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A method for spatio-temporal (4-D) data representation in confocal microscopy: application to neuroanatomical plasticity.

This paper describes a new method for data representation and visualization in four dimensions (three dimensions plus time). Sequential volumes, exhibiting morphological activity, are acquired non-invasively with a confocal scanning laser microscope, where each data set corresponds to a time sample. A pipelined processing includes packing of volumes and specific volume rendering techniques. Subsequent processing in HIS (hue, intensity, saturation)l colour space combines functional, packed images with shaded three-dimensional views. As a result, even subtle changes in morphology become visible and computational time is saved. Experimental findings obtained from investigations of synaptic plasticity in cultured retinal tissue are reported.

Algorithms↗

Molecular imaging of atherosclerotic plaques using a human antibody against the extra-domain B of fibronectin.

Current imaging modalities of human atherosclerosis, such as angiography, ultrasound, and computed tomography, visualize plaque morphology. However, methods that provide insight into plaque biology using molecular tools are still insufficient. The extra-domain B (ED-B) is inserted into the fibronectin molecule by alternative splicing during angiogenesis and tissue remodeling but is virtually undetectable in normal adult tissues. Angiogenesis and tissue repair are also hallmarks of advanced plaques. For imaging atherosclerotic plaques, the human antibody L19 (specific against ED-B) and a negative control antibody were labeled with radioiodine or infrared fluorophores and injected intravenously into atherosclerotic apolipoprotein E-null (ApoE-/-) or normal wild-type mice. Aortas isolated 4 hours, 24 hours, and 3 days after injection exhibited a selective and stable uptake of L19 when using radiographic or fluorescent imaging. L19 binding was confined to the plaques as assessed by fat staining. Comparisons between fat staining and autoradiographies 24 hours after 125I-labeled L19 revealed a significant correlation (r=0.89; P<0.0001). Minimal antibody uptake was observed in normal vessels from wild-type mice receiving the L19 antibody and in atherosclerotic vessels from ApoE-/- mice receiving the negative control antibody. Immunohistochemical studies revealed increased expression of ED-B not only in murine but also in human plaques, in which it was found predominantly around vasa vasorum and plaque matrix. In summary, we demonstrate selective targeting of atheromas in mice using the human antibody to the ED-B domain of fibronectin. Thus, our findings may set the stage for antibody-based molecular imaging of atherosclerotic plaques in the intact organism.

Adult↗

Effects of inverse ratio ventilation and positive end-expiratory pressure in oleic acid-induced lung injury.

Continuous as well as cyclic (with each expiration) lung collapse in acute respiratory failure can be reduced by positive end-expiratory pressure (PEEP) or short expiration times, as in inverse ratio ventilation (IRV). In 20 pigs with oleic acid-induced lung edema, we compared the effects of a PEEP of 20 cm H(2)O with IRV, using an inspiratory-to-expiratory ratio of 3:1 without external PEEP. During IRV, expiration times of 0.5 or 1.0 s were obtained with respiratory rates of 30 breaths/min or 15 breaths/min, respectively. In 15 animals, ventilation-perfusion relationships were studied through the multiple inert gas elimination technique, and lung morphology was studied with computed tomography. In another five pigs, blood flow distribution was studied with perfusion scintigraphy. All three ventilatory modes had similar effects on mean arterial blood pressure, cardiac output, oxygen delivery, and mean airway pressure. PEEP reduced shunt and improved oxygenation to a greater extent than the two modes of IRV, although there was a large variation within each group. The improvement, irrespective of which ventilatory mode was superior in a particular pig, was caused by greater and more even aeration of the lung, whereas the perfusion distribution with PEEP was the same as with IRV. Thus, the strategy of stabilizing the lungs through short expiration times, as in IRV, did not offer any advantages in our lung injury model.

Animals↗

Evaluation of successful PTCA by transstenotic flow velocity ratios.

