Purpose Develop a deflectable intracardiac MR imaging (ICMRI) guiding‐sheath to accelerate imaging during MR‐guided electrophysiological (EP) interventions for radiofrequency (500 kHz) ablation (RFA) of arrythmia. Requirements include imaging at three to five times surface‐coil SNR in cardiac chambers, vascular insertion, steerable‐active‐navigation into cardiac chambers, operation with ablation catheters, and safe levels of MR‐induced heating. Methods ICMRI’s 6 mm outer‐diameter (OD) metallic‐braided shaft had a 2.6 mm OD internal lumen for ablation‐catheter insertion. Miniature‐Baluns (MBaluns) on ICMRI’s 1 m shaft reduced body‐coil‐induced heating. Distal section was a folded “star”‐shaped imaging‐coil mounted on an expandable frame, with an integrated miniature low‐noise‐amplifier overcoming cable losses. A handle‐activated movable‐shaft expanded imaging‐coil to 35 mm OD for imaging within cardiac‐chambers. Four MR‐tracking micro‐coils enabled navigation and motion‐compensation, assuming a tetrahedron‐shape when expanded. A second handle‐lever enabled distal‐tip deflection. ICMRI with a protruding deflectable EP catheter were used for MR‐tracked navigation and RFA using a dedicated 3D‐slicer user‐interface. ICMRI was tested at 3T and 1.5T in swine to evaluate (a) heating, (b) cardiac‐chamber access, (c) imaging field‐of‐view and SNR, and (d) intraprocedural RFA lesion monitoring. Results The 3T and 1.5T imaging SNR demonstrated >400% SNR boost over a 4 × 4 × 4 cm 3 FOV in the heart, relative to body and spine arrays. ICMRI with MBaluns met ASTM/IEC heating limits during navigation. Tip‐deflection allowed navigating ICMRI and EP catheter into atria and ventricles. Acute‐lesion long‐inversion‐time‐T1‐weighted 3D‐imaging (TWILITE) ablation‐monitoring using ICMRI required 5:30 min, half the time needed with surface arrays alone. Conclusion ICMRI assisted EP‐catheter navigation to difficult targets and accelerated RFA monitoring.
BACKGROUND External defibrillators are used for arrhythmia cardioversion and for defibrillating during cardiac arrest. During defibrillation, short-duration biphasic pulses cause intense motion due to rapid chest-wall muscle contraction. A reduced motion external defibrillator (RMD) was constructed by integrating a commercial defibrillator with a Tetanizing-waveform generator. A long-duration, low-amplitude, tetanizing waveform slowly stimulated the chest musculature before the biphasic pulse, reducing muscle contraction during the shock. OBJECTIVE The purpose of this study was to evaluate RMD defibrillation in swine for subject motion during defibrillation pulses and for defibrillation effectiveness. RMD defibrillation can reduce the duration of arrhythmia ablation therapy or simplify cardioversion procedures. METHODS The tetanizing unit delivered a triangular 1-kHz pulse of 0.25- to 2.0-second duration and 10- to 100-V peak amplitude, subsequently triggering the conventional defibrillator to output standard 1- to 200-J energy biphasic pulses at the next R wave. Forward limb motion was evaluated by measuring peak acceleration and limb work during RMD (tetanizing + biphasic) or biphasic pulse-only waveforms at 10(-3)-second sampling rate. Seven swine were arrested electrically and subsequently defibrillated. Biphasic pulse-only and RMD defibrillations were repeated 25-35 times per swine, varying tetanizing parameters and biphasic pulse energy. Defibrillation thresholds (DFTs) were established by measuring the minimum energy required to restore sinus rhythm with biphasic pulse-only or RMD defibrillations. RESULTS Two forward-limb acceleration peaks occurred during both the tetanizing waveform and biphasic pulse, indicating rapid and slower nociceptic (pain sensation) nerve fiber activation. Optimal RMD tetanizing parameters (25-35 V, 0.25- to 0.75-second duration), relative to biphasic pulse-only defibrillations, resulted in 74% +/- 10% smaller peak accelerations and 85% +/- 10% reduced limb work. DFT energies were identical when comparing RMD to biphasic pulse-only defibrillations. CONCLUSION Relative to conventional defibrillations, RMD defibrillations maintain rhythm restoration efficiency with drastically reduced subject motion.
