Assessment of Femoral Head Revascularization in Legg-Calvé-Perthes Disease Using Serial Perfusion MRI

Kim, Harry K.W.; Burgess, Jamie; Thoveson, Alec; Gudmundsson, Paul; Dempsey, Molly; Jo, Chan Hee

doi:10.2106/jbjs.15.01477

Cited by 34 publications

(41 citation statements)

References 28 publications

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“…These vessels express high levels of hypoxia‐inducible factor‐1 and vascular endothelial growth factor . The pattern of neovascularization observed in the piglet model is consistent with the findings from a serial perfusion study in patients with LCPD using contrast‐enhanced magnetic resonance imaging (MRI), which demonstrated that revascularization in the SOC is first observed at the periphery of the femoral head . Interestingly, younger children with LCPD tend to have better clinical outcomes than older children, which may be related to their greater epiphyseal cartilage volume and, thus, greater capacity to repair and remodel the femoral head following ischemic injury .…”

supporting

confidence: 78%

“…The timing and rate of revascularization are important factors in determining the progression of femoral head healing and to predict clinical outcome. However, there is a lack of imaging technologies to noninvasively and serially assess revascularization patterns in both the SOC and the epiphyseal cartilage following ischemic injury …”

mentioning

confidence: 99%

“…However, there is a lack of imaging technologies to noninvasively and serially assess revascularization patterns in both the SOC and the epiphyseal cartilage following ischemic injury. 3 The vascular supply to the developing femoral head is provided by blood vessels passing through cartilage canals in the epiphyseal cartilage. 3,4 Unlike articular cartilage, which is an avascular tissue, epiphyseal cartilage is only present during childhood and is extensively vascularized via a network of cartilage canal vessels.…”

mentioning

confidence: 99%

“…3 The vascular supply to the developing femoral head is provided by blood vessels passing through cartilage canals in the epiphyseal cartilage. 3,4 Unlike articular cartilage, which is an avascular tissue, epiphyseal cartilage is only present during childhood and is extensively vascularized via a network of cartilage canal vessels. 5 Epiphyseal cartilage serves as a growth cartilage responsible for the volumetric growth of the SOC.…”

mentioning

confidence: 99%

“…6 The pattern of neovascularization observed in the piglet model is consistent with the findings from a serial perfusion study in patients with LCPD using contrastenhanced magnetic resonance imaging (MRI), which demonstrated that revascularization in the SOC is first observed at the periphery of the femoral head. 3 Interestingly, younger children with LCPD tend to have better clinical outcomes than older children, 7,8 which may be related to their greater epiphyseal cartilage volume and, thus, greater capacity to repair and remodel the femoral head following ischemic injury. 6 Clinically, it would be useful to image the vascularity of the epiphyseal cartilage in LCPD to better understand the recovery of the epiphyseal cartilage from ischemic injury, to identify restoration of epiphyseal growth, and to assess the efficacy of new angiogenic treatments.…”

mentioning

confidence: 99%

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Quantitative susceptibility mapping detects neovascularization of the epiphyseal cartilage after ischemic injury in a piglet model of legg‐calvé‐perthes disease

Johnson

Wang

Tóth

et al. 2018

Magnetic Resonance Imaging

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Background Legg‐Calvé‐Perthes disease (LCPD) is a childhood hip disorder thought to be caused by disruption of blood supply to the developing femoral head. There is potential for imaging to help assess revascularization of the femoral head. Purpose To investigate whether quantitative susceptibility mapping (QSM) can detect neovascularization in the epiphyseal cartilage following ischemic injury to the developing femoral head. Study Type Prospective. Animal Model Right femoral head ischemia was surgically induced in 6‐week‐old male piglets. The animals were sacrificed 48 hours (n = 3) or 4 weeks (n = 7) following surgery, and the operated and contralateral control femoral heads were harvested for ex vivo MRI. Field Strength/Sequence Preclinical 9.4T MRI to acquire susceptibility‐weighted 3D gradient echo (GRE) images with 0.1 mm isotropic spatial resolution. Assessment The 3D GRE images were used to manually segment the cartilage overlying the femoral head and were subsequently postprocessed using QSM. Vessel volume, cartilage volume, and vessel density were measured and compared between operated and control femoral heads at each timepoint. Maximum intensity projections of the QSM images were subjectively assessed to identity differences in cartilage canal appearance, location, and density. Statistical Tests Paired t‐tests with Bonferroni correction were used (P < 0.008 considered significant). Results Increased vascularity of the epiphyseal cartilage following ischemic injury was clearly identified using QSM. No changes were detected 48 hours after surgery. Vessel volume, cartilage volume, and vessel density were all increased in the operated vs. control femoral heads 4 weeks after surgery (P = 0.001, 0.002, and 0.001, respectively). Qualitatively, the increase in vessel density at 4 weeks was due to the formation of new vessels that were organized in a brush‐like orientation in the epiphyseal cartilage, consistent with the histological appearance of neovascularization. Data Conclusion QSM can detect neovascularization in the epiphyseal cartilage following ischemic injury to the femoral head. Level of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:106–113.

