Andrea Schenk

Influence of intrahepatic vessels on volume and shape of percutaneous thermal ablation zones: in vivo evaluation in a porcine model.

Objectives:Aim of the study was to evaluate the precise influence of different intrahepatic vessels, vessel sizes, and distances from the applicator on volume and shape of hepatic laser ablation zones in an in vivo porcine model. Materials and Methods:The study was approved by the institutional animal care and use committee. Eighteen computed tomography-guided Nd:YAG laser ablations were performed in the livers of 10 pigs at varying distances from hepatic veins and portal fields. After hepatectomy the livers were cut into 2-mm slices perpendicular to the laser applicator axes. For each ablation zone the maximum achievable (ideal) volume, the segmented (real) volume, the maximum radius, and the radius at the position of adjacent hepatic vessels were determined. The shapes of the ablation zones were evaluated qualitatively. Comparative statistics using the unpaired t test and a multiple linear regression analysis were performed. Results:Ideal and real ablation zone volumes differed by 27.3% (8.6 ± 1.5 mL vs. 6.4 ± 1.1 mL; P < 0.0001). Thirty-eight of 60 (63%) hepatic veins versus 28 of 31 (90%) portal veins within the central slices of the 18 ablation zones led to a reduction of the ablation zones radius, depending on the distance between the vessel and the applicator and the vessel type. Portal fields revealed stronger effects than hepatic veins. The vessel diameter showed no independent effect (P > 0.05). When influencing, all hepatic veins showed a focal indentation whereas portal fields always showed broad flattening of the ablation zone. Conclusions:Portal fields lead to more heat sink than hepatic veins. The effects decreased with the distance between vessel and applicator tip, but less so for portal fields. The 2 vessel types induced considerably different shape alterations of the ablation zones. These results were not dependent on vessel size. This should be considered in the planning of thermal tumor ablations.

Recovery of liver perfusion after focal outflow obstruction and liver resection.

Background. Live liver donation requires extended liver resection in the donor with transection of the middle hepatic vein. This leads to focal outflow obstruction in the remnant liver or the partial graft. This study was designed to characterize the pathophysiological correlate of focal outflow obstruction in a small-for-size liver and its course of recovery in a rat model. Methods. Ligation of the right median hepatic vein was combined with 50% hepatectomy. Microcirculation was visualized by orthogonal polarization spectroscopy after each operative step and before killing on days 1, 2, and 7. Histologic evaluation included morphological assessment, immunohistochemical determination of proliferation using BrdU, and laminin and von Willebrand factor expression, which both indicate vascularization of sinusoids. Results. After ligation of the right median hepatic vein, congestion was visible and no sinusoidal blood flow was detected in the obstruction zone. By day 1 confluent centrilobular necrosis developed. Sinusoidal perfusion in the obstruction zone recovered partially. Many dilated vascularized sinusoidal canals connecting the obstruction zone with the normal zone were visible. Proliferative activity in the obstruction zone was markedly reduced compared with the normal zone. By day 7, liver parenchyma in the obstruction zone looked normal as did sinusoidal perfusion. In the border zone, few dilated vascular canals were apparent. Conclusion. Confluent centrilobular necrosis in the early postoperative phase, resulting from focal outflow obstruction, may be crucial for the development of a small-for-size syndrome. The exclusion of the outflow-obstructed zone from the functional liver mass during preoperative radiological risk assessment seems to be the logical consequence. Recovery of focal outflow obstruction occurs spontaneously by means of dilated sinusoids in the border zone, forming vascularized sinusoidal canals, which could serve as intrahepatic anastomosis.

Spatio-temporal simulation of first pass drug perfusion in the liver.

