Whole body magnetic resonance with diffusion weighted sequence ...

Whole body magnetic resonance with diffusion weighted sequence with body signal suppression compared to 18F-FDG PET/CT in newly diagnosed lymphoma 1

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Cristina Ferrari1, MD*, Carla Minoia2, MD, PhD*, Artor Niccoli Asabella1, MD, PhD, Adriano Nicoletti1, MD, 1 1 2 2 3 Corinna Altini , MD, Filippo Antonica , MD, Michele Ficco , MD, Attilio Guarini , MD, Nicola Maggialetti MD, 1 Giuseppe Rubini MD, Associated Professor

1. D.I.M.- Diagnostic Imaging – Nuclear Medicine, University of Bari “Aldo Moro”, Bari, Italy, 2. Department of Medical and Experimental Oncology, IRCCS National Cancer Research Centre "Giovanni Paolo II", Bari, Italy, 3. Department of Medicine and Health Science, University of Molise, Campobasso, Italy * Cristina Ferrari and Carla Minoia contributed equally in writing paper.

Keywords: Lymphoma – WB-MR/DWIBS - 18F-FDG PET/CT - Bone marrow biopsy Correspondence address: Giuseppe RUBINI, MD, Associate Professor, Piazza G. Cesare, 11, 70124 Bari, Italy, Tel: +39 080 5592913, Fax: +39 080 5593250, E-mail: [email protected] Abstract Lymphomas are a heterogeneous group of lymphoid malignancies, which can be broadly divided into non-Hodgkin Lymphomas (NHL) and Hodgkin lymphoma (HL) that display different patterns of biological behavior and response to treatment. Their incidence is still increasing and for this reason they require a lot of effort in scientific research. The management of both NHL and HL follows well-established guidelines based on the initial staging assessment. Therefore an accurate staging is the basis for the selection of an appropriate therapeutic approach in order to prevent over or under treatment as well as to minimize 18 morbidity related to the radio-chemotherapy regimens given. F-FDG-PET is currently regarded as the reference standard imaging modality in the staging of the majority of lymphoma type, for evaluation of distribution of the disease by providing both functional and anatomic information in a single whole body examination. In particular its role is established in HL and high-grade NHL, confirmed also in Follicular Lymphoma, but its impact on the other histotypes remains to be demonstrated. Among the diagnostic tools currently available for a bio-molecular imaging assessment, of great interest is the Whole Body-Magnetic Resonance with DWIBS sequence (WB-MR/DWIBS), an emerging and promising functional whole body imaging modality to 18 evaluate oncologic and non-oncologic lesions, resulting in images that remarkably resemble F-FDG PET/CT studies. In our 18 research study we evaluated the role of WB-MR/DWIBS, compared with F-FDG-PET/CT in the initial staging of lymphomas, considering its impact on the management of these patients and how it could influence the therapeutic choice. We prospectively enrolled 27 consecutive patients with newly diagnosed lymphoma (13 HL, 14 NHL) histologically proven, who underwent 18FFDG-PET/CT and WB-MR/DWIBS (coronal T1-weighted, coronal STIR, axial sequences DWIBS) within 10 days from the diagnosis and before start the treatment. We evaluated the overall agreement between the two methods, the general agreement in evaluating both nodal and extra-nodal involvement and a specific site agreement according to lymph nodal basins or extranodal sites involvement. The agreement between the two diagnostic tools in relation to histological types (HL/NHL) and in relation to indolent and aggressive forms, within NHL histotypes, as well as in relation to the Ann Arbor stage was also 18 evaluated. We also analyzed the role of WB-MRI/DWIBS and F-FDG-PET/CT in bone marrow involvement detection by calculating their sensitivity and specificity, with bone marrow biopsy as the reference standard, and comparing them with 18 McNemar test. A total of 85 lesions, nodal (74) and extra-nodal (11), were detected by F-FDG-PET/CT. WB-MRI/DWIBS showed a total of 91 sites involved, (81) nodal and (13) extra-nodal lesions. The overall agreement between the two imaging modalities was very good (k=0.815; IC:0.739-0.890); however considering histotypes, the agreement comes down to good in evaluating NHL for both nodal and extra-nodal involvement (k=0.763, IC: 0.627-0.898; k=0.629, IC:-0.021-1.278). Considering 18 indolent or aggressive forms the agreement between WB-MR/DWIBS and F-FDG PET/CT findings was very good in 18 aggressive forms while it appeared to be lower in indolent forms. Sensitivity and specificity of WB-MRI/DWIBS and F-FDG 18 PET/CT in bone marrow involvement detection were respectively: 100% and 100% vs. 50% and 96%. The switch from F-FDG PET/CT to WB-MR/DWIBS in the AA Staging System resulted in an over-staging in 1/27 patient. The two methods were concordant in the staging in 26/27 patients (96%). In conclusion, our initial results show a good overall agreement between the 18 two diagnostic tools. F-FDG-PET/CT remains the gold standard for lymphoma staging, however WB-MRI/DWIBS can be useful 18 18 in histotypes not F-FDG-avid or in the evaluation of “critical” organs for F-FDG PET/CT. The integrated information provided by metabolic and tissutal functional imaging can be complementary to assist hematologic decision of tailored patient’s treatment.

