Pseudo-continuous Arterial Spin Labeling MRI Research Articles

Arterial spin labeled perfusion MRI for the assessment of radiation-treated meningiomas.

Conventional contrast-enhanced MRI is currently the primary imaging technique used to evaluate radiation treatment response in meningiomas. However, newer perfusion-weighted MRI techniques, such as 3D pseudocontinuous arterial spin labeling (3D pCASL) MRI, capture physiologic information beyond the structural information provided by conventional MRI and may provide additional complementary treatment response information. The purpose of this study is to assess 3D pCASL for the evaluation of radiation-treated meningiomas. Twenty patients with meningioma treated with surgical resection followed by radiation, or by radiation alone, were included in this retrospective single-institution study. Patients were evaluated with 3D pCASL and conventional contrast-enhanced MRI before and after radiation (median follow up 6.5 months). Maximum pre- and post-radiation ASL normalized cerebral blood flow (ASL-nCBF) was measured within each meningioma and radiation-treated meningioma (or residual resected and radiated meningioma), and the contrast-enhancing area was measured for each meningioma. Wilcoxon signed-rank tests were used to compare pre- and post-radiation ASL-nCBF and pre- and post-radiation area. All treated meningiomas demonstrated decreased ASL-nCBF following radiation (p < 0.001). Meningioma contrast-enhancing area also decreased after radiation (p = 0.008) but only for approximately half of the meningiomas (9), while half (10) remained stable. A larger effect size (Wilcoxon signed-rank effect size) was seen for ASL-nCBF measurements (r = 0.877) compared to contrast-enhanced area measurements (r = 0.597). ASL perfusion may provide complementary treatment response information in radiation-treated meningiomas. This complementary information could aid clinical decision-making and provide an additional endpoint for clinical trials.

Cerebral microcirculatory pulse wave propagation and pulse wave amplitude mapping in retrospectively gated MRI

To analyze cerebral arteriovenous pulse propagation and to generate phase-resolved pulse amplitude maps from a fast gradient-echo sequence offering flow-related enhancement (FREE). Brain MRI was performed using a balanced steady-state free precession sequence at 3T followed by retrospective k-space gating. The time interval of the pulse wave between anterior-, middle- and posterior cerebral artery territories and the superior sagittal sinus were calculated and compared between and older and younger groups within 24 healthy volunteers. Pulse amplitude maps were generated and compared to pseudo-Continuous Arterial Spin Labeling (pCASL) MRI maps by voxel-wise Pearson correlation, Sørensen-Dice maps and in regards to signal contrast. The arteriovenous delays between all vascular territories and the superior sagittal sinus were significantly shorter in the older age group (11 individuals, ≥ 31 years) ranging between 169 ± 112 and 246 ± 299 ms versus 286 ± 244 to 419 ± 299 ms in the younger age group (13 individuals) (P ≤ 0.04). The voxel-wise pulse wave amplitude values and perfusion-weighted pCASL values correlated significantly (Pearson-r = 0.33, P < 0.01). Mean Dice overlaps of high (gray) and low (white matter) regions were 73 ± 3% and 59 ± 5%. No differences in image contrast were seen in the whole brain and the white matter, but significantly higher mean contrast of 0.73 ± 0.23% in cortical gray matter in FREE-MRI compared to 0.52 ± 0.12% in pCASL-MRI (P = 0.01). The dynamic information of flow-related enhancement allows analysis of the cerebral pulse wave propagation potentially providing information about the (micro)circulation on a regional level. However, the pulse wave amplitude reveals weaknesses in comparison to true perfusion-weighting and could rather be used to calculate a pulsatility index.

Lateralization of interictal temporal lobe hypoperfusion in lesional and non-lesional temporal lobe epilepsy using arterial spin labeling MRI

