Imaging advances for the evaluation of brain tumors and
neuroinflammation
The measurement of metabolic and cell physiology parameters with
improved MRI techniques provides more detailed information on tissue
biochemical composition and blood perfusion, facilitating the
distinction between tumors and necrosis. Proton magnetic resonance (MR)
spectroscopic imaging is used to evaluate cell metabolism through the
detection of proton metabolites and their distribution. Chemicals
detected include compounds containing choline, creatine, lactate, lipid,
and N-acetylaspartate. Choline, a component of cell membrane
phospholipids, is particularly useful for differentiating tumors from
non-tumoral tissues because its content is increased in highly
proliferative cell populations. Overall, higher choline levels are
associated with disease progression or recurrence, whereas low levels of
choline are found in necrotic lesions. The analysis of increased ratios
of choline content in relation to other chemicals can result in an
accuracy of up to 97% in separating tumors from non-tumoral necrotic
tissues [31, 42].
Conventional MRI, with the T1/T2 mismatch criterion, had a specificity
of 75% and a sensitivity of only 44% in distinguishing between tumors
and inflamed lesions. PET scan combined the best sensitivity and
specificity, respectively of 92% and 69%. PET remained superior
compared to NMR spectroscopy for choline/N-acetylaspartate and
choline/creatin ratios across different thresholds [45]. A
retrospective study of 57 GBM patients examined with T2*-weighted
dynamic susceptibility-weighted contrast material–enhanced (DSC) MRI
found mean, maximum, and minimum relative peak height and relative
cerebral blood volume were significantly higher in GBM cases compared to
radiation necrosis cases. In contrast, mean, maximum, and minimum
relative percentage of signal intensity recovery values were
significantly lower in recurrent GBM compared to radiation necrosis
[46]. Proton MR spectroscopy showed a temporary elevation of choline
in 4 of 9 cases of necrosis, creating a confounding factor that could
result in false positive findings for tumor recurrence [47]. Another
study using proton MR spectroscopy in 11 patients who received high-dose
radiotherapy revealed that cases of radiation necrosis had either
increased lactate/creatine and phosphocreatine (Cr) ratio and decreased
choline-containing compounds/phosphocreatine ratio compared to recurrent
GBM, or reductions in all major metabolites [48]. A meta-analysis of
397 patients in 13 studies examined roles of several metabolites. MR
spectroscopy and MR perfusion using Cho/NAA and Cho/Cr ratios and rCBV
may increase the accuracy of differentiating necrosis from recurrent
tumor in patients with primary brain tumors or brain metastases
[49].
A meta-analysis of 6 studies with 118 patients and 134 scans indicated11C-choline PET as an accurate diagnostic method for
the differentiation of tumor relapse from radiation induced necrosis in
gliomas [50]. A study with 55 patients, followed up for at least 11
months, with suspected brain tumor recurrence or necrosis after
radiotherapy, examined MRI, (18)F-FDG, and11C-choline PET/CT, concluding for the superiority of11C-choline PET/CT [51]. In a F98 orthotopic rat
model of GBM, PET using (18)F-FDG and
(18)F-FET PET were effective in discriminating GBM
from radiation necrosis, with (18)F-FDG delayed PET
being particularly useful [52]. A study with 50 patients showed that
(11)C-methionine-PET was superior to both
(11)C-choline and (18)F-FDG -PET for
distinguishing GBM recurrence from radiation necrosis [53]. The LAT1
tumor-specific PET tracer 2-[18F]FELP PET is able
to differentiate glioblastoma from radiation necrosis, and
2-[18F]FELP uptake is less likely to be
contaminated by the presence of inflammation than the
[18F]FDG signal [35].