Biomedical subjects

J P Finn

Publications and source records attributed to J P Finn.

At least 19 recordsLinked to original sources

PubMed2006

[Cardiac MR tagging: optimization of sequence parameters and comparison at 1.5 T and 3.0 T in a volunteer study].

PURPOSE: The aim of this study was the optimization of a gradient echo (GRE) MR tagging sequence at 3.0 T in comparison to 1.5 T in order to obtain the best image contrast between the myocardium, tag lines and blood signal. Theoretically expected improvements of signal-to-noise (SNR) and contrast-to-noise ratios (CNR) were also calculated. MATERIALS AND METHODS: 14 healthy volunteers (8 male, 6 female; mean age 43.4 +/- 10.3 years) were scanned using a 3.0 T as well as a 1.5 T whole-body system. A GRE flash-2 D tagging sequence was evaluated (midventricular short axis view) by varying the flip angle (8 - 16 degrees ), slice thickness (4 - 8 mm; fixed flip angle 1.5/3.0 T: 12 degrees /8 degrees , tag size 8 mm) and tag size (4 - 8 mm, fixed flip angle 1.5/3.0 T: 12 degrees /8 degrees , slice thickness 6 mm). The field of view, acquisition time and temporal resolution (45 ms) were kept constant. Qualitative and quantitative image analysis was performed by calculating the SNR, CNR (tag) as well as the relative contrast between the myocardium and tag lines (RCMT). RESULTS: Based on individual comparison, the best imaging protocol was found at a slice thickness of 6 mm, tag size of 8 mm, optimized flip angle of 8 degrees (3.0 T) and 12 degrees (1.5 T), respectively. Compared to 1.5 T, a significantly higher overall image score was determined (mean +/- sd; 3.2 +/- 0.2 vs. 2.7 +/- 0.4) and a strong correlation between the CNR (tag) and RCMT for flip angle alpha and the slice thickness was found. A higher field strength resulted in an 80 % increase in the CNR (tag) compared to 1.5 T (mean 10.7/6.1). Furthermore, the SNR was improved by 35 % (mean 20.6/15.3) and the RCMT by 35 % (mean 0.47/0.35). CONCLUSION: Myocardial tagging at 3.0 T has shown superior image quality in comparison to 1.5 T due to a higher baseline SNR and an improved CNR as well as RCMT. The suppressed fading of the tags enables the accessibility to the diastolic phase of the cardiac cycle.

Adult↗

PubMed2005

The feasibility of spatial high-resolution magnetic resonance angiography (MRA) of the renal arteries at 3.0 T.

PURPOSE: To evaluate the feasibility of high-spatial resolution magnetic resonance angiography (MRA) of the renal arteries at 3.0 T. MATERIAL AND METHODS: Twelve healthy volunteers (mean age, 38.8 years) underwent renal MRA at 3.0 T. The application of parallel imaging with an acceleration factor of 3 allowed obtaining MR angiographic data with a voxel size of 0.9 x 0.8 x 0.9 mm in scan time of only 16 s. A dose of 0.2 mmol/kg body weight of 0.5-molar gadodiamide was administered at a flow rate of 2 ml/s. For image analysis, image quality, presence of artifacts, venous contamination and level of noise were rated by two radiologists in consensus. RESULTS: All examinations were of diagnostic quality. The image quality was rated good or very good in 91 % (11/12) of cases. Due to the high parallel imaging factor the level of noise was slightly increased without diagnostic impairment. Mild venous enhancement was found in 75 % (9/12) of the examinations. CONCLUSION: Renal MRA at 3.0 T is feasible with high spatial resolution and a short acquisition time.

Adult↗

PubMed2001

Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family.

