MRI imaging characteristics of brainstem and midbrain aqueduct in patients with iNPH

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We analyzed the head MRI data of 50 iNPH patients and 30 healthy middle-aged and elderly individuals. The study included an analysis of the length, diameter, and angle of the cerebral aqueduct, as well as the longitudinal cross-sectional areas of the midbrain and brainstem. Additionally, we evaluated the midbrain proportion, brainstem volume ratio, the angle between the brainstem and spinal cord, and the area and morphology of the pontine cistern. The findings revealed that, compared to healthy individuals, iNPH patients exhibited significant dilation of the midbrain aqueduct diameter, a reduced aqueduct angle, and a decreased longitudinal cross-sectional area of the brainstem, with the most pronounced reduction in the midbrain area. Notably, the cerebral pools surrounding the brainstem in iNPH patients were dilated, with the pontine cistern presenting a "hammer" shape, and the prevalence of this "hammer" shape was significantly positively correlated with the area of the pontine cistern. These unique imaging characteristics not only enhance the clinical recognition of iNPH, but also provide new imaging evidence for the early diagnosis and treatment of iNPH. Health sciences/Diseases/Neurological disorders/Hydrocephalus Biological sciences/Biological techniques/Imaging/Magnetic resonance imaging Idiopathic normal pressure hydrocephalus Characteristic imaging indicators Mesencephalic aqueduct Brainstem volume ratio Prepontine cistern “Hammer” shape Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Normal pressure hydrocephalus (NPH) is a syndrome of communicating hydrocephalus in which the ventricles are enlarged, but the cerebrospinal fluid pressure is within the normal range (70–200 mmH2O). NPH was first proposed by Hakim in 1964 [1] . According to its etiology, NPH can be classified as secondary (sNPH) or idiopathic (iNPH). sNPH often occurs after cranial trauma, cerebral hemorrhage, subarachnoid hemorrhage, or intracranial infection, and can occur at any age. The etiology of sNPH is clear, and symptoms appear after a certain period following the original disease, making it relatively easy to diagnose clinically. However, iNPH is more common in the elderly and is the most common form of hydrocephalus in this age group [2] . Patients with iNPH often have no clear etiology, and the early clinical manifestations are atypical, lacking characteristic imaging findings, making early diagnosis more challenging and prone to confusion with similar diseases, such as Parkinson’s disease and Alzheimer’s disease. However, the clinical manifestations of iNPH can be improved through surgery, and it is currently the only form of dementia that can be treated [3] . Surgery should be performed immediately after a clinical diagnosis is made, highlighting the importance of early diagnosis and identification of iNPH. The clinical features of iNPH include the following: A triad of gait disturbance, cognitive impairment, and urinary incontinence is the main clinical symptoms, with unsteady gait often being the primary symptom; enlargement of the ventricular system, with intracranial pressure values typically remaining normal; imaging studies showing non-obstructive ventricular enlargement, with the anterior horns of the lateral ventricles becoming “blunted,” and an Evan’s index > 0.3; normal cerebrospinal fluid (CSF) examination; and improvement in symptoms after a CSF release test (CST-TT) or continuous CSF drainage. At present, there is no reliable noninvasive method for the diagnosis of iNPH, with diagnosis mainly relying on the clinical symptoms, imaging examinations, CST-TT, or continuous CSF drainage. Some scholars believe that clinical improvement after shunt surgery is the “gold standard” for diagnosis [4] . Before patients undergo shunt surgery, a CST-TT or continuous CSF drainage is usually required, both of which are invasive, increasing the pain and infection risk to patients. Under the current diagnosis-related groups and other conditions, these invasive procedures are not conducive to the rapid diagnosis of iNPH. At the same time, with the discovery of modern imaging technology, imaging examinations have become increasingly important in the diagnosis of iNPH, the post-shunt response, and the prognosis, representing an important component of diagnosis and treatment [5,6] . In terms of imaging, many assessments of ventricular enlargement are used at home and abroad; these include the Evan’s index (EI), corpus callosum angle (CA), corpus callosum height (CH), temporal angle diameter (THW), central part of the lateral ventricle (CMW), and supraventricular tissue width (SVW). Among them, the EI, CMW, disproportionate ventricular enlargement (CCD), and THW have strong diagnostic ability [7-10] . Some studies have found that by measuring the intracranial volume [11,12] , it is also possible to predict changes in patients’ cognitive function after surgery. However, these studies have mainly focused on the brain and lateral ventricles. The brainstem is the connecting part between the brain and spinal cord, serving as a vital structure in the nervous system, which performs many important physiological functions, including life-sustaining function, motor and sensory conduction, sleep and wakefulness cycle, reflex activity, cranial nerve nucleus control, emotion and behavior regulation, muscle tension and posture control, coordinated eye movement, and language and cognitive function. Changes in the brainstem and midbrain structure of patients with iNPH will inevitably cause corresponding functional disorders. In addition to characteristic clinical manifestations, patients with iNPH may experience atypical clinical manifestations, such as dizziness, headache, vertigo, hearing loss, sleep disorders, hyposmia, and personality changes. However, whether these clinical manifestations are related to the changes in the brainstem structure of patients and how these structural changes are related to the clinical manifestations of patients require further study. At present, research on the aqueduct in patients with iNPH mainly focuses on the flow and flow rate of the aqueduct [4,13-19] . For example, Kameda et al. [20] found that CSF flow vacancies exist in iNPH, while Wei et al. [21] found that aqueduct flow vacancies are not a useful indicator for the diagnosis of INPH. Bradley et al. [22] reported that increased CSF flow in the aqueduct is associated with a good shunt response, which is helpful for the diagnosis and selection of patients undergoing shunt surgery and follow-up of such patients. However, Ringstad et al. [13] found that the aqueduct stroke volume does not reflect the intracranial pressure pulsatility or symptom score but rather the aqueduct area and ventricular volume, thus not supporting the use of aqueduct stroke volume for shunt surgery. These studies are theoretically contradictory and cannot provide guidance for clinical treatment. Nevertheless, most of these studies were experimental analyses with no morphological evaluation, and have no substantial significance for the clinical diagnosis of iNPH. To further improve the diagnostic value of imaging in patients with iNPH, reduce the need for invasive procedures before surgery through preoperative imaging evaluation, and improve clinical decision-making for rapid diagnosis, we took the brainstem and aqueduct as the entry points to study the MRI characteristics of the brainstem and cerebral aqueduct of patients with iNPH, identify characteristic imaging signs, and determine whether they could be used for diagnostic evaluation of patients. Research objects and methods General information A cross-sectional analysis was conducted from September 2021 to April 2024, including 50 patients with iNPH admitted to West China Hospital of Sichuan University, Mianyang Central Hospital, and the Third Affiliated Hospital of North Sichuan Medical College (36 males, 14 females, aged 47–89 years, with a mean age of 74.07 ± 8.44 years) and 30 healthy middle-aged and elderly individuals (12 males, 18 females, aged 46–88 years, with a mean age of 72.73 ± 7.51 years). The subjects underwent thin-section (≤1.5 mm) MRI using 1.5T or 3.0T scanners (patients with iNPH were imaged prior to CST-TT or surgical intervention). The images were reconstructed and analyzed at a postprocessing center, before using 3D-Slicer software for image reconstruction and data measurement. All statistical analyses were performed using IBM SPSS Statistics 27. The study protocol was approved by the Institutional Review Board of West China Hospital, Sichuan University (approval number: 2023 (442)), and all procedures were performed in accordance with the Declaration of Helsinki (2013 version) and the Ethical Review Measures for Life Sciences and Medical Research Involving Human Beings that issued by the China Science and Technology Ethics Committee. All the participants provided written informed consent. Inclusion and exclusion criteria for patients with iNPH I. The inclusion criteria were as follows: Age ≥ 50 years; in accordance with the 2022 Chinese Clinical Management Guidelines for Idiopathic Normal Pressure Hydrocephalus (iNPH): Clinical manifestations, at least one of gait disturbance, cognitive impairment, or urinary incontinence was present; cranial CT or MRI indicating ventricular enlargement (EI ≥ 0.3 or zEI ≥ 0.42); lumbar puncture upon admission at an intracranial pressure ≤ 200 mmHg; CSF examination showing no significant abnormalities; positive response to the lumbar puncture tap test or clinical symptom improvement following surgical intervention; height between 150 and 175 cm and weight between 50 and 70 kg; and MRI conducted prior to the CSF tap test or surgical intervention. II. The exclusion criteria were as follows: Patients who do not meet the abovementioned inclusion criteria; with secondary hydrocephalus; a definitive diagnosis of Parkinson’s disease, Alzheimer’s disease, or progressive supranuclear palsy; presenting with acute conditions; and individuals whose height and weight were not within the specified range. Inclusion criteria for healthy individuals I. The inclusion criteria were as follows: Age ≥ 50 years; absence of clinical symptoms; no underlying medical conditions; and height between 150 and 175 cm and body weight approximately 50–70 kg. II. The exclusion criteria were as follows: Patients who do not meet the abovementioned inclusion criteria; and who are unwilling to undergo the trial. Imaging scanning Using an MRI system of 1.5T or higher equipped with a head coil, routine head MRI scans were performed for both patients with iNPH and healthy individuals. A total of four sequences were conducted, including Sagittal T1W FLAIR, Axial T1W FLAIR, Axial T2W, and Axial T2 FLAIR scans. For localization, images that clearly display the mesencephalic aqueduct from the sagittal view were selected. Subsequently, three-dimensional thin-section (≤1.5 mm) scans of the brainstem, mesencephalic aqueduct, and surrounding areas were conducted in the coronal, sagittal, and axial planes, followed by reconstruction of the scanned images. Data measurement and processing All data were acquired in DICOM format and modeled using 3D Slicer software for the aqueduct, brainstem (midbrain, pons, medulla oblongata), and perimesencephalic cisterns. The morphology, size, length, and angles of the aqueduct, as well as the morphology, longitudinal cross-sectional area, midbrain ratio, brainstem-cistern volume ratio, and angle between the brainstem and spinal cord, were analyzed and measured. Differences between patients with iNPH and healthy individuals were compared. Mesencephalic aqueduct measurement The mesencephalic aqueduct originates at the posterior lateral aspect of the third ventricle and extends inferiorly to the opening of the fourth ventricle, with the dorsal side being the posterior commissure and the ventral side consisting of the posterior part of the third ventricle and the midbrain (Fig. 1a). The mesencephalic aqueduct has an overall arcuate shape and is divided into anterior-superior and posterior-inferior segments(Fig. 1b). The anterior-superior segment is the horizontal part, and the posterior-inferior segment is the vertical part, forming an angle at their intersection, which is located