Multislice algorithms revisited: solving the Schrödinger equation numerically for imaging with electrons.

For a long time, the high-energy approximation was sufficient for any image simulation in electron microscopy. This changed with the advent of aberration correctors that allow high-resolution imaging at low electron energies. To deal with this fact, we present a numerical solution of the exact Schrödinger equation that is novel in the field of electron microscopy. Furthermore, we investigate systematically the advantages and problems of several multislice algorithms, especially the real-space algorithms.

Magnetic resonance imaging of articular process joint geometry and intervertebral disk degeneration in the caudal lumbar spine (L5-S1) of dogs with clinical signs of cauda equina compression.

The geometry of the lumbosacral region has been suspected to play a role in the development of degenerative lumbosacral stenosis in the dog. In this study, 50 dogs (21 German Shepherd dogs and 29 dogs of other breeds) with clinical signs of cauda equina compression were studied by magnetic resonance (MR) imaging. The orientation of the articular process joints in the L5-S1 region and the angle difference between two adjacent motion segments were calculated. Intervertebral disc degeneration of the same region was identified and classified in four stages. A positive association between MR-imaging stage and articular process joint angle difference in the transverse plane was found in the two groups of animals. German Shepherd dogs and dogs of other breeds had different geometry of the lumbosacral region with different articular process joint angles in the transverse plane and statistically different stages of disc degeneration.

ECG-gated 23Na-MRI of the human heart using a 3D-radial projection technique with ultra-short echo times.

Pathological changes in tissue often manifest themselves in an altered sodium gradient between intra- and extracellular space due to a malfunctioning Na+-K+ pump, resulting in an increase in total sodium concentration in ischaemic regions. Therefore, 23Na-MRI has the potential to non-invasively differentiate viable from non-viable tissue by detecting concentration changes of intra- and extracellular sodium. As the in vivo sodium signal shows a bi-exponential T2 decay, with a short component of less than 1 ms, the accurate quantification of the total sodium content requires imaging techniques with ultra-short echo times (TE) below 0.5 ms. A 3D-radial projection technique has been developed which allows the acquisition of ECG-triggered sodium images of the human heart with a TE of 0.4 ms. With this pulse sequence 23Na-MRI volunteer measurements of the head or the heart were performed in less than 18 min on a 1.5-T clinical scanner with an isotropic resolution of 10 mm3. The signal to noise ratio of the radial projection technique is twofold higher than that of a Cartesian gradient echo pulse sequence (TE = 3.2 ms). Radial 23Na-MRI provides a tool for clinical studies, aiming at the differentiation of viable and non-viable tissue.

23Na-MRI of the human heart using a 3D radial projection technique.

Sodium MRI has the potential to differentiate viable and non-viable infarcted myocardium. The accurate quantification of the total sodium content requires imaging techniques with ultra short echo times below 0.5 ms. We present a 3D-radial projection technique which allows the acquisition of ECG-triggered sodium images of the human heart with echo times of 0.4 ms. A 3D-data set of the heart of a volunteer was acquired within less than 18 min on a clinical scanner (1.5 T), achieving a SNR of 10 in the myocardium with an isotropic resolution of 10 mm. This technique provides a tool for clinical studies of ischemic heart diseases.

Breath-hold 3D MR coronary angiography with a new intravascular contrast agent (feruglose)--first clinical experiences.

