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Biomedical subjects

D Li

Publications and source records attributed to D Li.

At least 955 records · Page 53Linked to original sources

Carotid plaque formation and its evaluation with angiography, ultrasound, and MR angiography.

The accurate assessment of carotid artery disease is an important challenge for magnetic resonance (MR) angiography. Studies indicate that the detection and grading of stenosis and the evaluation of plaque morphology are all important steps in the clinical assessment of atherosclerosis. The prevalence of significant carotid artery stenosis in the elderly population and even in patients with symptoms of carotid artery disease is low; clinical risk seems to correlate more closely with plaque morphology and surface characterization than with the degree of stenosis. This highlights the importance of MR angiography and ultrasound, which can help characterize plaque morphology in addition to showing the degree of stenosis. The authors review the present understanding of plaque formation, comparisons of plaque imaging with conventional angiography, ultrasound, and MR angiography, and recent progress in MR angiography techniques. Several studies, including the North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial, are discussed regarding the current objectives of carotid artery imaging. The sensitivity and specificity of plaque detection and morphologic evaluation continue to improve.

Aged↗

Magnetic resonance imaging of the brain with gadopentetate dimeglumine-DTPA: comparison of T1-weighted spin-echo and 3D gradient-echo sequences.

Short TR, short TE, high resolution, 3D gradient-recalled echo (GRE) imaging was evaluated for lesion detection in the brain. High resolution 3D GRE data acquisition was used to reduce partial volume effects and flow artifacts, to better visualize smaller structures, to minimize signal losses caused by field inhomogeneities, and to allow better image reformatting. Spin-echo (SE) and 3D GRE approaches were compared for lesion detection after the administration of an MR contrast agent, gadopentetate dimeglumine. Preliminary clinical studies demonstrated that the signal-to-noise ratio (SNR) in each slice of the GRE scan was worse than that of the SE scan because of the much thicker slices acquired with the SE technique. However, by averaging two adjacent 3D slices, the SNR of the two methods was essentially equivalent. In the averaged GRE slices, large lesions were seen just as well as in the SE images. More importantly, small lesions were better visualized in the thin 3D GRE images than in the thick SE images for the lesions studied in this work and the protocols used. These observations were confirmed by theoretical simulations.

Adolescent↗

Adaptive blood pool segmentation in three-dimensions: application to MR cardiac evaluation.

MRI is an established method of imaging the cardiac blood pool in four dimensions and evaluating global cardiac function. However, segmentation of the cardiac blood pool from the myocardial wall continues to be a time-consuming task and is operator dependent. This has hampered the widespread use of cardiac MRI in evaluating global cardiac function. We propose the use of an adaptive threshold-based, three-dimensional region-growing technique to segment the cardiac blood pool from the myocardium and to compute left ventricular blood volumes. It uses a unique double segmentation approach incorporating information from the myocardium to help better detect the edges of the blood pool. The adaptive threshold segmentation technique was evaluated on four human subjects by comparing with manual segmentation. Further, it requires minimal operator input and is robust and user friendly. The conclusion is that adaptive thresholds and a multidimensional region-growing approach is an appropriate method to segment the left ventricular blood pool.

Adult↗

Preliminary evaluation of a polyethyleneglycol-stabilized manganese-substituted hydroxylapatite as an intravascular contrast agent for MR angiography.

A blood-persistent particulate paramagnetic contrast agent has been formulated via size stabilization of manganese-substituted hydroxylapatite by a polyethylene glycol (PEG) bearing a terminal diphosphonate. At high PEG surface densities (35-40 mol%), particles with mean diameter 8 +/- 2 nm were obtained. Relaxivities of autoclaved samples (at 20 MHz proton Lamor frequency) were R1 = 18.7 +/- .8 mM-1 sec-1 and R2 = 22.3 +/- .7 mM-1 sec-1. The formulation persisted in rabbit blood with a biphasic clearance profile. Half-lives (with amplitudes in parenthesis) were 4 +/- 1 minutes (55%), and 49 +/- 3 minutes (45%), respectively, for the two phases. A dose of 40 mumol Mn/kg body weight enhanced the signal from rabbit vasculature for more than 45 minutes on MR angiograms. Thus, PEG-modified MnHA particles may find use as T1 agents for MR angiography.

Animals↗

A three-point Dixon method for water and fat separation using 2D and 3D gradient-echo techniques.

