Intracranial pressure modulates aqueous humour dynamics of the eye.

KEY POINTS: An elevation in intracranial pressure (ICP) lowers conventional outflow facility (increases aqueous outflow resistance) of rat eyes. The reduction in outflow facility correlates with an increase in intraocular pressure (IOP). The effect of ICP elevation on outflow facility and IOP is blocked by TTX. The results indicate that aqueous humour dynamics is modulated by ICP-driven neural feedback from the brain. This feedback mechanism may act to stabilize translaminar pressure across the optic nerve head and may provide a new avenue for glaucoma therapy. ABSTRACT: While intraocular pressure (IOP) is a well-known risk factor for glaucoma, intracranial pressure (ICP) is attracting heightened interest because of its influence on optic nerve head biomechanics. Studies have shown that ICP can have marked impacts on posterior eye health by modifying the translaminar pressure gradient across the optic nerve. There is also growing evidence that IOP and ICP may be interconnected, although the mechanism of their putative interaction is unknown. We sought to test the hypothesis that ICP modulates IOP by altering aqueous humour dynamics. The anterior chamber and lateral ventricle of anaesthetized Brown-Norway rats were cannulated with fine-gauge needles connected to a programmable pump and saline reservoir, respectively. ICP was manipulated by varying reservoir height, and eye outflow facility (C) was determined from the pump flow rate required to hold IOP at different levels. C was 22 ± 4 nl/min/mmHg at resting ICP and 13 ± 3 nl/min/mmHg when ICP was raised 15 mmHg, a reduction of 41 ± 13% (n = 18). The decrease in outflow facility was independent of blood pressure, reversible, scaled with ICP elevation and correlated with increases in resting IOP. It was physiological in origin because C returned to baseline values after the rats were killed and corneal application of TTX though ICP remained elevated. These results indicate that a neural feedback mechanism driven by ICP regulates conventional outflow facility in rats. The mechanism may protect the eye from translaminar pressure swings and may offer a new target for glaucoma treatment.

The impact of anthropometric patient-phantom matching on organ dose: a hybrid phantom study for fluoroscopy guided interventions.

PURPOSE: To investigate the benefits and limitations of patient-phantom matching for determining organ dose during fluoroscopy guided interventions. METHODS: In this study, 27 CT datasets representing patients of different sizes and genders were contoured and converted into patient-specific computational models. Each model was matched, based on height and weight, to computational phantoms selected from the UF hybrid patient-dependent series. In order to investigate the influence of phantom type on patient organ dose, Monte Carlo methods were used to simulate two cardiac projections (PA/left lateral) and two abdominal projections (RAO/LPO). Organ dose conversion coefficients were then calculated for each patient-specific and patient-dependent phantom and also for a reference stylized and reference hybrid phantom. The coefficients were subsequently analyzed for any correlation between patient-specificity and the accuracy of the dose estimate. Accuracy was quantified by calculating an absolute percent difference using the patient-specific dose conversion coefficients as the reference. RESULTS: Patient-phantom matching was shown most beneficial for estimating the dose to heavy patients. In these cases, the improvement over using a reference stylized phantom ranged from approximately 50% to 120% for abdominal projections and for a reference hybrid phantom from 20% to 60% for all projections. For lighter individuals, patient-phantom matching was clearly superior to using a reference stylized phantom, but not significantly better than using a reference hybrid phantom for certain fields and projections. CONCLUSIONS: The results indicate two sources of error when patients are matched with phantoms: Anatomical error, which is inherent due to differences in organ size and location, and error attributed to differences in the total soft tissue attenuation. For small patients, differences in soft tissue attenuation are minimal and are exceeded by inherent anatomical differences. For large patients, difference in soft tissue attenuation can be large. In these cases, patient-phantom matching proves most effective as differences in soft tissue attenuation are mitigated. With increasing obesity rates, overweight patients will continue to make up a growing fraction of all patients undergoing medical imaging. Thus, having phantoms that better represent this population represents a considerable improvement over previous methods. In response to this study, additional phantoms representing heavier weight percentiles will be added to the UFHADM and UFHADF patient-dependent series.

Experimental glaucoma model with controllable intraocular pressure history.

