PubMed Health⌕ Search

Biomedical subjects

Klaus Hahn

Publications and source records attributed to Klaus Hahn.

At least 19 recordsLinked to original sources

Sixty-four slice spiral CT angiography does not predict the functional relevance of coronary artery stenoses in patients with stable angina.

PURPOSE: The aim of this study was to evaluate spiral multidetector computed tomography (MDCT) angiography using 64-slice technique in the detection of functionally relevant coronary artery stenoses (CAS). METHODS: Thirty-eight patients (62+/-11 years, 28 men) with stable angina (26 with suspected and 12 with known coronary artery disease) were investigated using 64-slice MDCT angiography and gated myocardial perfusion SPECT (gated SPECT); a subgroup of 30 patients had additional invasive coronary angiography (ICA). Stenoses with luminal narrowing of >or=50% were defined as "significant" in MDCT angiography and ICA. MDCT angiography was compared with gated SPECT and the combination of gated SPECT plus ICA with respect to the detection of functionally relevant CAS. RESULTS: The sensitivity, specificity and negative and positive predictive values of MDCT angiography in detecting reversible perfusion defects on gated SPECT were 63%, 80%, 94% and 32%, respectively, in vessel-based analysis and 71%, 62%, 72% and 60%, respectively, in patient-based analysis. If only reversible perfusion defects on gated SPECT with CAS >or=50% on ICA were considered, the sensitivity, specificity and negative and positive predictive values were, respectively, 85%, 79%, 98% and 33% for vessel-based analysis and 85%, 59%, 83% and 61% for patient-based analysis. CONCLUSION: Sixty-four slice MDCT angiography failed to predict the functional relevance of CAS, but had a high negative predictive value in the exclusion of functionally relevant CAS in symptomatic patients.

Angina Pectoris↗

Value of PET/CT versus PET and CT performed as separate investigations in patients with Hodgkin's disease and non-Hodgkin's lymphoma.

PURPOSE: The aim of this study was to assess the clinical benefit of combined [(18)F]FDG PET/CT in patients with malignant lymphoma as compared to separately performed PET and CT. METHODS: Overall, 100 patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) were included in this study. Co-registered PET/CT with [(18)F]FDG and contrast medium was performed in 50 consecutive patients with NHL (n=38) or HD (n=12) for initial staging (IS) (n=12) or re-treatment staging (RS) (n=38). Another 50 patients with NHL (n=32) or HD (n=18) underwent separate PET and CT investigations within a time frame of 10 days for IS (n=22) or RS (n=28). Lymphoma involvement was separately evaluated for seven different regions in each patient. Each patient had clinical follow-up evaluation for >6 months. PET and CT data were analysed separately as well as side-by-side or in fused mode. RESULTS: In the PET/CT group, region-based evaluation for lymphoma involvement suggested a sensitivity/specificity of 85%/91% for CT, 98%/99% for PET and 98%/99% for PET/CT. In the PET and CT group, region-based evaluation showed a sensitivity/specificity of 87%/80% for CT, 98%/99% for PET and 98%/100% for PET and CT read side by side. CONCLUSION: PET was superior to CT alone and was improved further by side-by-side reading of both examinations. However, no significant difference was observed between PET/CT and separate PET and CT imaging in patients with lymphoma.

Adult↗

Neutrophil polarization: spatiotemporal dynamics of RhoA activity support a self-organizing mechanism.

Chemoattractants like fMet-Leu-Phe (fMLP) induce neutrophils to polarize with phosphatidylinositol 3,4,5-trisphosphate (PIP3) and protrusive F-actin at the front and actomyosin contraction at the sides and back. RhoA and its downstream effector, myosin II, mediate the "backness" response, which locally inhibits the "frontness" response and constrains its location to one part of the cell. In living HL-60 cells, we used a fluorescent PIP3 probe or a single-chain FRET biosensor for RhoA-GTP to assess spatial distribution of frontness or backness responses, respectively, during the first 3 min after exposure to a uniform concentration of fMLP. Increased PIP3 signal or RhoA activity initially localized randomly about the cell's periphery but progressively redistributed to the front or to the back and sides, respectively. Cells rendered unable to mount the frontness response (by inhibiting actin polymerization or Gi, a trimeric G protein) responded to a micropipette source of attractant by localizing RhoA activity at the up-gradient edge. We infer that protrusive F-actin, induced by the frontness response, constrains the spatial distribution of backness by locally reducing activation of RhoA, thereby reducing its active form at the front. Mutual incompatibility of frontness and backness is responsible for self-organization of neutrophil polarity.

