Application of x-ray phase imaging in the estimation of tissue optical scattering

The ability to non-invasively estimate the optical properties of biological tissues in vivo would enable the advancement of quantitative optical based techniques such as photoacoustic imaging. It has, to date, proven difficult to make such an estimation for large three-dimensional tissue sections and small animals using optical approaches. To overcome this limitation, the correlation between the optical scattering properties, and the dark field x-ray phase contrast (XPCi), or ‘x-ray scattering’ signal has been investigated. To do this, phantoms with unknown x-ray scattering, but controlled optical scattering were designed, and manufacturing methods developed, to enable simultaneous manufacture of phantoms suitable for either x-ray or optical imaging. Phantoms consisted of agarose, gel wax or silicone embedded with either TiO2 powder or silica microspheres. The x-ray phantoms were imaged using the edge illumination (EI) system at UCL. Due to the very low scattering and high absorption of many of the samples, along with the imperfect absorption of the masks in the EI system, existing scatter retrieval methods were unable to accurately determine the scattering properties of the phantoms. A novel, more sensitive x-ray scatter retrieval method was thus developed to overcome these problems. The optical scattering of phantoms was retrieved using a spectrophotometer combined the inverse adding doubling method. The optical and x-ray scattering of the phantoms was thus compared which did not reveal any correlation between the two. In order to assess a correlation between optical and x-ray scattering in biological tissue, Optical coherence tomography (OCT) was investigated as a method of determining the optical scattering properties. Along with the use of a controlled ‘calibration phantom’, the optical properties of such tissues were determined. Finally, biological tissue samples were imaged using both OCT and EI-XPCi, and the optical and x-ray scattering properties compared, with no correlation observed

An assessment of multimodal imaging of subsurface text in mummy cartonnage using surrogate papyrus phantoms

Ancient Egyptian mummies were often covered with an outer casing, panels and masks made from cartonnage: a lightweight material made from linen, plaster, and recycled papyrus held together with adhesive. Egyptologists, papyrologists, and historians aim to recover and read extant text on the papyrus contained within cartonnage layers, but some methods, such as dissolving mummy casings, are destructive. The use of an advanced range of different imaging modalities was investigated to test the feasibility of non-destructive approaches applied to multi-layered papyrus found in ancient Egyptian mummy cartonnage. Eight different techniques were compared by imaging four synthetic phantoms designed to provide robust, well-understood, yet relevant sample standards using modern papyrus and replica inks. The techniques include optical (multispectral imaging with reflection and transillumination, and optical coherence tomography), X-ray (X-ray fluorescence imaging, X-ray fluorescence spectroscopy, X-ray micro computed tomography and phase contrast X-ray) and terahertz-based approaches. Optical imaging techniques were able to detect inks on all four phantoms, but were unable to significantly penetrate papyrus. X-ray-based techniques were sensitive to iron-based inks with excellent penetration but were not able to detect carbon-based inks. However, using terahertz imaging, it was possible to detect carbon-based inks with good penetration but with less sensitivity to iron-based inks. The phantoms allowed reliable and repeatable tests to be made at multiple sites on three continents. The tests demonstrated that each imaging modality needs to be optimised for this particular application: it is, in general, not sufficient to repurpose an existing device without modification. Furthermore, it is likely that no single imaging technique will to be able to robustly detect and enable the reading of text within ancient Egyptian mummy cartonnage. However, by carefully selecting, optimising and combining techniques, text contained within these fragile and rare artefacts may eventually be open to non-destructive imaging, identification, and interpretation

Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis (New EPOC): long-term results of a multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: The interim analysis of the multicentre New EPOC trial in patients with resectable colorectal liver metastasis showed a significant reduction in progression-free survival in patients allocated to cetuximab plus chemotherapy compared with those given chemotherapy alone. The focus of the present analysis was to assess the effect on overall survival. METHODS: New EPOC was a multicentre, open-label, randomised, controlled, phase 3 trial. Adult patients (aged ≥18 years) with KRAS wild-type (codons 12, 13, and 61) resectable or suboptimally resectable colorectal liver metastases and a WHO performance status of 0-2 were randomly assigned (1:1) to receive chemotherapy with or without cetuximab before and after liver resection. Randomisation was done centrally with minimisation factors of surgical centre, poor prognosis cancer, and previous adjuvant treatment with oxaliplatin. Chemotherapy consisted of oxaliplatin 85 mg/m2 administered intravenously over 2 h, l-folinic acid (175 mg flat dose administered intravenously over 2 h) or d,l-folinic acid (350 mg flat dose administered intravenously over 2 h), and fluorouracil bolus 400 mg/m2 administered intravenously over 5 min, followed by a 46 h infusion of fluorouracil 2400 mg/m2 repeated every 2 weeks (regimen one), or oxaliplatin 130 mg/m2 administered intravenously over 2 h and oral capecitabine 1000 mg/m2 twice daily on days 1-14 repeated every 3 weeks (regimen two). Patients who had received adjuvant oxaliplatin could receive irinotecan 180 mg/m2 intravenously over 30 min with fluorouracil instead of oxaliplatin (regimen three). Cetuximab was given intravenously, 500 mg/m2 every 2 weeks with regimen one and three or a loading dose of 400 mg/m2 followed by a weekly infusion of 250 mg/m2 with regimen two. The primary endpoint of progression-free survival was published previously. Secondary endpoints were overall survival, preoperative response, pathological resection status, and safety. Trial recruitment was halted prematurely on the advice of the Trial Steering Committee on Nov 1, 2012. All analyses (except safety) were done on the intention-to-treat population. Safety analyses included all randomly assigned patients. This trial is registered with ISRCTN, number 22944367. FINDINGS: Between Feb 26, 2007, and Oct 12, 2012, 257 eligible patients were randomly assigned to chemotherapy with cetuximab (n=129) or without cetuximab (n=128). This analysis was carried out 5 years after the last patient was recruited, as defined in the protocol, at a median follow-up of 66·7 months (IQR 58·0-77·5). Median progression-free survival was 22·2 months (95% CI 18·3-26·8) in the chemotherapy alone group and 15·5 months (13·8-19·0) in the chemotherapy plus cetuximab group (hazard ratio [HR] 1·17, 95% CI 0·87-1·56; p=0·304). Median overall survival was 81·0 months (59·6 to not reached) in the chemotherapy alone group and 55·4 months (43·5-71·5) in the chemotherapy plus cetuximab group (HR 1·45, 1·02-2·05; p=0·036). There was no significant difference in the secondary outcomes of preoperative response or pathological resection status between groups. Five deaths might have been treatment-related (one in the chemotherapy alone group and four in the chemotherapy plus cetuximab group). The most common grade 3-4 adverse events reported were: neutrophil count decreased (26 [19%] of 134 in the chemotherapy alone group vs 21 [15%] of 137 in the chemotherapy plus cetuximab group), diarrhoea (13 [10%] vs 14 [10%]), skin rash (one [1%] vs 22 [16%]), thromboembolic events (ten [7%] vs 11 [8%]), lethargy (ten [7%] vs nine [7%]), oral mucositis (three [2%] vs 14 [10%]), vomiting (seven [5%] vs seven [5%]), peripheral neuropathy (eight [6%] vs five [4%]), and pain (six [4%] vs six [4%]). INTERPRETATION: Although the addition of cetuximab to chemotherapy improves the overall survival in some studies in patients with advanced, inoperable metastatic disease, its use in the perioperative setting in patients with operable disease confers a significant disadvantage in terms of overall survival. Cetuximab should not be used in this setting. FUNDING: Cancer Research UK

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Supplementary document for T staging esophageal tumors with x-rays - 6907077.pdf

additional document with more dat

Patterns of progression, treatment of progressive disease and post-progression survival in the New EPOC Study

