J P Kühn

University of Greifswald, Griefswald, Mecklenburg-Vorpommern, Germany

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Publications (27)83.58 Total impact

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    ABSTRACT: Aim To investigate the feasibility of gadoxetate disodium-enhanced magnetic resonance (MR) cholangiography in chronic obstructive cholestatic biliary disease in the clinical setting. Materials and methods Twenty-three patients with dilated bile duct trees and ten volunteers underwent gadoxetate disodium-enhanced liver MR cholangiography and were enrolled in the present retrospective study. Gadoxetate disodium was given in a standardized manner as a bolus injection at a dose of 0.25 mmol/kg of body weight (0.1 ml/kg). Region of interest-based measurement of mean enhancement of the dilated bile ducts was performed in series before gadoxetate disodium administration and during hepatobiliary phases. Results Direct comparison of mean bile duct enhancement during hepatobiliary phases in the clinical imaging window between healthy volunteers [4.7 ± 2.2 arbitrary units (au)] and patients with dilated bile ducts (0.1 ± 0.3 au) revealed significantly lower or absent enhancement in dilated bile ducts (p = 0.001). Conclusion Standard clinical gadoxetate disodium-enhanced MR cholangiography is not a reliable technique for the evaluation of the biliary trees, because of altered biliary gadoxetate disodium elimination in patients with chronic obstructive biliary diseases.
    Clinical Radiology. 01/2014;
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    ABSTRACT: The objectives of the study were to measure the pharmacokinetics and liver enhancement of gadoxetate (gadolinium-ethoxylbenzyl-diethylenetriamine-pentaacetic acid [Gd-EOB-DTPA], Eovist, Primovist) after oral and intravenous administration in wild-type and (multidrug resistance-associated protein 2) Mrp2-deficient rats and to evaluate the in vitro transport of the contrast agent via intestinal and hepatic transporter proteins. Gadolinium-ethoxylbenzyl-diethylenetriamine-pentaacetic acid-enhanced magnetic resonance imaging and pharmacokinetics of Gd-EOB-DTPA after intravenous and oral administration were evaluated in wild-type and Mrp2-deficient rats using T1-weighted magnetic resonance imaging and a validated liquid chromatography-mass spectrometry method, respectively. Cellular uptake of Gd-EOB-DTPA was measured in stably transfected human embrionic kidney 293-cells expressing oragnic anion-transporting polypeptide 1A2 or organic cation transporter 3 and Madin Darby canine kidney 2-cells expressing apical sodium dependent bile acid transporter. The affinity to MRP2 and multidrug resistance-associated protein 3 was measured using inside-out vesicles. In vitro, Gd-EOB-DTPA was demonstrated to be a substrate for OATP1A2 (mean [SD] of the Michaelis-Menten constant [Km], 1.0 [0.4] mmol/L; mean [SD] of the maximal uptake rate [Vmax], 101.3 [21.1] pmol/mg per minute), MRP2 (Km, 1.0 [0.5] mmol/L; Vmax, 86.8 [31.1] pmol/mg per minute), and multidrug resistance-associated protein 3 (Km, 1.8 [0.3] mmol/L; Vmax, 116 [15.9] pmol/mg per minute) but not for the apical sodium-dependent bile acid transporter and organic cation transporter 3. After the oral administration to the wild-type animals, Gd-EOB-DTPA was considerably absorbed from the small intestine (bioavailability, approximately 17%) and predominately eliminated via feces after intravenous dosing (approximately 96%). In the Mrp2-deficient rats, oral bioavailability increased to approximately 21% and Gd-EOB-DTPA was exclusively excreted into urine. Magnetic resonance enhancement of the liver was significantly prolonged in the Mrp2-deficient rats compared with the wild-type rats (mean [SD] area under the curve0-90, 36.4 [8.5] vs 14.8 [10.3] arbitary units per minute; P = 0.003; time to maximum plasma concentration, 48.6 [23.8] vs 6.0 [3.1] minutes; P = 0.001). The nonmetabolized Gd-EOB-DTPA may have some potentials to be used as a probe-contrast agent to evaluate transporter-mediated mechanisms along the enterohepatic absorption route for drugs by functional visualization in vivo.