between the superior and inferior colliculi(Fig. 1c). The diameter of the aqueduct is narrower in the anterior-superior segment and wider in the posterior-inferior segment(Fig. 1d). Brainstem measurements The brainstem is located beneath the cerebrum between the spinal cord and diencephalon and has an irregular cylindrical shape. The rostral end connects to the diencephalon through the midbrain, and the caudal end of the medulla oblongata continues with the spinal cord at the foramen magnum. The brainstem is divided from top to bottom into three parts: the midbrain, pons, and medulla oblongata. A line (Line A) was drawn through the superior aperture of the pons to the inferior edge of the quadrigeminal plate, before drawing a second line (Line B) parallel to the first line, passing through the inferior aperture of the pons. Then, a line was drawn along the foramen magnum and defined as Line C (Line C) (Fig. 2a). The midbrain area was calculated as (Fig. 2b) = the area of the midbrain above Line A, excluding the quadrigeminal plate. The pontine area was calculated as (Fig. 2c) = the area between the anterior and posterior edges of the pons and between Lines A and B. The brainstem area was calculated as (Fig. 2d) = the sum of the midbrain, pons, and medulla oblongata (up to the foramen magnum line). The longitudinal cross-sectional areas were measured through the mesencephalic aqueduct for the midbrain, midbrain plus pons, and midbrain plus pons plus medulla oblongata (up to the foramen magnum line). Midbrain proportion The longitudinal cross-sectional area of the midbrain was measured in the plane of the mesencephalic aqueduct. The sum of the longitudinal cross-sectional areas of the midbrain and pons was measured through the plane of the mesencephalic aqueduct. The proportion of the midbrain’s area to the combined midbrain and pons area was determined by calculating the following ratio: Measurement of brainstem and spinal cord angle When measuring the angle between the brainstem and spinal cord, the middle tangents of the brainstem and spinal cord were used for the measurement, passing through the plane of the cerebral aqueduct(Fig. 3), with the foramen magnum as the baseline, where the AB line is the line of the foramen magnum; the CD line is the midline of the brainstem; the EF line is the midline of the spinal cord; and ∠A is the angle formed by the intersection of the CE and EF. Brainstem peri-cistern measurement The brainstem peri-cistern refers to the enlarged CSF space formed around the brainstem, mainly including the interpeduncular cistern, prepontine cistern, pontocerebellar cistern, pre-medullary cistern, cerebellomedullary cistern, occipital cistern, and quadrigeminal cistern(Fig.4a). The measurement of the brain cistern in the longitudinal section mainly includes the interpeduncular cistern, pontine cistern, and medullary cistern (collectively called the prepontine cistern) (Fig. 4b), and the midbrain aqueduct, fourth ventricle, and cerebellomedullary cistern, where the lower edge is bounded by the foramen magnum). Volume ratio of brainstem and peribrainstem cisterns The brainstem-to-cistern volume ratio (BVR) was defined as the ratio of the longitudinal section area of the brainstem to the longitudinal section area of the peribrainstem cisterns, calculated using the following equation: Statistical methods Data were analyzed using SPSS software version 27. Continuous variables are reported as the mean ± standard deviation and were evaluated using the t-test. Distinct variables are presented as [number (%)] and were subjected to chi-squared tests. Statistical significance was set at P ≤ 0.05. The sensitivity and specificity of the imaging parameters were determined using receiver operating characteristic (ROC) curve analysis. Measurement results General data results In this study, the iNPH group comprised 36 males and 14 females, with a mean age of 74.07 ± 8.44 years, while the control group of middle-aged and elderly individuals comprised 12 males and 18 females, with a mean age of 72.73 ± 7.51 years, with no significant differences between the two groups with respect to age, sex, height, and body weight (P > 0.05) (Table 1). Measurement of mesencephalic aqueduct The results revealed significant differences in the lengths of the mesencephalic aqueduct between the two groups. Subsequent pairwise comparisons between individuals with iNPH and controls showed no significant difference in the length of the mesencephalic aqueduct between the two groups (P > 0.05) (Table 2). However, the diameter of the mesencephalic aqueduct in patients with iNPH was significantly larger than that in healthy individuals (P < 0.05) (Table 3). Furthermore, the angle of the mesencephalic aqueduct was decreased in patients with iNPH, and the curvature was more pronounced than that in healthy individuals (P < 0.05) (Table 4). Brainstem measurements In patients with iNPH, the brainstem area was reduced compared to that in healthy individuals (P < 0.05), with a particularly significant reduction in the midbrain area (P < 0.001) (Table 5) and the proportion of the midbrain (P 0.05) (Table 7). Measurement of brainstem peri-cisterns In patients with iNPH, the brainstem peri-cistern areas were dilated compared to those in healthy individuals, with the pontine cistern showing a particularly significant enlargement (P < 0.05) (Fig. 5). Additionally, the brainstem volume ratio was significantly reduced in patients with iNPH (P < 0.05) (Table 8). Measurement of anterior pontine cistern In individuals with iNPH, the pontine cistern was dilated and exhibited a shape that resembled a “hammer” (Fig. 6a, Fig. 6b, Fig. 6c). The prevalence of the “hammer sign” in patients with iNPH was 94.0%, compared to only 20.0% in healthy individuals (Table 9). We performed ROC curve analysis to evaluate the diagnostic efficacy of the dilation of the pontine cistern and the "hammer" sign, using sensitivity, specificity, and the area under the curve (AUC) (Fig.7a). Notably, the area of the anterior cingulate cortex with the "hammer" sign was significantly larger than that without the "hammer" sign in patients with iNPH (Fig. 7b). The AUCs for iNPH patients and healthy individuals were 0.926 and 0.605, respectively, both of which are greater than 0.5. However, in terms of asymptomatic significance, only the correlation between the area of the prepontine cistern in patients with iNPH and the number of patients with the "hammer" sign was statistically significant (P<0.05) (Table 10), with a sensitivity of 94.0% and specificity of 80.0%. Discussion iNPH is a unique form of communicating hydrocephalus with intracranial pressure within the normal range (70–200 mmHg). This condition predominantly affects the elderly and is the most common type of hydrocephalus in the elderly population. Patients often have no identifiable cause and lack characteristic imaging features. The clinical presentation of iNPH is characterized by a triad of gait disturbance, cognitive impairment, and urinary bladder dysfunction; however, only 50% of cases present with all three symptoms clinically [ 12 ] , with gait disturbance, including slow movement, shuffling gait, and magnetic gait, being the earliest clinical manifestation in patients with iNPH [ 23 ] . In both previous studies and guidelines, iNPH is indicated by non-obstructive ventricular dilation, making ventricular enlargement a necessary condition for the diagnosis of iNPH. This ventricular dilation not only includes the lateral, third, and fourth ventricles but also the perimedullary cisterns, consistent with our conclusions. Regarding ventricular dilation in iNPH, research suggests that multiple pathophysiological models are currently available to explain its inevitability [ 2 ] . The dilation of the ventricles leads to changes in several intracranial anatomical and angular parameters, and these changes may be regular. In guidelines and expert consensuses both domestically and internationally, an EI > 0.3 is the only mandatory morphological criterion that must be met. However, ventricular enlargement in patients with iNPH does not occur in a single direction, but along the X, Y, and Z axes. Therefore, some researchers have used the term zEI [ 24 ] to denote the dilation of the ventricles along the longitudinal axis. However, irrespective of whether it is EI or zEI, while they can indicate ventricular enlargement, they cannot be used alone to differentiate between different types of hydrocephalus. We performed measurements on the midbrain aqueduct, brainstem, and peribrainstem cisterns of patients with iNPH and healthy middle-aged and elderly individuals. Through routine examinations and measurements, we identified the differences between these regions to facilitate the diagnosis of patients with iNPH as quickly as possible without the need for additional examinations and costs. Analysis of the measurement data revealed no significant difference in the length of the aqueduct between patients with iNPH and healthy individuals; however, the diameter of the midbrain aqueduct was significantly dilated, with an average diameter of 2.24 ± 0.39 mm. However, dilation of the midbrain aqueduct can be seen in patients with communicating hydrocephalus, obstructive hydrocephalus, and those with obstruction below the midbrain aqueduct. The occurrence of this dilation requires further imaging data analysis for patients with communicating and obstructive hydrocephalus. The measurements obtained in our study demonstrate that the angle of the midbrain aqueduct is reduced in patients with iNPH compared to that in healthy individuals, which means that the curvature of the midbrain aqueduct is increased in patients with iNPH, and this morphological change is directly related to the patient’s ventricular dilation and DESH sign [ 25 ] . CSF accumulates in the lateral fissure pool, lower part of the cerebral convexity (below the lateral fissure pool), and ventral sulci and cerebral cistern in patients with iNPH, leading to morphological changes in the pressure on the bottom of the brain and the upper part of the brainstem. This change ultimately decreases the midbrain aqueduct angle and causes an increase in curvature. In the measurement of the brainstem in patients with iNPH, the angle between the brainstem and spinal cord in patients with iNPH does not significantly differ from that in healthy individuals. However, the area of the brainstem is reduced in patients with iNPH compared to healthy individuals, with a particularly noticeable reduction in the cross-sectional area of the midbrain, which can be as high as 32.4%. The midbrain serves as a bridge between the cerebrum and spinal cord, playing a crucial role in coordinating body movements, processing sensory information, and regulating emotions. A reduction in midbrain volume is likely to lead to these functional impairments, resulting in clinical symptoms. Luca et al. [ 26 ] conducted a study on the midbrain in patients with progressive supranuclear palsy, showing a significant positive correlation between the reduction in midbrain area and the fluency of speech. In addition to being related to the dysfunction of the frontal-striatal circuit [ 27 ] , dysfluency in speech and memory impairment in patients with iNPH is also closely associated with midbrain atrophy. Furthermore, Heikkinen et al. [ 28 ] and colleagues found that brainstem atrophy is related to extrapyramidal symptoms of frontotemporal dementia. In the measurement of the perimesencephalic cisterns, the area of the cisterns surrounding the brainstem was expanded in patients with iNPH, with the expansion of the pontine cistern being particularly pronounced, reaching an expansion rate of up to 29.7%. In the majority of patients with iNPH, the expansion of the pontine cistern presents a “hammer” shape, and through ROC curve analysis, the appearance of the “hammer” shape was found to be positively correlated with the area of the pontine cistern, with a sensitivity of 94.0% and a specificity of 80.0%. This indicates that the greater the expansion of the pontine cistern, the higher the probability of the “hammer” shape appearing. Comparing the “hammer” shapes, the proportion of patients with iNPH presenting the “hammer” shape was 94.0%, whereas in healthy individuals, it was 20.0%. However, even among patients with the “hammer” shape, there were differences in