New intravascular contrast agent applied to dynamic contrast enhanced MR imaging of human breast cancer.

PURPOSE: To evaluate the feasibility of using dynamic contrast-enhanced MR imaging with a new intravascular contrast agent in grading human breast cancer. MATERIAL AND METHODS: 23 patients with 27 breast tumors (21 carcinomas and 6 fibroadenomas) were examined with dynamic MR imaging after administration of Clariscan, an iron oxide nanoparticle with large T1 relaxivity and a long plasma half life. A 3D T1-weighted gradient echo sequence with an acquisition time of 60 s was repeated at regular intervals of 3-5 min before and up to 1 h after injection of 2 mg/kg b.w. of Clariscan. The endothelial transfer constant, Kps, which reflects overall vascular permeability, and the fractional plasma volume, fPV, were estimated from time-intensity curves acquired from three separate regions of interest (ROIs): whole tumor, a permeability hot spot, and a blood volume hot spot. Kps and fPV were compared to the results of histologic tumor grading (Scarff-Bloom-Richardson, SBR) and microvascular density, MVD. RESULTS: A statistically significant correlation between the MR-derived Kps parameters and the SBR score was obtained for the whole tumor ROI (R = 0.70), and for the permeability hot spot ROIs (R = 0.67). A correlation between fPV and SBR was detected for the blood volume hot spot ROIs (R = 0.48). There was no statistically significant correlation between Kps or fPV with MVD. CONCLUSION: The results support the hypothesis that dynamic MR with the intravascular contrast agent Clariscan may be used for non-invasive tumor grading.

An estimator for functional data with application to MRI.

We propose a method for restoring the underlying true signal in noisy functional images. The Nadaraya-Watson (NW) estimator described in, e.g., [1] is a classical nonparametric estimator for this problem. Since the true scene in many applications contains abrupt changes between pixels of different types, a modification of the NW estimator is needed. In the data we study, the characteristics of each pixel are given as a function of time. This means that a curve of data points is observed at each pixel. Utilizing this time information, the NW weights can be modified to obtain a weighted average over pixels with the same true value. Theoretical results showing the estimator's properties are developed. Several parameters play an important role for the restoration result. Practical guidelines are given for how these parameters can be selected. Finally, we demonstrate how the method can be successfully applied both to artificial data and Magnetic Resonance Images.

Analysis of contrast-enhanced dynamic MR images of the lung.

Recent studies have demonstrated the potential of dynamic contrast-enhanced magnetic resonance imaging (MRI) describing pulmonary perfusion. However, breathing motion, susceptibility artifacts, and a low signal-to-noise ratio (SNR) make automatic pixel-by-pixel analysis difficult. In the present work, we propose a novel method to compensate for breathing motion. In order to test the feasibility of this method, we enrolled 53 patients with pulmonary embolism (N = 24), chronic obstructive pulmonary disease (COPD) (N = 14), and acute pneumonia (N = 15). A crucial part of the method, an automatic diaphragm detection algorithm, was evaluated in all 53 patients by two independent observers. The accuracy of the method to detect the diaphragm showed a success rate of 92%. Furthermore, a Bayesian noise reduction technique was implemented and tested. This technique significantly reduced the noise level without removing important clinical information. In conclusion, the combination of a motion correction method and a Bayesian noise reduction method offered a rapid, semiautomatic pixel-by-pixel analysis of the lungs with great potential for research and clinical use.

Relationship between function and perfusion early after acute myocardial infarction.

To assess the relationship between baseline left ventricle function, functional reserve and resting myocardial perfusion in patients with acute myocardial infarction (AMI). After AMI the presence of dysfunctioning but viable myocardium plays a determinant role in clinical outcome. Regional ventricular function was evaluated by echocardiography both in resting conditions and during dobutamine infusion (10 microg/kg/min). Perfusion was assessed by magnetic resonance imaging in a single slice approach where the first pass of an intravenously injected bolus of gadolinium-based contrast agent was followed through six regions of interest within the myocardium. In each patient a region with normal function was used as reference and the cross-correlation coefficient (CCC), which described the myocardial perfusion relatively to the reference region (CCC = 1 means equivalent perfusion), was obtained for the other five myocardial regions. Twenty-two patients were enrolled into the study. Sixty-one segments had normal function and normal perfusion (CCC = 0.92+/-0.23). The perfusion deficit was more marked in the 29 regions with resting akinesia-dyskinesia than in the 20 hypokinetic regions (CCC = 0.71+/-0.45 vs. 0.84+/-0.23; p < 0.05). Out of the 29 regions with resting akinesia-dyskinesia the 13 segments which showed functional improvement following dobutamine had a higher resting perfusion than the 16 segments which were unresponsive to dobutamine (CCC = 0.83+/-0.32 vs. 0.61+/-0.52, p < 0.05). Similarly, out of the 20 regions with resting hypokinesia the 11 segments having functional reserve showed an higher resting perfusion than the segments which did not (0.96+/-0.21 vs. 0.69+/-0.19; p < 0.05). Early after AMI, the perfusion deficit reflects the severity of the mechanical dysfunction. In regions with baseline dyssynergy resting perfusion is, in general, higher when contractile reserve can be elicited by stress-echo.

