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Role of StructuralImaging in Lymphoma
Thomas C. Kwee, MD, PhDa,Rutger A.J. Nievelstein, MD, PhDa,Drew A. Torigian, MD, MAb,*KEYWORDS
� Structural imaging � CT � MR imaging � Ultrasonography� Lymphoma � Hodgkin � Non-Hodgkin
STAGING AND RESPONSE ASSESSMENT INLYMPHOMA
The lymphomas, Hodgkin lymphoma (HL) andnon-Hodgkin lymphoma (NHL), comprise approxi-mately 5% to 6% of all malignancies, and are thefifth most frequently occurring type of cancer inthe United States.1 Annually, in the United States,approximately 8490 new cases of HL and 65,540new cases of NHL are diagnosed, and an esti-mated number of 1320 patients with HL and20,120 patients with NHL die because of theirdisease.1 Once a lymphoma has been diagnosedhistologically (frequently by means of excisionalbiopsy), extent of disease has to be assessed (ie,staging), because this allows appropriate treat-ment planning, aids in the determination of prog-nosis, and knowledge of all sites of involvementpermits monitoring of the effects of therapy.2,3 InHL, the extent of disease directly influences choiceof the most appropriate therapy, whereas in NHL,therapy is influenced more by the pathologicsubtype of tumor bulk of disease and symptoms.In both HL and NHL, assessment of disease bulkprovides important prognostic information, asdoes the presence of extranodal disease. In NHLin particular, staging provides a baseline assess-ment against which future imaging studies canbe compared.4 Lymphomas are staged using theAnn Arbor staging system (Table 1).2,3 However,pediatric NHLs are staged using the St Judestaging system described by Murphy, which takes
a Department of Radiology, University Medical CenterNetherlandsb Department of Radiology, Hospital of the University o19102, USA* Corresponding author.E-mail address: [email protected]
PET Clin 7 (2012) 1–19doi:10.1016/j.cpet.2011.11.0021556-8598/12/$ – see front matter � 2012 Elsevier Inc. All
into account the more frequent presence of ex-tranodal disease (with frequent involvement ofthe gastrointestinal tract, solid abdominal viscera,and sites in the head and neck) in this condition(Table 2).4–6 The revised International WorkingGroup response criteria are used to assess thera-peutic response (Table 3).7,8
GROWTH AND DISTRIBUTION PATTERNS OFHL AND NHL
Lymphomas tend to form conglomerate massesand show expansive growth, but generally respectorgan boundaries and compartments (unlike othersolid tumors and their metastases). An importantdifference between HL and NHL is that spreadof disease in HL tends to be contiguous via thelymphatics from 1 nodal group to the next,whereas spread in NHL is hematogenous and,therefore, often discontiguous.4,9
Table 4 lists the differences in distributionpatterns that may differentiate HL from NHL. Ingeneral, NHL tends to have a generalized distribu-tion, whereas HL is often localized.4,9 Primarylymphomas of the internal organs are rare, andmost are NHLs. Secondary involvement is morecommon; it is characteristic of higher diseasestages, which usually are generalized. The inci-dence of organ involvement is also increased inlymphomas associated with immunosuppressionin patients after organ transplantation.4,9
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Table 1Ann Arbor staging classification of lymphoma
Stage Involvement
I Single lymphatic region (I) or 1 extralymphatic site (IE)
II Two or more lymph node regions on same side of diaphragm (II) or 1 localizedextralymphatic site plus 1 or more lymph node regions on same side of the diaphragm (IIE)
III Lymph node regions on both sides of diaphragm (III), which may be accompanied byextralymphatic extension (IIIE), splenic involvement (IIIS), or both (IIIE,S)
IV Diffuse involvement of 1 or more extralymphatic organs or sites
Suffix Features
A No B symptoms
B Presence of at least one of the following: unexplained weight loss >10% of usual bodyweight in 6 months before diagnosis; unexplained fever >38�C; drenching night sweats
X Bulky tumor is defined as either a single mass of tumor tissue exceeding 10 cm in largestdiameter or a mediastinal mass with size greater than or equal to one-third of themaximum intrathoracic diameter measured on a standard posterior-anterior chestradiograph
Data from Armitage JO. Staging non-Hodgkin lymphoma. CA Cancer J Clin 2005;55(6):368–76; and Connors JM. State-of-the-art therapeutics: Hodgkin’s lymphoma. J Clin Oncol 2005;23(26):6400–8.
Kwee et al2
ROLE OF CROSS-SECTIONAL STRUCTURALIMAGING IN LYMPHOMA
Cross-sectional imaging plays a crucial role instaging and follow-up of lymphoma, because itprovides a noninvasive means to evaluate lympho-matous lesions throughout the body. Imagingtechnologies used to assess patients with cancer,including lymphoma, may be grossly subdividedinto structural and functional imaging categories.Structural imaging entails the assessment of mor-phologic features of normal tissues and organs ofthe body and of malignant lesions within these
Table 2St Jude staging system described by Murphy for ped
Stage Involvement
I Single tumor (extranodal) or single anatom
II Single tumor (extranodal) with regional nTwo or more nodal areas, same side of diaTwo single extranodal sites, same side of dPrimary gastrointestinal tract tumor, comp
III Two single tumors (extranodal) on opposiTwo or more nodal areas above and belowAll primary intrathoracic tumors ORAll extensive primary intra-abdominal diseAll paraspinal or epidural tumors
IV Any of the above with initial central nerv
Data from Murphy SB. Classification, staging and end resultdissimilarities from lymphomas in adults. Semin Oncol 1980;7et al. Non-Hodgkin’s lymphomas of childhood: an analysis ofcases at a single institution. J Clin Oncol 1989;7(2):186–93.
