Multiple reference tissue method for contrast agent arterial input function estimation

AbstractPurposePhosphodiesterase (PDE) 7 is a potential therapeutic target for neurological and inflammatory diseases, although in-vivo visualization of PDE7 has not been successful. In this study, we aimed to develop [11C]MTP38 as a novel positron emission tomography (PET) ligand for PDE7.Methods[11C]MTP38 was radiosynthesized by 11C-cyanation of a bromo precursor with [11C]HCN. PET scans of rat and rhesus monkey brains and in-vitro autoradiography of brain sections derived from these species were conducted with [11C]MTP38. In monkeys, dynamic PET data were analyzed with an arterial input function to calculate the total distribution volume (VT). The non-displaceable binding potential (BPND) in the striatum was also determined by a reference tissue model with cerebellar reference. Finally, striatal occupancy of PDE7 by an inhibitor was calculated in monkeys according to changes in BPND.Results[11C]MTP38 was synthesized with radiochemical purity ≥ 99.4% and molar activity of 38.6 ± 12.6 GBq/μmol. Autoradiography revealed high radioactivity in the striatum and its reduction by non-radiolabeled ligands, in contrast with unaltered autoradiographic signals in other regions. In-vivo PET after radioligand injection to rats and monkeys demonstrated that radioactivity was rapidly distributed to the brain and intensely accumulated in the striatum relative to the cerebellum. Correspondingly, estimated VT values in the monkey striatum and cerebellum were 3.59 and 2.69 mL/cm3, respectively. The cerebellar VT value was unchanged by pretreatment with unlabeled MTP38. Striatal BPND was reduced in a dose-dependent manner after pretreatment with MTP-X, a PDE7 inhibitor. Relationships between PDE7 occupancy by MTP-X and plasma MTP-X concentration could be described by Hill’s sigmoidal function.ConclusionWe have provided the first successful preclinical demonstration of in-vivo PDE7 imaging with a specific PET radioligand. [11C]MTP38 is a feasible radioligand for evaluating PDE7 in the brain and is currently being applied to a first-in-human PET study.

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Dynamic contrast-enhanced QSM for perfusion imaging: a systematic comparison of ΔR2*- and QSM-based contrast agent concentration time curves in blood and tissue

Magnetic Resonance Materials in Physics Biology and Medicine ◽

10.1007/s10334-020-00831-x ◽

2020 ◽

Vol 33 (5) ◽

pp. 663-676

Author(s):

Emelie Lind ◽

Linda Knutsson ◽

Freddy Ståhlberg ◽

Ronnie Wirestam

Keyword(s):

Contrast Agent ◽

Arterial Input Function ◽

Tissue Concentration ◽

Input Function ◽

Dynamic Susceptibility ◽

Dynamic Susceptibility Contrast ◽

Concentration Data ◽

Concentration Time ◽

Dynamic Susceptibility Contrast Mri ◽

Dsc Mri

Abstract Objective In dynamic susceptibility contrast MRI (DSC-MRI), an arterial input function (AIF) is required to quantify perfusion. However, estimation of the concentration of contrast agent (CA) from magnitude MRI signal data is challenging. A reasonable alternative would be to quantify CA concentration using quantitative susceptibility mapping (QSM), as the CA alters the magnetic susceptibility in proportion to its concentration. Material and methods AIFs with reasonable appearance, selected on the basis of conventional criteria related to timing, shape, and peak concentration, were registered from both ΔR2* and QSM images and mutually compared by visual inspection. Both ΔR2*- and QSM-based AIFs were used for perfusion calculations based on tissue concentration data from ΔR2*as well as QSM images. Results AIFs based on ΔR2* and QSM data showed very similar shapes and the estimated cerebral blood flow values and mean transit times were similar. Analysis of corresponding ΔR2* versus QSM-based concentration estimates yielded a transverse relaxivity estimate of 89 s−1 mM−1, for voxels identified as useful AIF candidate in ΔR2* images according to the conventional criteria. Discussion Interestingly, arterial concentration time curves based on ΔR2* versus QSM data, for a standard DSC-MRI experiment, were generally very similar in shape, and the relaxivity obtained in voxels representing blood was similar to tissue relaxivity obtained in previous studies.

