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To develop a 2D multi-echo passband balanced SSFP (bSSFP) sequence using an echo-train readout with a sequential phase-encoding order (sequential multi-echo bSSFP), and evaluate its performance in fast functional brain imaging at 7 T.As images of sequential multi-echo bSSFP exhibit multiple ghosts due to periodic k-space modulations, a GRAPPA-based reconstruction method was proposed to eliminate ghosting artifacts. MRI experiments were performed to compare the image quality of multi-echo bSSFP and conventional single-echo bSSFP. Submillimeter-resolution fMRI using a checkerboard visual stimulus was conducted to compare the activation characteristics of multi-echo bSSFP, conventional single-echo bSSFP and standard gradient-echo EPI (GE-EPI).A higher mean structural similarity index was found between images of single-echo bSSFP and multi-echo bSSFP with a shorter echo train length (ETL). Multi-echo bSSFP (ETL = 3) showed higher temporal SNR (tSNR) values than GRAPPA-accelerated single-echo bSSFP (R = 2). In submillimeter-resolution fMRI experiments, multi-echo bSSFP (ETL = 3) approached the imaging speed of GRAPPA-accelerated single-echo bSSFP (R = 2), but without tSNR penalty and reduced activation due to acceleration. The median t-value and the number of significantly activated voxels were comparable between GE-EPI and multi-echo bSSFP (ETL = 3) that provides virtually distortion-free functional images and inherits the activation patterns of conventional bSSFP.Sequential multi-echo bSSFP (ETL = 3) is suitable for fast fMRI with submillimeter in-plane resolution, and offers an option to accelerate bSSFP imaging without tSNR penalty like parallel imaging.

Background and Hypothesis Mounting evidence supports cerebrovascular contributions to schizophrenia spectrum disorder (SSD) but with unknown mechanisms. The blood–brain barrier (BBB) is at the nexus of neural-vascular exchanges, tasked with regulating cerebral homeostasis. BBB abnormalities in SSD, if any, are likely more subtle compared to typical neurological insults and imaging measures that assess large molecule BBB leakage in major neurological events may not be sensitive enough to directly examine BBB abnormalities in SSD. Study Design We tested the hypothesis that neurovascular water exchange (Kw) measured by non-invasive diffusion-prepared arterial spin label MRI (n = 27 healthy controls [HC], n = 32 SSD) is impaired in SSD and associated with clinical symptoms. Peripheral vascular endothelial health was examined by brachial artery flow-mediated dilation (n = 44 HC, n = 37 SSD) to examine whether centrally measured Kw is related to endothelial functions. Study Results Whole-brain average Kw was significantly reduced in SSD (P = .007). Exploratory analyses demonstrated neurovascular water exchange reductions in the right parietal lobe, including the supramarginal gyrus (P = .002) and postcentral gyrus (P = .008). Reduced right superior corona radiata (P = .001) and right angular gyrus Kw (P = .006) was associated with negative symptoms. Peripheral endothelial function was also significantly reduced in SSD (P = .0001). Kw in 94% of brain regions in HC positively associated with peripheral endothelial function, which was not observed in SSD, where the correlation was inversed in 52% of brain regions. Conclusions This study provides initial evidence of neurovascular water exchange abnormalities, which appeared clinically associated, especially with negative symptoms, in schizophrenia.