Background: The addition of cetuximab (CTX) to perioperative chemotherapy (CT) for operable colorectal liver metastases resulted in a shorter progression-free survival. Details of disease progression are described to further inform the primary study outcome.Methods: A total of 257 KRAS wild-type patients were randomised to CT alone or CT with CTX. Data regarding sites and treatment of progressive disease were obtained for the 109 (CT n=48, CT and CTX n=61) patients with progressive disease at the cut-off date for analysis of November 2012.Results: The liver was the most frequent site of progression (CT 67% (32/48); CT and CTX 66% (40/61)). A higher proportion of patients in the CT and group had multiple sites of progressive disease (CT 8%, 4/48; CT and CTX 23%, 14/61 P=0.04). Further treatment for progressive disease is known for 84 patients of whom 69 received further CT, most frequently irinotecan based. Twenty-two patients, 11 in each arm, received CTX as a further line agent.Conclusions: Both the distribution of progressive disease and further treatment are as expected for such a cohort. The pattern of disease progression seen is consistent with failure of systemic micrometastatic disease control rather than failure of local disease control following liver surgery

Source of the quaternary alkalic basalts, picrites and basanites of the Potrillo Volcanic Field, New Mexico, USA: lithosphere or convecting mantle?

The <80 ka basalts–basanites of the Potrillo Volcanic Field (PVF) form scattered scoria cones, lava flows and maars adjacent to the New Mexico–Mexico border. MgO ranges up to 12·5%; lavas with MgO < 10·7% have fractionated both olivine and clinopyroxene. Cumulate fragments are common in the lavas, as are subhedral megacrysts of aluminous clinopyroxene (with pleonaste inclusions) and kaersutitic amphibole. REE modelling indicates that these megacrysts could be in equilibrium with the PVF melts at 1·6–1·7 GPa pressure. The lavas fall into two geochemical groups: the Main Series (85% of lavas) have major- and trace-element abundances and ratios closely resembling those of worldwide ocean-island alkali basalts and basanites (OIB); the Low-K Series (15%) differ principally by having relatively low K2O and Rb contents. Otherwise, they are chemically indistinguishable from the Main Series lavas. Sr- and Nd-isotopic ratios in the two series are identical and vary by scarcely more than analytical error, averaging 87Sr/86Sr = 0·70308 (SD = 0·00004) and 143Nd/144Nd = 0·512952 (SD=0·000025). Such compositions would be expected if both series originated from the same mantle source, with Low-K melts generated when amphibole remained in the residuum. Three PVF lavas have very low Os contents (<14 ppt) and appear to have become contaminated by crustal Os. One Main Series picrite has 209 ppt Os and has a Os value of +13·6, typical for OIB. This contrasts with published 187Os/188Os ratios for Kilbourne Hole peridotite mantle xenoliths, which give mostly negative Os values and show that Proterozoic lithospheric mantle forms a thick Mechanical Boundary Layer (MBL) that extends to 70 km depth beneath the PVF area. The calculated mean primary magma, in equilibrium with Fo89, has Na2O and FeO contents that give a lherzolite decompression melting trajectory from 2·8 GPa (95 km depth) to 2·2 GPa (70 km depth). Inverse modelling of REE abundances in Main Series Mg-rich lavas is successful for a model invoking decompression melting of convecting sub-lithospheric lherzolite mantle (Nd = 6·4; Tp 1400°C) between 90 and 70 km. Nevertheless, such a one-stage model cannot account for the genesis of the Low-K Series because amphibole would not be stable within convecting mantle at Tf 1400°C. These magmas can only be accommodated by a three-stage model that envisages a Thermal Boundary Layer (TBL) freezing conductively onto the 70 km base of the Proterozoic MBL during the 20 Myr tectonomagmatic quiescence before PVF eruptions. As it grew, this was veined by hydrous small-fraction melts from below. The geologically recent arrival of hotter-than-ambient (Tp 1400°C) convecting mantle beneath the Potrillo area re-melted the TBL and caused the magmatism