The liver is the central organ for detoxification of xenobiotics in the body. In pharmacokinetic modeling, hepatic metabolization capacity is typically quantified as hepatic clearance computed as degradation in well-stirred compartments. This is an accurate mechanistic description once a quasi-equilibrium between blood and surrounding tissue is established. However, this model structure cannot be used to simulate spatio-temporal distribution during the first instants after drug injection. In this paper, we introduce a new spatially resolved model to simulate first pass perfusion of compounds within the naive liver. The model is based on vascular structures obtained from computed tomography as well as physiologically based mass transfer descriptions obtained from pharmacokinetic modeling. The physiological architecture of hepatic tissue in our model is governed by both vascular geometry and the composition of the connecting hepatic tissue. In particular, we here consider locally distributed mass flow in liver tissue instead of considering well-stirred compartments. Experimentally, the model structure corresponds to an isolated perfused liver and provides an ideal platform to address first pass effects and questions of hepatic heterogeneity. The model was evaluated for three exemplary compounds covering key aspects of perfusion, distribution and metabolization within the liver. As pathophysiological states we considered the influence of steatosis and carbon tetrachloride-induced liver necrosis on total hepatic distribution and metabolic capacity. Notably, we found that our computational predictions are in qualitative agreement with previously published experimental data. The simulation results provide an unprecedented level of detail in compound concentration profiles during first pass perfusion, both spatio-temporally in liver tissue itself and temporally in the outflowing blood. We expect our model to be the foundation of further spatially resolved models of the liver in the future.

Interactive determination of robust safety margins for oncologic liver surgery

ObjectiveComplex oncologic interventions in the liver require an extensive and careful preoperative analysis. Particularly the achievement of an optimal safety margin around tumors remains a difficult task for surgeons.MethodsWe present new methods for evaluating different safety margins and their effect on the associated interruption of vascular supply or drainage. The characteristic of vascular risk distributions can be evaluated in real-time by exploiting precomputed safety maps that provide a volume curve for each vascular system. By applying fast visualization methods in 3D it is possible to assist the surgeon in the determination of a tumor-free safety margin while preserving sufficient vital hepatic parenchyma. The combination of risk analysis from different vascular systems and their sensitivity is considered.ResultsWe provide physicians with a novel computer-aided planning tool that allows for interactive determination of safety margins in real-time. The planning tool integrates smoothly into the preoperative workflow. Preliminary evaluations confirm that the width of safety margins can be determined more precisely, which may affect the proposed resection strategy.ConclusionOur new methods provide interactive feedback and support for decision making during the preoperative planning stage and thus might potentially improve the outcome of surgical interventions.

Matching of anatomical tree structures for registration of medical images

Many medical applications require a registration of different images of the same organ. In many cases, such a registration is accomplished by manual placement of landmarks in the images. In this paper, we propose a method which is able to find reasonable landmarks automatically. To achieve this, bifurcations of the vessel systems, which have been extracted from the images by a segmentation algorithm, are assigned by the so-called association graph method and the coordinates of these matched bifurcations can be used as landmarks for a non-rigid registration algorithm. Several constraints to be used in combination with the association graph method are proposed and evaluated on a ground truth consisting of anatomical trees from liver and lung. Furthermore, a method for preprocessing (tree pruning) as well as for postprocessing (clique augmentation) are proposed and evaluated on this ground truth. The proposed method achieves promising results for anatomical trees of liver and lung and for medical images obtained with different modalities and at different points in time.

Clinical relevance of model based computer-assisted diagnosis and therapy

The ability to acquire and store radiological images digitally has made this data available to mathematical and scientific methods. With the step from subjective interpretation to reproducible measurements and knowledge, it is also possible to develop and apply models that give additional information which is not directly visible in the data. In this context, it is important to know the characteristics and limitations of each model. Four characteristics assure the clinical relevance of models for computer-assisted diagnosis and therapy: ability of patient individual adaptation, treatment of errors and uncertainty, dynamic behavior, and in-depth evaluation. We demonstrate the development and clinical application of a model in the context of liver surgery. Here, a model for intrahepatic vascular structures is combined with individual, but in the degree of vascular details limited anatomical information from radiological images. As a result, the model allows for a dedicated risk analysis and preoperative planning of oncologic resections as well as for living donor liver transplantations. The clinical relevance of the method was approved in several evaluation studies of our medical partners and more than 2900 complex surgical cases have been analyzed since 2002.