HJNM 2014; 17(Suppl1): 40-49

Published also on line: 15 January 2014

Introduction

L

ymphomas are a heterogeneous group of lymphoid malignancies originating from mature or immature B cells, T cells or natural killer (NK) cells at various stages of differentiation. Mature B-cells lymphomas comprise over 90% of lymphoid neoplasms and include non-Hodgkin Lymphomas (NHL) and Hodgkin lymphoma (HL). They represent approximately 4% of new cancers each year and are more common in developed countries. Recent surveys indicate an

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Hellenic Journal of Nuclear Medicine January-April 2014 (Suppl)

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incidence rate per 100,000 persons per year of 33.6 for all lymphoid neoplasms, 26.1 for B-cell neoplasms, 2.6 for HL. The most common types are Follicular lymphoma (FL) and Diffuse large B-cell lymphoma (DLBCL). The incidence of lymphomas, and in particular of B-cell lymphomas, is increasing worldwide, with more than 280000 cases occurring annually each year, for this reason they require a lot of effort in scientific research [1, 2]. In recent years, technogical innovation has allowed to ameliorate the knowledge of lymphoma biology, diagnosis and prognosis, to perform an adequate staging and to assess the response to treatment. Fluorine 18-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) performed with not-enhanced computed tomography (CT) is the most important recent advance in not-invasive staging, with high sensitivity and specificity in detecting nodal and extra-nodal sites and it is currently regarded as the reference standard in the staging of the majority of lymphoma type, for evaluation of distribution of the disease by providing both functional and anatomic information in a single whole body examination. It leads to a change in stage of disease in about 15%-20% of patients with an impact on management in about 5%15% [3]. In addition, 18F-FDG uptake on PET, quantified by the standardized uptake value (SUV), has been shown to be a helpful semiquantitative index for determining disease aggressiveness, for objective treatment response assessment and for outcome prediction [4]. 18 F-FDG PET/CT value was extensively investigated during the years, becoming increasingly important in the management of several lymphoma types. In particular, its role is well established in HL and aggressive NHL, confirmed also in FL, but its impact on the other histotypes remains to be defined. This is the reason why scientific community is still working to optimize the management of these patients trying more specific PET radiotracers for the different lymphoma histotypes and/or comparing 18F-FDG PET/CT performance with other imaging modalities. Among the diagnostic tools currently available for a bio-molecular imaging assessment, of great interest is the Whole Body-Magnetic Resonance (WB-MR). Thanks to the development and availability of specific software for sufficiently fast and diagnostic sequences for whole-body study, with consequently reduction in execution time, WB-MR has been increasingly applied to the study of systemic oncologic diseases [5-7]. A further development of the WB-MR is the use of diffusion-weighted sequence with body signal suppression (DWIBS) introduced by Takahara et al. in 2004 [8] that intentionally uses free-breathing scanning rather than breathholding to visualize visceral organs and their lesions. This method is based on measurements of Brownian extra-, intraand trans-cellular motion of water molecules in biological tissue, highlighting an impeded (low) diffusivity, that is a high signal intensity, in different pathological conditions (e.g., an increased cellularity in tumors or cellular swelling in inflammatory or infectious lesions). In this way, DWIBS allows a “functional” evaluation of changes of tissue constitution that occur in different physio-pathological conditions. It allows a more accurate identification and evaluation of disease localizations, due to the high lesion-to-background contrast and it is also able to provide a better assessment of nodal involvement compared to conventional MR sequences [9]. Then, DWIBS is emerging as a promising functional whole body imaging modality to evaluate oncologic and nononcologic lesions, resulting in images that remarkably resemble 18F-FDG PET/CT studies. Currently, some studies have demonstrated the potential role of WB-MR study with DWIBS (WB-MR/DWIBS) in lymphoma staging. However, studies on the correlation and comparison between 18F-FDG PET/CT and WB-MR/DWIBS are still few and, most of them, suffer from several methodological shortcomings, as for example: patient selection criteria, small and not-homogeneous samples or different criteria to compare imaging methods [10-15]. The aim of this prospective study was to evaluate the role of WB-MR/DWIBS, compared to 18F-FDG PET/CT, in the initial staging of lymphomas, considering its impact on the management of these patients and how it could influence the therapeutic choice.

