Magnetic resonance imaging and computer tomography of brain lesions in water buffaloes and cattle stunned with handguns or captive bolts

Owing to the demand for genuine mozzarella, some 330 water buffaloes are being slaughtered every year in Switzerland albeit a stunning procedure meeting animal welfare and occupational safety requirements remains to be established. To provide a basis for improvements, we sized anatomical specifics in water buffaloes and cattle and we assessed brain lesions after stunning with captive bolts or handguns by diagnostic imaging. In water buffaloes and cattle, the median distance from the frontal skin surface to the inner bone table was 74.0 mm (56.0–100.0 mm) vs 36.6 mm (29.3–44.3 mm) and from skin to the thalamus 144.8 mm (117.1–172.0 mm) vs 102.0 (101.0–121.0 mm), respectively. Consequently, customary captive bolt stunners may be inadequate. Free bullets are potentially suitable for stunning buffaloes but involve occupational safety hazards. The results of the present study shall be used to develop a device allowing effective and safe stunning of water buffaloes.

Effectiveness of Fluorescence-based Methods in Monitoring Progression of Noncavitated Caries-like Lesions on Smooth Surfaces

Although there has been a significant decrease in caries prevalence in developed countries, the slower progression of dental caries requires methods capable of detecting and quantifying lesions at an early stage. The aim of this study was to evaluate the effectiveness of fluorescence-based methods (DIAGNOdent 2095 laser fluorescence device [LF], DIAGNOdent 2190 pen [LFpen], and VistaProof fluorescence camera [FC]) in monitoring the progression of noncavitated caries-like lesions on smooth surfaces. Caries-like lesions were developed in 60 blocks of bovine enamel using a bacterial model of Streptococcus mutans and Lactobacillus acidophilus . Enamel blocks were evaluated by two independent examiners at baseline (phase I), after the first cariogenic challenge (eight days) (phase II), and after the second cariogenic challenge (a further eight days) (phase III) by two independent examiners using the LF, LFpen, and FC. Blocks were submitted to surface microhardness (SMH) and cross-sectional microhardness analyses. The intraclass correlation coefficient for intra- and interexaminer reproducibility ranged from 0.49 (FC) to 0.94 (LF/LFpen). SMH values decreased and fluorescence values increased significantly among the three phases. Higher values for sensitivity, specificity, and area under the receiver operating characteristic curve were observed for FC (phase II) and LFpen (phase III). A significant correlation was found between fluorescence values and SMH in all phases and integrated loss of surface hardness (ΔKHN) in phase III. In conclusion, fluorescence-based methods were effective in monitoring noncavitated caries-like lesions on smooth surfaces, with moderate correlation with SMH, allowing differentiation between sound and demineralized enamel.

Different bacterial models for in vitro induction of non-cavitated enamel caries-like lesions: Microhardness and polarized light miscroscopy analyses

The aim of this study was to compare different bacterial models for in vitro induction of non-cavitated enamel caries-like lesions by microhardness and polarized light microscopy analyses. One hundred blocks of bovine enamel were randomly divided into four groups (n = 25) according to the bacterial model for caries induction: (A) Streptococcus mutans, (B) S. mutans and Lactobacillus acidophilus, (C) S. mutans and L. casei, and (D) S. mutans, L. acidophilus, and L. casei. Within each group, the blocks were randomly divided into five subgroups according to the duration of the period of caries induction (4-20 days). The enamel blocks were immersed in cariogenic solution containing the microorganisms, which was changed every 48 h. Groups C and D presented lower surface hardness values (SMH) and higher area of hardness loss (ΔS) after the cariogenic challenge than groups A and B (P < 0.05). As regards lesion depth, under polarized light microscopy, group A presented significantly lower values, and groups C and D the highest values. Group B showed a higher value than group A (P < 0.05). Groups A and B exhibited subsurface caries lesions after all treatment durations, while groups C and D presented erosion-type lesions with surface softening. The model using S. mutans, whether or not it was associated with L. acidophilus, was less aggressive and may be used for the induction of non-cavitated enamel caries-like lesions. The optimal period for inducing caries-like lesions was 8 days.

