Modulating Expression of Endogenous Interleukin 1 Beta in the Acute Phase of the Pilocarpine Model of Epilepsy May Change Animal Survival.

The pilocarpine-induced (PILO) model has helped elucidate the electrophysiological and molecular aspects related to mesial temporal lobe epilepsy. It has been suggested that the extensive cell death and edema observed in the brains of these animals could be induced by increased inflammatory responses, such as the rapid release of the inflammatory cytokine interleukin 1 beta (Il1b). In this study, we investigate the role of endogenous Il1b in the acute phase of the PILO model. Our aim is twofold. First, we want to determine whether it is feasible to silence Il1b in the central nervous system using a non-invasive procedure. Second, we aim to investigate the effect of silencing endogenous Il1b and its antagonist, Il1rn.We used RNA interference applied non-invasively to knockdown Il1b and its endogenous antagonist Il1rn. We found that knocking down Il1b prior to pilocarpine injection increased the mortality rate of treated animals. Furthermore, we observed that, when exposing the animals to more Il1b by silencing its endogenous antagonist Il1rn, there was a better response to status epilepticus with decreased animal mortality in the acute phase of the PILO model. Thus, we show the feasibility of using a novel, less invasive approach to study genes involved in the inflammatory response in the central nervous system. Furthermore, our results provide suggestive evidence that modulating endogenous Il1b improves animal survival in the acute phase of the PILO model and may have effects that extend into the chronic phase.

Schistosoma mansoni: evaluation of an RNAi-based treatment targeting HGPRTase gene.

Hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) is an essential gene of the parasite Schistosoma mansoni and it is well conserved in its hosts (mouse and human) at the protein but not at the RNA level. This feature prompted us to assess RNA interference (RNAi) to combat schistosomiasis. Small interfering RNAs (siRNAs) were produced against HGPRTase, injected in infected mice and the number of worms was counted six days after injection. The total number of parasites was reduced by approximately 27% after treatment. RT-PCR analyzes showed a significant reduction in parasite target mRNA but not in host's homologue. The use of low doses of molecules did not oversaturate si- or miRNA pathways as mice survival rates were not affected by siRNAs. This is the first successful in vivo demonstration of a RNAi-based treatment against schistosomiasis. We believe that improvements in molecule delivery and an increase on siRNA dose could rapidly eliminate parasite.

Detection limits of multi-spectral optical imaging under the skin surface.

The present work shows that the optical/biological information contained in a typical spectral image mainly reflects the properties of a small (conic like) volume of tissue situated vertically under each individual pixel. The objects appearing on a spectral image reasonably reproduce the correct geometrical shape and size (like a non-deformed shadow) of underlying inclusions of pathological tissue. The information contained in a spectral image comes from a depth that does not exceed approximately 2-3 mm. The number of photons that visit a given tissue voxel situated at a depth larger than approximately 2 mm represents less than the 1% of the total number of photons reaching the corresponding detection pixel (forming the image). A pathological inclusion (e.g. a pool of blood or vascular tumor) situated at a depth of approximately 0.5 mm with a thickness of 0.5 mm produces an image intensity contrast of approximately 5% (for images taken at wavelengths in the 600-1000 nm range) when compared to the normal skin background. The same inclusion at a depth of 20 microm provides a contrast decreasing from 55 to 20% with respect to an increase in wavelength. The dermis/hypodermis interface behaves as a partial barrier for the photons, limiting their access to deeper skin regions. The image contrast depends on the depth and the type of chromophore contained in the inclusion. An increase in the concentration of a given molecule may produce different contrast, independently of the depth, depending on the characteristics of the skin layer where this change occurs.

Skin and cutaneous melanocytic lesion simulation in biomedical optics with multilayered phantoms.