structures. Functional imaging comprises a multi-tude of quantitative imaging techniques that canbe used to study tumor physiology, to probe tumormolecular processes, and to study tumor mole-cules and metabolites in vitro and in vivo.10
Computed tomography (CT), magnetic resonance(MR) imaging, and ultrasonography (US) are theprototypical imaging technologies that are usedto perform oncological structural imaging. Thesetechnologies can be used to assess the morpho-logic features of lesions and of changes in thesefeatures over time through use of serial imaging.10
iatric NHL
ic area (nodal) outside mediastinum or abdomen
odal involvement ORphragm ORiaphragm ORletely resectable
te sides of diaphragm ORdiaphragm OR
ase, incompletely resectable OR
ous system or bone marrow involvement
s of treatment of childhood non-Hodgkin’s lymphomas:(3):332–9; and Murphy SB, Fairclough DL, Hutchison RE,the histology, staging, and response to treatment of 338
Table 3Revised International Working Group response criteria for clinical trials in lymphoma
Response Definition Nodal Masses Spleen, Liver Bone Marrow
Completeremission(CR)
Disappearanceof all evidenceof disease
a. FDG avid or PETpositive beforetherapy; mass ofany size permittedif PET negative
b. Variably FDG avidor PET negative;regression tonormal size on CT
Not palpable,nodulesdisappeared
Infiltrate cleared onrepeat biopsy; ifindeterminate bymorphology,immunohistochemistryshould be negative
Partialremission(PR)
Regression ofmeasurabledisease andno new sites
�50% decrease in sumof the product of thediameters (SPD) of upto 6 largest dominantmasses; no increase insize of other nodes
a. FDG avid or PETpositive beforetherapy; 1 ormore PET positiveat previouslyinvolved site
b. Variably FDG avidor PET negative;regression on CT
�50% decreasein SPD ofnodules (forsingle nodulein greatesttransversediameter); noincrease insize of liveror spleen
Irrelevant if positivebefore therapy;cell type shouldbe specified
Stabledisease
Failure toattain CR/PRor progressivedisease (PD)
a. FDG avid or PETpositive beforetherapy; PET positiveat prior sites ofdisease and nonew sites onCT or PET
b. Variably FDG avidor PET negative;no changein size of previouslesions on CT
– –
Relapseddiseaseor PD
Any new lesionor increase by�50% ofpreviouslyinvolvedsites fromnadir
Appearance of a newlesion(s) >1.5 cm inany axis, �50%increase in longestdiameter of apreviously identifiednode >1 cmin short axis orin SPD of more than1 node
Lesions PET positive ifFDG avid lymphomaor PET positivebefore therapy
>50% increasefrom nadir inSPD of anypreviouslesions
New or recurrentinvolvement
Data from Cheson BD, Pfistner B, Juweid ME, et al. International Harmonization Project on Lymphoma. Revised responsecriteria for malignant lymphoma. J Clin Oncol 2007;25(5):579–86; and Seam P, Juweid ME, Cheson BD. The role of FDG-PETscans in patients with lymphoma. Blood 2007;110(10):3507–16.
Role of Structural Imaging in Lymphoma 3
Table 4Differences between HL and NHL
Involvement HL (%) NHL (%)
Mediastinum 85 <50
Lung parenchyma 15 5
Para-aortic lymph nodes 25 50
Mesenteric lymph nodes 5 50
Liver 10 15
Diffuse liver involvement 1 1
Nodular liver involvement � 1
Liver involvement withhepatomegaly
<30 60
Spleen <40 >40
Gastrointestinal tract � 1
Kidney � 1
Adrenal gland � 1
Abbreviations: �, less common; 1, more common.Data from Van der Molen AJ, Schaefer-Prokop C,
Leppert A. Lymphatic system. In: Prokop M, Galanski M,editors. Spiral and multislice computed tomography ofthe body. New York: Georg Thieme Verlag; 2003. p. 755–7.
Kwee et al4
Accurate detection and delineation of disease alsoenable radiotherapy planning for localized lym-phoma. Furthermore, structural imaging may iden-tify relevant space-occupying consequences ofcancer such as spinal cord compression, bonelesions at risk of fracture, and vascular, biliary, orureteral obstruction (Fig. 1). Structural imaging iscomplementary to functional imaging. An exampleof a functional imaging method that currentlyplays a central role in the evaluation of lymphomais positron emission tomography (PET) usingthe radiotracer [18F]-2-fluoro-2-deoxy-D-glucose(FDG).7,11 Correlative structural imaging is usedto improve the anatomic localization, segmenta-tion, and quantification of areas with abnormal
Fig. 1. Axial contrast-enhanced CT image in patientwith HL shows large mediastinal mass (asterisks) com-pressing left brachiocephalic vein (arrow).
FDG uptake. The aim of this article is to reviewcross-sectional structural imaging modalities withan emphasis on CT and MR imaging, with somemention of US, because these are most oftenused in lymphoma.
CROSS-SECTIONAL STRUCTURAL IMAGINGMODALITIES IN LYMPHOMA: GENERALCONSIDERATIONSCT
Before the CT era, patients with a diagnosis of lym-phoma were subjected to a battery of radiologicstudies that included chest radiography, intrave-nous pyelography, lymphangiography, skeletalsurveys, and isotope scans. In addition, mostpatients with HD underwent staging laparotomy,with its attendant risks.12 The introduction of CTin the early 1970s was a breakthrough, and itspotential for evaluating lymphoma was soon re-cognized and investigated.13 Since then, CT hasgradually become the imaging modality of choicefor staging lymphoma. CT technology has contin-uously been developed and refined; major mile-stones include the introduction of spiral CT in theearly 1990s, the advent of multidetector row CTin 1998, and the more recent development ofdual-source and dual-energy CT systems. Usingstate-of-the-art CT technology (ie, �16-detectorrow CT), a volumetric whole-body CT scan canbe obtained within a few seconds, allowing forthe detection of lymph nodes of 5 mm or lessthroughout the body. In combination with poweredinjectors for rapid bolus administration of intrave-nous contrast medium, focal extranodal lesionson the order of a few millimeters can be identi-fied.4,14 CT is currently the mainstay for the struc-tural imaging evaluation of lymphoma, particularlyin combination with FDG-PET using integratedPET/CT systems. An important disadvantage ofCT is the use of ionizing radiation, which may beassociated with induction of second cancers inlater life.15 This health risk caused by ionizingradiation is especially of concern in children,because they have a higher radiosensitivity thanadults and have more years ahead in whichcancerous changes might occur.15 Another disad-vantage of CT is the administration of iodinatedcontrast agents, which may cause adverse reac-tions, including contrast-induced nephrotoxicityand rarely occurring but life-threatening anaphy-lactic shock.16
HL and NHL have identical CT morphologies.Lymph node enlargement is the most commonmanifestation of lymphoma at CT. Any lymphnode station in the body may be affected.4,9
Regardless of location, affected lymph nodes
Role of Structural Imaging in Lymphoma 5
have approximately the same CT attenuation asmuscle tissue (Fig. 2).4,9 Most lymphomas havea homogeneous appearance, but necrotic areasare occasionally seen, especially in large nodalmasses (particularly in the anterior mediastinum).However, the presence of necrosis does nothave any prognostic significance,4,9,17 nor does itindicate a certain pathologic subtype. Necrosismay also occur after radiation therapy or chemo-therapy. Calcification, although rare before ther-apy, can occur in large nodal masses. Althoughseen in the more aggressive subtypes, it toodoes not have any prognostic impact.4,9,18 It hasbeen suggested that in NHL, high-grade tumorstend to be more heterogeneous on precontrastand postcontrast scans than low-grade tumorsof comparable size,4,9,19 but the clinical impli-cations of this are uncertain. Most lymph nodesaffected by lymphomatous infiltration displayonly a slight degree of contrast enhancement.More intensely enhancing lymph nodes are occa-sionally found in certain types of NHL.4,9
One of the major limitations of CT scanning inlymphoma is that recognition of nodal involvementdepends almost entirely on size criteria. Theshort-axis diameter is accepted as being themost helpful measurement because it is the mostreproducible.4,9 Lymph nodes with a short-axisdiameter greater than or equal to 10 mm are gen-erally considered as positive. Detection of diseasein normal-sized nodes remains difficult, whereclustering of multiple normal-sized but prominentlymph nodes in areas such as the anterior medias-tinum (see Fig. 2) and the mesentery is suggestiveof disease, particularly when they are roundedin shape. Conversely, CT cannot distinguishbetween enlargement caused by reactive hyper-plasia and involvement with lymphoma. The useof intravenous contrast medium is not helpful,because moderate enhancement is typically
Fig. 2. B-mode US image of left axilla (A) in 48-year-old mhypoechoic enlarged lymphomatous lymph nodes. Color(arrowhead) in one of these lymphomatous lymph nodesame patient shows left cervical/supraclavicular, mediastintous lymph nodes with homogeneous attenuation (arroT2-weighted STIR MR images (E) and grayscale inverted DWwhich appear homogeneously slightly hyperintense to mumuscle on T2-weighted STIR MR imaging (E), and hyperintfat on DWI (F, arrowheads).
