| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Original Research |
1 Department of Radiodiagnosis, All India Institute of Medical Sciences, Ansari
Nagar AIIMS, New Delhi, India.
2 Department of Orthopaedics, All India Institute of Medical Sciences, New
Delhi, India.
3 Department of Nuclear Magnetic Resonance, All India Institute of Medical
Sciences, New Delhi, India.
Received June 30, 2007;
accepted after revision August 7, 2007.
Address correspondence to R. Sharma
(raju152{at}yahoo.com).
Abstract
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
SUBJECTS AND METHODS. MRI, dynamic contrast-enhanced MRI, and proton MR spectroscopy were performed in 33 patients with bone tumors on a 1.5-T MR scanner. Of these, 12 patients who had GCT of the bone form the subject material for this study. Dynamic contrast-enhanced MRI and single-voxel proton MR spectroscopy were performed after preliminary evaluation with radiography. Patients were divided into two groups, those with elevated choline levels and those without a choline peak on MR spectroscopy. The clinical and radiologic features, including the Campanacci stage and dynamic MRI findings, were compared in these two groups. Core biopsy was performed in all patients, and in 10 of 12 patients, histopathologic evaluation of the postoperative resected specimen was also performed.
RESULTS. Although all 12 tumors were benign on histopathology, four had elevated choline levels. Of these, three (75%) had an aggressive radiographic appearance (Campanacci stage 3). As opposed to this, only three of the eight (37.5%) tumors without a choline peak had an aggressive radiographic appearance. Except for a single case, all tumors showed early enhancement and washout of contrast material on dynamic MRI.
CONCLUSION. The results of this study indicate that GCT of bone may show raised choline levels on proton MR spectroscopy. This finding is not an indicator of malignancy in these tumors.
Keywords: bone • giant cell tumor • MR spectroscopy • musculoskeletal imaging
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Recent literature suggests encouraging results of in vivo proton MR spectroscopy in differentiating benign from malignant musculoskeletal tumors [5–7]. A diverse group of pathologic conditions, including benign and malignant bone and soft-tissue tumors and nonneoplastic lesions, were evaluated in these studies [5–7]. This precluded any specific conclusion regarding the spectroscopic finding of any particular disease entity, and the need for further studies focusing on a specific disease in a larger group of patients was recognized [6]. MR spectroscopy detection of elevated choline was reported to be 95% sensitive in differentiating benign from malignant musculoskeletal tumors [6]. However, the specificity was relatively less because few hypercellular benign tumors revealed an elevated choline peak.
A prospective study to determine the MR spectroscopy and dynamic MRI features in bone tumors is currently under progress in our institute. Considering that a prior study mentioned elevated choline level in a case of giant cell tumor (GCT) [6], we sought to study the spectroscopic findings in this benign tumor. The MRI and MR spectroscopy findings in the subset of our patients who had GCT are analyzed in this article to determine whether the presence of a choline peak is a frequent occurrence and whether MR spectroscopy features can be correlated with clinical, radiologic, and histopathologic findings.
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
MRI
MRI was performed in all patients on a 1.5-T whole-body MR scanner
(Magnetom Sonata and Avanto, Siemens Medical Solutions) using our routine
protocol for evaluating the extent of bone tumor. An appropriate surface coil
was used. A combination of transverse, sagittal, and coronal images was
obtained using a T1-weighted spin-echo sequence (TR range/TE range,
360–590/13–21; matrix size, 256 x 256; 2 signals acquired)
and a T2-weighted turbo spin-echo sequence with fat suppression
(3,000–5180/62–101; matrix size, 256 x 2 56; 2 signals
acquired). Gradient-echo images (TR/TE, 600/26; flip angle, 30°; 2 signals
acquired; matrix size, 256 x 256) in the axial plane were obtained
whenever there was a question of neurovascular bundle involvement. Field of
view, section thickness, and intersection gap varied depending on tumor
size.