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confidence: 78%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Quantitative susceptibility mapping detects neovascularization of the epiphyseal cartilage after ischemic injury in a piglet model of legg‐calvé‐perthes disease

Johnson

Wang

Tóth

et al. 2018

Magnetic Resonance Imaging

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Analysis of Trabecular Microstructure and Vascular Distribution of Capital Femoral Epiphysis Relevant to Legg–Calve–Perthes Disease

Morris

Liu

Chen

et al. 2019

Journal Orthopaedic Research

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Legg-Calve-Perthes disease is characterized by the capital femoral epiphyseal collapse, which occurs more reliably in the anterior quadrant than the more weight-bearing lateral quadrant. The purpose of this study was to determine whether there is a vascular or microstructural predisposition for anterior femoral epiphyseal collapse in Perthes disease. Thirty-two cadaveric proximal femoral epiphyses from 17 subjects (age 4-14 years old) underwent micro-computed tomography at 10-μm resolution. Each quadrant was analyzed for four markers of trabecular architecture: bone volume fraction (BV/TV), trabecular thickness, trabecular separation (TbSp), and trabecular number (TbN). Vascular channels were then mapped in each quadrant, identified by correlating surface topography with cross-sectional imaging. One-way analysis of variance revealed an overall difference between quadrants (p < 0.001) in BV/TV, TbN, and TbSp. However, post hoc analysis revealed there was no significant difference between the anterior and lateral quadrants for any of the four markers of trabecular architecture. Vascular channel mapping illustrated a predominance of vessels in the posterior half of the epiphysis compared to the anterior half (8.7 ± 4.0 vs. 3.4 ± 3.1 vascular channels, p < 0.001). The lack of microstructural differences between the anterior and lateral quadrants, and the predominance of vascular channels in the posterior half of the epiphysis with posteriorly-based medial femoral circumflex and ligamentum teres vessels suggests that the anterior femoral epiphysis may be a relative vascular watershed region, which predisposes it to collapse after the vascular insult of Perthes disease. Clinical significance: Improved understanding of the pathophysiology of anterior femoral epiphyseal collapse may inform future treatments aimed at revascularization.

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T1ρ and T2 mapping detect acute ischemic injury in a piglet model of Legg–Calvé–Perthes disease

Johnson

Tóth

Carlson

et al. 2021

Journal Orthopaedic Research

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This study investigated the sensitivity of T1ρ and T2 relaxation time mapping to detect acute ischemic injury to the secondary ossification center (SOC) and epiphyseal cartilage of the femoral head in a piglet model of Legg–Calvé–Perthes disease. Six piglets underwent surgery to induce global right femoral head ischemia and were euthanized 48 h later. Fresh operated and contralateral‐control femoral heads were imaged ex vivo with T1, T2, and T1ρ mapping using a 9.4T magnetic resonance imaging scanner. The specimens were imaged a second time after a freeze/thaw cycle and then processed for histology. T1, T2, and T1ρ measurements in the SOC, epiphyseal cartilage, articular cartilage, and metaphysis were compared between operated and control femoral heads using paired t tests. The effects of freeze/thaw, T1ρ spin‐lock frequency, and fat saturation were also investigated. Five piglets with histologically confirmed ischemic injury were quantitatively analyzed. T1ρ was increased in the SOC (101 ± 15 vs. 73 ± 16 ms; p = 0.0026) and epiphyseal cartilage (84.9 ± 9.2 vs. 74.3 ± 3.6 ms; p = 0.031) of the operated versus control femoral heads. T2 was also increased in the SOC (28.7 ± 2.0 vs. 22.7 ± 1.7; p = 0.0037) and epiphyseal cartilage (57.4 ± 4.7 vs. 49.0 ± 2.7; p = 0.0041). No changes in T1 were detected. The sensitivities of T1ρ and T2 mapping in detecting ischemic injury were maintained after a freeze/thaw cycle, and T1ρ sensitivity was maintained after varying spin‐lock frequency and applying fat saturation. In conclusion, T1ρ and T2 mapping are sensitive in detecting ischemic injury to the SOC and epiphyseal cartilage of the femoral head as early as 48 h after ischemia induction.

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Assessment of Femoral Head Revascularization in Legg-Calvé-Perthes Disease Using Serial Perfusion MRI

Abstract: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Cited by 34 publications

References 28 publications

Quantitative susceptibility mapping detects neovascularization of the epiphyseal cartilage after ischemic injury in a piglet model of legg‐calvé‐perthes disease

Quantitative susceptibility mapping detects neovascularization of the epiphyseal cartilage after ischemic injury in a piglet model of legg‐calvé‐perthes disease

Analysis of Trabecular Microstructure and Vascular Distribution of Capital Femoral Epiphysis Relevant to Legg–Calve–Perthes Disease

T1ρ and T2 mapping detect acute ischemic injury in a piglet model of Legg–Calvé–Perthes disease

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