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In utero mouse embryo phenotyping with high-frequency ultrasound

Award Number: R01EB022950
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2016
PERIOD OF PERFORMANCE END DATE: 06/30/2021

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In utero mouse embryo phenotyping with high-frequency ultrasound - Project Summary/Abstract The goal of this proposal is to phenotype early- to mid-gestational mouse embryos by segmenting select organ systems in 3D data sets acquired in utero with high-frequency ultrasound (HFU). The International Mouse Phe- notyping Consortium (IMPC), which includes the NIH Knockout (KO) Mouse Phenotyping Program (KOMP2), will generate 20,000 mouse strains in the next decade, including many important models of human structural birth defects and congenital diseases. The development of phenotyping methods that provide for efﬁcient pipeline analyses of defects in embryonic growth in the KO mouse strains is a high priority for this effort. An in utero 3D imaging approach, enabling volumetric and longitudinal analyses of a variety of organ systems over a range of early- to mid-gestational stage mouse embryos, would provide added beneﬁt and critical additional in vivo data not currently available. Commercial HFU systems are widely available in many research centers largely thanks to the NIH-funded Small Animal Imaging Research Programs and Shared Instrumentation Programs. HFU is therefore an excellent candidate modality to provide in utero 3D image data that can be quantitatively analyzed and archived to support the KOMP2/IMPC embryonic lethal phenotyping pipeline and future phenotyping efforts. We propose to develop and validate in utero 3D HFU image-acquisition protocols and image-processing meth- ods that permit noninvasive, longitudinal studies of embryonic development and, in particular, the detection and characterization of KO phenotypes. Volumetric HFU data will be collected in utero from mouse embryos staged between E9.5 to 15.5 in order to establish a database of normal development. Algorithms will be developed to segment 3D regions and extract parameters that quantify embryonic stage and identify regional changes between normal and KO embryos. We will acquire data with a custom, annular-array system and with a VisualSonics Vevo 2100. The ﬁne-resolution annular-array data will be used to initially develop the image-processing algorithms and then the algorithms will be adapted for Vevo 2100 data. We will compare the quantitative parameters derived from the segmentation results obtained from the two scanners to ensure that the Vevo 2100 is able to provide equivalent mutant detection and quantiﬁcation. Initial testing will be undertaken using wild-type and En1 and Gli2 mutants that have known defects. Finally, the acquisition and processing protocols will be applied to 3D Vevo 2100 data from 5-10 KOMP2 KO mouse lines with embryonic defects in a variety of organ systems to validate the HFU methods for detecting and characterizing phenotypes in these mutant embryos.


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: 2023 ( Subtotal = $12,527 )
2023	2019	RIVERSIDE RESEARCH INSTITUTE	100 WILLIAM ST	NEW YORK	NY	10038	NEW YORK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	11/23/2022	NON-COMPETING CONTINUATION	$12,527
														Subtotal = $12,527

Issue Date FY: 2022 ( Subtotal = -$26,257 )
2022	2019	RIVERSIDE RESEARCH INSTITUTE	156 WILLIAM ST 9TH FL	NEW YORK	NY	10038	NEW YORK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	12/30/2021	NON-COMPETING CONTINUATION	-$26,257
														Subtotal = -$26,257

Issue Date FY: 2019 ( Subtotal = $691,071 )
2019	2019	RIVERSIDE RESEARCH INSTITUTE	156 WILLIAM ST 9TH FL	NEW YORK	NY	10038	NEW YORK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	7/22/2019	NON-COMPETING CONTINUATION	$691,071
														Subtotal = $691,071

Issue Date FY: 2018 ( Subtotal = $691,071 )
2018	2018	RIVERSIDE RESEARCH INSTITUTE	156 WILLIAM ST 9TH FL	NEW YORK	NY	10038	NEW YORK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	7/17/2018	NON-COMPETING CONTINUATION	$691,071
														Subtotal = $691,071

Issue Date FY: 2017 ( Subtotal = $708,539 )
2017	2017	RIVERSIDE RESEARCH INSTITUTE	156 WILLIAM ST 9TH FL	NEW YORK	NY	10038	NEW YORK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	6/26/2017	NON-COMPETING CONTINUATION	$708,539
														Subtotal = $708,539

Issue Date FY: 2016 ( Subtotal = $757,759 )
2016	2016	RIVERSIDE RESEARCH INSTITUTE	156 WILLIAM STREET, NINTH FL	MANHATTAN	NY	10038	NEW YORK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	9/23/2016	NEW	$757,759
														Subtotal = $757,759

Grand Total All Awards = $2,834,711

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In utero mouse embryo phenotyping with high-frequency ultrasound

Award Number: R01EB022950

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2016

PERIOD OF PERFORMANCE END DATE: 06/30/2021

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