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MRI Diffusion in Tumors using Oscillating Gradients

Award Number: R01CA109106
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/15/2006
PERIOD OF PERFORMANCE END DATE: 12/31/2023

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MRI Diffusion in Tumors using Oscillating Gradients - Abstract / Summary This revised competitive renewal seeks to extend the technical developments of the previous funding period to validate and apply a novel diffusion-based MR imaging technique, quantitative temporal diffusion spectroscopy (qTDS), that provides unique information on tissue microstructure and in particular can reveal early changes in tumors after treatment. In the previous cycle we developed this innovative method and showed it is a sensitive indicator of changes in cell dimensions and tissue microstructure such as those that occur with cell division and during apoptosis, before frank changes occur in cell density or tumor volume. As such, qTDS has considerable potential for assessing whether specific treatment regimens are working, and so may inform the selection of optimal therapies for patients and the reduction of avoidable side-effects. QTDS is based on measurements of water diffusion rates over different time scales corresponding to different spatial dimensions. We have previously shown it can detect changes in intracellular structure and cell sizes and density, in cell cultures and in animal models, early in the course of a treatment and without some of the confounding factors that affect other diffusion techniques, such as changes in cell membrane permeability. We have performed theoretical analyses, computer simulations, and cell and in vivo animal studies, to understand the factors that affect qTDS measurements, and have implemented the first practical qTDS acquisitions on a human 3T scanner. In the current proposal we aim to extend our previous work and use qTDS as an in vivo imaging technique for non-invasive characterization of specific cellular changes which are currently assessable only via invasive biopsy. We propose to validate qTDS in cell and animal models of cancer, and determine whether qTDS is capable of detecting treatment-induced cell size changes early in specific therapeutic regimens. We also propose to translate qTDS clinically by demonstrating its performance in predicting neoadjuvant treatment response in breast cancer. We hypothesize that qTDS is capable of characterizing the distinct cellular changes associated with treatment-induced apoptosis, thereby providing an innovative and unique means of assessing tumor response at an early stage of therapy. Our specific aims are: [i] in a transgenic mouse model of breast cancer, we will quantitatively map tumor cell size and density in vivo, and validate the qTDS derived parameters on a voxel by voxel basis using using quantitative, co-registered histology: [ii] in mouse models of breast cancer treated by different targeted drugs, we will evaluate qTDS as an imaging biomarker capable of detecting treatment-induced apoptosis and predicting treatment efficacy early during therapy: [iii] In human breast cancer patients, we will evaluate qTDS as an imaging biomarker for assessing breast tumor early response to neoadjuvant chemotherapy and predicting treatment efficacy after the first and subsequent cycles of treatment by correlating imaging data with clinical and pathological responses. The proposed qTDS method has the potential to measure cell size changes in vivo and improve the assessment of treatment response and thereby contribute to personalized clinical cancer care.


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: 2024 ( Subtotal = $0 )
2024	2022	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	16	5/10/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $294,196 )
2022	2022	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	16	11/24/2021	NON-COMPETING CONTINUATION	$270,180
2022	2022	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	16	6/9/2022	NON-COMPETING CONTINUATION	$24,016
														Subtotal = $294,196

Issue Date FY: 2021 ( Subtotal = $300,200 )
2021	2021	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	15	1/21/2021	NON-COMPETING CONTINUATION	$15,010
2021	2021	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	15	12/7/2020	NON-COMPETING CONTINUATION	$285,190
														Subtotal = $300,200

Issue Date FY: 2020 ( Subtotal = $300,200 )
2020	2020	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	14	12/9/2019	NON-COMPETING CONTINUATION	$270,180
2020	2020	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	14	1/15/2020	NON-COMPETING CONTINUATION	$30,020
														Subtotal = $300,200

Issue Date FY: 2019 ( Subtotal = $291,194 )
2019	2019	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	13	11/29/2018	NON-COMPETING CONTINUATION	$291,194
														Subtotal = $291,194

Issue Date FY: 2018 ( Subtotal = $300,200 )
2018	2018	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	12	1/29/2018	COMPETING CONTINUATION	$1,900
2018	2018	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	12	1/12/2018	COMPETING CONTINUATION	$298,300
														Subtotal = $300,200

Issue Date FY: 2017 ( Subtotal = -$1,289 )
2017	2016	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	11	4/26/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$1,289
														Subtotal = -$1,289

Issue Date FY: 2016 ( Subtotal = $213,646 )
2016	2016	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	10	12/2/2015	EXTENSION WITH OR WITHOUT FUNDS	$213,646
2016	2016	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	11	5/6/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$121,001
2016	2016	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	002	10	5/6/2016	EXTENSION WITH OR WITHOUT FUNDS	-$121,001
														Subtotal = $213,646

Issue Date FY: 2015 ( Subtotal = $233,342 )
2015	2015	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	9	2/5/2015	NON-COMPETING CONTINUATION	$21,001
2015	2015	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	9	12/16/2014	NON-COMPETING CONTINUATION	$210,007
2015	2015	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	002	9	3/19/2015	NON-COMPETING CONTINUATION	$2,334
														Subtotal = $233,342

Issue Date FY: 2014 ( Subtotal = $222,495 )
2014	2014	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	8	3/28/2014	NON-COMPETING CONTINUATION	$222,495
														Subtotal = $222,495

Issue Date FY: 2013 ( Subtotal = $210,381 )
2013	2013	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	7	5/24/2013	NON-COMPETING CONTINUATION	$98,476
2013	2013	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	000	7	12/7/2012	NON-COMPETING CONTINUATION	$111,905
														Subtotal = $210,381

Issue Date FY: 2012 ( Subtotal = $268,871 )
2012	2012	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	001	6	12/27/2011	COMPETING CONTINUATION	$215,096
2012	2012	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Detection and Diagnosis Research	002	6	4/27/2012	COMPETING CONTINUATION	$53,775
2012	2010	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Treatment Research	000	5	12/27/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $268,871

Issue Date FY: 2010 ( Subtotal = $264,562 )
2010	2010	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Treatment Research	000	5	1/22/2010	NON-COMPETING CONTINUATION	$264,562
														Subtotal = $264,562

Issue Date FY: 2009 ( Subtotal = $264,562 )
2009	2009	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Treatment Research	000	4	1/12/2009	NON-COMPETING CONTINUATION	$238,106
2009	2009	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Treatment Research	001	4	3/18/2009	NON-COMPETING CONTINUATION	$26,456
														Subtotal = $264,562

Issue Date FY: 2008 ( Subtotal = $264,562 )
2008	2008	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Treatment Research	000	3	2/27/2008	NON-COMPETING CONTINUATION	$264,562
														Subtotal = $264,562

Issue Date FY: 2007 ( Subtotal = $264,274 )
2007	2007	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Treatment Research	000	2	2/26/2007	NON-COMPETING CONTINUATION	$264,274
														Subtotal = $264,274

Issue Date FY: 2006 ( Subtotal = $270,983 )
2006	2006	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Cancer Treatment Research	000	1	3/15/2006	NEW	$270,983
														Subtotal = $270,983

Grand Total All Awards = $3,962,379

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MRI Diffusion in Tumors using Oscillating Gradients

Award Number: R01CA109106

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/15/2006

PERIOD OF PERFORMANCE END DATE: 12/31/2023

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