Quantitative mapping of renal oxygen consumption using pseudo-continuous arterial spin labeling and quantitative susceptibility mapping in humans.

PURPOSE: To propose a new method for quantitatively mapping the renal metabolic rate of oxygen (RMRO2) and to evaluate the proposed method using a caffeine challenge. THEORY AND METHODS: Pseudo-continuous arterial spin labeling (pCASL) and QSM sequences were used to obtain MR images in the kidney. Six healthy volunteers were scanned on caffeine and control days. The pCASL and QSM images were registered using DICOM information and rigid translation. The Fick principle was applied to estimate RMRO2. The results on caffeine and control days were compared to evaluate the capability of the proposed method to estimate renal oxygen consumption. A paired t-test was used to assess the statistical significance. RESULTS: Estimated renal blood flow (RBF), QSM, and RMRO2 maps were consistent with those reported in the literature. RMRO2 values were higher than the cerebral metabolic rate of oxygen (CMRO2) and were significantly reduced on the caffeine days compared to the control days, consistent with findings from non-MRI literature. CONCLUSION: The feasibility of measuring renal oxygen consumption using pCASL and QSM images was demonstrated. To the best of our knowledge, this work provides quantitative maps of renal oxygen consumption in humans for the first time. The results were consistent with the literature, including the statistically significant reduction in renal oxygen consumption with caffeine challenge. These findings suggest the potential utility of our technique in measuring renal oxygen consumption noninvasively, especially for patients with complications associated with contrast agents.

Cervical spinal cord angiography and vessel-selective perfusion imaging in the rat.

Arterial spin labeling (ASL) has been widely used to evaluate arterial blood and perfusion dynamics, particularly in the brain, but its application to the spinal cord has been limited. The purpose of this study was to optimize vessel-selective pseudocontinuous arterial spin labeling (pCASL) for angiographic and perfusion imaging of the rat cervical spinal cord. A pCASL preparation module was combined with a train of gradient echoes for dynamic angiography. The effects of the echo train flip angle, label duration, and a Cartesian or radial readout were compared to examine their effects on visualizing the segmental arteries and anterior spinal artery (ASA) that supply the spinal cord. Lastly, vessel-selective encoding with either vessel-encoded pCASL (VE-pCASL) or super-selective pCASL (SS-pCASL) were compared. Vascular territory maps were obtained with VE-pCASL perfusion imaging of the spinal cord, and the interanimal variability was evaluated. The results demonstrated that longer label durations (200 ms) resulted in greater signal-to-noise ratio in the vertebral arteries, improved the conspicuity of the ASA, and produced better quality maps of blood arrival times. Cartesian and radial readouts demonstrated similar image quality. Both VE-pCASL and SS-pCASL adequately labeled the right or left vertebral arteries, which revealed the interanimal variability in the segmental artery with variations in their location, number, and laterality. VE-pCASL also demonstrated unique interanimal variations in spinal cord perfusion with a right-sided dominance across the six animals. Vessel-selective pCASL successfully achieved visualization of the arterial inflow dynamics and corresponding perfusion territories of the spinal cord. These methodological developments provide unique insights into the interanimal variations in the arterial anatomy and dynamics of spinal cord perfusion.

Insomnia in patients with MRI-negative epilepsy: The associated factors and 3D-pCASL cerebral blood flow perfusion changes.