The complex inner layered structure of skin influences the photon diffusion inside the cutaneous tissues and determines the reflectance spectra formation. Phantoms are very useful tools to understand the biophysical meaning of parameters involved in light propagation through the skin. To simulate the skin reflectance spectrum, we realized a multilayered skin-like phantom and a multilayered skin phantom with a melanoma-like phantom embedded inside. Materials used were Al(2)O(3) particles, melanin of sepia officinalis and a calibrator for haematology systems dispersed in transparent silicon. Components were optically characterized with indirect techniques. Reflectance phantom spectra were compared with average values of in vivo spectra acquired on a sample of 573 voluntary subjects and 132 pigmented lesions. The phantoms' reflectance spectra agreed with those measured in vivo, mimicking the optical behaviour of the human skin. Further, the phantoms were optically stable and easily manageable, and represented a valid resource in spectra formation comprehension, in diagnostic laser applications and simulation model implementation, such as the Monte Carlo code for non-homogeneous media.

Multispectral imaging and artificial neural network: mimicking the management decision of the clinician facing pigmented skin lesions.

Various instruments based on acquisition and elaboration of images of pigmented skin lesions have been developed in an attempt to in vivo establish whether a lesion is a melanoma or not. Although encouraging, the response of these instruments, e.g. epiluminescence microscopy, reflectance spectrophotometry and fluorescence imaging, cannot currently replace the well-established diagnostic procedures. However, in place of the approach to instrumentally assess the diagnosis of the lesion, recent studies suggest that instruments should rather reproduce the assessment by an expert clinician of whether a lesion has to be excised or not. The aim of this study was to evaluate the performance of a spectrophotometric system to mimic such a decision. The study involved 1794 consecutively recruited patients with 1966 doubtful cutaneous pigmented lesions excised for histopathological diagnosis and 348 patients with 1940 non-excised lesions because clinically reassuring. Images of all these lesions were acquired in vivo with a multispectral imaging system. The data set was randomly divided into a train (802 reassuring and 1003 excision-needing lesions, including 139 melanomas), a verify (464 reassuring and 439 excision-needing lesions, including 72 melanomas) and a test set (674 reassuring and 524 excision-needing lesions, including 76 melanomas). An artificial neural network (ANN(1)) was set up to perform the classification of the lesions as excision-needing or reassuring, according to the expert clinicians' decision on how to manage each examined lesion. In the independent test set, the system was able to emulate the clinicians with a sensitivity of 88% and a specificity of 80%. Of the 462 correctly classified as excision-needing lesions, 72 (95%) were melanomas. No major variations in receiver operating characteristic curves were found between the test and the train/verify sets. On the same data set, a further artificial neural network (ANN(2)) was then architected to perform classification of the lesions as melanoma or non-melanoma, according to the histological diagnosis. Having set the sensitivity in recognizing melanoma to 95%, ANN(1) resulted to be significantly better in the classification of reassuring lesions than ANN(2). This study suggests that multispectral image analysis and artificial neural networks could be used to support primary care physicians or general practitioners in identifying pigmented skin lesions that require further investigations.

Optical devices used for image analysis of pigmented skin lesions: a proposal for quality assurance protocol using tissue-like phantoms.

Different technological tools have been developed to aid in the diagnosis of pigmented skin lesions, including cameras working with conventional RGB colour systems, epiluminescence microscopy and spectrophotometric methods using visible and near infrared wavelengths. All the different procedures should provide in an objective and reproducible fashion quantitative measurements of the colour and shape features of a given skin mole. At present, many devices have been introduced in experimental stages for clinical diagnosis, mainly used to provide to the clinicians an objective, computer-assisted second opinion. As for any diagnostic instruments, optical devices should also be subjected to a dedicated quality assurance protocol in order to evaluate the response repeatability of each device (intra-instrument agreement) and to check the accordance among the responses of different devices (inter-instrument agreement). The aim of this study was to design a quality assurance protocol for optical devices dedicated to image analysis of pigmented skin lesions and, in case, to detect cutaneous melanoma by using suitable tissue-like phantoms as standard references that enable testing of both hardware and software components. As an example, we report the results of intra-instrument and inter-instrument agreement when the protocol was applied on a series of 30 SpectroShade instruments, a novel optical device based on multi-spectral image analysis of colour and shape features of pigmented skin lesion.

Optical imaging and automated melanoma detection: questions and answers.

