Amide proton transfer weighted imaging in pediatric neuro-oncology:initial experience

Amide proton transfer weighted (APTw) imaging enables in vivo assessment of tissue-bound mobile proteins and peptides through the detection of chemical exchange saturation transfer. Promising applications of APTw imaging have been shown in adult brain tumors. As pediatric brain tumors differ from their adult counterparts, we investigate the radiological appearance of pediatric brain tumors on APTw imaging. APTw imaging was conducted at 3 T. APTw maps were calculated using magnetization transfer ratio asymmetry at 3.5 ppm. First, the repeatability of APTw imaging was assessed in a phantom and in five healthy volunteers by calculating the within-subject coefficient of variation (wCV). APTw images of pediatric brain tumor patients were analyzed retrospectively. APTw levels were compared between solid tumor tissue and normal-appearing white matter (NAWM) and between pediatric high-grade glioma (pHGG) and pediatric low-grade glioma (pLGG) using t-tests. APTw maps were repeatable in supratentorial and infratentorial brain regions (wCV ranged from 11% to 39%), except those from the pontine region (wCV between 39% and 50%). APTw images of 23 children with brain tumor were analyzed (mean age 12 years ± 5, 12 male). Significantly higher APTw values are present in tumor compared with NAWM for both pHGG and pLGG (p &lt; 0.05). APTw values were higher in pLGG subtype pilocytic astrocytoma compared with other pLGG subtypes (p &lt; 0.05). Non-invasive characterization of pediatric brain tumor biology with APTw imaging could aid the radiologist in clinical decision-making.</p

Cortical glutamate and gamma-aminobutyric acid over the course of a provoked migraine attack, a 7 Tesla magnetic resonance spectroscopy study

Enhanced activity of the glutamatergic system has been linked to migraine pathophysiology. The present study aimed to assess the involvement of the glutamatergic system in the onset of attacks. We provoked attacks by infusion of glyceryl trinitrate (GTN; 0.5 µg/kg/min over 20 min) in 24 female episodic migraineurs without aura and 13 female age-matched healthy controls. Over the course of a single day participants were scanned three times at fixed time slots (baseline before GTN infusion, 90 min and 270 min after start of GTN infusion). Single-volume proton magnetic resonance spectra (1H–MRS) were acquired at 7 Tesla from a volume of interest (VOI, 2x2x3 cm) in the visual cortex. We assessed the concentrations of glutamate, its major precursor glutamine, and its product gamma-aminobutyric acid (GABA) over the course of a provoked attack. The preictal state was defined as the period after GTN infusion until the migraine-like headache started, independent of possible experienced premonitory symptoms, and the ictal state was defined as the period with provoked migraine-like headache. Data were analyzed using a linear mixed-effect model for repeated measures. Glutamate and glutamine levels did not change from interictal to the preictal and ictal state. GABA levels increased from interictal towards the preictal state for migraine patients compared with healthy controls. We conclude that high resolution 7T MRS is able to show changes in the glutamatergic system towards a triggered migraine attack, by revealing an increased GABA concentration associated with the onset of a migraine attack

Advanced intraoperative MRI in pediatric brain tumor surgery

Introduction: In the pediatric brain tumor surgery setting, intraoperative MRI (ioMRI) provides “real-time” imaging, allowing for evaluation of the extent of resection and detection of complications. The use of advanced MRI sequences could potentially provide additional physiological information that may aid in the preservation of healthy brain regions. This review aims to determine the added value of advanced imaging in ioMRI for pediatric brain tumor surgery compared to conventional imaging.Methods: Our systematic literature search identified relevant articles on PubMed using keywords associated with pediatrics, ioMRI, and brain tumors. The literature search was extended using the snowball technique to gather more information on advanced MRI techniques, their technical background, their use in adult ioMRI, and their use in routine pediatric brain tumor care.Results: The available literature was sparse and demonstrated that advanced sequences were used to reconstruct fibers to prevent damage to important structures, provide information on relative cerebral blood flow or abnormal metabolites, or to indicate the onset of hemorrhage or ischemic infarcts. The explorative literature search revealed developments within each advanced MRI field, such as multi-shell diffusion MRI, arterial spin labeling, and amide-proton transfer-weighted imaging, that have been studied in adult ioMRI but have not yet been applied in pediatrics. These techniques could have the potential to provide more accurate fiber tractography, information on intraoperative cerebral perfusion, and to match gadolinium-based T1w images without using a contrast agent.Conclusion: The potential added value of advanced MRI in the intraoperative setting for pediatric brain tumors is to prevent damage to important structures, to provide additional physiological or metabolic information, or to indicate the onset of postoperative changes. Current developments within various advanced ioMRI sequences are promising with regard to providing in-depth tissue information