the “hammer” shape of the pontine cistern, mainly in the distance between the posterior superior edge of the sella and the optic nerve; in patients with iNPH, the distance is generally greater than 3 mm, whereas in healthy individuals, it is less than 3 mm. Conclusion This study involved the measurement and analysis of the cerebral aqueduct, brainstem, and other structures in patients with iNPH and normal middle-aged and elderly individuals. Through a comparative analysis of the data from different groups, the following conclusions were drawn: The length of the cerebral aqueduct in patients with iNPH showed no significant difference compared to that of healthy individuals, but the diameter of the aqueduct was significantly dilated. Patients with iNPH also exhibited morphological changes characterized by a reduction in the angle of the cerebral aqueduct and an increase in the curvature of its arc. The cross-sectional area of the brainstem was also found to be reduced in patients with iNPH compared to healthy individuals, with a particularly noticeable reduction in the cross-sectional area of the midbrain. Additionally, there was no significant difference in the angle between the brainstem and spinal cord between patients with iNPH and healthy individuals. The surrounding cerebral cisterns were also found to be dilated in patients with iNPH, with the prepontine cistern exhibiting the most pronounced dilation. Most dilations in the prepontine cistern in patients with iNPH present a “hammer” shape, which is positively correlated with the cistern area and has clinical significance. As we only compared patients with iNPH to normal middle-aged and elderly individuals, further research is needed to determine whether these morphological changes are present in patients with communicating hydrocephalus, obstructive hydrocephalus, Parkinson’s disease, and dementia. Declarations Competing interests The authors declare no competing interests. Information on reprinting and sharing permissions is available at www.nature.com/reprints . Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Funding This work was supported by the National Natural Science Foundation of China under Grant 82201502, and it also supported by Sichuan Province Medical Research Project S22078 from Sichuan Medical Association. Author Contribution Liangxue Zhou designed the experiment. Kui Xiao and Xielin Tang conducted the experiment. Shenghua Liu, Ziang Deng, and Feilong Yang performed the statistical analysis, and Ziang Deng was responsible for medical ethics applications. Acknowledgement The authors thank Shan Wang for her assistance in data collection. The authors also thank LetPub (www.letpub.com.cn/) for its linguistic assistance during the preparation of this manuscript. Data Availability The data supporting the findings of this study are available from the corresponding author upon reasonable request. References Adams, R. D., Fisher, C. 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Cognitive impairment in idiopathic normal pressure hydrocephalus. Neurosci. Bull. 38, 1085–1096 (2022). Heikkinen, S. et al. Brainstem atrophy is linked to extrapyramidal symptoms in frontotemporal dementia. J. Neurol. 269, 4488–4497 (2022). Tables Table 1. Demographic data of iNPH and healthy groups. Group iNPH Healthy t-value P-value Age (years) 74.07 ± 8.44 72.73 ± 7.51 0.624 0.538 Sex (male:female) 35:15 20:10 −1.533 0.136 Height (cm) 158.83 ± 6.747 157.07 ± 6.11 0.977 0.337 Weight (Kg) 59.55 ± 6.93 57.82 ± 6.18 1.093 0.283 Table 2. Mesencephalic aqueduct length in each group. Group Length of mesencephalic aqueduct (mm) t-value P-value Paired t-value Paired P-value Patients with iNPH 19.72 ± 2.50 55.695 <0.001 −0.541 0.593 Healthy subjects 19.64 ± 1.88 57.226 <0.001 Table 3. Diameter of mesencephalic aqueduct in each group. Group Opening of the mesencephalic aqueduct (mm) t-value P-value Paired t-value Paired P-value Patients with iNPH 2.24 ± 0.39 40.45 <0.001 2.303 0.029 Healthy subjects 1.98 ± 0.42 25.99 <0.001 Group Stenosis of the mesencephalic aqueduct (mm) t-value P-value Paired t-value Paired P-value Patients with iNPH 1.58 ± 0.33 33.727 <0.001 4.095 <0.001 Healthy subjects 1.27 ± 0.23 30.508 <0.001 Group Outlet of mesencephalic aqueduct (mm) t-value P-value Paired t-value Paired P-value patients with iNPH 3.07 ± 0.78 27.771 <0.001 3.152 0.004 healthy subjects 2.49 ± 0.50 27.099 <0.001 Table 4. Mesencephalic aqueduct angle in each group. Group Angle of mesencephalic aqueduct (°) t-value P-value Paired t-value Paired P-value Patients with iNPH 125.92 ± 8.68 102.617 <0.001 −4.774 <0.001 Healthy subjects 135.15 ± 7.70 96.138 <0.001 Table 5. Longitudinal section area of the brainstem in each group (through the aqueductal plane). Group Midbrain + pons + medulla oblongata area (cm 2 ) t-value P-value Paired t-value Paired P-value Patients with iNPH 9.10 ± 0.87 74.076 <0.001 −3.138 0.004 Healthy subjects 9.80 ± 0.76 70.843 <0.001 Group Midbrain + pons area (cm 2 ) t-value P-value Paired t-value Paired P-value Patients with iNPH 5.88 ± 0.61 68.506 <0.001 −4.051 <0.001 Healthy subjects 6.60 ± 0.59 60.855 <0.001 Group Midbrain area (cm 2 ) t-value P-value Paired t-value Paired P-value Patients with iNPH 0.92 ± 0.19 34.263 <0.001 −6.915 <0.001 Healthy subjects 1.36 ± 0.28 25.993 <0.001 Group Pons area (cm 2 ) t-value P-value Paired t-value Paired P-value Patients with iNPH 4.95 ± 0.51 68.916 <0.001 −1.772 0.087 Healthy subjects 5.18 ± 0.43 64.908 <0.001 Table 6. Percentage of midbrain and pons in each group (through the aqueductal plane). Group Midbrain ratio t-value P-value Paired t-value Paired P-value Patients with iNPH 0.156 ± 0.026 42.995 <0.001 −3.837 <0.001 Healthy subjects 0.200 ± 0.051 21.588 <0.001 Group Pons ratio t-value P-value Paired t-value Paired P-value Patients with iNPH 0.844 ± 0.026 231.364 <0.001 2.607 0.014 Healthy subjects 0.765 ± 0.149 28.131 <0.001 Table 7. Brainstem angles (through the aqueductal plane) of each group. Group Brainstem angle t-value P-value Paired t-value Paired P-value Patients with iNPH 163.56 ± 5.99 193.037 <0.001 1.030 0.312 Healthy subjects 161.97 ± 6.66 133.288 <0.001 Table 8. Area of brainstem peri-cerebral and anterior pontine cisterns (cm 2 ) and brainstem volume ratio of each group. Group Anterior pontine cistern area t-value P-value Paired t-value Paired P-value Patients with iNPH 5.86 ± 1.24 33.311 <0.001 4.031 <0.001 Healthy subjects 4.54 ± 1.03 23.797 <0.001 Group Brainstem volume ratio t-value P-value Paired t-value Paired P-value Patients with iNPH 0.489 ± 0.049 70.687 <0.001 −5.494 <0.001 Healthy subjects 0.564 ± 0.062 50.047 <0.001 Table 9. Proportion of patients with a “hammer” sign in each group. Group Number of “hammer signs” “Hammer sign” proportion (%) Patients with iNPH 47\50 0.940 Healthy subjects 6\30 0.200 Table 10. Comparison of area under the receiver operating characteristic curve (AUC value) between the number of hammer sign individuals and area of the anterior pontine cistern. Inspection indicators AUC Standard error a Asymptotic significance b Asymptotic 95% confidence Interval Lower limit Upper limit Anterior pontine cistern area in the iNPH group 0.926 0.070 0.000 0.790 1.062 Anterior pontine cistern area in Healthy subjects 0.605 0.114 0.357 0.382 0.828 Note: AUC is the area under the receiver operating characteristic curve. a Based on nonparametric assumptions. b Null hypothesis: True area = 0.5. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 02 Jan, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 08 Oct, 2024 Reviews received at journal 04 Oct, 2024 Reviews received at journal 26 Sep, 2024 Reviewers agreed at journal 26 Sep, 2024 Reviews received at journal 16 Sep, 2024 Reviewers agreed at journal 06 Sep, 2024 Reviewers agreed at journal 27 Aug, 2024 Reviewers invited by journal 26 Aug, 2024 Editor assigned by journal 26 Aug, 2024 Editor invited by journal 20 Aug, 2024 Submission checks completed at journal 19 Aug, 2024 First submitted to journal 06 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4868789","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":352771693,"identity":"cd91af22-8373-428e-b419-1b82bd7739e7","order_by":0,"name":"Kui Xiao","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Kui","middleName":"","lastName":"Xiao","suffix":""},{"id":352771696,"identity":"d4e7e2e0-eb64-4651-bc91-c6b5c99c8713","order_by":1,"name":"Liangxue Zhou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAq0lEQVRIiWNgGAWjYDACCeYGhgcFFnJs7O0HiNXC2MCQYCBhzMdzJoE0LYnzJBwMiNMhP7uxTQKoJb1NgiGB4UfFNsJaGOccbDYAasltk248wNhz5jZhLcwSiY0PwFpkDiQwM7YRoYVNIrHhAMhhbEDnEaeFB2pLAvFaJCQSwX4xbAMG8kGi/CI/I/mYxIcKG3n59vaDD35UEKEFBRwgUf0oGAWjYBSMAlwAADMqNr4825ylAAAAAElFTkSuQmCC","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":true,"prefix":"","firstName":"Liangxue","middleName":"","lastName":"Zhou","suffix":""},{"id":352771697,"identity":"6e77aa36-7cb9-49a0-b546-feb8e650d5ef","order_by":2,"name":"Xielin Tang","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Xielin","middleName":"","lastName":"Tang","suffix":""},{"id":352771699,"identity":"ef1d52e5-a9f0-4d79-a7fa-d922006a23b8","order_by":3,"name":"Shenghua Liu","email":"","orcid":"","institution":"Santai People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shenghua","middleName":"","lastName":"Liu","suffix":""},{"id":352771700,"identity":"1c155dbb-a8d3-4705-8eb0-182efb66ad38","order_by":4,"name":"Ziang Deng","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Ziang","middleName":"","lastName":"Deng","suffix":""},{"id":352771701,"identity":"59bad0a4-44a8-40aa-9eec-7996fe68b927","order_by":5,"name":"Feilong Yang","email":"","orcid":"","institution":"Santai People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Feilong","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2024-08-06 13:21:48","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4868789/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4868789/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-83874-7","type":"published","date":"2025-01-02T15:57:01+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":66561998,"identity":"4a3c4896-d547-455a-a784-164ecc371402","added_by":"auto","created_at":"2024-10-14 10:21:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":304947,"visible":true,"origin":"","legend":"\u003cp\u003e(\u003cstrong\u003ea\u003c/strong\u003e) Boundary of the mesencephalic aqueduct. (\u003cstrong\u003eb\u003c/strong\u003e) Length of the midline axis of the mesencephalic aqueduct. (\u003cstrong\u003ec\u003c/strong\u003e) Angle between the anterior-superior and posterior-inferior segments of the mesencephalic aqueduct. (\u003cstrong\u003ed\u003c/strong\u003e) Diameters at the opening, constriction, and exit of the mesencephalic aqueduct.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4868789/v1/e57f298ccaa52218407fbbf9.png"},{"id":66563747,"identity":"5e6c4bc7-59e3-41d4-9f31-bb234cc07e29","added_by":"auto","created_at":"2024-10-14 10:29:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":649558,"visible":true,"origin":"","legend":"\u003cp\u003e(\u003cstrong\u003ea\u003c/strong\u003e) Line A, which passes through the superior cerebellar peduncle (brainstem’s upper notch) and the lower edge of the quadrigeminal plate; Line B, parallel to Line A and passing through the inferior cerebellar peduncle (brainstem’s lower notch); and Line C, the line drawn along the foramen magnum. (\u003cstrong\u003eb\u003c/strong\u003e) Midbrain area. (\u003cstrong\u003ec\u003c/strong\u003e) Pontine area. (\u003cstrong\u003ed\u003c/strong\u003e) Brainstem area.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4868789/v1/e12e801ac52b6485766faf89.png"},{"id":66561997,"identity":"acaf2d67-b731-4d8e-9e84-d5796d23a575","added_by":"auto","created_at":"2024-10-14 10:21:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":210566,"visible":true,"origin":"","legend":"\u003cp\u003eDiagram of pons-medulla angle. AB line: Line of foramen magnum; CD line: Midsagittal axis of brainstem; EF line: Midsagittal axis of spinal cord; and Angle A: Angle at CE–EF intersection.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4868789/v1/b8e80f7e89934b45e0500a2f.png"},{"id":66562001,"identity":"0d4a2afe-a4ad-4d0a-b58a-033a16d03482","added_by":"auto","created_at":"2024-10-14 10:21:10","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":416400,"visible":true,"origin":"","legend":"\u003cp\u003e(\u003cstrong\u003ea\u003c/strong\u003e) Cisterns around brainstem: Interpeduncular cistern, pontine cistern, medullary cistern, cerebellomedullary cistern, cerebral aqueduct, and fourth ventricle. (\u003cstrong\u003eb\u003c/strong\u003e) Prepontine cistern.