Structure and age-dependent development of the turkey liver: a comparative study of a highly selected meat-type and a wild-type turkey line

In this study the macroscopic and microscopic structure of the liver of a fast growing, meat-type turkey line (British United turkeys BUT Big 6, n = 25) and a wild-type turkey line (Wild Canadian turkey, n = 48) were compared at the age of 4, 8, 12, 16, and 20 wk. Because the growth plates of long bones were still detectable in the 20-week-old wild-type turkeys, indicating immaturity, a group of 8 wild-type turkeys at the age of 24 wk was included in the original scope of the study. Over the term of the study, the body and liver weights of birds from the meat-type turkey line increased at a faster rate than those of the wild-type turkey line. However, the relative liver weight of the meat-type turkeys declined (from 2.7 to 0.9%) to a greater extent than that of the wild-type turkeys (from 2.8 to 1.9%), suggesting a mismatch in development between muscle weights and liver weights of the meat-type turkeys. Signs of high levels of fat storage in the liver were detected in both lines but were greater in the wild-type turkey line, suggesting a better feed conversion by the extreme-genotype birds i.e., meat-type birds. For the first time, this study presents morphologic data on the structure and arrangement of the lymphatic tissue within the healthy turkey liver, describing two different types of lymphatic aggregations within the liver parenchyma, i.e., aggregations with and without fibrous capsules. Despite differences during development, both adult meat-type and adult wild-type turkeys had similar numbers of lymphatic aggregations

Perivascular vital cells in the ablation center after multibipolar radiofrequency ablation in an in vivo porcine model

Multibipolar radiofrequency ablation (RFA) is an advanced ablation technique for early stage hepatocellular carcinoma and liver metastases. Vessel cooling in multibipolar RFA has not been systematically investigated. The objective of this study was to evaluate the presence of perivascular vital cells within the ablation zone after multibipolar RFA. Multibipolar RFA were performed in domestic pigs in vivo. Three internally cooled bipolar RFA applicators were used simultaneously. Three experimental settings were planned: (1) inter-applicator-distance: 15 mm; (2) inter-applicator-distance: 20 mm; (3) inter-applicator-distance: 20 mm with hepatic inflow occlusion (Pringle maneuver). A vitality staining was used to analyze liver cell vitality around all vessels in the ablation center with a diameter>0.5 mm histologically. 771 vessels were identified. No vital tissue was seen around 423 out of 429 vessels (98.6%) situated within the central white zone. Vital cells could be observed around major hepatic vessels situated adjacent to the ablation center. Vessel diameter (>3.0 mm; p<0.05) and low vessel-to-ablation-center distance (<0.2 mm; p<0.05) were identified as risk factors for incomplete ablation adjacent to hepatic vessels. The vast majority of vessels, which were localized in the clinically relevant white zone, showed no vital perivascular cells, regardless of vessel diameter and vessel type. However, there was a risk of incomplete ablation around major hepatic vessels situated directly within the ablation center. A Pringle maneuver could avoid incomplete ablations

A morphometric study of the mandibular canal

This study reports morphometric and age-related data of the mandibular canal and the alveolar ridge of the Göttingen Minipig to avoid complications during in vivo testing of endosseus dental implants and to compare these data with the human anatomy. Using 3D computed tomography, six parameters of the mandibular canal as well as the alveolar bone height and the alveolar ridge width were measured in Göttingen Minipigs aged 12, 17 and 21 months. Our null hypothesis assumes that the age and the body mass have an influence on the parameters measured. The study found that the volume, length and depth of the mandibular canal all increase with age. The width of the canal does not change significantly with age. The body mass does not have an influence on any of the measured parameters. The increase in canal volume appears to be due to loss of deep spongy bone in the posterior premolar and molar regions. This reduces the available space for dental implantations, negatively affecting implant stability and potentially the integrity of the inferior alveolar neurovascular bundle. Dynamic anatomical changes occur until 21 months. On ethical grounds, using minipigs younger than 21 months in experimental implant dentistry is inadvisable. Paradoxically the measurements of the 12 months old pigs indicate a closer alignment of their mandibular anatomy to that of humans suggesting that they may be better models for implant studies. Given the variability in mandibular canal dimensions in similar age cohorts, the use of imaging techniques is essential for the selection of individual minipigs for dental prosthetic interventions and thus higher success rates

Histological and SEM Assessment of Blood Stasis in Kidney Blood Vessels after Repeated Intra-Arterial Application of Radiographic Contrast Media

