A nonrigid registration of MR breast images using complex-valued wavelet transform.

In this paper, a fast, slice-by-slice, nonrigid registration algorithm of dynamic magnetic resonance breast images is presented. The method is based on a multiresolution motion estimation of the breast using complex discrete wavelet transform (CDWT): the pyramid of oriented complex subimages is used to implement a hierarchical phase-matching-based motion estimation algorithm. The resulting motion estimate is nonrigid and pixel-independent. To assess the method performance, we computed the correlation coefficient and the normalized mutual information between pre- and postcontrast images with and without realignment. The indices increased after using our approach and the improvement was superior to rigid or affine registration. A set of clinical scores was also evaluated. The clinical validation demonstrated an increased readability in the subtraction images. In particular, CDWT registration allowed a best definition of breast and lesion borders and greater detail detectability.

New trends in antimicrobial development.

The continual evolution of microbial resistance to the available classes of antibiotics poses a serious threat to the efficacy of traditional antibacterial therapy. Today, there are two main approaches that are being applied to discover better and more effective anti-infective agents against common as well as resistant pathogens: (a) the improvement of the "classical" antimicrobial agents by targeting the so called "resistance factors", and (b) the search of new anti-infective agents with novel modes of actions. This review will highlight the most relevant aspects of both of these approaches and some of the latest findings in the field of antimicrobial discovery.

Recent advances in the chemistry of beta-lactam compounds as selected active-site serine beta-lactamase inhibitors.

The b-lactamases catalyze the hydrolysis of the b-lactam bond of a variety of b-lactam antibiotics destroying their antibacterial activity. During the last decades, there has been an inexorable spread of b-lactamase genes into species that previously were not known to possess them. One approach to combat the action of the b-lactamase is to inhibit the enzyme. However, inhibition of b-lactamase alone is not sufficient. The ability to penetrate the external membrane of Gram-negative bacteria, chemical stability, pharmacokinetics and other factors are also important in determining whether an inhibitor is suitable or not for therapeutic use. This review takes recent examples of synthetic b-lactam compounds developed as active-site serine b-lactamase inhibitors, emphasizing information on their structures and their activity against Ambler classes A, C and D b-lactamases. In addition, examples based on rational design by computerized molecular modeling of crystal structure of the native enzyme and mechanism of the enzyme action are highlighted.

New trends in antimicrobial development.

So far, two strategies have been applied to develop new anti-infective agents: (a) the synthesis of analogs of classical antibiotics with enhanced activity against resistant pathogens and (b) the screening of naturally occurring substances and libraries of synthetic compounds for antimicrobial activity in whole-cell assays. Today, the same principles are being used; however, the search for antimicrobial compounds with novel modes of action is based on targeting specific resistance and virulence factors. Novel targets for anti-infective agents are currently being discovered as a consequence of a better understanding of cell biology, the molecular basis of bacterial resistance, the gene-pathogenicity relationship and the mechanism of the infection process.

Telomerase activity and telomere length in human ovarian cancer and melanoma cell lines: correlation with sensitivity to DNA damaging agents.

Since telomerase plays a role in cellular resistance to apoptosis, which is the primary mode of cell death induced by several drugs, telomerase could be involved in determining the chemosensitivity profile of tumor cells. Thus, we investigated the relationship between telomerase activity, telomere length and chemosensitivity to effective antitumor agents in a panel of human melanoma and ovarian cancer cell lines. Telomerase activity, as detected by the telomeric repeat amplification protocol, ranged from 0.58 to 1.10 arbitrary units in individual cell lines, with similar median values for melanoma and ovarian carcinoma cell lines (0.80 vs. 0.90). Telomeres were generally longer in melanoma than in ovarian carcinoma cell lines, with a more than 2-fold median telomere restriction fragment length (7.74 vs. 3.82 kb). No significant correlation was evidenced between the two telomere-related parameters and cell population doubling time, DNA index or TP53 gene status. No precise relation was found between telomerase activity and cellular sensitivity to different DNA damaging agents including doxorubicin, cisplatin and the multinuclear platinum compound BBR 3464. In contrast, longer telomeres were associated to resistance to the drugs, even though the association reached statistical significance only for cisplatin. Since platinum compounds may have affinity for telomere sequences, it is conceivable that the interaction is relevant for drug sensitivity/resistance status depending on telomere length.

Chemical modification of tazobactam. Synthesis of 2 beta-[(4-substituted)-1,2,3-triazol-1-yl]methyl penicillanic acid sulfone derivatives.

A series of 2 beta-[(4-substituted)-1,2,3-triazol-1-yl] methyl penicillanic acid sulfones was synthesized as beta-lactamase inhibitors. Many of these compounds showed good in vitro inhibitory activity against penicillinase, cefotaximase and plasmid-mediated class III TEM enzymes, but exhibited weaker cephalosporinase inhibition. One member in this series--2 beta-[(4-pyridiniummethyl)-1,2,3-triazol- 1-yl]-6,6-dihydropenicillanate 1,1-dioxide (12a), when tested in combination with piperacillin, showed excellent synergistic activity against microorganisms producing plasmid-mediated enzymes, but had insufficient activity against microorganisms producing chromosomally mediated class I enzymes.

