Analysis of residual coronary artery motion for breath hold and navigator approaches using real-time coronary MRI.

Coronary artery MRI methods utilize breath holds, or diaphragmatic navigators, to compensate for respiratory motion. To increase image quality and navigator (NAV) gating efficiency, slice tracking is used, with more sophisticated affine motion models recently introduced. This study assesses the extent of remaining coronary artery motion in free breathing NAV and single and multi breath hold coronary artery MRI. Additionally, the effect of the NAV gating window size was examined. To visualize and measure the respiratory induced motion, an image containing a coronary artery cross section was acquired at each heartbeat. The amount of residual coronary artery displacement was used as a direct measure for the performance of the respiratory motion correction method. Free breathing studies with motion compensation (slice tracking with 5 mm gating window) had a similar amount of residual motion (0.76+/-0.17 mm) as a single breath hold (0.52+/-0.20 mm) and were superior to multiple breath holds (1.22+/-0.60 mm). Affine NAV methods allowed for larger gating windows ( approximately 10 mm windows) with similar residual motion (0.74+/-0.17 mm). In this healthy adult cohort (N=10), free-breathing NAV methods offered respiratory motion suppression similar to a single breath hold.

Myocardial wall tagging with undersampled projection reconstruction.

Azimuthally undersampled projection reconstruction (PR) acquisition is investigated for use in myocardial wall tagging with MR using grid tags to provide increased temporal and spatial resolution. PR can provide the high-resolution images required for tagging with very few projections, at the expense of artifact. Insight is provided into the PR undersampling artifact, in the context of measuring myocardial motion with tags. For Fourier transform imaging, at least 112 phase-encodings must be collected to image tagging grids spaced 7 pixels apart. PR requires about 80 projections, a 1.4-fold reduction in scan time. Magn Reson Med 45:562-567, 2001. Published 2001 Wiley-Liss, Inc.

3D MR DSA: effects of injection protocol and image masking.

The purpose of this study was to investigate the effect on three-dimensional (3D) magnetic resonance digital subtraction angiography (MR DSA) images of various injection protocol parameters (ie, injection order, volume, and rate), as well as image masking. The pelves of 10 normal volunteers were scanned using seven different contrast agent volume/injection rate combinations. Subtraction of a precontrast mask image resulted in vascular image contrast improvements of between 4.0 and 7.7 times. Image quality and smaller vessel image contrast in the masked data decreased with increasing injection number. Data acquired with a high (0.150 mmol kg(-1)) volume yielded the highest quality images, although only small nonsignificant differences in image quality and large vessel conspicuity were found between images obtained using the high and medium (0.075 mmol kg(-1)) volumes. Images acquired with a low (0. 038 mmol kg(-1)) volume, while of lower image contrast, were judged to be of reasonable quality, especially when acquired as the first or second injection. Injection rate (1 ml s(-1), 2 ml s(-1), and 4 ml s(-1)) was not found to affect the images significantly, although selection of an injection rate that gave an injection duration of approximately 10 seconds tended to give better vascular image contrast. Based on these data, a series of escalating volumes for multi-injection examination is proposed. J. Magn. Reson. Imaging 2000;12:476-487.

Phase-contrast with interleaved undersampled projections.

MR phase-contrast techniques provide velocity-sensitive angiograms and quantitative flow measurements but require long scan times. Recently it has been shown that undersampled projection reconstruction can acquire higher resolution per unit time than Fourier techniques with acceptable artifacts when used in contrast-enhanced MR angiography. Undersampled projection reconstruction has similar potential for phase-contrast acquisitions. Flow sensitization gradients are used with projection trajectories to acquire velocity-dependent phase information. An acquisition scheme that acquires three flow encoding directions on three sets of angular-interleaved projections is introduced. Depending on the resolution, acquisition times for 3D datasets can decrease by factors of two to four.

Undersampled projection-reconstruction imaging for time-resolved contrast-enhanced imaging.

