Genomic characteristics and clinical significance of CD56+ circulating tumor cells in small cell lung cancer.

Circulating tumor cells (CTC) have been studied in various solid tumors but clinical utility of CTC in small cell lung cancer (SCLC) remains unclear. The aim of the CTC-CPC study was to develop an EpCAM-independent CTC isolation method allowing isolation of a broader range of living CTC from SCLC and decipher their genomic and biological characteristics. CTC-CPC is a monocentric prospective non-interventional study including treatment-naïve newly diagnosed SCLC. CD56+ CTC were isolated from whole blood samples, at diagnosis and relapse after first-line treatment and submitted to whole-exome-sequencing (WES). Phenotypic study confirms tumor lineage and tumorigenic properties of isolated cells for the 4 patients analyzed with WES. WES of CD56+ CTC and matched tumor biopsy reveal genomic alteration frequently impaired in SCLC. At diagnosis CD56+ CTC were characterized by a high mutation load, a distinct mutational profile and a unique genomic signature, compared to match tumors biopsies. In addition to classical pathways altered in SCLC, we found new biological processes specifically affected in CD56+ CTC at diagnosis. High numeration of CD56+ CTC (> 7/ml) at diagnosis was associated with ES-SCLC. Comparing CD56+ CTC isolated at diagnosis and relapse, we identify differentially altered oncogenic pathways (e.g. DLL3 or MAPK pathway). We report a versatile method of CD56+ CTC detection in SCLC. Numeration of CD56+ CTC at diagnosis is correlated with disease extension. Isolated CD56+ CTC are tumorigenic and show a distinct mutational profile. We report a minimal gene set as a unique signature of CD56+ CTC and identify new affected biological pathways enriched in EpCAM-independent isolated CTC in SCLC.

Hepatic gene expression variations in response to high-fat diet-induced impaired glucose tolerance using RNAseq analysis in collaborative cross mouse population.

Hepatic gene expression is known to differ between healthy and type 2 diabetes conditions. Identifying these variations will provide better knowledge to the development of gene-targeted therapies. The aim of this study is to assess diet-induced hepatic gene expression of susceptible versus resistant CC lines to T2D development. Next-generation RNA-sequencing was performed for 84 livers of diabetic and non-diabetic mice of 41 different CC lines (both sexes) following 12 weeks on high-fat diet (42% fat). Data analysis revealed significant variations of hepatic gene expression in diabetic versus non-diabetic mice with significant sex effect, where 601 genes were differentially expressed (DE) in overall population (males and females), 718 genes in female mice, and 599 genes in male mice. Top prioritized DE candidate genes were Lepr, Ins2, Mb, Ckm, Mrap2, and Ckmt2 for the overall population; for females-only group were Hdc, Serpina12, Socs1, Socs2, and Mb, while for males-only group were Serpine1, Mb, Ren1, Slc4a1, and Atp2a1. Data analysis for sex differences revealed 193 DE genes in health (Top: Lepr, Cav1, Socs2, Abcg2, and Col5a3), and 389 genes DE between diabetic females versus males (Top: Lepr, Clps, Ins2, Cav1, and Mrap2). Furthermore, integrating gene expression results with previously published QTL, we identified significant variants mapped at chromosomes at positions 36-49 Mb, 62-71 Mb, and 79-99 Mb, on chromosomes 9, 11, and 12, respectively. Our findings emphasize the complexity of T2D development and that significantly controlled by host complex genetic factors. As well, we demonstrate the significant sex differences between males and females during health and increasing to extent levels during disease/diabetes. Altogether, opening the venue for further studies targets the discovery of effective sex-specific and personalized preventions and therapies.

Five-Years Outcome Analysis of 142 Consecutive Hepatocellular Carcinoma Patients Treated with Doxorubicin Eluting Microspheres 30-60 µm: Results from a Single-Centre Prospective Phase II Trial.

