ObjectiveIdiopathic normal pressure hydrocephalus (INPH) is a treatable neurological condition, yet predicting which patients will benefit from a cerebrospinal fluid shunt remains challenging. Structural brain MRI is a core part of the diagnostic workup, but traditional radiological measures show limited predictive accuracy. This study aimed to assess whether deep learning and radiomics-based machine learning approaches can provide clinically useful predictions of shunt outcome based on preoperative MRI.MethodsWe investigated 149 shunted INPH patients with available preoperative T1-weighted, T2-weighted, and FLAIR images. Patients were classified as responders (n = 113) or non-responders (n = 36) based on postoperative gait speed improvement. For INPH, this is a large sample with typical outcome distribution. Three artificial intelligence approaches were tested: a late-fusion ensemble of multiple 3D convolutional neural networks; a multimodal intermediate fusion model; and radiomics-based machine learning models trained on features extracted from whole-brain masks. Models were assessed using 10-fold cross-validation. The best performing model on the validation set was selected from each approach. Performance metrics included the area under the receiving operating characteristic curve (AUROC), sensitivity, and specificity.ResultsPerformance was considered poor in all models, and none reached an area under the receiving operating characteristic curve above 70%. Of the three methodologies, the best performance was achieved with a radiomics-based model (Linear Discriminant Analysis classifier on T1-weighted images) which achieved an AUROC of 63.7%. In a reduced subset of clearly separated responders and non-responders (n = 72), the best model (late fusion ensemble of 5 convolutional neural networks) reached an AUROC of 69.2%.ConclusionsDespite the use of advanced artificial intelligence techniques, structural MRI alone were insufficient for reliably predicting gait outcome after surgery in idiopathic normal pressure hydrocephalus. To capture the complexity of the condition and enable clinically meaningful predictions, our findings indicate the need for research investigating multimodal input and using large multi-center datasets.

BACKGROUND:Although clinical evaluation, radiological findings, and supplementary tests are routinely used to diagnose idiopathic normal pressure hydrocephalus (INPH), the large variability in surgical outcomes raises the question of whether diagnostic radiological markers truly reflect the typical clinical gait impairment. Gait disorder (GD) and ventriculomegaly (VM) are both common in older adults and may coincide by chance, potentially contributing to this inconsistency in results. This study aimed to determine the prevalence of typical INPH-related higher-level gait disorder (HLGD), diagnosed independently of imaging, and assess its association with VM and other MRI features. METHODS:In this case-control study, 6467 individuals age 65-84 years were screened for GD per questionnaire. Physicians with experience of neurological GD identified cases with HLGD and matched controls without GD through clinical evaluation of 1047 of these individuals. Subsequently, brain MRI (n = 909) or CT (n = 98) was performed. After exclusions, 81 with HLGD and 192 controls remained. Radiological hydrocephalus features were compared between the groups. RESULTS:The prevalence of HLGD in the general older population was 5.8%. For HLGD combined with Evans Index (EI)>0.3, it was 3.7%, and 1.7% had HLGD with Disproportionately Enlarged Subarachnoid space Hydrocephalus (DESH). The estimated prevalence of asymptomatic VM, i.e. EI > 0.3 without GD, was 24%, and 4.1% had asymptomatic VM with DESH. Individuals with HLGD were older and performed worse on cognitive tests. Radiology revealed higher ventricular volumes and EI, and a more acute callosal angle in HLGD versus controls. DESH was also more frequent in HLGD (29% vs 7%, p < 0.001). Despite group-level differences, individual overlap was substantial. MRI markers showed poor to moderate ability to discriminate HLGD (AUC 0.614-0.765) from normal gait. CONCLUSIONS:In this population-based case-control study, both HLGD and EI > 0.3 were common. EI > 0.3 occurred more frequently with HLGD, but it was also common in asymptomatic individuals, indicating that ventriculomegaly is not specific to HLGD. Most MRI biomarkers showed limited ability to distinguish HLGD from normal gait, although lateral ventricular volume divided by total intracranial volume (relative ventricular volume) was the most informative. The frequent occurrence of EI > 0.3 and DESH in asymptomatic individuals highlights the need for longitudinal studies to clarify prognosis in these individuals.

