Xingchen Wu

Diffusion-weighted MRI in early chemotherapy response evaluation of patients with diffuse large B-cell lymphoma – a pilot study: comparison with 2-deoxy-2-fluoro- D-glucose-positron emission tomography/computed tomography

To determine the feasibility of diffusion‐weighted MRI (DWI) in the evaluation of the early chemotherapeutic response in patients with aggressive non‐Hodgkins lymphoma (NHL), eight patients with histologically proven diffuse large B‐cell lymphoma were imaged by MRI, including DWI, and positron emission tomography/computed tomography (PET/CT) before treatment (E1), and after 1 week (E2) and two cycles (E3) of chemotherapy. In all patients, whole‐body screening using T1‐ and T2‐weighted images in the coronal plane was performed. To quantitatively evaluate the chemotherapeutic response, axial images including DWI were acquired. Apparent diffusion coefficient (ADC) maps were reconstructed, and the ADC value of the tumor was measured. In addition, the tumor volume was estimated on axial T2‐weighted images. The maximum standardized uptake value (SUVmax) and active tumor volume were measured on fused PET/CT images. Lymphomas showed high signal intensity on DW images and low signal intensity on ADC maps, except for necrotic foci. The mean pre‐therapy ADC was 0.71 × 10−3 mm2/s; it increased by 77% at E2 (p < 0.05) and 24% more at E3 (insignificant); the total increase was 106% (p < 0.05). The mean tumor volume by MRI was 276 mL at baseline; it decreased by 58% at E2 (p < 0.05) and 65% more at E3 (p < 0.05), giving a total decrease of 84% (p < 0.05). All the imaged pre‐therapy tumors were strongly positive on PET/CT, with a mean SUVmax of 20. The SUVmax decreased by 60% at E2 (p < 0.05) and 59% more at E3 (p < 0.05), giving a total decrease of 83% (p < 0.05). The active tumor burden decreased by 66% at E2 (p < 0.05). At baseline, both central and peripheral tumor ADC values correlated inversely with SUVmax (p < 0.05), and also correlated inversely with active tumor burden on PET/CT and with tumor volume on MRI at E2 (p < 0.05). In conclusion, the results of DWI in combination with whole‐body MRI were comparable with those of integrated PET/CT. Copyright

ADC measurements in diffuse large B-cell lymphoma and follicular lymphoma: a DWI and cellularity study

PURPOSE Diffusion-weighted magnetic resonance imaging (DW-MRI) allows quantifying the random motion of water molecules in tissue by means of apparent diffusion coefficient (ADC) measurements. The aim of the study was to determine whether ADC measurements allow discrimination of diffuse large B-cell lymphoma (DLBCL) from follicular lymphoma (FL), and to examine the relationship between cellularity and ADC value of the tumor using DWI. MATERIALS AND METHODS Thirty-two patients with histologically proven non-Hodgkin lymphoma (21 with DLBCL and 11 with FL, 17 males and 15 females, mean age 62±13 years) underwent conventional MRI and DWI examination before treatment. The ADC values of DLBCL were compared to those of FL. The ADC value of the tumor was also correlated with the tumor tissue cellularity. RESULTS The mean ADC value of DLBCL was not significantly different from that of FL (0.70±0.16×10(-3)mm(2)/s vs. 0.76±0.12×10(-3)mm(2)/s, P=0.21). The cellularity of DLBCL was significantly lower than that of FL (2991±351 cells/view vs. 4412±767 cells/view, P<0.001). There was no correlation between the ADC value and the tissue cellularity of the tumor in patients with DLBCL and FL. CONCLUSION ADC measurements could not differentiate between DLBCL and FL, and there was no correlation between the ADC value and cellularity of the tumor in patients with DLBCL and FL.

