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Biomedical subjects

L Dougherty

Publications and source records attributed to L Dougherty.

At least 19 recordsLinked to original sources

Cardiac imaging at 4 Tesla.

Although higher magnetic field strength is a means to increase SNR in MRI, cardiac imaging has been difficult at high fields due to decreased RF penetration. Using a tailored cardiac coil constructed of two transmit surface coils with a four-element multicoil for signal reception, the authors demonstrate high-quality heart images acquired on a 4-T scanner. These images show an increase in SNR of approximately 2.5-fold over imaging at 1.5 T. This improvement in image quality can be used to increase in-plane resolution, reduce slice thickness, or reduce total scan time. Magn Reson Med 45:176-178, 2001.

Heart↗

Simultaneous acquisition of multiple resolution images for dynamic contrast enhanced imaging of the breast.

An imaging technique is described that allows the reconstruction of a series of images at high temporal rates, while simultaneously providing images at high spatial resolution. The method allows one to arbitrarily choose from among several combinations of temporal/spatial resolutions during postprocessing. This flexibility is accomplished by strategically interleaving multiple undersampled projection reconstruction datasets (or subapertures), in which each set can be used to reconstruct a high temporal resolution image. Images with increasingly higher spatial resolutions can subsequently be formed by combining two or more subaperture datasets. The technique is demonstrated in vivo to assess the kinetics of contrast enhancement and to visualize the architectural features of suspicious breast lesions.

Aged↗

Pulmonary MR angiography with contrast agent at 4 Tesla: a preliminary result.

In this study, pulmonary MR angiography (MRA) using a tailored coil at 4 Tesla in conjunction with an intravenous injection of contrast agent is described. Three-dimensional gradient-echo images were obtained during the intravenous injection of 0.05, 0.1, and 0.2 mmol/kg body weight of gadodiamide to investigate the signal enhancement effect of the contrast agent in pulmonary arteries qualitatively and quantitatively. In the qualitative analysis, the subsegmental branches were visualized on every dose. In the quantitative analysis, the average contrast-to-noise ratios (CNRs) of the main pulmonary arteries increased in a dose-dependent manner. However, the CNRs of segmental arteries did not increase as the dose of contrast agent increased, as observed at 1.5 Tesla MRI. These observations demonstrate the feasibility of delineating the pulmonary vasculature using a contrast agent; however, our results also suggest possible high-field-related disabilities that need to be overcome before high-field (> or =4 Tesla) MRI can be used to full advantage.

Adult↗

NF-Y regulates LIF-induced transcription of the signaling adaptor SKAP55R in myeloid cells.

Previously, we have shown that interleukin-6 (IL-6) or leukemia inhibitory factor (LIF)-induced differentiation of the myeloid cell line M1 was associated with a rapid increase in the level of mRNA encoding the signaling adaptor protein, SKAP55R. Furthermore, enforced over-expression of SKAP55R in primary bone marrow cells inhibited colony growth. In this study, we have identified the cis-acting elements that control SKAP55R transcription in myeloid cells. The 980 bp genomic sequence upstream of the transcriptional start site was cloned into a GFP reporter vector for transient (293 cells) or stable (M1 cells) transfection assays. This region contained cis-acting elements necessary for transcriptional activity in unstimulated 293 cells (10-fold higher levels than the control vector) or unstimulated M1 cells (two-fold higher levels). Significant LIF-induced transcription was observed in M1 (3.4-fold induction, P < 0.001), but not 293 cells. Deletion reporter constructs defined a promoter region (-317/-137) essential for the transcriptional activity in M1 cells. This region contained a CCAAT element recently implicated in IL-6/LIF-induced transcriptional regulation of junB in M1 cells. Mutation of the CCAAT element (-250/-246) significantly reduced both basal and LIF-induced transcription (P < 0.01). Electrophoretic mobility shift assays demonstrated that NF-Y bound to the CCAAT element of both SKAP55R and junB. These results suggest NF-Y binding may be a common mechanism of IL-6/LIF-regulated transcription in myeloid cells.