IMPORTANCE: Antihypertensive treatments benefit cerebrovascular health and cognitive function in patients with hypertension, but it is uncertain whether an intensive blood pressure target leads to potentially harmful cerebral hypoperfusion. OBJECTIVE: To investigate the association of intensive systolic blood pressure (SBP) control vs standard control with whole-brain cerebral blood flow (CBF). DESIGN, SETTING, AND PARTICIPANTS: This substudy of the Systolic Blood Pressure Intervention Trial (SPRINT) randomized clinical trial compared the efficacy of 2 different blood pressure–lowering strategies with longitudinal brain magnetic resonance imaging (MRI) including arterial spin labeled perfusion imaging to quantify CBF. A total of 1267 adults 50 years or older with hypertension and increased cardiovascular risk but free of diabetes or dementia were screened for the SPRINT substudy from 6 sites in the US. Randomization began in November 2010 with final follow-up MRI in July 2016. Analyses were performed from September 2020 through December 2021. INTERVENTIONS: Study participants with baseline CBF measures were randomized to an intensive SBP target less than 120 mm Hg or standard SBP target less than 140 mm Hg. MAIN OUTCOMES AND MEASURES: The primary outcome was change in whole-brain CBF from baseline. Secondary outcomes were change in gray matter, white matter, and periventricular white matter CBF. RESULTS: Among 547 participants with CBF measured at baseline, the mean (SD) age was 67.5 (8.1) years and 219 (40.0%) were women; 315 completed follow-up MRI at a median (IQR) of 4.0 (3.7-4.1) years after randomization. Mean whole-brain CBF increased from 38.90 to 40.36 (difference, 1.46 [95% CI, 0.08-2.83]) mL/100 g/min in the intensive treatment group, with no mean increase in the standard treatment group (37.96 to 37.12; difference, –0.84 [95% CI, –2.30 to 0.61] mL/100 g/min; between-group difference, 2.30 [95% CI, 0.30-4.30; P = .02]). Gray, white, and periventricular white matter CBF showed similar changes. The association of intensive vs standard treatment with CBF was generally similar across subgroups defined by age, sex, race, chronic kidney disease, SBP, orthostatic hypotension, and frailty, with the exception of an indication of larger mean increases in CBF associated with intensive treatment among participants with a history of cardiovascular disease (interaction P = .05). CONCLUSIONS AND RELEVANCE: Intensive vs standard antihypertensive treatment was associated with increased, rather than decreased, cerebral perfusion, most notably in participants with a history of cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01206062

A novel denoising algorithm termed k-space weighted image average (KWIA) was proposed to improve the signal-to-noise ratio (SNR) of dynamic MRI, such as arterial spin labeling (ASL)-based dynamic magnetic resonance angiography (dMRA) and perfusion imaging. KWIA divides the k-space of each time frame into multiple rings, the central ring of the k-space remains intact to preserve the image contrast and temporal resolution, while outer rings are progressively averaged with neighboring time frames to increase SNR. Simulations and in-vivo dMRA and multi-delay ASL studies were performed to evaluate the performance of KWIA under various MRI acquisition conditions. SNR ratios and temporal signal errors between KWIA-processed and the original data were measured. Visualization of dynamic blood flow signals as well as quantitative parametric maps were evaluated for KWIA-processed images as compared to the original images. KWIA achieved a SNR ratio of 1.73 for dMRA and 2.0 for multi-delay ASL respectively, which were in accordance with the theoretical predictions. Improved visualization of dynamic blood flow signals was demonstrated using KWIA in distal small vessels in dMRA and small brain structures in multi-delay ASL. Approximately 5% temporal errors were observed in both KWIA-processed dMRA and ASL signals. Fine anatomical features were revealed in the quantitative parametric maps of dMRA, and the residuals of model fitting were reduced for multi-delay ASL. Compared to other conventional denoising methods, KWIA is a flexible denoising algorithm that improves the SNR of ASL-based dMRA and perfusion MRI by up to 2-fold without compromising spatial and temporal resolution or quantification accuracy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and heterozygous HTRA1 mutation-related cerebral small vessel disease (CSVD) are the two types of dominant hereditary CSVD. Blood–brain barrier (BBB) failure has been hypothesized in the pathophysiology of CSVD. However, it is unclear whether there is BBB damage in the two types of hereditary CSVD, especially in heterozygous HTRA1 mutation-related CSVD. In this study, a case-control design was used with two disease groups including CADASIL (n = 24), heterozygous HTRA1 mutation-related CSVD (n = 9) and healthy controls (n = 24). All participants underwent clinical cognitive assessments and brain MRI. Diffusion-prepared pseudo-continuous arterial spin labelling was used to estimate the water exchange rate across the BBB (kw). Correlation and multiple linear regression analyses were used to examine the association between kw and disease burden and neuropsychological performance, respectively. Compared with the healthy controls, kw in the whole brain and multiple brain regions was decreased in both CADASIL and heterozygous HTRA1 mutation-related CSVD patients (Bonferroni-corrected P < 0.007). In the CADASIL group, decreased kw in the whole brain (β = −0.634, P = 0.001), normal-appearing white matter (β = −0.599, P = 0.002) and temporal lobe (β = −0.654, P = 0.001) was significantly associated with higher CSVD score after adjusting for age and sex. Reduced kw in the whole brain was significantly associated with poorer neuropsychological performance after adjusting for age, sex and education in both CADASIL and heterozygous HTRA1 mutation-related CSVD groups (β = 0.458, P = 0.001; β = 0.884, P = 0.008). This study showed that there was decreased water exchange rate across the BBB in both CADASIL and heterozygous HTRA1 mutation-related CSVD patients, suggesting a common pathophysiological mechanism underlying the two types of hereditary CSVD. These results highlight the potential use of kw for monitoring the course of CADASIL and heterozygous HTRA1 mutation-related CSVD, a possibility which should be tested in future research.

