Pseudo-continuous Arterial Spin Labeling Research Articles

Three-dimensional pseudo-continuous arterial spin labeling for evaluation of cerebral hemodynamic changes after revascularization in adult patients with moyamoya disease

To evaluate cerebral hemodynamic changes using three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL) and its association with the changes of neurological symptoms in adult patients with moyamoya disease after revascularization. We prospectively collected the clinical and radiographic data of 40 adult patients with moyamoya disease diagnosed by digital subtraction angiography (DSA) or magnetic resonance angiography (MRA) undergoing unilateral superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. All the patients underwent 3D-pCASL examination before and after the surgery, and were followed up for 3 to 11 months after the operation. The region of interest (ROI) was located in the middle cerebral artery cortical territory covering the surgical side and ipsilateral cerebellar hemisphere. Cerebral blood flow (CBF) and relative CBF (rCBF) values were compared before and after the surgery, and the changes in cerebral hemodynamics were evaluated. The correlations were analyzed between preoperative rCBF and Suzuki stage and between the changes in postoperative neurological symptoms and rCBF. The mean CBF of the patients increased significantly from 53.96±10.04 mL·100 g-1·min-1 to 58.90±13.57 mL·100 g-1·min-1 after the operation (t=-3.068, P=0.004); the mean rCBF also increased significantly after the operation (0.96 ± 0.14 vs 1.15 ± 0.18; t=-7.155, P < 0.001). The changes in postoperative neurological symptoms were significantly correlated with the changes in rCBF (P=0.017) and the type of disease onset (P < 0.001). 3D-pCASL is an valuable means for noninvasive monitoring of hemodynamic changes after revascularization in adult patients with moyamoya disease without the use of contrast agent.

Altered cerebral neurovascular coupling in medication-overuse headache: A study combining multi-modal resting-state fMRI with 3D PCASL.

Structural and functional changes in the brain have been identified in individuals with medication-overuse headache (MOH) using MRI. However, it has not been clearly established whether neurovascular dysfunction occurs in MOH, which could be elucidated by examining neurovascular coupling (NVC) from the viewpoints of neuronal activity and cerebral blood flow. The aim of this study was to investigate potential alterations in NVC function of the brain in individuals with MOH using resting-state functional MRI (rs-fMRI) and 3D pseudo-continuous arterial spin labeling (3D PCASL) imaging techniques. A total of 40 patients with MOH and 32 normal controls (NCs) were recruited, and rs-fMRI and 3D PCASL data were obtained using a 3.0 T MR scanner. Standard preprocessing of the rs-fMRI data was performed to generate images representing regional homogeneity (ReHo), fractional amplitude of low-frequency fluctuation (fALFF), and degree centrality (DC); cerebral blood flow (CBF) images were generated using 3D PCASL sequence data. These functional maps were all normalized into Montreal Neurological Institute (MNI) space, and NVC was subsequently determined on the basis of Pearson correlation coefficients between the rs-fMRI maps (ReHo, fALFF, and DC) and CBF maps. The statistical significance of differences between the MOH and NC groups in terms of NVC in different brain regions was established via Z-test. Further analysis was performed to examine correlations between NVC in the brain regions with NVC dysfunction and clinical variables among patients with MOH. NVC mainly presented a negative correlation in patients with MOH and NCs. No significant difference between the two groups was detected in terms of average NVC over the entire gray matter area. However, several brain regions with significantly decreased NVC in patients with MOH compared to NCs were identified: the left orbital region of the superior frontal gyrus, the bilateral gyrus rectus, and the olfactory cortex (P < 0.05). A correlation analysis revealed that the DC of the brain regions with NVC dysfunction was significantly positively correlated with disease duration (r = 0.323, P = 0.042), and DC-CBF connectivity was negatively correlated with VAS score (r = -0.424, P = 0.035). The current study demonstrated that cerebral NVC dysfunction occurs in patients with MOH, and the NVC technique could function as a new imaging biomarker in headache research.

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.

