Evaluation of Whole Body Diffusion- Weighted Imaging in the Staging and Treatment Response of Lymphoma Compared With Fluoride-Oxyglucose (FDG) PET/CT as a Reference Standard

Tiffany Hennedige, David Chee, Miriam Tao, Richard Hong Hui Quek, Soon Thye Lim, Jin Wei Kwek

Oncologic Imaging, National Cancer Centre, 11 Hospital Drive, 169610 SingaporeSingapore
Nuclear Medicine, Singapore General Hospital, SingaporeSingapore
Medical Oncology, National Cancer Centre, SingaporeSingapore

DOI: https://doi.org/10.17140/roj-2-114 · Published 2017-04-10 · Licence: https://creativecommons.org/licenses/by/4.0 · © 2017 The Author(s)

Also available as PDF (figures and tables appear in the PDF).

Keywords: Diffusion magnetic resonance imaging; Lymphoma; Neoplasm staging; Positron-emission tomography; Whole body imaging

Introduction:

RHH, Lim ST, Kwek JW. Evaluation sidered standard of practice for the management of lymphoma with sensitivity and specificity of whole body diffusion-weighted imaging in the staging and treatment approaching 100%. However, it is expensive, time-consuming and requires exposure to ionizresponse of lymphoma compared ing radiation. Whole body-diffusion weighted imaging (WB-DWI), does not involve exposure with fluoride-oxyglucose (FDG) to ionizing radiation, is more widely available and can be performed within an acceptable time PET/CT as a reference standard.

frame. PET/CT will be used as a reference standard in the evaluation of the value of WB-DWI Radiol Open J. 2017; 2(1): 17-25.

doi: 10.17140/ROJ-2-114 in the initial staging and treatment response in patients with lymphoma.

Methods: Nine patients with newly diagnosed lymphoma and a pre-treatment PET/CT were

prospectively recruited. Patients were analyzed with both imaging modalities before treatment

initiation and at four-weeks post-completion of chemotherapy. The presence or absence of nod-

al and extra-nodal involvement was independently assessed by two radiologists blinded to the

PET/CT findings. The PET/CT images were assessed by a single nuclear medicine physician.

Results: Compared to PET/CT, the overall sensitivity, specificity and accuracy of WB-DWI in

staging were 62%, 98% and 87% respectively and the overall specificity and accuracy for treat-

ment response were both 99%. Majority of false negative findings were a result of small nodes

which showed uptake on PET/CT but were either not identified or did not show restricted dif-

fusion. Further false negative and positive findings were due to reduced spatial resolution and

increased motion and susceptibility artefact on magnetic resonance imaging (MRI).

Conclusion: WB-DWI may be a viable alternative to PET/CT in the treatment response of

lymphoma. However, in terms of staging, PET/CT probably remains the imaging modality of

choice.

KEY WORDS: Diffusion magnetic resonance imaging; Lymphoma; Neoplasm staging;

Positron-emission tomography; Whole body imaging.

ABBREVIATIONS: PET: Positron Emission Tomography; CT: Computed Tomography;

WB-DWI: Whole body diffusion weighted imaging; MRI: Magnetic Resonance Imaging;

Copyright

FDG: Fluoride-oxyglucose.; DLBCL: Diffuse large B-cell lymphoma; PTCL: Peripheral ©2017 Hennedige T. This is an open access article distributed un- T-cell lymphoma.

der the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the origi- Positron emission tomography/computed tomography (PET/CT) following administration of nal work is properly cited. radiotracer 18F fluorodeoxyglucose (18F-FDG) is currently considered standard of practice for

Introduction

the management of lymphoma.1 The diagnostic sensitivity and

specificity of PET/CT in the initial staging of intermediate or

high grade non-Hodgkin lymphoma has been found to approach

100%.2 It provides metabolic information by way of a semi-

quantitative index, the standardized uptake value (SUV) which

has been shown to be useful for determining disease prognosis 3,4 and treatment response.3,4

However, PET/CT is expensive, time-consuming, re-

quires exposure to ionizing radiation and is not widely available

as it involves the use of a cyclotron. In addition, FDG is not

entirely cancer-specific; brown fat, muscle tissue and other fac-

tors such as infection, inflammation and granulomatous disease

can also demonstrate increased FDG uptake. On the other hand,

magnetic resonance imaging (MRI) although expensive, does

not involve exposure to ionizing radiation, is more widely avail-

able and provides excellent soft tissue contrast. In addition, with

rapidly progressive MRI techniques such as echo planar imaging

and parallel imaging techniques, whole body MRI examinations

can be performed within an acceptable time frame.

