G. P. Schmidt, MD
Department of Clinical Radiology, University Hospitals – Gross hadern, Ludwig Maximilian University of Munich, Marchioni nistr. 15, 81377 Munich, Germany
C O N T E N T S
41.1 Introduction 461
41.2 Initial Experience with Whole-Body MRI 461 41.3 Protocol Setup 462
41.4 Patients and Study Design 464 41.5 Results: Image Quality 466 41.6 Results: Pathologies 466
41.7 Results: Comparison to PET-CT 468 41.8 Conclusion 468
References 470
Tumor Staging 41
Gerwin P. Schmidt
41.1
Introduction
Precise tumor staging is a fundamental precondi- tion when assessing the prognosis and therapeutic options in a patient with a neoplastic disease. The TNM-staging system proposed by the American Joint Committee on Cancer (2002) has become the international standard for this purpose. This three- grade system concerns primary tumor growth (T- stage), local lymph-node invasion (N-stage) as well as distant hematogenic metastatic spread (M-stage).
Besides interventional and operative procedures (e.g.,
tumor biopsy or thoracoscopy), particularly diagnos- tic imaging procedures are necessary to get a clear picture of the total tumor burden. At present, multi- modality diagnostic approaches are still widely used in the clinical routine, which can be time consuming, costly and often strain patients. However, whole-body imaging techniques are increasingly applied to give consideration to neoplastic disease as a systemic affection. In principle, MRI with its excellent tissue contrast at a high spatial resolution, detailed mor- phological information and lack of ionizing radiation seems suitable for tumor staging. With the advent of whole-body scanners covering the patient from head to toe, MRI has become a promising candidate for comprehensive, integrated high-resolution tumor imaging.
41.2
Initial Experience with Whole-Body MRI
In the past, MRI basically has been employed for the assessment of focal pathologies in specifi c anatomi- cal regions or organ systems, and a key problem for an application in whole-body imaging has been the integration of substantially different requirements in coil setup, contrast-media application, slice position- ing and sequence design into one single comprehen- sive protocol. Various attempts in the past have been made to establish whole-body MRI concepts for tumor staging. Originally, whole-body imaging on a conven- tional scanner required at least one patient and coil repositioning process, which substantially increased examination time far beyond an hour. The introduc- tion of a rolling platform (AngioSURF/BodySURF, MR-Innovation, Essen, Germany) mounted on top of the scanner table for the fi rst time enabled overcom- ing fi eld-of-view restrictions and extending the scan on the whole body without repositioning. Here, the patient glides in between a “coil sandwich” comprised
tial resolution, especially for the detection of lung and liver pathologies, had to be taken into account.
Certainly, the application of a body surface coil in the distal extremities or cervical region represents a compromise in spatial resolution.
The introduction of whole-body scanners, using a system of multiple phased-array coils covering the whole body like a matrix, fi nally allowed whole-body imaging with the use of parallel imaging in all three spatial dimensions; cf. Chap. 13. The combination of parallel imaging with a single-positioning exami- nation has reduced room time substantially and improved spatial resolution. So far, there are only a few experiences in whole-body tumor staging on these scanners. Schlemmer et al. (2005) examined 65 patients with different neoplasms and compared the diagnostic performance with a conventional spiral-CT scanner. More metastases were detected in whole-body MRI, especially in the liver, brain, lymph nodes and musculoskeletal system. Also, fi ndings led to a therapy change in 10% of the patients.
Recently, a combination of continuously-moving- table MRI with parallel imaging has been introduced for whole-body oncological imaging. For this pur- pose, the SENSE reconstruction algorithm has been successfully applied on stationary receiver coils with arbitrary coil dimensions for continuously 3D gradi- ent-echo imaging from head to toe at an acceleration factor of R=2 without signifi cant constraints in image quality (Keupp et al. 2005).
41.3
Protocol Setup
A whole-body MRI tumor protocol has to cover the different pathways of metastatic spread and at the same time must guarantee a high diagnostic accu- racy. Therefore, it should imply state-of-the-art imaging techniques, such as T1-weighted and STIR imaging, which have proved highly effi cient for the assessment of soft-tissue and bone structures, fast high-resolution imaging of the lung (e.g., HASTE MRI, cf. Chap. 21), as well as static and dynamic
The introduction of parallel imaging techniques has shortened scan times substantially without compro- mising spatial resolution (Pruessmann et al. 1999, Sodickson et al. 1997, Griswold et al. 2002). Finally, a fl exible protocol for high-resolution whole-body MRI with examination times below 60 min seems feasible. So far, at our institution experience on more than 100 patients with whole-body imaging for sys- temic tumor staging exists. The total scan time of the protocol presented below is 55 min.
