CO2 as an engine for neurofluid flow: Exploring the coupling between vascular reactivity, brain clearance, and changes in tissue properties.

The brain relies on an effective clearance mechanism to remove metabolic waste products for the maintenance of homeostasis. Recent studies have focused on elucidating the forces that drive the motion of cerebrospinal fluid (CSF), responsible for removal of these waste products. We demonstrate that vascular responses evoked using controlled manipulations of partial pressure of carbon dioxide (PaCO2 ) levels, serve as an endogenous driver of CSF clearance from the brain. To demonstrate this, we retrospectively surveyed our database, which consists of brain metastases patients from whom blood oxygen level-dependent (BOLD) images were acquired during targeted hypercapnic and hyperoxic respiratory challenges. We observed a correlation between CSF inflow signal around the fourth ventricle and CO2 -induced changes in cerebral blood volume. By contrast, no inflow signal was observed in response to the nonvasoactive hyperoxic stimulus, validating our measurements. Moreover, our results establish a link between the rate of the hemodynamic response (to elevated PaCO2 ) and peritumoral edema load, which we suspect may affect CSF flow, consequently having implications for brain clearance. Our expanded perspective on the factors involved in neurofluid flow underscores the importance of considering both cerebrovascular responses, as well as the brain mechanical properties, when evaluating CSF dynamics in the context of disease processes.

Detectability and accuracy of computational measurements of in-silico and physical representations of enlarged perivascular spaces from magnetic resonance images.

BACKGROUND: Magnetic Resonance Imaging (MRI) visible perivascular spaces (PVS) have been associated with age, decline in cognitive abilities, interrupted sleep, and markers of small vessel disease. But the limits of validity of their quantification have not been established. NEW METHOD: We use a purpose-built digital reference object to construct an in-silico phantom for addressing this need, and validate it using a physical phantom. We use cylinders of different sizes as models for PVS. We also evaluate the influence of 'PVS' orientation, and different sets of parameters of the two vesselness filters that have been used for enhancing tubular structures, namely Frangi and RORPO filters, in the measurements' accuracy. RESULTS: PVS measurements in MRI are only a proxy of their true dimensions, as the boundaries of their representation are consistently overestimated. The success in the use of the Frangi filter relies on a careful tuning of several parameters. Alpha= 0.5, beta= 0.5 and c= 500 yielded the best results. RORPO does not have these requirements and allows detecting smaller cylinders in their entirety more consistently in the absence of noise and confounding artefacts. The Frangi filter seems to be best suited for voxel sizes equal or larger than 0.4 mm-isotropic and cylinders larger than 1 mm diameter and 2 mm length. 'PVS' orientation did not affect measurements in data with isotropic voxels. COMPARISON WITH EXISTENT METHODS: Does not apply. CONCLUSIONS: The in-silico and physical phantoms presented are useful for establishing the validity of quantification methods of tubular small structures.

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.

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.

Assessment of aortic and cerebral haemodynamics and vascular brain injury with 3 and 7†T magnetic resonance imaging in patients with aortic coarctation.

Aims: Coarctation of the aorta (CoA) is characterized by a central arteriopathy resulting in increased arterial stiffness. The condition is associated with an increased risk of stroke. We aimed to assess the aortic and cerebral haemodynamics and the presence of vascular brain injury in patients with previous surgical CoA repair. Methods and results: Twenty-seven patients with CoA (median age 22 years, range 12-72) and 25 age- and sex-matched controls (median age 24 years, range 12-64) underwent 3 T (heart, aorta, and brain) and 7 T (brain) magnetic resonance imaging scans. Haemodynamic parameters were measured using two-dimensional phase-contrast images of the ascending and descending aorta, internal carotid artery (ICA), basilar artery (BA), middle cerebral artery (MCA), and perforating arteries. Vascular brain injury was assessed by rating white matter hyperintensities, cortical microinfarcts, lacunes, and microbleeds. Pulse wave velocities in the aortic arch and descending aorta were increased and ascending aortic distensibility was decreased in patients with CoA vs. controls. Patients with CoA showed a higher mean flow velocity in the right ICA, left ICA, and BA and a reduced distensibility in the right ICA, BA, and left MCA. Haemodynamic parameters in the perforating arteries, total cerebral blood flow, intracranial volumes, and vascular brain injury were similar between the groups. Conclusion: Patients with CoA show an increased flow velocity and reduced distensibility in the aorta and proximal cerebral arteries, which suggests the presence of a generalized arteriopathy that extends into the cerebral arterial tree. No substantial vascular brain injury was observed in this relatively young CoA population, although the study was inadequately powered regarding this endpoint.

