Author(s): Peter Touma
Mentor(s): Caroline Hoemann, Bioengineering
Author(s): Peter Touma
Mentor(s): Caroline Hoemann, Bioengineering
Author(s): Muhammad Sardar
Mentor(s): Shaghayegh Bagheri, Department of Mechanical Engineering
Author(s): SuJung Rodriguez
Mentor(s): Qi Wei, Department of Bioengineering
So the objective was to create a patient-specific three-d biomechanical model of the eye and the corresponding extraocular muscles
Some background on why we would want to model those muscles. So those muscles are responsible for eye movement, as you can see. Here you have 4 rectus muscles which are responsible for moving your eyes up down, left, right. Then you have your oblique muscles which are responsible for your eye being able to twist. So any deviations in those muscles from healthy physiology can cause vision disorders, a common one, being strabismus. That’s a case where your eyes cannot look at the same target at the same time. So modeling those muscles can provide valuable insight when planning treatment. And currently, when ophthalmologists are trying to treat vision disorders, they have no quantitative measures. So they go in and decide which muscles to recess, and how much to recess them by based on their own intuition and experience. So, being able to actually model those muscles, would be able to give them a quantitative measure and improve surgical outcomes
Some previous work that was done.
So Bassam Mutawak developed a pipeline which uses 2 MRI data sets to generate a patient-specific model of the eyeball and extracurricular muscles. Basically, those 2 MRI data sets, they’re collected in 2 different views. So you have what’s called the coronal view and the sagittal view. So in each data set, those extraocular muscles are traced. They’re sent into the pipeline, and an iterative closest point registration algorithm is used to register points from the 2 data sets. Basically what it does is it takes your points in the coronal view, and then it looks for points in the sagittal view that are the closest to those points, and then it computes the amount of translation and rotation necessary to have those 2 different points be aligned. Those 2 data sets be aligned. The traces of muscles are then plotted, and these centroids are computed, and from there the muscle paths are generated.
So here’s what those datasets look like. This is what the data in the coronal view looks like. As you can see, these dark bands are the extraocular muscles. Here’s what data in the sagittal view looks like. Again, those dark bands you see are the muscles. And here’s the model that gets generated.
So my task was to make this pipeline work when it only has one data set the coronal view available. The reason why is data collection is actually very long and uncomfortable for patients. So most of the times we are only able to get one view. We focus on the coronal view. The only issue is that the inferior oblique and superior oblique, their tendons are only reliably imaged in the sagittal view.
So we focus on one eye. First, the oculus dextrous or OD. Because MRI data is actually a 3D volume, we can actually take our coronal data and re-slice it essentially so that we can artificially generate our own sagittal data and try to get the inferior oblique and the tendon of the superior oblique. We then model the rectus muscles, the oblique muscles, and while we’re doing that, we’re checking against our ground truth measure, which is the model that was generated when we had data from the coronal and sagittal view available.
So to model the rectus muscles, the rectus muscles actually do not require sagittal data to be modeled. As you can see here, these green traces are the data from the coronal view. The black traces you see here are from the sagittal view. So you just modify the code as needed. And basically just making sure that this pipeline isn’t expecting 2 data sets when it’s only going to be getting one
Next is to model the interior oblique. So here we trace it in the coronal view. It’s this muscle here. You see here the point where it’s connecting to the socket. That’s actually the origin point which will be important for later. And here we also trace it in the sagittal view. As you can see, it’s this little black dot here. So we re-register the points from the generated sagittal data that we’ve created to the points in the coronal data. We hard code in the origin point based on values found in literature. The reason we do this is because, as you can see in our artificially generated sagittal data, the top of the eyeball gets cut off, and the inferior oblique is pretty far back. So it’s only visible in anterior slices, and it’s just not visible in our artificially generated satchel data. It’s only there in 2 or 3 image slices. So, after we hardcode in our origin point, we plot the coronal traces of the inferior oblique muscle, and compare it to the origin point that we hard-coded in. If the origin point that we hard-coded in is still very far from that point we see where it’s connecting to the socket, then we adjust it again.
