Spatial Distribution Of Lesions Research Articles

Central nervous system infectious diseases mimicking multiple sclerosis: recognizing distinguishable features using MRI

The current diagnostic criteria for multiple sclerosis (MS) confirm the relevant role of magnetic resonance imaging (MRI), supporting the possibility of characterizing the dissemination in space (DIS) and the dissemination in time (DIT) in a single scan. To maintain the specificity of these criteria, it is necessary to determine whether T2/FLAIR visible lesions and the gadolinium enhancement can be attributed to diseases that mimic MS. Several diseases are included in the MS differential diagnosis list, including diseases with exacerbation, remitting periods and numerous treatable infectious diseases, which can mimic the MRI features of MS. We discuss the most relevant imaging features in several infectious diseases that resemble MS and examine the primary spatial distributions of lesions and the gadolinium enhancement patterns related to MS. Recognizing imaging "red flags" can be useful for the proper diagnostic evaluation of suspected cases of MS, facilitating the correct differential diagnosis by assessing the combined clinical, laboratory and MR imaging information.

Biological Consequences of Radiation-induced DNA Damage: Relevance to Radiotherapy

DNA damage of exposed tumour tissue leading to cell death is one of the detrimental effects of ionising radiation that is exploited, with beneficial consequences, for radiotherapy. The pattern of the discrete energy depositions during passage of the ionising track of radiation defines the spatial distribution of lesions induced in DNA with a fraction of the DNA damage sites containing clusters of lesions, formed over a few nanometres, against a background of endogenously induced individual lesions. These clustered DNA damage sites, which may be considered as a signature of ionising radiation, underlie the deleterious biological consequences of ionising radiation. The concepts developed rely in part on the fact that ionising radiation creates significant levels of clustered DNA damage, including complex double-strand breaks (DSB), to kill tumour cells as clustered damage sites are difficult to repair. This reduced repairability of clustered DNA damage using specific repair pathways is exploitable in radiotherapy for the treatment of cancer. We discuss some potential strategies to enhance radiosensitivity by targeting the repair pathways of radiation-induced clustered damage and complex DNA DSB, through inhibition of specific proteins that are not required in the repair pathways for endogenous damage. The variety and severity of DNA damage from ionising radiation is also influenced by the tumour microenvironment, being especially sensitive to the oxygen status of the cells. For instance, nitric oxide is known to influence the types of damage induced by radiation under hypoxic conditions. A potential strategy based on bioreductive activation of pro-drugs to release nitric oxide is discussed as an approach to deliver nitric oxide to hypoxic tumours during radiotherapy. The ultimate aim of this review is to stimulate thinking on how knowledge of the complexity of radiation-induced DNA damage may contribute to the development of adjuncts to radiotherapy.

White Matter Hyperintensities on 1.5 and 3 Tesla Brain MRI in Healthy Individuals

Background : White matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging (MRI) are frequent incidental findings in brains of asymptomatic healthy individuals (HI). The morphological and spatial distribution of these WMH between standard 1.5T scanners and increasingly available 3T scanners in a large population of HI in clinical routine settings has not been investigated. Objectives: To investigate the effect of changing from a 1.5T to a 3T MRI scanner on the number, volume and spatial distribution of WMH on brain MRI in a population of clinically HI. Materials and Methods: Fifty-three (53) HI were examined using T2 weighted sequences on both 1.5T and 3T within one week in a random order. The WMH were outlined semi-automatically by two blinded operators. Number and volume of WMH were calculated. Spatial lesion distribution was assessed using WMH probability maps (WMHPM). Paired-wise analysis examined the proportion of WMH not found on 1.5T and/or 3T. A posteriori unblinded analysis was conducted to examine the non-overlapping identifications of WMH between the 1.5T and 3T. Results : For paired-wise WMH analysis, 3T showed significantly higher WMH number and individual volume compared to 1.5 T ( p <0.001). Logistic regression analysis showed that likelihood of missing WMH on 1.5T was significantly higher for smaller WMH. WMHPM revealed spatial WMH differences on 3T compared to 1.5T, with WMH more pronounced in the occipital regions with higher field strength. Conclusion: This study showed that use of higher magnetic field strength identified more WMH in healthy subjects with respect to both morphological and spatial characteristics. These WMH do not necessarily represent pathology; however, these findings should be taken into account in lesion segmentation on a 3T MRI and might suggest the use of universally accepted guidelines for lesions’ segmentation on higher magnetic field, especially when it is executed by different operators and/or centers.

