Functional ultrasound imaging of the human spinal cord.

Utilizing the first in-human functional ultrasound imaging (fUSI) of the spinal cord, we demonstrate the integration of spinal functional responses to electrical stimulation. We record and characterize the hemodynamic responses of the spinal cord to a neuromodulatory intervention commonly used for treating pain and increasingly used for the restoration of sensorimotor and autonomic function. We found that the hemodynamic response to stimulation reflects a spatiotemporal modulation of the spinal cord circuitry not previously recognized. Our analytical capability offers a mechanism to assess blood flow changes with a new level of spatial and temporal precision in vivo and demonstrates that fUSI can decode the functional state of spinal networks in a single trial, which is of fundamental importance for developing real-time closed-loop neuromodulation systems. This work is a critical step toward developing a vital technique to study spinal cord function and effects of clinical neuromodulation.

A network analysis of developing brain cultures.

We recorded electrical activity from four developing embryonic brain cultures (4-40 days in vitro) using multielectrode arrays (MEAs) with 60 embedded electrodes. Data were filtered for local field potentials (LFPs) and downsampled to 1 ms to yield a matrix of time series consisting of 60 electrode × 60 000 time samples per electrode per day per MEA. Each electrode time series was rendered stationary and nonautocorrelated by applying an ARIMA (25, 1, 1) model and taking the residuals (i.e. innovations). Two kinds of analyses were then performed. First, a pairwise crosscorrelation (CC) analysis (±25 1 ms lags) revealed systematic changes in CC with lag, day in vitro (DIV), and inter-electrode distance. Specifically, (i) positive CCs were 1.76× more prevalent and 1.44× stronger (absolute value) than negative ones, and (ii) the strength of CC increased with DIV and decreased with lag and inter-electrode distance. Second, a network equilibrium analysis was based on the instantaneous (1 ms resolution) logratio of the number of electrodes that were above or below their mean, called simultaneous departure from equilibrium, SDE. This measure possesses a major computational advantage over the pairwise crosscorrelation approach because it is very simple and fast to calculate, an important factor for the analysis of large networks. The results obtained with SDE covaried highly with CC over DIV, which further validates the usefulness of this measure as a computationally effective tool for large scale network analysis.

Ocular and orbital blood flow velocity in patients with peripheral vascular disease and diabetes treated with intravenous prostaglandin E1.

The purpose of this study was to evaluate the effect of intravenous prostaglandin E1 (PGE1) on the flow velocity of the ophthalmic artery and the central retinal artery in patients with peripheral vascular disease manifested by intermittent claudication. The flow velocity of these vessels is frequently decreased in vascular patients. Since these patients were already being treated with PGE1 for their intermittent claudication, the authors wanted to evaluate the effect on the flow velocity of the ocular vessels as well. A randomized 21-week study of two groups of vascular patients was performed. The first group had intermittent claudication. The second group had intermittent claudication and were also diabetics. Both groups were treated with intravenous PGE1 for their intermittent claudication. Using the color Doppler, the flow velocities of the ophthalmic artery and central retinal artery were measured before and after the intravenous treatment. Before treatment, the flow velocity of the ophthalmic artery and the central retinal artery was decreased when compared to that in the normals. After treatment, there was a significant increase in the systolic and diastolic phases of the flow velocity in both arteries. The systolic flow velocity increased by as much as 40%, and the diastolic flow velocity increased by as much as 80%. The flow velocities of the ophthalmic artery and the central retinal artery are frequently decreased in certain ocular diseases, and this decreased flow may contribute to the ocular pathology. If intravenous PGE1 is able to increase the flow velocity of these vessels in patients with peripheral vascular disease, it is possible that it is also able to increase the flow velocity of these vessels in patients with ocular disease as well. Intravenous PGE1 may prove to be a useful adjunct therapy in eyes when ischemia is part of the pathology.

Foveal cone function in nonproliferative diabetic retinopathy and macular edema.

