Early-stage macular telangiectasia type 2 vascular abnormalities are associated with interdigitation zone disruption

Purpose To investigate the relationship between disruption in different photoreceptor layers and deep capillary plexus (DCP) telangiectasias in eyes with macular telangiectasia type 2 (MacTel). Methods 35 eyes (21 patients) with MacTel imaged with optical coherence tomography angiography (OCTA) were included. Circumscribed areas of DCP telangiectasia were traced from OCTA slabs and the corresponding spectral-domain OCT (SD-OCT) slabs were used to visualize the photoreceptor layer interdigitation zone (IZ) and ellipsoid zone (EZ). IZ attenuation, IZ loss, and EZ loss were graded by reviewing en face SD-OCT slabs for hypo-reflective areas and confirming their status on cross-sectional views. Total area of photoreceptor disruption and overlap with DCP telangiectasia were evaluated with respect to OCT-based MacTel stage. Longitudinal changes were evaluated in a subset of patients with follow-up imaging. Results Overlap of DCP telangiectasia with IZ attenuation significantly decreased with MacTel severity, while overlap with IZ and EZ loss significantly increased. Overlap with IZ loss peaked in moderate MacTel (Stages 3–5). Longitudinal imaging showed that new EZ loss at 6 months was largely predicted by baseline IZ loss. Conclusions Worsening MacTel severity is characterized by greater overlap between DCP telangiectasia and zones of increasing severity of photoreceptor disruption, with EZ loss enlarging over time within areas of preexisting IZ disruption. We suggest that IZ disruption may indicate early photoreceptor dysfunction that eventually progresses to EZ loss, with IZ loss being a more reliable metric than IZ attenuation. Additional studies will be necessary to further explore long-term photoreceptor changes and evaluate their relationship with visual function in MacTel.

Long-term prognosis and educational determinants of brain network decline in older adult individuals

Older adults with lower education are at greater risk for dementia. It is unclear which brain changes lead to these outcomes. Longitudinal imaging-based measures of brain structure and function were examined in adult individuals (baseline age, 45–86 years; two to five visits per participant over 1–9 years). College degree completion differentiates individual-based and neighborhood-based measures of socioeconomic status and disadvantage. Older adults (~65 years and over) without a college degree exhibit a pattern of declining large-scale functional brain network organization (resting-state system segregation) that is less evident in their college-educated peers. Declining brain system segregation predicts impending changes in dementia severity, measured up to 10 years past the last scan date. The prognostic value of brain network change is independent of Alzheimer’s disease (AD)-related genetic risk (APOE status), the presence of AD-associated pathology (cerebrospinal fluid phosphorylated tau, cortical amyloid) and cortical thinning. These results demonstrate that the trajectory of an individual’s brain network organization varies in relation to their educational attainment and, more broadly, is a unique indicator of individual brain health during older age.

Individual variations in ‘brain age’ relate to early-life factors more than to longitudinal brain change

Brain age is a widely used index for quantifying individuals’ brain health as deviation from a normative brain aging trajectory. Higher-than-expected brain age is thought partially to reflect above-average rate of brain aging. Here, we explicitly tested this assumption in two independent large test datasets (UK Biobank [main] and Lifebrain [replication]; longitudinal observations ≈ 2750 and 4200) by assessing the relationship between cross-sectional and longitudinal estimates of brain age. Brain age models were estimated in two different training datasets (n ≈ 38,000 [main] and 1800 individuals [replication]) based on brain structural features. The results showed no association between cross-sectional brain age and the rate of brain change measured longitudinally. Rather, brain age in adulthood was associated with the congenital factors of birth weight and polygenic scores of brain age, assumed to reflect a constant, lifelong influence on brain structure from early life. The results call for nuanced interpretations of cross-sectional indices of the aging brain and question their validity as markers of ongoing within-person changes of the aging brain. Longitudinal imaging data should be preferred whenever the goal is to understand individual change trajectories of brain and cognition in aging.

Picroscope: low-cost system for simultaneous longitudinal biological imaging

Simultaneous longitudinal imaging across multiple conditions and replicates has been crucial for scientific studies aiming to understand biological processes and disease. Yet, imaging systems capable of accomplishing these tasks are economically unattainable for most academic and teaching laboratories around the world. Here, we propose the Picroscope, which is the first low-cost system for simultaneous longitudinal biological imaging made primarily using off-the-shelf and 3D-printed materials. The Picroscope is compatible with standard 24-well cell culture plates and captures 3D z-stack image data. The Picroscope can be controlled remotely, allowing for automatic imaging with minimal intervention from the investigator. Here, we use this system in a range of applications. We gathered longitudinal whole organism image data for frogs, zebrafish, and planaria worms. We also gathered image data inside an incubator to observe 2D monolayers and 3D mammalian tissue culture models. Using this tool, we can measure the behavior of entire organisms or individual cells over long-time periods.

Advances in Biomarkers for Lung Disease

Bringing together a collection of the most forward-thinking approaches to lung disease, the European Respiratory Society (ERS) International Congress 2021 hosted a virtual session on imaging biomarkers. Four insightful presentations discussed the shift towards more longitudinal imaging approaches for lung disease and provided an overview of quantitative analyses with computer-trained algorithms. Alongside this was a discussion of the use of novel biomarkers such as pleuroparenchymal fibroelastosis.

Optimal Combinations of Chemotherapy and Radiotherapy in Low-Grade Gliomas: A Mathematical Approach

Low-grade gliomas (LGGs) are brain tumors characterized by their slow growth and infiltrative nature. Treatment options for these tumors are surgery, radiation therapy and chemotherapy. The optimal use of radiation therapy and chemotherapy is still under study. In this paper, we construct a mathematical model of LGG response to combinations of chemotherapy, specifically to the alkylating agent temozolomide and radiation therapy. Patient-specific parameters were obtained from longitudinal imaging data of the response of real LGG patients. Computer simulations showed that concurrent cycles of radiation therapy and temozolomide could provide the best therapeutic efficacy in-silico for the patients included in the study. The patient cohort was extended computationally to a set of 3000 virtual patients. This virtual cohort was subject to an in-silico trial in which matching the doses of radiotherapy to those of temozolomide in the first five days of each cycle improved overall survival over concomitant radio-chemotherapy according to RTOG 0424. Thus, the proposed treatment schedule could be investigated in a clinical setting to improve combination treatments in LGGs with substantial survival benefits.

Preclinical Studies in Small Animals for Advanced Drug Delivery Using Hyperthermia and Intravital Microscopy

This paper presents three devices suitable for the preclinical application of hyperthermia via the simultaneous high-resolution imaging of intratumoral events. (Pre)clinical studies have confirmed that the tumor micro-environment is sensitive to the application of local mild hyperthermia. Therefore, heating is a promising adjuvant to aid the efficacy of radiotherapy or chemotherapy. More so, the application of mild hyperthermia is a useful stimulus for triggered drug release from heat-sensitive nanocarriers. The response of thermosensitive nanoparticles to hyperthermia and ensuing intratumoral kinetics are considerably complex in both space and time. To obtain better insight into intratumoral processes, longitudinal imaging (preferable in high spatial and temporal resolution) is highly informative. Our devices are based on (i) an external electric heating adaptor for the dorsal skinfold model, (ii) targeted radiofrequency application, and (iii) a microwave antenna for heating of internal tumors. These models, while of some technical complexity, significantly add to the understanding of effects of mild hyperthermia warranting implementation in research on hyperthermia.