Parsing neurobiological heterogeneity of the clinical high-risk state for psychosis: A pseudo-continuous arterial spin labelling study.

The impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways. Data from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects (n = 30 healthy controls [HCs], n = 80 APS, n = 20 BLIPS and n = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at p < 0.05. Whole-brain voxel-wise analyses and Bayesian ROI analyses were also conducted. No significant group differences were found in global [F(3,143) = 1,41, p = 0.24], bilateral frontal cortex [F(3,143) = 1.01, p = 0.39], hippocampus [F(3,143) = 0.63, p = 0.60] or striatum [F(3,143) = 0.52, p = 0.57] rCBF. Similar null findings were observed in lateralized ROIs (p > 0.05). All results were robust to addition of covariates (p > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses (p > 0.05FWE). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses. On this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia.

Free-breathing Arterial Spin Labeling MRI for the Detection of Pulmonary Embolism.

Background Arterial spin labeling (ASL) MRI can be used to assess organ perfusion but has yet to be implemented for perfusion evaluation of the lung. Purpose To evaluate pseudo-continuous ASL (PCASL) MRI for the detection of acute pulmonary embolism (PE) and its potential as an alternative to CT pulmonary angiography (CTPA). Materials and Methods Between November 2020 and November 2021, 97 patients (median age, 61 years; 48 women) with suspected PE were enrolled in this prospective study. PCASL MRI was performed within a 72-hour period following CTPA under free-breathing conditions and included three orthogonal planes. The pulmonary trunk was labeled during systole, and the image was acquired during diastole of the subsequent cardiac cycle. Additionally, multisection, coronal, balanced, steady-state free-precession imaging was carried out. Two radiologists blindly assessed overall image quality, artifacts, and diagnostic confidence (five-point Likert scale, 5 = best). Patients were categorized as positive or negative for PE, and a lobe-wise assessment in PCASL MRI and CTPA was conducted. Sensitivity and specificity were calculated on a patient level with the final clinical diagnosis serving as the reference standard. Interchangeability between MRI and CTPA was also tested with use of an individual equivalence index (IEI). Results PCASL MRI was performed successfully in all patients with high scores for image quality, artifact, and diagnostic confidence (κ ≥ .74). Of the 97 patients, 38 were positive for PE. PCASL MRI depicted PE correctly in 35 of 38 patients with three false-positive and three false-negative findings, resulting in a sensitivity of 35 of 38 patients (92% [95% CI: 79, 98]) and a specificity of 56 of 59 patients (95% [95% CI: 86, 99]). Interchangeability analysis revealed an IEI of 2.6% (95% CI: 1.2, 3.8). Conclusion Free-breathing pseudo-continuous arterial spin labeling MRI depicted abnormal lung perfusion caused by acute pulmonary embolism and may be useful as a contrast material-free alternative to CT pulmonary angiography for selected patients. German Clinical Trials Register no. DRKS00023599 © RSNA, 2023.

Navigator-based slice tracking for kidney pCASL using spin-echo EPI acquisition.

To apply a navigator-based slice-tracking method to prospectively compensate respiratory motion for kidney pseudo-continuous arterial spin labeling (pCASL), using spin-echo (SE) EPI acquisition. A single gradient-echo slice selection and projection readout at the location of the diaphragm along the inferior-superior direction was applied as a navigator. Navigator acquisition and fat suppression were inserted before each transverse imaging slice of the readouts of a 2D-SE-EPI-based pCASL sequence. Motion information was calculated after exclusion of the signal saturation in the navigator signal caused by EPI excitations. The motion information was then used to directly adjust the slice positioning in real time. The respiratory motion from the navigator signal was calculated, and slice positioning was changed in real time based on the motion information. We could show that motion compensation reduces kidney movement, and that the coefficients of variation across renal perfusion values were significantly reduced when motion correction was applied. The average reduction of coefficients of variation was approximately 20%, resulting in a more accurate and detailed structure of the respective perfusion maps. This study demonstrates the feasibility of a navigator-based slice-tracking technique in kidney imaging with a SE-EPI readout pCASL sequence to reduce kidney motion.