Early detection and prompt excision of cutaneous melanoma is of paramount importance to improve patient survival, and the clinician should be aware of the clinical features that suggest the presence of a malignant lesion. The clinical diagnosis is mainly based on observation of the colour and shape of a given skin lesion. Unfortunately, evaluation of a pigmented lesion is to a large extent subjective and is closely related to the experience of the clinician. To overcome this problem, optical imaging techniques using different instrumentation (i.e. colour video camera, epiluminescence microscopy, reflectance spectrophotometry) and computer image analysis have been proposed in an attempt to provide quantitative measurements in an objective and reproducible fashion. The different procedures employed to perform the diagnosis automatically all have a common denominator: mimicking the eye and the brain of the clinician by image processing and computerized analysis programs, respectively. Sensitivity and specificity data reported in the literature suggest that the computer-based diagnosis of melanoma does not greatly differ from the diagnostic capability of an expert clinician, and is independent of the optical acquisition method employed to analyse the lesions. Most of the computer-processed morphometric variables useful in automated diagnosis are not recognizable nor can be objectively evaluated by the human eye, except that of lesion dimension. However, several questions should be answered before assessing the actual usefulness, including the potential and limitations, of computer-based diagnostic procedures. The purpose of this study was to briefly review the different kinds of instrumentation being used to diagnose melanoma, and to raise questions and whenever possible provide answers in an attempt to establish whether there will be a future for these computerized systems.

Reed (Phragmites australis) decline in a brackish wetland in Italy.

A comparative field study was carried out at two sites (a healthy site and a declining site) in a brackish wetland in northern Italy, with the objective to investigate the symptoms and the possible causes leading to reed (Phragmites australis) decline in this area. The declining reed plants presented many of the symptoms (clumping habit, smaller size, weaker culms, abnormal rhizome and root anatomy, low starch levels in rhizomes) comprised within the so-called reed die-back syndrome, frequently observed in central European wetlands but never recorded previously in (Sub)Mediterranean regions. Soil nutrient levels did not differ much between the two sites, with nitrate concentrations in the soil being even higher at the healthy site (1.54 microg g(-1); die-back site 0.76 microg g(-1)). Hence, eutrophication did not seem to represent a major cause in determining reed decline in this area. High sulphate concentrations in saltwater associated with low soil redox potentials (-215 mV) due to waterlogging resulted in high soil sulphide concentrations. Concentrations of organic acids, especially acetic acid, did not differ remarkably between sites. High sulphide levels presumably accounted for abnormal anatomical formations (callus blocking aerenchyma channels), lower rates of net CO2 exchange and reduced reserve storage, observed at the die-back site. This was associated with a lower mechanical resistance of reed culms which accelerated reed mortality in the die-back areas. We concluded that high sulpihde levels in permanently waterlogged soils may result in die-back of reed stands in Mediterranean wetlands.

A phantom with tissue-like optical properties in the visible and near infrared for use in photomedicine.

BACKGROUND AND OBJECTIVE: Modeling of light transport in tissue requires development of theoretical models and experimental procedures, as well as tissue-simulating phantoms. Our purpose was to develop a phantom that matches the optical characteristics of human skin in the visible and near infrared spectral range. STUDY DESIGN/MATERIALS AND METHODS: The phantom consists of a transparent silicone rubber in which Al(2)O(3) particles and a cosmetic powder are embedded. Layers with thickness as thin as 0.1 mm can be made. The optical properties of Al(2)O(3) particles and cosmetic powder, i.e., total attenuation, absorption and scattering coefficients, and phase function, have been determined in the visible and near infrared spectral range, by using direct and indirect techniques. RESULTS: By varying the concentration of scattering and absorbing particles, tissue-like layers can be produced with predictable optical properties. In particular, mixing at suitable concentration Al(2)O(3) particles and cosmetic powder with the silicone rubber, the optical properties of human skin have been simulated over a range of wavelengths from 400 to 1,000 nm. The comparison between the phantom diffuse reflectance spectrum and that of human skin, averaged over a sample of 260 patients, showed a good agreement. CONCLUSION: The proposed technique allows to produce a stable and reproducible phantom, with accurately predictable optical properties, easy to make and to handle. This phantom is a useful tool for numerous applications involving light interaction with biologic tissue.

