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The University of Kansas Announces Grant Funding for Knee Imaging Biomarkers Acquired from Weight Bearing CT

Patient with knee pain

The University of Kansas Medical Center Research Institute Department of Rehabilitation Medicine has received a grant from the National Institute of Arthritis Musculoskeletal and Skin Diseases (NIAMS), one of the 27 Institutes and Centers at the National Institutes of Health (NIH), to fund three years of research on the usefulness of bilateral weight bearing CT imaging and the critical need for more sensitive and affordable imaging biomarkers.

Osteoarthritis (OA) is the most prevalent form of arthritis, and the knee is the most commonly affected weight-bearing joint. The high cost of clinical trials creates a barrier for effective treatment development. Therefore, introduction of more specific and sensitive biomarkers could help to advance therapeutic development by reducing the time and sample sizes required for clinical trials.

Proposed Outcomes

There is an urgent need for imaging biomarkers that allow for identification of the best time in which patients will respond to treatment, and a means to analyze the efficiency of interventions. Early studies demonstrated the diagnostic value of bilateral weight-bearing CT in identifying knee OA symptoms accurately, as well as the feasibility to detect meniscal tears not detected by non-weight bearing MRI.

The grant from NIAMS will fund a study to validate the proposed imaging biomarkers and begin the qualification process for more responsive OA imaging biomarkers acquired using low-dose, bilateral standing CT imaging. Substantial advantages are offered over traditional radiographic biomarkers, including increased responsiveness to temporal changes in the joints, and a better reflection of the symptoms and severity of the disease. Additionally, this research will determine the prognostic validity of standing CT findings for detecting progression and worsening pain in people who currently suffer from or are at risk for knee OA.

Long-Term Impact

With the support of NIAMS, this research holds promise to detect joint damage earlier, and accelerate the pace of scientific discovery and clinical trials. The continuing impact will be evident through a shift in knee joint imaging with an improved biomarkers for monitoring knee OA disease features. If the additional meniscal extrusions detected on bilateral standing CT are clinically relevant, then standing CT could improve identification of the most appropriate patients for clinical trials – those at risk of rapid OA progression. Successful completion will provide improved biomarkers that will help those who suffer from knee OA through making clinical trials more affordable and accelerating therapeutic improvement.

For more information on visualizing cartilage and menisci in the knee using standing CT arthrogram versus MRI, click here.

New, Reliable Technology for Measuring Tibiofemoral Joint Space

Recent work by Dr. Neil H. Segal examined the potential of a low-dose standing CT scan for evaluating changes in tibiofemoral joint space of patients suffering from knee osteoarthritis.

The results of Dr. Segal’s study were recently published in the medical journal Skeletal Radiology and reveal that when taken two weeks apart, standing CT images are even more reliable than plain radiographs. The insightful, 3-D, information-packed images suggest that the modified foot/ankle scanner by CurveBeam used to capture the data may soon become a valuable tool for doctors to evaluate and track the disease’s progression, as well as for researchers wanting to study it.

Measurements of the tibiofemoral joint space were obtained from two bilateral fixed-flexed standing CT images taken two weeks apart, utilizing a modified version of a CurveBeam scanner more commonly used to capture images of the foot and ankle. Participants were exposed to an extremely low dose of effective radiation, O.2 mSv – no more than the average person is typically exposed to from the natural environment itself in any two-week period.

The main purpose of the study was to determine whether or not standing CT scans might be a viable alternative to plain radiographs for studying patients’ knee osteoarthritis – and how reliable such scans might be. Thirty people with a range of osteoarthritis features took part, and the Institutional Review Board approved all aspects of the study.

The results suggest the data obtained is extremely reliable. Moreover, the 3D imaging of both the tibiofemoral and patellofemoral joints the standing CT scanner produces offers a wealth of enhanced information for doctors and researchers to draw upon.

All this, the study shows, without a clinically significant increase in either acquisition time or radiation dose.

Dr. Segal’s work comes as a response, in part, to the difficulties and challenges in acquiring meaningful, reliable tibiofemoral joint space measurements using traditional radiographs.

Past studies have shown that the replication of measurements has been poor, with limited information obtained. More aggravating still is the fact that months if not years are usually required between radiographs before any change in the patient’s condition can be detected. An efficient, accurate, time-saving alternative has long been needed.

The modified CurveBeam scanner, by contrast, has the potential to address these challenges. As evidence from the study showed, the standing scanner provided exceptionally reliable images with insignificant doses of radiation emitted.

The next step will be to assess the responsiveness of the standing CT scanner to changes in the tibiofemoral joint over time. If effective, the protocol will no doubt become an invaluable tool for doctors and researchers alike in their work to combat the ravages of knee osteoarthritis and related ailments.

Access the link to the article here.

