Estimating the viscoelastic properties of the human brain at 7 T MRI using intrinsic MRE and nonlinear inversion

Intrinsic actuation magnetic resonance elastography (MRE) is a phase-contrast MRI technique that allows for in vivo quantification of mechanical properties of the brain by exploiting brain motion that arise naturally due to the cardiac pulse. The mechanical properties of the brain reflect its tissue microstructure, making it a potentially valuable parameter in studying brain disease. The main purpose of this study was to assess the feasibility of reconstructing the viscoelastic properties of the brain using high-quality 7 T MRI displacement measurements, obtained using displacement encoding with stimulated echoes (DENSE) and intrinsic actuation. The repeatability and sensitivity of the method for detecting normal regional variation in brain tissue properties was assessed as secondary goal. The displacement measurements used in this analysis were previously acquired for a separate study, where eight healthy subjects (27 ± 7 years) were imaged with repeated scans (spatial resolution approx. 2 mm isotropic, temporal resolution 75 ms, motion sensitivity 0.35 mm/2π for displacements in anterior–posterior and left–right directions, and 0.7 mm/2π for feet–head displacements). The viscoelastic properties of the brain were estimated using a subzone based non-linear inversion scheme. The results show comparable consistency to that of extrinsic MRE between the viscoelastic property maps obtained from repeated displacement measurements. The shear stiffness maps showed fairly consistent spatial patterns. The whole-brain repeatability coefficient (RC) for shear stiffness was (mean ± standard deviation) 8 ± 8% relative to the mean whole-brain stiffness, and the damping ratio RC was 28 ± 17% relative to the whole-brain damping ratio. The shear stiffness maps showed similar statistically significant regional trends as demonstrated in a publicly available atlas of viscoelastic properties obtained with extrinsic actuation MRE at 50 Hz. The damping ratio maps showed less consistency, likely due to data-model mismatch of describing the brain as a viscoelastic material under low frequencies. While artifacts induced by fluid flow within the brain remain a limitation of the technique in its current state, intrinsic actuation based MRE allow for consistent and repeatable estimation of the mechanical properties of the brain. The method provides enough sensitivity to investigate regional variation in such properties in the normal brain, which is likely sufficient to also investigate pathological changes

Clinical applications of 7T MRI in the brain

AbstractThis review illustrates current applications and possible future directions of 7Tesla (7T) Magnetic Resonance Imaging (MRI) in the field of brain MRI, in clinical studies as well as clinical practice. With its higher signal-to-noise (SNR) and contrast-to-noise ratio (CNR) compared to lower field strengths, high resolution, contrast-rich images can be obtained of diverse pathologies, like multiple sclerosis (MS), brain tumours, aging-related changes and cerebrovascular diseases. In some of these diseases, additional pathophysiological information can be gained compared to lower field strengths. Because of clear depiction of small anatomical details, and higher lesion conspicuousness, earlier diagnosis and start of treatment of brain diseases may become possible. Furthermore, additional insight into the pathogenesis of brain diseases obtained with 7T MRI could be the basis for new treatment developments. However, imaging at high field comes with several limitations, like inhomogeneous transmit fields, a higher specific absorption rate (SAR) and, currently, extensive contraindications for patient scanning. Future studies will be aimed at assessing the advantages and disadvantages of 7T MRI over lower field strengths in light of clinical applications, specifically the additional diagnostic and prognostic value of 7T MRI

Abnormalities in cardiac-induced brain tissue deformations are now detectable with MRI: A case-report of a patient who underwent craniotomy after trauma

Background: Heartbeat and respiration induce cyclic brain tissue deformations, which receive increasing attention as potential driving force for brain clearance. These deformations can now be assessed using a novel 3D strain tensor imaging (STI) method at 7 T MRI. Methods: An 18-year-old man had suffered a traumatic brain injury and was treated with a craniotomy with a maximal diameter of 12 cm. STI was employed to capture cardiac-induced brain tissue deformations and additional time-resolved 2D flow measurements were acquired to capture cerebrospinal fluid (CSF) flow towards the spinal canal. Results: The craniotomy caused major changes in all aspects of the brain's mechanical dynamics as compared to healthy volunteer references. Tissue strains increased, particularly around the craniotomy, and directionality of deformations showed large abnormalities, also in the contralateral hemisphere. As the brain tissue could pulsate outward from the skull, physiological pulsatile CSF flow at the foramen magnum was abolished. Conclusions: This work illustrates how STI can assess physiological patterns of brain tissue deformation and how craniotomy leads to widespread deformation abnormalities that can be detected at a single patient level. While this case is meant to provide proof of concept, application of STI in other conditions of abnormal brain mechanical dynamics warrants further study