Assessment of Arterial Transit Time and Cerebrovascular Reactivity in Moyamoya Disease by Simultaneous PET/MRI.

We investigated the relationship between MRI-arterial spin labeling (ASL) parameters and PET-cerebral blood flow (CBF)/cerebrovascular reactivity (CVR) simultaneously obtained by PET/MRI in Moyamoya disease. Twelve patients underwent 15O-water PET/MRI with the acetazolamide (ACZ) challenge test. PET-CBF and PET-CVR were measured using 15O-water PET. Pseudo-continuous ASL obtained the robust arterial transit time (ATT) and ASL-CBF estimation. ASL parameters were compared with PET-CBF and PET-CVR. Before ACZ loading, absolute and relative ASL-CBF were significantly correlated with absolute and relative PET-CBF (r = 0.44, p < 0.0001, and r = 0.55, p < 0.0001, respectively). After ACZ loading, absolute and relative ASL-CBF were significantly correlated with absolute and relative PET-CBF (r = 0.56, p < 0.001, and r = 0.75, p < 0.0001, respectively), and ΔASL-CBF was significantly correlated with ΔPET-CBF (r = 0.65, p < 0.0001). Baseline ASL-ATT had strong negative correlations with ΔPET-CBF and PET-CVR (r = -0.72, p < 0.0001, and r = -0.66, p < 0.0001, respectively). Baseline ASL-ATT of MCA territories with CVR <30% (1546 ± 79 ms) was significantly higher than that with CVR > 30% (898 ± 197 ms). ASL-ATT ratio of MCA territories with CVR < 30% (94.0 ± 10.5%) was significantly higher than that with CVR > 30% (81.4 ± 11.3%). ATT correction using multiple postlabeling delays increased the accuracy of ASL-CBF quantitation. Baseline ASL-ATT is a hemodynamic parameter and may represent an efficient alternative to PET-CVR.

Blood flow perfusion in visual pathway detected by arterial spin labeling magnetic resonance imaging for differential diagnosis of ocular ischemic syndrome.

Ocular ischemic syndrome (OIS), attributable to chronic hypoperfusion caused by marked carotid stenosis, is one of the important factors that cause ocular neurodegenerative diseases such as optic atrophy. The current study aimed to detect blood flow perfusion in a visual pathway by arterial spin labeling (ASL) and magnetic resonance imaging (MRI) for the differential diagnosis of OIS. This diagnostic, cross-sectional study at a single institution was performed to detect blood flow perfusion in a visual pathway based on 3D pseudocontinuous ASL (3D-pCASL) using 3.0T MRI. A total of 91 participants (91 eyes) consisting of 30 eyes with OIS and 61 eyes with noncarotid artery stenosis-related retinal vascular diseases (39 eyes with diabetic retinopathy and 22 eyes with high myopic retinopathy) were consecutively included. Blood flow perfusion values in visual pathways derived from regions of interest in ASL images, including the retinal-choroidal complex, the intraorbital segments of the optic nerve, the tractus optics, and the visual center, were obtained and compared with arm-retinal circulation time and retinal circulation time derived from fundus fluorescein angiography (FFA). Receiver operating characteristic (ROC) curve analyses and the intraclass correlation coefficient (ICC) were performed to evaluate the accuracy and consistency. Patients with OIS had the lowest blood flow perfusion values in the visual pathway (all p < 0.05). The relative intraorbital segments of optic nerve blood flow values at post-labeling delays (PLDs) of 1.5 s (area under the curve, AUC = 0.832) and the relative retinal-choroidal complex blood flow values at PLDs of 2.5 s (AUC = 0.805) were effective for the differential diagnosis of OIS. The ICC of the blood flow values derived from the retinal-choroidal complex and the intraorbital segments of the optic nerve between the two observers showed satisfactory concordance (all ICC > 0.932, p < 0.001). The adverse reaction rates of ASL and FFA were 2.20 and 3.30%, respectively. 3D-pCASL showed that the participants with OIS had lower blood flow perfusion values in the visual pathway, which presented satisfactory accuracy, reproducibility, and safety. It is a noninvasive and comprehensive differential diagnostic tool to assess blood flow perfusion in a visual pathway for the differential diagnosis of OIS.