Inactivation of human cells exposed to fractionated doses of low energy protons: relationship between cell sensitivity and recovery efficiency.

Within the framework of radiation biophysics research in the hadrontherapy field, split-dose studies have been performed on four human cell lines with different radiation sensitivity (SCC25, HF19, H184B5 F5-1 M10, and SQ20B). Low energy protons of about 8 and 20 keV/micron LET and gamma-rays were used to study the relationship between the recovery ratio and the radiation quality. Each cell line was irradiated with two dose values corresponding to survival levels of about 5% and 1%. The same total dose was also delivered in two equal fractions separated by 1.5, 3, and 4.5 hours. A higher maximum recovery ratio was observed for radiosensitive cell lines as compared to radioresistant cells. The recovery potential after split doses was small for slow protons, compared to low-LET radiation. These data show that radiosensitivity may not be related to a deficient recovery, and suggest a possible involvement of inducible repair mechanisms.

Radiobiological studies on the 65 MeV therapeutic proton beam at Nice using human tumour cells.

PURPOSE: To determine the relative biological effectiveness (RBE) for initial and delayed inactivation of cells by a modulated proton beam suitable for the treatment of tumours of the eye, within the spread-out Bragg peak and in its distal declining edge. MATERIALS AND METHODS: Human tumour SCC25 cells were irradiated with the 65 MeV proton beam at the Cyclotron Medicyc in Nice. Perspex plates of different thickness were used to simulate five positions along the beam line: 2mm corresponding to the entrance beam; 15.6 and 25 mm in the spread-out Bragg peak; 27.2 and 27.8mm for the distal edge. At each position clonogenic survival of the irradiated cells and of their progeny were determined at various dose values. 60Co gamma-rays were used as reference radiation. RESULTS: RBE values evaluated at the survival level given by 2 Gy of gamma-rays increased with increasing depth from close to 1.0 at the proximal to about 1.2 at the distal part of the peak. Within the declining edge it reached the value of about 1.4 at 27.2 and about 2 at 27.8 mm. For the progeny of irradiated cells, the RBE value ranged from 1.0 to 1.1 within the spread-out Bragg peak and then increased up to a value of 2.0 at the last position. The dose-effect curves for the progeny always had a larger shoulder than for the irradiated progenitors, their alpha parameters being lower by a factor of about 4 and their beta parameters always being higher. The alpha/beta ratio was about 50 Gy for the progenitors and about 6 Gy for their progeny. The incidence of delayed effects increased with dose and with the depth within the beam. CONCLUSIONS: RBE values for the inactivation of cells irradiated in the spread-out Bragg peak are compatible with the value currently assumed in clinical applications. In the distal declining edge of the beam, the RBE values increased significantly to an extent that may be of concern when the region of the treatment volume is close to sensitive tissues. The yield of delayed reproductive cell death was significant at each position along the beam line.

Dosimetric verification of a commercial 3D treatment planning system for conformal radiotherapy with a dynamic multileaf collimator.

The dosimetric accuracy of a 3D treatment planning system (TPS) for conformal radiotherapy with a computer-assisted dynamic multileaf collimator (DMLC) was evaluated. The DMLC and the TPS have been developed for clinical applications where dynamic fields not greater than 10 x 10 cm2 and multiple non-coplanar arcs are required. Dosimetric verifications were performed by simulating conformal treatments of irregularly shaped targets using several arcs of irradiation with 6 MV x-rays and a spherical-shaped, tissue-simulating phantom. The accuracy of the delivered dose at the isocentre was verified using an ionization chamber placed in the centre of the phantom. Isodose distributions in the axial and sagittal planes passing through the centre of the phantom were measured using double-layer radiochromic films. Measured dose at the isocentre as well as isodose distributions were compared to those calculated by the TPS. The maximum percentage difference between measured and prescribed dose was less than 2.5% for all the simulated treatment plans. The mean (+/-SD) displacement between measured and calculated isodoses was, in the axial planes, 1.0 +/- 0.6 mm, 1.2 +/- 0.7 mm and 1.5 +/- 1.1 mm for 80%, 50% and 20% isodose curves, respectively, whereas in the sagittal planes it was 2.0 +/- 1.2 mm and 2.2 +/- 2 mm for 80% and 50% isodose curves, respectively. The results indicate that the accuracy of the 3D treatment planning system used with the DMLC is reasonably acceptable in clinical applications which require treatments with several non-coplanar arcs and small dynamic fields.