Demonstration of the initial results of breath-hold 3D MR coronary angiography with patients using a new intravascular contrast agent (feruglose). Contrast-enhanced 3D MR-coronary angiography was performed in 5 patients with coronary artery disease after administration of feruglose in three different doses (0.5 (n = 3), 2, 5 mg Fe/kg body weight for each patient). MR coronary angiography was performed with an ECG-triggered 3D-FLASH-sequence during breath-hold at 1.5 T (TR 6.8 ms, TE 2.5 ms, flip-angle 30 degrees ). To reduce data acquisition time, only the two anterior elements of the phased-array body coil were activated. The data acquisition window within the cardiac cycle ranged between 217-326 ms depending on the matrix. Signal-to-noise (SNR) and contrast-to-noise ratios (CNR) of the coronary arteries were analyzed, and the results for the detection of coronary artery stenoses were compared with those obtained by conventional coronary angiography. SNR and CNR revealed an improved image quality at a dose of 2 mg Fe/kg compared with the lower dose, but no further improvement was obtained by rising the dose to 5 mg Fe/kg. Except for the left circumflex artery of one patient, at minimum the proximal parts of all four main coronary arteries could be imaged for all patients. Within the visible parts of the coronary arteries, six of eight significant coronary stenoses were identified correctly. Imaging of the proximal parts of the coronary arteries including detection of stenoses is possible during breath-hold using an intravascular contrast agent.

The relationship between the BOLD-induced T(2) and T(2)(*): a theoretical approach for the vasculature of myocardium.

Recently the blood oxygenation level-dependent (BOLD)-related T(2)* of myocardium was derived as an analytical function of intracapillary blood volume, blood oxygenation, and nuclear spin diffusion. The basis of this approach was to approximate the diffusion-induced field fluctuations a nuclear spin is subjected to by strong collision dynamics, i.e., the field fluctuations are uncorrelated. The same analysis is now performed for spin echo experiments that gives myocardial T(2) as a function of the parameters above and the echotime. An analytical relationship between T(2) and T(2)* relaxation is derived. The dependence of T(2) on diffusion, echo time, and blood oxygenation is congruent with simulation and experimental data. Magn Reson Med 42:1004-1010, 1999.

BOLD-MRI in ten patients with coronary artery disease: evidence for imaging of capillary recruitment in myocardium supplied by the stenotic artery.

Changes of myocardial oxygenation can be studied by measurements of the apparent transverse relaxation time T2*, which is correlated with the oxygenation state of hemoglobin. In this study, ten patients with coronary artery disease (CAD) underwent blood oxygenation level dependent (BOLD) T2* measurements using a segmented gradient echo pulse sequence with ten echoes. T2* measurements were performed in a single short-axis slice of the heart at rest and under pharmacological stress with dipyridamole (DIP), which increases myocardial blood flow. For comparison, all patients underwent X-ray angiography and stress-echocardiography within 4 days after the MR exam. In one patient, MR examination was repeated 10 weeks after percutaneous transluminal coronary angioplasty (PTA). In the differential T2* maps, expected ischemic areas of myocardium were identified in six patients. In these regions, T2+ values (30 +/- 8 ms) were significantly reduced when compared to the remaining myocardium (48 +/- 9 ms, P < 0.01). In four patients, the myocardial region of interest could not be assessed owing to severe susceptibility artifacts in the ischemic region. The success of the PTA treatment could be visualized from a more homogeneous DIP induced increase in T2* within the ischemic myocardium (from 26 +/- 1 to 29 +/- 1 ms before PTA versus 26 +/- 1 to 31 +/- 4 ms after PTA, P < 0.001).

Changes in myocardial oxygenation and perfusion under pharmacological stress with dipyridamole: assessment using T*2 and T1 measurements.

The aim of this pilot-study was to evaluate changes in myocardial oxygenation and perfusion under pharmacological stress with dipyridamole (DIP) by means of MRI. Twenty healthy volunteers were examined using a multi-echo gradient-echo sequence. The differential myocardial signal response due to the blood oxygen level dependent (BOLD) effect was studied under variable conditions of myocardial oxygen supply caused by the vasodilator DIP. Unlike contrast agents (CA) methods, which require at least two injections of CA and DIP, the presented methods require only a single infusion of DIP. To assess changes in myocardial perfusion, a saturation recovery TurboFLASH (SRTFL) sequence with centric reordering for T1 measurements was used with global and slice-selective spin-preparation (five volunteers). The signal response was measured at baseline conditions and when myocardial blood flow was increased during pharmacological stress with DIP. Administration of DIP induced a 17 +/- 9% increase in T2*. Enhanced perfusion resulted in a 15 +/- 5% decrease of T1 after slice-selective spin preparation and a calculated increase in absolute perfusion of about 5.1 ml/(g x min), which reflects coronary reserve. The study shows that DIP-induced alterations in the relationship between myocardial oxygen supply and demand are detectable in healthy volunteers using T2* and T1 measurements. A combination of T2* and T1 examinations could become a useful diagnostic tool for the non-invasive assessment of myocardial oxygenation and perfusion in patients with coronary artery disease (CAD).

