Comparison of Histogram-based Textural Features between Cancerous and Normal Prostatic Tissue in Multiparametric Magnetic Resonance Images.

In the last decade, multiparametric magnetic resonance imaging (mpMRI) has been expanding its role in prostate cancer detection and characterization. In this work, 19 patients with clinically significant peripheral zone (PZ) tumours were studied. Tumour masks annotated on the whole-mount histology sections were mapped on T2-weighted (T2w) and diffusion-weighted (DW) sequences. Gray-level histograms of tumoral and normal tissue were compared using six first-order texture features. Multivariate analysis of variance (MANOVA) was used to compare group means. Mean intensity signal of ADC showed the highest showed the highest area under the receiver operator characteristics curve (AUC) equal to 0.85. MANOVA analysis revealed that ADC features allows a better separation between normal and cancerous tissue with respect to T2w features (ADC: P = 0.0003, AUC = 0.86; T2w: P = 0.03, AUC = 0.74). MANOVA proved that the combination of T2-weighted and apparent diffusion coefficient (ADC) map features increased the AUC to 0.88. Histogram-based features extracted from invivo mpMRI can help discriminating significant PZ PCa.

Predicting locally advanced rectal cancer response to neoadjuvant therapy with 18F-FDG PET and MRI radiomics features.

PURPOSE: Pathological complete response (pCR) following neoadjuvant chemoradiotherapy or radiotherapy in locally advanced rectal cancer (LARC) is reached in approximately 15-30% of cases, therefore it would be useful to assess if pretreatment of 18F-FDG PET/CT and/or MRI texture features can reliably predict response to neoadjuvant therapy in LARC. METHODS: Fifty-two patients were dichotomized as responder (pR+) or non-responder (pR-) according to their pathological tumor regression grade (TRG) as follows: 22 as pR+ (nine with TRG = 1, 13 with TRG = 2) and 30 as pR- (16 with TRG = 3, 13 with TRG = 4 and 1 with TRG = 5). First-order parameters and 21 second-order texture parameters derived from the Gray-Level Co-Occurrence matrix were extracted from semi-automatically segmented tumors on T2w MRI, ADC maps, and PET/CT acquisitions. The role of each texture feature in predicting pR+ was assessed with monoparametric and multiparametric models. RESULTS: In the mono-parametric approach, PET homogeneity reached the maximum AUC (0.77; sensitivity = 72.7% and specificity = 76.7%), while PET glycolytic volume and ADC dissimilarity reached the highest sensitivity (both 90.9%). In the multiparametric analysis, a logistic regression model containing six second-order texture features (five from PET and one from T2w MRI) yields the highest predictivity in distinguish between pR+ and pR- patients (AUC = 0.86; sensitivity = 86%, and specificity = 83% at the Youden index). CONCLUSIONS: If preliminary results of this study are confirmed, pretreatment PET and MRI could be useful to personalize patient treatment, e.g., avoiding toxicity of neoadjuvant therapy in patients predicted pR-.

Computer-aided diagnosis of prostate cancer using multi-parametric MRI: comparison between PUN and Tofts models.

Computer-aided diagnosis (CAD) systems are increasingly being used in clinical settings to report multi-parametric magnetic resonance imaging (mp-MRI) of the prostate. Usually, CAD systems automatically highlight cancer-suspicious regions to the radiologist, reducing reader variability and interpretation errors. Nevertheless, implementing this software requires the selection of which mp-MRI parameters can best discriminate between malignant and non-malignant regions. To exploit functional information, some parameters are derived from dynamic contrast-enhanced (DCE) acquisitions. In particular, much CAD software employs pharmacokinetic features, such as K trans and k ep, derived from the Tofts model, to estimate a likelihood map of malignancy. However, non-pharmacokinetic models can be also used to describe DCE-MRI curves, without any requirement for prior knowledge or measurement of the arterial input function, which could potentially lead to large errors in parameter estimation. In this work, we implemented an empirical function derived from the phenomenological universalities (PUN) class to fit DCE-MRI. The parameters of the PUN model are used in combination with T2-weighted and diffusion-weighted acquisitions to feed a support vector machine classifier to produce a voxel-wise malignancy likelihood map of the prostate. The results were all compared to those for a CAD system based on Tofts pharmacokinetic features to describe DCE-MRI curves, using different quality aspects of image segmentation, while also evaluating the number and size of false positive (FP) candidate regions. This study included 61 patients with 70 biopsy-proven prostate cancers (PCa). The metrics used to evaluate segmentation quality between the two CAD systems were not statistically different, although the PUN-based CAD reported a lower number of FP, with reduced size compared to the Tofts-based CAD. In conclusion, the CAD software based on PUN parameters is a feasible means with which to detect PCa, without affecting segmentation quality, and hence it could be successfully applied in clinical settings, improving the automated diagnosis process and reducing computational complexity.

