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The return of the dark neuron. A histological artifact complicating contemporary neurotoxicologic evaluation.

A common histological artifact of brain is the presence of contracted, intensely stained neurons. Such cells are termed dark neurons, and can be produced by post-mortem manipulation or trauma in brain tissue. In a number of recently published experimental neurotoxicology reports cells of this nature are interpreted as representing dying or degenerating neurons, thus assigning inappropriate neurotoxic potential to the compounds administered. The latter are the commonly used drugs and pesticides DEET (N,N-diethyl m-toluamide), malathion, permethrin and pyridostigmine bromide. In this paper I review the nature and genesis of the dark neuron, critically discuss the neuropathologic validity of indicated studies and make a plea for increased awareness of this common artifact.

Animals↗

Ballistocardiogram artifact reduction in the simultaneous acquisition of auditory ERPS and fMRI.

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are now being combined to analyze brain function. Confounding the EEG signal acquired in the MR environment is a ballistocardiogram artifact (BA), which is predominantly caused by cardiac-related body movement. The objective of this study was to develop and evaluate a method for reducing these MR-induced artifacts to retrieve small auditory event-related potentials (ERPs) from EEG recorded during fMRI. An algorithm for BA reduction was developed that relies on timing information obtained from simultaneous electrocardiogram (ECG) recordings and subsequent creation of an adaptive BA template. The BA template is formed by median-filtering 10 consecutive BA events in the EEG signal. The continuously updated template is then subtracted from each BA in the EEG. The auditory ERPs are obtained through signal averaging of the remaining EEG signal. Experimental and simulated ERP data were estimated to assess effectiveness of the BA reduction. Simulation showed that the algorithm reduced BA without significantly altering the morphology of a signal periodically inserted in the EEG. Auditory ERP data, obtained in a 1.5-T scanner during a passive auditory oddball paradigm and processed with the BA reduction algorithm, were comparable to data recorded in a mock scanner outside the magnetic field with the same experimental paradigm. It is concluded that through adequate reduction of the BA, relatively small auditory ERPs can be acquired in the MR environment.

Algorithms↗

Surface EMG measurements during fMRI at 3T: accurate EMG recordings after artifact correction.

In this experiment, we have measured surface EMG of the first dorsal interosseus during predefined submaximal isometric contractions (5, 15, 30, 50, and 70% of maximal force) of the index finger simultaneously with fMRI measurements. Since we have used sparse sampling fMRI (3-s scanning; 2-s non-scanning), we were able to compare the mean amplitude of the undisturbed EMG (non-scanning) intervals with the mean amplitude of the EMG intervals during scanning, after MRI artifact correction. The agreement between the mean amplitudes of the corrected and the undisturbed EMG was excellent and the mean difference between the two amplitudes was not significantly different. Furthermore, there was no significant difference between the corrected and undisturbed amplitude at different force levels. In conclusion, we have shown that it is feasible to record surface EMG during scanning and that, after MRI artifact correction, the EMG recordings can be used to quantify isometric muscle activity, even at very low activation intensities.

Artifacts↗

Artifacts in fetal pulse oximetry: incomplete sensor-to-skin contact.

OBJECTIVE: Our purpose was to investigate apposition of reflectance sensors as a possible source of artifact in fetal pulse oximetry. STUDY DESIGN: A laboratory model was created to examine the effect of varying the distance of a reflectance probe from a subject's finger. The setup used two wavelengths (660 and 940 nm) and pulsatile (AC) and nonpulsatile signals (DC). An investigator's finger was stabilized in a purposely built mold from where the distance between skin and sensors could be varied in 1 mm steps. RESULTS: The AC and DC components of the signal react differently to increasing the distance between sensor and skin. The overall effect is that the ratio [formula: see text] increases with skin to sensor distance, which results in falsely low readings of oxygen saturation. CONCLUSIONS: Poor sensor-to-skin contact in reflectance pulse oximetry may cause false readings despite the presence of good waveforms and hence go unrecognized. Probe and software design needs to be able to identify and exclude such artifact before this technique can become useful for intrapartum fetal monitoring.

Artifacts↗

Monsel's solution-induced artifact in the uterine cervix.

We documented and quantified Monsel's solution-related artifacts after cervical biopsies. All loop electrosurgical cone biopsy specimens over a 3-month period were reviewed for necrosis artifact of the surface epithelium. The degree of change was quantified and correlated with the antecedent use of Monsel's solution. Twenty-four cone biopsy specimens were evaluated. Three of the eight cone biopsy specimens obtained fewer than 10 days after the use of Monsel's solution showed definite changes. Between 10 and 18 days after the use of Monsel's solution, four of eight specimens showed change. After 18 days, none of eight specimens showed change. One specimen at 18 days showed focal changes that seemed to be related to the use of an unusually large amount of Monsel's solution, because the patient had had six biopsies within 2 days. The routine use of Monsel's solution may interfere with the ability to recognize and characterize disease process in cone biopsy specimens when the cone procedure is done within 3 weeks after the use of Monsel's solution.