Characterization of Enhancing MS Lesions by Dynamic Texture Parameter Analysis of Dynamic Susceptibility Perfusion Imaging

Purpose. The purpose of this study was to investigate statistical differences with MR perfusion imaging features that reflect the dynamics of Gadolinium-uptake in MS lesions using dynamic texture parameter analysis (DTPA). Methods. We investigated 51 MS lesions (25 enhancing, 26 nonenhancing lesions) of 12 patients. Enhancing lesions () were prestratified into enhancing lesions with increased permeability (EL+; ) and enhancing lesions with subtle permeability (EL−; ). Histogram-based feature maps were computed from the raw DSC-image time series and the corresponding texture parameters were analyzed during the inflow, outflow, and reperfusion time intervals. Results. Significant differences () were found between EL+ and EL− and between EL+ and nonenhancing inactive lesions (NEL). Main effects between EL+ versus EL− and EL+ versus NEL were observed during reperfusion (mainly in mean and standard deviation (SD): EL+ versus EL− and EL+ versus NEL), while EL− and NEL differed only in their SD during outflow. Conclusion. DTPA allows grading enhancing MS lesions according to their perfusion characteristics. Texture parameters of EL− were similar to NEL, while EL+ differed significantly from EL− and NEL. Dynamic texture analysis may thus be further investigated as noninvasive endogenous marker of lesion formation and restoration.

[Lung and pleural lesions before and after implementation of a national eradication program against enzootic pneumonia and actinobacillosis as well as changes of slaughter carcass organs in slaughter pigs in Switzerland].

In a representative cross-sectional study during 12 months of the years 2008/2009 in four abattoirs in Switzerland, lung and pleura lesions as well as lesions of slaughter carcasses and organs of 34 706 pigs were studied for frequency and type of macroscopic lesions. Of the 24276 examined pigs, 91.2% of the lungs, 94.4% of the heart and 95.5% of the livers showed no macroscopically visible lesions. Pigs that were produced for a label program had significantly less bronchopneumonia and pneumonia residuals, pleuritis and liver lesions due to echinococcosis. Pigs supervised by the Swiss Pig Health Service (SGD), showed significantly less bronchopneumonia and pneumonia residuals, diffuse pleuritis, pleuritis/pericarditis and milkspots compared to the non-SGD supervised farms. Thanks to the national eradication program for enzootic pneumonia (EP) and actinobacillosis, the health-status of lungs has been considerably improved and the prevalence of pleurisy decreased considerably. The results of this study indicate a good herd health in Swiss pig production.

Analysis of behavioral changes in dairy cows associated with claw horn lesions

Detecting lame cows is important in improving animal welfare. Automated tools are potentially useful to enable identification and monitoring of lame cows. The goals of this study were to evaluate the suitability of various physiological and behavioral parameters to automatically detect lameness in dairy cows housed in a cubicle barn. Lame cows suffering from a claw horn lesion (sole ulcer or white line disease) of one claw of the same hind limb (n=32; group L) and 10 nonlame healthy cows (group C) were included in this study. Lying and standing behavior at night by tridimensional accelerometers, weight distribution between hind limbs by the 4-scale weighing platform, feeding behavior at night by the nose band sensor, and heart activity by the Polar device (Polar Electro Oy, Kempele, Finland) were assessed. Either the entire data set or parts of the data collected over a 48-h period were used for statistical analysis, depending upon the parameter in question. The standing time at night over 12 h and the limb weight ratio (LWR) were significantly higher in group C as compared with group L, whereas the lying time at night over 12 h, the mean limb difference (△weight), and the standard deviation (SD) of the weight applied on the limb taking less weight were significantly lower in group C as compared with group L. No significant difference was noted between the groups for the parameters of heart activity and feeding behavior at night. The locomotion score of cows in group L was positively correlated with the lying time and △weight, whereas it was negatively correlated with LWR and SD. The highest sensitivity (0.97) for lameness detection was found for the parameter SD [specificity of 0.80 and an area under the curve (AUC) of 0.84]. The highest specificity (0.90) for lameness detection was present for Δweight (sensitivity=0.78; AUC=0.88) and LWR (sensitivity=0.81; AUC=0.87). The model considering the data of SD together with lying time at night was the best predictor of cows being lame, accounting for 40% of the variation in the likelihood of a cow being lame (sensitivity=0.94; specificity=0.80; AUC=0.86). In conclusion, the data derived from the 4-scale-weighing platform, either alone or combined with the lying time at night over 12 h, represent the most valuable parameters for automated identification of lame cows suffering from a claw horn lesion of one individual hind limb.