PURPOSE: To assess prospectively long-term results of doxorubicin-loaded HepaSphere 30-60 µm in consecutive patients with hepatocellular carcinoma (HCC) not amenable to curative treatments. PATIENTS AND METHODS: Single-center study from June 2011 to December 2015 in 151 patients treated with 75 mg of doxorubicin per HepaSphere vial. Baseline: Barcelona Clinic Liver Cancer BCLC A/B was 49.3%/50.7%, and median diameter 6.1 cm (mean 6.7 ± 2.0). Liver function, local response (mRECIST), liver time to progression (LTTP), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were recorded. RESULTS: Final analysis included 142 patients with median follow-up of 46.8 months (range 4-72) without grade 4/5 AEs, and 30-day mortality was 0%. Mean number of scheduled treatments was 2.6 (range 1-3) and on demand 3 (range 1-8). Complete response for single tumor ≤ 5 cm was 75.0% and 66.7% for Child A and Child B, while for > 5 cm was 28.6% and 11.8%, respectively. OS was 31.0 months (mean 33.3 ± 15.2; range 8-69), notably for BCLC A 41 months (mean 41.1 ± 15.3; range 13-69) and for BCLC B 26.0 (mean 26.0 ± 10.5; range 8-51). OS at 1, 3 and 5 years: 95.8%, 75.7% and 21.4% for BCLC A, and 94.4%, 36.1% and 2.7% for BCLC B. Median LTTP for BCLC A was 11 months (mean 11.9 ± 4.7; range 3-24) and 7.5 for BCLC B (mean 7.9 ± 2.9). Local response was significant for OS and LTTP (p < 0.0001), while size and lesion number affected LPFS and OS (p < 0.001). CONCLUSIONS: HepaSphere 30-60 µm loaded with doxorubicin provides a safe and effective treatment option for patients with HCC.

Feasibility of Using Crystal Geometry for a DOI Scintillation Detector.

We have used simulations and measurements to investigate the feasibility of using slanted scintillator crystal geometries as means to provide depth-of-interaction (DOI) information for a pixelated gamma ray imaging detector. The simulations were performed to estimate the fraction of scintillation light detected by the photodetector as a function of interaction location along the height of crystals with different geometries. In addition, physical measurements of the light output for these crystal geometries were obtained from individual crystals coupled to a solid state photodetector (Philips digital-SiPM DPC-3200). In agreement with previous work, we found a change in light output in the slanted region of the crystals compared to the rectangular region. The results from this study indicate the potential of using slanted crystals to gather DOI information based on light output changes as a function of the location of interaction. An examination of the measured energy spectra for the geometries evaluated here, suggests that for BGO crystals somewhere between 2 or 3 DOI bins could be implemented. Based on these results, we conceived a design for a DOI detector module that consists of two slanted crystals, each read-out by separate SiPM pixels.

Metabolic profile of human coelomic fluid.

AIM: Till now there is very limited knowledge on the molecular content of coelomic fluid and cells. This study presents the first attempt to elucidate the metabolic profile of such samples. METHODOLOGY: Samples were collected via coelocentesis from 41 women during the first trimester of gestation. Metabolic content was assessed using four different analytical platforms. For targeted analysis a hydrophilic interaction chromatography ultra high performance LC-MS/MS method was applied. Holistic analysis performed by GC-MS, NMR spectroscopy and ion cyclotron ultra-high resolution MS (FT-ICR-MS) instrumentation. RESULTS & CONCLUSIONS: Our observations suggest coelomic fluid and cells as promising biosamples, rich in metabolites with potential use in mammalian system biology studies.

SPNsim: A database of simulated solitary pulmonary nodule PET/CT images facilitating computer aided diagnosis.

The aim of the present work was to design and develop a database of simulated solitary pulmonary nodules (SPN) in pairs of computed tomography (CT) and positron emission tomography (PET) images, using Monte Carlo (MC) simulation methods. We have developed an SPN image modeling pipeline to feed the database entitled SPNsim. The database is web-accessible and it is contains two subsets of simulated PET/CT SPN images. The first subset is currently composed of 1000 cases containing pairs of the transaxial CT and the corresponding PET slice with various types of simulated SPNs, presented as individual records. The second subset contains pairs of the transaxial CT and the corresponding PET slice of simulated SPNs, presenting cases of graded difficulty in diagnosis. The users of the database will have the ability to set queries in order to retrieve cases with certain characteristics, as well as characterized image sets. All images are freely available and may be downloaded from the website. SPNsim provides a useful reference data set for training and evaluation of computer aided detection (CAD) and diagnosis (CADx) systems focusing on SPN.

A New Pulse Pileup Rejection Method Based on Position Shift Identification.

