Gunnar Brix

Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols

We describe a standard set of quantity names and symbols related to the estimation of kinetic parameters from dynamic contrast‐enhanced T1‐weighted magnetic resonance imaging data, using diffusable agents such as gadopentetate dimeglumine (Gd‐DTPA). These include a) the volume transfer constant Ktrans (min−1); b) the volume of extravascular extracellular space (EES) per unit volume of tissue ve (0 < ve < 1); and c) the flux rate constant between EES and plasma kep (min−1). The rate constant is the ratio of the transfer constant to the EES (kep = Ktrans/ve). Under flow‐limited conditions Ktrans equals the blood plasma flow per unit volume of tissue; under permeability‐limited conditions Ktrans equals the permeability surface area product per unit volume of tissue. We relate these quantities to previously published work from our groups; our future publications will refer to these standardized terms, and we propose that these be adopted as international standards. J. Magn. Reson. Imaging 10:223–232, 1999.

Pharmacokinetic Parameters in Cns Gd-dtpa Enhanced Mr Imaging

Dynamic MR imaging can be used to study tissue perfusion and vascular permeability. In the present article a procedure for dynamic MR is presented, which (a) accurately resolves the fast kinetics of tissue response during and after intravenous infusion of the paramagnetic contrast medium Gd-DTPA and (b) yields a linear relationship between the measured MR signal and the Gd-DTPA concentration in the tissue. According to these features, the measured signal-time curves can be analyzed within the framework of pharmacokinetic modeling. Tissue response has been parameterized using a linear two-compartment open model, with only negligible effects of the peripheral compartment on the central compartment. The three model parameters were fitted to the signal-time data pixel by pixel, based on a set of 64 rapid SE images (SE 100/10 ms, image scan time 13 s, interscan intervals 11 s). This makes it possible to construct parameter images, whereby structures become visible that cannot be distinguished in conventional Gd-DTPA enhanced MR. As a clinical example, the approach is discussed in a case of glioblastoma.

Pathophysiologic basis of contrast enhancement in breast tumors

While the diagnostic benefits of gadolinium (Gd)‐chelate contrast agents are firmly established in magnetic resonance imaging (MRI) of tumors, the pathophysiologic basis of the enhancement observed and its histopathologic correlate remained vague. Tumor angiogenesis is fundamental for growth and metastasis and also of interest in new therapeutic concepts. By correlative analysis of a) histology; b) vascular density (CD31); and c) vascular permeability (vascular permeability factor/vascular endothelial growth factor [VPF/VEGF]), we found a) significantly (P < 0.001) faster exchange rates in malignant compared with benign breast lesions; b) distinct differences in enhancement characteristics between the histologic types (invasive ductal carcinoma, invasive lobular carcinoma, and ductal carcinoma in situ); and c) dependence of enhancement kinetics on the VPF/VEGF expression. The pathophysiologic basis for the differences in contrast enhancement patterns of tumors detectable by MRI is mainly due to vascular permeability, which leads to more characteristic differences than vascular density. MRI is able to subclassify malignant breast tumors due to their different angiogenetic properties. J. Magn. Reson. Imaging 1999;10:260–266.

Microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic MR image series.

The purpose of this study was to quantify microcirculation and microvasculature in breast lesions by pharmacokinetic analysis of Gd‐DTPA‐enhanced MRI series. Strongly T1‐weighted MR images were acquired in 18 patients with breast lesions using a saturation‐recovery‐TurboFLASH sequence. Concentration‐time courses were determined for blood, pectoral muscle, and breast masses and subsequently analyzed by a two‐compartment model to estimate plasma flow and the capillary transfer coefficient per unit of plasma volume (F/VP, KPS/VP) as well as fractional volumes of the plasma and interstitial space (fP, fI). Tissue parameters determined for pectoral muscle (fP = 0.04 ± 0.01, fI = 0.09 ± 0.01, F/VP = 2.4 ± 1.3 min‐1, and KPS/VP = 1.2 ± 0.5 min‐1) and 10 histologically proven carcinomas (fP = 0.20 ± 0.07, fI = 0.34 ± 0.16, F/VP = 2.4 ± 0.7 min‐1, and KPS/VP = 0.86 ± 0.62 min‐1) agreed reasonable well with literature data. Best separation between malignant and benign lesions was obtained by the ratio KPS/F (0.35 ± 0.17 vs. 1.23 ± 0.65). The functional imaging technique presented appears promising to quantitatively characterize tumor pathophysiology. Its impact on diagnosis and therapy management of breast tumors, however, has to be evaluated in larger patient studies. Magn Reson Med 52:420–429, 2004.