The evaluation of nodal involvement by CT and con-

ventional MRI are dependent on morphology as determined by

the response evaluation criteria in solid tumors (RECIST) and

the World Health Organization (WHO). However, large nodes

may be reactive and small nodes can still harbor foci of disease.

Diffusion weighted imaging (DWI) is a non-invasive

technique used for imaging molecular movement or diffusion

that is responsive to changes in microstructure of biological

tissues. Apparent diffusion coefficient (ADC) is a quantita-

tive index of DWI which can be measured by fitting the MRI

signal intensity attained from images with different diffusion-

weighting to a monoexponential decay model. It is a relatively

simple method and can be attained with as few as two sets of

DWI data. DWI with ADC can provide useful physiological

and functional information with regards to the characterization 8,9 of lymph nodes.8,9 Due to high cellularity and high nuclear-to-

cytoplasmic ratio, lymphoma results in reduced extra-and intra-

cellular dimensions which leads to high signal intensity on DWI

and reduced ADC.

Post-treatment, organizing granulation tissue and fi-

brotic changes are paucicellular. As a result, DWI should be an

effective imaging modality to discriminate between viable lym-

phoma and treated disease. Several studies in varying cancers

have suggested that DWI may potentially be able to discrimi-

nate between viable residual tumor and non-neoplastic treatment 10-14 changes post-therapy.

PET/CT will be used as a reference standard in the

evaluation of the value of whole body DWI (WB-DWI) in

the initial staging and treatment response in patients with

lymphoma.

Methods

Patients

From January 2012 to January 2015, nine patients (6 men and 3

women; mean age, 53 years) with newly diagnosed lymphoma

and a pre-treatment PET/CT were prospectively recruited in this

single centre study.

The study was approved by the local institutional re- 5 view board and written informed consent was obtained from all

study participants. The study was performed in accordance with

the ethical standards laid down in the 1964, declaration of Hel-

sinki and all subsequent revisions. Inclusion criteria were as fol-

lows: Age between 21 to 80 years, histological diagnosis of lym-

phoma, scheduled for first line chemotherapy and nodal or extra

nodal disease measuring at least two centimeters in size. Exclu-

sion criteria were 1) General contraindications to MRI (such

as ferromagnetic implants, pacemakers and claustrophobia), 2)

Pregnant or lactating patients, 3) Non-FDG avid or structurally

non-measurable lesions in the pre-treatment PET/CT study.

A detailed medical history and physical examination

was obtained for all patients along with standard laboratory tests.

6,7 Symptoms such as unexplained weight loss, fever and night

sweats, co-morbidities, and ECOG (Eastern Cooperative Oncol-

ogy Group) score were recorded and patients were examined for

palpable nodes and presence of hepatosplenomegaly. Seven of

the nine patients were diagnosed with diffuse large B-cell lym-

phoma (DLBCL) and the remaining two had peripheral T-cell

lymphoma (PTCL). Ann Arbor staging at time of diagnosis was

stage IE in one, II in four and one each in IIE, III, IIIE and IV.

All pre-treatment whole body MRI studies were per-

formed from one to 34 days post PET/CT. All patients received

standard first-line chemotherapy after the baseline MRI studies.

Five patients received R-CHOP [Rituximab, Cyclophosphamide,

Hydroxydaunorucibin (Doxorubicin), Oncovin (Vincristine) and

Prednisolone], two received MR-CHOP (Methotrexate, CHOP)

and remaining two received CHOPE (CHOP, Etoposide).

Imaging Time-points and Techniques

All patients were followed clinically throughout the study and

evaluated with both MRI and PET/CT before treatment initiation

and at four weeks after completion of chemotherapy.

MRI was performed using a 1.5-T MR system (Sie-

mens, Aera). Patients were scanned from vertex to mid-thigh

using a 20-channel head and neck coil, 32-channel spine coil

and two 18-channel body coils. The MRI protocol included

axial HASTE TIRM, axial FL2D in and out phase, axial DWI

b=50, 800, coronal T1 and coronal TIRM. All MR images were

reviewed on a picture archiving and communication system

(PACS) workstation.

