Machine Learning Classification of Alzheimer's Disease Pathology Reveals Diffuse Amyloid as a Major Predictor of Cognitive Impairment in Human Hippocampal Subregions.

Analyzing Alzheimer's disease (AD) pathology within anatomical subregions is a significant challenge, often carried out by pathologists using a standardized, semi-quantitative approach. To augment traditional methods, a high-throughput, high-resolution pipeline was created to classify the distribution of AD pathology within hippocampal subregions. USC ADRC post-mortem tissue sections from 51 patients were stained with 4G8 for amyloid, Gallyas for neurofibrillary tangles (NFTs) and Iba1 for microglia. Machine learning (ML) techniques were utilized to identify and classify amyloid pathology (dense, diffuse and APP (amyloid precursor protein)), NFTs, neuritic plaques and microglia. These classifications were overlaid within manually segmented regions (aligned with the Allen Human Brain Atlas) to create detailed pathology maps. Cases were separated into low, intermediate, or high AD stages. Further data extraction enabled quantification of plaque size and pathology density alongside ApoE genotype, sex, and cognitive status. Our findings revealed that the increase in pathology burden across AD stages was driven mainly by diffuse amyloid. The pre and para-subiculum had the highest levels of diffuse amyloid while NFTs were highest in the A36 region in high AD cases. Moreover, different pathology types had distinct trajectories across disease stages. In a subset of AD cases, microglia were elevated in intermediate and high compared to low AD. Microglia also correlated with amyloid pathology in the Dentate Gyrus. The size of dense plaques, which may represent microglial function, was lower in ApoE4 carriers. In addition, individuals with memory impairment had higher levels of both dense and diffuse amyloid. Taken together, our findings integrating ML classification approaches with anatomical segmentation maps provide new insights on the complexity of disease pathology in AD progression. Specifically, we identified diffuse amyloid pathology as being a major driver of AD in our cohort, regions of interest and microglial responses that might advance AD diagnosis and treatment.

Pediatric Atypical Teratoid/Rhabdoid Tumors of the Brain: Identification of Metabolic Subgroups Using In Vivo 1H-MR Spectroscopy.

BACKGROUND AND PURPOSE: Atypical teratoid/rhabdoid tumors are rare, aggressive central nervous system tumors that are predominantly encountered in very young children. Our aim was to determine whether in vivo metabolic profiles correlate with molecular features of central nervous system pediatric atypical teratoid/rhabdoid tumors. MATERIALS AND METHODS: Twenty confirmed patients with atypical teratoid/rhabdoid tumors who underwent MR spectroscopy were included in this study. In vivo metabolite levels of atypical teratoid/rhabdoid tumors were compared with molecular subtypes assessed by achaete-scute homolog 1 expression. Additionally, brain-specific creatine kinase levels were determined in tissue samples. RESULTS: In vivo creatine concentrations were higher in tumors that demonstrated achaete-scute homolog 1 expression compared with those without achaete-scute homolog 1 expression (3.42 ± 1.1 versus 1.8 ± 0.8 IU, P < .01). Additionally, levels of myo-inositol (mI) (9.0 ± 1.5 versus 4.7 ± 3.6 IU, P < .05) were significantly different, whereas lipids approached significance (44 ± 20 versus 80 ± 30 IU, P = .07) in these 2 cohorts. Higher brain-specific creatine kinase levels were observed in the cohort with achaete-scute homolog 1 expression (P < .05). Pearson correlation analysis showed a significant positive correlation of brain-specific creatine kinase with absolute creatine (P < .05) and myo-inositol (P < .05) concentrations. CONCLUSIONS: In vivo MR spectroscopy may predict key molecular features of atypical teratoid/rhabdoid tumors at initial diagnosis, leading to timely patient risk stratification and accelerating the development of targeted therapies.

Evaluating Practitioner Training to Improve Competencies and Organizational Practices for Engaging Fathers in Parenting Interventions.

Fathers are consistently underrepresented in parenting interventions and practitioners are an important target for change in interventions to enhance father engagement. This research examined the effects of two practitioner training programs in improving practitioner rated competencies and organizational father-inclusive practices. Two studies were conducted, each with a single group, repeated measures (pre, post and 2-month follow-up) design. Study 1 (N = 233) examined the outcomes of face-to-face training in improving practitioner ratings of competencies in engaging fathers, perceived effectiveness and use of father engagement strategies, organizational practices and rates of father engagement. Study 2 (N = 356) examined online training using the same outcome measures. Practitioners in both training formats improved in their competencies, organizational practices and rates of father engagement over time, yet those in the online format deteriorated in three competencies from post-training to follow-up. The implications for delivering practitioner training programs to enhance competencies and rates of father engagement are discussed.

Examining Practitioner Competencies, Organizational Support and Barriers to Engaging Fathers in Parenting Interventions.

