Ultrashort echo time quantitative susceptibility mapping (UTE-QSM) for detection of hemosiderin deposition in hemophilic arthropathy: A feasibility study

Abstract

Purpose: The purpose of this study was to investigate the feasibility of ultrashort echo time quantitative susceptibility mapping (UTE-QSM) for assessment of hemosiderin deposition in the joints of hemophilic patients.

Methods: The UTE-QSM technique was based on three sets of dual-echo 3D UTE Cones data acquired with TEs of 0.032/2.8, 0.2/3.6, and 0.4/4.4 ms. The images were processed with iterative decomposition of water and fat with echo asymmetry and least-squares estimation to estimate the B₀ field map in the presence of fat. Then, the projection onto dipole field (PDF) algorithm was applied to acquire a local field map generated by tissues, followed by application of the morphology-enabled dipole inversion (MEDI) algorithm to estimate a final susceptibility map. Three healthy volunteers and three hemophilic patients were recruited to evaluate the UTE-QSM technique's ability to assess hemosiderin in the knee or ankle joint at 3T. One patient subsequently underwent total knee arthroplasty after the MR scan. The synovial tissues harvested from the knee joint during surgery were processed for histological analysis to confirm iron deposition.

Results: UTE-QSM successfully yielded tissue susceptibility maps of joints in both volunteers and patients. Multiple regions with high susceptibility over 1 ppm were detected in the affected joints of hemophilic patients, while no localized regions with high susceptibility were detected in asymptomatic healthy volunteers. Histology confirmed the presence of iron in regions where high susceptibility was detected by UTE-QSM.

Conclusion: The UTE-QSM technique can detect hemosiderin deposition in the joint, and provides a potential sensitive biomarker for the diagnosis and prognosis of hemophilic arthropathy.

Keywords: QSM; UTE; ankle; arthropathy; hemophilia; knee; susceptibility.

Figure 1.

3D dual-echo UTE Cones imaging. (A) Pulse sequence and (B) k-space trajectory. The dual-echo imaging is repeated to acquire multiple TEs (six in this study) at different TEs, TE1 and TE2, by delaying the readout gradient.

Figure 2.

Healthy volunteers (A: 35-year-old, B: 34-year-old, and C: 35-year-old male). The estimated susceptibility map shows very little spatial variation between tissues and no localized regions of high susceptibility.

Figure 3.

Reconstructed images from Patient A. (A) Magnitude and (B) phase images, and (C) a region of interest (yellow dotted line) in magnitude image at TE of 32 μs (left), the estimated R2* map from IDEAL (middle), and signal decay and T2* estimation (right). Rapid signal decay is shown in the regions indicated by red arrows in (A), which is due to the highly concentrated hemosiderin. The measured T2* in one region (yellow circle in C) is 0.36 ± 0.06 ms, which is impossible to capture with clinical MR sequences with long TE.

Figure 4.

QSM estimation in Patient A. (A) A water image, (B) a fat image, and (C) a total field map from IDEAL, (D) a local field map after PDF algorithm, and (E) the estimated susceptibility map. Signal from the hemosiderin regions is present in the water image, while it is not in the estimated fat image (red arrows). High susceptibility is detected in the regions indicated by yellow arrows.

Figure 5.

Clinical MR images and QSM in all three hemophilic patients. T1-weighted MRI (A, D, G), T2-weighted MRI (B, E, H), and QSM (C, F, I). The susceptibility estimated in the regions of interest indicated by white arrows are 4.9 ± 2.5 ppm, 2.4 ± 1.6 ppm, and 2.3 ± 1.9 ppm for Patients A, B, and C, respectively.

Figure 6.

Histology of osteochondral tissues from Patient A. Susceptibility map estimated in two representative slices (A and C) and the corresponding histological images (B and D). Perl’s reaction product (blue) in B and D demonstrate iron (arrows) with a concentration-dependent intensity, primarily shown in hypertrophic synovial tissue adherent to the joint. Bars represent 200 microns in widefield images and 50 microns in insets. Red hematoxylin counterstain was applied. The measured susceptibility with UTE-QSM is 4.5 ± 1.8 ppm for Tissue A and 2.7 ± 1.1 ppm for Tissue B, which agrees with the observation that Tissue A shows higher iron concentration than Tissue B in histology.