Animals↗

Cardiac-respiratory gating method for magnetic resonance imaging of the heart.

In studies of transmural myocardial function, acquisitions of high spatial and temporal resolution tagged cardiac images often exceed the practical time limit for breath-hold fast imaging techniques. Therefore, a dual cardiac-respiratory gating device has been constructed to acquire SPAMM-tagged cardiac MR images at or near end-expiration during spontaneous breathing, by providing an external trigger to a conventional MRI system. Combined cardiac and respiratory gating essentially eliminates the respiratory motion artifacts in tagged cardiac MR images. Compared to cardiac-gated images obtained during intermittent breath-holds, cardiac-respiratory gated images show improved tag-myocardium contrast due to magnetization recovery during inspiration.

Analysis of Variance↗

k-space weighted image contrast (KWIC) for contrast manipulation in projection reconstruction MRI.

A novel technique for manipulating contrast in projection reconstruction MRI is described. The method takes advantage of the fact that the central region of k-space is oversampled, allowing one to choose different filters to enhance or reduce the amount that each view contributes to the central region, which dominates image contrast. The technique is implemented into a fast spin-echo (FSE) sequence, and it is shown that multiple T(2)-weighted images can be reconstructed from a single image data set. These images are shown to be nearly identical to those acquired with the Cartesian-sampled FSE sequence at different effective echo times. Further, it is demonstrated that T(2) maps can be generated from a single image data set. This technique also has the potential to be useful in dynamic contrast enhancement studies, capable of yielding a series of images at a significantly higher effective temporal resolution than what is currently possible with other methods, without sacrificing spatial resolution.

Adult↗

Adaptor protein SKAP55R is associated with myeloid differentiation and growth arrest.

Activation of the SRC family of protein tyrosine kinases is an important component of intracellular signaling in hematopoiesis, but their critical substrates are less well understood. In this report, we describe the cloning and functional characterization of murine SKAP55R (mSKAP55R), an SRC family kinase substrate. Expression of mSKAP55R was examined by Northern blot. Phosphorylation of mSKAP55R was examined by transient transfection of COS cells. For overexpression studies, mSKAP55R was cloned into a bicistronic murine stem cell virus-based retrovirus. Transduced cells (FDC-P1 cell line and murine bone marrow) were FACS isolated by expression of the selectable marker green fluorescent protein.mSKAP55R showed 90% amino acid identity to the recently published human SKAP55R. mSKAP55R contained a central pleckstrin homology domain, a C-terminal SH3 domain, and a putative SRC kinase consensus substrate DEIY(260). mSKAP55R was expressed in all hematopoietic lineages, with relative mRNA levels greatest in cells of the myeloid and erythroid lineages. Induced myeloid differentiation of M1 and HL-60 cell lines was associated with an eight-fold increase in mSKAP55R mRNA. Transient expression of mSKAP55R in COS cells demonstrated that tyrosine 260 was the predominant site of phosphorylation by FYN kinase. Furthermore, this phosphotyrosine was essential for coimmunoprecipitation of FYN with mSKAP55R. Enforced expression of mSKAP55R inhibited in vitro growth of the myeloid FDC-P1 cell line and primary hematopoietic progenitors. In contrast, a tyrosine 260 mutant mSKAP55R had no effect on in vitro growth. These studies implicate mSKAP55R in the processes of myeloid differentiation and growth arrest.

Amino Acid Sequence↗

Expression of receptor tyrosine kinase Axl and its ligand Gas6 in rheumatoid arthritis: evidence for a novel endothelial cell survival pathway.