Cerebral blood flow in striatum is increased by partial dopamine agonism in initially antipsychotic-naïve patients with psychosis.

Resting cerebral blood flow (rCBF) in striatum and thalamus is increased in medicated patients with psychosis, but whether this is caused by treatment or illness pathology is unclear. Specifically, effects of partial dopamine agonism, sex, and clinical correlates on rCBF are sparsely investigated. We therefore assessed rCBF in antipsychotic-naïve psychosis patients before and after aripiprazole monotherapy and related findings to sex and symptom improvement. We assessed rCBF with the pseudo-Continuous Arterial Spin Labeling (PCASL) sequence in 49 first-episode patients (22.6 ± 5.2 years, 58% females) and 50 healthy controls (HCs) (22.3 ± 4.4 years, 63% females) at baseline and in 29 patients and 49 HCs after six weeks. RCBF in striatum and thalamus was estimated with a region-of-interest (ROI) approach. Psychopathology was assessed with the positive and negative syndrome scale. Baseline rCBF in striatum and thalamus was not altered in the combined patient group compared with HCs, but female patients had lower striatal rCBF compared with male patients (p = 0.009). Treatment with a partial dopamine agonist increased rCBF significantly in striatum (p = 0.006) in the whole patient group, but not significantly in thalamus. Baseline rCBF in nucleus accumbens was negatively associated with improvement in positive symptoms (p = 0.046), but baseline perfusion in whole striatum and thalamus was not related to treatment outcome. The findings suggest that striatal perfusion is increased by partial dopamine agonism and decreased in female patients prior to first treatment. This underlines the importance of treatment effects and sex differences when investigating the neurobiology of psychosis.

Comparison and optimization of pCASL and VSASL for rat thoracolumbar spinal cord MRI at 9.4T.

To evaluate pseudo-continuous arterial spin labeling (pCASL) and velocity-selective arterial spin labeling (VSASL) for quantification of spinal cord blood flow (SCBF) in the rat thoracolumbar spinal cord. Labeling efficiency (LE) was compared between pCASL and three VSASL variants in simulations and both phantom and in vivo experiments at 9.4T. For pCASL, the effects of label plane position and shimming were systematically evaluated. For VSASL, the effects of composite pulses and phase cycling were evaluated to reduce artifacts. Additionally, vessel suppression, respiratory, and cardiac gating were evaluated to reduce motion artifacts. pCASL and VSASL maps of spinal cord blood flow were acquired with the optimized protocols. LE of the descending aorta was larger in pCASL compared to VSASL variants. In pCASL, LE off-isocenter was improved by local shimming positioned at the label plane and the anatomical level of labeling for the thoracic cord was only viable at the level of the T10 vertebra. Cardiac gating was essential to reduce motion artifacts. Both pCASL and VSASL successfully demonstrated comparable SCBF values in the thoracolumbar cord. pCASL demonstrated high and consistent LE in the thoracic aorta, and VSASL was also feasible, but with reduced efficiency. A combination of cardiac gating and recording of actual post-label delays was important for accurate SCBF quantification. These results highlight the challenges and solutions to achieve sufficient ASL labeling and contrast at high field in organs prone to motion.

