Diffusion-Weighted Imaging Improves Accuracy in the Diagnosis of MRI Patterns of Marrow Involvement in Newly Diagnosed Myeloma: Results of a Prospective Study in 99 Patients

Abstract Multiple myeloma (MM) is characterized by the presence of four different patterns of marrow involvement on Magnetic Resonance Imaging (MRI): focal, normal, diffuse and variegated. Diffusion-Weighted Imaging (DWI), which derives its contrast mainly from differences in the diffusivity of water molecules in tissue, with calculation of Apparent Diffusion Coefficient (ADC) values may be used as an adjunct method to increase diagnostic confidence of MRI. This technique has, so far, been applied to a small number of MM patients with promising early results for initial assessment and prognosis. The aim of this prospective study was to evaluate ADC values in a large number of MM patients and establish mean values for each MRI pattern, in search for a more precise MRI technique, which may serve as yet another prognostic tool for this disease. Between 2012 and 2014, 99 patients with newly diagnosed, untreated MM (52M/47F, median age 65 years; range 37-89 years) underwent MRI of the thoracic and lumbosacral spine, including DWI: 34/99 had anemia (Hb <10 g/dl), 12/99 had renal impairment (serum creatinine >2 mg/dL) and 13/99 patients had LDH >250 U/L. The same MRI protocol was applied to 16 healthy, gender and age-matched controls to calculate mean ADC values of normal bone marrow. DWI of the lumbosacral spine was performed with an Echo Planar Imaging sequence using 5 b -values (0, 150, 250, 500, 750 sec/mm2) and ADC maps were generated. In MM patients with a normal or a diffuse MRI pattern, as well as in healthy controls, region of interest (ROI) measurements were obtained on the ADC map from each of the five lumbar vertebral bodies avoiding the region of the basivertebral vessels and any focal non-myelomatous lesion and the mean ADC value was calculated. In MM patients with a focal pattern, ROIs were placed on several focal lesions and the highest ADC value was recorded; in these patients an additional ROI was placed on an uninvolved vertebra in order to record the ADC value of apparently normal bone marrow. Based on visual assessment of T1-weighted images, 21 MM patients had focal, 26 diffuse, 3 variegated and 49 normal MRI pattern. Mean ADC values (±SD, x10-3 mm2/sec) of the bone marrow in MM patients were: 0.360±0.110 (range: 0.153-0.593) for the normal MM pattern, 1.046±0.232 (range: 0.715-1.536) for the focal MM pattern and 0.770±0.135 (range: 0.552-1.017) for the diffuse MM pattern. Mean ADC value of apparently normal marrow in patients with a focal MM pattern was 0.415±0.108 (range: 0.113-0.589), while that of healthy controls was 0.325±0.135 (range: 0.152-0.542). One way analysis of variance (ANOVA) showed a significant difference in ADC values within the groups of the study (p<0.0001). Further analysis using t-test revealed significant differences of ADC values between diffuse and focal MM pattern (p=0.003), diffuse and normal MM pattern (p<0.0001), focal and normal MM pattern (p<0.0001), diffuse MM pattern and healthy volunteers (p<0.0001), focal MM pattern and healthy volunteers (p<0.0001), diffuse MM pattern and apparently normal marrow in focal MM pattern (p<0.0001) and finally between focal MM pattern and apparently normal marrow in focal MM pattern (p<0.0001). No significant differences were found between normal MM pattern and healthy volunteers (p=0.442), normal MM pattern and apparently normal marrow in focal MM pattern (p=0.141), and between apparently normal marrow in focal MM pattern and healthy volunteers (p=0.175). The 95% confidence intervals of the ADC values for each group were calculated and a receiver operating characteristic (ROC) analysis was performed to determine a cut-off value with the highest accuracy to distinguish a diffuse myeloma pattern from normal patterns (normal MM pattern, apparently normal marrow in focal MM pattern, normal marrow in healthy controls). An ADC value above 0.548x10-3 mm2/sec had 100% sensitivity and 98% specificity for the diagnosis of a diffuse MRI pattern, whereas a value of 0.597x10-3 mm2/sec had 96.2% sensitivity and 100% specificity. To our knowledge, this is the first study that evaluates and compares ADC values in the different MRI patterns of MM. We have shown that ADC values of MRI myeloma patterns differ significantly. DWI, by providing a quantitative means of assessing bone marrow involvement, assists the interpretation of other MRI sequences and improves the accuracy of pattern assignment. Disclosures Terpos: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; Celgene: Honoraria, Other: travel expenses; Novartis: Honoraria. Dimopoulos:Genesis: Honoraria; Janssen-Cilag: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Onyx: Honoraria.