No correlation between glucose metabolism and apparent diffusion coefficient in diffuse large B-cell lymphoma: A PET/CT and DW-MRI study

PURPOSE Both positron emission tomography/computed tomography (PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) are oncologic feasible techniques for evaluating the malignancy of tumors. Standardized uptake value (SUV) is a marker of tumor glucose metabolism detected by PET/CT. Apparent diffusion coefficient (ADC) measured by DWI can provide information about tissue cellularity. The aim of the study was to evaluate the correlation between SUV and ADC in untreated diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS Fifteen pre-therapy patients with histologically proven DLBCL underwent PET/CT and DWI examinations within two days. Tumor glucose metabolism was evaluated by the maximum and mean SUV (SUV(max) and SUV(mean)) on the PET/CT images. The mean ADC value was measured directly on the parametric ADC maps. RESULTS In total, 28 lymphoma lesions with best match PET/CT and DWI were identified and evaluated. The mean SUV(max) and SUV(mean) were 16.8 and 11.1, respectively; the mean ADC was 0.74 × 10(-3)mm(2)/s. There was no correlation between the mean ADC and the SUV(max) or SUV(mean). CONCLUSION SUV determined from PET/CT and ADC value measured from DWI are different indices for the diagnosis of tumor malignancy, they may provide complimentary functional information of tumor tissue.

Cell surface adhesion molecules and cytokine profiles in primary progressive multiple sclerosis

Objective We evaluated the utility of adhesion molecule (AM) and cytokine/chemokine expressions in blood and cerebrospinal fluid (CSF) as markers of disease activity in primary progressive multiple sclerosis (PPMS). Methods The expressions of AMs and the levels of 17 cytokines in patients with PPMS (n = 25) were compared with those in secondary progressive MS (SPMS) (n = 18) and controls (n =11) and correlated with the volumes of focal and atrophic changes on MRI. Results The expressions of very late activation antigen 4 (VLA-4), lymphocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) in blood and CSF were higher in PPMS than in controls. Comparison between PPMS and SPMS showed higher levels of ICAM-1 in blood and CSF in PPMS, while the level of the vascular adhesion molecule (VCAM-1) was higher only in blood. There was no difference in the levels of cytokines in serum or CSF between PPMS and SPMS or controls, but evidence suggesting intrathecal synthesis of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) was found in PPMS. The expressions of CSF VLA-4 in PPMS correlated with the total volume of cerebral lesions and the number of diffuse brain lesions in MRI, while the amount of LFA-1 in CSF correlated with the number of spinal T2 lesions. The level of serum MIP-1β correlated with the T2 lesion load and EDSS score in PPMS. Conclusions The upregulated expressions of AMs in blood and CSF and evidence for intrathecal synthesis of MCP-1 and IL-8 in PPMS indicate the importance of inflammatory changes in the pathogenesis of PPMS. Multiple Sclerosis 2007; 13: 701-707. http://msj.sagepub.com

Comparison of different MRI sequences in lesion detection and early response evaluation of diffuse large B-cell lymphoma--a whole-body MRI and diffusion-weighted imaging study.

