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J Nuyts

Publications and source records attributed to J Nuyts.

At least 37 records · Page 2Linked to original sources

Only hibernating myocardium invariably shows early recovery after coronary revascularization.

BACKGROUND: The aims of this study were to identify hibernating myocardium (hypocontractile, hypoperfused viable myocardium that regains contractility after revascularization) in the clinical setting and to predict functional outcome in patients with coronary artery disease after coronary revascularization. METHODS AND RESULTS: Preoperative data related to the anterior free wall of the left ventricle were collected in 50 coronary bypass surgery candidates (positron emission tomography [PET], [13N]NH3 for flow, and [18F]FDG for metabolism [MET]; equilibrium-gated nuclear angiography [EGNA] for regional ejection fraction [REF]; and histological data from myocardial biopsies for percentage fibrosis and viable myocytes). Three months after surgery, the patients had follow-up PET and EGNA investigations. A principal-components analysis identified four patient clusters. Cluster 1 (n = 9) had normal viable myocardium. Cluster 2 (n = 18) had viable hypocontractile myocardium (REF, 39 +/- 12%) showing a PET mismatch pattern. Cluster 3 (n = 16) had viable hypocontractile myocardium associated with morphological myocyte injury showing a matched moderate decrease in flow (66 +/- 11%) and MET (70 +/- 11%). Cluster 4 (n = 7) had hypocontractile myocardium with mainly scar tissue (fibrosis, 74 +/- 12%). After surgery, only cluster 2, with hibernating myocardium, showed significant improvement in REF (from 39 +/- 12% to 50 +/- 13%, P < .05). Cluster 3, with sites of morphological myocyte injury, showed no recovery. The stepwise logistic regression showed a combination of low preoperative REF and high MET to be the best predictor of functional recovery (P < .008). CONCLUSIONS: Multivariate analysis identifies hibernating myocardium showing early postrevascularization recovery, as opposed to viable but myolytic myocardium with no early recovery. Postrevascularization recovery can be predicted (combination of low REF and high MET) by noninvasive techniques.

Adult↗

Prognostic significance of bone marrow trephine and peripheral blood smears in 55 patients with mantle cell lymphoma.

Bone marrow trephine and peripheral blood smears taken at diagnosis of 55 cases of well-documented mantle cell lymphomas were reviewed in order to analyse the leukaemic involvement in this non-Hodgkin's lymphoma: its incidence, morphological characteristics and prognostic significance. A median survival of 36 months was found. The median age was 61 and the male to female ratio was 4:1. Morphologically 7 cases presented with a mantle zone pattern, all the others had a diffuse pattern. Involvement of the bone marrow was found in 58% and a trend for prolonged survival in patients with a negative trephine was seen. An absolute lymphocytosis above 10,000 mu l was found at diagnosis in 5 cases (10%) and had a statistically significant impact on survival. An additional 5 cases developed frank leukaemia during the course of the disease and died within 1 to 6 months of this evolution, suggesting that marked lymphocytosis is more a terminal event associated with an extremely poor prognosis than a presenting symptom. Finally we identified an additional parameter with statistically prognostic significance, namely, the presence of atypical cells in the peripheral blood even in the absence of an increased lymphocytosis.

Adult↗

CD40 is a prognostic marker in primary cutaneous malignant melanoma.

CD40 is a receptor at the surface of B lymphocytes with important functions in the immune response. CD40 has also been found on a variety of carcinoma and melanoma cell lines where it has been suggested to serve as a possible receptor for mitogenic signals. We studied the expression and distribution of CD40 in paraffin sections of 71 uniformly treated malignant melanomas (MMs) with a long clinical follow-up using well known monoclonal antibodies. For comparison, 71 benign nevi were also studied. Common acquired nevi occasionally expressed CD40 in nests or single cells at the dermo-epidermal junction; no immunoreactivity was observed in the dermal part of acquired nevi, and all Spitz' nevi were entirely negative. One-third of large congenital nevi expressed CD40 in small clusters of heavily pigmented, epithelioid cells, corresponding to so-called proliferative nodules. In 41 of 71 MMs, CD40 was expressed in single or clustered neoplastic melanocytes; 9 cases showed CD40 expression only in the radial growth phase, and in 32 cases, the vertical growth phase showed CD40 expression. The same staining pattern was obtained with other anti-CD40 monoclonal antibodies, directed to different epitopes of the CD40 molecule. In 29 of 32 MMs showing CD40 in the vertical growth phase, expression of the CD40 ligand (CD40L) was studied; in 13 of these 29, CD40L was found in the same tumor areas that expressed CD40. Analysis of 28 metastases from 24 MM patients showed in the majority of cases a similar, scattered or nodular staining pattern as observed in the primary tumor. Patients expressing CD40 in the vertical growth phase of their MM did not differ significantly from CD40-negative patients with respect to any of the known prognostic parameters but showed a significantly shorter tumor-free survival. Patients with CD40+ CD40L+ MM tended to have a shorter tumor-free survival than those lacking CD40L. We conclude that CD40 represents a novel prognostic parameter in primary cutaneous MM. The co-localization of CD40 and CD40L suggests an autocrine growth loop in the vertical growth phase of MM.

