Optical coherence tomography reveals light-dependent retinal responses in Alzheimer's disease.

Spectral-domain optical coherence tomography (SD-OCT) is an accessible clinical tool for measuring structural changes to the retina, and increasingly as a biomarker for brain-predominant neurodegenerative diseases like Alzheimer's. Information about retinal function can also be extracted from OCT images, but is under-studied, with literature examples often employing challenging protocols or requiring specialized hardware. The first goal of this study was to verify that functional retinal imaging was feasible with a commercially-available SD-OCT device and a clinically practical protocol. Inspired by methods from other functional imaging modalities, we acquired images while repeatedly cycling lights on and off, and spatially normalized retinas to facilitate intra- and inter-individual analyses. In eight healthy young adults, light-dependent increases in reflectivity were easily demonstrated at photoreceptor inner and outer segments, changing by ~7% in bright light and ~3% in dim light. Bright light elicited a subtle (~2%) but consistent light-dependent decrease in reflectivity through much of the rest of the retina, including the avascular outer nuclear layer (ONL). We speculated that some of these changes are influenced by glial function - as through water management - a topic of high interest in neurodegenerative diseases that may involve the glymphatic system. Functional abnormalities in patients with antibodies against aquaporin-4 (n â€‹= â€‹3) supported this interpretation. We next compared patients with early-onset Alzheimer's disease (n â€‹= â€‹14) to age-matched controls (n â€‹= â€‹14), revealing that patients had a relatively exaggerated light-induced change in ONL reflectivity (p â€‹< â€‹0.05). Because these measurements can be obtained within 30 â€‹min, regular use in research and limited clinical settings is feasible.

Acute Stroke Despite Dabigatran Anticoagulation Treated with Idarucizumab and Intravenous Tissue Plasminogen Activator.

Dabigatran is a direct thrombin inhibitor used to reduce the risk of stroke in patients with nonvalvular atrial fibrillation. For patients who present with an acute stroke despite dabigatran therapy, clinical data on the use of intravenous tissue plasminogen activator (IV-tPA) is limited. There is an anticipated increased risk of symptomatic intracranial hemorrhage (sICH) when using IV-tPA in patients on dabigatran therapy. In 2015, the humanized monoclonal antibody fragment idarucizumab was approved for rapid (minutes) reversal of anticoagulant effects of dabigatran. Dabigatran reversal with idarucizumab before administration of IV-tPA might reduce the risk of sICH. We report a case of a 69-year-old stroke patient on dabigatran for paroxysmal atrial fibrillation who presented with an initial National Institutes of Health Stroke Scale (NIHSS) of 12. There was no early evidence of ischemic stroke or hemorrhage on head computed tomography, and coagulation studies implied therapeutic dabigatran levels. After controlling blood pressure, dabigatran was reversed with idarucizumab, and IV-tPA was administrated beginning 197 minutes after he was last seen at his baseline. Subsequent brain magnetic resonance imaging showed 2 punctate infarcts in the left temporal lobe and occipital lobe with no evidence of hemorrhage. The patient was discharged with an NIHSS of 1. Telephone follow-up 2 months later indicated that he was at his prestroke baseline, except for a complaint of worsened short-term memory. Idarucizumab reversal of dabigatran may reduce the risk of sICH and should be considered for acute stroke patients arriving in the IV-tPA time window.

Cocaine-induced locomotor sensitization in rats correlates with nucleus accumbens activity on manganese-enhanced MRI.

