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Imaging small blood and lymphatic vessel abnormalities of the olfactory system in schizophrenia

Award Number: R01NS108452
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT Olfactory deficits are a core feature and pre-clinical sign of numerous brain diseases, including schizophrenia. The olfactory system provides direct access to orbitofrontal-limbic neurocircuitry implicated in the disease con- ditions and holds a unique promise for understanding aberrant neurodevelopment processes. However, a major hurdle for studies of olfaction is the lack of non-invasive methods to capture the underlying neurophysiological substrates of olfactory loss. To date, clinical evaluation of olfaction has been limited to psychophysical as- sessment, which is subjective and uninformative regarding the underlying abnormalities. In the brain, small ar- terioles with diameters up to 100-150 microns are the primary regulator of local tissue perfusion. Lymphatic vessels have also been identified in the brain, which are believed to play a crucial role in the clearance of waste products. Quantitative measurement of the small blood and lymphatic vessels in the olfactory system would provide biologically meaningful information on olfactory loss, and would significantly enhance efforts for the prediction and staging of brain diseases. Here, we propose to develop and optimize MRI techniques for the quantitative measurement of small blood and lymphatic vessels in the human olfactory cortex with the following aims: Aim 1: To develop and optimize MRI methods for measuring blood volume in arteriolar and venous mi- crovessels separately in the olfactory cortex. The olfactory cortex is notoriously difficult for MRI due to the well-known signal loss caused by the susceptibility effects at the boundary between tissue and nasal cavity. We will develop and optimize new MRI sequences for the olfactory regions to recover signal loss close to the nasal cavity. Aim 2: To develop and optimize MRI methods for measuring dynamic signal changes in small lymphatic vessels in the brain. Lymphatic vessels have recently been found in the dura mater and around the cribriform plate in the olfactory area in the brain. Non-invasive imaging methods for the cerebral lymphatic vessels are extremely scarce and are mostly limited to large lymphatic ducts only. In addition, the existing methods cannot detect dynamic lymphatic signal changes with sufficient temporal resolution due the long scan time needed. Based on previous work, we propose to use contrast agent-based MRI methods to measure dynamic signal changes in small lymphatic vessels in the brain, from which vessel volume information can be deduced. Aim 3: To characterize small blood and lymphatic vessel abnormalities of the olfactory system in schizophrenia patients, and their association with the olfactory deficits assessed by behavioral tests. Taken together, the proposed studies will advance our understanding of the underlying physiological changes associated with olfactory deficits in schizophrenia, which may facilitate the development of disease biomarkers and potential treatment targets. Furthermore, the research will provide MRI methodologies that can be used to probe similar physiological changes in other brain regions and diseases.


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: 2025 ( Subtotal = $0 )
2025	2022	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	10/15/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $571,062 )
2022	2022	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	5/12/2022	NON-COMPETING CONTINUATION	$571,062
														Subtotal = $571,062

Issue Date FY: 2021 ( Subtotal = $576,637 )
2021	2021	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/13/2021	NON-COMPETING CONTINUATION	$576,637
														Subtotal = $576,637

Issue Date FY: 2020 ( Subtotal = $581,970 )
2020	2020	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	8/27/2020	NON-COMPETING CONTINUATION	$0
2020	2020	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	7/13/2020	NON-COMPETING CONTINUATION	$581,970
														Subtotal = $581,970

Issue Date FY: 2019 ( Subtotal = $952,346 )
2019	2019	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/23/2019	NON-COMPETING CONTINUATION	$545,656
2019	2019	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	7/22/2019	SUPPLEMENT FOR EXPANSION	$406,690
2019	2019	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	6/4/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $952,346

Issue Date FY: 2018 ( Subtotal = $555,773 )
2018	2018	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/20/2018	NEW	$571,173
2018	2018	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	9/3/2018	NEW	-$15,400
														Subtotal = $555,773

Grand Total All Awards = $3,237,788

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Imaging small blood and lymphatic vessel abnormalities of the olfactory system in schizophrenia

Award Number: R01NS108452

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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