In time-resolved contrast-enhanced 3D MR angiography, spatial resolution is traded for high temporal resolution. A hybrid method is presented that attempts to reduce this tradeoff in two of the spatial dimensions. It combines an undersampled projection acquisition in two dimensions with variable rate k-space sampling in the third. Spatial resolution in the projection plane is determined by readout resolution and is limited primarily by signal-to-noise ratio. Oversampling the center of k-space combined with temporal k-space interpolation provides time frames with minimal venous contamination. Results demonstrating improved resolution in phantoms and volunteers are presented using angular undersampling factors up to eight with acceptable projection reconstruction artifacts.

Undersampled projection reconstruction applied to MR angiography.

Undersampled projection reconstruction (PR) is investigated as an alternative method for MRA (MR angiography). In conventional 3D Fourier transform (FT) MRA, resolution in the phase-encoding direction is proportional to acquisition time. Since the PR resolution in all directions is determined by the readout resolution, independent of the number of projections (Np), high resolution can be generated rapidly. However, artifacts increase for reduced Np. In X-ray CT, undersampling artifacts from bright objects like bone can dominate other tissue. In MRA, where bright, contrast-filled vessels dominate, artifacts are often acceptable and the greater resolution per unit time provided by undersampled PR can be realized. The resolution increase is limited by SNR reduction associated with reduced voxel size. The hybrid 3D sequence acquires fractional echo projections in the k(x)-k(y) plane and phase encodings in k(z). PR resolution and artifact characteristics are demonstrated in a phantom and in contrast-enhanced volunteer studies.

Diclofenac/hyaluronic acid.

Topical gel containing 3% diclofenac in 2.5% hyaluronic acid (HYAL CT1101) is used for the treatment of actinic keratosis. In animal models, diclofenac in hyaluronic acid inhibited angiogenesis and induced neovascular regression in inflammatory tissue, and depleted substance P content in snout tissue. Diclofenac delivered in hyaluronic acid appears to accumulate in the epidermis of human skin in vitro and mice in vivo. Results of clinical trials indicate that topical HYAL CT1101 is effective in the treatment of actinic keratosis. A clinical cure (all lesions fully resolved) was seen in 47% of 108 patients using HYAL CT1101 compared with 19% of patients using placebo after 3 months in 1 randomised, double-blind study. Mild to moderate skin irritation has been reported in up to 72% of patients treated with HYAL CT1101 in clinical studies.

Aprotinin: an update of its pharmacology and therapeutic use in open heart surgery and coronary artery bypass surgery.

UNLABELLED: Cardiopulmonary bypass (CPB) is associated with defective haemostasis which results in bleeding and the requirement for allogenic blood product transfusions in many patients undergoing open heart surgery (OHS) and/or coronary artery bypass graft surgery (CABG) with CPB. Conservation of blood has become a priority during surgery because of shortages of donor blood, the risks associated with the use of allogenic blood products and the costs of these products. Aprotinin is a serine protease inhibitor isolated from bovine lung tissue which acts in a number of interrelated ways to provide an antifibrinolytic effect, inhibit contact activation, reduce platelet dysfunction and attenuate the inflammatory response to CPB. It is used to reduce blood loss and transfusion requirements in patients with a risk of haemorrhage and has clear advantages over placebo or no treatment. High dose aprotinin significantly reduces postoperative blood loss compared with aminocaproic acid and desmopressin, and decreases transfusion requirements compared with desmopressin. Results are less consistent with tranexamic acid: high dose aprotinin either reduces blood loss significantly more than, or to an equivalent level to, tranexamic acid. A variety of other lower aprotinin dosage regimens consistently result in similar reductions in blood loss to aminocaproic acid or tranexamic acid. Data from clinical trials indicate that aprotinin is generally well tolerated, and the adverse events seen are those expected in patients undergoing OHS and/or CABG with CPB. Hypersensitivity reactions occur in <0.1 to 0.6% of patients receiving aprotinin for the first time. The results of original reports indicating that aprotinin therapy may increase myocardial infarction rates or mortality have not been supported by more recent studies specifically designed to investigate this outcome. However, a tendency to early vein graft occlusion with aprotinin has been shown and care with anticoagulation and vessel grafts is required. No comparative tolerability data between aprotinin and the lysine analogues, aminocaproic acid and tranexamic acid, are available. CONCLUSION: Comparative tolerability and cost-effectiveness data for aprotinin and the lysine analogues are required to more fully assess their individual roles in reducing blood loss and transfusion requirements in patients undergoing CPB during OHS and/or CABG. However, clinical evidence to date supports the use of aprotinin over its competitors in patients at high risk of haemorrhage, in those for whom transfusion is unavailable or in patients who refuse allogenic transfusions.

