Prediction of mobilized hematopoietic stem cell yield in patients with multiple myeloma: Usefulness of whole-body MRI-derived indices.

INTRODUCTION: High-dose chemotherapy followed by autologous stem cell transplant is the mainstay of treatment for multiple myeloma (MM). The purpose of this study was to evaluate the ability of MRI-derived indices to predict mobilized hematopoietic stem cell yield. MATERIALS AND METHODS: In this exploratory pilot work, we retrospectively analyzed 38 mobilization procedures for MM. Successful mobilization procedure was defined as a total yield of >4.0×106 CD34+ cells/kg. Univariate and multivariate analyses were performed to identify factors with a significant effect on successful mobilization from among clinical characteristics including number of prior lines of therapy, period from diagnosis to harvest, type of monoclonal protein (M protein); and radiological characteristics including total diffusion volume (tDV), median apparent diffusion coefficient (ADC) of tDV, and mean fat fraction of bone marrow calculated by MRI. RESULTS: Univariate analyses showed that relatively poor mobilization was significantly associated with M protein of Bence-Jones type and with median ADC of tDV (P = 0.02 and P = 0.004, respectively). Multivariate analyses using these two indices showed that median ADC of tDV was a significant predictive factor for adequate mobilization (P = 0.01), with an area under the curve of 0.784 (cutoff value, 1.18×10-3 mm2/s; sensitivity, 72.7%; specificity, 87.5%). CONCLUSION: The present data indicate that median ADC of tDV is a predictive factor for relatively poor mobilization of hematopoietic stem cells in MM patients undergoing autologous stem cell transplant.

Prognosis Prediction Using Magnetic Resonance Spectroscopy and Oligoclonal Bands in Central Nervous System Methotrexate-associated Lymphoproliferative Disorder.

Central nervous system methotrexate-associated lymphoproliferative disorder (CNS-MTX-LPD) is rare, but its spontaneous regression has been observed in some patients after withdrawal of agents. We herein report three cases of primary CNS-MTX-LPD that received oral MTX for rheumatoid arthritis. Epstein-Barr virus and oligoclonal bands (OCBs) were positive, while proton magnetic resonance spectroscopy (1H-MRS) showed an elevated lipid peak and slightly elevated choline/N-acetylaspartate ratio in common. After MTX withdrawal, brain lesions showed spontaneous regression in all cases. Our patient's 1H-MRS findings and OCBs may reflect a non-monoclonal lymphoproliferative histology as benign-type lesions in CNS-MTX-LPD.

Does chemical shift imaging offer a biomarker for the diagnosis and assessment of disease severity in multiple myeloma?: A cross-sectional study.

ABSTRACT: To investigate whether chemical shift imaging (CSI) is useful for differentiating myelomatous infiltration from hematopoietic bone marrow (BM) and for quantitatively assessing disease severity.In this retrospective study, spinal MRI, including a sagittal iterative decomposition of water and fat with echo asymmetry and least-squares estimation T2 fast spin-echo sequence, was performed on 76 myeloma patients (45 men, 67.0 ±â€Š11.4 years; 31 women, 66.5 ±â€Š11.0 years) and 30 control subjects (20 men, 67.0 ±â€Š8.4 years; 10 women, 67.0 ±â€Š9.2 years). The fat-signal fraction (FF) and mean signal dropout ratio (DR) were calculated from lumbar BM that contained no focal lesions. The BM plasma cell percentage (BMPC%) and serological data were obtained. As DR is highest when FF = 50%, the patients were divided into 2 groups: a water-dominant group (FF < 50%) and a fat-dominant group (FF > 50%).Serum monoclonal protein (M protein), ß2-microglobulin, and BMPC% were significantly higher in the water-dominant group than in the fat-dominant group. In the water-dominant group, DR correlated significantly with BMPC% and M protein, whereas in the control group, DR showed a weak correlation with age but no correlation with other clinical factors. No significant differences in any clinical data were seen between high and low DR.CSI proved ineffective for differentiating myelomatous infiltration from hematopoietic BM. For myeloma patients with relatively high BM cellularity, a small signal drop on opposed-phase images indicated a higher tumor burden. For BM with relatively low cellularity, disease severity was not reflected by CSI.

