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Cerebrovascular reactivity (CVR) deficits may index vulnerability to vascular brain injury and cognitive impairment, but findings on age-related changes in CVR have been mixed, and no studies to date have directly compared age-related changes in CVR to hypercapnia versus hypocapnia. The present study compared CVR in 31 cognitively unimpaired older adults (ages 55-87) and 30 healthy younger adults (ages 18-28). Breath control tasks induced CVR to hypocapnia (0.1 Hz paced breathing) and hypercapnia (15s breath holds) during pseudo-continuous arterial spin labeling MRI. Relative to younger adults, cognitively unimpaired older adults displayed lower levels of global CVR under both hypocapnia and hypercapnia. In region-of-interest analyses, older adults exhibited attenuated CVR to hypocapnia in select frontal and temporal regions, and lower CVR to hypercapnia in all cortical, limbic, and subcortical regions examined, relative to younger adults. Results indicate age-related deficits in CVR are detectible even in cognitively unimpaired older adults and are disproportionately related to vasodilatory (hypercapnia) responses relative to vasoconstrictive (hypocapnia) responses. Findings may offer means for early detection of cerebrovascular dysfunction.

Noncontrast magnetic resonance imaging techniques for measuring brain perfusion include arterial spin labeling (ASL) and intravoxel incoherent motion (IVIM). These techniques provide noninvasive and repeatable assessment of cerebral blood flow or cerebral blood volume without the need for intravenous contrast. This article discusses the technical aspects of ASL and IVIM with a focus on normal physiologic variations, technical parameters, and artifacts. Multiple pediatric clinical applications are presented, including tumors, stroke, vasculopathy, vascular malformations, epilepsy, migraine, trauma, and inflammation.

ObjectiveTo test the hypothesis that cerebral blood flow (CBF) assessed with arterial spin labelling (ASL) MRI is increased and standardised neurological examination is altered in infants with neonatal opioid withdrawal syndrome (NOWS) compared with those without.DesignProspective cohort study.SettingLevel IV neonatal intensive care unit and outpatient primary care centre.ParticipantsInfants with NOWS receiving pharmacological treatment and unexposed controls matched for gestational age at birth and post-menstrual age at MRI.Main outcomesCBF assessed by ASL on non-sedated 3-Tesla MRI and standardised Hammersmith Neonatal Neurological Examination (HNNE) within 14 days of birth.ResultsThirty infants with NOWS and 31 control infants were enrolled and included in the final analysis. Global CBF across the brain was higher in the NOWS group compared with controls (14.2 mL/100 g/min±5.5 vs 10.7 mL/100 g/min±4.3, mean±SD, Cohen’s d=0.72). HNNE total optimality score was lower in the NOWS group compared with controls (25.9±3.6 vs 28.4±2.4, mean±SD, Cohen’s d=0.81). A penalised logistic regression model including both CBF and HNNE items discriminated best between the two groups.ConclusionsIncreased cerebral perfusion and neurological examination abnormalities characterise infants with NOWS compared with those without intrauterine drug exposure and suggest prenatal substance exposure affects fetal brain development. Identifying neurological and neuroimaging characteristics of infants with NOWS can contribute to understanding mechanisms underlying later outcomes and to designing potential new treatments.

Brain damage caused by small vessel disease (SVD) differs between males and females. We aimed to examine the pure sex-specific neuroanatomical mechanisms of SVD adjusted for voxel-based expected effects of age and sex on healthy brain volume. Thirty-one female and 32 male genetic SVD (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, CADASIL) patients and 55 sex- and age-matched healthy controls (HCs) underwent 7-Tesla MRI examinations. Voxel-based W-score maps were calculated from volumes and deformations of brain tissues, controlling for the expected effects of age and sex in HCs. Significant cognitive declines in working memory and executive function were identified in male CADASIL patients compared to female patients. Greater gray matter (GM) atrophy was found in the bilateral orbitofrontal cortex (OFC), left anterior cingulate cortex (ACC), left entorhinal cortex (EC), and right temporooccipital cortex in male CADASIL patients than in females. Working memory was associated with volumes in the right OFC specific to female CADASIL patients, whereas visuospatial ability was associated with the right hOcl (primary visual area, BA 17) volume specific to males. The current findings indicate that sex affects the pathogenesis of CADASIL, ranging from differences in neuroanatomy to those in behavioral performance, which may facilitate the development of more effective sex-specific therapeutic strategies for CADASIL and SVD.

Introduction We tested if water exchange across the blood-brain barrier (BBB), estimated with a noninvasive magnetic resonance imaging (MRI) technique, is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and neuropsychological function. Methods Forty cognitively normal older adults (67-86 years old) were scanned with diffusion-prepared, arterial spin labeling (DP-ASL), which estimates water exchange rate across the BBB (kw ). Participants also underwent CSF draw and neuropsychological testing. Multiple linear regression models were run with kw as a predictor of CSF concentrations and neuropsychological scores. Results In multiple brain regions, BBB kw was positively associated with CSF amyloid beta (Aβ)42 concentration levels. BBB kw was only moderately associated with neuropsychological performance. Discussion Our results suggest that low water exchange rate across the BBB is associated with low CSF Aβ42 concentration. These findings suggest that kw may be a promising noninvasive indicator of BBB Aβ clearance functions, a possibility which should be further tested in future research.

Ultrahigh field offers increased resolution and contrast for neurovascular imaging. Arterial spin labeling methods benefit from an increased intrinsic signal-to-noise ratio of MR imaging signal and a prolonged tracer half-life at ultrahigh field, allowing the visualization of layer-dependent microvascular perfusion. Arterial spin labeling-based time-resolved 4-dimensional MR angiography at 7T provides a detailed depiction of the vascular architecture and dynamic blood flow pattern with high spatial and temporal resolutions. High-resolution black blood MR imaging at 7T allows detailed characterization of small perforating arteries such as lenticulostriate arteries. All techniques benefit from advances in parallel radiofrequency transmission technologies at ultrahigh field.

Purpose Characterizing vessel territories can provide crucial information for evaluation of cerebrovascular disorders. In this study, we present a novel postprocessing pipeline for vascular territorial imaging of cerebral arteries based on a noncontrast enhanced time-resolved 4D magnetic resonance angiography (MRA). Methods Eight healthy participants, 1 Moyamoya patient, and 1 arteriovenous malformations patient were recruited. Territorial segmentation and relative blood flow rate calculations of cerebral arteries including left and right middle cerebral arteries and left and right posterior cerebral arteries were carried out based on the 4D MRA-derived arterial arrival time maps of intracranial vessels. Results Among healthy young subjects, the average relative blood flow rate values corresponding to left and right middle cerebral arteries and left and right posterior cerebral arteries were 35.9 ± 5.9%, 32.9 ± 7.5%, 15.4 ± 3.8%, and 15.9 ± 2.5%, respectively. Excellent agreement was observed between relative blood flow rate values obtained from the proposed 4D MRA-based method and reference 2D phase contrast MRI. Abnormal cerebral circulations were visualized and quantified on both patients using the developed technique. Conclusion The vascular territorial imaging technique developed in this study allowed for the generation of territorial maps with user-defined level of details within a clinically feasible scan time, and as such may provide useful information to assess cerebral circulation balance in different pathologies.