Molecular markers of human papillomavirus (HPV) infection and epidemiologic risk factors for squamous intraepithelial lesions (SIL) of the cervix

Infection with certain types of HPV is a necessary event in the development of cervical carcinoma; however, not all women who become infected will progress. While much is known about the molecular influence of HPV E6 and E7 proteins on the malignant transformation, little is known about the additional factors needed to drive the process. Currently, conventional cervical screening is insufficient at identifying women who are likely to progress from premalignant lesions to carcinoma. Aneuploidy and chromatin texture from image cytometry have been suggested as quantitative measures of nuclear damage in premalignant lesions and cancer, and traditional epidemiologic studies have identified potential factors to aid in the discrimination of those lesions likely to progress. ^ In the current study, real-time PCR was used to quantitate mRNA expression of the E7 gene in women exhibiting normal epithelium, LSIL, and HSIL. Quantitative cytometry was used to gather information about the DNA index and chromatin features of cells from the same women. Logistic regression modeling was used to establish predictor variables for histologic grade based on the traditional epidemiologic risk factors and molecular markers. ^ Prevalence of mRNA transcripts was lower among women with normal histology (27%) than for women with LSIL (40%) and HSIL (37%) with mean levels ranging from 2.0 to 4.2. The transcriptional activity of HPV 18 was higher than that of HPV 16 and increased with increasing level of dysplasia, reinforcing the more aggressive nature of HPV 18. DNA index and mRNA level increased with increasing histological grade. Chromatin score was not correlated with histology but was higher for HPV 18 samples and those with both HPV 18 and HPV 16. However, chromatin score and DNA index were not correlated with mRNA levels. The most predictive variables in the regression modeling were mRNA level, DNA index, parity, and age, and the ROC curves for LSIL and HSIL indicated excellent discrimination. ^ Real-time PCR of viral transcripts could provide a more efficient method to analyze the oncogenic potential within cells from cervical swabs. Epidemiological modeling of malignant progression in the cervix should include molecular markers, as well as the traditional epidemiological risk factors. ^

A systematic review examining the relationship between oral health care practices and the oral lesions commonly associated with HIV/AIDS, and the implications for people living in developing countries

Oral lesions, which may be bacterial, fungal or viral in nature may be characteristic of HIV/ AIDS, and have been observed on the oral mucosa as early signs of underlying disease. Some studies have suggested that there may be a correlation between poor oral hygiene, and the oral lesions seen among people living with HIV/AIDS.^ The objective of this study was to assess the nature of the relationship between oral health care practices, and the occurrence of oral lesions commonly seen in association with HIV/AIDS. A systematic review of the literature was conducted, and the databases searched were Medline and PubMed. Concepts that made up the search were oral hygiene promotion, HIV/AIDS and oral health care. Out of the 410 items identified through the search, only 11 met the inclusion criteria.^ The use of 0.12%–2% chlorhexidine gluconate, was found to be effective in reducing oral Candida counts in some studies, while other studies did not find such an association. However, 0.12%–2% chlorhexidine gluconate was consistently found to be effective in the management of periodontal lesions in people infected with HIV/AIDS. ^ Dental procedures such as treatment and filling of dental cavities, scaling and polishing, and use of fluoridated tooth paste were also found to be effective in the management of oral lesions seen in association with HIV/AIDS.^ The overall findings from the studies reviewed, suggest that effective oral health care may be necessary to reduce the morbidity, and mortality associated with the oral lesions seen among people living with HIV/AIDS. However, better designed studies with larger sample sizes need to be developed in order to ascertain the effectiveness of routine oral hygiene, and health care practices among people living with HIV/AIDS.^