BackgroundRepetitive peripheral nerve sensory stimulation (RPSS) is a potential add-on intervention to motor training for rehabilitation of upper limb paresis after stroke. Benefits of RPSS were reported in subjects in the chronic phase after stroke, but there is limited information about the effects of this intervention within the 1st weeks or months. The primary goal of this study is to compare, in a head-to-head proof-of-principle study, the impact of a single session of suprasensory vs. subsensory RPSS on the upper limb motor performance and learning in subjects at different phases after stroke subacute and chronic phases and mild upper limb motor impairments after stroke. In addition, we examine the effects of RPSS on brain perfusion, functional imaging activation, and γ-aminobutyric acid (GABA) levels. Subjects with mild upper limb motor impairments will be tested with MRI and clinical assessment either at an early (7 days to 3 months post-stroke) or at a chronic (>6 months) stage after stroke.MethodsIn this multicenter, randomized, parallel-group, proof-of-principle clinical trial with blinded assessment of outcomes, we compare the effects of one session of suprasensory or subsensory RPSS in patients with ischemic or hemorrhagic stroke and upper limb paresis. Clinical assessment and MRI will be performed only once in each subject (either at an early or at a chronic stage). The primary outcome is the change in performance in the Jebsen–Taylor test. Secondary outcomes: hand strength, cerebral blood flow assessed with arterial spin labeling, changes in the blood oxygenation level-dependent (BOLD) effect in ipsilesional and contralesional primary motor cortex (M1) on the left and the right hemispheres assessed with functional MRI (fMRI) during a finger-tapping task performed with the paretic hand, and changes in GABA levels in ipsilesional and contralesional M1 evaluated with spectroscopy. The changes in outcomes will be compared in four groups: suprasensory, early; subsensory, early; suprasensory, chronic; and subsensory, chronic.DiscussionThe results of this study are relevant to inform future clinical trials to tailor RPSS to patients more likely to benefit from this intervention.Trial RegistrationNCT03956407.

Objectives This study aimed at developing technical recommendations for the acquisition, processing and analysis of renal ASL data in the human kidney at 1.5 T and 3 T field strengths that can promote standardization of renal perfusion measurements and facilitate the comparability of results across scanners and in multi-centre clinical studies. Methods An international panel of 23 renal ASL experts followed a modified Delphi process, including on-line surveys and two in-person meetings, to formulate a series of consensus statements regarding patient preparation, hardware, acquisition protocol, analysis steps and data reporting. Results Fifty-nine statements achieved consensus, while agreement could not be reached on two statements related to patient preparation. As a default protocol, the panel recommends pseudo-continuous (PCASL) or flow-sensitive alternating inversion recovery (FAIR) labelling with a single-slice spin-echo EPI readout with background suppression and a simple but robust quantification model. Discussion This approach is considered robust and reproducible and can provide renal perfusion images of adequate quality and SNR for most applications. If extended kidney coverage is desirable, a 2D multislice readout is recommended. These recommendations are based on current available evidence and expert opinion. Nonetheless they are expected to be updated as more data become available, since the renal ASL literature is rapidly expanding.

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.

