Comparison of magnetic resonance imaging of inhaled SF6 with respiratory gas analysis

Magnetic resonance imaging of inhaled fluorinated inert gases ((19)F-MRI) such as sulfur hexafluoride (SF(6)) allows for analysis of ventilated air spaces. In this study, the possibility of using this technique to image lung function was assessed. For this, (19)F-MRI of inhaled SF(6) was compared with respiratory gas analysis, which is a global but reliable measure of alveolar gas fraction. Five anesthetized pigs underwent multiple-breath wash-in procedures with a gas mixture of 70% SF(6) and 30% oxygen. Two-dimensional (19)F-MRI and end-expiratory gas fraction analysis were performed after 4 to 24 inhaled breaths. Signal intensity of (19)F-MRI and end-expiratory SF(6) fraction were evaluated with respect to linear correlation and reproducibility. Time constants were estimated by both MRI and respiratory gas analysis data and compared for agreement. A good linear correlation between signal intensity and end-expiratory gas fraction was found (correlation coefficient 0.99+/-0.01). The data were reproducible (standard error of signal intensity 8% vs. that of gas fraction 5%) and the comparison of time constants yielded a sufficient agreement. According to the good linear correlation and the acceptable reproducibility, we suggest the (19)F-MRI to be a valuable tool for quantification of intrapulmonary SF(6) and hence lung function.

Disorders of paravertebral lumbar muscles: from pathology to cross-sectional imaging

Paravertebral lumbar muscles are important for spine stabilization and mobility. They may be abnormal in several disorders that may be associated with pain or functional impairment. Special attention should be paid to the paravertebral muscles during imaging, so that a possible muscular disease is not overlooked, especially in patients with low back pain. This article reviews such imaging abnormalities.

Wild-type and splice-variant secretin receptors in lung cancer: overexpression in carcinoid tumors and peritumoral lung tissue

Gastrointestinal peptide hormone receptors, like somatostatin receptors, are often overexpressed in human cancer, allowing receptor-targeted tumor imaging and therapy. A novel candidate for these applications is the secretin receptor recently identified in pancreatic and cholangiocellular carcinomas. In the present study, secretin receptors were assessed in a non-gastrointestinal tissue, the human lung. Non-small-cell lung cancers (n=26), small-cell lung cancers (n=10), bronchopulmonary carcinoid tumors (n=29), and non-neoplastic lung (n=46) were investigated for secretin receptor protein expression with in vitro receptor autoradiography, using (125)I-[Tyr(10)] rat secretin and for secretin receptor transcripts with RT-PCR. Secretin receptor protein expression was found in 62% of bronchopulmonary carcinoids in moderate to high density, in 12% of non-small cell lung cancers in low density, but not in small cell lung cancers. In tumors found to be secretin receptor positive by autoradiography, RT-PCR revealed transcripts for the wild-type secretin receptor and for novel secretin receptor splice variants. In the non-neoplastic lung, secretin receptor protein expression was observed in low density along the alveolar septa in direct tumor vicinity in cases of acute inflammation, but not in histologically normal lung. In the autoradiographically positive peritumoral lung, RT-PCR showed transcripts for the wild-type secretin receptor and for a secretin receptor spliceoform different from those occurring in lung and gut tumors. In conclusion, secretin receptors are new markers for bronchopulmonary carcinoid tumors, and represent the molecular basis for an in vivo targeting of carcinoid tumors for diagnosis and therapy. Furthermore, secretin receptors may play a role in peritumoral lung pathophysiology. Secretin receptor mis-splicing specifically occurs in tumor and non-tumor lung pathology.

Advanced morphological and biochemical magnetic resonance imaging of cartilage repair procedures in the knee joint at 3 Tesla

Morphological and biochemical magnetic resonance imaging (MRI) is due to high field MR systems, advanced coil technology, and sophisticated sequence protocols capable of visualizing articular cartilage in vivo with high resolution in clinical applicable scan time. Several conventional two-dimensional (2D) and three-dimensional (3D) approaches show changes in cartilage structure. Furthermore newer isotropic 3D sequences show great promise in improving cartilage imaging and additionally in diagnosing surrounding pathologies within the knee joint. Functional MR approaches are additionally able to provide a specific measure of the composition of cartilage. Cartilage physiology and ultra-structure can be determined, changes in cartilage macromolecules can be detected, and cartilage repair tissue can thus be assessed and potentially differentiated. In cartilage defects and following nonsurgical and surgical cartilage repair, morphological MRI provides the basis for diagnosis and follow-up evaluation, whereas biochemical MRI provides a deeper insight into the composition of cartilage and cartilage repair tissue. A combination of both, together with clinical evaluation, may represent a desirable multimodal approach in the future, also available in routine clinical use.

