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Objectives Treatment and outcomes of acute stroke have been revolutionised by mechanical thrombectomy. Deep learning has shown great promise in diagnostics but applications in video and interventional radiology lag behind. We aimed to develop a model that takes as input digital subtraction angiography (DSA) videos and classifies the video according to (1) the presence of large vessel occlusion (LVO), (2) the location of the occlusion, and (3) the efficacy of reperfusion. Methods All patients who underwent DSA for anterior circulation acute ischaemic stroke between 2012 and 2019 were included. Consecutive normal studies were included to balance classes. An external validation (EV) dataset was collected from another institution. The trained model was also used on DSA videos post mechanical thrombectomy to assess thrombectomy efficacy. Results In total, 1024 videos comprising 287 patients were included (44 for EV). Occlusion identification was achieved with 100% sensitivity and 91.67% specificity (EV 91.30% and 81.82%). Accuracy of location classification was 71% for ICA, 84% for M1, and 78% for M2 occlusions (EV 73, 25, and 50%). For post-thrombectomy DSA (n = 194), the model identified successful reperfusion with 100%, 88%, and 35% for ICA, M1, and M2 occlusion (EV 89, 88, and 60%). The model could also perform classification of post-intervention videos as mTICI Conclusions Our model can successfully identify normal DSA studies from those with LVO and classify thrombectomy outcome and solve a clinical radiology problem with two temporal elements (dynamic video and pre and post intervention). Key Points • DEEP MOVEMENT represents a novel application of a model applied to acute stroke imaging to handle two types of temporal complexity, dynamic video and pre and post intervention. • The model takes as an input digital subtraction angiograms of the anterior cerebral circulation and classifies according to (1) the presence or absence of large vessel occlusion, (2) the location of the occlusion, and (3) the efficacy of thrombectomy. • Potential clinical utility lies in providing decision support via rapid interpretation (pre thrombectomy) and automated objective gradation of thrombectomy outcomes (post thrombectomy).

Introduction: Cerebrovascular reserve (CVR) reflects the change in cerebral blood flow (CBF) in response to a vasoactive stimulus and can be measured using a brain stress test whereby CBF is augmented using vasodilators. Studies have demonstrated that impaired CVR was associated with a higher risk of acute stroke and that bypass can reduce the risk of strokes. Arterial spin labeling is a quantitative MRI technique that enables non-invasive CBF and CVR measurement. Studies have shown the effectiveness of ASL in identifying CVR impairment in Moyamoya patients. Here, we compare the CBF and CVR of Moyamoya patients before and after bypass using single and multiple delay ASL techniques. Methods: MRI data were acquired from 24 Moyamoya patients (16-54 years, 3 males) using a 3T MRI system. All patients had unilateral or bilateral vessel occlusion at ACA, MCA and/or PCA. The scanning parameters of the single post-labeling delay pseudo-continuous ASL (single-PLD PCASL), delay pseudo-continuous ASL (multi-PLD PCASL, 5 PLDs) 2. ASL data were acquired simultaneously at baseline and 15 minutes after the injection of the vasodilator acetazolamide (15 mg/kg with a maximum 1 g). CBF was computed using the general kinetic model. CVR was computed as the percentage of CBF change compared with baseline CBF. Flow territories (right and left ACA, MCA, and PCA) were defined based on the Harvard-Oxford cortical and subcortical structural atlases. Mean CVR within the territories affected by occlusion and normal territories was computed for each subject. T-tests were performed to compare the mean CVR between the affected and unaffected territories. Results: For this cohort, our quantitative analysis revealed that CVR of the affected regions increased significantly by 12% and 21% measured by single and multiple delay PCASL respectively, implying improved CBF and lower risk for strokes. Discussion: ASL was effective to detect improved CBF and CVR in Moyamoya patients after bypass surgeries.

Gadolinium chelates have been used as standard contrast agents for clinical MRI for several decades. However, several investigators recently reported that rare Earth metals such as gadolinium are deposited in the brain for months or years. This is particularly concerning for children, whose developing brain is more vulnerable to exogenous toxins compared to adults. Therefore, a search is under way for alternative MR imaging biomarkers. The United States Food and Drug Administration (FDA)-approved iron supplement ferumoxytol can solve this unmet clinical need: ferumoxytol consists of iron oxide nanoparticles that can be detected with MRI and provide significant T1- and T2-signal enhancement of vessels and soft tissues. Several investigators including our research group have started to use ferumoxytol off-label as a new contrast agent for MRI. This article reviews the existing literature on the biodistribution of ferumoxytol in children and compares the diagnostic accuracy of ferumoxytol- and gadolinium-chelate-enhanced MRI. Iron oxide nanoparticles represent a promising new class of contrast agents for pediatric MRI that can be metabolized and are not deposited in the brain.

