Adaptable texture-based segmentation by variance and intensity for automatic detection of semitranslucent and pink blush areas in basal cell carcinoma.

BACKGROUND: Pink blush is a common feature in basal cell carcinoma (BCC). A related feature, semitranslucency, appears as smooth pink or orange regions resembling skin color. We introduce an automatic method for detection of these features based on smoothness and brightness. We also introduce a neighborhood correction method for texture area correction. METHODS: Smoothness and brightness were analyzed over four bands: luminance, red, green, and blue, then merged using variance-based dynamic thresholding. Dermoscopic images of 100 biopsy-proven BCCs and 254 competitive benign mimics were used to train the algorithm. Sixteen color and texture features were extracted from the automatically detected areas. The confusion matrix for the algorithm showed 15 classification errors in the training set for the 354 images: three errors in the BCC set and 12 errors in the benign set. RESULTS: Logistic regression analysis on a separate 1024-image test set was able to achieve good separation of BCC from benign lesions with an area under the receiver operating characteristic curve (ROC) of 0.878 and 0.877 using manually-created and automatically-generated BCC border masks, respectively. CONCLUSION: This pilot study indicates that automatic detection of semitranslucent and pink blush areas in BCC is feasible using colors and first-order texture statistics.

Biologically inspired skin lesion segmentation using a geodesic active contour technique.

BACKGROUND/PURPOSE: Computer-aided diagnosis of skin cancer requires accurate lesion segmentation, which must overcome noise such as hair, skin color variations, and ambient light variability. METHODS: A biologically inspired geodesic active contour (GAC) technique is used for lesion segmentation. The algorithm presented here employs automatic contour initialization close to the actual lesion boundary, overcoming the 'sticking' at minimum local energy spots caused by noise artifacts such as hair. The border is significantly smoothed to mimic natural lesions. In addition, features that mimic biological parameters include spectral image subtraction and removal of peninsulas and inlets. Multiple boundary choices borders are created by parameter options used at different steps. These choices can allow future improvement over the basic default border. RESULTS: The basic GAC algorithm was tested on 100 images (30 melanomas and 70 benign lesions), yielding a median XOR border error of 6.7%, comparable to the median inter-dermatologist XOR border error (7.4%), and lower than the gradient vector flow snake median XOR error of 14.2% on the same image set. On a difficult low-contrast border set of 1238 images, which included 350 non-melanocytic lesions, a median XOR error of 23.9% is obtained. CONCLUSION: GAC techniques show promise in attaining the goal of automatic skin lesion segmentation.

Discrimination of squamous cell carcinoma in situ from seborrheic keratosis by color analysis techniques requires information from scale, scale-crust and surrounding areas in dermoscopy images.

Scale-crust, also termed "keratin crust", appears as yellowish-to-tan scale on the skin's surface. It is caused by hyperkeratosis and parakeratosis in inflamed areas of squamous cell carcinoma in situ (SCCIS, Bowen's disease) and is a critical dermoscopy feature for detecting this skin cancer. In contrast, scale appears as a white-to-ivory detaching layer of the skin, without crust, and is most commonly seen in benign lesions such as seborrheic keratoses (SK). Distinguishing scale-crust from ordinary scale in digital dermoscopy images holds promise for early SCCIS detection and differentiation from SK. Reported here are image analysis techniques that best characterize scale-crust in SCCIS and scale in SK, thereby allowing accurate separation of these two dermoscopic features. Classification using a logistic regression operating on color features extracted from these digital dermoscopy structures can reliably separate SCCIS from SK.

Seasonality of brown recluse populations is reflected by numbers of brown recluse envenomations.

A significant seasonal correlation was recently shown for brown recluse spider activity. Vetter (2011) observed brown recluse spiders were submitted by the general public predominantly during April-October. For patients with suspected brown recluse spider bites (BRSB), we have observed the same seasonality. Among 45 cases with features consistent of a BRSB, 43 (95.6%) occurred during April-October. Both the Vetter study and our study serve to demonstrate seasonal activity for brown recluse spiders.

Magnetic resonance contrast enhancement of neovasculature with alpha(v)beta(3)-targeted nanoparticles.

