The importance of precise plane selection for female adult Chiari Type I malformation midsagittal morphometrics.

INTRODUCTION: Morphometric assessment of Chiari malformation type I (CMI) is typically performed on a midsagittal MRI. However, errors arising from an imprecise selection of the midsagittal plane are unknown. We define absolute parasagittal error as the absolute difference between morphometric measurements at the midsagittal and parasagittal planes. Our objective was to determine the absolute parasagittal error at various lateral distances for morphometric parameters commonly used in CMI research. METHODS: Sagittal T1-weighted MRI scans of 30 CMI adult female subjects were included. Image sets were evaluated to assess 14 CMI morphometric parameters in the midsagittal plane and four parasagittal planes located 1 and 2 mm lateral (left and right). Comparisons between measurements at the midsagittal and parasagittal planes were conducted to determine the mean individual absolute and mean group parasagittal errors for all 14 parameters. RESULTS: The mean individual absolute parasagittal error was > 1 unit (1 mm for lengths and 1 degree for angles) for 9/14 parameters within a lateral distance of 2 mm. No significant group parasagittal errors were seen in 14/14 parameters, including tonsillar position within a lateral distance of 2 mm. CONCLUSION: Our results show that the absolute errors for imprecise midsagittal plane selection may impact the clinical assessment of an individual patient. However, the impact on group measurements, such as in a research setting, will be minimal.

Are Two-Dimensional Morphometric Measures Reflective of Disease Severity in Adult Chiari I Malformation?

BACKGROUND: Two-dimensional (2D) morphometric measures have been previously used to diagnose Chiari I malformation (CMI) and distinguish patients from healthy subjects. There is, however, a paucity of literature regarding whether morphometric differences exist across the range of CMI disease severity. We evaluated whether 2D morphometrics demonstrate significant changes across standardized grades of CMI severity in adults. METHODS: This retrospective observational study comprised 76 patients with symptomatic CMI with or without syringomyelia. Patients matched for age, sex, and body mass index were selected from each of the 3 severity grades of the Chiari Severity Index (CSI). The study used 17 2D craniocervical and posterior fossa morphometric variables that were previously found to differentiate patients with CMI from healthy subjects. The measurements were performed on midsagittal T1-weighted magnetic resonance imaging sequences using 2 custom in-house software tools, MorphPro and CerePro, and compared across CSI grades. RESULTS: Analysis of variance showed that none of the 17 morphometric variables were significantly different across the 3 CSI grades (P > 0.003). Bayes factor 10 scores ranged from 0.11 to 0.82. Of variables, 9 had Bayes factor 10 scores between 0.10 and 0.30, while 8 had scores between 0.30 and 1. None of the Bayes factor 10 scores provided support for the alternative hypothesis that the morphometric measures differed across the CSI grades. CONCLUSIONS: Our study indicated that 2D morphometrics are not reflective of CMI disease severity as indicated by the CSI grading system. The findings of our study support the need for further investigation into whether non-2D morphometric variables can be used as markers of disease severity.

Adult Age Differences in Self-Reported Pain and Anterior CSF Space in Chiari Malformation.

Chiari malformation type I (CMI) is a neural disorder with sensory, cognitive, and motor defects, as well as headaches. Radiologically, the cerebellar tonsils extend below the foramen magnum. To date, the relationships among adult age, brain morphometry, surgical status, and symptom severity in CMI are unknown. The objective of this study was to better understand the relationships among these variables using causal modeling techniques. Adult CMI patients (80% female) who either had (n = 150) or had not (n = 151) undergone posterior fossa decompression surgery were assessed using morphometric measures derived from magnetic resonance images (MRI). MRI-based morphometry showed that the area of the CSF pocket anterior to the cervico-medullary junction (anterior CSF space) correlated with age at the time of MRI (r = - .21). Also, self-reported pain increased with age (r = .11) and decreased with anterior CSF space (r = - .18). Age differences in self-reported pain were mediated by anterior CSF space in the cervical spine area-and this effect was particularly salient for non-decompressed CMI patients. As CMI patients age, the anterior CSF space decreases, and this is associated with increased pain-especially for non-decompressed CMI patients. It is recommended that further consideration of age-related decreases in anterior CSF space in CMI patients be given in future research.

Cerebellar and Brainstem Displacement Measured with DENSE MRI in Chiari Malformation Following Posterior Fossa Decompression Surgery.

