Short Acquisition Time PET Quantification Using MRI-Based Pharmacokinetic Parameter Synthesis

How far is arterial spin labeling MRI from a clinical reality? Insights from arterial spin labeling comparative studies in Alzheimer's disease and other neurological disorders.

Purpose:Arterial spin labeling (ASL) is an MRI perfusion imaging method from which quantitative cerebral blood flow (CBF) maps can be calculated. Acquisition with variable post‐labeling delays (PLD) and variable TRs allows for arterial transit time (ATT) mapping and leads to more accurate CBF quantification with a scan time saving of 48%. In addition, T1 and M0 maps can be obtained without a separate scan. In order to accurately estimate ATT and T1 of brain tissue from the ASL data, variable labeling durations were invented, entitled variable‐bolus ASL.Methods:All images were collected on a healthy subject with a 3T Siemens Skyra scanner. Variable‐bolus Psuedo‐continuous ASL (PCASL) images were collected with 7 TI times ranging 100‐4300ms in increments of 700ms with TR ranging 1000‐5200ms. All boluses were 1600ms when the TI allowed, otherwise the bolus duration was 100ms shorter than the TI. All TI times were interleaved to reduce sensitivity to motion. Voxel‐wise T1 and M0 maps were estimated using a linear least squares fitting routine from the average singal from each TI time. Then pairwise subtraction of each label/control pair and averaging for each TI time was performed. CBF and ATT maps were created using the standard model by Buxton et al. with a nonlinear fitting routine using the T1 tissue map.Results:CBF maps insensitive to ATT were produced along with ATT maps. Both maps show patterns and averages consistent with literature. The T1 map also shows typical T1 contrast.Conclusion:It has been demonstrated that variablebolus ASL produces CBF maps free from the errors due to ATT and tissue T1 variations and provides M0, T1, and ATT maps which have potential utility. This is accomplished with a single scan in a feasible scan time (under 6 minutes) with low sensivity to motion.

Objective To investigate alterations of blood perfusion in subcortical regions in patients with Parkinson′s disease (PD) by three dimentional arterial spin labeling (ASL) magnetic resonance imaging (MRI). Methods Thirty patients with PD and 40 control subjects were recruited from the inpatient and outpatient of the Department of Neurology of Northern Jiangsu People′s Hospital during October 2014 to October 2016, and routine brain MRI and 3D pseudo-continuous pulse ASL were performed on all the subjects. The cerebral blood flow (CBF) maps derived from 3D ASL were coregistered to the Montreal Neurological Institute brain space. The stereo-templates of bilateral caudate nucleus, putamen nucleus, globus pallidum and thalamus from Anatomical Automatic Labeling were used as region of interest (ROI) to exstract absolute CBF values in these subcortical regions, respectively. The CBF ratio (rCBF) values represented by individual whole brain CBF divided by each of the regional CBF were also calculated in consideration of the difference between individual whole brain CBF. The CBF and rCBF values were compared respectively between groups by one-way analysis of variance. Results The subcortical CBF values (ml·100 g-1·min-1) for each ROI in PD (caudate nucleus (left: 35.32±6.47, right: 36.17±7.07), globus pallidum (left: 40.42±5.83, right: 40.18±5.70), putamen nucleus (left: 41.97±6.12, right: 42.91±6.43) and thalamus (left: 46.58±7.71, right: 49.11±7.10)) were significantly lower than that in the control group (caudate nucleus (left: 41.38±7.05, right: 41.63±6.85), globus pallidum (left: 45.65±8.35, right: 45.53±8.94), putamen nucleus (left: 48.49±8.78, right: 48.99±8.88) and thalamus (left: 54.32±11.94, right: 56.21±11.98), F=13.58, 10.56, 12.11, 10.06, 8.59, 8.23, 9.57, 8.30, P=0.000, 0.002, 0.005, 0.005, 0.001, 0.002, 0.003, 0.005, respectively). The whole brain mean CBF values of each subject were also extracted and compared bewteen groups, and mean CBF values (ml·100 g-1·min-1) in PD patients (42.14±9.61) decreased significantly than those in the control group (51.59±9.67, F=16.42, P<0.01), and there was a 18.31% decrement in whole brain mean CBF in the patient group. However, rCBF values for almost all subcortical ROIs of the patients significantly increased when compared with the control group. Conclusions The decreased absolute cerebral blood perfusion involved not only subcortical regions, but also the whole brain level in the course of PD. The CBF metabolism in patients with PD may have been redistributed, with relative hyperperfusion in the subcortical brain regions contrast to the whole brain perfusion level of patients themselves. Key words: Parkinson disease; Brain; Regional blood flow; Magnetic resonance imaging; Arterial spin labeling