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The use of a reference tissue arterial input function with low-temporal-resolution DCE-MRI data

Physics in Medicine and Biology ◽

10.1088/0031-9155/55/16/016 ◽

2010 ◽

Vol 55 (16) ◽

pp. 4871-4883 ◽

Cited By ~ 18

Author(s):

M Heisen ◽

X Fan ◽

J Buurman ◽

N A W van Riel ◽

G S Karczmar ◽

...

Keyword(s):

Temporal Resolution ◽

Arterial Input Function ◽

Input Function ◽

Reference Tissue ◽

Dce Mri

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Evaluation of Simplified Kinetic Analyses for Measurement of Brain Acetylcholinesterase Activity Using N-[11C]Methylpiperidin-4-yl Propionate and Positron Emission Tomography

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/01.wcb.0000117689.98763.6a ◽

2004 ◽

Vol 24 (6) ◽

pp. 600-611 ◽

Cited By ~ 10

Author(s):

Koichi Sato ◽

Kiyoshi Fukushi ◽

Hitoshi Shinotoh ◽

Shinichiro Nagatsuka ◽

Noriko Tanaka ◽

...

Keyword(s):

Ache Activity ◽

Arterial Input Function ◽

Acetylcholinesterase Activity ◽

Input Function ◽

Previous Method ◽

Target Tissue ◽

Standard Analysis ◽

Reference Tissue ◽

Arterial Blood ◽

Positron Emission

The applicability of two reference tissue-based analyses without arterial blood sampling for the measurement of brain regional acetylcholinesterase (AChE) activity using N-[11C]methylpiperidin-4-yl propionate ([11C]MP4P) was evaluated in 12 healthy subjects. One was a linear least squares analysis derived from Blomqvist's equation, and the other was the analysis of the ratio of target-tissue radioactivity relative to reference-tissue radioactivity proposed by Herholz and coworkers. The standard compartment analysis using arterial input function provided reliable quantification of k3 (an index of AChE activity) estimates in regions with low (neocortex and hippocampus), moderate (thalamus), and high (cerebellum) AChE activity with a coefficient of variation (COV) of 12% to 19%. However, the precise k3 value in the striatum, where AChE activity is the highest, was not obtained. The striatum was used as a reference because its time-radioactivity curve was proportional to the time integral of the arterial input function. Reliable k3 estimates were also obtained in regions with low-to-moderate AChE activity with a COV of less than 21% by striatal reference analyses, though not obtained in the cerebellum. Shape analysis, the previous method of direct k3 estimation from the shape of time-radioactivity data, gave k3 estimates in the cortex and thalamus with a somewhat larger COV. In comparison with the standard analysis, a moderate overestimation of k3 by 9% to 18% in the linear analysis and a moderate underestimation by 2% to 13% in the Herholz method were observed, which were appropriately explained by the results of computer simulation. In conclusion, simplified kinetic analyses are practical and useful for the routine analysis of clinical [11C]MP4P studies and are nearly as effective as the standard analysis for detecting regions with abnormal AChE activity.

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Modeling tissues contrast agent concentration: A solution to the tissue homogeneity model using a simulated arterial input function

Magnetic Resonance in Medicine ◽

10.1002/mrm.1265 ◽

2001 ◽

Vol 46 (4) ◽

pp. 837-837 ◽

Cited By ~ 1

Author(s):

Jyrki T. Kuikka

Keyword(s):

Contrast Agent ◽

Arterial Input Function ◽

Input Function ◽

Contrast Agent Concentration

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A comparison of T2*-weighted magnitude and phase imaging for measuring the arterial input function in the rat aorta following intravenous injection of gadolinium contrast agent

Magnetic Resonance Imaging ◽

10.1016/j.mri.2005.02.016 ◽

2005 ◽

Vol 23 (5) ◽

pp. 619-627 ◽

Cited By ~ 14

Author(s):

Greg O. Cron ◽

Julia C. Wallace ◽

W. Dale Stevens ◽

Teresa Fortin ◽

Bruce A. Pappas ◽

...