This Viewpoint describes the diagnosis and treatment history of normal pressure hydrocephalus and then highlights recent trial results that may serve as a catalyst for renewed scientific and clinical efforts.

PURPOSE:The aim was to estimate T1 relaxivity of gadobutrol and gadoteric acid in cerebrospinal fluid (CSF) at 3T, to support research on CSF-flow and the glymphatic system in humans utilizing T1 mapping after intrathecal injection. METHODS:Using a phantom, relaxivity was estimated for gadobutrol and gadoteric acid in lumbar CSF and an isotonic solution. All samples were scanned simultaneously using the variable flip angle method with B1 correction, repeated six times on one 3T scanner, and once on a second 3T scanner. Difference in relaxivity between CSF and the isotonic solution were evaluated from the repeated measurements. RESULTS:There was a significant difference in relaxivity between CSF and the isotonic solution for both gadobutrol and gadoteric acid. The relaxivity for gadobutrol for the respective scanners was estimated to 3.02 ± 0.09 vs. 3.63 L mmol-1 s-1 in CSF and 2.35 ± 0.05 vs. 2.74 L mmol-1 s-1 in isotonic solution. For gadoteric acid, corresponding results were 2.47 ± 0.02 vs. 2.91 L mmol-1 s-1 in CSF and 2.37 ± 0.03 vs. 2.8 L mmol-1 s-1 in isotonic solution. Between the scanners, there was a high correlation (R2 0.998) but an 18% scaling difference in the T1 relaxation rates and corresponding relaxivities. CONCLUSIONS:The relaxivity was higher in CSF than in the isotonic solution, particularly for gadobutrol. Systematic differences in relaxivity between scanners may potentially be corrected using a scaling factor derived from the T1 time of baseline CSF. For CSF studies using T1 mapping with a gadolinium-based contrast agent, we recommend using a CSF-specific relaxivity constant.

Spaceflight-associated neuro-ocular syndrome (SANS) poses a significant risk for astronauts, being linked to intracranial pressure (ICP) changes in microgravity. Investigating ICP in space has been challenging. We evaluated a telemetric lumbar ICP monitoring system that shows promise for investigating microgravity-induced intracranial pressure changes in astronauts. Despite limitations in pulse amplitude analysis and pressure underestimation, the system’s long-term stability and overall performance support its recommendation for SANS research in space.

According to glymphatic system theory, cerebrospinal fluid (CSF) perfuses the brain's interstitial space to support waste clearance, but the magnitude of this flow and the outflow pathway of interstitial fluid (ISF) in humans remain uncertain. To achieve flow quantification, we applied a compartment-model approach applied in conjunction with serial quantitative MRI data acquired after intrathecal gadolinium administration. Using the method, we estimated CSF-to-ISF inflow to 45 ± 20 mL/h, in patients with suspected idiopathic normal pressure hydrocephalus. Tissue-specific contributions were 34 ± 14 mL/h in cortical gray matter, 11±6 mL/h in white matter, and 0.4 ± 0.3 mL/h in subcortical gray matter, suggesting that CSF perfusion occurs primarily in superficial regions near the subarachnoid space. A lack of correlation between inflow and total craniospinal system outflow (r = 0.03, P = 0.91) suggested that ISF recirculates back into CSF rather than exiting the craniospinal system via a separate route. Independent experiments in healthy older individuals using intravenous gadolinium administration supported ISF-to-CSF recirculation, where contrast material that presumably crossed the blood-brain barrier subsequently appeared in the subarachnoid space, allowing ISF-to-CSF flow quantification. These findings provide a quantitative framework for studying brain clearance in humans and support subarachnoid space recirculation as an important efflux route.

