Renal blood flow quantification in pigs using contrast-enhanced ultrasound: an ex vivo study.

PURPOSE: The aim of the study was to evaluate a new method for the quantification of renal blood flow using contrast-enhanced ultrasound (CEUS) in an ex vivo pig kidney model. MATERIAL AND METHODS: After approval by the animal ethics committee, 4 pig kidneys were explanted and perfused with Celsior liquid (Imtix Sangstat, Lyon, France) at different flow rates (30, 50, 70 and 90 ml/min) in an ex vivo phantom. A 50 % diluted solution of SonoVue (Bracco, Milano, Italy) was infused in the artery at 0.5 ml/min. CEUS was performed with an Aplio system (Toshiba, Nasu, Japan) using a broadband linear transducer and pulse subtraction imaging. A total of 152 destruction-reperfusion sequences were acquired and cine loops were digitally stored for further quantification. Three different ROIs were placed upon the anterior, posterior cortex and segmental artery. Signal intensity measurements were performed in linear units and perfusion parameters were automatically extracted using dedicated software. Curve fitting was performed using a monoexponential model in which a time delay parameter was introduced. This fit allowed the assessment of the local blood flow into the region of interest (called "contrast-enhanced blood flow" (CEBF)). The artery mean signal intensity was averaged from the ten frames prior to the destruction phase. The normalized CEBF (nCEBF) was calculated as the ratio between CEBF and the mean arterial signal intensity. The CEBF and nCEBF were compared to the true blood flow indicated by the pump flow rate. RESULTS: The CEBF was correlated to the true blood flow only for the posterior cortical ROI (R(2) = 0.45, p = 0.05). The normalization using arterial signals improved CEBF correlation to true blood flow: nCEBF became correlated to the true blood flow when considering all ROIs (R(2)= 0.94, p < 0.0001) and correlation was improved for both anterior and posterior cortical ROIs (R(2)= 0, 93, p = 0.0004; R(2)= 0, 90, p = 0.0005, respectively). However, a significant kidney-dependent effect was observed for the anterior cortical ROI (p = 0.017) but not for the posterior cortical ROI (p = 0.89). CONCLUSION: Normalization using arterial signals significantly improved the estimation of blood flow calculated with CEUS.

[Tissue attenuation in small animals on contrast enhanced ultrasound]. / Prise en compte de l'atténuation ultrasonore en présence d'agents de contraste chez le petit animal.

Despite recent advances in contrast-enhanced ultrasound imaging, evaluation of tissue perfusion with contrast-enhanced ultrasound is still impaired by shadowing effects. These effects are particularly relevant in small animal studies due to high frequency imaging. Current methods of tissue attenuation correction are not suited for contrast-enhanced ultrasound examinations, because microbubble acoustic response to ultrasound waves is far more complex than that of tissues. A method allowing in vivo tissue attenuation correction in the presence of contrast agents is presented.

A posteriori respiratory gating in contrast ultrasound for assessment of hepatic perfusion.

An original strategy is proposed to minimize the impact of respiratory motion on hepatic contrast-enhanced ultrasound studies. It is based on the a posteriori triggering of dynamic image sequences. It was tested on perfusion studies acquired with a high temporal resolution (8 images s-1) to enable parametric imaging. A respiratory component was first estimated by independent component analysis. The estimation of the local minima and maxima of this curve enabled us to select two subsets of frames, corresponding to the end-of-inspiration plane and to the end-of-expiration plane. Both subsets were simultaneously analysed using factor analysis of medical image sequences. This method identified the main contrast uptake kinetics and their associated localizations. The global strategy was validated firstly on a simulated study and then applied to 11 patients' studies. In both cases, the frame selection was judged relevant and a necessary preliminary step before applying methods of parametric imaging. In conclusion, the a posteriori gating method that is proposed is a first step towards local quantification of hepatic contrast-enhanced ultrasound studies.

Assessment of left ventricular contraction by parametric analysis of main motion (PAMM): theory and application for echocardiography.