For PET/CT, patients were scanned from vertex to mid-

thigh with an integrated PET/CT that was acquired approximate-

ly 60 mins after intravenous injection of a weight-related dose

of 18F-FDG tracer under fasting conditions (6 hours). All PET/

CT data was evaluated on a computer display in three orthogonal

planes (axial, coronal and sagittal).

Image Interpretation

The presence or absence of nodal involvement in each of twenty

regions (Table 1) was independently reviewed by two radiolo-

gists blinded to the PET/CT results. Any initial disagreements

between the two observers about the imaging findings were re-

solved in consensus. The PET/CT images were reviewed by a

single nuclear medicine physician. The presence or absence of

extra nodal involvement was also made in the following sites:

Lung, liver, spleen, bone marrow, stomach/other gastrointestinal

sites, kidneys and others. A total of 27 regions were assessed for

each patient with each imaging modality.

All DWI images were qualitatively interpreted in as-

sociation with ADC maps; hyperintensity on DWI with a cor-

responding ADC signal which was hypointense to muscle in-

dicated restricted diffusion. For PET/CT, nodal and extra nodal

involvement was diagnosed when any area of abnormal focal

increase in tracer uptake was visually evident. For quantitative

Table 1. Twenty Regions of Nodal Involvement that were Independently Assessed by Two Radiologists on WB-DWI and a Single Nuclear Medicine Physician on PET/CT.

No. Nodal region

evaluation of WB-DWI, the mean ADC value of the largest in-

volved node in a region was measured directly on ADC maps;

the region of interest (ROI) was manually drawn avoiding any

areas of necrosis. The SUV of the largest involved node in a

region was recorded for PET/CT.

During assessment of both imaging modalities post-

completion of chemotherapy, an evaluation of response to treat-

ment was made and categorized into progressive disease, stable

disease, partial response and complete response in comparison

to the pre-treatment study. New and/or larger foci of disease in-

volvement was interpreted as progressive disease, no significant

change in size and distribution of disease was regarded as stable

disease, decrease in size and/or number of lesions was interpret-

ed as partial response and no abnormal lesions in the follow-up

study was deemed complete response.

Statistical Analysis

Sensitivity, specificity and accuracy of PET/CT and WB-DWI

were compared to evaluate the difference between modalities

both in the pre-treatment studies and post-completion of chemo-

therapy. A correlation was also made between SUV and ADC

values to determine a possible relationship between the values

obtained. This could only be applied to lesions that were found

to be positive on both PET/CT and WB-DWI.

1 Waldeyer’s ring and retropharyngeal

2 Right cervical/supraclavicular/occipital/pre-auricular

3 Left cervical/supraclavicular/occipital/pre-auricular

4 Right axillary/Pectoral

5 Left axillary/Pectoral

6 Right internal mammary/diaphragmatic

7 Left internal mammary/diaphragmatic

8 Anterior mediastinal

9 Right paratracheal

10 Left paratracheal

11 Subcarinal/posterior Mediastinal

12 Right hilar

13 Left hilar

14 Retroperitoneal (paraaortic/paracaval/inter-aorta-caval/peripancreatic)

Abdominal (Periportal/Perisplenic/Periceliac/Perisuperior mesenteric artery/ Periinferior mesenteric artery)

16 Mesenteric

17 Right Iliac

18 Left Iliac

19 Right Inguinal/femoral

20 Left Inguinal/femoral

Results

Baseline Staging

In the nine patients, PET/CT defined a total of 72 out of 243

(29.6%) regions as positive for disease involvement with 171

out of 243 (70.4%) as being negative.

Compared to PET/CT, the sensitivity and specificity of

WB-DWI was 60.3% (38/63) and 100% (116/116) respectively,

for nodal disease and 75.0% (6/8) and 92.7% (51/55) respec-

tively for extra-nodal disease. Overall sensitivity, specificity and

accuracy of WB-DWI compared to PET/CT was 62.0% (44/71),

97.7% (167/171) and 86.8% (211/243).