PurposeNon-invasive imaging studies play a critical role in the presurgical evaluation of patients with drug-resistant temporal lobe epilepsy (TLE), particularly in helping to lateralize the seizure focus. Arterial Spin Labeling (ASL) MRI has been widely used to non-invasively study cerebral blood flow (CBF), with somewhat variable interictal alterations reported in TLE. Here, we compare temporal lobe subregional interictal perfusion and symmetry in lesional (MRI+) and non-lesional (MRI-) TLE compared to healthy volunteers (HVs). MethodsTwenty TLE patients (9 MRI+, 11 MRI-) and 14 HVs under went 3 T Pseudo-Continuous ASL MRI through an epilepsy imaging research protocol at the NIH Clinical Center. We compared normalized CBF and absolute asymmetry indices in multiple temporal lobe subregions. ResultsCompared to HVs, both MRI+ and MRI- TLE groups demonstrated significant ipsilateral mesial and lateral temporal hypoperfusion, specifically in the hippocampal and anterior temporal neocortical subregions, with additional hypoperfusion in the ipsilateral parahippocampal gyrus in the MRI+ and contralateral hippocampus in the MRI- TLE groups. Contralateral to the seizure focus, there was significant relative hypoperfusion in multiple subregions in the MRI- compared to the MRI+ TLE groups. The MRI+ group therefore had significantly greater asymmetry across multiple temporal subregions compared to the MRI- TLE and HV groups. No significant differences in asymmetry were found between the MRI- TLE and HV groups. ConclusionWe found a similar extent of interictal ipsilateral temporal hypoperfusion in MRI+ and MRI- TLE. However, significantly increased asymmetries were found only in the MRI+ group due to differences in perfusion contralateral to the seizure focus between the patient groups. The lack of asymmetry in the MRI- group may negatively impact the utility of interictal ASL for seizure focus lateralization in this patient population.

Cerebral blood flow patterns in preterm and term neonates assessed with pseudo-continuous arterial spin labeling perfusion MRI.

In preterm (PT) infants, regional cerebral blood flow (CBF) disturbances may predispose to abnormal brain maturation even without overt brain injury. Therefore, it would be informative to determine the spatial distribution of grey matter (GM) CBF in PT and full-term (FT) newborns at term-equivalent age (TEA) and to assess the relationship between the features of the CBF pattern and both prematurity and prematurity-related brain lesions. In this prospective study, we obtained measures of CBF in 66 PT (51 without and 15 with prematurity-related brain lesions) and 38 FT newborns through pseudo-continuous arterial spin labeling (pCASL) MRI acquired at TEA. The pattern of GM CBF was characterized by combining an atlas-based automated segmentation of structural MRI with spatial normalization and hierarchical clustering. The effects of gestational age (GA) at birth and brain injury on the CBF pattern were investigated. We identified 4 physiologically-derived clusters of brain regions that were labeled Fronto-Temporal, Parieto-Occipital, Insular-Deep GM (DGM) and Sensorimotor, from the least to the most perfused. We demonstrated that GM perfusion was associated with GA at birth in the Fronto-Temporal and Sensorimotor clusters, positively and negatively, respectively. Moreover, the presence of periventricular leukomalacia was associated with significantly increased Fronto-Temporal GM perfusion and decreased Insular-DGM perfusion, while the presence of germinal matrix hemorrhage appeared to mildly decrease the Insular-DGM perfusion. Prematurity and prematurity-related brain injury heterogeneously affect brain perfusion. ASL MRI may, therefore, have strong potential as a noninvasive tool for the accurate stratification of individuals at risk of domain-specific impairment.

Cerebral blood flow in children with persisting postconcussive symptoms and posttraumatic headache at 2 weeks postconcussion.

Persisting postconcussive symptoms (pPCS), particularly headache, can significantly disrupt children's recovery and functioning. However, the underlying pathophysiology of these symptoms remains unclear. The goal in this study was to determine whether pPCS are related to cerebral blood flow (CBF) at 2 weeks postconcussion. The authors also investigated whether variations in CBF can explain the increased risk of acute posttraumatic headache (PTH) in female children following concussion. As part of a prospective, longitudinal study, the authors recruited children 5-18 years old who were admitted to the emergency department of a tertiary pediatric hospital with a concussion sustained within 48 hours of admission. Participants underwent pseudocontinuous arterial spin labeling MRI at 2 weeks postconcussion to quantify global mean gray and white matter perfusion (in ml/100 g/min). Conventional frequentist analysis and Bayesian analysis were performed. Comparison of recovered (n = 26) and symptomatic (n = 12) groups (mean age 13.15 years, SD 2.69 years; 28 male) found no differences in mean global gray and white matter perfusion at 2 weeks postconcussion (Bayes factors > 3). Although female sex was identified as a risk factor for PTH with migraine features (p = 0.003), there was no difference in CBF between female children with and without PTH. Global CBF was not associated with pPCS and female PTH at 2 weeks after pediatric concussion. These findings provide evidence against the use of CBF measured by arterial spin labeling as an acute biomarker for pediatric concussion recovery.

