Spatial and Temporal Relationships Between Atrophy and Hypometabolism in Behavioral-Variant Frontotemporal Dementia.

PURPOSE: Individuals with behavioral-variant frontotemporal dementia (bvFTD) show changes in brain structure as assessed by MRI and brain function assessed by 18FDG-PET hypometabolism. However, current understanding of the spatial and temporal interplay between these measures remains limited. METHODS: Here, we examined longitudinal atrophy and hypometabolism relationships in 15 bvFTD subjects with 2 to 4 follow-up MRI and PET scans (56 visits total). Subject-specific slopes of atrophy and hypometabolism over time were extracted across brain regions and correlated with baseline measures both locally, via Pearson correlations, and nonlocally, via sparse canonical correlation analyses (SCCA). RESULTS: Notably, we identified a robust link between initial hypometabolism and subsequent cortical atrophy rate changes in bvFTD subjects. Network-level exploration unveiled alignment between baseline hypometabolism and ensuing atrophy rates in the dorsal attention, language, and default mode networks. SCCA identified 2 significant and highly localized components depicting the connection between baseline hypometabolism and atrophy slope over time. The first centered around bilateral orbitofrontal, frontopolar, and medial prefrontal lobes, whereas the second concentrated in the left temporal lobe and precuneus. CONCLUSIONS: This study highlights 18FDG-PET as a dependable predictor of forthcoming atrophy in spatially adjacent brain regions for individuals with bvFTD.

A systematic review of automated segmentation of 3D computed-tomography scans for volumetric body composition analysis.

Automated computed tomography (CT) scan segmentation (labelling of pixels according to tissue type) is now possible. This technique is being adapted to achieve three-dimensional (3D) segmentation of CT scans, opposed to single L3-slice alone. This systematic review evaluates feasibility and accuracy of automated segmentation of 3D CT scans for volumetric body composition (BC) analysis, as well as current limitations and pitfalls clinicians and researchers should be aware of. OVID Medline, Embase and grey literature databases up to October 2021 were searched. Original studies investigating automated skeletal muscle, visceral and subcutaneous AT segmentation from CT were included. Seven of the 92 studies met inclusion criteria. Variation existed in expertise and numbers of humans performing ground-truth segmentations used to train algorithms. There was heterogeneity in patient characteristics, pathology and CT phases that segmentation algorithms were developed upon. Reporting of anatomical CT coverage varied, with confusing terminology. Six studies covered volumetric regional slabs rather than the whole body. One study stated the use of whole-body CT, but it was not clear whether this truly meant head-to-fingertip-to-toe. Two studies used conventional computer algorithms. The latter five used deep learning (DL), an artificial intelligence technique where algorithms are similarly organized to brain neuronal pathways. Six of seven reported excellent segmentation performance (Dice similarity coefficients > 0.9 per tissue). Internal testing on unseen scans was performed for only four of seven algorithms, whilst only three were tested externally. Trained DL algorithms achieved full CT segmentation in 12 to 75 s versus 25 min for non-DL techniques. DL enables opportunistic, rapid and automated volumetric BC analysis of CT performed for clinical indications. However, most CT scans do not cover head-to-fingertip-to-toe; further research must validate using common CT regions to estimate true whole-body BC, with direct comparison to single lumbar slice. Due to successes of DL, we expect progressive numbers of algorithms to materialize in addition to the seven discussed in this paper. Researchers and clinicians in the field of BC must therefore be aware of pitfalls. High Dice similarity coefficients do not inform the degree to which BC tissues may be under- or overestimated and nor does it inform on algorithm precision. Consensus is needed to define accuracy and precision standards for ground-truth labelling. Creation of a large international, multicentre common CT dataset with BC ground-truth labels from multiple experts could be a robust solution.

Longitudinal Analysis of Bruch Membrane Opening Morphometry in Myopic Glaucoma.