Due to the use of improvised explosive devices, blast exposure and mild traumatic brain injury (mTBI) have become hallmark injuries of the Iraq and Afghanistan wars. Although the mechanisms of the effects of blast on human neurobiology remain active areas of investigation, research suggests that the cerebrovasculature may be particularly vulnerable to blast via molecular processes that impact cerebral blood flow. Given that recent work suggests that blast exposure, even without a subsequent TBI, may have negative consequences on brain structure and function, the current study sought to further understand the effects of blast exposure on perfusion. One hundred and eighty military personnel underwent pseudo-continuous arterial spin labeling (pCASL) imaging and completed diagnostic and clinical interviews. Whole-brain analyses revealed that with an increasing number of total blast exposures, there was significantly increased perfusion in the right middle/superior frontal gyri, supramarginal gyrus, lateral occipital cortex, and posterior cingulate cortex as well as bilateral anterior cingulate cortex, insulae, middle/superior temporal gyri and occipital poles. Examination of other neurotrauma and clinical variables such as close-range blast exposures, mTBI, and PTSD yielded no significant effects. These results raise the possibility that perfusion may be an important neural marker of brain health in blast exposure.

IntroductionTo evaluate the clinical validity of free water (FW), a diffusion tensor imaging-based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function.MethodsBaseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub-cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow-up time: 1.29 years).ResultsHigher mFW was found to be associated with lower EFC scores in MarkVCID legacy and sub-cohorts (p-values&nbsp

BACKGROUND: Perivascular spaces on brain magnetic resonance imaging (MRI) may indicate poor fluid drainage in the brain and have been associated with numerous neurological conditions. Cerebrovascular reactivity (CVR) is a marker of cerebrovascular function and represents the ability of cerebral blood vessels to regulate cerebral blood flow in response to vasodilatory or vasoconstrictive stimuli. We aimed to examine whether pathological widening of the perivascular space in older adults may be associated with deficits in CVR. METHODS: Independently living older adults free of dementia or clinical stroke were recruited from the community and underwent brain MRI. Pseudo-continuous arterial spin labeling MRI quantified whole brain cerebral perfusion at rest and during CVR to hypercapnia and hypocapnia induced by visually guided breathing exercises. Perivascular spaces were visually scored using existing scales. RESULTS: Thirty-seven independently living older adults (mean age = 66.3 years; SD = 6.8; age range 55–84 years; 29.7% male) were included in the current analysis. Multiple linear regression analysis revealed a significant negative association between burden of perivascular spaces and global CVR to hypercapnia (B = −2.0, 95% CI (−3.6, −0.4), p = 0.015), adjusting for age and sex. Perivascular spaces were not related to CVR to hypocapnia. DISCUSSION: Perivascular spaces are associated with deficits in cerebrovascular vasodilatory response, but not vasoconstrictive response. Enlargement of perivascular spaces could contribute to, or be influenced by, deficits in CVR. Additional longitudinal studies are warranted to improve our understanding of the relationship between cerebrovascular function and perivascular space enlargement.

PURPOSE To optimize pseudo-continuous arterial spin labeling (pCASL) for 7 T, and to further improve the labeling efficiency with parallel RF transmission transmit B1 ( B1+ ) shimming. METHODS pCASL parameters were optimized based on B1+/B0 field distributions at 7 T with simulation. To increase labeling efficiency, the B1+ amplitude at inflowing arteries was increased with parallel RF transmission B1+ shimming. The "indv-shim" with shimming weights calculated for each individual subject, and the "univ-shim" with universal weights calculated on a group of 12 subjects, were compared with circular polarized (CP) shim. The optimized pCASL sequences with three B1+ shimming modes (indv-shim, univ-shim, and CP-shim) were evaluated in 6 subjects who underwent two repeated scans 24 hours apart, along with a pulsed ASL sequence. Quantitative metrics including mean B1+ amplitude, perfusion, and intraclass correlation coefficient were calculated. The optimized 7T pCASL was compared with standard 3T pCASL on 5 subjects, using spatial SNR and temporal SNR. RESULTS The optimal pCASL parameter set (RF duration/gap = 300/250 us, Gave=0.6mT/m,gRatio=10 ) achieved robust perfusion measurement in the presence of B1+/B0 inhomogeneities. Both indv-shim and univ-shim significantly increased B1+ amplitude compared with CP-shim in simulation and in vivo experiment (P < .01). Compared with CP-shim, perfusion signal was increased by 9.5% with indv-shim (P < .05) and by 5.3% with univ-shim (P = .35). All three pCASL sequences achieved fair to good repeatability (intraclass correlation coefficient ≥ 0.5). Compared with 3T pCASL, the optimized 7T pCASL achieved 78.3% higher spatial SNR and 200% higher temporal SNR. CONCLUSION The optimized pCASL achieved robust perfusion imaging at 7 T, while both indv-shim and univ-shim further increased labeling efficiency.

Transcranial direct current stimulation (tDCS) is a low intensity neuromodulation technique shown to elicit therapeutic effects in a number of neuropsychological conditions. Independent randomized sham-controlled trials and meta- and mega-analyses demonstrate that tDCS targeted to the left dorsolateral prefrontal cortex can produce a clinically meaningful response in patients with major depressive disorder (MDD), but effects are small to moderate in size. However, the heterogeneous presentation, and the neurobiology underlying particular features of depression suggest clinical outcomes might benefit from empirically informed patient selection. In this review, we summarize the status of tDCS research in MDD with focus on the clinical, biological, and intrinsic and extrinsic factors shown to enhance or predict antidepressant response. We also discuss research strategies for optimizing tDCS to improve patient-specific clinical outcomes. TDCS appears suited for both bipolar and unipolar depression, but is less effective in treatment resistant depression. TDCS may also better target core aspects of depressed mood over vegetative symptoms, while pretreatment patient characteristics might inform subsequent response. Peripheral blood markers of gene and immune system function have not yet proven useful as predictors or correlates of tDCS response. Though further research is needed, several lines of evidence suggest that tDCS administered in combination with pharmacological and cognitive behavioral interventions can improve outcomes. Tailoring stimulation to the functional and structural anatomy and/or connectivity of individual patients can maximize physiological response in targeted networks, which in turn could translate to therapeutic benefits.

Objectives The lenticulostriate arteries (LSAs) with small diameters of a few hundred microns take origin directly from the high flow middle cerebral artery (MCA), making them especially susceptible to damage (e.g. by hypertension). This study aims to present high resolution (isotropic ∼0.5 mm), black blood MRI for the visualization and characterization of LSAs at both 3 T and 7 T. Materials and methods T1-weighted 3D turbo spin-echo with variable flip angles (T1w TSE-VFA) sequences were optimized for the visualization of LSAs by performing extended phase graph (EPG) simulations. Twenty healthy volunteers (15 under 35 years old, 5 over 60 years old) were imaged with the T1w TSE-VFA sequences at both 3 T and 7 T. Contrast-to-noise ratio (CNR) was quantified, and LSAs were manually segmented using ITK-SNAP. Automated Reeb graph shape analysis was performed to extract features including vessel length and tortuosity. All quantitative metrics were compared between the two field strengths and two age groups using ANOVA. Results LSAs can be clearly delineated using optimized 3D T1w TSE-VFA at 3 T and 7 T, and a greater number of LSA branches can be detected compared to those by time-of-flight MR angiography (TOF MRA) at 7 T. The CNR of LSAs was comparable between 7 T and 3 T. T1w TSE-VFA showed significantly higher CNR than TOF MRA at the stem portion of the LSAs branching off the medial middle cerebral artery. The mean vessel length and tortuosity were greater on TOF MRA compared to TSE-VFA. The number of detected LSAs by both TSE-VFA and TOF MRA was significantly reduced in aged subjects, while the mean vessel length measured on 7 T TSE-VFA showed significant difference between the two age groups. Conclusion The high-resolution black-blood 3D T1w TSE-VFA sequence offers a new method for the visualization and quantification of LSAs at both 3 T and 7 T, which may be applied for a number of pathological conditions related to the damage of LSAs.