In a third (3 out of 9) of the patients, PET/CT was

more sensitive in detecting disease in Waldeyer’s ring (Figure

1). In two patients, PET/CT was considerably more sensitive

with WB-DWI missing 50% (10/20) and 35% (7/20) of nodal

regions. This was primarily a result of small nodes which dem-

Figure 1. In 3 out of 9 Patients, PET/CT Dem- Figure 2: 57-Year-Old Male with Right-Sided Cervical Nodal Figure 3: A 57-Year-Old Male with DLBCL. onstrated an Asymmetrical Increased Uptake Involvement was Detected on both Modalities (thin arrow). A Small Right Axillary Node with Increased (a,d,g) in Waldeyer’s Ring which was Interpret- However, Only Left Cervical Adenopathy was Identified on Uptake was detected on PET/CT (a, thin ed as Lymphomatous Involvement. However, PET/CT (a, Thick Arrow) with No Evidence of Restricted Diffu- arrow). However, it was not seen on either Corresponding DWI (b,e,h) and ADC (c,f,i) sion on WB-DWI (b,c). Failed to Show Restricted Diffusion or Asym-

metry which may have Led the Readers to Suspect Lymphomatous Involvement.

onstrated uptake on PET/CT but were not identified or did not

show restricted diffusion on WB-DWI (Figures 2-5).

One of the patient also exhibited florid pulmonary le-

sions that were easily seen on PET/CT but did not demonstrate

significant signal change on DWI and were misinterpreted as

arte fact on ADC (Figure 5). In addition, two extra-nodal re-

gions in the same patient were found to be false positive on

WB-DWI, this was due to: 1). Misinterpretation of the spleen

as involved as it was hypointense relative to the liver on ADC,

PET/CT however, did not reveal increased uptake (Figure 6), 2).

Misinterpretation of the stomach as being involved (Figure 7),

this was primarily the result of superior spatial resolution of CT

compared to MRI as adjacent nodal involvement was misread as

gastric involvement on MRI.

WB-DWI was generally effective in the determination

of bone marrow infiltration where it was positive on PET/CT

(Figure 5). However, there was a false positive result wherein a

focus of restricted diffusion was noted in the left posterior ilium

DWI or ADC images. Note increased uptake on PET/CT in the left upper rib with corresponding restricted diffusion on WB-DWI (b,c, thick arrow)

lary Node (Thick Arrows) were Positive on both Modalities (a-c).

Dashed Arrow). Small Hilar Nodes (a, Thin Arrow) were not seen on WB- DWI. Note Increased FDG Uptake in the Vertebra, Sternum and Ribs with Corresponding Restricted Diffusion.

that was found to be negative on PET/CT (Figure 8).

Treatment Response

One patient withdrew from the study after the baseline studies.

As a result, treatment response could only be assessed for eight

patients. All except one patient were assessed as having com-

plete response on PET/CT with the remaining patient deemed as

having a partial response with a single extra-nodal region in the

caecum demonstrating persistent increased uptake. All except

one patient were also assessed as having complete response on

WB-DWI with the remaining patient deemed as having a partial

response with two false positive nodal regions.

As there was near complete response, true positive

findings were not found on WB-DWI compared to PET/CT.

Therefore, sensitivity could not be assessed. Compared to PET/

CT, the specificity of WB-DWI was 98.8% (158/160) for nodal

disease and 100% (55/55) for extra-nodal disease. Overall speci-

ficity and accuracy of WB-DWI when compared to PET/CT was

99.1% (213/215) and 98.6% (213/216).

The false negative finding on WB-DWI involved a cae-

cal lesion; it was picked up on pre-treatment WB-DWI as it was

distinctively hyperintense whilst the remaining bowel was hy-

pointense. However, on post-treatment images, segments with

scattered hyperintensity were also seen in the remaining bowel

which made the caecal lesion less conspicuous resulting in it

being missed. In contrast, the caecal lesion remained clearly and

visually perceptible on PET/CT in both the pre- and post-treat-

ment studies (Figure 9).

Correlation between SUV and ADC Values

Involved nodes showed increased uptake on PET/CT, high sig-

nal intensity on DWI and low signal intensity on ADC maps

(Figure 10). The SUV of the largest node in an involved region

was compared to the mean ADC value of the largest node in

an involved region. There was a total of 43 lesions that were

found to be positive both on PET/CT and WB-DWI. One would

expect an inverse correlation between the ADC value and the

SUV. However, no significant inverse correlation was seen in

our study (r=-0.024, p=0.88) (Figure 11).

