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

> **NIH NIH R01** · HUGO W. MOSER RES INST KENNEDY KRIEGER · 2020 · $581,970

## Abstract

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.
Fur...

## Key facts

- **NIH application ID:** 9920229
- **Project number:** 5R01NS108452-03
- **Recipient organization:** HUGO W. MOSER RES INST KENNEDY KRIEGER
- **Principal Investigator:** Jun Hua
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $581,970
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920229

## Citation

> US National Institutes of Health, RePORTER application 9920229, Imaging small blood and lymphatic vessel abnormalities of the olfactory system in schizophrenia (5R01NS108452-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9920229. Licensed CC0.

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