Arterial Spin Labeling Signal Research Articles

The Differentiation between Progressive Disease and Treatment-Induced Effects with Perfusion-Weighted Arterial Spin-Labeling in High-Grade Gliomas.

Treatment-induced effects are difficult to differentiate from progressive disease in radiologically progressing diffuse gliomas after treatment. This retrospective, single-center cohort study investigated the diagnostic value of arterial spin-labeling perfusion in differentiating progressive disease from treatment-induced effects in irradiated patients with a high-grade glioma. Adults with a high-grade glioma diagnosed between January 1, 2012, and December 31, 2018, with a new or increasing contrast-enhancing lesion after radiotherapy with or without chemotherapy and arterial spin-labeling were consecutively included. Arterial spin-labeling is part of the routine follow-up examinations of patients with a high-grade glioma. The outcomes of progressive disease or treatment-induced effects were defined after histologic or >6 weeks radiologic follow-up. Two neuroradiologists graded the arterial spin-labeling visually as negative (hypointense to gray matter) or positive (iso-/hyperintense). Additionally, the arterial spin-labeling signal intensity in the enhancing lesion was compared quantitatively with that in the contralateral normal brain. Diagnostic test properties and the Cohen κ inter- and intrarater reliability were determined. We present data according to the time after radiation therapy. We included 141 patients with 173 lesions (median age, 63 years). Ninety-four (54%) lesions showed treatment-induced effects, and 79 (46%), progressive disease. For visual analysis, the ORs of an arterial spin-labeling positive for progressive disease in the group with progression within 3, between 3 and 6, and after 6 months after radiation therapy were 0.65 (95% CI, 0.28-1.51; P = .319), 3.5 (95% CI, 0.69-17.89; P = .132), and 6.8 (95% CI, 1.48-32; P = .014). The areas under the curve were 0.456, 0.652, and 0.719. In quantitative analysis, the areas under the curve were 0.520, 0.588, and 0.587 in these groups. Inter- and intrarater reliability coefficients were 0.67 and 0.62. Arterial spin-labeling performed poorly in differentiating progressive disease from treatment-induced effects in high-grade gliomas within 6 months after radiation therapy, with fair performance after this period. Arterial spin-labeling may need to be combined with other imaging features and clinical information for better performance.

Comparison between supervised and physics-informed unsupervised deep neural networks for estimating cerebral perfusion using multi-delay arterial spin labeling MRI.

This study aimed to implement a physics-informed unsupervised deep neural network (DNN) to estimate cerebral blood flow (CBF) and arterial transit time (ATT) from multi-delay arterial spin labeling (ASL), and compare its performance with that of a supervised DNN and the conventional method. Supervised and unsupervised DNNs were trained using simulation data. The accuracy and noise immunity of the three methods were compared using simulations and in vivo data. The simulation study investigated the differences between the predicted and ground-truth values and their variations with the noise level. The in vivo study evaluated the predicted values from the original images and noise-induced variations in the predicted values from the synthesized noisy images by adding Rician noise to the original images. The simulation study showed that CBF estimated using the supervised DNN was not biased by noise, whereas that estimated using other methods had a positive bias. Although the ATT with all methods exhibited a similar behavior with noise increase, the ATT with the supervised DNN was less biased. The in vivo study showed that CBF and ATT with the supervised DNN were the most accurate and that the supervised and unsupervised DNNs had the highest noise immunity in CBF and ATT estimations, respectively. Physics-informed unsupervised learning can estimate CBF and ATT from multi-delay ASL signals, and its performance is superior to that of the conventional method. Although noise immunity in ATT estimation was superior with unsupervised learning, other performances were superior with supervised learning.

Optimizing background suppression for dual-module velocity-selective arterial spin labeling: Without using additional background-suppression pulses.

