Repurposing CPAP machines as stripped-down ventilators.

The worldwide shortage of medical-grade ventilators is a well-known issue, that has become one of the central topics during the COVID-19 pandemic. Given that these machines are expensive and have long lead times, one approach is to vacate them for patients in critical conditions while patients with mild to moderate symptoms are treated with stripped-down ventilators. We propose a mass-producible solution that can create such ventilators with minimum effort. The central part is a module that can be attached to CPAP machines and repurpose them as low-pressure ventilators. Here, we describe the concept and first measurements which underline the potential of our solution. Our approach may serve as a starting point for open-access ventilator technologies.

Hepatocyte Transplantation to the Liver via the Splenic Artery in a Juvenile Large Animal Model.

Hepatocyte transplantation (HcTx) is a promising approach for the treatment of metabolic diseases in newborns and children. The most common application route is the portal vein, which is difficult to access in the newborn. Transfemoral access to the splenic artery for HcTx has been evaluated in adults, with trials suggesting hepatocyte translocation from the spleen to the liver with a reduced risk for thromboembolic complications. Using juvenile Göttingen minipigs, we aimed to evaluate feasibility of hepatocyte transplantation by transfemoral splenic artery catheterization, while providing insight on engraftment, translocation, viability, and thromboembolic complications. Four Göttingen Minipigs weighing 5.6 kg to 12.6 kg were infused with human hepatocytes (two infusions per cycle, 1.00E08 cells per kg body weight). Immunosuppression consisted of tacrolimus and prednisolone. The animals were sacrificed directly after cell infusion (n=2), 2 days (n=1), or 14 days after infusion (n=1). The splenic and portal venous blood flow was controlled via color-coded Doppler sonography. Computed tomography was performed on days 6 and 18 after the first infusion. Tissue samples were stained in search of human hepatocytes. Catheter placement was feasible in all cases without procedure-associated complications. Repetitive cell transplantations were possible without serious adverse effects associated with hepatocyte transplantation. Immunohistochemical staining has proven cell relocation to the portal venous system and liver parenchyma. However, cells were neither present in the liver nor the spleen 18 days after HcTx. Immunological analyses showed a response of the adaptive immune system to the human cells. We show that interventional cell application via the femoral artery is feasible in a juvenile large animal model of HcTx. Moreover, cells are able to pass through the spleen to relocate in the liver after splenic artery infusion. Further studies are necessary to compare this approach with umbilical or transhepatic hepatocyte administration.

Radiation exposure during TACE procedures using additional cone-beam CT (CBCT) for guidance: safety and precautions.

Background During transarterial chemoembolization (TACE), cone-beam computed tomography (CBCT) can be used for tumor and feeding vessel detection as well as postembolization CT imaging. However, there will be additional radiation exposure from CBCT. Purpose To evaluate the additional dose raised through CBCT-assisted guidance in comparison to TACE procedures guided with pulsed digital subtraction angiography (DSA) alone. Material and Methods In 70 of 140 consecutive patients undergoing TACE for liver cancer, CBCT was used to facilitate the TACE. Cumulative dose area product (DAP), cumulative kerma(air), DAP values of DSA, total and cine specific fluoroscopy times (FT) of 1375 DSA runs, and DAP of 91 CBCTs were recorded and analyzed using Spearman's correlation, Mann-Whitney U-test, and Kruskal-Wallis test. P values < 0.05 were considered significant. Results Additional CBCT increased DAP by 2% ( P = 0.737), kerma(air) by 24.6% ( P = 0.206), and FT by 0.02% ( P = 0.453). Subgroup analysis revealed that postembolization CBCT for detection of ethiodized oil deposits added more DAP to the procedure. Performing CBCT-assisted TACE, DSA until first CBCT contributed about 38% to the total DAP. Guidance CBCT acquisitions conduced to 6% of the procedure's DAP. Additional DSA for guidance after CBCT acquisition required approximately 46% of the mean DAP. The last DSA run for documentation purposes contributed about 10% of the DAP. Conclusion CBCT adds radiation exposure in TACE. However, the capability of CBCT to detect vessels and overlay in real-time during fluoroscopy facilitates TACE with resultant reduction of DAPs up to 46%.

Engineering an endocrine Neo-Pancreas by repopulation of a decellularized rat pancreas with islets of Langerhans.

Decellularization of pancreata and repopulation of these non-immunogenic matrices with islets and endothelial cells could provide transplantable, endocrine Neo- Pancreata. In this study, rat pancreata were perfusion decellularized and repopulated with intact islets, comparing three perfusion routes (Artery, Portal Vein, Pancreatic Duct). Decellularization effectively removed all cellular components but conserved the pancreas specific extracellular matrix. Digital subtraction angiography of the matrices showed a conserved integrity of the decellularized vascular system but a contrast emersion into the parenchyma via the decellularized pancreatic duct. Islets infused via the pancreatic duct leaked from the ductular system into the peri-ductular decellularized space despite their magnitude. TUNEL staining and Glucose stimulated insulin secretion revealed that islets were viable and functional after the process. We present the first available protocol for perfusion decellularization of rat pancreata via three different perfusion routes. Furthermore, we provide first proof-of-concept for the repopulation of the decellularized rat pancreata with functional islets of Langerhans. The presented technique can serve as a bioengineering platform to generate implantable and functional endocrine Neo-Pancreata.