OBJECTIVE: This study aimed to identify the factors associated with insomnia in MRI-negative epilepsy and uncover the underlying pathological mechanism driving insomnia within the context of epilepsy. METHODS: We conducted a retrospective study of patients with MRI-negative epilepsy recruited consecutively from December 2021 to December 2022. All subjects completed the Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). Additionally, some subjects underwent the three-dimensional pseudo continuous arterial spin labeling(3D-pCASL) imaging examination. Bilateral frontal lobe, temporal lobe, hippocampus, thalamus, amygdala, caudate nucleus and lenticular nucleus were selected as regions of interest(ROI) and cerebral blood flow(CBF) values were measured in these regions. Subjects were classified into insomnia (ISI ≥ 10) or non-insomnia (ISI < 10) groups, and univariate and stepwise logistic regression analyses were employed to identify the factors associated with insomnia. Furthermore, CBF values in each ROI were compared between the two groups to identify the brain regions potentially related to the underlying pathological mechanism of insomnia in epilepsy. RESULTS: A total of 73 patients with MRI-negative epilepsy were recruited in this study(men, 49.3 %). Among them, 14 patients(19.2 %) had insomnia. Univariate regression revealed that nocturnal seizures, number of anti-seizure medication(ASM), anxiety, use of valproic acid(VPA), depression, and excessive daytime sleepiness(EDS) may be associated with insomnia in MRI-negative epilepsy (all p＜0.05). Stepwise regression demonstrated that nocturnal seizures, anxiety, and EDS were independently associated with insomnia in MRI-negative epilepsy (OR[95 %CI]P: 14.64[2.02-106.27]0.008,49.35[3.06-796.61]0.006, 13.28[1.25-140.66]0.032, respectively). Furthermore, CBF values in the left amygdala were significantly lower in patients with MRI- negative epilepsy who had insomnia. CONCLUSION: The prevalence of insomnia in MRI-negative epilepsy is 19.2%. Nocturnal seizures, anxiety, and EDS were independently associated with insomnia in MRI-negative epilepsy. The noteworthy decrease in CBF values in the left amygdala might be connected to the underlying pathological mechanism of insomnia in epilepsy.

Subject-specific timing adaption in time-encoded arterial spin labeling imaging.

OBJECTIVES: One challenge in arterial spin labeling (ASL) is the high variability of arterial transit times (ATT), which causes associated arterial transit delay (ATD) artifacts. In patients with pathological changes, these artifacts occur when post-labeling delay (PLD) and bolus durations are not optimally matched to the subject, resulting in difficult quantification of cerebral blood flow (CBF) and ATT. This is also true for the free lunch approach in Hadamard-encoded pseudocontinuous ASL (H-pCASL). MATERIAL AND METHODS: Five healthy volunteers were scanned with a 3 T MR-system. pCASL-subbolus timing was adjusted individually by the developed adaptive Walsh-ordered pCASL sequence and an automatic feedback algorithm. The quantification results for CBF and ATT and the respective standard deviations were compared with results obtained using recommended timings and intentionally suboptimal timings. RESULTS: The algorithm individually adjusted the pCASL-subbolus PLD for each subject within the range of recommended timing for healthy subjects, with a mean intra-subject adjustment deviation of 47.15 ms for single-shot and 44.5 ms for segmented acquisition in three repetitions. DISCUSSION: A first positive assessment of the results was performed on healthy volunteers. The extent to which the results can be transferred to patients and are of benefit must be investigated in follow-up studies.

Whole-Cerebrum distortion-free three-dimensional pseudo-continuous arterial spin labeling at 7T.

Fulfilling potentials of ultrahigh field for pseudo-Continuous Arterial Spin Labeling (pCASL) has been hampered by B1/B0 inhomogeneities that affect pCASL labeling, background suppression (BS), and the readout sequence. This study aimed to present a whole-cerebrum distortion-free three-dimensional (3D) pCASL sequence at 7T by optimizing pCASL labeling parameters, BS pulses, and an accelerated Turbo-FLASH (TFL) readout. A new set of pCASL labeling parameters (Gave = 0.4 mT/m, Gratio = 14.67) was proposed to avoid interferences in bottom slices while achieving robust labeling efficiency (LE). An OPTIM BS pulse was designed based on the range of B1/B0 inhomogeneities at 7T. A 3D TFL readout with 2D-CAIPIRINHA undersampling (R = 2 × 2) and centric ordering was developed, and the number of segments (Nseg) and flip angle (FA) were varied in simulation to achieve the optimal trade-off between SNR and spatial blurring. In-vivo experiments were performed on 19 subjects. The results showed that the new set of labeling parameters effectively achieved whole-cerebrum coverage by eliminating interferences in bottom slices while maintaining a high LE. The OPTIM BS pulse achieved 33.3% higher perfusion signal in gray matter (GM) than the original BS pulse with a cost of 4.8-fold SAR. Incorporating a moderate FA (8°) and Nseg (2), whole-cerebrum 3D TFL-pCASL imaging was achieved with a 2 × 2 × 4 mm3 resolution without distortion and susceptibility artifacts compared to 3D GRASE-pCASL. In addition, 3D TFL-pCASL showed a good to excellent test-retest repeatability and potential of higher resolution (2 mm isotropic). The proposed technique also significantly improved SNR when compared to the same sequence at 3T and simultaneous multislice TFL-pCASL at 7T. By combining a new set of labeling parameters, OPTIM BS pulse, and accelerated 3D TFL readout, we achieved high resolution pCASL at 7T with whole-cerebrum coverage, detailed perfusion and anatomical information without distortion, and sufficient SNR.

