Four-dimensional flow MRI for quantitative assessment of cerebrospinal fluid dynamics: Status and opportunities.

Neurological disorders can manifest with altered neurofluid dynamics in different compartments of the central nervous system. These include alterations in cerebral blood flow, cerebrospinal fluid (CSF) flow, and tissue biomechanics. Noninvasive quantitative assessment of neurofluid flow and tissue motion is feasible with phase contrast magnetic resonance imaging (PC MRI). While two-dimensional (2D) PC MRI is routinely utilized in research and clinical settings to assess flow dynamics through a single imaging slice, comprehensive neurofluid dynamic assessment can be limited or impractical. Recently, four-dimensional (4D) flow MRI (or time-resolved three-dimensional PC with three-directional velocity encoding) has emerged as a powerful extension of 2D PC, allowing for large volumetric coverage of fluid velocities at high spatiotemporal resolution within clinically reasonable scan times. Yet, most 4D flow studies have focused on blood flow imaging. Characterizing CSF flow dynamics with 4D flow (i.e., 4D CSF flow) is of high interest to understand normal brain and spine physiology, but also to study neurological disorders such as dysfunctional brain metabolite waste clearance, where CSF dynamics appear to play an important role. However, 4D CSF flow imaging is challenged by the long T1 time of CSF and slower velocities compared with blood flow, which can result in longer scan times from low flip angles and extended motion-sensitive gradients, hindering clinical adoption. In this work, we review the state of 4D CSF flow MRI including challenges, novel solutions from current research and ongoing needs, examples of clinical and research applications, and discuss an outlook on the future of 4D CSF flow.

Normative Cerebral Hemodynamics in Middle-aged and Older Adults Using 4D Flow MRI: Initial Analysis of Vascular Aging.

Background Characterizing cerebrovascular hemodynamics in older adults is important for identifying disease and understanding normal neurovascular aging. Four-dimensional (4D) flow MRI allows for a comprehensive assessment of cerebral hemodynamics in a single acquisition. Purpose To establish reference intracranial blood flow and pulsatility index values in a large cross-sectional sample of middle-aged (45-65 years) and older (>65 years) adults and characterize the effect of age and sex on blood flow and pulsatility. Materials and Methods In this retrospective study, patients aged 45-93 years (cognitively unimpaired) underwent cranial 4D flow MRI between March 2010 and March 2020. Blood flow rates and pulsatility indexes from 13 major arteries and four venous sinuses and total cerebral blood flow were collected. Intraobserver and interobserver reproducibility of flow and pulsatility measures was assessed in 30 patients. Descriptive statistics (mean ± SD) of blood flow and pulsatility were tabulated for the entire group and by age and sex. Multiple linear regression and linear mixed-effects models were used to assess the effect of age and sex on total cerebral blood flow and vessel-specific flow and pulsatility, respectively. Results There were 759 patients (mean age, 65 years ± 8 [SD]; 506 female patients) analyzed. For intra- and interobserver reproducibility, median intraclass correlation coefficients were greater than 0.90 for flow and pulsatility measures across all vessels. Regression coefficients ß ± standard error from multiple linear regression showed a 4 mL/min decrease in total cerebral blood flow each year (age ß = -3.94 mL/min per year ± 0.44; P < .001). Mixed effects showed a 1 mL/min average annual decrease in blood flow (age ß = -0.95 mL/min per year ± 0.16; P < .001) and 0.01 arbitrary unit (au) average annual increase in pulsatility over all vessels (age ß = 0.011 au per year ± 0.001; P < .001). No evidence of sex differences was observed for flow (ß = -1.60 mL/min per male patient ± 1.77; P = .37), but pulsatility was higher in female patients (sex ß = -0.018 au per male patient ± 0.008; P = .02). Conclusion Normal reference values for blood flow and pulsatility obtained using four-dimensional flow MRI showed correlations with age. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Steinman in this issue.

Accelerated 4D-flow MRI with 3-point encoding enabled by machine learning.