To describe the protocol and findings of the instrumental validation of three imaging-based biomarker kits selected by the MarkVCID consortium: free water (FW) and peak width of skeletonized mean diffusivity (PSMD), both derived from diffusion tensor imaging (DTI), and white matter hyperintensity (WMH) volume derived from fluid attenuation inversion recovery and T1-weighted imaging.The instrumental validation of imaging-based biomarker kits included inter-rater reliability among participating sites, test-retest repeatability, and inter-scanner reproducibility across three types of magnetic resonance imaging (MRI) scanners using intra-class correlation coefficients (ICC).The three biomarkers demonstrated excellent inter-rater reliability (ICC 0.94,The three biomarker kits demonstrated very high inter-rater reliability, test-retest repeatability, and inter-scanner reproducibility, offering robust biomarkers suitable for future multi-site observational studies and clinical trials in the context of vascular cognitive impairment and dementia (VCID).

Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC. Recent research indicates other and more complex risk factors and pathogenetic mechanisms. Here, we describe aspects of the unique architecture of brain arterioles, histomorphologic features of B-ASC, relevant neuroimaging findings, epidemiology and association with aging, established genetic risk factors, and the co-occurrence of B-ASC with other neuropathologic conditions such as Alzheimer's disease and limbic-predominant age-related TDP-43 encephalopathy (LATE). There may also be complex physiologic interactions between metabolic syndrome (e.g., hypertension and inflammation) and brain arteriolar pathology. Although there is no universally applied diagnostic methodology, several classification schemes and neuroimaging techniques are used to diagnose and categorize cerebral small vessel disease pathologies that include B-ASC, microinfarcts, microbleeds, lacunar infarcts, and cerebral amyloid angiopathy (CAA). In clinical-pathologic studies that factored incomorbid diseases, B-ASC was independently associated with impairments of global cognition, episodic memory, working memory, and perceptual speed, and has been linked to autonomic dysfunction and motor symptoms including parkinsonism. We conclude by discussing critical knowledge gaps related to B-ASC and suggest that there are probably subcategories of B-ASC that differ in pathogenesis. Observed in over 80% of autopsied individuals beyond 80years of age, B-ASC is a complex and under-studied contributor to neurologic disability.

Transcranial direct current stimulation (tDCS) can influence performance on behavioral tasks and improve symptoms of brain conditions. Yet, it remains unclear precisely how tDCS affects brain function and connectivity. Here, we measured changes in functional connectivity (FC) metrics in blood-oxygenation-level-dependent (BOLD) fMRI data acquired during MR-compatible tDCS in a whole-brain analysis with corrections for false discovery rate. Volunteers (n = 64) received active tDCS, sham tDCS, and rest (no stimulation), using one of three previously established electrode tDCS montages targeting left dorsolateral prefrontal cortex (DLPFC, n = 37), lateral temporoparietal area (LTA, n = 16), or superior temporal cortex (STC, n = 11). In brain networks where simulated E field was highest in each montage, connectivity with remote nodes decreased during active tDCS. During active DLPFC-tDCS, connectivity decreased between a fronto-parietal network and subgenual ACC, while during LTA-tDCS connectivity decreased between an auditory-somatomotor network and frontal operculum. Active DLPFC-tDCS was also associated with increased connectivity within an orbitofrontal network overlapping subgenual ACC. Irrespective of montage, FC metrics increased in sensorimotor and attention regions during both active and sham tDCS, which may reflect the cognitive-perceptual demands of tDCS. Taken together, these results indicate that tDCS may have both intended and unintended effects on ongoing brain activity, stressing the importance of including sham, stimulation-absent, and active comparators in basic science and clinical trials of tDCS.

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.