Associations between everyday activities and arterial spin labeling‐derived cerebral blood flow: A longitudinal study in community‐dwelling elderly volunteers

Cerebral blood flow (CBF) is critical for brain metabolism and function. Age-related changes in CBF are associated with increased risk of neurocognitive disorders and vascular events such as stroke. Identifying correlates and positive modifiers of age-related changes in CBF before the emergence of incipient clinical decline may inform public health advice and clinical practice. Former research has been inconclusive regarding the association between regular physical activity and CBF, and there is a lack of studies on the association between level of everyday activities and CBF, in older adults. To investigate these relationships, 118 healthy community-dwelling adults (65-89 years) underwent pseudo-continuous arterial spin labeling (ASL) MRI, neurocognitive, physical, and activity assessments at baseline. Eighty-six participants completed a follow-up ASL MRI, on average 506 (SD=113) days after the baseline scan. Cross-sectional analysis revealed credible evidence for positive associations between time spent on low intensity physical activity and CBF in multiple cortical and subcortical regions, time spent on moderate to vigorous intensity physical activity and accumbens CBF, participation in social activity and CBF in multiple cortical regions, and between reading and thalamic CBF, indicating higher regional CBF in more active adults. Longitudinal analysis revealed anecdotal evidence for an interaction between time and baseline level of gardening on occipital and parietal CBF, and baseline reading on pallidum CBF, indicating more change in CBF in adults with lower level of activity. The findings support that malleable lifestyle factors contribute to healthy brain aging, with relevance for public health guidelines.

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.

Cerebral blood flow quantification with multi-delay arterial spin labeling in ischemic stroke and the association with early neurological outcome

Restoring blood flow to brain tissue at risk of infarction is essential for tissue survival and clinical outcome. We used cerebral blood flow (CBF) quantified with multiple post-labeling delay (PLD) pseudocontinuous arterial spin labeling (ASL) MRI after ischemic stroke and assessed the association between CBF and early neurological outcome. We acquired ASL with 7 PLDs at 3.0 T in large vessel occlusion stroke patients at 24 h. We quantified CBF relative to the contralateral hemisphere (rCBF) and defined hyperperfusion as a ≥30% increase and hypoperfusion as a ≥40% decrease in rCBF. We included 44 patients (median age: 70 years, median NIHSS: 13, 40 treated with endovascular thrombectomy) of whom 37 were recanalized. Hyperperfusion in ischemic core occurred in recanalized but not in non-recanalized patients (65.8% vs 0%, p = 0.006). Hypoperfusion occurred only in the latter group (0% vs 85.7%, p < 0.001). In recanalized patients, hyperperfusion was also seen in salvaged penumbra (38.9%). Higher rCBF in ischemic core (aβ, −2.75 [95% CI: −4.11 to −1.40]) and salvaged penumbra (aβ, −5.62 [95% CI: −9.57 to −1.68]) was associated with lower NIHSS scores at 24 h. In conclusion, hyperperfusion frequently occurs in infarcted and salvaged brain tissue following successful recanalization and early neurological outcome is positively associated with the level of reperfusion.

Sex-dependent changes in emotional memory associated with cerebral blood flow alterations during Alzheimer's disease progression.

Sex differences in Alzheimer's disease (AD) progression provide clues to pathogenesis and better patient management. We examined sex differences in emotional memory among AD patients, amnesticmild cognitive impairment (aMCI) patients, and healthy controls (HCs) as well as potential associations with altered regional cerebral blood flow (rCBF). The recognition memory task with emotional pictures was applied to evaluate enhancement of emotional memory (EEM) and 3D pseudo-continuous arterial spin labeling MRI was performed to measure the rCBF in 74 AD patients (41 females), 74 aMCI patients (45 females), and 74 HCs (43 females). Group differences in EEM were tested by two-way analysis of covariance (ANCOVA) with repeated measures. The main effects of clinical group and sex as well as group × sex interactions on rCBF were assessed by two-way ANCOVA. Correlation analyses were conducted to investigate associations between EEM and rCBF. With disease progression, EEM gradually disappeared. Among aMCI patients, females exhibited a greater index of recollection (Pr) for positive/high-arousal and negative/low-arousal pictures versus neutral pictures (P = 0.005, P = 0.003), while males exhibited a greater Pr for negative/high-arousal versus neutral pictures (P = 0.001). There were significant sex × group effects on rCBF in left inferior parietal, supramarginal, superior temporal and middle temporal gyri, and rCBF of left inferior parietal gyrus was correlated with Pr for positive/high-arousal pictures among female aMCI patients (r = 0.584, q = 0.005). Males and females exhibit distinct changes in EEM associated with altered rCBF, which should be considered in future neuroimaging studies.

