Dennis W.J. Klomp

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.

Short echo time 1H‐MRSI of the human brain at 3T with minimal chemical shift displacement errors using adiabatic refocusing pulses

The chemical shift displacement error (CSDE) is an often‐underestimated problem in slice selection for localized proton spectroscopy at higher fields. With the proposed semi‐localized by adiabatic selective refocusing (LASER) pulse sequence, this problem is dealt with by using RF pulses with bandwidths in the order of 5 kHz. A combination of conventional nonadiabatic slice‐selective excitation of proton spins, together with double slice‐selective refocusing of the spins by two pairs of adiabatic full‐passage (APF) pulses, produces a spin echo in a volume of interest (VOI) at an echo time down to 30 ms. An illustration of the CSDE of conventional point‐resolved spectroscopy (PRESS) and the semi‐LASER sequence is shown with a measurement of the brain of a volunteer at 3T. With one application of the technique to a patient with a glioblastoma multiforme (GBM), its clinical functionality is demonstrated. With sharp selection profiles and a small CSDE, voxels close to the edge of the VOI can also be used for evaluation. With the additional advantage of being relatively insensitive for B1 inhomogeneities, the semi‐LASER technique can be viewed as a superior substitute for conventional PRESS MR spectroscopic imaging (MRSI) at 3T and beyond. Magn Reson Med, 2007.

Fast acquisition-weighted three-dimensional proton MR spectroscopic imaging of the human prostate.

The clinical application of 3D proton spectroscopic imaging (3D SI) of the human prostate requires a robust suppression of periprostatic lipid signal contamination, minimal intervoxel signal contamination, and the shortest possible measurement time. In this work, a weighted elliptical sampling of k‐space, combined with k‐space filtering and pulse repetition time (TR) reduction minimized lipid signals, intervoxel contamination, and measurement time. At 1.5 T, the MR‐visible prostate metabolites citrate, creatine, and choline can now be mapped over the entire human prostate with uncontaminated spherical voxels, with a volume down to 0.37 cm3, in measurement times of 7–15 min. Magn Reson Med 52:80–88, 2004.

Quantitative MR imaging of individual muscle involvement in facioscapulohumeral muscular dystrophy

The purpose of this study was to implement a quantitative MR imaging method for the determination of muscular and fat content in individual skeletal muscles of patients with facioscapulohumeral muscular dystrophy (FSHD). Turbo Inversion Recovery Magnitude (TIRM) and multiecho MR images were acquired from seven FSHD patients and healthy volunteers. Signal decay in the multiecho MR images was fitted to a biexponential function with fixed relaxation rates for muscle and fat tissue and used to calculate the degree of fatty infiltration in eight muscles in the lower leg. Considerable differences in fatty infiltration between different muscles were observed in FSHD patients, suggesting that this could be used as a biomarker for disease progression. TIRM imaging indicated an inflammatory component of the disease previously only observed in muscle biopsies. Typically, muscle involvement was non-uniform even within one muscle, indicating that MRI can be used as a valuable tool to study pathophysiology and therapy evaluation in FSHD.

Optimal timing for in vivo 1H-MR spectroscopic imaging of the human prostate at 3T.

Proton MR spectroscopic imaging (1H‐MRSI) of the human prostate, which has an interesting clinical potential, may be improved by increasing the magnetic field strength from 1.5T to 3T. Both theoretical and practical considerations are necessary to optimize the pulse timing for spectroscopic imaging of the human prostate at 3T. For in vivo detection of the strongly coupled spin system of citrate, not only should the spectral shape of the signal be easy to identify, but the timing used should produce MR signals at reasonably short echo times (TEs). In this study the spectral shape of the methylene protons of citrate was simulated with density matrix calculations and checked with phantom measurements. Different calculated optimal spectral shapes were measured in patients with prostate cancer with a 2D spectroscopic imaging sequence. T1 and T2 relaxation times were calculated for citrate and choline, the two major metabolites of interest in the prostate. We conclude that the optimum timing for in vivo point‐resolved spectroscopy (PRESS) imaging at 3T is an interpulse timing sequence of 90° ‐ 25 ms ‐ 180° ‐ 37.5 ms ‐ 180° ‐ 12.5 ms ‐ echo. A short repetition time (TR) of 750 ms partially saturates choline signals, but increases the SNR per unit time for citrate, and accommodates a maximum number of weighted averages of an elliptically sampled k‐space for accurate localization and minimal contamination of the individual spectra. This is illustrated by means of a 3D spectroscopic imaging experiment in a complete prostate in vivo. Magn Reson Med 53:1268–1274, 2005.

