Purpose: To use manganese-enhanced magnetic resonance imaging (MEMRI) at 25 × 25 × 800 μm3 to image different retinal and vascular layers in the rat retinas.
Materials and Methods: Manganese-chloride was injected intraocularly in normal (n = 5) and Royal College of Surgeons (RCS, an model of photoreceptor degeneration) (n = 5) rats at postnatal day 90. MEMRI at 4.7 T was performed 24 hours later. MRI was repeated following intravenous Gd-DTPA in the same animals to highlight the vasculatures. Layer assignment and thickness were compared to histology.
Results: MEMRI 24 hours after intravitreal manganese-chloride injection revealed seven bands of alternating hyper- and hypointensities, corresponding histologically to the ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, photoreceptor-segment layer, and choroidal vascular layer. Intravenous Gd-DTPA-which does not cross the blood-retinal barrier and the retinal pigment epithelium-further enhanced the two layers bounding the retina, corresponding to the retinal and choroidal vascular layers, but not the avascular outer nuclear layer and the photoreceptor-segment layer. MEMRI of the RCS retinas revealed the loss of the outer plexiform layer, outer nuclear layer, and photoreceptor-segment layer. Histological analysis corroborated the MRI laminar assignments and thicknesses.
Conclusion: Lamina-specific retinal structures neurodegenerative changes to structure in retinal diseases can be detected using MEMRI.
by
Lauren A. Baldassarre;
Subha V. Raman;
James K. Min;
Jennifer H. Mieres;
Martha Gulati;
Nanette Wenger;
Thomas H. Marwick;
Chiara Bucciarelli-Ducci;
C. Noel Bairey Merz;
Dipti Itchhaporia;
Keith C. Ferdinand;
Carl J. Pepine;
Mary Norine Walsh;
Jagat Narula;
Leslee Shaw
Declines in cardiovascular deaths have been dramatic for men but occur significantly less in women. Among patients with symptomatic ischemic heart disease (IHD), women experience relatively worse outcomes compared with their male counterparts. Evidence to date has failed to adequately explore unique female imaging targets and their correlative signs and symptoms of IHD as major determinants of IHD risk. We highlight sex-specific anatomic and functional differences in contemporary imaging and introduce imaging approaches that leverage refined targets that may improve IHD risk prediction and identify potential therapeutic strategies for symptomatic women.
Glaucoma is the second leading cause of blindness in the world. Disease progression is associated with reduced cellularity in the trabecular meshwork (TM), a fluid drainage tissue in the anterior eye. A promising therapy seeks to deliver stem cells to the TM to regenerate the tissue and restore its function. However, like many stem cell-based regenerative therapies, preclinical development relies heavily on histology to evaluate outcomes. To expedite clinical translation, we are developing an ultrasound/photoacoustic (US/PA) imaging platform for longitudinal tracking of stem cells in the anterior eye. Methods: Mesenchymal stem cells (MSCs) were labeled with gold nanospheres in vitro and injected through the cornea into the anterior chamber of ex vivo porcine eyes. Physiological pressure was imposed to mimic in vivo conditions. AuNS-labeled MSCs were injected through the cornea while single-wavelength US/PA images were acquired. At 5 hours post-injection, three-dimensional multi-wavelength US/PA datasets were acquired and spectroscopic analysis was used to detect AuNS-labeled MSCs. US/PA results were compared to fluorescent microscopy. Results: The US/PA imaging platform was able to provide real-time monitoring of the stem cell injection and distinguish AuNS-labeled MSCs from highly absorbing background tissues in the anterior segment. Conclusion: Our US/PA imaging approach can inform preclinical studies of stem cell therapies for glaucoma treatment, motivating further development of this theranostic imaging tool for ophthalmic applications.
We examined event-related electroencephalography (EEG) oscillations, including event-related spectral perturbations (ERSP) and intertrial coherence (ITC), to compare feedback processing during a chance-based reward vs. non-reward task in groups of 10-12-year-old (n= 42), 13-14-year-old (n= 34) and 15-17-year-olds (n= 32). Because few, if any studies have applied these analytic methods to examine feedback processing in children or adolescents, we used a fine-grained approach that explored one half hertz by 16. ms increments during feedback (no win vs. win events) in the theta (4-8. Hz) frequency band. Complex wavelet frequency decomposition revealed that no win feedback was associated with enhanced theta power and phase coherence. We observed condition and age-based differences for both ERSP and ITC, with stronger effects for ITC. The transition from childhood to early adolescence (13-14. yrs.) was a point of increased differentiation of ITC favoring no win vs. wins feedback and also compared to children or older adolescents, a point of heightened ITC for no win feedback (quadratic effect).