Magnetic resonance imaging (MRI) is a powerful radiologic tool with the ability to generate a variety of proton-based signal contrast from tissues. Owing to this immense flexibility in signal generation, new MRI techniques are constantly being developed, tested, and optimized for clinical utility. In addition, the safe and nonionizing nature of MRI makes it a suitable modality for imaging in children. In this review article, we summarize a few of the most popular advances in MRI techniques in recent years. In particular, we highlight how these new developments have affected brain, spine, and neuromuscular imaging and focus on their applications in pediatric patients. In the first part of the review, we discuss new approaches such as multiphase and multidelay arterial spin labeling for quantitative perfusion and angiography of the brain, amide proton transfer MRI of the brain, MRI of brachial plexus and lumbar plexus nerves (i.e., neurography), and T2 mapping and fat characterization in neuromuscular diseases. In the second part of the review, we focus on describing new data acquisition strategies in accelerated MRI aimed collectively at reducing the scan time, including simultaneous multislice imaging, compressed sensing, synthetic MRI, and magnetic resonance fingerprinting. In discussing the aforementioned, the review also summarizes the advantages and disadvantages of each method and their current state of commercial availability from MRI vendors.

Recently, the first 7-T MR system was approved for clinical use in the United States. Unfortunately, relatively few metallic implants have undergone testing to determine if they are acceptable or pose hazards to research subjects and patients at this ultra-high-field strength. Therefore, in lieu of not performing a research or clinical MRI exam at 7-T, the supervising physician may make a decision to scan the individual with an untested metallic implant based on an analysis of the risks vs. the benefits. We present a case report of a research subject with bilateral, total knee replacement implants that safely underwent MRI of the brain at 7-T and provide guidelines for healthcare professionals to follow in order to ensure safety in research subjects or patients with metallic implants referred for 7-T scans.

Photoacoustic computed tomography (PACT) has been extensively explored in animal brains but never in the human brain due to its limited field of view (FOV), imaging speed, penetration depth, and sensitivity. Here, we present the first application of PACT in functional human brain imaging. Motor and language functional tasks were employed and performed by post-hemicraniectomy patients. The brain activities were recorded at a 10-cm–diameter FOV, 350-μm/2-s spatiotemporal resolution, and ~2-cm penetration depth using a newly developed massively parallel three-dimensional PACT system. Quantitative validation of the PACT results against 7 Tesla MRI revealed comparable angiographic structures and functional activation in the same FOV. The obtained results represent a critical step toward broader-scope human brain imaging applications using PACT technology.

The MarkVCID consortium was formed under cooperative agreements with the National Institute of Neurologic Diseases and Stroke (NINDS) and National Institute on Aging (NIA) in 2016 with the goals of developing and validating biomarkers for the cerebral small vessel diseases associated with the vascular contributions to cognitive impairment and dementia (VCID). Rigorously validated biomarkers have consistently been identified as crucial for multicenter studies to identify effective strategies to prevent and treat VCID, specifically to detect increased VCID risk, diagnose the presence of small vessel disease and its subtypes, assess prognosis for disease progression or response to treatment, demonstrate target engagement or mechanism of action for candidate interventions, and monitor disease progression during treatment. The seven project sites and central coordinating center comprising MarkVCID, working with NINDS and NIA, identified a panel of 11 candidate fluid- and neuroimaging-based biomarker kits and established harmonized multicenter study protocols (see companion paper "MarkVCID cerebral small vessel consortium: I. Enrollment, clinical, fluid protocols" for full details). Here we describe the MarkVCID neuroimaging protocols with specific focus on validating their application to future multicenter trials. MarkVCID procedures for participant enrollment; clinical and cognitive evaluation; and collection, handling, and instrumental validation of fluid samples are described in detail in a companion paper. Magnetic resonance imaging (MRI) has long served as the neuroimaging modality of choice for cerebral small vessel disease and VCID because of its sensitivity to a wide range of brain properties, including small structural lesions, connectivity, and cerebrovascular physiology. Despite MRI's widespread use in the VCID field, there have been relatively scant data validating the repeatability and reproducibility of MRI-based biomarkers across raters, scanner types, and time intervals (collectively defined as instrumental validity). The MRI protocols described here address the core MRI sequences for assessing cerebral small vessel disease in future research studies, specific sequence parameters for use across various research scanner types, and rigorous procedures for determining instrumental validity. Another candidate neuroimaging modality considered by MarkVCID is optical coherence tomography angiography (OCTA), a non-invasive technique for directly visualizing retinal capillaries as a marker of the cerebral capillaries. OCTA has theoretical promise as a unique opportunity to visualize small vessels derived from the cerebral circulation, but at a considerably earlier stage of development than MRI. The additional OCTA protocols described here address procedures for determining OCTA instrumental validity, evaluating sources of variability such as pupil dilation, and handling data to maintain participant privacy. MRI protocol and instrumental validation The core sequences selected for the MarkVCID MRI protocol are three-dimensional T1-weighted multi-echo magnetization-prepared rapid-acquisition-of-gradient-echo (ME-MPRAGE), three-dimensional T2-weighted fast spin echo fluid-attenuated-inversion-recovery (FLAIR), two-dimensional diffusion-weighted spin-echo echo-planar imaging (DWI), three-dimensional T2*-weighted multi-echo gradient echo (3D-GRE), three-dimensional T2 -weighted fast spin-echo imaging (T2w), and two-dimensional T2*-weighted gradient echo echo-planar blood-oxygenation-level-dependent imaging with brief periods of CO2 inhalation (BOLD-CVR). Harmonized parameters for each of these core sequences were developed for four 3 Tesla MRI scanner models in widespread use at academic medical centers. MarkVCID project sites are trained and certified for their instantiation of the consortium MRI protocols. Sites are required to perform image quality checks every 2 months using the Alzheimer's Disease Neuroimaging Initiative phantom. Instrumental validation for MarkVCID MRI-based biomarkers is operationally defined as inter-rater reliability, test-retest repeatability, and inter-scanner reproducibility. Assessments of these instrumental properties are performed on individuals representing a range of cerebral small vessel disease from mild to severe. Inter-rater reliability is determined by distribution of an independent dataset of MRI scans to each analysis site. Test-retest repeatability is determined by repeat MRI scans performed on individual participants on a single MRI scanner after a short (1- to 14-day) interval. Inter-scanner reproducibility is determined by repeat MRI scans performed on individuals performed across four MRI scanner models. OCTA protocol and instrumental validation The MarkVCID OCTA protocol uses a commercially available, Food and Drug Administration-approved OCTA apparatus. Imaging is performed on one dilated and one undilated eye to assess the need for dilation. Scans are performed in quadruplicate. MarkVCID project sites participating in OCTA validation are trained and certified by this biomarker's lead investigator. Inter-rater reliability for OCTA is assessed by distribution of OCTA datasets to each analysis site. Test-retest repeatability is assessed by repeat OCTA imaging on individuals on the same day as their baseline OCTA and a different-day repeat session after a short (1- to 14-day) interval. Methods were developed to allow the OCTA data to be de-identified by the sites before transmission to the central data management system. The MarkVCID neuroimaging protocols, like the other MarkVCID procedures, are designed to allow translation to multicenter trials and as a template for outside groups to generate directly comparable neuroimaging data. The MarkVCID neuroimaging protocols are available to the biomedical community and intended to be shared. In addition to the instrumental validation procedures described here, each of the neuroimaging MarkVCID kits will undergo biological validation to determine its ability to measure important aspects of VCID such as cognitive function. The analytic methods for the neuroimaging-based kits and the results of these validation studies will be published separately. The results will ultimately determine the neuroimaging kits' potential usefulness for multicenter interventional trials in small vessel disease-related VCID.

