Color-neutral and reversible tissue transparency enables longitudinal deep-tissue imaging in live mice.

Light scattering in biological tissue presents a significant challenge for deep in vivo imaging. Our previous work demonstrated the ability to achieve optical transparency in live mice using intensely absorbing dye molecules, which created transparency in the red spectrum while blocking shorter-wavelength photons. In this paper, we extend this capability to achieve optical transparency across the entire visible spectrum by employing molecules with strong absorption in the ultraviolet spectrum and sharp absorption edges that rapidly decline upon entering the visible spectrum.

Disruption of the cerebrospinal fluid-plasma protein balance in cognitive impairment and aging.

The brain barrier system, including the choroid plexus, meninges and brain vasculature, regulates substrate transport and maintains differential protein concentrations between blood and cerebrospinal fluid (CSF). Aging and neurodegeneration disrupt brain barrier function, but proteomic studies of the effects on blood-CSF protein balance are limited. Here we used SomaScan proteomics to characterize paired CSF and plasma samples from 2,171 healthy or cognitively impaired older individuals from multiple cohorts, including the Global Neurodegeneration Proteomics Consortium.

Comparison of neural networks for classification of urinary tract dilation from renal ultrasounds: evaluation of agreement with expert categorization.

Background: Urinary tract dilation (UTD) is a frequent problem in infants. Automated and objective classification of UTD from renal ultrasounds would streamline their interpretations.

Objective: To develop and evaluate the performance of different deep learning models in predicting UTD classifications from renal ultrasound images.

Use of a Template-Matching Clavicle Fracture Atlas for Surrogate Dating of Humeral and Femoral Fractures in Young Infants: A Six-Reader Study.

Fracture dating is important in suspected infant abuse. Birth-related clavicle fractures are common and may provide surrogates to aid infant long bone fracture dating. To assess the impact of a template-matching clavicle fracture timeline atlas on radiologists' performance in dating birth-related clavicle, humerus, and femur fractures in young infants.

PLCG2 modulates TREM2 expression and signaling in response to Alzheimer's disease pathology.

Background: Phospholipase C gamma 2 (PLCG2) is an intracellular effector of microglial cell surface receptors, including triggering receptor expressed on myeloid cells 2 (TREM2). Variants which alter PLCG2 activity impact Alzheimer's disease (AD) risk, but the effects of PLCG2 deficiency in AD remain unclear.

Methods: 5xFAD mice were crossed with PLCG2- and TREM2-deficient mice to assess the role of PLCG2 in response to amyloid pathology.

Self-supervised denoising diffusion probabilistic models for abdominal DW-MRI.

Purpose: To improve the quality of abdominal diffusion-weighted MR images (DW-MRI) when acquired using single-repetition (NEX = 1) protocols, and thereby increase apparent diffusion coefficient (ADC) map accuracy and lesion conspicuity at high b-values. We aim to reduce the effect of blurring due to motion that obscures small lesions when averaging multiple repetition images at each b-value, which is the current clinical standard.

Methods: We propose a self-supervised denoising diffusion probabilistic model (ssDDPM) to improve DW-MRI quality given noisy single-repetition acquisitions in pediatric abdominal scans.

Color-neutral and reversible tissue transparency enables longitudinal deep-tissue imaging in live mice.

Light scattering in biological tissue presents a significant challenge for deep imaging. Our previous work demonstrated the ability to achieve optical transparency in live mice using intensely absorbing dye molecules, which created transparency in the red spectrum while blocking shorter-wavelength photons. In this paper, we extend this capability to achieve optical transparency across the entire visible spectrum by employing molecules with strong absorption in the ultraviolet spectrum and sharp absorption edges that rapidly decline upon entering the visible spectrum.

A high-throughput assay platform to discover small molecule activators of the phospholipase PLC-γ2 to treat Alzheimer's disease.

