Conventional 3D staging PET/CT in CT simulation for lung cancer: impact of rigid and deformable target volume alignments for radiotherapy treatment planning

Objective: Positron emission tomography (PET)/CT scans can improve target definition in radiotherapy for non-small cell lung cancer (NSCLC). As staging PET/CT scans are increasingly available, we evaluated different methods for co-registration of staging PET/CT data to radiotherapy simulation (RTP) scans.

Methods: 10 patients underwent staging PET/CT followed by RTP PET/CT. On both scans, gross tumour volumes (GTVs) were delineated using CT (GTVCT) and PET display settings. Four PET-based contours (manual delineation, two threshold methods and a source-to-background ratio method) were delineated. The CT component of the staging scan was co-registered using both rigid and deformable techniques to the CT component of RTP PET/CT. Subsequently rigid registration and deformation warps were used to transfer PET and CT contours from the staging scan to the RTP scan. Dice’s similarity coefficient (DSC) was used to assess the registration accuracy of staging-based GTVs following both registration methods with the GTVs delineated on the RTP PET/CT scan.

Results: When the GTVCT delineated on the staging scan after both rigid registration and deformation was compared with the GTVCT on the RTP scan, a significant improvement in overlap (registration) using deformation was observed (mean DSC 0.66 for rigid registration and 0.82 for deformable registration, p50.008). A similar comparison for PET contours revealed no significant improvement in overlap with the use of deformable registration.

Conclusions: No consistent improvements in similarity measures were observed when deformable registration was used for transferring PET-based contours from a staging PET/CT. This suggests that currently the use of rigid registration remains the most appropriate method for RTP in NSCLC.

Defining Target Volumes for Stereotactic Ablative Radiotherapy of Early-stage Lung Tumours:A Comparison of Three-dimensional F-fluorodeoxyglucose Positron Emission Tomography and Four-dimensional Computed Tomography

Aims: High local control rates are achieved in stage I lung cancer using stereotactic ablative radiotherapy. Target delineation is commonly based on four-dimensional computed tomography (CT) scans. Target volumes defined by positron emission tomography/computed tomography (PET/CT) are compared with those defined by four-dimensional CT and conventional ('three-dimensional') F-fluorodeoxyglucose (F-FDG) PET/CT. Materials and methods: For 16 stage I non-small cell lung cancer tumours, six approaches for deriving PET target volumes were evaluated: manual contouring, standardised uptake value (SUV) absolute threshold of 2.5, 35% of maximum SUV (35%SUV), 41% of SUV (41%SUV) and two different source to background ratio techniques (SBR-1 and SBR-2). PET-derived target volumes were compared with the internal target volume (ITV) from the modified maximum intensity projection (MIP ITV). Volumetric and positional correlation was assessed using the Dice similarity coefficient (DSC). Results: PET-based target volumes did not correspond to four-dimensional CT-based target volumes. The mean DSC relative to MIP ITV were: PET manual = 0.64, SUV2.5 = 0.64, 35%SUV = 0.63, 41%SUV = 0.57. SBR-1 = 0.52, SBR-2 = 0.49. PET-based target volumes were smaller than corresponding MIP ITVs. Conclusions: Conventional three-dimensional F-FDG PET-derived target volumes for lung stereotactic ablative radiotherapy did not correspond well with those derived from four-dimensional CT, including those in routine clinical use (MIP ITV). Caution is required in using three-dimensional PET for motion encompassing target volume delineation. © 2012 The Royal College of Radiologists.

Defining target volumes for stereotactic ablative radiotherapy of early-stage lung tumours: a comparison of three-dimensional 18F-fluorodeoxyglucose positron emission tomography and four-dimensional computed tomography.:PETCT versus 4DCT for SABR in Early Stage NSCLC

AIMS: High local control rates are achieved in stage I lung cancer using
stereotactic ablative radiotherapy. Target delineation is commonly based on
four-dimensional computed tomography (CT) scans. Target volumes defined by
positron emission tomography/computed tomography (PET/CT) are compared with those defined by four-dimensional CT and conventional ('three-dimensional')
(18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT.

MATERIALS AND METHODS: For 16 stage I non-small cell lung cancer tumours, six
approaches for deriving PET target volumes were evaluated: manual contouring,
standardised uptake value (SUV) absolute threshold of 2.5, 35% of maximum SUV
(35%SUV(MAX)), 41% of SUV(MAX) (41%SUV(MAX)) and two different source to
background ratio techniques (SBR-1 and SBR-2). PET-derived target volumes were compared with the internal target volume (ITV) from the modified maximum
intensity projection (MIP(MOD) ITV). Volumetric and positional correlation was
assessed using the Dice similarity coefficient (DSC).