Arterial spin labeled (ASL) perfusion MRI is an appealing neuroimaging technology to study brain development due to its entirely noninvasive nature and several physiological properties of a child brain. In this chapter, we discussed 1. How physiological parameter variations (blood T1, arterial transit time and blood flow velocity) of the pediatric population affect the accuracy of perfusion quantification; 2. Current research on perfusion across typical brain development and neurodevelopmental disorders; and 3. New technical developments to improve spatial resolution, quantification accuracy and robustness to motion for pediatric ASL studies.

PURPOSE Increased arterial stiffness has been shown to be one of the earliest markers of cerebrovascular dysfunction. As a surrogate marker of arterial stiffness, pulse wave velocity (PWV) quantifications are generally carried out on central and peripheral arteries. The purpose of this study was to develop and evaluate an MRI approach to assess carotid stiffness by measuring carotid PWV (cPWV) using a fast oblique-sagittal phase-contrast MRI sequence. METHODS In 29 volunteers, a single-slice oblique-sagittal phase-contrast MRI sequence with retrospective cardiac gating was used to quantify blood velocity waveforms along a vessel segment covering the common carotid artery (CCA) and the internal carotid artery (ICA). The CCA-ICA segment length was measured from a region of interest selected on the magnitude image. Phase-contrast MRI-measured velocities were also used to quantify the ICA pulsatility index along with cPWV quantification. RESULTS The mean value of cPWV calculated using the middle upslope area algorithm was 2.86 ± 0.71 and 3.97 ± 1.14 m/s in young and elderly subjects, respectively. Oblique-sagittal phase-contrast MRI-derived cPWV measurements showed excellent intrascan and interscan repeatability. cPWV and ICA pulsatility index were significantly greater in older subjects compared to those in the young subjects (P < .01 and P = .01, respectively). Also, increased cPWV values were associated with elevated systolic blood pressure (β = 0.05, P = .03). CONCLUSION This study demonstrated that oblique-sagittal phase-contrast MRI is a feasible technique for the quantification of both cPWV and ICA pulsatility index and showed their potential utility in evaluating cerebroarterial aging and age-related neurovascular disorders.

Introduction: Single ventricle heart disease (SVHD) adolescents with a single right ventricle (RV) have worse cognition and mood function compared to single left ventricle (LV) which may result from variability in ventricular function or structure related sequela after Fontan completion. However, it is unclear whether RV SVHD has worse cerebral blood flow (CBF) in cognitive and mood regulatory areas over LV SVHD compared to healthy controls. Methods: Cross-sectional, comparative design, 14 adolescents with RV SVHD (age 16.1±1.5 years; 7 male), 6 LV SVHD (age, 16.3±1.0 years; 4 male), and 25 healthy controls (age, 15.9±1.4 years; 13 male) were studied. SVHD participants were recruited who have undergone surgical palliation with Fontan completion from local pediatric cardiology clinics. Self-reported healthy controls were recruited from the community. Brain MRI studies were performed using a 3.0-Tesla MRI scanner and 3D pseudo-continuous arterial spin labelling data were collected. We calculated whole-brain CBF maps, normalized to a common space, and assessed brain changes between RV and LV SVHD and controls [ANCOVA; covariates, age and sex; p Results: Regional brain CBF was reduced in single RV over LV SVHD. Multiple brain sites showed more widespread reduced CBF values in RV over LV SVHD compared to controls (Figure 1, p Conclusion: Single RV adolescents show more widespread reduced CBF than single LV in cognitive and mood regulatory sites, which may result from variable function or structure related sequela between ventricle types. The findings indicate that the therapeutic approach should recognize the differences in CBF based on ventricle type and investigate interventions to optimize CBF in single RV SVHD.

PURPOSE To optimize and evaluate adiabatic pulses for pulsed arterial spin labeling at ultrahigh field 7 tesla. METHODS Four common adiabatic inversion pulses, including hyperbolic secant, wideband uniform rate smooth truncation, frequency offset corrected inversion, and time-resampled frequency offset corrected inversion pulses, were optimized based on a custom-defined loss function that included labeling efficiency and inversion band uniformity. The optimized pulses were implemented in flow-sensitive alternating inversion recovery sequences and tested on phantom and 11 healthy volunteers with 2 constraints: 1) specific absorption rate normalized; and 2) equal peak RF amplitude, respectively. A pseudo-continuous arterial spin labeling sequence was implemented for comparison. Quantitative metrics such as perfusion and relative labeling efficiency versus residual tissue signal were calculated. RESULTS Among the 4 pulses, the wideband uniform rate smooth truncation pulse yielded the lowest loss in simulation and achieved a good balance between labeling efficiency and residual tissue signal from both phantom and in vivo experiments. Wideband uniform rate smooth truncation-pulsed arterial spin labeling showed significantly higher relative labeling efficiency compared to the other sequences (P < .01), whereas the perfusion signal was increased by 40% when the highest B1+ amplitude was used. The 4 pulsed arterial spin labeling sequences yielded comparable perfusion signals compared to pseudo-continuous arterial spin labeling but with less than half the specific absorption rate. CONCLUSION Optimized wideband uniform rate smooth truncation pulse with the highest B1+ amplitude allowed was recommended for 7 tesla pulsed arterial spin labeling.

Despite being a popular neuromodulation technique, clinical translation of transcranial direct current stimulation (tDCS) is hampered by variable responses observed within treatment cohorts. Addressing this challenge has been difficult due to the lack of an effective means of mapping the neuromodulatory electromagnetic fields together with the brain’s response. In this study, we present a novel imaging technique that provides the capability of concurrently mapping markers of tDCS currents, as well as the brain’s response to tDCS. A dual-echo echo-planar imaging (DE-EPI) sequence is used, wherein the phase of the acquired MRI-signal encodes the tDCS current induced magnetic field, while the magnitude encodes the blood oxygenation level dependent (BOLD) contrast. The proposed technique was first validated in a custom designed phantom. Subsequent test–retest experiments in human participants showed that tDCS-induced magnetic fields can be detected reliably in vivo. The concurrently acquired BOLD data revealed large-scale networks characteristic of a brain in resting-state as well as a ‘cathodal’ and an ‘anodal’ resting-state component under each electrode. Moreover, ‘cathodal’s BOLD-signal was observed to significantly decrease with the applied current at the group level in all datasets. With its ability to image markers of electromagnetic cause as well as neurophysiological changes, the proposed technique may provide an effective means to visualize neural engagement in tDCS at the group level. Our technique also contributes to addressing confounding factors in applying BOLD fMRI concurrently with tDCS.