Theory of the BOLD effect in the capillary region: an analytical approach for the determination of T2 in the capillary network of myocardium.

This article presents an analytical approach for the quantification of the blood oxygen level dependent (BOLD) effect in the capillary region. The capillary geometry of myocardium is considered. The relaxation rate R*2 is determined as a function of the capillary radius Rc, the intracapillary volume fraction RBV, and the diffusion coefficient D. When the intracapillary volume fraction is small, the approximation R*2 = RBV x tau(-1) x (square root of (1+(taudeltaomega)2)-1) is valid, with the correlation time tau = (Rc2/4D) x (absolute value (ln RBV)/(1 - RBV)). The predictions of this model agree well with numerical simulations and experimental data of others and with data recently measured by our group.

Ultrasonographic comparison of adhesions induced by two different methods of gastropexy in the dog.

Ultrasonography was used to compare adhesions induced by two different methods of gastropexy in 16 dogs. An incisional gastropexy technique was used in eight dogs (group 1) and a 'modified' gastropexy technique in the remaining eight (group 2). The length and thickness of the gastropexy and the peristaltic activity of the stomach were measured ultrasonographically and compared between groups. Measurements for the two groups were taken in the early postoperative interval (two to four days), intermediate postoperative interval (eight to 20 days) and late postoperative interval (57 to 79 days). Both techniques were equally successful in forming permanent adhesions at two months postoperatively and there was no recurrence of gastric dilatation and volvulus. The length and thickness of the gastropexy were similar for both groups at two months postoperatively and there were no surgical complications with either technique. The modified gastropexy provides a technique that can easily be performed by a single surgeon, with no increased operative time or duration of anaesthesia, and with the formation of a permanent adhesion.

Ultrasonographic evaluation of adhesions induced by incisional gastropexy in 16 dogs.

A study was undertaken to evaluate the use of ultrasonography to assess the gastropexy site for permanent adhesion in clinical cases. Two groups, each comprising eight dogs, were studied, all 16 cases undergoing decompression, anatomical repositioning of the stomach and an incisional gastropexy after gastric dilatation-volvulus (GDV). Group 1 was set up as a prospective group in which ultrasonographic examinations were performed three times (mean three, 12 and 67 days) after surgery to evaluate the gastropexy region. The gastropexy site was assessed ultrasonographically at only one stage (mean 449 days after surgery) in the group 2 dogs. Criteria used to assess the usefulness of the ultrasonographic evaluation included the ability to identify the gastropexy site, to obtain measurements of the length and thickness of the site and to assess the ultrasonographic appearance of the different gastric wall layers. The average number of peristaltic contractions and degree of gastric filling were also evaluated. The fixation between the stomach and the abdominal wall was easily detected in all 16 cases. Ultrasonography proved to be a simple and non-invasive technique to assess the permanency of the gastropexy. The incisional gastropexy was relatively easy to perform and induced permanent adhesions in all 16 dogs, without recurrence of GDV.

The pulmonary artery acceleration time determined with the MR-RACE-technique: comparison to pulmonary artery mean pressure in 12 patients.