Quantitative Susceptibility Mapping: Initial Experience for Multiple Sclerosis Lesion Characterization (P03.058)

Objective: To assess whether quantitative susceptibility mapping (QSM) can function as a biomarker in patients with multiple sclerosis (MS) and provide an independent characterization of lesions commonly seen on T2-weighted images (T2WI). Background Although T2WI are used to support and confirm the clinical diagnosis of MS, T2 hyperintensity may indicate demyelination and/or edema. Previous studies have shown that iron deposition is associated with demyelination, but usually not appreciated on T2WI. Because QSM is sensitive to iron deposition, we hypothesize that QSM may provide a novel and independent biomarker in MS lesion characterization. Design/Methods: We retrospectively reviewed 181 white matter lesions in 16 consecutive confirmed MS patients (age=41±7, M/F=4/12) acquired with a protocol including T2W and QSM sequences. Lesions were identified on both T2W and QSM images with their sizes and signal intensities assessed. Differences were evaluated with a t-test. Results: A total of 181 lesions were detected on T2WI, 130(72%) of which presented on QSM. Lesion size on QSM was significantly smaller than that on T2WI(p 0.05ppm) compared to cortical gray matter. The size discrepancy was expected, since edema is hyperintense on T2WI but not on QSM. The increased signal on QSM lesions may be explained by the loss of myelin, whose susceptibility is usually negative. However, demyelination alone is unable to explain the strong paramagnetism seen in type (b) lesions, whose susceptibility is higher than cortical gray matter. In these lesions, iron may be responsible for the signal change. Further investigation may include correlation with clinical symptoms, spatial distribution of lesions, and global alternation in susceptibility value. Conclusions: MS lesions are smaller in size and demonstrate two distinct patterns on QSM when compared to routine T2WI. Disclosure: Dr. Chen has nothing to disclose. Dr. Comunale has nothing to disclose. Dr. Gauthier has received personal compensation for activities with Teva Neuroscience, Biogen Idec, Pfizer Inc, and Serono, Inc. as consultant. Dr. Gauthier has received research support from Biogen Idec, Pfizer Inc, and Serono, Inc. Dr. Heier has nothing to disclose. Dr. Liu has received personal compensation for activities with MedImageMetric LL as an employee. Dr. Tsiouris has nothing to disclose. Dr. Wang holds stock and/or stock options in MedImageMetric LLC.

Human brain atlas-based multimodal MRI analysis of volumetry, diffusimetry, relaxometry and lesion distribution in multiple sclerosis patients and healthy adult controls: Implications for understanding the pathogenesis of multiple sclerosis and consolidation of quantitative MRI results in MS

Multiple sclerosis (MS) is the most common immune-mediated disabling neurological disease of the central nervous system. The pathogenesis of MS is not fully understood. Histopathology implicates both demyelination and axonal degeneration as the major contributors to the accumulation of disability. The application of several in vivo quantitative magnetic resonance imaging (MRI) methods to both lesioned and normal-appearing brain tissue has not yet provided a solid conclusive support of the hypothesis that MS might be a diffuse disease. In this work, we adopted FreeSurfer to provide standardized macrostructure or volumetry of lesion free normal-appearing brain tissue in combination with multiple quantitative MRI metrics (T 2 relaxation time, diffusion tensor anisotropy and diffusivities) that characterize tissue microstructural integrity. By incorporating a large number of healthy controls, we have attempted to separate the natural age-related change from the disease-induced effects. Our work shows elevation in diffusivity and relaxation times and reduction in volume in a number of normal-appearing white matter and gray matter structures in relapsing–remitting multiple sclerosis patients. These changes were related in part with the spatial distribution of lesions. The whole brain lesion load and age-adjusted expanded disability status score showed strongest correlations in regions such as corpus callosum with qMRI metrics that are believed to be specific markers of axonal dysfunction, consistent with histologic data of others indicating axonal loss that is independent of focal lesions. Our results support that MS at least in part has a neurodegenerative component.

