Dennis W. J. Klomp

Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of 1H-MRS Studies

Schizophrenia is a severe chronic psychiatric illness, characterized by hallucinations and delusions. Decreased brain volumes have been observed in the disease, although the origin of these changes is unknown. Changes in the n-methyl-d-aspartate (NMDA)-receptor mediated glutamatergic neurotransmission are implicated, since it is hypothesized that NMDA-receptor dysfunction in schizophrenia leads to increased glutamate release, which can have excitotoxic effects. However, the magnitude and extent of changes in glutamatergic metabolites in schizophrenia are not clear. With (1)H magnetic resonance spectroscopy ((1)H-MRS), in vivo information about glutamate and glutamine concentrations can be obtained in the brain. A systematic search through the MEDLINE database was conducted to identify relevant (1)H-MRS studies that examined differences in glutamate and glutamine concentrations between patients with schizophrenia and healthy control subjects. Twenty-eight studies were identified and included a total of 647 patients with schizophrenia and 608 healthy-control subjects. For each study, Cohens d was calculated and main effects for group analyses were performed using the random-effects model. Medial frontal region glutamate was decreased and glutamine was increased in patients with schizophrenia as compared with healthy individuals. Group-by-age associations revealed that in patients with schizophrenia, glutamate and glutamine concentrations decreased at a faster rate with age as compared with healthy controls. This could reflect aberrant processes in schizophrenia, such as altered synaptic activity, changed glutamate receptor functioning, abnormal glutamine-glutamate cycling, or dysfunctional glutamate transport.

Design of a radiative surface coil array element at 7 T:the single-side adapted dipole antenna

Ultra high field MR imaging (≥7 T) of deeply located targets in the body is facing some radiofrequency‐field related challenges: interference patterns, reduced penetration depth, and higher Specific Absorbtion Ratio (SAR) levels. These can be alleviated by redesigning the elements of the transmit or transceive array. This is because at these high excitation field (B1) frequencies, conventional array element designs may have become suboptimal. In this work, an alternative design approach is presented, regarding coil array elements as antennas. Following this approach, the Poynting vector of the element should be oriented towards the imaging target region. The single‐side adapted dipole antenna is a novel design that fulfills this requirement. The performance of this design as a transmit coil array element has been characterized by comparison with three other, more conventional designs using finite difference time domain (FDTD) simulations and B  +1 measurements on a phantom. Results show that the B  +1 level at the deeper regions is higher while maintaining relatively low SAR levels. Also, the B  +1 field distribution is more symmetrical and more uniform, promising better image homogeneity. Eight radiative antennas have been combined into a belt‐like surface array for prostate imaging. T1‐weighted (T1W) and T2‐weighted (T2W) volunteer images are presented along with B  +1 measurements to demonstrate the improved efficiency. Magn Reson Med, 2011.

31P MRSI and 1H MRS at 7 T: initial results in human breast cancer

This study demonstrates the feasibility of the noninvasive determination of important biomarkers of human (breast) tumor metabolism using high‐field (7‐T) MRI and MRS. 31P MRSI at this field strength was used to provide a direct method for the in vivo detection and quantification of endogenous biomarkers. These encompass phospholipid metabolism, phosphate energy metabolism and intracellular pH. A double‐tuned, dual‐element transceiver was designed with focused radiofrequency fields for unilateral breast imaging and spectroscopy tuned for optimized sensitivity at 7 T. T1‐weighted three‐dimensional MRI and 1H MRS were applied for the localization and quantification of total choline compounds. 31P MRSI was obtained within 20 min per subject and mapped in three dimensions over the breast with pixel volumes of 10 mL. The feasibility of monitoring in vivo metabolism was demonstrated in two patients with breast cancer during neoadjuvant chemotherapy, validated by ex vivo high‐resolution magic angle spinning NMR and compared with data from an age‐matched healthy volunteer. Concentrations of total choline down to 0.4 mM could be detected in the human breast in vivo. Levels of adenosine and other nucleoside triphosphates, inorganic phosphate, phosphocholine, phosphoethanolamine and their glycerol diesters detected in glandular tissue, as well as in tumor, were mapped over the entire breast. Altered levels of these compounds were observed in patients compared with an age‐matched healthy volunteer; modulation of these levels occurred in breast tumors during neoadjuvant chemotherapy. To our knowledge, this is the first comprehensive MRI and MRS study in patients with breast cancer, which reveals detailed information on the morphology and phospholipid metabolism from volumes as small as 10 mL. This endogenous metabolic information may provide a new method for the noninvasive assessment of prognostic and predictive biomarkers in breast cancer treatment. Copyright

B 1+ Phase mapping at 7 T and its application for in vivo electrical conductivity mapping

