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Principal Investigator: Yajun Ma
Organization: UNIVERSITY OF CALIFORNIA, SAN DIEGO
Fiscal Year: 2024
Award: $666,914
Funding agency: National Institute of Arthritis and Musculoskeletal and Skin Diseases
Abstract
Intervertebral disc (IVD) degeneration and related low back pain (LBP) affect up to 85% of the U.S.
population over their lifetime, resulting in annual healthcare costs that exceed $100 billion. The IVD is largely
avascular and consists of a central proteoglycan (PG)-rich nucleus pulposus (NP), and a surrounding collagen-
rich annulus fibrosus (AF), as well as superiorly and inferiorly located endplates. The IVD relies on diffusion of
nutrients and waste through the cartilaginous endplate (CEP) to maintain its health. IVD degeneration is
characterized by loss of PGs, dehydration of the NP, collagen loss within the AF, and degradation of the CEP.
Dehydration and calcification of the CEP reduce its diffusivity, leading to a reduction in oxygen and glucose
transport to the remainder of the disc. Changes in the CEP may occur at the same time or even precede disc
degeneration. Evaluation of this complex situation requires a comprehensive, non-invasive imaging technique
that can assess PG in the NP, collagen in the AF, and diffusivity of the CEP. Magnetic resonance imaging
(MRI) is routinely used in the diagnosis of IVD degeneration. However, conventional MRI techniques do not
provide reliable assessment of disc biochemical content nor of CEP function. This study aims to further
develop a 3D ultrashort echo time (UTE) adiabatic T1r (UTE-AdiabT1r) sequence for robust mapping of PGs, a
UTE magnetization transfer (UTE-MT) sequence for mapping of macromolecular fraction (MMF), an adiabatic
inversion recovery UTE with fat saturation (IR-FS-UTE) sequence for T2* mapping of the CEP to evaluate
calcification and dehydration, and a UTE dual echo steady state (UTE-DESS) sequence to study its apparent
diffusion coefficient (ADC). In Aim 1 we will develop 3D UTE sequences to evaluate IVD in lumbar spines from
young (<40y, n=10), mid-age (40-70y, n=10), and elderly (>70y, n=10) donors, and correlate UTE (AdiabT1r,
MMF, T2*, ADC) and clinical MRI measures with reference including CT, µCT, histology, biochemistry, and
diffusion test of three groups of spine samples. In Aim 2 we will evaluate 3D UTE sequences to assess IVD
degeneration and regeneration using a mature rabbit annular puncture chronic disc degeneration model. We
will study IVD degeneration in four groups of rabbits (n=16 per group) at 4, 8, 16, and 28 weeks post-AF
puncture, as well as IVD regeneration using six groups of rabbits (n=16 per group) at 4, 12 and 24 weeks post-
injection of saline and growth differentiation factor-6 (GDF-6). We will correlate UTE and clinical MRI findings
with reference including µCT, histology, biochemistry, and diffusion test of ten groups of rabbit lumbar spines.
In Aim 3 we will translate UTE sequences to study IVD degeneration in patients with chronic LBP (n=40) and
normal IVDs in healthy volunteers (n=40), compare UTE and clinical MRI metrics of the NP, AF, and CEP of
the lumbar spine in the two groups, and correlate them with clinical evaluations. Our central hypothesis is
that UTE sequences can detect changes in PG and collagen in the disc as well as changes in diffusivity of the
CEP, allowing more comprehensive and accurate evaluation of disc degeneration than is now possible.
Terms: <3-D><3-Dimensional><3D><Address><Affect><Age><Animals><BMI><BMI percentile><BMI z-score><Biochemical><Biochemistry><Biological Chemistry><Biological Markers><Body Tissues><Body mass index><Calcified><Cell Communication and Signaling><Cell Signaling><Chronic><Chronic low back pain><Clinical><Clinical Evaluation><Clinical Testing><Collagen><Complex><Dehydration><Development><Diagnosis><Diffusion><Domestic Rabbit><Elderly><Evaluation><Fiber><Frequencies><GDF 6><GDF6><Goals><Health><Health Care Costs><Health Costs><Healthcare Costs><Histologic><Histologically><Histology><Hydration><Hydration status><Image><Imaging Procedures><Imaging Technics><Imaging Techniques><Inferior><Injections><Intervertebral Disc Degenerative Disease><Intervertebral Disc Degenerative Disorder><Intervertebral Disk><Intervertebral disc structure><Intracellular Communication and Signaling><Location><Low Back Ache><Low Back Pain><Low Backache><Lumbago><MR Imaging><MR Tomography><MRI><MRIs><Magic><Magnetic Resonance Imaging><Maps><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Modeling><NMR Imaging><NMR Tomography><Nuclear Magnetic Resonance Imaging><Nutrient><Oryctolagus cuniculus><Pain><Painful><Patients><Population><Proteoglycan><Puncture procedure><Punctures><QOL><Quality of life><Quetelet index><Rabbits><Rabbits Mammals><Recovery><Reference Standards><Relaxation><Research><Research Specimen><SF-36><Saline><Saline Solution><Sampling><Series><Signal Transduction><Signal Transduction Systems><Signaling><Specimen><Spinal Column><Spine><Techniques><Testing><Time><Tissues><Translating><Vertebral column><Zeugmatography><advanced age><ages><backbone><bio-markers><biologic marker><biological signal transduction><biomarker><body water dehydration><calcification><cartilaginous><clinical test><contrast imaging><degenerated intervertebral disc><degenerative disc disease><developmental><diffused><diffuses><diffusing><diffusions><disability><disc degeneration><disc regeneration><geriatric><glucose transport><growth differentiation factor 6><healthy volunteer><imaging><intervertebral disk degeneration><non-invasive imaging><noninvasive imaging><nucleus pulposus><oxygen transport><regenerate disc tissue><research clinical testing><saturated dietary fat><saturated dietary lipid><saturated fat><saturated lipid><senior citizen><sex><three dimensional><translational study><wasting>