Bertil Leidner

Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study

BACKGROUND Tracheal tumours can be surgically resected but most are an inoperable size at the time of diagnosis; therefore, new therapeutic options are needed. We report the clinical transplantation of the tracheobronchial airway with a stem-cell-seeded bioartificial nanocomposite. METHODS A 36-year-old male patient, previously treated with debulking surgery and radiation therapy, presented with recurrent primary cancer of the distal trachea and main bronchi. After complete tumour resection, the airway was replaced with a tailored bioartificial nanocomposite previously seeded with autologous bone-marrow mononuclear cells via a bioreactor for 36 h. Postoperative granulocyte colony-stimulating factor filgrastim (10 μg/kg) and epoetin beta (40,000 UI) were given over 14 days. We undertook flow cytometry, scanning electron microscopy, confocal microscopy epigenetics, multiplex, miRNA, and gene expression analyses. FINDINGS We noted an extracellular matrix-like coating and proliferating cells including a CD105+ subpopulation in the scaffold after the reseeding and bioreactor process. There were no major complications, and the patient was asymptomatic and tumour free 5 months after transplantation. The bioartificial nanocomposite has patent anastomoses, lined with a vascularised neomucosa, and was partly covered by nearly healthy epithelium. Postoperatively, we detected a mobilisation of peripheral cells displaying increased mesenchymal stromal cell phenotype, and upregulation of epoetin receptors, antiapoptotic genes, and miR-34 and miR-449 biomarkers. These findings, together with increased levels of regenerative-associated plasma factors, strongly suggest stem-cell homing and cell-mediated wound repair, extracellular matrix remodelling, and neovascularisation of the graft. INTERPRETATION Tailor-made bioartificial scaffolds can be used to replace complex airway defects. The bioreactor reseeding process and pharmacological-induced site-specific and graft-specific regeneration and tissue protection are key factors for successful clinical outcome. FUNDING European Commission, Knut and Alice Wallenberg Foundation, Swedish Research Council, StratRegen, Vinnova Foundation, Radiumhemmet, Clinigene EU Network of Excellence, Swedish Cancer Society, Centre for Biosciences (The Live Cell imaging Unit), and UCL Business.

Time-resolved computed tomography of the liver: retrospective, multi-phase image reconstruction derived from volumetric perfusion imaging

AbstractObjectiveTo assess feasibility and image quality (IQ) of a new post-processing algorithm for retrospective extraction of an optimised multi-phase CT (time-resolved CT) of the liver from volumetric perfusion imaging.MethodsSixteen patients underwent clinically indicated perfusion CT using 4D spiral mode of dual-source 128-slice CT. Three image sets were reconstructed: motion-corrected and noise-reduced (MCNR) images derived from 4D raw data; maximum and average intensity projections (time MIP/AVG) of the arterial/portal/portal-venous phases and all phases (total MIP/ AVG) derived from retrospective fusion of dedicated MCNR split series. Two readers assessed the IQ, detection rate and evaluation time; one reader assessed image noise and lesion-to-liver contrast.ResultsTime-resolved CT was feasible in all patients. Each post-processing step yielded a significant reduction of image noise and evaluation time, maintaining lesion-to-liver contrast. Time MIPs/AVGs showed the highest overall IQ without relevant motion artefacts and best depiction of arterial and portal/portal-venous phases respectively. Time MIPs demonstrated a significantly higher detection rate for arterialised liver lesions than total MIPs/AVGs and the raw data series.ConclusionTime-resolved CT allows data from volumetric perfusion imaging to be condensed into an optimised multi-phase liver CT, yielding a superior IQ and higher detection rate for arterialised liver lesions than the raw data series.Key Points• Four-dimensional computed tomography is limited by motion artefacts and poor image quality. • Time-resolved-CT facilitates 4D-CT data visualisation, segmentation and analysis by condensing raw data. • Time-resolved CT demonstrates better image quality than raw data images. • Time-resolved CT improves detection of arterialised liver lesions in cirrhotic patients.

