Biomedical subjects

J Keegan

Publications and source records attributed to J Keegan.

At least 19 recordsLinked to original sources

PubMed2002

Measurement of left ventricular volume after anterior myocardial infarction: comparison of magnetic resonance imaging, echocardiography, and radionuclide ventriculography.

We have compared echocardiography (echo) and radionuclide ventriculography (RNV) with magnetic resonance imaging (MRI) for the measurement of left ventricular (LV) volume and ejection fraction. Seventy asymptomatic patients were studied up to 12 days after first Q wave anterior myocardial infarction and again after 6 months. Each patient had LV volume measured by all three techniques within 24 hours of each other on each occasion. LV end-systolic and end-diastolic volume index (LVESVI and LVEDVI) and LV ejection fraction (LVEF) were measured using the modified Simpson formula (echo), a counts-based method (RNV), and a multislice area summation method (MRI). Radionuclide volumes were measured both with and without correction for attenuation of isotope. Echocardiography overestimated LV volume compared with MRI. Mean (SD) differences (echo-MRI) were: LVEDVI + 10.6 ml/m2 (16.8), LVESVI + 13.7 ml/m2 (12.9), LVEF -8.5% (11.2). RNV underestimated both volume and ejection fraction compared with MRI. Mean differences (RNV-MRI) were: LVEDVI -25.4 ml/m2 (23.8), LVESVI -5.0 ml/m2 (18.6), LVEF -13.8% (10.4). Variability in the difference between echo and MRI and between RNV and MRI was very similar for LVEF (coefficient of variation 23.9% echo, 22.2% RNV) but there was greater variability in the radionuclide than the echo measurements of absolute volume. Variability of the radionuclide measurements was reduced by not correcting for attenuation, and this finding may improve the radionuclide technique for serial measurements of percentage change in volume. Long-term inter-study reproducibility of MRI for LVEF (coefficient of reproducibility) was 10.9%, for echo it was 10.6%, and for RNV it was 14.6%. We conclude that measurements of LV volume depend on the method used and are not interchangeable. Echocardiography agrees more closely with MRI than RNV for the measurement of absolute volume, but the two techniques are similar for the measurement of LVEF.

Echocardiography↗

PubMed2001

Anion directed assembly of a dinuclear double helicate.

The synthesis and structural characterisation of the diamino-bis-pyridine ligand L2 and its diammonium-bispyridinium salt [(H4L2Cl)2].6Cl.H2O 1, are reported; X-ray diffraction studies reveal that chloride coordination causes the latter to adopt a double-helicate structure in the solid-state.

Journal Article↗

PubMed2001

Evaluation of free-breathing three-dimensional magnetic resonance coronary angiography with hybrid ordered phase encoding (HOPE) for the detection of proximal coronary artery stenosis.

We evaluated free-breathing, prospective navigator-gated, three-dimensional (3D) magnetic resonance coronary angiography (MRCA) with hybrid ordered phase-encoding (HOPE), in the detection of proximal coronary artery stenosis. The coronary arteries were imaged in 46 patients undergoing cardiac catheterization. The mean scan time was 48 minutes. The mean arterial length (mm) visualized was left main stem (LMS) 11.7 (SD 4.5), left anterior descending (LAD) 30.1 (SD 11.1), circumflex (LCx) 15.5 (SD 8.6), and right (RCA) 56.2 (SD 20.8). Twenty-three patients had coronary artery disease with 47 significant stenoses on cardiac catheterization. All LMS were normal on both catheterization and MRCA. MRCA sensitivity was highest for the LAD (89% CI 65%-99%) and RCA (76% CI 50%-93%), but lower for the LCx (50% CI 21%-79%). Specificity ranged from 72%-100%. Improvements in image quality, length of vessel seen, and specific imaging of the LCx are required for MRCA to become an alternative to cardiac catheterization.

Adult↗

PubMed2001

Dual contrast TrueFISP imaging for left ventricular segmentation.

Based on varying tissue contrasts at different RF flip angles, a new TrueFISP imaging strategy for cardiac function measurement is presented. A single breath-hold dual RF flip angle cine multi-slice TrueFISP imaging sequence was implemented which provides a significant increase in signal contrast between blood and myocardium. The increase in image contrast combined with different characteristics in RF response facilitates the delineation of cardiovascular borders. Based on this imaging strategy it is demonstrated how a simple 2D histogram clustering algorithm can be used for the fully automatic segmentation of the left ventricular (LV) blood pool. The method is validated with data acquired from 10 asymptomatic subjects, and the results are shown to be comparable to that of manual delineation by experienced observers.