Background suppression (BS) is recommended in arterial spin labeling (ASL) for improved SNR but is difficult to optimize in existing velocity-selective ASL (VSASL) methods. Dual-module VSASL (dm-VSASL) enables delay-insensitive, robust, and SNR-efficient perfusion imaging, while allowing efficient BS, but its optimization has yet to be thoroughly investigated. The inversion effects of the velocity-selective labeling pulses, such as velocity-selective inversion (VSI), can be used for BS, and were modeled for optimizing BS in dm-VSASL. In vivo experiments using dual-module VSI (dm-VSI) were performed to compare two BS strategies: a conventional one with additional BS pulses and a new one without any BS pulse. Their BS performance, temporal noise, and temporal SNR were examined and compared, with pulsed and pseudo-continuous ASL (PASL and PCASL) as the reference. The in vivo experiments validated the BS modeling. Strong positive linear correlations (r > 0.82, p < 0.0001) between the temporal noise and the tissue signal were found in PASL/PCASL and dm-VSI. Optimal BS can be achieved with and without additional BS pulses in dm-VSI; the latter improved the ASL signals by 8.5% in gray matter (p = 0.006) and 12.2% in white matter (p = 0.014) and tended to provide better temporal SNR. The dm-VSI measured significantly higher ASL signal (p < 0.016) and temporal SNR (p < 0.018) than PASL and PCASL. Complex reconstruction was found necessary with aggressive BS. Guided by modeling, optimal BS can be achieved without any BS pulse in dm-VSASL, further improving the ASL signal and the SNR performance.

Deeply Accelerated Arterial Spin Labeling Perfusion MRI for Measuring Cerebral Blood Flow and Arterial Transit Time.

Cerebral blood flow (CBF) indicates both vascular integrity and brain function. Regional CBF can be non-invasively measured with arterial spin labeling (ASL) perfusion MRI. By repeating the same ASL MRI sequence several times, each with a different post-labeling delay (PLD), another important neurovascular index, the arterial transit time (ATT) can be estimated by fitting the acquired ASL signal to a kinetic model. This process however faces two challenges: one is the multiplicatively prolonged scan time, making it impractically for clinical use due to the escalated risk of motions; the other is the reduced signal-to-noise-ratio (SNR) in the long PLD scans due to the T1 decay of the labeled spins. Increasing SNR needs more repetitions which will further increase the total scan time. Currently, there lacks a way to accurately estimate ATT from a parsimonious number of PLDs. In this paper, we proposed a deep learning-based algorithm to reduce the number of PLDs and to accurately estimate ATT and CBF. Two separate deep networks were trained: one is designed to estimate CBF and ATT from ASL data with a single PLD; the other is to estimate CBF and ATT from ASL data with two PLDs. The models were trained and tested using the large Human Connectome Project multiple-PLD ASL MRI. Performance of the DL-based approach was compared to the traditional full dataset-based data fitting approach. Our results showed that ATT and CBF can be reliably estimated using deep networks even with one PLD.

Effects of the Training Data Condition on Arterial Spin Labeling Parameter Estimation Using a Simulation-Based Supervised Deep Neural Network.

A simulation-based supervised deep neural network (DNN) can accurately estimate cerebral blood flow (CBF) and arterial transit time (ATT) from multidelay arterial spin labeling signals. However, the performance of deep learning depends on the characteristics of the training data set. We aimed to investigate the effects of the ground truth (GT) ranges of CBF and ATT on the performance of the DNN when training data were prepared using arterial spin labeling signal simulation. Deep neural networks were individually trained using 36 patterns of the training data sets. Simulation test data (1,000,000 points), 17 healthy volunteers, and 1 patient with moyamoya disease were included. The simulation test data were used to evaluate accuracy, precision, and noise immunity of the DNN. The best-performing DNN was determined by the normalized mean absolute error (NMAE), normalized root mean squared error (NRMSE), and normalized coefficient of variation over repeated training (CV Net ). Cerebral blood flow and ATT values and their histograms were compared between the GT and predicted values. For the in vivo data, the dependency of the predicted values on the GT ranges was visually evaluated by comparing CBF and ATT maps between the best-performing DNN and the other DNNs. Moreover, using the synthesized noisy images, noise immunity was compared between the best-performing DNN based on the simulation study and a conventional method. The simulation study showed that a network trained by the GT of CBF and ATT in the ranges of 0 to 120 mL/100 g/min and 0 to 4500 milliseconds, respectively, had the highest performance (NMAE CBF , 0.150; NRMSE CBF , 0.231; CV NET CBF , 0.028; NMAE ATT , 0.158; NRMSE ATT , 0.257; and CV NET ATT , 0.028). Although the predicted CBF and ATT varied with the GT range of the training data sets, the appropriate settings preserved the accuracy, precision, and noise immunity of the DNN. In addition, the same results were observed in in vivo studies. The GT ranges to prepare the training data affected the performance of the simulation-based supervised DNNs. The predicted CBF and ATT values depended on the GT range; inappropriate settings degraded the accuracy, whereas appropriate settings of the GT range provided accurate and precise estimates.