Subjects, materials materials and methods Patients We prospectively enrolled consecutive patients with newly diagnosed lymphoma. Classical HL (cHL) and B-cell NHL (BNHL) were included; among NHL we considered both indolent and aggressive histotypes. Inclusion criteria were: histological diagnosis performed on excisional biopsies of lymphoid tissue according to the 2008 World Health Organization classification, measurable nodal and/or extra-nodal disease and no previous chemotherapy. Exclusion criteria were represented by contraindications to MR such as pacemaker, claustrophobia and metal implants and/or previous diagnosis of malignancy. Patients underwent to 18F-FDG PET/CT and WB-MR/DWIBS within 10 days of diagnosis and before starting the treatment. The patient evaluation also included bone marrow biopsy (BMB) and whole body Contrast Enhanced CT (CECT) scan. Staging was performed based on Ann Arbor (AA) staging system considering patient's symptoms, BMB and the spread of disease observed on CECT and 18F-FDG PET/CT. The local ethics committee approved this prospective study and written informed consent was required for each patient.

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WholeWhole-Body MR/DWIBS protocol The WB-MR/DWIBS was performed on a 1.5 Tesla MR scanner (ACHIEVA, Philips Healthcare) using a rolling table platform, for a complete anatomical coverage. The examination was conducted by the head to the thighs, with 4 consecutive packages acquisitions (head/neckthorax, abdomen, pelvis). In according to literature, a coronal T1-weigheted (T1w) and STIR and axial DWIBS sequences were performed [9]. The coronal T1w sequence was acquired with the Q body coil for signal reception and the following parameters: singleshot turbo spin echo, TR/TE, shortest, slice thickness, 6mm, gap 1mm, number of slices for station, 39; field of view, 530x265; acquisition matrix, 208x287; reconstruction matrix 512; acquisition voxel size, 1.27x1.85x6.00; reconstructed voxel size, 1.04x1.04x6.00; number of acquisitions, 1; acquisition time\sequence, 63sec. The coronal STIR sequence was acquired with the Q body coil for signal reception and the following parameters: single-shot turbo spin echo, TR/TE, shortest/64; inversion time, 165 milliseconds; slice thickness, 6mm; gap, 1mm; number of slices for station, 39; field of view, 530x265; acquisition matrix, 336x121; reconstruction matrix, 512; acquisition voxel size, 1.58x2.18x6.00; reconstructed voxel size, 1.04x1.04x6.00; number of acquisitions, 2; acquisition time/ sequence, 62sec. Both T1w and STIR images were acquired in free-breathing except for the chest and abdomen, obtained with breath-hold. DWIBS sequences were acquired in the axial plane, with Q body coil for signal reception, in free-breathing and with the following parameters: single-shot EPI; TR/TE, shortest; inversion time, 180milliseconds; slice thickness, 6mm; gap, 0mm; number of slices for station, 44; field of view, 530x303; acquisition matrix,108x61; reconstruction matrix, 352; acquisition voxel size, 4.91x4.83x6.00; reconstructed voxel size, 1.51x1.50x6.00; half–scan factor, 0.627; EPI factor, 61; b values 0-500-1000 s\mm²; number of acquisitions, 2; acquisition time\sequence, 3min and 29sec. The total duration of the examination was 20-25min. Whole-body images coronal, both T1w and STIR sequences were obtained from the fusion of individual packages. DWIBS axial images were reconstructed both on a radial plane (15 number of projections), for a volumetric view, and on a coronal plane (slice thickness, 4mm; gap, 1mm; number of images 44); then the reconstructed images in the coronal plane for each station were merged to obtain a coronal whole-body/DWIBS images. 18

