Gernot M. Kaiser

Interventional magnetic resonance angiography with no strings attached: wireless active catheter visualization.

Active instrument visualization strategies for interventional MR angiography (MRA) require vascular instruments to be equipped with some type of radiofrequency (RF) coil or dipole RF antenna for MR signal detection. Such visualization strategies traditionally necessitate a connection to the scanner with either coaxial cable or laser fibers. In order to eliminate any wire connection, RF resonators that inductively couple their signal to MR surface coils were implemented into catheters to enable wireless active instrument visualization. Instrument background to contrast‐to‐noise ratio was systematically investigated as a function of the excitation flip angle. Signal coupling between the catheter RF coil and surface RF coils was evaluated qualitatively and quantitatively as a function of the catheter position and orientation with regard to the static magnetic field B0 and to the surface coils. In vivo evaluation of the instruments was performed in interventional MRA procedures on five pigs under MR guidance. Cartesian and projection reconstruction TrueFISP imaging enabled simultaneous visualization of the instruments and vascular morphology in real time. The implementation of RF resonators enabled robust visualization of the catheter curvature to the very tip. Additionally, the active visualization strategy does not require any wire connection to the scanner and thus does not hamper the interventionalist during the course of an intervention. Magn Reson Med 53:446–455, 2005.

Inductively coupled stent antennas in MRI

The development of intimal hyperplasia following stent deployment can lead to narrowing or even occlusion of the stent lumen. The underlying mechanisms leading to neointimal proliferation within stents remain largely unknown. Long‐term evaluation of stent patency requires a noninvasive means for assessing the stent lumen. MR angiography (MRA) has shown potential to provide noninvasive assessment of the vascular system. However, a detailed assessment of the stent lumen with MRI is often hampered by material‐dependent susceptibility artifacts, as well as by radiofrequency (RF) eddy currents generated inside the electrically conducting stent mesh. In this study, stent prototypes were designed to act as active resonant structures at the Larmor frequency of the MR system. Employing the principle of inductive coupling, the B1 fields of the stents were coupled to that of an outside surface coil. The stents thus acted as local RF signal amplifiers. Various stent designs were investigated regarding their coupling to an external coil, signal homogeneity, and suitability for mechanical expansion for implantation purposes. The dependency of flip angle amplification on the quality factor Q of the stents was systematically investigated. Phantom experiments revealed signal amplification in all stent prototypes. Signal enhancement inside and close to the surface of the stents enabled their localization with high contrast in MR images. In vivo imaging experiments in the iliac, renal, and splenic arteries of two pigs confirmed the in vitro findings. Wireless active visualization of stents allows for detailed analysis of the stent lumen with high contrast and spatial resolution. The proposed method could thus provide a powerful diagnostic means for the noninvasive long‐term follow‐up of stent patency, thereby enhancing our understanding of the mechanisms of restenosis. Magn Reson Med 48:781–790, 2002.

Efficacy, safety, and immunosuppressant adherence in stable liver transplant patients converted from a twice-daily tacrolimus-based regimen to once-daily tacrolimus extended-release formulation

The aim of this study was to determine the efficacy, safety, and immunosuppressant adherence in 125 stable liver transplant (LT) patients converted from twice‐daily tacrolimus (TAC BID) to once‐daily TAC (TAC OD). Tacrolimus trough levels, laboratory parameters, metabolic disorders, selected patient reported outcomes, and adverse events were assessed. Mean TAC trough level concentration was 6.1u2003±u20032.3u2003ng/ml at study entry, decreased to 5.5u2003±u20032.1u2003ng/ml (Pu2003=u20030.016) and 5.5u2003±u20032.2u2003ng/ml (Pu2003=u20030.019) after 1 and 2u2003weeks, respectively, and tended to equal the baseline value during further follow‐up. At week 1, TAC concentrations were lower in 62.4% of patients and higher in 36.0% when compared with baseline. Renal and cardiovascular risk factors remained stable and no rejection episodes occurred over 12u2003months. Adverse events were consistent with the safety profile known from previous studies with TAC BID. Nonadherence measured by the “Basel Assessment of Adherence Scale to Immunosuppressives” was evident in 66.4% at study entry and decreased to 30.9% postconversion (Pu2003<u20030.0001). Prevalence of nonadherence at baseline was significantly higher in patients converted >2u2003years after LT and in those ≤60u2003years of age. Conversion to TAC OD is safe, enhances immunosuppressant adherence and should be accompanied by a close TAC level monitoring during the initial period.