The formation of new blood vessels and the establishment of vascular networks are crucial during brain development, in the adult healthy brain, as well as in various diseases of the central nervous system. Here, we describe a step-by-step protocol for our recently developed method that enables hierarchical imaging and computational analysis of vascular networks in postnatal and adult mouse brains. The different stages of the procedure include resin-based vascular corrosion casting, scanning electron microscopy, synchrotron radiation and desktop microcomputed tomography imaging, and computational network analysis. Combining these methods enables detailed visualization and quantification of the 3D brain vasculature. Network features such as vascular volume fraction, branch point density, vessel diameter, length, tortuosity and directionality as well as extravascular distance can be obtained at any developmental stage from the early postnatal to the adult brain. This approach can be used to provide a detailed morphological atlas of the entire mouse brain vasculature at both the postnatal and the adult stage of development. Our protocol allows the characterization of brain vascular networks separately for capillaries and noncapillaries. The entire protocol, from mouse perfusion to vessel network analysis, takes ~10 d.
Purpose To develop an endovaginal MRI array that provides signal enhancement forward into the posterior parametrium and sideways into the vaginal wall, accelerating multiple-contrast detection of residual tumors that survive external beam radiation. The array's enclosure should form an obturator for cervical cancer brachytherapy, allowing integration with MRI-guided catheter placement, CT, and interstitial radiation dose delivery. Methods The endovaginal array consisted of forward-looking and sideways-looking components. The forward-looking element imaged the cervix and posterior endometrium, and the sideways-looking elements imaged the vaginal wall. Electromagnetic simulation was performed to optimize the geometry of a forward-looking coil placed on a conductive-metallic substrate, extending the forward penetration above the coil's tip. Thereafter, an endovaginal array with one forward-looking coil and four sideways-looking elements was constructed and tested at 1.5 Tesla in saline and gel phantoms, and three sexually mature swine. Each coil's tuning, matching, and decoupling were optimized theoretically, implemented with electronic circuits, and validated with network-analyzer measurements. The array enclosure emulates a conventional brachytherapy obturator, allowing use of the internal imaging array together with tandem coils and interstitial catheters, as well as use of the enclosure alone during CT and radiation delivery. To evaluate the receive magnetic field (B1-) spatial profile, the endovaginal array's specific absorption-rate (SAR) distribution was simulated inside a gel ASTM phantom to determine extreme heating locations in advance of a heating test. Heating tests were then performed during high SAR imaging in a gel phantom at the predetermined locations, testing compliance with MRI safety standards. To assess array imaging performance, signal-to-noise-ratios (SNR) were calculated in a saline phantom and in vivo. Swine images were acquired with the endovaginal array combined with the scanner's body and spine arrays. Results Simulated B1- profiles for the forward-looking lobe pattern, obtained while varying several geometric parameters, disclosed that a forward-looking coil placed on a metal-backed substrate could double the effective forward penetration from approximately 25 to similar to 40 mm. An endovaginal array, enclosed in an obturator enclosure was then constructed, with all coils tuned, matched, and decoupled. The ASTM gel-phantom SAR test showed that peak local SAR was 1.2 W/kg in the forward-looking coil and 0.3 W/kg in the sideways-looking elements, well within ASTM/FDA/IEC guidelines. A 15-min 4 W/kg average SAR imaging experiment resulted in less than 2(o)C temperature increase, also within ASTM/FDA/IEC heating limits. In a saline phantom, the forward-looking coil and sideways-looking array's SNR was four to eight times, over a 20-30 mm field-of-view (FOV), and five to eight times, over a 15-25 mm FOV, relative to the spine array's SNR, respectively. In three sexually mature swine, the forward-looking coil provided a 5 + 0.2 SNR enhancement factor within the cervix and posterior endometrium, and the sideways-looking array provided a 4 + 0.2 SNR gain factor in the vaginal wall, relative to the Siemens spine array, demonstrating that the array could significantly reduce imaging time. Conclusions Higher SNR gynecological imaging is supported by forward-looking and sideways-looking coils. A forward-looking endovaginal coil for cervix and parametrium imaging was built with optimized metal backing. Array placement within an obturator enhanced integration with the brachytherapy procedure and accelerated imaging for detecting postexternal-beam residual tumors.
