Wybe J. M. van der Kemp

Quantitative 31P magnetic resonance spectroscopy of the human breast at 7 T

This study presents quantified levels of phosphorylated metabolites in glandular tissue of human breast using 31P magnetic resonance spectroscopy at 7 T. We used a homebuilt 1H/31P radiofrequency coil to obtain artifact‐free 31P MR spectra of glandular tissue of healthy females by deploying whole breast free induction decay (FID) detection with adiabatic excitation and outer volume suppression. Using progressive saturation, the estimated apparent T1 relaxation time of 31P spins of phosphocholine and phosphoethanolamine was 4.4 and 5.7 s, respectively. Quantitative measures for phosphocholine and phosphoethanolamine levels in glandular tissue were established based on MR imaging. We used a 3D 1H image of the breast to segment the glandular tissue; this was matched to a 3D 31P image of the B  1− field of the 31P coil to correct for differences in glandular tissue volume and B1 inhomogeneity of the 31P coil. The 31P MR spectra were calibrated using a phantom with known concentration. Average levels of phosphocholine and phosphoethanolamine in 11 volunteers were 0.84 ± 0.21 mM and 1.18 ± 0.41 mM, respectively. In addition, data of three patients with breast cancer showed higher levels of phosphocholine and phosphoethanolamine compared with healthy volunteers. This may indicate a potential role for the use of 31P magnetic resonance spectroscopy for characterization, prognosis, and treatment monitoring in breast cancer. Magn Reson Med, 2012.

Multiparametric MRI With Dynamic Contrast Enhancement, Diffusion-Weighted Imaging, and 31-Phosphorus Spectroscopy at 7 T for Characterization of Breast Cancer.

ObjectivesTo describe and to correlate tumor characteristics on multiparametric 7 tesla (T) breast magnetic resonance imaging (MRI) with prognostic characteristics from postoperative histopathology in patients with breast cancer. Materials and MethodsInstitutional review board approval and written informed consent of 15 women (46–70 years) with 17 malignant lesions were obtained. In this prospective study (March 2013 to March 2014), women were preoperatively scanned using dynamic contrast-enhanced MRI, diffusion-weighted imaging, and 31-phosphorus spectroscopy (31P-MRS). The value of the protocol was assessed to quantify tumor differentiation and proliferation. Dynamic contrast-enhanced MRI was assessed according to the American College of Radiology Breast Imaging Reporting and Data System-MRI lexicon. Apparent diffusion coefficients (ADCs) were calculated from diffusion-weighted imaging. On 31P-MRS, at the location of the tumor, the amount of phosphorus components was obtained in a localized spectrum. In this spectrum, the height of phosphodiester (PDE) and phosphomonoester (PME) peaks was assessed to serve as a measure for metabolic activity, stratifying tumors into a PDE > PME, PDE = PME, or PDE < PME group. Tumor grade and mitotic count from resection specimen were compared with the MRI characteristics using explorative analyses. ResultsOn dynamic contrast-enhanced MRI, the mean tumor size was 24 mm (range, 6–55 mm). An inverse trend was seen between ADC and tumor grade (P = 0.083), with mean ADC of 867 × 10−6 mm2/s for grade 1 (N = 4), 751 × 10−6 mm2/s for grade 2 (N = 6), and 659 × 10−6 mm2/s for grade 3 (N = 2) tumors. Between 31P-MR spectra and mitotic count, a relative increase of PME over PDE showed significant association with increasing mitotic counts (P = 0.02); a mean mitotic count of 6 was found in the PDE greater than PME group (N = 7), 8 in the PDE = PME group (N = 1), and 17 in the PDE < PME group (N = 3). ConclusionsMultiparametric 7 T breast MRI is feasible in clinical setting and shows association between ADC and tumor grade, and between 31P-MRS and mitotic count.

Radiofrequency configuration to facilitate bilateral breast 31P MR spectroscopic imaging and high-resolution MRI at 7 Tesla

High‐resolution MRI combined with phospholipid detection may improve breast cancer grading. Currently, configurations are optimized for either high‐resolution imaging or 31P spectroscopy. To be able to perform both imaging as well as spectroscopy in a single session, we integrated a 1H receiver array into a 1H‐31P transceiver at 7T. To ensure negligible signal loss due to coupling between elements, we investigated the use of a floating decoupling loop to enable bilateral MRI and 31P MRS.