Background: After application of iodinated contrast media (CM), a pronounced deterioration of the microcirculation in skin and myocardium was reported. Clinically, the repeated application of CM, especially, led to an increase of the renal resistance index (RRI). With respect to the transiency of the RRI increase, it is reasonable to assume that the deterioration of blood flow could be due to transient blood stasis caused by reversible morphologic cell alterations due to osmotic discrepancies between CM and human blood. Therefore, the hypothesis was investigated whether CM are able to induce in vivo such blood stasis and cell deformations in the renal vasculature of well-hydrated pigs. Methods: The in vivo study was performed as a prospective randomized examination to compare the effects of two different CM in 16 pigs (German Landrace). Pigs were randomized to receive either Iodixanol (n= 8), or Iopromide (n= 8). Each animal received 10 injections separated by 5-min intervals via the suprarenal aorta at a rate of 10 mL/s according to the usual procedure during a cardiac catheter examination. Finally, the kidneys were explanted and processed for histology (H & E staining and fibrin staining according to Weigert) as well as for scanning electron microscopy (SEM) with regards to morphologic correlates explaining the changes in the microcirculation. Results: In each of the predefined four categories of vascular diameters, blood stasis were found, but clearly more often after application of Iopromide than after application of Iodixanol (p< 0.001). In addition, Iopromide induced more blood stasis in all of the examined kidney regions compared to Iodixanol (p= 0.0001). There were no obstructive events in the middle cortex following the application of Iodixanol. Except for the region around a puncture channel of a placed-in catheter probe, no fibrin was detected in Weigert's fibrin-stained samples, neither around the histologically assessed thrombi nor in vessels with blood stasis. Complementary SEM analyses revealed in a few cases only a slight generation of fibrin and thrombi and deformations, such as echinocyte and "box-like" deformations. Conclusions: According to previous in vitro studies, pathological erythrocyte deformations, such as echinocyte and box-like formation of erythrocytes, were observed also in vivo. In addition, blood stasis and/or thrombi could be detected in histological samples from explanted kidneys from young pigs after repeated in vivo administration of CM. In only a few cases, mural platelet aggregates within minimal fibrin meshes occurred only after the application of Iopromide