Objective: Cardiovascular interventional devices typically have long metallic braids or backbones to aid in steerability and pushability. However, electromagnetic coupling of metallic-based cardiovascular interventional devices with the radiofrequency (RF) fields present during Magnetic Resonance Imaging (MRI) can make a device unsafe for use in an MRI scanner. We aimed to develop MRI conditional actively-tracked cardiovascular interventional devices by sufficiently attenuating induced currents on the metallic braid/tube and internal-cabling using miniaturized resonant floating RF traps (MBaluns). Method: MBaluns were designed for placement at multiple locations along a conducting cardiovascular device to prevent the establishment of standing waves and to dissipate RF-induced energy. The MBaluns were constructed with loosely-wound solenoids to be sensitive to transverse magnetic fields created by both surface currents on the device's metallic backbone and common-mode currents on internal cables. Electromagnetic simulations were used to optimize MBalun parameters. Following optimization, two different MBalun designs were applied to MR-actively-tracked metallic guidewires and metallic-braided electrophysiology ablation catheters. Control-devices were constructed without MBaluns. MBalun performance was validated using network-analyzer quantification of current attenuation, electromagnetic Specific-Absorption-Rate (SAR) analysis, thermal tests during high SAR pulse sequences, and MRI-guided cardiovascular navigation in swine. Results: Electromagnetic SAR simulations resulted in ≈20 dB attenuation at the tip of the wire using six successive MBaluns. Network-analyzer tests confirmed ∼17 dB/MBalun surface-current attenuation. Thermal tests indicated temperature decreases of 5.9 °C in the MBalun-equipped guidewire tip. Both devices allowed rapid vascular navigation resulting from good torquability and MR-Tracking visibility. Conclusion: MBaluns increased device diameter by 20%, relative to conventional devices, providing a spatially-efficient means to prevent heating during MRI. Significance: MBaluns allow use of long metallic components, which improves mechanical performance in active MR-guided interventional devices.
Brain tumors are among the most malignant primary tumors, hallmarked by angiogenesis, neuronal destruction and brain swelling. Inhibition of the glutamate-cystein antiporter xCT (system xc−/SLC7A11) alleviates seizures, neuronal cell death and tumor-associated brain edema. Here we show enhanced tumor vessel growth and increased brain edema in xCT-expressing brain tumors. Furthermore, xCT-mediated glutamate impacts directly on endothelial cells in an N-methyl-D-aspartate receptor (NMDAR) dependent manner with intracellular Ca2+ release. Cerebral intravital microscopy revealed that xCT-driven tumor vessels are functional and display increased permeability. Endothelial-cell-specific NMDAR1 knockout mice (GRINiΔEC) show suppressed endothelial sprouting and vascular density compared to control littermates. In addition, implanted gliomas in GRINiΔEC mice display reduced tumor vessels in contrast to gliomas in wildtype animals. Moreover, therapeutic targeting of xCT in gliomas alleviates tumor angiogenesis to normalized levels comparable to controls. Our data reveal that xCT and its substrate glutamate specifically operate on endothelial cells and promote neoangiogenesis. Thus, targeting xCT expression and glutamate secretion in gliomas provides a novel therapeutic roadmap for normalizing tumor angiogenesis.
