Computed tomography findings in septic patients with acute respiratory distress syndrome: correlation with survival and pulmonary versus extrapulmonary septic focus.

OBJECTIVE: The objective of this study was to evaluate computed tomography (CT) findings in patients with sepsis with unknown inflammatory focus and acute respiratory distress syndrome. METHODS: Acute respiratory distress syndrome findings on CT of 36 patients with sepsis were graded on a 6-point scale, and the percentage of affected lung was estimated. Resulting CT scores were correlated to intensive care scores and survival. RESULTS: Forty-four percent of the patients died, revealing a significantly higher CT score than survivors (P = 0.01). Survivors showed larger areas of unaffected lung (P < 0.001), whereas patients with fatal outcome had more ground-glass opacities (P = 0.002; sensitivity, 73%; specificity, 57%) and traction bronchiectasis (P = 0.009; sensitivity, 54%; specificity, 68%). Pulmonary findings on CT did not allow discriminating between a pulmonary and extrapulmonary focus. No significant coherence between CT score and intensive care scores could be revealed. CONCLUSIONS: A CT scoring system based on pulmonary findings in patients with sepsis with acute respiratory distress syndrome comprises prognostic implications in terms of the patients' survival.

Feasibility of fast dynamic MRI for noninvasive monitoring during ectopic liver cell transplantation to the spleen in a porcine model.

OBJECTIVE: Liver cell transplantation is a promising approach for the treatment of metabolic liver disorders. However, a method for noninvasive monitoring during liver cell transplantation is not available clinically. The aim of this study was to investigate the feasibility of fast dynamic MRI monitoring during liver cell infusion to the spleen, which is considered an ectopic implantation site for liver cell transplantation. MATERIALS AND METHODS: Porcine liver cells were labeled with micron-sized iron oxide particles and infused to the spleens of pigs (n = 5) via the lineal artery. MRI was performed using a 3-T MR scanner. Initially, T1- and T2-weighted pulse sequences were tested. Thereafter, fast dynamic MRI was performed during cell infusion. MR findings were verified by immunohistological examinations. RESULTS: Images from static MRI (TR/TE, 2500/105.2) showed significantly lower signal intensity and signal-to-noise ratio after cell infusion compared with pretransplant images. T2-weighted fast dynamic MRI enabled visualization of signal decrease of the spleen during cell infusion. When cells were infused systemically, no signal changes in the spleen were observed. CONCLUSION: This study shows that fast dynamic MRI can enable noninvasive monitoring during liver cell transplantation to the spleen. This approach could be useful for preclinical studies and for quality control of clinical liver cell transplantation.

Development of a signal-inducing bone cement for magnetic resonance imaging.

PURPOSE: To develop a signal-inducing bone cement for musculoskeletal procedures in magnetic resonance imaging (MRI). MATERIALS AND METHODS: Acrylic resins were mixed with contrast agents (CAs) and water. We determined the ideal concentration of the components and assessed feasibility in cadaveric bones in an open high-field MR scanner. The contrast-to-noise ratio (CNR) in air and bone was evaluated and mechanical tests were achieved. We determined the amount of water that was not incorporated and measured the amount of CA released with photometric analysis. The cement was analyzed microscopically. RESULTS: Preparation and application of the CA-water-cement compound was feasible and its differentiation in MRI was clear. The maximal CNR(air) had a value of 157.5 (SD 18.3) in an interventional fast T1W turbo-spin echo (TSE) sequence. The compressive strength decreased with the amount of water added. Although nearly 50% of the water added was not incorporated in the cement, the CNR was sufficient for cement detection. The threshold for systemic toxicity of delivered CA was not reached and the microscopic analysis showed water bubbles in the cement. CONCLUSION: A signal-inducing bone cement is feasible for the use in MRI.

Sonographically guided placement of intravenous catheters in minipigs.

Many procedures in minipigs require establishment of reliable deep venous access with a large-bore catheter. In animal experiments, such catheters are typically implanted surgically. In clinical settings, however, ultrasound imaging is routinely used to facilitate safe, minimally invasive puncture of deep vessels. The authors describe a technique for using ultrasound guidance to puncture and cannulate the minipig femoral vein. They carried out the procedure in six minipigs for the purpose of injecting contrast agents for subsequent imaging scans. The procedure was ultimately successful in all pigs, took 10 min on average and resulted in no physiological complications. In one minipig, however, a 10-cm-long catheter became dislodged from the femoral vein; use of a longer (25-cm-long) catheter was optimal for establishing reliable intravenous access.

An orthotopic model of pancreatic somatostatin receptor (SSTR)-positive tumors allows bimodal imaging studies using 3T MRI and animal PET-based molecular imaging of SSTR expression.