Doppler probes mounted on the tip of a guidewire allow the measurement of coronary blood flow velocities, not only proximal but also distal to stenoses eligible for percutaneous transluminal coronary angioplasty (PTCA). The objective of this study was to determine the improvement of transstenotic Doppler flow velocity ratios following PTCA and to investigate the possible impact on restenosis during follow-up control angiography three months later. Doppler flow velocity measurements were performed in 29 patients with 29 stenoses eligible for PTCA. Results of PTCA were morphologically evaluated by computer-assisted quantitative coronary angiography (QCA) and measured hemodynamically by determining transstenotic Doppler flow velocity ratios. Successful PTCA according to QCA was present in all cases with a reduction of mean diameter stenosis from 66 +/- 8% to 35 +/- 7%. Resting spectral peak velocities and velocity integrals were markedly reduced distal to lesions (all P < 0.001), resulting in mean transstenotic flow velocity and velocity integral ratios of less than 0.60 prior to PTCA. Owing to endoluminal enlargement, significant improvement of transstenotic Doppler ratios was observed in mean ratios greater than 0.90 (all P < 0.0001). In patients with restenosis, transstenotic ratios following PTCA demonstrated a tendency to be smaller than in patients without restenosis. Transstenotic Doppler flow velocity ratios are diminished in severe coronary stenoses. Improvement of these ratios provides information on hemodynamic success of interventional procedures. Thus, the determination of intracoronary Doppler flow velocity ratios contributes, in addition to angiographic estimation, to the evaluation of stenoses severity and success of interventional procedures.

Angioplasty, Balloon, Coronary↗

Receptor imaging in oncology by means of nuclear medicine: current status.

To date, our understanding of the role of receptors and their cognate ligands in cancer is being successfully translated into the design and development of an arsenal of new, less toxic, and more specific anticancer drugs. Because most of these novel drugs are cytostatic, objective response as measured by morphologic imaging modalities (eg, computed tomography or magnetic resonance imaging) cannot be used as a surrogate marker for drug development or for clinical decision making. Positron emission tomography (PET) can be used to image and quantify the in vivo distribution of positron-emitting radioisotopes such as oxygen-15, carbon-11, and fluorine-18 that can be substituted or added into biologically relevant and specific receptor radioligands. Similarly, single-photon emission computed tomography (SPECT) can be used to image and quantify the in vivo distribution of receptor targeting compounds labeled with indium-111, technetium-99m, and iodine-123. By virtue of their whole-body imaging capacity and the absence of errors of sampling and tissue manipulation as well as preparation, both techniques have the potential to address locoregional receptor status noninvasively and repetitively. This article reviews available data on the in vivo evaluation of receptor systems by means of PET or SPECT for identifying and monitoring patients with sufficient receptor overexpression for tailored therapeutic interventions, and also for depicting tumor tissue and determining the currently largely unknown heterogeneity in receptor expression among different tumor lesions within and between patients.

Humans↗

Different effect of the pure Na+ channel-blocker pilsicainide on the ST-segment response in the right precordial leads in patients with normal left ventricular function.

BACKGROUND: The response of the ST-segment in the right precordial leads to Na+ channel blockers in patients without structural heart disease and a typical Brugada-type ECG has not been fully elucidated. METHODS AND RESULTS: A pilsicainide challenge test was performed in 161 patients and according to recently established ECG criteria and an organized computer algorithm, the ST morphology was classified and the maximum increase in the J wave amplitude (maxDeltaJ) from the standard and high right precordial leads V1-3 was examined. Before the test, subjects exhibiting type 1 ECG in the standard leads were excluded. After administering pilsicainide, type 1 ECGs in the standard leads were observed in 31 cases and a maxDeltaJ of >or=200 microV was observed in 29 cases (23 type 1, 2 type 2/3 and 4 normal ECGs). In the additional higher right precordial leads, type 1 ECGs were observed in 55 cases and a maxDeltaJ of >or=200 microV was observed in 45 cases (42 type 1 and 3 type 2/3 ECGs). CONCLUSIONS: A maxDeltaJ>or=200 microV induced by pilsicainide, including that measured in the high right precordial leads, was associated with a change mainly to a type 1 ECG.

Adult↗

The relationship between human semen characteristics and sperm apoptosis: a pilot study.

