Patrick Schuenke

A combined analytical solution for chemical exchange saturation transfer and semi-solid magnetization transfer

Off‐resonant RF irradiation in tissue indirectly lowers the water signal by saturation transfer processes: on the one hand, there are selective chemical exchange saturation transfer (CEST) effects originating from exchanging endogenous protons resonating a few parts per million from water; on the other hand, there is the broad semi‐solid magnetization transfer (MT) originating from immobile protons associated with the tissue matrix with kilohertz linewidths. Recently it was shown that endogenous CEST contrasts can be strongly affected by the MT background, so corrections are needed to derive accurate estimates of CEST effects. Herein we show that a full analytical solution of the underlying Bloch–McConnell equations for both MT and CEST provides insights into their interaction and suggests a simple means to isolate their effects. The presented analytical solution, based on the eigenspace solution of the Bloch–McConnell equations, extends previous treatments by allowing arbitrary lineshapes for the semi‐solid MT effects and simultaneously describing multiple CEST pools in the presence of a large MT pool for arbitrary irradiation. The structure of the model indicates that semi‐solid MT and CEST effects basically add up inversely in determining the steady‐state Z‐spectrum, as previously shown for direct saturation and CEST effects. Implications for existing previous CEST analyses in the presence of a semi‐solid MT are studied and discussed. It turns out that, to accurately quantify CEST contrast, a good reference Z‐value, the observed longitudinal relaxation rate of water, and the semi‐solid MT pool size fraction must all be known. Copyright

Simultaneous mapping of water shift and B1(WASABI)—Application to field-Inhomogeneity correction of CEST MRI data

Together with the development of MRI contrasts that are inherently small in their magnitude, increased magnetic field accuracy is also required. Hence, mapping of the static magnetic field (B0) and the excitation field (B1) is not only important to feedback shim algorithms, but also for postprocess contrast‐correction procedures.

Adiabatically prepared spin-lock approach for T1ρ-based dynamic glucose enhanced MRI at ultrahigh fields.

Chemical exchange sensitive spin‐lock and related techniques allow to observe the uptake of administered D‐glucose in vivo. The exchange‐weighting increases with the magnetic field strength, but inhomogeneities in the radiofrequency (RF) field at ultrahigh field whole‐body scanners lead to artifacts in conventional spin‐lock experiments. Thus, our aim was the development of an adiabatically prepared T1ρ‐based imaging sequence applicable to studies of glucose metabolism in tumor patients at ultrahigh field strengths.

T1ρ-weighted Dynamic Glucose-enhanced MR Imaging in the Human Brain

Purpose To evaluate the ability to detect intracerebral regions of increased glucose concentration at T1ρ-weighted dynamic glucose-enhanced (DGE) magnetic resonance (MR) imaging at 7.0 T. Materials and Methods This prospective study was approved by the institutional review board. Nine patients with newly diagnosed glioblastoma and four healthy volunteers were included in this study from October 2015 to July 2016. Adiabatically prepared chemical exchange-sensitive spin-lock imaging was performed with a 7.0-T whole-body unit with a temporal resolution of approximately 7 seconds, yielding the time-resolved DGE contrast. T1ρ-weighted DGE MR imaging was performed with injection of 100 mL of 20% d-glucose via the cubital vein. Glucose enhancement, given by the relative signal intensity change at T1ρ-weighted MR imaging (DGEρ), was quantitatively investigated in brain gray matter versus white matter of healthy volunteers and in tumor tissue versus normal-appearing white matter of patients with glioblastoma. The median signal intensities of the assessed brain regions were compared by using the Wilcoxon rank-sum test. Results In healthy volunteers, the median signal intensity in basal ganglia gray matter (DGEρ = 4.59%) was significantly increased compared with that in white matter tissue (DGEρ = 0.65%) (P = .028). In patients, the median signal intensity in the glucose-enhanced tumor region as displayed on T1ρ-weighted DGE images (DGEρ = 2.02%) was significantly higher than that in contralateral normal-appearing white matter (DGEρ = 0.08%) (P < .0001). Conclusion T1ρ-weighted DGE MR imaging in healthy volunteers and patients with newly diagnosed, untreated glioblastoma enabled visualization of brain glucose physiology and pathophysiologically increased glucose uptake and may have the potential to provide information about glucose metabolism in tumor tissue.

A comparison of various strategies to equalize the lower energy thresholds of a CdTe Medipix2 hexa detector for X-ray imaging applications

Technological advances have made possible the development of pixelized photon counting semiconductor detectors, many of which are used in X-ray imaging to resolve the spectral composition of the incident photons. Here, in a so-called Hexa detector, we employ a 3 × 2 array of Medipix2 MXR readout chips, bump bonded to a cadmium telluride sensor of 1 mm thickness with a pixel pitch of 165 μm. Each pixel in this assembly offers two variable energy thresholds, which enables counting of only those photons within an energy range of interest. As manufacturing tolerances cause deviations in each of the pixels responses, the two thresholds can be calibrated for every pixel to render their response to radiation more homogeneous. In this work, we compare various methods that we chose to equalize the lower thresholds: a) the noise edge of the detector electronics, the characteristic X-rays from b) silver and c) tantalum foils as well as flat fields obtained at d) 40 and e) 120 kVp. It will be shown that the energy dependence in the resulting adjustment bit maps are only small, whereas the question as to which strategy to choose (peak position vs. image homogeneity) will have a greater influence on the resulting corrections. Additionally, we observed a decrease in the mean adjustment values with increasing distance from the central axis of the Hexa detector under study.

