Biomedical subjects

K Nehrke

Publications and source records attributed to K Nehrke.

At least 19 recordsLinked to original sources

PubMed2005

3D motion adapted gating (3D MAG): a new navigator technique for accelerated acquisition of free breathing navigator gated 3D coronary MR-angiography.

This study aimed to evaluate the influence of a new navigator technique (3D MAG) on navigator efficiency, total acquisition time, image quality and diagnostic accuracy. Fifty-six patients with suspected coronary artery disease underwent free breathing navigator gated coronary MRA (Intera, Philips Medical Systems, 1.5 T, spatial resolution 0.9x0.9x3 mm3) with and without 3D MAG. Evaluation of both sequences included: 1) navigator scan efficiency, 2) total acquisition time, 3) assessment of image quality and 4) detection of stenoses >50%. Average navigator efficiencies of the LCA and RCA were 43+/-12% and 42+/-12% with and 36+/-16% and 35+/-16% without 3D MAG (P<0.01). Scan time was reduced from 12 min 7 s without to 8 min 55 s with 3D MAG for the LCA and from 12 min 19 s to 9 min 7 s with 3D MAG for the RCA (P<0.01). The average scores of image quality of the coronary MRAs with and without 3D MAG were 3.5+/-0.79 and 3.46+/-0.84 (P>0.05). There was no significant difference in the sensitivity and specificity in the detection of coronary artery stenoses between coronary MRAs with and without 3D MAG (P>0.05). 3D MAG provides accelerated acquisition of navigator gated coronary MRA by about 19% while maintaining image quality and diagnostic accuracy.

Aged↗

PubMed2005

Free breathing 3D balanced FFE coronary magnetic resonance angiography with prolonged cardiac acquisition windows and intra-RR motion correction.

A shortcoming of today's coronary magnetic resonance angiography (MRA) is its low total scan efficiency (<5%), as only small well-defined fractions of the respiratory (50%) and cardiac (10%) cycle are used for data acquisition. These precautions are necessary to prevent blurring and artifacts related to respiratory and cardiac motion. Hence, scan times range from 4 to 9 min, which may not be tolerated by patients. To overcome this drawback, an ECG-triggered, navigator-gated free breathing radial 3D balanced FFE sequence with intra-RR motion correction is investigated in this study. Scan efficiency is increased by using a long cardiac acquisition window during the RR interval. This allows the acquisition of a number of independent k-space segments during each cardiac cycle. The intersegment motion is corrected using a self-guided epicardial fat tracking procedure in a postprocessing step. Finally, combining the motion-corrected segments forms a high-resolution image. Experiments on healthy volunteers are presented to show the basic feasibility of this approach.

Artifacts↗

PubMed2005

Free-breathing whole-heart coronary MRA with 3D radial SSFP and self-navigated image reconstruction.

Respiratory motion is a major source of artifacts in cardiac magnetic resonance imaging (MRI). Free-breathing techniques with pencil-beam navigators efficiently suppress respiratory motion and minimize the need for patient cooperation. However, the correlation between the measured navigator position and the actual position of the heart may be adversely affected by hysteretic effects, navigator position, and temporal delays between the navigators and the image acquisition. In addition, irregular breathing patterns during navigator-gated scanning may result in low scan efficiency and prolonged scan time. The purpose of this study was to develop and implement a self-navigated, free-breathing, whole-heart 3D coronary MRI technique that would overcome these shortcomings and improve the ease-of-use of coronary MRI. A signal synchronous with respiration was extracted directly from the echoes acquired for imaging, and the motion information was used for retrospective, rigid-body, through-plane motion correction. The images obtained from the self-navigated reconstruction were compared with the results from conventional, prospective, pencil-beam navigator tracking. Image quality was improved in phantom studies using self-navigation, while equivalent results were obtained with both techniques in preliminary in vivo studies.

Adult↗

PubMed2005

[3D motion adapted gating: a new navigator technique to shorten the acquisition time for coronary MRA].