The routine use of arterial spin-labeling (ASL) in a clinical population has led to the depiction of diverse brain pathologic features. Unique challenges in the acquisition, postprocessing, and analysis of cerebral blood flow (CBF) maps are encountered in such a population, and high-quality ASL CBF maps can be generated consistently with attention to quality control and with the use of a dedicated postprocessing pipeline. Familiarity with commonly encountered artifacts can help avoid pitfalls in the interpretation of CBF maps. The purpose of this review was to describe our experience with a heterogeneous collection of ASL perfusion cases with an emphasis on methodology and common artifacts encountered with the technique. In a period of 1 year, more than 3000 pulsed ASL cases were performed as a component of routine clinical brain MR evaluation at both 1.5 and 3T. These ASL studies were analyzed with respect to overall image quality and patterns of perfusion on final gray-scale DICOM images and color Joint Photographic Experts Group (JPEG) CBF maps, and common artifacts and their impact on final image quality were categorized.

Because arterial spin labeling (ASL) is completely noninvasive and provides absolute cerebral blood flow (CBF) information within a brief period, the technique has been increasingly used for patients with acute or chronic cerebrovascular disease. However, the effect of delayed transit time on ASL can generate errors in the quantitative estimation of CBF using ASL. Furthermore, in the clinical setting, in which transit time is uncertain, the variability of the transit time in patients reduces the validity of CBF on ASL images. Therefore, we evaluated the effect of delayed transit time on ASL images compared with dynamic susceptibility contrast (DSC) perfusion magnetic resonance (MR) in patients with moyamoya disease. Arterial spin labeling and DSC perfusion MR images were acquired in 54 patients with moyamoya disease. Vascular territory and anatomical structure-based regions of interest (ROIs) were applied to the CBF and time-to-peak (TTP) maps from DSC and a CBF map using ASL. The change of the correlation coefficient (r) between normalized CBFs (nCBFs) from DSC and ASL was evaluated with categorization by the TTP. In addition, the dependence of the difference between the nCBF values from DSC and ASL on the TTP obtained using DSC was also analyzed. The nCBF values from DSC and ASL were strongly correlated (r = 0.877 and r = 0.867 for the internal carotid artery (ICA) and middle cerebral artery territory-based ROIs, respectively; P < 0.0002 for both; r = 0.783 for the anatomical structure-based ROIs; P < 0.0084). However, correlations between nCBFs from DSC and ASL tended to be weaker when the TTP increased, with recovery when the TTP was extremely delayed (>25 seconds). The TTP delay had a positive effect on the difference between the nCBF values from the DSC and ASL for the ICA territory-based and anatomical structure-based ROIs (standardized coefficients, 0.224 for the ICA territory-based ROIs; P = 0.0410; 0.189 for the anatomical structure-based ROIs; P < 0.0084). Our results demonstrate that the correlation between the CBF values from the ASL and DSC tends to be weaker when the transit time is more delayed, with the restoration of the strength of the correlation when the TTP is extremely delayed (>25 seconds). Understanding the effect of delayed transit time on the CBF from ASL perfusion MR in a clinical setting would facilitate the proper interpretation of ASL images.

Quantitative perfusion assessment with arterial spin labeling magnetic resonance imaging for predicting cognitive decline in Alzheimer's disease: A systematic review and meta-analysis.

Pharmacokinetic modelling on dynamic positron emission tomography (PET) data is a quantitative technique. However, the long acquisition time is prohibitive for routine clinical use. Instead, the semi-quantitative standardised uptake value ratio (SUVR) from a shorter static acquisition is used, despite its sensitivity to blood flow confounding longitudinal analysis. A method has been proposed to reduce the dynamic acquisition time for quantification by incorporating cerebral blood flow (CBF) information from arterial spin labelling (ASL) magnetic resonance imaging (MRI) into the pharmacokinetic modelling. In this work, we optimise and validate this framework for a study of ageing and preclinical Alzheimer's disease. This methodology adapts the simplified reference tissue model (SRTM) for a reduced acquisition time (RT-SRTM) and is applied to [18F]-florbetapir PET data for amyloid-β quantification. Evaluation shows that the optimised RT-SRTM can achieve amyloid burden estimation from a 30-min PET/MR acquisition which is comparable with the gold standard SRTM applied to 60 min of PET data. Conversely, SUVR showed a significantly higher error and bias, and a statistically significant correlation with tracer delivery due to the influence of blood flow. The optimised RT-SRTM produced amyloid burden estimates which were uncorrelated with tracer delivery indicating its suitability for longitudinal studies.