31P MR spectroscopic imaging combined with 1H MR spectroscopic imaging in the human prostate using a double tuned endorectal coil at 7T

Improved diagnostic sensitivity could be obtained in cancer detection and staging when individual compounds of the choline pool can be detected. Therefore, a novel coil design is proposed, providing the ability to acquire both 1H and 31P magnetic resonance spectroscopic imaging (MRSI) in patients with prostate cancer.

Detection of alterations in membrane metabolism during neoadjuvant chemotherapy in patients with breast cancer using phosphorus magnetic resonance spectroscopy at 7 Tesla

Here we investigate the feasibility of tumor metabolism monitoring in T1c to T3 breast cancer during neoadjuvant chemotherapy by means of phosphorus (31P) magnetic resonance spectroscopy at 7 tesla (T). Five breast cancer patients were examined using a 31P MRSI sequence, prior to-, halfway-, and after neoadjuvant chemotherapy. The 31P MRSI data were analyzed on group and individual level and compared to a spectrum of a group of healthy volunteers. Ratios of phosphomonoesters (PME) to phosphodiesters (PDE) and phosphomonoesters to inorganic phosphate (Pi) were determined. Histopathologic assessment showed four partial responders and one complete responder to chemotherapy. The 31P spectrum of the patient group was distinctly different from the 31P spectrum of healthy volunteers and transformed its shape during the course of chemotherapy towards the shape of the spectrum of the healthy volunteers. Prior to chemotherapy the PME to PDE signal ratio and the PME to Pi signal ratio were high, and during the course of the chemotherapy these ratios normalized to the value of the healthy volunteers. Metabolite T2 values in tumor tissue tended to be lower than those for healthy glandular tissue. Assessment of individual patients showed that four out of five had a significant drop of the PME to Pi ratio by a factor of 2 or more. On average, the pH of the tumor, calculated from chemical shift variation of Pi, was 0.19 units lower before chemotherapy. We have demonstrated that the sensitivity of 31P MRSI in breast cancer at 7 T is sufficient to detect alterations in membrane metabolism during neoadjuvant chemotherapy, which may be used for early assessment of treatment efficacy.

1H/31P polarization transfer at 9.4 Tesla for improved specificity of detecting phosphomonoesters and phosphodiesters in breast tumor models.

Purpose To assess the ability of a polarization transfer (PT) magnetic resonance spectroscopy (MRS) technique to improve the detection of the individual phospholipid metabolites phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC), and glycerophosphoethanolamine (GPE) in vivo in breast tumor xenografts. Materials and Methods The adiabatic version of refocused insensitive nuclei enhanced by polarization transfer (BINEPT) MRS was tested at 9.4 Tesla in phantoms and animal models. BINEPT and pulse-acquire (PA) 31P MRS was acquired consecutively from the same orthotopic MCF-7 (n = 10) and MDA-MB-231 (n = 10) breast tumor xenografts. After in vivo MRS measurements, animals were euthanized, tumors were extracted and high resolution (HR)-MRS was performed. Signal to noise ratios (SNRs) and metabolite ratios were compared for BINEPT and PA MRS, and were also measured and compared with that from HR-MRS. Results BINEPT exclusively detected metabolites with 1H-31P coupling such as PC, PE, GPC, and GPE, thereby creating a significantly improved, flat baseline because overlapping resonances from immobile and partly mobile phospholipids were removed without loss of sensitivity. GPE and GPC were more accurately detected by BINEPT in vivo, which enabled a reliable quantification of metabolite ratios such as PE/GPE and PC/GPC, which are important markers of tumor aggressiveness and treatment response. Conclusion BINEPT is advantageous over PA for detecting and quantifying the individual phospholipid metabolites PC, PE, GPC, and GPE in vivo at high magnetic field strength. As BINEPT can be used clinically, alterations in these phospholipid metabolites can be assessed in vivo for cancer diagnosis and treatment monitoring.