PRéCIS:: The Bruch membrane opening (BMO) was posteriorly bowed and the degree of nonplanarity increased in stable and progressive glaucoma subjects. BMO became more posterior relative to the Bruch membrane (BM) in control and both stable and progressive glaucoma subjects. PURPOSE: To investigate longitudinal changes in morphologic characteristics of the BMO in control and glaucomatous subjects. MATERIALS AND METHODS: A total of 53 myopic eyes (17 control, 6 suspect, 20 stable glaucoma, and 10 progressing glaucoma) were followed for an average of 4.2±1.4 years and imaged at the baseline and 2 follow-up appointments using a 1060 nm swept-source optical coherence tomography system. BM and BMO were segmented, and 4 morphometric BMO parameters (area, ellipse ratio, nonplanarity, and depth) were measured. RESULTS: There were no significant changes in BMO area or ellipse ratio for all groups. BMO nonplanarity was shown to increase in the glaucoma groups. BMO depth relative to BM increased in all groups except the suspects (control: 8.1 µm/y, P=0.0001; stable glaucoma: 3.5 µm/y, P=0.0001; progressing glaucoma: 14.0 µm/y, P=0.0026). In linear mixed-model analysis, axial length was positively associated with BMO area in all groups except for progressing glaucoma, and with BMO nonplanarity in stable glaucoma. It was not a significant factor to the slopes of the BMO parameters in the ANCOVA analysis of slopes. CONCLUSIONS: Longitudinally, BMO increased in nonplanarity in the glaucoma eyes, and its axial position relative to BM became more posterior in both control and glaucoma eyes.

Study the Longitudinal in vivo and Cross-Sectional ex vivo Brain Volume Difference for Disease Progression and Treatment Effect on Mouse Model of Tauopathy Using Automated MRI Structural Parcellation.

Brain volume measurements extracted from structural MRI data sets are a widely accepted neuroimaging biomarker to study mouse models of neurodegeneration. Whether to acquire and analyze data in vivo or ex vivo is a crucial decision during the phase of experimental designs, as well as data analysis. In this work, we extracted the brain structures for both longitudinal in vivo and single-time-point ex vivo MRI acquired from the same animals using accurate automatic multi-atlas structural parcellation, and compared the corresponding statistical and classification analysis. We found that most gray matter structures volumes decrease from in vivo to ex vivo, while most white matter structures volume increase. The level of structural volume change also varies between different genetic strains and treatment. In addition, we showed superior statistical and classification power of ex vivo data compared to the in vivo data, even after resampled to the same level of resolution. We further demonstrated that the classification power of the in vivo data can be improved by incorporating longitudinal information, which is not possible for ex vivo data. In conclusion, this paper demonstrates the tissue-specific changes, as well as the difference in statistical and classification power, between the volumetric analysis based on the in vivo and ex vivo structural MRI data. Our results emphasize the importance of longitudinal analysis for in vivo data analysis.

Anterior Segment Optical Coherence Tomography for Targeted Transconjunctival Suture Placement in Overfiltering Trabeculectomy Blebs.

PURPOSE: To demonstrate the utility of swept-source anterior segment optical coherence tomography (SS-AS-OCT) in guiding placement of transconjunctival sutures in hypotonous patients after a trabeculectomy. PATIENTS AND METHODS: This is a longitudinal case series of 10 eyes from 10 patients who required transconjunctival sutures after a trabeculectomy. SS-AS-OCT was used to aid in the placement of the sutures to improve the function of the overfiltering bleb. RESULTS: SS-AS-OCT reliably identified localized areas of overfiltering, allowing for targeted suture placement in 8 eyes. The 2 eyes in which localized areas of overfiltering were not found required further surgical intervention. CONCLUSIONS: SS-AS-OCT enhances transconjunctival suturing for overfiltering blebs when focal fluid accumulation is visualized.

Functional Assessment of Cardiac Responses of Adult Zebrafish (Danio rerio) to Acute and Chronic Temperature Change Using High-Resolution Echocardiography.