PURPOSE: A major problem of free breathing coronary MR angiography (MRA) with respiratory navigator gating is low navigator efficiency and prolonged scan time due to irregular breathing patterns. 3D motion adapted gating (MAG) is a new adaptive navigator technique, which adapts in real time to changes of the end-expiratory position of diaphragm. This study evaluates the influence of 3D MAG on coronary MRA. METHODS AND MATERIALS: In 3D MAG, two additional gating windows are grouped around the conventional window. Additionally, each gating window is divided into three bands assigned to different portions of the k-space. The scan is terminated when three consecutive bands are filled and one complete image data set is collected. Free breathing navigator-gated coronary MRA was performed on 48 patients with suspected coronary artery disease. In random order, each patient underwent an ECG-gated, a 3D segmented k-space gradient echo sequence using 3D MAG and a conventional navigator technique. The coronary MRA was evaluated and compared using the following parameters: 1. navigator efficiency and scan time; 2. visualized coronary artery length; 3. qualitative assessment of image quality; and 4. detection of stenoses > 50 % in comparison with catheter angiography. RESULTS: Coronary MRA with 3D MAG had a significant increase in the average navigator efficiency (46 % +/- 12 % vs. 38 % +/- 12 %, p < 0.05), resulting in a significantly shorter scan time (mean: 18 % +/- 4 %, p < 0.05) for coronary MRA with 3D MAG compared to conventional navigator technique. Scans with and without 3D MAG had no significant differences in the continuously visualized vessel lengths, in the assessed image quality and in the sensitivity and specificity (83 % and 89 % vs. 83 % and 88 %, p > 0.05) of detecting coronary artery stenoses > 50 %. CONCLUSION: The 3D MAG technique improves the navigator efficiency and significantly (p < 0.05) shortens the scan time of navigator gated coronary MRA while maintaining image quality and diagnostic accuracy in the detection of coronary artery stenoses.

Adult↗

PubMed2004

Efficient foldover suppression using SENSE.

Parallel imaging techniques, which in principle represent procedures of unfolding a reduced dataset, are well known and well established in MR imaging. This paper presents a further application of one particular reconstruction method, the SENSE algorithm, considered from a different point of view to remove potential foldover in conventional images acquired with multiple receive coils. Based on the coil sensitivity information, a body coverage map in the excited plane is calculated. This is used together with the measured raw data in a SENSE-type reconstruction to optimize the signal-to-noise ratio (SNR) as well as to remove foldover reliably by unfolding the image to a larger field of view. The reconstruction is performed automatically, without any user interaction, and does not affect data acquisition. Based on phantom and in vivo studies, which retain high image quality after the removal, the potential and limits of this approach are discussed, also taking into account future scanner hardware that will support a large number of parallel receiver channels.

Algorithms↗

PubMed2004

Fast isotropic volumetric coronary MR angiography using free-breathing 3D radial balanced FFE acquisition.

A shortcoming of current coronary MRA methods with thin-slab 3D acquisitions is the time-consuming examination necessitated by extensive scout scanning and precise slice planning. To improve ease of use and cover larger parts of the anatomy, it appears desirable to image the entire heart with high spatial resolution instead. For this purpose, an isotropic 3D-radial acquisition was employed in this study. This method allows undersampling of k-space in all three spatial dimensions, and its insensitivity to motion enables extended acquisitions per cardiac cycle. We present initial phantom and in vivo results obtained in volunteers that demonstrate large volume coverage with high isotropic spatial resolution. We were able to visualize all major parts of the coronary arteries retrospectively from the volume data set without compromising the image quality. The scan time ranged from 10 to 14 min during free breathing at a heart rate of 60 bpm, which is comparable to that of a thin-slab protocol comprising multiple scans for each coronary artery.

Artifacts↗

PubMed2001

The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor.

NIK, a recently identified Nck-interacting kinase, acts upstream of the MEK kinase MEKK1 to activate the c-Jun N-terminal kinase JNK. We now show that NIK binds to and divergently activates the plasma membrane Na(+)-H(+) exchanger NHE1. In a genetic screen, NHE1 interacted with NIK at a site N-terminal (amino acids 407-502) to the Nck-binding domain, and this site is critical for its association with NHE1 in vivo. NIK also phosphorylates NHE1; however, the phosphorylation sites, which are distal to amino acid 638, are distinct from the NIK-binding site on NHE1 (amino acids 538-638). Expression of wild-type, but not a kinase-inactive, NIK in fibroblasts increased NHE1 phosphorylation and activity. The kinase domain of NIK, however, was not sufficient for this response in vivo. Full phosphorylation and activation of NHE1 required both the kinase and the NHE1-binding domains of NIK, suggesting that the NHE1-binding site functions as a targeting signal. The functional significance of an interaction between NIK and NHE1 was confirmed by the ability of a kinase-inactive NIK to selectively inhibit activation of NHE1 by platelet-derived growth factor but not by thrombin. Moreover, although NIK activates JNK through a mechanism dependent on MEKK1, it phosphorylated and activated NHE1 independently of MEKK1. These findings indicate that NIK acts downstream of platelet-derived growth factor receptors to phosphorylate and activate NHE1 divergently of its activation of JNK.