Arterial spin labeling MRI using spiral acquisitions and concurrent field monitoring

Perfusion MRI based on arterial spin labeling (ASL) has intrinsically very low signal-to-noise ratio (SNR). Signal acquisition at shorter echo times (TE) is necessary to boost the SNR of the ASL images. Spiral trajectories provide substantially shorter TE yielding increased SNR and are among the fastest k-space sampling schemes to encode a given field of view and resolution. Moreover, they provide approximately isotropic point-spread functions and inherent refocusing of motion- and flow-induced phase errors. However, the efficiency of the spiral acquisitions in ASL-MRI has been limited because these advantages are counterbalanced by practical technical challenges. This is because spiral acquisitions are highly sensitive to encoding deficiencies such as static off-resonance in the main magnetic field manifested as blurring artifacts in the image. Moreover, deviation of the gradient fields from the nominal waveforms due to the imperfection of the employed hardware critically limits the practical utilization of spiral trajectories. In this work, I provide single- and multiple-shot spiral ASL images that are robust against typical spiral encoding drawbacks enabled by deploying a comprehensive signal model involving static off-resonance and coil sensitivity maps and actual B0 and gradient field dynamics up to third order in space. The spiral ASL signal acquisition was concurrently monitored using a 3rd order dynamic field camera based on NMR field probes. The reconstructed ASL images at 3 mm and 2 mm in-plane resolution associating with the monitored field dynamics and the static off-resonances exhibited strongly reduced blurring- and aliasing artifacts and distortion. Concurrent field monitoring also enables to account for quasi-static B0 drifts by encompassing the parametric input data with consistent encoding geometry and physiological field fluctuations. In conclusion, concurrent field monitoring in spiral ASL acquisition largely overcomes traditional vulnerability of spiral trajectories in practice providing high quality ASL images with increased SNR, speed and motion robustness.

Arterial Spin-Labeling MR Imaging for the Differential Diagnosis of Venous-Predominant AVMs and Developmental Venous Anomalies.

Venous-predominant AVMs are almost identical in appearance to developmental venous anomalies on conventional MR imaging. Herein, we compared and analyzed arterial spin-labeling findings in patients with developmental venous anomalies or venous-predominant AVMs, using DSA as the criterion standard. We retrospectively collected patients with either DVAs or venous-predominant AVMs, each available on both DSA and arterial spin-labeling images. Arterial spin-labeling imaging was visually assessed for the presence of hyperintense signal. CBF measured at the most representative section was normalized to the contralateral gray matter. The temporal phase of developmental venous anomalies or venous-predominant AVMs was measured on DSA as a delay between the first appearance of the intracranial artery and the lesion. Correlation between the normalized CBF and the temporal phase was evaluated. Analysis of 15 lesions (13 patients) resulted in categorization into 3 groups: typical venous-predominant AVMs (temporal phase, <2 seconds), intermediate group (temporal phase between 2.5 and 5 seconds), and classic developmental venous anomalies (temporal phase, >10 seconds). Arterial spin-labeling signal was markedly increased in the typical venous-predominant AVM group, while there was no discernible signal in the classic developmental venous anomaly group. In the intermediate group, however, 3 of 6 lesions showed mildly increased arterial spin-labeling signal. The normalized CBF on arterial spin-labeling and the temporal phase on DSA were moderately negatively correlated: r(13) = 0.66, P = .008. Arterial spin-labeling may predict the presence and amount of arteriovenous shunting in venous-predominant AVMs, and using arterial spin-labeling enables confirmation of typical venous-predominant AVMs without DSA. However, lesions with an intermediate amount of shunting suggest a spectrum of vascular malformations ranging from purely vein-draining developmental venous anomalies to venous-predominant AVMs with overt arteriovenous shunting.

Cortical high-flow sign on arterial spin labeling: a novel biomarker for IDH-mutation and 1p/19q-codeletion status in diffuse gliomas without intense contrast enhancement.