BACKGROUND Noninvasive measurement of placental blood flow is the major technical challenge for predicting ischemic placenta (IPD). Pseudocontinuous arterial spin labeling (pCASL) MRI was recently shown to be promising, but the potential value in predicting the subsequence development of IPD is not known. PURPOSE To derive global and regional placental blood flow parameters from longitudinal measurements of pCASL MRI and to assess the associations between perfusion-related parameters and IPD. STUDY TYPE Prospective. POPULATION Eighty-four women completed two pCASL MRI scans (first; 14-18 weeks and second; 19-24 weeks) from prospectively recruited 118 subjects. A total of 69 subjects were included for the analysis, of which 15 subjects developed IPD. FIELD STRENGTH/SEQUENCE 3T/T2 -weighted half-Fourier single-shot turbo spin-echo (HASTE) and pCASL. ASSESSMENT Four perfusion-related parameters in the placenta were derived: placenta volume, placental blood flow (PBF), high PBF (hPBF), and relative hPBF. The longitudinal changes of the parameters and their association with IPD were tested after being normalizing to the 16th and 20th weeks of gestation. STATISTICAL TESTS Comparisons between two gestational ages within subjects were performed using the paired Wilcoxon tests, and comparisons between normal and IPD groups were performed using the unpaired Wilcoxon tests. RESULTS The difference between the first and second MRI scans was statistically significant for volume (156.6 cm3 vs. 269.7 cm3 , P

Background and Purpose— Selection of patients with acute ischemic stroke for endovascular treatment generally relies on dynamic susceptibility contrast magnetic resonance imaging or computed tomography perfusion. Dynamic susceptibility contrast magnetic resonance imaging requires injection of contrast, whereas computed tomography perfusion requires high doses of ionizing radiation. The purpose of this work was to develop and evaluate a deep learning (DL)–based algorithm for assisting the selection of suitable patients with acute ischemic stroke for endovascular treatment based on 3-dimensional pseudo-continuous arterial spin labeling (pCASL). Methods— A total of 167 image sets of 3-dimensional pCASL data from 137 patients with acute ischemic stroke scanned on 1.5T and 3.0T Siemens MR systems were included for neural network training. The concurrently acquired dynamic susceptibility contrast magnetic resonance imaging was used to produce labels of hypoperfused brain regions, analyzed using commercial software. The DL and 6 machine learning (ML) algorithms were trained with 10-fold cross-validation. The eligibility for endovascular treatment was determined retrospectively based on the criteria of perfusion/diffusion mismatch in the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). The trained DL algorithm was further applied on twelve 3-dimensional pCASL data sets acquired on 1.5T and 3T General Electric MR systems, without fine-tuning of parameters. Results— The DL algorithm can predict the dynamic susceptibility contrast–defined hypoperfusion region in pCASL with a voxel-wise area under the curve of 0.958, while the 6 ML algorithms ranged from 0.897 to 0.933. For retrospective determination for subject-level endovascular treatment eligibility, the DL algorithm achieved an accuracy of 92%, with a sensitivity of 0.89 and specificity of 0.95. When applied to the GE pCASL data, the DL algorithm achieved a voxel-wise area under the curve of 0.94 and a subject-level accuracy of 92% for endovascular treatment eligibility. Conclusions— pCASL perfusion magnetic resonance imaging in conjunction with the DL algorithm provides a promising approach for assisting decision-making for endovascular treatment in patients with acute ischemic stroke.

Purpose To present a novel MR pulse sequence and modeling algorithm to quantify the water exchange rate (kw ) across the blood-brain barrier (BBB) without contrast, and to evaluate its clinical utility in a cohort of elderly subjects at risk of cerebral small vessel disease (SVD). Methods A diffusion preparation module with spoiling of non-Carr-Purcell-Meiboom-Gill signals was integrated with pseudo-continuous arterial spin labeling (pCASL) and 3D gradient and spin echo (GRASE) readout. The tissue/capillary fraction of the arterial spin labeling (ASL) signal was separated by appropriate diffusion weighting (b = 50 s/mm2 ). kw was quantified using a single-pass approximation (SPA) model with total generalized variation (TGV) regularization. Nineteen elderly subjects were recruited and underwent 2 MRIs to evaluate the reproducibility of the proposed technique. Correlation analysis was performed between kw and vascular risk factors, Clinical Dementia Rating (CDR) scale, neurocognitive assessments, and white matter hyperintensity (WMH). Results The capillary/tissue fraction of ASL signal can be reliably differentiated with the diffusion weighting of b = 50 s/mm2 , given ~100-fold difference between the (pseudo-)diffusion coefficients of the 2 compartments. Good reproducibility of kw measurements (intraclass correlation coefficient = 0.75) was achieved. Average kw was 105.0 ± 20.6, 109.6 ± 18.9, and 94.1 ± 19.6 min-1 for whole brain, gray and white matter. kw was increased by 28.2%/19.5% in subjects with diabetes/hypercholesterolemia. Significant correlations between kw and vascular risk factors, CDR, executive/memory function, and the Fazekas scale of WMH were observed. Conclusion A diffusion prepared 3D GRASE pCASL sequence with TGV regularized SPA modeling was proposed to measure BBB water permeability noninvasively with good reproducibility. kw may serve as an imaging marker of cerebral SVD and associated cognitive impairment.

Brain function, the brain’s metabolic activity, cerebral blood flow (CBF), and intracranial pressure are intimately linked within the tightly autoregulated regime of intracranial physiology in which the role of tissue viscoelasticity remains elusive. We applied multifrequency magnetic resonance elastography (MRE) paired with CBF measurements in 14 healthy subjects exposed to 5-min carbon dioxide-enriched breathing air to induce cerebral vasodilatation by hypercapnia. Stiffness and viscosity as quantified by the magnitude and phase angle of the complex shear modulus, | G*| and ϕ, as well as CBF of the whole brain and 25 gray matter sub-regions were analyzed prior to, during, and after hypercapnia. In all subjects, whole-brain stiffness and viscosity increased due to hypercapnia by 3.3 ± 1.9% and 2.0 ± 1.1% which was accompanied by a CBF increase of 36 ± 15%. Post-hypercapnia, | G*| and ϕ reduced to normal values while CBF decreased by 13 ± 15% below baseline. Hypercapnia-induced viscosity changes correlated with CBF changes, whereas stiffness changes did not. The MRE-measured viscosity changes correlated with blood viscosity changes predicted by the Fåhræus–Lindqvist model and microvessel diameter changes from the literature. Our results suggest that brain viscoelastic properties are influenced by microvessel blood flow and blood viscosity: vasodilatation and increased blood viscosity due to hypercapnia result in an increase in MRE values related to viscosity.