Assessment of early treatment response on MRI in multiple myeloma: Comparative study of whole-body diffusion-weighted and lumbar spinal MRI.

OBJECTIVES: To compare remission status at completion of chemotherapy for multiple myeloma (MM) with changes in total diffusion volume (tDV) calculated from whole-body diffusion-weighted imaging (WB-DWI) and fat fraction (FF) of lumbar bone marrow (BM) by modified Dixon Quant (mDixon Quant) soon after induction of chemotherapy, and to assess the predictive value of MRI. METHODS: Fifty patients (mean age, 66.9 ± 10.5 years) with symptomatic myeloma were examined before and after two cycles of chemotherapy. From WB-DWI data, tDV was obtained with the threshold for positive BM involvement. Mean FF was calculated from lumbar BM using the mDixon Quant sequence. At the completion of chemotherapy, patients were categorized into a CR/very good PR (VGPR) group (n = 15; mean age, 67.6 ± 10.3 years) and a PR, SD or PD group (n = 35; mean age, 69.1 ± 8.6 years). ROC curves were plotted to assess performance in predicting achievement of CR/VGPR. RESULTS: At second examination, serum M protein, ß2-microglobulin, and tDV were significantly decreased and hemoglobin, mean ADC, and FF were significantly increased in the CR/VGPR group and serum M protein was significantly increased in the PR/SD/PD group. The general linear model demonstrated that percentage changes in FF and M protein contributed significantly to achieving CR/VGPR (P = 0.02, P = 0.04, respectively). AUCs of ROC curves were 0.964 for FF and 0.847 for M protein. CONCLUSIONS: Early change in FF of lumbar BM and serum M protein soon after induction of chemotherapy contributed significantly to prediction of CR/VGPR.

How to Improve the Conspicuity of Breast Tumors on Computed High b-value Diffusion-weighted Imaging.

PURPOSE: The aim of this study was to compare the tumor conspicuity on actual measured diffusion-weighted images (aDWIs) and computed DWI (cDWI) of human breast tumors and to examine, by use of a phantom, whether cDWI improves their conspicuity. MATERIALS AND METHODS: We acquired DWIs (b-value 0, 700, 1400, 2100, 2800, and 3500 s/mm2) of 148 women with breast tumors. cDWIs with b-values of 1400, 2100, 2800, and 3500 s/mm2 were calculated from aDWI scans where b = 0 and 700 s/mm2; the tumor signal-to-noise ratio (SNR) was compared at each b-value. We also subjected a phantom harboring a breast tumor and mammary glands to DWI. For reference we used two models. The model with b = 0, 1000, 1500, 2000, 2500, and 3000 s/mm2 was our multiple b-value model. In the single b-value model, we applied b = 0 and 1000 s/mm2 and changed the number of excitations (NEX). cDWIs were generated at b = 0 and 1000 and used to compare the SNR, the contrast ratio (CR), and the contrast-to-noise ratio (CNR). RESULTS: In the phantom study, the CNR of cDWI generated from high SNR images obtained at lower b-values and a high NEX was outperformed aDWI. However, the CR and CNR on cDWI obtained using the same scanning parameters were inferior to aDWI scans. Similarly, in the clinical study, breast tumor conspicuity was worse on high b-value cDWIs than aDWIs. CONCLUSION: To improve tumor conspicuity on cDWI, the quality of the source images must be improved. It may easily cause inferior conspicuity to aDWIs if high b-value cDWIs were generated from insufficient SNR images.

[Trabecular bone changes in the spine after transarterial chemoembolization therapy for hepatocellular carcinoma].

The number of computed tomography(CT)-guided interventional procedures has increased because they are less invasive and more cost-effective than open surgery. Transarterial chemoembolization(TACE)is a method in which chemotherapeutic drugs are injected into the artery that supplies the tumor. It is also well known that multidetector-CT has tremendously advanced our diagnostic capabilities broadly throughout medicine. These diagnostic benefits have combined with the widespread availability and rapidity of scanning to marked increases in CT use, for example, dynamic contrast-enhanced CT, CT perfusion imaging, and CT during angiography. However, rapidly increasing use of CT has heightened concerns about the high levels of cumulative exposure that may occur in patients undergoing recurrent imaging for chronic conditions such as chronic hepatitis or hepatocellular carcinomas. So far, bone toxicity associated with CT has received little attention. The prevalence of osteoporosis and trabecular microstructural changes using clinical MDCT-based microstructural analysis in patients after TACE with the interventional-CT system to treat hepatocellular carcinoma have been demonstrated here.

Iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) magnetic resonance imaging as a biomarker for symptomatic multiple myeloma.

INTRODUCTION: To evaluate the effectiveness of iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) magnetic resonance imaging (MRI) to discriminate between symptomatic and asymptomatic myeloma in lumbar bone marrow without visible focal lesions. MATERIALS AND METHODS: The lumbar spine was examined with 3-T MRI in 11 patients with asymptomatic myeloma and 24 patients with symptomatic myeloma. The fat-signal fraction was calculated from the ratio of the signal intensity in the fat image divided by the signal intensity of the corresponding ROI in the in-phase IDEAL image. The t test was used to compare the asymptomatic and symptomatic groups. ROC curves were constructed to determine the ability of variables to discriminate between symptomatic and asymptomatic myeloma. RESULTS: Univariate analysis showed that ß2-microglobulin and bone marrow plasma cell percent (BMPC%) were significantly higher and fat-signal fraction was significantly lower with symptomatic myeloma than with asymptomatic myeloma. Areas under the curve were 0.847 for ß2;-microglobulin, 0.834 for fat-signal fraction, and 0.759 for BMPC%. CONCLUSION: The fat-signal fraction as a biomarker for multiple myeloma enables discrimination of symptomatic myeloma from asymptomatic myeloma. The fat-signal fraction offers superior sensitivity and specificity to BMPC% of biopsy specimens.

Multidetector computed tomography-based microstructural analysis reveals reduced bone mineral content and trabecular bone changes in the lumbar spine after transarterial chemoembolization therapy for hepatocellular carcinoma.

PURPOSE: It is well recognized that therapeutic irradiation can result in bone damage. However, long-term bone toxicity associated with computed tomography (CT) performed during interventional angiography has received little attention. The purpose of this study was to determine the prevalence of osteoporosis and trabecular microstructural changes in patients after transarterial chemoembolization (TACE) for hepatocellular carcinoma therapy using an interventional-CT system. MATERIALS AND METHODS: Spinal microarchitecture was examined by 64-detector CT in 81 patients who underwent TACE, 35 patients with chronic hepatitis, and 79 controls. For each patient, the volumetric CT dose index (CTDIv) during TACE (CTDIv (TACE)), the dose-length product (DLP) during TACE (DLP (TACE)), and CTDIv and DLP of routine dynamic CT scans (CTDIv (CT) and DLP (CT), respectively), were calculated as the sum since 2008. Using a three dimensional (3D) image analysis system, the tissue bone mineral density (tBMD) and trabecular parameters of the 12th thoracic vertebra were calculated. Using tBMD at a reported cutoff value of 68 mg/cm3, the prevalence of osteoporosis was assessed. RESULTS: The prevalence of osteoporosis was significantly greater in the TACE vs. the control group (39.6% vs. 18.2% for males, P<0.05 and 60.6% vs. 34.8% for females, P<0.01). Multivariate regression analysis demonstrated that sex, age, and CTDIv (CT) significantly affected the risk of osteoporosis. Of these indices, CTDIv (CT) had the highest area under the curve (AUC) (0.735). Correlation analyses of tBMD with cumulative radiation dose revealed weak correlations between tBMD and CTDIv (CT) (r2 = 0.194, P<0.001). CONCLUSION: The prevalence of osteoporosis was significantly higher in post TACE patients than in control subjects. The cumulative radiation dose related to routine dynamic CT studies was a significant contributor to the prevalence of osteoporosis.

A longitudinal computed tomography study of lenalidomide and bortezomib treatment for multiple myeloma: trabecular microarchitecture and biomechanics assessed using multidetector computed tomography.