Computed tomography-based survey of the vascular anatomy of the juvenile Göttingen minipig.

Over the past 50 years, image-guided procedures have been established for a wide range of applications. The development and clinical translation of new treatment regimens necessitate the availability of suitable animal models. The juvenile Göttingen minipig presents a favourable profile as a model for human infants. However, no information can be found regarding the vascular system of juvenile minipigs in the literature. Such information is imperative for planning the accessibility of target structures by catheterization. We present here a complete mapping of the arterial system of the juvenile minipig based on contrast-enhanced computed tomography. Four female animals weighing 6.13 ± 0.72 kg were used for the analyses. Imaging was performed under anaesthesia, and the measurement of the vascular structures was performed independently by four investigators. Our dataset forms a basis for future interventional studies in juvenile minipigs, and enables planning and refinement of future experiments according to the 3R (replacement, reduction and refinement) principles of animal research.

Nuclear Medicine Imaging of Prostate Cancer.

The new tracer Gallium-68 prostate-specific membrane antigen (Ga-68 PSMA) yields new promising options for the PET/CT diagnosis of prostate cancer (PCa) and its metastases. To overcome limitations of hybrid imaging, known from the use of choline derivatives, seems to be possible with the use of Ga-68 PSMA for PCa. The benefits of hybrid imaging with Ga-68 PSMA for PCa compared to choline derivatives shall be discussed in this article based on an overview of the current literature. Key Points: • Ga-68 PSMA PET/CT can achieve higher detection rates of PCa lesions than PET/CT performed with choline derivatives• The new tracer Ga-68 PSMA has the advantage of high specificity, independence of PSA-level and low nonspecific tracer uptake in surrounding tissue• The new tracer Ga-68 PSMA seems very suitable for MR-PET diagnostic Citation Format: • Schreiter V, Reimann C, Geisel D et al. Nuclear Medicine Imaging of Prostate Cancer. Fortschr Röntgenstr 2016; 188: 1037 - 1044.

Imaging-Based Liver Function Tests--Past, Present and Future.

UNLABELLED: Preoperative assessment of liver function and prediction of postoperative functional reserve are important in patients scheduled for liver resection. While determination of absolute liver function currently mostly relies on laboratory tests and clinical scores, postoperative remnant liver function is estimated volumetrically using imaging data obtained with computed tomography (CT) or magnetic resonance imaging (MRI). Accurate estimation of hepatic function is also relevant for intensive care patients, oncologic patients, and patients with diffuse liver disease. The indocyanine green (ICG) test is still the only established test for estimating true global liver function. However, more recent tools such as the LiMAx test also allow global assessment of hepatic function. These tests are limited when liver function is inhomogeneously distributed, which is the case in such conditions as unilateral cholestasis or after portal vein embolization. Imaging-based liver function tests were first developed in nuclear medicine and, compared with laboratory tests, have the advantage of displaying the spatial distribution of liver function. Nuclear medicine scans are obtained using tracers such as 99mTc galactosyl and 99mTc mebrofenin. Liver function is typically assessed using planar scintigraphy. However, three-dimensional volumetry is possible with single-photon emission computed tomography (SPECT-CT). Another technique for image-based liver function estimation is Gd-EOB-enhanced MRI. While metabolization of Gd-EOB in the body is similar to that of ICG and mebrofenin, its distribution in the liver can be displayed by MRI with higher temporal and spatial resolution. Moreover, MRI-based determination of liver function can be integrated into routine preoperative imaging. This makes MRI an ideal candidate for preoperative determination of liver function, though the best pulse sequence and the parameter to be derived from the image information remain to be identified. Another question to be answered is how the results may be affected by renal function and the presence of hyperbilirubinemia. As more results from clinical evaluation including comparison with postoperative liver function data become available, image-based liver function tests, especially with use of Gd-EOB as the contrast medium, have the potential to add another dimension to preoperative imaging. KEY POINTS: Liver function consists of a multitude of subfunctions such as biotransformation, excretion and storage. Global liver function tests are score-based tests such as Child-Pugh or MELD as well as the ICG- and LiMAx-test. Imaging-based liver function tests add spatial information. Current clinical standard is the 99mTc-Mebrofenin-scintigraphy. MRI-based function tests with Gd-EOB-DTPA have the potential to integrate seamlessly into clinical workup, feature a higher temporal and spatial resolution and do not rely on ionizing radiation.