Velocity Pulsatility and Arterial Distensibility Along the Internal Carotid Artery

Background Attenuation of velocity pulsatility along the internal carotid artery (ICA) is deemed necessary to protect the microvasculature of the brain. The role of the carotid siphon within the whole ICA trajectory in pulsatility attenuation is still poorly understood. This study aims to assess arterial variances in velocity pulsatility and distensibility over the whole ICA trajectory, including effects of age and sex. Methods and Results We assessed arterial velocity pulsatility and distensibility using flow-sensitized 2-dimensional phase-contrast 3.0 Tesla magnetic resonance imaging in 118 healthy participants. Velocity pulsatility index (vPI=(Vmax-Vmin)/Vmean) and arterial distensibility defined as area pulsatility index (Amax-Amin)/Amean) were calculated at C1, C3, and C7 segments of the ICA. vPI increased between C1 and C3 (0.85±0.13 versus 0.93±0.13, P<0.001 for averaged right+left ICA) and decreased between C3 and C7 (0.93±0.13 versus 0.84±0.13, P<0.001) with overall no effect (C1-C7). Conversely, the area pulsatility index decreased between C1 and C3 (0.18±0.06 versus 0.14±0.04, P<0.001) and increased between C3 and C7 (0.14±0.04 versus 0.31±0.09, P<0.001). vPI in men is higher than in women and increases with age (P<0.015). vPI over the carotid siphon declined with age but remained stable over the whole ICA trajectory. Conclusions Along the whole ICA trajectory, vPI increased from extracranial C1 up to the carotid siphon C3 with overall no effect on vPI between extracranial C1 and intracranial C7 segments. This suggests that the bony carotid canal locally limits the arterial distensibility of the ICA, increasing the vPI at C3 which is consequently decreased again over the carotid siphon. In addition, vPI in men is higher and increases with age

Histopathology of Cerebral Microinfarcts and Microbleeds in Spontaneous Intracerebral Hemorrhage

In patients with spontaneous intracerebral hemorrhage caused by different vasculopathies, cerebral microinfarcts have the same aspect on MRI and the same applies to cerebral microbleeds. It is unclear what pathological changes underlie these cerebral microinfarcts and cerebral microbleeds. In the current study, we explored the histopathological substrate of these lesions by investigating the brain tissue of 20 patients (median age at death 77 years) who died from ICH (9 lobar, 11 non-lobar) with a combination of post-mortem 7-T MRI and histopathological analysis. We identified 132 CMIs and 204 CMBs in 15 patients on MRI, with higher numbers of CMIs in lobar ICH patients and similar numbers of CMBs. On histopathology, CMIs and CMBs were in lobar ICH more often located in the superficial than in the deep layers of the cortex, and in non-lobar ICH more often in the deeper layers. We found a tendency towards more severe CAA scores in lobar ICH patients. Other histopathological characteristics were comparable between lobar and non-lobar ICH patients. Although CMIs and CMBs were found in different segments of the cortex in lobar ICH compared to non-lobar ICH patients, otherwise similar histopathological features of cortical CMIs and CMBs distant from the ICH suggest shared pathophysiological mechanisms in lobar and non-lobar ICH caused by different vasculopathies

Hemodynamic Parameters in the Parent Arteries of Unruptured Intracranial Aneurysms Depend on Aneurysm Size and Are Different Compared to Contralateral Arteries: A 7 Tesla 4D Flow MRI Study