CEP-1347 (KT7515) promotes neuronal survival at dosages that inhibit activation of the c-Jun amino-terminal kinases (JNKs) in primary embryonic cultures and differentiated PC12 cells after trophic withdrawal and in mice treated with 1-methyl-4-phenyl tetrahydropyridine. In an effort to identify molecular target(s) of CEP-1347 in the JNK cascade, JNK1 and known upstream regulators of JNK1 were co-expressed in Cos-7 cells to determine whether CEP-1347 could modulate JNK1 activation. CEP-1347 blocked JNK1 activation induced by members of the mixed lineage kinase (MLK) family (MLK3, MLK2, MLK1, dual leucine zipper kinase, and leucine zipper kinase). The response was selective because CEP-1347 did not inhibit JNK1 activation in cells induced by kinases independent of the MLK cascade. CEP-1347 inhibition of recombinant MLK members in vitro was competitive with ATP, resulting in IC(50) values ranging from 23 to 51 nm, comparable to inhibitory potencies observed in intact cells. In addition, overexpression of MLK3 led to death in Chinese hamster ovary cells, and CEP-1347 blocked this death at doses comparable to those that inhibited MLK3 kinase activity. These results identify MLKs as targets of CEP-1347 in the JNK signaling cascade and demonstrate that CEP-1347 can block MLK-induced cell death.

Animals↗

PubMed2001

Coronary artery imaging: 3D segmented k-space data acquisition with multiple breath-holds and real-time slab following.

The purpose of this work was to develop a multiple-breath-hold (BH) imaging method for coronary arteries in which a segment of k-space is acquired in each BH. The goal was to increase the resolution, or the signal-to-noise ratio (SNR) and coverage, of three-dimensional-(3D)-BH volume-targeted scanning (VCATS). To correct for slab position differences, a real-time slab following technique using navigator echoes for motion detection was used. Sixteen normal volunteers were imaged to compare the method with a single-BH scan. Results showed that higher resolution, or larger coverage and higher SNR, were achieved by the multiple-BH method without respiratory motion artifacts. In conclusion, 3D segmented k-space data acquisition with multiple-BHs and real-time slab following is a promising approach for extending the capabilities of VCATS further.

Adult↗

PubMed2001

Contrast-enhanced coronary MR angiography: relationship between coronary artery delineation and blood T1.

Contrast-enhanced coronary angiography has become an important technique for magnetic resonance (MR) coronary artery imaging. However, the relationship between the quality of the coronary artery images and blood T1 has not yet been fully explored. In this paper, we assessed this relationship in an animal model by using a prototypical blood pool agent. With accumulated injections of this agent, the blood T1 would be maintained at different levels. The measured blood T1 values in vivo were 147 +/- 3, 82 +/- 6, 48 +/- 4, 40 +/- 3, and 30 +/- 8 msec (N = 7). Fixed and variable flip angle schemes were used in coronary artery imaging. The signal to noise ratios (SNR) of coronary arteries were measured and the image quality was assessed. It was found that blood T1 less than 80 msec might be desired. No statistically significant difference was observed between two flip angle schemes. There was better vessel definition using variable flip angle at blood T1 lower than 50 msec. Understanding this relationship may be beneficial to optimizing image protocol and/or design of blood pool contrast agents for contrast-enhanced coronary angiography.

Animals↗

PubMed2001

Three-dimensional MR pulmonary perfusion imaging and angiography with an injection of a new blood pool contrast agent B-22956/1.

Initial evaluation of a new blood pool agent, B-22956/1, for pulmonary imaging was performed in five domestic pigs with artificial embolism. Pre-embolism 3D pulmonary perfusion images were first acquired by injecting an extravascular agent, gadoteridol. The pulmonary arteries of the pigs were then occluded by the artificial emboli. Post-embolism perfusion scans were subsequently performed by injecting B-22956/1. Additional post-embolism high-spatial-resolution angiograms were also acquired. Parenchyma perfusion deficits were well depicted in the post-embolism perfusion maps. The post-embolism angiography clearly revealed the location and extent of the filling defects in the pulmonary vessels. Signal intensities of perfusion maps on the normal parenchyma were significantly improved (30%) by using B-22956/1, in comparison with perfusion images using gadoteridol (P < 0.01). Many pulmonary angiograms with approximately equal contrast could be obtained even at 22 minutes after the injection of B-22956/1. Our initial results indicate that blood pool agent B-22956/1 may provide opportunities for whole-lung-coverage perfusion mapping and additional high-resolution target angiograms after a single injection.

Animals↗

PubMed2001

3D magnetization-prepared true-FISP: a new technique for imaging coronary arteries.