Imaging and surgical planning for perihilar cholangiocarcinoma

Recent advances in multidetector computed tomography (MDCT) offer several benefits for management of perihilar tumors. Resection planning for perihilar cholangiocarcinoma should consider two factors: safety and curability. Recognition of individual anatomic variations is particularly important for avoiding intraoperative injury. In particular, hepatic arterial variations often restrict resection procedures. Extent of both longitudinal and vertical invasion by biliary tumors can be estimated from multiplanar reconstruction (MPR) images. Longitudinal extent of resection can be planned based on two anatomic landmarks, the U point and the P point, readily identifiable in preoperative 3‐dimensional (3D) images and by intraoperative inspection. Concerning vertical invasion, when direct vascular invasion is suspected from a finding of attachment of tumor and vessels such as portal veins and/or hepatic arteries without a thin low‐density plane of separation shown by MPR, these vessels should be resected en bloc with the tumor. Surgical team members can plan and simulate details of vascular resection and reconstruction using 3D images. Reduced operative morbidity and increased R0 resection rates are expected because of better planning of procedures. These techniques soon may increase long‐term survival for patients with perihilar cholangiocarcinoma.

Practical quantification of necrosis in histological whole-slide images

Since the histological quantification of necrosis is a common task in medical research and practice, we evaluate different image analysis methods for quantifying necrosis in whole-slide images. In a practical usage scenario, we assess the impact of different classification algorithms and feature sets on both accuracy and computation time. We show how a well-chosen combination of multiresolution features and an efficient postprocessing step enables the accurate quantification necrosis in gigapixel images in less than a minute. The results are general enough to be applied to other areas of histological image analysis as well.

Small-for-Size Syndrome in the Rat: Does Size or Technique Matter?

BACKGROUND The incidence of the small-for-size syndrome (SFSS) is inversely correlated to the size of the remnant liver or the partial graft. The relevance of factors besides the absolute liver mass is discussed controversially. It is the aim of this study to test the effect of two different mass ligation techniques in comparison with our newly developed parenchyma-preserving vessel-oriented liver resection technique on the induction of a SFSS after extended 90% liver resection in the rat. MATERIALS AND METHODS Ninety percent liver resections were performed using three surgical techniques, two mass ligation techniques, and a vessel oriented technique. Diagnosis of SFSS was based on the combination of biochemical and morphological criteria on the first postoperative day and was related to the outcome on postoperative day 7 and the regenerative capacity of the liver. RESULTS Only the use of mass ligation techniques was associated with a low 1-wk survival rate (<40%), more pronounced histomorphological signs of liver damage at 24 h postoperatively, and a delayed onset of hepatocyte proliferation. Histological analysis revealed an extended stump necrosis in the paracaval liver and signs of sinusoidal damage in the remaining caudate lobes as morphological correlates of a putative outflow obstruction as the possible underlying reason. The lesions added up to a high small-for-size score in rats operated according to mass ligation techniques. CONCLUSIONS These results indicate that preservation of functional liver mass and prevention of an outflow obstruction by delicate surgery is essential to prevent a SFSS in a size-reduced liver.

Concepts for Liver Segment Classification: Neither Old Ones nor New Ones, but a Comprehensive One

Concepts dealing with the subdivision of the human liver into independent vascular and biliary territories are applied routinely in radiological, surgical, and gastroenterological practice. Despite Couinauds widely used eight-segments scheme, opinions on the issue differ considerably between authors. The aim of this article is to illustrate the scientific basis for understanding and harmonizing inconsistencies between seemingly contradictory observations. Possible clinical implications are addressed.