Somatostatin receptor (SSTR) scintigraphy is currently used as one standard imaging modality in neuroendocrine tumors (NETs). However, future optimization of NET imaging may be achieved with positron emission tomography based methods utilizing more sensitive and specific tracers in combination with computed tomography or magnetic resonance imaging. Here we established an orthotopic mouse model that reflects relevant aspects of human pancreatic NETs such as SSTR expression, dense vascularization and metastatic disease. This model was then utilized to test the feasibility of combined magnetic resonance imaging and animal positron emission tomography. Orthotopic implantation of amphicrine, SSTR-positive pancreatic AR42J cells resulted in rapidly growing tumors, with concomitant metastatic spread into abdominal lymph nodes and peritoneal cavity. Primary tumors as well as their metastases expressed the neuroendocrine markers chromogranin A and synaptophysin. For imaging experiments, the SSTR ligands (68)Ga-DOTATOC or (68)Ga-DOTANOC were injected intravenously, and animals were subsequently examined in an animal positron emission tomography scanner and a clinical 3T (tesla) magnetic resonance imager. All animals showed radionuclide accumulation in the primary tumor. Definite anatomical correlation was achieved using digital image fusion of the positron emission tomography and magnetic resonance imaging data. (68)Ga-DOTANOC strongly accumulated in the tumor tissue (mean 6.6-fold vs. control tissues) when compared to (68)Ga-DOTATOC, which showed a higher renal clearance. In good agreement with the biodistribution data, the kidney-to-tumor ratio was higher for (68)Ga-DOTATOC (2.43-fold vs. 1.75-fold). Consequently, (68)Ga-DOTANOC achieved better signal enhancement in the primary tumor and allowed for detection of metastatic lesions. In summary, we established a novel orthotopic pancreatic SSTR-positive tumor model and used this model to provide proof of principle for the diagnostic combination of SSTR-based molecular imaging and magnetic resonance imaging. Specifically, the animal model allowed the comparative evaluation of (68)Ga-DOTANOC and (68)Ga-DOTATOC, with (68)Ga-DOTANOC providing better tumor-specific accumulation and renal activity. We conclude that this animal model will be of innovative value for further investigation in the imaging of NETs.

Local arterial infusion of superparamagnetic iron oxide particles in hepatocellular carcinoma: A feasibility and 3.0 T MRI study.

OBJECTIVES: We sought to prove feasibility of selective arterial infusion of superparamagnetic iron oxide (SPIO) particles in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We studied 13 patients with HCC who underwent modified transarterial chemoembolization (TACE). Six patients received concurrent infusion of Ferucarbotran (Resovist, Schering, Berlin, Germany) in tumor-feeding arteries, and another 6 received MFL AS (MagForce, Nanotechnologies, Berlin, Germany). The iron content of both dispersions was 3.92 mg. One patient served as a control. All patients underwent magnetic resonance imaging (MRI) as baseline and immediate follow-up investigation. RESULTS: Selective arterial infusion of both SPIO particles resulted in significant intratumoral signal intensity decrease on T1-weighted sequences (P < 0.0001), which was greater after MagForce infusion compared with Resovist (P = 0.002). Only minimal amounts of dispersed particles were found in adjacent normal liver parenchyma. No change in intratumoral signal intensity was noted when ferromagnetic particles were omitted. CONCLUSIONS: Modified TACE with selective arterial infusion of SPIO particles can be used for precise tumor targeting in patients with HCC, for which MagForce appeared superior to Resovist.

Portable computed tomography performed on the intensive care unit.

OBJECTIVE: We report on the use of portable computed tomography (CT) in an ICU setting. The additional diagnostic gain and therapeutic consequences were assessed. PATIENTS: Ten ICU patients underwent 14 portable chest CT examinations. In 64% maximum intensive care was required, according to TISS28 (>40), and 42% were at a risk of mortality higher than 25% (MODS) on the day of portable CT examination. In three portable CT examinations the patients were considered not transportable and were examined directly in the patient room. All other examinations were performed in a special interventional suite directly on the ICU. RESULTS: Of 14 examinations 8 (57%) resulted in a change in patient management within 48 h. All patients profited from portable CT and no hazards occurred related to CT. CONCLUSIONS: To perform portable CT in the interventional suite on the ICU allows immediate minimally invasive therapeutic interventions and provides full ICU monitoring.

Modification of aminosilanized superparamagnetic nanoparticles: feasibility of multimodal detection using 3T MRI, small animal PET, and fluorescence imaging.

PURPOSE: The aim of our study was to modify an aminosilane-coated superparamagnetic nanoparticle for cell labeling and subsequent multimodal imaging using magnetic resonance imaging (MRI), positron emission tomography (PET), and fluorescent imaging in vivo. PROCEDURES: We covalently bound the transfection agent HIV-1 tat, the fluorescent dye fluorescein isothiocyanate, and the positron-emitting radionuclide gallium-68 to the particle and injected them intravenously into Wistar rats, followed by animal PET and MRI at 3.0 T. As a proof of principle hepatogenic HuH7 cells were labeled with the particles and observed for cell toxicity as well as detectability by MRI and biodistribution in vivo. RESULTS: PET imaging and MRI revealed increasing hepatic and splenic accumulation of the particles over 24 h. Adjacent in vitro studies in hepatogenic HuH7 cells showed a rapid intracellular accumulation of the particles with high labeling efficiency and without any signs of toxicity. In vivo dissemination of the labeled cells could be followed by dynamic biodistribution studies. CONCLUSIONS: We conclude that our modified superparamagnetic nanoparticles are stable under in vitro and in vivo conditions and are therefore applicable for efficient cell labeling and subsequent multimodal molecular imaging. Moreover, their multiple free amino groups suggest the possibility for further modifications and might provide interesting opportunities for various research fields.

