Beyond the nuclear border: single-cell analysis of in situ sequenced human brain tissue using cellular features.

Spatial transcriptomics has advanced our understanding of cellular heterogeneity at single-cell resolution. Here, we assess the suitability of in situ sequencing (ISS) for analyzing formalin-fixed, paraffin-embedded (FFPE) postmortem human brain tissue. A key challenge in ISS data analysis is optimizing transcript allocation while minimizing misallocation, particularly in the morphologically complex central nervous system (CNS).

Sex-dependent APOE4 neutrophil-microglia interactions drive cognitive impairment in Alzheimer's disease.

APOE4 is the strongest genetic risk factor for Alzheimer's disease (AD), with increased odds ratios in female carriers. Targeting amyloid plaques shows modest improvement in male non-APOE4 carriers. Leveraging single-cell transcriptomics across APOE variants in both sexes, multiplex flow cytometry and validation in two independent cohorts of APOE4 female carriers with AD, we identify a new subset of neutrophils interacting with microglia associated with cognitive impairment.

Mapping odorant sensitivities reveals a sparse but structured representation of olfactory chemical space by sensory input to the mouse olfactory bulb.

In olfactory systems, convergence of sensory neurons onto glomeruli generates a map of odorant receptor identity. How glomerular maps relate to sensory space remains unclear. We sought to better characterize this relationship in the mouse olfactory system by defining glomeruli in terms of the odorants to which they are most sensitive.

Single-scan dual-tracer FLT+FDG PET tumor characterization.

Rapid multi-tracer PET aims to image two or more tracers in a single scan, simultaneously characterizing multiple aspects of physiology and function without the need for repeat imaging visits. Using dynamic imaging with staggered injections, constraints on the kinetic behavior of each tracer are applied to recover individual-tracer measures from the multi-tracer PET signal. The ability to rapidly and reliably image both (18)F-fluorodeoxyglucose (FDG) and (18)F-fluorothymidine (FLT) would provide complementary measures of tumor metabolism and proliferative activity, with important applications in guiding oncologic treatment decisions and assessing response.

Estimating myocardial perfusion from dynamic contrast-enhanced CMR with a model-independent deconvolution method.

Background: Model-independent analysis with B-spline regularization has been used to quantify myocardial blood flow (perfusion) in dynamic contrast-enhanced cardiovascular magnetic resonance (CMR) studies. However, the model-independent approach has not been extensively evaluated to determine how the contrast-to-noise ratio between blood and tissue enhancement affects estimates of myocardial perfusion and the degree to which the regularization is dependent on the noise in the measured enhancement data. We investigated these questions with a model-independent analysis method that uses iterative minimization and a temporal smoothness regularizer.

Evaluation of rapid dual-tracer (62)Cu-PTSM + (62)Cu-ATSM PET in dogs with spontaneously occurring tumors.

We are developing methods for imaging multiple PET tracers in a single scan with staggered injections, where imaging measures for each tracer are separated and recovered using differences in tracer kinetics and radioactive decay. In this work, signal separation performance for rapid dual-tracer (62)Cu-PTSM (blood flow) + (62)Cu-ATSM (hypoxia) tumor imaging was evaluated in a large animal model. Four dogs with pre-existing tumors received a series of dynamic PET scans with (62)Cu-PTSM and (62)Cu-ATSM, permitting evaluation of a rapid dual-tracer protocol designed by previous simulation work.