Volume Localized In Vivo Proton MR Spectroscopy of Multiple Myeloma: Variation of Water-Fat Ratio in Patients Receiving Chemotherapy Correlates with Clinical Response.

Introduction. Bone marrow magnetic resonance (MR) imaging provides important information i<SPACER size="24">n the evaluation of patients with multiple myeloma (MM) but MR assessment of response to therapy is highly subjective. Proton nuclear magnetic resonance spectroscopy (¹H MRS) may be able to measure the ratio of lipid to water resonance signal intensities (LWR) and thus reflect the relative percentages of cellular and fatty bone marrow within a defined three-dimensional volume (voxel). These measurements could be used to quantify the degree of cytoreduction in MM patients.

Patients and Methods. Twenty-one consecutive patients (10 male; median age 65 years, range 44–82) with newly diagnosed multiple myeloma underwent a MR exploration of the fifth lumbar vertebral body before the initiation of treatment. Patients completing therapy were reevaluated. Dorso-lumbar imaging studies were carried out in a 1.5T system with a saggital spin-echo T1-weighted sequence (TR 437 ms / TE 15 ms). A 2-cm-thick transverse center section of the L5 lumbar vertebral body was sampled to place the voxel. Spectroscopic data were acquired with a stimulated echo acquisition mode (STEAM) sequence without water suppression with repetition time 5 s and echo time 40 ms. To calculate the area of the water signal, the peak was fit to a single Lorenzian curve centered at 4.75 ppm. The area of the lipid resonances was fit to 3 Lorenzian curves centered at 0.89 (-CH₃), 1.34 and 2.2 (-CH₂) ppm. The areas obtained were used to calculate the LWR for each voxel. The LWR was defined as the sum of the area of the 3 lipid fitted resonances divided by the area of the fitted water resonance.

Results. The spectra showed a water peak and a compounded lipid peak separated by approximately 3.1 ppm. LWRs ranged from 0 to 15 (mean 1.748, SD 3.741). Seven patients were treated with melphalan and prednisone (MP) and 14 received 3 cycles of vincristine, BCNU, cyclophosphamide, melphalan and prednisone alternating with 3 cyles of vincristine, BCNU, doxorrubicin and dexametasone (VBCMP/VBAD). Therapy was interrupted for at least 4 weeks before the MR evaluation. Two patients under MP could not be reevaluated. One patient under VBCMP/VBAD suffered extensive L5 collapse that invalidated a second MR study. Four patients progressed under treatment and only 1 of them could be re-submitted to MR. A patient who achieved a partial response after VBCMP/VBAD refused to undergo a MR re-evaluation. Pre and post treatment MR studies were available in 14 patients (progression 1, no response 3, partial response 3, complete response 7). LWR increased in 11/14 patients (78%) (p=0.034). However, 7/7 (100%) complete responders presented a LWR increase (p=0.018) while only 4/7 (57%) non-responders did. No significant differences were observed among partial responders or patients non-responding or progressing.

Conclusions. Changes i LWR as assessed by ¹H NMR correlated with response to chemotherapy in patients with multiple myeloma, thus this technique may be used to measure noninvasively the response to treatment in these patients.