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.

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.

Theory for a non-invasive diagnostic biomarker for craniospinal diseases.

Monitoring intracranial pressure (ICP) and craniospinal compliance (CC) is frequently required in the treatment of patients suffering from craniospinal diseases. However, current approaches are invasive and cannot provide continuous monitoring of CC. Dynamic exchange of blood and cerebrospinal fluid (CSF) between cranial and spinal compartments due to cardiac action transiently modulates the geometry and dielectric properties of the brain. The resulting impedance changes can be measured and might be usable as a non-invasive CC surrogate. A numerically robust and computationally efficient approach based on the reciprocity theorem was developed to compute dynamic impedance changes resulting from small geometry and material property changes. The approach was successfully verified against semi-analytical benchmarks, before being combined with experimental brain pulsation data to study the information content of the impedance variation. The results indicate that the measurable signal is dominated by the pulsatile displacement of the cortical brain surface, with minor contributions from the ventricular surfaces and from changes in brain perfusion. Different electrode setups result in complementary information. The information content from the investigated three electrode pairs was employed to successfully infer subject-specific brain pulsation and motion features. This suggests that non-invasive CC surrogates based on impedance monitoring could be established.

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

OBJECTIVE: 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 ± 10.1 years, 52% women) and 13 age- and sex-matched controls (46.1 ± 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 - 0.09 cm/s, p = 0.03 and 0.20, p = 0.009) and basal ganglia (mean difference - 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 -0.21%, 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 -0.29%, 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. ANN NEUROL 2023;93:29-39.

Reliability of velocity pulsatility in small vessels on 3Tesla MRI in the basal ganglia: a test-retest study.

OBJECTIVE: Recent work showed the feasibility of measuring velocity pulsatility in the perforating arteries at the level of the BG using 3T MRI. However, test-retest measurements have not been performed, yet. This study assessed the test-retest reliability of 3T MRI blood flow velocity measurements in perforating arteries in the BG. MATERIALS AND METHODS: Two-dimensional phase-contrast cardiac gated (2D-PC) images were acquired for 35 healthy controls and repeated with and without repositioning. 2D-PC images were processed and analyzed, to assess the number of detected perforating arteries (Ndetected), mean blood flow velocity (Vmean), and velocity pulsatility index (vPI). Paired t-tests and Bland-Altman plots were used to compare variance in outcome parameters with and without repositioning, and limits of agreement (LoA) were calculated. RESULTS: The LoA was smallest for Vmean (35%) and highest for vPI (79%). Test-retest reliability was similar with and without repositioning of the subject. DISCUSSION: We found similar LoA with and without repositioning indicating that the measurement uncertainty is dominated by scanner and physiological noise, rather than by planning. This enables to study hemodynamic parameters in perforating arteries at clinically available scanners, provided sufficiently large sample sizes are used to mitigate the contribution of scanner- and physiological noise.

Dynamic brain ADC variations over the cardiac cycle and their relation to tissue strain assessed with DENSE at high-field MRI.