Advances of dual source, dual-energy imaging in postmortem CT

This paper focuses on the use of multi-detector row dual-energy computed tomography (DECT) in the evaluation of postmortal examinations. The use of dual energy moves postmortem CT to an entirely new dimension of diagnostic sensitivity where contrast in the image is not merely limited to X-ray attenuation differences, but may include elements of functional and tissue characterization. This additional information may be used to improve the benefit postmortem imaging can provide to supplement and simplify the conventional autopsy.

Lung volume reduction surgery versus conservative treatment in severe emphysema

Lung volume reduction surgery (LVRS) has been proposed for patients with severe emphysema to improve dyspnoea and pulmonary function. It is unknown, however, whether prognosis and pulmonary function in these patients can be improved compared to conservative treatment. The effect of LVRS and conservative therapy were compared prospectively in 57 patients with emphysema, who fulfilled the standard criteria for LVRS. The patients were divided into two groups according to their own decision. Patients in group 1 (n=29, eight females, mean+/-SEM 58.8+/-1.7 yrs, forced expiratory volume in one second (FEV1) 27.6+/-1.3% of the predicted value) underwent LVRS. Patients in group 2 (n=28, five females, 58.5+/-1.8 yrs, FEV1 30.8+/-1.4% pred) preferred to postpone LVRS. There were no significant differences in lung function between the two groups at baseline; however, there was a tendency towards better functional status in the control group. The control group had a better modified Medical Research Council (MMRC) dyspnea score (3.1+/-0.15 versus 3.5+/-0.1, p<0.04). Model-based comparisons were used to estimate the differences between the two groups over 18 months. Significant improvements were observed in the LVRS group compared to the control group in FEV1, total lung capacity (TLC), Residual volume (RV), MMRC dyspnea score and 6-min walking distance on all follow up visits. The estimated difference in FEV1 was 33% (95% confidence interval 13-58%; p>0.0001), in TLC 12.9% (7.9-18.8%; p>0.0001), in RV 60.9% 32.6-89.2%; p>0.0001), in 6-min walking distance 230 m (138-322 m; p<0.002) and in MMRC dyspnoea score 1.17 (0.79-1.55; p<0.0001). In conclusion, lung volume reduction surgery is more effective than conservative treatment for the improvement of dyspnoea, lung function and exercise capacity in selected patients with severe emphysema.

miR-15a and miR-16 are implicated in cell cycle regulation in a Rb-dependent manner and are frequently deleted or down-regulated in non-small cell lung cancer

MicroRNAs (miRNA) are negative regulators of gene expression at the posttranscriptional level, which are involved in tumorigenesis. Two miRNAs, miR-15a and miR-16, which are located at chromosome 13q14, have been implicated in cell cycle control and apoptosis, but little information is available about their role in solid tumors. To address this question, we established a protocol to quantify miRNAs from laser capture microdissected tissues. Here, we show that miR-15a/miR-16 are frequently deleted or down-regulated in squamous cell carcinomas and adenocarcinomas of the lung. In these tumors, expression of miR-15a/miR-16 inversely correlates with the expression of cyclin D1. In non-small cell lung cancer (NSCLC) cell lines, cyclins D1, D2, and E1 are directly regulated by physiologic concentrations of miR-15a/miR-16. Consistent with these results, overexpression of these miRNAs induces cell cycle arrest in G(1)-G(0). Interestingly, H2009 cells lacking Rb are resistant to miR-15a/miR-16-induced cell cycle arrest, whereas reintroduction of functional Rb resensitizes these cells to miRNA activity. In contrast, down-regulation of Rb in A549 cells by RNA interference confers resistance to these miRNAs. Thus, cell cycle arrest induced by these miRNAs depends on the expression of Rb, confirming that G(1) cyclins are major targets of miR-15a/miR-16 in NSCLC. Our results indicate that miR-15a/miR-16 are implicated in cell cycle control and likely contribute to the tumorigenesis of NSCLC.