The prognosis for high-grade glioma (HGG) remains dismal and the extent of resection correlates with overall survival and progression free disease. Epidermal growth factor receptor (EGFR) is a biomarker heterogeneously expressed in HGG. We assessed the feasibility of detecting HGG using near-infrared fluorescent antibody targeting EGFR. Mice bearing orthotopic HGG xenografts with modest EGFR expression were imaged in vivo after systemic panitumumab-IRDye800 injection to assess its tumor-specific uptake macroscopically over 14 days, and microscopically ex vivo. EGFR immunohistochemical staining of 59 tumor specimens from 35 HGG patients was scored by pathologists and expression levels were compared to that of mouse xenografts. Intratumoral distribution of panitumumab-IRDye800 correlated with near-infrared fluorescence and EGFR expression. Fluorescence distinguished tumor cells with 90% specificity and 82.5% sensitivity. Target-to-background ratios peaked at 14 h post panitumumab-IRDye800 infusion, reaching 19.5 in vivo and 7.6 ex vivo, respectively. Equivalent or higher EGFR protein expression compared to the mouse xenografts was present in 77.1% HGG patients. Age, combined with IDH-wildtype cerebral tumor, was predictive of greater EGFR protein expression in human tumors. Tumor specific uptake of panitumumab-IRDye800 provided remarkable contrast and a flexible imaging window for fluorescence-guided identification of HGGs despite modest EGFR expression.

3D multi-echo gradient-recalled echo (ME-GRE) can simultaneously generate time-of-flight magnetic resonance angiography (pTOF) in addition to T2*-based susceptibility-weighted images (SWI). We assessed the clinical performance of pTOF generated from a 3D ME-GRE acquisition compared with conventional TOF-MRA (cTOF). Eighty consecutive children were retrospectively identified who obtained 3D ME-GRE alongside cTOF. Two blinded readers independently assessed pTOF derived from 3D ME-GRE and compared them with cTOF. A 5-point Likert scale was used to rank lesion conspicuity and to assess for diagnostic confidence. Across 80 pediatric neurovascular pathologies, a similar number of lesions were reported on pTOF and cTOF (43–40%, respectively, p > 0.05). Rating of lesion conspicuity was higher with cTOF (4.5 ± 1.0) as compared with pTOF (4.0 ± 0.7), but this was not significantly different (p = 0.06). Diagnostic confidence was rated higher with cTOF (4.8 ± 0.5) than that of pTOF (3.7 ± 0.6; p

Cerebrovascular reactivity (CVR), the capacity of the brain to increase cerebral blood flow (CBF) to meet changes in physiological demand, is an important biomarker to evaluate brain health. Typically, this brain “stress test” is performed by using a medical imaging modality to measure the CBF change between two states: at baseline and after vasodilation. However, since there are many imaging modalities and many ways to augment CBF, a wide range of CVR values have been reported. An understanding of CVR reproducibility is critical to determine the most reliable methods to measure CVR as a clinical biomarker. This review focuses on CVR reproducibility studies using neuroimaging techniques in 32 articles comprising 427 total subjects. The literature search was performed in PubMed, Embase, and Scopus. The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We identified 5 factors of the experimental subjects (such as sex, blood characteristics, and smoking) and 9 factors of the measuring technique (such as the imaging modality, the type of the vasodilator, and the quantification method) that have strong effects on CVR reproducibility. Based on this review, we recommend several best practices to improve the reproducibility of CVR quantification in neuroimaging studies.

Deep learning may enable a reduction in dose of fluorine 18 fluorodeoxyglucose in integrated PET/MRI scans of children and young adults with lymphoma for treatment response assessment without compr...

Background: The prognosis for high-grade glioma (HGG) remains dismal and extent of resection correlates with overall survival and progression free disease. Epidermal growth factor receptor (EGFR) is a biomarker heterogeneously expressed in HGG. We assessed the feasibility of detecting HGG using near-infrared fluorescent antibody targeting EGFR. Methods: Mice bearing orthotopic HGG xenografts with modest EGFR expression were imaged in vivo after systemic panitumumab-IRDye800 injection to assess its tumor-specific uptake macroscopically over 14 days, and microscopically ex vivo. EGFR immunohistochemical staining of 59 tumor specimens from 35 HGG patients during was scored by pathologists and expression levels were compared to that of mouse xenografts. Results: Intratumoral distribution of pan800 correlated with near-infrared fluorescence and EGFR expression. Fluorescence distinguished tumor cells with 90% specificity and 82.5% sensitivity. Target-to-background ratios peaked at 14 hours post panitumumab-IRDye800 infusion, reaching 19.5 in vivo and 7.6 ex vivo, respectively. Equivalent or higher EGFR protein expression compared to the mouse xenografts was present in 77.1% HGG patients. Age, combined with IDH-wildtype cerebral tumor, was predictive of greater EGFR protein expression in human tumors. Conclusion: Tumor specific uptake of pan800 provided remarkable contrast and a flexible imaging window for fluorescence-guided identification of HGGs despite modest EGFR expression.

