Comparison of 3 Methods of Automated Internal Carotid Segmentation in Human Brain PET Studies: Application to the Estimation of Arterial Input Function

Abstract Background Previous studies found that the positron emission tomography (PET) radioligand [18F]LSN3316612 accurately quantified O-GlcNAcase in human brain using a two-tissue compartment model (2TCM). This study sought to assess kinetic model(s) as an alternative to 2TCM for quantifying [18F]LSN3316612 binding, particularly in order to generate good-quality parametric images. Methods The current study reanalyzed data from a previous study of 10 healthy volunteers who underwent both test and retest PET scans with [18F]LSN3316612. Kinetic analysis was performed at the region level with 2TCM using 120-min PET data and arterial input function, which was considered as the gold standard. Quantification was then obtained at both the region and voxel levels using Logan plot, Ichise's multilinear analysis-1 (MA1), standard spectral analysis (SA), and impulse response function at 120 min (IRF120). To avoid arterial sampling, a noninvasive relative quantification (standardized uptake value ratio (SUVR)) was also tested using the corpus callosum as a pseudo-reference region. Venous samples were also assessed to see whether they could substitute for arterial ones. Results Logan and MA1 generated parametric images of good visual quality and their total distribution volume (VT) values at both the region and voxel levels were strongly correlated with 2TCM-derived VT (r = 0.96–0.99) and showed little bias (up to − 8%). SA was more weakly correlated to 2TCM-derived VT (r = 0.93–0.98) and was more biased (~ 16%). IRF120 showed a strong correlation with 2TCM-derived VT (r = 0.96) but generated noisier parametric images. All techniques were comparable to 2TCM in terms of test–retest variability and reliability except IRF120, which gave significantly worse results. Noninvasive SUVR values were not correlated with 2TCM-derived VT, and arteriovenous equilibrium was never reached. Conclusions Compared to SA and IRF, Logan and MA1 are more suitable alternatives to 2TCM for quantifying [18F]LSN3316612 and generating good-quality parametric images.

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Noninvasive Estimation of the Arterial Input Function in Positron Emission Tomography Imaging of Cerebral Blood Flow

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2012.143 ◽

2012 ◽

Vol 33 (1) ◽

pp. 115-121 ◽

Cited By ~ 33

Author(s):

Yi Su ◽

Ana M Arbelaez ◽

Tammie LS Benzinger ◽

Abraham Z Snyder ◽

Andrei G Vlassenko ◽

...

Keyword(s):

Positron Emission Tomography ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Carotid Artery ◽

Internal Carotid ◽

Arterial Input Function ◽

Input Function ◽

Emission Tomography ◽

Positron Emission ◽

Arterial Sampling

Positron emission tomography (PET) with 15O-labeled water can provide reliable measurement of cerebral blood flow (CBF). Quantification of CBF requires knowledge of the arterial input function (AIF), which is usually provided by arterial blood sampling. However, arterial sampling is invasive. Moreover, the blood generally is sampled at the wrist, which does not perfectly represent the AIF of the brain, because of the effects of delay and dispersion. We developed and validated a new noninvasive method to obtain the AIF directly by PET imaging of the internal carotid artery in a region of interest (ROI) defined by coregistered high-resolution magnetic resonance angiography. An ROI centered at the petrous portion of the internal carotid artery was defined, and the AIF was estimated simultaneously with whole brain blood flow. The image-derived AIF (IDAIF) method was validated against conventional arterial sampling. The IDAIF generated highly reproducible CBF estimations, generally in good agreement with the conventional technique.

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Quantification of human brain PDE4 occupancy by GSK356278: A [11C](R)-rolipram PET study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x17720868 ◽

2017 ◽

Vol 38 (11) ◽

pp. 2033-2040 ◽

Cited By ~ 3

Author(s):

Jasper van der Aart ◽

Cristian Salinas ◽

Rahul Dimber ◽

Sabina Pampols-Maso ◽

Ashley A Weekes ◽

...