Single-electron induced surface plasmons on a topological nanoparticle.

It is rarely the case that a single electron affects the behaviour of several hundred thousands of atoms. Here we demonstrate a phenomenon where this happens. The key role is played by topological insulators-materials that have surface states protected by time-reversal symmetry. Such states are delocalized over the surface and are immune to its imperfections in contrast to ordinary insulators. For topological insulators, the effects of these surface states will be more strongly pronounced in the case of nanoparticles. Here we show that under the influence of light a single electron in a topologically protected surface state creates a surface charge density similar to a plasmon in a metallic nanoparticle. Such an electron can act as a screening layer, which suppresses absorption inside the particle. In addition, it can couple phonons and light, giving rise to a previously unreported topological particle polariton mode. These effects may be useful in the areas of plasmonics, cavity electrodynamics and quantum information.

Texture features on T2-weighted magnetic resonance imaging: new potential biomarkers for prostate cancer aggressiveness.

To explore contrast (C) and homogeneity (H) gray-level co-occurrence matrix texture features on T2-weighted (T2w) Magnetic Resonance (MR) images and apparent diffusion coefficient (ADC) maps for predicting prostate cancer (PCa) aggressiveness, and to compare them with traditional ADC metrics for differentiating low- from intermediate/high-grade PCas. The local Ethics Committee approved this prospective study of 93 patients (median age, 65 years), who underwent 1.5 T multiparametric endorectal MR imaging before prostatectomy. Clinically significant (volume ≥0.5 ml) peripheral tumours were outlined on histological sections, contoured on T2w and ADC images, and their pathological Gleason Score (pGS) was recorded. C, H, and traditional ADC metrics (mean, median, 10th and 25th percentile) were calculated on the largest lesion slice, and correlated with the pGS through the Spearman correlation coefficient. The area under the receiver operating characteristic curve (AUC) assessed how parameters differentiate pGS = 6 from pGS ≥ 7. The dataset included 49 clinically significant PCas with a balanced distribution of pGS. The Spearman ρ and AUC values on ADC were: -0.489, 0.823 (mean); -0.522, 0.821 (median); -0.569, 0.854 (10th percentile); -0.556, 0.854 (25th percentile); -0.386, 0.871 (C); 0.533, 0.923 (H); while on T2w they were: -0.654, 0.945 (C); 0.645, 0.962 (H). AUC of H on ADC and T2w, and C on T2w were significantly higher than that of the mean ADC (p = 0.05). H and C calculated on T2w images outperform ADC parameters in correlating with pGS and differentiating low- from intermediate/high-risk PCas, supporting the role of T2w MR imaging in assessing PCa biological aggressiveness.

A new algorithm for automatic vascular mapping of DCE-MRI of the breast: Clinical application of a potential new biomarker.

BACKGROUND AND OBJECTIVE: Vascularity evaluation on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has a potential diagnostic value, but it represents a time consuming procedure, affected by intra- and inter-observer variability. This study tests the application of a recently published method to reproducibly quantify breast vascularity, and evaluates if the vascular volume of cancer-bearing breast, calculated from automatic vascular maps (AVMs), may correlate with pathologic tumor response after neoadjuvant chemotherapy (NAC). METHODS: Twenty-four patients with unilateral locally advanced breast cancer underwent DCE-MRI before and after NAC, 8 responders and 16 non-responders. A validated algorithm, based on multiscale 3D Hessian matrix analysis, provided AVMs and allowed the calculation of vessel volume before the initiation and after the last NAC cycle for each breast. For cancer bearing breast, the difference in vascular volume before and after NAC was compared in responders and non-responders using the Wilcoxon two-sample test. A radiologist evaluated the vascularity on the subtracted images (first enhanced minus unenhanced), before and after treatment, assigning a vascular score for each breast, according to the number of vessels with length ≥30mm and maximal transverse diameter ≥2mm. The same evaluation was repeated with the support of the simultaneous visualization of the AVMs. The two evaluations were compared in terms of mean number of vessels and mean vascular score per breast, in responders and non-responders, by use of Wilcoxon two sample test. For all the analysis, the statistical significance level was set at 0.05. RESULTS: For breasts harboring the cancer, evidence of a difference in vascular volume before and after NAC for responders (median=1.71cc) and non-responders (median=0.41cc) was found (p=0.003). A significant difference was also found in the number of vessels (p=0.03) and vascular score (p=0.02) before or after NAC, according to the evaluation supported by the AVMs. CONCLUSIONS: The encouraging, although preliminary, results of this study suggest the use of AVMs as new biomarker to evaluate the pathologic response after NAC, but also support their application in other breast DCE-MRI vessel analysis that are waiting for a reliable quantification method.