The computerized study of the regional contraction of the left ventricle has undergone numerous developments, particularly in relation to echocardiography. A new method, parametric analysis of main motion (PAMM), is proposed in order to synthesize the information contained in a cine loop of images in parametric images. PAMM determines, for the intensity variation time curves (IVTC) observed in each pixel, two amplitude coefficients characterizing the continuous component and the alternating component; the variable component is generated from a mother curve by introducing a time shift coefficient and a scale coefficient. Two approaches, a PAMM data driven and a PAMM model driven (simpler and faster), are proposed. On the basis of the four coefficients, an amplitude image and an image of mean contraction time are synthesized and interpreted by a cardiologist. In all cases, both PAMM methods allow better IVTC adjustment than the other methods of parametric imaging used in echocardiography. A preliminary database comprising 70 segments is scored and compared with the visual analysis, taken from a consensus of two expert interpreters. The levels of absolute and relative concordance are 79% and 97%. PAMM model driven is a promising method for the rapid detection of abnormalities in left ventricle contraction.

Validation of myocardial perfusion reserve measurements using regularized factor images of H(2)(15)O dynamic PET scans.

UNLABELLED: The use of H(2)(15)O PET scans for the measurement of myocardial perfusion reserve (MPR) has been validated in both animal models and humans. Nevertheless, this protocol requires cumbersome acquisitions such as C(15)O inhalation or (18)F-FDG injection to obtain images suitable for determining myocardial regions of interest. Regularized factor analysis is an alternative method proposed to define myocardial contours directly from H(2)(15)O studies without any C(15)O or FDG scan. The study validates this method by comparing the MPR obtained by the regularized factor analysis with the coronary flow reserve (CFR) obtained by intracoronary Doppler as well as with the MPR obtained by an FDG acquisition. METHODS: Ten healthy volunteers and 10 patients with ischemic cardiopathy or idiopathic dilated cardiomyopathy were investigated. The CFR of patients was measured sonographically using a Doppler catheter tip placed into the proximal left anterior descending artery. The mean velocity was recorded at baseline and after dipyridamole administration. All subjects underwent PET imaging, including 2 H(2)(15)O myocardial perfusion studies at baseline and after dipyridamole infusion, followed by an FDG acquisition. Dynamic H(2)(15)O scans were processed by regularized factor analysis. Left ventricular cavity and anteroseptal myocardial regions of interest were drawn independently on regularized factor images and on FDG images. Myocardial blood flow (MBF) and MPR were estimated by fitting the H(2)(15)O time-activity curves with a compartmental model. RESULTS: In patients, no significant difference was observed among the 3 methods of measurement-Doppler CFR, 1.73 +/- 0.57; regularized factor analysis MPR, 1.71 +/- 0.68; FDG MPR, 1.83 +/- 0.49-using a Friedman 2-way ANOVA by ranks. MPR measured with the regularized factor images correlated significantly with CFR (y = 1.17x - 0.30; r = 0.97). In the global population, the regularized factor analysis MPR and FDG MPR correlated strongly (y = 0.99x; r = 0.93). Interoperator repeatability on regularized factor images was 0.126 mL/min/g for rest MBF, 0.38 mL/min/g for stress MBF, and 0.34 for MPR (19% of mean MPR). CONCLUSION: Regularized factor analysis provides well-defined myocardial images from H(2)(15)O dynamic scans, permitting an accurate and simple measurement of MPR. The method reduces exposure to radiation and examination time and lowers the cost of MPR protocols using a PET scanner.

Factor analysis of dynamic magnetic resonance imaging in predicting the response of osteosarcoma to chemotherapy.