The proposed protocol is based on a 1.5-T whole- body MRI system (Magnetom Avanto, Siemens Medical Solutions, Erlangen, Germany) that allows the connection of up to 76 elements from multiple phased-array surface coils (matrix coil system) cov- ering the patient from head to toe with simultaneous signal reception from up to 32 independent receiver channels (Fig. 41.1). The coil setup consists of a head coil (12 elements), neck coil (4 elements), 2 or 3 body coils for imaging of the abdomen and pelvis (12 or 18 elements) and a peripheral-MRA coil for the lower extremities (8 elements). The spine coil consists of 24 elements and is embedded into the scanner table.
After one single positioning of the patient (supine, arms beside the body), the system allows parallel imaging in three spatial directions using automatic table motion at a total scan range of 205 cm.
The protocol (Fig. 41.2) begins with coronal STIR imaging of the complete anatomy at fi ve body levels:
head/neck, pelvis, thighs, and calves (TR/TE/TI 5,620 ms/92 ms/170 ms; slice thickness 5 mm; matrix 384×269), as well as thorax/abdomen (TR/TE/TI 3,380 ms/101 ms/150 ms) in breath-hold technique with prospective 2D navigator correction of the inspi- ration phase. A parallel-imaging acceleration factor of R=3 is normally used for coronal whole-body imaging, apart from the calves, which are scanned with an acceleration factor of R=2.
The lung is examined with fast single-shot half- Fourier turbo-spin-echo (HASTE) (TR/TE 1,100 ms/
27 ms; slice thickness 6 mm; matrix 320×156) and STIR sequences (TR/TE/TI 3,800 ms/100 ms/150 ms), followed by a navigator-triggered “free-breathing”
T2-weighted fat-saturated turbo-spin-echo (TSE) scan of the liver (TR/TE 2,010 ms/101 ms; slice thick- ness 6 mm; matrix 320×240). In this protocol, an
Fig. 41.1. a Matrix coil system for whole-body coverage from head to toe with parallel imaging in all three spatial orientations (courtesy of Siemens Medical Solutions, Erlangen, Germany). b T1-weighted whole-body MRI. c HASTE MRI of the lung. d T1-weighted MRI of the whole spine. e Contrast-enhanced T1-weighted MRI of the brain. f Fat-saturated T1-weighted gradi- ent-echo sequence of the abdomen/pelvis.
c
b f
e
d a
acceleration factor of R=2 is applied on sagittal and axial studies. Then, the fi ve body levels are examined again with T1-weighted spin-echo imaging (TR/TE 79 ms/12 ms, slice thickness 5 mm, matrix 448×385;
thorax/abdomen TR/TE 400 ms/8.2 ms), followed by sagittal T1-weighted (TR/TE 849 ms/11 ms; slice thickness 3 mm; matrix 384×384) and STIR imaging (TR/TE/TI 5,700 ms/59 ms/180 ms) of the upper and lower spine.
During contrast-material application, axial dynamic (3D VIBE; TR/TE 4.38 ms/1.61 ms; slice thickness 3 mm) liver scans and a fat-saturated T1- weighted gradient-echo sequence of the complete abdomen (TR/TE 179 ms/3.3 ms; matrix 320×193;
slice thickness 6 mm) are performed. In a last examination step, the brain is examined with axial T1-weighted (TR/TE 635 ms/17 ms; slice thickness 5 mm; matrix 320×240) and T2-weighted (TR/TE
1,420 ms/109 ms; matrix 512×250) sequences. The coronal imaging of fi ve body levels is later fused to one whole-body image, along with the studies of the spine (Fig. 41.1b-f, Fig. 41.3).
41.4
Patients and Study Design
Our experiences with patients suffering from differ- ent neoplasms are presented in the following. The aim was to compare the potential and performance of a whole-body MRI protocol using parallel imag- ing with a dual-modality PET-CT scanner (Gemini, Philips Medical systems, Cleveland, OH). For this pur- pose the examinations were analyzed by two board-
Fig. 41.2. Whole-body MRI protocol on a 32-receiver-channel system (Magnetom Avanto, Siemens Medical Solutions, Erlangen, Germany). Using parallel imaging, a total scan time of below 1 h is possible.
certifi ed radiologists (MRI) and one radiologist/one nuclear medicine physician (PET-CT). The location, size and extent of the primary or recurrent tumor, lymph nodes and distant metastases were described by both reader groups, and the TNM stage was defi ned according to the criteria of the AJCC (American Joint Committee on Cancer). For all detected lesions, avail- able clinical, histological and radiological data (CT, PET, bone scintigraphy, MRI, radiographs, and ultra- sound) were consulted within a period of 5 months as a reference method, especially to verify questionable or discrepant fi ndings. In an initial analysis, 38 indi-
viduals (mean age, 56 years; range, 21-81 years; 21 females/17 males) with different histologically proven primary tumor diagnoses were assessed (Fig. 41.4).