Background Arterial spin labeling (ASL) based-noncontrast-enhanced 4D MR angiography (NCE 4D MRA) shows potential in characterizing cerebrovascular hemodynamics in cerebrovascular disorders. Ultrahigh-field theoretically benefits ASL signal with increased inherent signal-to-noise ratio (SNR) and prolonged blood T1 , which may provide improved delineation of vasculature in 4D MRA. Purpose To investigate the feasibility of NCE 4D MRA using 3D Cartesian trajectory and stack-of-stars (SOS) golden angle radial trajectory at 7T. Study type A prospective study. Subjects Six normal volunteers and eight patients with arteriovenous malformation (AVM). Field strength/sequence NCE 4D MRA with Cartesian and radial trajectories were performed at 3T and 7T. Assessment Subjective image quality of 4D MRA was evaluated using a 4-point scale by two experienced neuroradiologists. The characterization of AVM components with 4D MRA and DSA was also graded using the Spetzler-Martin grading scale. Statistical tests Cohen's kappa coefficient was calculated to evaluate the agreement between two readers within each 4D MRA technique (Cartesian and Radial). A Wilcoxon signed-rank test was performed to compare the subjective image quality scores of 4D MRA between Cartesian and radial trajectories, and between 7T and 3T, respectively. Results Good-to-excellent image quality was achieved in 4D MRA with both Cartesian (3.83 ± 0.41) and radial (3.42 ± 0.49) acquisitions in healthy volunteers at 7T. However, markedly reduced scan time was needed with radial acquisition. 4D MRA at 7T (3.31 ± 0.59) shows better delineation of AVM lesion features, especially the vein drainage, compared with that of 3T (2.83 ± 0.75), although no statistical significance was achieved (P = 0.180). Data conclusion The feasibility of ASL based 4D MRA at 7T with Cartesian and SOS golden angle radial acquisition was demonstrated. The clinical evaluation of 4D MRA in AVMs between 3T and 7T suggested 7T 4D MRA images acquired with radial acquisition demonstrate excellent delineation of AVM features, especially the draining veins. Level of evidence 2 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2017.

Author(s): Martin, Thomas; Hoffman, John; Alger, Jeff R; McNitt-Gray, Michael; Wang, Danny Jj | Abstract: PurposeCT Perfusion (CTP) is a widely used clinical imaging modality. However, CTP typically involves the use of substantial radiation dose (CTDIvol ≥~200 mGy). The purpose of this study is to present a low-dose CTP technique using a projection view-sharing reconstruction algorithm originally developed for dynamic MRI - "K-space Weighted Image Contrast" (KWIC).MethodsThe KWIC reconstruction is based on an angle-bisection scheme. In KWIC, a Fourier transform was performed along each projection to form a "k-space"-like CT data space, based on the central-slice theorem. As a projection view-sharing technique, KWIC preserves the spatiotemporal resolution of undersampled CTP data by progressively increasing the number of projection views shared for more distant regions of "k-space". KWIC reconstruction was evaluated on a digital FORBILD head phantom with numerically simulated time-varying objects. The numerically simulated scans were undersampled using the angle-bisection scheme to achieve 50%, 25%, and 12.5% of the original dose (288, 144, and 72 projections, respectively). The area-under-the-curve (AUC), time-to-peak (TTP), and full width half maximum (FWHM) were measured in KWIC recons and compared to fully sampled filtered back projection (FBP) reconstructions. KWIC reconstruction and dose reduction was also implemented for three clinical CTP cases (45 s, 1156 projections per turn, 1 s/turn, CTDIvol 217 mGy). Quantitative perfusion metrics were computed and compared between KWIC reconstructed CTP data and those of standard FBP reconstruction.ResultsThe AUC, TTP, and FWHM in the numerical simzulations were unaffected by the undersampling/dose reduction (down to 12.5% dose) with KWIC reconstruction compared to the fully sampled FBP reconstruction. The normalized root-mean-square-error (NRMSE) of the AUC in the FORBILD head phantom is 0.04, 0.05, and 0.07 for 50%, 25%, and 12.5% KWIC, respectively, as compared to FBP reconstruction. The cerebral blood flow (CBF) and cerebral blood volume had no significant difference between FBP and 50%, 25%, and 12.5% KWIC reconstructions (P g 0.05).ConclusionsThis study demonstrates that KWIC preserves perfusion metrics for CTP with substantially reduced dose. Clinical implementation will require further investigation into methods of rapid switching of a CT x-ray source.

The purpose was to assess the difference of collaterals in symptomatic versus asymptomatic patients with unilateral middle cerebral artery (MCA) stenosis by comparing cerebral blood flow (CBF) at two post labeling delays (PLD) using three-dimensional pseudo-continuous arterial spin labeling (3D pCASL). Eighty-one patients (49 symptomatic and 32 asymptomatic) with unilateral MCA stenosis ≥50% who underwent pCASL with two PLDs were included. Mean CBF and CBF subtraction images between two PLDs of MCA territories were compared in symptomatic and asymptomatic groups, respectively. Compared with the asymptomatic group, patients with symptomatic MCA stenosis had significantly lower CBF in the MCA territory of stenotic side at each PLD. The CBF of stenotic territory showed greater increase than that of normal side from PLD 1.5 to 2.5 s. The CBF of asymptomatic MCA territory increased similarly with that of symptomatic MCA territory from PLD of 1.5 to 2.5 s in stenotic side, while symptomatic patients experienced significantly slower antegrade flow. On CBF subtraction images, asymptomatic patients showed larger volume of differences between PLD of 1.5 and 2.5 s compared with those of symptomatic patients ( p = 0.037). The results suggest that more robust collateral perfusion on two-delay 3D pCASL is present in asymptomatic patients compared with symptomatic patients.

Aims Heart failure (HF) patients show significant lateralized neural injury, accompanied by autonomic, mood and cognitive deficits. Both gray and white matter damage occurs and probably develops from altered cerebral blood flow (CBF), a consequence of impaired cardiac output. However, the distribution of regional CBF changes in HF patients is unknown, but is an issue in determining mechanisms of neural injury. Our aim was to compare regional CBF changes in HF with CBF in control subjects using non-invasive pseudo-continuous arterial spin labelling (ASL) procedures. Methods and results We collected pseudo-continuous ASL data from 19 HF patients [mean age 55.5 ± 9.1 years; mean body mass index 27.7 ± 5.3 kg/m2; 13 male) and 29 control subjects (mean age 51.4 ± 5.3 years; mean body mass index 25.7 ± 3.6 kg/m2; 18 male), using a 3.0-Tesla magnetic resonance imaging (MRI) scanner. Whole-brain CBF maps were calculated, normalized to a common space, smoothed and compared between groups using ANCOVA (covariates; age, gender and gray matter volume). Reduced CBF appeared in multiple sites in HF patients in comparison with controls, with principally lateralized lower flow in temporal, parietal and occipital regions. Areas with decreased CBF included the bilateral prefrontal, frontal, temporal and occipital cortex, thalamus, cerebellum, corona radiate, corpus callosum, hippocampus and amygdala. Conclusions Heart failure patients showed lower, and largely lateralized, CBF in multiple autonomic, mood and cognitive regulatory sites. The reduced CBF is likely to contribute to the lateralized brain injury, leading to the autonomic and neuropsychological deficits found in the condition.

