Multimodal imaging of gliomas in the context of evolving cellular and molecular therapies

Abstract

The vast majority of malignant gliomas relapse after surgery and standard radio-chemotherapy. Novel molecular and cellular therapies are thus being developed, targeting specific aspects of tumor growth. While histopathology remains the gold standard for tumor classification, neuroimaging has over the years taken a central role in the diagnosis and treatment follow up of brain tumors. It is used to detect and localize lesions, define the target area for biopsies, plan surgical and radiation interventions and assess tumor progression and treatment outcome. In recent years the application of novel drugs including anti-angiogenic agents that affect the tumor vasculature, has drastically modulated the outcome of brain tumor imaging. To properly evaluate the effects of emerging experimental therapies and successfully support treatment decisions, neuroimaging will have to evolve. Multi-modal imaging systems with existing and new contrast agents, molecular tracers, technological advances and advanced data analysis can all contribute to the establishment of disease relevant biomarkers that will improve disease management and patient care. In this review, we address the challenges of glioma imaging in the context of novel molecular and cellular therapies, and take a prospective look at emerging experimental and pre-clinical imaging techniques that bear the promise of meeting these challenges.

In vivo characterization of brain metabolism by 1H MRS, 13C MRS and 18FDG PET reveals significant glucose oxidation of invasively growing glioma cells

“…The determination of the altered metabolic profiles in GBM can be achieved in vivo in xenograft models using 1 H, 13 C magnetic resonance spectroscopy (MRS) and 18 FDG positron emission tomography ( 18 FDG PET). 2,3 The determination of neurochemical profiles with 1 H MRS in vivo at ultrahigh magnetic field (i.e., 14.1 T) using short echo-time sequences allows the simultaneous detection of a large number of metabolites that otherwise display highly superimposed signals, such as glutamate and glutamine, phosphocholine and glycerophosphocholine, creatine and phosphocreatine, myo-inositol and glycine. 4,5 The metabolites that become detectable provide insights into energy metabolism, myelination, neurotransmission, antioxidation and osmoregulation, as recently reported from rodent xenograft models of glioma.…”

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

“…284 Modern imaging techniques, such as magnetic resonance imaging (MRI), optical imaging, ultrasound, and single-photon-emission computed tomography (SPECT), are rapidly emerging as noninvasive modalities for detection and follow-up posttreatment of gliomas. 285,286 MRI is the preferred approach for glioma imaging, since it provides high-spatial-resolution anatomic images of this tumor type. 287 Optical imaging applied to glioma therapy has the potential to localize and identify intrinsic brain tumors for removal during surgery.…”

“…288 Ultrasound, unlike MRI, defines tumor volume and provides intraoperative localization of tumor tissue, although its use is limited by the presence of the skull. 285 SPECT yields growth rate and gives information about the heterogeneity of gliomas, but provides low-spatial-resolution images. 289 Positron-emission tomography (PET) provides functional information, since this technique is highly sensitive for measurements of biological processes, such as cell proliferation, angiogenesis, and glucose consumption.…”

Antiangiogenic Effect of Bevacizumab: Application of Arterial Spin-Labeling Perfusion MR Imaging in a Rat Glioblastoma Model

“…However, it was unclear whether perfusion MR imaging can be applied as an imaging biomarker to quantify the microvascular environment mainly due to significant intra-and intertumoral biologic heterogeneity of GBM. Although some researchers have investigated the potential of DSC perfusion MR imaging in GBMs treated with bevacizumab in animal models, 12,24 direct correlation between perfusion parameters and histologic features was not elucidated. In terms of the ASL perfusion MR imaging technique, a previous report has suggested the potential of using ASL perfusion MR imaging to evaluate the response to antiangiogenic therapy in a patient with recurrent GBM who received bevacizumab.…”