Morteza Esmaeili

IDH1 R132H mutation generates a distinct phospholipid metabolite profile in glioma.

Many patients with glioma harbor specific mutations in the isocitrate dehydrogenase gene IDH1 that associate with a relatively better prognosis. IDH1-mutated tumors produce the oncometabolite 2-hydroxyglutarate. Because IDH1 also regulates several pathways leading to lipid synthesis, we hypothesized that IDH1-mutant tumors have an altered phospholipid metabolite profile that would impinge on tumor pathobiology. To investigate this hypothesis, we performed (31)P-MRS imaging in mouse xenograft models of four human gliomas, one of which harbored the IDH1-R132H mutation. (31)P-MR spectra from the IDH1-mutant tumor displayed a pattern distinct from that of the three IDH1 wild-type tumors, characterized by decreased levels of phosphoethanolamine and increased levels of glycerophosphocholine. This spectral profile was confirmed by ex vivo analysis of tumor extracts, and it was also observed in human surgical biopsies of IDH1-mutated tumors by (31)P high-resolution magic angle spinning spectroscopy. The specificity of this profile for the IDH1-R132H mutation was established by in vitro (31)P-NMR of extracts of cells overexpressing IDH1 or IDH1-R132H. Overall, our results provide evidence that the IDH1-R132H mutation alters phospholipid metabolism in gliomas involving phosphoethanolamine and glycerophosphocholine. These new noninvasive biomarkers can assist in the identification of the mutation and in research toward novel treatments that target aberrant metabolism in IDH1-mutant glioma.

Coexistence of helical morphologies in columnar stacks of star-shaped discotic hydrazones.

Discotic hydrazone molecules are of particular interest as they form discotic phases where the discs are rigidified by intramolecular hydrogen bonds. Here, we investigate the thermotropic behavior and solid-state organizations of three discotic hydrazone derivatives with dendritic groups attached to their outer peripheries, containing six, eight, and ten carbons of linear alkoxy chains. On the basis of two-dimensional wide angle X-ray scattering (2DWAXS), the elevated temperature liquid crystalline (LC) phases were assigned to a hexagonal columnar (Colh) organization with nontilted hydrazone discs for all three compounds. With WAXS, advanced solid-state nuclear magnetic resonance (SSNMR) techniques, and ab initio computations, the compounds with six and ten carbons of achiral alkoxy side chains were further subjected to studies at 25 °C, revealing complex crystalline phases with rigid columns and flexible side chains. This combined approach led to models of coexisting helical columnar stacking morphologies for both systems with two different tilt/pitch angles between successive hydrazone molecules. The differences in tilt/pitch angles between the two compounds illustrate that the columns with short alkoxy chains (six carbons) are more influenced by the presence of other stacks in their vicinity, while those with long side chains are less tilted due to a larger alkoxy (ten carbons) buffer zone. The formation of different packing morphologies in the crystalline phase of a columnar LC has rarely been reported so far, which suggests the possibility of complex stacking structures of similar organic LC systems, utilizing small molecules as potential materials for applications in organic electronics.

In situ X-ray ptychography imaging of high-temperature CO2 acceptor particle agglomerates

Imaging nanoparticles under relevant reaction conditions of high temperature and gas pressure is difficult because conventional imaging techniques, like transmission electron microscopy, cannot be used. Here we demonstrate that the coherent diffractive imaging technique of X-ray ptychography can be used for in situ phase contrast imaging in structure studies at atmospheric pressure and elevated temperatures. Lithium zirconate, a candidate CO2 capture material, was studied at a pressure of one atmosphere in air and in CO2, at temperatures exceeding 600 °C. Images with a spatial resolution better than 200 nm were retrieved, and possibilities for improving the experiment are described.

Quantitative 31P HR-MAS MR spectroscopy for detection of response to PI3K/mTOR inhibition in breast cancer xenografts

Phospholipid metabolites are of importance in cancer studies, and have been suggested as candidate metabolic biomarkers for response to targeted anticancer drugs. The purpose of this study was to develop a phosphorus (31P) high resolution magic angle spinning magnetic resonance spectroscopy protocol for quantification of phosphorylated metabolites in intact cancer tissue.

In Vivo 31P magnetic resonance spectroscopic imaging (MRSI) for metabolic profiling of human breast cancer xenografts

To study cancer associated with abnormal metabolism of phospholipids, of which several have been proposed as biomarkers for malignancy or to monitor response to anticancer therapy. We explored 3D 31P magnetic resonance spectroscopic imaging (MRSI) at high magnetic field for in vivo assessment of individual phospholipids in two patient‐derived breast cancer xenografts representing good and poor prognosis (luminal‐ and basal‐like tumors).