Background: Different Circle of Willis (CoW) variants have variable prevalences of aneurysm development, but the hemodynamic variation along the CoW and its relation to presence and size of unruptured intracranial aneurysms (UIAs) are not well known. Purpose: Gain insight into hemodynamic imaging markers of the CoW for UIA development by comparing these outcomes to the corresponding contralateral artery without an UIA using 4D flow magnetic resonance imaging (MRI). Study Type: Retrospective, cross-sectional study. Subjects: Thirty-eight patients with an UIA, whereby 27 were women and a mean age of 62 years old. Field Strength/Sequence: Four-dimensional phase-contrast (PC) MRI with a 3D time-resolved velocity encoded gradient echo sequence at 7 T. Assessment: Hemodynamic parameters (blood flow, velocity pulsatility index [vPI], mean velocity, distensibility, and wall shear stress [peak systolic (WSSMAX), and time-averaged (WSSMEAN)]) in the parent artery of the UIA were compared to the corresponding contralateral artery without an UIA and were related to UIA size. Statistical Tests: Paired t-tests and Pearson Correlation tests. The threshold for statistical significance was P < 0.05 (two-tailed). Results: Blood flow, mean velocity, WSSMAX, and WSSMEAN were significantly higher, while vPI was lower, in the parent artery relative to contralateral artery. The WSSMAX of the parent artery significantly increased linearly while the WSSMEAN decreased linearly with increasing UIA size. Conclusions: Hemodynamic parameters and WSS differ between parent vessels of UIAs and corresponding contralateral vessels. WSS correlates with UIA size, supporting a potential hemodynamic role in aneurysm pathology. Level of Evidence: 2. Technical Efficacy: Stage 2

CADASIL Affects Multiple Aspects of Cerebral Small Vessel Function on 7T-MRI

International audienceObjective: Cerebral small vessel diseases (cSVDs) are a major cause of stroke and dementia. We used cutting-edge 7T-MRI techniques in patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), to establish which aspects of cerebral small vessel function are affected by this monogenic form of cSVD. Methods: We recruited 23 CADASIL patients (age 51.1 AE 10.1 years, 52% women) and 13 age-and sex-matched controls (46.1 AE 12.6, 46% women). Small vessel function measures included: basal ganglia and centrum semiovale perforating artery blood flow velocity and pulsatility, vascular reactivity to a visual stimulus in the occipital cortex and reactivity to hypercapnia in the cortex, subcortical gray matter, white matter, and white matter hyperintensities. Results: Compared with controls, CADASIL patients showed lower blood flow velocity and higher pulsatility index within perforating arteries of the centrum semiovale (mean difference À 0.09 cm/s, p = 0.03 and 0.20, p = 0.009) and basal ganglia (mean difference À 0.98 cm/s, p = 0.003 and 0.17, p = 0.06). Small vessel reactivity to a short visual stimulus was decreased (blood-oxygen-level dependent [BOLD] mean difference À0.21%, p = 0.04) in patients, while reactivity to hypercapnia was preserved in the cortex, subcortical gray matter, and normal appearing white matter. Among patients, reactivity to hypercapnia was decreased in white matter hyperintensities compared to normal appearing white matter (BOLD mean difference À0.29%, p = 0.02). Interpretation: Multiple aspects of cerebral small vessel function on 7T-MRI were abnormal in CADASIL patients, indicative of increased arteriolar stiffness and regional abnormalities in reactivity, locally also in relation to white matter injury. These observations provide novel markers of cSVD for mechanistic and intervention studies

Zooming in on cerebral small vessel function in small vessel diseases with 7T MRI: Rationale and design of the “ZOOM@SVDs” study

Background: Cerebral small vessel diseases (SVDs) are a major cause of stroke and dementia. Yet, specific treatment strategies are lacking in part because of a limited understanding of the underlying disease processes. There is therefore an urgent need to study SVDs at their core, the small vessels themselves. Objective: This paper presents the rationale and design of the ZOOM@SVDs study, which aims to establish measures of cerebral small vessel dysfunction on 7T MRI as novel disease markers of SVDs. Methods: ZOOM@SVDs is a prospective observational cohort study with two years follow-up. ZOOM@SVDs recruits participants with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL, N = 20), sporadic SVDs (N = 60), and healthy controls (N = 40). Participants undergo 7T brain MRI to assess different aspects of small vessel function including small vessel reactivity, cerebral perforating artery flow, and pulsatility. Extensive work-up at baseline and follow-up further includes clinical and neuropsychological assessment as well as 3T brain MRI to assess conventional SVD imaging markers. Measures of small vessel dysfunction are compared between patients and controls, and related to the severity of clinical and conventional MRI manifestations of SVDs. Discussion: ZOOM@SVDs will deliver novel markers of cerebral small vessel function in patients with monogenic and sporadic forms of SVDs, and establish their relation with disease burden and progression. These small vessel markers can support etiological studies in SVDs and may serve as surrogate outcome measures in future clinical trials to show target engagement of drugs directed at the small vessels