Cerebrospinal Fluid Flow and Brain Motion in Chiari I Malformation: Past, Present, and Future.

Cranio-spinal volume and pressure changes associated with the cardiac-cycle and respiration are altered in Chiari I malformation (CMI) due to obstruction of cerebrospinal fluid (CSF) flow at the foramen magnum. With the introduction of motion-sensitive MRI sequences, it was envisioned that these could provide noninvasive information about volume-pressure dynamics at the cranio-cervical junction in CMI hitherto available only through invasive pressure measurements. Since the early 1990s, multiple studies have assessed CSF flow and brain motion in CMI. However, differences in design and varied approaches in the presentation of results and conclusions makes it difficult to fully comprehend the role of MR imaging of CSF flow and brain motion in CMI. In this review, a cohesive summary of the current status of MRI assessment of CSF flow and brain motion in CMI is presented. Simplified versions of the results and conclusions of previous studies are presented by dividing the studies in distinct topics: 1) comparing CSF flow and brain motion between healthy subjects (HS) and CMI patients (before and after surgery), 2) comparing CSF flow and brain motion to CMI severity and symptoms, and 3) comparing CSF flow and brain motion in CMI with and without syringomyelia. Finally, we will discuss our vision of the future directions of MR imaging in CMI patients. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: 5.

Relationship of Morphometrics and Symptom Severity in Female Type I Chiari Malformation Patients with Biological Resilience.

In the present study we report the relationship among MRI-based skull and cervical spine morphometric measures as well as symptom severity (disability-as measured by Oswestry Head and Neck Pain Scale and social isolation-as measured by the UCLA Loneliness scale) on biomarkers of allostatic load using estrogen, interleukin-6, C-reactive protein, and cortisol in a sample of 46 CMI patients. Correlational analyses showed that McRae line length was negatively associated with interleukin-6 and C-reactive protein levels, and Analysis of Variance (ANOVA) showed joint effects of morphometric measures (McRae line length, anterior CSF space) and symptom severity (disability and loneliness) on estrogen and intereukin-6 levels. These results are consistent with allostatic load. That is, when the combination of CSF crowding and self-report symptom (disability and loneliness) severity exceed the capacity of biological resilience factors, then biomarkers such as neuroprotective estrogen levels drop, rather than rise, with increasing symptom severity.

Association between resistance to cerebrospinal fluid flow and cardiac-induced brain tissue motion for Chiari malformation type I.

PURPOSE: Chiari malformation type I (CMI) patients have been independently shown to have both increased resistance to cerebrospinal fluid (CSF) flow in the cervical spinal canal and greater cardiac-induced neural tissue motion compared to healthy controls. The goal of this paper is to determine if a relationship exists between CSF flow resistance and brain tissue motion in CMI subjects. METHODS: Computational fluid dynamics (CFD) techniques were employed to compute integrated longitudinal impedance (ILI) as a measure of unsteady resistance to CSF flow in the cervical spinal canal in thirty-two CMI subjects and eighteen healthy controls. Neural tissue motion during the cardiac cycle was assessed using displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) technique. RESULTS: The results demonstrate a positive correlation between resistance to CSF flow and the maximum displacement of the cerebellum for CMI subjects (r = 0.75, p = 6.77 × 10-10) but not for healthy controls. No correlation was found between CSF flow resistance and maximum displacement in the brainstem for CMI or healthy subjects. The magnitude of resistance to CSF flow and maximum cardiac-induced brain tissue motion were not statistically different for CMI subjects with and without the presence of five CMI symptoms: imbalance, vertigo, swallowing difficulties, nausea or vomiting, and hoarseness. CONCLUSION: This study establishes a relationship between CSF flow resistance in the cervical spinal canal and cardiac-induced brain tissue motion in the cerebellum for CMI subjects. Further research is necessary to understand the importance of resistance and brain tissue motion in the symptomatology of CMI.

Impact of Blood Rheology on Transition to Turbulence and Wall Vibration Downstream of a Stenosis.