Idiopathic multifocal choroiditis/punctate inner choroidopathy with acute photoreceptor loss or dysfunction out of proportion to clinically visible lesions.

PURPOSE To report acute/subacute vision loss and paracentral scotomata in patients with idiopathic multifocal choroiditis/punctate inner choroidopathy due to large zones of acute photoreceptor attenuation surrounding the chorioretinal lesions. METHODS Multimodal imaging case series. RESULTS Six women and 2 men were included (mean age, 31.5 ± 5.8 years). Vision ranged from 20/20-1 to hand motion (mean, 20/364). Spectral domain optical coherence tomography demonstrated extensive attenuation of the external limiting membrane, ellipsoid and interdigitation zones, adjacent to the visible multifocal choroiditis/punctate inner choroidopathy lesions. The corresponding areas were hyperautofluorescent on fundus autofluorescence and were associated with corresponding visual field defects. Full-field electroretinogram (available in three cases) showed markedly decreased cone/rod response, and multifocal electroretinogram revealed reduced amplitudes and increased implicit times in two cases. Three patients received no treatment, the remaining were treated with oral corticosteroids (n = 4), oral acyclovir/valacyclovir (n = 2), intravitreal/posterior subtenon triamcinolone acetate (n = 3), and anti-vascular endothelial growth factor (n = 2). Visual recovery occurred in only three cases of whom two were treated. Varying morphological recovery was found in six cases, associated with decrease in hyperautofluorescence on fundus autofluorescence. CONCLUSION Multifocal choroiditis/punctate inner choroidopathy can present with transient or permanent central photoreceptor attenuation/loss. This presentation is likely a variant of multifocal choroiditis/punctate inner choroidopathy with chorioretinal atrophy. Associated changes are best evaluated using multimodal imaging.

Aphasic seizures in patients with temporopolar and anterior temporobasal lesions: a video-EEG study

Studies of patients with temporal lobe epilepsy provide few descriptions of seizures that arise in the temporopolar and the anterior temporobasal brain region. Based on connectivity, it might be assumed that the semiology of these seizures is similar to that of medial temporal lobe epilepsy. However, accumulating evidence suggests that the anterior temporobasal cortex may play an important role in the language system, which could account for particular features of seizures arising here. We studied the electroclinical features of seizures in patients with circumscribed temporopolar and temporobasal lesions in order to identify specific features that might differentiate them from seizures that originate in other temporal areas. Among 172 patients with temporal lobe seizures registered in our epilepsy unit in the last 15 years, 15 (8.7%) patients had seizures caused by temporopolar or anterior temporobasal lesions (11 left-sided lesions). The main finding in our study is that patients with left-sided lesions had aphasia during their seizures as the most prominent feature. In addition, while all patients showed normal to high intellectual functioning in standard neuropsychological testing, semantic impairment was found in a subset of 9 patients with left-sided lesions. This case series demonstrates that aphasic seizures without impairment of consciousness can result from small, circumscribed left anterior temporobasal and temporopolar lesions. Thus, the presence of speech manifestation during seizures should prompt detailed assessment of the structural integrity of the basal surface of the temporal lobe in addition to the evaluation of primary language areas.