Narrow band imaging (NBI) during medical thoracoscopy: first impressions

Background This is the first ever evaluation of narrow band imaging (NBI), an innovative endoscopic imaging procedure, for the visualisation of pleural processes. Methods The pleural cavity was examined in 26 patients with pleural effusions using both white light and narrow band imaging during thoracoscopy under local anaesthesia. Results In the great majority of the patients narrow band imaging depicted the blood vessels more clearly than white light, but failed to reveal any differences in number, shape or size. Only in a single case with pleura thickened by chronic inflammation and metastatic spread of lung cancer did narrow band imaging show vessels that were not detectable under white light. Conclusion It is not yet possible to assess to what extent the evidence provided by NBI is superior to that achieved with white light. Further studies are required, particularly in the early stages of pleural processes.

A functional model for adult stem cells in epithelial tissues

Tissue turnover, regeneration, and repair take place throughout life. Stem cells are key players in these processes. The characteristics and niches of the stem cell populations in different tissues, and even in related tissues, vary extensively. In this review, stem cell differentiation and stem cell contribution to tissue maintenance and regeneration is compared in the epithelia of the skin, the cornea, the lung, and the intestine. A hierarchical model for adult stem cells is proposed, based on the potency of stem cell subpopulations in a specific tissue. The potency is defined in terms of the maintenance, the repair, and the regeneration of the tissue. The niche supplies cues to maintain the specific stem cell potency.

Visualization of alveolar recruitment in a porcine model of unilateral lung lavage using 3He-MRI

BACKGROUND: In the acute respiratory distress syndrome potentially recruitable lung volume is currently discussed. (3)He-magnetic resonance imaging ((3)He-MRI) offers the possibility to visualize alveolar recruitment directly. METHODS: With the approval of the state animal care committee, unilateral lung damage was induced in seven anesthetized pigs by saline lavage of the right lungs. The left lung served as an intraindividual control (healthy lung). Unilateral lung damage was confirmed by conventional proton MRI and spiral-CT scanning. The total aerated lung volume was determined both at a positive end-expiratory pressure (PEEP) of 0 and 10 mbar from three-dimensionally reconstructed (3)He images, both for healthy and damaged lungs. The fractional increase of aerated volume in damaged and healthy lungs, followed by a PEEP increase from 0 to 10 mbar, was compared. RESULTS: Aerated gas space was visualized with a high spatial resolution in the three-dimensionally reconstructed (3)He-MR images, and aeration defects in the lavaged lung matched the regional distribution of atelectasis in proton MRI. After recruitment and PEEP increase, the aerated volume increased significantly both in healthy lungs from 415 ml [270-445] (median [min-max]) to 481 ml [347-523] and in lavaged lungs from 264 ml [71-424] to 424 ml [129-520]. The fractional increase in lavaged lungs was significantly larger than that in healthy lungs (healthy: 17% [11-38] vs. lavage: 42% [14-90] (P=0.031). CONCLUSION: The (3)He-MRI signal might offer an experimental approach to discriminate atelectatic vs. poor aerated lung areas in a lung damage animal model. Our results confirm the presence of potential recruitable lung volume by either alveolar collapse or alveolar flooding, in accordance with previous reports by computed tomography.

The Src inhibitor AZD0530 blocks invasion and may act as a radiosensitizer in lung cancer cells

BACKGROUND: With the emergence of Src inhibitors in clinical trials, improved knowledge of the molecular responses of cancer cells to these agents is warranted. This will facilitate the development of tests to identify patients who may benefit from these agents, allow drug activity to be monitored and rationalize the combination of these agents with other treatment modalities. METHODS: This study evaluated the molecular and functional effects of Src inhibitor AZD0530 in human lung cancer cells, by Western blotting and reverse transcription-polymerase chain reaction, and by assays for cell viability, migration, and invasion. RESULTS: Src was activated in four of five cell lines tested and the level corresponded with the invasive potential and the histologic subtype. Clinically relevant, submicromolar concentrations of AZD0530 blocked Src and focal adhesion kinase, resulting in significant inhibition of cell migration and Matrigel invasion. Reactivation of STAT3 and up-regulation of JAK indicated a potential mechanism of resistance. AZD0530 gave a potent and sustained blockage of AKT and enhanced the sensitivity to irradiation. CONCLUSIONS: The results indicated that AZD0530, aside from being a potent inhibitor of tumor cell invasion which could translate to inhibition of disease progression in the clinic, may also lower resistance of lung cancer cells to pro-apoptotic signals.