The fractionated dipole antenna: A new antenna for body imaging at 7 Tesla.

Dipole antennas in ultrahigh field MRI have demonstrated advantages over more conventional designs. In this study, the fractionated dipole antenna is presented: a dipole where the legs are split into segments that are interconnected by capacitors or inductors.

Sensitivity-enhanced 13C MR spectroscopy of the human brain at 3 Tesla†

A new coil design for sensitivity‐enhanced 13C MR spectroscopy (MRS) of the human brain is presented. The design includes a quadrature transmit/receive head coil optimized for 13C MR sensitivity. Loss‐less blocking circuits inside the coil conductors allow this coil to be used inside a homogeneous circularly polarized 1H B1 field for 1H decoupled 13C MRS. A quadrature 1H birdcage coil optimized for minimal local RF heating makes broadband 1H decoupling in the entire human brain possible at 3 Tesla while remaining well within international safety guidelines for RF absorption. Apart from a substantial increase in sensitivity compared to conventional small linear coils, the quadrature 13C coil combined with the quadrature 1H birdcage coil allows efficient cross polarization (CP) in the brain, resulting in an additional 3.5‐fold sensitivity improvement compared to direct 13C measurements without nuclear Overhauser enhancement (NOE) or polarization transfer. Combined with the gain in power efficiency, this setup allows broadband 1H to 13C CP over large areas of the brain. Clear 13C resonances from glutamate (Glu), glutamine (Gln), aspartate (Asp), lactate (Lac), and γ‐aminobutyrate (GABA) carbon spins in the human brain demonstrate the quality of 13C MR spectra obtained in vivo with this coil setup. Magn Reson Med, 2006.

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.

Proton MR spectroscopy of wild-type and creatine kinase deficient mouse skeletal muscle: Dipole–dipole coupling effects and post-mortem changes

Localized proton MR spectra of mouse skeletal muscle obtained at 7 T show dipole–dipole coupling effects for creatine and putative taurine resonances and for the lactate methine signal. These effects are independent of the presence of creatine kinase. The intensity of the methylene 1H resonance of creatine is not different between wild‐type and creatine kinase deficient mice, which have a lower phosphocreatine content. 1H‐MR spectra acquired post‐mortem from wild‐type mouse skeletal muscle parallel to B0 show a linewidth decrease for the methyl resonance of creatine and a 20% signal intensity loss for its methylene peak concurrent with the total breakdown of phosphocreatine as observed by 31P‐MR spectroscopy. However, with the muscle at the magic angle no changes in the appearance and intensity of creatine (and taurine) resonances are observed. These results indicate that the changes observed for creatine resonances are related to altered dipolar couplings and that the intensity of the methylene peak does not necessarily reflect muscular phosphocreatine content. Magn Reson Med 43:517–524, 2000.

High‐field MRS of the human brain at short TE and TR

In vivo MRS of the human brain at 7 tesla allows identification of a large number of metabolites at higher spatial resolutions than currently possible at lower field strengths. However, several challenges complicate in vivo localization and artifact suppression in MRS at high spatial resolution within a clinically feasible scan time at 7 tesla. Published MRS sequences at 7 tesla suffer from long echo times, inherent signal‐to‐noise ratio (SNR) loss, large chemical shift displacement artifacts or long repetition times because of excessive radiofrequency (RF) power deposition. In the present study a pulse‐acquire sequence was used that does not suffer from these high field drawbacks. A slice selective excitation combined with high resolution chemical shift imaging for in‐plane localization was used to limit chemical shift displacement artifacts. The pulse‐acquire approach resulted in a very short echo time of 1.4 ms. A cost function guided shimming algorithm was developed to constrain frequency offsets in the excited slice, therefore adiabatic frequency selective suppression could be employed to minimize artifacts from high intensity lipids and water signals in the excited slice. The high sensitivity at a TR of 1 s was demonstrated both on a supraventricular slice as well as in an area very close to the skull in the frontal cortex at a nominal spatial resolution of 0.25 cc within a feasible scan time. Copyright