BACKGROUND: Bone disease is a common feature in patients with multiple myeloma. In this study, we investigated whether lenalidomide, similar to bortezomib, affects the microarchitecture and biomechanics of bones using clinical CT-based FEM. MATERIALS AND METHODS: Bone lesions were evaluated using whole-body 64-section multidetector CT scan. For microstructural- and CT/FEM analyses, the volume of interest was defined as a 10-mm thickness of the central part of the L3 vertebral body. Microstructural parameters and mechanical properties were calculated using a 3-D image analysis system. The changes from baseline to the second examination within groups were calculated. Relationships between baseline disease characteristics and percent changes of trabecular parameters were assessed using Spearman correlation analysis. RESULTS: Thirty-two patients were treated with bortezomib and 18 patients were treated with lenalidomide. At the second CT scan, apparent trabecular number, failure load, and stiffness were decreased in the bortezomib group and failure load and stiffness were increased significantly in the lenalidomide group. In the lenalidomide group, response to chemotherapy was positively associated with increases in failure load (ρ = 0.57; P < .05) and stiffness (ρ = 0.50; P < .05). CONCLUSION: Lenalidomide treatment resulted in significant increases in CT/FEM-derived estimates of bone strength. Response to chemotherapy predicted lenalidomide-induced bone changes and good responders had increased bone strength.

Magnetic resonance evaluation of multiple myeloma at 3.0 Tesla: how do bone marrow plasma cell percentage and selection of protocols affect lesion conspicuity?

PURPOSE: To compare various pulse sequences in terms of percent contrast and contrast-to-noise ratio (CNR) for detection of focal multiple myeloma lesions and to assess the dependence of lesion conspicuity on the bone marrow plasma cell percent (BMPC%). MATERIALS AND METHODS: Sagittal T1-weighted FSE, fat-suppressed T2-weighted FSE (FS- T2 FSE), fast STIR and iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) imaging of the lumbar spine were performed (n = 45). Bone marrow (BM)-focal myeloma lesion percent contrast and CNR were calculated. Spearman rank correlation coefficients were obtained between percent contrast, CNR and BMPC%. Percent contrasts and CNRs were compared among the three imaging sequences. RESULTS: BM-focal lesion percent contrasts, CNRs and BMPC% showed significant negative correlations in the three fat-suppression techniques. Percent contrast and CNRs were significantly higher for FS- T2 FSE than for STIR (P<0.01, P<0.05, respectively), but no significant differences were found among the three fat-suppression methods in the low tumor load BM group. CONCLUSION: The higher BMPC% was within BM, the less conspicuous the focal lesion was on fat-suppressed MRI. The most effective protocol for detecting focal lesions was FS- T2 FSE. In the high tumor load BM group, no significant differences in lesion conspicuity were identified among the three fat-suppression techniques.

Multiple antiplatelet therapy contributes to the reversible high signal spots on diffusion-weighted imaging in elective coiling of unruptured cerebral aneurysm.

INTRODUCTION: Our aim was to systematically investigate radiographic characteristics and outcome of diffusion-weighted imaging (DWI) changes in the elective coiling of unruptured cerebral aneurysm with analyzing the correlation of antiplatelet therapy (APT). METHODS: In a total of 34 consecutive patients with unruptured cerebral aneurysms initially treated by coiling without stent assist, 26 (76.5%) had DWI changes with 91 high signal spots within 24-48 h after the procedure. We recorded DWI parameters (location, volume, mean, and minimum values of the apparent diffusion coefficient: expressed as ADCAVE and ADCMIN) for each lesion, and evaluated its radiographic outcome on conventional MRI at follow-up (interval, 58.4 ± 37.2 days) in the modes of APT. RESULTS: All patients with DWI high spots had no clinical symptoms. There was a strong correlation between ADCAVE and ADCMIN (r = 0.82, p < 0.0001). The mean ADCAVE and rADCAVE were 0.74 ± 0.14 × 10(-3) mm(2)/s and 87 ± 10 %. DWI high spots were small with a mean volume of 0.13 ± 0.12 cm(3), ranging from 0.04 to 0.86 cm(3). A negative correlation was observed between the volume and values of ADCAVE (r = -0.48, p < 0.0001). The DWI volume was significantly larger in single APT than in multiple (0.15 ± 0.14 versus 0.10 ± 0.07 cm(3), p = 0.0091). The permanent signal change was more observed in single APT than in multiple (24.5% versus 5.2%, p = 0.02). CONCLUSION: DWI high spots after elective coiling were small without significant decrease of ADC, and do not correspond to brain infarction. Periprocedural use of multiple antiplatelet agents is expected to reduce the volume of thromboembolism and permanent tissue damages.

