Translation of Quantitative MR of Cartilage from Research to Clinical Care
Thomas M Link1
1UCSF School of Medicine, United States

Synopsis

In order to institute quantitative cartilage MRI in clinical practice a number of requirements need to be met. First of all, it is essential to define the exact clinical indications for quantitative imaging and how they would impact patient care. Second, image acquisition and analysis need to be standardized and meet clearly defined claims including reproducibility. Finally, sequences need to be approved by regulatory agencies and be available as a product from manufacturers. In this presentation we will discuss these different steps.

Purpose
To discuss requirements to institute quantitative MR of cartilage as part of clinical care considering both indications for imaging and methodological aspects.
Methods
Background: Cartilage loss is irreversible and up to now no effective pharmacotherapies are available to protect or regenerate cartilage. Quantitative or compositional MR imaging techniques have been developed to characterize the cartilage matrix quality at a stage where abnormal findings are early and potentially reversible, allowing prevention and life style interventions to halt disease progression (1). Studies have shown that cartilage quantitative imaging biomarkers allow earlier diagnosis, better prediction and more sensitive monitoring of early osteoarthritis of the knee (2, 3). The key advantage of these biomarkers is earlier detection before cartilage loss has happened and providing a truly quantitative, reproducible measurement. While T1ρ and T2 relaxation time measurements are the most frequently used cartilage compositional imaging biomarkers with the best available reproducibility data, other biomarkers have been developed which include T2*, delayed Gadolinium MRI of Cartilage (dGEMRIC), Sodium imaging and chemical exchange saturation transfer imaging of glycosaminoglycans (gagCEST).
In this presentation we will discuss the different steps that are required to translate quantitative, cartilage compositional imaging from research to clinical care.
Step 1: Define the exact clinical indications for quantitative imaging and how they would impact patient care (4).
The overall goal of cartilage quantitative imaging is risk assessment and monitoring of interventions/management. It should be noted, however, that quantitative imaging biomarkers are not indicated in advanced degenerative disease with significant loss of cartilage. Quantitative imaging may be used to assess cartilage quality and risk of disease progression in patients with early osteoarthritis without significant joint space narrowing (Kellgren-Lawrence grade 0-2) or with risk factors for osteoarthritis such as obesity, partial meniscectomy, family history, or high level of physical activity such as may be found in runners or other athletes. It may also be used in patients with chronic knee pain and no or limited evidence of degenerative changes on standard radiographs. In patients with acute or chronic injury cartilage quantitative imaging may provide information on the degree of cartilage matrix injury (5-7). T1ρ and T2 relaxation time measurements have also been used to monitor effectiveness of interventions such as weight loss (8, 9), physical activity (10) and pharmacotherapy (11). Moreover, studies have been performed that used T1ρ and T2 to monitor cartilage repair maturation (12, 13) as well cartilage changes after surgery (such as ACL reconstruction, meniscal repair) (14). A recent study (15) has also shown that a risk calculator including T2 relaxation time measurements can be used to predict the development of moderate to severe knee OA over 8 years. In summary quantitative cartilage MRI can identify and monitor early degeneration or injury of the cartilage matrix before cartilage is lost, thus allowing improved preventive interventions.
Step 2: Quantitative imaging needs to be standardized and meet clearly defined claims including reproducibility.
In order to use quantitative cartilage MRI as a clinical tool comparison across different sites and longitudinal evaluation are crucial. This requires standardization of image acquisition and analysis similar to what the International Society of Clinical Densitometry did for dual energy X-ray absorptiometry (DXA) in the setting of osteoporosis. Clear guidelines need to be available how to perform and analyze quantitative cartilage imaging, including detail on MRI sequences, patient related factors, image post-processing and image analysis as well as reproducibility. The first steps in this direction are currently performed by using the QIBA (Quantitative Imaging Biomarkers Alliance) mechanism of the RSNA. The recently published profile entitled “MR-based cartilage compositional biomarkers (T1ρ, T2) for the knee” (4) defines the behavioral performance levels and quality control specifications for T1ρ, T2 scans. While the emphasis is on clinical trials, this process is also intended to be applied for clinical practice. The aim of the QIBA Profile specifications is to minimize intra- and inter-subject, intra- and inter-platform, and inter-institutional variability of quantitative scan data due to factors other than the intervention under investigation. T1ρ and T2 studies performed according to the technical specifications of this QIBA Profile can provide quantitative data for single time-point assessments (e.g. disease burden, investigation of predictive and/or prognostic biomarker(s)) and/or for multi-time-point comparative assessments (e.g., response assessment, investigation of predictive and/or prognostic biomarkers of treatment efficacy). The QIBA profile claims are longitudinal, based on reproducibility and the major claim is defined as follows: Cartilage matrix T2 and T1ρ relaxation time values are measurable with MRI at 3T with a within-subject coefficient of variation of 4-5% (test-re-test from the same vendor).
Step 3: Sequences need to be approved by regulatory agencies and be available as a product from manufacturers.
To make quantitative cartilage imaging accessible to clinicians, MR imaging tools and analysis techniques need to be widely available as a product sequence from MRI manufacturers. They also need to be approved by regulatory agencies. Currently the only sequence which is available for cartilage compositional MR imaging is the CartiGram sequence from GE Healthcare, which measures cartilage T2 relaxation time and is also FDA approved.

Acknowledgements

I would like to acknowledge support through RSNA/QIBA and my QIBA Co-Chair Dr. Xiaojuan Li as well as NIH/NIAMS funding (R01AR077452, R01AR064771, R01AR078917, OAI).

References

References:

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Proc. Intl. Soc. Mag. Reson. Med. 30 (2022)