Automated detection and classification of brain injury lesions on structural magnetic resonance imaging

El daño cerebral adquirido (DCA) es un problema social y sanitario grave, de magnitud creciente y de una gran complejidad diagnóstica y terapéutica. Su elevada incidencia, junto con el aumento de la supervivencia de los pacientes, una vez superada la fase aguda, lo convierten también en un problema de alta prevalencia. En concreto, según la Organización Mundial de la Salud (OMS) el DCA estará entre las 10 causas más comunes de discapacidad en el año 2020. La neurorrehabilitación permite mejorar el déficit tanto cognitivo como funcional y aumentar la autonomía de las personas con DCA. Con la incorporación de nuevas soluciones tecnológicas al proceso de neurorrehabilitación se pretende alcanzar un nuevo paradigma donde se puedan diseñar tratamientos que sean intensivos, personalizados, monitorizados y basados en la evidencia. Ya que son estas cuatro características las que aseguran que los tratamientos son eficaces. A diferencia de la mayor parte de las disciplinas médicas, no existen asociaciones de síntomas y signos de la alteración cognitiva que faciliten la orientación terapéutica. Actualmente, los tratamientos de neurorrehabilitación se diseñan en base a los resultados obtenidos en una batería de evaluación neuropsicológica que evalúa el nivel de afectación de cada una de las funciones cognitivas (memoria, atención, funciones ejecutivas, etc.). La línea de investigación en la que se enmarca este trabajo de investigación pretende diseñar y desarrollar un perfil cognitivo basado no sólo en el resultado obtenido en esa batería de test, sino también en información teórica que engloba tanto estructuras anatómicas como relaciones funcionales e información anatómica obtenida de los estudios de imagen. De esta forma, el perfil cognitivo utilizado para diseñar los tratamientos integra información personalizada y basada en la evidencia. Las técnicas de neuroimagen representan una herramienta fundamental en la identificación de lesiones para la generación de estos perfiles cognitivos. La aproximación clásica utilizada en la identificación de lesiones consiste en delinear manualmente regiones anatómicas cerebrales. Esta aproximación presenta diversos problemas relacionados con inconsistencias de criterio entre distintos clínicos, reproducibilidad y tiempo. Por tanto, la automatización de este procedimiento es fundamental para asegurar una extracción objetiva de información. La delineación automática de regiones anatómicas se realiza mediante el registro tanto contra atlas como contra otros estudios de imagen de distintos sujetos. Sin embargo, los cambios patológicos asociados al DCA están siempre asociados a anormalidades de intensidad y/o cambios en la localización de las estructuras. Este hecho provoca que los algoritmos de registro tradicionales basados en intensidad no funcionen correctamente y requieran la intervención del clínico para seleccionar ciertos puntos (que en esta tesis hemos denominado puntos singulares). Además estos algoritmos tampoco permiten que se produzcan deformaciones grandes deslocalizadas. Hecho que también puede ocurrir ante la presencia de lesiones provocadas por un accidente cerebrovascular (ACV) o un traumatismo craneoencefálico (TCE). Esta tesis se centra en el diseño, desarrollo e implementación de una metodología para la detección automática de estructuras lesionadas que integra algoritmos cuyo objetivo principal es generar resultados que puedan ser reproducibles y objetivos. Esta metodología se divide en cuatro etapas: pre-procesado, identificación de puntos singulares, registro y detección de lesiones. Los trabajos y resultados alcanzados en esta tesis son los siguientes: Pre-procesado. En esta primera etapa el objetivo es homogeneizar todos los datos de entrada con el objetivo de poder extraer conclusiones válidas de los resultados obtenidos. Esta etapa, por tanto, tiene un gran impacto en los resultados finales. Se compone de tres operaciones: eliminación del cráneo, normalización en intensidad y normalización espacial. Identificación de puntos singulares. El objetivo de esta etapa es automatizar la identificación de puntos anatómicos (puntos singulares). Esta etapa equivale a la identificación manual de puntos anatómicos por parte del clínico, permitiendo: identificar un mayor número de puntos lo que se traduce en mayor información; eliminar el factor asociado a la variabilidad inter-sujeto, por tanto, los resultados son reproducibles y objetivos; y elimina el tiempo invertido en el marcado manual de puntos. Este trabajo de investigación propone un algoritmo de identificación de puntos singulares (descriptor) basado en una solución multi-detector y que contiene información multi-paramétrica: espacial y asociada a la intensidad. Este algoritmo ha sido contrastado con otros algoritmos similares encontrados en el estado del arte. Registro. En esta etapa se pretenden poner en concordancia espacial dos estudios de imagen de sujetos/pacientes distintos. El algoritmo propuesto en este trabajo de investigación está basado en descriptores y su principal objetivo es el cálculo de un campo vectorial que permita introducir deformaciones deslocalizadas en la imagen (en distintas regiones de la imagen) y tan grandes como indique el vector de deformación asociado. El algoritmo propuesto ha sido comparado con otros algoritmos de registro utilizados en aplicaciones de neuroimagen que se utilizan con estudios de sujetos control. Los resultados obtenidos son prometedores y representan un nuevo contexto para la identificación automática de estructuras. Identificación de lesiones. En esta última etapa se identifican aquellas estructuras cuyas características asociadas a la localización espacial y al área o volumen han sido modificadas con respecto a una situación de normalidad. Para ello se realiza un estudio estadístico del atlas que se vaya a utilizar y se establecen los parámetros estadísticos de normalidad asociados a la localización y al área. En función de las estructuras delineadas en el atlas, se podrán identificar