A water and fat separation technique based on a three-point Dixon method using two-dimensional (2D) and three-dimensional (3D) gradient-echo sequences and a new phase-unwrapping approach is presented. Using velocity-compensated sequences, three images, with water and fat protons in phase, opposed phase, and in phase, were acquired in an interleaved fashion for each phase-encoding line of the image. A fast 2D scan permitted acquisition of images within a single breath-hold, eliminating respiratory motion artifacts. The 3D sequence allowed coverage of a large region of interest with thin, contiguous slices. To correct field inhomogeneity effects, phase unwrapping was required. This was accomplished by comparing the corresponding pixels in the two water and fat in-phase images on a pixel-by-pixel basis. This phase-unwrapping approach is faster, more reliable, and requires less user interfacing than other methods. The water and fat separation method performed well in various parts of the body.

Adipose Tissue↗

In vivo correlation between blood T2* and oxygen saturation.

The in vivo relationship between blood T2* and oxygen saturation was investigated. A wide range of blood oxygen saturation levels was created in pigs by altering the ventilation rate. Blood T2* was measured in vivo in the abdominal aorta and the inferior vena cava, corresponding to each oxygen saturation level. Our results indicate that it is possible to measure blood T2* in vivo reliably with an MR technique we previously proposed. Blood T2* correlates closely with oxygen saturation levels over a wide range, and the relationship between blood T2* measured in vivo and oxygen saturation can be approximated by a linear function.

Animals↗

Response of hepatic function to hepatic copper deposition in rats fed a diet containing copper.

Fischer rats were a fed diet supplied with copper chloride (150-600 ppm) for 60 d from weaning. Serum (glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) activities were increased with the increase of Cu concentration in the diet. Biliary excretion of Cu was related to the dietary Cu level. Depositions of hepatic and renal Cu were also related to the dietary Cu level in a dose-dependent manner. In particular, hepatic (155.2 +/- 13.3 micrograms/g) and renal (44.9 +/- 4.4 micrograms/g) Cu concentrations increased abruptly in the Cu-600 ppm group. In the liver, about 60% of Cu was distributed in the soluble fraction (100,000 g supernatant). In the Cu-600 ppm group, 25% of cystosolic Cu was bound to metallothionein (MT). Our results suggest that chronic exposure to Cu appears to have a deleterious effect on the hepatic function, and further, that even in rats with normal biliary Cu excretion, clearance of Cu from the liver may be marginal when dietary Cu is near the 600-ppm level. Although Cu is an essential nutrient, an overload of Cu should be avoided.

Alanine Transaminase↗

Biliary excretion of copper in Fischer rats treated with copper salt and in Long-Evans cinnamon (LEC) rats with an inherently abnormal copper metabolism.

Increased biliary Cu excretion was found in Fischer rats injected with Cu. The biliary Cu was located at the void (large-molecule region) and total (small-molecule region) volume of a Sephadex G-75 column. The most Cu was found in the total volume. The two Cu peaks comigrated with absorbance at 280 nm. Although the bile from Cu-untreated Fischer rats did not show Cu absorbance in the total volume, absorbance at 280 nm was also found in this region. Even though Long-Evans Cinnamon (LEC) rats deposited a gross amount of Cu (194.0 +/- 27.8 micrograms/g liver) in the liver, they conversely showed reduced Cu excretion into the bile. LEC bile did not show Cu absorbance but rather absorbance at 280 nm in the total volume. Therefore, it seems unlikely that the small molecules found in the Sephadex G-75 regulate biliary Cu excretion in Cu-loaded rats, although the molecules bind to Cu. When the bile from Cu-untreated Fischer and LEC rats was incubated with CuCl2 solution, the most Cu was recovered in the total volume of this column. Our results suggest that reduced biliary Cu excretion in LEC rats is not related to the small molecules, and that Cu cannot be excreted in the form of macromolecules in rats to decrease Cu from the Cu-loaded liver.

Animals↗

The effect of head-down tilt on brain potentials related to visual attention.

To study the possible effect of simulated weightlessness on brain function state, the brain event-related potentials (ERPs) in a simple visual selective response task were compared between HDT and HUT in 9 normal subjects. The results were: The Target(T) and non-Target(NT) flash signals both induced significant slow positive potentials which were supposed to related to the attention state; the amplitude of the positive potentials in frontal regions decreased significantly especially for NT-ERPs during HDT compared with that during HUT. The data reported provide new evidence indicating that more attention should be paid on the brain function study during space flight.