In this study, a new approach to measure local electrical conductivity in tissue is presented, which is based on the propagating B  1+ phase and the homogeneous Helmholtz equation. This new MRI technique might open future opportunities for tumor and lesion characterization based on conductivity differences, while it may also find application in radio frequency safety assessment. Prerequisites for conductivity mapping using only the B  1+ phase (instead of the complex B  +1 field) are addressed. Furthermore it was found that the B  1+ phase can be derived directly from the measurable transceive phase arg(B  +1 B  −1 ) in the head. Validation for a human head excited by a 7 T‐birdcage coil using simulations and measurements showed that it is possible to measure in vivo conductivity patterns in the brain using B  1+ phase information only. Conductivity contrast between different brain tissues is clearly observed. The measured mean values for white matter, gray matter and cerebrospinal fluid differed 54%, 26%, and −13% respectively from literature values. The proposed method for B  1+ phase measurements is very suited for in vivo applications, as the measurement is short (less than a minute per imaged slice) and exposes the patient to low RF power, contrary to earlier proposed approaches. Magn Reson Med, 2012.

Feasibility of 7 Tesla breast magnetic resonance imaging determination of intrinsic sensitivity and high-resolution magnetic resonance imaging, diffusion-weighted imaging, and 1H-magnetic resonance spectroscopy of breast cancer patients receiving neoadjuvant therapy

Objectives:To evaluate the feasibility of 7T breast magnetic resonance imaging (MRI) by determining the intrinsic sensitivity gain compared with 3T in healthy volunteers and to explore clinical application of 7T MRI in breast cancer patients receiving neoadjuvant chemotherapy (NAC). Materials and Methods:In 5 volunteers, the signal-to-noise ratio (SNR) was determined on proton density MRI at 3T using a conventional 4-channel bilateral breast coil and at 7T using a dedicated 2-channel unilateral breast coil, both obtained at identical scan parameters. Subsequently, consecutive breast cancer patients on NAC were included. The 7T breast MRI protocol consisted of diffusion-weighted imaging, 3D high-resolution (450 &mgr;m isotropic) T1-weighted fat-suppressed gradient-echo sequences and quantified single voxel 1H-magnetic resonance spectroscopy. Morphology was scored according to the MRI Breast Imaging-Reporting and Data System (BI-RADS)-lexicon, and the images were compared with 3T and histopathologic findings. Image quality was evaluated using a 5-point scale. Results:A 5.7-fold higher SNR was measured at 7T than at 3T, which reflects the advantages of a higher field strength and the use of optimized radiofrequency coils. Three breast cancer patients were included and received a total of 13 7T MRI examinations. The image quality of the high-resolution examinations was at least satisfactory, and good to excellent in 9 of the 13 examinations performed. More anatomic detail was depicted at 7T than at 3T. In 1 case, a fat plane between the muscle and tumor was visible at 7T, but not at the clinically performed 3T examination, suggesting that there was no muscle invasion, which was confirmed by pathology. Changes in tumor apparent diffusion coefficient values could be monitored in 2 patients and were found to increase during NAC, consistent with published results from studies at lower field strengths. Apparent diffusion coefficient values increased respectively from 0.33 × 10−3 mm2/s to 1.78 × 10−3 mm2/s after NAC and from 1.20 × 10−3 mm2/s to 1.44 × 10−3 mm2/s during NAC. Choline concentrations as low as 0.77 mMol/kgwater could be detected. In 1 patient, choline levels showed an overall decrease from 4.2 mMol/kwwater to 2.6 mMol/kgwater after NAC and the tumor size decreased correspondingly from 3.9 × 4.1 × 5.6 cm3 to 2.0 × 2.7 × 2.4 cm3. All 7T MRI findings were consistent with pathology analysis. Conclusion:Dedicated 7T breast MRI is technically feasible, can provide more SNR than at 3T, and has diagnostic potential.

GABA and glutamate in schizophrenia: A 7 T 1H-MRS study

Schizophrenia is characterized by loss of brain volume, which may represent an ongoing pathophysiological process. This loss of brain volume may be explained by reduced neuropil rather than neuronal loss, suggesting abnormal synaptic plasticity and cortical microcircuitry. A possible mechanism is hypofunction of the NMDA-type of glutamate receptor, which reduces the excitation of inhibitory GABAergic interneurons, resulting in a disinhibition of glutamatergic pyramidal neurons. Disinhibition of pyramidal cells may result in excessive stimulation by glutamate, which in turn could cause neuronal damage or death through excitotoxicity. In this study, GABA/creatine ratios, and glutamate, NAA, creatine and choline concentrations in the prefrontal and parieto-occipital cortices were measured in 17 patients with schizophrenia and 23 healthy controls using proton magnetic resonance spectroscopy at an ultra-high magnetic field strength of 7 T. Significantly lower GABA/Cr ratios were found in patients with schizophrenia in the prefrontal cortex as compared to healthy controls, with GABA/Cr ratios inversely correlated with cognitive functioning in the patients. No significant change in the GABA/Cr ratio was found between patients and controls in the parieto-occipital cortex, nor were levels of glutamate, NAA, creatine, and choline differed in patients and controls in the prefrontal and parieto-occipital cortices. Our findings support a mechanism involving altered GABA levels distinguished from glutamate levels in the medial prefrontal cortex in schizophrenia, particularly in high functioning patients. A (compensatory) role for GABA through altered inhibitory neurotransmission in the prefrontal cortex may be ongoing in (higher functioning) patients with schizophrenia.