Actins↗

Functional proteometrics for cell migration.

BACKGROUND: Advances in living cellular fluorescence biosensors and computerized microscopy enable a vision of fully automated high-resolution measurements of the detailed intracellular molecular dynamics directly linked to cellular behaviors. Given the heterogeneity of cell populations, a statistically relevant study of molecular-cellular dynamics is a key motivation for improved automation. METHODS: We explored automating computerized, microscope-based data extraction and analyses that monitor cell locomotion, rates of mitoses, and spatiotemporal activities of intracellular proteins via ratiometric fluorescent biosensors in mouse fibroblasts. Novel image processing methods included K-means clustering segmentation preprocessing followed by modified discrete, normalized cross-correlational alignment of two-color images; ratiometric processing for fluorescence resonance energy transfer (FRET) measurements; and intracellular spatial distribution measurements of RhoA GTPase activity. RESULTS: The interdivision time was 19.4 h (mean) +/- 6.0 h (SD) (n = 7) for the GFP-histone cells in the two-by-two field that was scanned for 72 h. After registration and ratioing of the cells with the RhoA biosensor, increases in both cell protrusion and retraction were coincident with to increases in RhoA activity. CONCLUSIONS: These advances lay the foundation for extracting and correlating measurements characterizing the functional relationships of spatial localization and protein activation with features of cell migration such as velocity, polarization, protrusion, retraction, and mitosis.

Animals↗

Imaging and photobleach correction of Mero-CBD, sensor of endogenous Cdc42 activation.

This chapter details quantitative imaging of the Mero-CBD biosensor, which reports activation of endogenous Cdc42 in living cells. The procedures described are appropriate for imaging any biosensor that uses two different fluorophores on a single molecule, including FRET biosensors. Of particular interest is an algorithm to correct for fluorophore photobleaching, useful when quantitating activity changes over time. Specific topics include procedures and caveats in production of the Mero-CBD sensor, image acquisition, motion artifacts, shading correction, background subtraction, registration, and ratio imaging.

Biosensing Techniques↗

Digital autofocus methods for automated microscopy.

Automatic focusing of microscope images is an essential part of modern high-throughput microscopy. This chapter describes implementation of a robust autofocus system appropriate for using either air or oil immersion objectives in robotic imaging. Both hardware and software algorithms are described, and caveats of using viscous immersion media with multifield scanning are detailed.

Algorithms↗

Performance evaluation of the PET sub-systems of two PET/CT imagers according to NEMA standard NU 2-2001.

UNLABELLED: Performance and image quality of PET scanners are mainly determined by the choice of the detector material and the realised design of the scanner. The aim of this study was to measure the PET performance characteristics of two state-of-the-art PET/CT Systems. METHODS: Performance measurements following the NEMA NU 2-2001 standard were performed on a GSO-based system and on a system with LSO detectors. The following parameters were determined: spatial resolution, scatter fraction, sensitivity and count rate behaviour A body phantom was used to determine the image quality as well as the influence of differently performed attenuation corrections (low dose CT vs. 137Cs transmission source). RESULTS: Both scanners have partly different, but altogether good performance characteristics. The differences can be explained mostly by different physical properties of the detectors and by a different design of the scanners including the implemented electronics. CONCLUSION: If the data are to be compared quantitatively, the modality of the attenuation correction has to be taken into account, especially in regions with reduced uptake or reduced density. Both scanners achieve a very good image quality rich in contrast within short acquisition times which allows easy detection of small lesions.

Germany↗

Value of 99mTc-TRODAT-1 SPECT to predict clinical response to methylphenidate treatment in adults with attention deficit hyperactivity disorder.