The Relationship between Normal Cerebral Perfusion Patterns and White Matter Lesion Distribution in 1,249 Patients with Multiple Sclerosis

The pathological differences underlying the clinical disease phases in multiple sclerosis (MS) are poorly characterized. We sought to explore the relationship between the distribution of white matter (WM) lesions in relapsing-remitting (RR) and secondary progressive (SP) MS and the normal regional variability of cerebral perfusion. WM lesions were identified and quantified on a single magnetic resonance imaging scan from 1,249 patients with MS. The spatial distribution of lesions was compared between early RR, late RR, and SP MS in the context of normal cerebral perfusion patterns provided by a single-photon emission-computed tomography atlas of healthy individuals. Patients with SP MS had more distinct and larger lesions than patients with RR MS. Across all subjects, lesions were present in regions of relatively lower normal perfusion than normal appearing WM. Further, lesions in SP MS were more common in areas of lower perfusion as compared to the lesion distribution in early and late RR MS. Chronic plaques were more prevalent in WM regions with lower relative perfusion. Lesions in more highly perfused regions were more commonly observed in early RR MS and therefore, may be more likely to successfully remyelinate and resolve.

Genetic Correlations of Brain Lesion Distribution in Multiple Sclerosis: An Exploratory Study

In MS, the total brain lesion volume and spatial distribution of lesions across the brain vary widely among individual patients. We hypothesized that spatial distribution may be partially driven by genetic predisposition, and we aimed to explore relations among candidate genes and the spatial distribution of white matter brain lesions in MS. Genotypes of 69 SNPs in 208 patients with MS were related to the spatial distribution of T2 brain lesions. Lesions were manually outlined on MR images, and binary lesion masks were produced and registered to a common space. With Randomise software, the lesion masks were related to genotype by using a voxelwise nonparametric GLM approach, followed by clusterwise analysis. We used a DNA chip with SNPs selected from the literature on MS susceptibility, severity, and phenotypes. For 11 of these SNPs, 1 of the genotypes expressed significant clusters of increased or decreased lesion probability in varying, predominantly periventricular, brain regions. When we statistically controlled the voxelwise analyses for effects of total brain lesion volume, only 1 SNP remained significant: rs2227139, located within the MHC class II region. This SNP retained its periventricular cluster of significantly increased lesion probability for the heterozygote genotype. Heterozygosity of rs2227139 (MHC class II region) is associated with increased right frontal periventricular lesion probability (P<.01). Ten other SNPs showed associations between genotype and spatial lesion distribution that are partly explained by total lesion volume.

Correlation Between Local Hemodynamics and Lesion Distribution in a Novel Aortic Regurgitation Murine Model of Atherosclerosis

Following surgical induction of aortic valve regurgitation (AR), extensive atherosclerotic plaque development along the descending thoracic and abdominal aorta of Ldlr⁻/⁻ mice has been reported, with distinct spatial distributions suggestive of a strong local hemodynamic influence. The objective of this study was to test, using image-based computational fluid dynamics (CFD), whether this is indeed the case. The lumen geometry was reconstructed from micro-CT scanning of a control Ldlr⁻/⁻ mouse, and CFD simulations were carried out for both AR and control flow conditions derived from Doppler ultrasound measurements and literature data. Maps of time-averaged wall shear stress magnitude (TAWSS), oscillatory shear index (OSI) and relative residence time (RRT) were compared against the spatial distributions of plaque stained with oil red O, previously acquired in a group of AR and control mice. Maps of OSI and RRT were found to be consistent with plaque distributions in the AR mice and the absence of plaque in the control mice. TAWSS was uniformly lower under control vs. AR flow conditions, suggesting that levels (> 100 dyn/cm²) exceeded those required to alone induce a pro-atherogenic response. Simulations of a straightened CFD model confirmed the importance of anatomical curvature for explaining the spatial distribution of lesions in the AR mice. In summary, oscillatory and retrograde flow induced in the AR mice, without concomitant low shear, may exacerbate or accelerate lesion formation, but the distinct anatomical curvature of the mouse aorta is responsible for the spatial distribution of lesions.