RATIONALE AND OBJECTIVES: The response of osteosarcoma to preoperative chemotherapy was assessed using dynamic magnetic resonance imaging (MRI) processed by factor analysis of medical image sequences (FAMIS). METHODS: Forty-nine dynamic image sequences, acquired after a bolus injection of gadolinium in 10 patients, were processed by FAMIS: FAMIS is a means whereby physiologic contrast enhancement kinetics, called factors, and their spatial distribution, termed factor images, are estimated. Tumor volumes were measured on static MRIs, and factor images were compared with histologic maps of the resected specimens. RESULTS: A substantial increase in tumor volume reflected a poor response to chemotherapy. Viable tumor was precisely depicted by the early vascular factor image, reflecting rapid uptake by tumor vessels. This early uptake disappeared in all five patients who responded to chemotherapy, whereas it persisted in four of five nonresponders. CONCLUSION: FAMIS of dynamic MRI is proposed as a possible means of predicting the response of osteosarcoma to chemotherapy.

Radiologic assessment of intranodal vascularity in head and neck squamous cell carcinoma. Correlation with histologic vascular density.

RATIONALE AND OBJECTIVES: Nodal response to chemotherapy in head and neck squamous cell carcinoma depends on the vascularization. The authors assessed different techniques in detecting nodal vascularization. METHODS: Fourteen patients with head and neck tumor were included before surgical treatment. The largest metastatic lymph node (mean axial scanographic diameters 30 x 20 mm) was studied by color and pulsed Doppler, and dynamic magnetic resonance images, processed by factor analysis of medical image sequences (FAMIS), which estimates physiologic contrast enhancement kinetics (factors) and their spatial distributions (factor images). Results were compared with the histologic microvessel density (MVD). Using light microscopy, MVD was estimated by the vascular surface (by staining endothelial cells) to the stroma surface ratio x 100. RESULTS: Three factors were identified by FAMIS: a constant factor in necrosis, an earlier F1 factor and a later F2 factor in normal lymphoid areas and neoplastic stroma. Color flow signal was detected when the MVD was greater than 6.36. CONCLUSIONS: Only one model of vascularization was extracted by FAMIS, with no difference between neoplastic and spared lymphoid areas. The presence of color-flow signals could help predict the response of metastatic lymph nodes to chemotherapy.

Target apex-seeking in factor analysis of medical image sequences.

The aim of factor analysis of medical image sequences (FAMIS) is to estimate a limited number of physical or physiological fundamental functions. Its oblique rotation stage strongly affects the quality and the interpretation of the resulting estimates (factors and factor images). A new target apex-seeking method which integrates physical or physiological knowledge in this stage is described. This knowledge concerns some of the fundamental functions and reacts on the determination of all the factors. A simulated spectral study illustrates the method. We discuss its properties in comparison with the other approaches using a priori physical or physiological information.

A statistical model for the determination of the optimal metric in factor analysis of medical image sequences (FAMIS).

A statistical model is added to the conventional physical model underlying factor analysis of medical image sequences (FAMIS). It allows a derivation of the optimal metric to be used for the orthogonal decomposition involved in FAMIS. The oblique analysis of FAMIS is extended to take this optimal metric into account. The case of scintigraphic image sequences is used. We derive in this case that the optimal decomposition is obtained by correspondence analysis. A scintigraphic dynamic study illustrates the practical consequences of the use of the optimal metric in FAMIS.

Spatial regularization applied to factor analysis of medical image sequences (FAMIS).

Dynamic image sequences allow physiological mechanisms to be monitored after the injection of a tracer. Factor analysis of medical image sequences (FAMIS) hence creates a synthesis of the information in one image sequence. It estimates a limited number of structures (factor images) assuming that the tracer kinetics (factors) are similar at each point inside the structure. A spatial regularization method for computing factor images (REG-FAMIS) is proposed to remove irregularities due to noise in the original data while preserving discontinuities between structures. REG-FAMIS has been applied to two sets of simulations: (a) dynamic data with Gaussian noise and (b) dynamic studies in emission tomography (PET or SPECT), which respect real tomographic acquisition parameters and noise characteristics. Optimal regularization parameters are estimated in order to minimize the distance between reference images and regularized factor images. Compared with conventional factor images, the root mean square error between regularized images and reference factor images is improved by 3 for the first set of simulations, and by about 1.5 for the second set of simulations. In all cases, regularized factor images are qualitatively and quantitatively improved.