seen.4,9,20 Nevertheless, intravenous contrastfacilitates nodal recognition in the neck and retro-peritoneum of patients with a paucity of adiposetissue, and helps to differentiate nodal enlarge-ment from large venous tributaries.4,9 Generalcriteria for extranodal involvement are areas ofabnormal attenuation in the spleen, bone, bonemarrow, or liver; presence of a nodule or infiltrationin the lung; and presence of a soft tissue attenua-tion mass in other extranodal sites.4,9
MR Imaging
The concept that MR imaging might become theultimate whole-body imaging tool was initiallyproposed by Damadian21 and Lauterbur22 morethan 3 decades ago. The high spatial resolutionand excellent soft tissue contrast make MRimaging an ideal tool for the detection of paren-chymal and bone marrow lesions. Furthermore,MR imaging does not use ionizing radiation (whichis particularly advantageous in children and preg-nant women), and the safety profile of MR imagingcontrast agents is favorable when compared withthat of iodinated contrast agents for CT.23
However, because of long scan times, limitedavailability, and extensive costs, MR imagingwas previously used as a tool to image only limitedanatomic areas of the body. Considerable impro-vements in MR imaging technology (including thedevelopment of high-performance magnetic fieldgradients, multichannel surface coils, parallel ac-quisition techniques, multisource radiofrequencytransmission technology, and digital broadbandtechnology) have resulted in the availability ofsufficiently fast and diagnostic sequences forwhole-body MR imaging. In addition, the avail-ability of sliding table platforms and whole-bodysurface coil designs allows for sequential (orcontinuous) movement of the patient through the
an with mantle cell lymphoma shows homogeneouslyDoppler US image (B) shows striking hilar vascularitys (arrow). Coronal contrast-enhanced CT image (C) inal, and bilateral axillary enlarged/clustered lymphoma-ws) similar to muscle. Coronal T1-weighted (D) andI (F) show same lymphomatous lymph nodes (arrows),scle on T1-weighted MR imaging (D), hyperintense toense to spinal cord on DWI (F). Note poorly suppressed
Kwee et al6
bore of the magnet without patient repositioning,which further decreases scan times. As a result,whole-body MR imaging has become a clinicallyfeasible imaging modality for staging malignan-cies, including lymphoma (Fig. 3).24–29 A state-of-the-art whole-body MR imaging examination(including T1-weighted, T2-weighted, or shortinversion time inversion recovery [STIR], anddiffusion-weighted imaging [DWI] sequences) canbe performed in approximately 30 to 60 minutes.MR imaging systems operating at 1.5 T are widelyavailable and can provide diagnostic image qualityin most body regions within reasonable scantimes. Nevertheless, because signal-to-noise ratio(SNR) increases linearly with field strength, there isinterest to perform whole-body MR imaging athigher field strength (3.0 T). On the other hand,whole-body MR imaging at high field strength ischallenging because of the higher risk of B0 andB1 inhomogeneities and susceptibility artifacts.30
Whole-body MR imaging at 3.0 T has not yetproved to be superior to whole-body MR imagingat 1.5 T.30,31 The use of a phased-array surfacecoil is preferred because it provides an increasedSNR/spatial resolution compared with an inte-grated body coil. There is no standard whole-body MR imaging protocol for the evaluation oflymphoma; data regarding preferred sequences
Fig. 3. Coronal T1-weighted (A) and T2-weighted STIR MRcervical, bilateral supraclavicular, and mediastinal lymph nCT (C) shows same lesions (arrows).
and imaging planes are lacking. Nevertheless,commonly applied sequences for whole-bodyMR imaging tumor/lymphoma staging are T1-weighted (without and with intravenous contrastmaterial), fat-suppressed T2-weighted, STIR, andDWI.24–29 Because MR imaging is a versatileimaging tool that can be used to extract anat-omic, physiologic, and molecular informationfrom tumors, its role in the management ofpatients with lymphoma is expected to increase.In general, lymphomas are relatively homoge-
neous on T1-weighted and T2-weighted images.In general, solid portions of lymphoma are isoin-tense to slightly hyperintense relative to muscleon T1-weighted images and hyperintense relativeto muscle on T2-weighted images (see Fig. 2).Low-grade, intermediate-grade, and high-gradeNHLs have identical imaging characteristics.Lymphomas enhance variably after the adminis-tration of gadolinium-based contrast agents,although a lower degree of enhancement relativeto organ enhancement is usually observed, anddelayed enhancement may also occur becauseof presence of fibrosis.32
Although MR imaging provides excellent softtissue contrast and has the potential to charac-terize lesions from signal characteristics, T1 andT2 relaxation times of benign and malignant lymph
images (B) in 24-year-old woman with HL show rightode involvement (arrows). Coronal low-dose FDG-PET/
Role of Structural Imaging in Lymphoma 7
nodes show considerable overlap,33,34 as a resultof which assessment of nodal involvement is stillbased on size criteria, by which lymph nodeswith a short-axis diameter greater than or equalto 10 mm are generally considered positive (similarto CT). General criteria for extranodal involvementare any signal abnormalities or mass lesionsinvolving soft tissues, bone marrow, parenchymalorgans, and serosal cavities.