Adult↗

Exogenous and endogenous DNA modifications as monitored by 32P-postlabeling: relationships to cancer and aging.

32P-postlabeling analysis, a highly sensitive method for the detection and measurement of covalent carcinogen-DNA adducts and other DNA modifications, does not require radioactive test substances and, therefore, can be applied to DNA of mammals, including humans exposed to low doses of environmental or occupational genotoxicants. The basic procedure entails the enzymatic incorporation of 32P-label into hydrolysis products of DNA, followed by chromatographic mapping and autoradiography of the 32P-labeled digestion products and quantitative scintillation spectrometry. Microgram amounts of DNA are analyzed: Thus the assay is suited for limited amounts of cells or tissues. Various versions of the assay afford different sensitivities of adduct detection. A single aromatic or bulky/hydrophobic adduct in 10(8)-10(10) nucleotides can be detected and measured (corresponding to 0.3-30 amol adduct/micrograms DNA or 0.1-10 nmol adduct/mol DNA-P). In animal models, the assay has been successfully applied to a variety of mutagenic (genotoxic) as well as nonmutagenic carcinogens. In humans, DNA specimens from cigarette smokers, iron foundry workers, and coke oven workers whose total aromatic adduct levels ranged from 1 adduct in 10(6)-10(8) DNA nucleotides have been examined by 32P-postlabeling. The assay also detects DNA modifications--Indigenous (I)-compounds--that increase with age in untreated animals. I-compound profiles and levels are highly species-, strain-, sex-, and tissue-specific, and also depend on diet composition. Caloric restriction, a highly efficient method for improving resistance to carcinogenesis and extending life span, increased rather than decreased I-compound levels in various tissues of male rats. Nonmutagenic hepatocarcinogens reduced levels of I-compounds in the target organ. Because of the specificity of this effect, reduction of I-compound levels appears to represent a novel biomarker for the action of nonmutagenic carcinogens. DNA from various hepatomas was found largely devoid of I-compounds. The results support a possible antineoplastic and antiaging role of these DNA modifications.

Aging↗

Role of aldehyde dehydrogenase in the biological activity of spermine dialdehyde, a novel immunosuppressive/purging agent.

The antitumour and immunosuppressive activities of spermine dialdehyde (SDA), a synthetic, oxidized form of spermine, were examined using L1210 cell lines and murine bone marrow cells. SDA acted as a high affinity substrate for aldehyde dehydrogenase (ADH) derived from different sources, with kinetic profiles similar to other aldehyde substrates. The murine leukaemic, cyclophosphamide-resistant L1210/CPA cells, having high levels of intracellular ADH activity, were less sensitive to SDA compared to ADH deficient L1210/O cells as measured by [3H]-thymidine incorporation in proliferation studies. Furthermore, pretreatment of L1210/CPA cells with the ADH inhibitor, diethyl aminobenzaldehyde (DEAB), resulted in potentiation of the SDA response. Murine bone marrow cells were more resistant to SDA than splenic T cells. However, addition of DEAB to bone marrow cultures potentiated the sensitivity of progenitor cells to SDA, as measured by colony formation. The results indicate that levels of ADH in the target tissues would determine the potency of SDA and subsequently offer selectivity and specificity to the therapeutic potentials of this putative purging agent.

Aldehyde Dehydrogenase↗

Image accuracy improvements in microwave tomographic thermometry: phantom experience.

Evaluation of a laboratory-scale microwave imaging system for non-invasive temperature monitoring has previously been reported with good results in terms of both spatial and temperature resolution. However, a new formulation of the reconstruction algorithm in terms of the log-magnitude and phase of the electric fields has dramatically improved the ability of the system to track the temperature-dependent electrical conductivity distribution. This algorithmic enhancement was originally implemented as a way of improving overall imaging capability in cases of large, high contrast permittivity scatterers, but has also proved to be sensitive to subtle conductivity changes as required in thermal imaging. Additional refinements in the regularization procedure have strengthened the reliability and robustness of image convergence. Imaging experiments were performed for a single heated target consisting of a 5.1 cm diameter PVC tube located within 15 and 25 cm diameter monopole antenna arrays, respectively. The performance of both log-magnitude/phase and complex-valued reconstructions when subjected to four different regularization schemes has been compared based on this experimental data. The results demonstrate a significant accuracy improvement (to 0.2 degrees C as compared with 1.6 degrees C for the previously published approach) in tracking thermal changes in phantoms where electrical properties vary linearly with temperature over a range relevant to hyperthermia cancer therapy.

