# Quantitative Measurement of Joint pH with Magnetic Resonance Imaging

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2020 · —

## Abstract

The diagnosis of osteoarthritis (OA) is based on clinical, laboratory, and imaging findings. Although
diagnostic imaging is widely practiced, observations gained through diagnostic imaging do not necessarily reflect
the patient’s experience of pain, which is the most important presenting feature in the clinical syndrome of OA.
In fact, studies have estimated that less than 50% of individuals with radiographic knee OA report knee pain.
The determinants of pain in OA are not well understood, but multiple interactive pathways are involved
including psycho-social and physical components. From a biological perspective, neuronal activity in nociceptive
pathways is responsible for signal generation that is interpreted in the brain as pain.
 Extracellular acidification in tissues has been recognized for many years now as a major factor involved
in pain. Protons can directly activate cation channels, such as acid-sensing ion channels (ASICs), and have
become increasingly recognized over the past two decades as being involved in the initiation, modulation, and
sensitization of pain messages. In fact, an acidic milieu alone, without structural tissue damage, is sufficient to
decrease nociceptor threshold sensitivity and potentiate the pain matrix.
 Recently, a unique molecular imaging method, termed acidoCEST magnetic resonance imaging (MRI),
was introduced. This MRI technique uses a clinically approved X-ray/computed tomography contrast agent as a
probe to measure local extra-cellular pH through the chemical exchange saturation transfer (CEST) effect. Joints
are ideal targets for the acidoCEST technique since relatively large volumes and concentrations of iodinated
contrast are routinely and safely used during clinical arthrography. The acidoCEST-UTE sequence combines the
acidoCEST technique with an ultrashort echo time (UTE) acquisition to quantify the pH-sensitive CEST effect in
musculoskeletal structures with long T2 (including cartilage, synovium, and muscles) and short T2 (including
menisci, ligaments, capsule, and tendons). A minimally-invasive method to measure extracellular pH could
potentially provide a visual map of the chemistry involved in pain.
 In our first aim, we seek to optimize and accelerate the acidoCEST-UTE technique in phantoms and assess
sensitivity to pH throughout a range of experimental conditions. In our second aim, we translate our technique
to patients who will undergo total knee arthroplasty and to patients without knee pain. We hypothesize that
our technique will provide a minimally-invasive method to measure extracellular pH and will provide superior
correlations with clinical scores and immunohistochemical evaluation of ASICs compared with conventional
structural MRI evaluation. Ultimately, successful execution of the proposed study will provide information on
the nociceptive system in and around the joint, enable visualization of painful internal structures, and facilitate
diagnostic and management decision-making in clini...

## Key facts

- **NIH application ID:** 9870797
- **Project number:** 5I01RX002604-03
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Eric Y Chang
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870797

## Citation

> US National Institutes of Health, RePORTER application 9870797, Quantitative Measurement of Joint pH with Magnetic Resonance Imaging (5I01RX002604-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9870797. Licensed CC0.

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