Signal abnormalities on 1.5 and 3 Tesla brain MRI in multiple sclerosis patients and healthy controls. A morphological and spatial quantitative comparison study

Previous studies in patients with multiple sclerosis (MS) revealed increased lesion count and volume on 3 T compared to 1.5 T. Morphological and spatial lesion characteristics between 1.5 T and 3 T have not been examined. The aim of this study was to investigate the effect of changing from a 1.5 T to a 3 T MRI scanner on the number, volume and spatial distribution of signal abnormalities (SA) on brain MRI in a sample of MS patients and normal controls (NC), using pair- and voxel-wise comparison procedures. Forty-one (41) MS patients (32 relapsing-remitting and 9 secondary-progressive) and 38 NC were examined on both 1.5 T and 3 T within one week in random order. T2-weighted hyperintensities (T2H) and T1-weighted hypointensities (T1H) were outlined semiautomatically by two operators in a blinded fashion on 1.5 T and 3 T images. Spatial lesion distribution was assessed using T2 and T1 voxel-wise SA probability maps (SAPM). Pair-wise analysis examined the proportion of SA not simultaneously outlined on 1.5 T and 3 T. A posteriori unblinded analysis was conducted to examine the non-overlapping identifications of SA between the 1.5 T and 3 T. For pair-wise T2- and T1-analyses, a higher number and individual volume of SA were detected on 3 T compared to 1.5 T (p<0.0001) in both MS and NC. Logistic regression analysis showed that the likelihood of missing SA on 1.5 T was significantly higher for smaller SA in both MS and NC groups. SA probability map (SAPM) analysis revealed significantly more regionally distinct spatial SA differences on 3 T compared to 1.5 T in both groups (p<0.05); these were most pronounced in the occipital, periventricular and cortical regions for T2H. This study provides important information regarding morphological and spatial differences between data acquired using 1.5 T and 3 T protocols at the two scanner field strengths.

Location of acute coronary artery thromboses in patients with and without chronic kidney disease

Patients with chronic kidney disease have high rates of myocardial infarction and death following an initial attack. Proximal location of coronary atherosclerotic lesions has been linked to the risk of acute myocardial infarction and to infarction-associated mortality. To examine if the spatial distribution of lesions differs in patients with and without chronic kidney disease, we used quantitative coronary angiography to measure this in patients with acute coronary thromboses who were having angiography following acute myocardial infarction. Multivariable linear regression was used to adjust for differences in baseline characteristics. Among 82 patients with stage 3 or higher chronic kidney disease, 55.6% of lesions were located within 30 mm and 87.7% were within 50 mm of the coronary ostia. This compared to 34.7 and 71.8%, respectively, among 299 patients without significant kidney disease. Chronic kidney disease was independently and significantly associated with a 7.0 mm decrease in the distance from the coronary ostia to the problem lesion. Our study suggests that a causal link between a more proximal culprit lesion location in patients with chronic kidney disease and their high mortality rates after myocardial infarct is possible and may have important implications for interventions to prevent infarction.

Thresholding lesion overlap difference maps: Application to category-related naming and recognition deficits

Lesion overlap difference maps have been used in studies designed to test anatomical hypotheses regarding brain systems critical for various cognitive and behavioral tasks, including naming and recognition of concrete entities [Damasio, H., Tranel, D., Grabowski, T., Adolphs, R., Damasio, A., 2004. Neural systems behind word and concept retrieval. Cognition 92, 179–229]. To date, the interpretation of these results has focused on areas of maximum lesion overlap differences. Here we explore formal methods for statistical thresholding and power analysis. We derive exact voxel-wise statistics describing the behavior of lesion overlap difference maps and lesion proportion difference maps under the null hypothesis of no association between lesion and deficit, and we apply the statistics to a large subset of the subjects previously reported in [Damasio, H., Tranel, D., Grabowski, T., Adolphs, R., Damasio, A., 2004. Neural systems behind word and concept retrieval. Cognition 92, 179–229], in order to reassess the lesion correlates of deficits in naming and recognition for five categories of concrete entities. The thresholded maps confirmed many of the results reported previously, but also revealed some differences. Differences in spatial distribution of the lesion correlates of impaired naming of unique versus nonunique entities were confirmed in the inferotemporal region (IT), although overlapping components across categories became apparent in left IT. Additionally, the left inferior frontal gyrus (IFG) was implicated in naming both categories of nonunique natural entities (animals and fruits/vegetables). In corresponding power analyses, we estimated where significant effects could be found under an assumption of maximal effect size given the observed spatial distribution of lesions. Such “effective coverage maps” are valuable for the interpretation of the results, notably because of heterogeneity in lesion coverage encountered in lesion studies. We strongly suggest that when inferential statistics are used in voxel-wise lesion-deficit statistical mapping, these or other power maps be included in the reports.

