Keywords
18 F fluorodeoxy glucose -
11 C methionine - demyelinating disease
Introduction
18 F-fluorodeoxyglucose (FDG), the most available tracer for positron emission tomography (PET), has been used to diagnose various neoplastic diseases and to evaluate therapeutic response in these patients.[1 ]
[2 ]
11 C-methionine (MET) has also been widely used for imaging tumors in the brain and skull base.[3 ]
[4 ] MET is particularly useful for diagnosing radiation necrosis of the brain.[5 ]
Tumefactive multiple sclerosis (MS)[6 ] exhibits large demyelinating plaques with or without contrast enhancement on MRI that resemble brain tumors. The feasibility of PET using FDG, MET, and other tracers to differentiate between neoplastic and demyelinating diseases has been reported.[7 ]
[8 ]
[9 ]
[10 ]
[11 ] However, few studies have evaluated the accumulation of FDG, MET, and other PET tracers in patients with demyelinating disease.[12 ]
[13 ]
[14 ] In the present study, we discuss the imaging features of demyelinating disease with regard to uptake of FDG or MET in demyelinating lesions and provide a literature review.
Material and Methods
Patients
The Institutional Review Board of our hospital approved this study. A retrospective search of the patient database in our hospital identified five patients with demyelinating disease in whom PET studies performed in the past 10 years revealed accumulation of FDG or MET. There were two males and three females with age range of 40 to 63 years. The clinical diagnoses were multiple sclerosis (n =1), myelitis (n =1), limbic encephalitis (n =1), chronic inflammatory demyelinating polyneuropathy (CIDP; n =1), and acute demyelinating encephalomyelitis (ADEM; n =1; [Table 1 ]). The imaging diagnoses were as follows: cervical spinal cord lesion in case 1 ([Fig. 1 ]), CIDP with diffuse swelling of the bilateral nerve roots of the brachial plexus in case 2 ([Fig. 2 ]), right thalamic lesion in case 3 ([Fig. 3 ]), multiple lesions in the bilateral cerebral white matter in case 4 ([Fig. 4 ]), and a lesion in the left uncus and parahippocampal gyrus in case 5 who also had carcinoma of the lung ([Fig. 5 ]). All clinical diagnoses were made by a neurologist (C.K.) with 20 years' experience in neurology and were made based on the clinical manifestations and course (all cases), results of cerebrospinal fluid analysis (cases 1, 2, 4, and 5), nerve conduction velocity (case 2), and presence of malignancy (case 5; [Table 1 ]).
Table 1
Clinical data of the patients
Case no.
Clinical diagnosis
FDG PET/CT
MET PET/CT
Location of the lesion
Laboratory data
SUVmax L/N ratio
SUVmax L/N ratio
1
Myelitis
3.8/3.0
2.4/2.4
Cervical spinal cord
Increased total protein in CSF
2
CIDP
9.8/7.0
−
Brachial plexus
Increased total protein in CSF, conduction block of the median nerve
3
ADEM
10.3/1.7
2.6/1.6
rt. thalamus
Increased MBP in CSF, oligoclonal band (−) in CSF
4
MS
6.1/1.7
2.5/2.1
Cerebral white matter
Oligoclonal band (+) in CSF
5
Limbic encephalitis
7.8/1.8
−
lt medial tempotal lobe
Anti-GABAbR antibody (+) in CSF
Abbreviations: ADEM, acute disseminated encephalomyelitis; CIDP, chronic inflammatory polyneuritis; CSF, cerebrospinal fluid; FDG, F-18 fluorodeoxy glucose; GABAbR, γ-ami-nobutyric acid-B receptor; L/N ratio, lesion-to-normal area ratio; MBP; myelin basic protein; MET, C-11 methionine; MS, multiple sclerosis; PET, positron emission tomography; rt., right; SUVmax , maximum standardized uptake value.
Fig. 1 A 59-year-old male with myelitis (case 1). T2-weighted MRI (A ) shows a hyperintense lesion in the spinal cord (arrow). PET/CT depicts definite accumulation of 18 F-fluorodeoxyglucose (FDG) (B ), and faint uptake of 11 C-methionine (MET; arrow ) (C ) in the lesion (arrow ). CT, computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography.