Low tube voltage CT for improved detection of pancreatic cancer: detection threshold for small, simulated lesions

BackgroundPancreatic ductal adenocarcinoma is associated with dismal prognosis. The detection of small pancreatic tumors which are still resectable is still a challenging problem.The aim of this study was to investigate the effect of decreasing the tube voltage from 120 to 80 kV on the detection of pancreatic tumors.MethodsThree scanning protocols was used; one using the standard tube voltage (120 kV) and current (160 mA) and two using 80 kV but with different tube currents (500 and 675 mA) to achieve equivalent dose (15 mGy) and noise (15 HU) as that of the standard protocol.Tumors were simulated into collected CT phantom images. The attenuation in normal parenchyma at 120 kV was set at 130 HU, as measured previously in clinical examinations, and the tumor attenuation was assumed to differ 20 HU and was set at 110HU. By scanning and measuring of iodine solution with different concentrations the corresponding tumor and parenchyma attenuation at 80 kV was found to be 185 and 219 HU, respectively.To objectively evaluate the differences between the three protocols, a multi-reader multi-case receiver operating characteristic study was conducted, using three readers and 100 cases, each containing 0–3 lesions.ResultsThe highest reader averaged figure-of-merit (FOM) was achieved for 80 kV and 675 mA (FOM = 0,850), and the lowest for 120 kV (FOM = 0,709). There was a significant difference between the three protocols (p < 0,0001), when making an analysis of variance (ANOVA). Post-hoc analysis (students t-test) shows that there was a significant difference between 120 and 80 kV, but not between the two levels of tube currents at 80 kV.ConclusionWe conclude that when decreasing the tube voltage there is a significant improvement in tumor conspicuity.

Computed tomography staging of pancreatic cancer: A validation study addressing interobserver agreement

BACKGROUND/OBJECTIVES Ductal adenocarcinoma in the head of the pancreas (PDAC) is usually unresectable at the time of diagnosis due to the involvement of the peripancreatic vessels. Various preoperative classification algorithms have been developed to describe the relationship of the tumor to these vessels, but most of them lack a surgically based approach. We present a CT-based classification algorithm for PDAC based on surgical resectability principles with a focus on interobserver variability. METHODS Thirty patients with PDAC undergoing pancreaticoduodenectomy were examined by using a standard CT protocol. Nine radiologists, representing three different levels of expertise, evaluated the CT examinations and the tumors were classified into four categories (A-D) according to the proposed system. For the interobserver agreement, the Intraclass Correlation Coefficient (ICC) was estimated. RESULTS The overall ICC was 0.94 and the ICCs among the trainees, experienced radiologists, and experts were 0.85, 0.76, and 0.92, respectively. All tumors classified as category A1 showed no signs of vascular invasion at surgery. In category A2, 40% of the tumors had corresponding infiltration and required resection of the superior mesenteric vein/portal vein (SMV/PV). One of two tumors in category B2 and two of three in category C required SMV/PV resection. All six patients in category D had both arterial and venous involvement. CONCLUSION There is almost perfect agreement among radiologists with different levels of expertise in regards to the local staging of PDAC. For tumors in a more advanced preoperative category, an increased risk for vascular involvement was noticed at surgery.

Visualization of dialysis fistula by computed tomography using time-resolved 3D volume rendering.

BACKGROUND To evaluate the function of arteriovenous (AV) dialysis fistula using dynamic computed tomography (CT) and time-resolved 3-dimensional (3D) volume rendering (VR). METHODS Seven patients referred for angiographic CT examination of the AV dialysis fistula were enrolled. Twenty-four grams of iodine were administered intravenously (iomeprol 400 mg I/mL at 6 mL/sec) followed by a 50-mL saline flush. Dynamic scanning was performed for 15-24 sec. CT images were then postprocessed on a dedicated workstation creating time-resolved 3D VR images and movies. RESULTS All studies showed good image quality showing pathology in 6 of 7 patients. Unexpected findings were observed in 1 patient, aneurysm (n = 1). Radiation dose was 5 mSv. CONCLUSIONS The function of AV dialysis fistula can be visualized using dynamic CT and time-resolved 3D VR.