PURPOSE: To investigate the acceleration of 4D-flow MRI using a convolutional neural network (CNN) that produces three directional velocities from three flow encodings, without requiring a fourth reference scan measuring background phase. METHODS: A fully 3D CNN using a U-net architecture was trained in a block-wise fashion to take complex images from three flow encodings and to produce three real-valued images for each velocity component. Using neurovascular 4D-flow scans (n = 144), the CNN was trained to predict velocities computed from four flow encodings by standard reconstruction including correction for residual background phase offsets. Methods to optimize loss functions were investigated, including magnitude, complex difference, and uniform velocity weightings. Subsequently, 3-point encoding was evaluated using cross validation of pixelwise correlation, flow measurements in major arteries, and in experiments with data at differing acceleration rates than the training data. RESULTS: The CNN-produced 3-point velocities showed excellent agreements with the 4-point velocities, both qualitatively in velocity images, in flow rate measures, and quantitatively in regression analysis (slope = 0.96, R2  = 0.992). Optimizing the training to focus on vessel velocities rather than the global velocity error and improved the correlation of velocity within vessels themselves. The lowest error was observed when the loss function used uniform velocity weighting, in which the magnitude-weighted inverse of the velocity frequency uniformly distributed weighting across all velocity ranges. When applied to highly accelerated data, the 3-point network maintained a high correlation with ground truth data and demonstrated a denoising effect. CONCLUSION: The 4D-flow MRI can be accelerated using machine learning requiring only three flow encodings to produce three-directional velocity maps with small errors.

Age at natural menopause impacts cerebrovascular reactivity and brain structure.

Menopause is associated with adverse changes in vascular health coinciding with an increased risk of stroke and vascular cognitive impairment. However, there is significant variation in the age at menopause. The present study examined how the age at natural menopause impacts cerebrovascular reactivity and structural biomarkers of brain aging. Thirty-five healthy postmenopausal women were classified as early-onset menopause (Early; n = 19, age at menopause: 47 ± 2 yr) or later-onset menopause (Late; n = 16, age at menopause: 55 ± 2 yr). Middle cerebral artery blood velocity (MCAv), mean arterial blood pressure (MAP), and end-tidal carbon dioxide (ETCO2) were recorded during a stepped hypercapnia protocol. Reactivity was calculated as the slope of the relationship between ETCO2 and each variable of interest. Brain volumes and white matter hyperintensities (WMHs) were obtained with 3T MRI. Resting MAP was greater in the Early group (99 ± 9 mmHg) compared with the Late group (90 ± 12 mmHg; P = 0.02). Cerebrovascular reactivity, assessed using MCAv, was blunted in the Early group (1.87 ± 0.92 cm/s/mmHg) compared with the Late group (2.37 ± 0.75 cm/s/mmHg; P = 0.02). Total brain volume did not differ between groups (Early: 1.08 ± 0.07 L vs. Late: 1.07 ± 0.06 L; P = 0.66), but the Early group demonstrated greater WMH fraction compared with the Late group (Early: 0.36 ± 0.14% vs. Late: 0.25 ± 0.14%; P = 0.02). These results suggest that age at natural menopause impacts cerebrovascular function and WMH burden in healthy postmenopausal women.

Focused Abbreviated Survey MRI Protocols for Brain and Spine Imaging.

There has been extensive growth in both the technical development and the clinical applications of MRI, establishing this modality as one of the most powerful diagnostic imaging tools. However, long examination and image interpretation times still limit the application of MRI, especially in emergent clinical settings. Rapid and abbreviated MRI protocols have been developed as alternatives to standard MRI, with reduced imaging times, and in some cases limited numbers of sequences, to more efficiently answer specific clinical questions. A group of rapid MRI protocols used at the authors' institution, referred to as FAST (focused abbreviated survey techniques), are designed to include or exclude emergent or urgent conditions or screen for specific entities. These FAST protocols provide adequate diagnostic image quality with use of accelerated approaches to produce imaging studies faster than traditional methods. FAST protocols have become critical diagnostic screening tools at the authors' institution, allowing confident and efficient confirmation or exclusion of actionable findings. The techniques commonly used to reduce imaging times, the imaging protocols used at the authors' institution, and future directions in FAST imaging are reviewed to provide a practical and comprehensive overview of FAST MRI for practicing neuroradiologists. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Perioperative ischaemic brain injury and plasma neurofilament light: a secondary analysis of two prospective cohort studies.