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4868789/v1/8dbd9bbeebd35a465f084b0e.png"},{"id":66564568,"identity":"3de9fef7-b07c-4014-bb31-d688f0e2e68b","added_by":"auto","created_at":"2024-10-14 10:37:10","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":65521,"visible":true,"origin":"","legend":"\u003cp\u003eArea of the anterior pontine cistern in patients with iNPH and in healthy subjects.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-4868789/v1/f0dfece794f8a0741d6de71f.png"},{"id":66562003,"identity":"97a62c60-b6df-4388-bd92-186c41a11383","added_by":"auto","created_at":"2024-10-14 10:21:10","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":470526,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(a\u003c/strong\u003e) The 'hammer' shape of the anterior pontine cistern in patients with iNPH as seen on T1Flair images. (\u003cstrong\u003eb\u003c/strong\u003e) and (\u003cstrong\u003ec\u003c/strong\u003e) The 'hammer' shape of the anterior pontine cistern in patients with iNPH as seen on T2WI images.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-4868789/v1/9400e9e53fd848af15c9435a.png"},{"id":66563749,"identity":"a8a81e61-3976-4a53-976a-3e4794706192","added_by":"auto","created_at":"2024-10-14 10:29:10","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":123047,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(a\u003c/strong\u003e) Hammer sign and receiver operating characteristic curve of anterior pontine pool area in patients with iNPH. \u003cstrong\u003e(b\u003c/strong\u003e) Box-shaped relationship between hammer sign and anterior pontine pool area in patients with iNPH.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-4868789/v1/966ec4b5c42a145de07517e7.png"},{"id":73093147,"identity":"be06e5ee-edde-4090-9768-5429a6afbeef","added_by":"auto","created_at":"2025-01-06 16:07:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3644545,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4868789/v1/909ddd22-1669-498d-b6a2-bed78dc849ce.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"MRI imaging characteristics of brainstem and midbrain aqueduct in patients with iNPH","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNormal pressure hydrocephalus (NPH) is a syndrome of communicating hydrocephalus in which the ventricles are enlarged, but the cerebrospinal fluid pressure is within the normal range (70\u0026ndash;200 mmH2O). NPH was first proposed by Hakim in 1964\u003csup\u003e[1]\u003c/sup\u003e. According to its etiology, NPH can be classified as secondary (sNPH) or idiopathic (iNPH). sNPH often occurs after cranial trauma, cerebral hemorrhage, subarachnoid hemorrhage, or intracranial infection, and can occur at any age. The etiology of sNPH is clear, and symptoms appear after a certain period following the original disease, making it relatively easy to diagnose clinically. However, iNPH is more common in the elderly and is the most common form of hydrocephalus in this age group\u003csup\u003e[2]\u003c/sup\u003e. Patients with iNPH often have no clear etiology, and the early clinical manifestations are atypical, lacking characteristic imaging findings, making early diagnosis more challenging and prone to confusion with similar diseases, such as Parkinson\u0026rsquo;s disease and Alzheimer\u0026rsquo;s disease. However, the clinical manifestations of iNPH can be improved through surgery, and it is currently the only form of dementia that can be treated\u003csup\u003e[3]\u003c/sup\u003e. Surgery should be performed immediately after a clinical diagnosis is made, highlighting the importance of early diagnosis and identification of iNPH.\u003c/p\u003e\n\u003cp\u003eThe clinical features of iNPH include the following: A triad of gait disturbance, cognitive impairment, and urinary incontinence is the main clinical symptoms, with unsteady gait often being the primary symptom; enlargement of the ventricular system, with intracranial pressure values typically remaining normal; imaging studies showing non-obstructive ventricular enlargement, with the anterior horns of the lateral ventricles becoming \u0026ldquo;blunted,\u0026rdquo; and an Evan\u0026rsquo;s index \u0026gt; 0.3; normal cerebrospinal fluid (CSF) examination; and improvement in symptoms after a CSF release test (CST-TT) or continuous CSF drainage.\u003c/p\u003e\n\u003cp\u003eAt present, there is no reliable noninvasive method for the diagnosis of iNPH, with diagnosis mainly relying on the clinical symptoms, imaging examinations, CST-TT, or continuous CSF drainage. Some scholars believe that clinical improvement after shunt surgery is the \u0026ldquo;gold standard\u0026rdquo; for diagnosis\u003csup\u003e[4]\u003c/sup\u003e. Before patients undergo shunt surgery, a CST-TT or continuous CSF drainage is usually required, both of which are invasive, increasing the pain and infection risk to patients. Under the current diagnosis-related groups and other conditions, these invasive procedures are not conducive to the rapid diagnosis of iNPH. At the same time, with the discovery of modern imaging technology, imaging examinations have become increasingly important in the diagnosis of iNPH, the post-shunt response, and the prognosis, representing an important component of diagnosis and treatment\u003csup\u003e[5,6]\u003c/sup\u003e. In terms of imaging, many assessments of ventricular enlargement are used at home and abroad; these include the Evan\u0026rsquo;s index (EI), corpus callosum angle (CA), corpus callosum height (CH), temporal angle diameter (THW), central part of the lateral ventricle (CMW), and supraventricular tissue width (SVW). Among them, the EI, CMW, disproportionate ventricular enlargement (CCD), and THW have strong diagnostic ability\u003csup\u003e[7-10]\u003c/sup\u003e. Some studies have found that by measuring the intracranial volume\u003csup\u003e[11,12]\u003c/sup\u003e, it is also possible to predict changes in patients\u0026rsquo; cognitive function after surgery. However, these studies have mainly focused on the brain and lateral ventricles. The brainstem is the connecting part between the brain and spinal cord, serving as a vital structure in the nervous system, which performs many important physiological functions, including life-sustaining function, motor and sensory conduction, sleep and wakefulness cycle, reflex activity, cranial nerve nucleus control, emotion and behavior regulation, muscle tension and posture control, coordinated eye movement, and language and cognitive function. Changes in the brainstem and midbrain structure of patients with iNPH will inevitably cause corresponding functional disorders. In addition to characteristic clinical manifestations, patients with iNPH may experience atypical clinical manifestations, such as dizziness, headache, vertigo, hearing loss, sleep disorders, hyposmia, and personality changes. However, whether these clinical manifestations are related to the changes in the brainstem structure of patients and how these structural changes are related to the clinical manifestations of patients require further study. At present, research on the aqueduct in patients with iNPH mainly focuses on the flow and flow rate of the aqueduct\u003csup\u003e[4,13-19]\u003c/sup\u003e. For example, Kameda\u003cem\u003e\u0026nbsp;et al.\u003c/em\u003e\u003csup\u003e[20]\u003c/sup\u003e found that CSF flow vacancies exist in iNPH, while Wei\u003cem\u003e\u0026nbsp;et al.\u003c/em\u003e\u003csup\u003e[21]\u003c/sup\u003e found that aqueduct flow vacancies are not a useful indicator for the diagnosis of INPH. Bradley\u003cem\u003e\u0026nbsp;et al.\u003c/em\u003e\u003csup\u003e[22]\u003c/sup\u003e reported that increased CSF flow in the aqueduct is associated with a good shunt response, which is helpful for the diagnosis and selection of patients undergoing shunt surgery and follow-up of such patients. However, Ringstad\u003cem\u003e\u0026nbsp;et al.\u003c/em\u003e\u003csup\u003e[13]\u003c/sup\u003e found that the aqueduct stroke volume does not reflect the intracranial pressure pulsatility or symptom score but rather the aqueduct area and ventricular volume, thus not supporting the use of aqueduct stroke volume for shunt surgery. These studies are theoretically contradictory and cannot provide guidance for clinical treatment. Nevertheless, most of these studies were experimental analyses with no morphological evaluation, and have no substantial significance for the clinical diagnosis of iNPH.\u003c/p\u003e\n\u003cp\u003eTo further improve the diagnostic value of imaging in patients with iNPH, reduce the need for invasive procedures before surgery through preoperative imaging evaluation, and improve clinical decision-making for rapid diagnosis, we took the brainstem and aqueduct as the entry points to study the MRI characteristics of the brainstem and cerebral aqueduct of patients with iNPH, identify characteristic imaging signs, and determine whether they could be used for diagnostic evaluation of patients.\u003c/p\u003e"},{"header":"Research objects and methods","content":"\u003ch2\u003eGeneral information\u003c/h2\u003e\n\u003cp\u003eA cross-sectional analysis was conducted from September 2021 to April 2024, including 50 patients with iNPH admitted to West China Hospital of Sichuan University, Mianyang Central Hospital, and the Third Affiliated Hospital of North Sichuan Medical College (36 males, 14 females, aged 47\u0026ndash;89 years, with a mean age of 74.07 \u0026plusmn; 8.44 years) and 30 healthy middle-aged and elderly individuals (12 males, 18 females, aged 46\u0026ndash;88 years, with a mean age of 72.73 \u0026plusmn; 7.51 years). The subjects underwent thin-section (\u0026le;1.5 mm) MRI using 1.5T or 3.0T scanners (patients with iNPH were imaged prior to CST-TT or surgical intervention). The images were reconstructed and analyzed at a postprocessing center, before using 3D-Slicer software for image reconstruction and data measurement. All statistical analyses were performed using IBM SPSS Statistics 27. The study protocol was approved by the Institutional Review Board of West China Hospital, Sichuan University (approval number: 2023 (442)), and all procedures were performed in accordance with the Declaration of Helsinki (2013 version) and the Ethical Review Measures for Life Sciences and Medical Research Involving Human Beings that issued by the China Science and Technology Ethics Committee. All the\u0026nbsp;participants provided written informed consent.\u003c/p\u003e\n\u003ch2\u003eInclusion and exclusion criteria for patients with iNPH\u003c/h2\u003e\n\u003cp\u003eI. The inclusion criteria were as follows: Age \u0026ge; 50 years; in accordance with the 2022 Chinese Clinical Management Guidelines for Idiopathic Normal Pressure Hydrocephalus (iNPH): Clinical manifestations, at least one of gait disturbance, cognitive impairment, or urinary incontinence was present; cranial CT or MRI indicating ventricular enlargement (EI \u0026ge; 0.3 or zEI \u0026ge; 0.42); lumbar puncture upon admission at an intracranial pressure \u0026le; 200 mmHg; CSF examination showing no significant abnormalities; positive response to the lumbar puncture tap test or clinical symptom improvement following surgical intervention; height between 150 and 175 cm and weight between 50 and 70 kg; and MRI conducted prior to the CSF tap test or surgical intervention.\u003c/p\u003e\n\u003cp\u003eII. The exclusion criteria were as follows: Patients who do not meet the abovementioned inclusion criteria; with secondary hydrocephalus; a definitive diagnosis of Parkinson\u0026rsquo;s disease, Alzheimer\u0026rsquo;s disease, or progressive supranuclear palsy; presenting with acute conditions; and individuals whose height and weight were not within the specified range.\u003c/p\u003e\n\u003ch2\u003eInclusion criteria for healthy individuals\u003c/h2\u003e\n\u003cp\u003eI. The inclusion criteria were as follows: Age \u0026ge; 50 years;\u0026nbsp;absence of clinical symptoms; no underlying medical conditions; and height between 150 and 175 cm and body weight approximately 50\u0026ndash;70 kg.