Lesion probability maps of white matter hyperintensities in elderly individuals

White matter hyperintensities (WMH) are common on brain MRI of the elderly. Their size ranges from punctate to early confluent to confluent lesions. While this increase in extension is frequently seen as evidence for a continuum of changes, histological data and clinical follow-up suggest differences in underlying pathology and their progression. We tested this hypothesis by exploring the distributions of punctuate and confluent lesions using lesion probability maps (LPM) generated from MRI scans of 189 participants (mean age 60.8+/-6.2 years) in the Austrian Stroke Prevention Study. We dichotomised WMH according to the classification by Fazekas et al. [punctate (n=143) vs. early confluent and confluent (n=33)] to run voxel-based t-tests using permutation-based nonparametric inference. To test alternative hypotheses, we created similar LPM for age and arterial hypertension. We observed significant differences in the spatial distribution of lesions for the two WMH groups (p<0.01). Punctate lesions were more diffusely distributed throughout the cerebral white matter (peak probability approximately 5%) relative to confluent lesions (peak probability 45%). Confluent lesions had greatest likelihood of being found in perfusion "watershed" regions. These differences in distribution could not be explained by differences in age or hypertension only, as both greater age and the diagnosis of hypertension were associated with WMH abutting the occipital horns. Punctate and early confluent to confluent WMH show distinguishable differences in their spatial distribution within a normal elderly population. The pattern of punctate WMH is probably a consequence of mixed etiologies. Preferential localization of the more confluent WMH with arterial watershed areas implies a stronger ischemic component in their development.

MRI criteria for dissemination in space in patients with clinically isolated syndromes: a multicentre follow-up study

The McDonald International Panel accepted the Barkhof/Tintoré criteria for providing MRI evidence of dissemination in space to allow a diagnosis of multiple sclerosis in patients with clinically isolated syndromes (CIS). We applied these criteria in a large cohort of patients with CIS, representative of those seen in a general diagnostic setting, to assess their accuracy in predicting conversion to definite multiple sclerosis and to identify factors that affect this risk. In a collaborative study of seven centres, baseline MRI and clinical follow-up data for 532 patients with CIS were studied, with the development of a second clinical event used as the main outcome. All scans were scored for lesion counts and spatial lesion distribution to assess the fulfilment--ie, at least three out of four--of the Barkhof/Tintoré criteria. We used survival analysis and 2x2 tables to assess the test characteristics of the criteria at baseline. Overall conversion rate was 32.5% with a median survival time of 85.3 months. Fulfilment of the criteria at baseline showed, after a survival time of 2 years, a conversion rate of about 45% (95% CI 37-53) versus about 10% (6-16) in those with no asymptomatic lesions at baseline (p<0.0001). For patients with a follow-up of at least 2 years, the fulfilment of the MRI criteria showed an accuracy of 68% (sensitivity 49%, specificity 79%) for predicting conversion and an increase in risk of nearly four times for conversion compared with those not fulfilling the criteria (odds ratio 3.7, 95% CI 2.3-5.9; p<0.0001). Cox proportional hazards regression analysis accorded with this increased risk. No effects were recorded on the performance of the criteria by sex, presenting symptoms, or centre. Age at baseline did have a small but significant effect as predictor (hazard ratio 0.97, 0.95-0.99; p=0.002), but did not affect the prognostic value of the MRI criteria. MRI abnormalities have important prognostic value. The cut-off, based on the Barkhof/Tintoré criteria, as incorporated in the McDonald diagnostic scheme yields acceptable specificity, but could have lower sensitivity than previously reported.

Live Cell Imaging of Heavy-Ion-Induced Radiation Responses by Beamline Microscopy

To study the dynamics of protein recruitment to DNA lesions, ion beams can be used to generate extremely localized DNA damage within restricted regions of the nuclei. This inhomogeneous spatial distribution of lesions can be visualized indirectly and rapidly in the form of radiation-induced foci using immunocytochemical detection or GFP-tagged DNA repair proteins. To analyze faster protein translocations and a possible contribution of radiation-induced chromatin movement in DNA damage recognition in live cells, we developed a remote-controlled system to obtain high-resolution fluorescence images of living cells during ion irradiation with a frame rate of the order of seconds. Using scratch replication labeling, only minor chromatin movement at sites of ion traversal was observed within the first few minutes of impact. Furthermore, time-lapse images of the GFP-coupled DNA repair protein aprataxin revealed accumulations within seconds at sites of ion hits, indicating a very fast recruitment to damaged sites. Repositioning of the irradiated cells after fixation allowed the comparison of live cell observation with immunocytochemical staining and retrospective etching of ion tracks. These results demonstrate that heavy-ion radiation-induced changes in subnuclear structures can be used to determine the kinetics of early protein recruitment in living cells and that the changes are not dependent on large-scale chromatin movement at short times postirradiation.