BACKGROUND: Ischaemic brain infarction can occur without acute neurological symptoms (covert strokes) or with symptoms (overt strokes), both associated with poor health outcomes. We conducted a pilot study of the incidence of preoperative and postoperative (intraoperative or postoperative) covert strokes, and explored the relationship of postoperative ischaemic brain injury to blood levels of neurofilament light, a biomarker of neuronal damage. METHODS: We analysed 101 preoperative (within 2 weeks of surgery) and 58 postoperative research MRIs on postoperative days 2-9 from two prospective cohorts collected at the University of Wisconsin (NCT01980511 and NCT03124303). Participants were aged >65 yr and undergoing non-intracranial, non-carotid surgery. RESULTS: Preoperative covert stroke was identified in 2/101 participants (2%; Bayesian 95% confidence interval [CI], 0.2-5.4). This rate was statistically different from the postoperative ischaemic brain injury rate of 7/58 (12%, 4.9-21.3%; P=0.01) based on postoperative imaging. However, in a smaller group of participants with paired imaging (n=30), we did not identify the same effect (P=0.67). Patients with postoperative brain injury had elevated peak neurofilament light levels (median [inter-quartile range], 2.34 [2.24-2.64] log10 pg ml-1) compared with those without (1.86 [1.48-2.21] log10 pg ml-1; P=0.025). Delirium severity scores were higher in those with postoperative brain injury (19 [17-21]) compared with those without (7 [4-12]; P=0.01). CONCLUSION: Although limited by a small sample size, these data suggest that preoperative covert stroke occurs more commonly than previously anticipated. Plasma neurofilament light is a potential screening biomarker for postoperative ischaemic brain injury.

Motion-corrected 4D-Flow MRI for neurovascular applications.

Neurovascular 4D-Flow MRI has emerged as a powerful tool for comprehensive cerebrovascular hemodynamic characterization. Clinical studies in at risk populations such as aging adults indicate hemodynamic markers can be confounded by motion-induced bias. This study develops and characterizes a high fidelity 3D self-navigation approach for retrospective rigid motion correction of neurovascular 4D-Flow data. A 3D radial trajectory with pseudorandom ordering was combined with a multi-resolution low rank regularization approach to enable high spatiotemporal resolution self-navigators from extremely undersampled data. Phantom and volunteer experiments were performed at 3.0T to evaluate the ability to correct for different amounts of induced motions. In addition, the approach was applied to clinical-research exams from ongoing aging studies to characterize performance in the clinical setting. Simulations, phantom and volunteer experiments with motion correction produced images with increased vessel conspicuity, reduced image blurring, and decreased variability in quantitative measures. Clinical exams revealed significant changes in hemodynamic parameters including blood flow rates, flow pulsatility index, and lumen areas after motion correction in probed cerebral arteries (Flow: P<0.001 Lt ICA, P=0.002 Rt ICA, P=0.004 Lt MCA, P=0.004 Rt MCA; Area: P<0.001 Lt ICA, P<0.001 Rt ICA, P=0.004 Lt MCA, P=0.004 Rt MCA; flow pulsatility index: P=0.042 Rt ICA, P=0.002 Lt MCA). Motion induced bias can lead to significant overestimation of hemodynamic markers in cerebral arteries. The proposed method reduces measurement bias from rigid motion in neurovascular 4D-Flow MRI in challenging populations such as aging adults.

Simultaneous 3D-TOF angiography and 4D-flow MRI with enhanced flow signal using multiple overlapping thin slab acquisition and magnetization transfer.

PURPOSE: To investigate the fusion of 3D time-of-flight principles into 4D-flow MRI to enhance vessel contrast and signal without an exogenous contrast agent, enabling simultaneous in-flow based angiograms. METHODS: A 4D-flow MRI technique was developed consisting of multiple overlapping slabs with intermittent magnetization transfer preparation. The scan time penalty associated with multiple slab acquisitions was mitigated by using undersampled distributed spiral trajectories and compressed sensing reconstruction. A flow phantom was used to characterize in-flow enhancement, velocity noise improvement, and flow rate measurements against the single-slab 4D-flow MRI. In a patient-volunteer cohort (n = 15), magnitude-based angiograms were radiologically evaluated against 3D time-of-flight, and velocity measurements were compared pixel-wise against single-slab and contrast-enhanced 4D-flow MRI. RESULTS: Multiple-slab acquisitions, together with magnetization transfer preparation, substantially improved vessel signal, contrast, and vessel conspicuity in magnitude angiograms. Both clinical 3D time-of-flight and the proposed technique produced equivalent vessel depictions with no statistically significant difference (p < .1). Both techniques also produced clear depictions of brain aneurysms in all patients; however, very small vessels tended to show reduced conspicuity in the proposed technique. Velocity measurements agreed with contrast-enhanced and single-slab scans with high correlations (R2 = 0.941-0.974) and agreements (slopes = 0.994-1.071). Slab boundary and magnetization transfer-related artifacts were not observed in velocity measurements, and velocity noise was reduced with in-flow enhancement over single-slab scans (phantom). CONCLUSION: The vessel signal and contrast can be improved in 4D-flow MRI without exogenous contrast agents by utilizing in-flow enhancement, efficient sampling, and compressed sensing. The in-flow enhancement also enables simultaneous 3D time-of-flight angiograms useful for flow quantification and diagnosis.