The patients referred for primary staging, restaging or tumor search were examined with both modalities within a short period of time. Most common pri- mary diagnoses were tumors of the gastrointestinal tract (n=14) and breast carcinoma (n=11) (Fig. 41.4).
Patients with tumors that had experienced poor FDG uptake or did not fulfi ll indications for PET exami- nation (e.g., renal cell carcinoma) were not included in the population (Reske and Kotzerke 2001). The
Fig. 41.3a–d. Healthy 40-year-old male. Fused T1-weighted- and STIR-imaging at fi ve body levels in coronal orientation a and b and of the whole spine in sagittal orientation c and d. With a parallel-imaging acceleration factor of 3, whole-body STIR imaging is possible within a total scan time of 12:28 min at an in-plane resolution of 1.8×1.3 mm². The matrix coil system guarantees optimal coil geometry for each body part.
c b
a d
mean room time for whole-body MRI was 70 min (56-76 min; scan time, 55 min) and 103 min for PET- CT (60 min patient preparation; 43 min scan time).
41.5
Results: Image Quality
The substantial reduction of individual scan times due to parallel imaging enables the incorporation of fl exible sequence protocols for MRI tumor staging, even when potentially time-consuming sequence types, like STIR imaging, are used. The combination of T1-weighted and STIR sequences guarantees a highly resolved demonstration of bone marrow and soft-tissue structures. Especially tumor-induced edema and the replacement of bone marrow by water-containing tumor cells are readily detected as hyperintense signal in STIR with an excellent con- trast to the surrounding normal tissue (Fig. 41.5).
Using an acceleration factor of R=3, whole-body STIR imaging is possible within a total scan time of 12:28 min at an in-plane resolution of 1.8×1.3 mm².
Additionally, by using the total-imaging-matrix system on our whole-body scanner, optimal coil geometry for each body part is achieved, guarantee- ing high spatial resolution with an excellent signal- to-noise ratio. Our data show that bone lesions down to a cut-off size of 2 mm are readily detected with this protocol (Fig. 41.5b and 41.5c).
For the detection of lung pathologies, single-shot half-Fourier turbo-spin-echo sequences (such as HASTE) have proved to be highly effi cient (Vogt et
Fig. 41.4 Overview on the primary tumor diagnoses of 38 pa- tients scanned with whole-body MRI and PET-CT within a time period of 2 weeks.
T2 decay, such as lung parenchyma, the loss of the signal-to-noise ratio can be reduced. With a combi- nation of axial HASTE and STIR sequences using 6- mm sections, lung nodules of 7 mm minimum size are reliably visualized, coming close to the resolution and contrast achieved with a conventional spiral-CT scanner (Fig. 41.6).
Dynamic contrast-enhanced studies today are indispensable for the diagnosis of abdominal lesions, especially of the liver, and contrast-uptake behavior gives essential information on the dignity and classifi cation of a lesion (Semelka et al. 2001).
Parallel-imaging acceleration enables the incor- poration of a dynamic 3D VIBE sequence into the protocol, acquired within 2:17 min, comprising an early arterial, venous and late-phase T1-weighted TSE sequence. An advantage of parallel-imaging acceleration here is the larger anatomical coverage in one image stack during the transit of contrast media. When free-breathing T2-weighted imaging of the liver is performed, parallel imaging reduces scan time by half, from an 8- down to 4-min acqui- sition time, with higher spatial resolution (Zech et al. 2004). With this protocol, liver pathologies at a cutoff size of 3 mm are reliably localized with a high tissue contrast, revealing lesions invisible in the diagnostic spiral CT of the PET-CT examination in some patients (cutoff size 5 mm, Fig. 41.7).
41.6
Results: Pathologies
In the examined patient population, six of the seven present tumors, of which three were primaries and four were recurrences, were reliably detected by whole-body MRI. The low presence of primary tumors is explained by the fact that many patients were referred to our department for restaging after surgical therapy. One esophageal recurrence in stage T3 was missed with MRI, which hardly showed mor- phological changes of the esophageal wall and was impossible to delineate due to overlying breathing artefacts. Of 120 lymph nodes present, 60 nodes were
c b
a d e
Fig. 41.5a–e. A 27-year-old male with non-Hodgkin’s lymphoma. a STIR whole-body imaging reveals a tumor bulk in the right clavicular groove (arrow) and extensive infi ltration of the right pelvis (arrow). b, c Magnifi cation of the distal right femoral shows a multifocal bone infi ltration down to a size of 2 mm in STIR- and T1-weighted imaging. d, e Sagittal imaging of the spine depicts extensive multifocal boney infi ltration.
