Jeffrey W. Kiel

Volume rendering in radiation treatment planning

Successful treatment planning in radiation therapy depends in part on understanding the spatial relationship between patient anatomy and the distribution of radiation dose. Several visualizations based on volume rendering that offer potential solutions to this problem are presented. The visualizations use region boundary surfaces to display anatomy, polygonal meshes to display treatment beams, and isovalue contour surfaces to display dose. To improve perception of spatial relationships, metallic shading, surface and solid texturing, synthetic fog, shadows, and other artistic devices are used. Also outlined is a method based on 3-D mip maps for efficiently generating perspective volume renderings and beams-eye views.<<ETX>>

Effects of latanoprost and timolol-XE on hydrodynamics in the normal eye

PURPOSE To compare the effects of latanoprost and timolol-XE on ocular pressure and perfusion in healthy adults, with respect to episcleral venous pressure. METHODS A double-masked, placebo-controlled crossover study of weeklong bedtime treatment with one drop of drug, with placebo contralaterally, followed by a 3-week washout and alternate-drug/contralateral-placebo repeat. Intraocular pressure was measured by applanation and by pneumotonometry, providing pulsatile ocular circulatory estimates. Measurements of episcleral venous pressure were obtained (Friberg method). RESULTS Twenty subjects participated (five men, 15 women; mean age, 39 years (range, 21 to 55 years); mean baseline intraocular pressure, 13.4 mm Hg). A greater decrease in intraocular pressure was seen among these subjects the morning after initiating treatment with latanoprost (-2.0 mm Hg; P <.0001) than with timolol-XE (-0.9 mm Hg; P =.051) (latanoprost versus timolol DeltaP =.008). This ocular hypotensive effect remained significant that evening with latanoprost (-3.2 mm Hg; P <.0001) but not with timolol XE (-1.0 mm Hg; P =.2). By the morning of day 8, mean intraocular pressure remained 3.2 mm Hg below baseline with latanoprost and 2.3 mm Hg below baseline with timolol-XE (P <.0001 for both drugs). Neither drug altered episcleral venous pressure. Among a subgroup of nine subjects with comparable intraocular pressure reductions with the two drugs, latanoprost treatment was associated with a 16.7% increase in mean pulsatile ocular blood flow (P =.04) through the weeklong treatment interval, consistently higher than during timolol-XE treatment of the same subjects. CONCLUSION Latanoprost caused an overnight decrease in intraocular pressure in normotensive normal eyes, and both drugs significantly reduced intraocular pressure within 1 week. Intraocular pressure remained higher than episcleral venous pressure throughout treatment with both drugs. Latanoprost was associated with enhanced pulsatile ocular perfusion not seen with timolol-XE treatment.

Ocular blood flow

Anatomy of the Ocular Vasculatures.- Determination of Ocular Blood Flows with the Microsphere Method.- Laser Doppler Flowmetry in Animals.- Ocular Blood Flow.- Measurement of Ocular Blood Flow: Angiography.- Measurement of retinal vessel diameters.- Laser Doppler Techniques for Ocular Blood Velocity and Flow.- Color Doppler Imaging.- Other approaches.- Systemic determinants.- Local determinants.- Neural Control of Ocular Blood Flow.- Endothelial control.- Retinal ischemia in relation to glaucoma and neuroprotection.- Ocular blood flow in diabetes: contribution to the microvascular lesions of diabetic retinopathy.- Age-Related Macular Degeneration: Hemodynamic changes.- The Role of Ocular Blood Flow Abnormalities in the Pathogenesis of Glaucoma.- Ocular Blood Flow in Disease: Other diseases.- Systemic diseases.

Ciliary Blood Flow and Aqueous Humor Production

Aqueous humor production is a metabolically active process sustained by the delivery of oxygen and nutrients and removal of metabolic waste by the ciliary circulation. This article describes our investigations into the relationship between ciliary blood flow and aqueous humor production. The results presented indicate that there is a dynamic relationship between ciliary blood flow and aqueous humor production, with production being blood flow independent above a critical level of perfusion, and blood flow dependent below it. The results also show that the plateau portion of the relationship shifts up or down depending on the level of secretory stimulation or inhibition, and that oxygen is one critical factor provided by ciliary blood flow. Also presented is a theoretical model of ocular hydrodynamics incorporating these new findings.