Estimating germinability of Plasmopara viticola oospores by means of neural networks.

Neural networks are trained to estimate the germination percentages of Plasmopara viticola oospores, overwintered in natural conditions in two viticultural areas in northern Italy, by using climatic (temperature and rainfall) data, as well as the previous germination measurement, as input variables. The 288 available patterns consist of a set of selected independent variables associated with the corresponding germination percentage. All 12 networks investigated converge to a non-linear relationship between the selected independent variables and oospore germination. The highest correlation coefficient (equal to 0.83) between the real and estimated germination percentages is obtained by considering, as input to the network, the climatic data (both temperature and rainfall) recorded during the 40 days before sampling and the germination percentage assessed in the germination assay carried out immediately before the present sampling.

[Enlargement labial commissuroplasty using the Préaux-Texier-Réal method. Our personal experience]. / Commissuroplastica labiale d'allargamento sec. Préaux, Texier e Réal. Nostra esperienza personale.

The augmentation labial commissuroplasty technique, as described by Préaux, Texier and Réal, after reduction of the buccal opening by lip-to-lip autoplasty is presented. The results achieved, the feasibility and the advantages of this procedure are compared with those of traditional techniques.

[Standoli-Cecchi cheiloplasty in the treatment of cleft lip. Our personal experience]. / Cheiloplastica sec. Standoli e Cecchi nel trattamento delle schisi labiali. Nostra esperienza personale.

Labial repair by the "W-technique" in primary cleft lip surgery, as described by Standoli and Cecchi, is presented. The preliminary results achieved and the advantages of this procedure are compared with those of traditional techniques.

A practical dead time correction method in planar activity quantification for dosimetry during radionuclide therapy.

AIM: Gamma camera saturation is the first quantification problem in dosimetric studies following therapeutic administrations of 131I labeled radiopharmaceuticals. A new approach for dead time correction (DTC) is here proposed. It employs planar whole-body (WB) images without the need of standard radionuclide sources or of preliminary phantom calibrations. METHODS: Step and shoot WB acquisitions of the patient are required. A program was developed to compensate for the image discontinuities ("Continuity DTC method") between two adjacent static fields of view (FOVs) caused by different dead time count losses. For its validation, authors used two 99mTc 6 GBq phantom scans after administration of six patients with 131I labeled agents with different statistics and ten clinical scans taken between 16 h and 48 h after administration of 131I labeled agents, whose activity ranged from 4 to 10 GBq. The deviation from true decay corrected counts on phantoms and the constancy of monitor point-source counts in different patients' FOVs (root mean square error and maximum deviation) served as figures of merit. The accuracy of absorbed dose calculation was also estimated by comparison with the standard source correction method, computing the area under the time activity curve (AUC) of six lesions. RESULTS: With respect to the true phantom counts, corrected images gave excellent results, giving a 6% maximum deviation. For what concerns the other figures of merit, continuity DTC reduced the average root mean square error from 36% to 2% and the mean maximum deviation from 50% to 2%, on phantom, while from 51% to 32/28% (absence/presence of triple energy window scatter correction) and from 72% to 21/14% on patients. Mean compensation of AUC gave a correction of +56% with our method, while +78% with standard source method. CONCLUSIONS: The "Continuity DTC method" is a useful tool in dosimetry during nuclear medicine treatment, showing good accuracy. Moreover, since it does not require the use of any source, it provides with several advantages in terms of practicability and applicability, with respect to the standard source method and to methods based on the count rate characteristic curve.

A Fuzzy-C-means clustering algorithm for a volumetric analysis of paranasal sinus and nasal cavity cancers.

In this paper, a semi-automatic segmentation algorithm for volumetric analysis of paranasal sinus and nasal cavity cancers is presented and validated. The algorithm, based on a semi-supervised Fuzzy-C-means method, was applied to a Magnetic Resonance data sets (each of them composed by T1-weighted, Contrast Enhanced T1-weighted and T2-weighted images) for a total of 64 tumor-contained slices. Method performances are tested by both a numerical and a clinical validation. Results show that the proposed method has a higher accuracy in quantifying lesion area than a region growing algorithm and it can be applied in the evaluation of tumor response to therapy.

A Java viewer to publish Digital Imaging and Communications in Medicine (DICOM) radiologic images on the World Wide Web.

The world wide web is an exciting service that allows one to publish electronic documents made of text and images on the internet. Client software called a web browser can access these documents, and display and print them. The most popular browsers are currently Microsoft Internet Explorer (Microsoft, Redmond, WA) and Netscape Communicator (Netscape Communications, Mountain View, CA). These browsers can display text in hypertext markup language (HTML) format and images in Joint Photographic Expert Group (JPEG) and Graphic Interchange Format (GIF). Currently, neither browser can display radiologic images in native Digital Imaging and Communications in Medicine (DICOM) format. With the aim to publish radiologic images on the internet, we wrote a dedicated Java applet. Our software can display radiologic and histologic images in DICOM, JPEG, and GIF formats, and provides a a number of functions like windowing and magnification lens. The applet is compatible with some web browsers, even the older versions. The software is free and available from the author.