Discussion

DWI was initially applied in the brain and found to be exception-

Figure 9. A 65-Year-Old Female Patient with DLBCL, in the Pre-Treatment DWI (a), the Caecal Lesion was Distinctively Hyperintense (Thin Arrow) in Comparison to the Remaining Hypointense Bowel. However, on Post-treat- ment Studies DWI (d), this was Less Apparent as Other Bowel Loops also Showed Hyperintensity, such as in the Descending Colon (Thick Arrow). ADC Maps (b,e) were not Particularly Useful. In Contrast, the Caecal Le-

sion was Distinctive in both Pre- and Post-treatment PET/CT Studies (c,f).

ally useful for evaluation of restricted diffusion in the diagnosis

of acute infarction. However, in recent years, there has been pro-

gressively increased use of this technique in the rest of the body.

Lymphomatous tissue, due to increased cellularity and

reduced extracellular space results in restricted diffusion (hy-

perintensity on DWI and hypointensity on ADC). Whole body

imaging is desirable in the assessment of hematological ma-

lignancies such as lymphoma. Hence, WB-DWI is gaining in-

creased attention as an alternative to PET/CT in the staging and

treatment of lymphoma as it can assess the entire body, is radia-

tion-free, more accessible and does not require use of a contrast

agent. There are however deficiencies with the use of WB-DWI

relative to PET/CT, some of which were illustrated in this study

and will be discussed further below.

Figure 11. Plot of ADC against SUV of all Nodal and Extra-Nodal Regions that were found to be Positive on Both PET/CT and WB-DWI. Although an Inverse Correlation was Expected, it was not shown in this Study.

Waldeyer’s ring may exhibit normal high signal on

DWI due to relatively low diffusivity and long T2 value.15

Hence, detection of abnormality in this area on WB-DWI can

be difficult as was seen in a third of patients in this study. The

asymmetrical increased uptake on PET/CT was not depicted on

WB-DWI which may otherwise have led the readers to suspect

lymphomatous involvement; this was likely secondary to the

high baseline signal on DWI which obscured overlying patho-

logical involvement.

The use of DWI in the chest cavity is limited second-

ary to artefacts caused by respiratory or cardiac motion. This is

likely the cause of the false negative WB-DWI pulmonary find-

ings in one patient where florid lung lesions were depicted on

PET/CT. Use of cardiac or respiratory triggering WB-DWI may

help to overcome this.16

Liver or splenic involvement may be misinterpreted on

WB-DWI with the latter occurring in one patient. This may be

due to iron content which has been shown to affect DWI vis-

ibility and ADC quantification in normal hepatic parenchyma,

normal DWI liver visibility is also gender-and age-dependent

being superior in women before the age of fifty.17

Several artefacts are encountered while assessing

the bowel in DWI. Depending on luminal contents, T2-shine

through effect will result in hyperintense bowel loops. The true

presence of restricted diffusion can then be determined by evalu-

ation of corresponding ADC maps.18 However, due to inherent

heterogeneity of bowel contents, it is frequently challenging to

differentiate true restricted diffusion among T2-shine through

effect. In addition, bowel peristalsis resulting in motion artefact

and inferior spatial resolution of MRI contribute to the challeng-

es in diagnosis of bowel lesions in WB-DWI.

Majority of false negative nodes on WB-MRI were

small nodes that were either not even depicted on WB-DWI

or did not demonstrate convincing restricted diffusion. This is

likely a combination of inherent increased sensitivity of PET

imaging which is in the picomolar range19 and relative increased

susceptibility to motion artefact on MRI.20

A further shortcoming of WB-DWI is in the assessment

of bone marrow. This is particularly important during skeletal

maturation. During maturation, hematopoietic marrow is gradu-

ally converted to fatty marrow. On DWI, fatty marrow is hy-

pointense secondary to fat suppression whereas red marrow is

hyperintense due to relatively higher cellularity. Hence, residual

or reactivated islands of red marrow, may conceivably be misin-

terpreted as lymphomatous involvement in WB-DWI.15 In con-

trast, Albano et al21 conducted a study comparing whole-body

MRI, FDG-PET/CT and bone marrow biopsy and found that

both MRI and PET/CT were valuable tools for the assessment of

bone marrow involvement.