Abstract 129: Cerebral Oxygen Extraction Fraction Predicts White Matter Lesion Progression In Patients With A Monogenic Cerebral Small Vessel Disease

Background: A rare, monogenic cerebral small vessel disease (cSVD), retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S), is associated with progressive cerebral ischemia and accelerated vascular cognitive impairment, resulting in premature death. We hypothesized that low cerebral blood flow (CBF) and elevated oxygen extraction fraction (OEF), as metrics of microvascular ischemia, would predict growth of white matter lesions (WML) and other neuroimaging manifestations of cSVD. Methods: We prospectively performed sequential brain MRI in a cohort of RVCL-S participants. Pseudocontinuous arterial spin labeling and asymmetric spin echo quantified CBF and OEF in normal appearing white matter (NAWM), respectively. WMLs were manually delineated on FLAIR. WM volumes were segmented and quantified. Diffusion tensor imaging (DTI) was used to measure NAWM mean diffusivity (MD). Results: Each of 14 RVCL-S participants underwent a median of 4.5 scans (IQR 3 - 6.75) with a median of 6.5 months (IQR 5.8 - 8.6) between scans performed over 2.9 years (IQR 2.0 - 4.2). Elevated NAWM OEF from the previous MRI, but not CBF, was associated with WML growth (ρ = 0.672, p &lt; 0.0001), WM atrophy (ρ = 0.654, p &lt; 0.0001), and increased MD (ρ = 0.714, p &lt; 0.0001, Figure). After adjusting for age, sex, previous WML volume, and participant, previous OEF remained an independent predictor of WML growth (β = 7.04 (1.08, 13.01), p = 0.021). NAWM OEF was not retained in the mixed models predicting WM atrophy and MD. Conclusion: We found evidence that hypoxic-ischemic physiology, as measured by elevated OEF in NAWM, independently predicted WML growth. Previous OEF was associated with WM atrophy and decrease in microstructural integrity on follow-up. This work suggests that ischemia in normal brain regions may be a harbinger of disease progression in patients with RVCL-S, an inherited cSVD. Additionally, OEF may serve as a potential predictive biomarker in sporadic cSVD.

Abstract 109: Regional Cerebral Hypoperfusion In Patients Recovered From Mild COVID-19

Background: Cerebral hypoperfusion have been described in both severe and mild forms of symptomatic coronavirus disease 2019 (COVID-19) infection. The purpose of this study was to investigate global and regional gray matter (GM) and white matter (WM) cerebral blood flow (CBF) in asymptomatic COVID-19 infection patients compared with age-gender-race matched controls. Methods: Cases with mild COVID-19 infection and age-gender-race matched healthy controls, were drawn from the ABC@UofSC data repository. Demographics, risk factors and data from the Montreal Cognitive Assessment (MOCA score) were collected within a week of magnetic resonance imaging (MRI) perfusion image acquisition using pseudo-continuous arterial spin labeling. Mean CBF values for GM, WM and whole brain were calculated by averaging CBF values of standard space normalized CBF image values falling within GM and WM masks. Whole-brain, region of interest (ROI) based analyses were used to create standardized cerebral blood flow maps and further explore differences between the two groups. Results: Twenty-eight cases with prior mild COVID-19 infection were compared with 28 age-, gender-, race-matched controls. The MOCA score was similar between cases and controls. Whole-brain CBF (46.7±5.6 vs. 49.3±3.7, p=0.05), GM-specific CBF (64.2±8.9 vs. 67.6±6.0, p=0.10), and WM-specific CBF (29.3±2.6 vs. 31.0±1.6, p=0.03) were noted to be lower in COVID-19 cases as compared to controls. Further analysis identified several brain regions with lower CBF than the CONTROL group colors representing Z-scores shown in the figure. Predictive models based on these data predicted COVID-19 group membership with a high degree of accuracy (85.2%) suggesting CBF patterns as a key imaging marker of mild infection. Conclusion: In this study, lower white matter CBF, as well as widespread regional CBF changes identified using quantitative MRI, were found in patients recovered from mild to moderate COVID-19 infection.