Algorithms↗

PubMed2001

Tracking local volume 3D-echo-planar coronary artery imaging.

Aiming for robust high-resolution free respiration coronary artery imaging, localized tracking volume selective 3D-EPI at spatial resolution 1.25 x 1.25 x 3 mm and temporal resolution 65 ms was evaluated in 14 normal subjects. Subject-specific motion tracking factors were measured between diaphragm navigator and coronary artery in S-I and A-P directions. Imaging was repeated with and without tracking, accepting 128 cardiac cycles over a 20-mm range from free breathing. Reference images with minimal respiratory motion (5-mm range) used LED-guided multiple breathholds. Depending on accurate motion measurement, coronary arteries were imaged with tracking, in a 20-mm range of free breathing, with increased scan efficiency but without significant loss of image quality compared to multiple breathhold imaging.

Coronary Vessels↗

PubMed2001

The 62E early-late puff of Drosophila contains D-spinophilin, an ecdysone-inducible PDZ-domain protein dynamically expressed during metamorphosis.

At the onset of metamorphosis in Drosophila melanogaster, the steroid hormone 20-OH ecdysone induces a small number of early and early-late puffs in the polytene chromosomes of the third-instar larval salivary gland whose activity is required for regulating the activity of a larger set of late puffs. Most of the corresponding early and early-late genes have been found to encode transcription factors that regulate a much larger set of late genes. In contrast, we describe here the identification of an ecdysone-regulated gene in the 62E early-late puff, denoted D-spinophilin, that encodes a protein similar to the mammalian protein spinophilin/neurabin II. The D-spinophilin protein is predicted to contain a highly conserved PP1-binding domain and adjacent PDZ domain, as well as a coiled-coil domain and SAM domain, and belongs to a family of related proteins from diverse organisms. Transcription of D-spinophilin is correlated with 62E puff activity during the early stages of metamorphosis and is ecdysone-dependent, making this the first member of this gene family shown to be regulated by a steroid hormone. Examination of the dynamic patterns of D-spinophilin expression during the early stages of metamorphosis are consistent with a role in central nervous system metamorphosis as well as a more general role in other tissues. As D-spinophilin appears to be the only member of this gene family in Drosophila, its study provides an excellent opportunity to elucidate the role of an important adaptor protein in a genetic model organism.

Amino Acid Sequence↗

PubMed2001

Navigator echoes in cardiac magnetic resonance.

Navigator echoes are frequently used in cardiac magnetic resonance to monitor respiratory motion and have proved particularly useful in coronary artery imaging techniques where they allow the acquisition of data over multiple reproducible breathholds and during free breathing. The large number of variables involved in their use, however, is such that an optimal method of application may yet have to be developed. In this review article, we examine the issues relating to their implementation and describe the ways in which the navigator information obtained may be used.

Coronary Vessels↗

PubMed2001

Improved cine cardiovascular magnetic resonance using Clariscan (NC100150 injection).

We evaluated the use of Clariscan 0.75, 2, and 5 mg Fe/kg body weight in six patients to determine optimal dosing for short repetition time cine imaging. Breathhold cine images were acquired in the vertical and horizontal long axes and the short axis. Blood-pool signal-to-noise ratio increased significantly in all planes (p < 0.01) but was least marked in the short axis. Myocardial signal-to-noise ratio increased by a lesser amount (p < 0.05). Myocardial to blood-pool signal-difference-to-noise ratio improved significantly in the long axes (p < 0.05) and was greatest at 2 mg Fe/kg body weight, but changes in the short axis were minor. With the 5-mg Fe/kg body weight dose, the response was reduced or reversed due to T2* effects. Visual assessment improved in all planes (p < 0.05) and was optimal at 2 mg Fe/kg body weight. In conclusion, Clariscan improves short repetition time cardiac breathhold cine imaging, particularly in the long axis planes, with an optimal dose of 2 mg Fe/kg body weight.

Aged↗

PubMed2001

Anomalous coronary arteries: anatomic and functional assessment by coronary and perfusion cardiovascular magnetic resonance in three sisters.

Combined coronary and perfusion cardiovascular magnetic resonance was performed in three sisters with angina and suspected anomalous coronary arteries. Two sisters had anomalous coronary arteries passing between the aorta and right ventricular outflow tract and had abnormal myocardial perfusion. One sister had normal anatomy and perfusion. The combined approach identified the anatomy and functional significance of suspected anomalous coronary arteries.