Trandolapril. An update of its pharmacology and therapeutic use in cardiovascular disorders.

UNLABELLED: Trandolapril is an orally administered angiotensin converting enzyme (ACE) inhibitor that has been used in the treatment of patients with hypertension and congestive heart failure (CHF), and after myocardial infarction (MI). Trandolapril is a nonsulfhydryl prodrug that is hydrolysed to the active diacid trandolaprilat. Trandolapril 2 mg once daily provides effective control of blood pressure (BP) over 24 hours in patients with mild to moderate hypertension, with a trough/peak ratio of BP reduction (as determined by 24-hour ambulatory monitoring) consistently > or = 50%. Trandolapril has similar antihypertensive efficacy to enalapril as indicated by several clinical trials. Combined therapy with trandolapril and sustained-release verapamil has a significantly greater antihypertensive effect than either agent alone. Only limited data are available on the use of trandolapril in patients with CHF, although ACE inhibitors as a class are recommended as first line therapy in such patients. In the Trandolapril Cardiac Evaluation (TRACE) study, trandolapril 1 to 4 mg once daily resulted in an early and long term reduction in all-cause mortality, including cardiovascular mortality, in patients with left ventricular (LV) dysfunction after an MI. Trandolapril therapy was commenced a mean 4.5 days after acute MI and continued for 24 to 50 months. At study end, the relative risk of death from any cause with trandolapril versus placebo was 0.78 (p = 0.001). The tolerability profile of trandolapril is similar to that of other ACE inhibitors. Most adverse events are mild and transient in nature, and include cough, asthenia, dizziness, headache and nausea. Trandolapril has no adverse effect on lipid or carbohydrate metabolism. CONCLUSIONS: trandolapril has a favourable pharmacological profile and an antihypertensive efficacy at least comparable to that of other ACE inhibitors. The pharmacological characteristics of trandolapril allow it to provide good 24-hour control of BP with once-daily administration. Trandolapril has also demonstrated some efficacy in a small number of patients with CHF. In addition, trandolapril provides long term protection against all-cause mortality in patients with LV dysfunction after MI. The results of the Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) study will determine its potential as a cardioprotective agent in patients with coronary artery disease and preserved LV function. Thus, trandolapril represents an effective, well-tolerated and convenient treatment option for patients with mild to moderate hypertension or LV systolic dysfunction after MI.

Coronary flow and flow reserve in canines using MR phase difference and complex difference processing.

Coronary artery disease continues to be the leading cause of death for adults in the United States. Magnetic resonance imaging (MR) has the potential to dramatically impact the diagnosis of heart disease by noninvasively providing a wide range of anatomic and physiologic information. Previous research has shown that coronary flow, one component of a complete examination, can be accurately measured in the left anterior descending artery in vivo. The current work validates MR flow measurements in canine circumflex arteries using transit time ultrasound as a standard. The circumflex artery experiences greater in-plane motion and is a more stringent test for flow measurement accuracy. This work also compares two methods of processing MR velocity data, phase difference and complex difference techniques, and examines the sources of error present in the animal validation model. Phase difference processing with a 30% magnitude threshold best matched the mean ultrasound flow values (30% PD = 1.04 x US + 1.49, r = 0.94), but it was very sensitive to vessel boundary identification. The complex difference process was less sensitive to vessel boundary identification and correlated well with the transit time ultrasound despite systematic underestimations. The reasons for the discrepancies are shown to stem from a number of possible sources including variability of the ultrasound standard, low signal-to-noise ratios in the MR images, sensitivity of the MR technique to vessel boundary identification, and motion artifacts in the images.

3D time-resolved contrast-enhanced MR DSA: advantages and tradeoffs.