Reduced capillary perfusion and permeability in human tumour xenografts treated with the VEGF signalling inhibitor ZD4190: an in vivo assessment using dynamic MR imaging and macromolecular contrast media.

We describe the use of perfusion-permeability magnetic resonance imaging (ppMRI) to study hemodynamic parameters in human prostate tumor xenografts, following treatment with the vascular endothelial growth factor-A (VEGF) receptor tyrosine kinase inhibitor, ZD4190. Using a macromolecular contrast agent (P792), a fast MR imaging protocol and a compartmental data analysis, we were able to demonstrate a significant simultaneous reduction in tumor vascular permeability, tumor vascular volume and tumor blood flow (43%, 30% and 42%, respectively) following ZD4190 treatment (100 mg/kg orally, 24 h and 2 h prior to imaging). This study indicates that MR imaging can be used to measure multiple hemodynamic parameters in tumors, and that tumor vascular permeability, volume and flow, can change in response to acute treatment with a VEGF signaling inhibitor.

Processing by factor analysis of dynamic dual isotope studies using 99Tcm and 201Tl within a middle energy band. Evaluation in thyroid nodule malignancy.

Simultaneous investigations with two isotopes are currently restricted because of spectral overlap. The factor analysis of spectral and dynamic structures (FASDS) method is shown to achieve accurate spectral separation. In addition, it estimates underlying dynamic mechanisms. Twenty-six patients were injected simultaneously with 99Tcm-pertechnetate and 201Tl-chloride to assess the malignancy of solitary thyroid nodules. List-mode acquisition of spectral, temporal and spatial coordinates of events allows the reconstruction of an image sequence indexed by time and energy. FASDS proceeds in two steps. First it yields both dynamic and spatial information related to each isotope (99Tcm and 201Tl) and partially removes the scatter component. Then it estimates the underlying kinetics and associated spatial distributions of each isotope. Using the 201Tl component, an index was derived from the uptake ratio between nodules and normal thyroid tissue. Concerning the detection of malignant nodules the method indicated no false negative in our limited group of 26 patients. One false positive result was found which could not be classified by the investigation of the 201Tl dynamic components contained in the reconstructed 201Tl factor sequence.

Extraction of functional volumes from medical dynamic volumetric data sets.

A method based on factor analysis is presented to process dynamic volumetric (t + 3D) data sets acquired for flow, excretion, or metabolic studies. It estimates a reduced number of underlying physiological kinetics and their associated spatial distributions, corresponding to functional volumes, using dedicated algorithms. The global (t + 3D) approach is shown to be superior to the conventional one, which repeats estimations on each (t + 2D) data set, obtained for each slice or projection of the volume.

FAMIS: a software package for functional feature extraction from biomedical multidimensional images.

An increased number of image sequences is acquired in all modalities of the biomedical imaging field in order to study displacement or metabolism of a tracer or a contrast agent. It requires effective processing methods to estimate the underlying physiological components. We have developed a software package based on factor analysis algorithms which can adapt to various imaging modalities and its extension to double-indexed image sequences. We describe general characteristics of the software and present the main points of the user-friendly interface. The performances of the package are discussed and the possibilities of the methodology are illustrated using an example in magnetic resonance imaging.

[Value of factor analysis in a wall motion study: preliminary application in the detection of left ventricular segmental contraction ischemic disorders by echocardiography]. / Apport d'une analyse factorielle à l'étude de mouvements: application préliminaire à la détection par échocardiographie des troubles de la contraction segmentaire du ventricule gauche ischémique.