    Investigative radiology 09/2013; · 4.85 Impact Factor
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    ABSTRACT: The treatment of thoracic aortic diseases has undergone a paradigm shift due to the introduction and further development of interventional techniques in recent years. Thoracic endovascular aortic repair (TEVAR) of the descending aorta has significantly lower mortality and complication rates compared to open repair. Meanwhile this endovascular approach is the first option for the treatment of the majority of thoracic aortic diseases.
    RöFo - Fortschritte auf dem Gebiet der R 01/2012; 184(1):15-23. · 2.76 Impact Factor
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    ABSTRACT: Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function.
    Nature Genetics 11/2011; 43(11):1131-8. · 35.21 Impact Factor
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    ABSTRACT: Acute inversion injuries of the ankle are the most common sports accidents, accounting for approximately 10% of emergency room admissions. In up to 85%, an injury of the lateral collateral ligaments is observed. Classically, the assessment of these injuries has relied on clinical examination and radiographs, including stress views. The aim of our study was to correlate prospectively the findings of high-field 3 T MRI in acute ankle distortion with clinical outcome. During a 6-month period, 38 patients were prospectively included. MRI was performed within 48 h of trauma and clinical examination using a protocol consisting of axial T2-weighted and coronal and sagittal T1-weighted images and a sagittal proton density (PDw) sequence. Each ligament injury was graded on a three-point scale. Functional outcome was evaluated using the AOFAS ankle-hindfoot scale. In 24/38 patients (63.12%), ligament injury was observed. In 22/24 cases, this was an injury of the lateral ligaments and in 2/24 cases of the medial ligaments. Injury of the syndesmosis occurred in three patients, a bone bruise in four, and an osteochondral lesion in three cases. Patients with an injury of two or more ligaments or a bone bruise had a lower AOFAS score and returned to sports activities and full weight-bearing later (P < 0.01). MR imaging at 3 Tesla is an independent predictor for clinical outcome. Therefore MRI may be beneficial in those cases where the findings influence further treatment.
    Skeletal Radiology 04/2011; 40(4):423-30. · 1.74 Impact Factor
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    ABSTRACT: To retrospectively evaluate neurogenic heterotopic ossification in an early neurological rehabilitation population (phases B and C) with respect to epidemiology and morphology on conventional radiographs. Over a 4-year period, 1,463 patients treated at a clinic for early neurological rehabilitation were evaluated for clinical symptoms of neurogenic heterotopic ossification. In case of clinical suspicion, plain radiographs of the expected sites were obtained. If heterotopic ossification was detected, the initial and subsequent radiographs were retrospectively analyzed for sites, size, and morphology. Immature lesions were categorized as small (<10 mm) or large (10-100 mm). The prevalence rate of neurogenic heterotopic ossification was 2.05%. The condition was most common in young male adults. The hip was the most common site accounting for more than half of the cases. Two or more ossifications were seen in 56.7% of the affected patients with approximately two-thirds showing bilateral symmetric involvement of corresponding joint regions. The size of ossifications strongly varied interindividually. Small immature lesions demonstrated less progression in size than large lesions during maturation (P < 0.05). Standard radiographs, as a fast and inexpensive technique, allow the expected size progression of heterotopic ossifications during maturation to be estimated, which is relevant in terms of therapeutic decisions, patient mobilization, and neurological rehabilitation.
    Skeletal Radiology 02/2011; 41(1):61-6. · 1.74 Impact Factor
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    ABSTRACT: The purpose of this article is to compare the technical success and guidance of percutaneous transhepatic biliary drainage (PTBD) in patients with nondilated and dilated bile duct systems using different techniques to supplement the conventional approach. Between 2006 and 2008, 71 patients (mean age, 66.6 years) underwent PTBD with 97 interventions. According to sonographic evaluation of bile duct morphology, patients were divided into two groups: 50 patients with dilated and 21 patients with nondilated bile ducts. In a retrospective analysis, both groups were compared for technical success, fluoroscopy time, complications, and medical indications. The use of interventional guidance (deviations from the standard protocol) in patients with nondilated bile ducts was recorded. The technical success rate was 90% in patients with dilated bile ducts versus 81% in patients with nondilated ducts, with no significant difference (p = 0.36). The greater complexity of the intervention in patients with nondilated bile ducts resulted in longer fluoroscopy times (p = 0.04). Complication rates were not different between the two groups. The main indication for PTBD was relief of a compressed biliary system in patients with dilated ducts and postoperative management of complications or prevention of tumor-associated bile duct obstruction in patients with nondilated ducts. T-drainage, additional CT-guided puncture, and temporary gallbladder drainage were performed in 16 of 21 interventions for patients with nondilated bile ducts, resulting in a 100% success rate, versus a success rate of 60% in the five PTBDs of nondilated ducts performed in the conventional manner. T-drainage, additional CT-guided puncture, and temporary gallbladder drainage improve the technical success of PTBD when used in patients with nondilated bile ducts. With these measures, technical success and complication rates in patients with nondilated ducts are comparable to those for PTBD of dilated bile ducts.
