Biomedical subjects

Stephan Miller

Publications and source records attributed to Stephan Miller.

28 records · Page 2Linked to original sources

PubMed2005

Detection of regional myocardial perfusion deficit using rest and stress perfusion MRI: a feasibility study.

OBJECTIVE: Providing high temporal and spatial resolution, perfusion MRI is an attractive alternative to traditional radionuclide methods like SPECT and PET. Although first-pass perfusion MRI examinations have gained increasing attention during the past years, this technique still exhibits relatively low signal-to-noise ratio and cardiac coverage. Previous studies have suggested that refocused gradient sequence technology (e.g., true fast imaging with steady-state precession [FISP]) should improve perfusion MRI examinations. The aim of this study was to assess myocardial perfusion deficits in patients with proven coronary artery disease using a saturation recovery true FISP perfusion sequence. SUBJECTS AND METHODS: Rest and stress perfusion MRI studies were performed in 22 patients with coronary artery disease at 1.5 T using a multislice saturation recovery true FISP sequence after the bolus injection of 0.025 mmol/kg of body weight of gadopentetate dimeglumine. The myocardium of each slice was divided into 12 radial segments with subdivision into subendocardial and subepicardial subregions. Myocardial perfusion was assessed semiquantitatively and independently for each subregion. The standard of reference for myocardial perfusion was SPECT. Delayed enhancement images were acquired after the injection of 0.15 mmol/kg of body weight of gadopentetate dimeglumine. RESULTS: Sensitivity and specificity of perfusion MRI examinations for the detection of perfusion deficits were 81% and 89%, respectively, for the semiquantitative perfusion parameter upslope and 78% and 86% for the parameter peak signal intensity. More specifically, rest perfusion examinations were able to detect areas of infarction, whereas stress examinations increased the perfusion differences between normal and ischemic myocardial areas. Excellent correlation was observed between rest perfusion and late enhancement findings (r = 0.90). CONCLUSION: In patients with single-vessel coronary artery disease, perfusion deficits can reliably be detected using a saturation recovery true FISP sequence. Semiquantitative perfusion parameters upslope and peak signal intensity yielded similar results.

Adult↗

PubMed2004

Multislice first-pass myocardial perfusion imaging: Comparison of saturation recovery (SR)-TrueFISP-two-dimensional (2D) and SR-TurboFLASH-2D pulse sequences.

PURPOSE: To compare signal-to-noise ratio (SNR), contrast-to-noise (CNR) ratio, and diagnostic accuracy of a newly developed saturation recovery (SR)-TrueFISP-two-dimensional (2D) sequence with an SR-TurboFLASH-2D sequence. MATERIALS AND METHODS: In seven healthy subjects and nine patients with coronary artery disease (CAD), contrast-enhanced perfusion imaging (with Gd-DTPA) was performed with SR-TrueFISP and SR-TurboFLASH sequences. Hypoperfused areas were assessed qualitatively (scale = 0-4). Furthermore, SNR and CNR were calculated and semiquantitative perfusion parameters were determined from signal intensity (SI) time curves. Standard of reference for patient studies was single-photon emission computer tomography (SPECT) and angiography. RESULTS: The perception of perfusion deficits was superior in TrueFISP images (2.6 +/- 1.0) than in TurboFLASH (1.4 +/- 0.6) (P < 0.001). Phantom measurements yielded increased SNR (143 +/- 34%) and CNR (158 +/- 64%) values for TrueFISP. In patient/volunteer studies SNR was 61% to 100% higher and signal enhancement was 110% to 115% higher with TrueFISP than with TurboFLASH. Qualitative and semiquantitative assessment of perfusion defects yielded higher sensitivities for detection of perfusion defects with TrueFISP (68% to 78%) than with TurboFLASH (44% to 59%). CONCLUSION: SR-TrueFISP-2D perfusion imaging provides superior SNR and CNR than TurboFLASH imaging. Moreover, the dynamic range of SIs was found to be higher with TrueFISP, resulting in an increased sensitivity for detection of perfusion defects.

Adult↗

PubMed2004

Expression, purification, and characterization of rat interferon-beta, and preparation of an N-terminally PEGylated form with improved pharmacokinetic parameters.