Inactivation of human normal and tumour cells irradiated with low energy protons.

PURPOSE: To analyse the cell inactivation frequencies induced by low energy protons in human cells with different sensitivity to photon radiation. MATERIALS AND METHODS: Four human cell lines with various sensitivities to photon irradiation were used: the SCC25 and SQ20B derived from human epithelium tumours of the tongue and larynx, respectively, and the normal lines M/10, derived from human mammary epithelium, and HF19 derived from a lung fibroblast. The cells were irradiated with y-rays and proton beams with linear energy transfer (LET) from 7 to 33 keV/microm. Clonogenic survival was assessed. RESULTS: Survival curves are reported for each cell line following irradiation with gamma-rays and with various proton LETs. The surviving fraction after 2 Gy of gamma-rays was 0.72 for SQ20B cells, and 0.28-0.35 for the other cell lines. The maximum LET proton effectiveness was generally greater than that of gamma-rays. In particular there was a marked increase in beam effectiveness with increasing LET for the most resistant cells (SQ20B) whose 2 Gy-survival varied from 0.72 with gamma-radiation down to 0.37 with 30 keV/microm protons. The relative biological effectiveness (RBE(2 Gy gamma)) with the 30 keV/microm beam, evaluated as the ratio of 2 Gy to the proton dose producing the same inactivation level as that given by 2 Gy of gamma-rays, was 3.2, 1.8, 1.3 and 0.8 for SQ20B, M/10, SCC25, and HF19, respectively. CONCLUSIONS: RBE for inactivation with high-LET protons increased with the cellular radioresistance to gamma-rays. The cell line with the greatest resistance to gamma-rays was the most responsive to the highest LET proton beam. A similar trend has also been found in studies reported in the literature with He, C, N ions with LET in the range 20-125 keV/microm on human tumour cell lines.

Multispectral imaging approach in the diagnosis of cutaneous melanoma: potentiality and limits.

In an attempt to overcome the subjectiveness of clinical observation in the diagnosis of cutaneous melanoma, a computerized method is proposed. Reflectance images of 237 pigmented lesions (67 melanomas and 170 non-melanomas) were analysed using a telespectrophotometric technique. This device consists of a CCD camera with 17 interference filters. Images were acquired at selected wavelengths, from 420 to 1040 nm. Morphological and reflectance related parameters were extracted from the wavelength-dependent images of the lesions. The most significant features in the comparison between benign and malignant lesions were: lesion dimension (P < 10(-8) at 578 nm); mean value (P < 10(-7) at 940 nm) and standard deviation (P < 10(-4) at 904 nm) of lesion reflectance; lesion roundness (P < 10(-5) at 461 nm); and border irregularity (P < 10(-4) at 461 nm). Based on these parameters, a discriminant function between the two populations of lesions (naevi and melanomas) was obtained. By using the results of the analysis of the recruited lesions as 'training data', discriminant functions enabled the assignment of a score, or a 'risk probability', to each studied lesion. By imposing a sensitivity of 80% (a figure that mimics the diagnostic capability of an experienced clinician), entering or not entering the lesion dimension as input data in the discriminant analysis led to a specificity of 51% or 46% respectively. The high number of false-positive cases, which is a consequence of the selection criteria of the lesions, is, at present, the major limitation of the current technique. Nevertheless, our results suggest that an imaging-based computer-assisted device could be capable of discriminating malignant lesions mainly by evaluation of reflectance, especially in the infrared region, and shape properties. The dimension of a lesion should not be essential in the diagnosis of melanoma and, in our opinion, small melanomas should be recognized by a computer system as well as they are on clinical grounds.