To compare different MRI sequences for the detection of lesions and the evaluation of response to chemotherapy in patients with diffuse large B‐cell lymphoma (DLBCL), 18 patients with histology‐confirmed DLBCL underwent 3‐T MRI scanning prior to and 1 week after chemotherapy. The MRI sequences included T1‐weighted pre‐ and post‐contrast, T2‐weighted with and without fat suppression, and a single‐shot echo‐planar diffusion‐weighted imaging (DWI) with two b values (0 and 800 s/mm2). Conventional MRI sequence comparisons were performed using the contrast ratio between tumor and normal vertebral body instead of signal intensity. The apparent diffusion coefficient (ADC) of the tumor was measured directly on the parametric ADC map. The tumor volume was used as a reference for the evaluation of chemotherapy response. The mean tumor volume was 374 mL at baseline, and decreased by 65% 1 week after chemotherapy (p < 0.01). The T2‐weighted image with fat suppression showed a significantly higher contrast ratio compared with images from all other conventional MRI sequences, both before and after treatment (p < 0.01, respectively). The contrast ratio of the T2‐weighted image with fat suppression decreased significantly (p < 0.01), and that of the T1‐weighted pre‐contrast image increased significantly (p < 0.01), after treatment. However, there was no correlation between the change in contrast ratio and tumor volume. The mean ADC value was 0.68 × 10–3 mm2/s at baseline; it increased by 89% after chemotherapy (p < 0.001), and the change in ADC value correlated with the change in tumor volume (r = 0.66, p < 0.01). The baseline ADC value also correlated inversely with the percentage change in ADC after treatment (r = −0.62, p < 0.01). In conclusion, this study indicates that T2‐weighted imaging with fat suppression is the best conventional sequence for the detection of lesions and evaluation of the efficacy of chemotherapy in DLBCL. DWI with ADC mapping is an imaging modality with both diagnostic and prognostic value that could complement conventional MRI. Copyright

Correlations between Functional Imaging Markers Derived from PET/CT and Diffusion-Weighted MRI in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma

Objectives To investigate the correlations between functional imaging markers derived from positron emission tomography/computed tomography (PET/CT) and diffusion-weighted magnetic resonance imaging (DWI) in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Further to compare the usefulness of these tumor markers in differentiating diagnosis of the two common types of Non-Hodgkins lymphoma (NHL). Materials and Methods Thirty-four consecutive pre-therapy adult patients with proven NHL (23 DLBCL and 11 FL) underwent PET/CT and MRI examinations and laboratory tests. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and metabolic tumor burden (MTB) were determined from the PET/CT images. DWI was performed in addition to conventional MRI sequences using two b values (0 and 800 s/mm2). The minimum and mean apparent diffusion coefficient (ADCmin and ADCmean) were measured on the parametric ADC maps. Results The SUVmax correlated inversely with the ADCmin (r = −0.35, p<0.05). The ADCmin, ADCmean, serum thymidine kinase (TK), Beta 2-microglobulin (B2m), lactate dehydrogenase (LD), and C-reactive protein (CRP) correlated with both whole-body MTV and whole-body MTB (p<0.05 or 0.01). The SUVmax, TK, LD, and CRP were significantly higher in the DLBCL group than in the FL group. Receiver operating characteristic curve analysis showed that they were reasonable predictors in differentiating DLBCL from FL. Conclusions The functional imaging markers determined from PET/CT and DWI are associated, and the SUVmax is superior to the ADCmin in differentiating DLBCL from FL. All the measured serum markers are associated with functional imaging markers. Serum LD, TK, and CRP are useful in differentiating DLBCL from FL.

Intravenous immunoglobulins are a therapeutic option in the treatment of multiple sclerosis relapse.

Objective:The objective of the study is to evaluate the efficacy and tolerability of intravenous immunoglobulin (IVIG) monotherapy in the treatment of multiple sclerosis (MS) relapse. Background:High-dose intravenous methylprednisolone (IVMP) and plasmapheresis have been shown to shorten the recovery period of an MS relapse. Options for those who have contraindications for or are unresponsive to these treatments are very limited. Intravenous immunoglobulin has been used experimentally in these situations, even though there are no previous studies on its efficacy as monotherapy in MS relapse. Subjects and Methods:Twelve consecutive MS patients with acute MS relapse were treated with IVIG 0.4 g/kg per day for 5 days, and the next 5 patients received IVMP 1000 mg/d for 3 days. Volumetric brain magnetic resonance imaging (MRI) and clinical evaluation using expanded disability status scale (EDSS) were performed at baseline and at 3 weeks after treatment. EDSS score after 1 year of the treatment was collected from the patient records. MRI evaluation was performed blindly but not the clinical examination and EDSS scoring. Results:A significant reduction in the volumes of T2-, fluid-attenuated inversion recovery-, and gadolinium-enhanced lesions was detected in the IVIG-treated group, but not in the IVMP-treated patients. The difference between the groups did not reach statistical significance. The EDSS score improved equally in both groups. Conclusions:Intravenous immunoglobulin did not show inferiority compared with IVMP in the treatment of an acute MS relapse evaluated clinically and radiologically. Therefore, we suggest that IVIG may be tried as a therapy in acute MS relapse, especially in case of contraindications to IVMP and plasmapheresis.