PURPOSE: The ADC of brain tissue slightly varies over the cardiac cycle. This variation could reflect physiology, including mixing of the interstitial fluid, relevant for brain waste clearance. However, it is known from cardiac diffusion imaging that tissue deformation by itself affects the magnitude of the MRI signal, leading to artificial ADC variations as well. This study investigates to what extent tissue deformation causes artificial ADC variations in the brain. THEORY AND METHODS: We implemented a high-field MRI sequence with stimulated echo acquisition mode that simultaneously measures brain tissue deformation and ADC. Based on the measured tissue deformation, we simulated the artificial ADC variation by combining established theoretical frameworks and compared the results with the measured ADC variation. We acquired data in 8 healthy volunteers with diffusion weighting b = 300 and b = 1000 s/mm2 . RESULTS: Apparent diffusion coefficient variation was largest in the feet-to-head direction and showed the largest deviation from the mean ADC at peak systole. Artificial ADC variation estimated from tissue deformation was 1.3 ± 0.37·10-5  mm2 /s in the feet-to-head direction for gray matter, and 0.75 ± 0.29·10-5  mm2 /s for white matter. The measured ADC variation in the feet-to-head direction was 5.6·10-5 ± 1.5·10-5  mm2 /s for gray matter and 3.2·10-5 ± 1.0·10-5  mm2 /s for white matter, which was a factor of 3.5 ± 0.82 and 3.4 ± 0.57 larger than the artificial diffusion variations. The measured diffusion variations in the right-to-left/anterior-to-posterior direction were a factor of 1.5 ± 1.0/1.7 ± 1.4 and 2.0 ± 0.91/2.5 ± 0.94 larger than the artificial diffusion variations for gray matter and white matter, respectively. CONCLUSION: Apparent diffusion coefficient variations in the brain likely largely reflect physiology.

Does the Internal Carotid Artery Attenuate Blood-Flow Pulsatility in Small Vessel Disease? A 7 T 4D-Flow MRI Study.

BACKGROUND: Increased cerebral blood-flow pulsatility is associated with cerebral small vessel disease (cSVD). Reduced pulsatility attenuation over the internal carotid artery (ICA) could be a contributing factor to the development of cSVD and could be associated with intracranial ICA calcification (iICAC). PURPOSE: To compare pulsatility, pulsatility attenuation, and distensibility along the ICA between patients with cSVD and controls and to assess the association between iICAC and pulsatility and distensibility. STUDY TYPE: Retrospective, explorative cross-sectional study. SUBJECTS: A total of 17 patients with cSVD, manifested as lacunar infarcts or deep intracerebral hemorrhage, and 17 age- and sex-matched controls. FIELD STRENGTH/SEQUENCE: Three-dimensional (3D) T1-weighted gradient echo imaging and 4D phase-contrast (PC) MRI with a 3D time-resolved velocity encoded gradient echo sequence at 7 T. ASSESSMENT: Blood-flow velocity pulsatility index (vPI) and arterial distensibility were calculated for seven ICA segments (C1-C7). iICAC presence and volume were determined from available brain CT scans (acquired as part of standard clinical care) in patients with cSVD. STATISTICAL TESTS: Independent t-tests and linear mixed models. The threshold for statistically significance was P < 0.05 (two tailed). RESULTS: The cSVD group showed significantly higher ICA vPI and significantly lower distensibility compared to controls. Controls showed significant attenuation of vPI over the carotid siphon (-4.9% ± 3.6%). In contrast, patients with cSVD showed no attenuation, but a significant increase of vPI (+6.5% ± 3.1%). iICAC presence and volume correlated positively with vPI (r = 0.578) in patients with cSVD and negatively with distensibility (r = -0.386). CONCLUSION: Decreased distensibility and reduced pulsatility attenuation are associated with increased iICAC and may contribute to cSVD. Confirmation in a larger prospective study is required. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Blood Flow Velocity Pulsatility and Arterial Diameter Pulsatility Measurements of the Intracranial Arteries Using 4D PC-MRI.