Background Posterior fossa decompression (PFD) surgery is a treatment for Chiari malformation type I (CMI). The goals of surgery are to reduce cerebellar tonsillar crowding and restore posterior cerebral spinal fluid flow, but regional tissue biomechanics may also change. MRI-based displacement encoding with stimulated echoes (DENSE) can be used to assess neural tissue displacement. Purpose To assess neural tissue displacement by using DENSE MRI in participants with CMI before and after PFD surgery and examine associations between tissue displacement and symptoms. Materials and Methods In a prospective, HIPAA-compliant study of patients with CMI, midsagittal DENSE MRI was performed before and after PFD surgery between January 2017 and June 2020. Peak tissue displacement over the cardiac cycle was quantified in the cerebellum and brainstem, averaged over each structure, and compared before and after surgery. Paired t tests and nonparametric Wilcoxon signed-rank tests were used to identify surgical changes in displacement, and Spearman correlations were determined between tissue displacement and presurgery symptoms. Results Twenty-three participants were included (mean age ± standard deviation, 37 years ± 10; 19 women). Spatially averaged (mean) peak tissue displacement demonstrated reductions of 46% (79/171 µm) within the cerebellum and 22% (46/210 µm) within the brainstem after surgery (P < .001). Maximum peak displacement, calculated within a circular 30-mm2 area, decreased by 64% (274/427 µm) in the cerebellum and 33% (100/300 µm) in the brainstem (P < .001). No significant associations were identified between tissue displacement and CMI symptoms (r < .74 and P > .012 for all; Bonferroni-corrected P = .0002). Conclusion Neural tissue displacement was reduced after posterior fossa decompression surgery, indicating that surgical intervention changes brain tissue biomechanics. For participants with Chiari malformation type I, no relationship was identified between presurgery tissue displacement and presurgical symptoms. © RSNA, 2021 Online supplemental material is available for this article.

Impact of Surgical Status, Loneliness, and Disability on Interleukin 6, C-Reactive Protein, Cortisol, and Estrogen in Females with Symptomatic Type I Chiari Malformation.

Chiari malformation type I (CMI) provides an opportunity for examining possible moderators of allostatic load. CMI patients who had (n = 43) and had not (n = 19) undergone decompression surgery completed questionnaires regarding pain, disability, and loneliness, and provided serum samples for IL-6, CRP, estrogen, and free estradiol assays, and saliva samples to assess diurnal cortisol curves. ANOVAs examining surgical status (decompressed versus non-decompressed), loneliness (high vs. low), and disability (high vs. low) as independent variables and biomarker variables as dependent factors found that loneliness was associated with higher levels of cortisol, F(1, 37) = 4.91, p = .04, η2P = .11, and lower levels of estrogen, F(1, 36) = 7.29, p = .01, η2P = .17, but only in decompressed patients. Results highlight the possible impact of loneliness on biological stress responses and the need to intervene to reduce loneliness in patients with symptomatic CMI.

Regional Brain Tissue Displacement and Strain is Elevated in Subjects with Chiari Malformation Type I Compared to Healthy Controls: A Study Using DENSE MRI.

While the degree of cerebellar tonsillar descent is considered the primary radiologic marker of Chiari malformation type I (CMI), biomechanical forces acting on the brain tissue in CMI subjects are less studied and poorly understood. In this study, regional brain tissue displacement and principal strains in 43 CMI subjects and 25 controls were quantified using a magnetic resonance imaging (MRI) methodology known as displacement encoding with stimulated echoes (DENSE). Measurements from MRI were obtained for seven different brain regions-the brainstem, cerebellum, cingulate gyrus, corpus callosum, frontal lobe, occipital lobe, and parietal lobe. Mean displacements in the cerebellum and brainstem were found to be 106 and 64% higher, respectively, for CMI subjects than controls (p < .001). Mean compression and extension strains in the cerebellum were 52 and 50% higher, respectively, in CMI subjects (p < .001). Brainstem mean extension strain was 41% higher in CMI subjects (p < .001), but no significant difference in compression strain was observed. The other brain structures revealed no significant differences between CMI and controls. These findings demonstrate that brain tissue displacement and strain in the cerebellum and brainstem might represent two new biomarkers to distinguish between CMI subjects and controls.

Accuracy of cardiac-induced brain motion measurement using displacement-encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI): A phantom study.