[A visual displayer for publishing radiologic images on the World Wide Web]. / Un visualizzatore per la pubblicazione di immagini radiologiche su World Wide Web.

PURPOSE: To present a software suitable for publication of medical images on the World Wide Web and compatible with both the DICOM and other popular formats like GIF and JPEG. MATERIALS AND METHODS: DICOM viewer is a Java applet, written in Java 1.0. The tool offers the capability to publish medical images, to modify brightness and contrast (windowing) and to magnify the picture (magnification lens). Information related to the image is available for consultation only for DICOM images. RESULTS: The viewer was tested with many DICOM files, generated by our PACS or downloaded from Internet. It works well with the DICOM 3.0 file format, but correct functioning is not granted for previous releases. The software was compatible with all the most popular Web browsers (MS Internet Explorer 3.0 or newer, Netscape Navigator 4.5 or newer, Sun and HotJava) and it works well in Windows, Sun Solaris. Macintosh, Windows CE. A 512 kb image (a standard MR image) requires about 5 seconds to be shown on an Intel Pentium II PC with 32 Mbyte RAM connected on a 10 Mbit/s Ethernet network. About 3 seconds are needed to download the file and about 2 seconds to display the image. Windowing and zooming are quick enough. CONCLUSIONS: The applet allows to publish DICOM medical images directly on the World Wide Web, without converting them into another graphical format. Moreover, it supplies some image processing tools common in the radiological environment. The viewer characteristics make it suitable for preparing teaching radiology sites or clinical files on the Web. The viewer's performance is somewhat poor, particularly on the Internet. Better performances are achieved on local area network (intranet). To improve performance, we will introduce file compression and rewrite the software in Java 1.1. The software is available from the author free of charge.

A use of a neural network to evaluate contrast enhancement curves in breast magnetic resonance images.

For the diagnosis of breast cancer using magnetic resonance imaging (MRI), one of the most important parameters is the analysis of contrast enhancement. A three-dimensional MR sequence is applied before and five times after bolus injection of paramagnetic contrast medium (Gd-DTPA). The dynamics of absorption are described by a time/intensity enhancement curve, which reports the mean intensity of the MR signal in a small region of interest (ROI) for about 8 minutes after contrast injection. The aim of our study was to use an artificial neural network to automatically classify the enhancement curves as "benign" or "malignant." We used a classic feed-forward back-propagation neural network, with three layers: five input nodes, two hidden nodes, and one output node. The network has been trained with 26 pathologic curves (10 invasive carcinoma [K], two carcinoma-in-situ [DCIS], and 14 benign lesion [B]). The trained network has been tested with 58 curves (36 K, one DCIS, 21 B). The network was able to correctly identify the test curves with a sensitivity of 76% and a specificity of 90%. For comparison, the same set of curves was analyzed separately by two radiologists (a breast MR expert and a resident radiologist). The first correctly interpreted the curves with a sensitivity of 76% and a specificity of 90%, while the second scored 59% for sensitivity and 90% for specificity. These results demonstrate that a trained neural network recognizes the pathologic curves at least as well as an expert radiologist. This algorithm can help the radiologist attain rapid and affordable screening of a large number of ROIs. A complete automatic computer-aided diagnosis support system should find a number of potentially interesting ROIs and automatically analyze the enhancement curves for each ROI by neural networks, reporting to the radiologist only the potentially pathologic ROIs for a more accurate, manual, repeated evaluation.

Validation of an elastic matching algorithm based on complex wavelets for the realignment of dynamic MR breast images.

In this paper, a novel approach for the registration of dynamic magnetic resonance (MR) breast images is validated. The approach is fully automatic and it performs a multi-resolution motion field estimation based on complex discrete wavelets transform (CDWT). The validation was designed to assess the registration quality in patient breast data. A set of diagnostic features of MR breast image was defined and two expert radiologists were asked to score the capability to detect these features in the subtraction images. Two registration methods were compared: a rigid registration algorithm and the proposed approach. Results show that the novel approach is superior in terms of both lesion detectability and lesion definition.

Breast magnetic resonance imaging: a computer-based analysis of enhancement curves.

The aim of this work is to report our experience in contrast-enhanced magnetic resonance (MR) automatic analysis. This technique is usually used in our practice for the diagnosis of breast cancer. Study execution and semiautomatic data analysis require at least 1 hour of the radiologist. So, we decided to develop a tool that aids the radiologist in locating the regions of neoplastic angiogenesis and quickly plotting the enhancement curves. This is not a computer-aided diagnostic tool; of course, the curves are interpreting directly by the radiologist. We used a programmable graphical and calculus environment (Matlab, The Mathworks, Natick, MA) to develop a tool that interfaces directly with our picture archiving and communication system (PACS) via Digital Imaging and Communications in Medicine (DICOM), receives images, performs images subtraction, and shows some possible regions of interest (ROIs), each with an enhancement curve. The radiologist can also select other ROIs. The software shows a good performance (sensitivity, 100%). A low specificity (25%) is acceptable because the software allows the radiologist to save some time during each study.