Dynamic MRI
Dynamic images were obtained using a 3D T1-weighted gradient-echo sequence
(3D FLASH; 6.47/1.18; 1 signal acquired; bandwidth, 360 Hz/pixel; temporal
resolution, less than 8 seconds; total sequence time, 3 minutes; slice
thickness, field of view, section thickness, and intersection gap varied
depending on the size of the tumor) after the injection of 0.1 mmol/kg of body
weight of gadopentetate dimeglumine (Magnevist; Schering [now Bayer
HealthCare]) injected at 2 mL/s (using an MR-compatible power injector
[Spectris, Medrad]), followed by a 20-mL normal saline flush. Each dynamic
scan lasted no longer than 8 seconds, and the entire lesion was covered during
this period. Dynamic imaging was continued until 3 minutes after contrast
injection. Subsequent images were subtracted from the first unenhanced image
to show areas of early enhancement. Signal intensity was obtained by placing a
region of interest (ROI) in the early enhancing portion of the tumor and in an
adjacent artery. The size of the ROI varied according to the size of the
lesion and the area of early enhancement. The temporal progression of signal
intensity was plotted against time, and the progression of tumor enhancement
was evaluated according to the shape of the time–signal intensity curve
as described.
Type 1 curve—Maximum signal intensity was achieved rapidly after contrast agent administration, followed by a gradual decrease (washout).
Type 2 curve—Rapid initial enhancement was followed by a plateau phase or sustained late enhancement.
Type 3 curve—Gradual increase or no increase in signal intensity was seen until the end of dynamic imaging.
The onset of tumor enhancement was said to be early when it was within 8 seconds of arterial enhancement and late, when it was after 8 seconds of arterial enhancement. After the dynamic examination, T1-weighted high resolution contrast-enhanced spin-echo images with fat suppression were acquired in the transverse and sagittal or coronal planes.
MR Spectroscopy
Single-voxel spectroscopy data were acquired 10–15 minutes after
contrast administration using a point-resolved spectroscopy sequence (PRESS)
(2,000/30, 2,000/135, 2,000/270). The voxel was carefully positioned to
include the early-enhancing areas of the tumors, as shown on the subtracted
images; it ranged in size from 1 to 64 cm3. Automated optimization
of transmitter pulse power, gradient tuning, and water suppression were used.
Manual shimming was performed to obtain spectra of an acceptable line width.
Water and fat resonances were simultaneously suppressed using MEGA (Mescher
and Garwood) pulsewhenever necessary. Data were acquired at a spectral
bandwidth of 1,000 Hz and 128–256 signals were averaged. In all the
patients, at least two MR spectra were acquired at two different TEs from the
same lesion.
All MR spectra were analyzed using the commercially available software provided on Sonata and Avanto scanners. In the time domain, spectrum processing parameters were zero-filled to 2,048 data points, a 4-Hz gaussian line broadening filter was applied, and baseline and phase were corrected. Choline was said to be present in the lesion when there was a clearly identifiable peak at 3.2 ppm in at least two of the spectra acquired at different TEs. The signal-to-noise ratio (SNR) of the apparent choline peak at 3.2 ppm (defined as the ratio of amplitude of choline peak to the amplitude of baseline noise measured at a signal-free region in the spectrum) was measured whenever there was doubt as to the presence of choline. In such cases, choline was said to be present in the lesion if the SNR was greater than 2. The total examination time was approximately 50 minutes.
Core biopsy samples were obtained in all patients using a 16-gauge needle. Care was taken to obtain adequate tissue samples from different portions of the tumor to minimize sampling error. The diagnosis was further established on histopathology of the postoperative resected specimen in 10 of 12 patients. Both the radiologist and the pathologist were blinded to the MR spectroscopic measurements performed by the physicist.
Statistical Analysis
The two groups of GCT (those showing a choline peak and those not having
choline) were compared using a statistical software program (SPSS, version
10.0). The age of the patients and the size of the tumors were evaluated using
the Mann-Whitney test, whereas imaging findings such as the Campanacci stage,
onset of tumor enhancement, and the type of contrast-enhanced signal intensity
curve between the two groups were evaluated using Fisher's exact test. A
p value of less than 0.05 was considered significant.