31P T2s of phosphomonoesters, phosphodiesters, and inorganic phosphate in the human brain at 7T

Purpose: To determine the phosphorus-31 T2s of phosphomonoesters, phosphodiesters, and inorganic phosphate in the healthy human brain at 7T. Methods: A 3D chemical shift imaging multi-echo sequence with composite block pulses for refocusing was used to measure one free induction decay (FID) and seven full echoes with an echo spacing of 45 ms on the brain of nine healthy volunteers (age range 22–45 years; average age 27 ± 8 years). Spectral fitting was used to determine the change in metabolic signal amplitude with echo time. Results: The average apparent T2s with their standard deviation were 202 ± 6 ms, 129 ± 6 ms, 86 ± 2 ms, 214 ± 10 ms, and 213 ± 11 ms for phosphoethanolamine, phosphocholine, inorganic phosphate, glycerophosphoethanolamine, and glycerophosphocholine, respectively. Conclusion: The determined apparent T2 for phosphoethanolamine, glycerophosphocholine, and glycerophosphoethanolamine is approximately 200 ms. The lower apparent T2 value for phosphocholine is attributed to the overlap of this resonance with the 3-phosphorous resonance of 2,3-diphosphoglycerate from blood, with an apparent shorter T2. Omitting the FID signal and the first echo of phosphocholine leads to a T2 of 182 ± 7 ms, whereas a biexponential analysis leads to 203 ± 4 ms. These values are more in line with phosphoethanolamine and the phosphodiesters. The short T2 of inorganic phosphate is subscribed to the fast reversible exchange with γ-adenosine triphosphate, which is mediated by glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase within the glycolytic pathway. Magn Reson Med 80:29–35, 2018

Molecular causes of elevated phosphoethanolamine in breast and pancreatic cancer cells

Elevated phosphoethanolamine (PE) is frequently observed in MRS studies of human cancers and xenografts. The role of PE in cell survival and the molecular causes underlying this increase are, however, relatively underexplored. In this study, we investigated the roles of ethanolamine kinases (Etnk-1 and 2) and choline kinases (Chk-α and β) in contributing to increased PE in human breast and pancreatic cancer cells. We investigated the effect of silencing Etnk-1 and Etnk-2 on cell viability as a potential therapeutic strategy. Both breast and pancreatic cancer cells showed higher PE compared with their nonmalignant counterparts. We identified Etnk-1 as a major cause of the elevated PE levels in these cancer cells, with little or no contribution from Chk-α, Chk-β, or Etnk-2. The increase of PE observed in pancreatic cancer cells in culture was replicated in the corresponding tumor xenografts. Downregulation of Etnk-1 with siRNA resulted in cell cytotoxicity that correlated with PE levels in breast and pancreatic cancer cells. Etnk-1 may provide a potential therapeutic target in breast and pancreatic cancers

Molecular causes of elevated phosphoethanolamine in breast and pancreatic cancer cells

Elevated phosphoethanolamine (PE) is frequently observed in MRS studies of human cancers and xenografts. The role of PE in cell survival and the molecular causes underlying this increase are, however, relatively underexplored. In this study, we investigated the roles of ethanolamine kinases (Etnk-1 and 2) and choline kinases (Chk-α and β) in contributing to increased PE in human breast and pancreatic cancer cells. We investigated the effect of silencing Etnk-1 and Etnk-2 on cell viability as a potential therapeutic strategy. Both breast and pancreatic cancer cells showed higher PE compared with their nonmalignant counterparts. We identified Etnk-1 as a major cause of the elevated PE levels in these cancer cells, with little or no contribution from Chk-α, Chk-β, or Etnk-2. The increase of PE observed in pancreatic cancer cells in culture was replicated in the corresponding tumor xenografts. Downregulation of Etnk-1 with siRNA resulted in cell cytotoxicity that correlated with PE levels in breast and pancreatic cancer cells. Etnk-1 may provide a potential therapeutic target in breast and pancreatic cancers

Tailored spiral in-out spectral-spatial water suppression pulses for magnetic resonance spectroscopic imaging