Fig. 4. B-mode US image of right abdominal wall in38-year-old man with Burkitt lymphoma shows largerounded hypoechoic lymphomatous lesion in rightrectus abdominis muscle (continuous arrow) and2 more similar-appearing lymphomatous lesions insubcutis/anterior rectus sheath and peritoneum(dashed arrows).
US
US is a radiation-free and inexpensive imagingmodality that provides real-time high-resolutionimages, and has long been used to investigatelymphadenopathy.35 Lymphomatous nodal mas-ses are usually strikingly hypoechoic (see Fig. 2),and frequently have a septumlike hyperechoicborder. They should not be confused with cysts,the latter of which typically have posterior acousticenhancement.36 Before therapy, lymphomatouslymph nodes are rarely hyperechoic (which iseven less common than in nodal metastasesfrom other solid tumors).36 It has been reportedthat in low-grade lymphomas, the hyperechoichilum of the lymph node can often still be differen-tiated from the hypoechoic periphery. In contrast,in high-grade lymphomas, the hilum of the lymphnode can often not be recognized.36,37 ColorDoppler US can show increased hilar vascularity(see Fig. 2), although the presence of peripheralsubcapsular vessels, which is typical of metas-tasis, is rare in lymphoma (with the possibleexception in the uncommon subtypes of high-grade lymphomas).36,38 However, some investiga-tors39 suggest that lymphomatous lymph nodesmay have high perfusion both in the center andperiphery. The differentiation between lymphomaand lymphadenitis from color Doppler patterns isfrequently impossible.38
Despite the appearances of lymphoma de-scribed earlier, the short-axis diameter is still themain US criterion used to evaluate nodal diseasein staging lymphoma. As in CT, the detection oflymphomatous involvement in normal-sized lymphnodes and the discrimination between enlarge-ment caused by reactive hyperplasia and involve-ment by lymphoma is not possible based on sizecriteria alone. US may also be used to detect ex-tranodal involvement, such as in the liver, spleen,gastrointestinal tract, kidneys, and adrenal glands,which, like lymphoma elsewhere, typically appearsas 1 or more solid hypoechoic masses.
Although US is a useful method to evaluatesuperficial tissues (Fig. 4), it is less useful for theevaluation of deeper-lying tissues, and for tissueslocated behind bones or air-containing structures.
Therefore, US is of limited use in the chest, deepretroperitoneum, and in the evaluation of mostorgans in obese patients. US is also a highlyoperator-dependent imaging modality.36 As aresult, the main role of US in routine clinical prac-tice is to help ascertain the nature of palpablemasses and to guide biopsy procedures, althoughits role in staging of lymphoma is limited.4 There-fore, the following section mainly focuses on theusefulness of CT and MR imaging in severalbody regions.
USEFULNESS OF CT AND MR IMAGING(AND US) IN SEVERAL BODY REGIONSCentral and Peripheral Nervous System
Unlike primary central nervous system (CNS)lymphoma, which comprises approximately 5%of all primary brain tumors,40 secondary involve-ment of the CNS in lymphoma is uncommon.NHL occasionally involves the CNS (occurringmore often in high-grade cases, implicating apoor prognosis),41 whereas CNS involvement inHL is rare.42 Diagnosis is achieved by recognizingthe clinical manifestations, followed by neurora-diologic studies and laboratory examination ofthe cerebrospinal fluid. Nevertheless, normalstudies based on these methods do not excludesuch a diagnosis. Although MR imaging and CThave equivalent sensitivities in detecting intracere-bral lymphoma, MR imaging can showmore subtlemeningeal, subdural, and epidural disease withinthe cranium and spinal column because of itssuperior soft tissue contrast.4 Furthermore, MRimaging provides superior assessment of thespinal cord, and also allows for the evaluation ofneurolymphomatosis (ie, diffuse infiltration of
Kwee et al8
peripheral nerves including cranial nerves by lym-phoma, the least common metastatic presentationof CNS lymphoma) (Fig. 5).43 US is also a usefulmethod to evaluate (superficial) peripheral nerveinvolvement, and may be complementary to MRimaging.44
Extracranial Head and Neck
In HL, 70% to 80% of cases present as a painlessenlarging cervical mass, most frequently in thelower neck or supraclavicular region, often associ-ated with contiguous disease in the mediastinum.HL typically affects only lymph nodes, and an iso-lated extranodal or a combined nodal and extrano-dal presentation is uncommon. On the other hand,NHL accounts for 5% of head and neck cancer,and frequently presents as extranodal disease,with or without lymph node involvement. In thisrespect, the head and neck region is the secondmost common site of lymphoma after the gastroin-testinal tract. Most extranodal NHL lesions arelocated in the Waldeyer ring, whereas other areasof involvement include the paranasal sinuses,orbits, salivary glands, thyroid, larynx, and theear. Lymphoma of the paranasal sinuses, orbits,and temporal bones usually occur in an older agegroup. Fewer NHL patients have truly localizeddisease than those with HL, and 40% to 60% ofthose presenting with head and neck NHL alsohave systemic manifestations.45 US can be usedto assess for superficial cervical lymphadenop-athy, parotid and submandibular gland involve-ment, and thyroid gland involvement, but is ofless value in evaluating deeper-lying structures.MR imaging performs as well as or better thanCT in the imaging of nodal disease in the neckand supraclavicular fossa.4,46 Furthermore, MRimaging may be better than CT for the evaluationof extranodal disease in the extracranial headand neck region, and for the assessment of lym-phoma extension in the intracranial cavity,
Fig. 5. Coronal T1-weighted (A), T2-weighted STIR (B), animages (C) in 62-year-old man with HL, and motor deficitment of right-sided brachial plexus (arrows), consistent w
whereas CT is preferred for the evaluation ofcortical bone (eg, the temporal bone).46
Chest
Intrathoracic disease occurs in about 70% to 85%of patients with HL and in 25% to 50% of patientswith NHL. The frequency of intrathoracic diseasealso changes with age: children, especially thosewith HL, tend to have fewer thoracic manifesta-tions than adults. Anterior mediastinal, paratra-cheal, and tracheobronchial lymph nodes areinvolved in almost all cases of HLwith intrathoracicdisease. All mediastinal lymph nodes are seen tobe involved on imaging more frequently in patientswith HL (3–4 times more commonly than in thosewith NHLs), with the exception of the paracardiacand posterior mediastinal groups. Furthermore,anterior mediastinal lymphadenopathy is found inabout 90% of patients with HL showing intratho-racic localization of the disease. Involvement ofhilar lymph nodes is the next most common siteof disease in HL, occurring in up to 22% of patientswith intrathoracic disease, usually in associationwith mediastinal lymphadenopathy. Isolated hilarlymph node involvement is rare in HL, because ofthe characteristic contiguous pattern of spread,but can occasionally be seen. In patients withNHL, the involvement of different nodal groups ismore commonly observed, often without anteriormediastinal lymphadenopathy: enlarged subcari-nal, posterior mediastinal, and paracardiac nodescan be found in up to 13%, 10%, and 7% of cases,respectively. Enlarged posterior mediastinal andparacardiac nodes are sometimes the only sitesof intrathoracic manifestations of the disease inuntreated patients with NHL.47 Extranodal thoracicmanifestations of lymphoma include the thymus (inup to 30% of patients presenting with HL), lung (in10%–12% and 4% presenting with HL and NHL,respectively), pleura (in 26%–30% of cases atautopsy), pericardium (in 5%–8% of cases,
d fat-suppressed contrast-enhanced T1-weighted MRs of right arm show thickening and contrast enhance-ith neurolymphomatosis.
