Pseudo-extravasation rate constant of dynamic susceptibility contrast-MRI determined from pharmacokinetic first principles

Xin Li, Csanad G. Varallyay, Seymur Gahramanov, Rongwei (Rochelle) Fu, William Rooney, Edward Neuwelt

Research output: Contribution to journalArticle

Abstract

Dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) is widely used to obtain informative perfusion imaging biomarkers, such as the relative cerebral blood volume (rCBV). The related post-processing software packages for DSC-MRI are available from major MRI instrument manufacturers and third-party vendors. One unique aspect of DSC-MRI with low-molecular-weight gadolinium (Gd)-based contrast reagent (CR) is that CR molecules leak into the interstitium space and therefore confound the DSC signal detected. Several approaches to correct this leakage effect have been proposed throughout the years. Amongst the most popular is the Boxerman-Schmainda-Weisskoff (BSW) K2 leakage correction approach, in which the K2 pseudo-first-order rate constant quantifies the leakage. In this work, we propose a new method for the BSW leakage correction approach. Based on the pharmacokinetic interpretation of the data, the commonly adopted R2* expression accounting for contributions from both intravascular and extravasating CR components is transformed using a method mathematically similar to Gjedde-Patlak linearization. Then, the leakage rate constant (KL) can be determined as the slope of the linear portion of a plot of the transformed data. Using the DSC data of high-molecular-weight (~750 kDa), iron-based, intravascular Ferumoxytol (FeO), the pharmacokinetic interpretation of the new paradigm is empirically validated. The primary objective of this work is to empirically demonstrate that a linear portion often exists in the graph of the transformed data. This linear portion provides a clear definition of the Gd CR pseudo-leakage rate constant, which equals the slope derived from the linear segment. A secondary objective is to demonstrate that transformed points from the initial transient period during the CR wash-in often deviate from the linear trend of the linearized graph. The inclusion of these points will have a negative impact on the accuracy of the leakage rate constant, and even make it time dependent.

Original languageEnglish (US)
JournalNMR in Biomedicine
DOIs
StateAccepted/In press - 2017

Fingerprint

Pharmacokinetics
Magnetic resonance imaging
Rate constants
Magnetic resonance
Imaging techniques
Magnetic Resonance Imaging
Gadolinium
Molecular Weight
Molecular weight
Ferrosoferric Oxide
Perfusion Imaging
Biomarkers
Linearization
Software packages
Blood
Software
Iron
Molecules
Processing

Keywords

  • Ferumoxytol
  • Gadolinium
  • Gjedde-Patlak transformation
  • Intravascular contrast reagent
  • Leakage correction
  • Relative cerebral blood volume

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Spectroscopy

Cite this

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title = "Pseudo-extravasation rate constant of dynamic susceptibility contrast-MRI determined from pharmacokinetic first principles",
abstract = "Dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) is widely used to obtain informative perfusion imaging biomarkers, such as the relative cerebral blood volume (rCBV). The related post-processing software packages for DSC-MRI are available from major MRI instrument manufacturers and third-party vendors. One unique aspect of DSC-MRI with low-molecular-weight gadolinium (Gd)-based contrast reagent (CR) is that CR molecules leak into the interstitium space and therefore confound the DSC signal detected. Several approaches to correct this leakage effect have been proposed throughout the years. Amongst the most popular is the Boxerman-Schmainda-Weisskoff (BSW) K2 leakage correction approach, in which the K2 pseudo-first-order rate constant quantifies the leakage. In this work, we propose a new method for the BSW leakage correction approach. Based on the pharmacokinetic interpretation of the data, the commonly adopted R2* expression accounting for contributions from both intravascular and extravasating CR components is transformed using a method mathematically similar to Gjedde-Patlak linearization. Then, the leakage rate constant (KL) can be determined as the slope of the linear portion of a plot of the transformed data. Using the DSC data of high-molecular-weight (~750 kDa), iron-based, intravascular Ferumoxytol (FeO), the pharmacokinetic interpretation of the new paradigm is empirically validated. The primary objective of this work is to empirically demonstrate that a linear portion often exists in the graph of the transformed data. This linear portion provides a clear definition of the Gd CR pseudo-leakage rate constant, which equals the slope derived from the linear segment. A secondary objective is to demonstrate that transformed points from the initial transient period during the CR wash-in often deviate from the linear trend of the linearized graph. The inclusion of these points will have a negative impact on the accuracy of the leakage rate constant, and even make it time dependent.",
keywords = "Ferumoxytol, Gadolinium, Gjedde-Patlak transformation, Intravascular contrast reagent, Leakage correction, Relative cerebral blood volume",
author = "Xin Li and Varallyay, {Csanad G.} and Seymur Gahramanov and Fu, {Rongwei (Rochelle)} and William Rooney and Edward Neuwelt",
year = "2017",
doi = "10.1002/nbm.3797",
language = "English (US)",
journal = "NMR in Biomedicine",
issn = "0952-3480",
publisher = "John Wiley and Sons Ltd",