Background Iron oxide nanoparticles are an alternative contrast agent for MRI. Gadolinium deposition has raised safety concerns, but it is unknown whether ferumoxytol administration also deposits in the brain. Purpose To investigate whether there are signal intensity changes in the brain at multiecho gradient imaging following ferumoxytol exposure in children and young adults. Materials and Methods This retrospective case-control study included children and young adults, matched for age and sex, with brain arteriovenous malformations who received at least one dose of ferumoxytol from January 2014 to January 2018. In participants who underwent at least two brain MRI examinations (subgroup), the first and last available examinations were analyzed. Regions of interests were placed around deep gray structures on quantitative susceptibility mapping and R2* images. Mean susceptibility and R2* values of regions of interests were recorded. Measurements were assessed by linear regression analyses: a between-group comparison of ferumoxytol-exposed and unexposed participants and a within-group (subgroup) comparison before and after exposure. Results Seventeen participants (mean age ± standard deviation, 13 years ± 5; nine male) were in the ferumoxytol-exposed (case) group, 21 (mean age, 14 years ± 5; 11 male) were in the control group, and nine (mean age, 12 years ± 6; four male) were in the subgroup. The mean number of ferumoxytol administrations was 2 ± 1 (range, one to four). Mean susceptibility (in parts per million [ppm]) and R2* (in inverse seconds [sec-1]) values of the dentate (case participants: 0.06 ppm ± 0.04 and 23.87 sec-1 ± 4.13; control participants: 0.02 ppm ± 0.03 and 21.7 sec-1 ± 5.26), substantia nigrae (case participants: 0.08 ppm ± 0.06 and 27.46 sec-1 ± 5.58; control participants: 0.04 ppm ± 0.05 and 24.96 sec-1 ± 5.3), globus pallidi (case participants: 0.14 ppm ± 0.05 and 30.75 sec-1 ± 5.14; control participants: 0.08 ppm ± 0.07 and 28.82 sec-1 ± 6.62), putamina (case participants: 0.03 ppm ± 0.02 and 20.63 sec-1 ± 2.44; control participants: 0.02 ppm ± 0.02 and 19.65 sec-1 ± 3.6), caudate (case participants: -0.1 ppm ± 0.04 and 18.21 sec-1 ± 3.1; control participants: -0.06 ppm ± 0.05 and 18.83 sec-1 ± 3.32), and thalami (case participants: 0 ppm ± 0.03 and 16.49 sec-1 ± 3.6; control participants: 0.02 ppm ± 0.02 and 18.38 sec-1 ± 2.09) did not differ between groups (susceptibility, P = .21; R2*, P = .24). For the subgroup, the mean interval between the first and last ferumoxytol administration was 14 months ± 8 (range, 1-25 months). Mean susceptibility and R2* values of the dentate (first MRI: 0.06 ppm ± 0.05 and 25.78 sec-1 ± 5.9; last MRI: 0.06 ppm ± 0.02 and 25.55 sec-1 ± 4.71), substantia nigrae (first MRI: 0.06 ppm ± 0.06 and 28.26 sec-1 ± 9.56; last MRI: 0.07 ppm ± 0.06 and 25.65 sec-1 ± 6.37), globus pallidi (first MRI: 0.13 ppm ± 0.07 and 27.53 sec-1 ± 8.88; last MRI: 0.14 ppm ± 0.06 and 29.78 sec-1 ± 6.54), putamina (first MRI: 0.03 ppm ± 0.03 and 19.78 sec-1 ± 3.51; last MRI: 0.03 ppm ± 0.02 and 19.73 sec-1 ± 3.01), caudate (first MRI: -0.09 ppm ± 0.05 and 21.38 sec-1 ± 4.72; last MRI: -0.1 ppm ± 0.05 and 18.75 sec-1 ± 2.68), and thalami (first MRI: 0.01 ppm ± 0.02 and 17.65 sec-1 ± 5.16; last MRI: 0 ppm ± 0.02 and 15.32 sec-1 ± 2.49) did not differ between the first and last MRI examinations (susceptibility, P = .95; R2*, P = .54). Conclusion No overall significant differences were found in susceptibility and R2* values of deep gray structures to suggest retained iron in the brain between ferumoxytol-exposed and unexposed children and young adults with arteriovenous malformations and in those exposed to ferumoxytol over time. © RSNA, 2020.

3D multi-echo gradient-recalled echo (ME-GRE) can simultaneously generate time-of-flight magnetic resonance angiography (pTOF) in addition to T2*-based susceptibility-weighted images (SWI). We assessed the clinical performance of pTOF generated from a 3D ME-GRE acquisition compared with conventional TOF-MRA (cTOF).Eighty consecutive children were retrospectively identified who obtained 3D ME-GRE alongside cTOF. Two blinded readers independently assessed pTOF derived from 3D ME-GRE and compared them with cTOF. A 5-point Likert scale was used to rank lesion conspicuity and to assess for diagnostic confidence.Across 80 pediatric neurovascular pathologies, a similar number of lesions were reported on pTOF and cTOF (43-40%, respectively, p 0.05). Rating of lesion conspicuity was higher with cTOF (4.5 ± 1.0) as compared with pTOF (4.0 ± 0.7), but this was not significantly different (p = 0.06). Diagnostic confidence was rated higher with cTOF (4.8 ± 0.5) than that of pTOF (3.7 ± 0.6; p 0.001). Overall, the inter-rater agreement between two readers for lesion count on pTOF was classified as almost perfect (κ = 0.98, 96% CI 0.8-1.0).In this study, TOF-MRA simultaneously generated in addition to SWI from 3D MR-GRE can serve as a diagnostic adjunct, particularly for proximal vessel disease and when conventional TOF-MRA images are absent.