Abstract Background Aquaporin-4 (AQP4) is crucial for brain fluid regulation and glymphatic system function. Idiopathic normal pressure hydrocephalus (INPH) is characterized by impaired CSF flow and is treated with shunt surgery. This study investigated AQP4 levels in INPH patients to explore its role in pathophysiology and as a potential biomarker for shunt response. Methods CSF samples from 233 INPH patients and 29 controls were analysed. AQP4 levels were compared between preoperative patients and controls, before and after shunt surgery (110 patients), and between shunt responders and non-responders (204 patients). A bead-based assay was used to measure AQP4, and outcomes were assessed by postoperative changes in maximum gait velocity. Results In unadjusted analyses, preoperative AQP4 levels were lower in INPH patients than in controls; however, this difference did not remain after adjustment for pre-analytical and demographic confounders (p = 0.87). Postoperative AQP4 levels were higher (median 1646 AU IQR 1347–1976) than preoperative levels (1166 AU IQR: 976–1345; p < 0.001) and the magnitude of increase showed a modest correlation with gait improvement (rₛ = 0.22, p = 0.022). Shunt responders had lower preoperative AQP4 levels median 1089 AU, IQR 971–1277) than non-responders (median 1213 AU, IQR 1074–1361; p = 0.008). Pre-analytical factors, including storage duration and sample processing, were strong determinants of measured AQP4 levels. Conclusions CSF AQP4 levels in INPH did not differ from those in controls and were highly sensitive to pre-analytical sample handling. CSF AQP4 levels increased following shunt surgery. A potential prognostic value of CSF AQP4 is suggested but requires further investigation.

BACKGROUND AND OBJECTIVES:Glymphatic function affects brain health and could be part of the pathophysiology in idiopathic normal-pressure hydrocephalus. Elevated intracranial pressure pulsatility and increased resistance to cerebrospinal fluid (CSF) outflow (Rout) are commonly observed in idiopathic normal-pressure hydrocephalus. Whether such alterations indicate impaired glymphatic function or affect ventricle volumetrics in ordinary elderly is unknown. We investigated the associations between CSF dynamics and changes in cognitive performance, gait, and brain MRI parameters over a 10-year period in a cohort of healthy older adults. METHODS:Twenty-nine subjects (mean age 79 ± 6, range 71-92 years) were investigated with brain MRI, clinical testing, and a CSF infusion test. MRI and clinical testing were repeated after 10 years. An automated software program was used to calculate ventricle volumes, and linear ventricle radiological indices were calculated (Evan's index, callosal angle, and z-Evan's index). CSF dynamic parameters were correlated with longitudinal changes in clinical and MRI parameters. RESULTS:In a multivariable regression model including age, sex, baseline cognitive performance, and CSF dynamic parameters, lower CSF outflow resistance was associated with better cognitive performance after 10 years (standardized β = 0.37, P = .047, n = 29). In a bivariate analysis, outflow resistance had a negative correlation to the difference in cognitive testing score between baseline and follow-up (r = -.44, 95% CI -0.701 to -0.08, P = .017, n = 29, Spearman's rho). CSF dynamic parameters were not associated with changes in gait performance or ventricle volume. Intracranial pressure pulsatility was associated with reduced callosal angle (standardized β = -0.35, P = .02, n = 29) and intracranial pressure with increased z-Evan's index (standardized β = 0.18, P = .003, n = 29). CONCLUSION:Our results provide insight into the complexity of CSF physiology and its possible role in longitudinal change in brain function and structure. Measurement of CSF outflow characteristics hold potential in furthering the understanding of glymphatic performance with regard to change in cognitive function and warrants further investigation.

PURPOSE:Cerebrospinal fluid (CSF) flow oscillations have emerged as a potentially important marker related to brain clearance, but their acquisition often relies on specialized imaging MRI sequences. The purpose of this work was to enable quantitative assessment of CSF flow associated with cardiac, respiratory, and low-frequency cycles using widely available functional magnetic resonance imaging (fMRI) acquisitions. METHODS:A method was developed to translate fMRI-derived CSF inflow signals into quantitative flow rates. This approach modeled the spin-history of an oscillating ensemble of molecules. Validation was performed using phantom experiments with cardiac-, respiratory-, and low-frequency-like oscillatory flow. The method was further applied to resting-state data from 48 older adults (68-82 years, 19 women) to characterize CSF flow at the foramen magnum. RESULTS:Phantom experiments demonstrated excellent correlations between estimated and true velocities for cardiac- and respiratory-like frequencies (r = 0.94 and 0.97, respectively) and moderate correlation for the low-frequency-like oscillation (r = 0.58). In the population cohort, median CSF stroke volumes were 0.77 [0.57, 1.09] mL for the cardiac cycle, 0.38 [0.26, 0.88] mL for the respiratory cycle, and 0.26 [0.14, 0.39] mL for the low-frequency cycle. CONCLUSION:The proposed spin-history modeling method enabled quantitative estimation of CSF flow components using a conventional fMRI dataset and showed that the cardiac cycle dominates CSF motion at the foramen magnum.