BACKGROUND: In a previous study, binding of Tc-TRODAT-1 to the dopamine transporter (DAT) was found to be higher in patients with attention deficit hyperactivity disorder (ADHD) as compared to healthy controls. AIM: To determine whether the degree of Tc-TRODAT-1 binding to the striatal DAT may have a predictive role on the response to methylphenidate (MPH) in patients with ADHD. METHODS: Twenty-two adult patients suffering from ADHD underwent a brain SPECT scan with Tc-TRODAT-1. After the scan patients received MPH, individually medicated up to 60 mg.day. Severity of illness was estimated using the Clinical Global Impression (CGI-S) Scale before treatment. Ten weeks after the beginning of MPH treatment the improvement in global symptoms was rated by the Clinical Global Improvement Scale (CGI-I). RESULTS: Before treatment 17/22 patients with ADHD presented with higher striatal DAT binding as compared to age-matched healthy controls (+23.8%; P<0.01). After treatment with MPH a significant improvement of ADHD symptoms was demonstrated by the CGI-I in 16 of these 17 patients (CGI-S before: 4.8; CGI-I after MPH: 1.9; P<0.01). Five patients showed reduced DAT binding prior to therapy (-14.4%; P=0.04); these patients did not respond to MPH therapy (CGI-S before: 4.5; CGI-I after MPH: 4.2; P=0.40). CONCLUSION: Our findings suggest that ADHD patients with primarily elevated binding of Tc-TRODAT-1 to the striatal DAT responded better to therapy with MPH as compared to those with normal or low DAT binding. Consequently, our results - even if obtained on a small collective indicate that measurement of DAT may be an important prognostic predictor for therapy response to MPH.

Adult↗

Clinical validation of the gated blood pool SPECT QBS processing software in congestive heart failure patients: correlation with MUGA, first-pass RNV and 2D-echocardiography.

INTRODUCTION: Left (LVEF) and right ventricular ejection fraction (RVEF) as well as LV regional wall motion at rest are valuable tools to monitor and tailor treatment of congestive heart failure (CHF) patients. Gated blood pool SPECT (GBPS) is under evaluation as an "all-in-one" technique, providing information on LVEF, RVEF, and wall motion derived from a single examination. Aim of the study was to evaluate a commercially available automated GBPS processing software for EF measurements and wall motion analysis in heart failure patients. METHODS: Thirty-two patients (12 female; mean age+/-SD: 53+/-13 years), suffering from dilated (63%), ischemic (25%) or hypertrophic (13%) cardiomyopathy, were studied. First-pass radionuclide ventriculography (FP-RNV), planar multigated radionuclide angiography (MUGA), and GBPS were performed at rest after in vivo labeling of red blood cells, and LVEF and RVEF was calculated with each method. Later on the same day LVEF was calculated by echocardiography. LV wall motion (summed motion score and wall motion index) was derived from GBPS and echocardiography using the standard 16-segment model. RESULTS: Mean LVEF measured by GBPS, echocardiography, MUGA and FP-RNV was 33+/-13%, 37+/-15%, 41+/-14% and 45+/-13%, respectively. LVEF values calculated from GBPS showed moderate to good correlation with FP-RNV (r=0.61), MUGA (r=0.65) and ECHO (r=0.74; all p<0.01). Mean RVEF calculated by GBPS, FP-RNV and MUGA was 45+/-14%, 46+/-9% and 38+/-9%, respectively. RVEF values calculated from GBPS showed weak correlation with FP-RNV (r=0.33) and MUGA (r=0.26; all p=n.s.). Assessment of GBPS wall motion was qualitatively possible in all patients. The agreement between GBPS and ECHO was 82% (kappa=0.73). The wall motion index showed good correlation between both methods (r=0.88; p<0.001). CONCLUSION: An automated algorithm for LVEF calculation and wall motion analysis using GBPS is feasible for clinical routine diagnostic in CHF patients. The RVEF calculation method needs to be improved before routine clinical application can be recommended.

Algorithms↗

Initial evaluation of breast cancer using Tc-99m sestamibi scintimammography.