Objective Cerebral blood flow (CBF) mapping of single-photon emission tomography (SPECT) is considered a gold standard for evaluating cerebral perfusion. However, invasiveness, high costs and strict technical requirements can limit its clinical use. We aimed to evaluate the concordance of CBF maps obtained from SPECT and pseudo-continuous arterial spin labeling magnetic resonance (PCASL-MR) imaging for evaluating cerebral perfusion. Methods PCASL-MR/SPECT-CBF maps were obtained from 16 eligible patients with unilateral middle cerebral artery stenosis (MCAS). Three slices (basal ganglia, semi-oval center and cerebellum) on both PCASL-MR and SPECT maps were divided into different regions of interest (ROIs) according to the ASPECT criterion, arterial territories, and cerebral hemispheres, respectively. The concordance of the two types of CBF maps and the specificity and sensitivity of PCASL-MR imaging on predicting regional hypoperfusion were calculated. Results A total of 448 ROIs were divided according to the ASPECT criterion, 192 ROIs partitioned in accordance with arterial territories, and 96 ROIs delineated based on cerebral hemispheres were analyzed. PCASL-MR imaging exhibited 83.78% to 100% sensitivity, 90.19% to 95.83% specificity for detection of hypoperfusion. Qualitative analyses revealed a strong concordance between PCASL-MR and SPECT on reflecting regional cerebral hypoperfusion (Kappa coefficient = 0.662–0.920, p < 0.01). Semi-quantitative analysis by ΔCBF revealed moderate consistency (Spearman correlation coefficient = 0.610–0.571). Conclusions Our findings suggest that PCASL-MR may be a promising non-invasive, inexpensive alternative to SPECT for evaluating cerebral perfusion accurately in patients with symptomatic MCAS.

BackgroundWhite matter lesions (WMLs) have been linked to cognitive decline in Alzheimer’s disease (AD), but physiological mechanisms associated with microvascular dysfunction in white matter remain incompletely understood. The purpose of this study was to investigate associations between arterial spin labeling (ASL) magnetic resonance imaging (MRI) markers of white matter hemodynamics and aging, cognitive function, and WML burden.Method Study design. Participants (n=234) provided written consent for this IRB‐approved cross‐sectional study as part of the Human Connectome Aging Project. Participants underwent a range of health and cognitive assessments, including the Montreal Cognitive Assessment (MoCA), and 3 Tesla MRI. Structural imaging. High‐resolution T1‐weighted images were acquired for co‐registration and were processed with FreeSurfer for calculation of white matter signal abnormalities as a measure of WML burden. Hemodynamic imaging. ASL data were acquired using a labeling duration=1500 ms and five equally spaced post‐labeling delays from 200‐2200 ms with spatial resolution=2.5x2.5x2.5 mm3. ASL images were corrected for distortion and for motion. Cerebral blood flow (CBF) and arterial transit time (ATT) were computed using a cross‐correlation approach and a two‐compartment model. Data analysis. Mean CBF and ATT values were calculated inside white matter masks derived using FreeSurfer for each subject and assessed as a function of age, WML burden, and MoCA score.ResultWe found an inverse association between white matter CBF and age (p&lt;0.001) and a direct association between white matter ATT and age (p&lt;0.001), where increasing age corresponded to lower CBF and longer ATT. After including age as a covariate, we found a trend for an inverse relationship between white matter CBF and WML burden (p=0.064), with lower CBF indicating higher WML burden (Figure 2). Lastly, we also found a trend for an inverse association between white matter ATT and MoCA score (p=0.097), with longer ATT indicating lower MoCA scores (Figure 3).ConclusionPreliminary results indicate that impaired hemodynamic properties (lower white matter CBF and longer white matter ATT) may be associated with elevated WML burden and poorer cognition. Further longitudinal studies are necessary to determine whether white matter hemodynamic may represent a prospective marker of WML burden and associated cognitive impairment.

Purpose: Hyperperfusion detected on arterial spin labeling (ASL) cerebral blood flow (CBF) images acquired after acute ischemic stroke (AIS) onset has been shown to be significantly associated with development of intracerebral hemorrhage. ASL data is often too noisy for accurate voxel-based analysis alone. The purpose of this study was to develop a machine learning model for the voxel-based detection of tissue at risk for hemorrhagic transformation (HT) utilizing multiple MRI modalities. Materials and Methods: The present study utilized clinical MRI and ASL image data acquired from 67 AIS patients shortly after endovascular therapy. A novel regional cuboid sampling framework was developed for machine learning training, in which local cuboids were extracted from the CBF map, DWI, FLAIR, and TSE images before being matched with GRE-based manually drawn bleed groundtruth delineations. Kernel spectral regression (KSR) uses the eigenvectors of the graph representation to reveal low dimensional structure in high dimensional data. A two-layer feed-forward neural network was then built with 10 neurons in the sigmoid hidden layer and trained with scaled conjugate gradient backpropagation to classify cuboid inputs into likelihood of HT. Results: The proposed multimodal regional framework reached an accuracy of 80.59 ± 3% in detecting hemorrhage with KSR on our dataset (better than a voxel-based prediction on CBF with 72.80 ± 5% accuracy). Using the neural network training, the framework reached an improved accuracy of 95.1% ± 0.6%. Figure 1 shows how the regions with high likelihood of hemorrhage match well with the manually drawn regions in the reference GRE map. Conclusion: Kernel spectral regression and neural networks can provide more accurate detection of tissues at risk for HT. Although CBF can inform AIS patient clinical outcome, the addition of multi-modal MRI data into the regional cuboid framework substantially improves the voxel-based HT detection accuracy.