Site-directed contrast enhancement of angiogenic vessels in vivo was demonstrated using antibody targeting of an MRI contrast agent to the alpha(v)beta(3) integrin, a molecular marker characteristic of angiogenic endothelium. The agent was tested in a rabbit corneal micropocket model, in which neovasculature is induced in the cornea using basic fibroblast growth factor. The targeted contrast agent consists of Gd-perfluorocarbon nanoparticles linked to alpha(v)beta(3) integrin antibody DM101. The animal group receiving the targeted contrast agent displayed a 25% increase in the average MR signal intensity after 90 min. Control groups in which the nanoparticles are either used alone, linked to an isotype-matched antibody, or linked to DM101 and administered following receptor blocking did not display MR contrast enhancement at similar dose levels. These findings indicate that the antibody-targeted agent enhances MR signal intensity in the capillary bed in a corneal micropocket model of angiogenesis, and is selectively retained within the angiogenic region via specific interaction with the alpha(v)beta(3) epitope.

T cell activation is regulated by voltage-dependent and calcium-activated potassium channels.

Membrane potential (Vm) is tightly controlled in T cells through the regulated flux of ions across the plasma membrane. To investigate the functional role of voltage-dependent (Kv) and calcium-activated (KCa) potassium channels in T cell activation, we compared the effects of two K+ channel blockers, namely kaliotoxin (KTX) and charybdotoxin (CHTX), on Vm, calcium influx, and cell proliferation. KTX potently inhibited Kv (ID50 = 3 nM) but not KCa (ID50 = 5 microM) currents in T cells. Resting T cells exposed to KTX (300 nM) depolarized from -56 mV to -50 mV. KTX had no effect on the transient membrane hyperpolarization that characteristically follows receptor-mediated T cell stimulation. However, T cells stimulated in the presence of KTX subsequently depolarized to -40 mV. KTX also reduced the steady state intracellular free calcium concentration ([Ca2+]i) in stimulated cells by 19% and inhibited T cell proliferation by 35%. CHTX potently inhibited both Kv and KCa currents (ID50 = approximately 1 nM). CHTX (300 nM) depolarized resting T cells to -48 mV, equivalent to the effect observed for KTX. In stimulated T cells, 300 nM CHTX completely blocked the induced hyperpolarization and subsequently depolarized the cells to -21 mV. These effects were associated with a 45% reduction in peak [Ca2+]i, a 60% decrease in steady state [Ca2+]i, and 63% inhibition of T cell proliferation. These results suggest that both Kv and KCa conductances contribute to the underlying mechanisms of T cell activation.

Novel assay for the influenza virus M2 channel activity.

The influenza A M2 ion channel was expressed and activity characterized in Xenopus oocytes. Based on the activation properties of the channels, a high throughput, non-electrophysiological screening assay was developed in order to identify novel inhibitors of the channel. This will facilitate discovery of novel agents to treat influenza viral infections.

Cis-2,4-methanoglutamate is a potent and selective N-methyl-D-aspartate receptor agonist.

Cis- and trans-2,4-methanoglutamate were compared with L-glutamate as acidic amino acid ligands. Cis-2,4-methanoglutamate had a Ki of 0.052 microM against N-methyl-D-aspartate (NMDA)-specific L-[3H]glutamate binding compared with 0.050 microM for L-glutamate. Cis-2,4-methanoglutamate exhibited no significant affinity against [3H]kainate or [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate ([3H]AMPA) binding. Trans-2,4-methanoglutamate had no significant affinity for any of these sites. Cis-2,4-methanoglutamate increased [3H]N-1[2-thienyl]cyclohexyl-3,4-piperidine [( 3H]TCP) binding with EC50 of 0.35 +/- 0.14 microM. It produced an inward current in rat brain mRNA-injected Xenopus oocytes which was blocked by the NMDA antagonist, D-2-amino-7-phosphonoheptanoate (D-AP7). Cis-2,4-methanoglutamate (EC50 = 15.9 microM) was 100-fold more potent than L-glutamate (EC50 = 1,584 microM) in reducing the excitatory postsynaptic potential in CA1 of hippocampal slices. Cis-2,4-methanoglutamate is the most potent, selective NMDA agonist known.

Epileptiform activity in vitro can produce long-term synaptic failure and persistent neuronal depolarization.