Isoflavones in aglycone solution enhance ultraviolet B-induced DNA damage repair efficiency.

The isoflavones daidzein and genistein are natural compounds which have anti-inflammatory and photoprotective activities, and may be effective in the repair of ultraviolet (UV)-induced photodamage. In this study, an alcoholic solution of aglycone isoflavones with a genistein:daidzein ratio of 1:4 [Rottapharm (RPH)-aglycone] was examined for its effects on the repair of DNA damage induced by a single dose of UVB irradiation (20 mJ/cm(2)). For this purpose, human skin cells were first UVB-irradiated and then treated with RPH-aglycone. Comet assay analysis was used to estimate the UVB-induced DNA damage at different time points after treatment by measuring the tail moment parameter. We found that treatment with 10 µmol/L RPH-aglycone solution resulted in a significantly reduced tail moment at 1h after treatment, and 34-35% enhancement of damage repair at 4 h after treatment. These results suggest that isoflavone aglycones are protective against UVB-induced DNA damage.

Loss mitigation in plasmonic solar cells: aluminium nanoparticles for broadband photocurrent enhancements in GaAs photodiodes.

We illustrate the important trade-off between far-field scattering effects, which have the potential to provide increased optical path length over broad bands, and parasitic absorption due to the excitation of localized surface plasmon resonances in metal nanoparticle arrays. Via detailed comparison of photocurrent enhancements given by Au, Ag and Al nanostructures on thin-film GaAs devices we reveal that parasitic losses can be mitigated through a careful choice of scattering medium. Absorption at the plasmon resonance in Au and Ag structures occurs in the visible spectrum, impairing device performance. In contrast, exploiting Al nanoparticle arrays results in a blue shift of the resonance, enabling the first demonstration of truly broadband plasmon enhanced photocurrent and a 22% integrated efficiency enhancement.

Computer-aided diagnosis for dynamic contrast-enhanced breast MRI of mass-like lesions using a multiparametric model combining a selection of morphological, kinetic, and spatiotemporal features.

PURPOSE: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a radiological tool for the detection and discrimination of breast lesions. The aim of this study is to evaluate a computer-aided diagnosis (CAD) system for discriminating malignant from benign breast lesions at DCE-MRI by the combined use of morphological, kinetic, and spatiotemporal lesion features. METHODS: Fifty-four malignant and 19 benign breast lesions in 51 patients were retrospectively evaluated. Images were acquired at two centers at 1.5 T. Mass-like lesions were automatically segmented after image normalization and elastic coregistration of contrast-enhanced frames. For each lesion, a set of 28 3D features were extracted: ten morphological (related to shape, margins, and internal enhancement distribution); nine kinetic (computed from signal-to-time curves); and nine spatiotemporal (related to the variation of the signal between adjacent frames). A support vector machine (SVM) was trained with feature subsets selected by a genetic search. Best subsets were composed of the most frequent features selected by majority rule. The performance was measured by receiver operator characteristics analysis with a stratified tenfold cross-validation and bootstrap method for confidence intervals. RESULTS: SVM training by the three separated classes of features resulted in an area under the curve (AUC) of 0.90 ± 0.04 (mean ± standard deviation), 0.87 ± 0.06, and 0.86 ± 0.06 for morphological, kinetic, and spatiotemporal feature, respectively. Combined training with all 28 features resulted in AUC of 0.96 ± 0.02 obtained with a selected feature subset composed by two morphological, one kinetic, and two spatiotemporal features. CONCLUSIONS: Quantitative combination of morphological, kinetic, and spatiotemporal features is feasible and provides a higher discriminating power than using the three different classes of features separately.

Lattice resonances in antenna arrays for liquid sensing in the terahertz regime.

Terahertz antenna arrays supporting narrow lattice resonances are proposed as an alternative sensor-on-chip approach to liquid sensing. An array of metallic rectangular antennas fabricated on a polyethylene naphthalate (PEN) substrate is used to demonstrate the sensing of a number of fluids. Good agreement is shown between experiment and simulation with Q-factors of around 20 and a figure-of-merit (FOM) of 3.80 being achieved. Liquid sensing with antenna arrays is simple both in terms of fabrication and setup. The working frequency can be tuned with a suitable choice of substrates and array parameters. The nature of the lattice resonance means that the whole sample is used to provide the conditions required for resonance occurrence, eliminating the need to preferentially locate the sample in small areas of high field concentration. The antenna arrays could also potentially be coupled with a microfluidic system for in situ sensing or used in a reflection setup.