Previous experimental flow studies have demonstrated a delay (∼20%) in transition to turbulence for whole blood compared to a Newtonian analog fluid in both a straight pipe and eccentric stenosis model with ridged walls. The impact of wall compliance on the transition to turbulence of blood compared to Newtonian analog and on wall vibration is unknown. The present study employed flexible walls downstream of an eccentric stenosis model and examined the wall vibration during the transition to turbulence with whole blood and a Newtonian analog. Measurements of tube wall vibration velocity (WVV) were used as an indicator of the turbulence level within the flexible tube. WVV was measured at 5, 10, and 15 diameters downstream of the stenosis using a laser Doppler vibrometer at Reynolds numbers 0, 200, 300, 350, 400, 450, 500, 550, 600, 650, 700, and 750. The root mean squares (RMS) of the measured WVV were utilized as an indirect measure of fluid velocity fluctuations present at that location, and hence, an indicator of transition to turbulence. WVV RMS was near-constant until approximately Reynolds number 400. It increased monotonically with Reynolds number for both whole blood and the Newtonian fluid. No differences in the transition to turbulence were observed between whole blood and the Newtonian fluid, as the WVV RMS curves were remarkably similar in shape. This result suggests that rheology had minimal impact on the WVV downstream of a stenosis for transition to turbulence since the fluids had a similar level of vibration.

The Relationship Between Imbalance Symptom and Cardiac Pulsation Induced Mechanical Strain in the Brainstem and Cerebellum for Chiari Malformation Type I.

Chiari malformation Type I (CMI) is known to have an altered biomechanical environment for the brainstem and cerebellum; however, it is unclear whether these altered biomechanics play a role in the development of CMI symptoms. We hypothesized that CMI subjects have a higher cardiac-induced strain in specific neurological tracts pertaining to balance, and postural control. We measured displacement over the cardiac cycle using displacement encoding with stimulated echoes magnetic resonance imaging in the cerebellum, brainstem, and spinal cord in 37 CMI subjects and 25 controls. Based on these measurements, we computed strain, translation, and rotation in tracts related to balance. The global strain on all tracts was small (<1%) for CMI subject and controls. Strain was found to be nearly doubled in three tracts for CMI subjects compared to controls (p < 0.03). The maximum translation and rotation were ∼150 µm and ∼1 deg, respectively and 1.5-2 times greater in CMI compared to controls in four tracts (p < 0.005). There was no significant difference between strain, translation, and rotation on the analyzed tracts in CMI subjects with imbalance compared to those without imbalance. A moderate correlation was found between cerebellar tonsillar position and strain on three tracts. The lack of statistically significant difference between strain in CMI subjects with and without imbalance could imply that the magnitude of the observed cardiac-induced strain was too small to cause substantial damage to the tissue (<1%). Activities such as coughing, or Valsalva may produce a greater strain.

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.

MRI findings differentiating tonsillar herniation caused by idiopathic intracranial hypertension from Chiari I malformation.

PURPOSE: Some patients with idiopathic intracranial hypertension (IIH) have cerebellar tonsillar herniation ≥ 5 mm mimicking Chiari malformation I (CMI), which can result in misdiagnosis and unjustified treatment. Our purpose was to identify IIH patients with tonsillar herniation ≥ 5 mm (IIHTH) and compare with CMI patients to assess imaging findings that could distinguish the two conditions. METHODS: Ninety-eight patients with IIH, 81 patients with CMI, and 99 controls were retrospectively assessed. Two neuroradiologists blindly reviewed MR images. IIHTH patients were compared with CMI patients and controls regarding the extent of tonsillar herniation (ETH), bilateral transverse sinus stenosis (BTSS), hypophysis-sella ratio (HSR), and bilateral tortuosity of optic nerve (BTON). RESULTS: 13/98 (13.2%) IIH patients had tonsillar herniation ≥ 5 mm (IIHTH) and were significantly younger and had higher BMI compared with CMI patients and controls. ETH was significantly less in the IIHTH than CMI (6.5 ± 2.4 mm vs. 10.9 ± 4.4 mm; p < 0.001). BTSS and HSR < 0.5 were more common in IIHTH than CMI (p < 0.001 and p = 0.003, respectively). No differences were seen between CMI and controls. BTON was significantly more common in IIHTH compared to control (p = 0.01) but not to the CMI (p = 0.36). Sensitivity and specificity to differentiate IIHTH from CMI were 69.2% and 96.1% for BTSS and 69.2% and 75.3% for HSR < 0.5. CONCLUSION: The presence of BTSS and/or HSR < 0.5 in patients with ETH ≥ 5 mm should suggest further evaluation to exclude IIH before considering CMI surgery.

