MASSACHUSETTS GENERAL HOSPITAL, THE
Standard structural brain imaging protocols result in images that cannot resolve structures smaller than 1- 2mm in size. Achieving significantly higher resolution would be of fundamental clinical and neuroscientific value, as it would allow the in-vivo detection and analysis of cytoarchitectural features of the cortex, as well as substructures of brain regions such as the hippocampus, thalamus and amygdala. Unfortunately, such resolution is extremely difficult to obtain in-vivo, as the signal-to-noise ratio goes down with the third power of the linear dimension of each voxel. While some recent studies have pushed this limit to under 1A mm, this is at the cost of extremely long scan sessions and specialized imaging hardware, and even this is still a coarse resolution relative to what is required to visualize correlates of the cytoarchitecture with MRI. Here we take a different approach, and propose to image ex-vivo tissue samples, both blocks of tissue and whole hemispheres, in which exceedingly high-resolution is obtainable, on the order of lOOujns. In these images, many MR signatures of cytoarchitectural features are apparent, and hence they can be used for the construction of models including these cytoarchitectonically defined boundaries. For those features that are not distinguishable from the MR, we propose to perform histological analysis of the tissue, and use cross modal registration techniques to transfer the information from the histology back to the models. High dimensional mapping procedures are then proposed to map these models, obtained from ultra high-resolution imaging and histology, back to the more standard resolution in-vivo data to predict the probability of a given cytoarchitectural boundary occurring at each location in the in-vivo data. We focus on cortical areas in the medial temporal lobe as they are of great clinical relevance, as they are thought to be one of the earliest loci of Alzheimer's disease, and are critical to normal memory function. The ability to more accurately localize these cortical regions would be a critical step in the early diagnosis of AD, and in the assessment of the efficacy of potential clinical interventions.
| AWARD OVERVIEW |
| Award Number |
3R01EB006758-03S1 |
Funding Agency |
Department of Health and Human Services |
| Total Award Amount |
$36,355 |
Project Location - City |
Boston |
| Award Date |
06/05/2009 |
Project Location - State |
MA |
| Project Status |
Completed |
Project Location - Zip |
02114-0000
|
| Jobs Reported |
0.00 |
Congressional District |
09 |
| Project Location - Country |
US |
|
|
Recipient Information
(Grants)
| Recipient Information (Grants) |
|
Recipient Name
|
MASSACHUSETTS GENERAL HOSPITAL, THE |
| Recipient DUNS Number |
073130411
|
| Recipient Address |
55 FRUIT ST |
| Recipient City |
BOSTON |
| Recipient State |
Massachusetts |
| Recipient Zip |
02114-2621 |
| Recipient Congressional District |
09 |
| Recipient Country |
USA |
Required to Report Top 5
Highly Compensated Officials |
No |
Projects and Jobs Information
| Projects and Jobs Information |
| Project Title |
Inferring in vivo Cytoarchitectural Borders in the Medial Temporal Lobe |
| Project Status |
Completed |
| Final Project Report Submitted |
Yes |
| Project Activities Description |
General Medical and Surgical Hospitals |
| Quarterly Activities/Project Description |
We are pleased to report that we were able to accomplish our goals for this
summer project. It was a very enriching experience for our lab members and
for the students and teacher who participated.
The summer workers accomplished the following tasks:
-sectioned and mounted the brain tissue of three different brain blocks
-digitized 150 histological brain tissue slides
-learned how to stain and coverslip tissue slides
-manually segmented the hippocampus in 13 brain hemispheres
-created a Quality Assurance document for the manual segmentation of the
hippocampus so that future staff could easily take over the project
-manually segmented digitized histological images and block face photographs
of 2 MT cases
-visited the 7 Tesla MRI scanner and learned basic physics about the imaging
process
Aside from the objectives we outlined in our project summary, we were able
to provide our students and the teacher with the opportunity to participate
in various lectures and discussions with clinicians and scientists of
different backgrounds and fields. We got very positive feedback from the
students who greatly appreciated the chance to be exposed to cutting edge
research projects and to openly interact with senior members of our
scientific community. They were able to consider and discuss with us the
various career paths that they might consider in the future. They have left
this lab with advanced knowledge of brain anatomy, experience with standard
lab protocols, enhanced computer skills, and improved communication skills
for scientific projects.
|
| Jobs Created |
0.00 |
| Description of Jobs Created |
We proposed to hire three high school students, a high school teacher, and
two undergraduate students over the summer of 2009 in order to assist
us in the histology preparation process, the manual delineation of ex-vivo
structures, and the validation of our computational tools related to the
existing R01 grant entitled "Inferring in vivo cytoarchitectural borders
in the medial temporal lobe". During these summer internships our goal was
ex-vivo brain analysis and computational tools for image processing and
have them assist in processing three new data sets that will accelerate
the progress we were already making on the image analysis related part of
the grant.
