Multimodal, Longitudinal Profiling of SCA1 Identifies Predictors of Disease Severity and Progression.

Objectives: Spinocerebellar ataxia type 1 (SCA1) is a rare autosomal dominant neurodegenerative disease. Objective surrogate markers sensitive to detect changes in disease severity are needed to reduce sample sizes in interventional trials and identification of predictors of faster disease progression would facilitate patient selection, enrichment, or stratification in such trials.

Methods: We performed a prospective 1-year longitudinal, multimodal study in 34 ataxic SCA1 individuals and 21 healthy controls.

Diffusion-weighted MR spectroscopy of the prostate.

Purpose: Prostate tissue has a complex microstructure, mainly composed of epithelial and stromal cells, and of extracellular (acinar-luminal) spaces. Diffusion-weighted MR spectroscopy (DW-MRS) is ideally suited to explore complex microstructure in vivo with metabolites selectively distributed in different subspaces. To date, this technique has been applied to brain and muscle.

The Potential of Iron Oxide Nanoparticle-Enhanced MRI at 7 T Compared With 3 T for Detecting Small Suspicious Lymph Nodes in Patients With Prostate Cancer.

Background: Accurate detection of lymph node (LN) metastases in prostate cancer (PCa) is a challenging but crucial step for disease staging. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) enables distinction between healthy LNs and nodes suspicious for harboring metastases. When combined with MRI at an ultra-high magnetic field, an unprecedented spatial resolution can be exploited to visualize these LNs.

Post-acquisition water-signal removal in 3D water-unsuppressed H-MR spectroscopic imaging of the prostate.

Purpose: To develop a robust processing procedure of raw signals from water-unsuppressed MRSI of the prostate for the mapping of absolute tissue concentrations of metabolites.

Methods: Water-unsuppressed 3D MRSI data were acquired from a phantom, from healthy volunteers, and a patient with prostate cancer. Signal processing included sequential computation of the modulus of the FID to remove water sidebands, a Hilbert transformation, and k-space Hamming filtering.

Effect of lactate administration on cerebral blood flow during hypoglycemia in people with type 1 diabetes.

Introduction: Impaired awareness of hypoglycemia, clinically reflected by the inability to timely detect hypoglycemia, affects approximately 25% of the people with type 1 diabetes. Both altered brain lactate handling and increased cerebral blood flow (CBF) during hypoglycemia appear to be involved in the pathogenesis of impaired awareness of hypoglycemia. Here we examine the effect of lactate on CBF during hypoglycemia.

GABAergic changes in the thalamocortical circuit in Parkinson's disease.

Parkinson's disease is characterized by bradykinesia, rigidity, and tremor. These symptoms have been related to an increased gamma-aminobutyric acid (GABA)ergic inhibitory drive from globus pallidus onto the thalamus. However, in vivo empirical evidence for the role of GABA in Parkinson's disease is limited.

Distinct associations between fronto-striatal glutamate concentrations and callous-unemotional traits and proactive aggression in disruptive behavior.

Disruptive behavior is associated with societally and personally problematic levels of aggression and has been linked to abnormal structure and function of fronto-amygdala-striatal regions. Abnormal glutamatergic signalling within this network may play a role in aggression. However, disruptive behavior does not represent a homogeneous construct, but can be fractionated across several dimensions.

A comparison of sLASER and MEGA-sLASER using simultaneous interleaved acquisition for measuring GABA in the human brain at 7T.

γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter, is challenging to measure using proton spectroscopy due to its relatively low concentration, J-coupling and overlapping signals from other metabolites. Currently, the prevalent methods for detecting GABA at ultrahigh field strengths (≥ 7 T) are GABA-editing and model fitting of non-editing single voxel spectra. These two acquisition approaches have their own advantages: the GABA editing approach directly measures the GABA resonance at 3 ppm, whereas the fitting approach on the non-editing spectrum allows the detection of multiple metabolites, and has an SNR advantage over longer echo time (TE) acquisitions.

Effect of linewidth on estimation of metabolic concentration when using water lineshape spectral model fitting for single voxel proton spectroscopy at 7 T.

Good B field homogeneity is considered an essential requirement to obtain high-quality MRS data. Many commonly used spectral fitting methods assume that all metabolite signals have Lorentzian or Gaussian shapes. However, B inhomogeneity can both broaden the linewidth and modify the lineshape.