A large, extracellular negative DC shift, termed epileptic depolarization, could be elicited during zero magnesium-induced epileptic activity in the rat hippocampal slice. In 10 mM glucose medium, epileptic depolarization was elicited by high-frequency synaptic stimulation. During epileptic depolarization synaptic responses were abolished, but recovered in 10.4 +/- 2.1 min. In low glucose (2 mM) medium, epileptic depolarization either occurred spontaneously or could be elicited by high frequency synaptic stimulation, and no recovery of synaptic responses was observed for at least 30 min. This long-term synaptic failure was blocked by the competitive NMDA antagonists, 3-[+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP, 100 microM) and D-2-amino-7-phosphonoheptanoate (D-AP7, 100 microM) when added at the peak of epileptic depolarization, but not 5 min afterwards. Intracellular analysis showed that this extracellular DC shift was correlated with a membrane depolarization which approached 0 mV. With 10 mM glucose medium, the membrane potential returned to resting level in 6.3 +/- 1.9 min. In 2 mM glucose medium, neurons remained depolarized and no recovery was observed. This persistent depolarization could account for the loss of synaptic function recorded extracellularly. Application of 100 microM CPP blocked persistent depolarization and allowed for the recovery of the membrane potential. Epileptic depolarization was also observed during picrotoxin-induced epileptic activity. Both anoxic depolarization during experimental ischemia and epileptic depolarization can trigger long-term synaptic failure and persistent depolarization. Epileptic depolarization and anoxic depolarization may be triggers which can lead to neuronal failure in diseases associated with neuronal degeneration.

Experimental ischemia induces a persistent depolarization blocked by decreased calcium and NMDA antagonists.

Early physiological events induced by hypoxia plus low D-glucose were investigated by intracellular recording in the rat hippocampal slice. A rapid intracellular depolarization corresponded to the extracellularly recorded anoxic depolarization. This intracellular depolarization consisted of two pharmacologically distinct components, an initial depolarization and a persistent depolarization. The persistent phase of depolarization was selectively blocked by lowering calcium and raising magnesium and by N-methyl-D-aspartate (NMDA) antagonists. This persistent depolarization can account for the long-term synaptic failure seen following experimental ischemia in vitro.

DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) depletes noradrenaline in kitten visual cortex without altering the effects of monocular deprivation.

Kittens were given N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to deplete cortical noradrenaline (NA) in order to test whether this would affect the results of monocular deprivation. Seven kittens that received DSP-4 systemically had cortical NA depleted by 25 to 98%, and six kittens that received DSP-4 in the lateral ventricle had cortical NA depleted by 72 to 92%. In all of these kittens, suturing shut the eyelids of one eye for 1 to 2 weeks produced a visual cortex in which most neurons responded only or most strongly to the eye that remained open. These results are considered together with previous results from our laboratory on monocular deprivation and NA depletion. There is little difference between the ocular dominance histograms of depleted and undepleted animals and little correlation between the extent of the ocular dominance shift and the extent of NA depletion. We conclude that depletion of cortical NA by itself does not prevent the cortical effects of monocular deprivation and that, where such an effect has been found, it may be due to some other factor.

Substantial reduction of noradrenaline in kitten visual cortex by intraventricular injections of 6-hydroxydopamine does not always prevent ocular dominance shifts after monocular deprivation.

Ten kittens had cannulas inserted into their lateral ventricles for daily injections of 6-hydroxydopamine (6-OHDA). At 5-6 weeks of age one eye was sutured shut, and one week later recordings were made from the visual cortex to assay the ocular dominance of a sample of cells. In six kittens the injections of 6-OHDA were continued until the day before recording, while in four kittens the injections were stopped around the time of eye suture, on the assumption that continued injections of 6-OHDA over several days has effects that are not specific to the noradrenaline (NA) system and that the two procedures might show different results. In all animals the concentration of NA in the visual cortex near the site of recording was reduced by approximately 90%. In all animals the ocular dominance histograms recorded from the visual cortex were shifted so that the majority of cells (83 +/- 13%) were dominated by the open eye. There were no substantial differences between the two groups of experimental animals or between the experimental animals and two control animals that had cannulas implanted and ascorbate alone injected without 6-OHDA. We conclude that the concentration of NA in the visual cortex can be reduced substantially by injections of 6-OHDA into the lateral ventricle without preventing the shift in ocular dominance that usually occurs after suturing shut the eyelids of one eye.

The effect of norepinephrine on visual cortical neurons in kittens and adult cats.