Feature extraction and classification of dynamic contrast-enhanced T2*-weighted breast image data.

UNLABELLED: The relatively low specificity of dynamic contrast-enhanced T1-weighted magnetic resonance imaging (MR) imaging of breast cancer has lead several groups to investigate different approaches to data acquisition, one of them being the use of rapid T2*-weighted imaging. Analyses of such data are difficult due to susceptibility artifacts and breathing motion. MATERIALS AND METHODS: One-hundred-twenty-seven patients with breast tumors underwent MR examination with rapid, single-slice T2*-weighted imaging of the tumor. Different methods for classifying the image data set using leave-one-out cross validation were tested. Furthermore, a semi-automatic region of interest (ROI) definition tool was presented and compared with manual ROI definitions from a previous study. Finally, pixel-by-pixel analysis was done and compared with ROI analysis. The analyses were done with and without noise reduction. RESULTS: The minimum enhancement parameter was the most robust and accurate of the parameters tested. The semi-automatic ROI definition method was fast and produced similar results as the manually defined ROIs. Noise reduction improved both sensitivity and specificity, but the improvement was not statistically significant. The pixel-based analysis methods used in the present study did not improve classification results. CONCLUSIONS: Analysis of T2*-weighted breast images can be done in a rapid and robust manner by using semi-automatic ROI definition tools in combination with noise reduction. Minimum enhancement gives an indication of malignancy in T2*-weighted imaging.

Perfusion magnetic resonance imaging of the lung: characterization of pneumonia and chronic obstructive pulmonary disease. A feasibility study.

Perfusion magnetic resonance (MR) imaging is a promising new method for detection of perfusion defects in the diagnosis of pulmonary embolism. In the present study we evaluated the first-pass characteristics of perfusion MR imaging in patients with pneumonia or chronic obstructive pulmonary disease (COPD), frequent differential diagnoses to pulmonary embolism. Dynamic contrast-enhanced MR images of 12 patients with acute pneumonia and 13 patients with exacerbation of COPD were acquired in both the coronal and transaxial planes (an inversion recovery prepared gradient-echo sequence using 0.05 mmol/kg gadodiamide/injection). The MR images and the signal intensity (SI) versus time curves were characterized for each disease entity and compared with normal lung and the findings in pulmonary embolism from our previous study. The perfusion MR images of pneumonia showed distinct regions of increased contrast enhancement; in COPD with signs of emphysema (11 of the 13 COPD patients), the images showed a coarse pattern of reduced contrast enhancement. The SI versus time curves of pneumonia, COPD with signs of emphysema, and normal lung were statistically different, the respective pooled SI values (+/-95% CI) being as follows: mean baseline SI, 20.7 (1.1), 7.4 (0.4), and 8.5 (0.3); mean peak SI, no peak, 12.9 (1.5), and 27 (4.6); and mean max change of SI in percent, 110 (27), 79 (22), and 205 (52). Perfusion MR imaging of pneumonia and COPD with signs of emphysema showed first-pass that were characteristics promising for diagnostic use. Both the MR images and the SI versus time curves were different from the perfusion characteristics in normal lung and pulmonary embolism shown previously.

Use of the mean transit time of an intravascular contrast agent as an exchange-insensitive index of myocardial perfusion.

A simple two-compartment model was used to study the effects of water exchange on the signal produced by an inversion recovery prepared rapid gradient-echo sequence during the first passage of a low dose of an intravascular contrast agent. Water exchange at intermediate rates of exchange (1-10 Hz) between the vascular and extravascular spaces caused the form of the signal changes during the first pass to be dependent on both the fractional sizes of the vascular and extravascular compartments and on the exchange rate. Unless the effects of exchange are minimized by using a very short inversion time, parameters such as the peak height and area under the curve will be affected by regional and/or pathological variations in the exchange rate and the size of the vascular fraction. The mean transit time (MTT) is, however, less affected by water exchange. Experimental first-pass data produced by intravascular low-dose injections of iron oxide particles were studied in five pigs at 0.5 T. The MTT as derived from the first-pass curves, without deconvolution with the arterial input function, was well correlated with the myocardial blood flow (MBF) as measured using radioactive microspheres (r = 0.70, n = 52, P < 0.01). Other first-pass parameters such as the peak height or area under the curve exhibited either a poorer, or no, correlation with the MBF. The data suggest that the MTT of the first pass of an intravascular contrast agent may be a robust, quantitative method for assessing myocardial blood flow in patients.

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.

Image postprocessing and contrast agents in clinical MR imaging--an introductory overview.

Some fundamentals of image processing, its applications to MR imaging, and inherent problems are discussed. Processing of contrast-enhanced dynamic imaging studies is introduced and some clinical examples explain the applications in research and clinical routine.

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

PURPOSE: 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. MATERIAL AND METHODS: 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. RESULTS AND CONCLUSION: The system has been successfully tested in animal and patient examinations.