Angiogenesis and synovial cell hyperplasia are characteristic features of rheumatoid arthritis (RA). Many growth and survival factors use receptors belonging to the tyrosine kinase family that share conserved motifs within the intracellular catalytic domains. To understand further the molecular basis of cellular hyperplasia in RA, we have used degenerate primers based on these motifs and RNA obtained from the synovium of a patient with RA to perform reverse transcriptase-polymerase chain reaction. We report detection of the receptor tyrosine kinase (RTK) Axl in RA synovium and we document the expression pattern of Axl in capillary endothelium, in vascular smooth muscle cells of arterioles and veins, and in a subset of synovial cells in RA synovial tissue. Gas6 (for growth arrest-specific gene 6), which is a ligand for Axl and is related to the coagulation factor protein S, was found in synovial fluid and tissue from patients with RA and osteoarthritis. Axl expression and function was studied in human umbilical vein endothelial cells (HUVECs). Gas6 bound to HUVECs; soluble Axl inhibited this binding. Exogenous Gas6 protected HUVECs from apoptosis in response to growth factor withdrawal and from TNFalpha-mediated cytotoxicity. These findings may reveal a new aspect of vascular physiology, which may also be relevant to formation and maintenance of the abnormal vasculature in the rheumatoid synovium.

Arthritis, Rheumatoid↗

Validation of an optical flow method for tag displacement estimation.

We present a validation study of an optical-flow method for the rapid estimation of myocardial displacement in magnetic resonance tagged cardiac images. This registration and change visualization (RCV) software uses a hierarchical estimation technique to compute the flow field that describes the warping of an image of one cardiac phase into alignment with the next. This method overcomes the requirement of constant pixel intensity in standard optical-flow methods by preprocessing the input images to reduce any intensity bias which results from the reduction in stripe contrast throughout the cardiac cycle. To validate the method, SPAMM-tagged images were acquired of a silicon gel phantom with simulated rotational motion. The pixel displacement was estimated with the RCV method and the error in pixel tracking was <4% 1000 ms after application of the tags, and after 30 degrees of rotation. An additional study was performed using a SPAMM-tagged multiphase slice of a canine left ventricle. The true displacement was determined using a previously validated active contour model (snakes). The error between methods was 6.7% at end systole. The RCV method has the advantage of tracking all pixels in the image in a substantially shorter period than the snakes method.

Animals↗

Pulmonary perfusion: respiratory-triggered three-dimensional MR imaging with arterial spin tagging--preliminary results in healthy volunteers.

The authors used a spin-tagging method of magnetic resonance perfusion imaging to measure pulmonary perfusion in eight healthy volunteers with use of a respiratory-triggered three-dimensional pulse sequence. The average signal intensity (SI) decrease upon arterial labeling was 24%. The perfusion SI increased by 21% after exercise (P = .02). Focal blood flow abnormalities were observed in a patient with chronic obstructive pulmonary disease.

Adult↗

In vivo human cervical spinal cord deformation and displacement in flexion.

STUDY DESIGN: In vivo, quasi-static distortion of the human cervical spinal cord was measured in five volunteers during flexion of the neck using a motion-tracking magnetic resonance imaging technique. OBJECTIVES: To measure cord distortion and movement in living subjects. SUMMARY OF BACKGROUND DATA: In situ spinal cord measurements in human and rhesus monkey cadavers taken at full flexion demonstrate that the entire cervical cord elongates approximately 10% of its length at a neutral position, but no data are available at other angles of flexion, or in living subjects. METHODS: The spatial modulation of magnetization pulse sequence created a series of parallel lines in the image that deform with the tissue. A custom-designed device was built to guide the flexion of the neck and enhance motion reproducibility. Midsagittal plane images were acquired before and after flexion. The tagged line pattern in each pair of magnetic resonance images was compared to compute distortion and movement of the cervical spinal cord at varying degrees of flexion. RESULTS: Between a neutral posture and full flexion, the entire cord (C2-C7) elongated linearly with head flexion, increasing 10% and 6% of its initial length along the posterior and anterior surfaces, respectively. Average displacement was on the order of 1-3 mm, and varied with region. Specifically, the upper cord showed caudad movement in the spinal canal, and the lower cord moved cephalad, again with larger movements on the posterior surface. CONCLUSIONS: The cervical cord elongates and displaces significantly during head flexion in human volunteers, offering valuable information regarding the normal milieu of the cord.

Adult↗

Integrated MRI assessment of regional function and perfusion in canine myocardial infarction.