So, as you can see here in order to get our hard-coded origin point from literature, we take one model that was created by Dr. Wei and Bassam Mutawak. That was more generalized. It wasn’t data-driven, patient-specific. It was based on what we expect to find in the literature. And then we take the model that I’ve generated, as you can see here where it is, data-driven and line them up. So as you can see here, these green, these big green asterisks are from Dr. Wei’s model, and then these actual like muscle paths, are from mine. We line them up so as you can see here, because there just was not a lot of data to build it off of the inferior oblique isn’t going in the direction we needed to. It’s starting to point out. And we take this last point that you see here, and hard code that in as our origin point. We then rerun the model, plot the data on the coronal views, see if it’s close to that origin point. We see where it’s joining the socket and make an adjustment. And this is the model that we finally generate. So, as you can see here, it matches up what we see in our ground truth, measure, and the shape also looks as we expected it to, and when we check the muscle lengths they line up with what we see in literature.
Next step is to model the superior oblique. So because the superior oblique tendon is only visible in very anterior MRI images. It’s very difficult to model. When we artificially generate our sagittal data, it’s not visible in any slices. So a possible solution is to hardcode in where it inserts on the eyeball and fit a line to wrap around the eyeball, so that we’re still seeing that shape that we expect to.
So our future directions are to wrap up the superior oblique modeling. Then the model is done, so we’ll send it to a dynamic simulation environment, and what we’re going to do is we’re going to simulate how these patients were seeing before they had any surgery. And then, because we have these surgeon’s nodes, we have the notes of like which muscles they recessed, how much they recessed them by and how their vision was after, and we again in that dynamic simulator basically mimic what those surgeons did, and then see if the way the eye is moving is the same as what the surgeon documented. If that’s not the case and the model is not working, we would make adjustments as needed. But the end goal ultimately is to be able to send these to a dynamic simulation environment and simulate surgical outcomes
And for acknowledgments, thank you to my mentor, Dr. Wei, at the Department of Bioengineering, Dr. Demer for providing us with MRI images. Bassam Mutawak, who created the original pipeline and has helped, and OSCAR GMU for supporting this project.
Author(s): Leah Pistone
Mentor(s): Daniel Hanley, Biology
Author(s): Angela V. Rojas Rivera
Mentor(s): Marissa Howard, Center for Applied Proteomics and Molecular Medicine (CAPMM)
Author(s): Solyip Kim
Mentor(s): Yun Yu, Department of Chemistry & Biochemistry
https://youtu.be/vKrE_U-4xss
Atomically thin materials, also known as 2D materials, are emergent materials with unique properties. Using them for biosensing and healthcare offers benefits like high carrier mobility, significant surface-to-volume ratio, flexibility, and controllable reactive sites. Graphene is a prominent 2D material and has received considerable attention for biosensing applications.
Graphene offers strong π−π interaction with the aromatic rings of dopamine, making the molecule absorption favorable. However, its minimal charge density at pristine layers limits the electrochemical kinetics of dopamine electrooxidation. Here, we aim to mitigate these disadvantages by creating a heterostructure composed of Graphene and molybdenum trioxide (MoO3), also known as “Moo,” The high work function of Moo will efficiently induce hole doping of graphene, so that the carrier density of graphene can be enhanced. Our hypothesis is that charge doping on the graphene may enhance its surface reactivity.
To create the graphene-Moo heterostructure, we used scotch tape method to mechanically exfoliated bulk crystals . Then, transferred them onto a silicon wafer, and identified the flakes of interest with an optical microscope. Next, using a transfer stage, we picked up the bottom layer with a polymer film. Subsequently, we stacked the bottom layer with the top layer to form the desired heterostructure.
To verify effective charge doping, we performed electrical conductivity measurements across the graphene. A small potential was applied between the two contacts, and the conductance current was measured.
Then Moo was stacked on graphene to induce hole doping. The graph clearly demonstrates that the conductivity of graphene, represented by the slope of the IV curve, was significantly increased by more than two-fold when combined with Moo, as compared to using graphene alone. This enhancement in conductivity highlights the positive impact of stacking Moo with graphene to regulate its electronic property.