\u003c/p\u003e\n\u003cp\u003eII. The exclusion criteria were as follows: Patients who do not meet the abovementioned inclusion criteria; and who are unwilling to undergo the trial.\u003c/p\u003e\n\u003ch2\u003eImaging scanning\u003c/h2\u003e\n\u003cp\u003eUsing an MRI system of 1.5T or higher equipped with a head coil, routine head MRI scans were performed for both patients with iNPH and healthy individuals. A total of four sequences were conducted, including Sagittal T1W FLAIR, Axial T1W FLAIR, Axial T2W, and Axial T2 FLAIR scans. For localization, images that clearly display the mesencephalic aqueduct from the sagittal view were selected. Subsequently, three-dimensional thin-section (\u0026le;1.5 mm) scans of the brainstem, mesencephalic aqueduct, and surrounding areas were conducted in the coronal, sagittal, and axial planes, followed by reconstruction of the scanned images.\u003c/p\u003e\n\u003ch2\u003eData measurement and processing\u003c/h2\u003e\n\u003cp\u003eAll data were acquired in DICOM format and modeled using 3D Slicer software for the aqueduct, brainstem (midbrain, pons, medulla oblongata), and perimesencephalic cisterns. The morphology, size, length, and angles of the aqueduct, as well as the morphology, longitudinal cross-sectional area, midbrain ratio, brainstem-cistern volume ratio, and angle between the brainstem and spinal cord, were analyzed and measured. Differences between patients with iNPH and healthy individuals were compared.\u003c/p\u003e\n\u003ch2\u003eMesencephalic aqueduct measurement\u003c/h2\u003e\n\u003cp\u003eThe mesencephalic aqueduct originates at the posterior lateral aspect of the third ventricle and extends inferiorly to the opening of the fourth ventricle, with the dorsal side being the posterior commissure and the ventral side consisting of the posterior part of the third ventricle and the midbrain (Fig. 1a). The mesencephalic aqueduct has an overall arcuate shape and is divided into anterior-superior and posterior-inferior segments(Fig. 1b). The anterior-superior segment is the horizontal part, and the posterior-inferior segment is the vertical part, forming an angle at their intersection, which is located between the superior and inferior colliculi(Fig. 1c). The diameter of the aqueduct is narrower in the anterior-superior segment and wider in the posterior-inferior segment(Fig. 1d).\u003c/p\u003e\n\u003ch2\u003eBrainstem measurements\u003c/h2\u003e\n\u003cp\u003eThe brainstem is located beneath the cerebrum between the spinal cord and diencephalon and has an irregular cylindrical shape. The rostral end connects to the diencephalon through the midbrain, and the caudal end of the medulla oblongata continues with the spinal cord at the foramen magnum. The brainstem is divided from top to bottom into three parts: the midbrain, pons, and medulla oblongata. A line (Line A) was drawn through the superior aperture of the pons to the inferior edge of the quadrigeminal plate, before drawing a second line (Line B) parallel to the first line, passing through the inferior aperture of the pons. Then, a line was drawn along the foramen magnum and defined as Line C (Line C) (Fig. 2a). The midbrain area was calculated as (Fig. 2b) = the area of the midbrain above Line A, excluding the quadrigeminal plate. The pontine area was calculated as (Fig. 2c) = the area between the anterior and posterior edges of the pons and between Lines A and B. The brainstem area was calculated as (Fig. 2d) = the sum of the midbrain, pons, and medulla oblongata (up to the foramen magnum line). The longitudinal cross-sectional areas were measured through the mesencephalic aqueduct for the midbrain, midbrain plus pons, and midbrain plus pons plus medulla oblongata (up to the foramen magnum line).\u003c/p\u003e\n\u003ch2\u003eMidbrain proportion\u003c/h2\u003e\n\u003cp\u003eThe longitudinal cross-sectional area of the midbrain was measured in the plane of the mesencephalic aqueduct. The sum of the longitudinal cross-sectional areas of the midbrain and pons was measured through the plane of the mesencephalic aqueduct. The proportion of the midbrain\u0026rsquo;s area to the combined midbrain and pons area was determined by calculating the following ratio:\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\" width=\"819\" height=\"91\"\u003e\u003c/p\u003e\n\u003ch2\u003eMeasurement of brainstem and spinal cord angle\u003c/h2\u003e\n\u003cp\u003eWhen measuring the angle between the brainstem and spinal cord, the middle tangents of the brainstem and spinal cord were used for the measurement, passing through the plane of the cerebral aqueduct(Fig. 3), with the foramen magnum as the baseline, where the AB line is the line of the foramen magnum; the CD line is the midline of the brainstem; the EF line is the midline of the spinal cord; and \u0026ang;A is the angle formed by the intersection of the CE and EF.\u003c/p\u003e\n\u003ch2\u003eBrainstem peri-cistern measurement\u003c/h2\u003e\n\u003cp\u003eThe brainstem peri-cistern refers to the enlarged CSF space formed around the brainstem, mainly including the interpeduncular cistern, prepontine cistern, pontocerebellar cistern, pre-medullary cistern, cerebellomedullary cistern, occipital cistern, and quadrigeminal cistern(Fig.4a). The measurement of the brain cistern in the longitudinal section mainly includes the interpeduncular cistern, pontine cistern, and medullary cistern (collectively called the prepontine cistern)\u0026nbsp;(Fig. 4b),\u0026nbsp;and the midbrain aqueduct, fourth ventricle, and cerebellomedullary cistern, where the lower edge is bounded by the foramen magnum).\u003c/p\u003e\n\u003ch2\u003eVolume ratio of brainstem and peribrainstem cisterns\u003c/h2\u003e\n\u003cp\u003eThe brainstem-to-cistern volume ratio (BVR) was defined as the ratio of the longitudinal section area of the brainstem to the longitudinal section area of the peribrainstem cisterns, calculated using the following equation:\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\" width=\"791\" height=\"93\"\u003e\u003c/p\u003e\n\u003ch2\u003eStatistical methods\u003c/h2\u003e\n\u003cp\u003eData were analyzed using SPSS software version 27. Continuous variables are reported as the mean \u0026plusmn; standard deviation and were evaluated using the t-test. Distinct variables are presented as [number (%)] and were subjected to chi-squared tests. Statistical significance was set at P \u0026le; 0.05. The sensitivity and specificity of the imaging parameters were determined using receiver operating characteristic (ROC) curve analysis.\u003c/p\u003e"},{"header":"Measurement results","content":"\u003ch2\u003eGeneral data results\u003c/h2\u003e\n\u003cp\u003eIn this study, the iNPH group comprised 36 males and 14 females, with a mean age of 74.07 \u0026plusmn; 8.44 years, while the control group of middle-aged and elderly individuals comprised 12 males and 18 females, with a mean age of 72.73 \u0026plusmn; 7.51 years, with no significant differences between the two groups with respect to age, sex, height, and body weight (P \u0026gt; 0.05) (Table 1).\u003c/p\u003e\n\u003ch2\u003eMeasurement of mesencephalic aqueduct\u003c/h2\u003e\n\u003cp\u003eThe results revealed significant differences in the lengths of the mesencephalic aqueduct between the two groups. Subsequent pairwise comparisons between individuals with iNPH and controls showed no significant difference in the length of the mesencephalic aqueduct between the two groups (P \u0026gt; 0.05) (Table 2). However, the diameter of the mesencephalic aqueduct in patients with iNPH was significantly larger than that in healthy individuals (P \u0026lt; 0.05) (Table 3). Furthermore, the angle of the mesencephalic aqueduct was decreased in patients with iNPH, and the curvature was more pronounced than that in healthy individuals (P \u0026lt; 0.05) (Table 4).\u003c/p\u003e\n\u003ch2\u003eBrainstem measurements\u003c/h2\u003e\n\u003cp\u003eIn patients with iNPH, the brainstem area was reduced compared to that in healthy individuals (P \u0026lt; 0.05), with a particularly significant reduction in the midbrain area (P \u0026lt; 0.001)\u0026nbsp;(Table 5) and the proportion of the midbrain (P \u0026lt; 0.001)\u0026nbsp;(Table 6). However, no significant difference in the brainstem angle was observed between patients with iNPH and healthy individuals (P \u0026gt; 0.05)\u0026nbsp;(Table 7).\u003c/p\u003e\n\u003ch2\u003eMeasurement of brainstem peri-cisterns\u003c/h2\u003e\n\u003cp\u003eIn patients with iNPH, the brainstem peri-cistern areas were dilated compared to those in healthy individuals, with the pontine cistern showing a particularly significant enlargement (P \u0026lt; 0.05)\u0026nbsp;(Fig. 5). Additionally, the brainstem volume ratio was significantly reduced in patients with iNPH (P \u0026lt; 0.05)\u0026nbsp;(Table 8).\u003c/p\u003e\n\u003ch2\u003eMeasurement of anterior pontine cistern\u003c/h2\u003e\n\u003cp\u003eIn individuals with iNPH, the pontine cistern was dilated and exhibited a shape that resembled a \u0026ldquo;hammer\u0026rdquo;\u0026nbsp;(Fig. 6a, Fig. 6b, Fig. 6c). The prevalence of the \u0026ldquo;hammer sign\u0026rdquo; in patients with iNPH was 94.0%, compared to only 20.0% in healthy individuals\u0026nbsp;(Table 9).\u003c/p\u003e\n\u003cp\u003eWe performed ROC curve analysis to evaluate the diagnostic efficacy of the dilation of the pontine cistern and the \u0026quot;hammer\u0026quot; sign, using sensitivity, specificity, and the area under the curve (AUC) (Fig.7a). Notably, the area of the anterior cingulate cortex with the \u0026quot;hammer\u0026quot; sign was significantly larger than that without the \u0026quot;hammer\u0026quot; sign in patients with iNPH (Fig. 7b). The AUCs for iNPH patients and healthy individuals were 0.926 and 0.605, respectively, both of which are greater than 0.5. However, in terms of asymptomatic significance, only the correlation between the area of the prepontine cistern in patients with iNPH and the number of patients with the \u0026quot;hammer\u0026quot; sign was statistically significant (P\u0026lt;0.05) (Table 10), with a sensitivity of 94.0% and specificity of 80.0%.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eiNPH is a unique form of communicating hydrocephalus with intracranial pressure within the normal range (70\u0026ndash;200 mmHg). This condition predominantly affects the elderly and is the most common type of hydrocephalus in the elderly population. Patients often have no identifiable cause and lack characteristic imaging features. The clinical presentation of iNPH is characterized by a triad of gait disturbance, cognitive impairment, and urinary bladder dysfunction; however, only 50% of cases present with all three symptoms clinically\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e, with gait disturbance, including slow movement, shuffling gait, and magnetic gait, being the earliest clinical manifestation in patients with iNPH\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e In both previous studies and guidelines, iNPH is indicated by non-obstructive ventricular dilation, making ventricular enlargement a necessary condition for the diagnosis of iNPH. This ventricular dilation not only includes the lateral, third, and fourth ventricles but also the perimedullary cisterns, consistent with our conclusions. Regarding ventricular dilation in iNPH, research suggests that multiple pathophysiological models are currently available to explain its inevitability\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. The dilation of the ventricles leads to changes in several intracranial anatomical and angular parameters, and these changes may be regular. In guidelines and expert consensuses both domestically and internationally, an EI\u0026thinsp;\u0026gt;\u0026thinsp;0.3 is the only mandatory morphological criterion that must be met. However, ventricular enlargement in patients with iNPH does not occur in a single direction, but along the X, Y, and Z axes. Therefore, some researchers have used the term zEI\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e to denote the dilation of the ventricles along the longitudinal axis. However, irrespective of whether it is EI or zEI, while they can indicate ventricular enlargement, they cannot be used alone to differentiate between different types of hydrocephalus.