Gaucher disease: A review of MSK MRI protocol and peripheral skeletal MRI findings

Osteopenia/osteoporosis

GD patients of all ages are prone to decreased bone mineral density, which can be assessed with dual-energy X-ray absorptiometry. These reductions are classified as osteopenia or osteoporosis based on severity, with the latter being more severe. This complication is most prevalent in post-splenectomy patients.^[1,5,8] Regions at greatest risk are the lumbar spine, femoral neck, femoral trochanters, tibia, and distal radius. Fortunately, osteopenia/osteoporosis can be reversed with enzyme replacement therapy. Prompt treatment leads to better outcomes, highlighting the importance of imaging in aiding early diagnosis.^[16]

Bone marrow infiltration

Gaucher cells directly accumulate in the bone marrow. This infiltration initially involves the axial skeleton, followed by centrifugal involvement of the appendicular skeleton. Thus, the humerus and femur are commonly involved, while the epiphysis and apophysis are spared except in the most severe cases. This pattern is the reverse of the typical conversion of red to yellow marrow that occurs from childhood to adulthood. On MRI, bone marrow infiltration presents as T1 and T2 hyperintense yellow marrow getting replaced by T1 and T2 hypointense abnormal bone marrow.^[1,8,9] The evaluation of bone marrow infiltration in children is complicated by the fact that they have a greater concentration of red marrow, which is T1 and T2 hypointense, as well. The presence of an Erlenmeyer flask deformity can help clarify this dilemma [Figure 6]. Although not specific to Gaucher’s disease, it has been reported in 44–61% of patients.^[6,17,18] The deformity, due to under-tubulation of the distal meta-diaphysis of the distal femur, implies bone marrow involvement in childhood when the skeleton is developing. Once the deformity occurs, it persists into adulthood.

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Figure 6:

Erlenmeyer flask deformity. A 6-year-old male. AP radiograph of the bilateral femurs demonstrates the Erlenmeyer flask deformity (arrows) which results from undertubulation of the distal meta-diaphysis of the distal femur and implies bone marrow involvement in children with Gaucher’s disease.

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On STIR sequences, bone marrow infiltration is slightly hyperintense. Like T2, STIR is a fluid-sensitive sequence that suggests marrow edema and the presence of an “active” process such as osteomyelitis or osteonecrosis. On the other hand, IP-OP sequences are most helpful in identifying microscopic fat content by showing signal intensity drop on OP images compared to IP images. Expansion of the medullary cavity due to bone marrow infiltration by Gaucher cells can appear hypointense on OP images. Like osteopenia/osteoporosis, bone marrow infiltration can be reversed with enzyme replacement therapy.^[1,8,19]

Osteonecrosis

As glucosylceramide accumulates in the bones of GD patients, mounting intraosseous pressure can cause vaso-occlusion and resultant osteonecrosis.^[1,8,20,21] Other risk factors include splenectomy, male gender, thrombocytosis, and another focus on osteonecrosis.^[5,20]

Osteonecrosis can occur in either the corticocancellous bone or the medullary cavity of bones. The former is most common in the humeral and femoral heads, femoral condyles, and tibial plateaus. By contrast, medullary osteonecrosis, often referred to as medullary infarct, is often asymptomatic.

Clinically, osteonecrosis can be indistinguishable from osteomyelitis. In both diseases, patients may present with fever, swelling, pain, tenderness, and disability.^[5,12] Fortunately, MRI can aid in differentiating the two entities which require different treatments. While both may present as edema seen as T2 hyperintensity in the acute setting, progression of osteonecrosis will present as geographic serpiginous signal change outlining the dead bone with or without surrounding marrow edema-like signal^[8] [Figures 7-9]. In advanced cases, the articular surface can collapse and undergo secondary degenerative change, which mandates joint replacement. In addition, fractures or sub-periosteal hemorrhage can result.^[1,21]

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Figure 7:

Osteonecrosis. A 37-year-old female. (a) Coronal T1-weighted and (b) T2-weighted images demonstrate hypointensity of the right distal femoral diaphysis (ovals), corresponding to fibrosed and sclerosed bone marrow of chronic infarcted bone. (c) Coronal Short Tau Inversion Recovery (STIR) image demonstrates surrounding hyperintensity corresponding to reactive bone marrow edema and a serpiginous rim of hyperintensity representing granulation tissue (oval).

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Figure 8:

Osteonecrosis. A 55-year-old male. (a) Coronal T1-weighted and (b) T2-weighted images demonstrate hypointensity of the left proximal femoral diaphysis (ovals), corresponding to fibrosed and sclerosed bone marrow of chronic infarcted bone. (c) Coronal Short Tau Inversion Recovery (STIR) image demonstrates serpiginous outer rim of hypointensity demarcating the border between living and necrotic bone, as well as, inner rim of hyperintensity representing granulation tissue (oval).

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Figure 9:

Osteonecrosis. A 40-year-old male. AP radiograph of the bilateral femurs demonstrates serpiginous sclerosis (arrows) in the distal femurs, consistent with osteonecrosis in this patient with Gaucher’s disease.

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Osteomyelitis

Infarcted bone can be complicated by superimposed infection. Although diseased bone can serve as a nidus for infection, pancytopenia remains the main risk factor for osteomyelitis in GD patients.^[1] The mode of transmission is thought to be hematogenous. The following organisms are implicated most commonly: Staphylococcus aureus, Bacteroides, Group A – Hemolytic streptococcus, and Proteus mirabilis.^[22,23]

MRI has high sensitivity and specificity for detecting osteomyelitis.^[23-25] The first MRI feature of such is edema, occurring as early as 1–2 days and presenting as T1 hypointensity, T1 post-contrast hyperintensity, and T2 hyperintensity. An abscess would follow the same imaging pattern, with the addition of a thin rim of intermediate T1 signal intensity and T1 post-contrast hyperenhancement [Figure 10]. Chronic osteomyelitis can evolve into osteonecrosis (sequestrum) surrounded by a thick rind (involucrum). The sequestrum appears hypointense on all MRI sequences. Conversely, the involucrum can be isointense or edematous.^[26] Eventually, an opening referred to as a “cloaca” may form at the involucrum to allow drainage of purulent and necrotic material from dead bone. The cloaca, thus, presents as a linear, fluid-filled continuation to surrounding soft tissue. If it extends to the skin surface, it is called a sinus tract.

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Figure 10:

Intraosseous abscess. A 26-year-old male. An axial T1-weighted post-contrast image demonstrating an intraosseous abscess (arrow). Hyperintense signal is noted within the surrounding subcutaneous tissue representing reactive subcutaneous edema and hyperemia.

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Fractures

GD patients, including children, are prone to pathological fractures with poor healing due to a decrease in bone mineral density.^[1,27,28] Clinical presentations include pain and physical disability. The most commonly affected site is the spine, followed by the lower extremities. Children tend to have more distal and displaced femoral neck fractures.^[28]

Focal lytic lesions

GD can result in an increase in Cathepsin K, a biomarker for osteoclasts. Increased osteoclast activity expands the bony medulla and thins the cortex, which can result in endosteal scalloping, leading to the formation of focal lytic lesions called “Gaucheromas.” ^[1,29] These lytic lesions confer an increased risk of malignancy in GD patients, including multiple myeloma, lymphoma, sarcoma, and malignant epithelioid hemangioendothelioma.^[30]