Depth-resolved blood oxygen saturation measurement by dual-wavelength photothermal (DWP) optical coherence tomography

Non-invasive depth-resolved measurement of hemoglobin oxygen saturation (SaO2) levels in discrete blood vessels may have implications for diagnosis and treatment of various pathologies. We introduce a novel Dual-Wavelength Photothermal (DWP) Optical Coherence Tomography (OCT) for non-invasive depth-resolved measurement of SaO2 levels in a blood vessel phantom. DWP OCT SaO2 is linearly correlated with blood-gas SaO2 measurements. We demonstrate 6.3% precision in SaO2 levels measured a phantom blood vessel using DWP-OCT with 800 and 765 nm excitation wavelengths. Sources of uncertainty in SaO2 levels measured with DWP-OCT are identified and characterized.

Autoregulation of canine gastric mucosal blood flow

Although autoregulation of total blood flow has been demonstrated in the stomach, autoregulation of gastric mucosal blood flow has not been investigated due to the limitations of previously available mucosal blood flow measuring techniques. We recently evaluated laser-Doppler velocimetry for use in the stomach and found it to yield continuous, superficial measurements of either mucosal or muscularis blood flow. In the present study, simultaneous measurements of total, mucosal, and muscularis blood flows and arteriovenous oxygen difference were made during step decreases in perfusion pressure in chambered segments of resting canine stomach. As perfusion pressure was decreased from 180 to 35 mmHg, oxygen consumption remained relatively constant at 1.5 ml/min X 100 g and only became blood flow-dependent when perfusion pressure was set below 90 mmHg and total blood flow fell below 35 ml/min X 100 g. Oxygen consumption was maintained partly by increased oxygen extraction; however, there was also a progressive increase in the tendency for total blood flow autoregulation after each drop in perfusion pressure. Mucosal blood flow was also well autoregulated over the physiologic range of perfusion pressure and remained relatively constant during the plateau portion of the oxygen consumption curve. Our results indicate that in the resting stomach, oxygen consumption is maintained by changes in oxygen extraction in conjunction with autoregulation of mucosal and total blood flow.

Lamina-Specific Functional MRI of Retinal and Choroidal Responses to Visual Stimuli

PURPOSE To demonstrate lamina-specific functional magnetic resonance imaging (MRI) of retinal and choroidal responses to visual stimulation of graded luminance, wavelength, and frequency. MATERIALS AND METHODS High-resolution (60 × 60 μm) MRI was achieved using the blood-pool contrast agent, monocrystalline iron oxide nanoparticles (MION) and a high-magnetic-field (11.7 T) scanner to image functional changes in the normal rat retina associated with various visual stimulations. MION functional MRI measured stimulus-evoked blood-volume (BV) changes. Graded luminance, wavelength, and frequency were investigated. Stimulus-evoked fMRI signal changes from the retinal and choroidal vascular layers were analyzed. RESULTS MRI revealed two distinct laminar signals that corresponded to the retinal and choroidal vascular layers bounding the retina and were separated by the avascular layer in between. The baseline outer layer BV index was 2-4 times greater than the inner layer BV, consistent with higher choroidal vascular density. During visual stimulation, BV responses to flickering light of different luminance, frequency, and wavelength in the inner layer were greater than those in the outer layer. The inner layer responses were dependent on luminance, frequency, and wavelength, whereas the outer layer responses were not, suggesting differential neurovascular coupling between the two vasculatures. CONCLUSIONS This is the first report of simultaneous resolution of layer-specific functional responses of the retinal and choroid vascular layers to visual stimulation in the retina. This imaging approach could have applications in early detection and longitudinal monitoring of retinal diseases where retinal and choroidal hemodynamics may be differentially perturbed at various stages of the diseases.

Local control of canine gastric mucosal blood flow.