The purpose of this work was to develop an ECG-triggered, segmented 3D true-FISP (fast imaging with steady-state precession) technique to improve the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of breath-hold coronary artery imaging. The major task was to optimize an appropriate magnetization preparation scheme to permit saturation of the epicardial fat signal. An alpha/2 preparation pulse was used to speed up the approach to steady-state following a frequency-selective fat-saturation pulse in each heartbeat. The application of dummy cycles was found to reduce the oscillation of the magnetization during data acquisition. The fat saturation and magnetization preparation scheme was validated with simulations and phantom studies. Volunteer studies demonstrated substantially increased SNR (55%) and CNR (178%) for coronary arteries compared to FLASH (fast low-angle shot) with the same imaging time. In conclusion, true-FISP is a promising technique for coronary artery imaging.

Adult↗

PubMed2001

Assessment of regional differences in myocardial blood flow using T2-weighted 3D BOLD imaging.

The feasibility of detecting regional differences in myocardial blood flow based on the blood oxygen level-dependent (BOLD) effect was evaluated in vivo in dogs (N = 9) using a 3D T2-prepared segmented gradient-echo sequence at 1.5 T. Regional differences in myocardial blood flow were created by administering adenosine through a catheter placed in the left circumflex coronary artery (LCX). The difference in the R2 (1/T2) relaxation rate between the left ventricular myocardial region supplied by the LCX and regions supplied by the left anterior descending coronary artery (LAD) or septal artery during adenosine administration was correlated to the corresponding regional myocardial blood flow difference determined using fluorescent microspheres. A correlation coefficient of 0.80 was found between the MR BOLD measurements and the myocardial flow assessment. Our results show that the sequence used in this study allows fast 3D BOLD imaging of the heart, and is a promising technique for detecting regional myocardial perfusion differences.

Animals↗

PubMed2001

Effect of creatine supplementation on metabolism and performance in humans during intermittent sprint cycling.

This double blind study investigated the effect of oral creatine supplementation (CrS) on 4 x 20 s of maximal sprinting on an air-braked cycle ergometer. Each sprint was separated by 20 s of recovery. A group of 16 triathletes [mean age 26.6 (SD 5.1) years. mean body mass 77.0 (SD 5.8) kg, mean body fat 12.9 (SD 4.6)%, maximal oxygen uptake 4.86 (SD 0.7) l.min-1] performed an initial 4 x 20 s trial after a muscle biopsy sample had been taken at rest. The subjects were then matched on their total intramuscular creatine content (TCr) before being randomly assigned to groups to take by mouth either a creatine supplement (CRE) or a placebo (CON) before a second 4 x 20 s trial. A muscle biopsy sample was also taken immediately before this second trial. The CrS of 100 g comprised 4 x 5 g for 5 days. The initial mean TCr were 112.5 (SD 8.7) and 112.5 (SD 10.7) mmol.kg-1 dry mass for CRE and CON, respectively. After creatine loading and placebo ingestion respectively, CRE [128.7 (SD 11.8) mmol.kg-1 dry mass] had a greater (P = 0.01) TCr than CON [112.0 (SD 10.0) mmol.kg-1 dry mass]. While the increase in free creatine for CRE was statistically significant (P = 0.034), this was not so for the changes in phosphocreatine content [trial 1: 75.7 (SD 6.9), trial 2: 84.7 (SD 11.0) mmol.kg-1 dry mass, P = 0.091]. There were no significant differences between CRE and CON for citrate synthase activity (P = 0.163). There was a tendency towards improved performance in terms of 1 s peak power (in watts P = 0.07; in watts per kilogram P = 0.05), 5 s peak power (in watts P = 0.08) and fatigue index (P = 0.08) after CrS for sprint 1 of the second trial. However, there was no improvement for mean power (in watts P = 0.15; in watts per kilogram P = 0.1) in sprint 1 or for any performance values in subsequent sprints. Our results suggest that, while CrS elevates the intramuscular stores of free creatine, this does not have an ergogenic effect on 4 x 20 s all-out cycle sprints with intervening 20-s rest periods.

Adult↗

PubMed2001

Contrast-enhanced magnetic resonance angiography of the carotid circulation.