    American Journal of Roentgenology 10/2010; 195(4):851-7. · 2.90 Impact Factor
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    ABSTRACT: Automatic 3D liver segmentation in magnetic resonance (MR) data sets has proven to be a very challenging task in the domain of medical image analysis. There exist numerous approaches for automatic 3D liver segmentation on computer tomography data sets that have influenced the segmentation of MR images. In contrast to previous approaches to liver segmentation in MR data sets, we use all available MR channel information of different weightings and formulate liver tissue and position probabilities in a probabilistic framework. We apply multiclass linear discriminant analysis as a fast and efficient dimensionality reduction technique and generate probability maps then used for segmentation. We develop a fully automatic three-step 3D segmentation approach based upon a modified region growing approach and a further threshold technique. Finally, we incorporate characteristic prior knowledge to improve the segmentation results. This novel 3D segmentation approach is modularized and can be applied for normal and fat accumulated liver tissue properties.
    Magnetic Resonance Imaging 07/2010; 28(6):882-97. · 2.06 Impact Factor
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    ABSTRACT: Contrast-enhancing magnetic resonance imaging with the liver-specific agent gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) has been shown to improve the detection rate of focal lesions. There is evidence from preclinical studies that multidrug organic anion transporters are involved in hepatic uptake of Gd-EOB-DTPA. Therefore, we evaluated affinity of the contrast agent to human organic anion-transporting polypeptides (OATP1B1, OATP1B3, OATP2B1) and to the Na(+)/taurocholate cotransporting polypeptide (NTCP) using stable transfected human embryonic kidney (HEK) 293 cells. In competition assays, Gd-EOB-DTPA inhibited the uptake of bromosulfophthalein (BSP) by OATP1B1 (IC(50) = 0.6 mM) and OATP1B3 (IC(50) = 0.4 mM). In comparison, the IC(50) values for rifampicin were 11.9 (OATP1B1), 1.4 (OATP1B3), and 80.5 muM (OATP2B1), respectively. Uptake of BSP by OATP2B1, uptake of taurocholic acid by NTCP, and viability of all HEK cells were not influenced by Gd-EOB-DTPA in concentrations up to 10 mM. In uptake assays using a new liquid chromatography-tandem mass spectrometry method for quantification, Gd-EOB-DTPA was a substrate for OATP1B1 (K(m) = 0.7 mM, V(max) = 10.5 pmol/mg x min), OATP1B3 (K(m) = 4.1 mM, V(max) = 22.7 pmol/mg x min), and NTCP (K(m) = 0.04 mM, V(max) = 1.4 pmol/mg x min). The uptake by OATP2B1 was not different from the vector control. In conclusion, Gd-EOB-DTPA is a substrate of the liver-specific OATP1B1, OATP1B3, and NTCP.
    Drug metabolism and disposition: the biological fate of chemicals 07/2010; 38(7):1024-8. · 3.74 Impact Factor
  • Rofo-fortschritte Auf Dem Gebiet Der Rontgenstrahlen Und Der Bildgebenden Verfahren - ROFO-FORTSCHR RONTGENSTRAHL. 01/2010; 182.
  • Rofo-fortschritte Auf Dem Gebiet Der Rontgenstrahlen Und Der Bildgebenden Verfahren - ROFO-FORTSCHR RONTGENSTRAHL. 01/2010; 182.