Pulse pileup events degrade the signal-to-noise ratio (SNR) of nuclear medicine data. When such events occur in multiplexed detectors, they cause spatial misposition, energy spectrum distortion and degraded timing resolution, which leads to image artifacts. Pulse pileup is pronounced in PETbox4, a bench top PET scanner dedicated to high sensitivity and high resolution imaging of mice. In that system, the combination of high absolute sensitivity, long scintillator decay time (BGO) and highly multiplexed electronics lead to a significant fraction of pulse pileup, reached at lower total activity than for comparable instruments. In this manuscript, a new pulse pileup rejection method named position shift rejection (PSR) is introduced. The performance of PSR is compared with a conventional leading edge rejection (LER) method and with no pileup rejection implemented (NoPR). A comprehensive digital pulse library was developed for objective evaluation and optimization of the PSR and LER, in which pulse waveforms were directly recorded from real measurements exactly representing the signals to be processed. Physical measurements including singles event acquisition, peak system sensitivity and NEMA NU-4 image quality phantom were also performed in the PETbox4 system to validate and compare the different pulse pile-up rejection methods. The evaluation of both physical measurements and model pulse trains demonstrated that the new PSR performs more accurate pileup event identification and avoids erroneous rejection of valid events. For the PETbox4 system, this improvement leads to a significant recovery of sensitivity at low count rates, amounting to about 1/4th of the expected true coincidence events, compared to the LER method. Furthermore, with the implementation of PSR, optimal image quality can be achieved near the peak noise equivalent count rate (NECR).

A DOI Detector With Crystal Scatter Identification Capability for High Sensitivity and High Spatial Resolution PET Imaging.

A new phoswich detector is being developed at the Crump Institute, aiming to provide improvements in sensitivity, and spatial resolution for PET. The detector configuration is comprised of two layers of pixelated scintillator crystal arrays, a glass light guide and a light detector. The annihilation photon entrance (top) layer is a 48 × 48 array of 1.01 × 1.01 × 7 mm3 LYSO crystals. The bottom layer is a 32 × 32 array of 1.55 × 1.55 × 9 mm3 BGO crystals. A tapered, multiple-element glass lightguide is used to couple the exit end of the BGO crystal array (52 × 52 mm2) to the photosensitive area of the Position Sensitive Photomultiplier Tube (46 × 46 mm2), allowing the creation of flat panel detectors without gaps between the detector modules. Both simulations and measurements were performed to evaluate the characteristics and benefits of the proposed design. The GATE Monte Carlo simulation indicated that the total fraction of the cross layer crystal scatter (CLCS) events in singles detection mode for this detector geometry is 13.2%. The large majority of these CLCS events (10.1% out of 13.2%) deposit most of their energy in a scintillator layer other than the layer of first interaction. Identification of those CLCS events for rejection or correction may lead to improvements in data quality and imaging performance. Physical measurements with the prototype detector showed that the LYSO, BGO and CLCS events were successfully identified using the delayed charge integration (DCI) technique, with more than 95% of the LYSO and BGO crystal elements clearly resolved. The measured peak-to-valley ratios (PVR) in the flood histograms were 3.5 for LYSO and 2.0 for BGO. For LYSO, the energy resolution ranged from 9.7% to 37.0% full width at half maximum (FWHM), with a mean of 13.4 ± 4.8%. For BGO the energy resolution ranged from 16.0% to 33.9% FWHM, with a mean of 18.6 ± 3.2%. In conclusion, these results demonstrate that the proposed detector is feasible and can potentially lead to a high spatial resolution, high sensitivity and DOI PET system.

Optimization of the Energy Window for PETbox4, a Preclinical PET Tomograph With a Small Inner Diameter.

Small animal positron emission tomography (PET) systems are often designed by employing close geometry configurations. Due to the different characteristics caused by geometrical factors, these tomographs require data acquisition protocols that differ from those optimized for conventional large diameter ring systems. In this work we optimized the energy window for data acquisitions with PETbox4, a 50 mm detector separation (box-like geometry) pre-clinical PET scanner, using the Geant4 Application for Tomographic Emission (GATE). The fractions of different types of events were estimated using a voxelized phantom including a mouse as well as its supporting chamber, mimicking a realistic mouse imaging environment. Separate code was developed to extract additional information about the gamma interactions for more accurate event type classification. Three types of detector backscatter events were identified in addition to the trues, phantom scatters and randoms. The energy window was optimized based on the noise equivalent count rate (NECR) and scatter fraction (SF) with lower-level discriminators (LLD) corresponding to energies from 150 keV to 450 keV. The results were validated based on the calculated image uniformity, spillover ratio (SOR) and recovery coefficient (RC) from physical measurements using the National Electrical Manufacturers Association (NEMA) NU-4 image quality phantom. These results indicate that when PETbox4 is operated with a more narrow energy window (350-650 keV), detector backscatter rejection is unnecessary. For the NEMA NU-4 image quality phantom, the SOR for the water chamber decreases by about 45% from 15.1% to 8.3%, and the SOR for the air chamber decreases by 31% from 12.0% to 8.3% at the LLDs of 150 and 350 keV, without obvious change in uniformity, further supporting the simulation based optimization. The optimization described in this work is not limited to PETbox4, but also applicable or helpful to other small inner diameter geometry scanners.

