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The accuracy of perfusion measurements using dynamic, susceptibility-weighted, contrast-enhanced MRI depends on estimating contrast agent concentration in an artery, i.e., the arterial input function. One of the difficulties associated with obtaining an arterial input function are partial volume effects when both blood and brain parenchyma occupy the same pixel. Previous studies have attempted to correct arterial input functions which suffer from partial volume effects using contrast concentration in venous blood. However, the relationship between relaxation and concentration (C) in venous blood has not been determined in vivo. In this note, a previously employed fitting approach is used to determine venous relaxivity in vivo. In vivo relaxivity is compared with venous relaxivity measured in vitro in bulk blood. The results show that the fitting approach produces relaxivity calibration curves which give excellent agreement with arterial measurements., (Copyright © 2012 Wiley Periodicals, Inc.)

Dynamic contrast enhanced T(1)-weighted MRI using the contrast agent gadopentetate dimeglumine (Gd-DTPA) was performed on 10 patients with glioblastoma. Nested models with as many as three parameters were used to estimate plasma volume or plasma volume and forward vascular transfer constant (K(trans)) and the reverse vascular transfer constant (k(ep)). These constituted models 1, 2, and 3, respectively. Model 1 predominated in normal nonleaky brain tissue, showing little or no leakage of contrast agent. Model 3 predominated in regions associated with aggressive portions of the tumor, and model 2 bordered model 3 regions, showing leakage at reduced rates. In the patient sample, v(p) was about four times that of white matter in the enhancing part of the tumor. K(trans) varied by a factor of 10 between the model 2 (1.9 ↔ 10(-3) min(-1)) and model 3 regions (1.9 ↔ 10(-2) min(-1)). The mean calculated interstitial space (model 3) was 5.5%. In model 3 regions, excellent curve fits were obtained to summarize concentration-time data (mean R(2) = 0.99). We conclude that the three parameters of the standard model are sufficient to fit dynamic contrast enhanced T(1) data in glioblastoma under the conditions of the experiment., (Copyright © 2011 Wiley Periodicals, Inc.)

The hypothesis that the arterial input function (AIF) of gadolinium-diethylenetriaminepentaacetic acid injected by intravenous bolus and measured by the change in the T(1)-relaxation rate (Delta R(1); R(1) = 1/T(1)) of superior sagittal sinus blood (AIF-I) approximates the AIF of (14)C-labeled gadolinium-diethylenetriaminepentaacetic acid measured in arterial blood (reference AIF) was tested in a rat stroke model (n = 13). Contrary to the hypothesis, the initial part of the Delta R(1)-time curve was underestimated, and the area under the normalized curve for AIF-I was about 15% lower than that for the reference AIF. Hypothetical AIFs for gadolinium-diethylenetriaminepentaacetic acid were derived from the reference AIF values and averaged to obtain a cohort-averaged AIF. Influx rate constants (K(i)) and proton distribution volumes at zero time (V(p) + V(o)) were estimated with Patlak plots of AIF-I, hypothetical AIFs, and cohort-averaged AIFs and tissue Delta R(1) data. For the regions of interest, the K(i)s estimated with AIF-I were slightly but not significantly higher than those obtained with hypothetical AIFs and cohort-averaged AIF. In contrast, V(p) + V(o) was significantly higher when calculated with AIF-I. Similar estimates of K(i) and V(p) + V(o) were obtained with hypothetical AIFs and cohort-averaged AIF. In summary, AIF-I underestimated the reference AIF; this shortcoming had little effect on the K(i) calculated by Patlak plot but produced a significant overestimation of V(p) + V(o)., ((c) 2010 Wiley-Liss, Inc.)

Current clinical applications of dynamic contrast-enhanced MRI (DCE-MRI) are based on the extravasation of relatively small contrast agents (SCAs). SCAs are considered disadvantageous, as they require high image sampling rates. Medium-sized contrast agents (MCAs) leak more slowly into tissue and allow longer dynamic acquisition times, enabling improved image quality. The influence of molecular size on the reliability of pharmacokinetic parameters, including the transfer constant K(trans), was investigated. Computer simulations were performed, with in vivo measured arterial input functions (AIFs), to determine the bias and variance of pharmacokinetic parameters as a function of contrast agent size, sampling frequency, noise level, and acquisition time. Better reliability of all parameters was obtained for the MCA compared to the SCA. To obtain similar variance (10%) in K(trans), the sampling frequency for the SCA (28 min(-1)) had to be 20 times faster than for the MCA (1.3 min(-1)). Optimal reliability in parameter estimation required longer acquisition times for MCAs (13 min for the fraction of the extravascular extracellular space into which the contrast agent distributes (v(e)) and 5 min for K(trans)) than for SCAs (1.7 min for K(trans) and v(e)). Reliable estimation of the fractional blood plasma volume (v(p)) was only achieved with MCAs. In conclusion, MCAs provided superior reliability for pharmacokinetic parameter estimation compared to SCAs.

The goal of this study was to investigate the relationship between an empirical contrast kinetic parameter, the signal enhancement ratio (SER), for three-timepoint, high spatial resolution contrast-enhanced (CE) MRI, and a commonly analyzed pharmacokinetic parameter, kep, using dynamic high temporal resolution CE-MRI. Computer simulation was performed to investigate: 1) the relationship between the SER and the contrast agent concentration ratio (CACR) of two postcontrast timepoints (tp1 and tp2); 2) the relationship between the CACR and the redistribution rate constant (kep) based on a two-compartment pharmacokinetic model; and 3) the sensitivity of the relationship between the SER and kep to native tissue T1 relaxation time, T10, and to errors in an assumed vascular input function. The relationship between SER and kep was verified experimentally using a mouse model of breast cancer. The results showed that a monotonic mathematical relationship between SER and kep could be established if the acquisition parameters and the two postinjection timepoints of SER, tp1, tp2, were appropriately chosen. The in vivo study demonstrated a close correlation between SER and kep on a pixel-by-pixel basis (Spearman rank correlation coefficient=0.87+/-0.03). The SER is easy to calculate and may have a unique role in breast tissue characterization., (Copyright (c) 2007 Wiley-Liss, Inc.)

A method for measuring contrast agent concentration in blood was developed using a switchable RF tail coil to obtain MR signal from the mouse tail vein. The switchable RF coil was used to obtain quantitative high-resolution T1 maps of the tail in combination with a second coil used to obtain images from regions of interest in a mouse tumor model. The effect of flow rates on the T1 measurements was validated using a flow-phantom. Reliable estimates of blood T1 were obtained for flow rates up to 0.5 cm/sec in SCID mice. There was no significant difference between the in vivo tail coil measurements and in vitro blood sample relaxation rates of blood. The ability to measure the concentration of contrast agents in mouse blood in vivo is useful for several applications, such as obtaining quantitative values of tumor vascular volume and permeability, determining the effectiveness of drug delivery to tumors, or for detecting lymphatic drain., (Copyright 2004 Wiley-Liss, Inc.)