Artifacts↗

Potential risks and artifacts of magnetic resonance imaging of self-expandable esophageal stents.

BACKGROUND: Several types of coated and uncoated self-expandable stents composed of various metals are available for palliation of malignant esophageal stenoses and fistulas. We encountered poor visualization of the mediastinum and skeletal axis with magnetic resonance imaging in a patient with a Gianturco self-expandable stent. METHODS: To evaluate potential problems, such as stent migration in the magnetic field of the magnetic resonance scanner (MRI) and artifacts in the images, we studied four types of expandable stents: the Ultraflex (titanium alloy), the covered Wall stent (nitinol), the Gianturco stent (Cook), and the modified Gianturco stent (Song)-the last two being made of stainless steel. RESULTS: An appreciable attraction force and torque, as measured ex vivo by suspending the stent in a Perspex device, was found for both Gianturco stents. In particular, the Gianturco (Cook) stent is pulled toward the head with a force of 7g; however, it is uncertain whether this is a potential risk for dislodgement. In addition, gross artifacts in the images, studied by putting the stents in a cylindric phantom filled with a diluted gadolinium solution, made the magnetic resonance useless for imaging in a wide area around the Gianturco stents of stainless steel. No problems with magnetic resonance image quality were encountered for the titanium-based Ultraflex and Wall stents. CONCLUSIONS: Specific information on the type of stent is necessary before a magnetic resonance imaging examination is planned.

Artifacts↗

Estimation of artifacts induced by the Ilizarov device in quantitative computed tomographic analysis of tibiae.

This study concerns the estimation of the artifacts introduced by the metallic frame of an Ilizarov apparatus during quantitative computed tomography for the assessment of neoosteogenesis. Ten cadaver tibiae were tomographed before and after the mounting of an Ilizarov device. The increase in mean density and in the relative number of pixels were used as indicators of the artifacts induced by the apparatus. No significant influence by the device was recorded in regions corresponding to a corticotomy site. In regions close to the metallic rings of the Ilizarov apparatus, measurements are distorted significantly, but with no influence on the assessment of neoosteogenesis.

Artifacts↗

Characterization of a chemical artifact in the liquid chromatographic determination of 3-butyn-2-one using the 2,4-dinitrophenylhydrazine method.

This study reports the identification of a chemical artifact occurring in the liquid chromatographic analysis of 3-butyn-2-one by means of the 2,4-dinitrophenylhydrazine (DNPH) method. Besides the expected derivatization reaction to the corresponding butynone DNPhydrazone, a rearrangement was observed, thus leading to the formation of 3-methyl-1-(2',4'-dinitrophenyl)pyrazol (DNPP). Although the rearrangement product and the hydrazone can easily be separated by means of liquid chromatography, problems arise from coelution of the pyrazol with the formaldehyde DNPhydrazone. Identification of the artifact by means of UV-Vis spectroscopy using dual wavelength or diode array detection is discussed.

Artifacts↗

Artifact formation due to ethyl thio-incorporation into silylated steroid structures as determined in doping analysis.

Trimethylsilylation of target substances in a mixture of N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA), ammonium iodide and ethanethiol is frequently applied for the application of gas chromatography-mass spectrometry (GC-MS) in steroid analysis. However, artifacts were formed when using this mixture to silylate the steroids androsterone and etiocholanolone obtained from a urine matrix. The artifacts were identified as ethyl thio-containing products of the respective trimethylsilyl derivatives. The conversion of the studied products increased slowly as a function of time, was dependent on the presence of the urine matrix and was significantly accelerated by adding diethyl disulfide to the reagent before incubation. Also ethyl thio-incorporation into testosterone and epitestosterone was established. A mechanism for ethyl thio-incorporation is proposed. The conversion achieved after 120-h sample storage at room temperature was insufficient to significantly influence the analysis of androsterone and etiocholanolone under the studied conditions. However, the results provide fundamental insight into the mechanism of silylation and the occurring side-reactions. Moreover, when investigating the formation of new metabolites, the ethyl thio-incorporation can lead to misinterpretation.

Artifacts↗

Mutations in BRCA1 from fixed, paraffin-embedded tissue can be artifacts of preservation.