Interventional MRA using actively visualized catheters, TrueFISP, and real‐time image fusion

An integrated system for performing interventional magnetic resonance angiography (MRA) with actively visualized instruments and real‐time image fusion was implemented on a 1.5 T scanner. True fast imaging with steady precession (TrueFISP) imaging provided high acquisition speed paired with high signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR) for the simultaneous visualization of active instruments and arterial morphology. The system enabled simultaneous image reconstruction and image postprocessing of multiple receiver channels, with subsequent image fusion display in real time. Optional interleaved image acquisition in two planes provided additional important information for biplanar instrument guidance. Various vascular interventions, including selective catheterization and subsequent selective MRA of the abdominal aorta, renal arteries, superior mesenteric artery (SMA), hepatic artery, and aortic arch, were performed on 10 pigs under MR guidance. In terms of instrument contrast, image acquisition, reconstruction, and fusion speed, the setup represents a powerful platform for performing interventional MRA procedures. Magn Reson Med 49:129–137, 2003.

Systematic analysis of functional and structural changes after coronary microembolization: a cardiac magnetic resonance imaging study.

OBJECTIVESnOur study aimed to detect the morphological und functional effects of coronary microembolization (ME) in vivo by cardiac magnetic resonance (CMR) imaging in an established experimental animal model.nnnBACKGROUNDnPost-mortem morphological alterations of coronary ME include perifocal inflammatory edema and focal microinfarcts. Clinically, the detection of ME after successful coronary interventions identifies a population with a worse long-term prognosis.nnnMETHODSnIn 18 minipigs, ME was performed by intracoronary infusion of microspheres followed by repetitive in vivo imaging on a 1.5-T MR system from 30 min to 8 h after ME. Additionally, corresponding ex vivo CMR imaging and histomorphology were performed.nnnRESULTSnCine CMR imaging demonstrated a time-dependent increase of wall motion abnormalities from 9 of 18 animals after 30 min to all animals after 8 h (0.5 h, 50%; 2 h, 78%; 4 h, 75%; 8 h, 100%). Whereas T2 images were negative 30 min after ME, 4 of 18 animals showed myocardial edema at follow-up (0.5 h, 0%; 2 h, 6%; 4 h, 25%; 8 h, 17%). In vivo late gadolinium enhancement (LGE) was observed in none of the animals after 30 min, but in 33%, 50%, and 83% of animals at 2 h, 4 h, and 8 h, respectively, after ME. Ex vivo CMR imaging showed patchy areas of LGE in all but 1 animal (2 h, 83%; 4 h, 100%; 8 h, 100%). A significant correlation was seen between the maximum troponin I level and LGE in vivo (r = 0.63) and the spatial extent of ex vivo LGE (r = 0.76).nnnCONCLUSIONSnOur results show that in vivo contrast-enhanced CMR imaging allows us to detect functional and structural myocardial changes after ME with a high sensitivity. Ex vivo, the pattern of LGE of high-resolution, contrast-enhanced CMR imaging is different from the well-known pattern of LGE in compact myocardial damage. Thus, improvements in spatial resolution are thought to be necessary to improve its ability to visualize ME-induced structural alterations even in vivo.