Correlation with morphometric parameters

In den westlichen Industrieländern ist das Prostatakarzinom das häufigste Malignom beim Mann und das am zweithäufigsten zum Tode führende Tumorleiden des Mannes. Die bisher einzige Möglichkeit, ein Prostatakarzinom frühzeitig zu diagnostizieren, ist die histologische Untersuchung von Prostatagewebe. Eine sichere Differenzierung des Prostatakarzinoms gegenüber gesundem und gutartig verändertem Prostatagewebe anhand klinischer Untersuchungen, Laboranalysen und bildgebender Verfahren ist bislang nicht möglich. Dies führt zu einer erschwerten Detektion des Tumorareals für die Prostatabiopsie und damit bei einem größeren Teil der Patienten zu falsch negativen histologischen Befunden. Zielsetzung dieser Arbeit war die Etablierung eines Rattenmodells zur Differenzierung eines langsam wachsenden, orthotop implantierten Prostatakarzinoms gegenüber gesundem Drüsengewebe der Prostata an einem klinischen 1,5 Tesla MR-Ganzkörpertomographen mittels kontrastmittelgestützter dynamischer MRT. Ein weiteres Ziel war die Untersuchung der MRT als Methode zur Blutvolumenbestimmung von Prostatakarzinom und gesundem Prostatagewebe. Die vorliegende Arbeit ist die erste Studie, in der die Perfusionsparameter interstitielles Volumen, Permeablilitäts-Oberflächenprodukt, normalisierte Permeabilität und relatives Blutvolumen von Prostatakarzinom und gesundem Prostatagewebe mittels MRT bestimmt und zudem mit histologischen Vaskularisationsparametern korreliert wurden. Erfolgreich eingesetzt wurde das Tumormodell des G-Dunning Rattenprostatakarzinoms. Die Tumorinduktion erfolgte an 17 Copenhagen-Ratten durch orthotope Implantation von jeweils 1 × 106 Tumorzellen. Die MRT-Untersuchungen erfolgten 56 bis 60 Tage nach der Tumorzellimplantation mittels nativer T1-gewichteter SE und T2-gewichteter TSE sowie einer T1-gewichteten GRE-Sequenz für die kontrastmittelgestützten Untersuchungen. Verwendet wurden ein extravasierendes niedermolekulares Gd- haltiges Kontrastmittel (Gadodiamid) für die dynamischen Messungen sowie ein lang anhaltend intravasal verbleibendes eisenoxidpartikelhaltiges Kontrastmittel (VSOP-C 184) zur Blutvolumenbestimmung. Nach Durchführung der dynamischen Messungen wurden Kurven der Signalintensität in Abhängigkeit von der Zeit in Tumor und gesundem Gewebe generiert und quantitativ mittels pharmakokinetischer Modellierung ausgewertet. Die Bestimmung der relativen Blutvolumina von Tumor und gesundem Prostatagewebe erfolgte aus dem Verhältnis des Signalintensität sanstieges nach der Gabe von VSOP-C 184 und der Signalintensität im Vollblut der Tiere. Für die anschließende histologische und morphometrische Auswertung von Tumor und gesundem Prostatagewebe wurden eine H&amp;E-F;ärbung, eine modifizierte van Gieson-Färbung ohne Kernfärbung sowie eine Markierung der Gefäßendothelien mittels BSL I eingesetzt. In den nativen T2-gewichteten MRT-Bildern stellten sich die Tumoren bei allen Tieren, als hypointense Areale gegenüber dem gesunden Prostatagewebe und somit gleich einem humanen Prostatakarzinom dar. Die durchschnittliche Tumorgröße in der MRT lag in der axialen Schicht bei 10,93 mm² und zeigte eine hohe Korrelation (r = 0,75; p < 0,001) mit den Ergebnissen der histologischen Untersuchung. In den dynamischen MRT-Messungen zeigte sich ein deutlich beschleunigter sowie ein erhöhter Anstieg der Signalintensität im Tumor gegenüber dem gesunden Prostatagewebe. Das interstitielle Volumen und das Permeabilitäts- Oberflächenprodukt im Tumor waren gegenüber dem gesunden Prostatagewebe um 482 % (p<0.001) und 439 % (p<0.001) signifikant erhöht. Die in dieser Arbeit erstmals sowohl in der MRT als auch histologisch bestimmten interstitiellen Volumina weisen darauf hin, dass die Diffusionsstrecken in gesundem Prostatagewebe zu groß sind, um eine Verteilung des MRT-Kontrastmittels im gesamten Interstitium zu gewähren. Die Folge ist eine deutliche Unterschätzung des interstitiellen Volumens in MRT-Messungen, selbst mit einem stark extravasierenden Kontrastmittel. Die weiteren Ergebnisse zeigen, dass die Erhöhung des Permeabilitäts-Oberflächenprodukts im Tumor gegenüber dem gesunden Prostatagewebe in einer verstärkten Perfusion, bedingt durch ein erhöhtes Blutvolumen liegt und nicht, wie teilweise vermutet, in einer erhöhten Gefäßpermeabilität. Die ermittelten relativen Blutvolumina im Tumor lagen sowohl in der MRT mit 1,71 % zu 0,69 % als auch in den histologischen Schnitten mit 1,03 % zu 0,69 % signifikant über denen des gesunden Prostatagewebes. Die Gefäßanordnung im Gewebe zeigte viele kleine Gefäße im Tumor gegenüber wenigen Gefäßen mit einem größeren Durchmesser im gesunden Prostatagewebe. Dies könnte auf einen stärkeren Protonenaustausch im Tumor hindeuten und somit die im Tumor größere Überschätzung des Blutvolumens in der MRT im Vergleich zum gesunden Prostatagewebe erklären. In der vorliegenden Arbeit ist es erstmals gelungen, ein Rattenmodell zu etablieren, welches dazu geeignet ist, sowohl mit quantitativer Analyse von dynamischen MRT-Daten als auch durch eine Blutvolumenbestimmung in der MRT mittels eines lang anhaltend intravasal verweilenden Kontrastmittels ein kleines, langsam gewachsenes, orthotopes Prostatakarzinom von gesundem Drüsengewebe der Prostata zu