Fig. 2 A 63-year-old female with chronic inflammatory demyelinating polyneuropathy (CIDP) (case 2). Maximum intensity projection (MIP) image using short T1 inversion recovery sequence (A ) shows diffuse swelling of the brachial plexus (arrowheads ). FDG-PET/CT (B ) depicts accumulation of FDG in some parts of the brachial plexus lesion (arrows ). CT, computed tomography; FDG, fluorodeoxyglucose; PET, positron emission tomography.
Fig. 3 A 46-year-old male with suspected acute disseminated encephalomyelitis (ADEM) (case 3). Fluid-attenuated inversion recovery (FLAIR) MRI (A ) shows a hyperintense lesion in the right thalamus (arrow ). FDG-PET/CT (B ) depicts probable decreased uptake in the lesion (arrow ). MET-PET/CT (C ) shows definite accumulation of MET in the lesion (arrow ). CT, computed tomography; FDG, fluorodeoxyglucose; MET, methionine; MRI, magnetic resonance imaging; PET, positron emission tomography.
Fig. 4 A 40-year-old female with multiple sclerosis (case 4). FLAIR MRI (A ) shows multiple hyperintense lesions in the corona radiata (arrows ). FDG-PET/CT (B ) shows almost no uptake in the lesion. MET-PET/CT (C ) shows moderate uptake of MET in the right corona radiata (arrow ). CT, computed tomography; FDG, fluorodeoxyglucose; FLAIR, fluid-attenuated inversion recovery; MET, methionine; MRI, magnetic resonance imaging; PET, positron emission tomography.
Fig. 5 A 62-year-old female with limbic encephalitis (case 5). FLAIR MRI (A ) shows a hyperintense lesion in the left medial temporal lobe (arrow ). FDG-PET/CT (B ) depicts accumulation of FDG in the lesion (arrow ). CT, computed tomography; FDG, fluorodeoxyglucose; FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging; PET, positron emission tomography.
Positron Emission Tomography/Computed Tomography
PET/CT was performed using three different PET/CT units: GE Discovery 600 Motion (GE Healthcare, Milwaukee, Wisconsin), FWHM 5.1-mm, and 16-row CT in two patients (cases 1 and 2). GE Discovery 610 Motion (GE Healthcare), FWHM 5.1-mm, and 16-row CT in 1 patient (case 3); and GE IQ (GE Healthcare), FWHM 5.1-mm, and 16-row CT in two patients (cases 4 and 5). No intravenous contrast material was used. After CT, MET-PET was performed 20minutes after injecting MET. For FDG-PET, FDG was injected 60minutes after MET-PET, and FDG-PET was performed 60minutes after injection of FDG.
Two patients (cases 2 and 5) received FDG-PET alone, and three patients (cases 1, 3, and 4) received both FDG-PET/CT and MET-PET/CT on the same day. The protocol used in the PET/CT examinations has been described previously.[15 ] Coregistered images were displayed on a workstation (Advantage Workstation version 4.7, GE Healthcare).
Images were visually and conjointly reviewed by two radiologists (N.T. with 39 years' experience in neuroradiology and T.S. with 30 years' experience in radiology) who were aware of the clinical diagnoses.
In semiquantitative evaluation, the maximum standardized uptake value (SUVmax ) of the lesion was measured. The lesion-to-normal brain uptake ratio (L/N ratio) was calculated as the SUVmax of the lesion divided by the SUVmax of the same site in the contralateral cerebral hemisphere.
Results
In case 1 (myelitis of the cervical spinal cord), there was obvious FDG accumulation in the lesion and MET accumulation was faint ([Fig. 1 ]). Case 2 (CIDP) showed FDG accumulation in some lesions ([Fig. 2 ]). In case 3 (suspected ADEM), FDG accumulation in the lesion in the right thalamus was equal to normal tissue, and there was obvious MET uptake in the lesion ([Fig. 3 ]). In Case 4 (MS), there was MET uptake but no FDG accumulation ([Fig. 4 ]). In case 5 (limbic encephalitis), there was FDG uptake in the lesion, and reduced FDG accumulation in normal tissue due to high blood glucose levels ([Fig. 5 ]). [Table 1 ] lists the SUVmax values and L/N ratios for MET-PET/CT in the five patients.
