Sharon Portnoy

Dimensions of the human sclera: thickness measurement and regional changes with axial length

Scleral thickness, especially near the region of the optic nerve head (ONH), is a potential factor of interest in the development of glaucomatous optic neuropathy. Our goal was to characterize the scleral thickness distribution and other geometric features of human eyes. Eleven enucleated human globes (7 normal and 4 ostensibly glaucomatous) were imaged using high-field microMRI, providing 80 microm isotropic resolution over the whole eye. The MRI scans were segmented to produce 3-D corneoscleral shells. Each shell was divided into 15 slices along the anterior-posterior axis of the eye, and each slice was further subdivided into the anatomical quadrants. Average thickness was measured in each region, producing 60 thickness measurements per eye. Hierarchical clustering was used to identify trends in the thickness distribution, and scleral geometric features were correlated with globe axial length. Thickness over the whole sclera was 670 +/- 80 microm (mean +/- SD; range: 564 microm-832 microm) over the 11 eyes. Maximum thickness occurred at the posterior pole of the eye, with mean thickness of 996 +/- 181 microm. Thickness decreased to a minimum at the equator, where a mean thickness of 491 +/- 91 microm was measured. Eyes with a reported history of glaucoma were found to have longer axial length, smaller ONH canal dimensions and thinner posterior sclera. Several geometrical parameters of the eye, including posterior scleral thickness, axial length, and ONH canal diameter, appear linked. Significant intra-individual and inter-individual variation in scleral thickness was evident. This may be indicative of inter-individual differences in ocular biomechanics.

Modeling pulsed magnetization transfer

Modeling the effects of clinical magnetization transfer (MT) scans, which generate contrast using short, shaped radiofrequency (RF) pulses (pulsed MT), is complex and time‐consuming. As a result, several studies have proposed approximate methods for a simplified analysis of the experimental data. However, potential differences in the MT parameters estimated by each method may complicate the comparison of reported results. In this study we evaluated three approximate methods currently used in quantitative MT (qMT) studies. In the first part of the investigation, an MT modeling technique that makes minimal approximations, other than the use of a two‐pool tissue representation, was developed and validated. Subsequently, this technique served as a standard against which to evaluate the other, more approximate models. Each model was used to fit experimental data from samples of wild‐type (WT) and shiverer mouse spinal cord, as well as simulated data generated by our minimal approximation modeling technique. The results of this study demonstrate that the approximations used in pulsed MT modeling are quite robust. In particular, it was shown that the semisolid pool fraction, M0B, which is known to correlate strongly with myelin content, and the transverse relaxation time of macromolecular protons, T2B, could be evaluated with reasonable accuracy regardless of the model used. Magn Reson Med 58:144–155, 2007.

Comparative SNR for high-throughput mouse embryo MR microscopy

MR microscopy is being explored as a useful imaging tool to phenotype mouse embryos due to its volume coverage with three‐dimensional isotropic resolution. However, the main limitation for mouse embryo MR microscopy is the signal‐to‐noise ratio. Large numbers of embryos are needed for phenotypic screening, making high throughput essential. Two high‐throughput imaging approaches, multi‐embryo shared‐coil (shared) and multi‐embryo individual‐coil (individual), have been developed for phenotyping mouse embryos. This study quantitatively compares the signal‐to‐noise ratio at equivalent times between these two established methods by compensating for differences that result from field strength. While the individual method provides 3.3 times as much signal‐to‐noise ratio as the shared method at equivalent conditions, it is more difficult and expensive to implement. Furthermore, the number of embryos that can be imaged concurrently is limited by the number of receiver channels. The objective of this study is to provide measured comparative data to guide choices for high‐throughput mouse embryo MR microscopy and other similar applications. Magn Reson Med, 2010.

Relaxation properties of human umbilical cord blood at 1.5 Tesla

To characterize the MRI relaxation properties of human umbilical cord blood at 1.5 Tesla.

Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice

Cerebral ischemia is a significant source of morbidity in children with sickle cell anemia; however, the mechanism of injury is poorly understood. Increased cerebral blood flow and low hemoglobin levels in children with sickle cell anemia are associated with increased stroke risk, suggesting that anemia-induced tissue hypoxia may be an important factor contributing to subsequent morbidity. To better understand the pathophysiology of brain injury, brain physiology and morphology were characterized in a transgenic mouse model, the Townes sickle cell model. Relative to age-matched controls, sickle cell anemia mice demonstrated: (1) decreased brain tissue pO2 and increased expression of hypoxia signaling protein in the perivascular regions of the cerebral cortex; (2) elevated basal cerebral blood flow , consistent with adaptation to anemia-induced tissue hypoxia; (3) significant reduction in cerebrovascular blood flow reactivity to a hypercapnic challenge; (4) increased diameter of the carotid artery; and (5) significant volume changes in white and gray matter regions in the brain, as assessed by ex vivo magnetic resonance imaging. Collectively, these findings support the hypothesis that brain tissue hypoxia contributes to adaptive physiological and anatomic changes in Townes sickle cell mice. These findings may help define the pathophysiology for stroke in children with sickle cell anemia.

Non-invasive evaluation of blood oxygen saturation and hematocrit from T1 and T2 relaxation times: In-vitro validation in fetal blood

We propose an analytical method for calculating blood hematocrit (Hct) and oxygen saturation (sO2) from measurements of its T1 and T2 relaxation times.

New advances in fetal cardiovascular magnetic resonance imaging for quantifying the distribution of blood flow and oxygen transport: Potential applications in fetal cardiovascular disease diagnosis and therapy

Until recently, our modern understanding of fetal circulatory physiology has been largely based on invasive measurements made in fetal sheep. However, new MRI technology developed by our group has provided equivalent information about the distribution of blood flow and oxygen transport noninvasively. The initial findings largely confirm prior estimates about the human fetal circulation extrapolated from fetal sheep data and human ultrasound data. Here we describe the hemodynamics of the normal late gestation human fetal circulation by MRI and speculate about what the advent of this technology might mean in terms of the management of fetuses affected by placental insufficiency and congenital heart disease.

Human umbilical cord blood relaxation times and susceptibility at 3 T

To characterize the magnetic susceptibility and relaxation times (T1 and T2) of fetal blood at 3 T as a function of the hematocrit (Hct) and oxygen saturation (sO2).

Mechanics of Individual-Specific Corneoscleral Shell Models

Glaucoma is a group of diseases involving a progressive optic neuropathy of unknown etiology. It is one of the leading causes of blindness worldwide. It has been postulated that glaucomatous optic neuropathy may result from mechanical stresses on the optic nerve fibers passing through the lamina cribrosa (LC), from ischemia in the LC region, or from a combination of these two.Copyright