Role of Structural Imaging in Lymphoma 9
particularly in patients presenting with a largemediastinal mass), and chest wall (in 2%–5% ofcases, particularly in patients with bulky medias-tinal disease).
CT is themost frequently used structural imagingmodality for the evaluation of the chest. Its highscan speed minimizes the risk of motion artifacts,allowing for the detection of enlarged intrathoraciclymph nodes and pulmonary parenchymal involve-ment (which may appear as a mass or masslikeconsolidation, parenchymal nodules, peribronchialthickening, or alveolar and interstitial infiltrates)(Fig. 6).47 Despite its higher susceptibility tomotionartifacts and the risk of signal loss because ofmagnetic field inhomogeneities, MR imaging isalso a feasible method for the evaluation of intra-thoracic disease. MR imaging can readily detectenlarged lymph nodes in the chest (see Fig. 6),provided an appropriate respiratory motion
Fig. 6. Coronal CT image (A) in 13-year-old girl with HL sh(arrow), which shows high FDG uptake on coronal PET imMR images (D) also show same lesion (arrow), althoughartifacts.
compensation technique (ie, breath-hold orrespiratory-gated acquisition) is used. Further-more, although CT is still regarded as the methodof choice for the evaluation of the lung, it hasbeen shown that pulmonaryMR imaging is feasibleas part of a whole-body MR imaging protocol.Particularly, STIR imaging has been shown to yieldhigh accuracy (sensitivity greater than 90%)compared with chest CT for pulmonary lesions 3mmor larger in size.48 An advantage ofMR imagingis that it can readily depict pericardial, pleural, andchest wall involvement that may not be evident onCT.47,49,50 It has also been reported that MRimaging outperforms CT in detecting subpectoralor interpectoral lymphadenopathy and anteriorchest wall invasion.47,51 MR imaging also provedto be particularly beneficial in outlining diseaseextending from posterior mediastinal nodes intothe vertebral body or spinal canal.47
ows 1.3-cm lymphomatous nodule in right lower lobeage (B, arrow). T1-weighted (C) and T2-weighted STIRits visibility is poorer because of respiratory motion
Kwee et al10
Abdomen and Pelvis
Retroperitoneal nodal disease is seen at presenta-tion in up to 25% to 35% of patients with HL andup to 55% of patients with NHL. Sites commonlyinvolved by NHL include the mesentery, porta hep-atis, and splenic hilum. Furthermore, both HL andNHL can involve any nodal group in the pelvis.Involved lymph nodes in NHL tend to be markedlyenlarged, forming conglomerate masses, whereasin HL nodal enlargement may be minimal, compli-cating recognition of the affected nodes.4,52 BothCT and MR imaging are appropriate imagingmodalities to detect abdominal lymphadenopathy,whereas the use of US for this purpose is mainlylimited to the pediatric population.The abdomen is the most common location of
extranodal disease, which mostly occurs in NHL.Laparotomy data have shown that the spleenis involved in up to 30% to 40% of patientswith HL and 10% to 40% of those with NHL(Fig. 7).4,53,54 Unlike combined functional/struc-tural imaging modalities such as FDG-PET/CT,55
structural imaging alone may have difficulties indetecting splenic involvement. This situation is
Fig. 7. Coronal contrast-enhanced CT image (A),T1-weighted MR image (B), and T2-weighted STIRMR image (C) in 45-year-old man with follicular lym-phoma show hypoattenuating and hypointenselymphomatous nodules in spleen (arrows).
partly because involvement often takes the formof diffuse infiltration and nodules larger than1 cm occur in only a few cases. In addition, thesize of the spleen is not helpful because diffuseinfiltration may be present in spleens of normalsize, whereas mild to moderate reactive spleno-megaly occurs in about 30% of patients in theabsence of lymphoma deposits. On the otherhand, marked splenomegaly almost always indi-cates infiltration.4,42 Focal nodules larger than1 cm can be detected equally well by CT, MRimaging, and US. Nodules tend to be hypoattenu-ating at CT, enhance less than normal splenicparenchyma, generally have intermediate T2-weighted signal intensity relative to spleen at MRimaging, and are hypoechoic at US. Coexistentsplenic hilar lymphadenopathy detected by anyimaging modality is suggestive of presence ofsplenic lymphoma.4,42
Hepatic involvement is seenatpresentation in8%of patients with HL and 25% of those with NHL atlaparoscopy or laparotomy (Figs. 8 and 9).56,57
Hepatic involvement is usually diffuse, with discretenodular lesions seen in only 10%of cases. A combi-nation of the 2 patterns occurs in less than 3% ofpatients. Nodular liver disease has the same char-acteristics as splenic disease at CT, MR imaging,and US, whereas diffuse hepatic infiltration is moredifficult to detect with structural imaging.4,42
The gastrointestinal tract is the most commonsite of primary extranodal lymphoma, which isnearly always caused by NHL (Fig. 10).4 Thereare strict criteria for the diagnosis of primarygastrointestinal lymphoma, including the absenceof hepatosplenic involvement and nodal involve-ment confined to the drainage area of the affectedsegment of bowel. Gastric mucosa-associated
Fig. 8. B-mode US image of left hepatic lobe insagittal plane in 51-year-old, human immuno-deficiency virus-positive woman shows 2 lesions withhyperechoic centers and hypoechoic rims (arrows)(so-called target or bull’s eye lesions), which werehistologically proved to be Burkitt lymphoma.