4D phase contrast magnetic resonance imaging (PC-MRI) allows for the visualization and quantification of the cerebral blood flow. A drawback of software that is used to quantify the cerebral blood flow is that it oftentimes assumes a static arterial luminal area over the cardiac cycle. Quantifying the lumen area pulsatility index (aPI), i.e. the change in lumen area due to an increase in distending pressure over the cardiac cycle, can provide insight in the stiffness of the arteries. Arterial stiffness has received increased attention as a predictor in the development of cerebrovascular disease. In this study, we introduce software that allows for measurement of the aPI as well as the blood flow velocity pulsatility index (vPI) from 4D PC-MRI. The internal carotid arteries of seven volunteers were imaged using 7 T MRI. The aPI and vPI measurements from 4D PC-MRI were validated against measurements from 2D PC-MRI at two levels of the internal carotid arteries (C3 and C7). The aPI and vPI computed from 4D PC-MRI were comparable to those measured from 2D PC-MRI (aPI: mean difference: 0.03 (limits of agreement: -0.14 - 0.23); vPI: 0.03 (-0.17-0.23)). The measured blood flow rate for the C3 and C7 segments was similar, indicating that our proposed software correctly captures the variation in arterial lumen area and blood flow velocity that exists along the distal end of the carotid artery. Our software may potentially aid in identifying changes in arterial stiffness of the intracranial arteries caused by pathological changes to the vessel wall.

Non-Invasive Assessment of Damping of Blood Flow Velocity Pulsatility in Cerebral Arteries With MRI.

BACKGROUND: Damping of heartbeat-induced pressure pulsations occurs in large arteries such as the aorta and extends to the small arteries and microcirculation. Since recently, 7 T MRI enables investigation of damping in the small cerebral arteries. PURPOSE: To investigate flow pulsatility damping between the first segment of the middle cerebral artery (M1) and the small perforating arteries using magnetic resonance imaging. STUDY TYPE: Retrospective. SUBJECTS: Thirty-eight participants (45% female) aged above 50 without history of heart failure, carotid occlusive disease, or cognitive impairment. FIELD STRENGTH/SEQUENCE: 3 T gradient echo (GE) T1-weighted images, spin-echo fluid-attenuated inversion recovery images, GE two-dimensional (2D) phase-contrast, and GE cine steady-state free precession images were acquired. At 7 T, T1-weighted images, GE quantitative-flow, and GE 2D phase-contrast images were acquired. ASSESSMENT: Velocity pulsatilities of the M1 and perforating arteries in the basal ganglia (BG) and semi-oval center (CSO) were measured. We used the damping index between the M1 and perforating arteries as a damping indicator (velocity pulsatilityM1 /velocity pulsatilityCSO/BG ). Left ventricular stroke volume (LVSV), mean arterial pressure (MAP), pulse pressure (PP), and aortic pulse wave velocity (PWV) were correlated with velocity pulsatility in the M1 and in perforating arteries, and with the damping index of the CSO and BG. STATISTICAL TESTS: Correlations of LVSV, MAP, PP, and PWV with velocity pulsatility in the M1 and small perforating arteries, and correlations with the damping indices were evaluated with linear regression analyses. RESULTS: PP and PWV were significantly positively correlated to M1 velocity pulsatility. PWV was significantly negatively correlated to CSO velocity pulsatility, and PP was unrelated to CSO velocity pulsatility (P = 0.28). PP and PWV were uncorrelated to BG velocity pulsatility (P = 0.25; P = 0.68). PWV and PP were significantly positively correlated with the CSO damping index. DATA CONCLUSION: Our study demonstrated a dynamic damping of velocity pulsatility between the M1 and small cerebral perforating arteries in relation to proximal stress. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 1.

Detecting low blood concentrations in joints using T1 and T2 mapping at 1.5, 3, and 7 T: an in vitro study.