Is the spatial distribution of brain lesions associated with closed-head injury in children predictive of subsequent development of posttraumatic stress disorder?

To determine whether there is an association between the spatial distributions of lesions detected at magnetic resonance (MR) imaging of the brain in children, adolescents, and young adults after closed-head injury (CHI) and development of the reexperiencing symptoms of posttraumatic stress disorder (PTSD). Data obtained in 94 subjects without a history of PTSD as determined by parental interview were analyzed. MR images were obtained 3 months after CHI. Lesions were manually delineated and registered to the Talairach coordinate system. Mann-Whitney analysis of lesion distribution and PTSD status at 1 year (again, as determined by parental interview) was performed, consisting of an analysis of lesion distribution versus the major symptoms of PTSD: reexperiencing, hyperarousal, and avoidance. Of the 94 subjects, 41 met the PTSD reexperiencing criterion and nine met all three PTSD criteria. Subjects who met the reexperiencing criterion had fewer lesions in limbic system structures (eg, the cingulum) on the right than did subjects who did not meet this criterion (Mann-Whitney, P =.003). Lesions induced by CHI in the limbic system on the right may inhibit subsequent manifestation of PTSD reexperiencing symptoms in children, adolescents, and young adults.

A simulator for evaluating methods for the detection of lesion-deficit associations.

Although much has been learned about the functional organization of the human brain through lesion-deficit analysis, the variety of statistical and image-processing methods developed for this purpose precludes a closed-form analysis of the statistical power of these systems. Therefore, we developed a lesion-deficit simulator (LDS), which generates artificial subjects, each of which consists of a set of functional deficits, and a brain image with lesions; the deficits and lesions conform to predefined distributions. We used probability distributions to model the number, sizes, and spatial distribution of lesions, to model the structure-function associations, and to model registration error. We used the LDS to evaluate, as examples, the effects of the complexities and strengths of lesion-deficit associations, and of registration error, on the power of lesion-deficit analysis. We measured the numbers of recovered associations from these simulated data, as a function of the number of subjects analyzed, the strengths and number of associations in the statistical model, the number of structures associated with a particular function, and the prior probabilities of structures being abnormal. The number of subjects required to recover the simulated lesion-deficit associations was found to have an inverse relationship to the strength of associations, and to the smallest probability in the structure-function model. The number of structures associated with a particular function (i.e., the complexity of associations) had a much greater effect on the performance of the analysis method than did the total number of associations. We also found that registration error of 5 mm or less reduces the number of associations discovered by approximately 13% compared to perfect registration. The LDS provides a flexible framework for evaluating many aspects of lesion-deficit analysis.

Is the spatial distribution of brain lesions associated with closed-head injury predictive of subsequent development of attention-deficit/hyperactivity disorder? Analysis with brain-image database.

To determine whether there is an association between the spatial distribution of lesions detected at magnetic resonance (MR) imaging of the brain in children after closed-head injury and the development of secondary attention-deficit/hyperactivity disorder (ADHD). Data obtained from 76 children without prior history of ADHD were analyzed. MR images were obtained 3 months after closed-head injury. After manual delineation of lesions, images were registered to the Talairach coordinate system. For each subject, registered images and secondary ADHD status were integrated into a brain-image database, which contains depiction (visualization) and statistical analysis software. Using this database, we assessed visually the spatial distributions of lesions and performed statistical analysis of image and clinical variables. Of the 76 children, 15 developed secondary ADHD. Depiction of the data suggested that children who developed secondary ADHD had more lesions in the right putamen than children who did not develop secondary ADHD; this impression was confirmed statistically. After Bonferroni correction, we could not demonstrate significant differences between secondary ADHD status and lesion burdens for the right caudate nucleus or the right globus pallidus. Closed-head injury-induced lesions in the right putamen in children are associated with subsequent development of secondary ADHD. Depiction software is useful in guiding statistical analysis of image data.