Fig. 9. Coronal contrast-enhanced CT image (A) in47-year-old man with T-cell rich B-cell lymphomashows hypoattenuating lymphomatous lesion in righthepatic lobe (arrow). The lesion cannot be seen oncoronal T1-weighted MR image (B), but is clearlyseen on coronal T2-weighted STIR MR imaging withhyperintense signal intensity relative to liver paren-chyma and signal intensity similar to the spleen, whichis characteristic of malignancy (arrow).
Fig. 10. Axial contrast-enhanced CT image in 44-year-old woman with diffuse large B-cell lymphoma showsmoderate mural thickening of small bowel loop(continuous arrow) with surrounding infiltration ofmesenteric fat, and enlarged mesenteric lymph node(dashed arrow), which were histologically proved tobe lymphomatous.
Role of Structural Imaging in Lymphoma 11
lymphoid tissue lymphomas, especially low-gradeones, typically result in minimal gastric wall thick-ening, which may not be identified by CT or MRimaging. In this instance, endoscopic US is ofvalue. Multiorgan involvement can be seen in upto 25% of these patients and therefore extensivestaging may be necessary. In the small bowel,CT and MR imaging can show the complicationsof lymphoma, such as bowel obstruction, perfora-tion, and intussusception, in addition to muralthickening. Colonic lymphoma can cause luminal
narrowing or mural thickening, which is readilyrecognized by CT or MR imaging.4
All forms of renal lymphoma (seen in about 3%of patients undergoing abdominal staging scans)are well shown by CT, MR imaging, and US,including solitary or multiple renal masses, directinfiltration via the renal hilum, diffuse renal infiltra-tion with renal enlargement, and perirenal massessurrounding the kidney. CT, MR imaging, and UScan also document the presence and level of anyureteral obstruction.4,42
Although CT shows pelvic nodal disease andpelvic masses, MR imaging is the modality ofchoice for defining lymphoma of the pelvic viscera,whether primary or secondary.4 The use of US forthis purpose is again mainly limited to the pediatricpopulation.
In evaluation of the testis, which may beinvolved primarily or secondarily with NHL in afocal or diffuse form, sometimes bilaterally, bothMR imaging and US can be used for this purpose.4
Musculoskeletal System
Bone marrow involvement is found in 5% to 15%of patients with HL and in 20% to 40% of patientswith NHL (Fig. 11).58–61 Bone marrow biopsy(BMB) is considered as the reference standardfor diagnosing bone marrow involvement, but isinvasive and has a small but nonnegligible risk ofhemorrhagic complications.62 In addition, focalbone marrow involvement may be missed byBMB; previous studies showed that in patientswith unilaterally proven bone marrow infiltration,
Kwee et al12
contralateral BMB of the iliac crest was negative in10% to 60%.58–61 Although CT is an excellentmethod to assess cortical bone (see Fig. 11), it isnot suitable to evaluate the bone marrow, whichis the location where lymphomatous bone involve-ment first occurs (Fig. 12). However, MR imagingallows for direct visualization of the bonemarrow.63 Lymphomatous bone marrow lesionstypically have longer T1 and T2 relaxation timesthan normal yellow and red marrow (ie, low signalintensity on T1-weighted images and high signalintensity on fat-suppressed T2-weighted or STIRimages) because they contain larger amounts ofwater and lesser amounts of fat (see Fig. 12).Despite its potential, MR imaging techniques arenot sufficiently sensitive yet to (partially) replaceBMB64 (because false-negative results can occurwhere there is microscopic [<5%] infiltration4).Nevertheless, MR imaging and BMB can still beconsidered as complementary studies for im-proved bone marrow staging, especially giventhe often focal nature of bone marrow involve-ment. In addition, studies have shown that MRimaging-based assessment of the bone marrowhas prognostic implications, independent of BMB
Fig. 11. Lateral radiograph of lumbar spine (A) in 67-year-overtebral body (arrow) and destruction of its pedicles, coand axial contrast-enhanced CT images (C) show collapsed(continuous arrow). Also note prevertebral lymphomatouspine (B, dashed arrow; C, asterisk). Sagittal T1-weightedlesion, which is hypointense on T1-weighted MR imaT2-maging (continuous arrow) relative to skeletal musclelymphomatous mass can also be seen (D and E, dashed ar
results. More specifically, patients with a positiveMR imaging scan have a higher risk of relapseand a shorter survival compared with those witha negative MR imaging scan.65,66 Future technicaldevelopments are expected to further increase theclinical usefulness of MR imaging in the evaluationof the bone marrow in lymphoma.Muscles may occasionally be involved in HL and
NHL.42,67 In most HL cases, paravertebral massesare the result of invasion from retroperitoneallymph nodes.42 Intramuscular NHL mostly mani-fests as diffuse muscle enlargement.67 AlthoughCT and US may be used to evaluate the presenceand extent of lymphomatous muscle involvement,MR imaging is the imaging modality of choice forthis purpose (Fig. 13).
ADVANCED CT, MR IMAGING, AND USTECHNIQUESAdvanced CT Techniques: Dual-energy CT
CT is an important imaging modality that isroutinely used for the evaluation of patients withlymphoma. Recently introduced dual-energy CTsystems may further enhance the role of CT in
ld man with follicular lymphoma shows collapse of L2nsistent with lymphomatous involvement. Sagittal (B)L2 vertebral body with mixed lytic-sclerotic appearances mass that displaces abdominal aorta anteriorly from(D) and T2-weighted MR images (E) also show same
ging and mixed hypointense and hyperintense on, with associated central canal stenosis. Prevertebralrow).
Fig. 12. Coronal CT image (A) in 40-year-old woman with HL does not reveal osseous or bone marrow lesions.However, coronal T1-weighted (B) and T2-weighted STIR MR images (C) show diffuse signal abnormalities inpelvic and femoral bone marrow, consistent with lymphomatous involvement.
Fig. 13. Coronal T2-weighted STIR MR image in 65-year-old woman with extranodal marginal zonelymphoma shows high signal intensity of right bicepsfemoris muscle (arrow), consistent with lymphoma-tous involvement.
