Peter R. Luijten

Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS): features and potential applications in oncology

Diffusion-weighted magnetic resonance imaging (DWI) provides functional information and can be used for the detection and characterization of pathologic processes, including malignant tumors. The recently introduced concept of “diffusion-weighted whole-body imaging with background body signal suppression” (DWIBS) now allows acquisition of volumetric diffusion-weighted images of the entire body. This new concept has unique features different from conventional DWI and may play an important role in whole-body oncological imaging. This review describes and illustrates the basics of DWI, the features of DWIBS, and its potential applications in oncology.

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.

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.

Comparison and Reproducibility of ADC Measurements in Breathhold, Respiratory Triggered, and Free-Breathing Diffusion-Weighted MR Imaging of the Liver

To compare and determine the reproducibility of apparent diffusion coefficient (ADC) measurements of the normal liver parenchyma in breathhold, respiratory triggered, and free‐breathing diffusion‐weighted magnetic resonance imaging (DWI).

Subfields of the hippocampal formation at 7 T MRI: In vivo volumetric assessment

Animal and human autopsy studies suggest that subfields of the hippocampal formation are differentially affected by neuropsychiatric diseases. Therefore, subfield volumes may be more sensitive to effects of disease processes. The few human studies that segmented subfields of the hippocampal formation in vivo either assessed the subfields only in the body of the hippocampus, assessed only three subfields, or did not take the differential angulation of the head of the hippocampus into account. We developed a protocol using 7 Tesla MRI with isotropic voxels to reliably delineate the entorhinal cortex (ERC), subiculum (SUB), CA1, CA2, CA3, dentate gyrus (DG)&CA4 along the full-length of the hippocampus. Fourteen subjects (aged 54-74 years, 2 men and 12 women) were scanned with a 3D turbo spin echo (TSE) sequence with isotropic voxels of 0.7 × 0.7 × 0.7 mm(3) on a 7 T MRI whole body scanner. Based on previous protocols and extensive anatomic atlases, a new protocol for segmentation of subfields of the hippocampal formation was formulated. ERC, SUB, CA1, CA2, CA3 and DG&CA4 were manually segmented twice by one rater from coronal MR images. Good-to-excellent consistency was found for all subfields (Intraclass Correlation Coefficients (ICC) varying from 0.74 to 0.98). Accuracy as measured with the Dice Similarity Index (DSI) was above 0.82 for all subfields, with the exception of the smaller subfield CA3 (0.68-0.70). In conclusion, this study shows that it is possible to delineate the main subfields of the hippocampal formation along its full-length in vivo at 7 T MRI. Our data give evidence that this can be done in a reliable manner. Segmentation of subfields in the full-length of the hippocampus may bolster the study of the etiology neuropsychiatric diseases.

In vivo three-dimensional whole-brain pulsed steady-state chemical exchange saturation transfer at 7 T

Chemical exchange saturation transfer (CEST) is a technique to indirectly detect pools of exchangeable protons through the water signal. To increase its applicability to human studies, it is needed to develop sensitive pulse sequences for rapidly acquiring whole‐organ images while adhering to stringent amplifier duty cycle limitations and specific absorption rate restrictions. In addition, the interfering effects of direct water saturation and conventional magnetization transfer contrast complicate CEST quantification and need to be reduced as much as possible. It is shown that for protons exchanging with rates of less than 50–100 Hz, such as imaged in amide proton transfer experiments, these problems can be addressed by using a three‐dimensional steady state pulsed acquisition of limited B1 strength (∼1 μT). Such an approach exploits the fact that the direct water saturation width, magnetization transfer contrast magnitude, and specific absorption rate increase strongly with B1, while the size of the CEST effect for such protons depends minimally on B1. A short repetition time (65 ms) steady‐state sequence consisting of a brief saturation pulse (25 ms) and a segmented echo‐planar imaging train allowed acquisition of a three‐dimensional whole‐brain volume in approximately 11 s per saturation frequency, while remaining well within specific absorption rate and duty cycle limits. Magnetization transfer contrast was strongly reduced, but substantial saturation effects were found at frequencies upfield from water, which still confound the use of magnetization transfer asymmetry analysis. Fortunately, the limited width of the direct water saturation signal could be exploited to fit it with a Lorentzian function allowing CEST quantification. Amide proton transfer effects ranged between 1.5% and 2.5% in selected white and grey matter regions. This power and time‐efficient 3D pulsed CEST acquisition scheme should aid endogenous CEST quantification at both high and low fields. Magn Reson Med, 2011.

Clinical applications of 7 T MRI in the brain

This review illustrates current applications and possible future directions of 7 Tesla (7 T) Magnetic Resonance Imaging (MRI) in the field of brain MRI, in clinical studies as well as clinical practice. With its higher signal-to-noise (SNR) and contrast-to-noise ratio (CNR) compared to lower field strengths, high resolution, contrast-rich images can be obtained of diverse pathologies, like multiple sclerosis (MS), brain tumours, aging-related changes and cerebrovascular diseases. In some of these diseases, additional pathophysiological information can be gained compared to lower field strengths. Because of clear depiction of small anatomical details, and higher lesion conspicuousness, earlier diagnosis and start of treatment of brain diseases may become possible. Furthermore, additional insight into the pathogenesis of brain diseases obtained with 7 T MRI could be the basis for new treatment developments. However, imaging at high field comes with several limitations, like inhomogeneous transmit fields, a higher specific absorption rate (SAR) and, currently, extensive contraindications for patient scanning. Future studies will be aimed at assessing the advantages and disadvantages of 7 T MRI over lower field strengths in light of clinical applications, specifically the additional diagnostic and prognostic value of 7 T MRI.

In vivo detection of cerebral cortical microinfarcts with high-resolution 7T MRI

Cerebrovascular disease has an important role in cognitive decline and dementia. In this context, cerebral microinfarcts are attracting increasing attention, but these lesions could thus far not be detected in vivo. The aim of this study was to try to identify possible cortical microinfarcts on high-resolution 7T in vivo magnetic resonance imaging (MRI) and to perform a histopathologic validation study on similar appearing lesions on 7T ex vivo MRI of postmortem brain tissue. The study population consisted of 22 elderly subjects, who underwent 7T MRI. The fluid attenuated inversion recovery, T2, and T1 weighted scans of these subjects were examined for possible cortical microinfarcts. In the ex vivo MRI study, 15 formalin-fixed coronal brain slices of 6 subjects with Alzheimer and vascular pathology were examined and subjected to histopathologic verification. On the in vivo scans, 15 cortical lesions could be identified that were likely to be microinfarcts in 6 subjects. In the postmortem tissue, 6 similar appearing lesions were identified of which 5 were verified as cortical microinfarcts on histopathology. This study provides strong evidence that cortical microinfarcts can be detected in vivo, which will be of great value in further studies into the role of vascular disease in cognitive decline and dementia.

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

Whole-body diffusion-weighted magnetic resonance imaging

Diffusion-weighted magnetic resonance imaging (DWI) provides information on the diffusivity of water molecules in the human body. Technological advances and the development of the concept of diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) have opened the path for routine clinical whole-body DWI. Whole-body DWI allows detection and characterization of both oncological and non-oncological lesions throughout the entire body. This article reviews the basic principles of DWI and the development of whole-body DWI, illustrates its potential clinical applications, and discusses its limitations and challenges.