Many drugs have been reported to cause thrombotic microangiopathy (TMA), yet evidence supporting a direct association is often weak. In particular, TMA has been reported in association with recombinant type I interferon (IFN) therapies, with recent concern regarding the use of IFN in multiple sclerosis patients. However, a causal association has yet to be demonstrated. Here, we adopt a combined clinical and experimental approach to provide evidence of such an association between type I IFN and TMA. We show that the clinical phenotype of cases referred to a national center is uniformly consistent with a direct dose-dependent drug-induced TMA. We then show that dose-dependent microvascular disease is seen in a transgenic mouse model of IFN toxicity. This includes specific microvascular pathological changes seen in patient biopsies and is dependent on transcriptional activation of the IFN response through the type I interferon α/β receptor (IFNAR). Together our clinical and experimental findings provide evidence of a causal link between type I IFN and TMA. As such, recombinant type I IFN therapies should be stopped at the earliest stage in patients who develop this complication, with implications for risk mitigation.
Recently, we discovered a new role for the well-known axonal growth inhibitory molecule Nogo-A as a negative regulator of angiogenesis in the developing central nervous system. However, how Nogo-A affected the three-dimensional (3D) central nervous system (CNS) vascular network architecture remained unknown. Here, using vascular corrosion casting, hierarchical, synchrotron radiation μCT-based network imaging and computer-aided network analysis, we found that genetic ablation of Nogo-A significantly increased the three-dimensional vascular volume fraction in the postnatal day 10 (P10) mouse brain. More detailed analysis of the cerebral cortex revealed that this effect was mainly due to an increased number of capillaries and capillary branchpoints. Interestingly, other vascular parameters such as vessel diameter, -length, -tortuosity, and -volume were comparable between both genotypes for non-capillary vessels and capillaries. Taken together, our three-dimensional data showing more vessel segments and branchpoints at unchanged vessel morphology suggest that stimulated angiogenesis upon Nogo-A gene deletion results in the insertion of complete capillary micro-networks and not just single vessels into existing vascular networks. These findings significantly enhance our understanding of how angiogenesis, vascular remodeling, and three-dimensional vessel network architecture are regulated during central nervous system development. Nogo-A may therefore be a potential novel target for angiogenesis-dependent central nervous system pathologies such as brain tumors or stroke.
Malfunction of oxygen regulation in kidney and liver may lead to the pathogenesis of chronic diseases. The underlying mechanisms are poorly understood. In kidney, it is hypothesized that renal gas shunting from arteries to veins eliminates excess oxygen. Such shunting is highly dependent on the structure of the renal vascular network. The vascular tree has so far not been quantified under maintenance of its connectivity as three-dimensional imaging of the vessel tree down to the smallest capillaries, which in mouse model are smaller than 5 μm in diameter, is a challenging task. An established protocol uses corrosion casts and applies synchrotron radiation-based micro-computed tomography (SRμCT), which provides the desired spatial resolution with the necessary contrast. However, SRμCT is expensive and beamtime access is limited. We show here that measurements with a phoenix nanotomrm (General Electric, Wunstorf, Germany) can provide comparable results to those obtained with SRμCT, except for regions with small vessel structures, where the signal-to-noise level was significantly reduced. For this purpose the nanotom®m measurement was compared with its corresponding measurement acquired at the beamline P05 at PETRA III at DESY, Hamburg, Germany.