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

PURPOSE: 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. METHODS: The SNR of a conventional protocol with nine Look-Locker readouts and a 4 × $$ \times $$ 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. RESULTS: 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%. CONCLUSIONS: 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.

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

PURPOSE: 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. METHODS: 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. RESULTS: Using pCASL, a decrease in CBF of up to 29 . 6 ± 15 . 1 % $$ 29.6\pm 15.1\% $$ was observed in the target hemisphere, associated with an increase in arterial transit time. The latter was estimated to be 533 ± 121ms $$ 533\pm 12\mathrm{1ms} $$ in the BBB opening impacted regions against 409 ± 93ms $$ 409\pm 93\mathrm{ms} $$ in the contralateral hemisphere. The spatio-temporal analysis of CBF maps indicated a nonlocal hypoperfusion. DSC-MRI measurements were consistent with the obtained results. CONCLUSION: 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.

Hybrid B1+ -shimming and gradient adaptions for improved pseudo-continuous arterial spin labeling at 7 Tesla.

PURPOSE: To improve pseudo-continuous arterial spin labeling (pcASL) at 7T by exploiting a hybrid homogeneity- and efficiency-optimized B1+ -shim with adapted gradient strength as well as background suppression. METHODS: The following three experiments were performed at 7T, each employing five volunteers: (1) A hybrid (ie, homogeneity-efficiency optimized) B1+ -shim was introduced and evaluated for variable-rate selective excitation pcASL labeling. Therefore, B1+ -maps in the V3 segment and time-of-flight images were acquired to identify the feeding arteries. For validation, a gradient-echo sequence was applied in circular polarized (CP) mode and with the hybrid B1+ -shim. Additionally, the gray matter (temporal) signal-to-noise ratio (tSNR) in pcASL perfusion images was evaluated. (2) Bloch simulations for the pcASL labeling were conducted and validated experimentally, with a focus on the slice-selective gradients. (3) Background suppression was added to the B1+ -shimmed, gradient-adapted 7T sequence and this was then compared to a matched sequence at 3T. RESULTS: The B1+ -shim improved the signal within the labeling plane (23.6%) and the SNR/tSNR increased (+11%/+11%) compared to its value in CP mode; however, the increase was not significant. In accordance with the simulations, the adapted gradients increased the tSNR (35%) and SNR (45%) significantly. Background suppression further improved the perfusion images at 7T, and this protocol performed as well as a resolution-matched protocol at 3T. CONCLUSION: The combination of the proposed hybrid B1+ -phase-shim with the adapted slice-selective gradients and background suppression shows great potential for improved pcASL labeling under suboptimal B1+ conditions at 7T.

Optimization of pseudo-continuous arterial spin labeling using off-resonance compensation strategies at 7T.