Discussion
FDG is the most widely available PET tracer worldwide. FDG hypermetabolism in the lesion generally suggests neoplastic etiology. It is known that accumulation of FDG in the central nervous system can indicate inflammatory diseases such as abscess, meningitis, and encephalitis.[16 ]
[17 ]
[18 ] Although the feasibility of FDG has been reported for differentiating between neoplasms and demyelinating diseases, the possibility of FDG uptake in demyelinating disease has also been reported.[19 ]
[20 ]
[21 ]
[22 ]
[23 ]
[24 ]
[25 ]
[26 ] Our literature review revealed reports of FDG accumulation in limbic encephalitis,[12 ]
[19 ]
[21 ]
[25 ]
[26 ] active myelopathy,[13 ] progressive multifocal leukoencephalopathy,[14 ]
[20 ] and MS.[22 ]
[23 ]
[24 ] In particular, FDG uptake by lesions has been often reported in limbic encephalitis, and it has been suggested that hypermetabolism of FDG in limbic encephalitis might be related to subclinical seizures.[19 ] A seizure occurred 5 days before the PET study in the present case 5.
The usefulness of MET for differentiating between neoplastic and nonneoplastic lesions has been reported[11 ]; however, there are several reports of MET accumulation in tumefactive demyelinating lesions.[27 ]
[28 ] We found no reports of MET uptake in myelitis. In a semiquantitative analysis using L/N ratio to differentiate between tumefactive MS and high-grade glioma,[28 ] the L/N ratio in tumefactive MS was 1.89±0.55 which was significantly lower than that in high-grade astrocytoma (astrocytoma grade III: 3.37±1.36 and astrocytoma grade IV: 4.35±1.30). In the present study, L/N ratio of MET was less than 2.4 in cases 1, 3, and 4. Measurement of L/N ratio could be feasible in the case of MET accumulation in nonneoplastic lesions.
Previous studies have reported inflammatory cell infiltration as an important factor in brain abscess and encephalitis as a mechanism of FDG or MET accumulation in tumefactive MS.[24 ]
[28 ] These mechanisms could also be important for FDG or MET accumulation in demyelinating lesions. In the present case 2, although the brachial plexus was diffusely affected on the MRI, FDG accumulated in the most thickened nerve root. Symptoms were strong in the right side with FDG uptake. However, the mechanism of partial high uptake of FDG is unclear. Our literature review found no mention of FDG uptake by CIDP lesions. In case 4, the lesion showed no contrast enhancement on MRI, no FDG accumulation, and slight uptake of MET in the biggest one in multiple lesions. Symptoms seemed related to the lesion with MET uptake. Although MET uptake was faint in case 1, there was clear FDG uptake. In case 3, FDG uptake in the lesion was equal to that in normal tissue, and there was obvious uptake of MET. The mechanisms of uptake are quite different between MET and FDG. MET uptake is influenced by MET metabolism and active MET transport.[28 ] Decreased uptake of MET after treatment has been reported in a case of progressive multifocal leukoencephalopathy.[14 ] Case 5 showed decreased uptake of FDG in the lesion on follow-up FDG-PET study. No follow-up PET studies were performed in other cases.
In tracers other than FDG and MET, 18 F-fluoromethylcholine uptake has been reported in an MS lesion.[29 ] A recent study has shown a quantitative correlation of myelin histology with 18 F-florbetapir binding in demyelinated lesions,[29 ] and the authors suggested the potential of 18 F-florbetapir PET for quantitative assessment of the progression of demyelinating diseases.[30 ]
Limitations
There are several limitations in the present study. The number of cases was small. FDG and/or MET PET studies are usually not performed when demyelinating diseases are suspected. Although an experienced neurologist diagnosed every case according to the clinical symptoms, clinical course, radiological findings, and laboratory data, a pathological diagnosis was not obtained. In general, biopsy is not clinically practical in patients with demyelinating diseases. Patients with demyelinating disease without accumulation of FDG and/or MET were unclear in our patients database.
Conclusion
In conclusion, accumulation of FDG or MET was seen in patients with demyelinating diseases. Knowledge of the possibility of FDG and MET uptake in demyelinating lesions is of clinical importance.