PURPOSE: The goal of this study was to determine the accuracy of displacement-encoding with stimulated echoes (DENSE) MRI in a tissue motion phantom with displacements representative of those observed in human brain tissue. METHODS: The phantom was comprised of a plastic shaft rotated at a constant speed. The rotational motion was converted to a vertical displacement through a camshaft. The phantom generated repeatable cyclical displacement waveforms with a peak displacement ranging from 92 µm to 1.04 mm at 1-Hz frequency. The surface displacement of the tissue was obtained using a laser Doppler vibrometer (LDV) before and after the DENSE MRI scans to check for repeatability. The accuracy of DENSE MRI displacement was assessed by comparing the laser Doppler vibrometer and DENSE MRI waveforms. RESULTS: Laser Doppler vibrometer measurements of the tissue motion demonstrated excellent cycle-to-cycle repeatability with a maximum root mean square error of 9 µm between the ensemble-averaged displacement waveform and the individual waveforms over 180 cycles. The maximum difference between DENSE MRI and the laser Doppler vibrometer waveforms ranged from 15 to 50 µm. Additionally, the peak-to-peak difference between the 2 waveforms ranged from 1 to 18 µm. CONCLUSION: Using a tissue phantom undergoing cyclical motion, we demonstrated the percent accuracy of DENSE MRI to measure displacement similar to that observed for in vivo cardiac-induced brain tissue.

Clivus length distinguishes between asymptomatic healthy controls and symptomatic adult women with Chiari malformation type I.

PURPOSE: While the presence of cerebellar tonsillar descent in radiological images has been used as evidence of Chiari malformation type I (CMI), tonsillar ectopia alone is insufficient to identify individuals with symptomatic CMI. This study sought to identify differences in brain morphology between symptomatic CMI and healthy controls in adult females. METHODS: Two hundred and ten adult females with symptomatic CMI and 90 age- and body mass index-matched asymptomatic female controls were compared using seven brain morphometric measures visible on magnetic resonance images. The CMI and control groups were divided into four subgroups based on the tonsillar position (TP) relative to the foramen magnum: group 1 was made up of healthy controls with normal TP (TP < 0 mm); group 2 was comprised of control individuals with low-lying TP (1-5 mm); group 3 was comprised of symptomatic CMI patients with low-lying TP (1-5 mm); group 4 contained symptomatic CMI patients with severe tonsillar descent (6-13 mm). RESULTS: All morphometrics for symptomatic CMI with severe tonsillar descent were significantly different than those for both control groups. The CMI group with low-lying TP was significantly different for four measures when compared to controls with normal TP. However, only clivus length was statistically different between the CMI and healthy control groups with low-lying TP. CONCLUSION: This study demonstrates that clivus length distinguishes adult female healthy individuals with low-lying tonsils from those with symptomatic CMI. Further investigation is required to understand the importance of a shorter clivus length on CMI symptomatology and pathophysiology.

Evidence for sex differences in morphological abnormalities in type I Chiari malformation.

BACKGROUND AND PURPOSE: Relatively little is known about the influence of individual difference variables on the presentation of macro-level brain morphology in type I Chiari malformation (CMI). The goal of the present study is to examine how case-control differences in Chiari are affected by patient sex. MATERIALS AND METHODS: Patient-provided magnetic resonance images were acquired through the Chiari 1000 database. Twenty-four morphometric measurements were taken using mid-sagittal images of 104 participants (26 male CMI, 26 female CMI, 26 male controls, and 26 female controls) using internally developed and validated custom software, Morphpro. Case-control comparisons were conducted separately by sex using healthy controls matched by age and body mass index. Probability-based t-tests, effect sizes (Cohen's d), and confidence intervals were used to compare case-control differences separately by sex. RESULTS: Male and female case-control comparisons yielded largely the same trends of CMI-related morphometric abnormalities. Both groups yielded reductions in posterior cranial fossa (PCF) structure heights. However, there was evidence for greater PCF structure height reductions in male CMI patients as measured by Cohen's d. CONCLUSIONS: Case-control differences indicated strong consistency in the morphometric abnormalities of CMI malformation in males and females. However, despite the higher prevalence rates of CMI in females, the results from the present study suggest that male morphometric abnormalities may be greater in magnitude. These findings also provide insight into the inconsistent findings from previous morphometric studies of CMI and emphasize the importance of controlling for individual differences when conducting case-control comparisons in CMI.

Three-Dimensional CT Morphometric Image Analysis of the Clivus and Sphenoid Sinus in Chiari Malformation Type I.