Virtual injections using 4D flow MRI with displacement corrections and constrained probabilistic streamlines.

PURPOSE: Streamlines from 4D-flow MRI have been used clinically for intracranial blood-flow tracking. However, deterministic and stochastic errors degrade streamline quality. The purpose of this study is to integrate displacement corrections, probabilistic streamlines, and novel fluid constraints to improve selective blood-flow tracking and emulate "virtual bolus injections." METHODS: Both displacement artifacts (deterministic) and velocity noise (stochastic) inherently occur during phase-contrast MRI acquisitions. Here, two displacement correction methods, single-step and iterative, were tested in silico with simulated displacements and were compared with ground-truth velocity fields. Next, the effects of combining displacement corrections and constrained probabilistic streamlines were performed in 10 healthy volunteers using time-averaged 4D-flow data. Measures of streamline length and depth into vasculature were then compared with streamlines generated with no corrections and displacement correction alone using one-way repeated-measures analysis of variance and Friedman's tests. Finally, virtual injections with improved streamlines were generated for three intracranial pathology cases. RESULTS: Iterative displacement correction outperformed the single-step method in silico. In volunteers, the combination of displacement corrections and constrained probabilistic streamlines allowed for significant improvements in streamline length and increased the number of streamlines entering the circle of Willis relative to streamlines with no corrections and displacement correction alone. In the pathology cases, virtual injections with improved streamlines were qualitatively similar to dynamic arterial spin labeling images and allowed for forward/reverse selective flow tracking to characterize cerebrovascular malformations. CONCLUSION: Virtual injections with improved streamlines from 4D-flow MRI allow for flexible, robust, intracranial flow tracking.

Brain herniation (encephalocele) into arachnoid granulations: prevalence and association with pulsatile tinnitus and idiopathic intracranial hypertension.

PURPOSE: Brain herniation into arachnoid granulations (BHAG) of the dural venous sinuses is a recently described finding of uncertain etiology. The purpose of this study was to investigate the prevalence of BHAG in a cohort of patients with pulsatile tinnitus (PT) and to clarify the physiologic and clinical implications of these lesions. METHODS: The imaging and charts of consecutive PT patients were retrospectively reviewed. All patients were examined with MRI including pre- and post-contrast T1- and T2-weighted sequences. Images were reviewed separately by three blinded neuroradiologists to identify the presence of BHAG. Their location, signal intensity, size, presence of arachnoid granulation, and associated dural venous sinus stenosis were documented. Clinical records were further reviewed for idiopathic intracranial hypertension, history of prior lumbar puncture, and opening pressure. RESULTS: Two hundred sixty-two consecutive PT patients over a 4-year period met inclusion criteria. PT patients with BHAG were significantly more likely to have idiopathic intracranial hypertension than PT patients without BHAG (OR 4.2, CI 1.5-12, p = 0.006). Sixteen out of 262 (6%) patients were found to have 18 BHAG. Eleven out of 16 (69%) patients had unilateral temporal or occipital lobe herniations located in the transverse sinus or the transverse-sigmoid junction. Three out of 16 (19%) patients had unilateral cerebellar herniations and 2/16 (13%) patients had bilateral BHAG. CONCLUSION: In patients with PT, BHAG is a prevalent MRI finding that is strongly associated with the clinical diagnosis of IIH. The pathogenesis of BHAG remains uncertain, but recognition should prompt comprehensive evaluation for IIH.

Increased relative risk of delayed hemorrhage in patients taking anticoagulant/antiplatelet medications with concurrent aspirin therapy: implications for clinical practice based on 3-year retrospective analysis in a large health system.