Evidence-based parenting interventions have been developed and evaluated largely with mothers. This study examined practitioner reports of rates of father attendance, barriers to engagement, organizational support for father-inclusive practice, participation in training in father engagement, and competencies in working with fathers. It also explored predictors of practitioner competence and rates of father attendance. Practitioners (N = 210) who delivered parenting interventions completed an online survey. Participants reported high levels of confidence in engaging fathers, but only one in three had participated in training and levels of father attendance in parenting interventions were low. Logistic regressions showed that high levels of practitioner competence were predicted by participation in training. Moderate levels of father attendance (vs. low levels) were predicted by greater number of years of experience while high levels of attendance (vs. low levels) were predicted by greater experience, higher levels of competence and higher levels of organizational support. The implications of the findings to informing policy and practice for enhancing father engagement are discussed.

Mothers, Fathers, and Parental Systems: A Conceptual Model of Parental Engagement in Programmes for Child Mental Health-Connect, Attend, Participate, Enact (CAPE).

Parenting programmes are one of the best researched and most effective interventions for reducing child mental health problems. The success of such programmes, however, is largely dependent on their reach and parental engagement. Rates of parental enrolment and attendance are highly variable, and in many cases very low; this is especially true of father involvement in parenting programmes. This paper proposes a conceptual model of parental engagement in parenting programmes-the CAPE model (Connect, Attend, Participate, Enact) that builds on recent models by elaborating on the interdependent stages of engagement, and its interparental or systemic context. That is, we argue that a comprehensive model of parental engagement will best entail a process from connection to enactment of learned strategies in the child's environment, and involve consideration of individual parents (both mothers and fathers) as well as the dynamics of the parenting team. The model provides a framework for considering parent engagement as well as associated facilitators and mechanisms of parenting change such as parenting skills, self-efficacy, attributions, and the implementation context. Empirical investigation of the CAPE model could be used to further our understanding of parental engagement, its importance for programme outcomes, and mechanisms of change. This will guide future intervention refinement and developments as well as change in clinical practice.

Benefits of routine use of coronal and sagittal reformations in multi-slice CT examination of the abdomen and pelvis.

AIM: To evaluate the usefulness of coronal and sagittal reformations from isotropic abdomino-pelvic computed tomography (CT) examinations. METHODS: Fifty consecutive abdomino-pelvic CT examinations were reconstructed into two sets of axial source images: 0.9 mm section width with 0.45 mm reconstruction interval (isotropic) and 4 mm section width with 3 mm reconstruction interval. The isotropic dataset was reformatted into coronal and sagittal stacks with 4 mm section widths. Three readers independently reviewed the three image sets with 4 mm section widths. The coronal and sagittal reformations were compared with the axial images, in the same sitting, for depiction of lesions in various abdominal organs. RESULTS: There was better visualization of lesions in the liver, kidneys, mesentery, lumbar spine, major abdominal vessels, urinary bladder, diaphragm and hips on the coronal reformations compared with source axial images (p<0.05). Sagittal reformations scored better than axial source images for showing lesions in the liver, thoracic spine, abdominal vessels, uterus, urinary bladder, diaphragm and hips (p<0.05). The coronal and sagittal series showed significant additional information in 23 and 17% of patients, respectively. CONCLUSION: Radiologists should consider the routine review of at least one additional plane to the axial series in the interpretation of abdomino-pelvic CT studies.

Routine isotropic computed tomography scanning of the abdomen and pelvis.

For 30 years, abdominal CT has been imaged and reviewed in the axial plane. It is now possible to carry out isotropic imaging of the whole abdomen and pelvis using a 40-channel scanner. This allows creation of coronal and sagittal reformats with the same image quality as the axial images. In this study, we present our experience of reviewing routinely coronal and, occasionally, sagittal reformats. We discuss situations where these nonaxial reformats are most beneficial.

Hepatic peliosis (bacillary angiomatosis) in AIDS: CT findings.

Patients with acquired immunodeficiency syndrome are at risk of developing opportunistic infections and aggressive tumors. Computed tomographic examination is the usual method of evaluating the abdomen and pelvis in these patients. Although this technique is reasonably sensitive in detecting pathology, findings are often nonspecific. A case of hepatic peliosis (bacillary angiomatosis) in a patient with acquired immunodeficiency syndrome is presented.

Detection of occult metastasis in patients with breast cancer.

The most important factor affecting the outcome of patients with invasive cancer is whether the tumor has spread, either regionally (to regional lymph nodes) or systemically. However, a proportion of patients with no evidence of systemic dissemination will develop recurrent disease after primary "curative" therapy. Clearly, these patients had occult systemic spread of disease that was undetectable by routinely employed methods (careful pathological, clinical, biochemical, and radiological evaluation). In addition, the success of adjuvant therapy is assumed to stem from its ability to eradicate occult metastases before they become clinically evident. Therefore, methods for the detection of occult metastases in patients with the earliest stage of cancer, i.e., prior to detection of metastases by any other clinical or pathological analysis, have received a great deal of attention.

Occult metastases in patients with breast cancer.

The presence of occult metastases in the lymph nodes, bone marrow, or both of these compartments may not only define patients who are at higher risk for recurrence and death but also may identify biologically distinct mechanisms of tumor spread (e.g., lymphatic vs. vascular dissemination). Use of techniques to detect occult metastases may also allow the identification of a biologically important population of cells, i.e., those cells constituting the earliest metastatic population of tumor cells. Thus, techniques that identify occult metastases may be valuable in furthering our understanding of the events regulating tumor dissemination.