F-FDG PET/CT protocol

Patients were instructed to fast, except for glucose-free oral hydration, for at least 6h before intravenous injection of 370– 550MBq (3.7MBq/kg) of 18F-FDG. Blood glucose was measured before injection to ensure a level 0.4 to ≤0.6), good (=G; k>0.6 to ≤0.8) and very good (=VG; k>0.8 to ≤1) agreement. We evaluated the overall agreement between the two methods, the general agreement in evaluating both nodal and extra-nodal involvement and a specific site agreement according to lymph nodal basins or extra-nodal sites involvement. The agreement between the two diagnostic tools in relation to histological types (HL/NHL) and in relation to indolent and aggressive forms, within NHL histotypes, was also evaluated. Moreover, we specifically calculate sensitivity and specificity of WB-MR/DWIBS and 18F-FDG PET/CT in bone marrow involvement detection compared to BMB as the reference standard. The comparison between the two methods results was made with the McNemar test. Finally, the agreement between WB-MR/DWIBS staging compared to that defined with the AA stage (inclusive of18FFDG PET/CT) was assessed, considering how WB-MR/DWIBS can modify the patient management.

Results In a period of 4 months, we prospectively enrolled 27 consecutive patients (15 men, 12 women) with a mean age of 40.6 years (range: 23-81 years). 13 patients had a diagnosis of cHL and 14 had a diagnosis of B-NHL. Among B-NHL, 7 were aggressive (5 DLBCL, 2 Mantle cell lymphoma) and 7 indolent (4 FL, 2 Marginal zone lymphoma, 1 Small lymphocytic lymphoma). Patient’s characteristics are described in Table 1. Table 1. Patient’s characteristics divided into classical Hodgkin lymphoma (cHL) and B-cell non-Hodgkin lymphoma (B-

NHL) cHL 13

BNHL 14

Range

23-81

50-78

Mean

40.6

61

5 8

10 4

N° Patients Age

Sex Male Female

Histological subtype Nodular sclerosis cHL Mixed cellularity cHL Lymphocyte-rich cHL Follicular lymphoma (FL) Diffuse large B-cell lymphoma (DLBCL) Marginal zone lymphoma (MZL) Mantle cell lymphoma (MCL) Small lymphocytic lymphoma (SLL)

11 1 1 4 5 2 2 1

18 F-FDG PET/CT showed a total of 85 sites, including nodal basins (74), extra-nodal sites (4), spleen (4) and bone marrow involvement (3). Nodal basins involvement was in the neck (15), axilla (10), mediastinum (16), abdomen (11), pelvic (11) and inguinal-femoral (11). Extra-nodal sites included bone (1), Waldeyer (1) and breast (2). WB-MR/DWIBS showed a total of 94 sites involved: 81 nodal basins, 5 extra-nodal sites, 4 spleen and 4 bone marrow involvement. Nodal basins involvement was in the neck (15), axilla (10), mediastinum (16), abdomen (14), pelvic (14) and inguinal-femoral (12). Extra-nodal sites included bone (1), Waldeyer (1), breast (2) and kidney (1). Comparison between WB-MR/DWIBS

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and 18F-FDG PET/CT showed a very good overall agreement (k=0.815; IC:0.739-0.890) and same results were found in evaluating nodal and extra-nodal involvement (Fig. 1, 2). However considering histotypes, the agreement comes down to good in evaluating NHL for both nodal and extra-nodal involvement, as shown in Table 2. These data were also confirmed by the assessment of the specific site agreement. In particular WB-MR/DWIBS and 18 F-FDG PET/CT showed a lower agreement in evaluating all sub-diaphragmatic lymph nodal basins in NHL, especially in the abdominal site (k=0.429; IC:0.025-0.882), and in evaluating mediastinal basin in cHL (Fig. 3). While regarding specific extra-nodal agreement, discordant results were found in detecting bone marrow involvement for both cHL and NHL, and splenic involvement especially in NHL (Table 3). Considering indolent or aggressive forms within the NHL histotypes, the agreement between WB-MR/DWIBS and 18 F-FDG PET/CT findings was very good in aggressive forms while it appeared to be lower in indolent forms (Fig. 4), as displayed in detail in Table 4.

Figure 1. Male, DLBCL, stage IV. (A) Coronal DWIBS image and (B, C) 18F-FDG PET and fused PET/CT images show good agreement in detecting mediastinal lymph nodal basin, bone arrow and splenic (focal and diffuse) involvement with evident splenomegaly.