Keyword(s):

Contrast Agent ◽

Intravenous Injection ◽

Arterial Input Function ◽

Input Function ◽

Rat Aorta ◽

Phase Imaging ◽

Gadolinium Contrast ◽

Gadolinium Contrast Agent

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Automated Determination of Arterial Input Function for Dynamic Susceptibility Contrast MRI from Regions around Arteries Using Independent Component Analysis

Radiology Research and Practice ◽

10.1155/2016/2657405 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10

Author(s):

Sharon Chen ◽

Yu-Chang Tyan ◽

Jui-Jen Lai ◽

Chin-Ching Chang

Keyword(s):

Independent Component Analysis ◽

Contrast Agent ◽

Arterial Input Function ◽

Input Function ◽

Volume Effect ◽

Partial Volume Effect ◽

Independent Component ◽

Dynamic Susceptibility ◽

Dynamic Susceptibility Contrast ◽

Susceptibility Contrast

Purpose.Quantitative cerebral blood flow (CBF) measurement using dynamic susceptibility contrast- (DSC-) MRI requires accurate estimation of the arterial input function (AIF). The present work utilized the independent component analysis (ICA) method to determine the AIF in the regions adjacent to the middle cerebral artery (MCA) by the alleviated confounding of partial volume effect.Materials and Methods.A series of spin-echo EPI MR scans were performed in 10 normal subjects. All subjects received 0.2 mmol/kg Gd-DTPA contrast agent. AIFs were calculated by two methods:(1)the region of interest (ROI) selected manually and(2)weighted average of each component selected by ICA (weighted-ICA). The singular value decomposition (SVD) method was then employed to deconvolve the AIF from the tissue concentration time curve to obtain quantitative CBF values.Results. The CBF values calculated by the weighted-ICA method were 41.1 ± 4.9 and 22.1 ± 2.3 mL/100 g/min for cortical gray matter (GM) and deep white matter (WM) regions, respectively. The CBF values obtained based on the manual ROIs were 53.6 ± 12.0 and 27.9 ± 5.9 mL/100 g/min for the same two regions, respectively.Conclusion.The weighted-ICA method allowed semiautomatic and straightforward extraction of the ROI adjacent to MCA. Through eliminating the partial volume effect to minimum, the CBF thus determined may reflect more accurate physical characteristics of theT2⁎signal changes induced by the contrast agent.

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Reference Region Modeling Approaches for Amphetamine Challenge Studies with [11C]FLB 457 and PET

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.237 ◽

2015 ◽

Vol 35 (4) ◽

pp. 623-629 ◽

Cited By ~ 21

Author(s):

Christine M Sandiego ◽

Jean-Dominique Gallezot ◽

Keunpoong Lim ◽

Jim Ropchan ◽

Shu-fei Lin ◽

...

Keyword(s):

Arterial Input Function ◽

Input Function ◽

Brain Regions ◽

Reference Region ◽

Reference Tissue ◽

Modeling Approaches ◽

Positron Emission ◽

Dopaminergic Dysfunction ◽

Induced Changes ◽

Tissue Models

Detecting fluctuations in synaptic dopamine levels in extrastriatal brain regions with [11C]FLB 457 and positron emission tomography (PET) is a valuable tool for studying dopaminergic dysfunction in psychiatric disorders. The evaluation of reference region modeling approaches would eliminate the need to obtain arterial input function data. Our goal was to explore the use of reference region models to estimate amphetamine-induced changes in [11C]FLB 457 dopamine D2/D3 binding. Six healthy tobacco smokers were imaged with [11C]FLB 457 at baseline and at 3 hours after amphetamine (0.4 to 0.5 mg/kg, per os) administration. Simplified reference tissue models, SRTM and SRTM2, were evaluated against the 2-tissue compartmental model (2TC) to estimate [11C]FLB 457 binding in extrastriatal regions of interest (ROIs), using the cerebellum as a reference region. No changes in distribution volume were observed in the cerebellum between scan conditions. SRTM and SRTM2 underestimated binding, compared with 2TC, in ROIs by 26% and 9%, respectively, with consistent bias between the baseline and postamphetamine scans. Postamphetamine, [11C]FLB 457 binding significantly decreased across several brain regions as measured with SRTM and SRTM2; no significant change was detected with 2TC. These data support the sensitivity of [11C]FLB 457 for measuring amphetamine-induced dopamine release in extrastriatal regions with SRTM and SRTM2.

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