How Much Myocardial Damage Is Necessary to Enable Detection of Focal Late Gadolinium Enhancement at Cardiac MR Imaging

PURPOSEnTo assess the visibility of small myocardial lesions at magnetic resonance (MR) imaging and to estimate how much myocardial damage is necessary to enable detection of late gadolinium enhancement (LGE) in vivo.nnnMATERIALS AND METHODSnThe study was approved by the local bioethics committee. Coronary microembolization was performed by injecting 300,000 microspheres into the distal portion of the left anterior descending artery in 18 anesthetized minipigs to create multifocal areas of myocardial damage. In vivo MR imaging was performed a mean of 6 hours after microembolization by using an inversion-recovery spoiled gradient-echo sequence (repetition time msec/echo time msec, 8/4; inversion time, 240-320 msec; flip angle, 20 degrees; spatial resolution, 1.3 x 1.7 x 5.0 mm(3)) after injection of 0.2 mmol gadopentetate dimeglumine per kilogram of body weight. High-spatial-resolution imaging of the explanted heart was performed by using the same sequence with a higher spatial resolution (0.5 x 0.5 x 2.0 mm(3)). Imaging results were verified with histologic examination. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of in vivo and ex vivo images were calculated, and a t test was used to analyze observed differences.nnnRESULTSnMultifocal myocardial damage was successfully induced in all animals. Areas of LGE with low SNR (mean, 36.3 +/- 29.4 [standard deviation]) and CNR (23.7 +/- 19.8) were observed in vivo in 12 (67%) of 18 animals, whereas ex vivo imaging revealed spotted to streaky areas of LGE with higher SNR (91.4 +/- 27.8, P < .0001) and CNR (72.1 +/- 25.4, P < .0001) among normal-appearing myocardium in all cases (100%). Focal myocardial lesions exceeding 5% of myocardium per slice at histologic examination were detected in vivo with a sensitivity of 83%.nnnCONCLUSIONnFocal myocardial damage exceeding 5% of myocardium within the region of interest seems to be necessary for detection of LGE in vivo in an experimental model of coronary microembolization.

Three-year Outcomes in de Novo Liver Transplant Patients Receiving Everolimus with Reduced Tacrolimus: Follow-Up Results from a Randomized, Multicenter Study

Background Data are lacking regarding the long-term effect of preemptive conversion to everolimus from calcineurin inhibitors early after liver transplantation to avoid renal deterioration. Methods In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30 to (i) everolimus + reduced exposure tacrolimus (EVR + Reduced TAC), (ii) everolimus + tacrolimus elimination (TAC Elimination), or (iii) standard exposure tacrolimus (TAC Control). Results Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR) during TAC withdrawal. Of 370 patients who completed the 24-month core study on-treatment, 282 (76.2%) entered an additional 12-month extension phase. The composite efficacy failure endpoint (tBPAR, graft loss or death) occurred in 11.5% of EVR+Reduced TAC patients versus 14.6% TAC Controls from randomization to month 36 (difference, ‐3.2%; 95% confidence interval, ‐10.5% to 4.2%; P = 0.334). Treated BPAR occurred in 4.8% versus 9.2% of patients (P = 0.076). From randomization to month 36, mean (SD) estimated glomerular filtration rate decreased by 7.0 (31.3) mL/min per 1.73 m2 in the EVR+Reduced TAC group, and 15.5 (22.7) mL/min per 1.73 m2 in the TAC Control group (P = 0.005). Rates of adverse events, serious adverse events, and discontinuation due to adverse events were similar in both groups during the extension. Conclusions A clinically relevant renal benefit after introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation was maintained to 3 years in patients who continued everolimus therapy to the end of the core study, with comparable efficacy and no late safety concerns.

Liver Transplantation in Nonalcoholic Steatohepatitis Is Associated with High Mortality and Post-Transplant Complications: A Single-Center Experience

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) with its progressive form nonalcoholic steatohepatitis (NASH) is the most common chronic liver disease in western countries which is associated with end-stage liver disease and hepatocellular carcinoma (HCC). This entity is a consistently increasing indication for transplantation. However, data about postsurgery outcome and complications are still limited. Patients and Methods: Records of 432 consecutive transplanted patients between October 2007 and January 2011 were investigated retrospectively. Forty transplants were performed due to NASH-induced cirrhosis. Perioperative courses and short- and long-term outcomes were analyzed. Results: The NAFLD population consisted of 16 women and 24 men with a mean age of 55 years. The median MELD score was 27 at the time of liver transplantion. BMI before surgery ranged from 21 to 45 (mean 31). Sixteen of the initial 40 patients are still alive. Patients with sustained obesity and features of the metabolic syndrome had a worse 1-year mortality rate of 42%. Conclusions: A significant number of liver transplantations in our center was performed due to NASH; transplantation in this cohort was associated with high mortality and postoperative complications, most likely due to associated obesity and diabetes. Weight reduction prior to surgery may lead to a better outcome.

