Wash-in Slope Research Articles

Functional imaging by DCE-US as a surrogate for response in phase I/II of different targeted therapies by DCE-US: Which quantitative parameter and which timing

14093 Background: The early evaluation of targeted treatments is a major challenge in oncology. Functional approaches based on the measure of tumoral vascularization have been developed using different modalities of imaging (CT, MRI, US). We analyzed the response of tumors in three studies using different targeted treatments with dynamic contrast enhanced-ultrasonography (DCE-US). Seven parameters characterizing tumor perfusion were estimated. The objective of the study was to determine which parameter is the most appropriate and when to use it to confirm earlier the efficacy of treatment. Methods: A total of 157 DCE-US were performed in 30 responding patients (PFS>3 months) selected from 3 following studies (multikinase inhibitor targeting angiogenic-receptor with a cytotoxic, thyrosine-kinase inhibitor targeted angiogenic-receptor and C-kit, VEGF monoclonal antibody). Each DCE-US was performed using contrast agent (Sonovue,Bracco) with perfusion and quantification softwares (Toshiba) from raw linear data. Seven quantitative parameters of perfusion were estimated: peak intensity (PI) and area under the curve (AUC), area under the wash-in (AUWI), area under the wash-out (AUWO), time to PI, mean transit time (MTT), wash-in slope. DCE-US were performed before treatment and after during 5 periods (P) : 1–12 days(P1), 13–22 days(P2), 23–43 days(P3), 44–110 days (P4), > 111 days(P5). Results: 1099 parameters have benefited a statistical analysis. Significant modifications (P<0.05) of 4 parameters (PI, AUC, AUWI, AUWO) were observed for the 3 treatments. The earliest significant modifications were observed during the 3rd period for the first 2 studies and during the 4th period for the 3rd study. Conclusions: DCE-US is a sensitive tool to evaluate early tumor response to targeted drugs. Four functional parameters were significantly modified patients responding to treatment: PI, AUC, AUWI, AUWO. Those modifications appear earlier for the multikinase inhibitor targeting angiogenic receptor and the thyrosine-kinase inhibitor targeted angiogenic receptor and C-kit ( (23–43 d) compared to VEGF monoclonal antibody (44 -110 d). DCE- US represent a key add value to early evaluation of targeted therapies. No significant financial relationships to disclose.

Hip dGEMRIC in asymptomatic volunteers and patients with early osteoarthritis: The influence of timing after contrast injection

Eight asymptomatic volunteers and 10 patients with early hip osteoarthritis (OA) were investigated with hip delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at 30, 65, 100, and 135 min after IV injection with Gd-DTPA(2-). In asymptomatic volunteers there was a decrease in the dGEMRIC index (T(1)(Gd)) between 30 and 100 min. In patients the wash-in of Gd-DTPA(2-) was faster, with a low T(1)(Gd) at 30 min that did not change significantly over time. Therefore, earlier time points showed a larger separation in T(1)(Gd) between asymptomatic and OA hips, with more convenient timing logistics. However, T(1)(Gd) at 30 min had a larger standard deviation (SD) in the OA group, possibly due to variability of the steep slope of wash-in. This sensitivity to the imaging window may be less desirable for longitudinal studies in which reproducibility is a concern. At all time points, T(1)(Gd) was 20-30% lower in patients than in asymptomatic volunteers (P < 0.003), which demonstrates the sensitivity of dGEMRIC to early hip OA.

USPIO-enhanced dynamic MRI: evaluation of normal and transplanted rat kidneys.