Purpose Amplified magnetic resonance imaging (aMRI) was recently introduced as a new brain motion detection and visualization method. The original aMRI approach used a video-processing algorithm, Eulerian video magnification (EVM), to amplify cardio-ballistic motion in retrospectively cardiac-gated MRI data. Here, we strive to improve aMRI by incorporating a phase-based motion amplification algorithm. Methods Phase-based aMRI was developed and tested for correct implementation and ability to amplify sub-voxel motions using digital phantom simulations. The image quality of phase-based aMRI was compared with EVM-based aMRI in healthy volunteers at 3T, and its amplified motion characteristics were compared with phase-contrast MRI. Data were also acquired on a patient with Chiari I malformation, and qualitative displacement maps were produced using free form deformation (FFD) of the aMRI output. Results Phantom simulations showed that phase-based aMRI has a linear dependence of amplified displacement on true displacement. Amplification was independent of temporal frequency, varying phantom intensity, Rician noise, and partial volume effect. Phase-based aMRI supported larger amplification factors than EVM-based aMRI and was less sensitive to noise and artifacts. Abnormal biomechanics were seen on FFD maps of the Chiari I malformation patient. Conclusion Phase-based aMRI might be used in the future for quantitative analysis of minute changes in brain motion and may reveal subtle physiological variations of the brain as a result of pathology using processing of the fundamental harmonic or by selectively varying temporal harmonics. Preliminary data shows the potential of phase-based aMRI to qualitatively assess abnormal biomechanics in Chiari I malformation.

BACKGROUND: Whole-body diffusion-weighted (DW) MRI can help detect cancer with high sensitivity. However, the assessment of therapy response often requires information about tumor metabolism, which is measured with fluorine 18 fluorodeoxyglucose (FDG) PET. PURPOSE: To compare tumor therapy response with whole-body DW MRI and FDG PET/MRI in children and young adults. MATERIALS AND METHODS: In this prospective, nonrandomized multicenter study, 56 children and young adults (31 male and 25 female participants; mean age, 15 years ± 4 [standard deviation]; age range, 6–22 years) with lymphoma or sarcoma underwent 112 simultaneous whole-body DW MRI and FDG PET/MRI between June 2015 and December 2018 before and after induction chemotherapy (ClinicalTrials.gov identifier: NCT01542879). The authors measured minimum tumor apparent diffusion coefficients (ADCs) and maximum standardized uptake value (SUV) of up to six target lesions and assessed therapy response after induction chemotherapy according to the Lugano classification or PET Response Criteria in Solid Tumors. The authors evaluated agreements between whole-body DW MRI– and FDG PET/MRI–based response classifications with Krippendorff α statistics. Differences in minimum ADC and maximum SUV between responders and nonresponders and comparison of timing for discordant and concordant response assessments after induction chemotherapy were evaluated with the Wilcoxon test. RESULTS: Good agreement existed between treatment response assessments after induction chemotherapy with whole-body DW MRI and FDG PET/MRI (α = 0.88). Clinical response prediction according to maximum SUV (area under the receiver operating characteristic curve = 100%; 95% confidence interval [CI]: 99%, 100%) and minimum ADC (area under the receiver operating characteristic curve = 98%; 95% CI: 94%, 100%) were similar (P = .37). Sensitivity and specificity were 96% (54 of 56 participants; 95% CI: 86%, 99%) and 100% (56 of 56 participants; 95% CI: 54%, 100%), respectively, for DW MRI and 100% (56 of 56 participants; 95% CI: 93%, 100%) and 100% (56 of 56 participants; 95% CI: 54%, 100%) for FDG PET/MRI. In eight of 56 patients who underwent imaging after induction chemotherapy in the early posttreatment phase, chemotherapy-induced changes in tumor metabolism preceded changes in proton diffusion (P = .002). CONCLUSION: Whole-body diffusion-weighted MRI showed significant agreement with fluorine 18 fluorodeoxyglucose PET/MRI for treatment response assessment in children and young adults. © RSNA, 2020 Online supplemental material is available for this article.

ObjectiveTo validate quantitative diffusion-weighted imaging (DWI) MRI thresholds that correlate with poor outcome in comatose cardiac arrest survivors, we conducted a clinician-blinded study and prospectively obtained MRIs from comatose patients after cardiac arrest.MethodsConsecutive comatose post-cardiac arrest adult patients were prospectively enrolled. MRIs obtained within 7 days after arrest were evaluated. The clinical team was blinded to the DWI MRI results and followed a prescribed prognostication algorithm. Apparent diffusion coefficient (ADC) values and thresholds differentiating good and poor outcome were analyzed. Poor outcome was defined as a Glasgow Outcome Scale score of ≤2 at 6 months after arrest.ResultsNinety-seven patients were included, and 75 patients (77%) had MRIs. In 51 patients with MRI completed by postarrest day 7, the prespecified threshold of >10% of brain tissue with an ADC −6 mm2/s was highly predictive for poor outcome with a sensitivity of 0.63 (95% confidence interval [CI] 0.42–0.80), a specificity of 0.96 (95% CI 0.77–0.998), and a positive predictive value (PPV) of 0.94 (95% CI 0.71–0.997). The mean whole-brain ADC was higher among patients with good outcomes. Receiver operating characteristic curve analysis showed that ADC −6 mm2/s had an area under the curve of 0.79 (95% CI 0.65–0.93, p < 0.001). Quantitative DWI MRI data improved prognostication of both good and poor outcomes.ConclusionsThis prospective, clinician-blinded study validates previous research showing that an ADC −6 mm2/s in >10% of brain tissue in an MRI obtained by postarrest day 7 is highly specific for poor outcome in comatose patients after cardiac arrest.