Cerebral small vessel disease (cSVD) affects arterioles, capillaries, and venules and can lead to cognitive impairments and clinical symptomatology of vascular cognitive impairment and dementia (VCID). VCID symptoms are similar to Alzheimer’s disease (AD) but the neurophysiologic alterations are less well studied, resulting in no established biomarkers. The purpose of this study was to evaluate cerebral blood flow (CBF) measured by 3D pseudo-continuous arterial spin labeling (pCASL) as a potential biomarker of VCID in a cohort of elderly Latinx subjects at risk of cSVD. Forty-five elderly Latinx subjects (12 males, 69 ± 7 years) underwent repeated MRI scans ∼6 weeks apart. CBF was measured using 3D pCASL in the whole brain, white matter and 4 main vascular territories (leptomeningeal anterior, middle, and posterior cerebral artery (leptoACA, leptoMCA, leptoPCA), as well as MCA perforator). The test-retest repeatability of CBF was assessed by intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wsCV). Absolute and relative CBF was correlated with gross cognitive measures and domain specific assessment of executive and memory function, vascular risks, and Fazekas scores and volumes of white matter hyperintensity (WMH). Neurocognitive evaluations were performed using Montreal Cognitive Assessment (MoCA) and neuropsychological test battery in the Uniform Data Set v3 (UDS3). Good to excellent test-retest repeatability was achieved (ICC = 0.77–0.85, wsCV 3–9%) for CBF measurements in the whole brain, white matter, and 4 vascular territories. Relative CBF normalized by global mean CBF in the leptoMCA territory was positively correlated with the executive function composite score, while relative CBF in the leptoMCA and MCA perforator territory was positively correlated with MoCA scores, controlling for age, gender, years of education, and testing language. Relative CBF in WM was negatively correlated with WMH volume and MoCA scores, while relative leptoMCA CBF was positively correlated with WMH volume. Reliable 3D pCASL CBF measurements were achieved in the cohort of elderly Latinx subjects. Relative CBF in the leptomeningeal and perforator MCA territories were the most likely candidate biomarker of VCID. These findings need to be replicated in larger cohorts with greater variability of stages of cSVD.

Arterial input function (AIF) is estimated from perfusion images as a basic curve for the following deconvolution process to calculate hemodynamic variables to evaluate vascular status of tissues. However, estimation of AIF is currently based on manual annotations with prior knowledge. We propose an automatic estimation of AIF in perfusion images based on a multi-stream 3D CNN, which combined spatial and temporal features together to estimate the AIF ROI. The model is trained by manual annotations. The proposed method was trained and tested with 100 cases of perfusion-weighted imaging. The result was evaluated by dice similarity coefficient, which reached 0.79. The trained model had a better performance than the traditional method. After segmentation of the AIF ROI, the AIF was calculated by the average of all voxels in the ROI. We compared the AIF result with the manual and traditional methods, and the parameters of further processing of AIF, such as time to the maximum of the tissue residue function (Tmax), relative cerebral blood flow, and mismatch volume, which are calculated in the Section Results. The result had a better performance, the average mismatch volume reached 93.32% of the manual method, while the other methods reached 85.04 and 83.04%. We have applied the method on the cloud platform, Estroke, and the local version of its software, NeuBrainCare, which can evaluate the volume of the ischemic penumbra, the volume of the infarct core, and the ratio of mismatch between perfusion and diffusion images to help make treatment decisions, when the mismatch ratio is abnormal.

BACKGROUND: Placenta influences the health of both a woman and her fetus during pregnancy. Maternal blood supply to placenta can be measured non-invasively using arterial spin labeling (ASL). PURPOSE: To present a multi-delay pseudo-continuous arterial spin labeling (pCASL) combined with a fast 3D inner-volume Gradient-and Spin Echo (GRASE) imaging technique to simultaneously measure placental blood flow (PBF) and arterial transit time (ATT), and to study PBF and ATT evolution with gestational age during the second trimester. The PBF values were compared with uterine arterial Doppler ultrasound to assess its potential clinical utility. STUDY TYPE: This was a prospective study. SUBJECTS: Thirty-four pregnant women. FIELD STRENGTH/SEQUENCE: Multi-delay 3D inner-volume GRASE pCASL sequence on 3T MR scanners. ASSESSMENT: Subjects underwent two longitudinal MRI scans within the second trimester, conducted between 14–16 and 19–22 weeks of gestational age, respectively. Placental perfusion was measured using the free-breathing pCASL sequence at three post-labeling delays (PLDs), followed by offline motion correction and model fitting for estimation of PBF and ATT. STATISTICAL TESTS: Paired t-test was conducted to evaluate the significance of PBF/ATT variations with placental development. Two-sample t-test was conducted to evaluate the significance of PBF difference in subjects with and without early diastolic notch. RESULTS: The mean PBF and ATT for the second trimester were 111.4±26.7 ml/100g/min and 1387.5±88.0 ms respectively. The average PBF increased by 10.4% (P