PURPOSE: The sensitivity of pseudo-continuous arterial spin labeling (PCASL) to off-resonance effects (ΔB0 ) is a major limitation at ultra-high field (≥7T). The aim of this study was to assess the effectiveness of different PCASL ΔB0 compensation methods at 7T and measure the labeling efficiency with off-resonance correction. THEORY AND METHODS: Phase offset errors induced by ΔB0 at the feeding arteries can be compensated by adding an extra radiofrequency (RF) phase increment and transverse gradient blips into the PCASL RF pulse train. The effectiveness of an average field correction (AVGcor), a vessel-specific field-map-based correction (FMcor) and a vessel-specific prescan-based correction (PScor) were compared at 7T. After correction, the PCASL labeling efficiency was directly measured in feeding arteries downstream from the labeling location. RESULTS: The perfusion signal was more uniform throughout the brain after off-resonance correction. Whole-brain average perfusion signal increased by a factor of 2.4, 2.5, and 2.1, respectively, with AVGcor, FMcor and PScor compared to acquisitions without correction. With off-resonance correction, the maximum labeling efficiency was ~0.68 at mean B1 (B1mean ) of 0.70 µT when using a mean gradient (Gmean ) of 0.25 mT/m. CONCLUSION: Either a prescan or a field map can be used to correct for off-resonance effects and retrieve a good brain perfusion signal at 7T. Although the three methods performed well in this study, FMcor may be better suited for patient studies because it accounted for vessel-specific ΔB0 variations. Further improvements in image quality will be possible by optimizing the labeling efficiency with advanced hardware and software while satisfying specific absorption rate constraints.

3D pseudo-continuous arterial spin labeling-MRI (3D PCASL-MRI) in the differential diagnosis between glioblastomas and primary central nervous system lymphomas.

PURPOSE: The aim of the study was to compare the parameters of blood flow in glioblastomas and primary central nervous system lymphomas (PCNSLs), measured by pseudo-continuous arterial spin labeling MRI (3D PCASL), and to determine the informativeness of this method in the differential diagnosis between these lesions. METHODS: The study included MRI data of 139 patients with PCNSL (n = 21) and glioblastomas (n = 118), performed in the Burdenko Neurosurgical Center. No patients received chemotherapy, hormone therapy, or radiation therapy prior to MRI. On the 3D PCASL perfusion map, the absolute and normalized values of tumor blood flow were calculated in the glioblastoma and PCNSL groups (maxTBFmean and nTBF). RESULTS: MaxTBFmean and nTBF in the glioblastoma group were significantly higher than those in the PCNSL group: 168.9 ml/100 g/min versus 65.6 and 9.3 versus 3.7, respectively (p < 0.001). Arterial spin labeling perfusion had high sensitivity (86% for maxTBFmean, 95% for nTBF) and specificity (77% for maxTBFmean, 73% for nTBF) in the differential diagnosis between PCNSL and glioblastomas. Blood flow thresholds were 98.9 ml/100 g/min using absolute blood flow values and 6.1 using normalized values, AUC > 0.88. CONCLUSION: The inclusion of 3D PCASL in the standard MRI protocol can increase the specificity of the differential diagnosis between glioblastomas and PCNSL.

Single-shot pseudo-centric EPI for magnetization-prepared imaging.

PURPOSE: To implement a single-shot centric-reordered EPI (1sh-CenEPI), which reduces TE significantly, thus enabling to improve SNR for magnetization-prepared imaging. METHODS: We proposed a 1sh-CenEPI in which grouped oscillating readout gradients, phase-encoding blips within each group, and big phase-encoding jumps between two consecutive groups are incorporated to encode whole k-space from the center to the edges in a single shot. The concept was tested on phantoms and human brains at 3 T. In addition, the proposed reordering scheme was applied to pseudo-continuous arterial spin labeling for evaluating the efficiency of the centric reordering in magnetization-prepared imaging. RESULTS: The proposed 1sh-CenEPI reduced TE from 50 ms to 1.4 ms for gradient-echo EPI, and from 100 ms to 7 ms for spin-echo EPI, while the elongation of readout duration was below 10% of the whole readout duration in most cases. The 1sh-CenEPI images exhibited no distinct geometric distortion both in phantom and human brain, comparable to the conventional two-shot center-out EPI. In pseudo-continuous arterial spin labeling results, 3-fold temporal SNR increase and 2-fold spatial SNR increase in the perfusion-weighted images were achieved with 1sh-CenEPI compared with the conventional linear ordering, whereas the cerebral blood flow values were consistent with previous studies. CONCLUSION: The proposed 1sh-CenEPI significantly reduced TE while maintaining similar readout window and providing images comparable to the conventional linear and multishot center-out EPI images. It can be a qualified candidate as a new readout for various magnetization-prepared imaging techniques.