Higher arterial stiffness and systolic blood pressure are differentially associated with lower perfusion in subcortical and cortical gray matter regions

AbstractBackgroundHigher arterial stiffness is associated with lower regional cerebral blood flow (CBF) in older adults. Cortical CBF also correlates with higher systolic blood pressure (SBP). We examined relationships of lobar and deep gray matter CBF with both SBP and arterial stiffness.MethodParticipants of the Clinical Core of the Wake Forest Alzheimer’s Disease Research Center completed baseline clinical examination including measures of: arterial stiffness, blood pressure, medication review, APOE genotyping, 3T MRI, detailed cognitive testing, and cognitive adjudication. T1 structural and pseudocontinuous arterial spin labeling (pcASL) MRI were used to quantify gray matter (GM) CBF in AAL atlas regions. GM CBF was quantified into lobar (frontal, temporal, parietal, occipital), subcortical (caudate, putamen, pallidum, and thalamus), Cingulate/Insula, and posterior (cerebellum and vermis) regions. Arterial stiffness was measured twice in the supine position and averaged to quantify carotid‐femoral pulse wave velocity (cfPWV). Associations for cfPWV and systolic blood pressure (SBP) with GM CBF ROIs was examined by multivariable linear regression models adjusted for age, race, gender, education, hypertension medications, and APOE‐e4 carrier status.Result:Among 404 participants (70±8 years; 39 dementia, 139 MCI, 226 normal cognition), higher cfPWV and SBP were differentially associated with regional GM CBF (Fig 1 &amp; 2). Higher cfPWV was associated with lower subcortical GM CBF (p=0.04) (Table 1). Higher SBP was associated with lower GM CBF in frontal (p=0.03), temporal (p=0.02) and occipital lobes (p=0.01) (Table 1).ConclusionDeep subcortical brain structures may be at greater risk of damage from high arterial stiffness because they are perfused by arteries which branch relatively upstream of other branching arteries, as evidenced by lower GM CBF. High SBP may predict vascular damage in cortical regions manifested as lower GM CBF. These differential relationships with deep and cortical perfusion support and extend prior observations in this group relating vascular risk factors to abnormalities in white matter micro‐ and macro‐ structure, lower total CBF, and lower cognitive performance.

Higher arterial stiffness and systolic blood pressure are differentially associated with lower perfusion in subcortical and cortical gray matter regions

AbstractBackgroundHigher arterial stiffness is associated with lower regional cerebral blood flow (CBF) in older adults. Cortical CBF also correlates with higher systolic blood pressure (SBP). We examined relationships of lobar and deep gray matter CBF with both SBP and arterial stiffness.MethodParticipants of the Clinical Core of the Wake Forest Alzheimer’s Disease Research Center completed baseline clinical examination including measures of: arterial stiffness, blood pressure, medication review, APOE genotyping, 3T MRI, detailed cognitive testing, and cognitive adjudication. T1 structural and pseudocontinuous arterial spin labeling (pcASL) MRI were used to quantify gray matter (GM) CBF in AAL atlas regions. GM CBF was quantified into lobar (frontal, temporal, parietal, occipital), subcortical (caudate, putamen, pallidum, and thalamus), Cingulate/Insula, and posterior (cerebellum and vermis) regions. Arterial stiffness was measured twice in the supine position and averaged to quantify carotid‐femoral pulse wave velocity (cfPWV). Associations for cfPWV and systolic blood pressure (SBP) with GM CBF ROIs was examined by multivariable linear regression models adjusted for age, race, gender, education, hypertension medications, and APOE‐e4 carrier status.ResultAmong 404 participants (70±8 years; 39 dementia, 139 MCI, 226 normal cognition), higher cfPWV and SBP were differentially associated with regional GM CBF (Fig 1 &amp; 2). Higher cfPWV was associated with lower subcortical GM CBF (p=0.04) (Table 1). Higher SBP was associated with lower GM CBF in frontal (p=0.03), temporal (p=0.02) and occipital lobes (p=0.01) (Table 1).ConclusionDeep subcortical brain structures may be at greater risk of damage from high arterial stiffness because they are perfused by arteries which branch relatively upstream of other branching arteries, as evidenced by lower GM CBF. High SBP may predict vascular damage in cortical regions manifested as lower GM CBF. These differential relationships with deep and cortical perfusion support and extend prior observations in this group relating vascular risk factors to abnormalities in white matter micro‐ and macro‐ structure, lower total CBF, and lower cognitive performance.