Noninvasively evaluating the grade and IDH mutation status of gliomas by using mono-exponential, bi-exponential diffusion-weighted imaging and three-dimensional pseudo-continuous arterial spin labeling

ObjectivesTo noninvasively assess the diagnostic performance of diffusion-weighted imaging (DWI), bi-exponential intravoxel incoherent motion imaging (IVIM) and three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) in differentiating lower-grade gliomas (LGGs) from high-grade gliomas (HGGs), and predicting the isocitrate dehydrogenase (IDH) mutation status. Materials and methodsNinety-five patients with pathologically confirmed grade 2–4 gliomas with preoperative DWI, IVIM and 3D pCASL were enrolled in this study. The Student’s t test and Mann-Whitney U test were used to evaluate differences in parameters of DWI, IVIM and 3D pCASL between LGG and HGG as well as between mutant and wild-type IDH in grade 2 and 3 diffusion astrocytoma; receiver operator characteristic (ROC) analysis was used to assess the diagnostic performance. ResultsThe value of ADCmean, ADCmin, Dmean and Dmin in HGGs were lower than in LGGs, while the value of CBFmean and CBFmax in HGGs were higher than in LGGs. In ROC analysis, the AUC values of Dmean, Dmin and CBFmax were 0.827, 0.878 and 0.839, respectively. The combination of CBFmax and Dmin displayed the highest diagnostic performance to distinguish LGGs from HGGs, with AUC 0.906, sensitivity 82.4 %, and specificity 86.4 %. In grades 2 and 3 diffusion astrocytoma patients, ADCmin, Dmean, Dmin, CBFmean and CBFmax showed significant differences between IDHmut and IDHwt group (p < 0.05, 0.001, 0.001, 0.01 and 0.001, respectively) and the AUC values were 0. 709, 0.849, 0.919, 0.755 and 0.873, respectively. Similarly, the combination of CBFmax and Dmin demonstrated the highest AUC value (0.938) in prediction IDH mutation status, with sensitivity 92.9 %, and specificity 95.5 %. ConclusionThe combination of IVIM and 3D pCASL can be used in prediction histologic grade and IDH mutation status of glioma noninvasively.

Abstract WMP53: Revascularization Improves Cerebrovascular Reserve In Moyamoya Patients

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

Multidelay pseudocontinuous arterial spin labeling to measure blood flow in the head and neck.

Perfusion MRI is promising for the assessment, prediction, and monitoring of radiation toxicity in organs at risk in head and neck cancer. Arterial spin labeling (ASL) may be an attractive alternative for conventional perfusion MRI, that does not require the administration of contrast agents. However, currently, little is known about the characteristics and performance of ASL in healthy tissues in the head and neck region. Therefore, the purpose of this study was to optimize and evaluate multidelay pseudocontinuous ASL (pCASL) for the head and neck region and to explore nominal values and measurement repeatability for the blood flow (BF), and the transit time and T1 values needed for BF quantification in healthy tissues. Twenty healthy volunteers underwent a scan session consisting of four repeats of multidelay pCASL (postlabel delays: 1000, 1632, 2479 ms). Regions of interest were defined in the parotid glands, submandibular glands, tonsils, and the cerebellum (as a reference). Nominal values of BF were calculated as the average over four repeats per volunteer. The repeatability coefficient and within-subject coefficient of repeatability (wCV) of BF were calculated. The effect of T1 (map vs. cohort average) and transit time correction on BF was investigated. The mean BF (± SE) was 55.7 ± 3.1 ml/100 g/min for the parotid glands, 41.2 ± 2.8 ml/100 g/min for the submandibular glands, and 32.3 ± 2.2 ml/100 g/min for the tonsils. The best repeatability was found in the parotid glands (wCV = 13.3%-16.1%), followed by the submandibular glands and tonsils (wCV = 20.0%-24.6%). On average, the effect of T1 and transit time correction on BF was limited, although substantial bias occurred in individual acquisitions. In conclusion, we demonstrated the feasibility of BF measurements in the head and neck region using multidelay pCASL and reported on nominal BF values, BF repeatability, the effect of T1, and transit time in various tissues in the head and neck region.

Cerebral blood flow changes induced by high-frequency repetitive transcranial magnetic stimulation combined with cognitive training in Alzheimer's disease.