Role of Structural Imaging in Lymphoma 13
lymphoma. Technologic advances in dual-energyCT systems have been triggered by the introduc-tion of dual-source CT systems that were primarilydeveloped to achieve a higher temporal resolutionfor cardiac imaging. Unlike conventional CT sys-only 1 radiograph energy source and 1 radiographdetector at 1 time, dual-energy CT systems canuse 2 different radiograph energy sources (whichcan be operated at different voltage potentials)with 2 corresponding radiograph detectors at 1It is possible to simultaneously acquire 2 datasets at 2 different photon energies during a singleacquisition. By obtaining CT data at differentphoton energies and by using various dual-energy postprocessing algorithms that are basedon 3-material decomposition principles, differ-ences in material composition can be visualizedand quantified based on differences in photonabsorption. This system works especially well inmaterials with large atomic numbers such asiodine and calcium, because these materialsshow relatively large differences in photon absorp-tion at different (low and high) photon energysettings.68,69 A recent feasibility study70 has indi-cated that it may be possible to use dual-energyCT for the assessment of the bone marrow. Inthis study, Pache and colleagues70 reporteda novel dual-energy CT postprocessing algorithmbased on 3-material decomposition (bone mineral,yellow marrow, and red marrow), which wastermed virtual noncalcium. The dual-energy CTvirtual noncalcium technique subtracts calciumfrom trabecular bone, allowing for bone marrowassessment, and has shown promise for thedetection of posttraumatic bone bruises of theknee in a small series of 21 patients.70 This methodmay also allow for the detection of lymphomatousbone marrow involvement at an earlier stage thanconventional single-source CT systems. However,clinical studies on the use of dual-energy CT in theassessment of the bone marrow in patients withcancer, including lymphoma, are still lacking.
Material characterization is not the only advan-tage of dual-energy CT scanning. With every dual-energy CT scan, both low and high tube voltagedatasets can be separately evaluated. Scanningwith a low tube voltage markedly increases atten-uation of iodine (contrast enhancement) butimage noise also increases. Higher tube voltagedecreases image noise but at the expense of alower enhancement level. Moreover, the data ofa dual-energy CT scan can be mixed, generatingthe so-called weighted-average (WA) image data-set that combines the image data from the lowand high peak voltage acquisitions according tothe applied weighting factor. Any desired WA
Kwee et al14
mixture from the 2 acquisitions can be generated,which canbe used to improve lesion contrast/noiseratio compared with a standard single-source120-kVp dataset, as has been shown in pancreaticadenocarcinoma, hepatocellular carcinoma, (hy-povascular) liver metastases, and head and neckcancer.71–74 The usefulness of this approach stillhas to be investigated in lymphoma, but it can beforeseen that it may improve image quality andthe evaluation of lymphomatous lesions in differentbody regions.
Advanced MR Imaging Techniques: DWI,Dynamic Contrast-enhanced MR imaging,MR Imaging Spectroscopy, and UltrasmallSuperparamagnetic Iron Oxide-enhancedMR Imaging
The limitations of conventional (T1-weighted andT2-weighted) MR imaging are well recognizedgiven the continuing pursuit for MR imagingsequences that allow a more functional assess-ment of normal and abnormal tissues, which,in turn, may improve the characterization andfollow-up of lesions in patients with cancer or atrisk for cancer.10
DWI is one of the advanced MR imaging tech-niques that is under active investigation, especiallyfor body oncological imaging. DWI allows noninva-sive visualization and quantification of the randommicroscopic movement of water molecules (ie,Brownian motion) within biologic tissues.75 Patho-logic processes that lead to changes in the diffu-sivity of water molecules can be evaluated usingDWI. One of the main advantages of DWI overconventional MR imaging sequences is its abilityto highlight lesions (which often have a prolongedT2 relaxation time and decreased diffusivity, andtherefore high signal intensity at DWI), while sup-pressing signal from many unwanted backgroundstructures such as fat, flowing blood, cerebrospinalfluid, and gastrointestinal contents. This situation,in turn, may improve lesion detectability andstaging accuracy, and reduce image interpretationtime. Furthermore, the ability of DWI to quantifydiffusion in biologic tissue by means of diffusioncoefficient measurements may aid in the charac-terization and treatment response assessment ofcancerous lesions.75 The promising role of DWI inlymphoma is discussed in more detail by Kweeand colleagues elsewhere in this issue.Dynamic contrast-enhanced (DCE)-MR imaging
is another advanced MR imaging technique thatallows (quantitative) assessment of functionalaspects of tumor neovascularity in vivo in a nonin-vasive and repeatable way.76,77 DCE-MR imagingis performed by obtaining sequential MR images
before, during, and after the injection of a contrastagent (most often a small molecular weightgadolinium-containing compound such as gado-pentetate dimeglumine).76,77 DCE-MR imagingcan be performed using dynamic T2* methods ordynamic T1-weighted methods. Dynamic T2*methods use the fact that the first pass of acontrast agent through a tissue causes a transientsignal decrease because of local magnetic sus-ceptibility (T2*) effects. Dynamic T2* methodscan provide information about tumor perfusion,which may pathologically be related to tumorgrade and vessel density.76,77 On the other hand,dynamic T1-weighted methods use the T1 short-ening effects of the contrast agent that cause anincrease in signal intensity as it passes from theblood into the extracellular space of tissues.Dynamic T1 methods can provide informationabout blood vessel permeability, capillary surfacearea, and leakage space, which may pathologi-cally be related to tumor grade, microvesseldensity, and levels of vascular endothelial growthfactor expression.76,77 DCE-MR imaging may beused for tumor detection, characterization, grad-ing, and staging, determining prognosis, moni-toring treatment, and detecting tumor relapse, aswas shown in many types of cancer, includingthose involving the brain, breast, prostate, cervix,liver, lung, and rectum.76,77 Furthermore, DCE-MR imaging may be used to measure the effectsof antiangiogenic therapies. Research on theapplications of this advanced MR imaging tech-nique in lymphoma is still limited. Nevertheless,preliminary data have shown that DCE-MR im-aging may be used to detect, grade, and assessresponse to therapy in patients with hematologicalmalignancies (including lymphoma) as well asdiffuse bone marrow involvement.78,79