First magnetic resonance imaging-guided aortic stenting and cava filter placement using a polyetheretherketone-based magnetic resonance imaging-compatible guidewire in swine: proof of concept.

The purpose of this study was to demonstrate feasibility of percutaneous transluminal aortic stenting and cava filter placement under magnetic resonance imaging (MRI) guidance exclusively using a polyetheretherketone (PEEK)-based MRI-compatible guidewire. Percutaneous transluminal aortic stenting and cava filter placement were performed in 3 domestic swine. Procedures were performed under MRI-guidance in an open-bore 1.5-T scanner. The applied 0.035-inch guidewire has a PEEK core reinforced by fibres, floppy tip, hydrophilic coating, and paramagnetic markings for passive visualization. Through an 11F sheath, the guidewire was advanced into the abdominal (swine 1) or thoracic aorta (swine 2), and the stents were deployed. The guidewire was advanced into the inferior vena cava (swine 3), and the cava filter was deployed. Postmortem autopsy was performed. Procedural success, guidewire visibility, pushability, and stent support were qualitatively assessed by consensus. Procedure times were documented. Guidewire guidance into the abdominal and thoracic aortas and the inferior vena cava was successful. Stent deployments were successful in the abdominal (swine 1) and thoracic (swine 2) segments of the descending aorta. Cava filter positioning and deployment was successful. Autopsy documented good stent and filter positioning. Guidewire visibility through applied markers was rated acceptable for aortic stenting and good for venous filter placement. Steerability, pushability, and device support were good. The PEEK-based guidewire allows either percutaneous MRI-guided aortic stenting in the thoracic and abdominal segments of the descending aorta and filter placement in the inferior vena cava with acceptable to good device visibility and offers good steerability, pushability, and device support.

All-In-One: Advanced preparation of Human Parenchymal and Non-Parenchymal Liver Cells

Background & Aims Liver cells are key players in innate immunity. Thus, studying primary isolated liver cells is necessary for determining their role in liver physiology and pathophysiology. In particular, the quantity and quality of isolated cells are crucial to their function. Our aim was to isolate a large quantity of high-quality human parenchymal and non-parenchymal cells from a single liver specimen. Methods Hepatocytes, Kupffer cells, liver sinusoidal endothelial cells, and stellate cells were isolated from liver tissues by collagenase perfusion in combination with low-speed centrifugation, density gradient centrifugation, and magnetic-activated cell sorting. The purity and functionality of cultured cell populations were controlled by determining their morphology, discriminative cell marker expression, and functional activity. Results Cell preparation yielded the following cell counts per gram of liver tissue: 2.0±0.4×107 hepatocytes, 1.8±0.5×106 Kupffer cells, 4.3±1.9×105 liver sinusoidal endothelial cells, and 3.2±0.5×105 stellate cells. Hepatocytes were identified by albumin (95.5±1.7%) and exhibited time-dependent activity of cytochrome P450 enzymes. Kupffer cells expressed CD68 (94.5±1.2%) and exhibited phagocytic activity, as determined with 1μm latex beads. Endothelial cells were CD146+ (97.8±1.1%) and exhibited efficient uptake of acetylated low-density lipoprotein. Hepatic stellate cells were identified by the expression of α-smooth muscle actin (97.1±1.5%). These cells further exhibited retinol (vitamin A)-mediated autofluorescence. Conclusions Our isolation procedure for primary parenchymal and non-parenchymal liver cells resulted in cell populations of high purity and quality, with retained physiological functionality in vitro. Thus, this system may provide a valuable tool for determining liver function and disease.