A long-standing goal of substance abuse research has been to link drug-induced behavioral outcomes with the activity of specific brain regions to understand the neurobiology of addiction behaviors and to search for drug-able targets. Here, we tested the hypothesis that cocaine produces locomotor (behavioral) sensitization that correlates with increased calcium channel-mediated neuroactivity in brain regions linked with drug addiction, such as the nucleus accumbens (NAC), anterior striatum (AST) and hippocampus, as measured using manganese-enhanced MRI (MEMRI). Rats were treated with cocaine for 5 days, followed by a 2-day drug-free period. The following day, locomotor sensitization was quantified as a metric of cocaine-induced neuroplasticity in the presence of manganese. Immediately following behavioral testing, rats were examined for changes in calcium channel-mediated neuronal activity in the NAC, AST, hippocampus and temporalis muscle, which was associated with behavioral sensitization using MEMRI. Cocaine significantly increased locomotor activity and produced behavioral sensitization compared with saline treatment of control rats. A significant increase in MEMRI signal intensity was determined in the NAC, but not AST or hippocampus, of cocaine-treated rats compared with saline-treated control rats. Cocaine did not increase signal intensity in the temporalis muscle. Notably, in support of our hypothesis, behavior was significantly and positively correlated with MEMRI signal intensity in the NAC. As neuronal uptake of manganese is regulated by calcium channels, these results indicate that MEMRI is a powerful research tool to study neuronal activity in freely behaving animals and to guide new calcium channel-based therapies for the treatment of cocaine abuse and dependence.

Loss of caveolin-1 impairs retinal function due to disturbance of subretinal microenvironment.

Caveolin-1 (Cav-1), an integral component of caveolar membrane domains, is expressed in several retinal cell types, including photoreceptors, retinal vascular endothelial cells, Müller glia, and retinal pigment epithelium (RPE) cells. Recent evidence links Cav-1 to ocular diseases, including autoimmune uveitis, diabetic retinopathy, and primary open angle glaucoma, but its role in normal vision is largely undetermined. In this report, we show that ablation of Cav-1 results in reduced inner and outer retinal function as measured, in vivo, by electroretinography and manganese-enhanced MRI. Somewhat surprisingly, dark current and light sensitivity were normal in individual rods (recorded with suction electrode methods) from Cav-1 knock-out (KO) mice. Although photoreceptor function was largely normal, in vitro, the apparent K(+) affinity of the RPE-expressed α1-Na(+)/K(+)-ATPase was decreased in Cav-1 KO mice. Cav-1 KO retinas also displayed unusually tight adhesion with the RPE, which could be resolved by brief treatment with hyperosmotic medium, suggesting alterations in outer retinal fluid homeostasis. Collectively, these findings demonstrate that reduced retinal function resulting from Cav-1 ablation is not photoreceptor-intrinsic but rather involves impaired subretinal and/or RPE ion/fluid homeostasis.

Feasibility of Remote Unsupervised Cognitive Screening With SATURN in Older Adults.

Widespread cognitive test screening as part of tele-public health initiatives necessitates a test that is self-administered online and automatically scored, with no clinician effort. The feasibility of unsupervised cognitive screening is unclear. We adapted the Self-Administered Tasks Uncovering Risk of Neurodegeneration (SATURN) to make it suitable for self-administration and automatic scoring. A sample of 364 healthy older adults completed SATURN via a web browser, in a fully independent manner. SATURN's overall score was not modulated by gender, education, reading speed, the time of day at which the test was taken, or an individual's familiarity with technology. SATURN proved extremely portable across operating systems. Importantly, comments from participants reported satisfaction with the experience and the clarity of the instructions. SATURN represents a fast and easy screening tool that can be used for a first assessment, during a routine test or clinical evaluation, or during periodic health monitoring, in person or remotely.

Light-dependent changes in outer retinal water diffusion in rats in vivo.

PURPOSE: To test the hypothesis that in rats, intraretinal light-dependent changes on diffusion-weighted magnetic resonance imaging (MRI) in vivo are consistent with known retinal layer-specific physiology. METHODS: In male Sprague-Dawley rats, retinal morphology (thickness, extent, surface area, volume) and intraretinal profiles of the apparent diffusion coefficient (ADC, i.e., water mobility) parallel and perpendicular to the optic nerve were measured in vivo using quantitative MRI methods during light and dark stimulation. RESULTS: The parallel ADC in the posterior half of the avascular, photoreceptor-dominated outer retina was significantly higher in light than dark, and this pattern was reversed (dark>light) in the anterior outer retina. The perpendicular ADC in the posterior outer retina was similar in light and dark, but was significantly higher in dark than light in the anterior outer retina. No light-dark changes in the inner retina were noted. CONCLUSIONS: We identified light-dependent intraretinal diffusion changes that reflected established stimulation-based changes in outer retinal hydration. These findings are expected to motivate future applications of functional diffusion-based MRI in blinding disorders of the outer retina.