Three-dimensional gradient and spin-echo readout for time-encoded pseudo-continuous arterial spin labeling: Influence of segmentation factor and flow compensation.

PURPOSE: To monitor the complete passage of the labeled blood through the vascular tree into tissue and improve the quantification of ASL maps, we evaluated the effect of 3D gradient and spin-echo (GRASE) readout segments on temporal SNR (tSNR) and image blurriness for time-encoded pseudo-continuous arterial spin labeling and the effect of flow-compensation gradients on the presence of intravascular signal. METHODS: Fifteen volunteers were scanned using time-encoded pCASL with 2D EPI and single-segment, two-segments, and three-segments 3D-GRASE readouts with first-order flow compensation (FC) gradients. Two-segments 3D-GRASE scans were acquired with 25%, 50%, 75%, and 100% of full first-order FC. Temporal SNR was assessed, and cerebral blood flow and arterial blood volume were quantified for all readout strategies. RESULTS: For single-segment 3D GRASE, tSNR was comparable to 2D EPI for perfusion signal but worse for the arterial signal. Two-segments and three-segments 3D GRASE resulted in higher tSNR than 2D EPI for perfusion and arterial signal. The arterial signal was not well visualized for 3D-GRASE data without FC. Visualization of the intravascular signal at postlabeling delays of 660 ms and 1060 ms was restored with FC. Adequate visualization of the intravascular signal was achieved from 75% of FC gradient strength at a postlabeling delay of 660 ms. For a postlabeling delay of 1060 ms, full-FC gradients were the best option to depict intravascular signal. CONCLUSION: Segmented GRASE provided higher effective tSNR compared with 2D-EPI and single-segment GRASE. Flow compensation with GRASE readout should be carefully controlled when applying for time-encoded pCASL to visualize intravascular signal.

Optimization of pseudo-continuous arterial spin labeling for renal perfusion imaging.

PURPOSE: To evaluate labeling efficiency of pseudo-continuous arterial spin labeling (PCASL) and to find the gradient parameters that increase PCASL robustness for renal perfusion measurements. METHODS: Aortic blood flow was characterized in 3 groups: young healthy volunteers (YHV1), chronic kidney disease (CKD) patients (CKDP), and healthy controls (HCO). PCASL inversion efficiency was evaluated through numeric simulations considering the measured pulsatile flow velocity profiles and off-resonance effects for a wide range of gradient parameters, and the results were assessed in vivo. The most robust PCASL implementation was used to measure renal blood flow (RBF) in CKDP and HCO. RESULTS: Aortic blood velocities reached peak values of 120 cm/s in YHV1, whereas for elderly subjects values were lower by approximately a factor of 2. Simulations and experiments showed that by reducing the gradient average (Gave ) and the selective to average gradient ratio (Gmax /Gave ), labeling efficiency was maximized and PCASL robustness to off-resonance was improved. The study in CKDP and HCO showed significant differences in RBF between groups. CONCLUSION: An efficient and robust PCASL scheme for renal applications requires a Gmax /Gave ratio of 6-7 and a Gave value that depends on the aortic blood flow velocities (0.5 mT/m being appropriate for CKDP and HCO).

Utility of susceptibility weighted imaging (SWI) and pseudo-continuous arterial spin labeling (pCASL) in diagnosis of falcine venous thrombosis in a child with transient ischemic attack.