The 3D TRICKS method for contrast-enhanced, time-resolved MR DSA has been recently described. In this paper, computer simulations are used to investigate the relative frame rate, temporal window, artery-vein temporal separation, contrast-to-noise ratio, and spatial resolution of TRICKS and conventional scans for breath-hold and non-breath-hold applications. For non-breath-hold applications, TRICKS can be configured to provide increased CNR or spatial resolution at an increased frame rate, but with a longer temporal window when compared with a series of conventional scans in which the central portion of k-space is sampled at the same rate as for the TRICKS scans. For breath-hold applications, TRICKS typically provides three images with 75% of the conventional single acquisition spatial resolution and is more tolerant of variations in contrast curve shape within the field of view.

Steady-state and dynamic MR angiography with MS-325: initial experience in humans.

PURPOSE: To evaluate the imaging performance and patient tolerance of a blood-pool contrast agent (MS-325) for magnetic resonance (MR) angiography. MATERIALS AND METHODS: Imaging of peripheral and carotid vessels was performed in seven healthy volunteers in a phase I clinical trial of the gadolinium chelate MS-325. Each volunteer received an intravenous injection of 0.05 mmol/kg MS-325 over 30 seconds. Dynamic (arterial phase) and steady-state (arterial-venous phase) three-dimensional gradient-echo MR angiograms were acquired during, immediately after, and approximately 50 minutes after injection. Images were ranked (1 [poor] to 5 [excellent]) for overall image quality, and signal-to-noise ratio (S/N) and contrast-to-noise ratio (C/N) were measured by using standard techniques. RESULTS: All volunteers tolerated the procedure well. The MS-325-enhanced studies demonstrated intense vascular signal. Mean peripheral arterial C/N was 12.9 +/- 4.8 (standard deviation), 78.8 +/- 29.4, 46.1 +/- 10.9, and 41.9 +/- 14.1 for the two-dimensional (2D) time-of-flight (TOF) and the contrast material-enhanced dynamic, early steady-state, and late steady-state images, respectively. Image quality of steady-state postcontrast images was statistically significantly (P < .02) higher than that of 2D TOF images. Image quality of early and late postcontrast images was similar, but a small (10%) decrease in C/N was noted from early to late images. CONCLUSION: MS-325 provides excellent vascular and selective arterial enhancement during dynamic MR angiography. The long blood residence time also allows acquisition of steady-state images of the arteries and veins with excellent spatial resolution.

Generation of clonal diversity by sexual reproduction in the greenbug, Schizaphis graminum.

In the United States, the greenbug, Schizaphis graminum (Rondani), reproduces primarily by apomictic parthenogenesis. Although a periodic sexual cycle exists, the extent to which it occurs naturally and its influence on the genetic variability of greenbug populations is unclear. Length variation in the intergenic spacer (IGS) of the rRNA cistron in the greenbug indicates that populations are made up of many genetically distinct clones. Previous laboratory studies have shown the stability of the IGS within parthenogenetic clones. By inducing the sexual reproductive cycle of the greenbug, we conducted both Intra- and inter-clone matings and studied the inheritance of the IGS in the offspring. In both mating schemes, rearrangements in the IGS were apparent. IGS diversity found among the offspring could be attributed to unequal cross-over and probably other molecular drive events during meiosis. Periodic sexual reproduction is a primary mechanism for the generation and maintenance of genetic variability in greenbug populations, and explains the level of clonal diversity found in previous studies.

Tacalcitol.

Tacalcitol is a vitamin D3 analogue which is available in Japan as a 2 micrograms/g ointment for twice daily application and in Western markets as a 4 micrograms/g ointment for once daily application. Tacalcitol inhibits proliferation, and induces the differentiation, of keratinocytes. In addition, it appears to modulate inflammatory and immunological mediators in the skin which may be involved in the aetiology of psoriasis. No significant systemic drug absorption occurs after application of tacalcitol to the skin. Results of clinical trials indicate that topical tacalcitol is effective in the management of stable plaque psoriasis (and possibly pustular forms of the disease), and has a similar efficacy to topical betamethasone valerate in this setting. Application of tacalcitol ointment 4 micrograms/g once daily for up to 8 weeks did not cause hypercalcaemia or hypercalciuria. Mild local skin irritation has been reported in a variable proportion of patients (< or = 12%).