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    ABSTRACT: Approximately 4000 volunteers will undergo whole-body magnetic resonance imaging (WB-MRI) within the next 3 years in the population-based Study of Health in Pomerania (SHIP). Here we present a pilot study conducted (a) to determine the feasibility of adding a WB-MRI protocol to a large-scale population-based study, (b) to evaluate the reliability of standardized MRI interpretation, and (c) to establish an approach for handling pathological findings. The institutional review board approved the study, and oral and written informed consent was obtained from each participant. Two hundred healthy volunteers (99 women, 101 men; mean age 48.3 years) underwent a standardized WB-MRI protocol. The protocol was supplemented by contrast-enhanced cardiac MRI and magnetic resonance (MR) angiography in 61 men (60.4%) and cardiac MRI and MR mammography in 44 women (44.4%). MR scans were evaluated independently by two readers. Abnormalities were discussed by an advisory board and classified according to the need for further clinical work-up. One hundred ninety-four (97.0%) WB-MRI examinations were successfully completed in a mean scan time per subject of 90 minutes. There were 431 pathological findings in 176 (88%) of the participants. Of those 45 (10.4%) required further clinical work-up and 386 (89.6%) characterized as benign lesions did not. The interobserver agreement for the detection of pathological findings was excellent (kappa = 0.799). The preliminary results presented here indicate that a large prospective, population-based study using WB-MRI is feasible and that the results of image analysis are reproducible. A variety of positive findings provide valuable information regarding disease prevalence in a general adult population.
    RöFo - Fortschritte auf dem Gebiet der R 09/2009; 181(8):748-59. · 2.76 Impact Factor
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    ABSTRACT: Pulmonary metastatic lesions are present in 20-54% of all patients who die of cancer. Surgical studies have shown that local management of distant tumor metastasis as part of multimodal cancer therapy improves survival. Minimally invasive procedures such as thermal ablation are still to prove their clinical relevance. The aim of this study was to monitor therapeutic outcome and long-term results after percutaneous laser-induced thermal ablation. Sixty-four patients with metastasis to the lung underwent laser-induced thermal ablation in an ongoing prospective study. A total of 129 percutaneous procedures were performed to manage a total of 108 lung lesions. The median tumor size was 2.0 cm (range, 0.4-8.5 cm). Adequate management of all known individual tumor correlates was critical for definitive patient therapy. The Kaplan-Meier method was used to calculate survival and recurrence rates. Definitive management of initial pulmonary disease was achieved in 31 of 64 patients. The 1-, 2-, 3-, 4-, and 5-year survival rates after ablative therapy were 81%, 59%, 44%, 44%, and 27%. The median progression-free interval was 7.4 months. There were no therapy-related deaths. Pneumothorax occurred in 38% of the patients, necessitating periprocedural drainage in 5% of all cases. Parenchymal bleeding (13% of cases) always was self-limited. Laser ablative therapy for pulmonary metastasis is a promising option in multimodal cancer therapy. The procedure is safe and effective. The initial clinical outcome data strongly suggest that this technique has the potential to improve survival among selected patients.
    American Journal of Roentgenology 04/2009; 192(3):785-92. · 2.90 Impact Factor
  • Rofo-fortschritte Auf Dem Gebiet Der Rontgenstrahlen Und Der Bildgebenden Verfahren - ROFO-FORTSCHR RONTGENSTRAHL. 01/2009; 181.
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    ABSTRACT: To determine technical success, technique effectiveness, complications, and survival after laser ablation of liver metastases from colorectal cancer. Eighty-seven consecutive patients (65 men and 22 women; mean age, 62.8 years) with 180 liver metastases from colorectal carcinoma were included between 1998 and 2005. They underwent laser ablation with magnetic resonance (MR) thermometry in 170 sessions. Indications for laser ablation were locally unresectable tumors (16.1%), metastases in both liver lobes (34.5%), and refusal of surgery and/or general contraindications to surgery (49.4%). Technical success, technique effectiveness, and complication and survival rates were evaluated retrospectively. Technical success was achieved in 178 of 180 sessions (99%). Follow-up after 24-48 hours demonstrated an effectiveness rate of 85.6%. Local tumor progression rate was 10% after 6 months. Major complications included large pleural effusion, large subcapsular hematoma, abscess, large pneumothorax, pleuritis with fever, intrahepatic hemorrhage, and biloma. Mean survival from the time of diagnosis of the primary tumor was 50.6 months for all patients treated (95% CI, 44.9-56.3 months). Median survival time was 54 months and survival rates were 95.7% at 1 year, 86.2% at 2 years, 72.4% at 3 years, 50.1% at 4 years, and 33.4% at 5 years. The mean survival time after the first treatment was 31.1 months (95% CI, 26.9-35.3 months). Laser ablation of liver metastases of colorectal cancer with MR thermometry appears safe and efficacious. Although the results are encouraging, direct comparison with other ablative modalities in a prospective clinical trial would be necessary to definitely show one modality is superior.