This study aimed to investigate whether arterial spin labeling (ASL) features allow differentiation of oligodendroglioma, IDH-mutant and 1p/19q-codeleted (IDHm-codel) from diffuse glioma with IDH-wildtype (IDHw) or astrocytoma, IDH-mutant (IDHm-noncodel). Participants comprised 71 adult patients with pathologically confirmed diffuse glioma, classified as IDHw, IDHm-noncodel, or IDHm-codel. Subtraction images were generated from paired-control/label images on ASL and used to assess the presence of a cortical high-flow sign. The cortical high-flow sign was defined as increased ASL signal intensity within the tumor-affecting cerebral cortex compared with normal-appearing cortex. Regions without contrast enhancement on conventional MR imaging were targeted. The frequency of the cortical high-flow sign on ASL was compared among IDHw, IDHm-noncodel, and IDHm-codel. As a result, the frequency of the cortical high-flow sign was significantly higher for IDHm-codel than for IDHw or IDHm-noncodel. In conclusion, the cortical high-flow sign could represent a hallmark of oligodendroglioma, IDH-mutant, and 1p/19q-codeleted without intense contrast enhancement.

Detection of ictal and periictal hyperperfusion with subtraction of ictal-interictal 1.5-Tesla pulsed arterial spin labeling images co-registered to conventional magnetic resonance images (SIACOM).

Our recent report showed that 1.5-T pulsed arterial spin labeling (ASL) magnetic resonance (MR) perfusion imaging (1.5-T Pulsed ASL [PASL]), which is widely available in the field of neuroemergency, is useful for detecting ictal hyperperfusion. However, the visualization of intravascular ASL signals, namely, arterial transit artifact (ATA), is more remarkable than that of 3-T pseudocontinuous ASL and is easily confused with focal hyperperfusion. To eliminate ATA and enhance the detectability of (peri) ictal hyperperfusion, we developed the subtraction of ictal-interictal 1.5-T PASL images co-registered to conventional MR images (SIACOM). We retrospectively analyzed the SIACOM findings in four patients who underwent ASL during both (peri) ictal and interictal states and examined the detectability for (peri) ictal hyperperfusion. In all patients, the ATA of the major arteries was almost eliminated from the subtraction image of the ictal-interictal ASL. In patients 1 and 2 with focal epilepsy, SIACOM revealed a tight anatomical relationship between the epileptogenic lesion and the hyperperfusion area compared with the original ASL image. In patient 3 with situation-related seizures, SIACOM detected minute hyperperfusion at the site coinciding with the abnormal electroencephalogram area. SIACOM of patient 4 with generalized epilepsy diagnosed ATA of the right middle cerebral artery, which was initially thought to be focal hyperperfusion on the original ASL image. Although it is necessary to examine several patients, SIACOM can eliminate most of the depiction of ATA and clearly demonstrate the pathophysiology of each epileptic seizure.

Abstract TMP66: Correlation Of Cerebrovascular Reserve Assessed By Acetazolamide-stress Spect With Collaterals On Arterial Spin-labeling MRI In Patients With Carotid Occlusive Disease

Introduction: We investigated the relationship between the level of cerebral collateral circulation on arterial spin-labeling (ASL) magnetic resonance imaging (MRI) and cerebrovascular reserve (CVR) on acetazolamide (ACZ)-stress single photon emission computed tomography (SPECT) brain scans in internal carotid artery (ICA) stenosis. Methods: This study enrolled 129 patients with severe ICA stenosis (&gt;70%). Collateral circulation was assessed in pulsed ASL images based on the presence of arterial transit artifact (ATA) that late-arriving flow appears as serpiginous high ASL signal within cortical vessels. CVR based on rest-SPECT and ACZ-stress SPECT with Tc-99m-ECD was calculated. The ASL CBF maps were independently assessed by two neuroradiologists blinded to clinical information. The two neuroradiologists graded on two slices of ASL images corresponding to Alberta Stroke Program Early Computed Tomography Score (ASPECTS) location using a 4-point scale for ASL intensity. Results: With ACZ-stress SPECT, the 88/129 (68%) patients showed normal CVR and 41/129 (32%) patients showed decreased CVR. In 73/88 (82%) of the normal CVR group patients, ASL showed ATA in ipsilateral to the stenosis. In 19/41 (46%) of the decreased CVR group patients, ASL showed no evidence of ATA in ipsilateral to the stenosis. Significant positive relationship was observed between the normal CVR group and the ATA showing group in ICA stenosis patients (p = 0.001, chi-square test). The ASL-based ASPECTS scores of brain in the ipsilateral side was lower than the scores in the contralateral side to the ICA stenosis (p &lt; 0.0001, Wilcoxon signed rank test). The ASL-based ASPECTS scores of brain ipsilateral side to the ICA stenosis was lower in the reduced CVR group than normal CVR group (p = 0.005). Conclusion: This study demonstrated the statistically significant positive correlation between good collaterals on ASL MRI and intact CVR in patients with ICA stenosis.