Feasibility of flow-related enhancement brain perfusion MRI.

Brain perfusion imaging is of enormous importance for various neurological diseases. Fast gradient-echo sequences offering flow-related enhancement (FREE) could present a basis to generate perfusion-weighted maps. In this study, we obtained perfusion-weighted maps without contrast media by a previously described postprocessing algorithm from the field of functional lung MRI. At first, the perfusion signal was analyzed in fast low-angle shot (FLASH) and balanced steady-state free precession (bSSFP) sequences. Secondly, perfusion maps were compared to pseudo-continuous arterial spin labeling (pCASL) MRI in a healthy cohort. Thirdly, the feasibility of the new technique was demonstrated in a small selected group of patients with metastases and acute stroke. One participant was examined with bSSFP and FLASH sequences at 1.5T and 3T, different flip angles and slice thicknesses. Twenty-five volunteers had bSSFP imaging and pCASL MRI. Three patients with cerebral metastases and one with acute ischemic stroke had bSSFP imaging and were compared to T1 post-contrast images and CT perfusion. Frequency analyses, SNR and perfusion contrast were compared at different flip angles and slice thicknesses. Regional correlations and Sorensen-Dice overlap were calculated in the healthy cohort. Dice overlap of the pathologies in the patient cohort were calculated. The bSSFP sequence presented detectable perfusion signal within brain vessel and parenchyma together with superior SNR compared to FLASH. Perfusion contrast and its corticomedullary differentiation increased with flip angle. Mean regional correlation was 0.36 and highly significant between FREE maps and pCASL and grey and white matter Dice match were 72% and 60% in the healthy cohort. Pathologies presented good overlap between FREE perfusion-weighted and T1 post-contrast images. The feasibility of FREE brain perfusion imaging has been shown in a healthy cohort and selected patient cases with brain metastases and acute stroke. The study demonstrates a new approach for non-contrast brain perfusion imaging.

Altered serum amyloid beta and cerebral perfusion and their associations with cognitive function in patients with subcortical ischemic vascular disease.

Subcortical ischemic vascular disease (SIVD) is one of the important causes of cognitive dysfunction, altered amyloid-beta (Aβ) and cerebral perfusion may be involved in the pathophysiological mechanism of SIVD and are closely related to cognitive function. We aimed to investigate altered serum Aβ and cerebral perfusion in patients with SIVD and their correlation with cognitive function. Seventy-four healthy controls (HCs) and 74 SIVD patients, including 38 SIVD patients with no cognitive impairment (SIVD-NCI) and 36 SIVD patients with mild cognitive impairment (SIVD-MCI) underwent the measurement of serum Aβ40 and Aβ42 levels, pseudo-continuous arterial spin labeling MRI scanning, and cognitive evaluation. Compared to the healthy controls (HCs), the level of serum Aβ40 and Aβ40/42 ratio increased and Aβ42 decreased in SIVD patients. The serum Aβ40 level and Aβ40/42 ratio in patients with SIVD-MCI were significantly higher than those in the HCs and SIVD-NCI, and the level of Aβ42 in the SIVD-MCI was lower than the HCs. In addition, the serum Aβ40/42 ratio provided high diagnostic accuracy for SIVD and SIVD-MCI, it was further identified as an independent risk factor for cognitive impairment. Patients with SIVD-NCI and SIVD-MCI exhibited both increased and decreased cerebral blood flow (CBF) in regional. The Aβ40/42 ratio was associated with global CBF, while altered global and regional CBF was associated with cognitive deficits. In addition, white matter hyperintensities volume (WMHV) correlated with Aβ40/42 ratio, CBF, and cognition. The relationship between Aβ40/42 ratio and cognition was partially mediated by altered CBF. Based on these results, we conclude that the serum Aβ40/42 ratio may be a potential biomarker that can complement current methods for the prediction and diagnosis of cognitive impairment in SIVD patients. In addition, serum Aβ may play a role in cognitive function by regulating CBF, which provides new insights into the intervention, treatment, and prevention of cognitive impairment in SIVD.