Diagnosis of structural changes in fish gills—can biopsy replace necropsy?

The diagnostic value of gill biopsy was evaluated in the attempt to reduce terminal sampling for gill monitoring. Comparisons were made between biopsy and necropsy of gill samples to observe if there were any differences between the two sampling strategies. Lesions were quantified using two methods: determination of prevalence (percentage of fish showing the lesion) or number of lesions per filament. For both quantification methods, the number of lesions was lower and variation was greater in biopsy samples. These differences were statistically significant except for large plaques quantified as number of lesions per filament. Spatial distribution of lesions on a gill arch was investigated to determine the significance of biopsy sampling sites. The gill was divided into nine areas and lesions were counted for each area. Lesions were found in higher prevalence at the top and bottom of the gill arch (not in the middle) and mostly at the proximal and middle part of the filament. The distal part of the filament (one third to two thirds of a whole filament) was taken for biopsy samples which resulted in underestimation of lesion prevalence and numbers of lesions per filament. The biopsy technique cannot replace terminal sampling without further research to determine size of the biopsy, biopsy collection site (on the gill arch) as well as minimum number of biopsied fish.

Randomized clinical trial comparing low power-slow heating versus high power-rapid heating noncontact neodymium:yttrium-aluminum-garnet laser regimens for the treatment of benign prostatic hyperplasia

Objectives To evaluate and compare the safety and effectiveness of two noncontact laser regimens for the treatment of human benign prostatic hyperplasia (BPH), and to assess the impact of the spatial distribution of the laser-induced lesions on treatment outcome. Methods This was a prospective, double-blind, randomized study that included 29 patients with BPH (both the patients and the study physician assistant in charge of the follow-up evaluation were blinded to the treatment rendered). The patients were randomized to receive either a 15 W for 180 s (15 patients) or 50 W for 60 s (14 patients) laser regimen (powers measured at the fiber tip). There were two study phases for each treatment group: the irradiated sites were not overlapping during the first phase (lesions 1.5 cm apart), and were overlapping during the second phase (lesion less than 1.0 cm apart). Results Morbidity was minimal in both groups. At 1 year of follow-up, there was sig nificant improvement of the American Urological Association-7 symptom score, the peak urinary flow rate, and the postvoid residual in both treatment groups. These improve ments were not statistically significantly different regardless of time or the phase of the study for the two treatment groups. There were 3 treatment failures, 2 of whom were later successfully re-treated with larger amounts of laser energy. Furthermore, the peak flows in the second phase of the study were statistically significantly higher than those in the first phase of the study, regardless of the treatment group. Conclusions Our results suggest that both the 15 W for 180 s and the 50 W for 60 s are equally safe and effective treatments for BPH. Perhaps more importantly, they also suggest that the spatial distribution of lesions and overlapping of treated (irradiated) sites has significant impact on treatment outcome.

Histopathological Evaluation of Laser Thermocoagulation in the Human Prostate: Optimization of Laser Irradiation for Benign Prostatic Hyperplasia

We have previously shown in a canine prostate model that a noncontact low power neodymium: YAG laser regimen of 15 watts for 180 seconds yields a larger volume of coagulation necrosis than the currently recommended high power regimen of 50 watts for 60 seconds. These 2 regimens have not yet been compared in humans. The objective of this study was to evaluate histopathologically the thermocoagulation effect of these 2 laser regimens in the human prostate and the effect of the spatial distribution of the laser lesions on the extent of coagulation necrosis. The study was conducted in 10 patients undergoing radical prostatectomy or cystoprostatectomy. The laser treatment was given transurethrally 1 hour before removal of the specimen. There were no fractures of the prostate. The coagulation necrosis did not reach the peripheral zone and it was minimal in areas rich in fibromuscular tissue, such as the bladder neck. At times, nodular benign prostatic hyperplasia was unaffected. A 4-quadrant treatment in the same plane often yielded small nonconfluent lesions. Confluent lesions in the same plane yielded approximately 30 percent greater depth of coagulation necrosis, which was achieved when 3 or 4 lesions were created on each side of the prostate (per single transverse plane). Likewise, coagulation necrosis observed with 15 watts for 180 seconds was approximately 40 percent greater than that noted with the 50 watts for 60 seconds regimen. Our findings suggest that noncontact laser prostatectomy is a safe procedure that can be improved by modifying the laser regimen and the spatial distribution of lesions.