Effect of age on the fractional anisotropy (FA) value of peripheral nerves and clinical significance of the age-corrected FA value for evaluating polyneuropathies.

INTRODUCTION: We investigated the correlation between age and the fractional anisotropy (FA) values of peripheral nerves in healthy adults and compared the age-corrected FA values of peripheral nerves in healthy subjects and patients with polyneuropathy. METHODS: The institutional review board approved this study and informed consent was obtained from all participants before entry into the study. We optimized diffusion tensor imaging using a 3-T magnetic resonance scanner and an extremity coil for scanning tibial nerves. The effect of age and sex on the FA values of tibial nerves in healthy volunteers was investigated and the age-corrected FA values of tibial nerves in healthy volunteers and patients with polyneuropathy were compared. RESULTS: The maximum FA values of the tibial nerves remained constant until age 45 (approximately 0.516); they subsequently decreased by 0.004/year in healthy volunteers. After removing the effect of age with an age-adjusted equation, the median maximum FA values in the volunteers and patients were 0.518 (range, 0.406-0.616) and 0.442 (range, 0.376-0.530), respectively. The age-corrected FA values were significantly lower in the patients than the healthy volunteers (p < 0.001). There was no significant gender-related difference in the maximum FA values of the tibial nerves (p = 0.416). CONCLUSION: The age-corrected FA value of the peripheral nerves helps to differentiate between age-related peripheral nerve degeneration and polyneuropathies.

Iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) imaging of multiple myeloma: initial clinical efficiency results.

OBJECTIVES: To evaluate the effectiveness of the iterative decomposition of water and fat with echo asymmetric and least-squares estimation (IDEAL) MRI to quantify tumour infiltration into the lumbar vertebrae in myeloma patients without visible focal lesions. METHODS: The lumbar spine was examined with 3 T MRI in 24 patients with multiple myeloma and in 26 controls. The fat-signal fraction was calculated as the mean value from three vertebral bodies. A post hoc test was used to compare the fat-signal fraction in controls and patients with monoclonal gammopathy of undetermined significance (MGUS), asymptomatic myeloma or symptomatic myeloma. Differences were considered significant at P < 0.05. The fat-signal fraction and ß(2)-microglobulin-to-albumin ratio were entered into the discriminant analysis. RESULTS: Fat-signal fractions were significantly lower in patients with symptomatic myelomas (43.9 ±19.7%, P < 0.01) than in the other three groups. Discriminant analysis showed that 22 of the 24 patients (92%) were correctly classified into symptomatic or non-symptomatic myeloma groups. CONCLUSIONS: Fat quantification using the IDEAL sequence in MRI was significantly different when comparing patients with symptomatic myeloma and those with asymptomatic myeloma. The fat-signal fraction and ß(2)-microglobulin-to-albumin ratio facilitated discrimination of symptomatic myeloma from non-symptomatic myeloma in patients without focal bone lesions. KEY POINTS: • A new magnetic resonance technique (IDEAL) offers new insights in multiple myeloma. • Fat-signal fractions were lower in patients with symptomatic myelomas than in those with asymptomatic myelomas. • The ß2-microglobulin-to-albumin ratio also aided discrimination of symptomatic myeloma. • The fat-signal fraction may provide information about the myeloma cell mass.

Evaluation of lumber nerve root compression using thin-slice thickness coronal magnetic resonance imaging: three-dimensional fat-suppressed multi-shot balanced non-steady-state free precession versus three-dimensional T1-weighted spoiled gradient-recalled echo.

