Evaluation of augmented reality training for a navigation device used for CT-guided needle placement.

PURPOSE: Numerous navigation devices for percutaneous, CT-guided interventions exist and are, due to their advantages, increasingly integrated into the clinical workflow. However, effective training methods to ensure safe usage are still lacking. This study compares the potential of an augmented reality (AR) training application with conventional instructions for the Cube Navigation System (CNS), hypothesizing enhanced training with AR, leading to safer clinical usage. METHODS: An AR-tablet app was developed to train users puncturing with CNS. In a study, 34 medical students were divided into two groups: One trained with the AR-app, while the other used conventional instructions. After training, each participant executed 6 punctures on a phantom (204 in total) following a standardized protocol to identify and measure two potential CNS procedural user errors: (1) missing the coordinates specified and (2) altering the needle trajectory during puncture. Training performance based on train time and occurrence of procedural errors, as well as scores of User Experience Questionnaire (UEQ) for both groups, was compared. RESULTS: Training duration was similar between the groups. However, the AR-trained participants showed a 55.1% reduced frequency of the first procedural error (p > 0.05) and a 35.1% reduced extent of the second procedural error (p < 0.01) compared to the conventionally trained participants. UEQ scores favored the AR-training in five of six categories (p < 0.05). CONCLUSION: The AR-app enhanced training performance and user experience over traditional methods. This suggests the potential of AR-training for navigation devices like the CNS, potentially increasing their safety, ultimately improving outcomes in percutaneous needle placements.

Highly-efficient gene transfer with retroviral vectors into human T lymphocytes on fibronectin.

Genetically modified lymphocytes have been successfully used for correction of ADA deficiency in children and in controlling graft-versus-host disease (GvHD) after allogeneic bone marrow transplantation. Low transduction efficiencies are, however, limiting for gene therapeutic strategies based on lymphocytes. In this study we compared protocols for highly efficient gene transfer into human T cells using retroviral vector-containing supernatant. We showed that infection of both human primary T cells and CD4+ Jurkat cells is most efficient on the matrix component fibronectin. Transduction was carried out with a retroviral vector encoding both the human intracytoplasmatically truncated low-affinity nerve growth factor receptor (deltaLNGFR) as a gene transfer marker and the Herpes simplex virus thymidine kinase for negative selection. Based on LNGFR expression genetically modified cells were enriched to near purity by magnetic cell sorting (MACS). Enriched cells could be shown to be highly sensitive to ganciclovir.

Selective immunoaffinity-based enrichment of CD34+ cells transduced with retroviral vectors containing an intracytoplasmatically truncated version of the human low-affinity nerve growth factor receptor (deltaLNGFR) gene.

Human hematopoietic stem cells remain one of the most promising target cells for gene therapeutic approaches to treat malignant and nonmalignant diseases. To rapidly characterize transduced cells and to isolate these from residual nontransduced, but biologically equivalent, cells, we have used a Moloney murine leukemia virus (Mo-MuLV)-based retroviral vector containing the intracytoplasmatically truncated human low-affinity nerve growth factor receptor (deltaLNGFR) cDNA as a marker gene. Supernatant transduction of CD34+ cells (mean purity 97%) in fibronectin-coated tissue culture flasks resulted in 5.5-45% (mean 26%) transduced cells expressing deltaLNGFR (LNGFR+ cells). After transduction, more than 65% of the transduced cells remained CD34+. Compared with control (mock- and nontransduced) CD34+ cells, transduction did not decrease the cloning efficiency of CD34+ cells. Immunomagnetic selection of the transduced cells with a monoclonal anti-LNGFR antibody resulted in >90% LNGFR+ cells. Further phenotypic characterization of these highly enriched LNGFR+ cells indicated that the majority co-expressed the CD34 and CD38 antigens. These results show that transduced cells expressing an ectopic cell-surface protein can be rapidly and conveniently quantitated and characterized by fluorescence-activated cell sorting (FACS) analysis and fast and efficiently enriched by immunoadhesion using magnetic beads. The use of cell-surface reporters should facilitate optimization of methods of gene transfer into more primitive hematopoietic progenitors.