Purpose To evaluate the feasibility and performance of compressed sensing (CS) with magnitude subtraction regularization in accelerating non–contrast-enhanced dynamic intracranial MR angiography (NCE-dMRA). Methods A CS algorithm was introduced in NCE-dMRA by exploiting the sparsity of the magnitude difference of the control and label images. The NCE-dMRA data were acquired using golden-angle stack-of-stars trajectory on six healthy volunteers and one patient with arteriovenous fistula. Images were reconstructed using (i) the proposed magnitude-subtraction CS (MS-CS); (ii) complex-subtraction CS; (iii) independent CS; and (iv) view-sharing with k-space weighted image contrast (KWIC). The dMRA image quality was compared across the four reconstruction strategies. The proposed MS-CS method was further compared with KWIC for temporal fidelity of depicting dynamic flow. Results The proposed MS-CS method was able to reconstruct NCE-dMRA images with detailed vascular structures and clean background. It provided better subjective image quality than the other two CS strategies (P

Purpose To investigate whether arterial spin labeling (ASL) MRI could detect renal hemodynamic impairment in diabetes mellitus (DM) along different stages of chronic kidney disease (CKD). Materials and Methods Three Tesla (3T) ASL-MRI was performed to evaluate renal blood flow (RBF) in 91 subjects (46 healthy volunteers and 45 type 2 diabetic patients). Patients were classified according to their estimated glomerular filtration rate (eGFR) as group I (eGFR > 60 mL/min/1.73 m2), group II (60 ≥ eGFR>30 mL/min/1.73 m2), or group III (eGFR ≤ 30 mL/min/1.73 m2), to determine differences depending on renal function. Studies were performed at 3T using a 12-channel flexible body array combined with the spine array coil as receiver. Results A 28% reduction in cortical RBF was seen in diabetics in comparison with healthy controls (185.79 [54.60] versus 258.83 [37.96] mL/min/100 g, P 0.05; albumin-creatinine ratio [mg/g]: controls = 3.50 [4.45], group I = 17.50 [21.20], P > 0.05). A marked decrease in RBF was noted a long with progression of diabetic nephropathy (DN) through the five stages of CKD (χ2 = 43.58; P = 1.85 × 10−9). Strong correlation (r = 0.62; P = 4 × 10−10) was obtained between RBF and GFR estimated by cystatin C. Conclusion ASL-MRI is able to quantify early renal perfusion impairment in DM, as well as changes according to different CKD stages of DN. In addition, we demonstrated a correlation of RBF quantified by ASL and GFR estimated by cystatin C. Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1810–1817.

Purpose To present a constrained slice-dependent (CSD) background-suppression (BS) scheme in 2D arterial spin labeling (ASL) using simultaneous multislice acquisition with blipped-CAIPIRINHA (controlled aliasing in parallel imaging results in higher acceleration). Methods Background suppression for 2D acquisition is challenging because of the multiple nulling points required for sequential slice readout. Constrained slice-dependent BS exploits the simultaneous multislice technique to reduce the readout duration, and uses slice-dependent premodulation pulses to achieve BS across slice groups. The proposed scheme was evaluated by in vivo brain experiments at 3 Tesla with multiband acceleration factors up to four. The utility of CSD BS was demonstrated through comparison against standard 2D acquisitions as well as 3D-BS pseudo-continuous ASL (pCASL). Results An average of 95% background signal reduction was achieved with CSD BS. As a result, the temporal signal-to-noise ratio (SNR) increased 48.2/39.9/36.9/36.0% and spatial SNR increased 132.5/80.0/63.5/54.2 in CSD-BS MB-1/2/3/4 scans, respectively. Whole-brain coverage was achievable with CSD-BS pCASL with MB-4, which yielded comparable spatial SNR as 3D BS pCASL. Conclusions The proposed CSD-BS scheme for 2D-SMS pCASL offers a promising approach for effective suppression of background signals across a wide range of T1 to achieve whole-brain perfusion imaging. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Purpose To develop and evaluate an improved stack-of-stars radial sampling strategy for reducing streaking artifacts. Methods The conventional stack-of-stars sampling strategy collects the same radial angle for every partition (slice) encoding. In an undersampled acquisition, such an aligned acquisition generates coherent aliasing patterns and introduces strong streaking artifacts. We show that by rotating the radial spokes in a golden-angle manner along the partition-encoding direction, the aliasing pattern is modified, resulting in improved image quality for gridding and more advanced reconstruction methods. Computer simulations were performed and phantom as well as in vivo images for three different applications were acquired. Results Simulation, phantom, and in vivo experiments confirmed that the proposed method was able to generate images with less streaking artifact and sharper structures based on undersampled acquisitions in comparison with the conventional aligned approach at the same acceleration factors. By combining parallel imaging and compressed sensing in the reconstruction, streaking artifacts were mostly removed with improved delineation of fine structures using the proposed strategy. Conclusions We present a simple method to reduce streaking artifacts and improve image quality in 3D stack-of-stars acquisitions by re-arranging the radial spoke angles in the 3D partition direction, which can be used for rapid volumetric imaging. Magn Reson Med 78:2290–2298, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Introduction We investigated the hypothesis that retinal capillary perfusion is a biomarker of early cognitive decline and cerebrovascular perfusion associated with small vessel disease in a pilot data set of Latinx adults at high risk for vascular cognitive impairment and dementia. Methods High‐resolution optical coherence tomography angiography (OCTA) images were acquired from dilated eyes of Latinx subjects using a 3 × 3 mm2 scan pattern from a commercially available device. A previously validated method was used to quantify the density of perfused retinal capillaries as the retinal vessel skeleton density (VSD). The association of VSD with Clinical Dementia Rating Sum of Boxes, total Montreal Cognitive Assessment (MoCA) score, and individual MoCA test elements were analyzed using multivariate statistics that adjusted for confounders. VSD was also compared with magnetic resonance imaging (MRI) measures of cerebrovascular reactivity (CVR) and perfusion in the middle cerebral artery perforator (MCA‐Perf) territory. Results The mean (± SD) age of the subjects was 68 (± 6) years. For every 0.01‐unit lower VSD, the risk of having a CDR‐SOB >0 was 20% higher (95%CI = 5%–90%; P = .031). Similarly, a lower VSD was associated with lower total MoCA score (r = 0.3; P = .038). The Visuospatial/Executive domain of the MoCA assessment showed the strongest association with VSD (β = 0.02; P = .022). Lower retinal VSD was associated with worse MRI measure of CVR (r = 0.7, P = .04) and less perfusion in the MCA‐Perf territory (r = 0.45, P = .02). Discussion Impaired retinal capillary perfusion is associated with cognitive impairment and abnormalities in cerebrovascular perfusion and function. OCTA‐based retinal capillary assessment holds promise for identifying and quantifying retinal correlates of neurovascular abnormalities associated with vascular cognitive impairment.

Ketamine infusion therapy can produce fast-acting antidepressant effects in patients with major depressive disorder (MDD). Yet, how single and repeated ketamine treatment induces brain systems-level neuroplasticity underlying symptom improvement is unknown. Advanced multiband imaging (MB) pseudo-continuous arterial spin labeling (pCASL) perfusion MRI data was acquired from patients with treatment resistant depression (TRD) (N=22, mean age=35.2±9.95 SD, 27% female) at baseline, and 24h after receiving single, and four subanesthetic (0.5mg/kg) intravenous ketamine infusions. Changes in global and regional CBF were compared across time points, and relationships with overall mood, anhedonia and apathy were examined. Comparisons between patients at baseline and controls (N=18, mean age=36.11±14.5 SD, 57% female) established normalization of treatment effects. Results showed increased regional CBF in the cingulate and primary and higher-order visual association regions after first ketamine treatment. Baseline CBF in the fusiform, and acute changes in CBF in visual areas were related to symptom improvement after single and repeated ketamine treatment, respectively. In contrast, after serial infusion therapy, decreases in regional CBF were observed in the bilateral hippocampus and right insula with ketamine treatment. Findings demonstrate that neurophysiological changes occurring with single and repeated ketamine treatment follow both a regional and temporal pattern including sensory and limbic regions. Initial changes are observed in the posterior cingulate and precuneus and primary and higher-order visual areas, which relate to clinical responses. However, repeated exposure to ketamine, though not relating to clinical outcome, appears to engage deeper limbic structures and insula. ClinicalTrials.gov: Biomarkers of Fast Acting Therapies in Major Depression, https://clinicaltrials.gov/ct2/show/NCT02165449, NCT02165449.