Evidence of cerebral hypoperfusion consecutive to ultrasound-mediated blood-brain barrier opening in rats.

This work aims to explore the effect of Blood Brain Barrier (BBB) opening using ultrasound combined with microbubbles injection on cerebral blood flow in rats. Two groups of n = 5 rats were included in this study. The first group was used to investigate the impact of BBB opening on the Arterial Spin Labeling (ASL) signal, in particular on the arterial transit time (ATT). The second group was used to analyze the spatiotemporal evolution of the change in cerebral blood flow (CBF) over time following BBB opening and validate these results using DSC-MRI. Using pCASL, a decrease in CBF of up to was observed in the target hemisphere, associated with an increase in arterial transit time. The latter was estimated to be in the BBB opening impacted regions against in the contralateral hemisphere. The spatio-temporal analysis of CBF maps indicated a nonlocal hypoperfusion. DSC-MRI measurements were consistent with the obtained results. This study provided strong evidence that BBB opening using microbubble intravenous injection induces a transient hypoperfusion. A spatiotemporal analysis of the hypoperfusion changes allows to establish some points of similarity with the cortical spreading depression phenomenon.

Non-contrast assessment of blood-brain barrier permeability to water in mice: An arterial spin labeling study at cerebral veins

Blood-brain barrier (BBB) plays a critical role in protecting the brain from toxins and pathogens. However, in vivo tools to assess BBB permeability are scarce and often require the use of exogenous contrast agents. In this study, we aimed to develop a non-contrast arterial-spin-labeling (ASL) based MRI technique to estimate BBB permeability to water in mice. By determining the relative fraction of labeled water spins that were exchanged into the brain tissue as opposed to those that remained in the cerebral veins, we estimated indices of global BBB permeability to water including water extraction fraction (E) and permeability surface-area product (PS). First, using multiple post-labeling delay ASL experiments, we estimated the bolus arrival time (BAT) of the labeled spins to reach the great vein of Galen (VG) to be 691.2 ± 14.5 ms (N = 5). Next, we investigated the dependence of the VG ASL signal on labeling duration and identified an optimal imaging protocol with a labeling duration of 1200 ms and a PLD of 100 ms. Quantitative E and PS values in wild-type mice were found to be 59.9 ± 3.2% and 260.9 ± 18.9 ml/100 g/min, respectively. In contrast, mice with Huntington's disease (HD) revealed a significantly higher E (69.7 ± 2.4%, P = 0.026) and PS (318.1 ± 17.1 ml/100 g/min, P = 0.040), suggesting BBB breakdown in this mouse model. Reproducibility studies revealed a coefficient-of-variation (CoV) of 4.9 ± 1.7% and 6.1 ± 1.2% for E and PS, respectively. The proposed method may open new avenues for preclinical research on pathophysiological mechanisms of brain diseases and therapeutic trials in animal models.

Comparison between 1.5-Tesla pseudocontinuous and pulsed arterial spin labeling in visualizing peri-ictal hyperperfusion: A case report

Arterial spin labeling (ASL) imaging with multiple postlabeling delays (PLD) can demonstrate the hemodynamics of peri-ictal hyperperfusion. Labeling methods include pulsed ASL (PASL) and pseudocontinuous ASL (pCASL). Although PASL is more widely used in daily clinical practice, it has several disadvantages because of lower delivery of labeled magnetization. We compared pCASL and PASL images acquired after a 24-h interval, using a 1.5-Tesla machine, in a 62-year-old man with non-convulsive status epilepticus. The pCASL during electrographic status epilepticus clearly demonstrated that ASL signals in the grey matter of the right hemisphere, particularly in the posteromedial part of the right temporal lobe, increased at PLDs of 1.5 s and 1.75 s and were almost washed out at 2.0 s. Although PASL, which was obtained during the ictal-interictal continuum when there were no changes in ictal findings on diffusion-weighted images, showed a similar trend, the increased signals were less pronounced than those of pCASL, with more contamination of arte-rial transit artifact in the subarachnoid space. Although the electroencephalographic findings were not the same when both ASLs were performed, the present study confirms that PASL is somewhat inferior to pCASL in detecting peri-ictal hyperperfusion because of the greater effect of arterial transient artifacts.