\u003c/p\u003e \u003cp\u003eWe performed measurements on the midbrain aqueduct, brainstem, and peribrainstem cisterns of patients with iNPH and healthy middle-aged and elderly individuals. Through routine examinations and measurements, we identified the differences between these regions to facilitate the diagnosis of patients with iNPH as quickly as possible without the need for additional examinations and costs. Analysis of the measurement data revealed no significant difference in the length of the aqueduct between patients with iNPH and healthy individuals; however, the diameter of the midbrain aqueduct was significantly dilated, with an average diameter of 2.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.39 mm. However, dilation of the midbrain aqueduct can be seen in patients with communicating hydrocephalus, obstructive hydrocephalus, and those with obstruction below the midbrain aqueduct. The occurrence of this dilation requires further imaging data analysis for patients with communicating and obstructive hydrocephalus. The measurements obtained in our study demonstrate that the angle of the midbrain aqueduct is reduced in patients with iNPH compared to that in healthy individuals, which means that the curvature of the midbrain aqueduct is increased in patients with iNPH, and this morphological change is directly related to the patient\u0026rsquo;s ventricular dilation and DESH sign\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. CSF accumulates in the lateral fissure pool, lower part of the cerebral convexity (below the lateral fissure pool), and ventral sulci and cerebral cistern in patients with iNPH, leading to morphological changes in the pressure on the bottom of the brain and the upper part of the brainstem. This change ultimately decreases the midbrain aqueduct angle and causes an increase in curvature.\u003c/p\u003e \u003cp\u003eIn the measurement of the brainstem in patients with iNPH, the angle between the brainstem and spinal cord in patients with iNPH does not significantly differ from that in healthy individuals. However, the area of the brainstem is reduced in patients with iNPH compared to healthy individuals, with a particularly noticeable reduction in the cross-sectional area of the midbrain, which can be as high as 32.4%. The midbrain serves as a bridge between the cerebrum and spinal cord, playing a crucial role in coordinating body movements, processing sensory information, and regulating emotions. A reduction in midbrain volume is likely to lead to these functional impairments, resulting in clinical symptoms. Luca \u003cem\u003eet al.\u003c/em\u003e\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e conducted a study on the midbrain in patients with progressive supranuclear palsy, showing a significant positive correlation between the reduction in midbrain area and the fluency of speech. In addition to being related to the dysfunction of the frontal-striatal circuit\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e, dysfluency in speech and memory impairment in patients with iNPH is also closely associated with midbrain atrophy. Furthermore, Heikkinen \u003cem\u003eet al.\u003c/em\u003e\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e and colleagues found that brainstem atrophy is related to extrapyramidal symptoms of frontotemporal dementia.\u003c/p\u003e \u003cp\u003eIn the measurement of the perimesencephalic cisterns, the area of the cisterns surrounding the brainstem was expanded in patients with iNPH, with the expansion of the pontine cistern being particularly pronounced, reaching an expansion rate of up to 29.7%. In the majority of patients with iNPH, the expansion of the pontine cistern presents a \u0026ldquo;hammer\u0026rdquo; shape, and through ROC curve analysis, the appearance of the \u0026ldquo;hammer\u0026rdquo; shape was found to be positively correlated with the area of the pontine cistern, with a sensitivity of 94.0% and a specificity of 80.0%. This indicates that the greater the expansion of the pontine cistern, the higher the probability of the \u0026ldquo;hammer\u0026rdquo; shape appearing. Comparing the \u0026ldquo;hammer\u0026rdquo; shapes, the proportion of patients with iNPH presenting the \u0026ldquo;hammer\u0026rdquo; shape was 94.0%, whereas in healthy individuals, it was 20.0%. However, even among patients with the \u0026ldquo;hammer\u0026rdquo; shape, there were differences in the \u0026ldquo;hammer\u0026rdquo; shape of the pontine cistern, mainly in the distance between the posterior superior edge of the sella and the optic nerve; in patients with iNPH, the distance is generally greater than 3 mm, whereas in healthy individuals, it is less than 3 mm.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study involved the measurement and analysis of the cerebral aqueduct, brainstem, and other structures in patients with iNPH and normal middle-aged and elderly individuals. Through a comparative analysis of the data from different groups, the following conclusions were drawn: The length of the cerebral aqueduct in patients with iNPH showed no significant difference compared to that of healthy individuals, but the diameter of the aqueduct was significantly dilated. Patients with iNPH also exhibited morphological changes characterized by a reduction in the angle of the cerebral aqueduct and an increase in the curvature of its arc. The cross-sectional area of the brainstem was also found to be reduced in patients with iNPH compared to healthy individuals, with a particularly noticeable reduction in the cross-sectional area of the midbrain. Additionally, there was no significant difference in the angle between the brainstem and spinal cord between patients with iNPH and healthy individuals. The surrounding cerebral cisterns were also found to be dilated in patients with iNPH, with the prepontine cistern exhibiting the most pronounced dilation. Most dilations in the prepontine cistern in patients with iNPH present a \u0026ldquo;hammer\u0026rdquo; shape, which is positively correlated with the cistern area and has clinical significance. As we only compared patients with iNPH to normal middle-aged and elderly individuals, further research is needed to determine whether these morphological changes are present in patients with communicating hydrocephalus, obstructive hydrocephalus, Parkinson\u0026rsquo;s disease, and dementia.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eInformation on reprinting and sharing permissions\u003c/h2\u003e \u003cp\u003eis available at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003ca href=\"http://www.nature.com/reprints\" target=\"_blank\"\u003ewww.nature.com/reprints\u003c/a\u003e\u003c/span\u003e\u003cspan address=\"http://www.nature.com/reprints\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003ePublisher\u0026rsquo;s note\u003c/h2\u003e \u003cp\u003eSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis work was supported by the National Natural Science Foundation of China under Grant 82201502, and it also supported by Sichuan Province Medical Research Project S22078 from Sichuan Medical Association.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eLiangxue Zhou designed the experiment. Kui Xiao and Xielin Tang conducted the experiment. Shenghua Liu, Ziang Deng, and Feilong Yang performed the statistical analysis, and Ziang Deng was responsible for medical ethics applications.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors thank Shan Wang for her assistance in data collection. The authors also thank LetPub (www.letpub.com.cn/) for its linguistic assistance during the preparation of this manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data supporting the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAdams, R. D., Fisher, C. M., Hakim, S., Ojemann, R. G. \u0026amp; Sweet, W. H. Symptomatic occult hydrocephalus with normal cerebrospinal-fluid pressure. N. Engl. J. Med. 273, 117\u0026ndash;126 (1965).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilliams, M. A. \u0026amp; Malm, J. Diagnosis and treatment of idiopathic normal pressure hydrocephalus. Continuum 22, 579\u0026ndash;599 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHydrocephalus Group of Chinese Society of Microcirculation Neurode generative Diseases Committee \u003cem\u003eet al.\u003c/em\u003e Guidelines for clinical management of idiopathic normal pressure hydrocephalus in China (2022). Chin. J. Geriatr. 41, 123\u0026ndash;134 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJ\u0026oacute;hannsd\u0026oacute;ttir, A. M., Pedersen, C. B., Munthe, S., Poulsen, F. R. \u0026amp; J\u0026oacute;hannsson, B. Idiopathic normal pressure hydrocephalus: Validation of the DESH score as a prognostic tool for shunt surgery response. Clin. Neurol. Neurosurg. 241, 108295 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEide, P. K. \u0026amp; Pripp, A. H. Increased prevalence of cardiovascular disease in idiopathic normal pressure hydrocephalus patients compared to a population-based cohort from the HUNT3 survey. Fluids Barriers CNS 11, 19 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrasso, G., Teresi, G., Noto, M. \u0026amp; Torregrossa, F. Invasive preoperative investigations in idiopathic normal pressure hydrocephalus: A comprehensive review. World Neurosurg. 181, 178\u0026ndash;183 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBradley, W. G. Magnetic resonance imaging of normal pressure hydrocephalus. Semin. Ultrasound. CT MR 37, 120\u0026ndash;128 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuehiro, T. \u003cem\u003eet al.\u003c/em\u003e Changes in brain morphology in patients in the preclinical stage of idiopathic normal pressure hydrocephalus. Psychogeriatrics 19, 557\u0026ndash;565 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMantovani, P. \u003cem\u003eet al.\u003c/em\u003e Anterior callosal angle: A new marker of idiopathic normal pressure hydrocephalus? World Neurosurg. 139, e548\u0026ndash;e552 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTeng, Y. Diagnostic efficacy of novel imaging markers for idiopathic normal pressure hydrocephalus and their correlation with clinical symptoms. J. Imaging Res. Med. Appl. 6, 50\u0026ndash;52 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKong, S. \u003cem\u003eet al.\u003c/em\u003e Correlation between intracranial volume parameters and cognitive impairment in idiopathic normal pressure hydrocephalus. Chin. J. Magn. Reson. Imaging 13, 7\u0026ndash;12 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKazui, H., Miyajima, M., Mori, E. \u0026amp; Ishikawa, M. Lumboperitoneal shunt surgery for idiopathic normal pressure hydrocephalus (SINPHONI-2): An open-label randomised trial. Lancet Neurol. 14, 585\u0026ndash;594 (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRingstad, G., Emblem, K. E., Geier, O., Alperin, N. \u0026amp; Eide, P. K. Aqueductal stroke volume: Comparisons with intracranial pressure scores in idiopathic normal pressure hydrocephalus. AJNR Am. J. Neuroradiol. 36, 1623\u0026ndash;1630 (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaeda, S. \u003cem\u003eet al.\u003c/em\u003e Biomechanical effects of hyper-dynamic cerebrospinal fluid flow through the cerebral aqueduct in idiopathic normal pressure hydrocephalus patients. J. Biomech. 156, 111671 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGreen, L. M., Wallis, T., Schuhmann, M. U. \u0026amp; Jaeger, M. Intracranial pressure waveform characteristics in idiopathic normal pressure hydrocephalus and late-onset idiopathic aqueductal stenosis. Fluids Barriers CNS 18, 25 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYin, L. K. \u003cem\u003eet al.\u003c/em\u003e Reversed aqueductal cerebrospinal fluid net flow in idiopathic normal pressure hydrocephalus. Acta Neurol. Scand. 136, 434\u0026ndash;439 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRingstad, G., Emblem, K. E. \u0026amp; Eide, P. K. Phase-contrast magnetic resonance imaging reveals net retrograde aqueductal flow in idiopathic normal pressure hydrocephalus. J. Neurosurg. 124, 1850\u0026ndash;1857 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSankari, S. E. \u003cem\u003eet al.\u003c/em\u003e Correlation between tap test and CSF aqueductal stroke volume in idiopathic normal pressure hydrocephalus in \u003cem\u003eHydrocephalus. Acta Neurochirurgica Supplementum\u003c/em\u003e Vol. 113 (eds Gunes A. Aygok \u0026amp; Harold L. Rekate) 43\u0026ndash;46 (Springer, 2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlgin, O. Role of aqueductal CSF stroke volume in idiopathic normal-pressure hydrocephalus. AJNR Am. J. Neuroradiol. 