Our results for baseline staging demonstrate that the

nodal sensitivity and specificity of WB-DWI compared to PET/

CT was 60% and 100% respectively and extra-nodal sensitivity

and specificity was 75% and 93% respectively. Overall, WB-

DWI showed 62% sensitivity and 98% specificity as compared

to PET/CT. Results for treatment response were superior with

99-100% specificity and accuracy for nodal and extra-nodal dis-

ease. Compared to PET/CT, the reported sensitivity and speci-

ficity for assessment of lymphoma with WB-DWI is 89-100% 20,22-24 and 97-100% respectively. Our results for specificity of

WB-DWI are comparable to that of PET/CT (93-100%) and are

in line with previous observations. In contrast, our results for

sensitivity were inferior to that seen in previous studies; this may

be secondary to our small sample size. However, the reduced

sensitivity of WB-DWI compared to PET/CT is likely due to

inherent increased sensitivity of PET over MRI with many of

our false negative results due to small nodes. They demonstrated

uptake on PET/CT but were either not seen on or did not show

restricted diffusion on WB-DWI.

Our finding of inferiority of WB-MRI in comparison

to PET/CT in staging assessment contrasts with several stud- 16,24-27 ies that support DWI as an alternative imaging modality

for the initial staging of lymphoma. Although our sample size

is small, important differences have been illustrated between

the imaging modalities that demonstrate the strength of PET/

CT over WB-DWI which account for superiority of PET/CT

in baseline staging of lymphoma. This is supported in part by

a study conducted by Mayerhoefer et al20 that found that DWI

was slightly inferior to PET/CT with regards to pre-therapeutic

regional assessment and staging in patients with FDG-avid lym-

phoma. However, they found that this was not the case in pa-

tients with lymphoma subtypes that showed variable FDG avid-

ity. Another study22 found that in a minority of their patients with

newly diagnosed lymphoma, whole-body DWI led to clinically

important over-staging relative to the results of PET/CT thereby

concluding that PET/CT remain the reference standard for lym-

phoma staging lending support to our conclusion.

There were several limitations to this study, the first is

having a small number of patients. Despite this drawback, im-

portant false positive and false negative findings with respect to

WB-DWI were illustrated. We did not perform cardiac or respi-

ratory triggering for WB-DWI resulting in motion artefact limit-

ing evaluation of the mediastinum, lung and left hepatic lobe.28

The mean ADC value and SUV may have been derived from dif-

ferent nodes within an involved nodal region on WB-DWI and

PET/CT respectively; this might have contributed to the poor

inverse correlation seen in this study. Lastly, although PET/CT

is currently considered the standard of practice in management

of lymphoma, using it as a reference standard obscures possible

inherent limitations of this modality.

Conclusion

In conclusion, WB-DWI may be a viable alternative to PET/

CT in the treatment response of lymphoma, this is of particular

importance in younger patients to lower radiation burden and

future risk of radiation-induced malignancies. In terms of stag-

ing however, PET/CT is probably still the superior modality, but

if MRI is used instead, care should be taken to understand the

limitations of this modality such that has been illustrated above.

Funding

This study was funded by Cancer Research Grant from Singa-

pore Cancer Society.

Acknowledgement

Research administration support from Ms. Lim Tze Wei.

Conflicts Of Interest

The authors declare that they have no conflicts of interest.