PURPOSE: To develop short water suppression sequences for 7 T magnetic resonance spectroscopic imaging, with mitigation of subject-specific transmit RF field ( B1+) inhomogeneity. METHODS: Patient-tailored spiral in-out spectral-spatial saturation pulses were designed for a three-pulse WET water suppression sequence. The pulses' identical spatial subpulses were designed using patient-specific B1+ maps and a spiral in-out excitation k-space trajectory. The subpulse train was weighted by a spectral envelope that was root-flipped to minimize peak RF demand. The pulses were validated in in vivo experiments that acquired high resolution magnetic resonance spectroscopic imaging data, using a crusher coil for fast lipid suppression. Residual water signals and MR spectra were compared between the proposed tailored sequence and a conventional WET sequence. RESULTS: Replacing conventional spectrally-selective pulses with tailored spiral in-out spectral-spatial pulses reduced mean water residual from 5.88 to 2.52% (57% improvement). Pulse design time was less then 0.4 s. The pulses' specific absorption rate were compatible with magnetic resonance spectroscopic imaging TRs under 300 ms, which enabled spectra of fine in plane spatial resolution (5 mm) with good quality to be measured in 7.5 min. CONCLUSION: Tailored spiral in-out spectral-spatial water suppression enables efficient high resolution magnetic resonance spectroscopic imaging in the brain. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine

Homogeneous B1 + for bilateral breast imaging at 7 T using a five dipole transmit array merged with a high density receive loop array

To explore the use of five meandering dipole antennas in a multi-transmit setup, combined with a high density receive array for breast imaging at 7 T for improved penetration depth and more homogeneous B1 field. Five meandering dipole antennas and 30 receiver loops were positioned on two cups around the breasts. Finite difference time domain simulations were performed to evaluate RF safety limits of the transmit setup. Scattering parameters of the transmit setup and coupling between the antennas and the detuned loops were measured. In vivo parallel imaging performance was investigated for various acceleration factors. After RF shimming, a B1 map, a T1-weighted image, and a T2-weighted image were acquired to assess B1 efficiency, uniformity in contrast weighting, and imaging performance in clinical applications. The maximum achievable local SAR10g value was 7.0 W/kg for 5 × 1 W accepted power. The dipoles were tuned and matched to a maximum reflection of −11.8 dB, and a maximum inter-element coupling of −14.2 dB. The maximum coupling between the antennas and the receive loops was −18.2 dB and the mean noise correlation for the 30 receive loops 7.83 ± 8.69%. In vivo measurements showed an increased field of view, which reached to the axilla, and a high transmit efficiency. This coil enabled the acquisition of T1-weighted images with a high spatial resolution of 0.7 mm3 isotropic and T2-weighted spin echo images with uniformly weighted contrast

Homogeneous B\u3csub\u3e1\u3c/sub\u3e\u3csup\u3e+\u3c/sup\u3e for bilateral breast imaging at 7 T using a five dipole transmit array merged with a high density receive loop array

\u3cp\u3eTo explore the use of five meandering dipole antennas in a multi-transmit setup, combined with a high density receive array for breast imaging at 7 T for improved penetration depth and more homogeneous B\u3csub\u3e1\u3c/sub\u3e field. Five meandering dipole antennas and 30 receiver loops were positioned on two cups around the breasts. Finite difference time domain simulations were performed to evaluate RF safety limits of the transmit setup. Scattering parameters of the transmit setup and coupling between the antennas and the detuned loops were measured. In vivo parallel imaging performance was investigated for various acceleration factors. After RF shimming, a B\u3csub\u3e1\u3c/sub\u3e map, a T\u3csub\u3e1\u3c/sub\u3e-weighted image, and a T\u3csub\u3e2\u3c/sub\u3e-weighted image were acquired to assess B\u3csub\u3e1\u3c/sub\u3e efficiency, uniformity in contrast weighting, and imaging performance in clinical applications. The maximum achievable local SAR\u3csub\u3e10g\u3c/sub\u3e value was 7.0 W/kg for 5 × 1 W accepted power. The dipoles were tuned and matched to a maximum reflection of −11.8 dB, and a maximum inter-element coupling of −14.2 dB. The maximum coupling between the antennas and the receive loops was −18.2 dB and the mean noise correlation for the 30 receive loops 7.83 ± 8.69%. In vivo measurements showed an increased field of view, which reached to the axilla, and a high transmit efficiency. This coil enabled the acquisition of T\u3csub\u3e1\u3c/sub\u3e-weighted images with a high spatial resolution of 0.7 mm\u3csup\u3e3\u3c/sup\u3e isotropic and T\u3csub\u3e2\u3c/sub\u3e-weighted spin echo images with uniformly weighted contrast.\u3c/p\u3