To evaluate first-pass renal perfusion with ultrasmall superparamagnetic iron oxide (USPIO) particles by MRI, 40 normal rats (20 Dark Agouti (DA) rats and 20 Brown Norway (BN) rats) and 16 transplanted rats (12 allografts and four isografts) were studied on day 4 post-transplantation with different USPIO doses (3.0-18.1 mg Fe/kg/body weight). All animals underwent 128 consecutive snapshot fast low-angle shot (FLASH) coronal dynamic studies in 43 s. In the normal rats, a larger maximum signal decrease (MSD) in the cortex and the outer medulla is observed with an increasing dose of USPIO particles (P < 0.01). No significant differences were observed between the right and left kidneys at all doses studied. Higher MSD, time of occurrence of MSD (tMSD), and wash-in slope appear with higher doses of USPIO particles. The dynamic curves for DA rats show similar shapes when compared to those for BN rats. In the transplanted rats, allograft kidneys show lower MSD, longer tMSD, and lower wash-in slope compared to those in the normal kidneys. Isograft kidneys show perfusion patterns similar to those of normal kidneys in the cortex and the outer medulla. Histopathology indicates acute vascular rejection in all allografts and normal kidney architecture in all isografts. The results clearly show good agreement between the renal graft perfusion measurements and histopathological changes associated with rejection. This work also introduces a new signal analysis methodology for the automatic detection of transplanted organ rejection. This method compares the dynamics of the intrarenal signal intensities for native and transplanted kidneys. A quantitative measurement to detect significant differences between these signals was developed, and showed that this technique exhibits good performance in identifying renal rejection.

Echo‐planar magnetic resonance myocardial perfusion imaging: Parametric map analysis and comparison with thallium SPECT

Magnetic resonance (MR) perfusion FLASH imaging has been used for assessing coronary artery disease (CAD). Echo-planar MR techniques have advantages in speed and in making MR perfusion imaging results more clinically accessible through parametric maps, but have not been previously assessed. We implemented a spin-echo, echo-planar MR technique and applied it at rest and during adenosine stress in 26 patients with CAD and abnormal thallium single-photon-emission computed tomography (SPECT), and analyzed the results by using a newly developed parametric map analysis of time to peak, peak intensity, and slope of contrast washin. The results were compared with the results of conventional visual analysis of the perfusion cine series. For detecting abnormal coronary territories, MR and SPECT were comparable for sensitivity, specificity, and accuracy (thallium, 70%, 78%, and 73%; MR, 79% 83%, and 80%; P = NS). There was good agreement between thallium and MR during stress (kappa = 0.49), but defects were larger by MR (2.4 vs. 3.1 segments for slope; P < 0.01). Additional segments were detected at rest by MR (58 for slope vs. 25 for thallium), which correlated with areas that became abnormal with stress in the thallium (sensitivity, 100%; specificity, 63%). The parametric maps were easier and faster to interpret than review of the original first-pass series of images (χ2 = 10.8; P < 0.04). The diagnostic performance of echo-planar perfusion MR and SPECT was similar, and combining the results with parametric mapping was useful for interpretation and considerably improved data display for clinical interpretation. MR, however, was faster and yielded images of higher resolution with no radiation burden. In multislice mode, these new MR techniques may have clinical value. J. Magn. Reson. Imaging 2001;13:192–200. © 2001 Wiley-Liss, Inc.

Absolute renal blood flow quantification by dynamic MRI and Gd-DTPA.

The aim of this study was to demonstrate the feasibility of the absolute renal blood flow quantification using MRI and injection of contrast media. Using a T1-weighted fast gradient sequence following an intravenous bolus injection of Gd-DTPA, dynamic images of the kidney were obtained in patients with well-functioning native kidneys (n = 7) or transplant (n = 9), with significant renal artery stenosis (n = 4) and with renal failure (n = 7). After signal intensity calibration, the absolute renal perfusion was equal to the wash-in slope of the renal transit curve divided by the contrast medium concentration at the peak of the bolus in the aorta. The cortical blood flow was 2.54+/-1.16 ml/min per gram in well-functioning kidneys decreasing to 1.09+/-0.75 ml/min per gram in case of renal artery stenosis (p = 0.04) and to 0.51+/-0.34 ml/min per gram in case of renal failure (P<0.001). These measurements were in agreement with previous results obtained by other methods. A standard MRI imaging sequence and a simple model can provide realistic quantitative data on renal perfusion. This work justifies further studies to compare this model with a gold standard for renal blood flow measurements.