Animals↗

PubMed2001

Defective fluid secretion and NaCl absorption in the parotid glands of Na+/H+ exchanger-deficient mice.

Multiple Na(+)/H(+) exchangers (NHEs) are expressed in salivary gland cells; however, their functions in the secretion of saliva by acinar cells and the subsequent modification of the ionic composition of this fluid by the ducts are unclear. Mice with targeted disruptions of the Nhe1, Nhe2, and Nhe3 genes were used to study the in vivo functions of these exchangers in parotid glands. Immunohistochemistry indicated that NHE1 was localized to the basolateral and NHE2 to apical membranes of both acinar and duct cells, whereas NHE3 was restricted to the apical region of duct cells. Na(+)/H(+) exchange was reduced more than 95% in acinar cells and greater than 80% in duct cells of NHE1-deficient mice (Nhe1(-/-)). Salivation in response to pilocarpine stimulation was reduced significantly in both Nhe1(-/-) and Nhe2(-/-) mice, particularly during prolonged stimulation, whereas the loss of NHE3 had no effect on secretion. Expression of Na(+)/K(+)/2Cl(-) cotransporter mRNA increased dramatically in Nhe1(-/-) parotid glands but not in those of Nhe2(-/-) or Nhe3(-/-) mice, suggesting that compensation occurs for the loss of NHE1. The sodium content, chloride activity and osmolality of saliva in Nhe2(-/-) or Nhe3(-/-) mice were comparable with those of wild-type mice. In contrast, Nhe1(-/-) mice displayed impaired NaCl absorption. These results suggest that in parotid duct cells apical NHE2 and NHE3 do not play a major role in Na(+) absorption. These results also demonstrate that basolateral NHE1 and apical NHE2 modulate saliva secretion in vivo, especially during sustained stimulation when secretion depends less on Na(+)/K(+)/2Cl(-) cotransporter activity.

Animals↗

PubMed2001

Improved 3D spiral imaging for coronary MR angiography.

Thin-slab 3D spiral imaging has been used for MR angiography to image selected coronary arteries. Improved scan efficiency was achieved using a train of multiple spiral interleaves within each single R-R interval acquired in the late diastole. Data acquisition was performed during free breathing, using navigator gating. Additionally, prospective slice tracking was applied to further reduce the sensitivity to motion. The application of a T(2)-preparation pulse and fat suppression increased the contrast between blood and myocardium. Experiments performed on healthy volunteers are presented to show the feasibility of this approach, which allows coronary artery imaging of selected vessels within a few minutes. Magn Reson Med 45:172-175, 2001.

Coronary Vessels↗

PubMed2001

Accelerated coronary MRA by simultaneous acquisition of multiple 3D stacks.

The implementation and first in vivo results of a novel coronary magnetic resonance angiography (MRA) protocol allowing simultaneous acquisition of multiple geometrically independent 3D imaging stacks are presented. Each imaging stack is acquired in a separate cardiac phase using an individual magnetization preparation and navigator-based gating and prospective motion correction. Each stack covers one of the main coronary vessels. Thus, an improvement of scan efficiency was achieved, which was used in this study to reduce total scan time at standard image quality. Experiments performed in healthy volunteers and in patients using a two-stack approach yielded a total scan time reduction of 50% with an image quality equivalent to standard single-stack coronary MRA.

Adult↗

PubMed2001

Free-breathing cardiac MR imaging: study of implications of respiratory motion--initial results.

The respiratory motion of several anatomic regions (right hemidiaphragm, left ventricle of the heart, chest wall, abdominal wall) was investigated during free breathing in 10 healthy volunteers by using multinavigator technology and real-time magnetic resonance (MR) imaging. The respiratory motion shows hysteretic effects, which are strongly subject dependent and might have some effect on the quality of cardiac MR images.

Abdominal Muscles↗

PubMed2001

Acute inhibition of brain-specific Na(+)/H(+) exchanger isoform 5 by protein kinases A and C and cell shrinkage.