Monitoring of heavy metal deposition in Northern Italy by moss analysis.

A survey of heavy metal deposition in the mountainous territories of Northern Italy was carried out in 1995-96. Moss samples (mainly Hylocomium splendens) were collected in a dense network of sites (about 3.2 sites/1000 km(2)) and the data of metal concentrations in moss tissues were statistically correlated with environmental and climatic factors, as well as with bulk deposition of elements and elemental concentrations in the soil. Three main geographic patterns of metal concentration in mosses could be defined: (1) Fe, Ni, and Cr, all derived both by soil particulates and anthropogenic emissions connected with ferrous metal manufacturing, were mostly concentrated in Northwestern Italy; (2) Cu and Zn, as typical multi-source elements, showed rather high concentrations with little ranges of variation over the whole area and small peaks reflecting local source points; (3) Cd and Pb reflected long-distance transport and showed highest concentrations in the regions with highest precipitation, especially in the Eastern Alps.

Dosimetry of Gamma Knife and linac-based radiosurgery using radiochromic and diode detectors.

In stereotactic radiosurgery the choice of appropriate detectors, whether for absolute or relative dosimetry, is very important due to the steep dose gradient and the incomplete lateral electronic equilibrium. For both linac-based and Leksell Gamma Knife radiosurgery units, we tested the use of calibrated radiochromic film to measure absolute doses and relative dose distributions. In addition a small diode was used to estimate the relative output factors. The data obtained using radiochromic and diode detectors were compared with measurements performed with other conventional methods of dosimetry, with calculated values by treatment planning systems and with data prestored in the treatment planning system supplied by the Leksell Gamma Knife (LGK) vendor. Two stereotactic radiosurgery techniques were considered: Leksell Gamma Knife (using gamma-rays from 60Co) and linac-based radiosurgery (LR) (6 MV x-rays). Different detectors were used for both relative and absolute dosimetry: relative output factors (OFs) were estimated by using radiochromic and radiographic films and a small diode; relative dose distributions in the axial and coronal planes of a spherical polystyrene phantom were measured using radiochromic film and calculated by two different treatment planning systems (TPSs). The absolute dose at the sphere centre was measured by radiochromic film and a small ionization chamber. An accurate selection of radiochromic film was made: samples of unexposed film showing a percentage standard deviation of less than 3% were used for relative dose profiles, and for absolute dose and OF evaluations this value was reduced to 1.5%. Moreover a proper calibration curve was made for each set of measurements. With regard to absolute doses, the results obtained with the ionization chamber are in good correlation with radiochromic film-generated data, for both LGK and LR, showing a dose difference of less than 1%. The output factor evaluations, performed using different methods, are in good agreement with a maximum difference of 1.5% for all field sizes considered (LGK and LR) except the 4 mm helmet used in the LGK unit. In this case, differences exist between diode and radiochromic film measurements and both detectors show data values larger than the prestored OF value of 0.80. Dose profiles measured by radiochromic film and calculated are in excellent agreement for both LGK and LR with a maximum deviation of less than 1.0 mm, when full widths of the dose profiles at 20%, 50%, 80% levels are considered. When external photon beams are used in stereotactic radiosurgery, the 'well selected' radiochromic films are very accurate detectors both for relative and absolute dosimetry. The experimental results, obtained using both radiochromic and diode detectors, show that the 4 mm helmet relative output factor could be underestimated.

Monte Carlo simulation of light fluence in tissue in a cylindrical diffusing fibre geometry.