MRI for the evaluation of regional myocardial perfusion in an experimental animal model.

Myocardial perfusion was assessed in nine pigs using ultrafast gradient-echo MRI (.5 T, 15-mT/m gradients) at different levels of myocardial blood flow (range, .005-1.84 ml/min/g), generated either by adenosine infusion or by a mechanical occluder, and measured independently using radiolabeled microspheres. Sixty-four consecutive, ECG-triggered, diastolic, short axis images of the left ventricle were obtained during intravenous bolus injections (n = 30) of .05 mmol/kg of gadopentetate dimeglumine. Relative changes in peak intensity, time to peak intensity, washin slope, correlation coefficient, and cross-correlation coefficient were computed from the time-intensity curves obtained from four regions of interest, namely septal, anterior, lateral, and inferior walls. The values from the inferior wall acted as reference for evaluating relative changes in the other three regions. The cross-correlation coefficient (P < .001, rho = .60) and the peak intensity (P < .001, r = .72) showed the best correlation with myocardial blood flow. The washin slope showed a weak positive trend (P < .05), but the low value of r (r = .28) indicated that the use of this parameter to predict flow was invalid; the correlation coefficient and time to peak intensity were not correlated (P = ns). In conclusion, this study shows that it is possible to evaluate relative myocardial perfusion after the first pass of a an intravenously injected bolus of gadopentetate dimeglumine, using dynamic MRI on a conventional medium field MRI system. The cross-correlation coefficient and the peak intensity resulted in more efficient parameters to evaluate relative inhomogeneity of regional myocardial perfusion.

An independent software system for the analysis of dynamic MR images.

A computer system for the manual, semi-automatic, and automatic analysis of dynamic MR images was to be developed on UNIX and personal computer platforms. The system was to offer an integrated and standardized way of performing both image processing and analysis that was independent of the MR unit used. The system consists of modules that are easily adaptable to special needs. Data from MR units or other diagnostic imaging equipment in techniques such as CT, ultrasonography, or nuclear medicine can be processed through the ACR-NEMA/DICOM standard file formats. A full set of functions is available, among them cine-loop visual analysis, and generation of time-intensity curves. Parameters such as cross-correlation coefficients, area under the curve, peak/maximum intensity, wash-in and wash-out slopes, time to peak, and relative signal intensity/contrast enhancement can be calculated. Other parameters can be extracted by fitting functions like the gamma-variate function. Region-of-interest data and parametric values can easily be exported. The system has been successfully tested in animal and patient examinations.

Comparison of ultrafast dipyridamole magnetic resonance imaging with dipyridamole sestamibi SPECT for detection of perfusion abnormalities in patients with one‐vessel coronary artery disease: Assessment by quantitative model fitting

The value of ultrafast MRI for detection of myocardial perfusion abnormalities in patients with coronary artery disease (CAD) was assessed in 10 patients with stable angina pectoris and angiographically proven one-vessel CAD using double-level short-axis ultrafast MRI with bolus injection of gadolinium-DTPA and tomographic technetium-99m SestaMIBI imaging (SPECT) during dipyridamole-induced coronary hyperemia. Abnormally perfused regions were assessed with SPECT and MRI in all (100%) patients. Agreement in localization between arteriography and SPECT was 80%; between arteriography and MR, 70%; and between SPECT and MR, 90%. The signal intensity increase after the bolus injection of gadolinium-DTPA using a linear fit, and the slope of gadolinium-DTPA wash-in using double exponential model fitting were significantly different between abnormally and normally perfused regions. These preliminary results demonstrate the potential of dipyridamole ultrafast MR to monitor stress-induced flow maldistribution in patients with single vessel CAD.