Elevated brain glutamate levels in type 1 diabetes: correlations with glycaemic control and age of disease onset but not with hypoglycaemia awareness status.

Aims/hypothesis: Chronic hyperglycaemia in type 1 diabetes affects the structure and functioning of the brain, but the impact of recurrent hypoglycaemia is unclear. Changes in the neurochemical profile have been linked to loss of neuronal function. We therefore aimed to investigate the impact of type 1 diabetes and burden of hypoglycaemia on brain metabolite levels, in which we assumed the burden to be high in individuals with impaired awareness of hypoglycaemia (IAH) and low in those with normal awareness of hypoglycaemia (NAH).

Levels of choline-containing compounds in normal liver and liver metastases of colorectal cancer as recorded by H MRS.

Purpose: A relatively high signal for choline-containing compounds (total choline, tCho) is commonly found in H MR spectra of malignant tumors, but it is unclear if this also occurs in tumors in the liver. We evaluated the potential of the tCho signal in single voxel H MR spectra of the human liver to assess metastases of colorectal cancers.

Experiment: MR spectra of an 8 cm PRESS-localized voxel were obtained at 3 T from the livers of 12 healthy volunteers and from metastatic lesions in 20 patients in two different sessions.

Implications of the magnetic susceptibility difference between grey and white matter for single-voxel proton spectroscopy at 7 T.

Magnetic susceptibility differences between grey matter (GM) and white matter (WM) can potentially affect lineshapes and chemical shifts in single-voxel spectroscopy. This study aimed to investigate the consequences and potential utility of these effects. Spectroscopy voxels were segmented into GM, WM, and cerebrospinal fluid based on T-weighted images.

Increased levels of choline metabolites are an early marker of docetaxel treatment response in BRCA1-mutated mouse mammary tumors: an assessment by ex vivo proton magnetic resonance spectroscopy.

Background: Docetaxel is one of the most frequently used drugs to treat breast cancer. However, resistance or incomplete response to docetaxel is a major challenge. The aim of this study was to utilize MR metabolomics to identify potential biomarkers of docetaxel resistance in a mouse model for BRCA1-mutated breast cancer.

Improved volume selective (1) H MR spectroscopic imaging of the prostate with gradient offset independent adiabaticity pulses at 3 tesla.

Purpose: Volume selection in (1) H MR spectroscopic imaging (MRSI) of the prostate is commonly performed with low-bandwidth refocusing pulses. However, their large chemical shift displacement error (CSDE) causes lipid signal contamination in the spectral range of interest. Application of high-bandwidth adiabatic pulses is limited by radiofrequency (RF) power deposition.

Dietary lipids do not contribute to the higher hepatic triglyceride levels of fructose- compared to glucose-fed mice.

Fructose consumption has been associated with the surge in obesity and dyslipidemia. This may be mediated by the fructose effects on hepatic lipids and ATP levels. Fructose metabolism provides carbons for de novo lipogenesis (DNL) and stimulates enterocyte secretion of apoB48.

In vivo (1) H MR spectroscopic imaging of aggressive prostate cancer: can we detect lactate?

Purpose: A semi-LASER sequence was optimized for in vivo lactate detection in the prostate.

Methods: The ethical committee waived the need for informed consent to measure 17 patients with high grade prostate cancer on a 3T system. A semi-LASER sequence was used with an echo time of 144 ms and optimized interpulse timing for a spectral citrate shape with high signal intensity.

Factors affecting the unexpected failure of DCE-MRI to determine the optimal biological dose of the vascular targeting agent NGR-hTNF in solid cancer patients.

Introduction: To understand which factors could affect the assessment of anti-vascular treatment by DCE-MRI, we investigated possible causes that could have hampered the selection of an optimal biological dose in humans of the vascular targeted agent NGR-hTNF by DCE-MRI: (1) insufficient reproducibility of DCE-MRI; (2) less specific targeting of NGR-hTNF; (3) interference of vessel characteristics with NGR-hTNF efficacy; (4) interfering pharmacodynamic effects.

Experimental: In a phase I study NGR-hTNF, DCE-MRI was performed at baseline and 2 h after NGR-hTNF administration in 31 patients with advanced solid cancer. Reproducibility measurements were performed in 5 other non-treated patients with metastatic disease.