Hypoperfusion of the posterior cingulate cortex (PCC) and precuneus has consistently been reported in patients with Alzheimer's disease (AD). Repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training (COG) is effective in alleviating the symptoms of patients with mild AD. This study investigated the effects of rTMS-COG therapy on cerebral blood flow (CBF), with a special interest in the PCC/precuneus, and whether observed CBF changes are associated with changes in neuropsychological assessments in AD. Twenty-one patients with mild or moderate AD were randomly divided into real rTMS (n = 11) and sham treatment (n = 10) groups, both combined with COG. Neuro-navigated 10 Hz rTMS was used to stimulate the left dorsolateral prefrontal cortex (DLPFC) and then the left lateral temporal lobe (LTL) for 20 min each day for 4 weeks in the real rTMS group. All patients with AD underwent neuropsychological assessment, pseudo-continuous arterial spin labeling, and structural 3D T1-weighted MRI before treatment (T0), immediately after treatment (T1), and 4 weeks after treatment (T2). CBF in the precuneus, PCC, and stimulation targets at the region-of-interest (ROI) level, as well as whole-brain CBF changes at the voxel level, were compared between the two groups at three timepoints. rTMS-COG therapy revealed significant group × time interactions for the Mini-Mental State Examination (F = 5.339, p = 0.023, η2 = 0.433) and activities of daily living (F = 5.409, p = 0.039, η2 = 0.436) scores. The regional CBF in the precuneus showed a significant group × time interaction (F = 5.833, p = 0.027, η2 = 0.593). For voxel-level analysis, a significant group main effect was found in the left limbic lobe cluster, with the maximal peak in the left parahippocampus (p < 0.001, uncorrected, peak at [-16 -8 -24]). Simple effects analysis indicated that rTMS-COG therapy induced a decrease in CBF in the precuneus at T1 (p = 0.007) and an increase in the left parahippocampus at T2 (p=0.008). CBF decrease in the precuneus was correlated with better cognitive function immediately after treatment (T1) (r =-0.732, p=0.025). Neuropsychological assessments showed immediate and long-term effects on cognitive function and activities of daily living after rTMS-COG therapy. CBF changes induced by high-frequency rTMS-COG therapy are region-dependent, showing immediate effects in the precuneus and long-term effects in the left parahippocampus. These results provide imaging evidence to understand the underlying neurobiological mechanism for the application of rTMS-COG in AD.

The impact of hemodiafiltration on cognitive function in patients with end-stage renal disease.

Patients with end-stage renal disease are more likely to suffer cognitive impairment. Cognitive impairment may lead to long-term severe adverse consequences. To explore the impact of different blood purification therapy on cerebral blood flow and cognitive functions in end-stage renal disease. This prospective study evaluated patients with end-stage renal disease undergoing blood purification from January to March 2021. Matched healthy controls were also included. Participants performed neurocognitive measurements, including a mini-mental state examination, logical memory test-20-minutes delayed, verbal fluency test, digit span test, clock drawing test, and stroop color and word test C. In addition, we tested plasma amyloid-β protein levels, serum Fe and hemoglobin levels in blood samples. Cerebral blood flow was measured using pulsed pseudocontinuous arterial spin labeling. We analyzed and compared the correlation between cognitive function, biomarkers, and cerebral blood flow between patients and healthy subjects, as well as between patients with different treatments. A total of 44 patients with end-stage renal disease (mean age, 57.39 years ± 8.63) and 46 healthy controls (mean age, 56.15 years ± 6.40) were recruited. Patients receive hemodialysis three times a week, and 27 of them have been replaced hemodialysis for hemodiafiltration twice a month. The cognitive function of patients was worse than healthy controls (P < 0.05). The patients showed higher plasma concentrations of amyloid-β40, amyloid-β42, Tau, and pTau181 than healthy controls (P < 0.05). The group receiving both hemodialysis and hemodiafiltration had higher cerebral blood flow signal values in the left caudate nucleus (chuster-level P < 0.05, voxel-level P < 0.001). They also exhibited better verbal fluency function than the hemodialysis-only group (P < 0.05). Patients with the end-stage renal disease showed widespread cognitive declines. Cerebral blood flow generally decreased in the cerebral cortex and increased in subcortical regions. The hemodiafiltration may protect verbal function by increasing cerebral blood flow in the left caudate.