RESULTS: PET-based target volumes did not correspond to four-dimensional CT-based target volumes. The mean DSC relative to MIP(MOD) ITV were: PET manual = 0.64, SUV2.5 = 0.64, 35%SUV(MAX) = 0.63, 41%SUV(MAX) = 0.57. SBR-1 = 0.52, SBR-2 =0.49. PET-based target volumes were smaller than corresponding MIP ITVs.

CONCLUSIONS: Conventional three-dimensional (18)F-FDG PET-derived target volumes for lung stereotactic ablative radiotherapy did not correspond well with those derived from four-dimensional CT, including those in routine clinical use
(MIP(MOD) ITV). Caution is required in using three-dimensional PET for motion
encompassing target volume delineation.

Activation of Akt/PKB, increased phosphorylation of Akt substrates and loss and altered distribution of Akt and PTEN are features of Alzheimer's disease pathology

Studies suggest that activation of phosphoinositide 3-kinase-Akt may protect against neuronal cell death in Alzheimer's disease (AD). Here, however, we provide evidence of increased Akt activation, and hyperphosphorylation of critical Akt substrates in AD brain, which link to AD pathogenesis, suggesting that treatments aiming to activate the pathway in AD need to be considered carefully. A different distribution of Akt and phospho-Akt was detected in AD temporal cortex neurons compared with control neurons, with increased levels of active phosphorylated-Akt in particulate fractions, and significant decreases in Akt levels in AD cytosolic fractions, causing increased activation of Akt (phosphorylated-Akt/total Akt ratio) in AD. In concordance, significant increases in the levels of phosphorylation of total Akt substrates, including: GSK3ßSer9, tauSer214, mTORSer2448, and decreased levels of the Akt target, p27kip1, were found in AD temporal cortex compared with controls. A significant loss and altered distribution of the major negative regulator of Akt, PTEN (phosphatase and tensin homologue deleted on chromosome 10), was also detected in AD neurons. Loss of phosphorylated-Akt and PTEN-containing neurons were found in hippocampal CA1 at end stages of AD. Taken together, these results support a potential role for aberrant control of Akt and PTEN signalling in AD.

Children with stable asthma have reduced airway matrix metalloproteinase-9 and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio

Background Childhood asthma is characterized by inflammation of the airways. Structural changes of the airway wall may also be seen in some children early in the course of the disease. Matrix metalloproteinases (MMPs) are key mediators in the metabolism of the extracellular matrix (ECM). Objective To investigate the balance of MMP-8, MMP-9 and tissue inhibitor of metalloproteinases (TIMP)-1 in the airways of children with asthma. Methods One hundred and twenty-four children undergoing elective surgical procedures also underwent non-bronchoscopic bronchoalveolar lavage (BAL). MMP-8, MMP-9 and TIMP-1 were measured by ELISA. Results There was a significant reduction in MMP-9 in atopic asthmatic children (n=31) compared with normal children (n=30) [median difference: 0.57 ng/mL (95% confidence interval: 0.18–1.1 ng/mL)]. The ratio of MMP-9 to TIMP-1 was also reduced in asthmatic children. Levels of all three proteins were significantly correlated to each other and to the relative proportions of particular inflammatory cells in BAL fluid (BALF). Both MMP-8 and MMP-9 were moderately strongly correlated to the percentage neutrophil count (r=0.40 and 0.47, respectively, P

Guiding contact by coupling the taus of gaps

Animals control contact with surfaces when locomoting, catching prey, etc. This requires sensorily guiding the rate of closure of gaps between effecters such as the hands, feet or jaws and destinations such as a ball, the ground and a prey. Control is generally rapid, reliable and robust, even with small nervous systems: the sensorimotor processes are therefore probably rather simple. We tested a hypothesis, based on general tau theory, that closing two gaps simultaneously, as required in many actions, might be achieved simply by keeping the taus of the gaps coupled in constant ratio. tau of a changing gap is defined as the time-to-closure of the gap at the current closure-rate. General tau theory shows that tau of a gap could, in principle, be directly sensed without needing to sense either the gap size or its rate of closure. In our experiment, subjects moved an effector (computer cursor) to a destination zone indicated on the computer monitor, to stop in the zone just as a moving target cursor reached it. The results indicated the subjects achieved the task by keeping tau of the gap between effector and target coupled to tau of the gap between the effector and the destination zone. Evidence of tau -coupling has also been found, for example, in bats guiding landing using echolocation. Thus, it appears that a sensorimotor process used by different species for coordinating the closure of two or more gaps between effecters and destinations entails constantly sensing the taus of the gaps and moving so as to keep the taus coupled in constant ratio.