This work was undertaken to explore the association between human semen characteristics and apoptosis in ejaculated sperm. We collected semen samples from 23 consecutive male patients who presented to the Andrology Laboratory at Massachusetts General Hospital (MGH) for routine semen analysis. Sperm concentration and motility were measured using computer-assisted sperm analysis. Morphology was assessed using Tygerberg strict criteria. The DNA diffusion assay was used to assess the percentage of apoptosis in ejaculated sperm. In this assay, cells were mixed with agarose and placed into a microgel on a microscopic slide. The cells were stained with YOYO-1 dye, and apoptotic cells were viewed under a fluorescent microscope. Among 23 men, the mean (SD) sperm concentration, percent motility, percent progressive motility, and normal morphology were 125.5 (92.3) million/mL, 45.6% (22.2), 28.4% (15.2), and 8.0 (4.6), respectively. The mean (SD) percent of apoptosis in ejaculated sperm was 8.3% (6.2) with a range from 1.1% to 20.1%. There were inverse associations between percent apoptosis and sperm motility (P = .0025), progressive motility (P = .0051), and morphology with a normal or good pattern of fertilization by Kruger strict criteria (P = .0045), and a positive relationship between percent apoptosis and sperm tail defects (P = .0053). In ejaculated semen, the percent sperm apoptosis was associated with several measures of semen quality.

Adult↗

The clinical application of positron emission tomography to colorectal cancer management.

Colorectal cancer (CRC) is the second commonest cancer in the Western World. Successful treatment relies significantly on accurate detection and staging of primary disease as well as the early identification of the presence and extent of recurrence. Morphological imaging techniques, particularly computed tomography (CT), are well established and widely available to carry out these tasks in addition to predicting and monitoring response to therapy. This review analyses the current inadequacies for imaging CRC and critically assesses the potential role of functional imaging with positron emission tomography (PET). We review the current literature, use our experience from the first 1000 PET studies carried out at our Institution and the perspective of surgical colleagues. We find little evidence for the use of 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-PET for screening asymptomatic individuals and current modalities appear better suited for detection of symptomatic primary CRC. There is evidence of increased accuracy for FDG-PET in staging primary disease, but this area remains controversial and larger studies are necessary. The situation is quite the reverse with respect to imaging suspected recurrent disease with FDG-PET being more sensitive and specific than conventional techniques. This benefit manifests itself through alteration in patient management and results in cost savings. PET also appears to have a specific place in the evaluation of patients undergoing radiotherapy and chemotherapy, a role that will expand. The evidence suggests that PET will ultimately become routinely incorporated into CRC patient management algorithms. Technological advances coupled with novel tracer research will facilitate this.

Colorectal Neoplasms↗

[When the Egyptian mummies are speaking about the infections that have made them ill].

The microbiological study of mummies has started in 1910 when Sir M.A. Ruffer first applied the histologic methods to the study of mummified tissues and found Schistosoma haematobium ovas dated from the XXth dynasty. Up to the 1990 years, morphological methods including radiology, computed tomography, endoscopy, history, electron microscopy, and serology have been the main tools used in Paleopathology. They led to identify schistosomiasis, dracunculiasis, trichinosis, ascariasis and bone tuberculosis as the most prevalent diseases of the ancient residents of Egypt. The recent introduction of molecular methods (PCR) allowed t confirm the high prevalence of helminth diseases and tuberculosis among these populations, but also added new data exemplified by the widespread distribution of Plasmodium falciparum malaria. In addition, cases of bacterial septicemias and diphteria possibily occurred. Thousands of human and animal mummies remain to be studied with the hope to discover another pathogens responsible for viral or zoonotic infections prevalent during the pharaons' times.

Egypt↗

[The measurement of cerebral perfusion and hemodynamic reserve using SPECT: use in cerebral vascular pathology].

The isolated measurement of cerebral blood flow can lead to gross errors in vascular disease, particularly ischaemic disease, because of disruption of the relations between blood flow and metabolism. In contrast, the measurement of cerebral blood flow combined with measurement of the haemodynamic reserve overcomes these difficulties, regardless of the method of evaluation: reactivity to CO2 or to acetazolamide; measurement of the flow/volume ratio. The author demonstrates that these measurements are even more valuable in situations in which morphological examinations (MRI or computed tomography) are of little value: transient ischaemic attacks, asymptomatic carotid artery stenosis, etc. However, these measurements are useful in constituted infarctions or in vasospasm to assess the distant effects or to guide the therapeutic adjustment or even to provide prognostic elements. Combined measurement of perfusion and haemodynamic reserve, although it does not constitute a formal proof, is now largely accessible by means of non-specialized gamma cameras with determination of the flow/volume ratio.