A single integrated examination using regional measurements of perfusion from contrast-enhanced MRI and three-dimensional (3D) strain from tissue-tagged MRI was developed to differentiate infarcted myocardium from adjacent tissue with functional abnormalities. Ten dogs were studied at baseline and 10 days after a 2-hour occlusion of the left anterior descending coronary artery (LAD). Strain was determined using a 3D finite element model. Two-dimensional measurements of hypoenhancing regions were highly correlated with myocardial viability (r = 0.96). Signal intensity versus time curves obtained from contrast-enhanced MRI were used for quantitative perfusion analysis. The remote and adjacent noninfarcted tissue of the dogs with LAD occlusion, as well as the infarcted tissue, exhibited abnormal deformation patterns as compared to normal dogs (positive predictive value (PPV) of strain determination of infarction = 66%). Integration of contrast-enhanced MRI results with 3D strain analysis enabled the delineation of the myocardial infarction (PPV = 100%) from functionally compromised myocardium. This integrated cardiac examination shows promise for noninvasive serial assessment of potentially jeopardized noninfarcted myocardium to study the process of infarct remodeling and expansion.

Animals↗

Maintaining vascular access devices: the nurse's role.

The role of the nurse in maintaining vascular access devices has altered dramatically with the advance in vascular access device technology and the greater involvement in selection of the device and its insertion, maintenance and removal. Up-to-date knowledge and the use of evidence-based practice underpinned by good scientific research is the key to vascular access device maintenance. The routine maintenance of vascular access devices is a shared responsibility between the nurse and the patient, so that the nurse has an important part to play in the adequate preparation and education of the patient. The nurse therefore has a responsibility to ensure the maintenance of vascular access devices in order to increase the benefits to the patient and decrease the risk of serious complications.

Bandages↗

Establishing ambulatory chemotherapy at home.

The use of infusional ambulatory chemotherapy is increasing. Careful patient selection and a structured programme of teaching and home support is required. Continuous ambulatory chemotherapy can improve clinical outcomes and provide both psychological and financial benefits.

Ambulatory Care↗

Use of monoclonal antibodies to detect disease associated HLA-DRB1 alleles and the shared epitope in rheumatoid arthritis.

OBJECTIVE: To use a panel of monoclonal antibodies (Mab) which recognise HLA class II alleles associated with rheumatoid arthritis for fluorescence activated cell sorter (FACS) analysis of peripheral blood mononuclear cells (PBMNC) from patients with early and established rheumatoid arthritis and to compare these results against DNA oligotyping of HLA class II molecules in the same patients. METHODS: 27 patients (18 from an early arthritis clinic, nine with established rheumatoid arthritis) were studied using both techniques. PBMNC were stained with Mab which recognise the shared epitope, the HLA-DRB1*04 molecule and its* 0401, *0404 subtypes in the presence of bound peptide. Mab stained cells were analysed by FACS. Genomic DNA was prepared from PBMNC and use for DNA oligotyping and sequencing by standard methods. RESULTS: FACS analysis of Mab stained PBMNC gave identical results to those obtained by DNA oligotyping in 26/27 patients. The antibodies identified the shared epitope in 14/14 cases and the presence of an HLA-DRB1*04 molecule in 12/12 cases. HLA-DRB1*0404 was identified in 4/4 cases. HLA-DRB1*0401 was identified in 5/6 cases. One patient oligotyped as HLA-DRB1*0401, but consistently failed to react with the *0401 Mab. DNA sequencing of the second exon of the HLA-DRB1*0401 allele in this patient confirmed a normal HLA-DRB1*0401 genotype. CONCLUSIONS: FACS analysis of PBMNC stained with Mab recognising the shared epitope and rheumatoid arthritis associated HLA susceptibility molecules provides a rapid, reliable, and more accessible alternative to DNA oligotyping. The apparent discordance between phenotypic and genetic analysis of HLA-DRB1*0401 in one patient, may reflect variability in HLA-DRB1*0401 gene expression or in class II peptide presentation.