Transition to Turbulence Downstream of a Stenosis for Whole Blood and a Newtonian Analog Under Steady Flow Conditions.

Blood, a multiphase fluid comprised of plasma, blood cells, and platelets, is known to exhibit a shear-thinning behavior at low shear rates and near-Newtonian behavior at higher shear rates. However, less is known about the impact of its multiphase nature on the transition to turbulence. In this study, we experimentally determined the critical Reynolds number at which the flow began to transition to turbulence downstream of eccentric stenosis for whole porcine blood and a Newtonian blood analog (water-glycerin mixture). Velocity profiles for both fluids were measured under steady-state flow conditions using an ultrasound Doppler probe placed 12 diameters downstream of eccentric stenosis. Velocity was recorded at 21 locations along the diameter at 11 different flow rates. Normalized turbulent kinetic energy was used to determine the critical Reynolds number for each fluid. Blood rheology was measured before and after each experiment. Tests were conducted on five samples of each fluid inside a temperature-controlled in vitro flow system. The viscosity at a shear rate of 1000 s-1 was used to define the Reynolds number for each fluid. The mean critical Reynolds numbers for blood and water-glycerin were 470 ± 27.5 and 395 ± 10, respectively, indicating a ∼19% delay in transition to turbulence for whole blood compared to the Newtonian fluid. This finding is consistent with a previous report for steady flow in a straight pipe, suggesting some aspect of blood rheology may serve to suppress, or at least delay, the onset of turbulence in vivo.

Influence of Pain on Cognitive Dysfunction and Emotion Dysregulation in Chiari Malformation Type I.

It has been well demonstrated that the cerebellum is associated with cognitive and affective processing as well as the traditionally conceptualized motor function. In the present chapter, we explore the behavioral and neurobiological implications of a common congenital cerebellar condition, Chiari malformation Type I, on cognitive and affective processing. We also emphasize the associations between Chiari-related chronic pain, cognitive dysfunction, and emotion dysregulation. Based on our review of the literature, we argue that chronic pain can account for a substantial amount of the cognitive dysfunction and emotion dysregulation in Chiari malformation Type I. Yet, there also exists aspects of Chiari-related cognitive dysfunction and emotion dysregulation that appear to be at least partially independent of chronic pain and more directly associated with abnormalities in cerebrospinal fluid flow dynamics and cerebro-cerebellar communication pathways.

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.

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.

Imaging and health metrics in incidental cerebellar tonsillar ectopia: findings from the Adolescent Brain Cognitive Development Study (ABCD).

PURPOSE: Incidental cerebellar tonsillar ectopia (ICTE) that meets the radiographic criterion for Chiari malformation type I (CMI) is an increasingly common finding in the clinical setting, but its significance is unclear. The present study examined posterior cranial fossa (PCF) morphometrics and a broad range of health instruments of pediatric ICTE cases and matched controls extracted from the Adolescent Brain Cognitive Development (ABCD) dataset. METHODS: One-hundred-six subjects with ICTE and 106 matched controls without ICTE were identified from 11,411 anatomical MRI of healthy screened pediatric subjects from the ABCD project. Subjects were matched by sex, age, body mass index, race, and ethnicity. Twenty-two brain morphometrics and 22 health instruments were compared between the two groups to identify unrecognized CMI symptoms and assess the general health impact of ICTE. RESULTS: Twelve and 15 measures were significantly different between the ICTE and control groups for females and males, respectively. Notably, for females, the anterior CSF space was significantly smaller (p = 0.00005) for the ICTE group than controls. For males, the clivus bone length was significantly shorter (p = 0.0002) for the ICTE group compared to controls. No significant differences were found among the 22 health instruments between the two groups. CONCLUSION: This study demonstrated that pediatric ICTE subjects have similar PCF morphometrics to adult CMI. ICTE alone did not appear to cause any unrecognized CMI symptoms and had no impact on the subjects' current mental, physical, or behavioral health. Still, given their cranial and brain morphology, these cases may be at risk for adult-onset symptomatic CMI.