PURPOSE: Factor Analysis of Medical Image Sequences (FAMIS) was tested to study the regional wall motion of the left ventricle at echocardiography. MATERIALS AND METHODS: FAMIS analyzed the time signal curves of each pixel. One flat curve and one curve describing the contraction-relaxation of the left ventricle were first estimated. The contributions of the curve of each pixel to the two previous curves were computed, yielding two "factor images". The spatial distribution of positive and negative coefficients of the second factor image was analyzed. The evaluation was carried out on 222 segments (20 patients, 18 parasternal short-axis views, 17 apical four-chamber views, and 15 apical two-chamber views). A first echocardiographer reviewed the factor images and the reading was compared to the conventional reading of the cine-loops by two other echocardiographers. Each segment was scored as normal, hypokinetic, akinetic, or dyskinetic. RESULTS: On normal segments, the positive coefficients of the second factor image were on the inner side, the negative coefficients were on the outer side. Dyskinesis yields the opposite pattern. Hypokinesis and akinesis give intermediate images. An absolute concordance was obtained on 71.2% of all segments between the two types of reading. Larger discrepancies were found for akinetic and hypokinetic segments. CONCLUSION: FAMIS is a promising tool to study regional wall motion of the left ventricle.

[Image analysis in contrast echocardiography]. / Les traitements d'image en échocardiographie de contraste.

The visualization of contrast agents in echocardiography is obtained with complex acquisition sequences and their analysis is dependent on operator experience. In order to be more accessible, images analysis is essential and the main objective is to integrate qualitative and quantitative data in one single image.

Descending aorta subject-specific one-dimensional model validated against in vivo data.

The aorta plays a major role in the cardiovascular system and its function and structure are primarily affected by aging, eating habits, life style and other cardiovascular risk factors, inducing increased stiffness which is associated with cardiovascular and cerebral morbi-mortality. Our objective was to develop and validate a robust subject-specific one-dimensional wave propagation numerical model of the descending aorta. This model with a cross-sectional area, velocity and pressure formulation is built using geometric and hemodynamic data measured on a specific person and is validated against in vivo data acquired on the same subject at three distinct anatomical locations along the thoracic aorta. We studied seven healthy volunteers, who underwent carotid applanation tonometry and aortic cardiovascular magnetic resonance (CMR). Responses of our model in terms of changes in central pressure waveform with arterial alterations were consistent with previously described physiological knowledge. Quantitative validation averaged over the three descending aortic locations and the seven subjects provided low rms errors (given in percentage of the maximal clinical value) between simulated and CMR data, i.e. area: 10±6%, velocity: 11±3%, flow rate: 9±3%. Finally, we also found low rms (5±2%) when comparing simulated pressure in the proximal aortic location against tonometric carotid pressure curves. In conclusion, this simple model performs similar to more complex models of the entire systemic arterial tree at a fraction of the cost, and could be of major usefulness in the non-invasive and local estimation of proximal biomechanical and hemodynamic indices.

Comparison of various methods for quantitative evaluation of myocardial infarct volume from magnetic resonance delayed enhancement data.

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) enables the estimation of myocardial infarct (MI) extent. Nevertheless, manual quantification is time consuming and subjective. We sought to assess MI volume with different quantitative methods in both acute (AMI) and chronic MI (CMI). METHODS: CMR was performed 50 ± 21 h after MI in 52 patients and was repeated 100 ± 21 days later in a subgroup of 34 patients. Then, necrosis volumes were quantified using: 1) manual delineation, 2) automated fuzzy c-means method, and 3) +2 to 6 SD thresholding approaches. Results were compared against peak values of serum Troponin I (TnI), creatine kinase (CK) and left ventricular (LV) functional parameters: LV ejection fraction (LVEF), indexed end-diastolic (EDVi), end-systolic volumes (ESVi) and the number of hypokinetic segments (NbHk). RESULTS: For CMI, quantitative evaluation of infarct size using manual, +2SD, +3 SD and fuzzy c-means provided equivalent results in terms of correlation coefficients for comparisons of MI volumes against LV function parameters (LVEF: r>0.79, p<0.0001; ESVi: r>0.82, p<0.0001, EDVi: r>0.67, p<0.0001, NbHk: r>0.54, p<0.0009). For AMI, +2SD and fuzzy c-means approaches provided higher correlations for comparisons of AMI volumes against biochemical markers (CK: r>0.79, p<0.0001,TnI: r>0.77, p<0.0001) and chronic LV function parameters (LVEF: r>0.82, p<0.0001, NbHk: r>0.59, p<0.0002). CONCLUSIONS: The fuzzy c-means and 2SD methods provided highest correlations with biochemical MI quantification as well as LV function parameters. The fuzzy c-means approach which does not require an arbitrary identification of the remote myocardium is fast and reproducible. It may be clinically useful in the evaluation of patients with MI.