High-dose multidrug resistance in primary human hematopoietic progenitor cells transduced with optimized retroviral vectors.

Retroviral transfer of the multidrug-resistance 1 (mdr1) cDNA into primary human hematopoietic progenitor cells (HPC) of cancer patients undergoing high-dose chemotherapy has been proposed to protect the bone marrow from the dose-limiting cytotoxicity of cytostatic agents. Preclinical studies performed with vectors derived from the Moloney murine leukemia virus (MoMuLV) or the related Harvey murine sarcoma virus have established that chemoprotection of HPC is feasible. The efficacy of vector-mediated multidrug-resistance under high doses of cytostatic agents, however, remained unclear. We report here that this goal can only be achieved with improved vector design. Novel vectors termed SF-MDR and MP-MDR, which are based on the spleen focus-forming virus or the myeloproliferative sarcoma virus for the enhancer and the murine embryonic stem cell virus for the leader, significantly elevate survival of transduced primary human HPC under moderate doses of colchicine and paclitaxel in vitro when compared with a conventional MoMuLV-based vector. Importantly, SF-MDR and also MP-MDR confer an absolute advantage at high doses of paclitaxel in vitro corresponding to peak plasma levels achieved in patients during chemotherapy. This observation has important consequences for a variety of ongoing and planned gene therapy trials.

Improved retroviral vectors for hematopoietic stem cell protection and in vivo selection.

Therapeutic gene transfer into hematopoietic cells is critically dependent on the evolution of methods that allow ex vivo expansion, high-frequency transduction, and selection of gene-modified long-term repopulating cells. Progress in this area needs elaboration of defined culture and transduction conditions for long-term repopulating cells and improvement of gene transfer systems. We have optimized retroviral vector constructions based on murine leukemia viruses (MuLV) to overcome the transcriptional repression encountered with the use of conventional Moloney MuLV (MoMuLV) vectors in early hematopoietic progenitor cells (HPC). Novel retroviral vectors, termed FMEV (for Friend-MCF/MESV hybrid vectors), were cloned that mediate greatly improved gene expression in the myeloerythroid compartment. Transfer of the selectable marker multidrug resistance 1 (mdr1), FMEV, in contrast to conventional MoMuLV-related vectors currently in use for clinical protocols, mediated background-free selectability of transduced human HPC in the presence of myeloablative doses of the cytostatic agent paclitaxel in vitro. Furthermore, FMEV also greatly improved chemo-protection of hematopoietic progenitor cells in a murine model system in vivo. Finally, when a second gene was transferred along with mdr1 in an FMEV-backbone, close to 100% coexpression was observed in multidrug-resistant colonies. These observations have significant consequences for a number of ongoing and planned gene therapy trials, for example, stem cell protection to reduce the myelotoxic side effects of anticancer chemotherapy, correction of inherited disorders involving hematopoietic cells, and antagonism of HIV infection.

Calculation of internal costs in a department of diagnostic radiology.

Even though high technology accounts for less than 1% of health care costs in industrialized countries, radiology is often blamed for their escalation. In a squeezed health care economy it is important to know the real cost of diagnostic radiological procedures in order to set priorities and realistic budgets, and to bill (actually or fictively) referring departments, physician's patients, insurance companies etc., and to demonstrate real costs of radiology for politicians and clinicians. The so-called Radiology Points used in the Nordic countries are in our opinion not adequate as basis for "price tags", even if to some extent they do reflect work and expenses involved in an examination. The real costs of ultrasonography (US) and excretory urography (UG) of the upper urinary tract have been compared in a study being performed to determine whether US can replace UG as the first examination in upper urinary tract disease. The cost of US is 53% (high osmolar contrast media) or 27% (anionic contrast media) of UG. If US can replace UG as the first examination in upper urinary tract disease the cost savings will be dramatic, especially if low osmolar or anionic contrast media are routinely used.