A semi-automated vascular access system for preclinical models.

Murine models are used extensively in biological and translational research. For many of these studies it is necessary to access the vasculature for the injection of biologically active agents. Among the possible methods for accessing the mouse vasculature, tail vein injections are a routine but critical step for many experimental protocols. To perform successful tail vein injections, a high skill set and experience is required, leaving most scientists ill-suited to perform this task. This can lead to a high variability between injections, which can impact experimental results. To allow more scientists to perform tail vein injections and to decrease the variability between injections, a vascular access system (VAS) that semi-automatically inserts a needle into the tail vein of a mouse was developed. The VAS uses near infrared light, image processing techniques, computer controlled motors, and a pressure feedback system to insert the needle and to validate its proper placement within the vein. The VAS was tested by injecting a commonly used radiolabeled probe (FDG) into the tail veins of five mice. These mice were then imaged using micro-positron emission tomography to measure the percentage of the injected probe remaining in the tail. These studies showed that, on average, the VAS leaves 3.4% of the injected probe in the tail. With these preliminary results, the VAS system demonstrates the potential for improving the accuracy of tail vein injections in mice.

Betabox: a beta particle imaging system based on a position sensitive avalanche photodiode.

A beta camera has been developed that allows planar imaging of the spatial and temporal distribution of beta particles using a 14 × 14 mm(2) position sensitive avalanche photodiode (PSAPD). This camera system, which we call Betabox, can be directly coupled to microfluidic chips designed for cell incubation or other biological applications. Betabox allows for imaging the cellular uptake of molecular imaging probes labeled with charged particle emitters such as (18)F inside these chips. In this work, we investigate the quantitative imaging capabilities of Betabox for (18)F beta particles, in terms of background rate, efficiency, spatial resolution, and count rate. Measurements of background and spatial resolution are considered both at room temperature (21 °C ± 1 °C) and at an elevated operating temperature (37 °C ± 1 °C), as is often required for biological assays. The background rate measured with a 4 keV energy cutoff is below 2 cph mm(-2) at both 21 and 37 °C. The absolute efficiency of Betabox for the detection of (18)F positron sources in contact with a PSAPD with the surface passivated from ambient light and damage is 46% ± 1%. The lower detection limit is estimated using the Rose Criterion to be 0.2 cps mm(-2) for 1 min acquisitions and a 62 × 62 µm(2) pixel size. The upper detection limit is approximately 21 000 cps. The spatial resolution at both 21 and 37 °C ranges from 0.4 mm FWHM at the center of the field of view (FOV), and degrades to 1 mm at a distance of 5 mm away from center yielding a useful FOV of approximately 10 × 10 mm(2). We also investigate the effects on spatial resolution and sensitivity that result from the use of a polymer based microfluidic chip. For these studies we place varying layers of low-density polyethylene (LDPE) between the detector and the source and find that the spatial resolution degrades by ∼180 µm for every 100 µm of LDPE film. Sensitivity is reduced by half with the inclusion of ∼200 µm of additional LDPE film. Lastly, we demonstrate the practical utilization of Betabox, with an imaging test of its linearity, when coupled to a polydimethylsiloxane microfluidic chip designed for cell based assays.

NEMA NU-4 performance evaluation of PETbox4, a high sensitivity dedicated PET preclinical tomograph.