Cerebrovascular lesions related to congophilic amyloid angiopathy (CAA) often accompany deposition of β-amyloid (Aβ) in Alzheimer’s disease (AD), leading to disturbed cerebral blood flow and cognitive dysfunction, posing the question how cerebrovascular pathology contributes to the pathology of AD. To address this question, we characterised the morphology, biochemistry and functionality of brain blood vessels in transgenic arctic β-amyloid (arcAβ) mice expressing human amyloid precursor protein (APP) with both the familial AD-causing Swedish and Arctic mutations; these mice are characterised by strong CAA pathology. Mice were analysed at early, mid and late-stage pathology. Expression of the glucose transporter GLUT1 at the blood–brain barrier (BBB) was significantly decreased and paralleled by impaired in vivo blood-to-brain glucose transport and reduced cerebral lactate release during neuronal activation from mid-stage pathology onwards. Reductions in astrocytic GLUT1 and lactate transporters, as well as retraction of astrocyte endfeet and swelling consistent with neurovascular uncoupling, preceded wide-spread β-amyloid plaque pathology. We show that CAA at later disease stages is accompanied by severe morphological alterations of brain blood vessels including stenoses, BBB leakages and the loss of vascular smooth muscle cells (SMCs). Together, our data establish that cerebrovascular and astrocytic pathology are paralleled by impaired cerebral metabolism in arcAβ mice, and that astrocyte alterations occur already at premature stages of pathology, suggesting that astrocyte dysfunction can contribute to early behavioural and cognitive impairments seen in these mice.
Recent evidence suggests a close functional relationship between osteogenesis and angiogenesis as well as between bone remodeling and bone vascularization. Consequently, there is a need for visual inspection and quantitative analysis of the bone vasculature. We therefore adapted and implemented two different vascular corrosion casting (VCC) protocols using a polyurethane-based casting resin in mice for a true three-dimensional (3D), direct, and simultaneous measurement of bone tissue and vascular morphology by micro-computed tomography (microCT). For assessment of vascular replicas at the level of capillaries, a vascular contrast perfusion (VCP) protocol was devised using a contrast modality based on a barium sulfate suspension in conjunction with synchrotron radiation (SR) microCT. The vascular morphology quantified using the VCP protocol was compared quantitatively with the results of a previously established method, where the vascular network of cortical bone was derived indirectly from cortical porosity. The presented VCC and VCP protocols have the potential of serving as a valuable method for concomitant 3D quantitative morphometry of the bone tissue and its vasculature.
Brain edema is a hallmark of human malignant brain tumors and contributes to the clinical course and outcome of brain tumor patients. The so-called perifocal edema or brain swelling imposes in T2-weighted MR scans as high intensity areas surrounding the bulk tumor mass. The mechanisms of this increased fluid attraction and the cellular composition of the microenvironment are only partially understood. In this study, we focus on imaging perifocal edema in orthotopically implanted gliomas in rodents and correlate perifocal edema with immunohistochemical markers. We identified that areas of perifocal edema not only include the tumor invasion zone, but also are associated with increased glial fibrillary acidic protein (GFAP) and aquaporin-4 expression surrounding the bulk tumor mass. Moreover, a high number of activated microglial cells expressing CD11b and macrophage migration inhibitory factor (MIF) accumulate at the tumor border. Thus, the area of perifocal edema is mainly dominated by reactive changes of vital brain tissue. These data corroborate that perifocal edema identified in T2-weighted MR scans are characterized with alterations in glial cell distribution and marker expression forming an inflammatory tumor microenvironment. (Cancer Sci 2009; 100: 1856-1862).
Several soft-tissue imprints and attachment sites have been discovered on the inside of the shell wall and on the apertural side of the septum of various fossil and Recent ectocochleate cephalopods. In addition to the scars of the cephalic retractors, steinkerns of the body chambers of bactritoids and some ammonoids from the Moroccan and the German Emsian (Early Devonian) display various kinds of striations; some of these striations are restricted to the mural part of the septum, some start at the suture and terminate at the anterior limit of the annular elevation. Several of these features were also discovered in specimens of Mesozoic and Recent nautilids. These structures are here interpreted as imprints of muscle fibre bundles of the posterior and especially the septal mantle, blood vessels as well as the septal furrow. Most of these structures were not found in ammonoids younger than Middle Devonian. We suggest that newly formed, not yet mineralized (or only slightly), septa were more tightly stayed between the more numerous lobes and saddles in more strongly folded septa of more derived ammonoids and that the higher tension in these septa did not permit soft-parts to leave imprints on the organic preseptum. It is conceivable that this permitted more derived ammonoids to replace the chamber liquid faster by gas and consequently, new chambers could be used earlier than in other ectocochleate cephalopods, perhaps this process began even prior to mineralization. This would have allowed faster growth rates in derived ammonoids.