Cerebral blood flow alterations in migraine patients with and without aura: An arterial spin labeling study

BackgroundMigraine aura is a transient, fully reversible visual, sensory, or other central nervous system symptom that classically precedes migraine headache. This study aimed to investigate cerebral blood flow (CBF) alterations of migraine with aura patients (MwA) and without aura patients (MwoA) during inter-ictal periods, using arterial spin labeling (ASL).MethodsWe evaluated 88 migraine patients (32 MwA) and 44 healthy control subjects (HC) who underwent a three-dimensional pseudo-continuous ASL MRI scanning. Voxel-based comparison of normalized CBF was conducted between MwA and MwoA. The relationship between CBF variation and clinical scale assessment was further analyzed. The mean CBF values in brain regions showed significant differences were calculated and considered as imaging features. Based on these features, different machine learning–based models were established to differentiate MwA and MwoA under five-fold cross validation. The predictive ability of the optimal model was further tested in an independent sample of 30 migraine patients (10 MwA).ResultsIn comparison to MwoA and HC, MwA exhibited higher CBF levels in the bilateral superior frontal gyrus, bilateral postcentral gyrus and cerebellum, and lower CBF levels in the bilateral middle frontal gyrus, thalamus and medioventral occipital cortex (all p values < 0.05). These variations were also significantly correlated with multiple clinical rating scales about headache severity, quality of life and emotion. On basis of these CBF features, the accuracies and areas under curve of the final model in the training and testing samples were 84.3% and 0.872, 83.3% and 0.860 in discriminating patients with and without aura, respectively.ConclusionIn this study, CBF abnormalities of MwA were identified in multiple brain regions, which might help better understand migraine-stroke connection mechanisms and may guide patient-specific decision-making.

Quantitative cerebrovascular reactivity MRI in mice using acetazolamide challenge.

To develop a quantitative MRI method to estimate cerebrovascular reactivity (CVR) in mice. We described an MRI procedure to measure cerebral vasodilatory response to acetazolamide (ACZ), a vasoactive agent previously used in human clinical imaging. Vascular response was determined by cerebral blood flow (CBF) measured with phase-contrast or pseudo-continuous arterial spin labeling MRI. Vasodilatory input intensity was determined by plasma ACZ level using high-performance liquid chromatography. We verified the source of the CVR MRI signal by comparing ACZ injection to phosphate-buffered saline injection and noninjection experiments. Dose dependence and feasibility of regional CVR measurement were also investigated. Cerebral blood flow revealed an exponential increase following intravenous ACZ injection, with a time constant of 1.62 min. In contrast, phosphate-buffered saline or noninjection exhibited a slow linear CBF increase, consistent with a gradual accumulation of anesthetic agent, isoflurane, used in this study. When comparing different ACZ doses, injections of 30, 60, 120, and 180 mg/kg yielded a linear increase in plasma ACZ concentration (p < 0.0001). On the other hand, CBF changes under these doses were not different from each other (p=0.50). The pseudo-continuous arterial spin labeling MRI with multiple postlabeling delays revealed similar vascular responses at different postlabeling delay values. There was a regional difference in CVR (p=0.005), with isocortex (0.81 ± 0.17%/[μg/ml]) showing higher CVR than deep-brain regions. Mice receiving multiple ACZ injections lived for a minimum of 6months after the study without noticeable aberrant behavior or appearance. We demonstrated the proof-of-principle of a new quantitative CVR mapping technique in mice.