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).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.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 0.05). Compared with KWIC, MS-CS showed similar image quality, but reduced temporal blurring in delineating the fine distal arteries.The MS-CS method is a promising CS technique for accelerating NCE-dMRA acquisition without compromising image quality and temporal fidelity. Magn Reson Med 79:867-878, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Changes in cerebral blood flow (CBF) during a hyperglycemic challenge were mapped, using perfusion-weighted MRI, in a group of non-human primates. Seven female baboons were fasted for 16 h prior to 1-h imaging experiment, performed under general anesthesia, that consisted of a 20-min baseline, followed by a bolus infusion of glucose (500 mg/kg). CBF maps were collected every 7 s and blood glucose and insulin levels were sampled at regular intervals. Blood glucose levels rose from 51.3 ± 10.9 to 203.9 ± 38.9 mg/dL and declined to 133.4 ± 22.0 mg/dL, at the end of the experiment. Regional CBF changes consisted of four clusters: cerebral cortex, thalamus, hypothalamus, and mesencephalon. Increases in the hypothalamic blood flow occurred concurrently with the regulatory response to systemic glucose change, whereas CBF declined for other clusters. The return to baseline of hypothalamic blood flow was observed while CBF was still increasing in other brain regions. The spatial pattern of extra-hypothalamic CBF changes was correlated with the patterns of several cerebral networks including the default mode network. These findings suggest that hypothalamic blood flow response to systemic glucose levels can potentially be explained by regulatory activity. The response of extra-hypothalamic clusters followed a different time course and its spatial pattern resembled that of the default-mode network.

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.

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).Conventional magnetic resonance imaging (MRI) including TThe lesions of both MELAS and AIS showed high signal intensity on TThe whole-brain 3D pCASL technique might be useful in differentiating MELAS from AIS.3 J. Magn. Reson. Imaging 2017;45:199-206.

To develop a free-breathing multidelay pseudocontinuous arterial spin labeling (pCASL) technique for quantitative measurement of liver perfusion of the hepatic artery and portal vein, respectively.A navigator-gated pCASL sequence with balanced steady-state free precession (bSSFP) readout was developed and applied on five healthy young volunteers at 3T. Two labeling schemes were performed with the labeling plane applied on the descending aorta above the liver, and perpendicular to the portal vein before its entry to liver to label the hepatic artery and portal vein, respectively. For each labeling scheme, pCASL scans were performed at five or six postlabeling delays between 200 and 2000 msec or 2500 msec with an interval of 400 or 500 msec. Multidelay pCASL images were processed offline with nonrigid motion correction, outlier removal, and fitted for estimation of liver perfusion and transit time.Estimated liver perfusion of the hepatic artery and hepatic portal vein were 21.8 ± 1.9 and 95.1 ± 8.9 mL/100g/min, with the corresponding transit time of 1227.3 ± 355.5 and 667.2 ± 85.0 msec, respectively. The estimated liver perfusion and transit time without motion correction were less reliable with greater residual variance compared to those processed with motion correction (P0.05).The liver perfusion measurement using multidelay pCASL showed good correspondence with values noted in the literature. The capability to noninvasively and selectively label the hepatic artery and portal vein is a unique strength of pCASL as compared to other liver perfusion imaging techniques, such as computed tomography perfusion and dynamic contrast-enhanced MRI.