Lighting up multipolar surface plasmon polaritons by collective resonances in arrays of nanoantennas.

We demonstrate the coupling of multipolar surface plasmons with photonic modes in periodic arrays of metallic nanoantennas. This coupling leads to sharp resonances known as lattice surface modes. In spite of the weak interaction of multipolar surface plasmons with light, lattice surface modes provide an efficient radiative decay channel for emitters in the proximity of the array. We observe a tenfold emission enhancement of dyes coupled to lattice resonances. Lattice surface modes light up multipolar plasmonic resonances, opening new possibilities for fluorescence spectroscopies.

Shaping the fluorescent emission by lattice resonances in plasmonic crystals of nanoantennas.

We demonstrate that the emission of light by fluorescent molecules in the proximity of periodic arrays of nanoantennas or plasmonic crystals can be strongly modified when the arrays are covered by a dielectric film. The coupling between localized surface plasmon resonances and photonic states leads to surface modes which increase the density of optical states and improve light extraction. Excited dye molecules preferentially decay radiatively into these modes, exhibiting an enhanced and directional emission.

Long-range surface polaritons in ultra-thin films of silicon.

We present an experimental and theoretical study of the optical excitation of long-range surface polaritons supported by thin layers of amorphous silicon (a-Si). The large imaginary part of the dielectric constant of a-Si at visible and ultraviolet (UV) frequencies allows the excitation of surface polariton modes similar to long-range surface plasmon polaritons on metals. Propagation of these modes along considerable distances is possible because the electric field is largely excluded from the absorbing thin film. We show that by decreasing the thickness of the Si layer these excitations can be extended up to UV frequencies, opening the possibility to surface polariton UV optics compatible with standard Si technology.

Excitation and emission enhancement of single molecule fluorescence through multiple surface-plasmon resonances on metal trimer nanoantennas.

We study theoretically the light scattering from trimers of metal nanowires, with emphasis on the occurrence of multiple surface-plasmon resonances, showing that such resonances can be exploited to achieve twofold-enhanced fluorescence from a single molecule placed in the nanotrimer gaps, even if excitation and emission frequencies are separated. Pump enhancement stems from the local field enhancement coinciding with one of the resonances, whereas a strong enhancement of the radiative decay rate (and quantum yield) is revealed at a different resonance, leading to a large overall signal emission.

Strong enhancement of the radiative decay rate of emitters by single plasmonic nanoantennas.

We demonstrate a strong, 5-fold enhancement of the radiative decay rate from highly efficient fluorescent dye molecules around resonant optical nanoantennas. The plasmonic modes of individual gold dimer antennas are tuned by the particle length and the antenna gap, providing control over both the spectral resonance position and the near-field mode profile of the nanoantenna. Resonant enhancement of the radiative and nonradiative decay rates of a fluorescent dye is observed, resulting in an increase of the internal quantum efficiency from 40% up to 53% for single antennas, and up to 59% for antenna clusters. This improvement of the already high quantum efficiency of the dye molecules is in agreement with electrodynamic model calculations that predict a maximum attainable efficiency around 80% due to nonradiative losses in the metal.

Electromagnetic model and calculations of the surface-enhanced Raman-shifted emission from Langmuir-Blodgett films on metal nanostructures.

We present a theoretical study of the electromagnetic contribution to surface-enhanced Raman scattering (SERS) from a Langmuir-Blodgett film close to a metal surface. This macroscopic dipolar model fully accounts for the Raman-shifted emission so that meaningful SERS (electromagnetic) enhancement factors that do not depend only on the local electromagnetic field enhancement at the pump frequency are defined. For a plane metal surface, analytical SERS enhancement factors that are consistent for all pump beam polarization and molecular orientation are obtained. In order to investigate SERS on complex nanostructured metal surfaces, we introduce this model into the formally exact, Green's theorem surface integral equation formulation of the scattered electromagnetic field. This formulation is thus employed to calculate numerically the near-field and far-field emissions at the Raman-shifted frequency for very rough, random nanostructured surfaces, with emphasis on the impact of collective processes for varying pump frequency and Raman shift. Our results reveal that the widely used |E|4 approximation tends to overestimate average SERS enhancement factors.

Optical scattering resonances of single and coupled dimer plasmonic nanoantennas.