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
In four patients, a resonance at 3.2 ppm attributed to a choline-containing compound was detected (Fig. 1F). Choline was not detected in the other eight patients (Fig. 2A, 2B, 2C). Of the four tumors showing a choline peak, three (75%) had an aggressive radiographic appearance (Campanacci stage 3). In contrast, only three of eight (37.5%) tumors without choline peak had an aggressive radiographic appearance. However, this difference between the two groups was not statistically significant. The mean age of the patients and the tumor size were not statistically different between the two groups. Almost all tumors (11 of 12) showed early enhancement and a type 1 curve (Fig. 1E). Most tumors (9/12) were of intermediate signal intensity on the T2-weighted images.
|
|
|
|
|
|
|
|
|
Table 1 summarizes the clinical, radiographic, MRI, MR spectroscopy, and histopathologic features in all patients, and Table 2 shows a comparison of findings in tumors with and those without elevated choline levels.
|
|
All tumors were benign on preoperative histology, which was further confirmed in the postoperative resected specimens in 10 patients. Of the two patients who did not undergo surgery, one was treated with radiation therapy because of the large size of the tumor and one refused surgery.
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Proton MR spectroscopy detects 1H-containing metabolites other than water, providing a unique insight into the biochemical profile of tissues in vivo. MR spectroscopy has been shown to improve diagnostic accuracy and specificity of MRI in brain tumors and breast and prostate cancers [9–11]. Common to all these tumors is an elevation of choline-containing metabolites, a finding that is a widely established characteristic of malignant cells [12]. Choline-containing metabolites (in particular phosphocholine) play an important role in cancer progression, invasion, and metastasis [13]. The degree of choline rise is related to the histologic aggressiveness of gliomas and breast and prostate cancers, with higher levels being found in higher-grade tumors [9, 12, 14]. The reappearance of choline after radiation therapy is useful in detecting tumor recurrence [15], and a reduction in the choline level is recognized as a surrogate indicator of response to chemotherapy [16]. However, raised choline on MR spectroscopy is not a tumor-specific marker and cannot be considered a sine qua non for malignancy. Uncommonly, increased choline levels can be seen in nonneoplastic lesions and benign tumors. Because there are hardly any published data on MR spectroscopy findings of benign bone tumors, we can only draw an analogy from other sites such as the breast and the brain.
A wide range of breast lesions, including fibroadenoma, fibrocystic disease, tubular adenoma, chronic inflammatory lesions with atypia, and atypical ductal hyperplasia may occasionally show a choline peak on MR spectroscopy [10, 17]. Likewise MR spectroscopy of the brain in adrenoleukodystrophy [18], posttraumatic cognitive disorders [19], liver transplant patients [20], the subacute phase of global hypoxic-ischemic injury [20], progressive multifocal leukoencephalopathy [21], demyelinating lesions [22], encephalitis [22], toxoplasmosis [23], tuberculoma [24], and fungal granuloma [24] can show a choline peak. Physiologic increase has also been described in breasts of lactating mothers [25] and in the brains of neonates [26]. Our results reaffirm this nonspecific nature of a choline signal on MR spectroscopy.
A choline peak (at 3.2 ppm) obtained by in vivo proton MR spectroscopy encompasses three metabolites: phosphocholine, glycerophosphocholine, and free choline, the chemical shifts of which cannot be resolved in vivo at 1.5 T. These metabolites are markers of cellular proliferation and membrane turnover and are not malignancy per se [27]. Elevated levels are seen in malignant lesions (which, being hypercellular, have increased membrane turnover) and occasionally also in nonmalignant lesions with increased proliferative activity [22, 24].
Dynamic contrast-enhanced MRI is a proven technique for evaluating the degree of angiogenesis, which plays a central role in the growth and spread of tumors [28]. Parameters such as shape of the signal enhancement–time curve and time to peak enhancement are used to asses the contrast dynamics in the tumor bed. Rapid wash-in and washout of contrast material (type 1 curve) are the hallmarks of malignancy in breast [29] and soft-tissue tumors [30]. Although GCT is a benign tumor, all but one case in our study showed early enhancement and a type 1 curve that can be attributed to their hypervascular nature. We used dynamic contrast-enhanced MRI primarily to select the metabolically active areas of the tumor, which were then subjected to MR spectroscopic evaluation.