PURPOSE: The incidence of delayed posttraumatic intracranial hemorrhage (DH) in patients on anticoagulant (AC) and antiplatelet (AP) medications, especially with concurrent aspirin therapy, is not well established, with studies reporting disparate results with between 1-10% risk of DH and 0-3% mortality. The purpose of this 3-year retrospective study is to evaluate the true risk of DH in patients on AP/AC medications with or without concurrent aspirin therapy. METHODS: One thousand forty-six patients taking AP and AC medications presenting to network emergency departments with head trauma who had repeat CT to evaluate for DH were included in the study. Repeat examinations were typically performed within 24 h (average follow-up time was 21 h and 99% were within 3 days). Mean time to DH was 20 h. All positive studies were reviewed by two board-certified neuroradiologists. Patients were excluded from the study if hemorrhage was retrospectively identified on the initial examination. Cases were reclassified as negative if hemorrhage on the follow-up examination was thought to be not present or artifactual. Cases were considered positive if the initial examination was negative and the follow-up examination demonstrated new hemorrhage. RESULTS: Overall, there was 1.91% incidence (20 patients) of DH and 0.3% overall mortality (3 patients). The group of patients taking warfarin or AP agents demonstrated a significantly higher rate of DH (3.2% compared to 0.9%) and higher mortality (0.9% compared to 0.0%) compared to the DOAC group (p < 0.01). The risk of DH in patients taking AC or AP agents with aspirin (13/20 cases) was significantly higher (RR 3.8, p < 0.01) than that of patients taking AC or AP alone (7/20 cases). CONCLUSION: The risk of DH was significantly higher in patients taking aspirin in addition to AC/AP medications. Repeat imaging should be obtained for trauma patients taking AC/AP agents with concurrent aspirin. The rate of DH was also significantly higher in patients taking warfarin or AP agents when compared to patients taking DOACs. Repeat examination should be strongly considered on patients taking warfarin or AP agents without aspirin. Given the relatively low risk of DH in patients taking DOACs alone, repeat imaging could be reserved for patients with external signs of trauma or dangerous mechanism of injury.

Spatial dependency and the role of local susceptibility for velocity selective arterial spin labeling (VS-ASL) relative tagging efficiency using accelerated 3D radial sampling with a BIR-8 preparation.

PURPOSE: Velocity selective arterial spin labeling (VS-ASL) is a promising approach for non-contrast perfusion imaging that provides robustness to vascular geometry and transit times; however, VS-ASL assumes spatially uniform tagging efficiency. This work presents a mapping approach to investigate VS-ASL relative tagging efficiency including the impact of local susceptibility effects on a BIR-8 preparation. METHODS: Numerical simulations of tagging efficiency were performed to evaluate sensitivity to regionally varying local susceptibility gradients and blood velocity. Tagging efficiency mapping was performed in susceptibility phantoms and healthy human subjects (N = 7) using a VS-ASL preparation module followed by a short, high spatial resolution 3D radial-based image acquisition. Tagging efficiency maps were compared to 4D-flow, B1 , and B0 maps acquired in the same imaging session for six of the seven subjects. RESULTS: Numerical simulations were found to predict reduced tagging efficiency with the combination of high blood velocity and local gradient fields. Phantom experiments corroborated numerical results. Relative efficiency mapping in normal volunteers showed unique efficiency patterns depending on individual subject anatomy and physiology. Uniform tagging efficiency was generally observed in vivo, but reduced efficiency was noted in regions of high blood velocity and local susceptibility gradients. CONCLUSION: We demonstrate an approach to map the relative tagging efficiency and show application of this methodology to a novel BIR-8 preparation recently proposed in the literature. We present results showing rapid flow in the presence of local susceptibility gradients can lead to complicated signal modulations in both tag and control images and reduced tagging efficiency.

Wall enhancement on black-blood MRI is independently associated with symptomatic status of unruptured intracranial saccular aneurysm.