PURPOSE: The aim of this study was to compare the three-dimensional fat-suppressed balanced non-steady-state free precession (3D FS-nSSFP) sequence and the 3D T1-weighted spoiled gradient-recalled echo (3D T1-GRE) sequence for evaluating lumbar nerve root compression with continuous thin-slice coronal magnetic resonance (MR) images. MATERIALS AND METHODS: The institutional review board approved this study, and written informed consent was obtained from all 35 patients. We optimized continuous 2.5-mm thick lumbar coronal images with 3D FS-nSSFP and 3D T1-GRE. We calculated the contrast-to-noise ratio (CNR) for nerve roots and other structures on images with the two sequences. With knowledge of the final diagnosis, we assessed the visibility of nerve root compression on these images. RESULTS: The CNR values of nerve roots were significantly higher on images with 3D FS-nSSFP than on those with 3D T1-GRE. These continuous thin-slice coronal images facilitated visualization of nerve root compression in >91% of patients. There was no statistically significant difference between the two sequences in the detection of nerve root compression. CONCLUSION: Continuous thin-slice coronal MR images using 3D FS-nSSFP and 3D T1-GRE sequences are sufficient to evaluate lumbar nerve root compression, and 3D FS-nSSFP is superior to 3D T1-GRE for depiction of lumbar nerve roots.

Multiple myeloma: microstructural analysis of lumbar trabecular bones in patients without visible bone lesions--preliminary results.

PURPOSE: To evaluate the accuracy of trabecular analysis of the lumbar spine by using multidetector computed tomography (CT) in differentiating multiple myeloma patients without spinal fractures from control subjects. MATERIALS AND METHODS: This retrospective single-institution study was approved by the institutional review board, with a waiver of informed consent. Spinal microarchitecture was examined by using 64-detector row CT in 29 patients with multiple myeloma and 51 control subjects. The patients were 13 men and 16 women (mean ages, 71.1 and 69.2 years, respectively). By using multidetector CT data, eight parameters were calculated for the L3 vertebral trabeculae with a three-dimensional image analysis system. The χ(2) test was used to select a preliminary set of predictors for multiple myeloma. A multivariable generalized linear model was constructed to identify parameters that could be used to differentiate between patients and controls. Parameters with findings of P < .05 were included in the multivariable model. RESULTS: Generalized linear models showed that mean trabecular thickness (TbTh) (patients, 703.7 µm ± 46.7 [standard deviation]; controls, 661.1 µm ± 35.7) and fractal dimension (FD) (patients, 2.23 ± 0.24; controls, 2.41 ± 0.15) in men (P = .05 and .03, respectively) and degree of anisotropy (DA) (patients, 1.63 ± 0.23; controls, 1.38 ± 0.10) in women (P = .02) had significant effects in differentiation between patients and controls. CONCLUSION: Significant differences were observed in spinal microarchitecture between control subjects and multiple myeloma patients without pathologic fractures. Independent predictors of multiple myeloma included TbTh and FD in male patients and DA in female patients.

Diffusion tensor imaging of peripheral nerve in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a feasibility study.

INTRODUCTION: The purpose of this study was to assess the clinical feasibility of diffusion tensor imaging (DTI) for the evaluation of peripheral nerves in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Using a 3-T magnetic resonance imaging scanner, we obtained DTI scans of the tibial nerves of 10 CIDP patients and 10 sex- and age-matched healthy volunteers. We prepared fractional anisotropy (FA) maps, measured the FA values of tibial nerves, and compared these values in the two study groups. In nine patients, we also performed tibial nerve conduction studies and analyzed the correlation between the FA values and parameters of the nerve conduction study. RESULTS: The tibial nerve FA values in CIDP patients (median 0.401, range 0.312-0.510) were significantly lower than those in healthy volunteers (median 0.530, range 0.469-0.647) (Mann-Whitney test, p < 0.01). They were significantly correlated with the amplitude of action potential (Spearman correlation coefficient, p = 0.04, r = 0.86) but not with nerve conduction velocity (p = 0.79, r = 0.11). CONCLUSION: Our preliminary data suggest that the noninvasive DTI assessment of peripheral nerves may provide useful information in patients with CIDP.

A case of MELAS: hyperperfused lesions detected by non-invasive perfusion-weighted MR imaging.

We report a case of MELAS in which lesions were detected by perfusion-weighted MR imaging. Perfusion-weighted MRI using contrast media (PWI) and FAIR (flow-sensitive alternating inversion recovery), an arterial spin labeling method, clearly showed these lesions as hyperperfused areas. One of these lesions, diminished after steroid therapy, could also be detected by FAIR.