This study evaluated three-dimensional (3D) volumetric image reconstructions to identify morphological differences of the clivus and sphenoid sinus on computed tomography (CT) scans of Chiari malformation type I (CMI) and control subjects. Axial CT images of adult females for 30 CMI subjects and 30 age and body mass index (BMI) matched controls were used for this retrospective study. 3D volumetric reconstructions were created from the bone windows of axial data following image registration for position and orientation correction of the head. The volume, surface area, linear dimensions and spatial position in the x, y, and z-axes were computed separately for the clivus and the sphenoid sinus for each subject. Eleven parameters were found to be significantly different between CMI subjects compared to controls. Most notably, clivus volume was reduced by 31% on average in CMI subjects. In contrast, we found that the sphenoid sinus volume was 38% greater on average in CMI subjects. Moreover, clivus length, height, width, and thickness were 3.7, 2.8, 3.0 and 9.4 mm reduced, respectively, in CMI subjects. This is the first study to demonstrate cephalometric differences in the 3D morphology of the clivus and sphenoid sinus between CMI subjects and controls.

Quantification of changes in brain morphology following posterior fossa decompression surgery in women treated for Chiari malformation type 1.

PURPOSE: While 84% of patients surgically treated for Chiari malformation type 1 (CM1) demonstrate improved quality of life after posterior fossa decompression surgery, there are many risks associated with this surgery. Surgical planning to identify candidates likely to improve postoperatively may benefit from an improved understanding of morphological changes after decompression surgery. To evaluate these changes, we quantified 59 morphological parameters on 42 CM1 adult female patients before and after CM1 decompression surgery. METHODS: Fifty-nine morphological parameters in the posterior cranial fossa, cranio-cervical, and intracranial regions in the midsagittal plane were evaluated using 42 T1-weighted magnetic resonance images of female CM1 patients before and after surgery, and 42 healthy female controls. Morphological differences before and after surgery were compared through the development of a technique to establish the opisthion location, a key reference point not present after surgery. RESULTS: In addition to the expected reduction of the cranio-caudal dimension of the cerebellum, objective analyses showed a significant increase in the area of the cerebrospinal fluid spaces, posterior (6×) and inferior (2.6×) to the cerebellum (+ 112 ± 102 and + 140 ± 127 mm2, respectively). This increased area was primarily impacted by an average reduction in the occipital bone length of 24.5 ± 7.3 mm following surgery. Based on multiple angles, results demonstrated a 2°-4° anterior rotation of the cerebellum after surgery. CONCLUSION: Our results show that decompression surgery results in significant changes in the cerebellum and cerebrospinal fluid spaces. Further investigation should determine how these morphological changes impact clinical outcomes.

Type I Chiari malformation, RBANS performance, and brain morphology: Connecting the dots on cognition and macrolevel brain structure.

BACKGROUND: Idiopathic descent of cerebellar tonsils into the cervical spine in Chiari malformation Type I (CMI) is typically associated with occipital headache. Accumulating evidence from experimental studies suggests cognitive effects of CMI. The aim of the current study was to examine the relationship between cognition and CMI using a battery of standardized neuropsychological and symptom inventory instruments. METHOD: Eighteen untreated adults with CMI, and 18 gender, age, and education matched healthy controls completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and standardized measures of pain, mood, and disability. Morphometric measurements of key neural and osseous elements were also obtained from structural brain magnetic resonance images, for correlation with symptom outcomes. RESULTS: CMI patients exhibited deficits in RBANS attention, immediate memory, delayed memory, and total score. After controlling for pain and associated affective disturbance, the significant group effect for RBANS attention remained. CMI patients also presented seven morphometric differences comprising the cerebellum and posterior cranial fossa compartment that differed from healthy controls, some of which were associated with self-reported pain and disability. Notably, group differences in tonsillar position were associated with self-reported pain, disability, and delayed memory. CONCLUSION: Adult CMI is associated with domain-specific cognitive change, detectable using a standard clinical instrument. The extent of cognitive impairment is independent of pain or affective symptomatology and may be related to the key pathognomonic feature of the condition. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Quantification of Cerebellar Crowding in Type I Chiari Malformation.