Three-dimensional pseudocontinuous arterial spin labeling perfusion imaging shows cerebral blood flow perfusion decline in attention-deficit/hyperactivity disorder children.

To investigate the feasibility of three-dimensional pseudocontinuous arterial spin labeling (3D-pcASL) perfusion imaging in the brain of children with Attention-deficit/hyperactivity disorder (ADHD). A total of 78 ADHD children aged 5-13 years were prospectively selected as the study group, and 89 healthy children matched in age and sex were selected as the control group. All children underwent MRI conventional sequence, 3D-pcASL, and 3D-T1 sequence scans. The brain gray and white matter volume and cerebral blood flow (CBF) perfusion values were obtained by software post-processing, and were compared and analyzed in the two groups to find out their characteristics in the brain of ADHD children. The total brain volume and total CBF values were lower in ADHD children than in healthy children (P < 0.05); the gray and white matter volumes in the frontal lobe, temporal lobe, hippocampus, caudate nucleus, putamen, globus pallidus and other brain regions were lower in ADHD children than in healthy children (P < 0.05); the gray matter CBF values in the frontal lobe, temporal lobe, hippocampus, caudate nucleus, putamen, globus pallidus and other brain regions were lower in ADHD children than in healthy children (P < 0.05); the differences between the white matter CBF values of white matter in the said brain regions of ADHD children and healthy children were not statistically significant (P > 0.05); and the CBF values in frontal lobe and caudate nuclei could distinguish ADHD children (AUC > 0.05, P < 0.05). The 3D-pcASL technique showed reduced cerebral perfusion in some brain regions of ADHD children.

Hemodynamic MRI parameters to predict asymptomatic unilateral carotid artery stenosis with random forest machine learning.

Internal carotid artery stenosis (ICAS) can cause stroke and cognitive decline. Associated hemodynamic impairments, which are most pronounced within individual watershed areas (iWSA) between vascular territories, can be assessed with hemodynamic-oxygenation-sensitive MRI and may help to detect severely affected patients. We aimed to identify the most sensitive parameters and volumes of interest (VOI) to predict high-grade ICAS with random forest machine learning. We hypothesized an increased predictive ability considering iWSAs and a decreased cognitive performance in correctly classified patients. Twenty-four patients with asymptomatic, unilateral, high-grade carotid artery stenosis and 24 age-matched healthy controls underwent MRI comprising pseudo-continuous arterial spin labeling (pCASL), breath-holding functional MRI (BH-fMRI), dynamic susceptibility contrast (DSC), T2 and T2* mapping, MPRAGE and FLAIR. Quantitative maps of eight perfusion, oxygenation and microvascular parameters were obtained. Mean values of respective parameters within and outside of iWSAs split into gray (GM) and white matter (WM) were calculated for both hemispheres and for interhemispheric differences resulting in 96 features. Random forest classifiers were trained on whole GM/WM VOIs, VOIs considering iWSAs and with additional feature selection, respectively. The most sensitive features in decreasing order were time-to-peak (TTP), cerebral blood flow (CBF) and cerebral vascular reactivity (CVR), all of these inside of iWSAs. Applying iWSAs combined with feature selection yielded significantly higher receiver operating characteristics areas under the curve (AUC) than whole GM/WM VOIs (AUC: 0.84 vs. 0.90, p = 0.039). Correctly predicted patients presented with worse cognitive performances than frequently misclassified patients (Trail-making-test B: 152.5s vs. 94.4s, p = 0.034). Random forest classifiers trained on multiparametric MRI data allow identification of the most relevant parameters and VOIs to predict ICAS, which may improve personalized treatments.

Decreased water exchange rate across blood-brain barrier in hereditary cerebral small vessel disease.

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.