31, E26\u0026ndash;E27; author reply E28 (2010).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKameda, M. \u003cem\u003eet al.\u003c/em\u003e Cost-effectiveness analysis of shunt surgery for idiopathic normal pressure hydrocephalus based on the SINPHONI and SINPHONI-2 trials. Acta Neurochir. (Wien.) 159, 995\u0026ndash;1003 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWei, Y. \u003cem\u003eet al.\u003c/em\u003e The analysis of MRI structural imaging features in idiopathic normal pressure hydrocephalus. J. Imaging Res. Med. Appl. 4, 28\u0026ndash;30 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBradley, W. G. \u003cem\u003eet al.\u003c/em\u003e Marked cerebrospinal fluid void: Indicator of successful shunt in patients with suspected normal-pressure hydrocephalus. Radiology 178, 459\u0026ndash;466 (1991).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNakajima, M. \u003cem\u003eet al.\u003c/em\u003e Guidelines for management of idiopathic normal pressure hydrocephalus (third edition): Endorsed by the Japanese society of normal pressure hydrocephalus. Neurol. Med. Chir. (Tokyo) 61, 63\u0026ndash;97 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRyska, P. \u003cem\u003eet al.\u003c/em\u003e Radiological markers of idiopathic normal pressure hydrocephalus: Relative comparison of their diagnostic performance. J. Neurol. Sci. 408, 116581 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCraven, C. L., Toma, A. K., Mostafa, T., Patel, N. \u0026amp; Watkins, L. D. The predictive value of DESH for shunt responsiveness in idiopathic normal pressure hydrocephalus. J. Clin. Neurosci. 34, 294\u0026ndash;298 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuca, A. \u003cem\u003eet al.\u003c/em\u003e Phonemic verbal fluency and midbrain atrophy in progressive supranuclear palsy. J. Alzheimers Dis. 80, 1669\u0026ndash;1674 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiao, H., Hu, F., Ding, J. \u0026amp; Ye, Z. Cognitive impairment in idiopathic normal pressure hydrocephalus. Neurosci. Bull. 38, 1085\u0026ndash;1096 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeikkinen, S. \u003cem\u003eet al.\u003c/em\u003e Brainstem atrophy is linked to extrapyramidal symptoms in frontotemporal dementia. J. Neurol. 269, 4488\u0026ndash;4497 (2022).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eDemographic data of iNPH and healthy groups.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eiNPH\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHealthy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\" valign=\"top\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003e74.07 \u0026plusmn; 8.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e72.73 \u0026plusmn; 7.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" valign=\"top\"\u003e\n \u003cp\u003e0.624\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e0.538\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\" valign=\"top\"\u003e\n \u003cp\u003eSex (male:female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003e35:15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e20:10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;1.533\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e0.136\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\" valign=\"top\"\u003e\n \u003cp\u003eHeight (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003e158.83 \u0026plusmn; 6.747\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e157.07 \u0026plusmn; 6.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" valign=\"top\"\u003e\n \u003cp\u003e0.977\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e0.337\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\" valign=\"top\"\u003e\n \u003cp\u003eWeight (Kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003e59.55 \u0026plusmn; 6.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e57.82 \u0026plusmn; 6.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" valign=\"top\"\u003e\n \u003cp\u003e1.093\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e0.283\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Mesencephalic aqueduct length in each group.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.708333333333332%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.416666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLength of mesencephalic aqueduct (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.541666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired t-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired P-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.708333333333332%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with iNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.416666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e19.72 \u0026plusmn; 2.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\" valign=\"top\"\u003e\n \u003cp\u003e55.695\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.541666666666666%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;0.541\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.593\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.63768115942029%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.27536231884058%\" valign=\"top\"\u003e\n \u003cp\u003e19.64 \u0026plusmn; 1.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.043478260869565%\" valign=\"top\"\u003e\n \u003cp\u003e57.226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.043478260869565%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e Diameter of mesencephalic aqueduct in each group.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOpening of the mesencephalic aqueduct (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired t-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired P-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with iNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\" valign=\"top\"\u003e\n \u003cp\u003e2.24 \u0026plusmn; 0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e40.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e2.303\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.029\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.555555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e1.98 \u0026plusmn; 0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e25.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eStenosis of the mesencephalic aqueduct (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired t-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired P-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with iNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\" valign=\"top\"\u003e\n \u003cp\u003e1.58 \u0026plusmn; 0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e33.727\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e4.095\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.555555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e1.27 \u0026plusmn; 0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e30.508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutlet of mesencephalic aqueduct (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired t-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired P-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003epatients with iNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\" valign=\"top\"\u003e\n \u003cp\u003e3.07 \u0026plusmn; 0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e27.771\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e3.152\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003ehealthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.555555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e2.49 \u0026plusmn; 0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e27.099\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4.\u003c/strong\u003e Mesencephalic aqueduct angle in each group.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.98969072164948%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAngle of mesencephalic aqueduct (\u0026deg;)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired t-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired P-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with iNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.98969072164948%\" valign=\"top\"\u003e\n \u003cp\u003e125.92 \u0026plusmn; 8.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\" valign=\"top\"\u003e\n \u003cp\u003e102.617\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;4.774\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.08695652173913%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.3768115942029%\" valign=\"top\"\u003e\n \u003cp\u003e135.15 \u0026plusmn; 7.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.492753623188406%\" valign=\"top\"\u003e\n \u003cp\u003e96.138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.043478260869565%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5.\u003c/strong\u003e Longitudinal section area of the brainstem in each group (through the aqueductal plane).\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.11340206185567%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMidbrain + pons + medulla oblongata area (cm\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired t-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired P-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with iNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.11340206185567%\" valign=\"top\"\u003e\n \u003cp\u003e9.10 \u0026plusmn; 0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e74.076\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;3.138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48%\" valign=\"top\"\u003e\n \u003cp\u003e9.80 \u0026plusmn; 0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\" valign=\"top\"\u003e\n \u003cp\u003e70.843\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.11340206185567%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMidbrain + pons area (cm\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired t-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired P-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with iNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.11340206185567%\" valign=\"top\"\u003e\n \u003cp\u003e5.88 \u0026plusmn; 0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e68.506\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;4.051\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48%\" valign=\"top\"\u003e\n \u003cp\u003e6.60 \u0026plusmn; 0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\" valign=\"top\"\u003e\n \u003cp\u003e60.855\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.11340206185567%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMidbrain area (cm\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired t-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired P-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with iNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.11340206185567%\" valign=\"top\"\u003e\n \u003cp\u003e0.92 \u0026plusmn; 0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e34.263\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;6.915\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48%\" valign=\"top\"\u003e\n \u003cp\u003e1.36 \u0026plusmn; 0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\" valign=\"top\"\u003e\n \u003cp\u003e25.993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.11340206185567%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePons area (cm\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired t-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired P-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with iNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.11340206185567%\" valign=\"top\"\u003e\n \u003cp\u003e4.95 \u0026plusmn; 0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e68.916\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;1.772\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48%\" valign=\"top\"\u003e\n \u003cp\u003e5.18 \u0026plusmn; 0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\" valign=\"top\"\u003e\n \u003cp\u003e64.908\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 6.