Obstructive sleep apnea (OSA) subjects show brain injury in sites that control autonomic, cognitive, and mood functions that are deficient in the condition. The processes contributing to injury may include altered blood-brain barrier (BBB) actions. Our aim was to examine BBB function, based on diffusion-weighted pseudo-continuous arterial spin labeling (DW-pCASL) procedures, in OSA compared to controls.We performed DW-pCASL imaging in nine OSA and nine controls on a 3.0-Tesla MRI scanner. Global mean gray and white matter arterial transient time (ATT, an index of large artery integrity), water exchange rate across the BBB (Kw, BBB function), DW-pCASL ratio, and cerebral blood flow (CBF) values were compared between OSA and control subjects.Global mean gray and white matter ATT (OSA vs. controls; gray matter, 1.691 ± .120 vs. 1.658 ± .109 second, P = .49; white matter, 1.700 ± .115 vs. 1.650 ± .114 second, P = .44), and CBF values (gray matter, 57.4 ± 15.8 vs. 58.2 ± 10.7 ml/100 g/min, P = .67; white matter, 24.2 ± 7.0 vs. 24.6 ± 6.7 ml/100 g/min, P = .91) did not differ significantly, but global gray and white matter Kw (gray matter, 158.0 ± 28.9 vs. 220.8 ± 40.6 min(-1) , P = .002; white matter, 177.5 ± 57.2 vs. 261.1 ± 51.0 min(-1) , P = .006), and DW-pCASL ratio (gray matter, .727 ± .076 vs. .823 ± .069, P = .011; white matter, .722 ± .144 vs. .888 ± .100, P = .004) values were significantly reduced in OSA over controls.OSA subjects show compromised BBB function, but intact large artery integrity. The BBB alterations may introduce neural damage contributing to abnormal functions in OSA, and suggest a need to repair BBB function with strategies commonly used in other fields.

Although much attention has recently been focused on single-subject functional networks, using methods such as resting-state functional MRI, methods for constructing single-subject structural networks are in their infancy. Single-subject cortical networks aim to describe the self-similarity across the cortical structure, possibly signifying convergent developmental pathways. Previous methods for constructing single-subject cortical networks have used patch-based correlations and distance metrics based on curvature and thickness. We present here a method for constructing similarity-based cortical structural networks that utilizes a rotation-invariant representation of structure. The resulting graph metrics are closely linked to age and indicate an increasing degree of closeness throughout development in nearly all brain regions, perhaps corresponding to a more regular structure as the brain matures. The derived graph metrics demonstrate a four-fold increase in power for detecting age as compared to cortical thickness. This proof of concept study indicates that the proposed metric may be useful in identifying biologically relevant cortical patterns.

Reduced speed of cerebral information processing is a cognitive deficit associated with schizophrenia. Normal information processing speed (PS) requires intact white matter (WM) physiology to support information transfer. In a cohort of 107 subjects (47/60 patients/controls), we demonstrate that PS deficits in schizophrenia patients are explained by reduced WM integrity, which is measured using diffusion tensor imaging, mediated by the mismatch in WM/gray matter blood perfusion, and measured using arterial spin labeling. Our findings are specific to PS, and testing this hypothesis for patient-control differences in working memory produces no explanation. We demonstrate that PS deficits in schizophrenia can be explained by neurophysiological alterations in cerebral WM. Whether the disproportionately low WM integrity in schizophrenia is due to illness or secondary due to this disorder deserves further examination.

To explore the feasibility of 2D and 3D golden-angle radial acquisition strategies in conjunction with k-space weighted image contrast (KWIC) temporal filtering to achieve noncontrast enhanced dynamic MRA (dMRA) with high spatial resolution, low streaking artifacts and high temporal fidelity.Simulations and in vivo examinations in eight normal volunteers and an arteriovenous malformation patient were carried out. Both 2D and 3D golden angle radial sequences, preceded by spin tagging, were used for dMRA of the brain. The radial dMRA data were temporally filtered using the KWIC strategy and compared with matched standard Cartesian techniques.The 2D and 3D dynamic MRA image series acquired with the proposed radial techniques demonstrated excellent image quality without discernible temporal blurring compared with standard Cartesian based approaches. The image quality of radial dMRA was equivalent to or higher than that of Cartesian dMRA by visual inspection. A reduction factor of up to 10 and 3 in scan time was achieved for 2D and 3D radial dMRA compared with the Cartesian-based counterparts.The proposed 2D and 3D radial dMRA techniques demonstrated image quality comparable or even superior to those obtained with standard Cartesian methods, but within a fraction of the scan time.