Background Impairment in prediction and appreciation for choice outcomes could contribute to several core symptoms of ASD. We examined electroencephalography (EEG) oscillations in 27 youth and young adults diagnosed with autism spectrum disorder (ASD) and 22 IQ-matched neurotypical controls while they performed a chance-based reward prediction task. Method We re-analyzed our previously published ERP data (Larson et al., 2011) and examined theta band oscillations (4–8 Hz) at frontal midline sites, within a timing window that overlaps with the feedback-related negativity (FRN). We focused on event-related changes after presentation of feedback for reward (WIN) and punitive (LOSE) outcomes, both for spectral power and inter-trial phase coherence. Results In our reward prediction task, for both groups, medial frontal theta power and phase coherence were greater following LOSE compared to WIN feedback. However, compared to controls, inter-trial coherence of medial frontal theta was significantly lower overall (across both feedback types) for individuals with ASD. Our results indicate that while individuals with ASD are sensitive to the valence of reward feedback, comparable to their neurotypical peers, they have reduced synchronization of medial frontal theta activity during feedback processing. Conclusions This finding is consistent with previous studies showing neural variability in ASD and suggest that the processes underlying decision-making and reinforcement learning may be atypical and less efficient in ASD.
by
J Sauk;
E Coron;
L Kava;
M Suter;
M Gora;
K Gallagher;
M Rosenberg;
A Ananthakrishnan;
N Nishioka;
G Lauwers;
Kevin Woods;
W Brugge;
D Forcione;
BE Bouma;
G Tearney
Background: Optical frequency domain imaging (OFDI) is a second-generation form of optical coherence tomography (OCT) providing comprehensive cross-sectional views of the distal esophagus at a resolution of ~7 μm.
Aim: Using validated OCT criteria for squamous mucosa, gastric cardia mucosa, and Barrett's esophagus (BE), the objective of this study was to determine the inter- and intra-observer agreements by a large number of OFDI readers for differentiating these tissues.
Methods: OFDI images were obtained from nine subjects undergoing screening and surveillance for BE. Sixty-four OFDI image regions of interest were randomly selected for review. A training set of 19 images was compiled distinguishing squamous mucosa from gastric cardia and BE using previously validated OCT criteria. The ten readers then interpreted images in a test set of 45 different images of squamous mucosa (n = 15), gastric cardia (n = 15), or BE (n = 15). Interobserver agreement differentiating the three tissue types and BE versus non-BE mucosa was determined using multi-rater Fleiss's κ value. The images were later randomized again and four readers repeated the test 3 weeks later to assess intraobserver reliability.
Results: All ten readers showed excellent agreement for the differentiation of BE versus non-BE mucosa (κ = 0.811 p < 0.0001) and for differentiating BE versus gastric cardia versus squamous mucosa (κ = 0.866, p < 0.0001). For the four readers who repeated the test, the median intraobserver agreement (BE vs. non-BE) was high (κ = 0.975, IQR: 0.94, 1.0).
Conclusions: Trained readers have a high interobserver agreement for differentiating BE, squamous, and gastric cardia mucosa using OFDI.
In recent years, there has been a growing interest for using mouse models in refractive development and myopia research. The crystalline lens is a critical optical component of the mouse eye that occupies greater than 50% of the ocular space, and significant increases in thickness with age. However, changes in refractive index of the mouse crystalline lens are less known. In this study, we examined the changes in thickness and refractive index of the mouse crystalline lens for two different strains, wild-type (WT) and a nyx mutant (nob) over the course of normal visual development or after form deprivation. Refractive index and lens thickness measurements were made on exvivo lenses using spectral domain optical coherence tomography (SD-OCT). Comparison of refractive index measurements on 5 standard ball lenses using the SD-OCT and their known refractive indices (manufacturer provided) indicated good precision (intra-class correlation coefficient, 0.998 and Bland-Altman coefficient of repeatability, 0.116) of the SD-OCT to calculate mouse lens refractive index exvivo. During normal visual development, lens thickness increased significantly with age for three different cohorts of mice, aged 4 (average thickness from both eyes; WT: 1.78±0.03, nob: 1.79±0.08mm), 10 (WT: 2.02±0.05, nob: 2.01±0.04mm) and 16 weeks (WT: 2.12±0.06, nob: 2.09±0.06mm, p<0.001). Lens thickness was not significantly different between the two strains at any age (p=0.557). For mice with normal vision, refractive index for isolated crystalline lenses in nob mice was significantly greater than WT mice (mean for all ages; WT: 1.42±0.01, nob: 1.44±0.001, p<0.001). After 4 weeks of form deprivation to the right eye using a skull-mounted goggling apparatus, a thinning of the crystalline lens was observed in both right and left eyes of goggled animals compared to their naïve controls (average from both the right and the left eye) for both strains (p=0.052). In form deprived mice, lens refractive index was significantly different between the goggled animals and non-goggled naïve controls in nob mice, but not in WT mice (p=0.009). Both eyes of goggled nob mice had significantly greater lens refractive index (goggled, 1.49±0.01; opposite, 1.47±0.03) compared to their naïve controls (1.45±0.02, p<0.05). The results presented here suggest that there are genetic differences in the crystalline lens refractive index of the mouse eye, and that the lens refractive index in mice significantly increase with form deprivation. Research applications requiring precise optical measurements of the mouse eye should take these lens refractive indices into account when interpreting SD-OCT data.
Genetic and environmental factors have been shown to control visually-guided eye growth and influence myopia development. However, investigations into the intersection of these two factors in controlling refractive development have been limited by the lack of a genetically modifiable animal model. Technological advances have now made it possible to assess refractive state and ocular biometry in the small mouse eye and therefore to exploit the many genetic mouse mutants to investigate mechanisms of visually-guided eye growth. This review considers the benefits and challenges of studying refractive development in mice, compares the results of refractive error and ocular biometry from wild-type strains and genetic models in normal laboratory visual environments or with disrupted visual input, and discusses some of the remaining challenges in interpreting data from the mouse to validate and standardize methods between labs.