PURPOSE: To study results of foveal cone electroretinography (ERG) in patients with nonproliferative diabetic retinopathy (NPDR), with and without clinically significant macular edema (CSME). METHODS: Electroretinograms of foveal cones were elicited, with a dual-beam stimulator-ophthalmoscope, from 18 consecutive patients with bilateral NPDR and unilateral CSME. RESULTS: Analysis of resulting data revealed that mean amplitude was significantly lower in eyes with CSME and in eyes without CSME., compared with that in normal eyes. Mean implicit time was significantly longer in eyes with CSME compared with that in normal eyes, but in eyes of diabetic patients without CSME., mean implicit time was the same as that in normal eyes. Amplitudes were directly correlated and implicit times were inversely correlated with best-corrected Snellen visual acuity in eyes with and without CSME. Eyes with CSME had significantly lower amplitudes and longer implicit times than their fellow eyes without CSME. In addition, eyes with NPDR, with or without CSME, did not exhibit the normal rise in amplitude with increasing duration of light exposure. CONCLUSIONS: Electroretinographic findings showed abnormalities in foveal cone responses in eyes with NPDR, particularly in the presence of CSME. These results may support a functional role for outer retinal dysfunction in patients with diabetic retinopathy and loss of central vision.

Doppler ultrasonography of the central retinal artery by duplex scanning.

PURPOSE: To present duplex scanning of the central retinal artery, which the authors have termed duplex scanner imaging, as an alternative to color Doppler imaging in the evaluation of retinal blood flow velocity, and to show the difference in measurements obtained with the two different techniques. METHODS: The high-resolution ATL-Ultramark 4 duplex scanner (Advanced Technology Laboratories, Bothell, WA) with the variable focus access probe was used to measure blood flow velocity of the central retinal artery in the eyes of 48 healthy volunteers. RESULTS: Using this technique the peak systolic flow velocity (+/- standard deviation [SD]) of the central retinal artery was 36.6 +/- 10.8 cm/sec, and the end diastolic flow velocity was 12.6 +/- 3.7 cm/sec. CONCLUSION: The flow velocity measurements of the central retinal artery obtained with this technique were much higher than those obtained by other authors using color Doppler imaging (9.6 cm/sec for the peak systolic flow velocity, and 4.7 cm/sec for the end diastolic flow velocity). The authors propose duplex scanner imaging as an alternative to color Doppler imaging for evaluating retinal blood flow velocity. The duplex scanner also can be used to measure the flow velocity of orbital vessels.

Doppler ultrasonography of the central retinal artery in patients with diabetes and vascular disease treated with topical timolol.

Using high-resolution duplex scanning it is possible to evaluate the blood flow velocity in the central retinal artery of the eye. Four different patient groups were studied with this technique: normals, diabetics with a decreased flow, diabetics with an increased flow and vascular patients with a decreased flow. The eyes of these patients were then treated with topical timolol and the flow measured again. An increase in the flow was found in three of the four groups. This increased flow velocity may be due to a vasodilatory effect of timolol. The results are presented and discussed.

Doppler ultrasonography in giant cell arteritis.

A patient with biopsy negative giant cell arteritis was examined and treated by our group. Since in some cases the visual loss in this disease is due to a central retinal artery occlusion, a technique to evaluate the blood flow velocity in this artery would be useful. The Duplex scanner was utilized by us in this patient to study the blood flow velocity of the central retinal artery. The flow velocity was reduced. The patient was treated with systemic steroids which lead to clinical and symptomatic improvement. After the treatment with steroids the Duplex scanner was again used to study the flow velocity of the central retinal artery. The blood flow velocity improved. We think that Doppler ultrasonography may be useful in the diagnosis of and in monitoring the treatment of some cases of giant cell arteritis.

Emergence of cornea guttata in donor tissue: a cause of late graft failure.

Analysis of 321 failed full-thickness corneal transplant specimens submitted for histopathological examination over a 10-year period has identified 10 instances in which the defect appeared to have been caused by the development of cornea guttata in the donor tissue. The primary condition necessitating keratoplasty in 5 of the 10 patients was Fuchs' endothelial dystrophy but, given the limited capacity of corneal endothelium for regeneration, it is considered unlikely that the defect in the grafts represented a recurrence. In 7 of 8 cases for which the duration of graft survival was known the endothelial disorder presented as a long-term event and it is assumed that the condition was not present at the time of the keratoplasty. The rare emergence of Fuchs' dystrophy in donor transplant tissue should be added to the potential causes of late graft failure.