BACKGROUND: Intra-articular blood causes irreversible joint damage, whilst clinical differentiation between haemorrhagic joint effusion and other effusions can be challenging. An accurate non-invasive method for the detection of joint bleeds is lacking. The aims of this phantom study were to investigate whether magnetic resonance imaging (MRI) T1 and T2 mapping allows for differentiation between simple and haemorrhagic joint effusion and to determine the lowest blood concentration that can be detected. METHODS: Solutions of synovial fluid with blood concentrations ranging from 0 to 100% were scanned at 1.5, 3, and 7 T. T1 maps were generated with an inversion recovery technique and T2 maps from multi spin-echo sequences. In both cases, the scan acquisition times were below 5 min. Regions of interest were manually drawn by two observers in the obtained T1 and T2 maps for each sample. The lowest detectable blood concentration was determined for all field strengths. RESULTS: At all field strengths, T1 and T2 relaxation times decreased with higher blood concentrations. The lowest detectable blood concentrations using T1 mapping were 10% at 1.5 T, 25% at 3 T, and 50% at 7 T. For T2 mapping, the detection limits were 50%, 5%, and 25%, respectively. CONCLUSIONS: T1 and T2 mapping can detect different blood concentrations in synovial fluid in vitro at clinical field strengths. Especially, T2 measurements at 3 T showed to be highly sensitive. Short acquisition times would make these methods suitable for clinical use and therefore might be promising tools for accurate discrimination between simple and haemorrhagic joint effusion in vivo.

Double delay alternating with nutation for tailored excitation facilitates banding-free isotropic high-resolution intracranial vessel wall imaging.

The purpose of this study was to evaluate the use of a double delay alternating with nutation for tailored excitation (D-DANTE)-prepared sequence for banding-free isotropic high-resolution intracranial vessel wall imaging (IC-VWI) and to compare its performance with regular DANTE in terms of signal-to-noise ratio (SNR) as well as cerebrospinal fluid (CSF) and blood suppression efficiency. To this end, a D-DANTE-prepared 3D turbo spin echo sequence was implemented by interleaving two separate DANTE pulse trains with different RF phase-cycling schemes, but keeping all other DANTE parameters unchanged, including the total number of pulses and total preparation time. This achieved a reduction of the banding distance compared with regular DANTE enabling banding-free imaging up to higher resolutions. Bloch simulations assuming static vessel wall and flowing CSF spins were performed to compare DANTE and D-DANTE in terms of SNR and vessel wall/CSF contrast. Similar image quality measures were assessed from measurements on 13 healthy middle-aged volunteers. Both simulation and in vivo results showed that D-DANTE had only slightly lower vessel wall/CSF and vessel wall/blood contrast-to-noise ratio values compared with regular DANTE, which originated from a 10%-15% reduction in vessel wall SNR but not from reduced CSF or blood suppression efficiency. As anticipated, IC-VWI acquisitions showed that D-DANTE can successfully remove banding artifacts compared with regular DANTE with equal scan time or DANTE preparation length. Moreover, application was demonstrated in a patient with an intracranial aneurysm, indicating improved robustness to slow flow artifacts compared with clinically available 3D turbo spin echo scans. In conclusion, D-DANTE provides banding artifact-free IC-VWI up to higher isotropic resolutions compared with regular DANTE. This allows for a more flexible choice of DANTE preparation parameters in high-resolution IC-VWI protocols.

Strain Tensor Imaging: Cardiac-induced brain tissue deformation in humans quantified with high-field MRI.