To identify potential new clinical uses and routes of administration for human interferon-beta-1a (IFN-beta-1a), we have developed an expression and purification procedure for the preparation of highly purified rat interferon-beta (IFN-beta) suitable for testing in rat models of human disease. An expression vector containing the rat IFN-beta signal sequence and structural gene was constructed and transfected into Chinese hamster ovary (CHO) cells. The protein was purified from CHO cell conditioned medium and purified to > 99.5% purity using standard chromatographic techniques. Analytical characterization indicated that the protein was a heavily glycosylated monomeric protein, with two of the four predicted N-glycosylation sites occupied. Analysis of the attached oligosaccharides showed them to be a complex mixture of bi-antennary, tri-antennary, and tetra-antennary structures with a predominance of sialylated tri-antennary and tetra-antennary structures. Peptide mapping, N-terminal sequencing, and mass spectrometry confirmed the identity and integrity of the purified protein. The purified protein had a specific activity of 2.1x10(8)U/mg when assayed on rat RATEC cells, which is similar in magnitude to the potencies observed for murine IFN-beta and human IFN-beta-1a assayed on murine and human cells, respectively. We also prepared an N-terminally PEGylated form of rat IFN-beta in which a 20 kDa methoxy polyethylene glycol (PEG)-propionaldehyde was attached to the N-terminal alpha-amino group of Ile-1. The PEGylated protein, which retained essentially full in vitro antiviral activity, had improved pharmacokinetic parameters in rats as compared to the unmodified protein. Both the unmodified and PEGylated forms of rat IFN-beta will be useful for testing in rat models of human disease.

Animals↗

PubMed2004

Semiquantitative assessment of myocardial perfusion using magnetic resonance imaging: evaluation of appropriate thresholds and segmentation models.

RATIONALE AND OBJECTIVES: The aim of the study was to determine optimal thresholds for semiquantitative perfusion parameters and to evaluate the influence of different segmentation models in detecting malperfused regions. MATERIAL AND METHODS: In 6 healthy subjects and 13 patients with coronary artery disease, contrast-enhanced first-pass perfusion imaging was performed using a SR-TrueFISP-sequence. Thresholds for semiquantitative parameters were established, and different segmentation models of the left ventricular myocardium were tested. The standard of reference for patient studies was single photon emission computed tomography. RESULTS: Optimal thresholds were determined in healthy subjects for the perfusion parameters upslope, AUC, and peak SI of mv-0.5*std, mv-1.5*std, and mv-1.0*std, respectively. Using the optimal threshold for each parameter/segmentation combination sensitivities and specificities of stress studies were between 66% and 93% and 77% and 92%, respectively. Subdivision of radial segments into subendo/subepicardial segments increased sensitivities for perfusion deficits. CONCLUSIONS: Subdivision of radial myocardial segments is essential in analysis of magnetic resonance first-pass perfusion series. Semiquantitative perfusion parameters possess different sensitivities for the detection of perfusion deficits.

Adult↗

PubMed2003

Multiple actions of systemic artemin in experimental neuropathy.

The clinical management of neuropathic pain is particularly challenging. Current therapies for neuropathic pain modulate nerve impulse propagation or synaptic transmission; these therapies are of limited benefit and have undesirable side effects. Injuries to peripheral nerves result in a host of pathophysiological changes associated with the sustained expression of abnormal pain. Here we show that systemic, intermittent administration of artemin produces dose- and time-related reversal of nerve injury-induced pain behavior, together with partial to complete normalization of multiple morphological and neurochemical features of the injury state. These effects of artemin were sustained for at least 28 days. Higher doses of artemin than those completely reversing experimental neuropathic pain did not elicit sensory or motor abnormalities. Our results indicate that the behavioral symptoms of neuropathic pain states can be treated successfully, and that partial to complete reversal of associated morphological and neurochemical changes is achievable with artemin.

Animals↗

PubMed2003

Scimitar syndrome: morphological diagnosis and assessment of hemodynamic significance by magnetic resonance imaging.

Scimitar syndrome has a variable presentation depending on the age at which the diagnosis is made. We report a case of a young woman (age 18 years) with suspected right pulmonary hypoplasia in whom a scimitar syndrome was diagnosed. Using MRI morphological findings and hemodynamic significance of the syndrome were assessed. Left-to-right shunt was calculated from blood flow measurements performed in the ascending aorta, the main pulmonary artery, and the aberrant scimitar vein.

Adolescent↗

PubMed2002

Disruption of dendritic translation of CaMKIIalpha impairs stabilization of synaptic plasticity and memory consolidation.