Adult↗

PubMed2000

The E23 early gene of Drosophila encodes an ecdysone-inducible ATP-binding cassette transporter capable of repressing ecdysone-mediated gene activation.

At the onset of Drosophila metamorphosis, the steroid hormone 20-OH ecdysone directly induces a small number of early puffs in the polytene chromosomes of the larval salivary gland. Proteins encoded by the early genes corresponding to these transcriptional puffs then regulate the activity of both the early puffs themselves and a much larger set of late puffs. Three of these early genes encode transcription factors that play critical regulatory roles during metamorphosis. Here we report the cloning, DNA sequence, genomic structure, ecdysone inducibility, and temporal expression of an early gene residing in the 23E early puff and denoted E23 (Early gene at 23). In contrast to other early genes, E23 encodes a protein with similarity to ATP-binding cassette transporters. Using heat shock-inducible transgenes, we found that E23 overexpression not only produces phenotypic abnormalities and lethality, but also interferes with ecdysone-mediated gene activation, demonstrating that E23 is capable of modulating the ecdysone response. Our results suggest the existence of a previously unrecognized regulatory mechanism for modulating steroid hormone signaling in Drosophila.

ATP-Binding Cassette Transporters↗

PubMed2000

Coronary artery imaging in grown up congenital heart disease: complementary role of magnetic resonance and x-ray coronary angiography.

BACKGROUND: There is a high incidence of anomalous coronary arteries in subjects with congenital heart disease. These abnormalities can be responsible for myocardial ischemia and sudden death or be damaged during surgical intervention. It can be difficult to define the proximal course of anomalous coronary arteries with the use of conventional x-ray coronary angiography. Magnetic resonance coronary angiography (MRCA) has been shown to be useful in the assessment of the 3-dimensional relationship between the coronary arteries and the great vessels in subjects with normal cardiac morphology but has not been used in patients with congenital heart disease. METHODS AND RESULTS: Twenty-five adults with various congenital heart abnormalities were studied. X-ray coronary angiography and respiratory-gated MRCA were performed in all subjects. Coronary artery origin and proximal course were assessed for each imaging modality by separate, blinded investigators. Images were then compared, and a consensus diagnosis was reached. With the consensus readings for both magnetic resonance and x-ray coronary angiography, it was possible to identify the origin and course of the proximal coronary arteries in all 25 subjects: 16 with coronary anomalies and 9 with normal coronary arteries. Respiratory-gated MRCA had an accuracy of 92%, a sensitivity of 88%, and a specificity of 100% for the detection of abnormal coronary arteries. The MRCA results were more likely to agree with the consensus for definition of the proximal course of the coronary arteries (P<0.02). CONCLUSIONS: For the assessment of anomalous coronary artery anatomy in patients with congenital heart disease, the use of the combination of MRCA with x-ray coronary angiography improves the definition of the proximal coronary artery course. MRCA provides correct spatial relationships, whereas x-ray angiography provides a view of the entire coronary length and its peripheral run-off. Furthermore, respiratory-gated MRCA can be performed without breath holding and with only limited subject cooperation.

Adult↗

PubMed2000

Direct identification and quantitation of prednisone in the presence of overlapping hydrocortisone by liquid chromatography with electrospray and atmospheric-pressure chemical-ionisation mass spectrometry.

The paper describes the application of liquid chromatography interfaced to a triple quadrupole mass spectrometer utilising the multiple reaction monitoring (MRM) mode. The technique was shown to provide detection limits lower than 0.01% for the analysis of prednisone in the presence of hydrocortisone. Prednisone was mixed in concentrations from 0.500 to 0.0005 ppm (corresponding to 1% to 0.001% of the hydrocortisone concentration). These solutions were assayed using MRM observing the product ion transitions of 359.2-->147.1 and 359.2-->171.2 and was shown to be capable of detecting co-eluting impurities at concentrations of less than 0.001% of the major component. The assay of prednisone was shown to be linear over the range 0.500-0.0005 ppm with a correlation coefficient of 0.999 and a precision of 6.9% at the concentration of 0.005 ppm. The analysis was carried out using both atmospheric pressure chemical ionisation (APCI) and electrospray ionisation (ESI) as an interface. However, for these compounds APCI provided significantly more sensitive data compared to ESI.

Atmospheric Pressure↗

PubMed2000

A comparison between segmented k-space FLASH and interleaved spiral MR coronary angiography sequences.