In our electrochemical measurement, the analyte, dopamine molecule, diffuses to the graphene surface. With a suitable potential applied, dopamine underwent oxidation reactions, releasing electrons onto the electrode and generating an electrochemical current that we measured and used to quantify the analyte.
In the graph, the red curve shows the voltammogram of dopamine oxidation obtained from graphene/moo, while the black curve is the data of our control sample, graphene/hbn. hBN is an insulator and does not induce any doping of graphene. The half wave potential of the red curve is lower than the black curve, indicating that the electrochemical kinetic of dopamine reaction at graphene/moo is more rapid.
Our results so far have demonstrated that engineering heterostructures indeed has positive effects in promoting the reactivity. Based on these results, our future work aims for more systematic study of the electrochemistry of Gr/moo heterostrucutre, including investigating the thickness dependence, concentration dependence and other factors that could impact the performance of the dopamine sensor. Ultimately, our goal is to develop real-life applications that can be utilized for monitoring dopamine levels in the human body.
For this project, I would like to thank my mentor Dr. Yun Yu for his support as well as OSCAR for their funding support.
Author(s): Joelle Nguyen
Mentor(s): Caroline Hoemann, Bioengineering
This project involved creating a lipidomic and proteomic profile of human blood plasma and serum samples. All samples were from de-identified healthy donors under IRB-approved protocols with written informed consent. Liquid Chromatography – Mass Spectrometry (LCMS) is the ideal method of creating lipidomic profiles of lipid analytes due to its high specificity and sensitivity. Plasma samples’ lipids contents were extracted using 2:1:1 v/v chloroform/methanol/water or 3:2 v/v hexane/isopropanol. These extraction methods were compared for their sensitivity in detecting certain analytes, and it was found that 3:2 v/v hexane/isopropanol was the better extraction method. Nanotraps, made of various types of nanoparticles, were utilized to bind to sLOX-1 in sample and deplete them for analysis using ELISA, where it was discovered that the majority of sLOX-1 fraction was depleted by the Nanotraps in citrated plasma/serum with recombinant sLox-1 but not much in human blood serum alone. Future sample preparation modifications are needed before LC-MS analyses of Nanotrap-associated sLOX-1.
So to move on to the methodology of my project, there were two approaches. One was comparing two different extraction methods for the lipid analytes found in blood plasma samples for a lipidomic mass spectrometry analysis, and the other was examining the extent of depletion using nanotraps on the sLox-1 protein receptor in plasma/serum samples for a proteomic mass spectrometry analysis. To go into more detail on the lipidomic experiment, I had compared 2:1:1 v/v chloroform/methanol/water with 3:2 v/v hexane/isopropanol as potential extraction solvents. To compare these methods, I analyzed the peak areas of lipid analytes from duplicate citrated plasma samples and used JMP to provide a descriptive statistical analysis. For the proteomic experiment, there were six dyed nanoparticles used as Nanotraps to deplete sLox-1 in plasma/serum samples and an ELISA test was done to analyze the concentration of depleted sLox-1. The samples were not analyzed with mass spectrometry quite yet but the ELISA results provided future directions for sample preparation and LCMS analysis.
Here are the results for the lipidomic profile made using LCMS. The experiment had two different blood donors, and for this donor here you can see that there is a higher peak area for lipid analytes extracted by hexane on the JMP graph to the left and visually to the right you see that 3:2 v/v hexane/isopropanol has a higher peak area for the specific lipid analytes called 4-HNE-H2O. The same can be said for the second donor in my experiment where again the hexane extracted analytes had a higher peak area both on the JMP plot and the mass spectra graph for 4 HNE-H2O. Now for the mass spectrometry proteomics experiment, there was the ELISA data collected which showed that not a lot of sLox-1 depleted from the nanotraps, only around 20% or less for serum with free sLox-1. The figure to the right shows that citrated blood plasma combined with recombinant sLox-1 protein had a much higher depletion of sLox-1 with 90-100% depleted.