Local protein translation in dendrites could be a means for delivering synaptic proteins to their sites of action, perhaps in a spatially regulated fashion that could contribute to plasticity. To directly test the functional role of dendritic translation of calcium/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) in vivo, we mutated the endogenous gene to disrupt the dendritic localization signal in the mRNA. In this mutant mouse, the protein-coding region of CaMKIIalpha is intact, but mRNA is restricted to the soma. Removal of dendritic mRNA produced a dramatic reduction of CaMKIIalpha in postsynaptic densities (PSDs), a reduction in late-phase long-term potentiation (LTP), and impairments in spatial memory, associative fear conditioning, and object recognition memory. These results demonstrate that local translation is important for synaptic delivery of the kinase and that local translation contributes to synaptic and behavioral plasticity.

Animals↗

PubMed2002

MR imaging at rest early after myocardial infarction: detection of preserved function in regions with evidence for ischemic injury and non-transmural myocardial infarction.

Patients with subacute myocardial infarction were studied to detect regions of ischemic injury but with preserved myocardial function combining different MRI techniques. On a 1.5-T imaging system 27 patients were examined 7-14 days after acute myocardial infarction. The imaging protocol included T2-weighted fast spin-echo imaging, a cine fast low-angle shot (FLASH) 2D technique to determine regional function at rest, and a first pass as well as late contrast enhancement perfusion study injecting 0.1 mmol/kg Gd-DTPA. Preserved function was compared with the transmural extent of first-pass perfusion phenomena, increased T2 signal intensity (SI), and late contrast enhancement. Semi-quantitative first-pass perfusion parameters were correlated with quantitative myocardial wall thickening (MWT) and degree of coronary artery stenosis. Indicating ischemic injury increased T2 SI and late enhancement was present in 29 and 26% of segments. Preserved function was found predominantly in segments with non-transmural late enhancement (112 of 338 segments with late enhancement) and transmural increase of T2 SI (129 of 386 segments with increased T2 SI). A high-grade perfusion deficit was detected in 4% of all segments and regularly associated with markedly decreased systolic function. Correlation of first-pass perfusion parameters was observed with MWT (r=0.50-0.90, p<0.001) but not with the degree of coronary artery stenosis. Our data suggest that preserved function was detected in non-transmural myocardial infarction demonstrated by non-transmural late enhancement and increase of T2 SI.

Aged↗

PubMed2002

MR Imaging of the heart with cine true fast imaging with steady-state precession: influence of spatial and temporal resolutions on left ventricular functional parameters.

The influence of changes in spatial and temporal resolutions on functional parameters in the left ventricle (LV) were investigated with magnetic resonance (MR) imaging with a modified true fast imaging with steady-state precession, or FISP, two-dimensional sequence that provided temporal resolution of 21-90 msec and spatial resolution of 1-3 mm. MR imaging in the heart was performed in 15 healthy volunteers. A decrease in LV functional parameters was observed with reduced spatial and temporal resolutions. The influence of temporal resolution was more relevant.

Adult↗

PubMedDate not supplied

A non-heart-beating donor model to evaluate functional and morphologic outcomes in resuscitated pig hearts.

A non-heart-beating donor model was considered to examine whether pig hearts from the abattoir could be resuscitated by whole blood reperfusion. For preservation, machine perfusion using University of Wisconsin (UW) solution was compared with storage on ice. Nineteen hearts from abattoir pigs, harvested 25 +/- 3 min after exsanguination, were harvested and transported to the laboratory. Controls (n = 7) were immediately reperfused with homologous whole pig blood in an isolated heart model for 60 min with monitoring of left ventricular developed pressure (LVDP), contractility, and coronary flow. UW solution hearts (UW, n = 6) were perfused for 4 h with 10 degrees C cold UW solution before blood reperfusion. In the cold storage group (CS, n = 6), the organs were stored for an additional 4 h on ice before blood reperfusion. In all hearts, histology was performed after 60 min of blood reperfusion to evaluate myocardial reperfusion injury. All three groups showed significant increases in LVDP (p <.001), although this functional recovery was earliest in the control group and latest in the UW group. Significant declines were observed for both LVDP and contractility from the peak values in each group to the end of blood reperfusion. Coronary flow increased steadily over the time course for the UW group, whereas in the control and CS groups flow increased during the first 15 min of blood reperfusion and then decreased. In the UW and CS groups, there were significant positive correlations between coronary flow and LVDP (p <.001). Microscopic examination revealed no differences between the three groups. Thus, hearts from an abattoir with 25 min of warm ischemic time can be resuscitated. For storage of these organs, continuous machine perfusion with UW solution is superior to cold storage on ice.

Adenosine↗