3D Ultrasound imaging--a useful non-invasive tool to detect AV fistulas in transplanted kidneys

BACKGROUND: A precise, non-invasive, non-toxic, repeatable, convenient and inexpensive follow-up of renal transplants, especially following biopsies, is in the interest of nephrologists. Formerly, the rate of biopsies leading to AV fistulas had been underestimated. Imaging procedures suited to a detailed judgement of these vascular malformations are to be assessed. METHODS: Three-dimensional (3D) reconstruction techniques of ultrasound flow-directed and non-flow-directed energy mode pictures were compared with a standard procedure, gadolinium-enhanced nuclear magnetic resonance imaging angiography (MRA) using the phase contrast technique. RESULTS: Using B-mode and conventional duplex information, AV fistulas were localized in the upper pole of the kidney transplant of the index patient. The 3D reconstruction provided information about the exact localization and orientation of the fistula in relation to other vascular structures, and the flow along the fistula. The MRA provided localization and orientation information, but less functional information. Flow-directed and non-flow-directed energy mode pictures could be reconstructed to provide 3D information about vascular malformations in transplanted kidneys. CONCLUSION: In transplanted kidneys, 3D-ultrasound angiography may be equally as effective as MRA in localizing and identifying AV malformations. Advantages of the ultrasound method are that it is cheaper, non-toxic, non-invasive, more widely availability and that it even provides more functional information. Future prospective studies will be necessary to evaluate the two techniques further.

High-density electrode array for imaging in vitro electrophysiological activity

The development of a high-density active microelectrode array for in vitro electrophysiology is reported. Based on the Active Pixel Sensor (APS) concept, the array integrates 4096 gold microelectrodes (electrode separation 20 microm) on a surface of 2.5 mmx2.5 mm as well as a high-speed random addressing logic allowing the sequential selection of the measuring pixels. Following the electrical characterization in a phosphate solution, the functional evaluation has been carried out by recording the spontaneous electrical activity of neonatal rat cardiomyocytes. Signals with amplitudes from 130 microVp-p to 300 microVp-p could be recorded from different pixels. The results demonstrate the suitability of the APS concept for developing a new generation of high-resolution extracellular recording devices for in vitro electrophysiology.

Dose optimization approach to fast X-ray microtomography of the lung alveoli

A basic prerequisite for in vivo X-ray imaging of the lung is the exact determination of radiation dose. Achieving resolutions of the order of micrometres may become particularly challenging owing to increased dose, which in the worst case can be lethal for the imaged animal model. A framework for linking image quality to radiation dose in order to optimize experimental parameters with respect to dose reduction is presented. The approach may find application for current and future in vivo studies to facilitate proper experiment planning and radiation risk assessment on the one hand and exploit imaging capabilities on the other.

Visualization and stereological characterization of individual rat lung acini by high-resolution X-ray tomographic microscopy

The small trees of gas-exchanging pulmonary airways which are fed by the most distal purely conducting airways are called acini and represent the functional gas-exchanging units. The three-dimensional architecture of the acini has a strong influence on ventilation and particle deposition. Due to the difficulty to identify individual acini on microscopic lung sections the knowledge about the number of acini and their biological parameters like volume, surface area, and number of alveoli per acinus are limited. We developed a method to extract individual acini from lungs imaged by high-resolution synchrotron radiation based X-ray tomographic microscopy and estimated their volume, surface area and number of alveoli. Rat acini were isolated by semiautomatically closing the airways at the transition from conducting to gas-exchanging airways. We estimated a mean internal acinar volume of 1.148mm(3), a mean acinar surface area of 73.9mm(2), and a mean of 8470 alveoli per acinus. Assuming that the acini are similarly sized throughout different regions of the lung, we calculated that a rat lung contains 5470±833 acini. We conclude that our novel approach is well suited for the fast and reliable characterization of a large number of individual acini in healthy, diseased, or transgenic lungs of different species including humans.