Volume Localized In Vivo Proton MR Spectroscopy of Multiple Myeloma: Variation of Water-Fat Ratio in Patients Receiving Chemotherapy Correlates with Clinical Response.
Authors: Oriol Albert , Valverde Daniel , Capellades Jaume , Cabañas Miquel , Arús Carles , Ribera Josep-Maria 
Published: April 2020

Abstract
Introduction. Bone marrow magnetic resonance (MR) imaging provides important information i&lt;SPACER size="24"&gt;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.