The goal of this study was to introduce a new noncontrast enhanced 4D dynamic MR angiography (dMRA) technique termed multibolus TrueFISP-based spin tagging with alternating radiofrequency (TrueSTAR).Multibolus TrueFISP-based spin tagging with alternating radiofrequency was developed by taking advantage of the phenomenon that the steady-state signal of TrueFISP is minimally disturbed by periodically inserted magnetization preparations (e.g., spin tagging) that are sandwiched by two α/2 RF pulses. Both theoretical analysis and experimental studies were carried out to optimize the proposed method which was compared with both pulsed and pseudo-continuous arterial spin labeling-based dMRA in healthy volunteers. Optimized multibolus dMRA was also applied in a patient with arteriovenous malformation to demonstrate its potential clinical utility.Multibolus dMRA offered a prolonged tagging bolus compared to the standard single-bolus dMRA, and allowed improved visualization of the draining veins in the arteriovenous malformation patient. Compared to pseudo-continuous arterial spin labeling-based dMRA, multibolus dMRA provided visualization of the full passage of the labeled blood with the flexibility for both static and dynamic magnetic resonance angiography.By combining the benefits of pulsed and pseudo-continuous arterial spin labeling-based dMRA, multibolus TrueFISP-based spin tagging with alternating radiofrequency can prolong and enhance the tagging bolus without sacrificing imaging speed or temporal resolution.

This study aimed to quantitatively investigate two main magnetization transfer effects at low B1: the nuclear Overhauser enhancement (NOE) and amide proton transfer in the human brain at 7 T.The magnetization transfer effects in the human brain were characterized using a four-pool proton model, which consisted of bulk water, macromolecules, an amide group of mobile proteins and peptides, and NOE-related protons resonating upfield. The pool sizes, exchange rates, and relaxation times of these proton pools were investigated quantitatively by fitting, and the net signals of amide proton transfer and NOE were simulated based on the fitted parameters.The results showed that the four-pool model fitted the experimental data quite well, and the NOE effects in human brain at 7 T had a broad spectrum distribution. The NOE effects peaked at a B1 of ∼ 1-1.4 μT and were significantly stronger in the white matter than in the gray matter, corresponding to a pool-size ratio ∼ 2:1. As the amide proton transfer effect was relatively small compared with the NOE effects, magnetization transfer asymmetry analysis yielded an NOE-dominated contrast in the healthy human brain in this range of B1.These findings are important to identify the source of NOE effects and to quantify amide proton transfer effects in human brain at 7 T.

Information on renal perfusion is essential for the diagnosis and prognosis of kidney function. Quantification using gadolinium chelates is limited as a result of filtration through renal glomeruli and safety concerns in patients with kidney dysfunction. Arterial spin labeling MRI is a noninvasive technique for perfusion quantification that has been applied to humans and animals. However, because of the low sensitivity and vulnerability to motion and susceptibility artifacts, its application to mice has been challenging. In this article, mouse renal perfusion was studied using flow-sensitive alternating inversion recovery at 7 T. Good perfusion image quality was obtained with spin-echo echo-planar imaging after controlling for respiratory, susceptibility and fat artifacts by triggering, high-order shimming and water excitation, respectively. High perfusion was obtained in the renal cortex relative to the medulla, and signal was absent in scans carried out post mortem. Cortical perfusion increased from 397 ± 36 (mean ± standard deviation) to 476 ± 73 mL/100 g/min after switching from 100% oxygen to carbogen with 95% oxygen and 5% carbon dioxide. The perfusion in the medulla was 2.5 times lower than that in the cortex and changed from 166 ± 41 mL/100 g/min under oxygen to 203 ± 40 mL/100 g/min under carbogen. T1 decreased in both the cortex (from 1570 ± 164 to 1377 ± 72 ms, p 0.05) and medulla (from 1788 ± 107 to 1573 ± 144 ms, p 0.05) under carbogen relative to 100% oxygen. The results showed the potential of the use of ASL for perfusion quantification in mice and in models of renal diseases.