Adult↗

[Rational diagnosis of pancreatic diseases].

Diagnosis and differential diagnosis of pancreatic disease are frequently difficult, and patience and diagnostic skill are required of the physician. Diagnosis is based on clinical findings, morphological imaging procedures (ultrasound, computer tomography, ERCP) and changes in biochemical parameters in serum, urine duodenal secretion and feces. History and clinical findings are starting-points for further chemical and technical investigations. The various diagnostic procedures and their importance in the diagnosis of acute and chronic pancreatitis and of pancreatic carcinoma are discussed and evaluated.

Amylases↗

[Noninvasive imaging methods and angiography in the diagnosis of chronic viscero-visceral arterial collateral circulation in stenosis of the celiac trunk].

Stenosis or even occlusion of truncus coeliacus represents the most frequent cause in the development of collateral blood circulation with caudiocranial flow through extended pancreatic-duodenal arcades. In a group of 32 patients with such mesenteric-coeliacal collateral circulation their arteriographic picture was evaluated. The authors evaluated differences and specific diagnostic contribution of individual visualization methods for demonstration of arteries. The non-invasive visualization methods are of exceptional contribution in the examination of abdominoretroperitoneal region by considerably decreasing the needs of invasive angiographic examination of catheterization technique. This leads to a decrease in the number of diagnosed chronically developed viscerovisceral arterial collateral circulations of various etiologies. Ultrasonography and computer tomography well depicts morphological changes in the aorta diameter as well as unpaired visceral arteries in the segment of their branching. The viscerovisceral arterial collateral circulations, however, may not be detected or at least not to a sufficient degree. They are represented in detail in the whole course only by selective arteriography. The authors draw attention to supplementary role of arteriography within the framework of non-invasive visualization methods.

Adult↗

Castleman's disease, plasma-cell type. Diagnosis of central nervous system involvement by cerebrospinal fluid cytology.

A case of Castleman's disease of the plasma-cell type is reported in which central nervous system (CNS) involvement was diagnosed by cerebrospinal fluid (CSF) cytology. The patient had multicentric disease with constitutional symptoms, immunologic abnormalities and peripheral blood cytopenias requiring cytotoxic agents and steroids for treatment. CNS symptoms and diagnostic cytologic findings in CSF occurred in the absence of morphologic lesions demonstrable by computed tomography or magnetic resonance imaging of the brain.

Bone Marrow↗

[Retrospective evaluations on the importance of laparoscopy in the differentiation of acute oedematous and acute hemorrhagic necrotising pancreatitis in the early stage of the disease (author's transl)].

Of 32 patients with acute pancreatitis on whom laparoscopy was performed within 3 days after the pain symptoms started, the type of inflammation could be assessed in 31 cases. Technically, the intervention did not cause any problems. In one case the examination had to be stopped prematurely due to hypotension, in another case the pain reaction led to premature discontinuance of the examination; other complications did not occur. The present experiences with this morphological diagnostic method have proven to be particularly useful for the indication regarding surgical interventions; it is, therefore, justifiable to compare the value of this method with that of noninvasive morphological methods (ultrasonography, and computer tomography).

Acute Disease↗

[Imaging of COPD].

Standard chest radiographs have been shown to be insensitive for the diagnosis of morphologic abnormalities of airways. Computed tomography is the most sensitive and specific investigation to diagnose emphysema. However, as emphysema may be missed on computed tomography, this investigation cannot be used to definitely rule out the diagnosis. Computed tomography may contribute to the investigation of bronchiolitis, and it is now considered as the gold standard for establishing the diagnosis of bronchiectasis. Imaging may contribute to identify complications such as bronchopulmonary infection, pulmonary hypertension, pneumothorax, cancer of the lung, compressive bullae, and pulmonary embolism.

Bronchiolitis↗

[The outlook for the development of computerized cyto-histopathology].

Concise information is given on quantitative pathologic morphology and on developing computer cyto-histopathology. Technical characteristics of the image analyzers are presented when cells and histologic sections are studied. Fields of their application in differential pathological diagnosis and in the research are outlined.

Animals↗