Phase I clinical and magnetic resonance imaging study of the vascular agent NGR-hTNF in patients with advanced cancers (European Organization for Research and Treatment of Cancer Study 16041).

Purpose: This phase I trial investigating the vascular targeting agent NGR-hTNF aimed to determine the (a) dose-limiting toxicities, (b) maximum tolerated dose (MTD), (c) pharmacokinetics and pharmacodynamics, (d) vascular response by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and (e) preliminary clinical activity in solid tumors.

Experimental Design: NGR-hTNF was administered once every 3 weeks by a 20- to 60-minute i.v.

Short echo time 1H MRSI of the human brain at 3T with adiabatic slice-selective refocusing pulses; reproducibility and variance in a dual center setting.

Purpose: To assess the reproducibility of (1)H-MR spectroscopic imaging (MRSI) of the human brain at 3T with volume selection by a double spin echo sequence for localization with adiabatic refocusing pulses (semi-LASER).

Materials And Methods: Twenty volunteers in two different institutions were measured twice with the same pulse sequence at an echo time of 30 msec. Magnetic resonance (MR) spectra were analyzed with LCModel with a simulated basis set including an experimentally acquired macromolecular signal profile.

Chemotherapy response monitoring of colorectal liver metastases by dynamic Gd-DTPA-enhanced MRI perfusion parameters and 18F-FDG PET metabolic rate.

Unlabelled: In this study, we examined the in vivo relationship between functional tumor vasculature, determined by dynamic contrast-enhanced (DCE-) MRI, and tumor metabolism, determined by dynamic (18)F-FDG PET, during cytotoxic treatment of patients with colorectal liver metastases.

Methods: Twenty-three patients underwent DCE-MRI (using gadolinium dimeglumine) and dynamic (18)F-FDG PET at baseline and after 3 treatment cycles, unless treatment was terminated because of toxicity. Parameters for vasculature (rate constant between extravascular extracellular space and blood plasma [k(ep)] and volume transfer constant [K(trans)]), extracellular space (v(e)), tumor size (the maximal axial diameter of each included lesion [MAD]), and metabolism (glucose metabolic rates [MR(glc)]) were derived, and changes during treatment were correlated.

High resolution magic angle spinning NMR spectroscopy for metabolic assessment of cancer presence and Gleason score in human prostate needle biopsies.

Objectives: Histopathology of prostate needle biopsies (PNBs) is an important part in the diagnosis, prognosis and treatment evaluation of prostate cancer. The determination of metabolite levels in the same biopsies may have additional clinical value. Here, we demonstrate the use of non-destructive high resolution magic angle spinning (HRMAS) proton NMR Spectroscopy for the assessment of metabolic profiles of prostate tissue in PNBs as commonly obtained in standard clinical practice.

Combination of feature-reduced MR spectroscopic and MR imaging data for improved brain tumor classification.

The purpose of this paper is to evaluate the effect of the combination of magnetic resonance spectroscopic imaging (MRSI) data and magnetic resonance imaging (MRI) data on the classification result of four brain tumor classes. Suppressed and unsuppressed short echo time MRSI and MRI were performed on 24 patients with a brain tumor and four volunteers. Four different feature reduction procedures were applied to the MRSI data: simple quantitation, principal component analysis, independent component analysis and LCModel.

Metabolic profile of the hippocampus of Zucker Diabetic Fatty rats assessed by in vivo 1H magnetic resonance spectroscopy.

Localized in vivo 1H magnetic resonance spectroscopy (MRS) was used to investigate metabolite levels in the brain of adult Zucker Diabetic Fatty (ZDF) rats, an animal model for type 2 diabetes mellitus. This study focussed on the hippocampus, assumed to be one of the main brain areas affected by this disease. Together with an almost 5-fold increase in blood glucose concentration measured by glucose oxidation, significant increases were found in the hippocampal concentrations of glucose (4.

MR spectroscopy of muscle and brain in guanidinoacetate methyltransferase (GAMT)-deficient mice: validation of an animal model to study creatine deficiency.

As a model for guanidinoacetate methyltransferase (GAMT) deficiency in humans, a gene knockout mouse model was generated. Here we report on several metabolic abnormalities in these mice, observed by in vivo and in vitro MR spectroscopy. In (1)H MR spectra of brain and hindleg muscle a clearly reduced signal of creatine (Cr) was observed in GAMT-deficient (GAMT-/-) animals.