359-OR: Imaging Pancreatic Blood Flow during Stimulation of Insulin Secretion in Humans

Non-invasive imaging of endocrine pancreatic function could provide valuable insights into the magnitude and temporal pattern of β-cell dysfunction in diabetes. Islets comprise 1-2% of pancreatic mass, but receive about 10-20% of pancreatic blood flow, which increases further during stimulation of insulin secretion. We examined the relationship between pancreatic blood flow (PBF) and insulin secretory dynamics in 12 healthy volunteers (6M / 6F, age = 29 ± 5 yrs, BMI = 24.0 ± 2.7 kg/m², HbA1c = 5.1 ± 0.3 %, FPG = 88 ± mg/dl, fasting insulin = 3.7 ± 2.3 μU/ml) . PBF was measured by pseudo-continuous arterial spin labeling (ASL) MRI, with the labeling plane positioned 5-6 cm superior to the imaging slice to label blood in the descending aorta. Fasting subjects were placed in a 3T scanner, and PBF was measured during 1) a 15 min basal period, 2) a +100 mg/dl hyperglycemic clamp for 40 min, followed by 3) a 5 gm bolus of arginine to assess maximal acute insulin response (AIRmax) . First phase (0-min) insulin response to hyperglycemia was 181 ± 96 μU/ml · min, and AIRmax after arginine + hyperglycemia (40-50 min) was 1097 ± 629 μU/ml · min. Basal PBF (188 ± 53 ml/100 gm/min) increased during first phase insulin release, peaking at 212 ± 66 at 12 min, subsequently returned to basal levels (176 ± 59) from 10-40 min during sustained hyperglycemia,and peaked again at 2± 62 at 2 min after arginine. Although there were no significant correlations between glucose, insulin or c-peptide levels and PBF, time-series Granger causality analysis demonstrated that the time-derivative of c-peptide and insulin concentrations, reflectingacute changes in insulin secretion, preceded the increase in PBF (p=0.03 for d[c-peptide]/dt, and p = 0.for d[insulin]/dt) . Conclusions: 1) Changes in PBF during stimulation of insulin secretion in humans can be imaged non-invasively by ASL, 2) Insulin secretion precedes changes in PBF, and 3) The rate of change in insulin and c-peptide release predicts subsequent modulation of PBF. Disclosure D.C.Simonson: Stock/Shareholder; GI Windows, Phase V Technologies, Inc. M.Taso: Research Support; GE Healthcare Systems. C.Mcgrath: None. S.A.Waldman: None. F.Papadopoulou: None. D.C.Alsop: Other Relationship; GE Healthcare Systems, Hitachi, Ltd., Philips Healthcare, Siemens, UIH America, Research Support; GE Healthcare Systems.

The Role of 3D-pCASL MRI in the Differential Diagnosis of Glioblastoma and Brain Metastases.

PurposeThe first aim of this study was to compare the intratumoral and peritumoral blood flow parameters in glioblastomas and brain metastases measured by pseudocontinuous arterial spin labeling MRI (3D pCASL). The second aim of this study was to determine whether pCASL could aid in identifying the source of brain metastases.Materials and MethodsThis study included 173 patients aged 12 to 83 years (median age—61 years), who were observed at the National Medical Research Center for Neurosurgery. All patients underwent preoperative MRI with pCASL perfusion. Thereafter patients were operated on and received histological diagnosis. No patients received preoperative chemo or radiotherapy.ResultsThe values of maximum and normalized intratumoral blood flow were significantly higher in the group with gliblastoma than in the group with brain metastases: 168.98 + −91.96 versus 152.1 + −173.32 and 7.6 + −8.4 versus 9.3 + −5.33 respectively (p <0.01). However, ROC analysis showed low AUC specificity and sensitivity (0.64, 70%, 60% for mTBF and 0.66, 77%, 62% for nTBF). Peritumoral blood flow parameters were also higher in the glioblastoma group (29.61 + −22.89 versus 16.58 + −6.46 for mTBF and 1.63 + −1.14 versus 0.88 + −0.38 for nTBF, respectively; p <0.01). ROC analysis showed the following measurements of AUC, specificity, and sensitivity (0.75, 68%, 73% for mTBF and 0.77, 58%, 91% for nTBF). Regarding pCASL and various histological subsets of brain metastases, the study found statistically significant differences between the lung and melanoma metastases and the lung and kidney metastases. ROC analysis gave the following values for lung and melanoma metastases: AUC—0.76, specificity—75%, and sensitivity—73% for mTBF; 0.83, 67%, and 93% respectively, for nTBF. For lung and kidney metastases: AUC—0.74, specificity—70%, and sensitivity—93% for mTBF; 0.75, 70%, and 93% respectively, for nTBF.ConclusionspCASL could aid in differential diagnosis between glioblastoma and brain metastases. Measurement of peritumoral blood flow demonstrates higher specificity and sensitivity than with intratumoral blood flow. Moreover, pCASL provides the ability to distinguish lung metastases from kidney and melanoma metastases.