This study was focused on a semi-automated morphometric analysis of the cerebellum in the mid-sagittal plane as an alternative to tonsillar descent alone in the evaluation of Chiari malformation type 1 (CMI) patients. Morphometric analyses of posterior fossa structures were performed on mid-sagittal MRI images of 375 individuals (females, > 18 years, 235 CMI and 140 healthy controls). Twenty-six parameters including linear, angular and area measurements together with non-dimensional ratios were calculated. Eighteen parameters were found to be significantly different between CMI and control subjects. Smaller posterior cranial fossa (PCF) area in CMI subjects was attributed to a smaller PCF area anterior to the brainstem. The cerebellar area was found to be larger in CMI subjects as compared to controls (15.1%), even without inclusion of the tonsillar area below the foramen magnum (FM) (8.4%). The larger cerebellar area in CMI subjects was due to cranial-caudal elongation of the cerebellum, predominately below the fastigium. The cerebrospinal fluid spaces below the FM were smaller in CMI subjects as compared to controls. Overall, greater cerebellar crowding was identified in CMI subjects relative to healthy controls. These observations may improve our understanding of the pathophysiology of CMI in adult female patients.

A Retrospective 2D Morphometric Analysis of Adult Female Chiari Type I Patients with Commonly Reported and Related Conditions.

Purpose: Researchers have sought to better understand Chiari type I malformation (CMI) through morphometric measurements beyond tonsillar position (TP). Soft tissue and bone structures within the brain and craniocervical junction have been shown to be different for CMI patients compared to healthy controls. Yet, several morphological characteristics have not been consistently associated with CMI. CMI is also associated with different prevalent conditions (PCs) such as syringomyelia, pseudotumor, Ehlers-Danlos syndrome (EDS), scoliosis, and craniocervical instability. The goal of this study was two-fold: (1) to identify unique morphological characteristics of PCs, and (2) to better explain inconsistent results from case-control comparisons of CMI. Methods: Image, demographic, and PC information was obtained through the Chiari1000, a self-report web-accessed database. Twenty-eight morphometric measurements (MMs) were performed on the cranial MR images of 236 pre-surgery adult female CMI participants and 140 female healthy control participants. Custom software was used to measure 28 structures within the posterior cranial fossa (PCF) compartment, craniocervical junction, oral cavity, and intracranial area on midsagittal MR images for each participant. Results: Morphometric analysis of adult females indicated a smaller McRae line length in CMI participants with syringomyelia compared to those without syringomyelia. TP was reduced in CMI participants with EDS than those without EDS. Basion to posterior axial line was significantly longer in CMI participants with scoliosis compared to those without scoliosis. No additional MMs were found to differ between CMI participants with and without a specific PC. Four morphometric differences were found to be consistently different between CMI participants and healthy controls regardless of PC: larger TP and a smaller clivus length, fastigium, and corpus callosum height in CMI participants. Conclusion: Syringomyelia, EDS, and scoliosis were the only PCs that showed significant morphometric differences between CMI participants. Additionally, four midsagittal MR-based MMs were found to be significantly different between healthy controls and CMI participants regardless of the presence of one or more PCs. This study suggests that the prevalence of comorbid conditions are not strongly related to CMI morphology, and that inconsistent findings in the radiographic literature cannot be explained by varying prevalence of comorbid conditions in CMI study samples.

A morphometric assessment of type I Chiari malformation above the McRae line: A retrospective case-control study in 302 adult female subjects.

PURPOSE: Type I Chiari malformation (CMI) is a radiologically-defined structural dysmorphism of the hindbrain and posterior cranial fossa (PCF). Traditional radiographic identification of CMI relies on the measurement of the cerebellar tonsils in relation to the foramen magnum with or without associated abnormalities of the neuraxis. The primary goal of this retrospective study was to comprehensively assess morphometric parameters above the McRea line in a group of female CMI patients and normal controls. MATERIAL AND METHODS: Twenty-nine morphological measurements were taken on 302 mid-sagittal MR images of adult female CMI patients (n=162) and healthy controls (n=140). All MR images were voluntarily provided by CMI subjects through an online database and control participant images were obtained through the Human Connectome Project and a local hospital system. RESULTS: Analyses were performed on the full dataset of adult female MR images and a restricted dataset of 229 participants that were equated for age, race, and body mass index. Eighteen group differences were identified in the PCF area that we grouped into three clusters; PCF structures heights, clivus angulation, and odontoid process irregularity. Fourteen group differences persisted after equating our CMI and control groups on demographic characteristics. CONCLUSION: PCF structures reliably differ in adult female CMI patients relative to healthy controls. These differences reflect structural abnormalities in the osseous and soft tissue structures of the clivus, odontoid process, and cerebellum. Clinical and pathophysiological implications are discussed.