Arterial spin labeling signal in the CSF: Implications for partial volume correction and blood-CSF barrier characterization.

For better quantification of perfusion with arterial spin labeling (ASL), partial volume correction (PVC) is used to disentangle the signals from gray matter (GM) and white matter within any voxel. Based on physiological considerations, PVC algorithms typically assume zero signal in the cerebrospinal fluid (CSF). Recent measurements, however, have shown that CSF-ASL signal can exceed 10% of GM signal, even when using recommended ASL labeling parameters. CSF signal is expected to particularly affect PVC results in the choroid plexus. This study aims to measure the impact of CSF signal on PVC perfusion measurements, and to investigate the potential use of PVC to retrieve pure CSF-ASL signal for blood-CSF barrier characterization. In vivo imaging included six pCASL sequences with variable label duration and post-labeling delay (PLD), and an eight-echo 3D-GRASE readout. A dataset was simulated to estimate the effect of CSF-PVC with known ground-truth parameters. Differences between the results of CSF-PVC and non-CSF-PVC were estimated for regions of interest (ROIs) based on GM probability, and a separate ROI isolating the choroid plexus. In vivo, the suitability of PVC-CSF signal as an estimate of pure CSF was investigated by comparing its time course with the long-TE CSF signal. Results from both simulation and in vivo data indicated that including the CSF signal in PVC improves quantification of GM CBF by approximately 10%. In simulated data, this improvement was greater for multi-PLD (model fitting) quantification than for single PLD (~1-5% difference). In the choroid plexus, the difference between CSF-PVC and non-CSF-PVC was much larger, averaging around 30%. Long-TE (pure) CSF signal could not be estimated from PVC CSF signal as it followed a different time course, indicating the presence of residual macrovascular signal in the PVC. The inclusion of CSF adds value to PVC for more accurate measurements of GM perfusion, and especially for quantification of perfusion in the choroid plexus and study of the glymphatic system.

Time-encoded pseudo-continuous arterial spin labeling: Increasing SNR in ASL dynamic angiography.

Dynamic angiography using arterial spin labeling (ASL) can provide detailed hemodynamic information. However, the long time-resolved readouts require small flip angles to preserve ASL signal for later timepoints, limiting SNR. By using time-encoded ASL to generate temporal information, the readout can be shortened. Here, the SNR improvements from using larger flip angles, made possible by the shorter readout, are quantitatively investigated. The SNR of a conventional protocol with nine Look-Locker readouts and a 4 3 time-encoded protocol with three Look-Locker readouts (giving nine matched timepoints) were compared using simulations and in vivo data. Both protocols were compared using readouts with constant flip angles (CFAs) and variable flip angles (VFAs), where the VFA scheme was designed to produce a consistent ASL signal across readouts. Optimization of the background suppression to minimize physiological noise across readouts was also explored. The time-encoded protocol increased in vivo SNR by 103% and 96% when using CFAs or VFAs, respectively. Use of VFAs improved SNR compared with CFAs by 25% and 21% for the conventional and time-encoded protocols, respectively. The VFA scheme also removed signal discontinuities in the time-encoded data. Preliminary data suggest that optimizing the background suppression could improve in vivo SNR by a further 16%. Time encoding can be used to generate additional temporal information in ASL angiography. This enables the use of larger flip angles, which can double the SNR compared with a non-time-encoded protocol. The shortened time-encoded readout can also lead to improved background suppression, reducing physiological noise and further improving SNR.

Arterial Spin Labeling Imaging Characteristics of Anti-leucine-rich Glioma-Inactivated 1 Encephalitis: A Qualitative and Quantitative Analysis.