The goal of our study was to evaluate a rapid noninvasive MR technique for quantification of the pulmonary artery acceleration time (PAT) and other parameters of pulmonary hemodynamics and to correlate with pulmonary artery mean pressure (mPAP). The PAT known as "time-to-peak" out of Doppler echocardiographic measurements normally shows significant inverse correlation with mPAP. With the MR-RACE-Technique (RACE: Real time ACquisition and Evaluation of motion) blood velocity measurements can be obtained with a total acquisition time of a few seconds. The application of this technique to the pulmonary artery has not been reported before. Out of the RACE velocity wave form PAT can be obtained with a temporal resolution of about 15 ms. To explore the relationship between PAT and mPAP, right heart catheterization and MR-RACE measurements were performed in 12 patients with different pulmonary vascular abnormalities. Results of MR-RACE were compared with those of mPAP measured by right heart catheter and showed significant inverse correlation (r = -0.82, p = .0011, n = 12). The ability of MR-RACE to enable measurements of blood flow with profiles may be important for characterizing pulmonary and cardiovascular abnormalities.

Nitrosation of the antimicrobial drug hexetidine: nitrosamines derived from a triamine decomposition product.

Five new nitrosamines were identified as nitrosation products of N1,N3-bis(2-ethylhexyl)-2-methyl-1,2,3-propantriamine, a hydrolysis product usually found in preparations of the antimicrobial drug hexetidine. All nitrosamines are formed after deamination of the primary amino group by nitrosation of one of the two secondary amino groups. The propantriamine derivative is very easily nitrosatable, with total nitrosamine yields in the upper range of a comparative scale of drug nitrosatability.

Caffeine-derived N-nitroso compounds. II. Synthesis and characterization of nitrosation products from caffeidine and caffeidine acid.

Caffeine on alkaline hydrolysis produces caffeidine [1-methyl-4-(methylamino)-5-(N-methylcarbamoyl)imidazole] and caffeidine acid [N-[4-(5-carboxy-1-methylimidazolyl)]-N,N'-dimethylurea]. We now report the synthesis and chemical characterization of mononitrosocaffeidine [1-methyl-4-(N-methyl-N-nitrosoamino)-5-(N-methylcarbamoyl)i midazole], dinitroso-caffeidine [1-methyl-4-(N-methyl-N-nitrosoamino)-5-(N-methyl-N-nitrosocarb amo yl) imidazole], and mononitrosamidocaffeidine [1-methyl-4-(methylamino)-5-(N-methyl-N-nitrosocarbamoyl)-Imidazole] based on spectral analysis. The characterization of nitrosated byproducts obtained during the synthesis of these compounds is also presented. Caffeidine is shown to undergo rapid nitrosation in acidic medium to form mononitrosocaffeidine (MNC), an asymmetric N-nitrosamine, and dinitrosocaffeidine (DNC), a N-nitrosamide. Although the reaction proceeds with preferential nitrosation of the amino group in caffeidine, the results also support partial involvement of a mononitrosamide intermediate in the formation of MNC and DNC through transnitrosation of the amino group. The stability data suggest that the nitroso group at the amino nitrogen in DNC influences the reactivity of amide nitroso group. The presence of a trisubstituted ureide moiety in caffeidine acid has been confirmed by NMR nuclear Overhauser effect experiments. Nitrosation of caffeidine acid under acidic conditions produced N,N'-dimethylparabanic acid (DMPA, N,N'-dimethylimidazolidinetrione) as a major product with low amounts of mononitrosocaffeidine and N,N'-dimethyl-N-nitrosourea, whereas nitrosation with NOBF4/pyridine in aprotic medium gave rise to an anhydride, 1,4-dimethyl-4,5-dihydro-5,7-dioxo-1H,7H-imidazo[4,5-d][1,3]oxazine. The nitrosation of methyl ester of caffeidine acid resulted in the formation of a N-nitrosourea derivative, N-[4-(5-carboxy-1-methylimidazolyl)]-N'-nitroso-N,N'-dimethylurea. (ABSTRACT TRUNCATED AT 250 WORDS)

Caffeine-derived N-nitroso compounds--I: Nitrosatable precursors from caffeine and their potential relevance in the etiology of oesophageal and gastric cancers in Kashmir, India.