Substantial evidence from epidemiological, pathological, and clinical reports suggests that vascular factors are critical in the pathogenesis of Alzheimer's disease (AD), and changes in blood flow are currently the most reliable indicators of the disease. We previously reported that older APP23 transgenic (tg) mice have significant blood flow alterations correlated with structural modifications of blood vessels. For the present study, our objective was to analyze the age-dependent morphological and architectural changes of the cerebral vasculature of APP23 tg mice. To visualize the 3D arrangement of the entire brain vasculature, we used vascular corrosion casts. Already at young ages, when typically parenchymal amyloid plaques are not yet present, APP23 tg mice had significant alterations, particularly of the microvasculature, often accompanied by small deposits attached to the vessels. In older animals, vasculature abruptly ended at amyloid plaques, resulting in holes. Often, small deposits were sitting near or at the end of truncated vessels. Between such holes, the surrounding vascular array appeared more dense and showed features typical for angiogenesis. We propose that small amyloid aggregates associated with the microvasculature lead to morphological and architectural alterations of the vasculature, resulting in altered local blood flow. The characteristic early onset of vascular alterations suggests that imaging blood flow and/or vasculature architecture could be used as a tool for early diagnosis of the disease and to monitor therapies.
To adequately supply tissues with oxygen and nutrients, the formation of functional vascular networks requires generation of normal, healthy vessels and their arrangement into an effective network architecture. While our knowledge about the development of single vessels significantly increased during the last years, mechanisms responsible for network formation are still poorly understood. This is probably due to the lack of suitable methods for quantification of structural properties of microvascular networks. Previously we showed that cerebral blood flow is not increased in mice exhibiting a 2- to 3-fold higher density of normal and perfused capillaries as a result of transgenic overexpression of the human vascular endothelial growth factor (VEGF165). Here we used vascular corrosion casting and hierarchical micro-computed tomography combined with a new network analysis tool to characterize the vascular architecture in gray and white matter of these mice. Our results indicate that VEGF overexpression leads to formation of additional micro-networks connected to higher order vessels rather than insertion of individual capillaries into the existing vessel structure. This implies that the smallest "angiogenic quantum", i.e. the final, stable result of angiogenesis and subsequent remodeling, is not a single microvessel, but a complete micro-network. In conclusion, high-resolution 3D imaging combined with network analysis can substantially improve our understanding of vascular architecture, beneficial for the development of therapeutic angiogenesis as a clinical tool for applications such as wound healing or treatment of ischemic diseases.
Two tubular, segmented hearts propel blood through the closed circulatory system of the medicinal leech and switch every 20 - 40 beats between two constriction patterns. We showed recently that within one heartbeat cycle, heart segments on one side constrict peristaltically rear-to-front ('peristaltic heart'), followed by nearly synchronous front-to-rear constrictions in the contralateral heart segments ('synchronous heart'). Using optical recordings from intact leeches, we now characterize the hemodynamic properties of the cardiac cycle of individual heart segments in different regions to ask whether the reversal of constrictions affects flow into, out of, and along the hearts. We measured total vessel capacity in corrosion casts and blood volume in individual heart segments of dissected leeches. We show that the peristaltic heart provides the propulsive force for forward and rearward flow and supplies the peripheral circulation through segmental efferent vessels. In comparison, the synchronous heart pumps less blood, most of which enters the segmental circulation. The heart sphincter, located in the posterior section of each heart segment, directs blood flow differently in the two modes. In the peristaltic heart, the sphincter prevents backflow and promotes longitudinal, forward flow while in the synchronous heart the sphincter restricts longitudinal, rearward flow and instead promotes flow into the segmental circulation. Blood is shunted via the contractile latero-dorsal arches from the dorsal intestinal vessel into the peristaltic heart in posterior segments 14 to 18. Switching between the two constriction patterns provides nutrient-rich blood to the vascular beds on both sides.