    Journal of vascular and interventional radiology: JVIR 01/2009; 20(2):225-34. · 1.81 Impact Factor
  • JP Kühn, S Hadlich
    Rofo-fortschritte Auf Dem Gebiet Der Rontgenstrahlen Und Der Bildgebenden Verfahren - ROFO-FORTSCHR RONTGENSTRAHL. 01/2009; 181.
  • J P Kühn, K Hegenscheid, R Puls
    RöFo - Fortschritte auf dem Gebiet der R 11/2008; 180(10):922-4. · 2.76 Impact Factor
  • RöFo - Fortschritte auf dem Gebiet der R 11/2008; 180(12):1131-3. · 2.76 Impact Factor
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    ABSTRACT: This article reports on the use of magnetic resonance imaging to access the post-interventional necrosis volume of liver metastases immediately after and 48 hours after LITT. In this prospective study, 56 liver metastases from 39 patients (16 females, 23 males, mean age 60.4 years) underwent LITT. The 56 metastases were divided into 4 groups according to the ablation strategy (dependent on multi-applicator technique and laser duration). Groups I and II were treated with an applicator and a time of ablation greater than 15 minutes and 20 minutes, respectively. In groups III and IV the multi-applicator technology with 3 or 4 applicators and a constant ablation time of 20 minutes were used. With the help of heightened contrast MRI of the liver, the portrayal of the post-interventional necrosis was conducted immediately after LITT and 48 hours after LITT. The post-interventional controls after 48 hours were performed during the inpatient stay. The protocol was complemented by an outpatient long-term control after more than 3 months. The local tumor control rate was initially 96.4%. After 3 months it decreased to 92.1%. The mean necrosis volume directly after LITT was: Group I (n = 11; 1 applicator, 30 watt, 10-15 minutes) 6.69 cm(3); Group II (n = 13; 1 applicator, 30 watt, 20 minutes) 10.95 cm(3); Group III (n = 28; 2 applicator, 30 watt, 10-15 minutes) 21.47 cm(3); Group IV (n = 4; 3 applicator, 30 watt, 20 minutes) 40.20 cm(3). In comparison, the necrosis volume after 48 hours increased: Group I 10.56 cm(3); Group II 15.11 cm(3); Group III 31.33 cm(3), Group IV 55.73 cm(3)). After 48 hours a progressive increase of post-interventional necrosis volumes compared to volumes directly after LITT was able to be observed. An MRI control after 48 hours, as opposed to an MRI control directly after intervention, is a better indicator for post-interventional success after LITT.
    RöFo - Fortschritte auf dem Gebiet der R 10/2008; 180(9):816-20. · 2.76 Impact Factor
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    ABSTRACT: Two patients with dissecting (n = 1) and saccular (n = 1) aneurysms of the infrarenal abdominal aorta with very narrow proximal and distal aortic necks underwent treatment with percutaneous implantation of self-expandable polytetrafluoroethylene (PTFE)-covered nitinol stent-grafts on an off-label basis. The stent-grafts had maximum diameters of 13.5 mm and were deployed via 10-F introducer sheaths. Complete coverage of both aneurysms was achieved without evidence of endoleaks. The only complication observed was a pseudoaneurysm of the femoral access site in one patient, which was treated conservatively. Based on the experience described in this report, an aortic aneurysm with a narrow aortic neck can be safely treated with a PTFE-covered nitinol stent-graft.
    Journal of vascular and interventional radiology: JVIR 10/2008; 19(9):1378-81. · 1.81 Impact Factor