AIM: Aim of the study was to elaborate on the diagnostic role of Tc-99m sestamibi scintimammography (SMM) in the initial diagnosis of breast cancer, partially in comparison to MRI. The study presents an update of previously published data. MATERIALS AND METHODS: Out of a total of 464 scintimammograms findings of 252 studies were correlated with the histopathologic outcome. A subgroup of 68 patients with indeterminate preliminary diagnosis underwent additional MRI. SMM and MRI findings were correlated to the final hisopathological outcome. RESULTS: Overall sensitivity and specificity for SMM were 84 and 85%, respectively. Depending on tumor size sensitivity ranged from 60% for stage pT1a,b carcinomas to 94% stage pT1c or higher. In the subgroup with indeterminate preliminary diagnosis sensitivity of SMM decreased to 76% which was lower as compared to MRI (84%). Specificity of SMM was 86% in this subgroup which was evidently higher as compared to MRI (51%). CONCLUSION: SMM has severe limitations in the diagnosis of small carcinoma and therefore should not be used for breast cancer screening. SMM can be used to further evaluate indeterminate or probably benign mammographic findings, especially when conventional mammography is inconclusive due to dense breast tissue.

Breast Neoplasms↗

Diagnostic performance of a 3-D automated quantification method of dopamine D2 receptor SPECT studies in the differential diagnosis of parkinsonism.

BACKGROUND: Assessment of post-synaptic D2 receptors with 123I-IBZM SPECT is helpful in distinguishing idiopathic (IPS) from other parkinsonian syndromes (non-IPS). AIM: To evaluate the diagnostic performance of a recently introduced three-dimensional automated quantification method in a large group of parkinsonian patients. METHODS: IBZM SPECT was performed in 101 consecutive patients with IPS (n = 49) and non-IPS (n = 52). Striatal/frontal cortex binding ratios were assessed by a standard manual quantification method and by the automated method. For the latter patient studies were registered to a mean template of healthy controls (n = 13). IBZM binding was calculated from a 3-D volume-of-interest map established on the normal template. The diagnostic performance of the automated and manual approaches were assessed by receiver operating characteristic (ROC) analyses. RESULTS: Specific striatal binding ratios of both quantification methods showed a close linear relationship (y = 0.81x + 0.1188; R2 = 0.8062). At optimal decision thresholds sensitivity and specificity were 87% and 90% for the automated, and 85% and 90% for the manual method, respectively. The area under the ROC curve was 0.92 for the automated and 0.93 for the manual method, showing no statistical difference. The area under the ROC curve corresponding to a false positive fraction from 0% to 20% was 0.163 for the automated and 0.166 for the manual evaluation. CONCLUSIONS: The diagnostic performance of an automated 3-D quantification method for IBZM SPECT studies has been shown to be equal to, or even better than, a standard manual technique. Advantages of automated quantifications are observer independence and fast processing times. This method may be also used as a platform for processing large data sets/multicentre studies in order to objectively evaluate basal ganglia disorders.

Adult↗

Dobutamine myocardial scintigraphy for the prediction of cardiac events after heart transplantation.

BACKGROUND: The long-term outcome after heart transplantation (HTx) is essentially influenced by the occurrence and extent of cardiac allograft vasculopathy (CAV). Single photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI) has been shown to be a useful and cost-effective non-invasive method in patients with known or suspected coronary artery disease, but its role in detecting CAV remains unclear. AIM: To evaluate the accuracy and predictive value of dobutamine MPI in patients after HTx during a 12-month follow-up. METHODS: Seventy-seven patients (60 males, 17 females) underwent a total of 216 dobutamine MPI examinations over a period of 5 years. Examinations were obtained an average of 89+/-42 months after orthotopic HTx according to a 1-day protocol using 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) with and without attenuation correction. For the present study, findings from 77 MPI examinations (one MPI examination per patient) were analysed visually and semiquantitatively using a 20-segment model. Summed stress scores (SSS) and summed rest scores (SRS) were calculated and receiver operating characteristic (ROC) analysis was performed to detect optimum threshold values. Patients were followed up for 12 months and cardiac events were registered. RESULTS: Cardiac events were observed in 10 of the 77 patients. Good interobserver agreement was found for global visual and SRS-/SSS-based analysis (kappa=0.74 and 0.66, respectively). SSS was superior to SRS in the detection of cardiac events. ROC analysis showed an optimized SSS threshold value of three. For predicting a cardiac event during the 12-month follow-up, global visual and semiquantitative analysis reached sensitivities of 90% and 90%, specificities of 72% and 88%, accuracies of 74% and 87%, positive predictive values of 32% and 53% and negative predictive values of 98% and 98%, respectively. The sensitivity, specificity, accuracy and positive and negative predictive values for MPI to detect clinically relevant coronary artery stenoses (> or =50%) at conventional coronary angiography were 83%, 87%, 86%, 56% and 96%, respectively. CONCLUSIONS: Non-invasive dobutamine MPI reliably identifies patients at risk for subsequent cardiac events in cases of CAV, with a high negative predictive value of 98% and an accuracy of 87%.