The hemodynamic responses to venous pressure elevation and the effect of metabolic stimulation on reactive hyperemia and autoregulation were assessed in chambered segments of the canine gastric corpus perfused by a pressurized reservoir. Arteriovenous oxygen difference, mucosal pH, and total, mucosal, and muscularis blood flow were monitored continuously. Pentagastrin increased acid secretion, oxygen consumption, and both total and mucosal blood flow. Before and after pentagastrin, the magnitude of reactive hyperemia was correlated with the occlusion duration. During stepwise reductions in perfusion pressure, oxygen consumption was relatively constant and blood flow-independent over most of the pressure range. Mucosal blood flow was well maintained except at the lowest perfusion pressure. Pentagastrin did not enhance autoregulation in the mucosa or muscularis, but did enhance the autoregulation of total blood flow. A myogenic vasoconstriction occurred during 20-mmHg venous pressure elevations. Our results indicate that both metabolic and myogenic mechanisms regulate the gastric mucosal circulation.

Effect of AR-13324 on episcleral venous pressure in Dutch belted rabbits

Abstract Purpose: AR-13324 is a potential new drug for the treatment of patients with glaucoma that has been shown to lower intraocular pressure (IOP) by increasing trabecular outflow facility and decreasing aqueous production. The present study tested the hypothesis that AR-13324 also lowers IOP by reducing episcleral venous pressure (EVP). Methods: In Dutch Belted (DB) rabbits (n=11), arterial pressure (AP), IOP, carotid blood flow (BFcar), heart rate (HR), and EVP were measured invasively. Animals were dosed with AR-13324 (0.04%, topical, n=6) once daily for 3 days. On day 3, the animals were anesthetized, and then, measurements were obtained before dosing with AR-13324 or vehicle (n=5) and for 3 h after dosing. The data (mean±standard error of the mean) were analyzed by repeated measures ANOVA with post hoc testing. Retrospective baseline data from prior similar studies in New Zealand White rabbits were also compiled. Results: Baseline values were as follows: AP, 101±3 mmHg; IOP; 33±3 mmHg; EVP, 16±1 mmHg; BFcar, 41±4 mL/min; and HR, 330±6 bpm. Three hours after AR-13324 dosing, IOP was reduced by 39%±7% (P<0.001) and EVP decreased by 35%±4% (P<0.05); after vehicle dosing, IOP was reduced by 24%±4% (P<0.05) and EVP increased by 25%±5% (P<0.05). AP, BFcar, and HR were unchanged. Conclusions: AR-13324 produces statistically significant lowering of EVP in DB rabbits. In addition, the baseline values for AP, IOP, EVP, BFcar, and HR in the DB rabbit are higher than those previously reported in the New Zealand rabbit.

Effects of Dorzolamide on Choroidal Blood Flow, Ciliary Blood Flow, and Aqueous Production in Rabbits

PURPOSE To determine the effects of topical dorzolamide (a carbonic anhydrase inhibitor) on choroidal and ciliary blood flow and the relationship between ciliary blood flow and aqueous flow. METHODS The experiments were performed in four groups of pentobarbital-anesthetized rabbits treated with topical dorzolamide (2%, 50 microL). In all groups, intraocular pressure (IOP) and mean arterial pressure (MAP) at the eye level were measured continuously by direct cannulation. In group 1, aqueous flow was measured by fluorophotometry before and after dorzolamide treatment. In group 2, aqueous flow was measured after dorzolamide at normal MAP and while MAP was held constant at 80, 55, or 40 mm Hg with occluders on the aorta and vena cava. In group 3, the same MAP levels were used, and ciliary blood flow was measured transsclerally by laser Doppler flowmetry (LDF). In group 4, choroidal blood flow was measured by LDF with the probe tip positioned in the vitreous over the posterior pole during ramp increases and decreases in MAP before and after dorzolamide. RESULTS Dorzolamide lowered IOP by 19% (P < 0.01) and aqueous flow by 17% (P < 0.01), and increased ciliary blood flow by 18% (P < 0.01), which was associated with a significant reduction in ciliary vasculature resistance (-7%, P < 0.01). Dorzolamide shifted the relationship between ciliary blood flow and aqueous flow downward relative to the previously determined control relationship in the rabbit. Dorzolamide did not alter choroidal blood flow, choroidal vascular resistance, or the choroidal pressure flow relationship. CONCLUSIONS Acute topical dorzolamide is a ciliary vasodilator and has a direct inhibitory effect on aqueous production, but it does not have a detectable effect on choroidal hemodynamics at the posterior pole in the rabbit.