OBJECTIVE: This study aims to investigate whether aneurysm wall enhancement (AWE) is independently associated with symptomatic status of unruptured intracranial aneurysms (UIAs). METHODS: One hundred thirty-nine consecutive patients (67 male, mean age 58 ± 11 years) with 79 symptomatic and 87 asymptomatic UIAs were imaged using black-blood MRI pre- and post-gadolinium contrast administration and 3D DSA. Symptoms related to aneurysms were identified including cranial nerve deficits and headache. AWE grade and area were characterized, and aneurysm size was measured on DSA. Multivariate binary logistic regression analysis was used to identify factors associated with symptoms. Further subgroup analysis was performed for aneurysms size < 10 mm. RESULTS: Symptomatic UIAs had significantly larger aneurysm size (11.2 ± 6.2 mm vs. 6.4 ± 3.3 mm), enhancement grade (1.3 ± 0.6 vs. 0.4 ± 0.6), enhancement area (2.0 ± 0.9 vs. 0.4 ± 0.7), and higher prevalence of thick enhancement (39% vs. 3%) compared with asymptomatic UIAs, all p < 0.001. In multivariate analysis, only AWE area (odds ratio [OR] 6.9, 95% confidence interval [4.0, 11.7]) was independently associated with symptoms. AWE area had an area under curve (AUC) value of 0.888, with 72.2% sensitivity and 92.0% specificity for symptoms, which was superior to aneurysm size (AUC of 0.771, with 75.9% sensitivity and 65.5% specificity). In the subgroup analysis of aneurysms smaller than 10 mm (n = 118), AWE area (OR, 7.0, p < 0.001) remained the only independent risk factor associated with symptoms. CONCLUSIONS: Larger AWE area is independently associated with symptomatic UIAs, which may provide additional value to guide UIA management and improve patient outcomes. KEY POINTS: • Symptomatic intracranial aneurysms are larger and more often demonstrate significant wall enhancement than asymptomatic aneurysms. • Larger wall enhancement area is independently associated with symptomatic intracranial aneurysm.

Visualizing wall enhancement over time in unruptured intracranial aneurysms using 3D vessel wall imaging.

BACKGROUND: Few studies directed at assessing the visualization of the walls of unruptured aneurysms have used higher-resolution 3D MRI vessel wall imaging. Prospective longitudinal studies are also needed to screen vessel wall changes in unruptured aneurysms. PURPOSE: To compare the aneurysm wall visualization on pre- and post-3D isotropic T1 -weighted Sampling Perfection with Application-optimized Contrasts by using different flip angle Evolutions (SPACE) images and to explore whether there is a change in wall enhancement at follow up. STUDY TYPE: Prospective. POPULATION: Twenty-nine patients with a total of 35 unruptured intracranial aneurysms. SEQUENCE: 3D T1 -weighted pre- and postcontrast SPACE (0.5 mm isotropic) at 3.0T. ASSESSMENT: The aneurysm wall visibility (0-5 scale) between pre- and postcontrast images as well as the wall enhancement (0-5 scale) between follow-up and baseline studies (6-30 months, average 12.7 months) were compared. Differences in wall visibility and enhancement were also investigated as a function of aneurysm diameter and location. STATISTICAL TEST: The Wilcoxon signed rank paired test was used to compare the wall visibility score between pre- and postcontrast SPACE images, as well as wall enhancement between follow-up and baseline. The Mann-Whitney and Kruskal-Wallis tests were used to investigate the enhancement difference between different diameters and locations. RESULTS: Postcontrast images had significantly higher wall visibility (P = 0.01). A wall enhancement score ≥2 was found in 71% of the aneurysms. Changes in levels of wall enhancement were found in 17% of the aneurysms at follow-up studies, but those changes were small. Wall visibility and enhancement scores of large aneurysms were significantly higher than small ones (P < 0.001). DATA CONCLUSION: 3D T1 -weighted higher resolution SPACE can be used to assess changes in enhancement at follow-up studies. Contrast SPACE image provides better aneurysm wall visibility and improves visualization of the aneurysm wall. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:193-200.

Magnetic Resonance Imaging and Clinical Factors Associated With Ischemic Stroke in Patients Suspected of Cervical Artery Dissection.