Coronary Disease↗

D2 receptor occupancy during high- and low-dose therapy with the atypical antipsychotic amisulpride: a 123I-iodobenzamide SPECT study.

UNLABELLED: Amisulpride appears to be an effective agent for treating positive or negative symptoms of schizophrenia, depending on dose. The aim of this study was to assess striatal dopamine D(2) receptor availability by means of (123)I-iodobenzamide (IBZM) SPECT in patients treated with high and low doses of this atypical antipsychotic drug. METHODS: Twenty-nine patients (19 men and 10 women, age range, 19-68 y) with schizophrenia treated with high doses (15 patients; 400-1,200 mg/d; mean dose, 666.7 +/- 219.3 mg/d) or low doses (14 patients; 50-300 mg/d; mean dose, 228.6 +/- 93.5 mg/d) of amisulpride were examined. For assessment of plasma amisulpride concentration, blood samples were taken. Brain SPECT was performed 2 h after intravenous injection of 185 MBq of (123)I-IBZM. For semiquantitative evaluation, transverse slices corrected for attenuation (Chang's first-order method) were used to calculate specific binding in the striatum, with the frontal cortex used as background. RESULTS: In all patients treated with amisulpride, specific binding of (123)I-IBZM to D(2) receptors was significantly lower (P < 0.001) than in healthy controls (0.95). Both groups treated with amisulpride differed significantly in specific binding of (123)I-IBZM to dopamine D(2) receptors (0.20 vs. 0.31, P < 0.05). D(2) receptor blockade correlated well with the administered dose of amisulpride and with amisulpride plasma concentration. CONCLUSION: Our findings suggest that amisulpride treatment leads to a significant occupancy of postsynaptic dopamine D(2) receptors. The blockade of D(2) receptors tends to be significantly lower in patients receiving low-dose amisulpride therapy than in patients receiving high-dose therapy.

Adult↗

Comparison of spiral multidetector CT angiography and myocardial perfusion imaging in the noninvasive detection of functionally relevant coronary artery lesions: first clinical experiences.

UNLABELLED: Compared with conventional coronary angiography, spiral multidetector CT (MDCT) angiography has delivered promising accuracy in the detection and validation of coronary lesions. Myocardial perfusion imaging (MPI) using SPECT is an established method for noninvasively assessing the functional significance of coronary stenoses and delivers valuable information for risk stratification. This retrospective analysis compared the accuracies of MDCT angiography and MPI in the detection of hemodynamically relevant lesions of the coronary arteries. METHODS: Twenty-five patients with suspected or known coronary artery disease were studied. Electrocardiographically gated MPI and 16-MDCT angiography were performed. Myocardial perfusion images were analyzed by 2 experienced observers, and reversible and fixed perfusion defects were detected and allocated to their corresponding coronary vessels. For the evaluation of MDCT angiography, image quality was determined, and lesions > or = 50% and luminal narrowing < 50% were visually assessed and characterized by 2 independent observers unaware of the results of MPI. RESULTS: Ninety-nine coronary vessels were analyzed, and the quality of MDCT angiography images was assessed for 330 coronary segments. Coronary artery diameter was interpretable for 231 (70%) of 330 segments, whereas in 99 (30%) of 330 segments, vessel diameter could not be evaluated because of heavy calcifications, blurring, motion artifacts, or intracoronary stents. MDCT angiography detected stenoses > or = 50% in 15 of 100 coronary arteries. Eight (53%) of 15 stenoses > or = 50% showed reversible or fixed perfusion defects in the corresponding myocardial areas on MPI. Sensitivity, specificity, and negative and positive predictive values were 100%, 87%, 100%, and 29%, respectively, for the ability of MDCT angiography to detect reversible perfusion defects in the corresponding myocardial areas. CONCLUSION: MDCT angiography detected myocardial ischemia, as defined by reversible perfusion defects on MPI, with a positive predictive value of 29% in a nonselected study cohort. Compared with MPI alone, MDCT angiography added important morphologic information, but MPI remains mandatory for evaluating the functional relevance of coronary artery lesions.