Algorithms↗

Detection of 2-amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP)-DNA adducts in human pancreatic tissues.

Recent epidemiological investigations have observed an association between the consumption of grilled or barbecued meat and an increased risk of pancreatic cancer, suggesting that dietary exposure to heterocyclic aromatic amines (HCA) may contribute to the development of this disease. 2-Amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP) is the most abundant HCA found in well-done and grilled meats. To determine whether HCA-induced DNA damage is present in the human pancreas, immunohistochemistry and computer-assisted image analysis were used to measure PhIP-DNA adducts in 54 normal pancreatic tissues (N) from persons without pancreatic cancer and in 38 normal adjacent pancreatic tissues (A) and in 39 cancer tissues (T) from 68 patients with pancreatic adenocarcinoma. PhIP-DNA adducts were detected in 53 N, 34 A and 39 T samples. Mean values (+/-SD) of the absorbency for PhIP staining were 0.22+/-0.04, 0.24+/-0.04, and 0.24+/-0.03 for N, A, and T samples, respectively (p=0.004). Using the median absorbency (0.21) of the samples from normal controls as the cut-off, 71% of A and 77% of T tissues, compared with 48% of N tissues, were distributed in the higher range (p=0.009). The odds ratio of pancreatic cancer was 3.4 (95% confidence interval 1.5-7.5, p=0.002) for individuals with a higher level of PhIP-DNA adducts. This is the first report of the detection of PhIP-DNA adducts in human pancreatic tissue samples obtained from patients with unknown exposure to HCA. Although limited by the small sample size, these preliminary results suggest that PhIP exposure may contribute to human pancreatic cancer development.

Adenocarcinoma↗

The Fusarium solani gene encoding kievitone hydratase, a secreted enzyme that catalyzes detoxification of a bean phytoalexin.

Among the antimicrobial phytoalexins produced by Phaseolus vulgaris (French bean) is the prenylated isoflavonoid, kievitone. The bean pathogen, Fusarium solani f. sp. phaseoli, secretes a glycoenzyme, kievitone hydratase (EC 4.2.1.95), which catalyzes conversion of kievitone to a less toxic metabolite. Among F. solani strains, those that are highly virulent to P. vulgaris also produce kievitone hydratase constitutively, suggesting that the enzyme is a virulence factor. Based on the N-terminal amino acid sequence of purified enzyme, the kievitone hydratase cDNA and gene (khs) were cloned. The identities of khs and the cDNA were confirmed by their expression in transgenic Neurospora crassa and Emericella nidulans. Based on the gene and cDNA sequences, khs is predicted to encode a preprotein of 350 amino acids, from which a 19 amino acid N-terminal transit peptide is removed during maturation and secretion. The predicted mass of the mature polypeptide, 37 kDa, contrasts with the 47 to 49 kDa size estimated by electrophoresis of purified enzyme, confirming that the enzyme is extensively glycosylated. The inferred polypeptide sequence has seven canonical sites for N-glycosylation. Southern blot-hybridization analysis of F. s. f. sp. phaseoli DNA indicates one khs locus and an additional locus with weak hybridization to the khs probe. Sequences related to khs were also detected in several isolates of F. solani and the related teleomorph, Nectria haematococca. However, strains of F. oxysporum known to exhibit inducible kievitone hydratase activity (but not pathogenic to bean) did not have detectable khs homology. Nevertheless, all isolates known to cause severe disease on bean possessed khs sequence.

Amino Acid Sequence↗

Ultrasmall superparamagnetic iron oxide to enhance MRA of the renal and coronary arteries: studies in human patients.