Figure 2. Three different patients in which the two diagnostic tools showed good agreement in evaluating extra-nodal involvement: (A, B) DLBCL, stage IE. PET axial image (A) shows high 18F-FDG-uptake in left breast, confirmed on DWIBS axial image (B); (C, D) DLBCL, stage IV. PET axial image (C) shows high 18F-FDG-uptake in right breast with more extended high signal intensity on DWIBS axial image (D); (E, F) Mantle cell lymphoma, stage IV. PET axial image (E) shows high 18F-FDG-uptake in Waldeyer ring (E) confirmed on DWIBS axial image (F). Table 2. Agreement between WB-MRI/DWIBS and 18F-FDG PET/CT in all patients and in cHL and NHL separately Parameter Agreement Overall All nodal basins All extra-nodal basins

K (95% CI) 0.815 (0.739-0.890) =VG 0.815 (0.726-0.904) =VG 0.833 (0.611-1.055) =VG

K (95% CI) cHL

B-NHL

0.868 (0.756-0.980) =VG 0.811 (0.460-1.162) =VG

0.763 (0.627-0.898) =G 0.629 (-0.021-1.278) =G

With a changeover of these results in a clinical management, we found that 3/27 patients (11%) showed a different stage between the two methods. In particular, 2 were over-staged and 1 was under-staged by WB-MR/DWIBS compared to 18F-FDG PET/CT. The patients over-staged by WB-MR/DWIBS were affected by Small lymphocytic lymphoma (SLL) and Lymphocyte-rich cHL, while the one under-staged was a Nodular sclerosis cHL patient (Table 5). According to the AA Staging System, disease was stage I in 3 patients (1 cHL, 2 NHL), II in 10 patients (8 cHL, 2 www.nuclmed.gr


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NHL), III in 7 patients (3 cHL, 4 NHL) and IV in 7 patients (1 cHL, 6 NHL), as summarized in Table 5. The switch from 18FFDG PET/CT to WB-MR/DWIBS in the AA Staging System resulted in an over-staging in 1/27 patient affected by Lymphocyte-rich cHL. The two methods were concordant in the staging in 26/27 patients (96%).

Figure 3. Male, Nodular sclerosis classical HL, stage III. 18F-FDG PET/CT axial images (A, B): radiofarmaceutical uptake in carenal and right hilar lymph nodes (red arrows). DWIBS axial image (C): no detection of mediastinal lymph nodal involvement.

Figure 4. Female, Splenic marginal zone lymphoma, stage IV. (A) Coronal WB-DWIBS: high signal intensity in cervical, axillary, abdominal, pelvic and femoral lymph nodal basins but also spleen and bone marrow involvement. (B) 18F-FDG PET/CT, MIP and axial fused images B, C, D: mild radiofarmaceutical uptake in left axillary lymph nodes and diffuse uptake in the spleen. BMB confirmed bone marrow involvement. Table 3. Specific site agreement between WB-MRI/DWIBS and 18F-FDG PET/CT in cHL and NHL patients Parameter Specific site agreement Nodal basins cervical axillary mediastinal abdominal pelvic femoural Extra-nodal basins spleen bone marrow others

K (95% CI) cHL

B-NHL

0.847 (0.562-1.132) =VG 1 (1-1)=VG 0.755 (0.307-1.203) =G 0.831 (0.518-1.145) =VG 0.831 (0.518-1.145) =VG 0.806 (0.448-1.164) =VG

0.851 (0.573-1.129) =VG 1 (1-1)=VG 0.851 (0.573-1.129) =VG 0.429 (-0.025-0.882)=M 0.714 (0.363-1.066) =G 0.714 (0.363-1.066) =G

1 (1-1)=VG 0.629 (-0.021-1.278) =G NA

0.576 (0.050-1.101) =M 0.759 (0.316-1.201) =G 0.811 (0.460-1.162) =VG

In our study BMB resulted positive in 4/27 patients. WB-MR/DWIBS identified bone marrow infiltration in all cases www.nuclmed.gr


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with a perfect agreement with BMB, while 18F-FDG PET/CT showed 2 false negative and 1 false positive compared to BMB (Table 6). The sensitivity and specificity of WB-MRI/DWIBS and 18F-FDG PET/CT in bone marrow involvement detection, considering BMB as the reference standard, were respectively: 100% and 100% vs. 50% and 96%. The comparison between both sensitivities and both specificities didn’t show a statistically significant difference with the McNemar test (P>0.005). Table 4. Specific site agreement between WB-MRI/DWIBS and