Background and SignificanceAutoimmune encephalitis (AE) is a rare group of diseases that can present with stroke-like symptoms. Anti-leucine-rich glioma inactivated 1 (LGI1) encephalitis is an AE subtype that is infrequently associated with neoplasms and highly responsive to prompt immunotherapy treatment. Therefore, accurate diagnosis of LGI1 AE is essential in timely patient management. Neuroimaging plays a critical role in evaluating stroke and stroke mimics such as AE. Arterial Spin Labeling (ASL) is an MRI perfusion modality that measures cerebral blood flow (CBF) and is increasingly used in everyday clinical practice for stroke and stroke mimic assessment as a non-contrast sequence. Our goal in this preliminary study is to demonstrate the added value of ASL in detecting LGI1 AE for prompt diagnosis and treatment.MethodsIn this retrospective single center study, we identified six patients with seropositive LGI1 AE who underwent baseline MRI with single delay 3D pseudocontinuous ASL (pCASL), including five males and one female between ages 28 and 76 years, with mean age of 55 years. Two neuroradiologists qualitatively interpreted the ASL images by visual inspection of CBF using a two-point scale (increased, decreased) when compared to both the ipsilateral and contralateral unaffected temporal and non-temporal cortex. The primary measures on baseline ASL evaluation were a) presence of ASL signal abnormality, b) if present, signal characterization based on the two-point scale, c) territorial vascular distribution, d) localization, and e) laterality. Quantitative assessment was also performed on postprocessed pCASL cerebral blood flow (CBF) maps. The obtained CBF values were then compared between the affected temporal cortex and each of the unaffected ipsilateral parietal, contralateral temporal, and contralateral parietal cortices.ResultsOn consensus qualitative assessment, all six patients demonstrated ASL hyperperfusion and corresponding FLAIR hyperintensity in the hippocampus and/or amygdala in a non-territorial distribution (6/6, 100%). The ASL hyperperfusion was found in the right hippocampus or amygdala in 5/6 (83%) of cases. Four of the six patients underwent initial follow-up imaging where all four showed resolution of the initial ASL hyperperfusion. In the same study on structural imaging, all four patients were also diagnosed with mesial temporal sclerosis (MTS). Quantitative assessment was separately performed and demonstrated markedly increased CBF values in the affected temporal cortex (mean, 111.2 ml/min/100 g) compared to the unaffected ipsilateral parietal cortex (mean, 49 ml/min/100 g), contralateral temporal cortex (mean, 58.2 ml/min/100 g), and contralateral parietal cortex (mean, 52.2 ml/min/100 g).DiscussionIn this preliminary study of six patients, we demonstrate an ASL hyperperfusion pattern, with a possible predilection for the right mesial temporal lobe on both qualitative and quantitative assessments in patients with seropositive LGI1. Larger scale studies are necessary to further characterize the strength of these associations.

Assessment of functional shunting in patients with sickle cell disease.

Silent cerebral infarcts (SCI) are common in patients with sickle cell disease (SCD) and are thought to be caused by a mismatch between oxygen delivery and consumption. Functional cerebrovascular shunting is defined as reduced oxygen offloading due to the rapid transit of blood through the capillaries caused by increased flow and has been suggested as a potential mechanism underlying reduced oxygenation and SCI. We investigated the venous arterial spin labeling signal (VS) in the sagittal sinus as a proxy biomarker of cerebral functional shunting, and its association with hemodynamic imaging and hematological laboratory parameters. We included 28 children and 38 adults with SCD, and ten healthy racematched adult controls. VS, cerebral blood flow (CBF), velocity in the brain feeding arteries, oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) were measured before and after acetazolamide administration. VS was higher in patients with SCD compared to controls (P<0.01) and was increased after acetazolamide administration in all groups (P<0.01). VS was primarily predicted by CBF (P<0.01), but CBF-corrected VS was also associated with decreased CMRO2 (P<0.01). Additionally, higher disease severity defined by low hemoglobin and increased hemolysis was associated with higher CBF-corrected VS. Finally, CMRO2 was negatively correlated with fetal hemoglobin, and positively correlated with lactate dehydrogenase, which could be explained by changes in oxygen affinity. These findings provide evidence for cerebral functional shunting and encourage future studies investigating the potential link to aberrant capillary exchange in SCD.