Acute systemic 11-cis-retinal intervention improves abnormal outer retinal ion channel closure in diabetic mice.

PURPOSE: To test the hypothesis that in dark-adapted diabetic mice subnormal manganese uptake in the outer retina can be ameliorated with exogenous 11-cis-retinal intervention. METHODS: Three groups were studied: age-matched controls and mice that had been diabetic for 3 months with and without acute, systemic 11-cis-retinal treatment administered 30 min before the manganese injection. Mice in each group were examined with manganese-enhanced magnetic resonance imaging (MEMRI) to assess central intraretinal manganese uptake and extraocular muscle manganese uptake. Bodyweights and glycated hemoglobin were determined. RESULTS: Both diabetic groups had lower bodyweights and higher glycated hemoglobin levels relative to controls; no differences in these parameters between diabetic groups were noted. No substantial differences in muscle uptake were noted between any of the groups. Diabetes produced a subnormal intraretinal uptake of manganese; acute exogenous 11-cis-retinal significantly corrected only outer retinal uptake, although not to control levels. CONCLUSIONS: The present results provide for the first time evidence that raises the possibility of a critical role of 11-cis-retinal, a key participant of the visual cycle, in diabetes-evoked outer retinal dysfunction.

Same-session functional assessment of rat retina and brain with manganese-enhanced MRI.

Manganese-enhanced MRI (MEMRI) is a powerful non-invasive approach for objectively measuring either retina or binocular visual brain activity in vivo. In this study, we investigated the sensitivity of MEMRI to monocular stimulation using a new protocol for providing within-subject functional comparisons in the retina and brain in the same scanning session. Adult Sprague Dawley or Long-Evans rats had one eye covered with an opaque patch. After intraperitoneal Mn(2+) administration on the following day, rats underwent visual stimulation for 8h. Animals were then anesthetized, and the brain and each eye examined by MEMRI. Function was assessed through pairwise comparisons of the patched (dark-adapted) versus unpatched (light-exposed) eyes, and of differentially-stimulated brain structures - the dorsal lateral geniculate nucleus, superior colliculus, and visual cortical regions - contralateral to the patched versus unpatched eye. As expected, Mn(2+) uptake was greater in the outer retina of dark-adapted, relative to light-exposed, eyes (P<0.05). Contralateral to the unpatched eye, significantly more Mn(2+) uptake was found throughout the visual brain regions than in the corresponding structures contralateral to the patched eye (P<0.05). Notably, this regional pattern of activity corresponded well to previous work with monocular stimulation. No stimulation-dependent differences in Mn(2+) uptake were observed in negative control brain regions (P>0.05). Post-hoc assessment of functional data by animal age and strain revealed no significant effects. These results demonstrate, for the first time, the acquisition of functional MRI data from the eye and visual brain regions in a single scanning session.

Intraretinal calcium channels and retinal morbidity in experimental retinopathy of prematurity.