differenzieren. Eine Anwendung der hier verwendeten MRT-Techniken beim Menschen könnte in Zukunft dazu dienen, die Differenzierung des Prostatakarzinoms gegenüber gesundem Prostatagewebe sowie seinen Differentialdiagnosen, wie der Prostatitis oder der benignen Prostatahyperplasie, zu verbessern.Prostate cancer is still the most common malignant tumor in men in Western countries and the second most common cause of cancer death in men. Histological examination is currently the only method that enables early diagnosis of prostate cancer. Clinical examination, laboratory tests, and imaging techniques do not allow reliable differentiation of prostate cancer from normal prostate tissue or benign processes. The lack of a reliable diagnostic tool may lead to a false-negative histological diagnosis in some patients because suspicious areas are missed by prostate biopsy. The aim of this study was to establish a rat model for the differentiation of slow- growing, orthotopically implanted prostate cancer from healthy prostate tissue by means of contrast-enhanced dynamic magnetic resonance imaging (MRI) on a 1.5-Tesla clinical whole-body scanner. Another aim was to test the capability of MRI in determining the blood volume of prostate cancer and healthy prostate tissue. This is the first study that uses MRI to determine the perfusion parameters interstitial volume, permeability surface area product, normalized permeability, and relative blood volume in prostate cancer and healthy prostate tissue and correlates the results with histologic parameters of vascularization. The tumor model successfully used in this study was the G-Dunning rat prostatic cancer. Tumors were induced in 17 Copenhagen rats by means of orthotopic implantation of 1 × 106 tumor cells per animal. The MRI studies were performed 56 to 60 days after tumor cell implantation using unenhanced T1-weighted SE and T2-weighted TSE sequences and a contrast- enhanced T1-weighted GRE sequence. Two contrast agents were used, an extravasating low-molecular-weight gadolinium-based contrast agent (gadodiamide) for dynamic studies and an iron oxide particle agent (VSOP-C 184) with a long intravascular residence time for blood volume determination. Following dynamic MRI, signal intensity-time curves were generated for tumor and healthy prostate tissue and quantitatively analyzed using a pharmacokinetic model. The relative blood volumes of tumor and healthy prostate tissue were determined from the ratio of the signal intensity increase after VSOP-C 184 administration and the signal intensity of whole blood. The tissue specimens for histologic and morphometric analysis of tumor and prostate tissue were prepared using H&amp;E; and modified Van Gieson stain without nuclear staining and labeling of the vascular endothelium with BSL I. The unenhanced T2-weighted MR images depicted the tumors as low-signal- intensity areas relative to normal surrounding prostate tissue in all rats, which corresponds to the signal pattern of human prostate cancer. The mean tumor size determined on axial MR images was 10.93 mm² and highly correlated (r = 0.75; p < 0.001) with the results of the histological determined size. On contrast-enhanced dynamic MRI the tumors enhanced much earlier and more intensely than healthy prostate tissue. The interstitial volumes and permeability-surface area products of the tumors were significantly higher compared with normal prostate tissue (482 % and 439 %, respectively; both p<0.001). The interstitial volumes, which were determined in the present study for the first time using both MRI and histology, suggest that the diffusion pathways in healthy prostate tissue are too long for distribution of the MR contrast agent throughout the interstitial space. As a consequence, MRI markedly underestimates interstitital volume even if a contrast agent with pronounced extravasation is used. The results show that the higher permeability surface area product of prostate tumors compared with normal prostate tissue is due to increased perfusion secondary to an increased blood volume rather than an increased vessel permeability, as suggested by some investigators. The relative tumor blood volumes determined by MRI and histologic examination were significantly higher than in healthy prostate tissue (1.71 % versus 0.69 % and 1.03 % versus 0.69 %, respectively). Analysis of vascular patterns revealed many small vessels in the tumor while there were fewer but larger vessels in the normal prostate. These patterns might suggest a higher proton exchange rate in prostate tumors and possibly explain the greater overestimation by MRI of the tumor blood volumes compared with normal prostate tissue. This study for the first time established a rat model that can be used to differentiate slow-growing orthotopic prostate cancer from healthy prostate tissue by using quantitative analysis of dynamic MRI data as well as MRI blood volume determination following administration of a contrast agent with a long intravascular half-life. The MRI technique investigated here might in the future improve the differentiation of prostate cancer from healthy prostate tissue and from the differential diagnosis of prostate cancer such as prostatitis or benign prostate hyperplasia in humans