The zebrafish (Danio rerio) is an important organism as a model for understanding vertebrate cardiovascular development. However, little is known about adult ZF cardiac function and how contractile function changes to cope with fluctuations in ambient temperature. The goals of this study were to: 1) determine if high resolution echocardiography (HRE) in the presence of reduced cardiodepressant anesthetics could be used to accurately investigate the structural and functional properties of the ZF heart and 2) if the effect of ambient temperature changes both acutely and chronically could be determined non-invasively using HRE in vivo. Heart rate (HR) appears to be the critical factor in modifying cardiac output (CO) with ambient temperature fluctuation as it increases from 78 ± 5.9 bpm at 18°C to 162 ± 9.7 bpm at 28°C regardless of acclimation state (cold acclimated CA- 18°C; warm acclimated WA- 28°C). Stroke volume (SV) is highest when the ambient temperature matches the acclimation temperature, though this difference did not constitute a significant effect (CA 1.17 ± 0.15 µL at 18°C vs 1.06 ± 0.14 µl at 28°C; WA 1.10 ± 0.13 µL at 18°C vs 1.12 ± 0.12 µl at 28°C). The isovolumetric contraction time (IVCT) was significantly shorter in CA fish at 18°C. The CA group showed improved systolic function at 18°C in comparison to the WA group with significant increases in both ejection fraction and fractional shortening and decreases in IVCT. The decreased early peak (E) velocity and early peak velocity / atrial peak velocity (E/A) ratio in the CA group are likely associated with increased reliance on atrial contraction for ventricular filling.

Comparison of the clinical disc margin seen in stereo disc photographs with neural canal opening seen in optical coherence tomography images.

PURPOSE: To compare neural canal opening (NCO) with the clinical optic disc margin (DM) seen and to investigate the planarity of the NCO in normal human optic nerve heads (ONH). METHODS: Sixteen eyes were imaged. Twelve healthy eyes were selected for planarity and 9 for NCO and DM correspondence. All subjects were subjected to a visual field examination, stereo disc photograph (SDP), scanning laser ophthalmoscopy, clinical examination with a fellowship trained glaucoma specialist, and optical coherence tomography imaging. Three reviewers delineated the NCO and inner limiting membrane on optical coherence tomography images. The clinical DM was delineated by a glaucoma specialist while viewing SDPs. Plane error was calculated for NCO and for Bruch membrane (BM) at distances 80 and 120 µm from NCO. RESULTS: The NCO segmentation interrater variability was low with an average coefficient of variation of 2.7%. A regional variation of the SDP and NCO correspondence was observed, wherein the temporal region had the largest coefficient of variation. The plane error of the NCO and BM were similar and was approximately 12 µm, which is small relative to an average DM diameter of 1.7 mm. CONCLUSIONS: The BM opening has a good correspondence with the clinical DM seen in SDPs. NCO delineation seemed to be reliable. The BM and NCO are relatively planar in normal humans and can be further evaluated for longitudinal studies to observe stability.

Evidence of structural remodeling in the dyssynchronous failing heart.

Ventricular remodeling of both geometry and fiber structure is a prominent feature of several cardiac pathologies. Advances in MRI and analytical methods now make it possible to measure changes of cardiac geometry, fiber, and sheet orientation at high spatial resolution. In this report, we use diffusion tensor imaging to measure the geometry, fiber, and sheet architecture of eight normal and five dyssynchronous failing canine hearts, which were explanted and fixed in an unloaded state. We apply novel computational methods to identify statistically significant changes of cardiac anatomic structure in the failing and control heart populations. The results demonstrate significant regional differences in geometric remodeling in the dyssynchronous failing heart versus control. Ventricular chamber dilatation and reduction in wall thickness in septal and some posterior and anterior regions are observed. Primary fiber orientation showed no significant change. However, this result coupled with the local wall thinning in the septum implies an altered transmural fiber gradient. Further, we observe that orientation of laminar sheets become more vertical in the early-activated septum, with no significant change of sheet orientation in the late-activated lateral wall. Measured changes in both fiber gradient and sheet structure will affect both the heterogeneity of passive myocardial properties as well as electrical activation of the ventricles.