To maintain cerebral blood flow (CBF), cerebral blood vessels dilate and contract in response to blood supply through cerebrovascular reactivity (CR).Cardiovascular (CV) disease is associated with increased stroke risk, but which risk factors specifically impact CR is unknown.Prospective longitudinal.Fifty-three subjects undergoing carotid endarterectomy or stenting.3T, 3D pseudo-continuous arterial spin labeling (PCASL) ASL, and TWe evaluated group differences in CBF changes for multiple cardiovascular risk factors in patients undergoing carotid revascularization surgery.PRE (baseline), POST (48-hour postop), and 6MO (6 months postop) whole-brain CBF measurements, as 129 CBF maps from 53 subjects were modeled as within-subject analysis of variance (ANOVA). To identify CV risk factors associated with CBF change, the CBF change from PRE to POST, POST to 6MO, and PRE to 6MO were modeled as multiple linear regression with each CV risk factor as an independent variable. Statistical models were performed controlling for age on a voxel-by-voxel basis using SPM8. Significant clusters were reported if familywise error (FWE)-corrected cluster-level was P 0.05, while the voxel-level significance threshold was set for P 0.001.The entire group showed significant (cluster-level P 0.001) CBF increase from PRE to POST, decrease from POST to 6MO, and no significant difference (all voxels with P 0.001) from PRE to 6MO. Of multiple CV risk factors evaluated, only elevated systolic blood pressure (SBP, P = 0.001), chronic renal insufficiency (CRI, P = 0.026), and history of prior stroke (CVA, P 0.001) predicted lower increases in CBF PRE to POST. Over POST to 6MO, obesity predicted lower (P 0.001) and cholesterol greater CBF decrease (P 0.001).The CV risk factors of higher SBP, CRI, CVA, BMI, and cholesterol may indicate altered CR, and may warrant different stroke risk mitigation and special consideration for CBF change evaluation.1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2020;51:734-747.

We describe diachronic evidence of moisture reduction and its consequences for coastal irrigation, agriculture, and settlement at Quebrada Tacahuay, a large drainage south of the Osmore River in far southern Peru. These observations are the first for a drainage of this size and for one with occupation spanning over 12,000 years for southern Peru. Following several millennia of occupation by coastal foragers, farming populations settled the lower elevations of the drainage. Our analysis indicates that agricultural production was well developed in the fourteenth century prior to a previously documented, catastrophic El Nino Southern Oscillation (ENSO) flood that took place sometime during the early-fourteenth century. Later in the fifteenth century the Inca conquest of the region and establishment of a coastal tambo and village was accompanied by agricultural expansion and the creation of new terraces. Subsequent Spanish colonization took place during the Little Ice Age and a period of increased coastal moi...

INTRODUCTION: The goal of this study was to assess the changes in arterial spin labeling (ASL) cerebral blood flow (CBF) and arterial transit time (ATT), and in apparent diffusion coefficient (ADC), before and after an acetazolamide challenge in moyamoya patients, as function of arterial stenosis severity. METHODS: Pre-operative patients diagnosed with moyamoya disease who could undergo MRI at 3.0T were recruited for this study. A multi-delay pseudo-continuous ASL and a diffusion-weighted sequence were acquired before and 15 min after acetazolamide injection. The severity of anterior, middle, and posterior cerebral artery pathology was graded on time-of-flight MR angiographic images. CBF, ATT, and ADC were measured on standardized regions of interest as function of the vessel stenosis severity. RESULTS: Thirty patients were included. Fifty-four percent of all vessels were normal, 28% mildly/moderately stenosed, and 18% severely stenosed/occluded. Post-acetazolamide, a significantly larger CBF (ml/100 g/min) increase was observed in territories of normal (+19.6 ± 14.9) compared to mildly/moderately stenosed (+14.2 ± 27.2, p = 0.007), and severely stenosed/occluded arteries (+9.9 ± 24.2, p < 0.0001). ATT was longer in territories of vessel anomalies compared with normal regions at baseline. ATT decreases were observed in all territories post-acetazolamide. ADC did not decrease after acetazolamide in any regions, and no correlation was found between ADC changes and baseline ATT, change in ATT, or CVR. CONCLUSION: The hemodynamic response in moyamoya disease, as measured with ASL CBF, is impaired mostly in territories with severe arterial stenosis/occlusion, while ATT was prolonged in all non-normal regions. No significant changes in ADC were observed after acetazolamide.

Measurement of the ability of blood vessels to dilate and constrict, known as vascular reactivity, is often performed with breath-holding tasks that transiently raise arterial blood carbon dioxide (PaCO2) levels. However, following the proper commands for a breath-holding experiment may be difficult or impossible for many patients. In this study, we evaluated two approaches for obtaining vascular reactivity information using blood oxygenation level-dependent signal fluctuations obtained from resting-state functional magnetic resonance imaging data: physiological fluctuation regression and coefficient of variation of the resting-state functional magnetic resonance imaging signal. We studied a cohort of 28 older adults (69 ± 7 years) and found that six of them (21%) could not perform the breath-holding protocol, based on an objective comparison with an idealized respiratory waveform. In the subjects that could comply, we found a strong linear correlation between data extracted from spontaneous resting-state functional magnetic resonance imaging signal fluctuations and the blood oxygenation level-dependent percentage signal change during breath-holding challenge ( R2 = 0.57 and 0.61 for resting-state physiological fluctuation regression and resting-state coefficient of variation methods, respectively). This technique may eliminate the need for subject cooperation, thus allowing the evaluation of vascular reactivity in a wider range of clinical and research conditions in which it may otherwise be impractical.

Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied ‘off label’ to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies.