Standing CT vs. MRI for Advanced Visualization of Knee Cartilage and Meniscus

At the 2016 OARSI World Congress in Amsterdam, Netherlands, Dr. Neil Segal, MD, MS, and Dr. Ali Guermazi, MD, PhD , presented a poster describing “Advances In Visualization Of Knee Cartilage And Meniscus With Standing Computed Tomography Arthrography”.

Standing CT arthrography (SCTa) has also been shown to have some distinct advantages over MRI, according to the poster presentation. “Potential advantages of SCTa over non-weight-bearing MRI/MRA include: 3D measures of meniscal position and morphology; detection of pathology not detected in unloaded positions; and ability to bear weight bilaterally in a functional position, better recreating the magnitude of muscle and external forces acting about the knee during usual standing….  SCTa can be obtained in multiple knee flexion angles, while an MRI knee coil may permit imaging only with the knee in extension, and SCTa is less expensive than MRI.”

Figure 1: SCTa and corresponding MR arthrography demonstrating outstanding delineation of tibiofemoral and patellofemoral articular cartilage, with better differentiation between the cartilage and subchondral bone on SCTa. Visualization of the boundaries of the menisci was achieved to a similar degree on SCTa and MRA.
Figure 1: SCTa and corresponding MR arthrography demonstrating outstanding delineation of tibiofemoral and patellofemoral articular cartilage, with better differentiation between the cartilage and subchondral bone on SCTa. Visualization of the boundaries of the menisci was achieved to a similar degree on SCTa and MRA.

As part of the background for their presentation, Drs. Segal and Guermazi stated that “MRI is the standard for non-invasive visualization of cartilage and menisci, and … Absence of weight bearing limits evaluation of the functional position and configuration of these structures…Advances in standing CT (SCT) have allowed 3D imaging of the knees while under physiological loads, similar to fixed-flexed or semi-flexed radiograph protocols.”

Their objective was to evaluate a protocol for SCTa for imaging weight bearing cartilage and menisci and to assess potential advantages over non-weight bearing MRI.

figure 2
Figure 2: Sagittal reformatted SCTa and its corresponding MRA demonstrated outstanding delineation of articular cartilage with better differentiation between the cartilage and subchondral bone on SCTa, while also visualizing the ACL and PCL in the femoral notch.

Although the sample size was small, the results were noteworthy. As shown in the images, SCTa permits evaluation of cartilage and menisci in three dimensions, while the patient is standing and under physiological load. Furthermore, SCTa, “may be useful for assessment of menisci as well as tibiofemoral and patellofemoral cartilage in functional stance,” according to the presentation.

The two participants in the study were a 42-year-old man without osteoarthritis (Figures 1 and 2), and a 67-year-old woman with KL2 knee osteoarthritis (figures 3-5). The participants had a similar contrast agent applied.

Figure 3a: Sagittal SCTa demonstrating minimal cartilage thinning on the left medial tibial plateau Figure 3b: Axial image depicting location of the sagittal slice in Figure 3a
Figure 3a: Sagittal SCTa demonstrating minimal cartilage thinning on the left medial tibial plateau
Figure 3b: Axial image depicting location of the sagittal slice in Figure 3a

The actual imaging techniques used were fixed-flexed (approximately 20°) SCTa (INVESTIGATIONAL ONLY cone beam CT knee imaging system*, CurveBeam, Warrington, PA, USA) and non-weight bearing MRI (Siemens TrioTim, Washington DC, USA).

“Following 2-3 minutes of unloaded knee flexion and extension, a low-dose SCT scan was acquired utilizing cone beam reconstruction. Participants were positioned with the tips of the great toes, patellae, and the anterior superior iliac spines coplanar to each other and the feet 10°externally rotated. Scans were acquired with a 0.3mm isotropic voxel size (20x 35x35cm) with an effective radiation dose of approximately 0.1 mSv. 10 minutes following SCTa, MR arthrography was acquired (NEX=1, ETL=3, Slice thickness=2 mm, Slice spacing 2 mm, Matrix= 240 x 320, FOV=140 mm with axial T1 fat-sat (TR=712 msec, TE=12 msec); coronal T1 fat sat (TR=730 msec, TE=10 msec); and sagittal T1 fat sat (TR=796 msec, TE=10 msec).

Figure 4a: Coronal SCTa demonstrating minimal cartilage thinning on the left medial tibial plateau Figure 4b: Axial image depicting location of coronal slice in Figure 4a
Figure 4a: Coronal SCTa demonstrating minimal cartilage thinning on the left medial tibial plateau
Figure 4b: Axial image depicting location of coronal slice in Figure 4a
Figure 5a: Sagittal SCTa image demonstrating a small tear of the tibial surface of the post. horn of the medial meniscus Figure 5b: Axial image depicting location of sagittal slice in Figure 5a
Figure 5a: Sagittal SCTa image demonstrating a small tear of the tibial surface of the post. horn of the medial meniscus
Figure 5b: Axial image depicting location of sagittal slice in Figure 5a

*The CurveBeam knee imaging system is investigational only and is not available for sale in the US.