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TY - JOUR

T1 - Pseudo-extravasation rate constant of dynamic susceptibility contrast-MRI determined from pharmacokinetic first principles

AU - Li, Xin

AU - Varallyay, Csanad G.

AU - Gahramanov, Seymur

AU - Fu, Rongwei (Rochelle)

AU - Rooney, William

AU - Neuwelt, Edward

PY - 2017

Y1 - 2017

N2 - Dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) is widely used to obtain informative perfusion imaging biomarkers, such as the relative cerebral blood volume (rCBV). The related post-processing software packages for DSC-MRI are available from major MRI instrument manufacturers and third-party vendors. One unique aspect of DSC-MRI with low-molecular-weight gadolinium (Gd)-based contrast reagent (CR) is that CR molecules leak into the interstitium space and therefore confound the DSC signal detected. Several approaches to correct this leakage effect have been proposed throughout the years. Amongst the most popular is the Boxerman-Schmainda-Weisskoff (BSW) K2 leakage correction approach, in which the K2 pseudo-first-order rate constant quantifies the leakage. In this work, we propose a new method for the BSW leakage correction approach. Based on the pharmacokinetic interpretation of the data, the commonly adopted R2* expression accounting for contributions from both intravascular and extravasating CR components is transformed using a method mathematically similar to Gjedde-Patlak linearization. Then, the leakage rate constant (KL) can be determined as the slope of the linear portion of a plot of the transformed data. Using the DSC data of high-molecular-weight (~750 kDa), iron-based, intravascular Ferumoxytol (FeO), the pharmacokinetic interpretation of the new paradigm is empirically validated. The primary objective of this work is to empirically demonstrate that a linear portion often exists in the graph of the transformed data. This linear portion provides a clear definition of the Gd CR pseudo-leakage rate constant, which equals the slope derived from the linear segment. A secondary objective is to demonstrate that transformed points from the initial transient period during the CR wash-in often deviate from the linear trend of the linearized graph. The inclusion of these points will have a negative impact on the accuracy of the leakage rate constant, and even make it time dependent.

AB - Dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) is widely used to obtain informative perfusion imaging biomarkers, such as the relative cerebral blood volume (rCBV). The related post-processing software packages for DSC-MRI are available from major MRI instrument manufacturers and third-party vendors. One unique aspect of DSC-MRI with low-molecular-weight gadolinium (Gd)-based contrast reagent (CR) is that CR molecules leak into the interstitium space and therefore confound the DSC signal detected. Several approaches to correct this leakage effect have been proposed throughout the years. Amongst the most popular is the Boxerman-Schmainda-Weisskoff (BSW) K2 leakage correction approach, in which the K2 pseudo-first-order rate constant quantifies the leakage. In this work, we propose a new method for the BSW leakage correction approach. Based on the pharmacokinetic interpretation of the data, the commonly adopted R2* expression accounting for contributions from both intravascular and extravasating CR components is transformed using a method mathematically similar to Gjedde-Patlak linearization. Then, the leakage rate constant (KL) can be determined as the slope of the linear portion of a plot of the transformed data. Using the DSC data of high-molecular-weight (~750 kDa), iron-based, intravascular Ferumoxytol (FeO), the pharmacokinetic interpretation of the new paradigm is empirically validated. The primary objective of this work is to empirically demonstrate that a linear portion often exists in the graph of the transformed data. This linear portion provides a clear definition of the Gd CR pseudo-leakage rate constant, which equals the slope derived from the linear segment. A secondary objective is to demonstrate that transformed points from the initial transient period during the CR wash-in often deviate from the linear trend of the linearized graph. The inclusion of these points will have a negative impact on the accuracy of the leakage rate constant, and even make it time dependent.

KW - Ferumoxytol

KW - Gadolinium

KW - Gjedde-Patlak transformation

KW - Intravascular contrast reagent

KW - Leakage correction

KW - Relative cerebral blood volume

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