References

1. ChesonBDFisherRIBarringtonSF. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: The Lugano classification. J Clin Oncol. 2014; 32(27): 3059-3068. doi: 10.1200/ jco.2013.54.8800 la Fougere C, Hundt W, Brockel N, et al. Value of PET/CT versus PET and CT performed as separate investigations in patients with Hodgkin’s disease and non-Hodgkin’s lymphoma. Eur J Nucl Med Mol Imaging. 2006; 33(12): 1417-1425. doi: 10.1007/s00259-006-0171-x10.1007/s00259-006-0171-x https://doi.org/10.1007/s00259-006-0171-x
2. LinCIttiEHaiounC. Early 18F-FDG PET for prediction of prognosis in patients with diffuse large B-cell lymphoma: SUV-based assessment versus visual analysis. J Nucl Med. 2007; 48(10): 1626-1632. Web site. http://jnm.snmjournals.org/ content/48/10/1626.long. Accessed February 18, 2017
3. HutchingsMLoftAHansenM. FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood. 2006; 107(1): 52-59. doi: 10.1182/blood-2005-06-225210.1182/blood-2005-06-2252 https://doi.org/10.1182/blood-2005-06-2252
4. WuXKellokumpu-LehtinenPLPertovaaraH. 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. NMR Biomed. 2011; 24(10): 1181-1190. doi: 10.1002/nbm.168910.1002/nbm.1689 https://doi.org/10.1002/nbm.1689
5. TherassePArbuckSGEisenhauerEA. New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, national cancer institute of the united states, national cancer institute of canada. J Natl Cancer Inst. 2000; 92(3): 205-216. doi: 10.1093/ jnci/92.3.205
6. MillerABHoogstratenBStaquetMWinklerA. Reporting results of cancer treatment. Cancer. 1981; 47(1): 207- 214. doi: 10.1002/1097-0142(19810101)47:1<207::AID-CNCR2820470134>3.0.CO;2-610.1002/1097-0142(19810101)47:1 https://doi.org/10.1002/1097-0142(19810101)47:1
7. SumiMIchikawaYNakamuraT. Diagnostic ability of apparent diffusion coefficients for lymphomas and carcinomas in the pharynx. Eur Radiol. 2007; 17(10): 2631-2637. doi: 10.1007/ s00330-007-0588-z
8. PerroneAGuerrisiPIzzoL. Diffusion-weighted MRI in cervical lymph nodes: Differentiation between benign and malignant lesions. Eur J Radiol. 2011; 77(2): 281-286. doi: 10.1016/j.ejrad.2009.07.03910.1016/j.ejrad.2009.07.039 https://doi.org/10.1016/j.ejrad.2009.07.039
9. WieduwiltMJVallesFIssaS. Immunochemotherapy with intensive consolidation for primary CNS lymphoma: A pilot study and prognostic assessment by diffusion-weighted MRI. Clin Cancer Res. 2012; 18(4): 1146-1155. doi: 10.1158/1078- 0432.CCR-11-062510.1158/1078-0432.ccr-11-0625 https://doi.org/10.1158/1078-0432.ccr-11-0625
10. WangHJPuiMHGuoYYangDPanBTZhouXH. Diffusion-weighted MRI in bladder carcinoma: The differentiation between tumor recurrence and benign changes after resection. Abdom Imaging. 2014; 39(1): 135-141. doi: 10.1007/s00261- 013-0038-010.1007/s00261-013-0038-0 https://doi.org/10.1007/s00261-013-0038-0
11. NuralMSDanaciMSoyucokAOkumusNO. Efficiency of apparent diffusion coefficients in differentiation of colorectal tumor recurrences and post-therapeutical soft-tissue changes. Eur J Radiol. 2013; 82(10): 1702-1709. doi: 10.1016/j. ejrad.2013.05.02510.1016/j.ejrad.2013.05.025 https://doi.org/10.1016/j.ejrad.2013.05.025
12. KimSLoevnerLQuonH. Diffusion-weighted magnetic resonance imaging for predicting and detecting early response to chemoradiation therapy of squamous cell carcinomas of the head and neck. Clin Cancer Res. 2009; 15(3): 986-994. doi: 10.1158/1078-0432.CCR-08-128710.1158/1078-0432.ccr-08-1287 https://doi.org/10.1158/1078-0432.ccr-08-1287
13. FujimotoHKazamaTNagashimaT. Diffusionweighted imaging reflects pathological therapeutic response and relapse in breast cancer. Breast Cancer. 2014; 21(6): 724-731. doi: 10.1007/s12282-013-0449-310.1007/s12282-013-0449-3 https://doi.org/10.1007/s12282-013-0449-3