Glaucoma-like neuropathies can be experimentally induced by disturbing aqueous outflow from the eye, resulting in intraocular pressure (IOP) changes that are variable in magnitude and time course and permanent in duration. This study introduces a novel method of glaucoma induction that offers researchers round-the-clock measurement and reversible control of IOP for the first time. One eye of Brown-Norway rats was implanted with a cannula tethered to a pressure sensor and aqueous reservoir. IOP was raised 10 mmHg for weeks-to-months in treated animals and unaltered in control animals. Counts of Brn3a-expressing retinal ganglion cells (RGCs) in implanted eyes were indistinguishable from non-implanted eyes in control animals and 15 ± 2%, 23 ± 4%, and 38 ± 4% lower in animals exposed to 2, 4, and 9 weeks of IOP elevation. RGC loss was greater in peripheral retina at 2 weeks and widespread at longer durations. Optic nerves also showed progressive degeneration with exposure duration, yet conventional outflow facility of implanted eyes was normal (24.1 ± 2.9 nl/min/mmHg) even after 9-weeks elevation. Hence, this infusion-based glaucoma model exhibits graded neural damage with unimpaired outflow pathways. The model further revealed a potentially-significant finding that outflow properties of rat eyes do not remodel in response to chronic ocular hypertension.

Aqueous Humor Dynamics of the Brown-Norway Rat.

Purpose: The study aimed to provide a quantitative description of aqueous humor dynamics in healthy rat eyes. Methods: One eye of 26 anesthetized adult Brown-Norway rats was cannulated with a needle connected to a perfusion pump and pressure transducer. Pressure-flow data were measured in live and dead eyes by varying pump rate (constant-flow technique) or by modulating pump duty cycle to hold intraocular pressure (IOP) at set levels (modified constant-pressure technique). Data were fit by the Goldmann equation to estimate conventional outflow facility (C) and unconventional outflow rate (Fun). Parameter estimates were respectively checked by inserting a shunt of similar conductance into the eye and by varying eye hydration methodology. Results: Rat IOP averaged 14.6 ± 1.9 mm Hg at rest. Pressure-flow data were repeatable and indistinguishable for the two perfusion techniques, yielding C = 0.023 ± 0.002 µL/min/mm Hg and Fun = 0.096 ± 0.024 µL/min. C was similar for live and dead eyes and increased upon shunt insertion by an amount equal to shunt conductance, validating measurement accuracy. At 100% humidity Fun dropped to 0.003 ± 0.030 µL/min. Physiological washout was not observed (-0.35 ± 0.65%/h), and trabecular anatomy looked normal. Conclusions: Rat aqueous humor dynamics are intermediate in magnitude compared to those in mice and humans, consistent with species differences in eye size. C does not change with time or death. Evaporation complicates measurement of Fun even when eyes are not enucleated. Absence of washout is a notable finding seen only in mouse and human eyes to date.

Physical validation of a Monte Carlo-based, phantom-derived approach to computed tomography organ dosimetry under tube current modulation.

PURPOSE: To physically validate the accuracy of a Monte Carlo-based, phantom-derived methodology for computed tomography (CT) dosimetry that utilizes organ doses from precomputed axial scans and that accounts for tube current modulation (TCM). METHODS: The output of a Toshiba Aquilion ONE CT scanner was modeled, based on physical measurement, in the Monte Carlo radiation transport code MCNPX (v2.70). CT examinations were taken of two anthropomorphic phantoms representing pediatric and adult patients (15-yr-old female and adult male) at various energies, in which physical organ dose measurements were made using optically stimulated luminescence dosimeters (OSLDs). These exams (chest-abdomen-pelvis) were modeled using organ dose data obtained from the computationally equivalent phantom of each anthropomorphic phantom. TCM was accounted for by weighting all organ dose contributions by both the relative attenuation of the phantom and the image-derived mA value (from the DICOM header) at the same z-extent (cranial-caudal direction) of the axial dose data. RESULTS: The root mean squares of percent difference in organ dose when comparing the physical organ dose measurements to the computational estimates were 21.2, 12.1, and 15.1% for the uniform (no attenuation weighting), weighted (computationally derived), and image-based methodologies, respectively. CONCLUSIONS: Overall, these data suggest that the Monte Carlo-based dosimetry presented in this work is viable for CT dosimetry. Additionally, for CT exams with TCM, local attenuation weighting of organ dose contributions from precomputed axial dosimetry libraries increases organ dose accuracy.