PETbox4 is a new, fully tomographic bench top PET scanner dedicated to high sensitivity and high resolution imaging of mice. This manuscript characterizes the performance of the prototype system using the National Electrical Manufacturers Association NU 4-2008 standards, including studies of sensitivity, spatial resolution, energy resolution, scatter fraction, count-rate performance and image quality. The PETbox4 performance is also compared with the performance of PETbox, a previous generation limited angle tomography system. PETbox4 consists of four opposing flat-panel type detectors arranged in a box-like geometry. Each panel is made by a 24 × 50 pixelated array of 1.82 × 1.82 × 7 mm bismuth germanate scintillation crystals with a crystal pitch of 1.90 mm. Each of these scintillation arrays is coupled to two Hamamatsu H8500 photomultiplier tubes via a glass light guide. Volumetric images for a 45 × 45 × 95 mm field of view (FOV) are reconstructed with a maximum likelihood expectation maximization algorithm incorporating a system model based on a parameterized detector response. With an energy window of 150-650 keV, the peak absolute sensitivity is approximately 18% at the center of FOV. The measured crystal energy resolution ranges from 13.5% to 48.3% full width at half maximum (FWHM), with a mean of 18.0%. The intrinsic detector spatial resolution is 1.5 mm FWHM in both transverse and axial directions. The reconstructed image spatial resolution for different locations in the FOV ranges from 1.32 to 1.93 mm, with an average of 1.46 mm. The peak noise equivalent count rate for the mouse-sized phantom is 35 kcps for a total activity of 1.5 MBq (40 µCi) and the scatter fraction is 28%. The standard deviation in the uniform region of the image quality phantom is 5.7%. The recovery coefficients range from 0.10 to 0.93. In comparison to the first generation two panel PETbox system, PETbox4 achieves substantial improvements on sensitivity and spatial resolution. The overall performance demonstrates that the PETbox4 scanner is suitable for producing high quality images for molecular imaging based biomedical research.

A collaborative biomedical image mining framework: application on the image analysis of microscopic kidney biopsies.

The analysis and characterization of biomedical image data is a complex procedure involving several processing phases, like data acquisition, preprocessing, segmentation, feature extraction and classification. The proper combination and parameterization of the utilized methods are heavily relying on the given image data set and experiment type. They may thus necessitate advanced image processing and classification knowledge and skills from the side of the biomedical expert. In this work, an application, exploiting web services and applying ontological modeling, is presented, to enable the intelligent creation of image mining workflows. The described tool can be directly integrated to the RapidMiner, Taverna or similar workflow management platforms. A case study dealing with the creation of a sample workflow for the analysis of kidney biopsy microscopy images is presented to demonstrate the functionality of the proposed framework.

Intra-arterial prostaglandin e(1) infusion in patients with rest pain: short-term results.

PURPOSE: To present our results after short-term (1 month) intra-arterial infusion therapy of PGE1-alprostadil via a port system implanted in the ipsilateral external iliac artery (EIA) in patients with severe rest pain. METHODS: Ten patients with severe rest pain were included. All patients showed extensive peripheral vascular disease below the knee. The tip of the catheter was introduced via a retrograde puncture in the ipsilateral external iliac artery (EIA). The patients received intraarterial infusion of PGE1, 20 mgr alprostadil daily, via the port catheter for 1 month. RESULTS: Clinical success was evaluated according to subjective grading of pain (group A significant decrease, group B moderate decrease and group C no response). A significant decrease of rest pain was observed in 8 (group A, 80%) patients, a moderate decrease in 2 (Group B, 20%), whereas no patients demonstrated any significant response. Both patients of group B had Buergers' disease and continue to smoke during therapy. No peripheral thrombosis or clinical deterioration was noticed. CONCLUSION: Intraarterial infusion of PGE1 alprostadil on a daily basis, using a port catheter into the ipsilateral EIA, in selected patients with severe rest pain, seems to be very effective, without any serious complications.

Transcatheter arterial embolization as therapy of renal angiomyolipomas: the evolution in 15 years of experience.

OBJECTIVE: This study aims at presenting the evolution of the embolization technique in treating renal angiomyolipomas (AMLs) either diagnosed in patients with acute bleeding or discovered accidentally. METHODS: Ten patients with renal AMLs have been through thirteen selective transcatheter arterial embolizations for 15 years. Two patients had tuberous sclerosis complex (TSC) with bilateral tumors and were embolized twice. Four embolic materials were employed: PVA particles, Gianturco coils, microspheres and microcoils. Catheterization was achieved by means of 5F Cobra 2 catheters and coaxial microcatheter systems. RESULTS: On an emergency basis, embolization was a first-line treatment. In one case, surgery was necessary; in two patients, a second embolization was performed. When treatment was preventive, a single embolization proved to be sufficient, as well. There was no significant deterioration of the serum creatinine levels in the post-embolization period. CONCLUSION: Selective arterial embolization is a rather safe and effective technique to treat AMLs both urgently and preventively. Different embolic materials can be employed. Microspheres and microcatheters stand for new promising materials.

Evaluating the effect of various background correction methods regarding noise reduction, in two-channel microarray data.