Background and Purpose- Cervical artery dissection is a major cause of ischemic stroke in the young and presents with various imaging findings, including stenosis and intramural hematoma (IMH). Our goal was to determine the relative contribution of lumen findings and IMH to acute ischemic stroke and whether a heavily T1-weighted sequence could more reliably detect IMH. Methods- Institutional review board approval was obtained for this retrospective study of 254 patients undergoing magnetic resonance imaging/magnetic resonance angiography for suspected dissection. Imaging included standard turbo spin-echo (TSE) T1-fat saturation and heavily T1-weighted flow-suppressed magnetization-prepared rapid acquisition gradient-recalled echo sequences. Subjects with stents (1) or atherosclerotic disease (26) were excluded, leaving 227 subjects. Kappa analysis was used to determine IMH interrater reliability on magnetization-prepared rapid acquisition gradient-recalled echo and T1-fat saturation in 4 vessels per subject. Lumen findings, cardiovascular risk factors, medications, and nondissection stroke sources were recorded. Mixed-effects multivariate Poisson regression was used to determine the prevalence ratio of each factor with acute ischemic stroke, accounting for 4 vessels per patient with backward elimination to a threshold P value of 0.10. Results- Patients were 41.9% men, mean age of 47.3±16.6 years, with 114 dissections and 107 strokes. IMH interrater reliability was significantly higher for magnetization-prepared rapid acquisition gradient-recalled echo (κ=0.83; 95% CI, 0.78-0.86) versus T1-fat saturation (0.58; 95% CI, 0.57-0.68). The final acute stroke prediction model included magnetization-prepared rapid acquisition gradient-recalled echo-detected IMH (prevalence ratio, 2.0; 95% CI, 1.1-3.9; P=0.034), stenosis, pseudoaneurysm, male sex, current smoking, and nondissection stroke sources. The final model had high discrimination for acute stroke (area under the curve, 0.902; 95% CI, 0.872-0.932), compared with models without stenosis (0.861; 95% CI, 0.821-0.902), and without stenosis and IMH (0.831; 95% CI, 0.783-0.879). All 3 models were significantly different at P<0.05. Conclusions- Along with stenosis, IMH detection significantly contributed to acute ischemic stroke pathogenesis in patients with suspected cervical artery dissection. In addition, IMH detection can be made more reliable with heavily T1-weighted sequences.

Accelerated whole brain intracranial vessel wall imaging using black blood fast spin echo with compressed sensing (CS-SPACE).

OBJECTIVE: Develop and optimize an accelerated, high-resolution (0.5 mm isotropic) 3D black blood MRI technique to reduce scan time for whole-brain intracranial vessel wall imaging. MATERIALS AND METHODS: A 3D accelerated T1-weighted fast-spin-echo prototype sequence using compressed sensing (CS-SPACE) was developed at 3T. Both the acquisition [echo train length (ETL), under-sampling factor] and reconstruction parameters (regularization parameter, number of iterations) were first optimized in 5 healthy volunteers. Ten patients with a variety of intracranial vascular disease presentations (aneurysm, atherosclerosis, dissection, vasculitis) were imaged with SPACE and optimized CS-SPACE, pre and post Gd contrast. Lumen/wall area, wall-to-lumen contrast ratio (CR), enhancement ratio (ER), sharpness, and qualitative scores (1-4) by two radiologists were recorded. RESULTS: The optimized CS-SPACE protocol has ETL 60, 20% k-space under-sampling, 0.002 regularization factor with 20 iterations. In patient studies, CS-SPACE and conventional SPACE had comparable image scores both pre- (3.35 ± 0.85 vs. 3.54 ± 0.65, p = 0.13) and post-contrast (3.72 ± 0.58 vs. 3.53 ± 0.57, p = 0.15), but the CS-SPACE acquisition was 37% faster (6:48 vs. 10:50). CS-SPACE agreed with SPACE for lumen/wall area, ER measurements and sharpness, but marginally reduced the CR. CONCLUSION: In the evaluation of intracranial vascular disease, CS-SPACE provides a substantial reduction in scan time compared to conventional T1-weighted SPACE while maintaining good image quality.

Clinical implementation of synthesized mammography with digital breast tomosynthesis in a routine clinical practice.