Magnetic resonance spectroscopy (MRS) is amethod that allows for separation of the MRimaging signal from a given tissue into its differentchemical components. This situation is possiblebecause the magnetic field experienced by anatomic nucleus is minutely shielded or modifiedby the fields produced by neighboring atoms onthe same molecule. This phenomenon producesa chemical shift or small variation in the nuclearresonance frequency. A display of MR imagingsignal amplitude as a function of nuclear reso-nance frequency forms a spectrum, with differentchemical environments of a particular type ofatomic nucleus within and between moleculesforming peaks at characteristic chemical shiftpositions. It is possible to quantitatively assessthe amount, type, and location of small molecularcompounds within a tissue or organ of interestat the same time conventional MR imaging is
Role of Structural Imaging in Lymphoma 15
performed.80 The data are typically displayed asa grid of spectra of chemical compound abun-dances obtained at either single or multiple loca-tions in a tissue or organ of interest. Thesespectra are collected from spinning nuclei (spins),most often 1H given the abundance of water intissue. 1H MRS enables accurate quantitativeassessment of the spatial distribution of tissuemetabolites such as creatinine, choline, aminoacids, nucleotides, lactate, and lipids.81 Phos-phorus is another element that has attracted a lotof attention for in vivo MRS, because it is funda-mental to several cellular processes, includingenergy metabolism and membrane construction.MRS of phosphorus offers insight into processessuch as cell energy metabolism, tissue oxygena-tion state, pH, and membrane turnover; further-more, the 31P MRS signal can be collected withrelative technical ease.80 Because NHL is a preva-lent form of cancer that shows approximately 50%response to therapy and often presents with largesuperficial lesions easily accessible to multinu-clear MRS measurements, it is an ideal test bedfor development of MRS methods to predict anddetect early response. A multicenter study hasalready shown that pretreatment 31P MRS mea-surement of the phosphate monoester/nucleosidetriphosphate ratio can identify about two-thirds ofthe patients who are destined not to show acomplete clinical response to a variety of thera-peutic agents.82 Because 31P MRS is limited torelatively large superficial tumors, 1H MRSmethods have also been explored for early detec-tion of therapeutic response in lymphoma. Usingxenografts of diffuse large B-cell lymphoma, ther-apeutic response could be detected within 1 cycleof therapy with CHOP (cyclophosphamide, doxo-rubicin, vincristine, prednisone), rituximab plusCHOP (RCHOP) or radiation (15 Gy) throughdetection of a decrease in lactic acid (Lac) or totalcholine (tCho).82 1H MRS has also been performedin patients with NHL in a clinical scanner. It hasbeen reported that 1 of the patients showed a70% decrease in Lac within 48 hours of treatmentwith RCHOP.82
The discrimination between normal-sizednonmalignant lymph nodes and normal-sized lym-phomatous lymph nodes is essentially impossiblewith structural imaging. Ultrasmall superparamag-netic iron oxide (USPIO)-enhanced MR imagingwas introduced in the early 1990s as a promisingimaging modality for evaluating lymph nodes,83
allowing for the identification of malignant nodalinfiltration independent of lymph node size. Intra-venously administered USPIO particles are takenup by macrophages in the reticuloendothelialsystem, predominantly within the lymph nodes
but also in the Waldeyer ring, spleen, and bonemarrow. Normal homogeneous uptake of USPIOparticles in nonmetastatic lymph nodes shortensthe T2 and T2* values, making these lymph nodeshypointense on T2-weighted and T2*-weightedimages, whereas malignant lymph nodes lack up-take and remain hyperintense.83 USPIO-enhancedMR imaging has been shown to achieve higherdiagnostic precision than conventional, unen-hanced MR imaging for the detection of lymphnode metastases of various tumors.84 However,USPIO-enhanced MR imaging indirectly revealscancer sites in lymph nodes. Therefore, the spec-ificity of this methodmay prove to be suboptimal inlymph nodes that are involved by nonneoplasticprocesses. Besides its potential usefulness forlymph node imaging, another possible advantageof USPIO-enhanced MR imaging is the suppres-sion of the normal Waldeyer ring, spleen, andnormal or hyperplastic red bone marrow, whereaslymphomatous lesions in these organs can theo-retically be highlighted.85 The value of this methodin lymphoma still has to be investigated. USPIOcontrast agents are not approved by the USFood and Drug Administration for these applica-tions in humans.
Advanced US Techniques: Compound, TissueHarmonic, and Contrast-enhanced US
Novel techniques have opened new prospects forUS. Compound US generates an image frommultiple scanning lines that strike the target fromdifferent angles, thus reducing artifacts and noise.Tissue harmonic US is based on the nonlinearinteraction of an acoustic signal as it propagatesthrough tissues, and also reduces image noiseand artifacts and improves SNR, contrast, andlateral resolution.86 Injected gas-filled microbub-bles rapidly reach the capillary bed in the paren-chymal phase and enhance the vessel texturebecause they do not leak out of the vessels. Theresults of contrast-enhanced US are higher-resolution examinations and improved detectionof malignant nodules compared with those atconventional US.87 A recent study of 100 patientswith HL has shown that harmonic compound USwith contrast enhancement for the characteriza-tion of possible nodules provides a higher sensi-tivity than does CT or FDG-PET in the detectionof splenic involvement.87 However, another studyof 250 patients with lymphoma (both HL andNHL) reported that contrast-enhanced US has noclear advantage over standard B-mode US fordiagnosis of splenic involvement.88 More studiesare required to support the use of contrast-enhanced US as an adjunct to standard staging
Kwee et al16
procedures (CT and FDG-PET/CT) for the evalua-tion of the spleen in the staging workup of patientswith lymphoma.
SUMMARY
Of all cross-sectional structural imaging modalitiesavailable, CT is the mainstay for evaluating lym-phoma, particularly because of its whole-bodyimaging capability, high spatial resolution, highscan speed, and successful hardware integrationof CT with PET. MR imaging is emerging as a radi-ation-free alternative to CT for staging and follow-up of patients with lymphoma, currently capable ofwhole-body imaging with high soft tissue contrastresolution within a clinically acceptable scan time.Because MR imaging is a versatile imaging toolthat can be used to extract both anatomic andfunctional information from tumors, its role in themanagement of patients with lymphoma is ex-pected to further increase. The role of US in theevaluation of lymphoma is still limited, mainlybecause of its inability to accurately evaluate thechest, deep retroperitoneum, and most organsin obese patients, as well as its operator-dependency, although it is cheap and easy to per-form and is useful for guidance of tissue sampling.CT, MR imaging, and US each have advantagesand disadvantages, and it is important to un-derstand these to maximize their usefulness inthe management of patients with lymphoma.Advanced CT, MR imaging, and US techniquessuch as dual-energy CT, DWI, DCE-MR imaging,MRS, USPIO-enhanced MR imaging, andcontrast-enhanced USmay improve the detection,characterization, and response assessment oflymphomatous lesions in the body.
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