Fast and Quantitative T1ρ-weighted Dynamic Glucose Enhanced MRI

Common medical imaging techniques usually employ contrast agents that are chemically labeled, e.g. with radioisotopes in the case of PET, iodine in the case of CT or paramagnetic metals in the case of MRI to visualize the heterogeneity of the tumor microenvironment. Recently, it was shown that natural unlabeled D-glucose can be used as a nontoxic biodegradable contrast agent in Chemical Exchange sensitive Spin-Lock (CESL) magnetic resonance imaging (MRI) to detect the glucose uptake and potentially the metabolism of tumors. As an important step to fulfill the clinical needs for practicability, reproducibility and imaging speed we present here a robust and quantitative T1ρ-weighted technique for dynamic glucose enhanced MRI (DGE-MRI) with a temporal resolution of less than 7 seconds. Applied to a brain tumor patient, the new technique provided a distinct DGE contrast between tumor and healthy brain tissue and showed the detailed dynamics of the glucose enhancement after intravenous injection. Development of this fast and quantitative DGE-MRI technique allows for a more detailed analysis of DGE correlations in the future and potentially enables non-invasive diagnosis, staging and monitoring of tumor response to therapy.

Assessing the predictability of IDH mutation and MGMT methylation status in glioma patients using relaxation-compensated multi-pool CEST MRI at 7.0 Tesla

Background Early identification of prognostic superior characteristics in glioma patients such as isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is of great clinical importance. The study purpose was to investigate the non-invasive predictability of IDH mutation status, MGMT promoter methylation, and differentiation of low-grade versus high-grade glioma (LGG vs HGG) in newly diagnosed patients employing relaxation-compensated multipool chemical exchange saturation transfer (CEST) MRI at 7.0 Tesla. Methods Thirty-one patients with newly diagnosed glioma were included in this prospective study. CEST MRI was performed at a 7T whole-body scanner. Nuclear Overhauser effect (NOE) and isolated amide proton transfer (APT; downfield NOE-suppressed APT = dns-APT) CEST signals (mean value and 90th signal percentile) were quantitatively investigated in the whole tumor area with regard to predictability of IDH mutation, MGMT promoter methylation status, and differentiation of LGG versus HGG. Statistics were performed using receiver operating characteristic (ROC) and area under the curve (AUC) analysis. Results were compared with advanced MRI methods (apparent diffusion coefficient and relative cerebral blood volume ROC/AUC analysis) obtained at 3T. Results dns-APT CEST yielded highest AUCs in IDH mutation status prediction (dns-APTmean = 91.84%, P < 0.01; dns-APT90 = 97.96%, P < 0.001). Furthermore, dns-APT metrics enabled significant differentiation of LGG versus HGG (AUC: dns-APTmean = 0.78, P < 0.05; dns-APT90 = 0.83, P < 0.05). There was no significant difference regarding MGMT promoter methylation status at any contrast (P > 0.05). Conclusions Relaxation-compensated multipool CEST MRI, particularly dns-APT imaging, enabled prediction of IDH mutation status and differentiation of LGG versus HGG and should therefore be considered as a non-invasive MR biomarker in the diagnostic workup.

Dual-frequency irradiation CEST-MRI of endogenous bulk mobile proteins

A novel MRI contrast is proposed which enables the selective detection of endogenous bulk mobile proteins in vivo. Such a non‐invasive imaging technique may be of particular interest for many diseases associated with pathological alterations of protein expression, such as cancer and neurodegenerative disorders. Specificity to mobile proteins was achieved by the selective measurement of intramolecular spin diffusion and the removal of semi‐solid macromolecular signal components by a correction procedure. For this purpose, the approach of chemical exchange saturation transfer (CEST) was extended to a radiofrequency (RF) irradiation scheme at two different frequency offsets (dualCEST). Using protein model solutions, it was demonstrated that the dualCEST technique allows the calculation of an image contrast which is exclusively sensitive to changes in concentration, molecular size and the folding state of mobile proteins. With respect to application in humans, dualCEST overcomes the selectivity limitations at relatively low magnetic field strengths, and thus enables examinations on clinical MR scanners. The feasibility of dualCEST examinations in humans was verified by a proof‐of‐principle examination of a brain tumor patient at 3 T. With its specificity for the mobile fraction of the proteome, its comparable sensitivity to conventional water proton MRI and its applicability to clinical MR scanners, this technique represents a further step towards the non‐invasive imaging of proteomic changes in humans.

Chemical exchange saturation transfer (CEST) signal intensity at 7T MRI of WHO IV° gliomas is dependent on the anatomic location: Location Dependency of CEST MRI

Chemical exchange saturation transfer (CEST) is a novel MRI technique applied to brain tumor patients.