A direct comparison of segmented fast low-angle short (FLASH) imaging and interleaved spiral magnetic resonance coronary angiography (MRCA) during free respiration using navigator echo has been performed. MRCA images were acquired in 30 normal subjects and 15 patients with coronary artery disease (CAD). Images of the right coronary artery were acquired during free respiration using navigator echo gating for both a segmented k-space FLASH sequence (8 views/segment, segment duration 105 msec) and an interleaved spiral sequence (20 interleaves, spiral read-out period 19 msec). Image quality was scored by three independent blinded observers, and coronary artery signal-to-noise ratio (SNR) and coronary artery/epicardial fat contrast-to-noise ratio (CNR) were measured. There was a significant improvement in image quality when coronary images were acquired with the interleaved spiral sequence (spiral 2. 3 vs. FLASH 1.8; P = 0.002). This was associated with an increase in the coronary artery SNR (16.6 +/- 6.9 vs. 11.8 +/- 5.0; P < 0.001), the coronary artery/epicardial fat CNR (12.5 +/- 6.1 vs. 7.4 +/- 4.0, P < 0.001), and the image resolution (256 x 256 vs. 256 x 128). However, there was a 12% increase in acquisition time for the interleaved spiral sequence. Image quality, SNR, CNR, and resolution can be improved using an interleaved spiral sequence. These improvements are secondary to the intrinsic characteristics of spiral imaging and the short acquisition period, which reduces the effects of both cardiac and respiratory motion.

Adult↗

PubMed2000

Left ventricular quantification in heart failure by cardiovascular MR using prospective respiratory navigator gating: comparison with breath-hold acquisition.

Cardiovascular magnetic resonance (CMR) is the reference standard for the assessment of cardiac function. Faster sequences, such as breath-hold (BH) fast low-angle shot, have made CMR more clinically acceptable and cost effective. In a significantly large patient group, however, holding their breath is difficult, resulting in poor-quality images. We compared prospective navigator-echo respiratory gating (NE), which allows image acquisition during free breathing, and BH imaging in 14 patients with heart failure and 10 normal volunteers. There was good agreement between both NE and BH volumes, mass, and ejection fraction. The image quality of both NE basal and apical slices was significantly better than the corresponding BH slices in both the heart failure (P < 0.01) and normal groups (P < 0.05). The NE image acquisition was more time efficient than the BH acquisition in the heart failure group (P < 0. 01), with no difference in the normal group (P = 0.2). Thus, prospective navigator-echo gating, previously only described in coronary artery imaging, can be used in the assessment of cardiac function. It is particularly useful in patients who find it difficult to hold their breath in whom NE provides good-quality, time-efficient images.

Electrocardiography↗

PubMed2000

Phase ordering with automatic window selection (PAWS): a novel motion-resistant technique for 3D coronary imaging.

Navigator acceptance imaging methods are hindered by the loss in scan efficiency which results from the changes in the breathing pattern of a subject over time. The diminishing variance algorithm (DVA), which does not use a predefined acceptance window, is less influenced by such changes. The use of phase ordering and weighting techniques has been shown to significantly improve image quality over nonordered window methods. However, the use of an acceptance window is inherent in all these techniques as a decision to accept or reject data must still be made. A technique is presented which is resistant to changes in breathing while allowing the use of phase ordering to provide effective motion artifact reduction in optimal time. The basic principle is described and illustrated for this automatic window-selection technique with in vitro results to demonstrate the feasibility of this method. Results of an in vivo study are also presented which demonstrate significant improvement in image quality over the DVA (p < 0.01) and hybrid-ordered phase encoding methods (p < 0.05).

Algorithms↗

PubMed2000

Interleaved spiral cine coronary artery velocity mapping.

Navigator-echo controlled interleaved spiral cine coronary-artery velocity maps were acquired in eight free-breathing volunteers. Good quality data were achieved in all subjects with phasic flow being clearly demonstrated. The improved efficiency of spiral k-space coverage compared to that of more conventional spin-warp techniques resulted in a mean scan time for 256 x 256 pixel-matrix studies of 94 sec (range 69 - 123 sec, SD = 20 sec), the navigator acceptance rate being typically 40-45%. Repeat scans in five subjects showed a high degree of reproducibility, with no significant differences occurring in the peak velocities (14.6+/-1.4 cm/sec vs. 14.5+/-1.5 cm/sec, P = ns) nor in the mean velocities measured over all cine phases (8.3+/-2.1 cm/sec vs. 8.7+/-1.6 cm/sec, P = ns). The potential benefits of using this sequence for assessing coronary blood flow and flow reserve are discussed. Magn Reson Med 43:787-792, 2000.