Biomarkers, Tumor↗

Impaired myocardial tissue perfusion early after successful thrombolysis. Impact on myocardial flow, metabolism, and function at late follow-up.

BACKGROUND: Impaired tissue reperfusion after successful recanalization of an epicardial coronary artery has been documented both in animals and in patients with acute myocardial infarction. Whether this phenomenon can be demonstrated with positron emission tomography (PET) and whether it has an effect on late recovery of flow, metabolism, and function are unknown. METHODS AND RESULTS: Thirty patients with an acute myocardial infarction and TIMI flow grade 3 of the infarcted vessel at 90 minutes after thrombolytic therapy were studied. Within 24 hours after thrombolysis, at 5 days and at 3 months, myocardial blood flow was measured with 13NH3. 18FDG uptake was measured at 5 days. Radionuclide left ventricular angiograms were acquired at 5 days and at 3 months. In 11 patients (37%), regional myocardial flow was severely impaired (< 50% of normally perfused myocardium) despite successful thrombolysis. No recovery of left ventricular function occurred in any of these patients at 3 months. In 12 patients (40%), intermediate flows (50% to 75% of normal) were found, with functional improvement after angioplasty only in regions with a PET mismatch. Seven patients (23%) had high flow values early after successful thrombolysis (> 75% of normal) and showed preserved regional contractile function at 3 months. CONCLUSIONS: This study is the first demonstration with PET of impaired myocardial tissue perfusion in patients with an acute myocardial infarction after successful thrombolysis. Functional recovery of the reperfused myocardium is observed only when adequate tissue flow is restored. PET may be helpful in selecting patients in whom additional revascularization can improve recovery of left ventricular function.

Aged↗

Regional myocardial blood flow, glucose utilization and contractile function before and after revascularization and ultrastructural findings in patients with chronic coronary artery disease.

In patients with chronic coronary artery disease, follow-up measurements of myocardial blood flow, metabolism and function were correlated with histology. In 41 patients with chronic coronary artery disease and a severely stenosed left anterior descending coronary artery, a positron emission tomographic (PET) flow/metabolism study and nuclear angiography were performed immediately before and 3 months after bypass surgery. Biopsies were taken from the left ventricular anterior wall at the time of surgery. Control biopsies were taken from donor hearts for cardiac transplantation and from hearts of patients with a defect of the atrial septum. A significant improvement of flow (P<0.01) and regional contractile function (P<0.01) was observed in the mismatch group. Glucose utilization was significantly lower (P<0.001) as compared to preoperative values. The group with preserved flow and the PET match group revealed no significant changes in flow, metabolism or function. Control biopsies revealed significantly less myolytic cells as compared to biopsies taken from both match and mismatch groups (P<0.01) and less fibrosis as compared to biopsies taken from the match group (P<0.01). Postoperatively, linear relationships were found between flow and both % fibrosis (r = 0.71, P<0.001) and regional anterior ejection fraction (r = 0.7, P<0.001). Only mismatch areas revealed significant recovery of both flow and function after revascularization with a disappearance of enhanced glucose uptake. The better linear correlation between flow and % fibrosis after surgery as compared to preoperatively was probably due to improvement of flow values in the mismatch group.

Coronary Artery Bypass↗

Metabolism of nitrogen-13 labelled ammonia in different conditions in dogs, human volunteers and transplant patients.