BACKGROUND: Most published studies evaluating digital breast tomosynthesis (DBT) included a separate 2-dimensional full-field digital mammogram (FFDM) for DBT screening protocols, increasing radiation from screening mammography. Synthesized mammography (SM) creates a 2-dimensional image from the DBT source data, and if used in place of FFDM, it reduces radiation of DBT screening. This study evaluated the implementation of SM + DBT in routine screening practice in terms of recall rates, cancer detection rates (CDR), % of minimal cancers, % of node-positive cancers, and positive predictive values (PPV). MATERIALS AND METHODS: A multivariate retrospective institutional analysis was performed on 31,979 women who obtained screening mammography (10/2013-12/2015) with cohorts divided by modality (SM + DBT, FFDM + DBT, and FFDM). We adjusted for comparison mammograms, age, breast density, and the interpreting radiologist. Recall type was analyzed for differences (focal asymmetry, asymmetry, masses, calcifications, architectural distortion). RESULTS: SM + DBT significantly decreased the recall rate compared to FFDM (5.52 vs. 7.83%, p < 0.001) with no differences in overall CDR (p = 0.66), invasive and/or in situ CDR, or percentages of minimal and node-negative cancers. PPV1 significantly increased with SM + DBT relative to FFDM (9.1 vs. 6.2%, p = 0.02). SM + DBT did not differ significantly in recall rate or overall CDR compared to FFDM + DBT. There were statistically significant differences in certain findings recalled by screening modality (e.g., focal asymmetries). CONCLUSIONS: SM + DBT reduces false positives compared to FFDM, while maintaining the CDR and other desirable audit outcome data. SM + DBT is more accurate than FFDM alone, and is a desirable alternative to FFDM + DBT, given the added benefit of radiation reduction.

Motion-insensitive carotid intraplaque hemorrhage imaging using 3D inversion recovery preparation stack of stars (IR-prep SOS) technique.

PURPOSE: Carotid artery imaging is important in the clinical management of patients at risk for stroke. Carotid intraplaque hemorrhage (IPH) presents an important diagnostic challenge. 3D magnetization prepared rapid acquisition gradient echo (MPRAGE) has been shown to accurately image carotid IPH; however, this sequence can be limited due to motion- and flow-related artifact. The purpose of this work was to develop and evaluate an improved 3D carotid MPRAGE sequence for IPH detection. We hypothesized that a radial-based k-space trajectory sequence such as "Stack of Stars" (SOS) incorporated with inversion recovery preparation would offer reduced motion sensitivity and more robust flow suppression by oversampling of central k-space. MATERIALS AND METHODS: A total of 31 patients with carotid disease (62 carotid arteries) were imaged at 3T magnetic resonance imaging (MRI) with 3D IR-prep Cartesian and SOS sequences. Image quality was determined between SOS and Cartesian MPRAGE in 62 carotid arteries using t-tests and multivariable linear regression. Kappa analysis was used to determine interrater reliability. RESULTS: In all, 25 among 62 carotid plaques had carotid IPH by consensus from the reviewers on SOS compared to 24 on Cartesian sequence. Image quality was significantly higher with SOS compared to Cartesian (mean 3.74 vs. 3.11, P < 0.001). SOS acquisition yielded sharper image features with less motion (19.4% vs. 45.2%, P < 0.002) and flow artifact (27.4% vs. 41.9%, P < 0.089). There was also excellent interrater reliability with SOS (kappa = 0.89), higher than that of Cartesian (kappa = 0.84). CONCLUSION: By minimizing flow and motion artifacts and retaining high interrater reliability, the SOS MPRAGE has important advantages over Cartesian MPRAGE in carotid IPH detection. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:410-417.

Unraveling diurnal and technical variability in cerebral hemodynamics from neurovascular 4D-Flow MRI.

Neurovascular 4D-Flow MRI enables non-invasive evaluation of cerebral hemodynamics including measures of cerebral blood flow (CBF), vessel pulsatility index (PI), and cerebral pulse wave velocity (PWV). 4D-Flow measures have been linked to various neurovascular disorders including small vessel disease and Alzheimer's disease; however, physiological and technical sources of variability are not well established. Here, we characterized sources of diurnal physiological and technical variability in cerebral hemodynamics using 4D-Flow in a retrospective study of cognitively unimpaired older adults (N = 750) and a prospective study of younger adults (N = 10). Younger participants underwent repeated MRI sessions at 7am, 4 pm, and 10 pm. In the older cohort, having an MRI earlier on the day was significantly associated with higher CBF and lower PI. In prospective experiments, time of day significantly explained variability in CBF and PI; however, not in PWV. Test-retest experiments showed high CBF intra-session repeatability (repeatability coefficient (RPC) =7.2%), compared to lower diurnal repeatability (RPC = 40%). PI and PWV displayed similar intra-session and diurnal variability (PI intra-session RPC = 22%, RPC = 24% 7am vs 4 pm; PWV intra-session RPC = 17%, RPC = 21% 7am vs 4 pm). Overall, CBF measures showed low technical variability, supporting diurnal variability is from physiology. PI and PWV showed higher technical variability but less diurnal variability.