\u0026nbsp;\u003c/strong\u003ePercentage of midbrain and pons in each group (through the aqueductal plane).\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMidbrain ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.52577319587629%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired t-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired P-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with iNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e0.156 \u0026plusmn; 0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e42.995\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.52577319587629%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;3.837\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.096774193548384%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.032258064516128%\" valign=\"top\"\u003e\n \u003cp\u003e0.200 \u0026plusmn; 0.051\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.741935483870968%\" valign=\"top\"\u003e\n \u003cp\u003e21.588\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePons ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.52577319587629%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired t-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired P-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with iNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e0.844 \u0026plusmn; 0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e231.364\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.52577319587629%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e2.607\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.096774193548384%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.032258064516128%\" valign=\"top\"\u003e\n \u003cp\u003e0.765 \u0026plusmn; 0.149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.741935483870968%\" valign=\"top\"\u003e\n \u003cp\u003e28.131\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 7.\u003c/strong\u003e Brainstem angles (through the aqueductal plane) of each group.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.46938775510204%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBrainstem angle\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.224489795918368%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.204081632653061%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired t-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired P-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.46938775510204%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with iNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e163.56 \u0026plusmn; 5.99\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.224489795918368%\" valign=\"top\"\u003e\n \u003cp\u003e193.037\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.204081632653061%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e1.030\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.312\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.507936507936506%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.158730158730158%\" valign=\"top\"\u003e\n \u003cp\u003e161.97 \u0026plusmn; 6.66\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.46031746031746%\" valign=\"top\"\u003e\n \u003cp\u003e133.288\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.873015873015873%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 8.\u003c/strong\u003e Area of brainstem peri-cerebral and anterior pontine cisterns (cm\u003csup\u003e2\u003c/sup\u003e) and brainstem volume ratio of each group.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.896907216494846%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnterior pontine cistern area\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired t-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired P-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with iNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.896907216494846%\" valign=\"top\"\u003e\n \u003cp\u003e5.86 \u0026plusmn; 1.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e33.311\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e4.031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.88235294117647%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.64705882352941%\" valign=\"top\"\u003e\n \u003cp\u003e4.54 \u0026plusmn; 1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.235294117647058%\" valign=\"top\"\u003e\n \u003cp\u003e23.797\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.235294117647058%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.896907216494846%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBrainstem volume ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired t-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaired P-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with iNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.896907216494846%\" valign=\"top\"\u003e\n \u003cp\u003e0.489 \u0026plusmn; 0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e70.687\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;5.494\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.88235294117647%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.64705882352941%\" valign=\"top\"\u003e\n \u003cp\u003e0.564 \u0026plusmn; 0.062\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.235294117647058%\" valign=\"top\"\u003e\n \u003cp\u003e50.047\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.235294117647058%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 9.\u003c/strong\u003e Proportion of patients with a \u0026ldquo;hammer\u0026rdquo; sign in each group.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.35353535353536%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of \u0026ldquo;hammer signs\u0026rdquo;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026ldquo;Hammer sign\u0026rdquo; proportion (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with iNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.35353535353536%\" valign=\"top\"\u003e\n \u003cp\u003e47\\50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"top\"\u003e\n \u003cp\u003e0.940\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.35353535353536%\" valign=\"top\"\u003e\n \u003cp\u003e6\\30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"top\"\u003e\n \u003cp\u003e0.200\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 10.\u003c/strong\u003e Comparison of area under the receiver operating characteristic curve (AUC value) between the number of hammer sign individuals and area of the anterior pontine cistern.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.6530612244898%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eInspection indicators\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAUC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eStandard error\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAsymptotic significance\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.510204081632654%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAsymptotic 95% confidence Interval\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLower limit\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eUpper limit\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.98969072164948%\" valign=\"top\"\u003e\n \u003cp\u003eAnterior pontine cistern area in the iNPH group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" valign=\"top\"\u003e\n \u003cp\u003e0.926\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e0.070\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" valign=\"top\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" valign=\"top\"\u003e\n \u003cp\u003e0.790\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" valign=\"top\"\u003e\n \u003cp\u003e1.062\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.98969072164948%\" valign=\"top\"\u003e\n \u003cp\u003eAnterior pontine cistern area in Healthy subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" valign=\"top\"\u003e\n \u003cp\u003e0.605\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" valign=\"top\"\u003e\n \u003cp\u003e0.357\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" valign=\"top\"\u003e\n \u003cp\u003e0.382\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" valign=\"top\"\u003e\n \u003cp\u003e0.828\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: AUC is the area under the receiver operating characteristic curve.\u0026nbsp;\u003csup\u003ea\u003c/sup\u003eBased on nonparametric assumptions. \u003csup\u003eb\u003c/sup\u003eNull hypothesis: True area = 0.5.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Idiopathic normal pressure hydrocephalus, Characteristic imaging indicators, Mesencephalic aqueduct, Brainstem volume ratio, Prepontine cistern, “Hammer” shape","lastPublishedDoi":"10.21203/rs.3.rs-4868789/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4868789/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study explores the specific magnetic resonance imaging (MRI) indicators of the brainstem and mesencephalic aqueduct in patients with idiopathic normal pressure hydrocephalus (iNPH). We analyzed the head MRI data of 50 iNPH patients and 30 healthy middle-aged and elderly individuals. The study included an analysis of the length, diameter, and angle of the cerebral aqueduct, as well as the longitudinal cross-sectional areas of the midbrain and brainstem. Additionally, we evaluated the midbrain proportion, brainstem volume ratio, the angle between the brainstem and spinal cord, and the area and morphology of the pontine cistern. The findings revealed that, compared to healthy individuals, iNPH patients exhibited significant dilation of the midbrain aqueduct diameter, a reduced aqueduct angle, and a decreased longitudinal cross-sectional area of the brainstem, with the most pronounced reduction in the midbrain area. Notably, the cerebral pools surrounding the brainstem in iNPH patients were dilated, with the pontine cistern presenting a \"hammer\" shape, and the prevalence of this \"hammer\" shape was significantly positively correlated with the area of the pontine cistern. These unique imaging characteristics not only enhance the clinical recognition of iNPH, but also provide new imaging evidence for the early diagnosis and treatment of iNPH.\u003c/p\u003e","manuscriptTitle":"MRI imaging characteristics of brainstem and midbrain aqueduct in patients with iNPH","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-14 10:21:05","doi":"10.21203/rs.3.rs-4868789/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-08T05:23:20+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-04T07:43:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-26T21:02:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"256085471321721341096806839760505882408","date":"2024-09-26T15:11:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-16T21:54:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"253906560995353475870464561747678215966","date":"2024-09-06T14:07:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"128429754428830648933225714437784583678","date":"2024-08-27T20:34:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-26T13:05:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-26T13:01:52+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-08-20T12:54:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-19T06:07:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-08-06T13:20:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6880d4c3-fdd4-4982-9dc4-f45b7e80857f","owner":[],"postedDate":"October 14th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":37471539,"name":"Health sciences/Diseases/Neurological disorders/Hydrocephalus"},{"id":37471540,"name":"Biological sciences/Biological techniques/Imaging/Magnetic resonance imaging"}],"tags":[],"updatedAt":"2025-01-06T15:59:06+00:00","versionOfRecord":{"articleIdentity":"rs-4868789","link":"https://doi.org/10.1038/s41598-024-83874-7","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-01-02 15:57:01","publishedOnDateReadable":"January 2nd, 2025"},"versionCreatedAt":"2024-10-14 10:21:05","video":"","vorDoi":"10.1038/s41598-024-83874-7","vorDoiUrl":"https://doi.org/10.1038/s41598-024-83874-7","workflowStages":[]},"version":"v1","identity":"rs-4868789","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4868789","identity":"rs-4868789","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}