Salted tea prepared in Kashmir by adding sodium bicarbonate shows high methylating activity (equivalent to 3 p.p.m. N-methylnitrosourea) upon in vitro nitrosation. Pure caffeine treated under conditions of the tea preparation formed caffeidine and caffeidine acid. We report here the formation of two new compounds, mononitrosocaffeidine, an asymmetric nitrosamine, and dinitrosocaffeidine, a N-nitrosamide, on in vitro nitrosation of caffeidine. Mononitrosocaffeidine is also found after nitrosation of the typical Kashmir tea. The nitrosation of caffeidine acid produced N,N'-dimethyl-parabanic acid, mononitrosocaffeidine and N,N'-dimethyl-N-nitrosourea. In view of the well-known structure-activity relationships of these N-nitroso compounds, their possible endogenous formation due to high consumption of salted tea may be a critical risk factor for the high occurrence of oesophageal and gastric cancers in Kashmir.

Effect of dietary nitrate on endogenous nitrosation of piperazine in humans.

The effect of dietary nitrate on endogenous nitrosation of a therapeutic dose of piperazine has been described in five human volunteers who acted as their own controls. The urinary excretion of endogenously formed N-nitro-somonopiperazine (MNPz) ranged between 9.2 and 80.1 micrograms/24 h on a normal uncontrolled diet which increased from 25.7 to 163.7 micrograms/24 h when the diet was supplemented with 250 mg nitrate. The corresponding urinary nitrate was 63.0-122.7 mg/24 h and 119.2-322.0 mg/24 h, respectively. The dinitroso derivative of piperazine was detected only in trace amounts and no detectable increase in its excretion was observed during high nitrate exposure. The unchanged piperazine (range 294-784 mg/24 h) in urine showed a decrease under high nitrate regimen (range 185-399 mg/24 h).

[Measurement of the blood flow velocity in the pulmonary arteries using the magnetic resonance technique]. / Messung der Blutflussgeschwindigkeit in den Pulmonalarterien mit Hilfe der Magnetresonanztechnik.

MR blood velocity measurements were performed by the RACE technique in a plane perpendicular to the flow of the pulmonary arteries. MR findings were correlated with those of perfusion scintigraphy, Doppler US and right heart catheter (thermodilution). The ratio of MR blood flow measurements of right and left pulmonary arteries correlated well with the results of perfusion scintigraphy (RPA to LPA) and Doppler. Poor correlation was found when comparing MR blood flow measurements with right heart catheter since absolute flow measurements can be superimposed by neighboring blood vessels in complex anatomic situations.

New sulfenamide accelerators derived from 'safe' amines for the rubber and tyre industry.

A reduction of the high exposures to N-nitrosamines in the rubber and tyre industry is possible using the concept of 'safe' amines, in which vulcanization accelerators contain amine moieties that are both difficult to nitrosate and, on nitrosation, yield noncarcinogenic N-nitroso compounds. The toxicological and technological properties of more than 50 benzothiazole sulfenamides derived from 'safe' amines have been evaluated. Some of the new compounds show excellent vulcanization properties and seem suitable as replacements for traditional accelerators in this class of compounds.

Arterial-venous perfusion without anticoagulation: the impeller centrifugal pump.

A study was designed to test the effects of the absence of anticoagulation in the extracorporeal circuit. Five swine were subjected to this experiment utilizing the impeller centrifugal pump during which neither heparin nor any other anticoagulant was used. The extracorporeal circuit consisted of polyvinylchloride tubing, a Centri-Med pump and an external stainless steel heat exchanger that was primed with albuminized Ringer's solution. An arterial-venous circuit was employed with oxygenation supplied from the subject's lungs. A series of blood aliquots were analyzed for coagulation at various times throughout the procedure. Following total body cooling using topically applied ice water, the subjects were rewarmed utilizing bypass. Within 10 minutes after the initiation of bypass, the circuits became clotted, rendering perfusion and subsequent warming ineffective. The lab values indicated that intrinsically activated coagulation occurred upon exposure to the extracorporeal apparatus. Flow visualization studies revealed a source of stagnant blood flow in the area around the hub of the pump head. Blood clot was similarly located in this area, with clot extension throughout the return circuit being realized. It is imperative that areas of stagnation be eliminated from extracorporeal circuits, since they may be potential sites for clot formation.