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F-FDG PET/CT in indolent and aggressive forms,

within NHL Parameter Specific site agreement

B-NHL , K (95% CI) Indolent

Aggressive

0.588 (-0.093-1.269) =M 1 (1-1) =Perfect 0.720 (0.232-1.208) =G 0.364 (-0.211-0.939) =P NA NA

1 (1-1)=VG 1 (1-1) =VG 1 (1-1) =VG 0.417 (-0.263-1.097)=M 1 (1-1) =VG 1 (1-1) =VG

0.300 (-0.467-1.067) =P 0.364 (-0.211-0.939) =P NA

1 (1-1) =VG 1 (1-1) =Perfect 0.811 (0.460-1.162) =VG

Nodal basins cervica axillary mediastinal abdominal pelvic femoural

Extra-nodal basins spleen bone marrow others

Table 5. Staging resulted considering 18F-FDG PET/CT and WB-MR/DWIBS findings (on the left) and Ann Arbor staging resulted considering 18F-FDG PET/CT and WB-MR/DWIBS findings (on the right)

Pts 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27

cHL/B-NHL Nodular sclerosis cHL FL grade 2 DLBCL FL grade 3A MZL MCL FL grade 1 Nodular sclerosis cHL DLBCL FL grade 2 Splenic MZL DLBCL DLBCL SLL Nodular sclerosis cHL Nodular sclerosis cHL Nodular sclerosis cHL Nodular sclerosis cHL Nodular sclerosis cHL Mixed cellularity cHL MCL DLBCL Lymphocyte rich cHL Nodular sclerosis cHL Nodular sclerosis cHL Nodular sclerosis cHL Nodular sclerosis cHL

PET/CT 2 4 1 2 3 4 3 3 4 3 4 4 1 2 2 4 2 2 2 3 3 2 1 2 3 2 2

MRI/DWIBS 2 4 1 2 3 4 3 3 4 3 4 4 1 4 2 4 2 2 1 3 3 2 2 2 3 2 2

Ann Arbor Stage PET/CT MRI/DWIBS IIA IIA IVB IVB IE IE IIA IIA IIIA IIIA IVA IVA IIIA IIIA IIIA IIIA IVB IVB IIIA IIIA IVA IVA IVA IVA IA IA IVA IVA IIB IIB IVA IVA IIA IIA IIA IIA IIA IIA IIIA IIIA IIIA IIIA II II I II IIA IIA IIIB IIIB IIA IIA IIA IIA

Table 6. WB-MR/DWIBS and 18F-FDG PET/CT results in bone marrow involvement detection, considering BMB as the

reference standard

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BMB positive

WB-MRI/DWIBS positive negative 4 /

negative

/

1

23

F-FDG PET/CT positive negative 2 2 22


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Discussion To date 18F-FDG PET/CT is the reference standard imaging modality in lymphoma staging with a diagnostic sensitivity and specificity in cHL and aggressive NHL, near to 100% [16]. WB-MR/DWIBS is an emerging functional imaging modality under active investigation. Its clinical application, in comparison with 18F-FDG PET/CT, is of special interest because both diagnostic tools provides functional, not-invasive and whole-body imaging. The advantages of WB-MR/DWIBS consist in no patient preparation, no radiopharmaceutical administration and the absence of ionizing radiation exposure. In the present study, we evaluated the role of WB-MR/DWIBS, compared to 18F-FDG PET/CT, in the newly diagnosed lymphoma, assessing its impact on the staging and the following therapeutic choice. The selection of patients with newly diagnosed lymphoma makes the study group more homogeneous and allows us to study the biology and tissue constitution without the interference of treatments. Regarding the lymph nodal involvement, our results show a general good agreement (k=0.815; IC: 0.726-0.904) between the two methods. However, in some cases 18F-FDG PET/CT revealed a nodal involvement not detected by WBMR/DWIBS (Fig. 3). One of the reasons of these discrepancies is the images interpretation based on size parameter adopted by WB-MR/DWIBS, but not by 18F-FDG PET/CT. As reported in the literature, we used the size parameter for lymph nodal involvement (longest transverse diameter >10mm) because normal lymph nodes have a high cellularity as well as pathologic lymph nodes, presenting similar aspect on DWIBS sequence with impeded water diffusion and high signal intensity [9, 13-14, 17-18]. In 3/27 patients we found small lymph nodes with high 18F-FDG uptake and high signal DWIBS, but they were not considered pathological on WB-MR/DWIBS because of their size (