A meta-analysis of the polyunsaturated fatty acid composition of erythrocyte membranes in schizophrenia

BACKGROUND Membrane abnormalities in polyunsaturated fatty acids (PUFAs) have been reported in schizophrenia and have been associated with brain tissue loss in normal ageing. Therefore PUFA may be involved in the excessive brain tissue loss reported in schizophrenia. METHODS A systematic MEDLINE database search was conducted to identify studies that compared PUFAs in erythrocyte membranes in patients and controls. Patients were categorized by medication regime in medication naive first-episode patients, and patients receiving typical or atypical antipsychotics. SAMPLE Fourteen studies were included, comprising a total of 429 patients with schizophrenia and 444 healthy control subjects. Cohens d effect sizes were calculated for PUFAs in erythrocyte membranes using the random-effects model. Combined Cohens d was calculated separately for patients on different medication regime. RESULTS Medication-naive patients and patients taking typical antipsychotics showed significantly (p<0.01) decreased concentrations of arachidonic (AA), docosahexaenoic (DHA), and docosapentaenoic (DPA) acid. In addition, patients taking typical antipsychotics showed decreased linoleic (LA), dihomo-γ-linolenic acid (DGLA), eicosapentaenoic (EPA) and docosatetraenoic (DTA) acid (p<0.01). Patients taking atypical antipsychotics showed decreased DHA (p<0.01) only. CONCLUSIONS PUFA concentrations in erythrocyte membranes are decreased in schizophrenia. Of particular importance in patients are lower concentrations of DHA and AA, two fatty acids that are abundant in the brain and important precursors in the cell-signalling cascade.

SAR and power implications of different RF shimming strategies in the pelvis for 7T MRI

To determine the best radiofrequency (RF) shimming method for 7 T body imaging that provides sufficient B1+ excitation inside the target region while energy deposition (SAR) and power demands are as low as possible and that does not incorporate anatomy specific electric field information inside the patient models, as this information is not available in practice.

Direct B0 field monitoring and real-time B0 field updating in the human breast at 7 Tesla

Large dynamic fluctuations of the static magnetic field (B0) are observed in the human body during MR scanning, compromising image quality and detection sensitivity in several MR imaging and spectroscopy sequences. Partially, these dynamic B0 fluctuations are due to physiological motion such as breathing, but other sources of temporal B0 field fluctuations are also present in the MR system (e.g., eddy currents). Especially at ultrahigh field (≥7 T), the increased susceptibility effects lead to large B0 field variations over time. Direct measurement and correction of these temporal field variations of up to 70 Hz will lead to a significant reduction of artifacts and improved measurement stability/reproducibility. For direct measurement of the temporally changing B0 field, a simple field probe was developed, that was placed in proximity to the tissue of interest. In this work, it is shown how such a field probe system can be used to monitor temporal B0 field variations in the human body during MRI and magnetic resonance spectroscopy. Furthermore, it is shown how the acquired temporal B0 field information can drive a dynamic shim module to directly correct the B0 magnetic field in real time. Magn Reson Med, 2012.

7-T 1H MRS with adiabatic refocusing at short TE using radiofrequency focusing with a dual-channel volume transmit coil

In vivo MRS of the human brain at ultrahigh field allows for the identification of a large number of metabolites at higher spatial resolutions than currently possible in clinical practice. However, the in vivo localization of single‐voxel spectroscopy has been shown to be challenging at ultrahigh field because of the low bandwidth of refocusing radiofrequency (RF) pulses. Thus far, the proposed methods for localized MRS at 7 T suffer from long TE, inherent signal loss and/or a large chemical shift displacement artifact that causes a spatial displacement between resonances, and results in a decreased efficiency in editing sequences. In this work, we show that, by driving a standard volume coil with two RF amplifiers, focusing the B  1+ field in a certain location and using high‐bandwidth adiabatic refocusing pulses, a semi‐LASER (semi‐localized by adiabatic selective refocusing) localization is feasible at short TE in the human brain with full signal acquisition and a low chemical shift displacement artifact at 7 T. Copyright