Little is known of the functional properties of the mammalian, brain-specific Na(+)/H(+) exchanger isoform 5 (NHE5). Rat NHE5 was stably expressed in NHE-deficient PS120 cells, and its activity was characterized using the fluorescent pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. NHE5 was insensitive to ethylisopropyl amiloride. The transport kinetics displayed a simple Michaelis-Menten relationship for extracellular Na(+) (apparent K(Na) = 27 +/- 5 mM) and a Hill coefficient near 3 for the intracellular proton concentration with a half-maximal activity at an intracellular pH of 6.93 +/- 0.03. NHE5 activity was inhibited by acute exposure to 8-bromo-cAMP or forskolin (which increases intracellular cAMP by activating adenylate cyclase). The kinase inhibitor H-89 reversed this inhibition, suggesting that regulation by cAMP involves a protein kinase A (PKA)-dependent process. In contrast, 8-bromo-cGMP did not have a significant effect on activity. The protein kinase C (PKC) activator phorbol 12-myristrate 13-acetate inhibited NHE5, and the PKC antagonist chelerythrine chloride blunted this effect. Activity was also inhibited by hyperosmotic-induced cell shrinkage but was unaffected by a hyposmotic challenge. These results demonstrate that rat brain NHE5 is downregulated by activation of PKA and PKC and by cell shrinkage, important regulators of neuronal cell function.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2001

Targeted disruption of the Nhe1 gene fails to inhibit beta(1)-adrenergic receptor-induced parotid gland hypertrophy.

Chronic beta(1)-adrenergic receptor activation results in hypertrophy and hyperplasia of rodent salivary gland acinar cells. Na(+)/H(+) exchanger isoform 1 (NHE1) regulates cell volume and the induction of cell proliferation in many tissues. To investigate the relationship between NHE1 and the response of parotid glands to beta(1)-adrenergic agonists, we examined by Northern blot analysis NHE1 expression in saline-treated mice and mice 30 min and 2, 6, and 24 h after isoproterenol injection. NHE1 transcripts increased approximately 50% by 2 h, and a more than twofold increase was noted at 24 h. Isoproterenol did not acutely increase Na(+)/H(+) exchanger activity; however, exchanger activity was significantly elevated by 24 h. To test whether NHE1 activity is essential for inducing salivary gland hypertrophy in vivo, mice with targeted disruption of Nhe1 were treated with isoproterenol. Na(+)/H(+) exchanger activity was absent in acinar cells from Nhe1(-/-) mice, nevertheless, the lack of NHE1 failed to inhibit isoproterenol-induced hypertrophy. These data directly demonstrate that acinar cell hypertrophy induced by chronic beta(1)-adrenergic receptor stimulation occurs independently of NHE1 activity.

Adrenergic beta-Agonists↗

PubMed2000

Into ion channel and transporter function. Caenorhabditis elegans ClC-type chloride channels: novel variants and functional expression.

Six ClC-type chloride channel genes have been identified in Caenorhabditis elegans, termed clh-1 through clh-6. cDNA sequences from these genes suggest that clh-2, clh-3, and clh-4 may code for multiple channel variants, bringing the total to at least nine channel types in this nematode. Promoter-driven green fluorescent protein (GFP) expression in transgenic animals indicates that the protein CLH-5 is expressed ubiquitously, CLH-6 is expressed mainly in nonneuronal cells, and the remaining isoforms vary from those restricted to a single cell to those expressed in over a dozen cells of the nematode. In an Sf9 cell expression system, recombinant CLH-2b, CLH-4b, and CLH-5 did not form functional plasma membrane channels. In contrast, both CLH-1 and CLH-3b produced strong, inward-rectifying chloride currents similar to those arising from mammalian ClC2, but which operate over different voltage ranges. Our demonstration of multiple CLH protein variants and comparison of expression patterns among the clh gene family provides a framework, in combination with the electrical properties of the recombinant channels, to further examine the physiology and cell-specific role each isoform plays in this simple model system.

Amino Acid Sequence↗

PubMed1999

On the performance and accuracy of 2D navigator pulses.