The nuclei of hydrogen and 31P are the most commonly used in MR spectroscopy. Phosphorous-31 MR spectroscopy has been used to characterize the metabolic activity of bone tumors in the past [31]. However, proton MR spectroscopy is easier to perform, is more widely available, and provides a much higher SNR. A study of in vivo proton MR spectroscopy for the evaluation of musculoskeletal tumors [6] concluded that differentiation of benign from malignant musculoskeletal tumors is possible with high accuracy based on the presence or absence of choline metabolites. This study comprised a heterogeneous group of patients with soft-tissue and bone tumors. Notably, only two patients had GCT, and one of those showed a choline peak. Studies of proton MR spectroscopy focused on specific types of bone tumor are lacking. Although most malignant bone tumors have an elevated choline level [6], our results show that the converse is not true because few GCTs, which account for 20% of all benign bone tumors [32], also show this finding. To our knowledge, this fact has not been highlighted so far in the scant literature available on MR spectroscopy in bone tumors.
Likewise, although most malignant bone tumors reveal a type 1 curve, this is also seen in many benign tumors, including aneurysmal bone cyst, osteoblastoma, osteoid osteoma, eosinophilic granuloma, and, notably, in most patients with GCT [30]. This lack of specificity is so pronounced that dynamic contrast-enhanced MRI was not considered useful in differentiating benign from malignant bone tumors [30]. A recent study of breast cancer patients suggested that overall there is a correlation between choline metabolism and dynamic MRI findings because cell replication (reflected in choline levels) requires angiogenesis to support tumor growth [33]. Our results show that although most (11/12) benign GCTs have a type 1 curve, only a small proportion (4/12) show a concomitant increase in choline levels. It is reasonable to infer that raised choline concentration in a bone tumor is a relatively more specific marker of malignancy than is presence of a type 1 curve. This is also reflected in MR spectroscopy studies of breast cancer in which the presence of choline has been shown to be more specific for malignancy than dynamic contrast-enhanced MRI [34].
The findings of our study reemphasize that, despite the evolution of new techniques such as dynamic contrast-enhanced MRI and MR spectroscopy, radiography retains its central role in the differential diagnosis of bone tumors, and MRI should be used primarily to delineate the precise extent of tumor. This is contrary to the experience with soft-tissue tumors, in which dynamic contrast-enhanced MRI has shown more promising results in differentiating benign from malignant tumors with increased sensitivity and specificity [30]. Intermediate signal on T2-weighted images indicative of chronic hemosiderin deposition [35, 36] is a well-recognized MRI feature of GCT, which was also seen in most of our patients.
The raised choline levels seen in some benign GCTs and not in others may be related to the degree of their local aggressiveness. Three of four GCTs with elevated choline concentration showed aggressive imaging features, including soft-tissue extension. Because only two of these four patients underwent surgery and none was followed up to determine the rate of recurrence or tumor growth, we cannot show any relationship between the presence of choline and the biologic behavior of the tumor. Another limitation of our study was that we did not perform DNA analysis or study the status of proliferation markers in our patients.
GCT is a locally aggressive tumor that typically causes bone expansion and thinning (Campanacci stage 2). Aggressive GCT can destroy the bone and extend into the soft tissue (Campanacci stage 3) [8]. Curettage with or without local adjuvant therapy such as bone cementing has been the preferred treatment for most GCTs, but curettage is plagued by a high rate of local recurrence, necessitating reoperation in many cases, which adds to patient morbidity [14]. Histopathologic features and radiologic findings have not accurately reflected the ultimate clinical outcome in GCT of bone [36–38]. Various proliferation markers such as the p53 gene and DNA analysis are promising in predicting the clinical behavior of GCTs [39, 40]. Elevated choline may represent a growing phase of the tumor, as was true in a reported case of breast fibroadenoma with an elevated choline level [41]. In the context of GCT of the bone, detection of elevated choline levels may have implications on the type of surgical treatment. Further studies are required to test this hypothesis.
In conclusion, this study has shown that benign GCT of bone may show elevated choline levels on proton MR spectroscopy, the clinical significance of which is not clear at present.
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