This study aimed to determine whether measurements of cerebrovascular reserve and oxygenation, assessed with spin relaxation rate R2′, yield similar information about pathology in pre-operative Moyamoya disease patients, and to assess whether R2′ is a better measure of oxygenation than other proposed markers, such as R2* and R2. Twenty-five pre-operative Moyamoya disease patients were scanned at 3.0T with acetazolamide challenge. Cerebral blood flow mapping with multi-delay arterial spin labeling, and R2*, R2, and R2′ mapping with Gradient-Echo Sampling of Free Induction Decay and Echo were performed. No baseline cerebral blood flow difference was found between angiographically abnormal and normal regions (49 ± 12 vs. 48 ± 11 mL/100 g/min, p = 0.44). However, baseline R2′ differed between these regions (3.2 ± 0.7 vs. 2.9 ± 0.6 s−1, p

While brain connectivity analyses have been demonstrated to identify ill patients for a number of diseases, their ability to predict cognitive impairment after brain injury is not well established. Traditional post brain injury models, such as stroke, are limited for this evaluation because pre-injury brain connectivity patterns are infrequently available. Patients with severe carotid stenosis, in contrast, often undergo non-emergent revascularization surgery, allowing the collection of pre and post-operative imaging, may experience brain insult due to perioperative thrombotic/embolic infarcts or hypoperfusion, and can suffer post-operative cognitive decline. We hypothesized that a distributed function such as memory would be more resilient in patients with brains demonstrating higher degrees of modularity. To test this hypothesis, we analyzed preoperative structural connectivity graphs (using T1 and DWI MRI) for 34 patients that underwent carotid intervention, and evaluated differences in graph metrics using the Brain Connectivity Toolbox. We found that patients with lower binary component number, binary community number and weighted community number prior to surgery were at greater risk for developing cognitive decline. These findings highlight the promise of brain connectivity analyses to predict cognitive decline following brain injury and serve as a clinical decision support tool. Hum Brain Mapp 37:2185-2194, 2016. © 2016 Wiley Periodicals, Inc.

PURPOSE: To investigate ferumoxytol-enhanced MRI as a noninvasive imaging biomarker of macrophages in adults with high-grade gliomas. MATERIALS AND METHODS: In this prospective study, adults with high-grade gliomas were enrolled between July 2015 and July 2017. Each participant was administered intravenous ferumoxytol (5 mg/kg) and underwent 3.0-T MRI 24 hours later. Two sites in each tumor were selected for intraoperative sampling on the basis of the degree of ferumoxytol-induced signal change. Susceptibility and the relaxation rates R2* (1/T2*) and R2 (1/T2) were obtained by region-of-interest analysis by using the respective postprocessed maps. Each sample was stained with Prussian blue, CD68, CD163, and glial fibrillary acidic protein. Pearson correlation and linear mixed models were performed to assess the relationship between imaging measurements and number of 400× magnification high-power fields with iron-containing macrophages. RESULTS: Ten adults (four male participants [mean age, 65 years ± 9 {standard deviation}; age range, 57–74 years] and six female participants [mean age, 53 years ± 12 years; age range, 32–65 years]; mean age of all participants, 58 years ± 12 [age range, 32–74 years]) with high-grade gliomas were included. Significant positive correlations were found between susceptibility, R2*, and R2’ and the number of high-power fields with CD163-positive (r range, 0.64–0.71; P < .01) and CD68-positive (r range, 0.55–0.57; P value range, .01–.02) iron-containing macrophages. No significant correlation was found between R2 and CD163-positive (r = 0.33; P = .16) and CD68-positive (r = 0.24; P = .32) iron-containing macrophages. Similar significance results were obtained with linear mixed models. At histopathologic analysis, iron particles were found only in macrophages; none was found in glial fibrillary acidic protein–positive tumor cells. CONCLUSION: MRI measurements of susceptibility, R2*, and R2’ (R2* – R2) obtained after ferumoxytol administration correlate with iron-containing macrophage concentration, and this shows their potential as quantitative imaging markers of macrophages in malignant gliomas. © RSNA, 2018 Online supplemental material is available for this article.

OBJECTIVEPatients with brain arteriovenous malformations (AVMs) often require repeat imaging with MRI or MR angiography (MRA), CT angiography (CTA), and digital subtraction angiography (DSA). The ideal imaging modality provides excellent vascular visualization without incurring added risks, such as radiation exposure. The purpose of this study is to evaluate the performance of ferumoxytol-enhanced MRA using a high-resolution 3D volumetric sequence (fe-SPGR) for visualizing and grading pediatric brain AVMs in comparison with CTA and DSA, which is the current imaging gold standard.METHODSIn this retrospective cohort study, 21 patients with AVMs evaluated by fe-SPGR, CTA, and DSA between April 2014 and August 2017 were included. Two experienced raters graded AVMs using Spetzler-Martin criteria on all imaging studies. Lesion conspicuity (LC) and diagnostic confidence (DC) were assessed using a 5-point Likert scale, and interrater agreement was determined. The Kruskal-Wallis test was performed to assess the raters’ grades and scores of LC and DC, with subsequent post hoc pairwise comparisons to assess for statistically significant differences between pairs of groups at p < 0.05.RESULTSAssigned Spetzler-Martin grades for AVMs on DSA, fe-SPGR, and CTA were not significantly different (p = 0.991). LC and DC scores were higher with fe-SPGR than with CTA (p < 0.05). A significant difference in LC scores was found between CTA and fe-SPGR (p < 0.001) and CTA and DSA (p < 0.001) but not between fe-SPGR and DSA (p = 0.146). A significant difference in DC scores was found among DSA, fe-SPGR, and CTA (p < 0.001) and between all pairs of the groups (p < 0.05). Interrater agreement was good to very good for all image groups (κ = 0.77–1.0, p < 0.001).CONCLUSIONSFe-SPGR performed robustly in the diagnostic evaluation of brain AVMs, with improved visual depiction of AVMs compared with CTA and comparable Spetzler-Martin grading relative to CTA and DSA.