Association Between Resistance to Cerebrospinal Fluid Flow Near the Foramen Magnum and Cough-Associated Headache in Adult Chiari Malformation Type I.

Cough-associated headaches (CAHs) are thought to be distinctive for Chiari malformation type I (CMI) patients and have been shown to be related to the motion of cerebrospinal fluid (CSF) near the foramen magnum (FM). We used computational fluid dynamics (CFD) to compute patient-specific resistance to CSF motion in the spinal canal for CMI patients to determine its accuracy in predicting CAH. Fifty-one symptomatic CMI patients with cerebellar tonsillar position (CTP) ≥ 5 mm were included in this study. The patients were divided into two groups based on their symptoms (CAH and non-CAH) by review of the neurosurgical records. CFD was utilized to simulate CSF motion, and the integrated longitudinal impedance (ILI) was calculated for all patients. A receiver operating characteristic (ROC) curve was evaluated for its accuracy in predicting CAH. The ILI for CMI patients with CAH (776 dyn/cm5, 288-1444 dyn/cm5; median, interquartile range) was significantly larger compared to non-CAH (285 dyn/cm5, 187-450 dyn/cm5; p = 0.001). The ILI was more accurate in predicting CAH in CMI patients than the CTP when the comparison was made using the area under the ROC curve (AUC) (0.77 and 0.70, for ILI and CTP, respectively). ILI ≥ 750 dyn/cm5 had a sensitivity of 50% and a specificity of 95% in predicting CAH. ILI is a parameter that is used to assess CSF blockage in the spinal canal and can predict patients with and without CAH with greater accuracy than CTP.

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 of Neural Microstructure Abnormalities in Type I Chiari Malformation: Associations Among Fiber Tract Integrity, Pain, and Cognitive Dysfunction.

BACKGROUND: Previous case-control investigations of type I Chiari malformation (CMI) have reported cognitive deficits and microstructural white matter abnormalities, as measured by diffusion tensor imaging (DTI). CMI is also typically associated with pain, including occipital headache, but the relationship between pain symptoms and microstructure is not known. METHODS: Eighteen CMI patients and 18 adult age- and education-matched control participants underwent DTI, were tested using digit symbol coding and digit span tasks, and completed a self-report measure of chronic pain. Tissue microstructure indices were used to examine microstructural abnormalities in CMI as compared with healthy controls. Group differences in DTI parameters were then reassessed after controlling for self-reported pain. Finally, DTI parameters were correlated with performance on the digit symbol coding and digit span tasks within each group. RESULTS: CMI patients exhibited greater fractional anisotropy (FA), lower radial diffusivity, and lower mean diffusivity in multiple brain regions compared with controls in diffuse white matter regions. Group differences no longer existed after controlling for self-reported pain. A significant correlation between FA and the Repeatable Battery for the Assessment of Neuropsychological Status coding performance was observed for controls but not for the CMI group. CONCLUSIONS: Diffuse microstructural abnormalities appear to be a feature of CMI, manifesting predominantly as greater FA and less diffusivity on DTI sequences. These white matter changes are associated with the subjective pain experience of CMI patients and may reflect reactivity to neuroinflammatory responses. However, this hypothesis will require further deliberate testing in future studies.

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.

An Electrophysiological Study of Cognitive and Emotion Processing in Type I Chiari Malformation.