14. KweeTCTakaharaTVermoolenMABieringsMBMaliWPNievelsteinRA. Whole-body diffusion-weighted imaging for staging malignant lymphoma in children. Pediatr Radiol. 2010; 40(10): 1592-602. doi: 10.1007/s00247-010-1775-710.1007/s00247-010-1775-7 https://doi.org/10.1007/s00247-010-1775-7
15. FischerMANanzDHanyT. Diagnostic accuracy of whole-body MRI/DWI image fusion for detection of malignant tumours: A comparison with PET/CT. Eur Radiol. 2011; 21: 246-255. doi: 10.1007/s00330-010-1929-x10.1007/s00330-010-1929-x https://doi.org/10.1007/s00330-010-1929-x
16. MetensTFerraresiKFFarchioneAMorenoCBaliMAMatosC. Normal hepatic parenchyma visibility and ADC quantification on diffusion-weighted MRI at 3 T: Influence of age, gender, and iron content. Eur Radiol. 2014; 24(12): 3123-3133. doi: 10.1007/s00330-014-3353-010.1007/s00330-014-3353-0 https://doi.org/10.1007/s00330-014-3353-0
17. DohanATaylorSHoeffelC. Diffusion-weighted MRI in Crohn’s disease: Current status and recommendations. J Magn Reson Imaging. 2016; 44(6): 1381-1396. doi: 10.1002/ jmri.25325
18. Cavalcanti Filho JL, de Souza Leao Lima R, de Souza Machado Neto L, Kayat Bittencourt L, Domingues RC, da Fonseca LM. PET/CT and vascular disease: Current concepts. Eur J Radiol. 2011; 80: 60-67. doi: 10.1016/j.ejrad.2010.12.102 https://doi.org/10.1016/j.ejrad.2010.12.102
19. MayerhoeferMEKaranikasGKletterK. Evaluation of diffusion-weighted MRI for pretherapeutic assessment and staging of lymphoma: Results of a prospective study in 140 patients. Clin Cancer Res. 2014; 20(11): 2984-2993. doi: 10.1158/1078-0432.CCR-13-335510.1158/1078-0432.ccr-13-3355 https://doi.org/10.1158/1078-0432.ccr-13-3355
20. AlbanoDPattiCLagallaRMidiriMGaliaM. Wholebody MRI, FDG-PET/CT, and bone marrow biopsy, for the assessment of bone marrow involvement in patients with newly diagnosed lymphoma. J Magn Reson Imaging. 2017; 45(4): 1082-1089. doi: 10.1002/jmri.25439 van Ufford HM, Kwee TC, Beek FJ, et al. Newly diagnosed lymphoma: Initial results with whole-body T1-weighted, STIR, and diffusion-weighted MRI compared with 18F-FDG PET/ CT. AJR Am J Roentgenol. 2011; 196: 662-669. doi: 10.2214/ AJR.10.474310.1002/jmri.25439 https://doi.org/10.1002/jmri.25439
21. StephaneVSamuelBVincentD. Comparison of PET-CT and magnetic resonance diffusion weighted imaging with body suppression (DWIBS) for initial staging of malignant lymphomas. Eur J Radiol. 2013; 82(11): 2011-2017. doi: 10.1016/j. ejrad.2013.05.04210.1016/j.ejrad.2013.05.042 https://doi.org/10.1016/j.ejrad.2013.05.042
22. GuJChanTZhangJLeungAYKwongYLKhongPL. Whole-body diffusion-weighted imaging: The added value to whole-body MRI at initial diagnosis of lymphoma. AJR Am J Roentgenol. 2011; 197(3): W384-W391. doi: 10.2214/ AJR.10.5692
23. AbdulqadhrGMolinDAstromG. Whole-body diffusion-weighted imaging compared with FDG-PET/CT in staging of lymphoma patients. Acta Radiol. 2011; 52(2): 173-180. doi: 10.1258/ar.2010.10024610.1258/ar.2010.100246 https://doi.org/10.1258/ar.2010.100246
24. Balbo-MussettoACirilloSBrunaR. Whole-body MRI with diffusion-weighted imaging: A valuable alternative to contrast-enhanced CT for initial staging of aggressive lymphoma. Clin Radiol. 2016; 71(3): 271-279. doi: 10.1016/j. crad.2015.11.01810.1016/j.crad.2015.11.018 https://doi.org/10.1016/j.crad.2015.11.018
25. ChenYZhongJWuHChenN. The clinical application of whole-body diffusion-weighted imaging in the early assessment of chemotherapeutic effects in lymphoma: The initial experience. Magn Reson Imaging. 2012; 30(2): 165-170. doi: 10.1016/j.mri.2011.09.01910.1016/j.mri.2011.09.019 https://doi.org/10.1016/j.mri.2011.09.019
26. NaganawaSKawaiHFukatsuH. Diffusion-weighted imaging of the liver: Technical challenges and prospects for the future. Magn Reson Med Sci. 2005; 4(4): 175-186