Increased disability and MRI lesions after discontinuation of IFN‐β‐1a in secondary progressive MS

Objective –  To examine neurological and magnetic resonance imaging (MRI) changes following discontinuation of interferon (IFN)‐β‐1a treatment in secondary progressive multiple sclerosis (SPMS).

Glucose metabolism correlated with cellular proliferation in diffuse large B-cell lymphoma

Abstract Standardized uptake value (SUV) is a marker of tumor glucose metabolism detected by [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT). The maximum SUV of the whole-body (BmSUVmax) reflects the tumor aggressiveness in non-Hodgkin lymphoma. To evaluate the correlation between SUVmax at biopsy site (BxSUVmax) and proliferation potential of tumor cells in untreated diffuse large B-cell lymphoma (DLBCL), fifteen pre-therapy PET/CT scans in patients with histologically proven DLBCL were retrospectively analyzed together with Ki-67 proliferation index. The BmSUVmax and BxSUVmax were evaluated from the fused PET/CT images. Ki-67 proliferation index was measured in the biopsy specimens using an immunohistochemical technique in archival paraffin-embedded sections. The BmSUVmax was significantly higher than the BxSUVmax (mean 19.6 vs.16.6, p < 0.01). The BxSUVmax correlated with the Ki-67 proliferation index (r = 0.7, p < 0.01), but no correlation was detected between the BmSUVmax and the Ki-67 proliferation index. The results indicate that tumor proliferation potential might be predicted in vivo by FDG-PET/CT images. Thus, PET/CT is useful to guide biopsy by selecting sites with the BmSUVmax when clinically appropriate.

Differentiation of Diffuse Large B-cell Lymphoma From Follicular Lymphoma Using Texture Analysis on Conventional MR Images at 3.0 Tesla.

RATIONAL AND OBJECTIVES Diffuse large B-cell lymphoma (DLBCL) represents the most common type of aggressive non-Hodgkin lymphoma (NHL); follicular lymphoma (FL) is the most frequent indolent NHL. The aim of this study was to investigate whether texture-based analysis of conventional magnetic resonance imaging (MRI) allows discrimination of DLBCL from FL, and further, to correlate the MRI texture features with diffusion-weighted imaging apparent diffusion coefficient (ADC) value and tumor tissue cellularity. MATERIALS AND METHODS Forty-one patients with histologically proven NHL (30 DLBCL and 11 FL) underwent conventional MRI and diffusion-weighted imaging examination before treatment. Based on regions of interest, texture analysis was performed on T1-weighted images pre- and postcontrast enhancement and on T2-weighted images with and without fat suppression, and features derived from the run-length matrix- and co-occurrence matrix-based methods were analyzed. Receiver operating characteristic curves were performed for the three most discriminative texture features for the differentiation of the two most common types of lymphoma. The analyzed MRI texture features were correlated with the ADC value and the tumor tissue cellularity. RESULTS We found that on T1-weighted images postcontrast enhancement, run-length matrix-based texture analysis for lesion classification differentiated DLBCL from FL, with specificity and sensitivity of 76.6% and 76.5%, respectively. There was no correlation between the texture features and the ADC value or tumor tissue cellularity. CONCLUSIONS DLBCL and FL can be differentiated by means of texture analysis on T1-weighted MRI postcontrast enhancement. These results could serve as a basis for the use of the texture features on conventional MRI as adjunct to clinical examination to distinguish DLBCL from FL.