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Comprehensive Evaluation of OGSE DWI for Assessing Tumor Treatment Response

Award Number: R01CA173593
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2012
PERIOD OF PERFORMANCE END DATE: 01/31/2018

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Comprehensive Evaluation of OGSE DWI for Assessing Tumor Treatment Response - DESCRIPTION (provided by applicant): This proposal is being submitted as a companion grant to our application 2R01 CA109106 which was reviewed by the BMIT-B Study Section in June 2011 and awarded a priority score of 12 (2nd percentile) with no recommended budget cuts. Our overall aims are to continue the development, evaluation and validation of a novel magnetic resonance imaging (MRI) technique that is a sensitive indicator of tumor status, before and after treatment, and which provides unique information non-invasively on tissue microstructure. Grant CA109106 was subsequently awarded with a 62% budget reduction compared to what the Study Section recommended. The work being performed with that grant has therefore been amended and substantially reduced in scope, and it no longer will support most of the animal studies or comparisons of treatment effects that were proposed and approved. This proposal aims to secure supplementary support for those studies that were approved but not funded, and which we (and the Study Section) consider essential as part of our evaluation of this new methodology. Previous studies have convincingly shown that diffusion weighted MRI (DW-MRI) can report on changes in tumors during growth and following treatment. However, detectable changes occur only after a critical time has elapsed, when cell density has altered sufficiently, and conventional DW-MRI is not sensitive to earlier or more subtle changes within cells. We have developed an alternative technique, oscillating gradient spin-echo (OGSE) DW-MRI, which is uniquely sensitive to microstructural features much smaller than a cell which restrict the free diffusion of tissue water. OGSE measurements may be sensitized selectively to features of different sizes, they appear to be able to detect changes within cells before there are changes in cell density, and they provide a new type of spectral data which can be analyzed to obtain quantitative structural information. We have shown that OGSE imaging reveals greater heterogeneity within tumors, and at higher contrast, that it is sensitive to intra-cellular features such as nuclear size, and that it seems more sensitive to earlier changes in tumors following treatment. We propose to apply optimized OGSE methods to measure changes that occur with the growth of tumors, and in response to three different classes of targeted treatments, in mouse models in vivo. We will establish how early OGSE methods can detect the response of tumors to treatments, how well these changes predict later outcomes, and which OGSE parameters correlate with changes in cellularity, apoptosis and proliferation. The OGSE data will be correlated with co-registered quantitative histological and immunohistochemical sections of the same tumor to verify the interpretation of the measurements. We will also further assist the interpretation of OGSE data by performing elaborate computer simulations of water in compartmental systems of appropriate complexity. Our overall aim is to validate OGSE methods as an experimental tool for pre-clinical studies of tumors.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2018 ( Subtotal = -$46 )
2018	2017	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	6	5/11/2018	NON-COMPETING CONTINUATION	-$46
2018	2017	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	6	3/5/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = -$46

Issue Date FY: 2017 ( Subtotal = $262,280 )
2017	2017	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	003	6	6/6/2017	NON-COMPETING CONTINUATION	$25,896
2017	2017	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	6	11/3/2016	NON-COMPETING CONTINUATION	$233,064
2017	2017	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	004	6	7/12/2017	NON-COMPETING CONTINUATION	$3,320
2017	2016	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	002	5	2/21/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$6,319
2017	2016	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	4	2/21/2017	EXTENSION WITH OR WITHOUT FUNDS	-$6,319
														Subtotal = $262,280

Issue Date FY: 2016 ( Subtotal = $233,064 )
2016	2016	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	4	11/24/2015	EXTENSION WITH OR WITHOUT FUNDS	$233,064
2016	2016	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	002	5	5/9/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$163,861
2016	2016	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	4	5/6/2016	EXTENSION WITH OR WITHOUT FUNDS	-$163,861
														Subtotal = $233,064

Issue Date FY: 2015 ( Subtotal = $258,960 )
2015	2015	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	3	2/5/2015	NON-COMPETING CONTINUATION	$25,896
2015	2015	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	3	11/26/2014	NON-COMPETING CONTINUATION	$233,064
														Subtotal = $258,960

Issue Date FY: 2014 ( Subtotal = $251,191 )
2014	2014	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	2	4/29/2014	NON-COMPETING CONTINUATION	$18,127
2014	2014	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	2	12/3/2013	NON-COMPETING CONTINUATION	$233,064
														Subtotal = $251,191

Issue Date FY: 2013 ( Subtotal = $258,960 )
2013	2013	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	1	6/28/2013	NEW	$64,740
2013	2013	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	1	12/11/2012	NEW	$194,220
														Subtotal = $258,960

Grand Total All Awards = $1,264,409

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Comprehensive Evaluation of OGSE DWI for Assessing Tumor Treatment Response

Award Number: R01CA173593

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/15/2012

PERIOD OF PERFORMANCE END DATE: 01/31/2018

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