Spacer-Supported Thermal Ablation to Prevent Carbonisation and Improve Ablation Size: A Proof of Concept Study

Thermal ablation offers a minimally invasive alternative in the treatment of hepatic tumours. Several types of ablation are utilised with different methods and indications. However, to this day, ablation size remains limited due to the formation of a central non-conductive boundary layer. In thermal ablation, this boundary layer is formed by carbonisation. Our goal was to prevent or delay carbonisation, and subsequently increase ablation size. We used bovine liver to compare ablation diameter and volume, created by a stand-alone laser applicator, with those created when utilising a spacer between laser applicator and hepatic tissue. Two spacer variants were developed: one with a closed circulation of cooling fluid and one with an open circulation into hepatic tissue. We found that the presence of a spacer significantly increased ablation volume up to 75.3 cm3, an increase of a factor of 3.19 (closed spacer) and 3.02 (open spacer) when compared to the stand-alone applicator. Statistical significance between spacer variants was also present, with the closed spacer producing a significantly larger ablation volume (p Diff = 3.053, 95% CI[1.612, 4.493]) and diameter (p Diff = 4.467, 95% CI[2.648, 6.285]) than the open spacer. We conclude that the presence of a spacer has the potential to increase ablation size

Extra Domain B Fibronectin as a Target for Near-Infrared Fluorescence Imaging of Rheumatoid Arthritis Affected Joints In Vivo

We investigated a molecular imaging approach for the detection of collagen-induced arthritis in rats by targeting the extra domain B (ED-B) of the extracellular matrix protein fibronectin. ED-B is a highly conserved domain (identical in human and rats) that is produced by alternative splicing during embryonic development and during vascular remodeling such as angiogenesis. The hallmark of rheumatoid arthritis is synovitis leading to both angiogenesis in the synovium and the promotion of cartilage and bone disruption. For in vivo diagnostics, the ED-B-binding single-chain antibody fragment AP39 was used as a targeting probe. It was covalently linked to the near-infrared dye tetrasulfocyanine (TSC) to be visualized by near-infrared fluorescence imaging. The resulting AP39-TSC conjugate was intravenously administered to rats with collagen-induced arthritis and the respective controls. Ovalbumin-TSC was used as control conjugate. Optical imaging over a time period of 24 hours using a planar imaging setup resulted in a clear enhancement of fluorescence intensity in joints with moderate to severe arthritis compared with control joints between 3 and 8 hours postinjection. Given that AP39 is a fully human antibody fragment, this molecular imaging approach for arthritis detection might be translated to humans

Refining experimental dental implant testing in the Göttingen Minipig using 3D computed tomography-A morphometric study of the mandibular canal.

This study reports morphometric and age-related data of the mandibular canal and the alveolar ridge of the Göttingen Minipig to avoid complications during in vivo testing of endosseus dental implants and to compare these data with the human anatomy. Using 3D computed tomography, six parameters of the mandibular canal as well as the alveolar bone height and the alveolar ridge width were measured in Göttingen Minipigs aged 12, 17 and 21 months. Our null hypothesis assumes that the age and the body mass have an influence on the parameters measured. The study found that the volume, length and depth of the mandibular canal all increase with age. The width of the canal does not change significantly with age. The body mass does not have an influence on any of the measured parameters. The increase in canal volume appears to be due to loss of deep spongy bone in the posterior premolar and molar regions. This reduces the available space for dental implantations, negatively affecting implant stability and potentially the integrity of the inferior alveolar neurovascular bundle. Dynamic anatomical changes occur until 21 months. On ethical grounds, using minipigs younger than 21 months in experimental implant dentistry is inadvisable. Paradoxically the measurements of the 12 months old pigs indicate a closer alignment of their mandibular anatomy to that of humans suggesting that they may be better models for implant studies. Given the variability in mandibular canal dimensions in similar age cohorts, the use of imaging techniques is essential for the selection of individual minipigs for dental prosthetic interventions and thus higher success rates

Influence of interapplicator distance on multibipolar radiofrequency ablation during physiological and interrupted liver perfusion in an in vivo porcine model

Radiofrequency ablation (RFA) is a curative treatment option for early stage hepatocellular carcinoma (HCC). Vascular inflow occlusion to the liver (Pringle manoeuvre) and multibipolar RFA (mbRFA) represent possibilities to generate large ablations. This study evaluated the impact of different interapplicator distances and a Pringle manoeuvre on ablation area and geometry of mbRFA. 24 mbRFA were planned in porcine livers in vivo. Test series with continuous blood flow had an interapplicator distance of 20 mm and 15 mm, respectively. For a Pringle manoeuvre, interapplicator distance was predefined at 20 mm. After liver dissection, ablation area and geometry were analysed macroscopically and histologically. Confluent and homogenous ablations could be achieved with a Pringle manoeuvre and an interapplicator distance of 15 mm with sustained hepatic blood flow. Ablation geometry was inhomogeneous with an applicator distance of 20 mm with physiological liver perfusion. A Pringle manoeuvre led to a fourfold increase in ablation area in comparison to sustained hepatic blood flow (p < 0.001). Interapplicator distance affects ablation geometry of mbRFA. Strict adherence to the planned applicator distance is advisable under continuous blood flow. The application of a Pringle manoeuvre should be considered when compliance with the interapplicator distance cannot be guaranteed

Visualization of the changes in mandibular canal volume over time.

<p>The white arrow shows the incisive canal, which is the anterior prolongation of the mandibular canal. The lower image shows the merged segmentations to enable a better visual comparison. The orange segmentation is at 17m and the bright blue at 21m.</p