We at the University of Pennsylvania
are investigating the utility of advanced neuroimaging techniques in monitoring treatment-related temporal characteristics and assessing response to this unique treatment modality. Anatomic magnetic resonance imaging (MRI) of the brain provides excellent soft tissue contrast and is routinely used for the noninvasive characterization of brain tumors. However, conventional imaging utilizing “Response Assessment in Neuro-Oncology” (RANO) criteria is usually not reliable for assessment of the treatment response in patients with GBM
due to the lack of specificity [
13]. Consequently, there is an urgent need to develop increasingly accurate quantitative imaging biomarkers for early evaluation of treatment response. These biomarkers are the premise of personalized treatment, enabling change or discontinuation of therapy to prevent ineffective treatment or unfavorable events. Moreover, identification of treatment failure may help reduce adverse economic consequences. This is highly relevant because the cost of TTFields therapy
is considerably high at $21,000 per month [
14]. Advanced MR imaging techniques such as diffusion-tensor imaging (DTI)
[
15], dynamic susceptibility contrast (DSC)-perfusion weighted imaging (PWI)
[
16,
17], and proton MR spectroscopy (
1H MRS) [
18,
19] have shown great potential in evaluating treatment response to different therapeutic regimens in GBM patients. DTI is an MR imaging technique
used to noninvasively investigate the cyto-architectural integrity of brain structures by measuring the anisotropy of microscopic water diffusivity. Along with more commonly used DTI parameters such as mean diffusivity (MD) and fractional anisotropy (FA), geometrical DTI indices such as the coefficients of linear anisotropy (CL) and planar anisotropy (CP) can be helpful in characterizing tissue organization and orientation of white matter tracts in the brain. Relative cerebral blood volume (rCBV)
derived from PWI reflects tumor angiogenesis and vascularity.
1H MRS is a method that measures metabolic markers of neoplastic activity [
20]. Spectra from brain tumors have increased choline (Cho), which correlates with membrane biosynthesis by proliferating cells, and reduced N-acetylasparate (NAA), which indicates loss of neuronal integrity due to tumor cell infiltration [
21]. 3D-Echo planar spectroscopic imaging (EPSI)
allows acquisition of volumetric metabolite maps with high spatial resolution, minimizing partial-volume averaging effects [
22,
23]. Thus, 3D-EPSI
may be helpful in providing metabolite information from the entire volume of a neoplasm. The potential of 3D-EPSI has been reported in characterizing glioma grades [
24], mapping glycine distribution in gliomas [
25], planning radiation therapy for GBM patients [
26], identifying residual tumors following radiation therapy [
27], evaluating response to epigenetic modifying agents in recurrent GBM [
28], in assessing the effect of whole brain radiation therapy on normal brain parenchyma in patients with metastases [
29] and in distinguishing true progression (TP) from pseudoprogression (PsP) in GBM
patients [
30].