MRI is a noninvasive diagnostic modality that reveals anatomy, physiology, and function in vivo without depth limitation or optical interference. MRI application to the retina, however, remains challenging. We improved spatial resolution to resolve layerspecific structure and functional responses in the retina and confirmed the laminar resolution in an established animal model of retinal degeneration. Structural MRI of normal rat retinas revealed three bands corresponding histologically to (i) the combined ganglion cell layer͞inner nuclear layer plus the embedded retinal vessels, (ii) the avascular outer nuclear (photoreceptor) layer and its photoreceptor segments, and (iii) the choroidal vascular layer. Imaging with an intravascular contrast agent (gadolinium-diethylene-tri-amine-pentaacetic acid) enhanced the retinal and choroidal vascular layers bounding the retina, but not the avascular outer nuclear layer and the vitreous. Similarly, blood-oxygen-leveldependent (BOLD) functional MRI revealed layer-specific responses to hyperoxia and hypercapnia. Importantly, layer-specific BOLD responses in the two vascular layers were divergent, suggesting the two vasculatures are differentially regulated. To corroborate sensitivity and specificity, we applied layer-specific MRI to document photoreceptor degeneration in Royal College of Surgeons rats. Consistent with histology, layer-specific MRI detected degeneration of the outer nuclear layer. Surprisingly, MRI revealed increased thickness in the choroidal vascular layer and diminished BOLD responses to hyperoxia and hypercapnia in the Royal College of Surgeons rat retinas, suggesting perturbation of vascular reactivity secondary to photoreceptor loss. We conclude that MRI is a powerful investigative tool capable of resolving lamina-specific structures and functional responses in the retina as well as probing lamina-specific changes in retinal diseases.columnar resolution ͉ high-resolution functional MRI ͉ lamina-specific MRI ͉ retinal degeneration

A two-dimensional map of blood flow is crucial for physiological studies. We present a modified laser speckle imaging method (LSI) that is based on the temporal statistics of a time-integrated speckle. A model experiment was performed for the validation of this technique. The spatial and temporal resolutions of this method were studied in theory and compared with current laser speckle contrast analysis (LASCA); the comparison indicates that the spatial resolution of the modified LSI is five times higher than that of current LASCA. Cerebral blood flow under different temperatures was investigated by our modified LSI. Compared with the results obtained by LASCA, the blood flow map obtained by the modified LSI possessed higher spatial resolution and provided additional information about changes in blood perfusion in small blood vessels. These results suggest that this is a suitable method for imaging the full field of blood flow without scanning and provides much higher spatial resolution than that of current LASCA and other laser Doppler perfusion imaging methods.

Combined functional, perfusion and diffusion magnetic resonance imaging (MRI) with a temporal resolution of 30 mins was performed on permanent and transient focal ischemic brain injury in rats during the acute phase. The apparent diffusion coefficient (ADC), baseline cerebral blood flow (CBF), and functional MRI (fMRI) blood-oxygen-level-dependent (BOLD), CBF, and CMRO(2) responses associated with CO(2) challenge and forepaw stimulation were measured. An automated cluster analysis of ADC and CBF data was used to track the spatial and temporal progression of different tissue types (e.g., normal, 'at risk,' and ischemic core) on a pixel-by-pixel basis. With permanent ischemia (n=11), forepaw stimulation fMRI response in the primary somatosensory cortices was lost, although vascular coupling (CO(2) response) was intact in some animals. Control experiments in which the right common carotid artery was ligated without causing a stroke (n=8) showed that the delayed transit time had negligible effect on the fMRI responses in the primary somatosensory cortices. With temporary (15-mins, n=8) ischemia, transient CBF and/or ADC declines were observed after reperfusion. However, no T(2) or TTC lesions were observed at 24 h except in two animals, which showed very small subcortical lesions. Vascular coupling and forepaw fMRI response also remained intact. Finally, comparison of the relative and absolute fMRI signal changes suggest caution when interpreting percent changes in disease states in which the baseline signals are physiologically altered; quantitative CBF fMRI are more appropriate measures. This approach provides valuable information regarding ischemic tissue viability, vascular coupling, and functional integrity associated with ischemic injury and could have potential clinical applications.

Temporal-statistical analysis of laser-speckle image (TS-LSI) preserves the original spatial resolution, in contrast to conventional spatial-statistical analysis (SS-LSI). Concerns have been raised regarding the temporal independency of TS-LSI signals and its insensitivity toward stationaryspeckle contamination. Our results from flow phantoms and in vivo rat retinas demonstrated that the TS-LSI signals are temporally statistically independent and TS-LSI minimizes stationary-speckle contamination. The latter is because the stationary speckle is "non-random" and thus non-ergodic where the temporal average of stationary speckle needs not equal its spatial ensemble average. TS-LSI detects blood flow in smaller blood vessels and is less susceptible to stationary-speckle artifacts.

