Cai, Xinwei Li；Software: Yuhan Zhang, Fengwei Yu；Supervision: Mingshan Du, Wei Chen；Validation: Mingshan Du, Wei Chen, Wei Chen；Visualization: Yuhan Zhang, Fengwei Yu, Meng Zeng；Writing-original draft: Yuhan Zhang, Fengwei Yu；Writing-review & editing: Mingshan Du, Wei Chen, Wei Chen, Chen Liu, Ping Cai. All authors reviewed the manuscript.

Funding

This study was supported by 7.0T Magnetic Resonance Translational Medicine Research Center Special Fund (Project No. 424Z2Q31) and Chongqing Medical Leadership Talent Program (No. YXLJ202518).

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The clinical research and clinical project implementation were performed in accordance with the Declaration of Helsinki and its subsequent amendments, as well as relevant Chinese clinical research norms and regulations. Institutional Review Board approval was obtained. This study was approved by the Ethics Committee of the First Affiliated Hospital of Army Medical University. The approval number is(B)KY2026062). Informed consent was waived due to the retrospective design.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.