A total of 52 paediatric patients with non-tumorous musculoskeletal lesions underwent routine MRI with regional diffusion-weighted MRI (DWI) in addition to standard MRI sequences. The presence of neoplasm had been ruled out in all patients based on clinical history, imaging characteristics, biopsy and/or follow-up prior to inclusion in this retrospective study. Patients with proven or suspected musculoskeletal tumours were excluded from the study. All study work was conducted in accordance with the requirements of the Helsinki Declaration. The study work based on retrospective analysis of data from routine examinations does not require institutional review board approval at our institution. The treatment contract between patients and our university hospital covers the use of anonymized data for scientific purposes. Informed written consent was obtained from the legal guardians of all patients for all diagnostic and therapeutic measures.
Our study group included 23 females and 29 males with a mean age of 11 ± 5 years (median 13 years, range 12 months - 21 years). Indication for whole-body MRI was suspected CNO and follow-up for known CNO in 13 patients. All other patients had regional MRI for further diagnostic work-up of local symptoms after clinical evaluation, radiography and/or ultrasonography had failed to provide all required diagnostic information.
Sedation was required for five examinations of patients aged 1 to 6 years. The standard scan protocol comprised coronal T2W TIRM, pre-contrast T1W TSE and contrast-enhanced T1W TSE with fat saturation. Typical scanning parameters at 1.5 Tesla were: T2W TIRM (TR 7350 ms, TE 75 ms, TI 120 ms, flip angle 180°, field of view 380 mm, slice thickness 4 mm, in-plane spatial resolution 0.94 mm × 0.94 mm) and T1W TSE (TR 795 ms, TE 11 ms, flip angle 160°, field of view 380 mm, slice thickness 4 mm, in-plane spatial resolution 1.07 mm × 1.07 mm). Additional sequences were acquired in transversal or sagittal cross-sections as needed for diagnostic purposes. Thirteen patients had whole-body standard MRI for suspected bacterial or non-bacterial osteomyelitis. We used phased-array body coils for whole-body scanning in combination with the head coil for skull and feet. The remaining patients had regional MRI for local complaints with dedicated MRI coils (head, coil, knee coil, spine coil) or flex coils.
Based on signal alterations observed on conventional sequences, all patients underwent regional transversal single-shot diffusion-weighted echo-planar imaging at 1.5 Tesla (n = 50, Magnetom Avanto and Magnetom Symphony, Siemens Medical, Erlangen, Germany) and 3 Tesla (n = 2, Magnetom Skyra, Siemens Medical, Erlangen, Germany) during the same MRI examination. Typical scanning parameters at 1.5 Tesla included TR 4600 ms, TE 137 ms, flip angle 90°, fatsat, b-values of 0-50 s2/mm and 800-1000 s2/mm, bandwidth 976 Hz/pixel, echo spacing 1.17 ms, epi factor 128, slice thickness 6 mm, scanning time 41s to 2 min 50s with 2 to 6 averages. Isotropic diffusion-weighted images acquired at low and high b-values were used for lesion detection. Additional regional DWI sequences with coronal or sagittal slice orientations were acquired in eight patients in order to study feasibility of non-transversal DWI acquisition.
Among our 52 study patients, we identified 31 manifestations of bone marrow oedema, 20 manifestations of soft-tissue oedema and 15 cases of synovitis. One lesion per patient only was included for evaluation in each diagnostic category. The differential diagnosis of non-bacterial versus bacterial osteomyelitis was supported with biopsy and microbiological analysis of biopsy specimen.
ADC maps were automatically generated by the scanner software. The underlying algorithm is based on mono-exponential fit and per-pixel calculation according to the formula ADC = -1/(b2 - b1)ln(S2/S1), where S1 and S2 are the signal intensities with two different diffusion gradients b1 and b2. Mean ADCtotal was measured with ROI technique off-line on Syngo Plaza workstations (Siemens Medical, Erlangen, Germany), using one circular ROI in bone marrow oedema and soft-tissue oedema and calculating the average value of three small circular ROIs for synovial ADC. Size of the circular ROI equalled the smallest transversal lesion diameter in small foci < 10 mm and was chosen 10 to 15 mm in diameter in larger lesion. Mean ROI area and standard deviation were 1.1 ± 0.5 cm2 for bone marrow lesions, 0.9 ± 0.5 cm2 for soft-tissue lesions and 5.2 ± 2.9 mm2 for synovitis.
All DWI measurements were performed by the same board-certified radiologist with 4 years of experience in extra-neurological diffusion-weighted MRI, who was blinded to clinical data. As a measure of relative signal intensity and detectability, we determined signal intensities of pathological lesions and adjacent normal tissue with ROI techniques corresponding to ADC measurement, comparing altered signal of oedematous bone marrow with normal bone marrow, soft-tissue oedema with adjacent unaffected soft tissue, as well as synovial signal alterations with joint effusion and periarticular soft tissue. For signal quantification, we employed a signal intensity (SI) ratio calculated as SI = SIpathological / SInormal. Commercially available software (3D fusion, version A30, Siemens Medical, Erlangen, Germany) was used for semi-automatic image fusion of standard sequences with DWI image sets.
Normally distributed data is presented as mean ± standard deviation. Between-groups comparison was performed with the independent sample t test for variables following normal distribution and the Mann-Whitney test for variables deviating from normal distribution. Kendall's W was calculated for between-groups comparison of more than two groups. For analysis of differences in lesion size, the difference of the longest transversal lesion diameter on DWI and T1W post-contrast images was tested with a one-sample t test against a test value of zero. A p value < 0.05 was considered as indicating statistical significance. Analyses were performed with the PASW (SPSS) Statistics 18 software package (SPSS Inc., Chicago, USA).