DNA isolated from paraffin-embedded tissues has been used for analysis of DNA alterations in disease states. Use of archival tissue can expedite the gathering of large numbers of specimens from rare disease subtypes that would take years to accumulate prospectively. Therefore, archival tissues from 70 ovarian cancer cases diagnosed before or at age 40 were retrieved for analysis of BRCA1 mutations. DNA was isolated from paraffin-embedded tissue of 70 ovarian cancer cases diagnosed before or at age 40. BRCA1 mutation analysis was conducted by single-strand conformation polymorphism analysis and DNA sequencing. Fifty-eight BRCA1 mutations were found in 34 of the 70 ovarian cancer cases. Twenty-two cases had one mutation each and 12 cases had multiple mutations. Multiple mutations found in histologically normal tissue of 2 cases were not present in matched tumor tissue. For another case, DNA from two separate blocks of normal tissue contained different mutations. These observations were anomalous and suggested that mutations detected in fixed tissues may be artifacts of tissue preservation and not present in the original unfixed tissues. To test this suggestion, blood was obtained from 2 patients for whom mutations were found in fixed, normal tissue. DNA from their unfixed lymphocytes did not contain the mutations found in fixed normal tissue. Thus, mutations found in fixed, paraffin-embedded tissues can be artifacts of tissue preservation. The reliability of DNA sequence data derived from such tissues must be questioned in the absence of corroborating data from unfixed tissues. This severely limits the use of fixed tissues as a source of DNA for retrospective research and for clinical genetic testing in families for which a disease-affected member is not alive.

Adult↗

[Diffusion-weighted imaging of the brain: normal patterns, traps and artifacts].

Owing to its rapid acquisition time and high sensitivity, diffusion-weighted imaging has turned into a routine sequence for brain imaging. This is the case not only for stroke, but also for various diseases such as abscesses or tumors. Being aware of the artifacts is important for optimal interpretation. After a brief review of the normal patterns, the most frequent artifacts, inherent to the echoplanar imaging technique, are described and we provide suggestions to avoid them. Most current traps are caused by T2-weighting of the diffusion images; the key for avoiding erroneous interpretation relies on the ADC map.

Artifacts↗

Artifacts that may be present on a blood film.

Many artifacts or pseudoartifacts may be noted during the examination of a blood film. Artifactual results also may be generated by automated hematology analyzers, which in turn may be investigated by blood film examination. Some artifacts are misdiagnosed, and this in turn leads to inappropriate investigations or treatment. An awareness of the spectrum of spurious or artifactual results may help to prevent such an unfortunate occurrence.

Artifacts↗

Overcoming electrically induced artifacts in penetration studies with fluorescent tracers.

The use of model molecules in transdermal transport studies reveals transport behavior while providing an economical setup by detection of readily measured quantities such as fluorescence, radioactivity or absorbance of low-cost substances. Water soluble fluorescent tracers such as calcein have been repeatedly used as model molecules in transdermal transport studies. However, if electrically enhanced calcein transport across the human skin barrier is measured, artifacts due to interaction between calcein and electrode byproducts influence the result. Here, we describe an experimental setup which avoids known artifacts and makes calcein or other fluorescent tracers a suitable model for transdermal transport studies.

Artifacts↗

Motion artifact reduction technique for dual-contrast FSE imaging.

There is considerable similarity between proton density-weighted (PDw) and T2-weighted (T2w) images acquired by dual-contrast fast spin-echo (FSE) sequences. The similarity manifests itself in image space as consistency between the phases of PDw and T2w images and in k-space as correspondence between PDw and T2w k-space data. A method for motion artifact reduction for dual-contrast FSE imaging has been developed. The method uses projection onto convex sets (POCS) formalism and is based on image space phase consistency and the k-space similarity between PDw and T2w images. When coupled with a modified dual-contrast FSE phase encoding scheme the method can yield considerable artifact reduction, as long as less than half of the acquired data is corrupted by motion. The feasibility and efficiency of the developed method were demonstrated using phantom and human MRI data.

Artifacts↗

On the origin of respiratory artifacts in BOLD-EPI of the human brain.

BOLD-based functional MRI (fMRI) can be used to explicitly measure hemodynamic aspects and functions of human neuro-physiology. As fMRI measures changes in regional cerebral blood flow and volume as well as blood oxygenation, rather than neuronal brain activity directly, other processes that may change the above parameters have to be examined closely to assess sensitivity and specificity of fMRI results. Physiological processes that can cause artifacts include cardiac action, breathing and vasomotion. Although there has been substantial research on physiological artifacts and appropriate compensation methods, controversy still remains on the mechanisms that cause the fMRI signal fluctuations. Respiratory-correlated fluctuations may either be induced by changes of the magnetic field homogeneity due to moving organs, intra-thoracic pressure differences, respiration-dependent vasodilation or oxygenation differences. The aim of this study was to characterize the impact of different breathing patterns by varying respiration frequency and/or tidal volume on EPI time courses of the resting human brain. The amount of respiration-related oscillations during three respiration patterns was quantified, and statistically significant differences were obtained in white matter only: p < 0.03 between 6 vs. 12 ml/kg body weight end tidal volume at a respiration frequency of 15/min, p < 0.03 between 12 vs. 6 ml/kg body weight and 15 vs. 10 respiration cycles/min. There was no significant difference between 15 vs. 10 respiration cycles/min at an end tidal volume of 6 ml/kg body weight (p = 0.917). In addition, the respiration-affected brain regions were very similar with EPI readout in the a-p and l-r direction. Based on our results and published literature we hypothesize that venous oxygenation oscillations due to changing intra-thoracic pressure represent a major factor for respiration-related signal fluctuations and increase significantly with increasing end tidal volume in white matter only.