A naturally occurring missense variant of the phospholipase C isozyme, PLC-γ2, harboring a single substitution (P522R) protects against several neurodegenerative diseases, including Alzheimer's disease. The phospholipase activity of PLC-γ2 (P522R) is slightly elevated relative to its WT counterpart, and the general consensus is that this increased activity in microglia confers protection against neurodegeneration. In order to phenocopy this protection, we have developed a high-throughput assay to identify small molecule activators of PLC-γ2.

Skeletal surveys for suspected infant abuse: patient-specific radiation dose estimation using a hybrid computational phantom.

Background: Radiographic skeletal survey plays an important role in the diagnosis of infant abuse. Some practitioners have expressed concerns about the radiation exposure from this examination.

Objective: To utilize state-of-the-art hybrid computational phantoms to more accurately estimate radiation doses of skeletal surveys performed for suspected infant abuse.

Advancements in Immunity and Dementia Research: Highlights from the 2023 AAIC Advancements: Immunity Conference.

The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell-mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in the brain in the context of AD and related dementias (ADRD) remain unclear. Furthermore, the roles of the peripheral immune system in driving ADRD pathology remain incompletely elucidated.

Mitigating mitochondrial dysfunction and neuroinflammation by hematoma aspiration in a new surgical model for severe intracerebral hemorrhage.

Background: Intracerebral hemorrhage (ICH) is associated with a large hematoma that causes compression, increased intracranial pressure (IICP), midline shift, and brain herniation, and may ultimately lead to death. Urgent surgical removal of the large hematoma can ameliorate these injuries, which would be life-saving, but has not improved clinical outcome. A suitable animal model that mimics the clinically relevant human severe ICH injury requiring surgical hematoma evacuation is urgently needed.

Deep generative model of the distal tibial classic metaphyseal lesion in infants: assessment of synthetic images.

Background: The classic metaphyseal lesion (CML) is a distinctive fracture highly specific to infant abuse. To increase the size and diversity of the training CML database for automated deep-learning detection of this fracture, we developed a mask conditional diffusion model (MaC-DM) to generate synthetic images with and without CMLs.

Purpose: To objectively and subjectively assess the synthetic radiographic images with and without CMLs generated by MaC-DM.

Deep learning MR reconstruction in knees and ankles in children and young adults. Is it ready for clinical use?

Objective: To evaluate the diagnostic performance and image quality of accelerated Turbo Spin Echo sequences using deep-learning (DL) reconstructions compared to conventional sequences in knee and ankle MRIs of children and young adults.

Materials And Methods: IRB-approved prospective study consisting of 49 MRIs from 48 subjects (10 males, mean age 16.4 years, range 7-29 years), with each MRI consisting of both conventional and DL sequences.

Improving the radiographic image analysis of the classic metaphyseal lesion via conditional diffusion models.

The classic metaphyseal lesion (CML) is a unique fracture highly specific for infant abuse. This fracture is often subtle in radiographic appearance and commonly occurs in the distal tibia. The development of an automated model that can accurately identify distal tibial radiographs with CMLs is important to assist radiologists in detecting these fractures.

Case 326: Intra-Articular Osteoid Osteoma.

A 15-year-old male patient presented with a 3-week history of inner left thigh pain provoked by activity and experienced occasionally at rest. The patient denied nighttime pain, fever, or chills. Laboratory investigation revealed the following normal values: hemoglobin level of 15.

Free-Breathing High-Resolution, Swap-Free, and Motion-Corrected Water/Fat Separation in Pediatric Abdominal MRI.

Objectives: The T1-weighted GRE (gradient recalled echo) sequence with the Dixon technique for water/fat separation is an essential component of abdominal MRI (magnetic resonance imaging), useful in detecting tumors and characterizing hemorrhage/fat content. Unfortunately, the current implementation of this sequence suffers from several problems: (1) low resolution to maintain high pixel bandwidth and minimize chemical shift; (2) image blurring due to respiratory motion; (3) water/fat swapping due to the natural ambiguity between fat and water peaks; and (4) off-resonance fat blurring due to the multipeak nature of the fat spectrum. The goal of this study was to evaluate the image quality of water/fat separation using a high-resolution 3-point Dixon golden angle radial acquisition with retrospective motion compensation and multipeak fat modeling in children undergoing abdominal MRI.