To investigate the rate of metabolism of nitrogen-13 labelled ammonia (13NH3) in different conditions, we have determined the relative amount of unchanged 13NH3 in the blood of dogs, volunteers and transplant patients at different times following injection. In dogs, the determinations were made under basal conditions, during adenosine administration and after coronary occlusion. The results show that adenosine administration increases the metabolic rate whereas coronary occlusion does not affect 13NH3 metabolism. For both human volunteers and transplant patients the metabolic rate of 13NH3 was assessed under basal conditions and during adenosine administration. 13NH3 metabolism proceeds faster in transplant patients than in volunteers under both conditions. Adenosine administration causes a faster 13NH3 turnover in volunteers but not in transplant patients. Application of individual metabolite correction resulted in a 16% decrease in the calculated blood flow compared to uncorrected values. A smaller difference (5%) was observed between correction with mean metabolite values and individually acquired metabolite values.

Adenosine↗

A study of the liver-heart artifact in emission tomography.

UNLABELLED: With the introduction of 99mTc-teboroxime, a previously undocumented artifact has shown up in cardiac SPECT imaging. In the images, the uptake values near the inferior wall are lower than expected. The artifact has been reported in the literature, but an adequate explanation has not yet been provided. The high uptake of 99mTc-teboroxime in the liver has been demonstrated to be the cause of this artifact. METHODS: With simulations we show that an artifact can be reproduced by applying filtered backprojection (without corrections for attenuation) of attenuated and blurred projections. The conclusions from the simulations are validated with SPECT and PET phantom measurements. Maximum likelihood expectation maximization (ML-EM) reconstruction is applied to evaluate the effect of accurate attenuation correction. The influence of the high liver uptake on the convergence of ML-EM was also evaluated. RESULTS: The artifact results mainly when the photon attenuation during reconstruction is ignored. This results in a distorted reconstruction of the liver. These distortions affect the neighboring inferior wall of the myocardium. While the use of opposite projections reduces the effect, accurate attenuation correction nearly eliminates it. A small additional deformation is caused by the position dependence of the spatial resolution of the gamma camera. It was also noted that the presence of the liver slows down the convergence of ML-EM in the heart region. CONCLUSION: The liver-heart artifact is an attenuation effect and is eliminated by attenuation correction. The local convergence of ML-EM is affected by the total image content.

Animals↗

Acquisition and processing of the radio-frequency signal in echocardiography: a new global approach.

Recently there has been an increasing interest in the use of the "raw" radio-frequency (RF) signal generated in echocardiography for use in tissue-characterization to distinguish between normal and pathological myocardium, for automatic delineation of the endocardial border without being limited by the weak contrast of the traditional video images, and for use in contrast echography, where it could offer the possibility to visualize perfusion using intravenous contrast injections. One of the main problems in this kind of research is the acquisition of the signal having a high frequency and large bandwidth. We have developed a new global method for the acquisition of this RF signal. To digitize the data, a video sequencer is used. In this way it becomes possible to sample all available data generated by the echographic equipment during at least 1 s. This means that all data of the complete sector scan during a complete heart-cycle can be digitized without using any data reduction technique or triggering on the electrocardiogram. The advantage of this approach is that all characteristics of the signal can be studied, without being limited by data reduction techniques used during acquisition. This method enables us to calculate parameters such as "integrated backscatter," or to investigate the signal more extensively, e.g., by using spectrum analysis. We can compare different regions of the myocardium and examine them during the heart-cycle, all within the same beat. We have also written a software package for the processing of the large amount of data resulting from the acquisition.

Animals↗

Histological alterations in chronically hypoperfused myocardium. Correlation with PET findings.

BACKGROUND: In patients with chronic coronary artery disease (CAD) and left ventricular dysfunction, flow/metabolic studies of the myocardium with positron emission tomography (PET) are able to distinguish viable but dysfunctional myocardium from irreversible ischemic injury and scar tissue. In this study, PET findings of blood flow and metabolism in chronically hypoperfused myocardium were correlated with histology. METHODS AND RESULTS: We studied 33 patients suffering from CAD. In each patient, myocardial blood flow and metabolism were measured with PET 1 or 2 days before revascularization. During surgery, transmural biopsies were taken from the left ventricular anterior wall and planimetrically scored for the degree of myolysis (sarcomere loss). The amount of connective tissue was calculated using morphometric techniques. Contrast ventriculography demonstrated abnormal wall motion in 23 patients. Fourteen patients with a mismatch pattern (decreased flow with preserved metabolism) in the biopsy region after quantitative analysis of the PET data showed 11 +/- 6 vol% fibrosis and 25 +/- 13% cells with sarcomere loss. The space formerly occupied by sarcomeres was mainly replaced by glycogen and mitochondria. A significant wall motion improvement was noted 3 months after surgery. Nine patients showed a match pattern (concordant flow/metabolism defects). The biopsies revealed 35 +/- 25% fibrosis and 24 +/- 15% glycogen-storing cells. The biopsies of the 10 patients with normal anterior wall motion showed 8 +/- 4% fibrosis and 12 +/- 8% glycogen-accumulating cells. CONCLUSIONS: It can be concluded that areas with impaired wall motion and a PET match pattern show extensive fibrosis. Regions with reduced flow and preserved FDG metabolism, however, contain predominantly viable cells. In these regions, significant recovery of wall motion is found after revascularization. Regions with normal wall motion contain predominantly viable cells. Cells with reduced contractile material and increased glycogen content are mainly found in areas with wall motion impairment but are also present in areas with normal wall motion and a severe stenosis of the coronary vessel.