Caveolin-1 Promoted Collateral Vessel Formation in Patients With Moyamoya Disease.

BackgroundCaveolin-1 (Cav-1) plays pivotal roles in the endothelial function and angiogenesis postischemia. Moyamoya disease (MMD) is characterized by progressive artery stenosis with unknown etiology. We aim to determine whether serum Cav-1 levels of patients with MMD were associated with collateral vessel formation after bypass surgery.MethodsWe studied serum Cav-1 levels of 130 patients with MMD (16 with RNF213 p.R4810K mutation and 114 without RNF213 p.R4810K mutation), 15 patients with acute stroke, and 33 healthy controls. Cerebral perfusion and collateral circulation were evaluated preoperation and at 6 months after operation using pseudocontinuous arterial spin labeling MRI (pCASL-MRI) and digital subtraction angiography (DSA), respectively. Endothelial expression of Cav-1 was verified in the superficial temporal artery (STA) wall of patients with MMD by immunofluorescence double staining. We also investigated whether overexpression of Cav-1 affects cell migration and tube formation using human microvascular endothelial cells (HMECs).ResultsThe serum Cav-1 level of patients with MMD intermediated between the stroke group and healthy controls and it was enhanced after the bypass surgery (681.87 ± 311.63 vs. 832.91 ± 464.41 pg/ml, p = 0.049). By 6 months after bypass surgery, patients with MMD with better collateral compensation manifested higher postoperative/preoperative Cav-1 ratio (rCav-1) than bad compensation patients. Consistently, cerebral blood flow (CBF) determined by pCASL-MRI (nCBFMCA ratio) was positively in line with rCav-1 ratio (r = 0.8615, p < 0.0001). Cav-1 was expressed in the endothelial cells of the STA vessels of patients with MMD. Overexpression of Cav-1 by plasmid transfection in HMECs promoted tube formation and cell migration.ConclusionThis study indicated that Cav-1 may be a potential driver to promote angiogenesis and collateral formation after bypass surgery in patients with MMD, providing a better understanding of MMD pathophysiology and potential non-surgical targets of MMD.

Cerebrovascular reactivity deficits in cognitively unimpaired older adults: vasodilatory versus vasoconstrictive responses

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

The Contribution of Working Memory Areas to Verbal Learning and Recall in Primary Progressive Aphasia.

Recent evidence of domain-specific working memory (WM) systems has identified the areas and networks which are involved in phonological, orthographic, and semantic WM, as well as in higher level domain-general WM functions. The contribution of these areas throughout the process of verbal learning and recall is still unclear. In the present study, we asked, what is the contribution of domain-specific specialized WM systems in the course of verbal learning and recall? To answer this question, we regressed the perfusion data from pseudo-continuous arterial spin labeling (pCASL) MRI with all the immediate, consecutive, and delayed recall stages of the Rey Auditory Verbal Learning Test (RAVLT) from a group of patients with Primary Progressive Aphasia (PPA), a neurodegenerative syndrome in which language is the primary deficit. We found that the early stages of verbal learning involve the areas with subserving phonological processing (left superior temporal gyrus), as well as semantic WM memory (left angular gyrus, AG_L). As learning unfolds, areas with subserving semantic WM (AG_L), as well as lexical/semantic (inferior temporal and fusiform gyri, temporal pole), and episodic memory (hippocampal complex) become more involved. Finally, a delayed recall depends entirely on semantic and episodic memory areas (hippocampal complex, temporal pole, and gyri). Our results suggest that AG_L subserving domain-specific (semantic) WM is involved only during verbal learning, but a delayed recall depends only on medial and cortical temporal areas.