Blood Flow Velocity↗

PubMed1999

Magnetic resonance navigator echo diaphragm monitoring in patients with suspected diaphragm paralysis.

Real-time magnetic resonance (MR) navigator echo (NE) monitoring of the diaphragm is now possible. Using this technique, temporal changes in diaphragm position can be analyzed in a non-invasive fashion, without x-ray exposure. In this preliminary study, we have optimized three NE parameters (the NE column area, the NE repeat time, and the location of the NE on the diaphragm surface), and demonstrated the clinical application of MR NE diaphragm monitoring in patients with suspected diaphragm paralysis. The NE parameters were defined in 10 healthy volunteers, and diaphragm traces were scored for variance in NE diaphragm position registration. Using the optimal NE column parameters, we investigated four patients with diaphragm paralysis, one of whom required positive pressure ventilation while in the MR scanner, to show the utility of this technique. The NE diaphragm position registration was significantly affected by the area of the NE column, with poor position registration for the smallest column area (2.25 cm2 vs. 4 cm2 vs. 6.25 cm2, variance 6.3 vs. 0.6 vs. 0.3, P = 0.006). Diaphragm position registration was also significantly affected by the NE repeat time, with misregistration for the shortest repeat time (250 msec vs. 500 msec vs. 1000 msec, variance 11.9 vs. 0.6 vs. 1.0, P = 0.02), and data clipping, with loss of end-expiratory and end-inspiratory position registration, for the longest repeat time. Finally, if the NE was positioned too anteriorly, the diaphragm traces were of poor quality (anterior vs. dome vs. posterior, variance 11.8vs. 0.6vs. 3.2, P < 0.001). Application of the technique confirmed diaphragm paralysis in all four patients. The technique can be applied during positive pressure ventilation if necessary. The optimal NE parameters for diaphragm monitoring at 0.5 T were: column area, 400 mm2; NE repeat time; 500 msec; NE column positioned on the diaphragm dome. MR NE diaphragm monitoring provides a safe, non-invasive method of assessing diaphragm motion in patients with suspected diaphragm paralysis and may prove useful for long-term follow-up and monitoring of therapeutic interventions in these subjects.

Adult↗

PubMed1999

Safety and preliminary findings with the intravascular contrast agent NC100150 injection for MR coronary angiography.

In this Phase I clinical study, a novel ultrasmall superparamagnetic iron oxide contrast agent, NC100150 Injection (Nycomed Imaging, Oslo, Norway, a part of Nycomed Amersham), was used in two-dimensional magnetic resonance coronary angiography (MRCA). Safety and imaging data were acquired from 18 healthy male volunteers at both 0.5 and 1.5 T, before and after the administration of NC100150 Injection. Through-plane and in-plane images of the right coronary artery were analyzed. The postcontrast imaging sequences used prepulses and a high flip angle, to introduce T1 weighting. At 1.5 T (TE 2.6 msec), the through-plane coronary artery signal-to-noise ratio (SNR) (P = 0.04), coronary artery-to-fat signal difference-to-noise ratio (SDNR) (P = 0.001), coronary artery-to-myocardium SDNR (P<0.001), and coronary artery delineation (P<0.001) were improved by the administration of NC100150 Injection. For in-plane imaging, coronary artery delineation improved, but there were no significant changes in the SNR and SDNR. At 0.5 T, with the longer TE (6.7 msec) imaging sequence used, there was a reduction in the SNR (P = 0.01), the fat SDNR (through-plane P = 0.02; in-plane P = 0.25), and the coronary artery diameter (P<0.01 in both imaging planes). There was a trend toward improvement in the myocardial SDNR and coronary artery delineation. In conclusion, NC 100150 Injection was given safely to 18 healthy subjects, with no major adverse reactions. Coronary artery delineation was improved in both imaging planes at 1.5 T, with a trend toward improvement at 0.5 T. At 1.5 T, with a short TE imaging sequence, the marked T1 shortening effects of NC100150 Injection were dominant, leading to an improvement in the quantitative parameters for the through-plane images. At 0.5 T, with a longer TE imaging sequence, the T2* effects of the contrast agent played a role in reducing the quantitative image parameters. With further optimization of imaging sequences, to take advantage of the long-lived intravascular T1 shortening effect of NC100150 Injection, further improvements in MRCA will be possible.

Adult↗