Background Recent advancements in simultaneous multi-slice (SMS) imaging techniques have enabled whole-brain resting-state fMRI (rs-fMRI) scanning at sub-second temporal resolution, providing spectral ranges much wider than the typically used range of 0.01–0.1 Hz. However, the advantages of this accelerated acquisition for rs-fMRI have not been evaluated. New method In this study, we used SMS Echo Planar Imaging (EPI) to probe whole-brain functional connectivity with a short repetition time (TR = 350 ms) and compared it with standard EPI with a longer TR of 2000 ms. We determined the effect of scan length and investigated the temporal filtration strategies that optimize results based on metrics of signal-noise separation and test-retest reliability using both seed-based and independent component analysis (ICA). Results We found that use of either the entire frequency range of 0.01–1.4 Hz or the entire frequency range with the exclusion of typical cardiac and respiratory frequency values tended to provide the best functional connectivity maps. Comparison with existing methods We found that the SMS-acquired rs-fMRI scans had improved the signal-noise separation, while preserving the same level of test-retest reliability compared to conventional EPI, and enabled the detection of reliable functional connectivity networks with scan times as short as 3 min. Conclusions Our findings suggest that whole-brain rs-fMRI studies may benefit from the increased temporal resolution enabled by the SMS-EPI acquisition, leading to drastic scan time reductions, which in turn should enable the more widespread use of rs-fMRI in clinical research protocols.

Purpose This work describes a new method called amplified MRI (aMRI), which uses Eulerian video magnification to amplify the subtle spatial variations in cardiac-gated brain MRI scans and enables better visualization of brain motion. Methods The aMRI method takes retrospective cardiac-gated cine MRI data as input, applies a spatial decomposition, followed by temporal filtering and frequency-selective amplification of the MRI cardiac-gated frames before synthesizing a motion-amplified cine data set. Results This approach reveals deformations of the brain parenchyma and displacements of arteries due to cardiac pulsatility, especially in the brainstem, cerebellum, and spinal cord. Conclusion aMRI has the potential for widespread neuro- and non-neuro clinical use because it can amplify and characterize small, often barely perceptible motion and can visualize the biomechanical response of tissues using the heartbeat as an endogenous mechanical driver. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.

PURPOSE: Amplified Magnetic Resonance Imaging (aMRI) was recently introduced as a new brain motion detection and visualization method. The original aMRI approach used a video-processing algorithm, Eulerian Video Magnification (EVM), to amplify cardio-ballistic motion in retrospectively cardiac-gated MRI data. Here we strive to improve aMRI by incorporating a phase-based motion amplification algorithm. METHODS: Phase-based aMRI was developed and tested for correct implementation and ability to amplify sub-voxel motions using digital phantom simulations. The image quality of phase-based aMRI was compared with EVM-based aMRI in healthy volunteers at 3T, and its amplified motion characteristics were compared with phase-contrast MRI. Data were also acquired on a patient with Chiari I malformation, and qualitative displacement maps were produced using free form deformation (FFD) of the aMRI output. RESULTS: Phantom simulations showed that phase-based aMRI has a linear dependence of amplified displacement on true displacement. Amplification was independent of temporal frequency, varying phantom intensity, Rician noise, and partial volume effect. Phase-based aMRI supported larger amplification factors than EVM-based aMRI, and was less sensitive to noise and artifacts. Abnormal biomechanics were seen on FFD maps of the Chiari I malformation patient. CONCLUSION: Phase-based aMRI might be used in the future for quantitative analysis of minute changes in brain motion, and may reveal subtle physiological variations of the brain due to pathology using processing of the fundamental harmonic, or by selectively varying temporal harmonics. Preliminary data shows the potential of phase-based aMRI to qualitatively assess abnormal biomechanics in Chiari I malformation.

BACKGROUND AND PURPOSE: Identifying cerebral microhemorrhage burden can aid in the diagnosis and management of traumatic brain injury, stroke, hypertension, and cerebral amyloid angiopathy. MR imaging susceptibility-based methods are more sensitive than CT for detecting cerebral microhemorrhage, but methods other than quantitative susceptibility mapping provide results that vary with field strength and TE, require additional phase maps to distinguish blood from calcification, and depict cerebral microhemorrhages as bloom artifacts. Quantitative susceptibility mapping provides universal quantification of tissue magnetic property without these constraints but traditionally requires a mask generated by skull-stripping, which can pose challenges at tissue interphases. We evaluated the preconditioned quantitative susceptibility mapping MR imaging method, which does not require skull-stripping, for improved depiction of brain parenchyma and pathology. MATERIALS AND METHODS: Fifty-six subjects underwent brain MR imaging with a 3D multiecho gradient recalled echo acquisition. Mask-based quantitative susceptibility mapping images were created using a commonly used mask-based quantitative susceptibility mapping method, and preconditioned quantitative susceptibility images were made using precondition-based total field inversion. All images were reviewed by a neuroradiologist and a radiology resident. RESULTS: Ten subjects (18%), all with traumatic brain injury, demonstrated blood products on 3D gradient recalled echo imaging. All lesions were visible on preconditioned quantitative susceptibility mapping, while 6 were not visible on mask-based quantitative susceptibility mapping. Thirty-one subjects (55%) demonstrated brain parenchyma and/or lesions that were visible on preconditioned quantitative susceptibility mapping but not on mask-based quantitative susceptibility mapping. Six subjects (11%) demonstrated pons artifacts on preconditioned quantitative susceptibility mapping and mask-based quantitative susceptibility mapping; they were worse on preconditioned quantitative susceptibility mapping. CONCLUSIONS: Preconditioned quantitative susceptibility mapping MR imaging can bring the benefits of quantitative susceptibility mapping imaging to clinical practice without the limitations of mask-based quantitative susceptibility mapping, especially for evaluating cerebral microhemorrhage–associated pathologies, such as traumatic brain injury.