Methodology for jointly assessing myocardial infarct extent and regional contraction in 3-D CMRI.

Automated extraction of quantitative parameters from cardiac magnetic resonance images is crucial for the management of patients with myocardial infarct. This paper proposes a postprocessing procedure to jointly analyze Cine and delayed-enhanced (DE) acquisitions, in order to provide an automatic quantification of myocardial contraction and enhancement parameters and a study of their relationship. For that purpose, the following processes are performed: 1) DE/Cine temporal synchronization and 3-D scan alignment, 2) 3-D DE/Cine rigid registration in a region about the heart, 3) myocardium segmentation on Cine-MRI and superimposition of the epicardial and endocardial contours on the DE images, 4) quantification of the myocardial infarct extent (MIE), 5) study of the regional contractile function using a new index, the amplitude to time ratio (ATR). The whole procedure was applied to ten patients with clinically proven myocardial infarction. The comparison between the MIE and the visually assessed regional function scores demonstrated that the MIE is highly related to the severity of the wall motion abnormality. In addition, it was shown that the newly developed regional myocardial contraction parameter (ATR) decreases significantly in delayed enhanced regions. This largely automated approach enables the combined study of regional MIE and left ventricular function.

An automatic respiratory gating method for the improvement of microcirculation evaluation: application to contrast-enhanced ultrasound studies of focal liver lesions.

Contrast-enhanced ultrasound (CEUS), with the recent development of both contrast-specific imaging modalities and microbubble-based contrast agents, allows noninvasive quantification of microcirculation in vivo. Nevertheless, functional parameters obtained by modeling contrast uptake kinetics could be impaired by respiratory motion. Accordingly, we developed an automatic respiratory gating method and tested it on 35 CEUS hepatic datasets with focal lesions. Each dataset included fundamental mode and cadence contrast pulse sequencing (CPS) mode sequences acquired simultaneously. The developed method consisted in (1) the estimation of the respiratory kinetics as a linear combination of the first components provided by a principal components analysis constrained by a prior knowledge on the respiratory rate in the frequency domain, (2) the automated generation of two respiratory-gated subsequences from the CPS mode sequence by detecting end-of-inspiration and end-of-expiration phases from the respiratory kinetics. The fundamental mode enabled a more reliable estimation of the respiratory kinetics than the CPS mode. The k-means algorithm was applied on both the original CPS mode sequences and the respiratory-gated subsequences resulting in clustering maps and associated mean kinetics. Our respiratory gating process allowed better superimposition of manually drawn lesion contours on k-means clustering maps as well as substantial improvement of the quality of contrast uptake kinetics. While the quality of maps and kinetics was satisfactory in only 11/35 datasets before gating, it was satisfactory in 34/35 datasets after gating. Moreover, noise amplitude estimated within the delineated lesions was reduced from 62 ± 21 to 40 ± 10 (p < 0.01) after gating. These findings were supported by the low residual horizontal (0.44 ± 0.29 mm) and vertical (0.15 ± 0.16 mm) shifts found during manual motion correction of each respiratory-gated subsequence. The developed technique could be used as a basis for accurate quantification of perfusion parameters for the evaluation and follow-up of patients under antiangiogenic therapies.