Alleles↗

Breath-hold ultrafast three-dimensional gadolinium-enhanced MR angiography of the aorta and the renal and other visceral abdominal arteries.

OBJECTIVES: The objectives of this study were to develop and show the efficacy of a breath-hold ultrafast three-dimensional (3D) spoiled gradient-echo (SPGR) gadolinium-enhanced MR angiographic technique for imaging the aorta and the renal and other visceral arteries of the abdomen; and to compare breath-hold ultrafast 3D SPGR with two-dimensional (2D) time-of-flight (TOF) and non-breath-hold ultrafast 3D SPGR in the same patients. SUBJECTS AND METHODS: We prospectively studied the abdominal aorta and the renal and other visceral arteries 68 times in 63 consecutive patients with 2D TOF and ultrafast 3D SPGR MR angiography. Thirty-two patients had contrast angiography (n = 23) and/or surgery (n = 24) to serve as a gold standard. All MR imaging studies were performed on a 1.5-T scanner (General Electric Medical Systems, Milwaukee, WI) using an enhanced gradient system with maximum gradient strength of 2.3 gauss/cm reached in 150 microseconds. Axial 2D TOF parameters were: TR/TE, 33/5.5 msec; flip angle, 45 degrees; slice thickness, 2 mm; and no presaturation pulses. Coronal ultrafast 3D SPGR was performed before and after the i.v. administration of 40-60 cc of gadolinium. For the coronal ultrafast 3D SPGR, our parameters were: TR/TE, 4.8-7/1.1; flip angle, 60 degrees; 28-50 slices of 2.0-2.6 mm thickness; and acquisition time, 18-32 sec. Studies were read by a single radiologist [corrected] and were evaluated for the degree of stenosis in the renal, celiac, superior mesenteric, and inferior mesenteric arteries; any vascular anomalies (i.e., retroaortic renal veins and accessory renal or variant hepatic arteries) were noted. RESULTS: Breath-hold ultrafast 3D SPGR correctly identified 31 of 31 stenoses of the renal artery for a sensitivity, specificity, and accuracy of 100%. Two-dimensional TOF detected 23 of 31 renal artery stenoses for a sensitivity, specificity, and accuracy of 74%, 98%, and 87% respectively. Breath-hold ultrafast 3D SPGR underestimated two renal arteries as having severe osteal stenoses that were graded correctly by 2D TOF and by angiography as occlusions. Eight of nine (89%) accessory renal arteries were correctly identified with breath-hold ultrafast 3D SPGR: Two-dimensional TOF identified six of nine (67%). Breath-hold ultrafast 3D SPGR identified one accessory and two reconstituted renal arteries missed by 2D TOF and conventional contrast angiography that were confirmed at surgery. Ultrafast 3D SPGR and 2D TOF correctly identified 20 of 20 celiac, superior mesenteric, and inferior mesenteric artery osteal stenoses or occlusions for a sensitivity, specificity, and accuracy of 100%. Three Riolan's arcs were correctly identified by breath-hold 3D SPGR but were missed by 2D TOF: Forty of the 63 patients did not have conventional contrast angiography and were managed surgically (n = 9) or medically (n = 31) based on the results of the MR angiograms and clinical data. Breath-hold ultrafast 3D SPGR MR angiography correctly identified and graded 48 of 51 renal, celiac, superior mesenteric, and inferior mesenteric artery stenoses or occlusions. Two-dimensional TOF MR angiography correctly identified and graded 45 of 51 renal, celiac, superior mesenteric, and inferior mesenteric artery stenoses and occlusions. CONCLUSION: Breath-hold ultrafast 3D SPGR when combined with 2D TOF accurately identified and graded all (51 of 51) renal, celiac, superior mesenteric, and inferior mesenteric artery stenoses or occlusions.

Adolescent↗

The benefits of an i.v. team in hospital practice.

I.v. teams can benefit the patient, the hospital and the nursing profession. I.v. teams reduce fear, non-compliance and infection. Standardised procedures lead to safe and cost-effective care.

Cost-Benefit Analysis↗