PURPOSE: To test the hypothesis that intraretinal calcium channels participate in retinal morbidity in a variable oxygen (VO) model of retinopathy of prematurity. METHODS: In control and VO Long Evans (LE) rats, either untreated or treated with voltage- or ligand-gated calcium channel antagonists, we measured retinal neovascular (NV) incidence and severity (adenosine diphosphatase staining), and retinal thickness and intraretinal ion channel activity (manganese-enhanced magnetic resonance imaging). Comparisons with the commonly studied Sprague Dawley rats were performed. Visual performance (optokinetic tracking) in untreated VO LE rats was also evaluated. RESULTS: In control LE rats, specific L-type voltage calcium channel antagonism, but not ligand-gated channel blockers, suppressed retinal manganese accumulation, while the inhibition of L-type channels normalized intraretinal uptake in VO LE rats. VO LE rats developed more severe NV than VO Sprague Dawley rats. Following VO, both strains demonstrated significant and similar degrees of retinal thinning and supernormal intraretinal manganese uptake. However, over time, intraretinal uptake remained elevated only in VO LE rats. Visual performance was subnormal in VO LE rats. L-type voltage-gated calcium channel antagonism reduced NV severity by 28% (p<0.05) in experimental LE rats compared to that in the control group. CONCLUSIONS: Abnormal intraretinal calcium channel activity is linked with retinal morbidity in experimental retinopathy of prematurity.

A clinical decision rule predicting outcomes of emergency department patients with altered mental status.

STUDY OBJECTIVE: Approximately 5% of emergency department patients present with altered mental status (AMS). AMS is diagnostically challenging because of the wide range of causes and is associated with high mortality. We sought to develop a clinical decision rule predicting admission risk among emergency department (ED) patients with AMS. METHODS: Using retrospective chart review of ED encounters for AMS over a 2-month period, we recorded causes of AMS and numerous clinical variables. Encounters were split into those admitted to the hospital ("cases") and those discharged from the ED ("controls"). Using the first month's data, variables correlated with hospital admission were identified and narrowed using univariate and multivariate statistics, including recursive partitioning. These variables were then organized into a clinical decision rule and validated on the second month's data. The decision rule results were also compared to 1-year mortality. RESULTS: We identified 351 encounters for AMS over a 2-month period. Significant contributors to AMS included intoxication and chronic disorder decompensation. ED data predicting hospital admission included vital sign abnormalities, select lab studies, and psychiatric/intoxicant history. The decision rule sorted patients into low, moderate, or high risk of admission (11.1%, 44.3%, and 89.1% admitted, respectively) and was predictive of 1-year mortality (low-risk group 1.8%, high-risk group 34.3%). CONCLUSIONS: We catalogued common causes for AMS among patients presenting to the ED, and our data-driven decision tool triaged these patients for risk of admission with good predictive accuracy. These methods for creating clinical decision rules might be further studied and improved to optimize ED patient care.

Functional regulation of an outer retina hyporeflective band on optical coherence tomography images.

Human and animal retinal optical coherence tomography (OCT) images show a hyporeflective band (HB) between the photoreceptor tip and retinal pigment epithelium layers whose mechanisms are unclear. In mice, HB magnitude and the external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness appear to be dependent on light exposure, which is known to alter photoreceptor mitochondria respiration. Here, we test the hypothesis that these two OCT biomarkers are linked to metabolic activity of the retina. Acetazolamide, which acidifies the subretinal space, had no significant impact on HB magnitude but produced ELM-RPE thinning. Mitochondrial stimulation with 2,4-dinitrophenol reduced both HB magnitude and ELM-RPE thickness in parallel, and also reduced F-actin expression in the same retinal region, but without altering ERG responses. For mice strains with relatively lower (C57BL/6J) or higher (129S6/ev) rod mitochondrial efficacy, light-induced changes in HB magnitude and ELM-RPE thickness were correlated. Humans, analyzed from published data captured with a different protocol, showed a similar light-dark change pattern in HB magnitude as in the mice. Our results indicate that mitochondrial respiration underlies changes in HB magnitude upstream of the pH-sensitive ELM-RPE thickness response. These two distinct OCT biomarkers could be useful indices for non-invasively evaluating photoreceptor mitochondrial metabolic activity.

Light-dependant intraretinal ion regulation by melanopsin in young awake and free moving mice evaluated with manganese-enhanced MRI.