Type I Chiari malformation (CMI) is a neurological condition in which the cerebellar tonsils descend into the cervical spinal subarachnoid space resulting in cervico-medullary compression. Early case-control investigations have indicated cognitive deficits in the areas of attention, memory, processing speed, and visuospatial function. The present study further examined cognitive and emotional processing deficits associated with CMI using a dual-task paradigm. Nineteen CMI patients were recruited during pre-surgical consultation and 19 matched control participants identified emotional expressions in separate single and asynchronous dual-task designs. To extend earlier behavioral studies of cognitive effects in CMI, we recorded event-related potentials (ERPs) in the dual-task design. Though response times were slower for CMI patients across the two tasks, behavioral and ERP analyses indicated that patients did not differ from matched controls in the ability to allocate attentional resources between the two tasks. P1 ERP component analyses provided no indication of an emotional arousal deficit in our CMI sample while P3 ERP component analyses suggested a CMI-related deficit in emotional regulation. P3 analysis also yielded evidence for a frontalization of neurophysiological activity in CMI patients. Pain and related depression and anxiety factors accounted for CMI deficits in single-task, but not dual-task, response times. Results are consistent with a dysfunctional fronto-parietal attentional network resulting from either the indirect effects of chronic pain or the direct effects of CMI pathophysiology stemming from cervico-medullary compression.

Regional Quantification of Brain Tissue Strain Using Displacement-Encoding With Stimulated Echoes Magnetic Resonance Imaging.

Intrinsic cardiac-induced deformation of brain tissue is thought to be important in the pathophysiology of various neurological disorders. In this study, we evaluated the feasibility of utilizing displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) to quantify two-dimensional (2D) neural tissue strain using cardiac-driven brain pulsations. We examined eight adult healthy volunteers with an electrocardiogram-gated spiral DENSE sequence performed at the midsagittal plane on a 3 Tesla MRI scanner. Displacement, pixel-wise trajectories, and principal strains were determined in seven regions of interest (ROI): the brain stem, cerebellum, corpus callosum, and four cerebral lobes. Quantification of small neural tissue motion and strain along with their spatial and temporal variations in different brain regions was found to be feasible using DENSE. The medial and inferior brain structures (brain stem, cerebellum, and corpus callosum) had significantly larger motion and strain compared to structures located more peripherally. The brain stem had the largest peak mean displacement (PMD) (187 ± 50 µm, mean ± SD). The largest mean principal strains in compression and extension were observed in the brain stem (0.38 ± 0.08%) and the corpus callosum (0.37 ± 0.08%), respectively. Measured values in percent strain were altered by as much as 0.1 between repeated scans. This study showed that DENSE can quantify regional variations in brain tissue motion and strain and has the potential to be utilized as a tool to evaluate the changes in brain tissue dynamics resulting from alterations in biomechanical stresses and tissue properties.

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.

Quantifying the influence of respiration and cardiac pulsations on cerebrospinal fluid dynamics using real-time phase-contrast MRI.

PURPOSE: To validate a real-time phase contrast magnetic resonance imaging (RT-PCMRI) sequence in a controlled phantom model, and to quantify the relative contributions of respiration and cardiac pulsations on cerebrospinal fluid (CSF) velocity at the level of the foramen magnum (FM). MATERIALS AND METHODS: To validate the 3T MRI techniques, in vitro studies used a realistic model of the spinal subarachnoid space driven by pulsatile flow waveforms mimicking the respiratory and cardiac components of CSF flow. Subsequently, CSF flow was measured continuously during 1-minute RT-PCMRI acquisitions at the FM while healthy subjects (N = 20) performed natural breathing, deep breathing, breath-holding, and coughing. Conventional cardiac-gated PCMRI was obtained for comparison. A frequency domain power ratio analysis determined the relative contribution of respiration versus cardiac ([r/c]) components of CSF velocity. RESULTS: In vitro studies demonstrating the accuracy of RT-PCMRI within 5% of input values showed that conventional PCMRI measures only the cardiac component of CSF velocity (0.42 ± 0.02 cm/s), averages out respiratory effects, and underestimates the magnitude of CSF velocity (0.96 ± 0.07 cm/s). In vivo RT-PCMRI measurements indicated the ratio of respiratory to cardiac velocity pulsations averaged over all subjects as [r/c = 0.14 ± 0.27] and [r/c = 0.40 ± 0.47] for natural and deep breathing, respectively. During coughing, the peak CSF velocity increased by a factor of 2.27 ± 1.40. CONCLUSION: RT-PCMRI can noninvasively measure instantaneous CSF velocity driven by cardiac pulsations, respiration, and coughing in real time. A comparable contribution of respiration and cardiac pulsations on CSF velocity was found during deep breathing but not during natural breathing. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:431-439.