Intra-articular Osteoid Osteomas: Imaging Manifestations and Mimics.

Osteoid osteoma (OO) is the third most prevalent benign bone neoplasm in children. Although it predominantly affects the diaphysis of long bones, OO can assume an intra-articular location in the epiphysis or the intracapsular portions of bones. The most common location of intra-articular OO is the hip joint.

Near-pair patch generative adversarial network for data augmentation of focal pathology object detection models.

Purpose: The limited volume of medical training data remains one of the leading challenges for machine learning for diagnostic applications. Object detectors that identify and localize pathologies require training with a large volume of labeled images, which are often expensive and time-consuming to curate. To reduce this challenge, we present a method to support distant supervision of object detectors through generation of synthetic pathology-present labeled images.

Lower Extremity Growth according to AI Automated Femorotibial Length Measurement on Slot-Scanning Radiographs in Pediatric Patients.

Background Commonly used pediatric lower extremity growth standards are based on small, dated data sets. Artificial intelligence (AI) enables creation of updated growth standards. Purpose To train an AI model using standing slot-scanning radiographs in a racially diverse data set of pediatric patients to measure lower extremity length and to compare expected growth curves derived using AI measurements to those of the conventional Anderson-Green method.

APOE4/4 is linked to damaging lipid droplets in Alzheimer's disease microglia.

Several genetic risk factors for Alzheimer's disease implicate genes involved in lipid metabolism and many of these lipid genes are highly expressed in glial cells. However, the relationship between lipid metabolism in glia and Alzheimer's disease pathology remains poorly understood. Through single-nucleus RNA sequencing of brain tissue in Alzheimer's disease, we have identified a microglial state defined by the expression of the lipid droplet-associated enzyme ACSL1 with ACSL1-positive microglia being most abundant in patients with Alzheimer's disease having the APOE4/4 genotype.

Case 326.

A 15-year-old boy presented with a 3-week history of inner left thigh pain provoked by activity and experienced occasionally at rest. He denied nighttime pain, fever, or chills. Laboratory investigation revealed the following normal values: hemoglobin level of 15.

Functional 3'-UTR Variants Identify Regulatory Mechanisms Impacting Alcohol Use Disorder and Related Traits.

Although genome-wide association studies (GWAS) have identified loci associated with alcohol consumption and alcohol use disorder (AUD), they do not identify which variants are functional. To approach this, we evaluated the impact of variants in 3' untranslated regions (3'-UTRs) of genes in loci associated with substance use and neurological disorders using a massively parallel reporter assay (MPRA) in neuroblastoma and microglia cells. Functionally impactful variants explained a higher proportion of heritability of alcohol traits than non-functional variants.

Perioperative Factors and Radiographic Severity Scores for Predicting the Duration of Mechanical Ventilation After Arterial Switch Surgery.

Objectives: Cardiac surgery on cardiopulmonary bypass (CPB) during the neonatal period can cause perioperative organ injuries. The primary aim of this study was to determine the incidence and risk factors associated with postoperative mechanical ventilation duration and acute lung injury after the arterial switch operation (ASO). The secondary aim was to examine the utility of the Brixia score for characterizing postoperative acute lung injury (ALI).

Pelvis radiographs in children with cerebral palsy: effects of patient positioning on calculating migration percentages.

Background: Hip displacement in children with cerebral palsy (CP) is monitored by measuring migration percentage on anteroposterior pelvis radiographs. However, proper positioning for radiography in children with spasticity is difficult. The reliability and accuracy of migration percentage as a function of patient positioning is unknown.