Background Susceptibility-weighted imaging (SWI) in neuroimaging can be challenging due to long scan times of three-dimensional (3D) gradient recalled echo (GRE), while faster techniques such as 3D interleaved echo-planar imaging (iEPI) are prone to motion artifacts. Here we outline and implement a 3D short-axis propeller echo-planar imaging (SAP-EPI) trajectory as a faster, motion-correctable approach for SWI. Methods Experiments were conducted on a 3T MRI system. The 3D SAP-EPI, 3D iEPI, and 3D GRE SWI scans were acquired on two volunteers. Controlled motion experiments were conducted to test the motion-correction capability of 3D SAP-EPI. The 3D SAP-EPI SWI data were acquired on two pediatric patients as a potential alternative to 2D GRE used clinically. Results The 3D GRE images had a better target resolution (0.47 × 0.94 × 2 mm, scan time = 5 min), iEPI and SAP-EPI images (resolution = 0.94 × 0.94 × 2 mm) were acquired in a faster scan time (1:52 min) with twice the brain coverage. SAP-EPI showed motion-correction capability and some immunity to undersampling from rejected data. Conclusion While 3D SAP-EPI suffers from some geometric distortion, its short scan time and motion-correction capability suggest that SAP-EPI may be a useful alternative to GRE and iEPI for use in SWI, particularly in uncooperative patients. J. Magn. Reson. Imaging 2015;41:1447–1453. © 2014 Wiley Periodicals, Inc.

BACKGROUND AND PURPOSE: Patients with β-thalassemia require blood transfusion to prolong their survival, which could cause iron overload in multiple organs, including the heart, liver, and brain. In this study, we aimed to quantify iron loading in the brains of patients with β-thalassemia major through the use of MR quantitative susceptibility imaging. MATERIALS AND METHODS: Thirty-one patients with thalassemia with a mean (± standard deviation) age of 25.3 (±5.9) years and 33 age-matched healthy volunteers were recruited and underwent MR imaging at 3T. Quantitative susceptibility images were reconstructed from a 3D gradient-echo sequence. Susceptibility values were measured in the caudate nucleus, putamen, globus pallidus, red nucleus, substantia nigra, dentate nucleus, and choroid plexus. General linear model analyses were performed to compare susceptibility values of different ROIs between the patients with thalassemia and healthy volunteers. RESULTS: Of the 31 patients, 27 (87.1%) had abnormal iron deposition in one of the ROIs examined. Significant positive age effect on susceptibility value was found in the putamen, dentate nucleus, substantia nigra, and red nucleus (P = .002, P = .017, P = .044, and P = .014, respectively) in the control subjects. Compared with healthy control subjects, patients with thalassemia showed significantly lower susceptibility value in the globus pallidus (P < .001) and substantia nigra (P = .003) and significantly higher susceptibility value in the red nucleus (P = .021) and choroid plexus (P < .001). CONCLUSIONS: A wide range of abnormal susceptibility values, indicating iron overloading or low iron content, was found in patients with thalassemia. MR susceptibility imaging is a sensitive method for quantifying iron concentration in the brain and can be used as a potentially valuable tool for brain iron assessment.

Purpose To investigate if delays in resting-state spontaneous fluctuations of the BOLD (sfBOLD) signal can be used to create maps similar to time-to-maximum of the residue function (Tmax) in Moyamoya patients and to determine whether sfBOLD delays affect the results of brain connectivity mapping.

Despite the global impact and advances in understanding the pathophysiology of cerebrovascular diseases, the term “stroke” is not consistently defined in clinical practice, in clinical research, or in assessments of the public health. The classic definition is mainly clinical and does not account for advances in science and technology. The Stroke Council of the American Heart Association/American Stroke Association convened a writing group to develop an expert consensus document for an updated definition of stroke for the 21st century. Central nervous system infarction is defined as brain, spinal cord, or retinal cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury. Central nervous system infarction occurs over a clinical spectrum: Ischemic stroke specifically refers to central nervous system infarction accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. The updated definition of stroke incorporates clinical and tissue criteria and can be incorporated into practice, research, and assessments of the public health.

The evaluation of neuropathologies using MRI methods that leverage tissue susceptibility have become standard practice, especially to detect blood products or mineralization. Additionally, emerging MRI techniques have the ability to provide new information based on tissue susceptibility properties in a robust and quantitative manner. This paper discusses these advanced susceptibility imaging techniques and their clinical applications.