Saturated multi‐delay renal arterial spin labeling technique for simultaneous perfusion and T1 quantification in kidneys

To propose a free-breathing simultaneous multi-delay arterial spin labeling (ASL) and T1 mapping technique with a stepwise kinetic model for renal assessment in a single 4-min scan at 3T. The proposed saturated multi-delay renal arterial spin labeling (SAMURAI) sequence used flow-sensitive alternating inversion recovery (FAIR) preparation, followed by acquisition of 9 images with Look-Locker spoiled gradient recalled echo (SPGR). Pre-saturation at the imaging slice was used to achieve saturation-based T1 mapping. A 4-step 2-compartment kinetic model was proposed to characterize water transition through artery- and tissue-compartment. The impact of the Look-Locker sampling scheme on the ASL signal was corrected in this model. T1 estimation with dictionary searching method and perfusion quantification based on the proposed kinetic model fitting were conducted after groupwise registration of the acquired images. The feasibility and repeatability of SAMURAI were validated in healthy subjects (n=11) and patients with different renal diseases (n=4). The proposed SAMURAI technique can provide accurate T1 map with strong correlation (R2 =0.98) with inversion recovery spin echo (IR-SE) on phantom. SAMURAI provided equally reliable whole kidney and cortical ASL and T1 quantification results compared with multi-TI FAIR (intraclass correlation coefficient [ICC], 0.880-0.958) and IR-SPGR (ICC, 0.875-0.912), respectively. Low renal blood flow and increased T1 were detected by SAMURAI in the affected kidneys of the patients. SAMURAI had excellent scan-rescan repeatability (ICC, 0.905-0.992) and significantly reduced scan time (4 min 6 s vs. 45 min for 9 TIs) compared to multi-TI FAIR. The proposed SAMURAI technique is feasible and repeatable for simultaneously quantifying T1 and perfusion of kidneys with high time-efficiency.

Improvement of Shunt Detection with Arterial Spin-Labeling MR Imaging in Follow-Up of a Treated Cerebral Arteriovenous Malformation

Objective: To identify and evaluate the pitfalls of using arterial spin labeling (ASL) to diagnose cerebral arteriovenous malformation (AVM) and improve its accuracy in clinical practice. Materials and Methods: A retrospective study of 54 patients with cerebral AVM was performed. Each patient underwent magnetic resonance imaging (MRI) studies, including pseudo-continuous ASL (pCASL) and conventional cerebral angiography with a digital subtraction angiography (DSA) during a 3-year period. The consensus of the results of the imaging studies was used to evaluate the diagnostic performance of the MRI technique, with DSA used as the gold standard. Results: Diagnostic accuracy was 94.4% when a positive arteriovenous shunt (AVS) was defined as a high ASL signal in the venous structure or nidus, compared to magnetic resonance angiography (MRA). The misinterpretations of the ASL images of cerebral AVM were due to an arterial transit artifact (ATA) associated with a residual AVS. The other pitfalls were micro-AVMs and very slow-flow AVSs. Conclusion: To improve the accuracy of ASL in evaluating an AVS in cerebral AVM, it is mandatory to detect high ASL signals in venous structures by comparing with MRA. Keywords: Arterial spin labeling; Arteriovenous malformation; Arteriovenous shunt; Magnetic resonance angiography

404 Can MRI Non-Invasively Measure Blood-Brain-Barrier Permeability?

Abstract Aim Blood brain barrier (BBB) integrity in neurological disease is tested with gadolinium-enhanced Magnetic Resonance Imaging (MRI). Pathology studies have shown gadolinium deposits in brains with intact BBBs, thus raising concern. We propose a novel use of Arterial Spin Labelling (ASL) –a MRI technique which ‘tags’ blood-water making it a tracer– as a safer alternative in assessing BBB permeability. ASL’s ability to capture T2 (transverse relaxation time) changes of tagged water in blood vs. in tissue (post-exchange across the BBB) supports its feasibility. Method We developed an ASL protocol and collected data from healthy volunteers (n=5) on a 3T Achieva Scanner with the parameters: echo times (TEs) 30, 40, 50, 60, 70ms; repetition time 4200ms; field of view 240x240x47mm and post label delays (PLDs) 1,000ms and 1,500ms. We calculated mean ASL signal (arb units) from the images at each TE, and then extracted T2(ms) values for each volunteer at each PLD. The primary outcome was the change in T2 across PLDs. Results Calculated mean T2s demonstrated a majority of increasing T2s across longer PLDs (n=3) with mean T2 of 55.3+5.3ms at PLD 1,000ms and 62.1+10.8ms at PLD 1,500ms. However, the results are inconclusive as the sample size precluded statistical testing. Conclusions We developed an ASL protocol that demonstrated changes in T2 of blood water with time passage, indicating water exchange through the BBB. This supports the use of ASL in assessing BBB permeability, but more wide-scale studies need to be performed.