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Below is a brief summary of some of the collaborative projects that are currently being undertaken within the different research groups.

TR & D 1

T1rho-weighted magnetic resonance imaging as a quantitative biomarker of lumbar disc degeneration and associated low back pain

aims to develop T1ρ MRI as a biomarker for disc degeneration as such all pulse sequence and data processing strategies have been developed at the Resource. Innovation lies in our imaging modality, 3D spin lock T1ρ-weighted MRI, which we apply to a patient population for the first time. Notably, innovation is present not only in the imaging methods, but also in our approach to the study design to investigate DDD in a patient population. The project brings together researchers in MR imaging from the Resource as well as disc basic scientists and clinicians highly skilled and experienced with both discography and spine surgery for an innovative approach to translational patient-based research.

MRI Assessment of a Model of Osteoarthritis

aims to develop sensitive and noninvasive approaches for quantifying the early biochemical and structural changes associated with arthritis in small animal models.

TR & D 2

Diffuse optics for acute stroke management

concerns the development and validation of diffuse correlation spectroscopy (DCS) for use in bedside optical monitoring of CBF in patients with acute stroke. One of the principle means of validating DCS is through comparisons with ASL CBF obtained concurrently. This will be carried out as part of Aim 3 of the project. TR&D 2 investigators are involved in this endeavor, and TR&D 2 resources will be used to develop concurrent MRI and DCS measurements for this as well as other projects involving DCS validation. Validation in clinical populations will be carried out at 3T.

Perfusion MRI for Multisite Studies of Brain Function

will develop matching ASL imaging sequences for use on the two most common scanning platforms: Siemens and GE. These sequences will incorporate the latest advances in ASL technology, some of which were developed and validated under this RR. As part of this project, parameters affecting CBF quantification will also be assessed to develop the most robust procedures for absolute quantification of CBF data. Although this project focuses on applications at clinical field strengths, the biophysical studies carried out at 7T under Aim 2 of this Core will contribute valuable information to this overall effort.

TR & D 3

Quantitative structural and functional imaging of the lung

will focus on the use of hyperpolarized 3He MRI for the systematic study of the structure and function of the lung in healthy and diseased human subjects. This BRP will also extend the methods of hyperpolarized gas production and imaging with the goal of making 3He MRI a more practical research and clinical tool. The project will bring together the expertise of three organizations which share the long-term objective of understanding lung physiology. This project’s more immediate objective is to characterize the progression of 3He imaging assessments over time and to identify which of those assessments have the potential to detect the early stages of Chronic Obstructive Pulmonary Disease (COPD).

Development of hyperpolarized helium for assessing ILD

Our central hypothesis is that fibrotic lung disease (UIP) will be characterized by regional areas of decreased compliance with an increase in distil airway size (honeycomb lung) in contrast to inflammatory interstitial lung disease which will be characterized by areas of decreased compliance with a decrease in distil airway size. In addition, we hypothesize that the distil airways in fibrotic lung disease will have relatively maintained alveolar oxygen levels while in inflammatory interstitial lung disease the distil airway/alveolar oxygen levels will be decreased. We will address the central hypothesis by pursuing the following specific aims:

Surfactant-Protein Innate Immunity in an Asthma Model

to define the role and regulation of the innate immune surfactant protein D (SP-D) in the pathogenesis of allergen-induced airway hyperresponsiveness. In order to better define the role of SP-D and to further elucidate the characteristics of airway obstruction caused by exposure to Af, we will utilize novel technique in magnetic resonance imaging (MRI) with gaseous contrast agents. While the conventional MRI may fall short of being a suitable technique to view structural and functional alterations of the lung, hyperpolarized 3He MRI has recently emerged as a potentially important method for structural and functional lung imaging. We aim to investigate regional ventilation changes in the mouse lung following sensitization and challenge with Af.

Imaging regional physiologic and structural parameters of airway remodeling

The central hypothesis of this proposal is that quantitative regional measurement of lung function with hyperpolarized helium-3 MRI is a sensitive tool to detect airway and alveolar inflammation and remodeling associated with asthma, and that it is a more powerful diagnostic tool than conventional pulmonary function tests.

Imaging Regional Physiologic Parameters of Lung Function

The central hypothesis of this proposal is that a smoking model of emphysema will be characterized by increased concentrations of known molecular instigators of apoptosis, which will precede structural changes to the lung. Further, the course of structural changes can be altered using interventions that block specific apoptotic pathways.

TR & D 4

Cerebrovascular Physiology of Infants with Congenital Heart Defects

to reduce the incidence of brain injury in newborn infants, particularly in the context of those newborns who must undergo surgical repair of congenital heart defects (CHD). More specifically, the broad aims of the research are two-fold: (1) To improve understanding of the relative contribution of cerebral hypoperfusion and poor vascular reactivity towards the development of structural brain abnormalities, and (2) to improve understanding about the structural consequences of periventricular leukomalacia (PVL) on brain development for survivors of surgical repair of severe congenital heart defects (CHD) in neonates. Unfortunately, specific data on cerebral blood flow (CBF) in this population are scarce, and methods for CBF measurement can be quite invasive and are sometimes unreliable.

Functional Activation During Cerebral Ischemia

is to develop and explore new methods for neuroprotection of brain tissue following cerebral ischemia or stroke using animal models. Broadly, this research is driven by the large complement of deleterious events that occur during and following cerebral ischemia, and by the subsequent resulting burden on patients, their families and society. Indeed, the development of novel chemical compounds designed to interfere with the cascade of events that occur in tissue following cerebral ischemia has grown enormously over the years. In the present proposal it is hypothesized that functional forepaw stimulation improves outcome from focal forebrain ischemia because the activation flow coupling (AFC) response produces an incremental cerebral blood flow (CBF) increase, probably through collateral flow sources, that exceeds the metabolic demands of stimulation, thus allowing an increase in basal tissue metabolism. Preliminary data demonstrate a neuroprotective effect of functional forepaw stimulation contralateral, but not ipsilateral, to the ischemic hemisphere in the rat intraluminal filament model of MCA stroke. We are conducting a series of studies to examine the effects of functional stimulation on CBF and ischemic injury in acute middle cerebral artery (MCA) stroke to better characterize the effects of functional stimulation on cerebrovascular pathophysiology, brain injury, and neurological outcome in rats. This collaborative project focuses on the effect of functional stimulation on neuronal ischemic damage.

Concurrent MR-NIR Imaging for Breast Cancer Diagnosis

concerns application of multi-modal diffuse optics to breast cancer screening, diagnosis and therapy monitoring. Multi-modal imaging, combining high resolution anatomical information (MR) with high spatial and temporal resolution quantitative functional information (NIR), will potentially improve breast cancer diagnosis. While concurrent MR-NIR breast imaging has been studied before, primarily to validate NIR, a clinical study to evaluate the diagnostic value of MR-NIR compared to stand alone NIR has not been performed. This collaborative study aims to evaluate the diagnostic value of concurrent MR-NIR imaging, the proposed research activity will result in better understanding of breast tumor physiology, and the potential of optical methods in early detection, screening, and staging.