The cardiac cycle induces blood volume pulsations in the cerebral microvasculature that cause subtle deformation of the surrounding tissue. These tissue deformations are highly relevant as a potential source of information on the brain's microvasculature as well as of tissue condition. Besides, cyclic brain tissue deformations may be a driving force in clearance of brain waste products. We have developed a high-field magnetic resonance imaging (MRI) technique to capture these tissue deformations with full brain coverage and sufficient signal-to-noise to derive the cardiac-induced strain tensor on a voxel by voxel basis, that could not be assessed non-invasively before. We acquired the strain tensor with 3 mm isotropic resolution in 9 subjects with repeated measurements for 8 subjects. The strain tensor yielded both positive and negative eigenvalues (principle strains), reflecting the Poison effect in tissue. The principle strain associated with expansion followed the known funnel shaped brain motion pattern pointing towards the foramen magnum. Furthermore, we evaluate two scalar quantities from the strain tensor: the volumetric strain and octahedral shear strain. These quantities showed consistent patterns between subjects, and yielded repeatable results: the peak systolic volumetric strain (relative to end-diastolic strain) was 4.19⋅10-4 ± 0.78⋅10-4 and 3.98⋅10-4 ± 0.44⋅10-4 (mean ± standard deviation for first and second measurement, respectively), and the peak octahedral shear strain was 2.16⋅10-3 ± 0.31⋅10-3 and 2.31⋅10-3 ± 0.38⋅10-3, for the first and second measurement, respectively. The volumetric strain was typically highest in the cortex and lowest in the periventricular white matter, while anisotropy was highest in the subcortical white matter and basal ganglia. This technique thus reveals new, regional information on the brain's cardiac-induced deformation characteristics, and has the potential to advance our understanding of the role of microvascular pulsations in health and disease.

An anomaly detection approach to identify chronic brain infarcts on MRI.

The performance of current machine learning methods to detect heterogeneous pathology is limited by the quantity and quality of pathology in medical images. A possible solution is anomaly detection; an approach that can detect all abnormalities by learning how 'normal' tissue looks like. In this work, we propose an anomaly detection method using a neural network architecture for the detection of chronic brain infarcts on brain MR images. The neural network was trained to learn the visual appearance of normal appearing brains of 697 patients. We evaluated its performance on the detection of chronic brain infarcts in 225 patients, which were previously labeled. Our proposed method detected 374 chronic brain infarcts (68% of the total amount of brain infarcts) which represented 97.5% of the total infarct volume. Additionally, 26 new brain infarcts were identified that were originally missed by the radiologist during radiological reading. Our proposed method also detected white matter hyperintensities, anomalous calcifications, and imaging artefacts. This work shows that anomaly detection is a powerful approach for the detection of multiple brain abnormalities, and can potentially be used to improve the radiological workflow efficiency by guiding radiologists to brain anomalies which otherwise remain unnoticed.

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.

Arterial Remodeling of the Intracranial Arteries in Patients With Hypertension and Controls: A Postmortem Study.

The intracranial arteries play a major role in cerebrovascular disease, but arterial remodeling due to hypertension has not been well described in humans. We aimed to quantify this remodeling for: the basilar artery, the vertebral, internal carotid, middle/anterior (inferior)/posterior cerebral, posterior communicating, and superior cerebellar arteries of the circle of Willis. Ex vivo circle of Willis specimens, selected from individuals with (n=24) and without (n=25) a history of hypertension, were imaged at 7T magnetic resonance imaging using a 3-dimensional gradient-echo sequence. Subsequently, histological analysis was performed. We validated the vessel wall thickness and area measurements from magnetic resonance imaging against histology. Next, we investigated potential differences in vessel wall thickness and area between both groups using both techniques. Finally, using histological analysis, we investigated potential differences in arterial wall stiffness and atherosclerotic plaque severity and load. All analyses were unadjusted. Magnetic resonance imaging and histology showed comparable vessel wall thickness (mean difference: 0.04 mm (limits of agreement:-0.12 to 0.19 mm) and area (0.43 mm2 [-0.97 to 1.8 mm2]) measurements. We observed no statistically significant differences in vessel wall thickness and area between both groups using either technique. Histological analysis showed early and advanced atherosclerotic plaques in almost all arteries for both groups. The arterial wall stiffness was significantly higher for the internal carotid artery in the hypertensive group. Concluding, we did not observe vessel wall thickening in the circle of Willis arteries in individuals with a history of hypertension using either technique. Using histological analysis, we observed a difference in vessel wall composition for the internal carotid artery.