PURPOSE: To test the hypothesis that in young, functionally blind mice, light-dependent intraretinal ion regulation occurs via melanopsin. METHODS: Postnatal day (P) 7 wild type (WT, C57Bl/6) and melanopsin knockout (KO, opn4-/-, B6129) mice were light or dark adapted. Awake and freely moving animals were injected intraperitoneally (ip) with MnCl(2). Four hours later, the mice in both groups were anesthetized and studied with manganese-enhanced MRI (MEMRI) to measure the extent of intraretinal uptake of manganese and whole retinal thicknesses. RESULTS: In control P7 mice, light exposure increased (p<0.05) retinal manganese uptake over that in dark. This difference was observed throughout most of the retina. In P7 KO mice, intraretinal manganese uptake did not differ from that in age-matched dark-adapted WT mice, and was not light-dependent. No differences in whole retinal thickness were noted between groups. CONCLUSIONS: First time evidence is presented which demonstrates intraretinal ion regulation by melanopsin in vivo.

Retinal channelrhodopsin-2-mediated activity in vivo evaluated with manganese-enhanced magnetic resonance imaging.

PURPOSE: Ectopic expression of light-sensitive proteins, such as channelrhodopsin-2, represent a novel approach for restoring light-detection capabilities to degenerated retina. A noninvasive method that can detect light-mediated activities of such light-sensitive proteins in the retina in vivo would be important for correlating expression patterns and retinal function. In this study, we tested the hypothesis that retinal uptake of manganese, measured noninvasively with manganese-enhanced magnetic resonance imaging (MEMRI), is a biomarker of channelrhodopsin-2-mediated activity in vivo. METHODS: The eyes of 3-month-old rd1/rd1 mice were either untreated ("uninjected," negative control) or injected intravitreally with either saline ("saline," negative control) or adeno-associated virus carrying a fusion construct of channelopsin-2 (Chop2) and green fluorescent protein (GFP; "Chop2-GFP"). MEMRI examination was performed 2 months later on either dark or continuous bright blue light-exposed mice to assess the distribution and extent of manganese uptake in the retina and optic nerve. In separate experiments, MEMRI was used to map laminar accumulation of manganese vertically through the retina. For comparison, Chop2-GFP expression was evaluated in whole mounts and vertical sections of virus-infected retinas and optic nerve. RESULTS: In the two control groups (regardless of lighting exposure) and between the control groups and the dark-exposed virus-treated eyes, retinal and optic nerve uptake of manganese did not differ. In light-exposed virus-treated eyes, manganese uptake in the retina and optic nerve was significantly greater relative to the other groups. In a retinal cross-section, manganese accumulation in light-exposed virus-treated eyes was spatially matched with Chop2-GFP expression in the optic nerve and all remaining retinal layers except the inner nuclear layer. CONCLUSIONS: First-time evidence is presented indicating the usefulness of measuring intraretinal manganese accumulation as a noninvasive biomarker of channelrhodopsin-2-mediated activity in vivo.

Validation of SATURN, a free, electronic, self-administered cognitive screening test.

BACKGROUND: Cognitive screening is limited by clinician time and variability in administration and scoring. We therefore developed Self-Administered Tasks Uncovering Risk of Neurodegeneration (SATURN), a free, public-domain, self-administered, and automatically scored cognitive screening test, and validated it on inexpensive (<$100) computer tablets. METHODS: SATURN is a 30-point test including orientation, word recall, and math items adapted from the Saint Louis University Mental Status test, modified versions of the Stroop and Trails tasks, and other assessments of visuospatial function and memory. English-speaking neurology clinic patients and their partners 50 to 89 years of age were given SATURN, the Montreal Cognitive Assessment (MoCA), and a brief survey about test preferences. For patients recruited from dementia clinics (n = 23), clinical status was quantified with the Clinical Dementia Rating (CDR) scale. Care partners (n = 37) were assigned CDR = 0. RESULTS: SATURN and MoCA scores were highly correlated (P < .00001; r = 0.90). CDR sum-of-boxes scores were well-correlated with both tests (P < .00001) (r = -0.83 and -0.86, respectively). Statistically, neither test was superior. Most participants (83%) reported that SATURN was easy to use, and most either preferred SATURN over the MoCA (47%) or had no preference (32%). DISCUSSION: Performance on SATURN-a fully self-administered and freely available (https://doi.org/10.5061/dryad.02v6wwpzr) cognitive screening test-is well-correlated with MoCA and CDR scores.