Fig. 41.6a–c A 65-year old female with breast carcinoma. a Axial HASTE imaging reveals a singular lung node in the right upper lobe. b STIR imaging depicts the node with high contrast comparable to the corresponding spiral CT c The node was confi rmed as a lung metastasis. The use of parallel imaging leads to a signifi cant reduction of blurring when single shot sequences are used.
Additionally, by reducing the echo time and length of echo train, the loss of signal-to-noise ratio in lung tissue is reduced.
c c b
a
especially when nodes are located in areas impaired by artefacts, such as the hilar or retrocrural regions.
Still, compared to the published literature, diagnos- tic accuracy is signifi cantly higher for lymph node detection when parallel imaging with a combination of axial HASTE/STIR imaging is used (Antoch et al. 2004). Image analysis revealed 268 distant lesions in 29 patients, of which 191 were malignant and 77 benign, and in the lesion-by-lesion analysis, whole- body MRI reached an excellent accuracy of 92% for the detection of distant metastases.
41.7
Results: Comparison to PET-CT
The introduction of combined PET-CT scanners has made a new modality available for whole-body imag- ing. PET-CT increases diagnostic accuracy compared to PET and CT alone by providing “anato-metabolic”
information through the fusion of data given by pathologic tumor glucose-uptake in the PET exami- nation and accurate delineation of anatomical struc- tures through improved spatial resolution provided by the spiral CT scan (Beyer et al. 2000, Pelosi et al. 2004). Our observations indicate that PET-CT has advantages in the detection of lymph node metas- tases due to the facilitated localization and classifi -
whole body MRI in tumor staging. Several concepts have been developed to enhance traceability, e.g., with the use of diffusion-weighted MR imaging, a so-called “MRI PETgraphy” (Takahara et al. 2004).
The main strength of whole-body MRI certainly is refl ected by the detection of distant metastatic dis- ease: in our study MRI (n=76) detected signifi cantly more bone metastases than PET-CT (n=50), as well as liver metastases (n=71 vs. n=62) and was practically equivalent in the detection of lung pathologies (n=36 vs. n=37). Also due to the larger fi eld of view used in whole-body MRI (PET-CT usually is acquired with a neck-thorax-pelvis CT scan) additional malignant lesions were revealed in the distal femoral bones and cerebrum (Fig. 41.9). Altogether, our data showed an equal and robust performance of both modalities with an excellent overall accuracy of 96% for PET-CT and 91% for whole-body MRI for the correct assess- ment of the TNM stage.
41.8 Conclusion
With the introduction of whole-body MRI and PET- CT scanners, two modalities for systemic tumor staging and promising alternatives to the estab- lished multimodality approach have become more
Fig. 41.7a–c. A 70-year-old female with liver metastases. a Dynamic contrast-enhanced 3D VIBE imaging of the liver reveals multiple punctual lesions with an indicated ring-like enhancement (arrows). Parallel imaging allows larger anatomical cover- age in one image stack during transit of contrast media. b The lesions are clearly distinguishable in T2-weighted imaging with a hyperintense signal (arrows). With the use of parallel imaging, acquisition time is reduced by half without a loss of spatial resolution. c Contrast-enhanced spiral CT falsely shows inconspicuous liver parenchyma.
c b
a
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Fig. 41.8a,b. A 66-year-old male with pancreatic carcinoma. a Axial STIR imaging of the lung shows a hyperintense structure (8 mm) on the left hilus that is diffi cult to allocate. b Fused axial PET-CT imaging of the same area shows a small hilar lymph node with pathological FDG uptake (SUV=2.8). This lymph node was confi rmed as a metastasis.
Fig. 41.9a–e. a, b Axial T1-weighted post-contrast and T2-weighted imaging of the brain of a 60-year-old male with carcinoma of the esophagus indicates a brain metastasis in the left frontal lobe. c, d Due to the larger fi eld of view compared to PET-CT, coronal T1-weigthed- and STIR-whole-body MRI depicts multifocal metastatic disease to the distal femoral bones in a 45-year- old female with breast carcinoma. e Coronal reconstruction of a whole-body PET-CT scan. Due to the high physiological FDG uptake in the brain and the smaller fi eld of view, lesions in the brain and the distal extremities are not identifi ed.
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d e
tumors with known poor FDG-uptake, (e.g., renal- cell carcinoma) or in patients with counter-indica- tions to ionizing radiation (e.g., young patients) or to the application of iodine-based contrast agents, whole-body MRI is the method of fi rst choice (Reske and Kotzerke 2001). The use of parallel imaging in combination with multi-channel whole-body scan- ners fi nally makes a fl exible, high-resolution whole- body tumor staging protocol lasting less than an hour feasible. Still, more experiences with these new techniques are needed to assess thoroughly their full potential as a more cost effi cient and accurate tumor imaging.
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