Disproportionately enlarged subarachnoid space hydrocephalus (DESH) is a radiological biomarker for idiopathic normal pressure hydrocephalus (iNPH). DESH is a subjective measure, based on visual assessments, which may limit its reliability. The aim of this study was to develop and validate a method for the objective quantification of DESH. By using a semiautomatic quantitative method, we calculated quantitative DESH (qDESH), defined as a ratio between CSF volumes at high convexities and Sylvian fissures. The analysis was based on three-dimensional T1-weighted images from 35 subjects with iNPH (mean age 74 yrs; 10 females) and 45 controls (mean age 72 yrs; 13 females). The interrater agreement for qDESH was evaluated by the intraclass correlation coefficient, and qDESH was compared with visual assessments performed by two neuroradiologists. All subjects with iNPH and 13

A single, arterial-optimized 4D-flow MRI acquisition may enable fast assessment of both cerebral arterial and venous flow. However, arteries and veins require different velocity encoding (VENC) settings for optimal velocity-to-noise ratio (VNR). Consequently, venous measurements using arterial-optimized VENC settings are subject to reduced VNR and require further evaluation. This study compared cerebral venous flow and pulsatility assessments using a high-VENC (110 cm/s, adapted to the arterial system) and a low-VENC (40 cm/s, adapted to the venous system) 4D-flow MRI sequence at 3 Tesla. Flow and pulsatility index (PI) were calculated for cerebral veins, sinuses and internal jugular veins in 36 elderly volunteers (79 ± 5 years). The high-VENC acquisitions allowed visualization of nearly all venous structures. Mean flow differences were small and the correlation, strong, when comparing both acquisitions across sinuses (R = 0.90–0.99, difference = -8–7%) and cortical veins (R = 0.93, difference = − 6%). Inflow-outflow differences at the confluence of sinuses were similar between acquisitions. PI showed moderate to strong agreement except in the straight sinus. Both the vein of Galen and the jugular veins suffered from aliasing in the venous VENC acquisitions. In summary, this study demonstrated that a VENC setting adapted for the arterial cerebral circulation was feasible for studying cerebral venous flow and pulsatility.

Background:Higher-level gait disorders (HLGDs) are slow, unsteady neurological GDs in older people. GDs can reduce quality of life (QoL) and cause depression. This has not been investigated in HLGD even though some HLGD causes are treatable, potentially affecting associated problems. We aimed to investigate gait and balance confidence, depressive symptoms and QoL in HLGD. Methods:In a population (n=3769, 65-84y), 798 reported gait impairment (questionnaire) and were clinically examined together with 249 age- and sex-matched controls. Gait property groups were formed: 'HLGD', 'other neurological GD', 'non-neurological GD' or 'no GD'. Swedish Falls Efficacy Scale (FES(S)), Modified Gait Efficacy Scale (mGES), Euro Quality of Life 5-Dimension 5-Level index, Euro Quality of Life Visual Analogue Scale (EQ VAS) and Geriatric Depression Scale-15 (GDS-15) were compared. Results:In the general population, 38% had GDs, of which 16% (n=87/561) were HLGDs, giving an HLGD prevalence of 5.8%; 26% (n=145/561) were other neurological GDs; and 59% (n=329/561) non-neurological GDs. HLGD had more depressive symptoms than non-neurological GD and no GD (GDS-15 HLGD, 3.9±3.4; non-neurological GD, 2.5±2.8; no GD, 1.4±2.0; p<0.05), lower EQ VAS (HLGD, 63±17; non-neurological GD, 71±18; no GD, 82±14; p<0.001), lower gait confidence (mGES HLGD, 60±22; non-neurological GD, 74±21; no GD, 90±13; p<0.001) and lower balance confidence (FES(S) HLGD, 93±32; non-neurological GD, 111±25; no GD, 124±13; p<0.001). Conclusions:HLGDs are common and associated with reduced QoL, reduced confidence in gait and balance, and depressive symptoms, emphasising awareness of mental health among older people with slow unsteady gait.