Biopsy↗

Different perceptual tasks performed with the same visual stimulus attribute activate different regions of the human brain: a positron emission tomography study.

To investigate the processing of visual form in human cerebral cortex, we used the PET (positron emission tomography) activation technique to compare the human brain regions that are involved in a visual detection task and two orientation discrimination tasks: the temporal same-different (TSD) task, which includes a short-term memory component, and the identification (ID) task, which is without this component. As a control task we used passive viewing. Stimuli were identical in all four tasks. Subtraction of passive viewing from detection showed that the detection task activates early visual cortical regions (areas 17/18) as well as several motor brain regions, while decreasing activity in several higher order frontal, temporal, and parietal regions. Comparing the ID task to the detection task revealed no further visual cortical activation, while comparison of the TSD task to the detection task revealed an activation of several right visual cortical regions, one of which remained significant after the subtraction of ID from TSD (right area 19). These experiments demonstrate the task dependence of visual processing, even for very closely related tasks, and the localization of the temporal comparison component involved in orientation discrimination in human area 19.

Adult↗

A new quantitative method for the analysis of cardiac perfusion tomography (SPET): validation in post-infarct patients treated with thrombolytic therapy.

In this study a new method for assessment of perfusion defects (PDs) derived from myocardial perfusion tomograms was evaluated in patients treated with thrombolytic therapy. Using global constraints and dynamic programming, a model-based delineation algorithm defined myocardial borders, the basal plane and absolute and relative PD size in 49 thallium-201 chloride (201TL CL) and 60 technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) tomograms. Tomographic (single-photon emission tomography: SPET) and planar quantification of PDs was compared to enzymatic infarct size as well as to global (LVEF) and regional ventricular function (RWM) obtained by contrast angiography. The algorithm delineated the myocardium and the valve plane in most cases, even when large PDs were present. Manual correction of the automatic delineation of the basal plane was necessary in less than 20% of the studies. Using 201Tl Cl, LVEF correlated better with tomographic PD (r = -0.67) than with planar PD (r = -0.54). Comparing planar to tomographic imaging using 99mTc-MIBI, a higher correlation with enzymatic infarct size (r = 0.73 vs 0.57) and with global ventricular function (r = 0.64 vs -0.52) was found when tomographic techniques were used. No close correlation between PD and RWM was found. The beneficial effect of thrombolysis was shown by a significant difference of PD in patients with open versus occluded infarct-related vessels. It can be concluded that this new automated algorithm for quantification of SPET perfusion defect size provides a useful tool in evaluating thrombolytic therapy.

Algorithms↗

Experimental validation of a new quantitative method for the analysis of infarct size by cardiac perfusion tomography (SPECT).