Pediatric stroke and transient ischemic attack (TIA) are uncommon but true emergencies with a wide differential diagnosis. Diagnostic imaging plays a critical role in differentiating the diverse range of etiologies. In this case, we report a 3-year-old female with no medical history who developed acute neurological deficits and demonstrate how adjunct advanced imaging including susceptibility weighted imaging (SWI) and pseudo-continuous arterial spin labeling (pCASL) can play a significant diagnostic role in the emergent setting. Imaging was performed with a Philips Ingenia 3.0T MRI. MRI brain, MR angiography (MRA), and phase contrast angiography MR Venography (PCA-MRV) were obtained. pCASL and SWI sequences were performed using SENSE (sensitivity encoding) parallel imaging techniques. MRI/MRA brain showed no restricted diffusion, abnormal T1/T2/FLAIR signal, arterial occlusion, or irregular angioarchitecture. SWI revealed increased susceptibility along the posterior falx cerebri and right posterior parietal and occipital lobes, and pCASL showed decreased blood flow within these same regions. No falcine sinus was visualized on PCA-MRV, but SWI and pCASL findings led to diagnosis of falcine sinus thrombosis and initiation of appropriate treatment. Repeat MRI one month later showed interval resolution of the abnormal SWI findings and a now patent persistent falcine sinus visualized on PCA-MRV imaging. Routine use of SWI imaging on all brain MRIs and addition of pCASL imaging when there is concern for ischemia or infarction in the emergent setting can limit the risk of missed occult diagnoses like a thrombosed falcine sinus.

The effect of spiral trajectory correction on pseudo-continuous arterial spin labeling with high-performance gradients on a compact 3T scanner.

PURPOSE: To demonstrate the feasibility of pseudo-continuous arterial-spin-labeled (pCASL) imaging with 3D fast-spin-echo stack-of-spirals on a compact 3T scanner (C3T), to perform trajectory correction for eddy-current-induced deviations in the spiral readout of pCASL imaging, and to assess the correction effect on perfusion-related images with high-performance gradients (80 mT/m, 700T/m/s) of the C3T. METHODS: To track eddy-current-induced artifacts with Archimedean spiral readout, the spiral readout in pCASL imaging was performed with 5 different peak gradient slew rate (Smax ) values ranging from 70 to 500 T/m/s. The trajectory for each Smax was measured using a dynamic field camera and applied in a density-compensated gridding image reconstruction in addition to the nominal trajectory. The effect of the trajectory correction was assessed with perfusion-weighted (ΔM) images and proton-density-weighted images as well as cerebral blood flow (CBF) maps, obtained from 10 healthy volunteers. RESULTS: Blurring artifact on ΔM images was mitigated by the trajectory correction. CBF values on the left and right calcarine cortices showed no significant difference after correction. Also, the signal-to-noise ratio of ΔM images improved, on average, by 7.6% after correction (P < .001). The greatest improvement of 12.1% on ΔM images was achieved with a spiral readout using Smax of 300~400 T/m/s. CONCLUSION: Eddy currents can cause spiral trajectory deviation, which leads to deformation of the CBF map even in cases of low value Smax . The trajectory correction for spiral-readout-based pCASL produces more reliable results for perfusion imaging. These results suggest that pCASL is feasible on C3T with high-performance gradients.

Increased cerebral blood flow with increased amyloid burden in the preclinical phase of alzheimer's disease.

BACKGROUND: Arterial spin labeling (ASL) is an emerging MRI technique for noninvasive measurement of cerebral blood flow (CBF) that has been used to show hemodynamic changes in the brains of people with Alzheimer's disease (AD). CBF changes have been measured using positron emission tomography (PET) across the AD spectrum, but ASL showed limited success in measuring CBF variations in the preclinical phase of AD, where amyloid ß (Aß) plaques accumulate in the decades prior to symptom onset. PURPOSE: To investigate the relationship between CBF measured by multiphase-pseudocontinuous-ASL (MP-PCASL) and Aß burden as measured by 11 C-PiB PET imaging in a study of cognitively normal (CN) subjects age over 65. STUDY TYPE: Cross-sectional. POPULATION: Forty-six CN subjects including 33 with low levels of Aß burden and 13 with high levels of Aß. FIELD STRENGTH/SEQUENCE: 3T/3D MP-PCASL. ASSESSMENT: The MP-PCASL method was chosen because it has a high signal-to-noise ratio. Furthermore, the data were analyzed using an efficient processing pipeline consisting of motion correction, ASL motion correction imprecision removal, temporal and spatial filtering, and partial volume effect correction. STATISTICAL TESTS: General Linear Model. RESULTS: In CN subjects positive for Aß burden (n = 13), we observed a positive correlation between CBF and Aß burden in the hippocampus, amygdala, caudate (P < 0.01), frontal, temporal, and insula (P < 0.05). DATA CONCLUSION: To the best of our knowledge, this is the first study using MP-PCASL in the study of AD, and the results suggest a potential compensatory hemodynamic mechanism that protects against pathology in the early stages of AD. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:505-513.