Imaging of primary human hepatocytes performed with micron-sized iron oxide particles and clinical magnetic resonance tomography.

Transplantation of primary human hepatocytes is a promising approach in certain liver diseases. For the visualization of the hepatocytes during and following cell application and the ability of a timely response to potential complications, a non-invasive modality for imaging the transplanted cells has to be established. The aim of this study was to label primary human hepatocytes with micron-sized iron oxide particles (MPIOs), enabling the detection of cells by clinical magnetic resonance imaging (MRI). Primary human hepatocytes isolated from 13 different donors were used for the labelling experiments. Following the dose-finding studies, hepatocytes were incubated with 30 particles/cell for 4 hrs in an adhesion culture. Particle incorporation was investigated via light, fluorescence and electron microscopy, and labelled cells were fixed and analysed in an agarose suspension by a 3.0 Tesla MR scanner. The hepatocytes were enzymatically resuspended and analysed during a 5-day reculture period for viability, total protein, enzyme leakage (aspartate aminotransferase [AST], lactate dehydrogenase [LDH]) and metabolic activity (urea, albumin). A mean uptake of 18 particles/cell could be observed, and the primary human hepatocytes were clearly detectable by MR instrumentation. The particle load was not affected by resuspension and showed no alternations during the culture period. Compared to control groups, labelling and resuspension had no adverse effects on the viability, enzyme leakage and metabolic activity of the human hepatocytes. The feasibility of preparing MPIO-labelled primary human hepatocytes detectable by clinical MR equipment was shown in vitro. MPIO-labelled cells could serve for basic research and quality control in the clinical setting of human hepatocyte transplantation.

The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma.

Thermotherapy using magnetic nanoparticles is a new technique for interstitial hyperthermia and thermoablation based on magnetic field-induced excitation of biocompatible superparamagnetic nanoparticles. To evaluate the potential of this technique for minimally invasive treatment, we carried out a systematic analysis of its effects on experimental glioblastoma multiforme in a rat tumor model. Tumors were induced by implantation of RG-2-cells into the brains of 120 male Fisher rats. Animals were randomly allocated to 10 groups of 12 rats each, including controls. Animals received two thermotherapy treatments following a single intratumoral injection of two different magnetic fluids (dextran- or aminosilane-coated iron-oxide nanoparticles). Treatment was carried out on days four and six after tumor induction using an alternating magnetic field applicator system operating at a frequency of 100 kHz and variable field strength of 0-18 kA/m. The effectiveness of treatment was determined by the survival time of the animals and histopathological examinations of the brain and the tumor.Thermotherapy with aminosilane-coated nanoparticles led up to 4.5-fold prolongation of survival over controls, while the dextran-coated particles did not indicate any advantage. Intratumoral deposition of the aminosilane-coated particles was found to be stable, allowing for serial thermotherapy treatments without repeated injection. Histological and immunohistochemical examinations after treatment revealed large necrotic areas close to particle deposits, a decreased proliferation rate and a reactive astrogliosis adjacent to the tumor.Thus, localized interstitial thermotherapy with magnetic nanoparticles has an antitumoral effect on malignant brain tumors. This method is suitable for clinical use and may be a novel strategy for treating malignant glioma, which cannot be treated successfully today. The optimal treatment schedules and potential combinations with other therapies need to be defined in further studies.

Imaging of single human carcinoma cells in vitro using a clinical whole-body magnetic resonance scanner at 3.0 T.

The purpose of the present study was to examine whether single human carcinoma cells labeled with iron oxide nanoparticles could be detected by magnetic resonance (MR) imaging on a clinical 3-T scanner using a surface coil only. WiDr human colon carcinoma cells were loaded with two kinds of iron oxide nanoparticles differing by coating and size: aminosilan-coated (MagForce) and carboxy-dextran-coated particles (Resovist). The latter were preferred by the colon carcinoma cell line used here and taken up much faster (12 h) than the smaller carboxydextran-coated Resovist (48 h). Labeled single carcinoma cells, distributed in an agarose gel in a monodisperse layer as controlled by light microscopy, became detectable as punctuate signal extinctions when using a small circularly polarized surface coil in conjunction with a T(2)*-weighted GE sequence at 3 T. The threshold for the detectability of labeled colon carcinoma cells ranged at a load of 4-5 mug iron/10(6) cells. Obviating the need for special hardware additions, this study opens a new lane for single-cell tracking on clinical 3-T MR scanners amenable to patient studies.