Absolute and regional cerebral perfusion assessment feasibility in head-down position with arterial spin-labeling magnetic resonance. A preliminary report on healthy subjects

Robust collateral blood vessels have been associated with better neurologic outcome following acute ischemic stroke (AIS). The most commonly used methods for identifying collaterals are contrast-based angiographic imaging techniques, which are not possible in all patients after AIS. To assess the association between the presence of collateral vessels identified using arterial spin labeling (ASL) magnetic resonance imaging, a technique that does not require exogenous administration of contrast, and neurologic outcome in patients after AIS. This retrospective cohort study examined 38 patients after AIS admitted to a tertiary academic medical center between 2012 and 2014 who underwent MRI with ASL. According to a prespecified hypothesis, ASL images were graded for the presence of collaterals by 2 neuroradiologists. Modified Rankin Scale (mRS) scores at discharge and other composite data were abstracted from the medical record by a neurologist blinded to radiologic data. Of the 38 patients, 19 (50.0%) were male, and the mean (SD) age was 61 (20) years. In 25 of 38 patients (65.8%), collaterals were detected using ASL, which were significantly associated with both a good outcome (mRS score of 0-2 at discharge; P = .02) and a 1-point decrease in mRS score at discharge (odds ratio, 6.4; 95% CI, 1.7-23.4; P = .005). In a multivariable ordinal logistic regression model, controlling for admission National Institutes of Health Stroke Scale score, history of atrial fibrillation, premorbid mRS score, and stroke parent artery status, there was a strong association between the presence of ASL collaterals and a 1-point decrease in the mRS score at discharge (odds ratio, 5.1; 95% CI, 1.2-22.1; P = .03). Following AIS, the presence of ASL collaterals is strongly associated with better neurological outcome at hospital discharge. This novel association between ASL collaterals and improved neurologic outcome may help guide prognosis and management, particularly in patients who are unable to undergo contrast-based radiological studies.

To determine the most suitable postprocessing technique for magnetic resonance (MR) perfusion imaging in patients with vascular stenosis, by comparing the cerebral blood flow (CBF) maps of single photon emission tomography (SPECT) and perfusion MR imaging (MRI). In 15 consecutive patients (14 men and one woman, mean age 73.9 +/- 6.0 years) with stenosis of common carotid artery (CCA) or internal carotid artery (ICA) of more than 75%, both brain perfusion MRI and brain perfusion SPECT were performed. From perfusion MR images, CBF maps were calculated with the first moment, singular value decomposition (SVD), and block circulant SVD (b-SVD) methods, and CBF maps from each algorithm were compared with those from SPECT. The b-SVD method had the best correlation with SPECT (R = 0.814), followed by the first moment method (R = 0.776) and the SVD method (R = 0.723). The b-SVD method has the least mean difference with SPECT (0.118), the first moment method also had less difference (0.121), and the SVD had greatest mean difference (0.164). Our results suggest that in patients with vascular impairment the b-SVD method will be the technique of choice rather than SVD or first moment method.

To evaluate the effectiveness of a fully automated postprocessing filter algorithm in pulsed arterial spin labeling (PASL) MRI perfusion images in a large clinical population. A mean and standard deviation-based filter was implemented to remove outliers in the set of perfusion-weighted images (control - label) before being averaged and scaled to quantitative cerebral blood flow (CBF) maps. Filtered and unfiltered CBF maps from 200 randomly selected clinical cases were assessed by four blinded raters to evaluate the effectiveness of the filter. The filter salvaged many studies deemed uninterpretable as a result of motion artifacts, transient gradient, and/or radiofrequency instabilities, and unexpected disruption of data acquisition by the technologist to communicate with the patient. The filtered CBF maps contained significantly (P < 0.05) fewer artifacts and were more interpretable than unfiltered CBF maps as determined by one-tail paired t-test. Variations in MR perfusion signal related to patient motion, system instability, or disruption of the steady state can introduce artifacts in the CBF maps that can be significantly reduced by postprocessing filtering. Diagnostic quality of the clinical perfusion images can be improved by performing selective averaging without a significant loss in perfusion signal-to-noise ratio.

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