The optical resonances of individual plasmonic dimer antennas are investigated using confocal darkfield spectroscopy. Experiments on an array of antennas with varying arm lengths and interparticle gap sizes show large spectral shifts of the plasmon modes due to a combination of geometrical resonances and plasmon hybridization. The resonances of the coupled-dimer antennas are considerably broadened compared to those of single nanorods, which is attributed to a superradiant damping of the coupled antenna modes. The scattering spectra are compared with electrodynamic model calculations that demonstrate both the near-field and far-field characteristics of a half-wave antenna.

A randomized trial (ISS 902) of didanosine versus zidovudine in previously untreated patients with mildly symptomatic human immunodeficiency virus infection.

In this multicenter study (ISS 902), 554 previously untreated patients with <500 CD4 cells/mm3 and mildly symptomatic human immunodeficiency virus disease were randomized to receive zidovudine or didanosine (ddI). After a mean follow-up of 20 months, 80 patients (40 zidovudine, 40 ddI) had died and 146 had at least one AIDS-defining event (73 zidovudine, 73 ddI). Overall, no difference was found between treatments with respect to progression to AIDS or death. The analysis of relative risk (RR) of progression over time, however, showed an initially minor risk for zidovudine patients and an inversion in the zidovudine-ddI RR in the second and third years of follow-up. Didanosine showed a greater effect on CD4 cell count response. The two drugs confirmed the toxicity patterns already reported in other trials, with a low occurrence of pancreatitis (ddI 1.3%, zidovudine 0.4%). The overall results suggest that, in this population, zidovudine and ddI monotherapies have comparable long-term clinical efficacy and that more powerful regimens should be preferred.

[Changed etiopathogenic and clinical features of infective endocarditis]. / Mutati aspetti etiopatogenetici e clinici dell'endocardite infettiva.

The authors report their experience on etiological and clinical aspects of infective endocarditis (IE). A series of 182 consecutive patients, including 83 cases of medical IE, 73 cases of IE in intravenous drug abusers (DA), 22 cases of IE on late prosthetic valves and 4 cases of IE on early prosthetic valves were evaluated since 1976. Medical IE occurred frequently in the elderly patients and in most of the cases (80%) involved natural valves with underlying abnormalities, either rheumatic (42%) or degenerative (33%) or malphormative (25%). Pre-existing valvular pathology was not needed for IE in DA, occurring in 13%, mainly due to a previous IE. In most of the cases IE in DA was a staphylococcal IE (80%) and a right-sided IE (77%). Streptococci were frequent agent both in medical and late prosthetic valves IE (55%): however, a wide pattern of microorganisms, including "unusual" pathogens like nutritionally variant Streptococci, Haemophylus parainfluenzae, Haemophylus paraphrophylus, Coxiella burnetii and the so-called "non pathogen microorganisms" (e.g. Neisseria sicca) was identified as etiological agent. As regards the clinical approach and diagnosis, the Authors underline some atypical clinical presentations of IE: the pulmonary presentation, occurring in right-sided IE, mainly in DA; the neurological presentation, suggesting staphylococcal etiology and left-sided IE; the vasculitis presentation, miming connective tissue diseases; the cardiac presentation, observed in aortic localization (1 case). One or more severe complications occurred in 65% of the patients, contributing to adverse outcomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and mycological evaluation of fluconazole in the secondary prophylaxis of esophageal candidiasis in AIDS patients. An open, multicenter study.

A prospective, multicenter, open study of fluconazole prophylaxis was performed in AIDS patients to evaluate the efficacy and toxicity of the drug in preventing relapses of esophageal candidiasis. To this aim, 99 AIDS patients who presented a first episode of clinically and microbiologically confirmed esophageal candidiasis were enrolled in eleven clinical centers scattered throughout the Italian territory. After resolution of this initial esophagitis, all subjects were given fluconazole, 100 mg/die, and followed up for a 6 month period. Only 7 out of the 99 patients enrolled had a relapse of Candida esophagitis, during a mean follow-up period of 138.5 days. All relapsing patients had CD4+ cell number < 100/microliters at baseline. Mild side effects were reported in only eight patients. However, 14 of the 27 subjects from whom serial serum samples were available became (12) or remained (2) antigenemic during fluconazole prophylaxis, independently from relapse, suggesting the persistence of tissue-invasive, proliferating Candida cells. Overall, the data of this study suggest a beneficial effect of prophylactic maintenance therapy with fluconazole against Candida esophagitis, particularly in the population with > 100 CD4+/microliters. However, the data on Candida antigenemia in these patients invite the consideration of a relative inefficiency of the drug to eradicate the microrganism from the esophageal tissue.