Performance evaluation of the whole-body PET scanner ECAT EXACT HR/sup +/ following the IEC standard

The performance parameters of the whole-body PET scanner ECAT EXACT HR/sup +/ (CTI/Siemens, Knoxville, TN) were determined following the standard proposed by the International Electrotechnical Commission (IEC). The tests were expanded by some measurements concerning the accuracy of the correction algorithms and the geometric fidelity of the reconstructed images. The scanner consists of 32 rings, each with 576 BGO detectors (4.05/spl times/4.39/spl times/30 mm/sup 3/), covering an axial field-of-view of 15.5 cm and a patient port of 56.2 cm. The transaxial FWHM determined by a Gaussian fit in the 2D (3D) mode is 4.5 (4.3) mm at the center. It increases to 8.9 (8.3) mm radially and to 5.8 (5.2) mm tangentially at a radial distance of r=20 cm. The average axial resolution varies between 4.9 (4.1) mm FWHM at the center and 8.8 (8.1) mm at r=20 cm. The system sensitivity for unscattered true events is 5.85 (26.4) cps/Bq/ml (measured with a 20 cm cylinder). The 50% dead-time losses were reached for a true event count rate (including scatter) of 286 (500) kcps at an activity concentration of 74 (25) kBq/ml. The system scatter fraction is 0.24 (0.35). With the exception of the 3D attenuation correction algorithm, all correction algorithms work reliably. The results reveal that the ECAT EXACT HR/sup +/ has a good and nearly isotropic spatial resolution. Due to the small detector elements, however, it has a low slice sensitivity which is a limiting factor for image quality.

Fast and precise T1 imaging using a TOMROP sequence

Proton spin-lattice (T1) relaxation time images were computed from a data set of 32 gradient-echo images acquired with a fast TOMROP (T One by Multiple Read Out Pulses) sequence using a standard whole-body MR imager operating at 64 MHz. The data acquisition and analysis method which permits accurate pixel-by-pixel estimation of T1 relaxation times is described. As an example, the T1 parameter image of a human brain is shown demonstrating an excellent image quality. For white and gray brain matter, the measured longitudinal relaxation processes are adequately described by a single-component least-squares fit, while more than one proton component has to be considered for fatty tissue. A quantitative analysis yielded T1 values of 547 +/- 36 msec and 944 +/- 73 msec for white and gray matter, respectively.

Multicompartment Analysis of Gadolinium Chelate Kinetics: Blood-Tissue Exchange in Mammary Tumors as Monitored by Dynamic MR Imaging

The blood‐tissue exchange kinetics of gadopentetate were studied in 49 malignant and benign mammary tumors. Signal enhancement was monitored simultaneously in the aorta and in tumor for 10.5 minutes after the beginning of a 1 minute i.v. infusion of the contrast medium (CM). Kinetic analysis was based on a model with two compartments for systemic pharmacokinetics and up to three kinetically distinct compartments for tumor. Kinetic heterogeneity, ie, two or more compartments with different exchange rate constants in a given tumor, was found in 85% of carcinomas, 38% of fibroadenomas, and 14% of mastopathic tumors. The within‐tumor average of CM exchange rates was 1.22 (0.62–1.65) min−1 in carcinomas, 0.38 (0.26–0.60) min−1 in fibroadenomas, and 0.16 (0.12–0.20) min−1 in mastopathies (median and interquartile distances). The area under the signal enhancement‐time curve of the aorta varied 4.5‐fold between individuals. It is concluded that individual CM kinetics in arterial blood should be taken into account when CM exchange rates between blood and tumor are to be determined and that a kinetic model for potentially malignant tumors should allow for kinetic heterogeneity. J. Magn. Reson. Imaging 1999;10:233–241.

