<p>Knowledge of the relationship between <i>in vivo</i> contrast agent concentration and magnetic resonance (MR) signal response is an important requirement in contrast enhanced MR imaging in general and in MR based perfusion imaging in particular. This relationship is a complex function of the properties of the contrast agent as well as the structure of the target tissue. The aim of the present work was to quantify the effects of the iron oxide nanoparticle based intravascular contrast agent, NC100150 Injection, on proton relaxation rates in different tissue systems <i>in vivo</i> in a pig model and <i>ex vivo</i> in phantoms containing whole blood. Methods that enabled accurate relaxation rate measurements in these organs were developed, and validated. From these measurements, trans-compartmental water exchange rates and blood volume could be estimated and the MR signal response could be predicted as a function of contrast agent concentration under relevant imaging conditions. </p><p>Using a 1.5 Tesla clinical MR system, the longitudinal (R<sub>1</sub>=1/T<sub>1</sub>) proton relaxation rates in blood, renal cortex, paraspinal muscle and myocardium were measured <i>in vivo</i> as a function of plasma concentration (C<sub>p</sub>) of NC100150 Injection. The transverse (R<sub>2</sub><sup>*</sup> = 1/T<sub>2</sub><sup>*</sup>) relaxation rates were measured <i>in vivo</i> in blood, renal cortex and muscle as a function of C<sub>p</sub> and <i>ex vivo</i> in blood as a function of C<sub>p</sub> and blood oxygenation tension. The proton nuclear MR (NMR) linewidth and lineshape were analysed as a function of C<sub>p</sub> and blood oxygen tension <i>ex vivo</i> at 7.05 T. </p><p>In muscle and renal cortex, there was a linear correlation between R<sub>2</sub><sup>*</sup> and C<sub>p</sub> whereas R<sub>2</sub><sup>*</sup> increased as a quadratic function of C<sub>p </sub>in blood. The NMR linewidth increased linearly with C<sub>p</sub> in fully oxygenated blood whereas in deoxygenated blood the linewidth initially decreased with increasing Cp, reaching a minimum and then increasing again with further increase in C<sub>p</sub>. R<sub>1</sub> increased linearly with C<sub>p</sub> in blood and from the slope of R<sub>1</sub> vs. C<sub>p</sub> the T<sub>1</sub>-relaxivity (r<sub>1</sub>) of NC100150 Injection in blood at 1.5 T was estimated to be (mean ± SD) 13.9 ± 0.9 s<sup>-1</sup>mM<sup>-1</sup>. In tissue, the maximum increase in R<sub>1</sub> was limited by the rate of water exchange between the intravascular and interstitial tissue compartments. Using a two-compartment exchange-limited relaxation model, the permeability surface area (PS) product was estimated to be 61.9 ± 2.9 mL/min/g in renal cortex and 10.1 ± 1.5 mL/min/g in muscle and the total myocardial water exchange rate, <i>k</i><i>t</i>, was 13.5 ± 6.4 s<sup>-1</sup>. The estimated blood volumes obtained from the same model were 19.1 ± 1.4 mL/100 g, 2.4 ± 1.4 mL/100 g and 11.2 ± 2.1 mL/100 g, respectively in renal cortex, muscle and myocardium.</p><p>Current T<sub>2</sub><sup>*</sup> based first-pass MR perfusion methods assume a linear correlation between R<sub>2</sub><sup>*</sup> and C<sub>p</sub> both in blood and tissue and our results therefore suggest that quantitative perfusion values can not easily be obtained with existing tracer kinetic models. The correlation between MR signal response and C<sub>p</sub> is further complicated in the kidney by a significant first-pass increase in R<sub>1</sub> which may lead to an underestimation of C<sub>p</sub>. In T<sub>1</sub>-based perfusion methods, low concentrations of NC100150 Injection must be used in order to maintain a linear dose-response relationship between R<sub>1</sub> and C<sub>p</sub>. The effect of blood oxygenation on the NMR linewidth in the presence of NC100150 Injection enabled accurate estimation of magnetic susceptibility of deoxyhemoglobin and the effect can potentially be used to determine blood oxygenation status.</p><p>In conclusion, NC100150 Injection is well suited as a T<sub>2</sub><sup>*</sup> perfusion agent due to the large magnetisation and intravascular biodistribution of this agent. T<sub>1</sub>-based perfusion imaging with this agent is limited by water exchange effects and large T<sub>2</sub><sup>*</sup> effects at higher contrast agent concentrations. Quantitative perfusion assessment is unlikely to be feasible with any of these approaches due to the non-linear dose response.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-2150 |
| Date | January 2002 |
| Creators | Bjørnerud, Atle |
| Publisher | Uppsala University, Department of Oncology, Radiology and Clinical Immunology, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 0282-7476 ; 1160 |
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