Keyword(s):

Human Brain ◽

Arterial Input Function ◽

Compartment Model ◽

Input Function ◽

Post Dose ◽

Emission Data ◽

Pet Tracer ◽

Positron Emission ◽

Tolerability Data

We characterized the relationship between the plasma concentration of the phospodiesterase (PDE)-4 inhibitor GSK356278 and occupancy of the PDE4 enzyme in the brain of healthy volunteers, using the positron emission tomography (PET) tracer [11C](R)-rolipram. To this end, PET scans were acquired in eight male volunteers before and at 3 and 8 h after a single 14 mg oral dose of GSK356278. A metabolite-corrected arterial input function was used in conjunction with the dynamic PET emission data to estimate volumes of distribution (VT) from a two-tissue compartment model. The administration of GSK356278 reduced [11C](R)-rolipram whole brain VT by 17% at 3 h post-dose (p = 0.01) and by 4% at 8 h post-dose. The mean plasma Cmax was 42.3 ng/ml, leading to a PDE4 occupancy of 48% at Tmax. The in vivo affinity of GSK356278 was estimated as EC50 = 46 ± 3.6 ng/ml. We present the first report of a direct estimation of PDE4 blockade in the living human brain. In vivo affinity of GSK356278 for the PDE4, estimated in this early phase study, was combined with GSK356278 safety and tolerability data to decide on a therapeutic dose for future clinical development.

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Simultaneous Recordings of Gadolinium-based MRI Contrast Agent and PET Tracer Arterial Input Function in Mice Using an Extracorporeal Shunt

10.1055/s-0039-1683687 ◽

2019 ◽

Author(s):

P Backhaus ◽

F Büther ◽

L Wachsmuth ◽

L Frohwein ◽

KP Schäfers ◽

...

Keyword(s):

Contrast Agent ◽

Arterial Input Function ◽

Input Function ◽

Mri Contrast Agent ◽

Mri Contrast ◽

Pet Tracer

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Automated determination of arterial input function in DCE-MR images of the kidney

2018 Signal Processing: Algorithms, Architectures, Arrangements, and Applications (SPA) ◽

10.23919/spa.2018.8563431 ◽

2018 ◽

Author(s):

Artur Klepaczko ◽

Martyna Muszelska ◽

Eli Eikefjord ◽

Jarle Rorvik ◽

Arvid Lundervold

Keyword(s):

Arterial Input Function ◽

Input Function ◽

Mr Images ◽

Automated Determination

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Normative distribution of posterior circulation tissue time-to-maximum: Effects of anatomic variation, tracer kinetics, and implications for patient selection in posterior circulation ischemic stroke

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x20982395 ◽

2021 ◽

pp. 0271678X2098239

Author(s):

Adam E Goldman-Yassen ◽

Matus Straka ◽

Michael Uhouse ◽

Seena Dehkharghani

Keyword(s):

Ischemic Stroke ◽

Selection Criteria ◽

Arterial Input Function ◽

Anatomic Variation ◽

Input Function ◽

Posterior Circulation ◽

Anterior Circulation ◽

Vessel Occlusion ◽

Perfusion Time

The generalization of perfusion-based, anterior circulation large vessel occlusion selection criteria to posterior circulation stroke is not straightforward due to physiologic delay, which we posit produces physiologic prolongation of the posterior circulation perfusion time-to-maximum (Tmax). To assess normative Tmax distributions, patients undergoing CTA/CTP for suspected ischemic stroke between 1/2018-3/2019 were retrospectively identified. Subjects with any cerebrovascular stenoses, or with follow-up MRI or final clinical diagnosis of stroke were excluded. Posterior circulation anatomic variations were identified. CTP were processed in RAPID and segmented in a custom pipeline permitting manually-enforced arterial input function (AIF) and perfusion estimations constrained to pre-specified vascular territories. Seventy-one subjects (mean 64 ± 19 years) met inclusion. Median Tmax was significantly greater in the cerebellar hemispheres (right: 3.0 s, left: 2.9 s) and PCA territories (right: 2.9 s; left: 3.3 s) than in the anterior circulation (right: 2.4 s; left: 2.3 s, p < 0.001). Fetal PCA disposition eliminated ipsilateral PCA Tmax delays (p = 0.012). Median territorial Tmax was significantly lower with basilar versus any anterior circulation AIF for all vascular territories (p < 0.001). Significant baseline delays in posterior circulation Tmax are observed even without steno-occlusive disease and vary with anatomic variation and AIF selection. The potential for overestimation of at-risk volumes in the posterior circulation merits caution in future trials.

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