Relative volume‐average murine tumor blood flow measurement via deuterium nuclear magnetic resonance spectroscopy

Abstract

A deuterium NMR spectroscopic method to determine relative tumor blood flow (TBF) by measuring the increase in tumor HOD concentration after intravenous injection of 100 microliters D2O (0.9% NaCl) is presented. An integration approach analogous to that validated for positron emission tomographic measurement of cerebral blood flow was implemented. Computer simulations indicated that integration from 30 to 120 s minimizes the sensitivity of the uptake integral to the shape of the arterial input function, which cannot be assessed in each mouse, while maintaining both a nearly linear relationship between TBF and the integral and high NMR signal-to-noise. A strong positive linear correlation was observed between the uptake integral and TBF measured by D2O clearance in both untreated tumors (n = 19; P less than 0.001) and tumors after hyperthermia (n = 16; P less than 0.001). This method can measure relative TBF in tumors with heterogeneous blood flow and is ideally suited to concurrent or interleaved measurement of TBF and metabolism via multinuclear NMR spectroscopy.

Effects of the mycelial extract of cultured Cordyceps sinensis on in vivo hepatic energy metabolism and blood flow in dietary hypoferric anaemic mice

“…The present study revealed that Cs extract treatment in both normal and anaemic groups increased liver blood flow, as determined by D 2 O uptake-2 H NMR spectroscopy performed according to a modification of the methods of Mattiello et al (1991) and Zhao et al (1995), which were suitable for rats. We established a technique appropriate for mice and estimated the mouse liver blood flow by in vivo 2 H NMR spectroscopy of D 2 O uptake after intravenous injection of D 2 O.…”

“…In vivo 31 P NMR analysis of the liver was performed on Fe-deficient anaemic mice administered Cs extract. As blood flow and energy metabolism are thought to be linked (Okunieff et al 1988;Tozer et al 1990), 2 H NMR spectroscopy of deuterated water (D 2 O) uptake after intravenous injection of D 2 O was used to measure hepatic blood flow in the anaemic mice treated with Cs extract (Mattiello & Evelhoch, 1991;Zhao et al 1995). The in vivo structurebiological assessment techniques for energy metabolism and blood flow are useful not only for pharmaceutical and toxicological sciences but also for nutritional sciences.…”

“…Spectra were acquired under optimized signal-to-noise conditions where a repetition time : T 1 value of 0⋅93 was used to acquire both 2 H and 1 H spectra. 2 H spectra were acquired with a 60Њ flip angle and 0⋅25 s repetition time (Mattiello & Evelhoch, 1991). For blood flow measurement, 100 l/mouse of 9 g NaCl/l in D 2 O was injected into the tail vein via a catheter.…”

“…Time domain data (2 × 256 points) were averaged into ninety consecutive 4 s time blocks. Relative volume average blood flow values were calculated by computer integration with JEOL software using the D 2 O uptake integral approach as described by Mattiello & Evelhoch, (1991). Blood flow rates are expressed as a percentage of the mean value for normal controls on day 0 (0 week).…”

Parametric imaging of tumor perfusion using flow‐ and permeability‐limited tracers

“…Analysis was performed utilizing a nonlinear Levenberg-Marquardt least-squares fitting algorithm based on Eq. [10]. A more detailed description of the analysis can be found in the work of Furman-Haran et al (28).…”