Coronary Angiography↗

18F-FDG PET/CT for staging of penile cancer.

UNLABELLED: The value of PET or PET/CT with (18)F-FDG for the staging of penile cancer has yet to be determined. The objective of this study was to investigate the pattern of (18)F-FDG uptake in the primary malignancy and its metastases and to determine the diagnostic value of (18)F-FDG PET/CT in the staging and restaging of penile cancer. METHODS: Thirteen patients (mean +/- SD age, 64 +/- 14.0 y) with suspected penile cancer or suspected recurrent disease were examined with a Gemini PET/CT system (200 MBq of (18)F-FDG). The reference standard was based on histopathologic findings obtained at biopsy or during surgery. RESULTS: Both the primary tumor and regional lymph node metastases exhibited a pattern of (18)F-FDG uptake typical for malignancy. Sensitivity in the detection of primary lesions was 75% (6/8), and specificity was 75% (3/4). On a per-patient basis, sensitivity in the detection of lymph node metastases was 80% (4/5), and specificity was 100% (8/8). On a nodal-group basis, PET/CT showed a sensitivity of 89% (8/9) in the detection of metastases in the superficial inguinal lymph node basins and a sensitivity of 100% (7/7) in the deep inguinal and obturator lymph node basins. The mean +/- SD maximum standardized uptake value for the 8 primary lesions was 5.3 +/- 3.7, and that for the 16 lymph node metastases was 4.6 +/- 2.0. CONCLUSION: According to our results, the main indication for (18)F-FDG PET in the primary staging or follow-up of penile cancer patients may be the prognostically crucial search for lymph node metastases. With the use of a PET/CT unit, the additional information provided by CT may be especially useful for planning surgery. Implementing (18)F-FDG PET and PET/CT in future staging algorithms may lead to a more precise and stage-appropriate therapeutic strategy. Furthermore, invasive procedures with a high morbidity rate, such as general bilateral lymphadenectomy, may be avoided.

Adult↗

Preoperative imaging of Charcot neuroarthropathy in diabetic patients: comparison of ring PET, hybrid PET, and magnetic resonance imaging.

INTRODUCTION: The treatment of Charcot neuroarthropathy in the feet of diabetic patients has undergone fundamental changes in the last few years. Formerly, treatment was almost exclusively limited to nonoperative measures; since the late 1990s, however, current practice has shifted to early, stage-appropriate surgical therapy. The objective of this prospective study was to investigate the value of two types of positron emission tomography (PET) in the preoperative evaluation of diabetic patients with Charcot foot deformities. MATERIALS AND METHODS: Ring [(18)F]FDG (2-fluoro-2-deoxy-glucose) and hybrid PET were compared to magnetic resonance imaging (MRI). MRI, ring PET, and hybrid PET imaging were used as part of the preoperative evaluation of 16 patients with type II diabetes mellitus. The diagnosis of Charcot neuropathy of the foot requiring operative treatment had been made on the basis of clinical and radiographic criteria. RESULTS: Of 39 Charcot lesions confirmed at surgery, 37 were detected by ring PET, 30 by hybrid PET, and 31 by MRI. CONCLUSIONS: PET (ring or hybrid) can be used in the evaluation of patients with metal implants that would compromise the accuracy of MRI. Another advantage of PET is its ability to distinguish between inflammatory and infectious soft-tissue lesions, and between osteomyelitis and Charcot neuroarthropathy. The differentiation between Charcot neuroarthropathy and florid osteomyelitis provides the surgeon with important additional information that often is unavailable from MRI. Because it provides important additional data, ring PET may be preferable to radiography and MRI in the preoperative evaluation of patients with Charcot neuroarthropathy of the foot. Hybrid PET, because of its poorer resolution compared to ring PET, appears less suitable for routine clinical application.

Aged↗