OBJECTIVE: Our goal was to determine the feasibility of using an intravascular MR contrast agent to improve 3D MRA. MATERIALS AND METHODS: Three-dimensional TOF MRA was performed in nine patients both prior to and following the administration of an ultrasmall particle superparamagnetic iron oxide contrast agent (AMI 227). The lengths of both renal arteries were measured from the maximum intensity projection (MIP) images as well as the individual partitions. Seven of these patients also were studied by a 3D coronary artery MRA sequence. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) measurements of the right coronary artery were determined both prior to and following the administration of AMI 227. Statistical analysis of both renal artery lengths and right coronary SNR and CNR was performed using a one tailed paired t test comparing pre- and postcontrast images. RESULTS: The renal artery lengths significantly increased (right and artery: 30%, p = 0.001; left renal artery: 25%, p < 0.008) when measured from the individual axial slice partitions. No significant increase in length was observed on the MIP images following contrast. In the right coronary artery, the SNR increased by an average of 80% (p = 0.008) and CNR increased by an average of 109% (p = 0.007). Increased background signal and superimposed venous structures reduced the measurable lengths of the renal arteries from the MIP images. CONCLUSION: These studies support the hypothesis that 3D MRA in the body will benefit from the use of intravascular contrast agents. Nevertheless, conventional MIP processing is unable to reveal the full advantage of the contrast improvement.

Contrast Media↗

3D breath-hold contrast-enhanced MRA: a preliminary experience in aorta and iliac vascular disease.

PURPOSE: Our goal was to describe a 3D breath-hold (3D BH) contrast-enhanced MRA technique and apply the technique to patients with known or suspected aortic and iliac artery disease. METHOD: A fat-suppressed 3D GRE pulse sequence was designed with a total of 16 partition encodings. This took < 24 s for data acquisition in the abdomen and pelvis and was easily achieved during a single breath-hold. The technique was applied to 26 patients who presented with either known or suspected abdominal aortic or iliac vascular diseases. For comparison, in 19 patients a 2D TOF MRA pulse sequence with a traveling saturation band was used. Angiographic correlation was made in 18 studies. RESULTS: The 3D BH MRA was easily applicable in the evaluation of vascular anatomy and pathology. In three cases, it was superior to 2D TOF and conventional angiography for visualizing clot within the wall of an aneurysm in the abdominal aorta. In 20 cases, both MRA techniques overestimated the degree of stenosis in the lower peripheral vessels; however, this was more pronounced on 2D TOF. In five cases, the aneurysm wall was clearly defined by 3D BH MRA, whereas there was considerable signal loss in 2D TOF due to complex flow. With 3D BH MRA, the entire vessel territory both in abdominal aorta and in iliac vessels was visualized in all cases without signal falloff in the FOV. Breath-holding provided static images of the vessels that were free of blurring due to respiratory motion. CONCLUSION: Preliminary experience suggests that 3D BH with its distinct advantage of speed may serve as a useful screening tool for patients who cannot have conventional angiography or tolerate a lengthy MR examination of the abdominal aorta and iliac arteries.

Adult↗

Localization of a gene responsible for arrhythmogenic right ventricular dysplasia to chromosome 3p23.

BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD), a familial cardiomyopathy occurring with a prevalence of 1 in 5000, is characterized by replacement of myocytes with fatty and fibrous tissue. Clinical manifestations include structural and functional abnormalities of the right ventricle and arrhythmias, leading to a sudden death rate of 2.5% per year. Four loci have been mapped, but no gene has been identified as yet. METHODS AND RESULTS: We identified a large family of >200 members with ARVD segregating as an autosomal dominant trait affecting 10 living individuals. The diagnosis of ARVD was based on international diagnostic criteria including history, physical examination, ECG, echocardiogram, right ventricular angiogram, endomyocardial biopsy, and 24-hour ambulatory ECG. Blood was collected for DNA from 149 family members. Analysis of 257 polymorphic microsatellite markers by genetic linkage excluded previously known loci for ARVD and identified a novel locus at 3p23. Analysis of an additional 20 markers further defined the region. A peak logarithm of the odds score of 6.91 was obtained with marker D3S3613 at theta=0% recombination. Haplotype analysis identified a shared region between markers D3S3610 and D3S3659 of 9. 3 cM. CONCLUSIONS: A novel locus for ARVD has been mapped to 3p23 and the region narrowed to 9.3 cM. Identification of the gene will allow genetic screening and a specific diagnosis for a disease with protean nonspecific findings. It should also provide insight fundamental to understanding cardiac chamber-specific gene expression and/or the mechanism of myocyte apoptosis observed in this disease.

Adult↗