White matter lesions (WML) and dilated perivascular spaces (PVS) are features of small vessel disease (SVD), commonly observed in aging and dementia, with unknown pathophysiology. Human studies have documented contrast accumulation within and in proximity of SVD-lesions. However, whether such observations mainly reflect excessive blood-brain barrier (BBB) leakage, or altered microvascular density in the investigated regions, remains unclear. To evaluate the roles of BBB leakage and vascular density in aging and SVD, dynamic contrast enhanced (DCE) MRI was used to estimate the permeability-surface area product (PS) and fractional plasma volume ( v_p ) in normal-appearing brain tissue and in proximity of and within WML and PVS in a population-based cohort (N = 56; 34/22 m/f; age 64 to 84 years). Analysis of variance (ANOVA) was used to assess regional differences in PS and v_p and analysis of covariance (ANCOVA) was used to assess regional differences in PS with v_p and vascular risk as covariates. Pronounced increases in PS and v_p were observed from normal-appearing white matter (NAWM) to WML peripheries to WMLs. Similar PS and v_p increases were observed from basal ganglia (BG) to BG-PVS. Further, PS in NAWM and white matter (WM) PVS were found to increase with cortex-to-ventricular depth. However, ANCOVA models with v_p as a covariate showed that variance in PS was mainly explained by vp (η2=0.17 to η2=0.35; all p < 10− 3), whereas the effect of region was only borderline-significant when comparing NAWM, WML peripheries and WML (p = 0.03) and non-significant for the other comparisons (p > 0.29). Our findings support the notion that contrast leakage across the BBB accumulates within and in proximity of SVD-related lesions. However, high contrast accumulation may mainly reflect high vascularization, and to a lesser degree than previously recognized BBB dysfunction.

Variations in cerebral blood flow and blood volume interact with intracranial pressure and cerebrospinal fluid dynamics, all of which play a crucial role in brain homeostasis. A key physiological modulator is respiration, but its impact on cerebral blood flow and volume has not been thoroughly investigated. Here we used 4D flow MRI in a population-based sample of 65 participants (mean age = 75 ± 1) to quantify these effects. Two gating approaches were considered, one using respiratory-phase and the other using respiratory-time (i.e. raw time in the cycle). For both gating methods, the arterial inflow was significantly larger during exhalation compared to inhalation, whereas the venous outflow was significantly larger during inhalation compared to exhalation. The cerebral blood volume variation per respiratory cycle was 0.83 [0.62, 1.13] ml for respiratory-phase gating and 0.78 [0.59, 1.02] ml for respiratory-time gating. For comparison, the volume variation of the cardiac cycle was 1.01 [0.80, 1.30] ml. Taken together, our results clearly demonstrate respiratory influences on cerebral blood flow. The corresponding vascular volume variations appear to be of the same order of magnitude as those of the cardiac cycle, highlighting respiration as an important modulator of cerebral blood flow and blood volume.