Impacts of MR spectroscopic imaging on glioma patient management.

Abstract Magnetic resonance (MR) modalities are routine imaging tools in the diagnosis and management of gliomas. MR spectroscopic imaging (MRSI), which relies on the metabolic characteristics of tissues, has been developed to accelerate the understanding of gliomas and to aid in effective clinical decision making and development of targeted therapies. In this review, the potentials and practical challenges to frequently use this technique in clinical management of gliomas are discussed. The applications of new biomarkers detectable by MRSI in differential glioma diagnosis, pre- and post-treatment evaluations, and neurosurgery are also addressed.

In vivo 31P MRSI for metabolic profiling of human breast cancer xenografts

To study cancer associated with abnormal metabolism of phospholipids, of which several have been proposed as biomarkers for malignancy or to monitor response to anticancer therapy. We explored 3D 31P magnetic resonance spectroscopic imaging (MRSI) at high magnetic field for in vivo assessment of individual phospholipids in two patient‐derived breast cancer xenografts representing good and poor prognosis (luminal‐ and basal‐like tumors).

Monitoring moisture distribution in textile materials using grating interferometry and ptychographic X-ray imaging

Employing two recently developed X-ray imaging techniques, we investigated methods for observing moisture at different length scales in organic fibers and textiles. Using the coherent diffractive imaging technique of ptychographic tomography, structural features in a single coated wool fiber in both dry and humid conditions were observed at about 200 nm resolution. The reconstructed three-dimensional images yield quantitative information about the spatial density distribution in the fiber, showing that the fiber swells laterally by 8–9% in humid conditions. We further explore the applicability of grating interferometry, also known as Talbot imaging, for studying humidity transport in woven cotton, with a resolution on the order of 100 µm and a field of view of a few square centimeters. Grating interferometry inherently gives access to three complementary imaging modalities, namely absorption-, phase- and dark-field contrast, and we demonstrate that all of them are valuable and provide complementary information for the purpose of monitoring moisture in textiles.

The Direction of Tumour Growth in Glioblastoma Patients

Generating MR-derived growth pattern models for glioblastoma multiforme (GBM) has been an attractive approach in neuro-oncology, suggesting a distinct pattern of lesion spread with a tendency in growing along the white matter (WM) fibre direction for the invasive component. However, the direction of growth is not much studied in vivo. In this study, we sought to study the dominant directions of tumour expansion/shrinkage pre-treatment. We examined fifty-six GBMs at two time-points: at radiological diagnosis and as part of the pre-operative planning, both with contrast-enhanced T1-weighted MRIs. The tumour volumes were semi-automatically segmented. A non-linear registration resulting in a deformation field characterizing the changes between the two time points was used together with the segmented tumours to determine the dominant directions of tumour change. To compute the degree of alignment between tumour growth vectors and WM fibres, an angle map was calculated. Our results demonstrate that tumours tend to grow predominantly along the WM, as evidenced by the dominant vector population with the maximum alignments. Our findings represent a step forward in investigating the hypothesis that tumour cells tend to migrate preferentially along the WM.

In vivo MR spectroscopy predicts high tumor grade in endometrial cancer

Background In vivo magnetic resonance spectroscopy (MRS) enables non-invasive measurements of tumor metabolites. Choline-containing metabolites play a key role in tumor metabolism. Purpose To explore whether preoperative MRS-derived tumor choline levels are associated with clinical and histological features in endometrial carcinomas. Material and Methods Preoperative pelvic magnetic resonance imaging (MRI) (1.5T), including structural and diffusion-weighted imaging and localized multivoxel proton MR (1H-MR) spectroscopy, was performed in 77 prospectively included patients with histologically confirmed endometrial carcinomas. Relative levels of total choline-containing metabolites (tCho) in tumor and myometrium were measured using the ratios: tCho/Creatine; tCho/Water; and tCho/Noise. MRS parameters were analyzed in relation to histological subtype and grade, surgicopathological staging parameters, MRI-measured tumor volume, and tumor apparent diffusion coefficient (ADC) value and clinical outcome. Results Tumor tissue had significantly higher ratios for tCho/Creatine, tCho/Water, and tCho/Noise than normal myometrial tissue (P < 0.001 for all). High tumor tCho/Water ratio was significantly associated with high tumor grade in endometrioid tumors (P = 0.02). Tumor tCho/Creatine ratio was positively correlated to MRI-measured tumor volume (rs = 0.25; P = 0.03). Conclusion High choline levels in tumor are associated with high-risk features. In vivo MRS may potentially aid in the preoperative risk stratification in endometrial cancer.