más o menos estructuras anatómicas, siendo nuestra metodología independiente del atlas seleccionado. En general, esta tesis doctoral corrobora las hipótesis de investigación postuladas relativas a la identificación automática de lesiones utilizando estudios de imagen médica estructural, concretamente estudios de resonancia magnética. Basándose en estos cimientos, se han abrir nuevos campos de investigación que contribuyan a la mejora en la detección de lesiones. ABSTRACT Brain injury constitutes a serious social and health problem of increasing magnitude and of great diagnostic and therapeutic complexity. Its high incidence and survival rate, after the initial critical phases, makes it a prevalent problem that needs to be addressed. In particular, according to the World Health Organization (WHO), brain injury will be among the 10 most common causes of disability by 2020. Neurorehabilitation improves both cognitive and functional deficits and increases the autonomy of brain injury patients. The incorporation of new technologies to the neurorehabilitation tries to reach a new paradigm focused on designing intensive, personalized, monitored and evidence-based treatments. Since these four characteristics ensure the effectivity of treatments. Contrary to most medical disciplines, it is not possible to link symptoms and cognitive disorder syndromes, to assist the therapist. Currently, neurorehabilitation treatments are planned considering the results obtained from a neuropsychological assessment battery, which evaluates the functional impairment of each cognitive function (memory, attention, executive functions, etc.). The research line, on which this PhD falls under, aims to design and develop a cognitive profile based not only on the results obtained in the assessment battery, but also on theoretical information that includes both anatomical structures and functional relationships and anatomical information obtained from medical imaging studies, such as magnetic resonance. Therefore, the cognitive profile used to design these treatments integrates information personalized and evidence-based. Neuroimaging techniques represent an essential tool to identify lesions and generate this type of cognitive dysfunctional profiles. Manual delineation of brain anatomical regions is the classical approach to identify brain anatomical regions. Manual approaches present several problems related to inconsistencies across different clinicians, time and repeatability. Automated delineation is done by registering brains to one another or to a template. However, when imaging studies contain lesions, there are several intensity abnormalities and location alterations that reduce the performance of most of the registration algorithms based on intensity parameters. Thus, specialists may have to manually interact with imaging studies to select landmarks (called singular points in this PhD) or identify regions of interest. These two solutions have the same inconvenient than manual approaches, mentioned before. Moreover, these registration algorithms do not allow large and distributed deformations. This type of deformations may also appear when a stroke or a traumatic brain injury (TBI) occur. This PhD is focused on the design, development and implementation of a new methodology to automatically identify lesions in anatomical structures. This methodology integrates algorithms whose main objective is to generate objective and reproducible results. It is divided into four stages: pre-processing, singular points identification, registration and lesion detection. Pre-processing stage. In this first stage, the aim is to standardize all input data in order to be able to draw valid conclusions from the results. Therefore, this stage has a direct impact on the final results. It consists of three steps: skull-stripping, spatial and intensity normalization. Singular points identification. This stage aims to automatize the identification of anatomical points (singular points). It involves the manual identification of anatomical points by the clinician. This automatic identification allows to identify a greater number of points which results in more information; to remove the factor associated to inter-subject variability and thus, the results are reproducible and objective; and to eliminate the time spent on manual marking. This PhD proposed an algorithm to automatically identify singular points (descriptor) based on a multi-detector approach. This algorithm contains multi-parametric (spatial and intensity) information. This algorithm has been compared with other similar algorithms found on the state of the art. Registration. The goal of this stage is to put in spatial correspondence two imaging studies of different subjects/patients. The algorithm proposed in this PhD is based on descriptors. Its main objective is to compute a vector field to introduce distributed deformations (changes in different imaging regions), as large as the deformation vector indicates. The proposed algorithm has been compared with other registration algorithms used on different neuroimaging applications which are used with control subjects. The obtained results are promising and they represent a new context for the automatic identification of anatomical structures. Lesion identification. This final stage aims to identify those anatomical structures whose characteristics associated to spatial location and area or volume has been modified with respect to a normal state. A statistical study of the atlas to be used is performed to establish which are the statistical parameters associated to the normal state. The anatomical structures that may be identified depend on the selected anatomical structures identified on the atlas. The proposed methodology is independent from the selected atlas. Overall, this PhD corroborates the investigated research hypotheses regarding the automatic identification of lesions based on structural medical imaging studies (resonance magnetic studies). Based on these foundations, new research fields to improve the automatic identification of lesions in brain injury can be proposed.