Therefore based on the results of my experiments, the 3:2 v/v hexane/isopropanol is the better solvent to use for extracting lipids from citrated blood plasma samples for a lipidomic profile. For the proteomic experiment, the nanotraps shown in the excel bar graphs showed that they did not interfere with ELISA detection of sLox-1 in control samples. The nanotraps only depleted 0 to 20% of free sLox-1 in serum and depleted 40-100% of recombinant sLox-1 in citrated plasma. The next steps for my project would include doing more experimental trials with both extraction methods to see that 3:2 v/v hexane/isopropanol produces reproducible data. There could also be future modifications to plasma/serum sample preparation to improve sLox-1 binding to the nanotraps.
Thank you for listening and I’d like to acknowledge Dr. Hoemann, Dr. Girgis, Dr. Karen Lee, Dr. Luchini, Rayan Ibrahim Alhammad, and Julia Leonard for their help throughout this project.
Author(s): Sydney Reuter
Mentor(s): Dr. Evan M. Lowder
Author(s): Tashianna Patterson
Mentor(s): Dr. David Corwin, Women and Gender Studies
Author(s): Solyip Kim
Mentor(s): Pritha G. Roy, Chemistry & Biochemistry
Author(s): Sanskruthi Sreepangi
Mentor(s): Ramin M Hakami, School of Systems Biology
Author(s): Maharun Mia
Mentor(s): Adam Winsler, Psychology
there also has been some research looking at racial differences in age of diagnoses but these results have been mixed and there isn’t really a clear consensus on what that relationship might be and it really depends on like what variables the studies have been controlling for
For this study I’m actually looking at Special Education Service receipt because although this isn’t age of diagnosis this is also an important indication of when students are actually receiving services for autism. in this case Special Education Service receipt refers to when a student is receiving a primary exceptionality for autism, a primary exceptionality being the code that a student must receive in their individualized education program in order to be given accommodations and services
One thing that’s significant is that autism research has historically involved mostly Advantage white and male samples which does not reflect entirety of the autistic population which kind of brings us to the importance of this study which is looking at a primarily low-income Hispanic in Black sample and looking for race and gender differences And the timing of primary exceptionality classification attainment
These are my research questions.
We used data from the Miami School Readiness project which primarily composed of low-income students who had received Child Care subsidies for community-based child care or attended a Miami-Dade Public Schools pre-k programs at age four
The final sample composed of 851 MSRP students who had received autism as a primary exceptionality at some point between kindergarten and 12th grade
The table here shows the race and gender breakdown of the sample, Which shows that the sample was 70% Hispanic 16% were black and 87% of the sample was male
The dependent variable is the first year or grade that the students received ASD as a primary exceptionality the covariates were poverty status English language learner status cognitive functioning at age 4 which was measured through the scores that these students received on the LAP-D, ELAP, or DIBELS
As well as behavioral concerns at Age 4 via their DECA scores.
I performed a series of ANCOVAs first without any covariates than adding in poverty status and ell status, And then finally with different combinations of the different cognitive functioning scores we had and the DECA scores.
We actually found no significant differences between any of the groups in terms of the average grade of first time ASD exceptionality no matter what covariates we added. I have a little graphic here that shows that while there are some small group differences between all of the groups none of these were significant. The overall average grade that students received their ASD exceptionality was between first and second grade.
The last thing we looked at was to see if any of the students had received a different exceptionality code before autism as we thought that well if they had received some other exceptionality prior to autism just might have created a delay in the receipt of services. Around 27% of the sample had received something other than autism.this table here shows the breakdown of what these other exceptionality codes were the top three were specific learning disability developmental delay and speech / language impairment. There were no significant gender effects but there was a significant race effect in that white/Asian students were More likely to have received a different exceptionality code prior to autism compared to Hispanic and black students.
I also found out while Hispanic black students had the same top three categories as the overall sample white asian students were more likely to have received a gifted status compared to the other race categories Giftedness being an exceptionality code given to students who are receiving Services accommodations for Accelerated classes such as in reading or math
so in conclusion Despite the literature there weren’t any evidence of race or gender-based delays in autism service received within schools within this predominantly Latino and black sample in Miami which is great news since this means that all students are receiving ASD services on time
however it’s important to note that this might not generalize to other communities or school systems that are not majority Latino and black as there could just be like other resources or factors in Miami not found in other parts of the US.