BACKGROUND:Idiopathic normal-pressure hydrocephalus is a neurologic disorder characterized by impaired gait, balance, cognition, and bladder control in older adults. The disorder is treated with shunt surgery, but the effectiveness of shunting is unclear. METHODS:We conducted a double-blind, randomized, placebo-controlled trial involving participants selected for shunt surgery on the basis of gait-velocity improvement with cerebrospinal fluid (CSF) drainage. Participants were randomly assigned to an open-shunt valve setting (opening pressure, 110 mm of water) or a placebo valve setting (opening pressure, >400 mm of water) of a noninvasively adjustable shunt. The primary outcome was the change in gait velocity 3 months after surgery. Secondary outcomes were the change at 3 months in the Tinetti scale total score (range, 0 to 28; lower scores indicate worse gait and balance), Montreal Cognitive Assessment (MoCA) score (range, 0 to 30; lower scores indicate worse cognition), and Overactive Bladder Questionnaire score (range, 0 to 100; higher scores indicate worse urinary incontinence). RESULTS:A total of 99 participants underwent randomization and received the assigned intervention. At 3 months, gait velocity had increased in the open-shunt group (mean [±SD] change, 0.23±0.23 m per second; assessed in 49 participants) and was unchanged in the placebo group (mean change, 0.03±0.23 m per second; assessed in 49 participants), resulting in a treatment difference of 0.21 m per second (95% confidence interval, 0.12 to 0.31; P<0.001). A significantly greater improvement in the open-shunt group than the placebo group was seen for the Tinetti scale score (mean change, 2.9 points vs. 0.5 points; P = 0.003) but not the MoCA score (1.3 points vs. 0.3 points) or the Overactive Bladder Questionnaire score (-3.3 points vs. -1.5 points). The results regarding adverse events were mixed, with more participants in the placebo group reporting falls (46% vs. 24%), an equal percentage having cerebral bleeding (2% in both groups), and more participants in the open-shunt group having subdural bleeding (12% vs. 2%) and positional headaches (59% vs. 28%). CONCLUSIONS:Among participants with idiopathic normal-pressure hydrocephalus who had a response to temporary CSF drainage, shunting resulted in significant improvements at 3 months in gait velocity and a measure of gait and balance but not in measures of cognition or incontinence. (Funded by the National Institute of Neurological Disorders and Stroke and the Trial Innovation Network; PENS ClinicalTrials.gov number, NCT05081128.).

Studying cerebrospinal fluid (CSF) flow can reveal physiological and neural drivers of potential importance in brain clearance. CSF flow may be acquired in functional magnetic resonance imaging (fMRI) scans by considering the inflow effect in an edge-slice. Such measurements have large potential considering the broad availability of fMRI, and the already extensive databases focusing on e.g. aging and dementia. However, limiting factors are that the measurements are not quantitative and can rarely separate contributions from different driving mechanisms due to insufficient sampling rate. Here, we present a method that translates fMRI CSF signals into quantitative flow rates associated with cardiac, respiratory and slow-vasomotion cycles, by modeling the spin-history of an oscillating ensemble of molecules. Phantom experiments showed excellent correlations between estimated and true velocities for cardiac- and respiratory-like frequencies, and moderate correlations for a slow vasomotion-like frequency (r = 0.94, 0.97, 0.58 respectively). We also applied the method in a cohort of 48 subjects from the population (68-82 years, 19 women) to characterize CSF flow at the foramen magnum at resting state. These measurements showed a CSF stroke volume of 0.86 [0.61, 1.17] mL for the cardiac, 0.44 [0.25, 0.94] mL for the respiratory, and 0.28 [0.14, 0.45] mL for the slow vasomotion cycle. In conclusion, the method presented here enabled quantitative assessments of CSF flow compatible with typical fMRI acquisitions and showed that the cardiac cycle is a dominant driver of CSF flow. ### Competing Interest Statement The authors have declared no competing interest. Swedish Research Council, 2022-04263 Swedish Heart-Lung Foundation, 20210653 Swedish Foundation for Strategic Research, RMX18-0152

Blood–brain barrier (BBB) disruption may contribute to cognitive decline, but questions remain whether this association is more pronounced for certain brain regions, such as the hippocampus, or represents a whole-brain mechanism. Further, whether human BBB leakage is triggered by excessive vascular pulsatility, as suggested by animal studies, remains unknown. In a prospective cohort (N = 50; 68–84 years), we used contrast-enhanced MRI to estimate the permeability-surface area product (PS) and fractional plasma volume ($${v}_{p}$$ v p ), and 4D flow MRI to assess cerebral arterial pulsatility. Cognition was assessed by the Montreal Cognitive Assessment (MoCA) score. We hypothesized that high PS would be associated with high arterial pulsatility, and that links to cognition would be specific to hippocampal PS. For 15 brain regions, PS ranged from 0.38 to 0.85 (·10−3 min−1) and $${v}_{p}$$ v p from 0.79 to 1.78%. Cognition was related to PS (·10−3 min−1) in hippocampus (β = – 2.9; p = 0.006), basal ganglia (β = – 2.3; p = 0.04), white matter (β = – 2.6; p = 0.04), whole-brain (β = – 2.7; p = 0.04) and borderline-related for cortex (β = – 2.7; p = 0.076). Pulsatility was unrelated to PS for all regions (p > 0.19). Our findings suggest PS–cognition links mainly reflect a whole-brain phenomenon with only slightly more pronounced links for the hippocampus, and provide no evidence of excessive pulsatility as a trigger of BBB disruption.