Dynamic contrast-enhanced MRI using Gd-DTPA: interindividual variability of the arterial input function and consequences for the assessment of kinetics in tumors.

Gd‐DTPA kinetics in arterial blood was investigated by dynamic MRI in 47 patients with malignant and benign mammary tumors. Signal enhancement was monitored for 10 min after the beginning of a 1‐min infusion of 0.1 mmol/kg Gd‐DTPA. Kinetics in blood was biexponential with median half‐lives of 21 sec and 11.1 min, respectively. Peak signal enhancement and the area under the signal enhancement–time curve varied 2.5‐ and 3.7‐fold between patients. The shortest mean residence time in one of up to three tumor compartments, MRT*, was estimated using either the individual (reference) or a mean population (surrogate) arterial input function (AIF). MRT* (reference estimate) was 1.0 (0–1.5), 1.9 (1.5–2.3), and 2.5 (2.3–2.8) min in carcinomas, fibroadenomas, and mastopathies, respectively (median and interquartile distance). Surrogate estimates were unbiased but differed from the reference estimates 1.5‐fold or more in 23% of cases. AIFs should be monitored individually if accurate estimates of individual MRT* are desired. Magn Reson Med 45:1030–1038, 2001.

Cerebral blood flow and cerebrovascular reserve capacity: estimation by dynamic magnetic resonance imaging.

We have developed a new method for estimation of regional CBF (rCBF) and cerebrovascular reserve capacity on a pixel-by-pixel basis by means of dynamic magnetic resonance imaging (MRI). Thirteen healthy volunteers, 8 patients with occlusion and/or high grade stenosis of the internal carotid artery (ICA), and 2 patients with acute stroke underwent dynamic susceptibility-weighted contrast enhanced MRI. Using principles of indicator dilution theory and deconvolution analysis, maps of rCBF, regional cerebral blood volume, and of the mean transit time (MTT) were calculated. In patients with ICA occlusion/stenosis, cerebrovascular reserve capacity was assessed by the rCBF increase after acetazolamide stimulation. Mean gray and white matter rCBF values in normals were 67.1 and 23.7 mL · 100 g−1 · min−1, respectively. Before acetazolamide stimulation, six of eight patients with ICA occlusions showed decreased rCBF values; and in seven patients increased MTT values were observed in tissue ipsilateral to the occlusion. After acetazolamide stimulation, decreased cerebrovascular reserve capacity was observed in five of eight patients with ICA occlusion. In acute stroke, rCBF in the central core of ischemia was less than 8 mL · 100 g−1 · min−1. In peri-infarct tissue, rCBF and MTT were higher than in unaffected tissue but rCBF was normal. Dynamic MRI provides important clinical information on the hemodynamic state of brain tissue in patients with occlusive cerebrovascular disease or acute stroke.

Assessment of cerebral blood volume with dynamic susceptibility contrast enhanced gradient-echo imaging

Objective Dynamic susceptibility contrast (DSC) enhanced MRI was used to study relative cerebral blood volume (rCBV). Materials and Methods We examined 15 healthy subjects and 47 patients with vascular stenosis or occlusion, with brain infarctions, and with cerebral neoplasms. During bolus injection of Gd-diethylenetriamine pentaacetic acid, a series of rapid T2*-weighted fast low angle shot two-dimensional images were recorded from the same slice. From these images, changes in signal intensity during bolus passage were computed pixel-by-pixel and converted into contrast agent concentration curves. Applying the principles of indicator dilution theory, images of rCBV were calculated. Results and Conclusion Regions of infarctions show almost zero rCBV. In patients with high-grade vascular stenosis or occlusion a bolus delay in comparison to the unaffected side and an increased mean transit time can be observed. Some of the affected areas show an increased rCBV, which is a well-known physiological mechanism that takes place to compensate for the reduced cerebral blood pressure. In brain tumors, rCBV imaging reveals focal or homogeneous areas of increased blood volume. This can even be observed in low-grade astrocytomas with unaffected blood-brain barrier. In CBV imaging, the effects of radiotherapy on tumor tissue can be monitored as a significant decrease of rCBV in tumor tissue after therapy.