Low density lipoprotein receptor-negative mice expressing human apolipoprotein B-100 develop complex atherosclerotic lesions on a chow diet: No accentuation by apolipoprotein(a)

We have generated mice with markedly elevated plasma levels of human low density lipoprotein (LDL) and reduced plasma levels of high density lipoprotein. These mice have no functional LDL receptors [LDLR−/−] and express a human apolipoprotein B-100 (apoB) transgene [Tg(apoB+/+)] with or without an apo(a) transgene [Tg(apoa+/−)]. Twenty animals (10 males and 10 females) of each of the following four genotypes were maintained on a chow diet: (i) LDLR−/−, (ii) LDLR−/−;Tg(apoa+/−), (iii) LDLR−/−;Tg(apoB+/+), and (iv)LDLR−/−;Tg(apoB+/+);Tg(apo+/−). The mice were killed at 6 mo, and the percent area of the aortic intimal surface that stained positive for neutral lipid was quantified. Mean percent areas of lipid staining were not significantly different between the LDLR−/− and LDLR−/−;Tg(apoa+/−) mice (1.0 ± 0.2% vs. 1.4 ± 0.3%). However, the LDLR−/−;Tg(apoB+/+) mice had ≈15-fold greater mean lesion area than the LDLR−/− mice. No significant difference was found in percent lesion area in the LDLR−/−;Tg(apoB+/+) mice whether or not they expressed apo(a) [18.5 ± 2.5%, without lipoprotein(a), Lp(a), vs. 16.0 ± 1.7%, with Lp(a)]. Histochemical analyses of the sections from the proximal aorta of LDLR−/−;Tg(apoB+/+) mice revealed large, complex, lipid-laden atherosclerotic lesions that stained intensely with human apoB-100 antibodies. In mice expressing Lp(a), large amounts of apo(a) protein colocalized with apoB-100 in the lesions. We conclude that LDLR−/−; Tg(apoB+/+) mice exhibit accelerated atherosclerosis on a chow diet and thus provide an excellent animal model in which to study atherosclerosis. We found no evidence that apo(a) increased atherosclerosis in this animal model.