The neurobiology of schizophrenia (SZ) may be altered in older versus younger adults with SZ, as less frequent episodes of symptom exacerbation and increased sensitivity to medications are observed in older age. The goal of this study was to examine the effect of age and diagnosis on glutamate and cerebral blood flow (rCBF) in adults with SZ and healthy controls. Young and older adults with SZ and healthy controls were recruited to participate in this study. Participants completed a neuropsychological battery and neuroimaging that included optimized magnetic resonance spectroscopy to measure anterior cingulate (AC) glutamate (Glu) and glutamine (Gln) and arterial spin labeling evaluation for rCBF. Regression analyses revealed significant effects of age with Glu, Gln, Gln/Glu, and AC white matter (WM) rCBF. Glu and WM rCBF decreased linearly with age while Gln and Gln/Glu increased linearly with age. Glu was lower in adults with SZ compared with healthy controls and in older adults versus younger adults but there was no interaction. Glu and WM rCBF were correlated with the UCSD Performance-Based Skills Assessment (UPSA) and processing speed, and the correlations were stronger in the SZ group. In the largest sample to date, lower Glu and elevated Gln/Glu levels were observed in adults with SZ and in older subjects. Contrary to expectation, these results do not show evidence of accelerated Glu aging in the anterior cingulate region in SZ compared with healthy controls.

Purpose To evaluate the efficacy of 3D pseudocontinuous arterial spin labeling (3D pCASL) in the differential diagnosis between mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) and acute ischemic stroke (AIS). Materials and Methods Conventional magnetic resonance imaging (MRI) including T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), and 3D pCASL perfusion data were obtained on a 3.0T MR scanner in 16 newly appearing lesions in nine patients with MELAS and 14 acute lesions in 12 patients with AIS. A postlabeling delay (PLD) time of 2025 msec was applied. The cerebral blood flow (CBF) values were measured in the central part and the peripheral part of the lesions and the CBF values were compared between MELAS and AIS patients. Results The lesions of both MELAS and AIS showed high signal intensity on T2WI and demonstrated hyperintensity on DWI. Compared with the perfusion defects or hypoperfusion in all AIS, hyperperfusion was revealed in 16 acute MELAS lesions, especially in the peripheral part of the lesions. The CBF values of 16 lesions in MELAS were 11.20–73.11 ml/100g/min in the central part and 65.33–169.11 ml/100g/min in the peripheral part. The CBF values of 14 lesions in AIS were 12.32–19.94 ml/100g/min in the central part and 11.66–18.37 ml/100g/min in the peripheral part. The CBF value of the peripheral part (119.80 ± 35.41) in MELAS was significantly higher than that (14.66 ± 2.61) in AIS (P = 0.0001). Conclusion The whole-brain 3D pCASL technique might be useful in differentiating MELAS from AIS. J. Magn. Reson. Imaging 2016.

Arterial spin labeling and phase contrast magnetic resonance imaging provide independent non-invasive methods for measuring cerebral blood flow. We compared global cerebral blood flow measurements obtained using pseudo-continuous arterial spin labeling and phase contrast in 436 middle-aged subjects acquired at two sites in the NHLBI CARDIA multisite study. Cerebral blood flow measured by phase contrast (CBFPC: 55.76 ± 12.05 ml/100 g/min) was systematically higher ( p PCASL: 47.70 ± 9.75). The correlation between global cerebral blood flow values obtained from the two modalities was 0.59 ( p PCASL and CBFPC. CBFPC also demonstrated statistically significant site differences, whereas no such differences were observed in CBFPCASL. No consistent velocity-dependent effects on pseudo-continuous arterial spin labeling were observed, suggesting that pseudo-continuous labeling efficiency does not vary substantially across typical adult carotid and vertebral velocities, as has previously been suggested. Conclusions: Although CBFPCASL and CBFPC values show substantial similarity across the entire cohort, these data do not support calibration of CBFPCASL using CBFPC in individual subjects. The wide-ranging cerebral blood flow values obtained by both methods suggest that cerebral blood flow values are highly variable in the general population.

PURPOSE Noncontrast enhanced dynamic magnetic resonance angiography delineates the pattern of dynamic blood flow of the cerebral vasculature. A model-free solution was proposed to quantify arterial blood flow (aBF) by using the monotonic property of the residual function. THEORY AND METHODS Analytical simulations and in-vivo studies were performed to evaluate the performance of the proposed method by comparing the aBF values generated from the proposed and conventional singular value decomposition methods. The aBF values were compared with blood flow velocity measured by 2D phase contrast MRI, and compared between balanced steady-state free precession-based radial and spoiled GRE-based Cartesian acquisitions. Hemodynamic parametric maps were generated in 1 patient with arteriovenous malformation. RESULTS The proposed method generates reliable aBF measurement at different signal-to-noise ratio levels, whereas overestimation/underestimation of aBF was observed when a high/low threshold was applied in the singular value decomposition method. Average aBF in large vascular branches was 214.4 and 214.5 mL/mL/min with radial and Cartesian acquisitions, respectively. Significant correlations were found between aBF and blood flow velocity measured by phase contrast MRI (P = 0.0008), and between Cartesian and radial acquisitions (P < 0.0001). Altered hemodynamics were observed at the lesion site of the arteriovenous malformation patient. CONCLUSION A robust analytical solution was proposed for quantifying aBF. This model-free method is robust to noise, and its clinical value in the diagnosis of cerebrovascular disorders awaits further evaluation.

3D pseudocontinuous arterial spin labeling (pCASL) with a single post-labeling delay time is commonly used to measure cerebral blood flow (CBF). Multi-phase pCASL has been developed to simultaneously estimate CBF and arterial transit time (ATT).To evaluate the clinical feasibility of multi-phase 3D pCASL in pediatric patients, and to compare the estimation of ATT and CBF via linear weighted-delay and traditional non-linear iterative curve-fitting routines.Forty patients (average age: 8.6 y, 5 d-22.4 y) referred for routine brain MRI underwent additional 5-7 min of pCASL scans at 3T using 5 PLDs between 300 and 2300 ms. Data were post-processed by two algorithms for estimating CBF and ATT. Average CBF and ATT values were computed for vascular territories including the anterior, middle and posterior cerebral arteries as well as regions based on the Alberta Stroke Program Early CT Score template. Pearson correlation coefficients and linear regression were used for statistical analysis. The clinical value of multi-phase CASL was evaluated by a neuroradiologist based on asymmetric CBF and ATT maps in patients.All pCASL scans were successfully completed, generating diagnostic results. CBF computed from weighted-delay and curve-fitting methods agreed strongly, with Pearson correlation coefficients ranging from 0.97-0.99 across the measured regions (p 0.05). Correlation coefficients for ATT ranged from 0.87-0.96 (p 0.05). CBF and ATT maps were found to add valuable information to clinical diagnosis in 17 of 40 pediatric patients.Our preliminary results demonstrate the feasibility and potential clinical utility of multi-phase pCASL for simultaneous CBF and ATT quantification in pediatric patients.