Laser speckle imaging (LSI) is widely used to study blood flow at high spatiotemporal resolution. Several papers recently pointed out that the commonly used LSI equation involves an approximation that could result in incorrect data analysis. We investigated the impact of such an approximation and introduced a simplified analysis method to improve computation time. Flow phantom studies were performed for validation. Moreover, we demonstrated a novel LSI application by imaging blood flow of rat retinas under normal and physiologic-challenge conditions. Because blood-flow abnormality is implicated in many retinal diseases, LSI could provide valuable physiologic, and potentially diagnostic, information.Laser speckle imaging (LSI) [1] can be used to image instantaneous velocity distribution in vivo at very high spatiotemporal resolution, an improvement over the single point techniques, such as laser Doppler flowmetry [2]. Laser speckle is an optical interference effect. The speckle pattern fluctuates if the illuminated area contains moving particles such as moving red blood cells. By integrating the intensity fluctuations of the speckle pattern over a finite time, information about the motion of the scattering particles could be derived. LSI has recently been applied to image changes in cerebral blood flow associated with focal brain ischemia and cortical spreading depression in rats [3]. LSI has since proven to be a cost-effective technique for measuring dynamic blood flow changes at very high spatiotemporal resolution [4,5]. However, several papers [6][7][8] recently pointed out that the commonly used LSI equation involves an approximation that could result in incorrect data analysis.In this study, we investigated the contribution of such approximation and its impact on LSI data analysis and proposed a simplified LSI analysis method to speed up computation time. For validation, we performed flow phantoms experiments at different physiological flow rates and different camera exposure times. Moreover, we demonstrated a novel in vivo application by imaging blood flow of the rat retinas in which the animals breathed air or oxygen. The latter was used to modulate blood flow for testing sensitivity. LSI blood-flow index maps and physiologically induced percent-change maps were analyzed.Speckle contrast (K) is defined in terms of the standard deviation (σ s ) and the mean local spatial speckle intensity fluctuations (〈I〉). Per Fercher and Briers' formalism, the relation between speckle contrast and spatial variance of the time-averaged speckle pattern is [1]

BackgroundA two-year longitudinal study composed of morphometric MRI measures and cognitive behavioral evaluation was performed on a transgenic Huntington’s disease (HD) monkey. rHD1, a transgenic HD monkey expressing exon 1 of the human gene encoding huntingtin (HTT) with 29 CAG repeats regulated by a human polyubiquitin C promoter was used together with four age-matched wild-type control monkeys. This is the first study on a primate model of human HD based on longitudinal clinical measurements.ResultsChanges in striatal and hippocampal volumes in rHD1 were observed with progressive impairment in motor functions and cognitive decline, including deficits in learning stimulus-reward associations, recognition memory and spatial memory. The results demonstrate a progressive cognitive decline and morphometric changes in the striatum and hippocampus in a transgenic HD monkey.ConclusionsThis is the first study on a primate model of human HD based on longitudinal clinical measurements. While this study is based a single HD monkey, an ongoing longitudinal study with additional HD monkeys will be important for the confirmation of our findings. A nonhuman primate model of HD could complement other animal models of HD to better understand the pathogenesis of HD and future development of diagnostics and therapeutics through longitudinal assessment.

Highly flexible and stable plasmonic nanopaper comprised of silver nanocubes and cellulose nanofibres was fabricated through a self-assembly-assisted vacuum filtration method.

This study describes a novel MRI application to image basal blood flow, physiologically induced blood-flow changes, and the effects of isoflurane concentration on blood flow in the retina. Continuous arterial-spin-labeling technique with a separate neck coil for spin labeling was used to image blood flow of the rat retina at 90×90×1500-μm resolution. The average blood flow of the whole retina was 6.3±1.0 ml/g/min under 1% isoflurane, consistent with the high blood flow in the retina reported using other techniques. Blood flow is relatively constant along the length of the retina, except it dipped slightly around the optic nerve head and dropped significantly at the distal edges where the retina terminates. Hyperoxia (100% O 2 ) decreased blood flow 25± 6% relative to baseline (air) due to vasoconstriction. Hypercapnia (5% CO 2 +21% O 2 ) increased blood flow 16±6% due to vasodilation. Increasing isoflurane (a potent vasodilator) concentration to 1.5% increased blood flow to 9.3±2.7 ml/g/min. Blood-flow signals were confirmed to be genuine by repeating measurements after the animals were sacrificed in the MRI scanner. This study demonstrates a proof of concept that quantitative blood flow of the retina can be measured using MRI without depth limitation. Bloodflow MRI has the potential to provide unique insights into retinal physiology, serve as an early biomarker for some retinal diseases, and could complement optically based imaging techniques.