The Institutional Review Board of our Radiology Department approved the design of the study and the use of clinical data. Written consent was obtained from the patients or their parents prior to the procedures.
This study included 25 patients (10 females and 15 males), their ages range from 7 to 46 years with mean age 22 years. They were referred to radiology department from the surgical and clinical oncology departments.
The flow chart of our study is illustrated in Fig. 1.
Inclusion criteria
Patients who are primary diagnosed to have osteosarcoma, candidates or already had MR imaging and will follow the neoadjuvant chemotherapy regimens.
All patients are histologically proven to be osteosarcoma patients.
Exclusion criteria
Patients with other concurrent systematic diseases that would harm the safety of the patient or the patient’s ability to complete the study were excluded.
General criteria of contra-indication to MRI are as follows: patients with pace maker, cochlear implants, cerebral aneurysm clips, and ocular metallic foreign body.
All patients were subjected to the following:
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1.
Clinical assessment and history taking.
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2.
Laboratory investigations including renal function tests and bleeding profile tests.
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3.
Revision of previous radiological investigations and histopathological reports.
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4.
Two MR examinations were performed as follow: the first before the neoadjuvant chemotherapy, and the second after 3 to 6 months after the preoperative neoadjuvant chemotherapy.
MRI protocol
MRI was performed on high field system (1.5 Tesla) closed magnet unit (Phillips Achieva XR). A Sense –XL –torso (16 channels) phased array coil was used for chest and pelvis while surface coil was used for lesions of the extremities. A combination of axial, sagittal, and coronal images was obtained using T1-weighted spin-echo sequence (TR “average”, 500 ms; TE, 10–15 ms), T2-weighted fast spin-echo sequence (TR, 4000–5000 ms; TE, 110–120 ms; TF, 17–25) and short time inversion recovery “STIR” sequence (TR “average”, 5000 ms; TE, 25 ms; TI, 160 ms; TF, 17). These sequences were obtained with 5-mm slice thickness, 1-mm interslice gap, and 256 × 196 matrix size.
DWI was performed in the axial plane with parallel image and sensitivity phase encoding (SENSE) with the following parameters: TR, 4000–5000 ms; TE, 110–120 ms; 220 mm FOV; 128 × 64 pixel matrix size; 5-mm slice thickness; and 1-mm interslice gap. DWI was acquired with diffusion gradient encoding in 3 orthogonal directions with b values (0/50/400/800 s/mm2). In all images, a fat-saturated pulse was used to exclude chemical-shift artifacts. ADC map images and quantitative DWI analysis (ADC measurement) were done.
Contrast-enhanced images of axial, sagittal, and coronal plane were obtained using a T1-weighted spin-echo sequence with and without fat suppression (TR, 450–650 ms; TE, 10–16 m; matrix size, 256 × 256; slice thickness, 5 mm; 1-mm interslice gap) after the injection of 0.1 mmol/kg of body weight of gadopentetate dimeglumine injected at 2 ml/s, followed by a 20 ml normal saline flush.
THRIVE (T1-weighted high-resolution isotropic volume excitation, fast gradient, 3D and Fat-sat) was obtained with following parameters (TR, 4.5 ms; TE, 2.2 ms; matrix size, 300 × 300; FOV, 220 mm; slice thickness, 3.6 mm; 3D thickness 3, 0-mm interslice gap).
Image analysis
All pre- and post-chemotherapy MRI studies were downloaded from DICOM server to workstation, and two radiologists experienced on musculoskeletal radiology analyzed the images. The assessment of the lesions was done first in the conventional MRI then in the DWI with ADC calculation.
Standard MRI analysis
In the initial pre-therapy MRI study, each lesion was identified on conventional MRI and the morphological features were recorded including site, size, signal characteristics, tumor breakdown, pattern, and intensity of contrast uptake. Assessment of the osteosarcoma behavior was reported including medullary involvement, pattern of bony cortex affection (either subtle cortical breaching or frank cortical destruction), associated soft tissue component, and skip lesions. The extent of local infiltration in each lesion was assessed including muscle invasion, crossing of fascial boundaries, and neurovascular compromise.
DWI analysis
Qualitative analysis
This was done by studying the signal intensity of different lesions on DWIs (at the highest b-value, i.e., at 800 s/mm2) and the ADC map. If all or part of the lesion is of high signal in DWI and low in ADC map, it is considered as diffusion restriction.
Quantitative analysis
Measurements of the ADC value were made using electronic cursor on the ADC map in different regions of interest (ROI) of the lesion. As the osteosarcoma shows inhomogeneous signal intensity, ADC measurements can highly change from a slice to another and from an area to another in the same slice. So we do the following to overcome these obstacles:
Place the ROI in solid and preferably enhancing parts of the lesion.
Avoid including areas that may influence the ADCs as necrotic, fibrotic, and hemorrhagic areas as well as adjacent fat, normal tissue, and bone. This was facilitated by using the pre- and post-contrast MR images, mainly the T2 and post-contrast THRIVE MR images as source images for the ROI placement.
We follow the methods of Lee SK et al. [4] and Lee SY et al. [10] in ADC measurement. We measure the mean ADC (obtained from the single-section ROI) that contained the largest part of the tumor. Also we measure minimum ADC (obtained from the single-section ROI) but placing ROI in the lowest signal intensity within the solid part of the tumor on the ADC map that presented as a hyperintense SI on DWI. To select the lowest ADC value, small ROI (minimum area, 0.5 cm2) were drawn 3–5 times and the minimum was recorded.
Also, in patients complicated with pathological fractures. This could affect the ADC measurements. However in our study, we avoid placement of ROI in and adjacent to site of fracture to reduce as much as possible error in ADC value.
Follow-up MRI
Follow-up MRI examinations of average 3–6 months after chemotherapy administration were done. The lesions were evaluated in the same way of the pre-therapy MRI. The changes that occurred between the imaging dates before the start of initial treatment and the most recent follow-up examination were evaluated and documented to assess the response to treatment.
In addition, the ADC ratio was calculated by using the following formula to evaluate the relative change in the pre- and post-chemotherapy ADC values of osteosarcomas: ADCratio = (ADCpost − ADCpre)/ADCpre.
To assess the tumor response to chemotherapy, we depend upon the rule of the ADC value is inversely correlated with tissue cellularity of the lesion. Treatment with chemotherapy can result in loss of the cell membrane integrity which can be detected as an increase in the mean ADC value for the tumor [9]. So, the response to treatment was classified in good response and poor response according to degree increase in ADC value and ADCratio. Also, we evaluate the changes in tumor size, breakdown, and pattern of enhancement.
Statistical analysis
Statistical analysis was performed using the statistical software: SPSS statistical package version 21 (SPSS Inc., Chicago, IL).
Numerical data were expressed as mean and standard deviation or median and range as appropriate. Qualitative data were expressed as frequency and percentage.
MRI features that were analyzed included the location, size, shape, and margins of the lesion, signal characteristics, enhancement patterns, pattern of diffusion, and ADC value.