The responses of visual cortical neurons during iontophoresis of norepinephrine (NE) were compared in kittens and adult cats. One type of neuronal "plasticity" (the ability of visual cortical neurons to have their response properties markedly altered during exposure to a restricted visual environment) normally occurs only in young kittens and has been hypothesized to depend on the presence of NE. We investigated this hypothesis in terms of a model of synaptic plasticity which suggested that NE would selectively enhance the evoked responses of neurons and that this enhancement might exist to a greater extent in kittens than in adult cats. The responses of 72% (43 of 60) of all neurons sampled decreased during NE iontophoresis, while the responses of only a few neurons (3 of 60) increased. Reduced activity occurred in roughly equal percentages of simple and complex cells. We also looked for differences in NE modulation of the "signal-to-noise" ratio of neurons. Most neurons had little spontaneous activity, but, of those that did, the signal-to-noise ratio increased in some instances and decreased in others. No difference in any of the effects of NE was observed between kittens and adult cats. The role of NE in cortical plasticity is discussed.

Substantial reduction of cortical noradrenaline by lesions of adrenergic pathway does not prevent effects of monocular deprivation.

We tested the theory that depletion of noradrenaline reduces the plasticity of the visual cortex in kittens by using another method of depletion. Lesions were made in the lateral hypothalamus to interrupt fibers in the dorsal noradrenergic bundle going from the locus ceruleus to the telencephalon. The lesions were induced at approximately 3 1/2 weeks of age in kittens; approximately 2 weeks later one eye was sutured shut, and about 10 days after that cells were recorded in the visual cortex. The location of the lesions was verified histologically, and the effect of the lesions was verified by noradrenaline analyses (high pressure liquid chromatography-electrochemistry) of samples from the visual cortex. The noradrenaline content of the visual cortex was reduced by 70 to 90%. However, the majority of cells recorded in the visual cortex could not be driven through the eye that had been sutured closed. The ocular dominance histograms for cells in the visual cortex were indistinguishable from those of kittens that were monocularly deprived for a similar period in the "critical period" and that had normal amounts of noradrenaline in their visual cortex. Therefore, we conclude that reduction of the noradrenaline content of the visual cortex by 70 to 90% is insufficient, by itself, to prevent the physiological changes that occur in the visual cortex after monocular deprivation.

Effects of 6-hydroxydopamine on visual deprivation in the kitten striate cortex.

We tested the effects of 6-hydroxydopamine (6-OHDA) on two forms of visual deprivation--monocular and directional deprivation. In normal kittens monocular deprivation leads to a change in the ocular dominance histogram recorded from the visual cortex, and directional deprivation leads to a change in the percentage of directionally sensitive cells responding to the appropriate direction of movement. 6-OHDA was infused into the occipital cortex prior to the peak of the critical period for the effects of visual deprivation. In agreement with the results of Kasamatsu et al. (Kasamatsu, T., and J. D. Pettigrew (1979) J. Comp. Neurol. 185: 139-162; Kasamatsu, T., J. D. Pettigrew, and M. Ary (1979) J. Comp. Neurol. 185: 163-182), suture of one eye (monocular deprivation) after the 6-OHDA treatment did not lead to a shift in ocular dominance in the area of striate cortex infused. Moreover, rearing kittens in an environment continually moving past them in one direction (directional deprivation) did not lead to a change in the percentage of cells preferring movement in that direction. In both rearing procedures the 6-OHDA did not make the cells in the cortex nonspecific, compared to cells recorded from the cortex of animals reared similarly but without infusion of 6-OHDA. Monocular and directional deprivation are forms of visual deprivation with different critical periods, probably involving different synapses. Therefore, the effect of 6-OHDA on visual deprivation is a general one, involving more than one kind of visual deprivation. In both cases 6-OHDA abolishes the plasticity of the visual cortex.

Rhythmicity in rabbit retinal ganglion cell responses.

An interesting pattern of rhythmic spike bursts was observed in the light responses of rabbit retinal ganglion cells when using a fast time scale. This rhythmicity was found in all ganglion cell types tested in all parts of the retina. The presence and extent of rhythmicity was related to the intensity, size and shape of the light stimulus. The best stimulus extended into the receptive field surround yet still evoked a strong response from the center. We suggest that rhythmicity results from time delays in the inhibitory interactions between central and surround pathways to the ganglion cells.