Contrast-enhanced MR angiography (CE MR angiography) is rapidly becoming the investigation of first choice for evaluating disease of the vascular system. It is particularly applicable to the carotid circulation and has replaced more traditional time-of-flight imaging because of shorter acquisition times and fewer artifacts. With recent advances in gradient hardware, shorter repetition times allow high spatial resolution imaging of the entire carotid circulation form the aortic arch to the circle of Willis in less than 20 seconds. Additional acquisitions can be utilized as part of the same study to accurately time the arrival of contrast in the arterial system and overcome the problem of early venous enhancement. A number of techniques have been developed recently that allow CE MR angiography to be implemented with high temporal resolution. Both atherosclerotic and nonatherosclerotic carotid artery disease can be comprehensively assessed with CE MR angiography, preventing the need for conventional diagnostic angiography.

Arteriosclerosis↗

PubMed2001

An improved MR imaging technique for the visualization of myocardial infarction.

PURPOSE: To design a segmented inversion-recovery turbo fast low-angle shot (turboFLASH) magnetic resonance (MR) imaging pulse sequence for the visualization of myocardial infarction, compare this technique with other MR imaging approaches in a canine model of ischemic injury, and evaluate its utility in patients with coronary artery disease. MATERIALS AND METHODS: Six dogs and 18 patients were examined. In dogs, infarction was produced and images were acquired by using 10 different pulse sequences. In patients, the segmented turboFLASH technique was used to acquire contrast material-enhanced images 19 days +/- 7 (SD) after myocardial infarction. RESULTS: Myocardial regions of increased signal intensity were observed in all animals and patients at imaging. With the postcontrast segmented turboFLASH sequence, the signal intensity of the infarcted myocardium was 1,080% +/- 214 higher than that of the normal myocardium in dogs-nearly twice that of the next best sequence tested and approximately 10-fold greater than that in previous reports. All 18 patients with myocardial infarction demonstrated high signal intensity at imaging. On average, the signal intensity of the high-signal-intensity regions in patients was 485% +/- 43 higher than that of the normal myocardium. CONCLUSION: The segmented inversion-recovery turboFLASH sequence produced the greatest differences in regional myocardial signal intensity in animals. Application of this technique in patients with infarction substantially improved differentiation between injured and normal regions.

Adult↗

PubMed2001

Coronary arteries: magnetization-prepared contrast-enhanced three-dimensional volume-targeted breath-hold MR angiography.

A volume-targeted contrast agent-enhanced breath-hold coronary magnetic resonance angiographic technique was optimized and evaluated in 16 volunteers. Substantial increases in coronary signal-to-noise ratio, contrast-to-noise ratio, lengths of depiction, and vessel sharpness were observed on enhanced images. The imaging approach with two 20-mL injections of contrast agent covers the left and right coronary arteries in two breath holds and is a promising method for coronary imaging.

Adult↗

PubMed2001

Cine MR angiography of the heart with segmented true fast imaging with steady-state precession.

In five healthy subjects and 18 patients, cine magnetic resonance (MR) imaging of the heart was performed with a true fast imaging with steady-state precession (FISP) sequence. Results were compared both quantitatively and qualitatively with those at cine fast low-angle shot (FLASH) MR imaging. The blood-myocardial contrast-to-noise ratio (CNR) was 2.0 times higher and the normalized (for measurement time and pixel size) blood-myocardial CNR was 4.0 times higher for true FISP compared with FLASH MR imaging. Qualitative scores for image quality were significantly higher with true FISP MR imaging. Segmented cine true FISP MR imaging generated high-contrast MR images of the heart in healthy subjects and in patients with heart disease and produced image quality superior to that with cine FLASH MR imaging.

Adult↗

PubMed2001

Usefulness of segmented trueFISP cardiac pulse sequence in evaluation of congenital and acquired adult cardiac abnormalities.