Manganese-enhanced MRI of layer-specific activity in the visual cortex from awake and free-moving rats.

Cortical responses to visual stimulation have been studied extensively in the rodent, but often require post-stimulation ex vivo examination of the tissue. Here, we test the hypothesis that visual stimulus-dependent cortical activity from awake and free-moving rats can be encoded following systemically administered MnCl(2), and activity subsequently readout using manganese-enhanced MRI (MEMRI), a technique that can be performed without sacrificing the animal. Unanesthetized Sprague-Dawley rats, with or without systemic injection of MnCl(2), were maintained for 8 h in either a visually stimulating environment or darkness. To identify vision-dependent changes in cortical activity, animals were anesthetized and cortices were examined by 3D RARE MEMRI. Mean signal intensities in sub-cortical regions (e.g., superior colliculus and the lateral geniculate), and cortical regions (primary and accessory visual cortices) were compared. Cortex linearization was performed to aid in layer-specific signal intensity comparisons. Manganese administration alone globally increased signal intensity in the brain (P<0.0001). In visually stimulated and unstimulated rats, layer-specific analysis revealed that stimulated rats had on average significantly (P<0.05) higher signal intensities in layers IV and V of the primary visual cortex, as well as in deeper portions of the superficial superior colliculus, relative to dark adapted rats. Such differences went undetected without layer-specific analysis. We demonstrate, for the first time, the feasibility of layer-specific stimulus-dependant non-invasive MEMRI readout after encoding activity in awake and free moving rats. Future MEMRI studies are envisioned that measure the effects on cortical activity of sensory stimulation, as well as normal development, disease, plasticity, and therapy in longitudinal studies.

Global & Community Health: Brief in-hospital cognitive screening anticipates complex admissions and may detect dementia.

OBJECTIVE: With the long-term goal of improving community health by screening for dementia, we tested the utility of integrating the Six-Item Screener (SIS) into our emergency department neurology consultations. METHODS: In this cross-sectional observational study, we measured SIS performance within 24 hours of hospital arrival in 100 consecutive English-speaking patients aged ≥45 years. Performance was compared to patient age, previously charted cognitive impairment, and proxies for in-hospital complexity: whether or not a patient was admitted to the hospital and the number of medical studies ordered. RESULTS: Those with poor SIS performance were older (p = 0.02) and more likely to have previously charted cognitive impairment (p < 0.01; sensitivity 86%, specificity 77%). Poor performers were more likely to be admitted to the hospital (p = 0.04; odds ratio 3.6) and were subjected to more tests once admitted (p < 0.01), relationships that persisted after accounting for age and history of cognitive impairment. CONCLUSIONS: Poor performance on the SIS was associated with previously charted cognitive impairment, justifying future study of its ability to detect unrecognized dementia cases. Until then, its ability to inexpensively anticipate medically complex hospital admissions motivates broader emergency department use of the SIS.

Clinical characteristics and outcomes of methamphetamine-associated intracerebral hemorrhage.