BACKGROUND:Compromised cerebral blood flow can contribute to future ischemic events in patients with symptomatic carotid artery disease. However, there is limited knowledge of the effects on cerebral hemodynamics resulting from a reduced internal carotid artery (ICA) blood flow rate (BFR). PURPOSE:Investigate how reduced ICA-BFR, relates to BFR in the cerebral arteries. STUDY TYPE:Prospective. SUBJECTS:Thirty-eight patients, age 72 ± 6 years (11 female). FIELD STRENGTH/SEQUENCE:3-Tesla, four-dimensional phase-contrast magnetic resonance imaging (4D-PCMRI). ASSESSMENT:Patients with ischemic stroke or transient ischemic attack were evaluated regarding the degree of stenosis. 4D-PCMRI was used to measure cerebral BFR in 38 patients with symptomatic carotid stenosis (≥50%). BFR in the cerebral arteries was assessed in two subgroups based on symptomatic ICA-BFR: reduced ICA-flow (<160 mL/minutes) and preserved ICA-flow (≥160 mL/minutes). BFR laterality was defined as a difference in the paired ipsilateral-contralateral arteries. STATISTICAL TESTS:Patients were grouped based on ICA-BFR (reduced vs. preserved). Statistical tests (independent sample t-test/paired t-test) were used to compare groups and hemispheres. Significance was determined at P < 0.05. RESULTS:The degree of stenosis was not significantly different, 80% (95% confidence interval [CI] = 73%-87%) in the reduced ICA-flow vs. 72% (CI = 66%-76%) in the preserved ICA-flow; P = 0.09. In the reduced ICA-flow group, a significantly reduced BFR was found in the ipsilateral middle cerebral artery and anterior cerebral artery (A1), while significantly increased in the contralateral A1. Retrograde BFR was found in the posterior communicating artery and ophthalmic artery. Significant BFR laterality was present in all paired arteries in the reduced ICA-flow group, contrasting the preserved ICA-flow group (P = 0.14-0.93). DATA CONCLUSIONS:4D-PCMRI revealed compromised cerebral BFR due to carotid stenosis, not possible to detect by solely analyzing the degree of stenosis. In patients with reduced ICA-flow, collaterals were not sufficient to maintain symmetrical BFR distribution to the two hemispheres. EVIDENCE LEVEL:2 TECHNICAL EFFICACY: Stage 3.

Selective antegrade cerebral perfusion (SACP) is a protective procedure to ascertain adequate brain perfusion during aortic arch surgeries requiring moderate hypothermic circulatory arrest. SACP entails catheterization of arteries feeding the brain, which can be done bilaterally (bSACP) or unilaterally (uSACP), but there is no consensus on when to use each approach. bSACP may increase the risk of embolization, while uSACP risks hypoperfusion due to insufficient perfusion pressure in the contralateral hemisphere, since a single catheter must perfuse both hemispheres. We developed and tested the feasibility of a new method for predicting cerebral perfusion pressures (CPP) during SACP, which could potentially aid clinicians in preoperatively identifying which SACP approach to use. Feasibility of the method was evaluated in five patients eligible for aortic arch surgery (65 ± 7 years, 3 men). Patients were investigated preoperatively with computed tomography angiography (CTA) and 4D flow magnetic resonance imaging (MRI) to assess patient-specific arterial anatomy and blood flows. From the imaging, computational fluid dynamics (CFD) simulations estimated the patients' vascular resistances. Applying these resistances and intraoperative SACP pressure/flow settings to the model's boundary conditions allowed for predictions of contralateral CPP during SACP. Predicted pressures were compared to corresponding intraoperative pressure measurements. The method showed promise for predicting contralateral CPP during both uSACP (median error (range): 2.4 (-0.2-18.0) mmHg) and bSACP (0.8 (-3.3-5.4) mmHg). Predictions were most sensitive to collateral artery size. This study showed the feasibility of CPP predictions of SACP, and presents key features needed for accurate modelling.