OBJECTIVE: The purpose of this study is to compare ultrashort TR, segmented trueFISP (fast imaging with steady-state precession) cine MR imaging with segmented FLASH (fast low-angle shot) cine MR imaging for the detection and characterization of congenital and acquired adult cardiac abnormalities. SUBJECTS AND METHODS: Twenty-five patients with known or clinically suspected cardiac abnormalities were imaged on a 1.5-T scanner. Valve plane movies were obtained in patients with suspected valve morphology or function abnormalities or whose horizontal long-axis images showed jets. For each patient, three radiologists independently compared corresponding matched cine FLASH and trueFISP movies for image quality in evaluating anatomy and function of the great vessels and heart. Image quality was rated on a five-point scale, and data were analyzed using both a Wilcoxon's signed rank test and a repeated-measures analysis of variance. RESULTS: Image quality ratings of trueFISP and FLASH showed a statistically significant difference (F = 58.67; df = 1, 72; p < 0.0001), with the average rating for the trueFISP images being significantly higher (mean rating, 4.1 +/- 0.92) than that for the FLASH images (mean, 3.0 +/- 1.0). However, valve architecture in the aortic valves appeared to be better visualized and was more easily measured in valve plane images with FLASH. No statistically significant differences among the ratings of the interpreters (F = 0.018; df = 2, 72; p = 0.9821) were evident, and, therefore, no suggestion of bias was indicated (F = 0.775; df = 1, 2; p = 0.4645). TrueFISP yielded the correct diagnosis prospectively in 13 (100%) of 13 patients, whereas FLASH yielded the correct diagnosis in 12 (92%) of 13 patients. CONCLUSION: TrueFISP images depict morphologic and functional abnormalities with greater clarity and provide greater diagnostic confidence than FLASH images-and in a fraction of the time. A specific exception is in the assessment of valve leaflet architecture and cross-sectional area calculation (i.e., bicuspid aortic valves); in these evaluations, FLASH maintains a complementary diagnostic imaging role.

Adult↗

PubMed2000

Neurotoxicity studies on sucralose and its hydrolysis products with special reference to histopathologic and ultrastructural changes.

Comparative neuropathological studies of 1,6-dichloro-1, 6-dideoxy-beta-D-fructofuranosyl-4-chloro-4-deoxy-alpha-D-galactopyra noside (sucralose), an equimolar mixture of 1,6-dichloro-1, 6-dideoxyfructose (1,6-DCF) and 4-chloro-4-deoxygalactose (4-CG), the hydrolysis products of sucralose, and 6-chloro-6-deoxyglucose (6-CG) were conducted in male and female mice and male marmoset monkeys, focusing on morphological changes in the central nervous system. 6-Chloro-6-deoxyglucose, previously reported to produce neurotoxic effects, served as the positive control and was administered by gavage at a daily dose of 500mg/kg. Sucralose and the sucralose hydrolysis products (sucralose-HP) were similarly administered to mice and marmosets at doses of up to 1000mg/kg for 21 and 28 days, respectively. No changes were detected in the central nervous system by light or electron microscopy in either of the species that received sucralose or its hydrolysis products. 6-Chloro-6-deoxyglucose, in contrast, induced symmetrical lesions in the deep nuclei of the cerebellum, brain stem and spinal cord with definitive neurological signs of CNS involvement.

Administration, Oral↗

PubMed2000

A combined chronic toxicity/carcinogenicity study of sucralose in Sprague-Dawley rats.