Effects of through-plane myocardial motion on phase-difference and complex-difference measurements of absolute coronary artery flow.

We have previously reported on a complex-difference (CD) flow measurement technique that produces more accurate results than the phase-difference (PD) flow measurement technique due to the greater immunity of the former method to partial volume effects. We report here on some of the ways in which through-plane myocardial motion affects the accuracy of absolute coronary artery flow measurements obtained using the PD and CD techniques. We also discuss motion correction schemes that can be applied to the PD and CD processing methods to improve their accuracy. Computer simulations have been performed to assess the magnitude of the errors associated with these flow measurement techniques when they are applied to small vessels that are attached to a moving background. Laminar and plug flow, with and without complete background suppression, have been considered. Experiments with a moving vessel phantom have been conducted to test the performance of the PD and CD flow measurement techniques in circumstances similar to those simulated. The simulations and the experiments showed that, after corrections for through-plane motion are made, the CD method generally yields more accurate flow results than the PD method. As shown by the simulations, however, both methods yield compromised results due to subtle saturation effects that occur when the direction of myocardial motion is opposite the direction of blood flow. Unvalidated PD and CD measurements of coronary artery flow waveforms in human volunteers are presented to illustrate the magnitude of the proposed through-plane motion effects in vivo.

High-speed chromosome sorting.

Dual-beam high-speed sorting has been developed to facilitate purification of chromosomes based on DNA staining with the fluorescent dyes Hoechst 33258 and chromomycin A3. Approximately 200 chromosomes per second of two types can be sorted from a suspension of chromosomes isolated from human lymphoblasts while fluorescent objects (chromosomes, debris fragments, chromosome clumps, and nuclei) are processed at the rate of about 20,000 per second. This sorting rate is approximately ten times that possible with conventional sorters. Chromosomes of a single type can be sorted with a purity of about 90 percent. DNA from the sorted chromosomes is suitable for construction of recombinant DNA libraries and for gene mapping.

Centromeric index measurement by slit-scan flow cytometry.

We report here the application of slit-scan flow cytometry (SSFCM) in the classification of muntjac, Chinese hamster, and human chromosomes according to centromeric index (CI) and total fluorescence. Chromosomes were isolated from mitotic cells, stained with propidium iodide and processed through the SSFCM where fluorescence profiles were measured. The centromere for each profile was taken as the point of maximum difference between the measured profile and a standard profile having no centromeric dip. The areas under the profile on either side of the centromere were then calculated and the CI was calculated as the ratio of the larger area to the total area under the profile. Relative DNA contents for each chromosome were taken to be proportional to the total fluorescence. Mean CI's for muntjac chromosomes 1, 2, and X + 3 were 0.52, 0.88, and 0.73, respectively; CI's for Chinese hamster M3-1 chromosomes 1, 2, 5, 8, and M2 were 0.53, 0.55, 0.57, 0.77, and 0.86, respectively; and average CI's for chromosome groups 4 + t (X;5), 6 + 7 + Y, 9 + M1, and 10 + 11 were 0.56, 0.82, 0.58, and 0.60, respectively. These results were, on average, within 4.4% of CI measurements made by image cytometry. CI's measured for human chromosomes 9 through 12, were, on average, within 2.0% of those made by image cytometry.

Multi-parameter, computer controlled operation of a FACS II cell sorter.

The ease of operation and versatility of a FACS II cell sorter were improved by replacing the original pulse height analyzer (PHA) with a computer-based dual parameter PHA and a single channel analyzer (SCA). An ND620 LSI-11 based PHA is now used to generate the sorting decisions. Sorting windows are created by intensifying one or more regions of any shape on the PHA single or dual parameter histograms. For three parameter operation, the third parameter SCA contols the dual parameter information sent to the analyzer. The SCA can also trigger an abort circuit during the PHA 15 microsecond analyzing dead time, improving the purity of the sorted fraction. The electronics that interfaces the new PHA to the sorter replaces all of the original FACS II analog signal processing circuitry with an interchangeable circuit board. The principles involved should apply to any cell sorter.