Vascular factors associated with Alzheimer's disease (AD) have recently gained increased attention. To investigate changes in vascular, particularly microvascular architecture, we developed a hierarchical imaging framework to obtain large-volume, high-resolution 3D images from brains of transgenic mice modeling AD. In this paper, we present imaging and data analysis methods which allow compiling unique characteristics from several hundred gigabytes of image data. Image acquisition is based on desktop micro-computed tomography (mu CT) and local synchrotron-radiation mu CT (SR mu CT) scanning with a nominal voxel size of 16 mu m and 1.4 mu m, respectively. Two visualization approaches were implemented: stacks of Z-buffer projections for fast data browsing, and progressive-mesh based surface rendering for detailed 3D visualization of the large datasets. In a first step, image data was assessed visually via a Java client connected to a central database. Identified characteristics of interest were subsequently quantified using global morphometry software. To obtain even deeper insight into microvascular alterations, tree analysis software was developed providing local morphometric parameters such as number of vessel segments or vessel tortuosity. In the context of ever increasing image resolution and large datasets, computer-aided analysis has proven both powerful and indispensable. The hierarchical approach maintains the context of local phenomena, while proper visualization and morphometry provide the basis for detailed analysis of the pathology related to structure. Beyond analysis of microvascular changes in AD this framework will have significant impact considering that vascular changes are involved in other neurodegenerative diseases as well as in cancer, cardiovascular disease, asthma, and arthritis.
A multitude of various materials are available for the visualization of cadaveric vessels, ranging from natural materials like gelatin and latex to synthetic materials like silicone rubber or acrylates. To achieve a detailed overview of the vascular architecture in microvascular studies in experimental flap surgery, the injected material should have low viscosity to assure perfusion of even the smallest vessels. In addition, the material ideally should have either no or only minimal shrinkage, and should harden within a reasonable time, but retain sufficient elasticity and resistance to withstand tearing off the delicate vessels during subsequent dissection or casting. Because none of the available injection materials adequately combines these attributes, we evaluated the polyurethane elastomer "PU4ii" in latissimus dorsi muscles as a new material for the visualization of cadaveric vessels in comparison with the frequently used silicone rubber. The dissection of vessels injected with PU4ii proved easy largely because of its exceptional hardness. Even if not visible before dissection, the completely perfused vessels were easily palpated in the surrounding fat or muscle tissue of the microsurgical latissimus dorsi model. Despite the significantly higher hardness of PU4ii over silicone rubber (98 Sh-A vs. 12 Sh-A), PU4ii proved enough elasticity (20-25 N/mm(2) E modulus) and a high tear resistance (64-68 N/mm vs. 15 N/mm) preventing breakage during dissection even within the smallest vessels. In contrast to silicone rubber (and latex or gelatin), the high corrosion resistance and form stability of PU4ii also allowed building of casts for qualitative examination by scanning electron microscopy and quantitative analysis of the vessel density using micro-computed tomography with accurate 3D representation. In this study we show that PU4ii has physical characteristics that make it a multi-purpose material that allows at the same breath an excellent gross visualization of the architecture of cadaveric blood vessels as well as a detailed evaluation of casts by modern microscopic and or radiologic tools. Thus, the new polyurethane elastomer PU4ii is in many respects superior to the widely used silicone rubber and can be strongly recommended as a visualization material for a comprehensive evaluation of cadaveric blood vessels in microsurgery.