Imaging Pulmonary Blood Flow Using Pseudocontinuous Arterial Spin Labeling (PCASL) With Balanced Steady-State Free-Precession (bSSFP) Readout at 1.5T.

BACKGROUND: Quantitative assessment of pulmonary blood flow and visualization of its temporal and spatial distribution without contrast media is of clinical significance. PURPOSE: To assess the potential of electrocardiogram (ECG)-triggered pseudocontinuous arterial spin labeling (PCASL) imaging with balanced steady-state free-precession (bSSFP) readout to measure lung perfusion under free-breathing (FB) conditions and to study temporal and spatial characteristics of pulmonary blood flow. STUDY TYPE: Prospective, observational. SUBJECTS: Fourteen volunteers; three patients with pulmonary embolism. FIELD STRENGTH/SEQUENCES: 1.5T, PCASL-bSSFP. ASSESSMENT: The pulmonary trunk was labeled during systole. The following examinations were performed: 1) FB and timed breath-hold (TBH) examinations with a postlabeling delay (PLD) of 1000 msec, and 2) TBH examinations with multiple PLDs (100-1500 msec). Scan-rescan measurements were performed in four volunteers and one patient. Images were registered and the perfusion was evaluated in large vessels, small vessels, and parenchyma. Mean structural similarity indices (MSSIM) was computed and time-to-peak (TTP) of parenchymal perfusion in multiple PLDs was evaluated. Image quality reading was performed with three independent blinded readers. STATISTICAL TESTS: Wilcoxon test to compare MSSIM, perfusion, and Likert scores. Spearman's correlation to correlate TTP and cardiac cycle duration. The repeatability coefficient (RC) and within-subject coefficient of variation (wCV) for scan-rescan measurements. Intraclass correlation coefficient (ICC) for interreader agreement. RESULTS: Image registration resulted in a significant (P < 0.05) increase of MSSIM. FB perfusion values were 6% higher than TBH (3.28 ± 1.09 vs. 3.10 ± 0.99 mL/min/mL). TTP was highly correlated with individuals' cardiac cycle duration (Spearman = 0.89, P < 0.001). RC and wCV were better for TBH than FB (0.13-0.19 vs. 0.47-1.54 mL/min/mL; 6-7 vs. 19-60%). Image quality was rated very good, with ICCs 0.71-0.89. DATA CONCLUSION: ECG-triggered PCASL-bSSFP imaging of the lung at 1.5T can provide very good image quality and quantitative perfusion maps even under FB. The course of labeled blood through the lung shows a strong dependence on the individuals' cardiac cycle duration. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2 J. MAGN. RESON. IMAGING 2020;52:1767-1782.

Robust pCASL perfusion imaging using a 3D Cartesian acquisition with spiral profile reordering (CASPR).

PURPOSE: To improve the robustness of arterial spin-labeled measured perfusion using a novel Cartesian acquisition with spiral profile reordering (CASPR) 3D turbo spin echo (TSE) in the brain and kidneys. METHODS: The CASPR view ordering followed a pseudo-spiral trajectory on a Cartesian grid, by sampling the center of k-space at the beginning of each echo train of a segmented 3D TSE acquisition. With institutional review board approval and written informed consent, 14 normal subjects (9 brain and 5 kidneys) were scanned with pCASL perfusion imaging using 3D CASPR and compared against 3D linear TSE (brain and kidneys), the established 2D EPI and 3D gradient and spin echo perfusion (brain), and 2D single-shot turbo spin-echo perfusion (kidneys). The SNR and the quantitative perfusion values were compared among different acquisitions. RESULTS: 3D CASPR TSE achieved robust perfusion across all slices compared to 3D linear TSE in the brain and kidneys. Compared to 2D EPI, 3D CASPR TSE showed higher SNR across the brain (P < 0.01), and exhibited good agreement (36.4 ± 4.7 and 36.9 ± 5.3 mL/100 g/min with 2D EPI and 3D CASPR, respectively), and with 3D gradient and spin echo (27.9 ± 7.2 mL/100 g/min). Compared to a single slice 2D single-shot turbo spin-echo acquisition, 3D CASPR TSE achieved robust perfusion across the entire kidneys in similar scan time with comparable quantified perfusion values (154.1 ± 74.6 and 151.7 ± 70.6 mL/100 g/min with 2D single-shot turbo spin-echo and 3D CASPR, respectively). CONCLUSION: The CASPR view ordering with 3D TSE achieves robust arterial spin-labeled perfusion in the brain and kidneys because of the sampling of the center of k-space at the beginning of each echo train.