The purpose of this study was to investigate and to optimize the performance of two-dimensional spatially selective excitation pulses used for navigator applications on a clinical scanner. The influence of gradient imperfections, off-resonance effects, and incomplete k-space covering on the pencil beam-shaped spatial excitation profile of the 2D RF pulse was studied. The studies involved experiments performed on phantoms and in vivo. In addition, simulations were carried out by numerical integration of the Bloch equations. The accuracy of positioning of the pencil beam was increased by a factor of three by employing a simple correction scheme for the compensation of gradient distortions. The spatial selectivity of the 2D RF pulse was improved by taking sampling density corrections into account. The 2D RF pulse performance was found to be sufficient to monitor the diaphragm motion even at moderate gradient strength. For applications, where a high spatial resolution is required or a less characteristic contrast is present a strong gradient system is recommended.

Artifacts↗

PubMed1998

cDNA cloning and expression of a family of UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase sequence homologs from Caenorhabditis elegans.

The initiation of mucin-type O-glycosylation is catalyzed by a family of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (ppGaNTase) (EC 2.4.1.41). By screening two mixed-stage Caenorhabditis elegans cDNA libraries, a total of 11 distinct sequence homologs of the ppGaNTase gene family were cloned, sequenced, and expressed as truncated recombinant proteins (gly-3, gly-4, gly-5a, gly-5b, gly-5c, gly-6a, gly-6b, gly-6c, gly-7, gly-8, and gly-9). All clones encoded type II membrane proteins that shared 60-80% amino acid sequence similarity with the catalytic domain of mammalian ppGaNTase enzymes. Two sets of cDNA clones (gly-5 and gly-6) contained variants that appeared to be produced by alternative message processing. gly-6c contained a reading frameshift and premature termination codon in the C-terminal lectin-like domain found in most other ppGaNTase proteins, and a second clone (gly-8) lacked the typical C-terminal region completely. Homogenates of nematodes and immunopurified preparations of the recombinant GLY proteins demonstrated that worms express functional ppGaNTase enzymes (GLY-3, GLY-4, GLY-5A, GLY-5B, and GLY-5C), which can O-glycosylate mammalian apomucin peptide sequences in vitro. In addition to demonstrating the existence of ppGaNTase enzymes in a nematode organism, the substantial diversity of these isoforms in C. elegans suggests that mucin O-glycosylation is catalyzed by a complex gene family, which is conserved among evolutionary-distinct organisms.

Amino Acid Sequence↗

PubMed1998

Isoform-specific O-glycosylation by murine UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-T3, in vivo.

Multiple isoforms of UDP-GalNAc:polypeptide N-acetylgalactosaminyl- transferase (ppGaNTase) have been cloned and expressed from a variety of organisms. In general, these isoforms display different patterns of tissue-specific expression, but exhibit overlapping substrate specificities, in vitro . A peptide substrate, derived from the sequence of the V3 loop of the HIV gp120 protein (HIV peptide), has previously been shown to be glycosylated in vitro exclusively by the ppGaNTase-T3 (Bennett et al. , 1996). To determine if this isoform-specificity is maintained in vivo , we have examined the glycosylation of this substrate when it is expressed as a reporter peptide (rHIV) in a cell background (COS7 cells) which lacks detectable levels of the ppGaNTase-T3. Glycosylation of rHIV was greatly increased by coexpression of a recombinant ppGaNTase-T3. Overexpression of ppGaNTase-T1 yielded only partial glycosylation of the reporter. We have also determined that the introduction of a proline residue at the +3 position flanking the potential glycosylation site eliminated ppGaNTase-T3 selectivity toward rHIV observed both in vivo and in vitro .

Amino Acid Sequence↗

PubMed1997

Biosynthesis of a low-molecular-mass rat submandibular gland mucin glycoprotein in COS7 cells.

We have examined the biosynthesis of a low-molecular-mass mucin from rat submandibular gland (RSMG) expressed recombinantly in COS7 tissue culture cells, focusing primarily on the addition of carbohydrate to the protein core of the mucin. We find evidence for N-linked glycosylation, but this modification is not required for secretion of the mucin. Similarly, although the recombinant RSMG mucin, like its native counterpart, contains large amounts of O-linked carbohydrate, chain extension beyond the initial O-linked GalNAc moiety is not required for secretion. We have identified partially glycosylated mucin by a combination of metabolic pulse-chase and lectin precipitations of the biosynthetic intermediates. Our results suggest that the addition of GalNAc to threonine and serine in the RSMG mucin does not occur simultaneously, as has been described for other O-glycosylated proteins.

Acetylgalactosamine↗