The proposed supplement, in particular, is related to Aim 2 and 3. As part
of Aim 2 we have been developing registration tools in order to align
histological sections of ex-vivo brain samples to digital photographs
taken during tissue sectioning and eventually to a 3D MRI acquisition. The
photographic images of the ex-vivo samples are taken during and following
the histology slicing procedure where the sample is cut, sliced, mounted
and digitized to then be analyzed under a microscope. The histology
analysis is a complex and time-consuming procedure which requires long
hours of manual labor. We are planning on utilizing help from the summer
personnel along this process in order to speed up the testing and
validation of our tools. With respect to Aim 2, we have identified two
major areas where they could be helpful to this project: histology
preparation and sectioning; and manual segmentation of 2D images of the
histology images. The former includes preparing the slides and stain,
preparing the brain samples for slicing, cutting the brain samples using a
microtome and then mounting these slices on glass slides prior to
staining. The mounted slides are then digitized and compared to the
digital color photographs (blockface images) that are taken during the
sectioning process. The latter concerns the manual tracing of the
boundaries of the imaged samples both in the digitized histology and the
blockface images in order to obtain ground truth measurements to be used
when quantitatively evaluating the performance of our new registration
methods. In addition, the high school teacher will assist with code
development and testing of the image processing tools. With respect to Aim
3, the summer personnel will work on manually delineating Brodmann areas
in the primary visual cortex and the medial temporal lobe.
Our lab has extensive experience in training and supervising graduate
students in general and high school students in the above tasks. We
believe that the proposed summer project could be beneficial not only for
our project but also for the summer staff. The students will get
introduced to laboratory research and have the opportunity to interact
with both junior and senior members of our research group and the science
teacher will have the opportunity to establish a close collaboration with
a leading research institute and to create a mechanism for the future to
involve his own students in similar summer employment opportunities. Such
an experience could be invaluable for young individuals deciding on
careers in health-related research fields.
We have completed this project, and have been very please with the results in terms of educational quality for the students as well as their productivity in helping our high resolution hippocampal segmentation. |
Purchaser Information
(Grants)
| Purchaser Information |
| Contracting Office ID |
Not Reported |
| Contracting Office Name |
Not Available |
| Contracting Office Region |
Not Available |
| TAS Major Program |
75-0899 |
| Award Information |
| Award Date |
06/05/2009 |
| Award Number |
3R01EB006758-03S1 |
| Order Number |
|
| Award Type |
Grants |
| Funding Agency ID |
75 |
| Funding Agency Name |
Department of Health and Human Services |
| Funding Office Name |
Not Available |
| Awarding Agency ID |
75 |
| Awarding Agency Name |
Department of Health and Human Services |
| Amount of Award |
$36,355 |
| Funds Invoiced/Received |
$36,354 |
| Expenditure Amount |
$36,354 |
| Infrastructure Expenditure Amount |
$0 |
| Infrastructure Purpose and Rationale |
Not Reported |
| Infrastructure Point of Contact Name |
Not Reported |
| Infrastructure Point of Contact Email |
Not Reported |
| Infrastructure Point of Contact Phone |
Not Reported |
| Infrastructure Point of Contact Address |
Not Reported |
| Infrastructure Point of Contact City |
Not Reported |
| Infrastructure Point of Contact State |
Not Reported |
| Infrastructure Point of Contact Zip |
Not Reported |
Product or Service Information
(Grants)
| Product or Service Information |
| Primary Activity Code |
622110 |
| Activity Description |
General Medical and Surgical Hospitals |
| Sub-Awards Information |
| Sub-awards to Organizations |
0 |
| Sub-award Amounts to Organizations |
$0 |
| Sub-Awards to Individuals |
0 |
| Sub-Award Amounts to Individuals |
$0 |
| Number of Sub-awards less than $25,000/award |
0 |
| Amount of Sub-awards less than $25,000/award |
$0 |
| Number of payments to vendors greater than $25,000 |
0 |
| Total Amount of payments to vendors greater than $25,000/award |
$0 |
| Number of payments to vendors less than $25,000/award |
0 |
| Total Amount of payments to vendors less than $25,000/award |
$0 |
| Location Information |
| Latitude, Longitude |
42º 21' 44",
-71º 4' 11" |
| Congressional District |
09 |
| Address 1 |
55 Fruit Street |
| Address 2 |
|
| City |
Boston |
| County |
Suffolk |
| State |
MA |
| Zip |
02114-0000 |
|
 |