In this work, two novel background correction (BC) methods, along with several commonly used ones, are evaluated regarding noise reduction in eleven two-channel self-versus-self (SVS) hybridizations. The evaluation of each BC method is investigated under the use of four statistical criteria combined into a single measure, the polygon area measure. Overall, our proposed BC approaches perform very well in terms of the proposed measure for most of the cases and provide an improved effect regarding technical noise reduction.

Arteriovenous malformation: An unusual cause of rectus sheath hematoma, following laparoscopic cholecystectomy.

Rectus sheath hematoma (RSH) is an accumulation of blood in the rectus abdominis muscle sheath, secondary to several conditions which may cause the epigastric vessel rupture or muscular tear, but mostly affecting patients undergoing anticoagulation therapy.We present a rare case of a 67-year-old woman who underwent laparoscopic cholecystectomy and developed RSH on the 12th postoperative day. The patient was under anticoagulation therapy with acenocoumarole due to mitral valve replacement. The bleeding source was an arteriovenous malformation (AVM) rupture as indicated by the angiogram images and it was embolized succefully. The patient was discharged seven days later.

Performance Characteristics of BGO Detectors for a Low Cost Preclinical PET Scanner.

PETbox is a low-cost benchtop PET scanner dedicated to high throughput preclinical imaging that is currently under development at our institute. This paper presents the design and characterization of the detectors that are used in the PETbox system. In this work, bismuth germanate scintillator was used for the detector, taking advantage of its high stopping power, high photoelectric event fraction, lack of intrinsic background radiation and low cost. The detector block was segmented into a pixelated array consisting of 20 × 44 elements, with a crystal pitch of 2.2 mm and a crystal cross section of 2 mm × 2 mm. The effective area of the array was 44 mm × 96.8 mm. The array was coupled to two Hamamatsu H8500 position sensitive photomultiplier tubes, forming a flat-panel type detector head with a sensitive area large enough to cover the whole body of a typical laboratory mouse. Two such detector heads were constructed and their performance was characterized. For one detector head, the energy resolution ranged from 16.1% to 38.5% full width at half maximum (FWHM), with a mean of 20.1%; for the other detector head, the energy resolution ranged from 15.5% to 42.7% FWHM, with a mean of 19.6%. The intrinsic spatial resolution was measured to range from 1.55 mm to 2.39 mm FWHM along the detector short axis and from 1.48 mm to 2.33 mm FWHM along the detector long axis, with an average of 1.78 mm. Coincidence timing resolution for the detector pair was measured to be 4.1 ns FWHM. These measurement results show that the detectors are suitable for our specific application.

Delineation and interpretation of gene networks towards their effect in cellular physiology- a reverse engineering approach for the identification of critical molecular players, through the use of ontologies.

Exploiting ontologies, provides clues regarding the involvement of certain molecular processes in the cellular phenotypic manifestation. However, identifying individual molecular actors (genes, proteins, etc.) for targeted biological validation in a generic, prioritized, fashion, based in objective measures of their effects in the cellular physiology, remains a challenge. In this work, a new meta-analysis algorithm is proposed for the holistic interpretation of the information captured in -omic experiments, that is showcased in a transcriptomic, dynamic, DNA microarray dataset, which examines the effect of mastic oil treatment in Lewis lung carcinoma cells. Through the use of the Gene Ontology this algorithm relates genes to specific cellular pathways and vice versa in order to further reverse engineer the critical role of specific genes, starting from the results of various statistical enrichment analyses. The algorithm is able to discriminate candidate hub-genes, implying critical biochemical cross-talk. Moreover, performance measures of the algorithm are derived, when evaluated with respect to the differential expression gene list of the dataset.

Dual-energy attenuation coefficient decomposition with differential filtration and application to a microCT scanner.

Dual-energy x-ray computed tomography (DECT) has the capability to decompose attenuation coefficients using two basis functions and has proved its potential in reducing beam-hardening artifacts from reconstructed images. The method typically involves two successive scans with different x-ray tube voltage settings. This work proposes an approach to dual-energy imaging through x-ray beam filtration that requires only one scan and a single tube voltage setting. It has been implemented in a preclinical microCT tomograph with minor modifications. Retrofitting of the microCT scanner involved the addition of an automated filter wheel and modifications to the acquisition and reconstruction software. Results show that beam-hardening artifacts are reduced to noise level. Acquisition of a mu-Compton image is well suited for attenuation-correction of PET images while dynamic energy selection (4D viewing) offers flexibility in image viewing by adjusting contrast and noise levels to suit the task at hand. All dual-energy and single energy reference scans were acquired at the same soft tissue dose level of 50 mGy.