Adult↗

Truncation artifact reduction in spectroscopic imaging using a dual-density spiral k-space trajectory.

Truncation artifacts arise in magnetic resonance spectroscopic imaging (MRSI) of the human brain due to limited coverage of k-space necessitated by low SNR of metabolite signal and limited scanning time. In proton MRSI of the head, intense extra-cranial lipid signals "bleed" into brain regions, thereby contaminating signals of metabolites therein. This work presents a data acquisition strategy for reducing truncation artifact based on extended k-space coverage achieved with a dual-SNR strategy. Using the fact that the SNR in k-space increases monotonically with sampling density, dual-SNR is achieved in an efficient manner with a dual-density spiral k-space trajectory that permits a smooth transition from high density to low density. The technique is demonstrated to be effective in reducing "bleeding" of extra-cranial lipid signals while preserving the SNR of metabolites in the brain.

Artifacts↗

Chemical shift artifact-free imaging: a new option in MRI?

A high-speed proton spectroscopic imaging method with high spatial resolution was used for obtaining water, fat, and chemical shift artifact-free images on a 1.5 T MR scanner. The technique is based on a fast radiofrequency (RF) spoiled gradient-echo sequence. The chemical shift information is encoded by incrementing the echo time in a series of image records. Suppression of water or fat signals is not used. The technique does not require a highly homogeneous magnetic field. Spectroscopic images of a human volunteer were compared with corresponding conventional images obtained using the short inversion time inversion recovery (STIR) and the selective partial inversion recovery (SPIR) methods. The results demonstrate that it is possible to produce images entirely free from chemical shift artifacts using only a few chemical shift encoding steps. The technique also produces pure water and fat images which are significantly better than those produced by using the conventional methods STIR and selective partial inversion recovery. The described method appears to be promising for routine clinical applications because it can be fully automated.

Adipose Tissue↗

Shoulder MRI refinements: differentiation of rotator cuff tear from artifacts and tendonosis, and reassessment of normal findings.

One of the difficulties with rotator cuff imaging lies in the normal variability of the tendon's signal. There may be intermediate signal present within the tendon because of magic-angle phenomenon, muscle and tendon fiber interdigitation, or tendinopathy related to degenerative changes or overuse injury. Partial and complete rotator cuff tears should be distinguishable from these causes of intermediate signal if water signal is reliably identified. This article reviews the important issue of distinguishing between rotator cuff tear and other causes of high signal in the rotator cuff, including artifacts and tendonosis. We include a review of the literature and a brief report of a study we conducted on 20 shoulders of 14 asymptomatic, young volunteers. In this study, the rotator cuff tendons were evaluated for abnormal signal at different TE values to determine at what TE the interpreters were able to confidently distinguish the high-signal intensity of a tear (water) from the intermediate signal intensity associated with artifact and tendinopathy. Readers were able to distinguish water and tendon signal in 70% to 100% of fast-spin echo (FSE) fat-saturated images with TE of 66, but there was interobserver variability at this TE, suggesting that it is less reliable than 88 ms in the identification of rotator cuff tears. By using FSE fat-saturated sequences with TE of 88 and fast spin echo inversion recovery (FSEIR) sequences, readers at all levels of experience were able to differentiate water signal intensity from tendon signal intensity in 100% of cases. Therefore, we suggest that either FSEIR images or FSE fat-saturated images with TE greater than 66 be used to facilitate the differentiation of fluid signal from intermediate increased signal intensity in rotator cuff imaging. Additionally, this article reviews the normal findings of shoulder magnetic resonance imaging (MRI) as revealed by the asymptomatic subjects included in our study, and assesses these findings in respect to previous publications. The normal features reviewed include the subacromion-subdeltoid (SA/SD) bursa, the biceps tendon sheath, the acromioclavicular (AC) joint, and the greater tuberosity of the humerus. A small amount of fluid was commonly seen in the SA/SD bursa, as well as the biceps tendon sheath. Subjective down-sloping of the acromion in the coronal plane, mild degenerative change of the AC joint, and undersurface spurring of the AC joint were uncommon in our normal subjects. Cystic change limited to the posterior aspect of the greater tuberosity was identified in 15% to 45% of shoulders.

Artifacts↗