The propagation of light emitted by a linear light diffuser in a cylindrical hollow organ was investigated by means of the Monte Carlo (MC) method. The height and radius of the cavity, scattering (mu(s)) (or reduced scattering, mu'(s)) and absorption (mu(a)) coefficients, anisotropy (g), and refractive indices of the media involved (n1, n2) are required as input data by the MC code, as are characteristics of the light diffuser (length, delivered power and emission profile). Results of our MC model were tested by measuring the light fluence rate in a tissue-simulating phantom (mu(a) = 0.5 cm(-1), mu(s) = 23 cm(-1) and g = 0.75) irradiated at 633 nm with a cylindrical diffuser. Since geometric and optical parameters determine the behaviour of light propagation in tissue, MC simulations with different sets of input parameters were carried out to provide qualitative as well as quantitative data useful in planning photodynamic therapy. Data are reported on light penetration and fluence rate build-up at mu(a) and mu'(s) values ranging between 0.1 and 5 cm(-1) and 2.5 and 50 cm(-1), respectively. Furthermore, results suggest that a shift and spread could occur in the isofluence curves along the symmetry axis, which depend on the diameter of the treated lumen as well as on the emission profile of the light diffuser. Using our data it is possible to estimate how inaccuracy in knowledge of the optical coefficients can affect (i.e. usually by increasing) the light dose scheduled at a certain depth into tissue.

Accuracy evaluation of fusion of CT, MR, and spect images using commercially available software packages (SRS PLATO and IFS).

PURPOSE: A problem for clinicians is to mentally integrate information from multiple diagnostic sources, such as computed tomography (CT), magnetic resonance (MR), and single photon emission computed tomography (SPECT), whose images give anatomic and metabolic information. METHODS AND MATERIALS: To combine this different imaging procedure information, and to overlay correspondent slices, we used commercially available software packages (SRS PLATO and IFS). The algorithms utilize a fiducial-based coordinate system (or frame) with 3 N-shaped markers, which allows coordinate transformation of a clinical examination data set (9 spots for each transaxial section) to a stereotactic coordinate system. The N-shaped markers were filled with fluids visible in each modality (gadolinium for MR, calcium chloride for CT, and 99mTc for SPECT). The frame is relocatable, in the different acquisition modalities, by means of a head holder to which a face mask is fixed so as to immobilize the patient. Position errors due to the algorithms were obtained by evaluating the stereotactic coordinates of five sources detectable in each modality. RESULTS: SPECT and MR position errors due to the algorithms were evaluated with respect to CT: deltax was < or = 0.9 mm for MR and < or = 1.4 mm for SPECT, deltay was < or = 1 mm and < or = 3 mm for MR and SPECT, respectively. Maximal differences in distance between estimated and actual fiducial centers (geometric mismatch) were in the order of the pixel size (0.8 mm for CT, 1.4 mm for MR, and 1.8 mm for SPECT). In an attempt to distinguish necrosis from residual disease, the image fusion protocol was studied in 35 primary or metastatic brain tumor patients. CONCLUSIONS: The image fusion technique has a good degree of accuracy as well as the potential to improve the specificity of tissue identification and the precision of the subsequent treatment planning.

The ABCD system of melanoma detection: a spectrophotometric analysis of the Asymmetry, Border, Color, and Dimension.

BACKGROUND: The ABCD (Asymmetry, Border, Color, and Dimension) criteria represent a commonly used clinical guide for the diagnosis of early melanoma. The authors revised these criteria in the light of objective measurements of the features of pigmented skin lesions obtained by telespectrophotometric analysis (TS) in the visible and near-infrared wavelengths. METHODS: This study involves a consecutive series of 186 patients with 195 cutaneous pigmented lesions (53 melanomas and 142 nonmelanoma lesions). Each lesion was subjected to TS in vivo, before surgery. For this purpose, the authors used four spectrophotometric parameters that could be closely related to the four criteria of the ABCD guide, namely, roundness (an estimate of how a lesion contour resembles a circle), smoothness (an indicator of the regularity of a lesion border), mean reflectance (the ability of a lesion to diffuse or reflect the incident light), and size (the greatest dimension of a lesion). RESULTS: When melanomas and nonmelanoma lesions were compared by univariate analysis, all four spectrophotometric parameters considered proved to be significantly different (P=0.05). Multivariate logistic analysis showed that mean reflectance in the infrared (P < 0.01) and size (P=0.03) were parameters independently associated with melanoma. Melanoma showed lower reflectance and greater size than benign lesions. CONCLUSIONS: Information provided by TS substantially validates the importance of the ABCD clinical guide and suggests that color is the most important parameter in discriminating melanoma from nevi. In particular, melanoma appears darker than other pigmented lesions.