Using global constraints and dynamic programming, a new model-based segmentation algorithm was developed to determine myocardial borders and basal plane. The segmented image is transformed to a countrate polar map and the infarct size (I.S.) is determined by comparison with a reference polar map. In order to evaluate our method the algorithm was applied to heart phantoms, to software simulations and to animal studies. In the last experiments, Tc-99m Sestamibi was used as a perfusion agent. The total myocardial volume and infarct size of a Jasczack phantom were overestimated, especially when I.S. was expressed in absolute rather than relative values. It was proven by software simulations of cardiac Spect studies that those errors were mainly due to finite resolution effects causing a clear overestimation of myocardial thickness. Implementation of a constant thickness in the algorithm resulted in a much better correlation with actual values. In a dog experiment the size of total myocardial volume of the area at risk during occlusion and of the final infarct size after thrombolysis was correlated with the histologic values obtained by planimetry after TTC staining. In 8 studies, an excellent correlation between the histologic area at risk versus the estimated perfusion defects was obtained (r = 0.97). The automatic delineation of myocardial borders and valve plane was excellent even when perfusion defects were present. Manual intervention was only necessary in certain slices where a clear overlap between liver and myocardium was present in the dog studies. Segmental polar maps expressing count rate and volume information provided a visual and quantitative tool to evaluate the influence of thrombolysis in acute ligation experiments. It is concluded that the new algorithm is ready to be used in a clinical environment for the quantitative evaluation of perfusion defects after acute myocardial infarction and for the follow-up of the therapeutic strategy.

Animals↗

Image segmentation: methods and applications in diagnostic radiology and nuclear medicine.

We review and discuss different classes of image segmentation methods. The usefulness of these methods is illustrated by a number of clinical cases. Segmentation is the process of assigning labels to pixels in 2D images or voxels in 3D images. Typically the effect is that the image is split up into segments, also called regions or areas. In medical imaging it is essential for quantification of outlined structures and for 3D visualization of relevant image data. Based on the level of implemented model knowledge we have classified these methods into (1) manual delineation, (2) low-level segmentation, and (3) model-based segmentation. Pure manual delineation of structures in a series of images is time-consuming and user-dependent and should therefore be restricted to quick experiments. Low-level segmentation analyzes the image locally at each pixel in the image and is practically limited to high-contrast images. Model-based segmentation uses knowledge of object structure such as global shape or semantic context. It typically requires an initialization, for example in the form of a rough approximation of the contour to be found. In practice it turns out that the use of high-level knowledge, e.g. anatomical knowledge, in the segmentation algorithm is quite complicated. Generally, the number of clinical applications decreases with the level and extent of prior knowledge needed by the segmentation algorithm. Most problems of segmentation inaccuracies can be overcome by human interaction. Promising segmentation methods for complex images are therefore user-guided and thus semi-automatic. They require manual intervention and guidance and consist of fast and accurate refinement techniques to assist the human operator.

Algorithms↗

Model-based quantification of myocardial perfusion images from SPECT.

A system for quantitative analysis of myocardial perfusion tomograms is proposed. The system starts with an automated delineation of the total left ventricle, including possible perfusion defects, to determine the mass and shape of the myocardium. Next, polar maps or bulls-eyes are computed from the delineation, which can then be compared to reference bulls-eyes to detect perfusion defects. The proposed system differs in three main aspects from currently available bulls-eye algorithms. First, radial slices are used rather than short-axis slices. In this way three-dimensional gradient information is retained, in particular near the base and the apex of the left ventricle. Moreover, the reproducibility of this method is expected to be superior, since the interactive selection of short axis slices through the left ventricle is eliminated. Second, the left ventricle is automatically delineated using a flexible computer model in order to obtain higher reproducibility. The resulting delineation contains both mass and shape information. Third, in addition to the classic count rate bulls-eye, a mass bulls-eye is computed, which contains the myocardial mass corresponding to each bulls-eye pixel. Analysis of the count rate bulls-eye reveals perfusion defects, the quantification of the defects is carried out with the mass bulls-eye.

Algorithms↗

A new thresholding method for volume determination by SPECT.

The quantification of organ volumes from SPECT images suffers from two major problems: image segmentation and imperfect system transfer function. Image segmentation defines the borders of an organ and allows volume measurements by counting the voxels inside this contour in all slices containing parts of this organ. A review of the literature, showed that several investigators use a fixed threshold (FT) to determine the organ pixels. It is our aim to demonstrate that the threshold has to be adapted to every single case because its value is dependent upon several factors, such as size and contrast. Therefore a threshold selection algorithm, based on the gray level histogram (GLH), is evaluated. It is nearly impossible to calculate and eliminate errors induced by the complex system response function. A correction method based on linear regression is proposed. By minimizing the relative error (sigma), a linear correlation (Y = AX + B) between the true volume (Y) and the measured volume (X) is established for three fixed thresholds (30%, 40%, 50%) and for the GLH method. The methods are evaluated on a series of nineteen phantoms with a volume range between 9.8 and 202.5 ml. The relative error is minimal for the GLH method. The whole procedure is semi-automated and virtually operator independent.

Algorithms↗