MRI and 31P magnetic resonance spectroscopy hardware for axillary lymph node investigation at 7T

Neoadjuvant treatment response in lymph nodes predicts patient outcome, but existing methods do not track response during therapy accurately. In this study, specialized hardware was used to adapt high‐field (7T) 31P magnetic resonance spectroscopy (MRS), which has been shown to track treatment response in small breast tumors, to monitor axillary lymph nodes.

The melting properties of the earth alkaline oxides; thermodynamic analysis of the binary system (1-X)MgO+XCaO

Abstract A critical selection of the melting properties of the earth alkaline oxides available in literature was made. For magnesium oxide and calcium oxide this lead to melting temperatures of 3105 and 3172 K and entropies of fusion of 35.4 and 37.0 J·mol −1 ·K −1 respectively. Using this result and a selection of available phase diagram data, a thermodynamic analysis was made of the binary system (1− x ) MgO + xCaO . For the solid state this gave rise to: H E(sol) (x) kJ·mol −1 = x·(1−x)·[90.50 + 7.00·(1−2·x)] , S E(sol) (x) J·K −1 ·mol −1 = x·(1−x)·[13.62 − 2.09·(1−2·x)] and for the liquid state: G E(liq) (x) kJ·mol −1 =x·(1−x)·[ −21.4 + 23.4·(1−2·x)] .

Proton and phosphorus magnetic resonance spectroscopy of the healthy human breast at 7 T

In vivo water‐ and fat‐suppressed 1H magnetic resonance spectroscopy (MRS) and 31P magnetic resonance adiabatic multi‐echo spectroscopic imaging were performed at 7 T in duplicate in healthy fibroglandular breast tissue of a group of eight volunteers. The transverse relaxation times of 31P metabolites were determined, and the reproducibility of 1H and 31P MRS was investigated. The transverse relaxation times for phosphoethanolamine (PE) and phosphocholine (PC) were fitted bi‐exponentially, with an added short T2 component of 20 ms for adenosine monophosphate, resulting in values of 199 ± 8 and 239 ± 14 ms, respectively. The transverse relaxation time for glycerophosphocholine (GPC) was also fitted bi‐exponentially, with an added short T2 component of 20 ms for glycerophosphatidylethanolamine, which resonates at a similar frequency, resulting in a value of 177 ± 6 ms. Transverse relaxation times for inorganic phosphate, γ‐ATP and glycerophosphatidylcholine mobile phospholipid were fitted mono‐exponentially, resulting in values of 180 ± 4, 19 ± 3 and 20 ± 4 ms, respectively. Coefficients of variation for the duplicate determinations of 1H total choline (tChol) and the 31P metabolites were calculated for the group of volunteers. The reproducibility of inorganic phosphate, the sum of phosphomonoesters and the sum of phosphodiesters with 31P MRS imaging was superior to the reproducibility of 1H MRS for tChol. 1H and 31P data were combined to calculate estimates of the absolute concentrations of PC, GPC and PE in healthy fibroglandular tissue, resulting in upper limits of 0.1, 0.1 and 0.2 mmol/kg of tissue, respectively.

Glycerophosphocholine and Glycerophosphoethanolamine Are Not the Main Sources of the In Vivo (31)P MRS Phosphodiester Signals from Healthy Fibroglandular Breast Tissue at 7 T.

Purpose The identification of the phosphodiester (PDE) 31P MR signals in the healthy human breast at ultra-high field. Methods In vivo 31P MRS measurements at 7 T of the PDE signals in the breast were performed investigating the chemical shifts, the transverse- and the longitudinal relaxation times. Chemical shifts and transverse relaxation times were compared with non-ambiguous PDE signals from the liver. Results The chemical shifts of the PDE signals are shifted −0.5 ppm with respect to glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE), and the transverse and longitudinal relaxation times for these signals are a factor 3 to 4 shorter than expected for aqueous GPC and GPE. Conclusion The available experimental evidence suggests that GPC and GPE are not the main source of the PDE signals measured in fibroglandular breast tissue at 7 T. These signals may predominantly originate from mobile phospholipids.