Cavity length control for Fourier domain mode locked (FDML) lasers with µm precision

In highly dispersion compensated Fourier domain mode locked (FDML) lasers, an ultra-low noise operation can only be achieved by extremely precise and stable matching of the filter tuning period and light circulation time in the cavity. We present a robust and high precision closed-loop control algorithm and an actively cavity length controlled FDML laser. The cavity length control achieves a stability of ∼0.18 mHz at a sweep repetition rate of ∼418 kHz which corresponds to a ratio of 4×10⁻¹⁰. Furthermore, we prove that the rapid change of the cavity length has no negative impact on the quality of optical coherence tomography using the FDML laser as light source.     

Repeatability of hypoxia PET imaging using [<Superscript>18</Superscript>F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial

Purpose

Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [¹⁸F]HX4 in patients with head and neck and lung cancer.

Methods

Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [¹⁸F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUV_max and SUV_mean) were defined and the tumor-to-background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV_1.2). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient.

Results

All parameters of [¹⁸F]HX4 uptake were significantly correlated between scans: SUV_max (r?=?0.958, p?<?0.001), SUV_mean (r?=?0.946, p?<?0.001), TBR_max (r?=?0.962, p?<?0.001) and HV_1.2 (r?=?0.995, p?<?0.001). The relative coefficients of repeatability were 15 % (SUV_mean), 17 % (SUV_max) and 17 % (TBR_max). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65?±?0.14.

Conclusion

Repeated hypoxia PET scans with [¹⁸F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [¹⁸F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments.

     

Acute effects and long-term outcome of pulmonary vein isolation in combination with electrogram-guided substrate ablation for persistent atrial fibrillation

Complex fractionated atrial electrographic (CFAE) catheter ablation is a new approach for the treatment of atrial fibrillation (AF). It is unclear if acute results of this approach correspond to long-term outcome. The purpose of this study was to prospectively assess acute and long-term successes of an ablation approach combining pulmonary vein isolation (PVI) and ablation of CFAE areas for treatment of persistent AF. PVI and ablation of CFAE areas were performed in 35 patients with persistent AF (30 men, 57+/-9 years of age). At the end of the ablation procedure AF had terminated in 23 of 35 patients (66%) by conversion to sinus rhythm (8 of 23 patients, 35%) or organization to atrial tachycardia (15 of 23 patients, 65%). AF persisted in 12 of 35 patients (34%). At the end of the follow-up period (19+/-12 months), sinus rhythm was present in 26 of 35 patients (74%), including 9 patients with a repeat procedure. This group of 26 patients consisted of 7 of 8 patients (88%) with acute sinus rhythm after the first ablation, 11 of 15 patients (73%) with organization, and 8 of 12 patients (66%) with ongoing AF (p=0.32). In conclusion, a combined approach of PVI and CFAE ablation in persistent AF leads to acute AF termination in 66% and long-term maintenance of sinus rhythm in 74% of cases. However, long-term outcome was not predictable by acute results of the ablation procedure.     

The small heat‐shock protein αB‐crystallin is essential for the nuclear localization of Smad4: impact on pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by the proliferation of myofibroblasts and the accumulation of extracellular matrix (ECM) in the lungs. TGF‐β1 is the major profibrotic cytokine involved in IPF and is responsible for myofibroblast proliferation and differentiation and ECM synthesis. αB‐crystallin is constitutively expressed in the lungs and is inducible by stress, acts as a chaperone and is known to play a role in cell cytoskeleton architecture homeostasis. The role of αB‐crystallin in fibrogenesis remains unknown. The principal signalling pathway involved in this process is the Smad‐dependent pathway. We demonstrate here that αB‐crystallin is strongly expressed in fibrotic lung tissue from IPF patients and in vivo rodent models of pulmonary fibrosis. We also show that αB‐crystallin‐deficient mice are protected from bleomycin‐induced fibrosis. Similar protection from fibrosis was observed in αB‐crystallin KO mice after transient adenoviral‐mediated over‐expression of IL‐1β or TGF‐β1. We show in vitro in primary epithelial cells and fibroblasts that αB‐crystallin increases the nuclear localization of Smad4, thereby enhancing the TGF‐β1–Smad pathway and the consequent activation of TGF‐β1 downstream genes. αB‐crystallin over‐expression disrupts Smad4 mono‐ubiquitination by interacting with its E3–ubiquitin ligase, TIF1γ, thus limiting its nuclear export. Conversely, in the absence of αB‐crystallin, TIF1γ can freely interact with Smad4. Consequently, Smad4 mono‐ubiquitination and nuclear export are favoured and thus TGF‐β1–Smad4 pro‐fibrotic activity is inhibited. This study demonstrates that αB‐crystallin may be a key target for the development of specific drugs in the treatment of IPF or other fibrotic diseases. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Angiogenesis in pulmonary fibrosis: too much or not enough?

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and usually fatal disease, based on a multifaceted and incompletely understood pathogenesis. Some of the cellular and molecular mechanisms of vascular remodeling have been experimentally explored, and it is obvious that alterations of microvessels are involved in IPF. These can, among others, lead to the development of pulmonary hypertension. In order to understand the process of vascular integrity and repair, it is necessary to identify the factors associated with angiogenesis in IPF. A delicate balance of angiogenic and angiostatic factors regulates vessel homeostasis in normal physiologic conditions in the lungs. Although earlier studies have proposed that IPF is associated with an increase of angiogenesis, there is some more recent evidence that angiogenesis in fibrotic lungs may actually be decreased, causing some controversy in the literature in this area. This review, therefore, discusses the concept of angiogenesis in pulmonary fibrosis and speculates on how the spatial and temporal heterogeneity of IPF might explain the controversial findings about vessel density in fibrotic lungs.     

Comparison of the Classically Conditioned Withdrawal Reflex in Cerebellar Patients and Healthy Control Subjects During Stance: I. Electrophysiological Characteristics

The aim of this study was to demonstrate the involvement of the human cerebellum in the classically conditioned lower limb withdrawal reflex in standing subjects. Electromyographic activity was recorded from the main muscle groups of both legs of eight patients with cerebellar disease (CBL) and eight control subjects (CTRL). The unconditioned stimulus (US) consisted of electrical stimulation of the tibial nerve at the medial malleolus. The conditioning stimulus (CS) was an auditory signal given via headphones. Experiments started with 70 paired conditioning stimulus–unconditioned stimulus(CSUS) trials followed by 50 US-alone trials. The general reaction consisted of lifting and flexing the stimulated (stepping) leg with accompanying activation of the contralateral (supporting) leg. In CTRL, the ipsilateral (side of stimulation) flexor and contralateral extensor muscles were activated characteristically. In CBL, the magnitudes of ipsilateral flexor and contralateral extensor muscle activation were reduced comparably. In CTRL, the conditioning process increased the incidence of conditioned responses (CR), following a typical learning curve, while CBL showed a clearly lower CR incidence with a marginal increase, albeit, at a shorter latency. Conditioning processes also modified temporal parameters by shortening unconditioned response (UR) onset latencies and UR times to peak and, more importantly in CBL, also the sequence of activation of muscles, which became similar to that of CTRL. The expression of this reflex in standing subjects showed characteristic differences in the groups tested with the underlying associative processes not being restricted exclusively to the CR but also modifying parameters of the innate UR.