OBJECTIVE: To compare the clinical characteristics and outcomes of primary intracerebral hemorrhage (ICH) with and without methamphetamine exposure. METHODS: We performed a retrospective analysis of patients diagnosed with spontaneous, nontraumatic ICH over a 3-year period between January 2013 and December 2016. Demographics, clinical measures, and outcomes were compared between ICH patients with positive methamphetamine toxicology tests vs those with negative methamphetamine toxicology tests. RESULTS: Methamphetamine-positive ICH patients were younger than methamphetamine-negative ICH patients (52 vs 67 years, p < 0.001). Patients with methamphetamine-positive ICH had higher diastolic blood pressure (115 vs 101, p = 0.003), higher mean arterial pressure (144 vs 129, p = 0.01), longer lengths of hospital (18 vs 8 days, p < 0.001) and intensive care unit (ICU) stay (10 vs 5 days, p < 0.001), required more days of IV antihypertensive medications (5 vs 3 days, p = 0.02), and had more subcortical hemorrhages (63% vs 46%, p = 0.05). The methamphetamine-positive group had better premorbid modified Rankin Scale (mRS) scores (p < 0.001) and a greater change in functional ability as measured by mRS at the time of hospital discharge (p = 0.001). In multivariate analyses, methamphetamine use predicted both hospital length of stay (risk ratio [RR] 1.54, confidence interval [CI] 1.39-1.70, p < 0.001) and ICU length of stay (RR 1.36, CI 1.18-1.56, p < 0.001), but did not predict poor outcome (mRS 4-6). CONCLUSIONS: Methamphetamine use is associated with earlier age at onset of ICH, longer hospital stays, and greater change in functional ability, but did not predict outcome.

Manganese-enhanced MRI studies of alterations of intraretinal ion demand in models of ocular injury.

PURPOSE: To provide proof-of-concept that the extent of intraretinal manganese uptake after systemic MnCl(2) injection, detected with manganese-enhanced MRI (MEMRI), assesses alterations in intraretinal ion demand in models of ocular insult. METHODS: In Sprague-Dawley rats, retinal ion demand and thickness were measured from MEMRI data collected before, 4 hours after, or 1, 3, and 7 days after intraperitoneal injection of MnCl(2). Choroidal contribution or blood-retinal barrier permeability surface area product (BRB PS') was determined using MRI after Gd-DTPA injection. Ocular injury was evaluated 24 hours after intravitreal injection of phosphate-buffered saline (PBS, vehicle) or PBS + ouabain, or after intraperitoneal injection of sodium iodate. Manganese retinal toxicity was assessed by comparing full-field, white-flash electroretinographic (ERG) data obtained before and after systemic MnCl(2) administration. Rat choroidal thickness was measured from cross-sections prepared from paraformaldehyde-perfused adult rats. RESULTS: Comparing pre- and post-Gd-DTPA images demonstrated minimal choroidal contribution to intraretinal analysis. Intraretinal signal intensity returned to baseline by 7 days after MnCl(2) injection. After ouabain injection, receptor and postreceptor uptake of manganese were subnormal (P < 0.05). After sodium iodate exposure, intraretinal manganese uptake was supernormal (P < 0.05) and did not increase with increasing BRB PS'. ERG data did not show any effect of MnCl(2) on photoreceptor a-wave and postreceptor b-wave relative to baseline at either observation time. CONCLUSIONS: MEMRI measurements of uptake of systemically administered and nontoxic doses of manganese appear to be a powerful approach for measuring alteration in intraretinal ion demand in models of ocular injury.

MRI of rod cell compartment-specific function in disease and treatment in vivo.

Rod cell oxidative stress is a major pathogenic factor in retinal disease, such as diabetic retinopathy (DR) and retinitis pigmentosa (RP). Personalized, non-destructive, and targeted treatment for these diseases remains elusive since current imaging methods cannot analytically measure treatment efficacy against rod cell compartment-specific oxidative stress in vivo. Over the last decade, novel MRI-based approaches that address this technology gap have been developed. This review summarizes progress in the development of MRI since 2006 that enables earlier evaluation of the impact of disease on rod cell compartment-specific function and the efficacy of anti-oxidant treatment than is currently possible with other methods. Most of the new assays of rod cell compartment-specific function are based on endogenous contrast mechanisms, and this is expected to facilitate their translation into patients with DR and RP, and other oxidative stress-based retinal diseases.