Pancreatic perfusion and arterial-transit-time quantification using pseudocontinuous arterial spin labeling at 3T.

PURPOSE: To demonstrate the feasibility of noninvasively measuring pancreatic perfusion using pseudocontinuous arterial spin labeling (ASL) and to derive quantitative blood-flow and transit-time measurements in healthy volunteers. METHODS: A pseudocontinuous ASL sequence with background suppression and a single-slice single-shot fast-spin-echo readout was acquired at 3 T in 10 subjects with a single standard postlabeling delay (PLD) of 1.5 s and in 4 additional subjects with 4 PLD from 0.7 to 2 s. An imaging synchronized breathing approach was used to minimize motion artifacts during the 3 min of acquisition. Scan-rescan reproducibility was assessed in 3 volunteers with single-delay ASL. Quantitative blood flow and arterial transit time (ATT) were derived and the impact of ATT correction was studied using either subject-specific ATT in the second group or an average ATT derived from the group with multidelay ASL for subjects with single-delay ASL. RESULTS: Successful ASL acquisitions were performed in all volunteers. An average pancreatic blood flow of 201 ± 40 mL/100 g/min was measured in the single-delay group using an assumed ATT of 750 ms Average ATT measured in the multidelay group was 1029 ± 89 ms Using the longer, measured ATT reduced the measured flow to 162 ± 12 and 168 ± 28 mL/100 g/min with subject-specific or average ATT correction, respectively. ASL signal heterogeneities were observed at shorter PLD, potentially linked to its complex vascular supply and islet distribution. CONCLUSIONS: ASL enables reliable measurement of pancreatic perfusion in healthy volunteers. It presents a valuable alternative to contrast-enhanced methods and may be useful for diagnosis and characterization of several inflammatory, metabolic, and neoplastic diseases affecting the pancreas.

Optimization of the spatial modulation function of vessel-encoded pseudo-continuous arterial spin labeling and its application to dynamic angiography.

PURPOSE: In vessel-encoded pseudo-continuous arterial spin labeling (ve-pCASL), vessel-selective labeling is achieved by modulation of the inversion efficiency across space. However, the spatial transition between the labeling and control conditions is rather gradual, which can cause partial labeling of vessels, reducing SNR-efficiency and necessitating complex postprocessing to decode the vessel-selective signals. The purpose of this study is to optimize the pCASL labeling parameters to obtain a sharper spatial inversion profile of the labeling and thereby minimizing the risk of partial labeling of untargeted arteries. METHODS: Bloch simulations were performed to investigate how the inversion profile was influenced by the pCASL labeling parameters: the maximum (Gmax ) and mean (Gmean ) labeling gradient were varied for ve-pCASL with unipolar and bipolar gradients. The findings in the simulation study were subsequently confirmed in an in vivo volunteer study. Moreover, conventional and optimized settings were compared for 4D-MRA using four-cycle Hadamard ve-pCASL; the visualization of arteries and the presence of the partial labeling were assessed by an expert observer. RESULTS: When using unipolar gradient, lower Gmean resulted in a steeper spatial transition, whereas the width of the control region was broader for higher Gmax . The in vivo study confirmed these findings. When using bipolar gradients, the control region was always very narrow. Qualitative comparison of the 4D-MRA demonstrated lower occurrence of partial labeling when using the optimized gradient parameters. CONCLUSION: The shape of the ve-pCASL inversion profile can be optimized by changing Gmean and Gmax to reduce partial labeling of untargeted arteries.