The chronic toxicity and potential carcinogenicity of sucralose was evaluated by exposing Sprague-Dawley rats to dietary concentrations of this low-calorie sweetener both in utero and for up to 104 weeks following parturition. The rats assigned to the toxicity phase of this investigation were administered diets containing either 0% (control), 0.3% (3000 ppm), 1.0% (10,000 ppm) or 3.0% (30,000 ppm) sucralose. Each treatment group comprised 30 male and 30 female rats, of which 15 males and 15 females were sacrificed after 52 weeks of treatment. The surviving rats were killed following 78 weeks of sucralose administration. In the carcinogenicity phase of this investigation, groups of 50 male and 50 female rats were administered dietary sucralose at concentrations of 0% (control 1), 0% (control 2), 0.3%, 1.0% or 3.0% for 104 weeks. Evaluation of the data obtained from the two phases of this study showed that sucralose was not carcinogenic. Sucralose did not adversely affect the survival or clinical condition of the rats, and there were no toxicologically significant findings. Group mean body weight gain and food consumption were significantly decreased in a dose-dependent manner in sucralose-treated rats throughout the treatment period as compared to the controls. The primary effect of sucralose on food consumption, and secondarily on body weight gain, was established in later studies to be due to the fact that diets containing high concentrations of sucralose are unpalatable to rats. These subsequent studies established that the reduction of body weight gain seen in previous rat studies using sucralose in the diet at concentrations of 1% and below resulted from reduced food intake as a direct consequence of the unpalatable nature of sucralose. Similarly, at concentrations of 3% in the diet, it was shown that approximately 95% of the effect on body weight gain could be attributed to the reduction in food intake due to the reduced palatability of the diet, the remainder apparently due to a physiologic response to the high concentrations of non-digestible sucralose in the rats' diet. Complete toxicological evaluations of gavage studies with histopathological evaluations demonstrated that even at the 3% dietary level, toxicity was not responsible for the small body weight gain decrement. Gross and histopathologic examinations revealed that the administration of sucralose affected neither the types nor incidence of the tumours observed. The incidences of some non-neoplastic findings were statistically significantly increased in the sucralose treated groups relative to the controls. These included: renal pelvic epithelial hyperplasia in all female treatment groups, renal pelvic mineralization in females administered the intermediate or highest dietary concentrations of sucralose, adrenal cortical haemorrhagic degeneration in high-dose group female rats, and the histopathologic incidence of cataracts at necropsy in high-dose group male rats. The non-neoplastic findings that occurred were of no toxicological significance since they were either spontaneous findings commonly observed in aged rats of this strain or the physiological response to high dietary levels of a poorly absorbed compound.

Administration, Oral↗

PubMed2000

A carcinogenicity study of sucralose in the CD-1 mouse.

The potential carcinogenicity of sucralose was evaluated by feeding groups of 52 male and 52 female CD-1 mice a diet containing sucralose at 0.3% (3000 ppm), 1.0% (10,000 ppm) or 3.0% (30,000 ppm) for 104 weeks. A group of 72 male and 72 female mice received diet without sucralose and served as controls. Week 1 achieved doses ranging from 543 to 5870mg/kg body weight/day in the low-dose males and high-dose females, respectively. Sucralose had no adverse effect on survival. No significant changes attributable to sucralose were found in the clinical condition or behaviour of the mice. Organ weights and the gross appearance of tissues were unaffected by treatment. The mean erythrocyte counts of females receiving the highest dietary concentration were slightly, but statistically significantly, lower than those of the controls after 104 weeks of treatment. Group mean body weight gain at the highest dietary concentration of sucralose was significantly less than that of the control in mice of both sexes. Food consumption, after correction for sucralose content, was lower for female mice, but not statistically significant. Water consumption for male mice receiving the highest dietary concentration was approximately 9% higher than that of the controls. There were statistically significant increases in the incidence of several non-neoplastic findings, but these were not considered to be related to sucralose administration. Treatment with sucralose did not increase the incidence of any tumour or influence the types of tumours observed. It was concluded that sucralose is not carcinogenic in CD-1 mice. The body weight gain and erythrocyte observations at the 3.0% dietary level were of limited biological significance as they were not accompanied by any histopathologic finding and had no impact on survival. The remaining dose levels were judged to have no effects.

Administration, Oral↗

PubMed2000

Air-braked cycle ergometers: validity of the correction factor for barometric pressure.

Barometric pressure exerts by far the greatest influence of the three environmental factors (barometric pressure, temperature and humidity) on power outputs from air-braked ergometers. The barometric pressure correction factor for power outputs from air-braked ergometers is in widespread use but apparently has never been empirically validated. Our experiment validated this correction factor by calibrating two air-braked cycle ergometers in a hypobaric chamber using a dynamic calibration rig. The results showed that if the power output correction for changes in air resistance at barometric pressures corresponding to altitudes of 38, 600, 1,200 and 1,800 m above mean sea level were applied, then the coefficients of variation were 0.8-1.9% over the range of 160-1,597 W. The overall mean error was 3.0 % but this included up to 0.73 % for the propagated error that was associated with errors in the measurement of: a) temperature b) relative humidity c) barometric pressure d) force, distance and angular velocity by the dynamic calibration rig. The overall mean error therefore approximated the +/- 2.0% of true load that was specified by the Laboratory Standards Assistance Scheme of the Australian Sports Commission. The validity of the correction factor for barometric pressure on power output was therefore demonstrated over the altitude range of 38-1,800 m.

Altitude↗